Science.gov

Sample records for advanced hematologic cancer

  1. Chemotherapy in Treating Patients With Refractory Advanced Solid Tumors or Hematologic Cancer

    ClinicalTrials.gov

    2013-06-20

    Bladder Cancer; Breast Cancer; Colorectal Cancer; Gastric Cancer; Head and Neck Cancer; Kidney Cancer; Leukemia; Lung Cancer; Melanoma (Skin); Ovarian Cancer; Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  2. Cancer associated fibroblasts in hematological malignancies

    PubMed Central

    Raffaghello, Lizzia; Vacca, Angelo; Pistoia, Vito; Ribatti, Domenico

    2015-01-01

    Tumor microenvironment plays an important role in cancer initiation and progression. In hematological malignancies, the bone marrow represents the paradigmatic anatomical site in which tumor microenvironment expresses its morphofunctional features. Among the cells participating in the composition of this microenvironment, cancer associated fibrobasts (CAFs) have received less attention in hematopoietic tumors compared to solid cancers. In this review article, we discuss the involvement of CAFs in progression of hematological malignancies and the potential targeting of CAFs in a therapeutic perspective. PMID:25474039

  3. DCB - Cancer Immunology, Hematology, and Etiology Research

    Cancer.gov

    Part of NCI’s Division of Cancer Biology’s research portfolio, studies supported include the characterization of basic mechanisms relevant to anti-tumor immune responses and hematologic malignancies.

  4. Microscale functional cytomics for studying hematologic cancers

    PubMed Central

    Young, Edmond W. K.; Pak, Chorom; Kahl, Brad S.; Yang, David T.; Callander, Natalie S.; Miyamoto, Shigeki

    2012-01-01

    An important problem in translational cancer research is our limited ability to functionally characterize behaviors of primary patient cancer cells and associated stromal cell types, and relate mechanistic understanding to therapy selection. Functional analyses of primary samples face at least 3 major challenges: limited availability of primary samples for testing, paucity of functional information extracted from samples, and lack of functional methods accessible to many researchers. We developed a microscale cell culture platform that overcomes these limitations, especially for hematologic cancers. A key feature of the platform is the ability to compartmentalize small populations of adherent and nonadherent cells in controlled microenvironments that can better reflect physiological conditions and enable cell-cell interaction studies. Custom image analysis was developed to measure cell viability and protein subcellular localizations in single cells to provide insights into heterogeneity of cellular responses. We validated our platform by assessing viability and nuclear translocations of NF-κB and STAT3 in multiple myeloma cells exposed to different conditions, including cocultured bone marrow stromal cells. We further assessed its utility by analyzing NF-κB activation in a primary chronic lymphocytic leukemia patient sample. Our platform can be applied to myriad biological questions, enabling high-content functional cytomics of primary hematologic malignancies. PMID:22262772

  5. Common emergencies in cancer medicine: hematologic and gastrointestinal syndromes.

    PubMed Central

    Thomas, C. R.; Carter, I. K.; Leslie, W. T.; Sutton, F.

    1992-01-01

    A myriad of both primary and secondary hematologic and gastrointestinal system-related clinical problems may exist in the cancer patient. This review outlines a standard approach to the prompt diagnosis and therapeutic intervention for these clinical issues. PMID:1602515

  6. Chemotherapy tolerance after radioimmunotherapy with 90Y-CC49 monoclonal antibody in patients with advanced non-small cell lung cancer: clinical effects and hematologic toxicity.

    PubMed

    Robert, Francisco; Busby, Elizabeth M; LoBuglio, Albert F

    2003-06-01

    The purpose of this retrospective analysis was to evaluate the hematologic toxicity and clinical outcome of salvage chemotherapy following (90)Y-CC49 radioimmunotherapy (RIT) in patients with non-small cell lung cancer (NSCLC). Sixteen patients from a total of 37 who were enrolled in a phase I trial of (90)Y-CC49 monoclonal therapy were treated with post-RIT salvage chemotherapy at our institution. Five patients had received chest radiation therapy prior to RIT, and seven patients had prior chemotherapy. The majority of these patients were treated with doses of (90)Y of >/= 14 mCi/m(2) (8-20 mCi/m(2)), and four of them received concurrent 96-hour taxol infusion. The maximum tolerated dose of this study was exceeded at 17 mCi/m(2), and grade 4 thrombocytopenia/neutropenia were the dose-limiting toxicities. Twelve patients received one chemotherapy regimen as salvage therapy, and four patients had more than one regimen. Four patients (25%) experienced reversible grade 4 neutropenia, but no grade 4 thrombocytopenia was observed. Five patients had stable disease. The median survival from start of salvage therapy was 5.5 months. Our data suggest that therapy with RIT did not significantly affect survival of these patients. Taking into consideration the potential clinical relevance of integration of RIT with other treatment modalities, it is important to expand this clinical experience in order to support combined modality strategies. PMID:12954119

  7. Cardiovascular and Hematological Medicine in 2013 - Advances and Insights.

    PubMed

    Mukherjee, Debabrata

    2012-12-11

    Welcome to the first issue of Cardiovascular & Hematological Agents in Medicinal Chemistry (CHAMC) for 2013. I hope everyone has had an enjoyable holiday season and I want to wish everyone a wonderful New Year. As you know, our journal (CHAMC) aims to cover the latest and outstanding developments in medicinal chemistry, rational drug design for the discovery of novel cardiovascular and hematological Agents and discusses such therapies in clinical practice. Each issue contains a series of timely in-depth reviews, original research articles and drug clinical trial studies written by leaders in the field covering a range of current topics in cardiovascular and hematological sciences. I feel that CHAMC is an essential journal for every medicinal chemist, clinician and healthcare provider who wishes to be kept informed and up-to-date with the latest and most important developments in cardiovascular and hematological drug discovery and their clinical uses. In the coming issues of the journal, we will discuss several important topics pertinent to chemists and clinicians in the cardiovascular and hematology fields such as curcumin and resveratrol as alternative medicinal agents against metabolic syndrome, interrelationship between chronic kidney disease and risk of cardiovascular diseases and effects of direct renin inhibitor, aliskiren, on arterial hypertension, chronic kidney disease and cardiovascular disease among others. The journal also delves into hot topics such as genetic testing and personalized medicine, use of literature-based discovery to identify novel therapeutic approaches, pharmacologic mechanism and clinical relevance of P2Y12 inhibitors and intracoronary injection of glycoprotein IIb/IIIa, abciximab, as adjuvant therapy in primary coronary intervention. Cardiovascular medicine and hematology are both very dynamic fields with rapid advances and we will continue to work to keep you up to date on new advances and therapies. I would also take this

  8. Awakening the Hippo co-activator YAP1, a mercurial cancer gene, in hematologic cancers

    PubMed Central

    Cottini, Francesca; Anderson, Kenneth C; Tonon, Giovanni

    2014-01-01

    Unrestrained oncogene activity triggers DNA damage. Cancer cells exploit various stratagems to deal with this potentially lethal event. We found that hematologic cancer cells inactivate the Hippo co-activator Yes-associated protein 1 (YAP1). A synthetic lethal approach is proposed whereby inhibition of the serine/threonine kinase 4 (STK4) could be exploited to restore YAP1 levels in hematologic cancers.

  9. A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers

    PubMed Central

    LaBelle, James L.; Katz, Samuel G.; Bird, Gregory H.; Gavathiotis, Evripidis; Stewart, Michelle L.; Lawrence, Chelsea; Fisher, Jill K.; Godes, Marina; Pitter, Kenneth; Kung, Andrew L.; Walensky, Loren D.

    2012-01-01

    Cancer cells subvert the natural balance between cellular life and death, achieving immortality through pathologic enforcement of survival pathways and blockade of cell death mechanisms. Pro-apoptotic BCL-2 family proteins are frequently disarmed in relapsed and refractory cancer through genetic deletion or interaction-based neutralization by overexpressed antiapoptotic proteins, resulting in resistance to chemotherapy and radiation treatments. New pharmacologic strategies are urgently needed to overcome these formidable apoptotic blockades. We harnessed the natural killing activity of BCL-2–interacting mediator of cell death (BIM), which contains one of the most potent BH3 death domains of the BCL-2 protein family, to restore BH3-dependent cell death in resistant hematologic cancers. A hydrocarbon-stapled peptide modeled after the BIM BH3 helix broadly targeted BCL-2 family proteins with high affinity, blocked inhibitory antiapoptotic interactions, directly triggered proapoptotic activity, and induced dose-responsive and BH3 sequence–specific cell death of hematologic cancer cells. The therapeutic potential of stapled BIM BH3 was highlighted by the selective activation of cell death in the aberrant lymphoid infiltrates of mice reconstituted with BIM-deficient bone marrow and in a human AML xenograft model. Thus, we found that broad and multimodal targeting of the BCL-2 family pathway can overcome pathologic barriers to cell death. PMID:22622039

  10. Nurses’ Health Study Contributions on the Epidemiology of Less Common Cancers: Endometrial, Ovarian, Pancreatic, and Hematologic

    PubMed Central

    Barnard, Mollie E.; Bertrand, Kimberly A.; Bao, Ying; Crous-Bou, Marta; Wolpin, Brian M.; De Vivo, Immaculata; Tworoger, Shelley S.

    2016-01-01

    Objectives. To review the contributions of the Nurses’ Health Study (NHS) to epidemiologic knowledge of endometrial, ovarian, pancreatic, and hematologic cancers. Methods. We reviewed selected NHS publications from 1976 to 2016, including publications from consortia and other pooled studies. Results. NHS studies on less common cancers have identified novel risk factors, such as a reduced risk of endometrial cancer in women of advanced age at last birth, and have clarified or prospectively confirmed previously reported associations, including an inverse association between tubal ligation and ovarian cancer. Through biomarker research, the NHS has furthered understanding of the pathogenesis of rare cancers, such as the role of altered metabolism in pancreatic cancer risk and survival. NHS investigations have also demonstrated the importance of the timing of exposure, such as the finding of a positive association of early life body fatness, but not of usual adult body mass index, with non-Hodgkin lymphoma risk. Conclusions. Evidence from the NHS has informed prevention strategies and contributed to improved survival from less common but often lethal malignancies, including endometrial, ovarian, pancreatic, and hematologic cancers. PMID:27459458

  11. TET proteins and 5-methylcytosine oxidation in hematological cancers

    PubMed Central

    An, Jungeun; Pastor, William A.; Ko, Myunggon; Rao, Anjana

    2015-01-01

    Summary DNA methylation has pivotal regulatory roles in mammalian development, retrotransposon silencing, genomic imprinting and X-chromosome inactivation. Cancer cells display highly dysregulated DNA methylation profiles characterized by global hypomethylation in conjunction with hypermethylation of promoter CpG islands (CGIs) that presumably lead to genome instability and aberrant expression of tumor suppressor genes or oncogenes. The recent discovery of Ten-Eleven-Translocation (TET) family dioxygenases that oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in DNA has led to profound progress in understanding the mechanism underlying DNA demethylation. Among the three TET genes, TET2 recurrently undergoes inactivating mutations in a wide range of myeloid and lymphoid malignancies. TET2 functions as a bona fide tumor suppressor particularly in the pathogenesis of myeloid malignancies resembling chronic myelomoncytic leukemia (CMML) and myelodysplastic syndromes (MDS) in human. Here we review diverse functions of TET proteins and the novel epigenetic marks that they generate in DNA methylation/demethylation dynamics and normal and malignant hematopoietic differentiation. The impact of TET2 inactivation in hematopoiesis and various mechanisms modulating the expression or activity of TET proteins are also discussed. Furthermore, we also present evidence that TET2 and TET3 collaborate to suppress aberrant hematopoiesis and hematopoietic transformation. A detailed understanding of the normal and pathological functions of TET proteins may provide new avenues to develop novel epigenetic therapies for treating hematological malignancies. PMID:25510268

  12. Phosphoproteomics data classify hematological cancer cell lines according to tumor type and sensitivity to kinase inhibitors

    PubMed Central

    2013-01-01

    Background Tumor classification based on their predicted responses to kinase inhibitors is a major goal for advancing targeted personalized therapies. Here, we used a phosphoproteomic approach to investigate biological heterogeneity across hematological cancer cell lines including acute myeloid leukemia, lymphoma, and multiple myeloma. Results Mass spectrometry was used to quantify 2,000 phosphorylation sites across three acute myeloid leukemia, three lymphoma, and three multiple myeloma cell lines in six biological replicates. The intensities of the phosphorylation sites grouped these cancer cell lines according to their tumor type. In addition, a phosphoproteomic analysis of seven acute myeloid leukemia cell lines revealed a battery of phosphorylation sites whose combined intensities correlated with the growth-inhibitory responses to three kinase inhibitors with remarkable correlation coefficients and fold changes (> 100 between the most resistant and sensitive cells). Modeling based on regression analysis indicated that a subset of phosphorylation sites could be used to predict response to the tested drugs. Quantitative analysis of phosphorylation motifs indicated that resistant and sensitive cells differed in their patterns of kinase activities, but, interestingly, phosphorylations correlating with responses were not on members of the pathway being targeted; instead, these mainly were on parallel kinase pathways. Conclusion This study reveals that the information on kinase activation encoded in phosphoproteomics data correlates remarkably well with the phenotypic responses of cancer cells to compounds that target kinase signaling and could be useful for the identification of novel markers of resistance or sensitivity to drugs that target the signaling network. PMID:23628362

  13. [Cancer-related fatigue in hematological cancer: hematologist's and patient's view].

    PubMed

    La Verde, Giacinto; Arienti, Danilo

    2002-09-01

    Fatigue is a common complication in cancer patients, particularly in those receiving chemotherapy, with important negative effects on quality of life. It is not sufficiently studied, not completely understood and does not receive adequate consideration. The aim of this study is to improve knowledge on epidemiology, aetiology and treatment of fatigue in cancer patients in Italy. Answers to a questionnaire administered to 300 hematologists and a similar number of patients with hematological cancer have been evaluated. According to the opinion of hematologists and the experience of patients, fatigue is the most frequent and long-lasting symptom in patients with hematological cancer compromising their quality of life. The majority of the patients of the study group reports fatigue along the course of their disease, and this symptom is prominent in how it affects the different aspects of quality of life: their daily routine, working and social interaction according to clinicians; physical and emotional well-being according to patients. The results of the hematologist study group found anemia to be the leading cause of cancer-related fatigue. For the management of the symptom, the treatment of anemia is mainly done with transfusion and drugs, and it is advisable in the majority of the patients. There is still debate on the definition of anemia: hemoglobin (Hb) levels < 8 g/dl according to one third of the clinicians and greater values up to 10-11 g/dl for the others. According to the hematologists of the study group, a treatment for fatigue is generally recommended for the majority of the cancer patients, yet patients reported that, on the contrary, 50% of their hematologists did not suggest any specific treatment for this aim. PMID:12355982

  14. Advances in haploidentical stem cell transplantation for hematologic malignancies.

    PubMed

    Montoro, Juan; Sanz, Jaime; Sanz, Guillermo F; Sanz, Miguel A

    2016-08-01

    One of the most important advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the use of alternative donors and cell sources, such as haploidentical transplants (haplo-HSCT) from family donors. Several approaches have been developed to overcome the challenging bidirectional alloreactivity. We discuss these approaches, including ex vivo T-cell-depleted grafts with megadose of CD34(+) cells, not requiring immunosuppression after allogeneic transplantation for graft-versus-host disease (GVHD) prophylaxis, and other strategies using unmanipulated T-cell-replete grafts with intensive immunosuppression or post-transplantation cyclophosphamide to minimize the GVHD. We also address the role of other strategies developed in the context of the haplo-HSCT platforms, such as ex vivo selective depletion of alloreactive donor T-cell subpopulations, infusion of antigen-specific T-cells against several pathogens, and infusion of regulatory T-cells, among other experimental approaches. Finally, some considerations about the selection of the most suitable donor, when more than one family member is available, are also addressed. PMID:27424663

  15. Alterations in the ribosomal machinery in cancer and hematologic disorders

    PubMed Central

    2012-01-01

    Ribosomes are essential components of the protein translation machinery and are composed of more than 80 unique large and small ribosomal proteins. Recent studies show that in addition to their roles in protein translation, ribosomal proteins are also involved in extra-ribosomal functions of DNA repair, apoptosis and cellular homeostasis. Consequently, alterations in the synthesis or functioning of ribosomal proteins can lead to various hematologic disorders. These include congenital anemias such as Diamond Blackfan anemia and Shwachman Diamond syndrome; both of which are associated with mutations in various ribosomal genes. Acquired uniallelic deletion of RPS14 gene has also been shown to lead to the 5q syndrome, a distinct subset of MDS associated with macrocytic anemia. Recent evidence shows that specific ribosomal proteins are overexpressed in liver, colon, prostate and other tumors. Ribosomal protein overexpression can promote tumorigenesis by interactions with the p53 tumor suppressor pathway and also by direct effects on various oncogenes. These data point to a broad role of ribosome protein alterations in hematologic and oncologic diseases. PMID:22709827

  16. Clinical trials of dendritic cell-based cancer vaccines in hematologic malignancies

    PubMed Central

    Pyzer, Athalia R; Avigan, David E; Rosenblatt, Jacalyn

    2015-01-01

    The potential for the immune system to target hematological malignancies is demonstrated in the allogeneic transplant setting, where durable responses can be achieved. However, allogeneic transplantation is associated with significant morbidity and mortality related to graft versus host disease. Cancer immunotherapy has the capacity to direct a specific cytotoxic immune response against cancer cells, particularly residual cancer cells, in order to reduce the likelihood of disease relapse in a more targeted and tolerated manner. Ex vivo dendritic cells can be primed in various ways to present tumor associated antigen to the immune system, in the context of co-stimulatory molecules, eliciting a tumor specific cytotoxic response in patients. Several approaches to prime dendritic cells and overcome the immunosuppressive microenvironment have been evaluated in pre-clinical and early clinical trials with promising results. In this review, we summarize the clinical data evaluating dendritic cell based vaccines for the treatment of hematological malignancies. PMID:25625926

  17. Residential radon exposure and risk of incident hematologic malignancies in the Cancer Prevention Study-II Nutrition Cohort.

    PubMed

    Teras, Lauren R; Diver, W Ryan; Turner, Michelle C; Krewski, Daniel; Sahar, Liora; Ward, Elizabeth; Gapstur, Susan M

    2016-07-01

    Dosimetric models show that radon, an established cause of lung cancer, delivers a non-negligible dose of alpha radiation to the bone marrow, as well as to lymphocytes in the tracheobronchial epithelium, and therefore could be related to risk of hematologic cancers. Studies of radon and hematologic cancer risk, however, have produced inconsistent results. To date there is no published prospective, population-based study of residential radon exposure and hematologic malignancy incidence. We used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort established in 1992, to examine the association between county-level residential radon exposure and risk of hematologic cancer. The analytic cohort included 140,652 participants (66,572 men, 74,080 women) among which 3019 incident hematologic cancer cases (1711 men, 1308 women) were identified during 19 years of follow-up. Cox proportional hazard regression was used to calculate multivariable-adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for radon exposure and hematologic cancer risk. Women living in counties with the highest mean radon concentrations (>148Bq/m(3)) had a statistically significant higher risk of hematologic cancer compared to those living in counties with the lowest (<74Bq/m(3)) radon levels (HR=1.63, 95% CI:1.23-2.18), and there was evidence of a dose-response relationship (HRcontinuous=1.38, 95% CI:1.15-1.65 per 100Bq/m(3); p-trend=0.001). There was no association between county-level radon and hematologic cancer risk among men. The findings of this large, prospective study suggest residential radon may be a risk factor for lymphoid malignancies among women. Further study is needed to confirm these findings. PMID:27015563

  18. Stem Cell Transplantation in Treating Patients With Hematologic Cancer

    ClinicalTrials.gov

    2012-05-31

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

  19. Genomic Hallmarks of Genes Involved in Chromosomal Translocations in Hematological Cancer

    PubMed Central

    Shugay, Mikhail; Ortiz de Mendíbil, Iñigo; Vizmanos, José L.; Novo, Francisco J.

    2012-01-01

    Reciprocal chromosomal translocations (RCTs) leading to the formation of fusion genes are important drivers of hematological cancers. Although the general requirements for breakage and fusion are fairly well understood, quantitative support for a general mechanism of RCT formation is still lacking. The aim of this paper is to analyze available high-throughput datasets with computational and robust statistical methods, in order to identify genomic hallmarks of translocation partner genes (TPGs). Our results show that fusion genes are generally overexpressed due to increased promoter activity of 5′ TPGs and to more stable 3′-UTR regions of 3′ TPGs. Furthermore, expression profiling of 5′ TPGs and of interaction partners of 3′ TPGs indicates that these features can help to explain tissue specificity of hematological translocations. Analysis of protein domains retained in fusion proteins shows that the co-occurrence of specific domain combinations is non-random and that distinct functional classes of fusion proteins tend to be associated with different components of the gene fusion network. This indicates that the configuration of fusion proteins plays an important role in determining which 5′ and 3′ TPGs will combine in specific fusion genes. It is generally accepted that chromosomal proximity in the nucleus can explain the specific pairing of 5′ and 3′ TPGS and the recurrence of hematological translocations. Using recently available data for chromosomal contact probabilities (Hi-C) we show that TPGs are preferentially located in early replicated regions and occupy distinct clusters in the nucleus. However, our data suggest that, in general, nuclear position of TPGs in hematological cancers explains neither TPG pairing nor clinical frequency. Taken together, our results support a model in which genomic features related to regulation of expression and replication timing determine the set of candidate genes more likely to be translocated in

  20. Risk of Non-hematologic Cancer in Individuals with High Count Monoclonal B-Cell Lymphocytosis (MBL)

    PubMed Central

    Solomon, Benjamin M.; Chaffee, Kari G.; Moreira, Jonathan; Schwager, Susan M.; Cerhan, James R.; Call, Timothy G.; Kay, Neil E.; Slager, Susan L.; Shanafelt, Tait D.

    2015-01-01

    It is unknown whether individuals with monoclonal B-cell lymphocytosis (MBL) are at risk for adverse outcomes associated with chronic lymphocytic leukemia (CLL), such as the risk of non-hematologic cancer. We identified all locally-residing individuals diagnosed with high count MBL at Mayo Clinic between 1999 and 2009 and compared their rates of non-hematologic cancer to that of patients with CLL and two control cohorts: general medicine patients and patients who underwent clinical evaluation with flow cytometry but who had no hematologic malignancy. After excluding individuals with prior cancers, there were 107 high count MBL cases, 132 CLL cases, 589 clinic controls, and 482 flow cytometry controls. With 4.6 years median follow-up, 14 (13%) individuals with high count MBL, 21 (4%) clinic controls (comparison MBL p<0.0001), 18 (4%) flow controls (comparison MBL p=0.0001), and 16 (12%) CLL patients (comparison MBL p=0.82) developed non-hematologic cancer. On multivariable Cox regression analysis, individuals with high count MBL had higher risk of non-hematologic cancer than flow controls (HR=2.36; p=0.04) and borderline higher risk than clinic controls (HR=2.00; p=0.07). Patients with high count MBL appear to be at increased risk for non-hematologic cancer, further reinforcing that high count MBL has a distinct clinical phenotype despite low risk of progression to CLL. PMID:26310541

  1. Risk of non-hematologic cancer in individuals with high-count monoclonal B-cell lymphocytosis.

    PubMed

    Solomon, B M; Chaffee, K G; Moreira, J; Schwager, S M; Cerhan, J R; Call, T G; Kay, N E; Slager, S L; Shanafelt, T D

    2016-02-01

    It is unknown whether individuals with monoclonal B-cell lymphocytosis (MBL) are at risk for adverse outcomes associated with chronic lymphocytic leukemia (CLL), such as the risk of non-hematologic cancer. We identified all locally residing individuals diagnosed with high-count MBL at Mayo Clinic between 1999 and 2009 and compared their rates of non-hematologic cancer with that of patients with CLL and two control cohorts: general medicine patients and patients who underwent clinical evaluation with flow cytometry but who had no hematologic malignancy. After excluding individuals with prior cancers, there were 107 high-count MBL cases, 132 CLL cases, 589 clinic controls and 482 flow cytometry controls. With 4.6 years median follow-up, 14 (13%) individuals with high-count MBL, 21 (4%) clinic controls (comparison MBL P<0.0001), 18 (4%) flow controls (comparison MBL P=0.0001) and 16 (12%) CLL patients (comparison MBL P=0.82) developed non-hematologic cancer. On multivariable Cox regression analysis, individuals with high-count MBL had higher risk of non-hematologic cancer compared with flow controls (hazard ratio (HR)=2.36; P=0.04) and borderline higher risk compared with clinic controls (HR=2.00; P=0.07). Patients with high-count MBL appear to be at increased risk for non-hematologic cancer, further reinforcing that high-count MBL has a distinct clinical phenotype despite low risk of progression to CLL. PMID:26310541

  2. Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers.

    PubMed

    Cottini, Francesca; Hideshima, Teru; Xu, Chunxiao; Sattler, Martin; Dori, Martina; Agnelli, Luca; ten Hacken, Elisa; Bertilaccio, Maria Teresa; Antonini, Elena; Neri, Antonino; Ponzoni, Maurilio; Marcatti, Magda; Richardson, Paul G; Carrasco, Ruben; Kimmelman, Alec C; Wong, Kwok-Kin; Caligaris-Cappio, Federico; Blandino, Giovanni; Kuehl, W Michael; Anderson, Kenneth C; Tonon, Giovanni

    2014-06-01

    Oncogene-induced DNA damage elicits genomic instability in epithelial cancer cells, but apoptosis is blocked through inactivation of the tumor suppressor p53. In hematological cancers, the relevance of ongoing DNA damage and the mechanisms by which apoptosis is suppressed are largely unknown. We found pervasive DNA damage in hematologic malignancies, including multiple myeloma, lymphoma and leukemia, which leads to activation of a p53-independent, proapoptotic network centered on nuclear relocalization of ABL1 kinase. Although nuclear ABL1 triggers cell death through its interaction with the Hippo pathway coactivator YAP1 in normal cells, we show that low YAP1 levels prevent nuclear ABL1-induced apoptosis in these hematologic malignancies. YAP1 is under the control of a serine-threonine kinase, STK4. Notably, genetic inactivation of STK4 restores YAP1 levels, triggering cell death in vitro and in vivo. Our data therefore identify a new synthetic-lethal strategy to selectively target cancer cells presenting with endogenous DNA damage and low YAP1 levels. PMID:24813251

  3. Alternative donor transplants for patients with advanced hematologic malignancies, conditioned with thiotepa, cyclophosphamide and antithymocyte globulin.

    PubMed

    Lamparelli, T; van Lint, M T; Gualandi, F; Raiola, A M; Barbanti, M; Sacchi, N; Ficai, G; Ghinatti, C; Bregante, S; Berisso, G; Dominietto, A; Di Grazia, C; Bruno, B; Sessarego, M; Casarino, L; Verdiani, S; Bacigalupo, A

    2000-12-01

    Preparative regimens without total body irradiation (TBI) have been reported for alternative donor hemopoietic stem cell transplants (HSCT). Between 7 September 1994 and 7 June 1999 48 patients with advanced hematologic malignancies were conditioned with thiotepa (THIO) 15 mg/kg, cyclophosphamide (CY) 150 mg/kg and antithymocyte globulin (ATG). Donors were HLA mismatched family members (1-2 antigens) (FAM) (n = 24, median age 31 years) or HLA matched unrelated donors (UD) (n = 24, median age 34 years). GVHD prophylaxis was cyclosporine and methotrexate. Stem cell source was peripheral blood (n = 8) or bone marrow (n = 40). Hematologic recovery was seen in 42/46 (91%) evaluable patients and complete chimerism in 31/37 patients (85%). Acute GVHD grades III-IV were seen in 10/46 patients surviving 10 days (21%) and extensive chronic GVHD in 2/36 patients surviving 100 days (5%). Twenty-six patients died (54%), eight of recurrent disease (17%) and 18 of transplant-related complications (37%): main causes of TRM were GVHD (15%), infections (15%) and graft failure (4%). Twenty-two patients (46%) survive with a median follow-up of 877 days (287-1840). The actuarial 3-year survival is 49% for FAM and 42% for UD transplants. Results obtained with this regimen in unrelated grafts for advanced CML (n = 15) were not significantly different when compared to 21 concurrent UD grafts for advanced CML prepared with CY-TBI. In conclusion, the combination of THIO-CY-ATG allows engraftment of alternative donor hemopoietic stem cells. Results are similar when using unrelated matched donors or partially mismatched family donors, and not significantly different when compared to patients conditioned with CY-TBI. PMID:11223970

  4. Bloodstream infections in patients with hematological malignancies: which is more fatal – cancer or resistant pathogens?

    PubMed Central

    Gedik, Habip; Şimşek, Funda; Kantürk, Arzu; Yildirmak, Taner; Arica, Deniz; Aydin, Demet; Demirel, Naciye; Yokuş, Osman

    2014-01-01

    Background The primary objective of this study was to report the incidence of bloodstream infections (BSIs) and clinically or microbiologically proven bacterial or fungal BSIs during neutropenic episodes in patients with hematological malignancies. Methods In this retrospective observational study, all patients in the hematology department older than 14 years who developed febrile neutropenia during chemotherapy for hematological cancers were evaluated. Patients were included if they had experienced at least one neutropenic episode between November 2010 and November 2012 due to chemotherapy in the hematology ward. Results During 282 febrile episodes in 126 patients, 66 (23%) episodes of bacteremia and 24 (8%) episodes of fungemia were recorded in 48 (38%) and 18 (14%) patients, respectively. Gram-negative bacteria caused 74% (n=49) of all bacteremic episodes. Carbapenem-resistant Gram-negative bacteria (n=6) caused 12% and 9% of Gram-negative bacteremia episodes and all bacteremia episodes, respectively. Carbapenem-resistant Gram-negative bacteria included Acinetobacter baumannii (n=4), Pseudomonas aeruginosa (n=1), and Serratia marcescens (n=1). Culture-proven invasive fungal infection occurred in 24 episodes in 18 cases during the study period, with 15 episodes in ten cases occurring in the first study year and nine episodes in eight cases in the second study year. In 13 of 18 cases (72%) with bloodstream yeast infections, previous azole exposure was recorded. Candida parapsilosis, C. glabrata, and C. albicans isolates were resistant to voriconazole and fluconazole. Conclusion BSIs that occur during febrile neutropenic episodes in hematology patients due to Gram-negative bacteria should be treated initially with non-carbapenem-based antipseudomonal therapy taking into consideration antimicrobial stewardship. Non-azole antifungal drugs, including caspofungin and liposomal amphotericin B, should be preferred as empirical antifungal therapy in the events of possible

  5. Coping Styles, Health Status and Advance Care Planning in Patients with Hematologic Malignancies

    PubMed Central

    Loberiza, Fausto R; Swore-Flecther, Barbara A.; Block, Susan D.; Back, Anthony L.; Goldman, Roberta E.; Tulsky, James A.; Lee, Stephanie J.

    2014-01-01

    This study evaluated if measures of psychological well-being, including coping style are associated with advance care planning (ACP). Data were from the HEMA-COMM study, a prospective observational study of physician-patient communication in patients with hematologic malignancies. ACP was defined as having a living will, having a health care proxy, discussing life support with family or friends, and discussing life support with a doctor or nurse. 293 patients participated: only 45 (15%) had all the elements of ACP, 215 (73%) had at least 1 element of ACP, while 33 (11%) did not engage in ACP. In multivariate analysis, specific coping styles but not other measures of psychosocial well being were associated with having written ACP. Verbal ACP was associated with patient-reported health and physician estimate of life expectancy. Our study suggests that tailoring ACP discussions to a patient’s coping style may increase engagement in ACP. PMID:21851220

  6. Advances in haplo-identical stem cell transplantation in adults with high-risk hematological malignancies

    PubMed Central

    Ricci, Michael J; Medin, Jeffrey A; Foley, Ronan S

    2014-01-01

    Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatment-related toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental pre-clinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase II trials that will be summarized in this review. PMID:25258660

  7. Advances in haplo-identical stem cell transplantation in adults with high-risk hematological malignancies.

    PubMed

    Ricci, Michael J; Medin, Jeffrey A; Foley, Ronan S

    2014-09-26

    Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatment-related toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental pre-clinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase II trials that will be summarized in this review. PMID:25258660

  8. Immunotherapy of hematological cancers: PD-1 blockade for the treatment of Hodgkin's lymphoma

    PubMed Central

    Kroemer, Guido; Galluzzi, Lorenzo

    2015-01-01

    The blockade of immunological checkpoints has been successfully employed for the treatment of various solid neoplasms including melanoma, mesothelioma, non-small cell lung carcinoma, and renal cell carcinoma. A recent study indicates that the vast majority of patients with advanced, heavily pretreated Hodgkin's lymphoma (HL) also respond to a monoclonal antibody targeting programmed cell death 1 (PDCD1, best known as PD-1). Thus, checkpoint blockers may soon become part of our therapeutic armamentarium against hematological tumors. This would be particularly important as it would spare (at least some) patients the deleterious toxic effects of combinatorial chemotherapies and bone marrow transplantation. We anticipate that the realm of immunotherapy will eventually conquer vast portions of the territory that now belongs to hematological malignancies. PMID:26155425

  9. PIM serine/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers

    PubMed Central

    Brault, Laurent; Gasser, Christelle; Bracher, Franz; Huber, Kilian; Knapp, Stefan; Schwaller, Jürg

    2010-01-01

    The identification as cooperating targets of Proviral Integrations of Moloney virus in murine lymphomas suggested early on that PIM serine/threonine kinases play an important role in cancer biology. Whereas elevated levels of PIM1 and PIM2 were mostly found in hematologic malignancies and prostate cancer, increased PIM3 expression was observed in different solid tumors. PIM kinases are constitutively active and their activity supports in vitro and in vivo tumor cell growth and survival through modification of an increasing number of common as well as isoform-specific substrates including several cell cycle regulators and apoptosis mediators. PIM1 but not PIM2 seems also to mediate homing and migration of normal and malignant hematopoietic cells by regulating chemokine receptor surface expression. Knockdown experiments by RNA interference or dominant-negative acting mutants suggested that PIM kinases are important for maintenance of a transformed phenotype and therefore potential therapeutic targets. Determination of the protein structure facilitated identification of an increasing number of potent small molecule PIM kinase inhibitors with in vitro and in vivo anticancer activity. Ongoing efforts aim to identify isoform-specific PIM inhibitors that would not only help to dissect the kinase function but hopefully also provide targeted therapeutics. Here, we summarize the current knowledge about the role of PIM serine/threonine kinases for the pathogenesis and therapy of hematologic malignancies and solid cancers, and we highlight structural principles and recent progress on small molecule PIM kinase inhibitors that are on their way into first clinical trials. PMID:20145274

  10. Cancer stem-like cells: the dark knights of clinical hematology and oncology.

    PubMed

    Frinc, Ioana; Muresan, Mihai-Stefan; Zaharie, Florin; Petrov, Ljubomir; Irimie, Alexandra; Berce, Cristian; Berindan-Neagoe, Ioana; Tomuleasa, Ciprian

    2014-01-01

    According to recent epidemiological studies, malignant diseases represent the second cause of mortality worldwide and metastasis is the main cause of morbidity and mortality in most cancers. Even if the concept of "cancer stem cells" (CSCs) was anticipated by the genius of Rudolph Virchow, the father of modern pathology, more than 150 years ago, it is only in last few years that that scientists have begun to develop strategies aimed at inhibiting CSCs at a molecular level, the only way cancer can truly be attacked, by crossing the border between histology and molecular biology. The current concise review aims at emphasizing the main characteristics of tumor initiating cells, bridging the basic science to clinical hematology and oncology. PMID:24965388

  11. Recent advances in cancer immunotherapy with an emphasis on vaccines.

    PubMed

    Cavallo, Federica; Forni, Guido

    2009-01-01

    Recent Advances in Cancer Immunotherapy with an Emphasis on Vaccines was the first meeting organized by the European Society of Cancer Immunology and Immunotherapy and Progress in Vaccine against Cancer, in collaboration with the Institute of Biological Research and Biotechnology of the National Hellenic Research Foundation, in a joint effort towards the setting up of a new generation of cancer vaccines. The main topics of the meeting included: the role of the tumor microenvironment in protecting the tumor from immune attack; differences in immunotherapy outcome in hematological malignancies versus solid tumors; rationale of multi-epitope vaccines; Treg cell elimination/inactivation, tumor stroma destruction, angiogenesis inhibition and the potentiality of 'preventive' vaccination in breast, colon, prostate and ovarian cancer in the early stages and during the 'wait-and-see' period. The ninth Progress in Vaccines against Cancer meeting will be held in Sofia, Bulgaria, 8-10 October 2009, at the Hilton Hotel. PMID:19093768

  12. Low acute hematological toxicity during chemotherapy predicts reduced disease control in advanced Hodgkin's disease.

    PubMed

    Brosteanu, O; Hasenclever, D; Loeffler, M; Diehl, V

    2004-03-01

    Chemotherapy-treated patients with advanced Hodgkin's disease (HD) differ considerably in acute hematotoxicity. Hematotoxicity may be indicative of pharmacological and metabolic heterogeneity. We hypothesized that low hematotoxicity might correlate with reduced systemic dose and thus reduced disease control. A total of 266 patients with advanced HD treated with cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP-ABVD) were analyzed (HD6 trial of the German Hodgkin's Lymphoma Study Group). The reported WHO grade of leukocytopenia was averaged over chemotherapy cycles given and weighted with the reciprocal dose intensity of the corresponding cycle. The low and high toxicity groups were defined in retrospect as having had an averaged WHO grade of leukocytopenia 2.1, respectively. The independent impact of low hematological toxicity on freedom from treatment failure (FFTF) was assessed multivariately adjusting for the international prognostic score for advanced HD. The results were validated in two independent cohorts [181 patients treated with COPP-ABVD (HD9-trial) and 250 patients treated with COPP-ABV-ifosfamide, methotrexate, etoposide, and prednisone (IMEP) (HD6 trial)]. The 5-year FFTF rates were 68% for patients with high toxicity vs 47% for patients with low toxicity [multivariate relative risk (RR) 2.0, 95% confidence interval (CI) 1.4-3.0, p=0.0002]. Patients with low toxicity received significantly higher nominal dose ( p=0.02) and dose intensity ( p<0.0001). This finding was confirmed in both validation cohorts (multivariate RR 2.1, 95% CI 1.2-3.8, p=0.01 and RR 1.5, 95% CI 1.01-2.26, p=0.04, respectively). Patients with low hematotoxicity have significantly higher failure rates despite higher doses and dose intensity. Hematotoxicity is an independent prognostic factor for treatment outcome. This observation suggests a strategy of individualized dosing adapted to hematotoxicity

  13. Total body irradiation, fludarabine, melphalan, and allogeneic hematopoietic stem cell transplantation for advanced pediatric hematologic malignancies.

    PubMed

    Petropoulos, D; Worth, L L; Mullen, C A; Madden, R; Mahajan, A; Choroszy, M; Ha, C S; Champlin, R C; Chan, K W

    2006-03-01

    We evaluated the efficacy and toxicity of adding 9 Gy of total body irradiation (TBI), in three single daily fractions of 3 Gy, to the reduced intensity regimen of fludarabine 30 mg/m2 i.v. x 4 days and melphalan 140 mg/m2 i.v. x 1 day in advanced pediatric hematologic malignancies. Twenty-two acute lymphoblastic leukemia (ALL), six acute myeloid leukemia (AML), and one non-Hodgkin lymphoma patients were transplanted. Of these, 13 were beyond second remission, and five had prior hematopoietic stem cell transplant (HSCT). Twenty-one donors were unrelated, of which 19 were from cord blood (CB) units. Three of the eight related donors were genotypically disparate. Oral mucositis and diarrhea were the most common toxicities. Twenty-seven patients achieved neutrophil engraftment (median 16 days), and 23 had platelet engraftment (median 42 days). One patient had primary graft failure. Seven patients died of non-relapse causes in the first 100 days. With a median follow-up of 52 months, seven of 22 ALL, five of six AML, and one of one lymphoma patients are alive and in remission. The regimen of TBI, fludarabine, and melphalan allows the engraftment of allogeneic hematopoietic stem cells (including mismatched CB). It was fairly well tolerated in pediatric patients, even for second transplants. Its efficacy requires further evaluation. PMID:16435013

  14. Hematologic Toxicity in RTOG 0418: A Phase 2 Study of Postoperative IMRT for Gynecologic Cancer

    SciTech Connect

    Klopp, Ann H.; Moughan, Jennifer; Portelance, Lorraine; Miller, Brigitte E.; Salehpour, Mohammad R.; Hildebrandt, Evangeline; Nuanjing, Jenny; D'Souza, David; Souhami, Luis; Small, William; Gaur, Rakesh; Jhingran, Anuja

    2013-05-01

    Purpose: Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional setting. Methods and Materials: Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRT and weekly cisplatin (40 mg/m{sup 2}). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by Common Terminology Criteria for Adverse Events, version 3.0, criteria. Results: Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% (P =.025). Cervical cancer patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥2 HT than did those with a dose of ≤34.2 Gy (74% vs 43%, P=.049). Conclusions: Pelvic IMRT with weekly cisplatin is

  15. Coping with Advanced Cancer

    MedlinePlus

    ... Currents Blog Research Findings Drug Approvals Precision Medicine Leadership Views All Press Releases 2016 2015 2014 2013 ... NCI NCI Overview History Contributing to Cancer Research Leadership Director's Page Previous NCI Directors NCI Organization Advisory ...

  16. Pyoluteorin derivatives induce Mcl-1 degradation and apoptosis in hematological cancer cells

    PubMed Central

    Doi, Kenichiro; Gowda, Krishne; Liu, Qiang; Lin, Jyh-Ming; Sung, Shen-Shu; Dower, Christopher; Claxton, David; Loughran, Thomas P; Amin, Shantu; Wang, Hong-Gang

    2014-01-01

    Mcl-1, a pro-survival member of the Bcl-2 protein family, is an attractive target for cancer therapy. We have recently identified the natural product marinopyrrole A (maritoclax) as a novel small molecule Mcl-1 inhibitor. Here, we describe the structure-activity relationship study of pyoluteorin derivatives based on maritoclax. To date, we synthesized over 30 derivatives of maritoclax and evaluated their inhibitory actions and cytotoxicity toward Mcl-1-dependent cell lines. As a result, several functional groups were identified in the pyoluteorin motif that significantly potentiate biological activity. A number of such derivatives, KS04 and KS18, interacted with Mcl-1 in a conserved fashion according to NMR spectroscopy and molecular modeling. KS04 and KS18 induced apoptosis selectively in Mcl-1-dependent but not Bcl-2-dependent K562 cells through selective Mcl-1 down-regulation, and synergistically enhanced apoptosis in combination with ABT-737. Moreover, the intraperitoneal administration of KS18 (10 mg/kg/d) and ABT-737 (20 mg/kg/d) significantly suppressed the growth of ABT-737-resistant HL-60 xenografts in nude mice without apparent toxicity. Overall, we identified the pharmacophore of pyoluteorin derivatives that act as potent and promising Mcl-1 antagonists against Mcl-1-dependent hematological cancers. PMID:25535900

  17. Advances in cancer immunology and cancer immunotherapy.

    PubMed

    Voena, Claudia; Chiarle, Roberto

    2016-02-01

    After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models. PMID:27011048

  18. Hematologic malignancies in South Africa 2000-2006: analysis of data reported to the National Cancer Registry.

    PubMed

    Schonfeld, Sara J; Erdmann, Friederike; Wiggill, Tracey; Singh, Elvira; Kellett, Patricia; Babb, Chantal; Schüz, Joachim

    2016-04-01

    Little is known about the incidence patterns of hematologic malignancies in Sub-Saharan Africa, including South Africa. We estimated incidence rates of pathology-confirmed adult cases of leukemia, myeloma and related diseases (myeloma), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) reported to the National Cancer Registry of South Africa (NCR) between 2000 and2006, by age, gender, and population group (Black, White, Coloured, Asian/Indian). Gender-specific age-standardized rates were calculated overall and by population group and incidence rate ratios (IRRs) were estimated using Poisson regression models. Between 2000 and 2006, there were 14662 cases of leukemia, myeloma, HL, and NHL reported to the registry. Incidence rates of reported hematologic malignancies were generally 20-50% higher among males than females. Our analyses suggested marked differences in the rates of reported hematologic malignancies by population group which were most pronounced when comparing the White versus Black population groups (IRRs ranging from 1.6 for myeloma to 3.8 for HL for males and females combined). Challenges related to diagnosis and reporting of cancers may play a role in the patterns observed by population group while the set-up of the NCR (pathology-based) could lead to some degree of under-ascertainment in all groups. This is the first country-wide report of the incidence of hematologic malignancies in South Africa. Despite challenges, it is important to analyze and report available national cancer incidence data to raise awareness of the cancer burden and to characterize patterns by demographic characteristics so as ultimately to improve the provision of cancer-related health care. PMID:26773310

  19. Recent advances in the development of Aurora kinases inhibitors in hematological malignancies

    PubMed Central

    Choudary, Iqra; Barr, Paul M.; Friedberg, Jonathan

    2015-01-01

    Over the last two decades, since the discovery of Drosophila mutants in 1995, much effort has been made to understand Aurora kinase biology. Three mammalian subtypes have been identified thus far which include the Aurora A, B and C kinases. These regulatory proteins specifically work at the cytoskeleton and chromosomal structures between the kinetochores and have vital functions in the early phases of the mitotic cell cycle. Today, there are multiple phase I and phase II clinical trials as well as numerous preclinical studies taking place looking at Aurora kinase inhibitors in both hematologic and solid malignancies. This review focuses on the preclinical and clinical development of Aurora kinase inhibitors in hematological malignancy and discusses their therapeutic potential. PMID:26622997

  20. Identification of Anti-tumor Cells Carrying Natural Killer (NK) Cell Antigens in Patients With Hematological Cancers.

    PubMed

    Krzywinska, Ewelina; Allende-Vega, Nerea; Cornillon, Amelie; Vo, Dang-Nghiem; Cayrefourcq, Laure; Panabieres, Catherine; Vilches, Carlos; Déchanet-Merville, Julie; Hicheri, Yosr; Rossi, Jean-François; Cartron, Guillaume; Villalba, Martin

    2015-10-01

    Natural killer (NK) cells, a cytotoxic lymphocyte lineage, are able to kill tumor cells in vitro and in mouse models. However, whether these cells display an anti-tumor activity in cancer patients has not been demonstrated. Here we have addressed this issue in patients with several hematological cancers. We found a population of highly activated CD56(dim)CD16(+) NK cells that have recently degranulated, evidence of killing activity, and it is absent in healthy donors. A high percentage of these cells expressed natural killer cell p46-related protein (NKp46), natural-killer group 2, member D (NKG2D) and killer inhibitory receptors (KIRs) and a low percentage expressed NKG2A and CD94. They are also characterized by a high metabolic activity and active proliferation. Notably, we found that activated NK cells from hematological cancer patients have non-NK tumor cell antigens on their surface, evidence of trogocytosis during tumor cell killing. Finally, we found that these activated NK cells are distinguished by their CD45RA(+)RO(+) phenotype, as opposed to non-activated cells in patients or in healthy donors displaying a CD45RA(+)RO(-) phenotype similar to naïve T cells. In summary, we show that CD45RA(+)RO(+) cells, which resemble a unique NK population, have recognized tumor cells and degranulate in patients with hematological neoplasias. PMID:26629531

  1. RESCUE OF HIPPO CO-ACTIVATOR YAP1 TRIGGERS DNA DAMAGE-INDUCED APOPTOSIS IN HEMATOLOGICAL CANCERS

    PubMed Central

    Cottini, Francesca; Hideshima, Teru; Xu, Chunxiao; Sattler, Martin; Dori, Martina; Agnelli, Luca; Hacken, Elisa ten; Bertilaccio, Maria Teresa; Antonini, Elena; Neri, Antonino; Ponzoni, Maurilio; Marcatti, Magda; Richardson, Paul G.; Carrasco, Ruben; Kimmelman, Alec C.; Wong, Kwok-Kin; Caligaris-Cappio, Federico; Blandino, Giovanni; Kuehl, W. Michael; Anderson, Kenneth C.; Tonon, Giovanni

    2014-01-01

    Oncogene–induced DNA damage elicits genomic instability in epithelial cancer cells, but apoptosis is blocked through inactivation of the tumor suppressor p53. In hematological cancers, the relevance of ongoing DNA damage and mechanisms by which apoptosis is suppressed are largely unknown. We found pervasive DNA damage in hematologic malignancies including multiple myeloma, lymphoma and leukemia, which leads to activation of a p53–independent, pro-apoptotic network centered on nuclear relocalization of ABL1 kinase. Although nuclear ABL1 triggers cell death through its interaction with the Hippo pathway co–activator YAP1 in normal cells, we show that low YAP1 levels prevent nuclear ABL1–induced apoptosis in these hematologic malignancies. YAP1 is under the control of a serine–threonine kinase, STK4. Importantly, genetic inactivation of STK4 restores YAP1 levels, triggering cell death in vitro and in vivo. Our data therefore identify a novel synthetic–lethal strategy to selectively target cancer cells presenting with endogenous DNA damage and low YAP1 levels. PMID:24813251

  2. A clinical-molecular update on azanucleoside-based therapy for the treatment of hematologic cancers.

    PubMed

    Diesch, Jeannine; Zwick, Anabel; Garz, Anne-Kathrin; Palau, Anna; Buschbeck, Marcus; Götze, Katharina S

    2016-01-01

    The azanucleosides azacitidine and decitabine are currently used for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) in patients not only eligible for intensive chemotherapy but are also being explored in other hematologic and solid cancers. Based on their capacity to interfere with the DNA methylation machinery, these drugs are also referred to as hypomethylating agents (HMAs). As DNA methylation contributes to epigenetic regulation, azanucleosides are further considered to be among the first true "epigenetic drugs" that have reached clinical application. However, intriguing new evidence suggests that DNA hypomethylation is not the only mechanism of action for these drugs. This review summarizes the experience from more than 10 years of clinical practice with azanucleosides and discusses their molecular actions, including several not related to DNA methylation. A particular focus is placed on possible causes of primary and acquired resistances to azanucleoside treatment. We highlight current limitations for the success and durability of azanucleoside-based therapy and illustrate that a better understanding of the molecular determinants of drug response holds great potential to overcome resistance. PMID:27330573

  3. Proteogenomic-based discovery of minor histocompatibility antigens with suitable features for immunotherapy of hematologic cancers.

    PubMed

    Granados, D P; Rodenbrock, A; Laverdure, J-P; Côté, C; Caron-Lizotte, O; Carli, C; Pearson, H; Janelle, V; Durette, C; Bonneil, E; Roy, D C; Delisle, J-S; Lemieux, S; Thibault, P; Perreault, C

    2016-06-01

    Pre-clinical studies have shown that injection of allogeneic T cells primed against a single minor histocompatibility antigen (MiHA) could cure hematologic cancers (HC) without causing any toxicity to the host. However, translation of this approach in humans has been hampered by the paucity of molecularly defined human MiHAs. Using a novel proteogenomic approach, we have analyzed cells from 13 volunteers and discovered a vast repertoire of MiHAs presented by the most common HLA haplotype in European Americans: HLA-A*02:01;B*44:03. Notably, out of >6000 MiHAs, we have identified a set of 39 MiHAs that share optimal features for immunotherapy of HCs. These 'optimal MiHAs' are coded by common alleles of genes that are preferentially expressed in hematopoietic cells. Bioinformatic modeling based on MiHA allelic frequencies showed that the 39 optimal MiHAs would enable MiHA-targeted immunotherapy of practically all HLA-A*02:01;B*44:03 patients. Further extension of this strategy to a few additional HLA haplotypes would allow treatment of almost all patients. PMID:26857467

  4. Ionizing Particle Radiation as a Modulator of Endogenous Bone Marrow Cell Reprogramming: Implications for Hematological Cancers

    PubMed Central

    Muralidharan, Sujatha; Sasi, Sharath P.; Zuriaga, Maria A.; Hirschi, Karen K.; Porada, Christopher D.; Coleman, Matthew A.; Walsh, Kenneth X.; Yan, Xinhua; Goukassian, David A.

    2015-01-01

    Exposure of individuals to ionizing radiation (IR), as in the case of astronauts exploring space or radiotherapy cancer patients, increases their risk of developing secondary cancers and other health-related problems. Bone marrow (BM), the site in the body where hematopoietic stem cell (HSC) self-renewal and differentiation to mature blood cells occurs, is extremely sensitive to low-dose IR, including irradiation by high-charge and high-energy particles. Low-dose IR induces DNA damage and persistent oxidative stress in the BM hematopoietic cells. Inefficient DNA repair processes in HSC and early hematopoietic progenitors can lead to an accumulation of mutations whereas long-lasting oxidative stress can impair hematopoiesis itself, thereby causing long-term damage to hematopoietic cells in the BM niche. We report here that low-dose 1H- and 56Fe-IR significantly decreased the hematopoietic early and late multipotent progenitor (E- and L-MPP, respectively) cell numbers in mouse BM over a period of up to 10 months after exposure. Both 1H- and 56Fe-IR increased the expression of pluripotent stem cell markers Sox2, Nanog, and Oct4 in L-MPPs and 10 months post-IR exposure. We postulate that low doses of 1H- and 56Fe-IR may induce endogenous cellular reprogramming of BM hematopoietic progenitor cells to assume a more primitive pluripotent phenotype and that IR-induced oxidative DNA damage may lead to mutations in these BM progenitors. This could then be propagated to successive cell lineages. Persistent impairment of BM progenitor cell populations can disrupt hematopoietic homeostasis and lead to hematologic disorders, and these findings warrant further mechanistic studies into the effects of low-dose IR on the functional capacity of BM-derived hematopoietic cells including their self-renewal and pluripotency. PMID:26528440

  5. Ionizing Particle Radiation as a Modulator of Endogenous Bone Marrow Cell Reprogramming: Implications for Hematological Cancers.

    PubMed

    Muralidharan, Sujatha; Sasi, Sharath P; Zuriaga, Maria A; Hirschi, Karen K; Porada, Christopher D; Coleman, Matthew A; Walsh, Kenneth X; Yan, Xinhua; Goukassian, David A

    2015-01-01

    Exposure of individuals to ionizing radiation (IR), as in the case of astronauts exploring space or radiotherapy cancer patients, increases their risk of developing secondary cancers and other health-related problems. Bone marrow (BM), the site in the body where hematopoietic stem cell (HSC) self-renewal and differentiation to mature blood cells occurs, is extremely sensitive to low-dose IR, including irradiation by high-charge and high-energy particles. Low-dose IR induces DNA damage and persistent oxidative stress in the BM hematopoietic cells. Inefficient DNA repair processes in HSC and early hematopoietic progenitors can lead to an accumulation of mutations whereas long-lasting oxidative stress can impair hematopoiesis itself, thereby causing long-term damage to hematopoietic cells in the BM niche. We report here that low-dose (1)H- and (56)Fe-IR significantly decreased the hematopoietic early and late multipotent progenitor (E- and L-MPP, respectively) cell numbers in mouse BM over a period of up to 10 months after exposure. Both (1)H- and (56)Fe-IR increased the expression of pluripotent stem cell markers Sox2, Nanog, and Oct4 in L-MPPs and 10 months post-IR exposure. We postulate that low doses of (1)H- and (56)Fe-IR may induce endogenous cellular reprogramming of BM hematopoietic progenitor cells to assume a more primitive pluripotent phenotype and that IR-induced oxidative DNA damage may lead to mutations in these BM progenitors. This could then be propagated to successive cell lineages. Persistent impairment of BM progenitor cell populations can disrupt hematopoietic homeostasis and lead to hematologic disorders, and these findings warrant further mechanistic studies into the effects of low-dose IR on the functional capacity of BM-derived hematopoietic cells including their self-renewal and pluripotency. PMID:26528440

  6. [Weekly administration of paclitaxel with a short course of premedication for advanced or recurrent gastric cancer].

    PubMed

    Yamamoto, Shigetaka; Tanaka, Yasuhiro; Ito, Toshinori; Nakai, Sumio; Morimoto, Yoshikazu; Kitagawa, Tohru; Kurihara, Youjirou; Nishimura, Junichi

    2003-01-01

    Weekly administration of paclitaxel with a short course of premedication was performed for 8 patients with advanced or recurrent gastric cancer. In this regimen, 500 ml of physiological saline with vitamins was administered in a 3-hour infusion. After 30 minutes of infusion, dexamethasone 10 mg, chlorpheniramine maleate 5 mg, famotidine 20 mg and ramosetron hydrochloride 0.3 mg were administered intravenously. After 30 more minutes of infusion, paclitaxel at a dose of 65 mg/m2 was admixed in the residual normal physiological saline and administered over 2 hours. Administration was continued for 3 weeks with a 1 week rest. Though the partial response rate was 25%, clinical symptoms improved in all patients. Moreover, both hematological and non-hematological toxicities were mild. Weekly administration of paclitaxel with a short course of premedication is an effective and well-tolerated method for patients with advanced or recurrent gastric cancer. PMID:12557707

  7. Molecular and clinical profiles of syndecan-1 in solid and hematological cancer for prognosis and precision medicine

    PubMed Central

    Akl, Mohamed R.; Nagpal, Poonam; Ayoub, Nehad M.; Prabhu, Sathyen A.; Gliksman, Matthew; Tai, Betty; Hatipoglu, Ahmet; Goy, Andre; Suh, K. Stephen

    2015-01-01

    Syndecan-1 (SDC1, CD138) is a key cell surface adhesion molecule essential for maintaining cell morphology and interaction with the surrounding microenvironment. Deregulation of SDC1 contributes to cancer progression by promoting cell proliferation, metastasis, invasion and angiogenesis, and is associated with relapse through chemoresistance. SDC1 expression level is also associated with responses to chemotherapy and with prognosis in multiple solid and hematological cancers, including multiple myeloma and Hodgkin lymphoma. At the tissue level, the expression levels of SDC1 and the released extracellular domain of SDC1 correlate with tumor malignancy, phenotype, and metastatic potential for both solid and hematological tumors in a tissue-specific manner. The SDC1 expression profile varies among cancer types, but the differential expression signatures between normal and cancer cells in epithelial and stromal compartments are directly associated with aggressiveness of tumors and patient's clinical outcome and survival. Therefore, relevant biomarkers of SDC signaling may be useful for selecting patients that would most likely respond to a particular therapy at the time of diagnosis or perhaps for predicting relapse. In addition, the reciprocal expression signature of SDC between tumor epithelial and stromal compartments may have synergistic value for patient selection and the prediction of clinical outcome. PMID:26293675

  8. Exploring correlations between positive psychological resources and symptoms of psychological distress among hematological cancer patients: a cross-sectional study.

    PubMed

    Wang, Zi-Yue; Liu, Li; Shi, Meng; Wang, Lie

    2016-07-01

    Hematological cancer patients experience high levels of psychological distress during diagnoses and intensive treatments. The aim of the present study is to explore the effects of positive psychological resources on depressive and anxiety symptoms in hematological cancer patients. This survey was conducted in a hospital during the period from July 2013 to April 2014. A total of 300 inpatients were recruited and finally 227 of them completed the questionnaires. Questionnaires included demographic and clinical variables, the Center for Epidemiologic Studies Depression Scale, the Self-Rating Anxiety Scale, the Life Orientation Scale-Revised, the General Perceived Self-Efficacy Scale, and the Resilience Scale-14. Results showed that the prevalence of depressive and anxiety symptoms was 66.1 and 45.8%, respectively. Both optimism (β = -.479, p < .001) and resilience (β = -.174, p < .05) were negatively associated with depressive symptoms, and optimism (β = -.393, p < .001) was negatively associated with anxiety symptoms. However, resilience (β = -.133, p > .05) was not significantly associated with anxiety symptoms, and self-efficacy was not significantly associated with depressive (β = -.032, p > .05) or anxiety symptoms (β = -.055, p > .05). The results suggest that hematological cancer patients who possess high levels of positive psychological resources may have fewer symptoms of psychological distress. The findings indicate that enhancing positive psychological resources can be considered in developing intervention strategies for decreasing depressive and anxiety symptoms. PMID:26708250

  9. Genetically Engineered Immunotherapy for Advanced Cancer

    Cancer.gov

    In this trial, doctors will collect T lymphocytes from patients with advanced mesothelin-expressing cancer and genetically engineer them to recognize mesothelin. The gene-engineered cells will be multiplied and infused into the patient to fight the cancer

  10. Advances in cancer pain from bone metastasis

    PubMed Central

    Zhu, Xiao-Cui; Zhang, Jia-Li; Ge, Chen-Tao; Yu, Yuan-Yang; Wang, Pan; Yuan, Ti-Fei; Fu, Cai-Yun

    2015-01-01

    With the technological advances in cancer diagnosis and treatment, the survival rates for patients with cancer are prolonged. The issue of figuring out how to improve the life quality of patients with cancer has become increasingly prominent. Pain, especially bone pain, is the most common symptom in malignancy patients, which seriously affects the life quality of patients with cancer. The research of cancer pain has a breakthrough due to the development of the animal models of cancer pain in recent years, such as the animal models of mouse femur, humerus, calcaneus, and rat tibia. The establishment of several kinds of animal models related to cancer pain provides a new platform in vivo to investigate the molecular mechanisms of cancer pain. In this review, we focus on the advances of cancer pain from bone metastasis, the mechanisms involved in cancer pain, and the drug treatment of cancer pain in the animal models. PMID:26316696

  11. [Innovation in Surgery for Advanced Lung Cancer].

    PubMed

    Nakano, Tomoyuki; Yasunori, Sohara; Endo, Shunsuke

    2016-07-01

    Thoracoscopic surgery can be one of less invasive surgical interventions for early stage lung cancer. Locally advanced lung cancer, however, cannot avoid aggressive procedures including pneumonectomy and/or extended combined resection of chest wall, aorta, esophagus, etc. for complete resection. Surgical approach even for advanced lung cancer can be less invasive by benefit from new anti-cancer treatment, innovated manipulations of bronchoplasty and angioplasty, and bench surgery( lung autotransplantation technique). We herein reviewed the strategy to minimize invasive interventions for locally advanced lung cancer, introducing 2 successful cases with advanced lung cancer. The 1st patient is a 62-year old man with centrally advanced lung cancer invading to mediastinum. Right upper sleeve lobectomy with one-stoma carinoplasty following induction chemoradiation therapy was successful. The operation time was 241 minutes. The performance status is good with no recurrence for 60 months after surgery. The 2nd is a 79-year old man with advanced lung cancer invading to the distal aortic arch. Left upper segmentectomy following thoracic endovascular aortic repair with stentgraft was successful with no extracorporeal circulation. The operation time was 170 minutes. The performance status is good with no recurrence for 30 months after surgery. The invasiveness of surgical interventions for local advanced lung cancer can be minimized by innovated device and new anti-cancer drugs. PMID:27440037

  12. A Phase 1 Dose Escalation Study of TAK-901 in Subjects With Advanced Hematologic Malignancies

    ClinicalTrials.gov

    2013-07-01

    Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Multiple Myeloma; Waldenstrom's Macroglobulinemia; Myelodysplastic Syndrome; Philadelphia Chromosome-negative CML; Myeloid Metaplasia; Myelofibrosis; Advanced Polycythemia; Non-Hodgkins Lymphoma

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

    ClinicalTrials.gov

    2014-09-09

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

  14. Advanced epithelial ovarian cancer: toxicity of whole abdominal irradiation after operation, combination chemotherapy, and reoperation

    SciTech Connect

    Schray, M.F.; Martinez, A.; Howes, A.E.; Ballon, S.C.; Podratz, K.C.; Sikic, B.I.; Malkasian, G.D.

    1986-05-01

    Thirty-five patients with advanced ovarian cancer have received, as salvage therapy, irradiation consisting of 30 Gy to the entire abdominal contents with partial liver/kidney shielding and boosts to 42 and 51 Gy for the paraaortic/diaphragmatic and pelvic regions, respectively. These patients had received 6 to 25 cycles (median, 11 cycles) of prior combination chemotherapy (included cisplatin in 30), with second-look laparotomy performed in 33; 24 (68%) had three or more laparotomies. Acute gastrointestinal toxicity was generally mild. Significant hematologic toxicity (leukocytes less than 2000/mm3; or platelets less than 100,000/mm3) was seen in 19 (54%); platelet suppression occurred in 18 of these 19. Nine patients failed to complete the prescribed course of therapy; in seven, this was secondary to hematologic toxicity. Amount of prior chemotherapy and advanced age correlated with degree of hematologic toxicity. Five patients without evidence of disease (laparotomy confirmed) have developed treatment-related bowel obstruction. No other chronic toxicity of clinical significance has been observed. Seven patients have developed bowel obstruction associated with progressive neoplasm. Irradiation was well tolerated symptomatically, but hematologic toxicity associated with prior chemotherapy prevented its completion in 20% of patients. Clinical manifestations of radiation bowel toxicity have been moderate to date and should be interpreted in the context of the aggressive combined modality program.

  15. Role of Extracellular Vesicles in Hematological Malignancies

    PubMed Central

    Raimondo, Stefania; Corrado, Chiara; Raimondi, Lavinia; De Leo, Giacomo; Alessandro, Riccardo

    2015-01-01

    In recent years the role of tumor microenvironment in the progression of hematological malignancies has been widely recognized. Recent studies have focused on how cancer cells communicate within the microenvironment. Among several factors (cytokines, growth factors, and ECM molecules), a key role has been attributed to extracellular vesicles (EV), released from different cell types. EV (microvesicles and exosomes) may affect stroma remodeling, host cell functions, and tumor angiogenesis by inducing gene expression modulation in target cells, thus promoting cancer progression and metastasis. Microvesicles and exosomes can be recovered from the blood and other body fluids of cancer patients and contain and deliver genetic and proteomic contents that reflect the cell of origin, thus constituting a source of new predictive biomarkers involved in cancer development and serving as possible targets for therapies. Moreover, due to their specific cell-tropism and bioavailability, EV can be considered natural vehicles suitable for drug delivery. Here we will discuss the recent advances in the field of EV as actors in hematological cancer progression, pointing out the role of these vesicles in the tumor-host interplay and in their use as biomarkers for hematological malignancies. PMID:26583135

  16. Episodic pain in patients with advanced cancer.

    PubMed

    Zeppetella, Giovambattista; Ribeiro, Maria D C

    2002-01-01

    Episodic pain is a common problem for patients with advanced cancer and is often difficult to manage successfully. In this article, the daily variations in cancer-related episodic pain in a patient with metastatic lung cancer are described. The definition, etiology, prevalence, and pharmacological management of episodic pain are also reviewed PMID:12141792

  17. Global controversies and advances in skin cancer.

    PubMed

    Baldwin, Louise; Dunn, Jeff

    2013-01-01

    Advances and controversies of skin cancer prevention in the Asian-Pacific region are to be examined the world's first Global Controversies and Advances in Skin Cancer Conference to be held in Brisbane, Australia this November. APOCP Members are cordially invited to register early for the opportunity to contribute to the debate on a cancer which continues to be a prominent issue in the Asia Pacific and indeed worldwide. We need answers to the questions of why a cancer that is so preventable and easily detectable is still shrouded in controversy. Primary focuses will be on issues like viral involvement, vaccines and novel clinical approaches. PMID:23725105

  18. Radiation Therapy and Late Mortality From Second Sarcoma, Carcinoma, and Hematological Malignancies After a Solid Cancer in Childhood

    SciTech Connect

    Tukenova, Markhaba; Guibout, Catherine; Hawkins, Mike; Quiniou, Eric; Mousannif, Abddedahir; Pacquement, Helene; Winter, David; Bridier, Andre; Lefkopoulos, Dimitri; Oberlin, Odile; Diallo, Ibrahima; Vathaire, Florent de

    2011-06-01

    Purpose: To compare patterns of long-term deaths due to secondary carcinomas, sarcomas, and hematological malignancies occurring after childhood cancer in a cohort of patients followed over a median of 28 years. Methods and Materials: The study included 4,230 patients treated at eight institutions, who were at least 5-year survivors of a first cancer, representing 105,670 person-years of observation. Complete clinical, chemotherapeutic, and radiotherapeutic data were recorded, and the integral radiation dose was estimated for 2,701 of the 2,948 patients who had received radiotherapy. The integral dose was estimated for the volume inside the beam edges. The causes of death obtained from death certificates were validated. Results: In total, 134 events were due to second malignant neoplasm(s) (SMN). We found that the standardized mortality ratio decreased with increasing follow-up for second carcinomas and sarcomas, whereas the absolute excess risk (AER) increased for a second carcinoma but decreased for second sarcomas. There was no clear variation in SMN and AER for hematological malignancies. We found a significant dose-response relationship between the radiation dose received and the mortality rate due to a second sarcoma and carcinoma. The risk of death due to carcinoma and sarcoma as SMN was 5.2-fold and 12.5-fold higher, respectively, in patients who had received a radiation dose exceeding 150 joules. Conclusions: Among patients who had received radiotherapy, only those having received the highest integral radiation dose actually had a higher risk of dying of a second carcinoma or sarcoma.

  19. The Mediating Role of Mental Adjustment in the Relationship between Perceived Stress and Depressive Symptoms in Hematological Cancer Patients: A Cross-Sectional Study

    PubMed Central

    Li, Yingchun; Yang, Ying; Zhang, Rong; Yao, Kun; Liu, Zhuogang

    2015-01-01

    Background Depression is a particularly common psychological disorder that affects cancer patients. Diagnosed with hematological malignancies constitute a serious unpredictable and uncontrollable medical stress situation and patients are susceptible to suffer from depressive symptoms. The aims of the study were to explore the correlation between perceived stress and depressive symptoms in patients with hematological malignancies, and assess the mediating role of mental adjustment between these variables. Methods A single center, cross-sectional study was performed by convenience sampling between July 2013 and April 2014 in a hospital of China. The Center for Epidemiologic Studies Depression Scale, Perceived Stress Scale, and Mini-Mental Adjustment Scale, as well as questions about demographic and clinical factors was distributed to 300 hematological cancer patients. Completed questionnaires were received from 227 inpatients. Results The results showed that perceived stress was positively correlated with depressive symptoms. The mental adjustment significantly mediated the relationship between perceived stress and depressive symptoms. Conclusions Among hematological cancer patients perceived stress may be a risk factor for depressive symptoms, whereas positive coping style might be protective against depressive symptoms. Results showed that medical managers could support the development of mental adjustment in the patients to alleviate psychological disorders. PMID:26587991

  20. Integrated Molecular Profiling in Advanced Cancers Trial

    ClinicalTrials.gov

    2016-08-19

    Breast Cancer; Non-small Cell Lung Cancer; Colorectal Cancer; Genitourinary Cancer; Pancreatobiliary Gastrointestinal Cancer; Upper Aerodigestive Tract Cancer; Gynecological Cancers; Melanoma Cancers; Rare Cancers; Unknown Primary Cancers

  1. Precision medicine for advanced prostate cancer

    PubMed Central

    Mullane, Stephanie A.; Van Allen, Eliezer M.

    2016-01-01

    Purpose of review Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Recent findings Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Summary Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients. PMID:26909474

  2. Novel agents for advanced pancreatic cancer

    PubMed Central

    Akinleye, Akintunde; Iragavarapu, Chaitanya; Furqan, Muhammad; Cang, Shundong; Liu, Delong

    2015-01-01

    Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer. PMID:26369833

  3. Advances in bronchoscopy for lung cancer

    PubMed Central

    Dhillon, Samjot Singh; Dexter, Elisabeth U.

    2012-01-01

    Bronchoscopic techniques have seen significant advances in the last decade. The development and refinement of different types of endobronchial ultrasound and navigation systems have led to improved diagnostic yield and lung cancer staging capabilities. The complication rate of these minimally invasive procedures is extremely low as compared to traditional transthoracic needle biopsy and surgical sampling. These advances augment the safe array of methods utilized in the work up and management algorithms of lung cancer. PMID:23346012

  4. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

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

  5. Gene and virotherapy for hematological malignancies.

    PubMed

    Domingo-Musibay, Evidio; Yamamoto, Masato

    2016-07-01

    Recent years have seen a transformation in the treatment of hematological malignancies. Advances in gene therapy and molecular techniques and significant gains in computational abilities have supported the rapid development of safer and better tolerated therapies for many patients with hematologic cancers. In this review, we discuss novel applications of gene therapy, including immunomodulation and gene silencing, and report on the rise of oncolytic viruses for use in the treatment of malignancies arising in cells of the blood, lymph, and marrow. We discuss the relationship of the tropism of wildtype viruses and their oncolytic behavior as well as the tumoricidal and immunostimulatory properties of a number of attenuated and recombinant viruses currently in clinical development in countries around the world. While we have focused on promising virotherapy applications for future development, we also present a historical perspective and identify areas of potential clinical and regulatory practice change. We outline several of the virus systems being developed for applications in hematology, and summarize efficacy data in the context of ongoing or future human clinical testing. We also present the advantages and limitations of gene and virus therapy, including challenges and opportunities for improved treatment tolerability and outcomes for patients with hematologic malignancies. PMID:27289361

  6. Candidemia in Cancer Patients: Focus Mainly on Hematological Malignancyand Hematopoietic Stem Cell Transplantation.

    PubMed

    Okinaka, Keiji

    2016-01-01

    Although many new antifungals have become commercially available since 2000, candidemia remains an important public health issue because of its poor prognosis. Some studies have suggested that early antifungal therapy is associated with decreased mortality; however, it is difficult to promptly diagnose candidemia because of the poor sensitivity of blood cultures. Thus, prophylaxis against Candida infection is recommended in patient groups in whom the risk of infection is high, such as allogeneic hematopoietic stem cell transplant recipients or those undergoing intensive remission-induction chemotherapy for acute leukemia. Non-Candida albicans candidemia is dominant among hematology patients, and the use of an echinocandin is recommended as the initial therapy. However, echinocandin-resistant Candida have been reported with increasing frequency, mainly in Candida glabrata. Several studies have reported that echinocandin resistance is associated with prior exposure to an echinocandin. Therefore, susceptibility testing is vital in treating severe or refractory candidemia, and the introduction of an antifungal stewardship program is recommended. PMID:27581780

  7. Donor Stem Cell Transplant or Donor White Blood Cell Infusions in Treating Patients With Hematologic Cancer

    ClinicalTrials.gov

    2012-07-02

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unusual Cancers of Childhood

  8. Reptile Hematology.

    PubMed

    Sykes, John M; Klaphake, Eric

    2015-09-01

    The basic principles of hematology used in mammalian medicine can be applied to reptiles. The appearances of the blood cells are significantly different from those seen in most mammals, and vary with taxa and staining method used. Many causes for abnormalities of the reptilian hemogram are similar to those for mammals, although additional factors such as venipuncture site, season, hibernation status, captivity status, and environmental factors can also affect values, making interpretation of hematologic results challenging. Values in an individual should be compared with reference ranges specific to that species, gender, and environmental conditions when available. PMID:26297412

  9. Scientific Advances in Lung Cancer 2015.

    PubMed

    Tsao, Anne S; Scagliotti, Giorgio V; Bunn, Paul A; Carbone, David P; Warren, Graham W; Bai, Chunxue; de Koning, Harry J; Yousaf-Khan, A Uraujh; McWilliams, Annette; Tsao, Ming Sound; Adusumilli, Prasad S; Rami-Porta, Ramón; Asamura, Hisao; Van Schil, Paul E; Darling, Gail E; Ramalingam, Suresh S; Gomez, Daniel R; Rosenzweig, Kenneth E; Zimmermann, Stefan; Peters, Solange; Ignatius Ou, Sai-Hong; Reungwetwattana, Thanyanan; Jänne, Pasi A; Mok, Tony S; Wakelee, Heather A; Pirker, Robert; Mazières, Julien; Brahmer, Julie R; Zhou, Yang; Herbst, Roy S; Papadimitrakopoulou, Vassiliki A; Redman, Mary W; Wynes, Murry W; Gandara, David R; Kelly, Ronan J; Hirsch, Fred R; Pass, Harvey I

    2016-05-01

    Lung cancer continues to be a major global health problem; the disease is diagnosed in more than 1.6 million new patients each year. However, significant progress is underway in both the prevention and treatment of lung cancer. Lung cancer therapy has now emerged as a "role model" for precision cancer medicine, with several important therapeutic breakthroughs occurring during 2015. These advances have occurred primarily in the immunotherapy field and in treatments directed against tumors harboring specific oncogenic drivers. Our knowledge about molecular mechanisms for oncogene-driven tumors and about resistance to targeted therapies has increased quickly over the past year. As a result, several regulatory approvals of new agents that significantly improve survival and quality of life for patients with lung cancer who have advanced disease have occurred. The International Association for the Study of Lung Cancer has gathered experts in different areas of lung cancer research and management to summarize the most significant scientific advancements related to prevention and therapy of lung cancer during the past year. PMID:27013409

  10. Chemotherapy advances in locally advanced head and neck cancer.

    PubMed

    Georges, Peter; Rajagopalan, Kumar; Leon, Chady; Singh, Priya; Ahmad, Nadir; Nader, Kamyar; Kubicek, Gregory J

    2014-12-10

    The management of locally advanced unresectable head and neck squamous cell cancer (HNSCC) continues to improve. One of the major advances in the treatment of HNSCC was the addition of chemotherapy to radiation in the treatment of non-surgical patients. The majority of the data regarding chemotherapy in HNSCC involve cisplatin chemotherapy with concurrent radiation. However, several new approaches have included targeted therapy against epidermal growth factor receptor and several recent studies have explored the role of induction chemotherapy in the treatment of HNSCC. The purpose of this article is to provide an overview of the role of chemotherapy in the treatment of locally advanced HNSCC. PMID:25493232

  11. A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers

    ClinicalTrials.gov

    2016-04-05

    CD27 Expressing B-cell Malignancies, (for Example: Hodgkin's Lymphoma,; Chronic Lymphocytic Leukemia, Burkett's Lymphoma,; Mantle Cell Lymphoma, Primary Lymphoma of the Central Nervous System,; Marginal Zone B Cell Lymphoma);; Any T-cell Malignancy;; Solid Tumors (Metastatic Melanoma, Renal (Clear) Cell Carcinoma,; Hormone-refractory Prostate Adenocarcinoma, Ovarian Cancer; Colorectal Adenocarcinoma, Non-small Cell Lung Cancer)

  12. Advances in cryoablation for pancreatic cancer

    PubMed Central

    Luo, Xiao-Mei; Niu, Li-Zhi; Chen, Ji-Bing; Xu, Ke-Cheng

    2016-01-01

    Pancreatic carcinoma is a common cancer of the digestive system with a poor prognosis. It is characterized by insidious onset, rapid progression, a high degree of malignancy and early metastasis. At present, radical surgery is considered the only curative option for treatment, however, the majority of patients with pancreatic cancer are diagnosed too late to undergo surgery. The sensitivity of pancreatic cancer to chemotherapy or radiotherapy is also poor. As a result, there is no standard treatment for patients with advanced pancreatic cancer. Cryoablation is generally considered to be an effective palliative treatment for pancreatic cancer. It has the advantages of minimal invasion and improved targeting, and is potentially safe with less pain to the patients. It is especially suitable in patients with unresectable pancreatic cancer. However, our initial findings suggest that cryotherapy combined with 125-iodine seed implantation, immunotherapy or various other treatments for advanced pancreatic cancer can improve survival in patients with unresectable or metastatic pancreatic cancer. Although these findings require further in-depth study, the initial results are encouraging. This paper reviews the safety and efficacy of cryoablation, including combined approaches, in the treatment of pancreatic cancer. PMID:26811625

  13. Palbociclib for Advanced Breast Cancer

    Cancer.gov

    An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

  14. Hematologic malignancies

    SciTech Connect

    Hoogstraten, B.

    1986-01-01

    The principle aim of this book is to give practical guidelines to the modern treatment of the six important hematologic malignancies. Topics considered include the treatment of the chronic leukemias; acute leukemia in adults; the myeloproliferative disorders: polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis/agnogenic myeloid metaplasia; Hodgkin's Disease; non-Hodgkin's lymphoma; and Multiple Myeloma.

  15. Review of hematological indices of cancer patients receiving combined chemotherapy & radiotherapy or receiving radiotherapy alone.

    PubMed

    Shahid, Saman

    2016-09-01

    We observed the outcomes of chemotherapy with radiotherapy (CR) or radiotherapy (RT) alone for cancer patients of larynx, breast, blood and brain origins through complete blood count (CBC). Following were more depressed in CR patients: mean corpuscular hemoglobin-MCH & lymphocytes-LYM, hematocrit, mean corpuscular hemoglobin concentration-MCHC, hemoglobin-HB and red blood cells-RBC. In RT patients, following were more depressed: LYM, MCH and MCHC. Overall, in all cancer patients, the lymphocytes were depressed 52%. There existed a significant difference between white blood cells and RBC in both CR and RT patients. A significant moderate negative correlation is found in HB with the dose range 30-78 (Gray) given to the CR cancer patients. More number of CBC parameters affected in patients treated with CR and RT; but in less percentage as compared to patients who treated with RT alone. The cancer patients suffered from anemia along with immune modulations from the treatments. PMID:27423975

  16. Fertility issues in patients with hematologic malignancies.

    PubMed

    Loren, Alison W

    2015-01-01

    An essential component of a cancer patient's comprehensive care is addressing potential threats to his or her reproductive health. Providers should discuss the risk of infertility with newly diagnosed patients and offer the chance to consult with a reproductive specialist as early as possible. Standard fertility preservation options include embryo or oocyte cryopreservation for women and sperm banking for men; all options for pre-pubertal children are experimental. Patients with hematologic malignancies are a distinct population in whom standard options may present special challenges, and alternative management strategies are being explored. Unique approaches in hematologic malignancy patients include experimental techniques, such as hormonal therapy, referrals to reproductive specialists after cancer treatment, or discontinuation of tyrosine kinase inhibitor therapy in appropriate chronic myelogenous leukemia patients. Importantly, expedited communication between hematologists and reproductive specialists may greatly enhance the quality of care for these patients. Facilitation of referrals will both improve the quality-of-life and expand the prospect of parenthood in survivors. There are ample opportunities to advance the field of oncofertility through additional research, especially in hematologic malignancy patients. PMID:26637713

  17. Photodynamic Cancer Therapy - Recent Advances

    SciTech Connect

    Abrahamse, Heidi

    2011-09-22

    The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when 'photoradiation therapy' was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first or second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular

  18. Advances in gastric cancer prevention

    PubMed Central

    Giordano, Antonio; Cito, Letizia

    2012-01-01

    Gastric cancer is a multifactorial neoplastic pathology numbering among its causes both environmental and genetic predisposing factors. It is mainly diffused in South America and South-East Asia, where it shows the highest morbility percentages and it is relatively scarcely diffused in Western countries and North America. Although molecular mechanisms leading to gastric cancer development are only partially known, three main causes are well characterized: Helicobacter pylori (H. pylori) infection, diet rich in salted and/or smoked food and red meat, and epithelial cadherin (E-cadherin) mutations. Unhealthy diet and H. pylori infection are able to induce in stomach cancer cells genotypic and phenotypic transformation, but their effects may be crossed by a diet rich in vegetables and fresh fruits. Various authors have recently focused their attention on the importance of a well balanced diet, suggesting a necessary dietary education starting from childhood. A constant surveillance will be necessary in people carrying E-cadherin mutations, since they are highly prone in developing gastric cancer, also within the inner stomach layers. Above all in the United States, several carriers decided to undergo a gastrectomy, preferring changing their lifestyle than living with the awareness of the development of a possible gastric cancer. This kind of choice is strictly personal, hence a decision cannot be suggested within the clinical management. Here we summarize the key points of gastric cancer prevention analyzing possible strategies referred to the different predisposing factors. We will discuss about the effects of diet, H. pylori infection and E-cadherin mutations and how each of them can be handled. PMID:23061031

  19. Telomerase Activation in Hematological Malignancies.

    PubMed

    Ropio, Joana; Merlio, Jean-Philippe; Soares, Paula; Chevret, Edith

    2016-01-01

    Telomerase expression and telomere maintenance are critical for cell proliferation and survival, and they play important roles in development and cancer, including hematological malignancies. Transcriptional regulation of the rate-limiting subunit of human telomerase reverse transcriptase gen (hTERT) is a complex process, and unveiling the mechanisms behind its reactivation is an important step for the development of diagnostic and therapeutic applications. Here, we review the main mechanisms of telomerase activation and the associated hematologic malignancies. PMID:27618103

  20. EZH2 in normal hematopoiesis and hematological malignancies.

    PubMed

    Herviou, Laurie; Cavalli, Giacomo; Cartron, Guillaume; Klein, Bernard; Moreaux, Jérôme

    2016-01-19

    Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2, inhibits gene expression through methylation on lysine 27 of histone H3. EZH2 regulates normal hematopoietic stem cell self-renewal and differentiation. EZH2 also controls normal B cell differentiation. EZH2 deregulation has been described in many cancer types including hematological malignancies. Specific small molecules have been recently developed to exploit the oncogenic addiction of tumor cells to EZH2. Their therapeutic potential is currently under evaluation. This review summarizes the roles of EZH2 in normal and pathologic hematological processes and recent advances in the development of EZH2 inhibitors for the personalized treatment of patients with hematological malignancies. PMID:26497210

  1. Advanced endoscopic technologies for colorectal cancer screening

    PubMed Central

    Obstein, Keith L; Valdastri, Pietro

    2013-01-01

    Colorectal cancer is the third most common cancer in men and the second most common cancer in women worldwide. Diagnosing colorectal has been increasingly successful due to advances in technology. Flexible endoscopy is considered to be an effective method for early diagnosis and treatment of gastrointestinal cancer, making it a popular choice for screening programs. However, millions of people who may benefit from endoscopic colorectal cancer screening fail to have the procedure performed. Main reasons include psychological barriers due to the indignity of the procedure, fear of procedure related pain, bowel preparation discomfort, and potential need for sedation. Therefore, an urgent need for new technologies addressing these issues clearly exists. In this review, we discuss a set of advanced endoscopic technologies for colorectal cancer screening that are either already available or close to clinical trial. In particular, we focus on visual-inspection-only advanced flexible colonoscopes, interventional colonoscopes with alternative propulsion mechanisms, wireless capsule colonoscopy, and technologies for intraprocedural bowel cleansing. Many of these devices have the potential to reduce exam related patient discomfort, obviate the need for sedation, increase diagnostic yield, reduce learning curves, improve access to screening, and possibly avert the need for a bowel preparation. PMID:23382621

  2. Radiation treatment for breast cancer. Recent advances.

    PubMed Central

    Chow, Edward

    2002-01-01

    OBJECTIVE: To review recent advances in radiation therapy in treatment of breast cancer. QUALITY OF EVIDENCE: MEDLINE and CANCERLIT were searched using the MeSH words breast cancer, ductal carcinoma in situ, sentinel lymph node biopsy, and postmastectomy radiation. Randomized studies have shown the efficacy of radiation treatment for ductal carcinoma in situ (DCIS) and for invasive breast cancer. MAIN MESSAGE: Lumpectomy followed by radiation is effective treatment for DCIS. In early breast cancer, shorter radiation schedules are as efficacious for local control and short-term cosmetic results as traditional fractionation regimens. Sentinel lymph node biopsy is done in specialized cancer centres; regional radiation is recommended for patients with four or more positive axillary lymph nodes. Postmastectomy radiation has been shown to have survival benefits for high-risk premenopausal patients. Systemic metastases from breast cancer usually respond satisfactorily to radiation. CONCLUSION: Radiation therapy continues to have an important role in treatment of breast cancer. There have been great advances in radiation therapy in the last decade, but they have raised controversy. Further studies are needed to address the controversies. PMID:12113193

  3. Pain in far-advanced cancer.

    PubMed

    Twycross, R G; Fairfield, S

    1982-11-01

    Hundred patients with far-advanced cancer and pain were interviewed within a few days of admission to a special care unit. Eighty had more than one pain; 34 had four or more. A total of 303 anatomically distinct pains were recorded. Ninety-one patients had pain caused by the cancer itself. Twelve had treatment-related pain; and 19 had pain related to chronic disease or debility ('associated pain'). Thirty-nine patients had one or more pains unrelated to cancer or treatment; the most common of these was myofascial pain. In 41 patients only was all the pain caused directly by the cancer. Bone involvement and nerve compression were the most common forms of cancer-related pain; soft tissue and visceral pains also occurred frequently. Fifty-seven patients had pain for more than 4 months. PMID:6218464

  4. Phase 1/2 trial of total marrow and lymph node irradiation to augment reduced-intensity transplantation for advanced hematologic malignancies

    PubMed Central

    Wong, Jeffrey; Stein, Anthony; Qian, Dajun; Hitt, Debbie; Naeem, Hossameldin; Dagis, Andrew; Thomas, Sandra H.; Forman, Stephen

    2011-01-01

    This phase 1/2 study assessed the augmentation of reduced-intensity conditioning (RIC) with total marrow and lymph node irradiation (TMLI), for peripheral blood stem cell transplantation, in patients with advanced hematologic disease. The regimen consisted of fludarabine 25 mg/m2 per day for 5 days, melphalan 140 mg/m2 for one day, and TMLI radiation at 150 cGy/fraction in 8 fractions over 4 days. Eligible patients were over 50 years old and/or had compromised organ function. Median age of the 33 evaluable patients was 55.2 years. Eighteen events of nonhematologic grade III or higher toxicities occurred in 9 patients. Day 30 and day 100 mortalities were 3% and 15%, respectively. Patients achieved myeloid and platelet engraftment at a median of 14 days after transplantation. Long-term toxicities occurred in 2 patients: hypokalemia and tremor, both grade III, on days 370 and 361 after transplantation. Fourteen patients died, 7 of relapse-related causes and 7 of non–relapse-related causes. With a median follow-up for living patients of 14.7 months, 1-year overall survival, event-free survival, and non–relapse-related mortality were 75%, 65%, and 19%, respectively. Addition of TMLI to RIC is feasible and safe and could be offered to patients with advanced hematologic malignancies who might not otherwise be candidates for RIC. PMID:20876852

  5. Beyond pancreatic cancer: irinotecan and gemcitabine in solid tumors and hematologic malignancies.

    PubMed

    Rocha Lima, C M; Urbanic, J J; Lal, A; Kneuper-Hall, R; Brunson, C Y; Green, M R

    2001-06-01

    Non-platinum combinations including gemcitabine and irinotecan (Gemzar; Eli Lilly and Company, Indianapolis, IN) for the management of a variety of malignancies have started to emerge. Gemcitabine and irinotecan are well-tolerated single agents, each with a broad spectrum of antitumor activity. Preclinical data suggests synergy for the two drugs when used in combination. A phase I trial has defined a well-tolerated combination regimen using both drugs on a day-1, -8 schedule every 3 weeks. Phase II data suggest activity for the combination in pancreatic cancer, and a phase III trial of the two-drug combination versus gemcitabine alone is underway in previously untreated pancreatic cancer patients. Other phase II trials evaluating the impact of this combination on a variety of other tumors, such as non-small cell lung, small cell lung, breast, colorectal, and non-Hodgkin's lymphoma, are either forthcoming or in progress. Semin Oncol 28 (suppl 10):34-43. PMID:11510032

  6. Advances and Challenges in Treatment of Locally Advanced Rectal Cancer

    PubMed Central

    Smith, J. Joshua; Garcia-Aguilar, Julio

    2015-01-01

    Dramatic improvements in the outcomes of patients with rectal cancer have occurred over the past 30 years. Advances in surgical pathology, refinements in surgical techniques and instrumentation, new imaging modalities, and the widespread use of neoadjuvant therapy have all contributed to these improvements. Several questions emerge as we learn of the benefits or lack thereof for components of the current multimodality treatment in subgroups of patients with nonmetastatic locally advanced rectal cancer (LARC). What is the optimal surgical technique for distal rectal cancers? Do all patients need postoperative chemotherapy? Do all patients need radiation? Do all patients need surgery, or is a nonoperative, organ-preserving approach warranted in selected patients? Answering these questions will lead to more precise treatment regimens, based on patient and tumor characteristics, that will improve outcomes while preserving quality of life. However, the idea of shifting the treatment paradigm (chemoradiotherapy, total mesorectal excision, and adjuvant therapy) currently applied to all patients with LARC to a more individually tailored approach is controversial. The paradigm shift toward organ preservation in highly selected patients whose tumors demonstrate clinical complete response to neoadjuvant treatment is also controversial. Herein, we highlight many of the advances and resultant controversies that are likely to dominate the research agenda for LARC in the modern era. PMID:25918296

  7. Therapeutic advances in ovarian cancer.

    PubMed

    Rader, J S

    1992-02-01

    The propensity of ovarian cancer to recur--even after initial chemotherapeutic responses--is a problem that has been given a great deal of attention during the past year in the literature dealing with the treatment of ovarian cancer. Most of the articles address techniques to improve the percent of initial and secondary treatment responses. Several studies have described cytoreductive techniques to decrease the remaining tumor size for improved chemotherapeutic response. Cross-resistance between platinum analogues has been reconfirmed. However, improved secondary responses were seen when repeat treatment with platinum agents were preceded by a longer interval from initial platinum agent therapy. Radiation therapy has been shown to offer little solution to recurrent disease except possibly in a select group of patients with microscopic disease at second-look laparotomy. Reports on the use of carboplatin continue to demonstrate good initial responses, with decreased toxicity compared with cisplatin. Granisetron has been shown to significantly decrease the nausea and vomiting caused by emetogenic chemotherapy like cisplatin. PMID:1543823

  8. Immunotherapy for lung cancer: advances and prospects.

    PubMed

    Yang, Li; Wang, Liping; Zhang, Yi

    2016-01-01

    Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment. PMID:27168951

  9. Immunotherapy for lung cancer: advances and prospects

    PubMed Central

    Yang, Li; Wang, Liping; Zhang, Yi

    2016-01-01

    Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment. PMID:27168951

  10. Treatment of advanced esophageal cancer

    SciTech Connect

    Kelsen, D.

    1982-12-01

    When radiation therapy is used for palliation of obstruction in patients with advanced esophageal carcinoma, an improvement in dysphagia can be expected in approximately 50% of patients. Major objective responses have rarely been quantitied but, in one study, were seen in 33% patients. Recurrence of dysphagia is usually seen within 2-6 months of treatment. Radiation toxicities and complications, even when used with palliative intent, can be substantial and include esophagitis, tracheoesophageal or esophageal-aortic fistula, mediastinitis, hemorrhage, pneumonitis, and myelosuppression. (JMT)

  11. Two-Pronged Chemo Helps Some with Advanced Ovarian Cancer

    MedlinePlus

    ... html Two-Pronged Chemo Helps Some With Advanced Ovarian Cancer Study found using both abdomen drip and ... 4, 2016 (HealthDay News) -- Some women with advanced ovarian cancer may fare better if chemotherapy is dripped ...

  12. The MIF -173G/C gene polymorphism increase gastrointestinal cancer and hematological malignancy risk: evidence from a meta-analysis and FPRP test

    PubMed Central

    Tong, Xiang; Zheng, Bing; Tong, Qiaoyi; Liu, Sitong; Peng, Sifeng; Yang, Xin; Fan, Hong

    2015-01-01

    The macrophage migration inhibitory factor (MIF) -173G/C gene polymorphism has been implicated in the susceptibility to cancer, but the results are not conclusive. So the aim of study to investigate the association between MIF -173G/C gene polymorphism and cancer risk by a comprehensive meta-analysis. We searched the PubMed, Embase, Wanfang and China National Knowledge Internet (CNKI) databases, with the last updated search being performed on May 24, 2015. The odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the association. Statistical analysis was performed by STATA 11.0 software. Finally, 7,253 participants from 15 studies were included in the meta-analysis. The results of meta-analysis indicated the significant association between MIF -173G/C gene polymorphism and cancer susceptibility, especially in Asians (C vs. G, OR: 1.22, 95% CI=1.00-1.50). In addition, the significant relationship between MIF -173G/C gene polymorphism and gastrointestinal tumors (CC+CG vs. GG, OR: 1.25, 95% CI=1.05-1.50), hematological malignancy (CC+CG vs. GG, OR: 1.27, 95% CI=1.03-1.56), gynecolgical tumors (CC vs. CG+GG, OR: 1.51, 95% CI=1.04-2.19) risk was found. However, to avoid the “false positive report”, we investigated the significant associations observed in the present meta-analysis by the false positive report probabilities (FPRPs) test. Interestingly, the results of FPRP test indicated the MIF -173G/C gene polymorphism only associated with gastrointestinal cancer and hematological malignancy risk (FPRP=0.132, 0.067 respectively) at the level of a prior probability is 0.1. Therefore, the meta-analysis suggested MIF -173G/C gene polymorphism would be a risk factor for the gastrointestinal cancer and hematological malignancy. PMID:26629098

  13. Synthesis and antiproliferative activity of α-branched α,β-unsaturated ketones in human hematological and solid cancer cell lines.

    PubMed

    Karpavičienė, Ieva; Valiulienė, Giedrė; Raškevičius, Vytautas; Lebedytė, Indrė; Brukštus, Algirdas; Kairys, Visvaldas; Navakauskienė, Rūta; Čikotienė, Inga

    2015-06-15

    A series of α-branched α,β-unsaturated ketones were prepared via boron trifluoride etherate mediated reaction between arylalkynes and carboxaldehydes. The evaluation of the antiproliferative activity over hematological (NB4) and solid cancer (A549, MCF-7) cell lines provided a structure-activity relationship. 5-Parameter QSAR equations were built which were able to explain 80%-92% of the variance in activity. The resulting selective lead compound showed IC50 value 0.6 μM against the hematological cell line and did not cause apoptosis, but blocked cell cycle in G0/G1. Moreover, it was demonstrated that this compound enhances and accelerates retinoic acid induced granulocytic differentiation. PMID:26005022

  14. Advanced research on vasculogenic mimicry in cancer

    PubMed Central

    Qiao, Lili; Liang, Ning; Zhang, Jiandong; Xie, Jian; Liu, Fengjun; Xu, Deguo; Yu, Xinshuang; Tian, Yuan

    2015-01-01

    Vasculogenic mimicry (VM) is a brand-new tumour vascular paradigm independent of angiogenesis that describes the specific capacity of aggressive cancer cells to form vessel-like networks that provide adequate blood supply for tumour growth. A variety of molecule mechanisms and signal pathways participate in VM induction. Additionally, cancer stem cell and epithelial-mesenchymal transitions are also shown to be implicated in VM formation. As a unique perfusion way, VM is associated with tumour invasion, metastasis and poor cancer patient prognosis. Due to VM's important effects on tumour progression, more VM-related strategies are being utilized for anticancer treatment. Here, with regard to the above aspects, we make a review of advanced research on VM in cancer. PMID:25598425

  15. Important drugs for cough in advanced cancer.

    PubMed

    Homsi, J; Walsh, D; Nelson, K A

    2001-11-01

    Cough is a defense mechanism that prevents the entry of noxious materials into the respiratory system and clears foreign materials and excess secretions from the lungs and respiratory tract. In advanced cancer, it is a common symptom that interferes with the patient's daily activity and quality of life. Empiric treatment with antitussive agents is often needed. Two classes of antitussive drugs are available: (1) centrally acting: (a) opioids and (b) non-opioids; (2) peripherally acting: (a) directly and (b) indirectly. Antitussive availability varies widely around the world. Many antitussives, such as benzonatate, codeine, hydrocodone, and dextromethorphan, were extensively studied in the acute and chronic cough settings and showed relatively high efficacy and safety profiles. Benzonatate, clobutinol, dihydrocodeine, hydrocodone, and levodropropizine were the only antitussives specifically studied in cancer and advanced cancer cough. They all have shown to be effective and safe in recommended daily dose for cough. In advanced cancer the patient's current medications, previous antitussive use, the availability of routes of administration, any history of drug abuse, the presence of other symptoms and other factors, all have a role in the selection of antitussives for prescription. A good knowledge of the pharmacokinetics, dosage, efficacy, and side effects of the available antitussives provides for better management. PMID:11762966

  16. Inflammation and cancer: advances and new agents.

    PubMed

    Crusz, Shanthini M; Balkwill, Frances R

    2015-10-01

    Tumour-promoting inflammation is considered one of the enabling characteristics of cancer development. Chronic inflammatory disease increases the risk of some cancers, and strong epidemiological evidence exists that NSAIDs, particularly aspirin, are powerful chemopreventive agents. Tumour microenvironments contain many different inflammatory cells and mediators; targeting these factors in genetic, transplantable and inducible murine models of cancer substantially reduces the development, growth and spread of disease. Thus, this complex network of inflammation offers targets for prevention and treatment of malignant disease. Much potential exists in this area for novel cancer prevention and treatment strategies, although clinical research to support targeting of cancer-related inflammation and innate immunity in patients with advanced-stage cancer remains in its infancy. Following the initial successes of immunotherapies that modulate the adaptive immune system, we assert that inflammation and innate immunity are important targets in patients with cancer on the basis of extensive preclinical and epidemiological data. The adaptive immune response is heavily dependent on innate immunity, therefore, inhibiting some of the tumour-promoting immunosuppressive actions of the innate immune system might enhance the potential of immunotherapies that activate a nascent antitumour response. PMID:26122183

  17. New advances in targeted gastric cancer treatment.

    PubMed

    Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

    2016-08-14

    Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

  18. New advances in targeted gastric cancer treatment

    PubMed Central

    Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

    2016-01-01

    Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

  19. Advances in the treatment of testicular cancer.

    PubMed

    Ehrlich, Yaron; Margel, David; Lubin, Marc Alan; Baniel, Jack

    2015-06-01

    Germ cell tumors (GCT) are relatively uncommon, accounting for only 1% of male malignancies in the United States. It has become an important oncological disease for several reasons. It is the most common malignancy in young men 15-35 years old. GCTs are among a unique numbers of neoplasms where biochemical markers play a critical role. Finally, it is a model of curable cancer. In this review we discuss cancer epidemiology, genetics, and therapeutic principles. Recent advances in the management of stage I GCT and controversies in the management of post chemotherapy residual mass are presented. PMID:26816836

  20. [Advance Care Planning in Cancer Care].

    PubMed

    Kizawa, Yoshiyuki; Yamaguchi, Takashi; Yotani, Nobuyuki

    2016-03-01

    Advance care planning (ACP) is one of the most important issues to consider in providing quality end of life care for cancer patients. ACP has been described as a process whereby a patient, in consultation with health care providers, family members, and important others, makes decisions about his or her future health care, in the event he or she becomes incapable of participating in medical treatment decisions. ACP improves rates of following end of life wishes, increases patient and family satisfaction, and reduces family stress, anxiety, and depression. This article clarifies the differences among ACP, advance directives, and living wills. Additionally, we describe, based on clinical experience, how to introduce ACP most effectively for all stages of cancer care. PMID:27067841

  1. Management of dysphagia in advanced oropharyngeal cancer.

    PubMed

    Penner, Jamie L; McClement, Susan E; Sawatzky, Jo-Ann V

    2007-05-01

    Individuals with advanced oropharyngeal cancer often experience dysphagia as a result of their illness and its treatment. Research consistently demonstrates that dysphagia and difficulty with oral intake have many implications, including a negative impact on quality of life. Nurses are in a key position to provide support and initiate appropriate interventions for individuals with dysphagia. Using the Human Response to Illness model (Mitchell et al, 1991) as an organising framework, this paper presents a critical review of the empirical literature regarding dysphagia in individuals with advanced oropharyngeal cancer that will: i) provide the reader with a comprehensive understanding of dysphagia; ii) identify current gaps in our knowledge; and iii) establish the foundation for appropriate evidence-based interventions to optimise functioning and quality of life in this patient population. PMID:17577172

  2. Advances in biomarkers of biliary tract cancers.

    PubMed

    Hu, Jun; Yin, Baobing

    2016-07-01

    Tumor biomarkers can be applied for early diagnosis or precise treatment, thereby leading to personalized treatment and better outcomes. Biliary tract cancers (BTCs) are a group of cancers that occurs in different locations and have different clinical or genetic properties. Though the incidence of BTCs is rare, BTCs are among the most lethal cancers in the world and all have very low 5-year survivals. Lack of efficient early diagnostic approaches or adjuvant therapies for BTCs are main reasons. These urge us to broaden the researches into BTC biomarkers. Although few progresses of diagnostic biomarkers for BTCs have been achieved, there are still some advances in prognostic, predictive and therapeutic areas. In this review, we will focus on these achievements. PMID:27261586

  3. New treatment options for advanced pancreatic cancer.

    PubMed

    Middleton, Gary; Ghaneh, Paula; Costello, Eithne; Greenhalf, William; Neoptolemos, John P

    2008-10-01

    Pancreatic cancer has a very high mortality rate and affects approximately 230,000 individuals worldwide. Gemcitabine has become established as the standard therapy for advanced pancreatic cancer; however, the survival advantage is small. Adjuvant chemotherapy using either 5-fluorouracil or gemcitabine is now established in pancreatic cancer as an alternative therapy. Combinations of gemcitabine with either platin agents or capecitabine may be advantageous. Anti-EGFR and anti-VEGF agents have been unsuccessful but multiple tyrosine kinase inhibitors are under investigation. Of the increasing number of immunological agents, the GV1001 antitelomerase vaccine holds some interest. Targeted agents against important mitogenic pathways, including MEK/ERK, Src, PI3K/Akt, mTOR, Hedgehog and NF-kappaB, as well as agents targeting histone deacetylase, poly(ADP-ribose) polymerase, heat shock protein 90 and other agents such as beta-lapachone, hold considerable interest for further development. However, the probability of individual success is low. PMID:19072345

  4. Systemic Chemotherapy in Advanced Pancreatic Cancer

    PubMed Central

    Lee, Hee Seung; Park, Seung Woo

    2016-01-01

    Pancreatic cancer remains one of the most lethal cancers. These patients often have multiple symptoms, and integrated supportive care is critical in helping them remain well for as long as possible. Fluorouracil-based chemotherapy is known to improve overall survival (OS) by approximately 3 months, compared to the best supportive care alone. A 1997 study comparing gemcitabine and fluorouracil treatment of advanced pancreatic cancer patients showed an improvement in OS of 1 month in patients receiving gemcitabine. Over the next 10 years, multiple randomized studies compared single-agent gemcitabine with combination chemotherapy and showed no effective survival improvement. However, the addition of erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, was associated with a significant improvement in OS of approximately 2 weeks. However, adoption of this regimen has not been widespread because of its limited effect and added toxicity. Two clinical trials have recently prolonged OS in advanced pancreatic cancer patients by almost 1 year. The first compared FOLFIRINOX with gemcitabine alone, and was associated with a significant improvement in median survival. The second compared gemcitabine and nab-paclitaxel with gemcitabine alone, and was associated with improvements in OS. At present, these regimens are considered standard treatment for patients with good performance statuses. PMID:27114434

  5. Management of advanced medullary thyroid cancer.

    PubMed

    Hadoux, Julien; Pacini, Furio; Tuttle, R Michael; Schlumberger, Martin

    2016-01-01

    Medullary thyroid cancer arises from calcitonin-producing C-cells and accounts for 3-5% of all thyroid cancers. The discovery of a locally advanced medullary thyroid cancer that is not amenable to surgery or of distant metastases needs careful work-up, including measurement of serum calcitonin and carcinoembryonic antigen (and their doubling times), in addition to comprehensive imaging to determine the extent of the disease, its aggressiveness, and the need for any treatment. In the past, cytotoxic chemotherapy was used for treatment but produced little benefit. For the past 10 years, tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors and RET (rearranged during transfection) have been used when a systemic therapy is indicated for large tumour burden and documented disease progression. Vandetanib and cabozantinib have shown benefits on progression-free survival compared with placebo in this setting, but their toxic effect profiles need thorough clinical management in specialised centres. This Review describes the management and treatment of patients with advanced medullary thyroid cancer with emphasis on current targeted therapies and perspectives to improve patient care. Most treatment responses are transient, emphasising that mechanisms of resistance need to be better understood and that the efficacy of treatment approaches should be improved with combination therapies or other drugs that might be more potent or target other pathways, including immunotherapy. PMID:26608066

  6. Acute hematologic and mucosal toxicities in head and neck cancer patients undergoing chemoradiotherapy: a comparison of 3D-CRT, IMRT, and helical tomotherapy.

    PubMed

    Kruser, Tim J; Rice, Stephanie R; Cleary, Kevin P; Geye, Heather M; Tome, Wolfgang A; Harari, Paul M; Kozak, Kevin R

    2013-10-01

    IMRT and helical tomotherapy for head and neck cancer (HNC) treatment are associated with higher doses to certain non-target tissues than traditional static beam techniques. We hypothesized that this may lead to higher acute mucosal and hematologic toxicities. This analysis was limited to 178 patients receiving ≥60 Gy with concurrent weekly cisplatin. Radiation delivery used 3D-CRT in 41 patients (23%), conventional IMRT in 56 patients (31%), and helical tomotherapy in 81 patients (46%). Acute mucositis rates, weekly hematologic parameters, and ability to deliver planned chemotherapy cycles were examined for each patient during their course of chemoradiotherapy. Analysis showed patients were well balanced with regard to sex, age, and stage. Treatment time, as assessed by delivered monitor units, varied significantly between the 3D-CRT (median = 502), IMRT (median = 1087), and tomotherapy (median = 6757) cohorts. Acute mucositis grades did not significantly differ between the three subsets. Through six weeks of chemoradiotherapy, the median decline in hemoglobin was 15.6%, the median decline in platelets was 30.6%, and the median decline in leukocytes was 51.5%, but these drops were not significantly different between treatment cohorts. Chemotherapy was discontinued or held secondary to hematologic toxicity in 12% of 3D-CRT patients, 5% of IMRT patients and 15% of tomotherapy patients (p = 0.14). In conclusion, HNC patients undergoing high dose radiation with concurrent weekly cisplatin chemotherapy, the longer beam-on times and larger volumes of low-to-moderate radiation doses to non-target tissues associated with modern IMRT delivery techniques do not appear to result in increased acute hematologic or mucosal toxicities. PMID:23547974

  7. Advances in the management of thyroid cancer.

    PubMed

    Shaha, Ashok R

    2005-01-01

    The incidence of thyroid cancer is rapidly increasing in the United States. A large number of incidentalomas are found during routine head and neck evaluations. The diagnostic workup still revolves around fine needle aspiration biopsy. Ultrasound guided fine needle aspiration biopsy is likely to yield the best results. Surgical resection offers the best treatment choice. Controversy continues in relation to total versus less than total thyroidectomy. The incidence of complications is inversely proportional to the extent of surgery and obviously related to the experience of the operating surgeon. The decision regarding the extent of thyroidectomy should be based on prognostic factors and risk groups. Prognostic factors are well defined, such as age, grade of the tumor, extrathyroidal extension, size, distant metastasis, and histology. Nodal metastasis has minimal implications. Based on prognostic factors, thyroid cancer can be divided into low, intermediate and high risk groups. In the high risk group and in selected intermediate risk patients, radioactive iodine dosimetry and ablation should be considered after total thyroidectomy. PET scanning and the use of recombinant TSH have been major advances in follow-up care for patients with thyroid cancer. Thyroglobulin appears to be a very good tumor marker for follow-up. No major breakthrough is noted in the management of anaplastic thyroid cancer, however, identification of RET mutation has been extremely helpful in evaluating the family members of the patient with medullary thyroid cancer with strong consideration given to total thyroidectomy. PMID:17462286

  8. Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care

    Cancer.gov

    Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care, a 2010 workshop sponsored by the Epidemiology and Genomics Research Program.

  9. Epigenetics Advancing Personalized Nanomedicine in Cancer Therapy

    PubMed Central

    Liu, Shujun

    2012-01-01

    Personalized medicine aims to deliver the right drug to a right patient at the right time. It offers unique opportunities to integrate new technologies and concepts to disease prognosis, diagnosis and therapeutics. While selective personalized therapies are conceptually impressive, the majority of cancer therapies have dismal outcome. Such therapeutic failure could result from no response, drug resistance, disease relapse or severe side effect from improper drug delivery. Nanomedicine, the application of nanotechnology in medicine, has a potential to advance the identification of diagnostic and prognostic biomarkers and the delivery of right drug to disease sites. Epigenetic aberrations dynamically contribute to cancer pathogenesis. Given the individualized traits of epigenetic biomarkers, epigenetic considerations would significantly refine personalized nanomedicine. This review aims to dissect the interface of personalized medicine with nanomedicine and epigenetics. I will outline the progress and highlight challenges and areas that can be further explored perfecting the personalized health care. PMID:22921595

  10. Radiation-Related Predictors of Hematologic Toxicity After Concurrent Chemoradiation for Cervical Cancer and Implications for Bone Marrow-Sparing Pelvic IMRT

    SciTech Connect

    Albuquerque, Kevin; Giangreco, David; Morrison, Courtney; Siddiqui, Mohammed; Sinacore, Jim; Potkul, Ronald; Roeske, John

    2011-03-15

    Purpose: To determine factors predictive for hematologic toxicity (HT) associated with concurrent chemoradiation for Stage II through IV cervical cancer. Methods and Materials: The medical records of 40 women receiving concurrent chemoradiation for cervical cancer were reviewed. Hematologic toxicity was defined by use of Common Terminology Criteria for Adverse Events (version 3.0). Variables predicting for HT including age, body mass index, transfusions, and bone marrow volumes irradiated were included in the data analysis. Results: Of the patients, 13 (32.5%) had Grade 0 or 1 HT and 27 (67.5%) had Grade 2 through 4 HT (HT2+). Multiple logistic regression analysis of potential predictors showed that only the volume of bone receiving 20 Gy (V20) for whole pelvic bone tended toward significance for predicting HT2+. A strong correlation was noted between HT2+ and V20 (r = 0.8, p < 0.0001). A partitioning analysis to predict HT2+ showed a cutoff value of 79.42% (approximately 80%) for V20 of whole pelvic bone. That is, if the V20 of the whole pelvis exceeds 80%, the risk of HT2+ developing increases by a factor (odds ratio) of 4.5 (95%, confidence interval, 1.08-18.69) (p < 0.05). Conclusions: We have shown a correlation between bone marrow volume radiated and development of HT. This has implications for use of pelvic intensity-modulated radiation therapy, which can potentially decrease the volume of bone marrow radiated.

  11. The psychosocial outcomes of individuals with hematological cancers: Are we doing enough high quality research, and what is it telling us?

    PubMed

    Bryant, Jamie; Mansfield, Elise; Hall, Alix; Waller, Amy; Boyes, Allison; Jayakody, Amanda; Dodd, Natalie; Sanson-Fisher, Rob

    2016-05-01

    This systematic review assessed the quantity and quality of research examining the psychosocial outcomes among hematological cancer patients. Studies were categorised as either measurement, descriptive or intervention. Intervention studies were further assessed according to Effective Practice and Organisation of Care (EPOC) methodological criteria. A total of 261 eligible papers were identified. The number of publications increased by 8.8% each year (95% CI=7.5-10.2%; p<0.0001). The majority of studies were descriptive (n=232; 89%), with few measurement (n=8; 3%) and intervention (n=21; 8%) studies identified. Ten intervention studies met EPOC design criteria, however only two interventions, one targeted at individuals with Hodgkin's or Non-Hodgkin's lymphoma and one targeted at individuals with leukaemia, lymphoma or myelomatosis were successful in improving patients' psychosocial outcomes. Despite an increasing volume of research examining psychosocial outcomes of hematological cancer patients, there is a need for robust measurement and methodologically rigorous intervention research in this area. PMID:26951994

  12. Targeting angiogenesis in advanced cervical cancer.

    PubMed

    Eskander, Ramez N; Tewari, Krishnansu S

    2014-11-01

    Patients with advanced stage or recurrent cervical cancer represent a population with limited chemotherapeutic options. More specifically, patients with recurrent disease have a poor salvage rate, with a 5-year survival rate of less than 10%. This year, the first prospective phase III clinical trial exploring the anti-angiogenic agent, bevacizumab, was published, meeting its primary endpoint, with a significant improvement in overall survival. As such, a review of anti-angiogenic therapy in the treatment of this disease is warranted. PMID:25364393

  13. [Advancement in the treatment against prostate cancer].

    PubMed

    Shinohara, Nobuo; Abe, Takashige; Maruyama, Satoru

    2016-01-01

    With the advancement of basic science and medical technology, the treatment against prostate cancer (PC) has dramatically changed. Although the introduction of robotic radical prostatectomy and particle therapies in patients with early stage PC is of much note, the issues on the over-treatment and treatment cost should be heeded. From these points, active surveillance has been an important strategy in these patients. In patients with metastatic hormone-sensitive PC, especially high volume metastases, androgen deprivation therapy (ADT) with docetaxel has been reported to prolong overall survival compared with ADT alone. Lastly, several novel therapeutic agents have been investigated and shown to be favorable outcomes in patients with castration resistant PC. This review focuses on the recent advancement in the treatment against PCs. PMID:26793875

  14. Direct therapeutic intervention for advanced pancreatic cancer

    PubMed Central

    Takakura, Kazuki; Koido, Shigeo

    2015-01-01

    Currently, chemotherapy is an accredited, standard treatment for unresectable, advanced pancreatic cancer (PC). However, it has been still showed treatment-resistance and followed dismal prognosis in many cases. Therefore, some sort of new, additional treatments are needed for the better therapeutic results for advanced PC. According to the previous reports, it is obvious that interventional endoscopic ultrasonography (EUS) is a well-established, helpful and low-risky procedure in general. As the additional treatments of the conventional therapy for advanced PC, many therapeutic strategies, such as immunotherapies, molecular biological therapies, physiochemical therapies, radioactive therapies, using siRNA, using autophagy have been developing in recent years. Moreover, the efficacy of the other potential therapeutic targets for PC using EUS-fine needle injection, for example, intra-tumoral chemotherapeutic agents (paclitaxel, irinotecan), several ablative energies (radiofrequency ablation and cryothermal treatment, neodymium-doped yttrium aluminum garnet laser, high-intensity focused ultrasound), etc., has already been showed in animal models. Delivering these promising treatments reliably inside tumor, interventional EUS may probably be indispensable existence for the treatment of locally advanced PC in near future. PMID:26677434

  15. Direct therapeutic intervention for advanced pancreatic cancer.

    PubMed

    Takakura, Kazuki; Koido, Shigeo

    2015-12-10

    Currently, chemotherapy is an accredited, standard treatment for unresectable, advanced pancreatic cancer (PC). However, it has been still showed treatment-resistance and followed dismal prognosis in many cases. Therefore, some sort of new, additional treatments are needed for the better therapeutic results for advanced PC. According to the previous reports, it is obvious that interventional endoscopic ultrasonography (EUS) is a well-established, helpful and low-risky procedure in general. As the additional treatments of the conventional therapy for advanced PC, many therapeutic strategies, such as immunotherapies, molecular biological therapies, physiochemical therapies, radioactive therapies, using siRNA, using autophagy have been developing in recent years. Moreover, the efficacy of the other potential therapeutic targets for PC using EUS-fine needle injection, for example, intra-tumoral chemotherapeutic agents (paclitaxel, irinotecan), several ablative energies (radiofrequency ablation and cryothermal treatment, neodymium-doped yttrium aluminum garnet laser, high-intensity focused ultrasound), etc., has already been showed in animal models. Delivering these promising treatments reliably inside tumor, interventional EUS may probably be indispensable existence for the treatment of locally advanced PC in near future. PMID:26677434

  16. Endoscopic palliation of advanced esophageal cancer

    PubMed Central

    Mocanu, A; Bârla, R; Hoara, P; Constantinoiu, S

    2015-01-01

    Esophageal cancer represents one of the most aggressive digestive tumors, with a survival rate at 5 years of only 10%. Globally, during the last three decades, there has been an increasing incidence of the esophageal cancer, approx. 400,000 new esophageal cancers being currently diagnosed annually. This represents the eighth leading cause of cancer incidence and the sixth leading cause of cancer death overall. Taking into account the population’s global aging and thus, the increase in the number of patients who will not bear surgery, PCT and radiation, or the fact that they do not want it especially because of deficiencies and associated pathology, the endoscopic ablative techniques with palliation purposes represent the alternative. If we refer to the Western Europe countries and North America, we notice an increase of esophageal adenocarcinoma rate versus squamous cancer. As for the Asian region, referring in particular to China and Japan, 9 out of 10 esophageal cancers are squamous cell carcinomas. For at least half of the patients with EC (esophageal cancer) there is no hope of healing because of the advanced regional malignant invasion (T3-4, N+, M+) with no chemo and radiotherapy response, poor preoperative patients’ conditions or systemic metastasis. The low life expectancy does not justify the risky medical procedures, the goal of the therapy consisting in the improvement of the quality of life by eliminating dysphagia (reestablishing oral feeding) which represents the most common complication of EC, the respiratory tract complication caused by eso-tracheal fistulas or by eliminating chest pain. To treat dysphagia, which is the main target of palliation, combined methods like endoscopic, chemo and radio-therapy, can be used, each one with indications, benefits and risks. Abbreviations: SEPS = self expanding plastic stent, SREMS = self expanding metal stent, EBRT = Endoscopic brachy radiotherapy, EUS = Ultra sound endoscopy, CT = Computer tomograph, UGE

  17. Cytoxan, epirubicin, methotrexate and 5-fluorouracil with hormonal synchronization (tamoxifen/premarin) in advanced breast cancer. Preliminary results.

    PubMed

    Zaniboni, A; Simoncini, E; Marpicati, P; Gorni, F; Cervi, G C; Marini, G

    1986-10-01

    Thirty-three patients with advanced breast cancer were treated with combination chemotherapy and hormonal synchronization in an attempt to increase the overall response rate generally obtained with traditional modalities of treatment. Among the 31 evaluable patients 1 complete (3%), 7 partial (22%), 13 stable disease (42%) and 10 progression of disease (53%) were obtained. Side effects were quite manageable although there were two episodes of life-threatening hematological toxicity. Taking into account the poor prognostic characteristics of our patients (high percentage of dominant visceral disease, 21/31 previously treated patients), our preliminary results with this regimen are interesting and the treatment deserves further evaluation. PMID:3024851

  18. Correlation Between Radiation Dose to {sup 18}F-FDG-PET Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

    SciTech Connect

    Rose, Brent S.; Liang Yun; Lau, Steven K.; Jensen, Lindsay G.; Yashar, Catheryn M.; Hoh, Carl K.; Mell, Loren K.

    2012-07-15

    Purpose: To test the hypothesis that radiation dose to {sup 18}F-fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG-PET)-defined active bone marrow (BM{sub ACT}) subregions is correlated with hematologic toxicity in cervical cancer patients treated with chemoradiotherapy. Methods and Materials: The conditions of 26 women with cervical cancer who underwent {sup 18}F-FDG-PET before treatment with concurrent cisplatin and intensity-modulated radiation therapy were analyzed. BM{sub ACT} was defined as the subregion of total bone marrow (BM{sub TOT}) with a standardized uptake value (SUV) equal to or above the mean for that individual. Inactive bone marrow (BM{sub INACT}) was defined as BM{sub TOT} - BM{sub ACT}. Generalized linear modeling was used to test the correlation between BM{sub ACT} and BM{sub INACT} dose-volume metrics and hematologic nadirs, particularly white blood cell count (WBC) and absolute neutrophil count (ANC). Results: Increased BM{sub ACT} mean dose was significantly associated with decreased log(WBC) nadir ({beta} = -0.04; 95% CI, -0.07to -0.01; p = 0.009), decreased log(ANC) nadir ({beta} = -0.05; 95% CI, -0.08 to -0.02; p = 0.006), decreased hemoglobin nadir ({beta} = -0.16; 95% CI, -0.27 to -0.05; p = 0.010), and decreased platelet nadir ({beta} = -6.16; 95% CI, -9.37 to -2.96; p < 0.001). By contrast, there was no association between BM{sub INACT} mean dose and log(WBC) nadir ({beta} = -0.01; 95% CI, -0.06 to 0.05; p = 0.84), log(ANC) nadir ({beta} = -0.03; 95% CI, -0.10 to 0.04; p = 0.40), hemoglobin nadir ({beta} = -0.09; 95% CI, -0.31 to 0.14; p = 0.452), or platelet nadir ({beta} = -3.47; 95% CI, -10.44 to 3.50; p = 0.339). Conclusions: Irradiation of BM subregions with higher {sup 18}F-FDG-PET activity was associated with hematologic toxicity, supporting the hypothesis that reducing dose to BM{sub ACT} subregions could mitigate hematologic toxicity. Future investigation should seek to confirm these findings and to identify

  19. Belinostat and Azacitidine in Treating Patients With Advanced Hematologic Cancers or Other Diseases

    ClinicalTrials.gov

    2014-12-22

    Accelerated Phase of Disease; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndrome; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  20. Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other Disorders

    ClinicalTrials.gov

    2015-12-30

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

  1. New advances in genitourinary cancer: evidence gathered in 2014.

    PubMed

    Suárez, C; Puente, J; Gallardo, E; Méndez-Vidal, M J; Climent, M A; León, L; Olmos, D; García del Muro, X; González-Billalabeitia, E; Grande, E; Bellmunt, J; Mellado, B; Maroto, P; González del Alba, A

    2015-09-01

    This review provides updated information published in 2014 regarding advances and major achievements in genitourinary cancer. Sections include the best in prostate cancer, renal cancer, bladder cancer, and germ cell tumors. In the field of prostate cancer, data related to treatment approach of hormone-sensitive disease, castrate-resistant prostate cancer, mechanisms of resistance, new drugs, and molecular research are presented. In relation to renal cancer, relevant aspects in the treatment of advanced renal cell carcinoma, immunotherapy, and molecular research, including angiogenesis and von Hippel-Lindau gene, molecular biology of non-clear cell histologies, and epigenetics of clear renal cell cancer are described. New strategies in the management of muscle-invasive localized bladder cancer and metastatic disease are reported as well as salient findings of biomolecular research in urothelial cancer. Some approaches intended to improve outcomes in poor prognosis patients with metastatic germ cell cancer are also reported. Results of clinical trials in these areas are discussed. PMID:26227584

  2. Dietary intake of advanced cancer patients.

    PubMed

    Walsh, T D; Bowman, K B; Jackson, G P

    1983-02-01

    A state registered dietitian assessed the voluntary dietary intake of 13 advanced cancer inpatients on one ward of St. Christopher's Hospice for five consecutive days. There were 11 females, two males; median age 74 years (range 56 to 83). Two patients died on the fourth day of the study. A partially individualised weighed technique was used. Standard sized scoops and spoons were used to serve the food in small, medium or large standard portions (depending on appetite) and were weighed as served. Individual plate waste (by weight) was subtracted to give estimated individual intake. Foods provided by visitors was not included. The median and range of individual mean daily intakes (estimated) were: energy 5760 (938-8945) kJ, 1376 (224-2137) kcal; protein 44 (11-86) g; fat 52 (9-93) g; carbohydrate 169 (21-194) g; calcium 748 (268-1457) mg; iron 4.8 (0.5-21.0) mg; dietary fibre 5.0 (0.5-21.0) g. Compared to recommended amounts, energy, iron and dietary fibre intakes were low; calcium intake was high. Nutritional status may affect prognosis and/or subjective well-being in advanced cancer. The value of nutritional supplementation and the role of appetite stimulants in improving nutritional status needs investigation. PMID:6841131

  3. Novel therapy for advanced gastric cancer

    PubMed Central

    Zhang, Yue; Wu, Shenhong

    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. PMID:26600926

  4. Recent advances in the treatment of colon cancer.

    PubMed

    Xu, R; Zhou, B; Fung, P C W; Li, X

    2006-08-01

    Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Although surgical resection is still the only treatment capable of curing colon cancer, adjuvant therapy continues to play an important role in preventing recurrence and metastasis. In recent years remarkable progress has been made in the treatment of colon cancer. This review discusses recent advances in adjuvant therapy for colon cancer, including chemotherapy, immunotherapy, antiangiogenic therapy and apoptosis induction. In the meantime, molecular therapy is also elucidated in the above methods. All these new advances will provide new promises for patients of colon cancer. PMID:16691539

  5. Analysis of baseline hepatitis B virus DNA levels in chronic hepatitis B patients with non-hematological malignancies prior to the initiation of cancer chemotherapy

    PubMed Central

    YOUNG, SHIH-HAO; WEI, TIEN-HSIN; LIN, CHUNG-CHI; CHU, CHI-JEN; LEE, FA-YAUH; YU, MAY-ING; LU, REI-HWA; CHANG, CHIAO-YU; YANG, PEI-LING; WANG, MEI-HUI; LIN, HAN-CHIEH

    2016-01-01

    Reactivation of hepatitis B virus (HBV) infection is common (~20–50%) during cancer chemotherapy. Baseline HBV replication status is an important risk factor for HBV reactivation. To date, data on the baseline HBV DNA level for chronic hepatitis B (CHB) patients prior to chemotherapy, particularly for non-hematological malignancies, are limited. A total of 105 consecutive CHB patients with solid tumors who received prophylactic antiviral therapy prior to chemotherapy from November, 2011 to December, 2014, were enrolled in this study. The patients' tumors included: Breast cancer (37.1%), lung cancer (18.1%), colon cancer (17.1%), head and neck cancer (10.5%), other gastrointestinal tract malignancies (8.6%), gynecological cancer (4.8%) and others (3.8%). The mean age of the enrolled patients was 55.2±1.1 years, 48 of the patients were male, 3 were hepatitis B e antigen-positive, and 26.7% had abnormal alanine aminotransferase (ALT) levels at baseline. The median HBV DNA level measured by quantitative polymerase chain reaction assay prior to chemotherapy was 3.30 log10 IU/ml and 49.5% of the enrolled patients had a baseline HBV DNA level >2,000 IU/ml. A wide range of HBV distribution was found: <20 IU/ml (15.2%), 20≤DNA<2,000 IU/ml (35.3%), 2,000≤DNA<20,000 IU/ml (26.6%), 20,000≤DNA<106 IU/ml (17.2%) and <106 IU/ml (5.7%). Age and baseline ALT level were not strongly associated with virological activity. The mean HBV DNA and the percentage of patients with HBV DNA >2,000 IU/ml were comparable between different cancer groups. Quantitative HBsAg level was a major determinant of baseline HBV DNA, and a significant correlation was noted between log10 hepatitis B surface antigen and log10 HBV DNA levels (γ=0.641, P<0.001). Our study demonstrated a wide distribution of baseline HBV DNA level among CHB patients diagnosed with non-hematological malignancies. Of note, approximately half of the patients (i.e., those with HBV DNA >2,000 IU/ml) had a higher risk of HBV

  6. Population-Based Analysis of Hematologic Malignancy Referrals to a Comprehensive Cancer Center, Referrals for Blood and Marrow Transplantation, and Participation in Clinical Trial, Survey, and Biospecimen Research by Race.

    PubMed

    Clay, Alyssa; Peoples, Brittany; Zhang, Yali; Moysich, Kirsten; Ross, Levi; McCarthy, Philip; Hahn, Theresa

    2015-08-01

    Racial and ethnic disparities have been reported in clinical trial/research participation, utilization of autologous and allogeneic blood and marrow transplantation (BMT), and availability of allogeneic donors. We performed a population-based cohort study to investigate adult hematologic malignancy referrals to a US tertiary cancer center, utilization of BMT, and participation in clinical trial, survey, and biospecimen research by race. US Census Data and the New York State Public Access Cancer Epidemiology Database identified the racial distribution of the general population and new hematologic malignancy cases in the primary catchment area. From 2005 to 2011, 1106 patients aged 18 to 75 years were referred for BMT consultation; although the rate of BMT among hematologic malignancy referrals did not differ by race, the reasons for not receiving a BMT did. Participation in biospecimen research did not vary by race; however, African Americans and other minorities were significantly less likely to participate in survey research than European Americans. Although rates of hematologic malignancy referrals and use of BMT for minorities appear to be low (<10%), they closely reflect the race distribution of all hematologic malignancy cases and the western New York population. African Americans are equally likely as other races to participate in biospecimen banking, but further study is needed to understand reasons for lower participation in survey research. PMID:25899454

  7. Phase II clinical trial of ex vivo-expanded cytokine-induced killer cells therapy in advanced pancreatic cancer.

    PubMed

    Chung, Moon Jae; Park, Jeong Youp; Bang, Seungmin; Park, Seung Woo; Song, Si Young

    2014-09-01

    Second-line chemotherapy in patients with gemcitabine-refractory advanced pancreatic cancer has shown disappointing survival outcomes due to rapid disease progression and performance deterioration. The aim of this phase II trial was to evaluate the efficacy and safety of adoptive immunotherapy using ex vivo-expanded, cytokine-induced killer (CIK) cells in gemcitabine-refractory advanced pancreatic cancer. Patients with advanced pancreatic cancer who showed disease progression during gemcitabine-based chemotherapy were enrolled in this study. For generation of CIK cells, peripheral blood samples were collected from each patient and cultured with anti-CD3 monoclonal antibody and IL-2. Patients received CIK cells intravenously 10 times, every week for 5 weeks and then every other week for 10 weeks. Twenty patients were enrolled between November 2009 and September 2010. The disease control rate was 25 % (4/16 patients). The median progression-free survival (PFS) was 11.0 weeks (95 % CI 8.8-13.2), and the median overall survival (OS) was 26.6 weeks (95 % CI 8.6-44.6). Grade 3 toxicities included general weakness in two patients and thrombocytopenia in one patient. Grade 4 hematologic or non-hematologic toxicity was not observed. Patients showed improvement in pancreatic pain, gastrointestinal distress, jaundice, body image alterations, altered bowel habits, health satisfaction, and sexuality when assessing quality of life (QoL). Adoptive immunotherapy using CIK cells showed comparable PFS and OS to survival data of previous trials that assessed conventional chemotherapies while maintaining tolerability and showing encouraging results in terms of patient QoL in gemcitabine-refractory advanced pancreatic cancer (clinicalTrials.gov number NCT00965718). PMID:24916038

  8. Lactobacillus in Preventing Infection in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2015-03-18

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

  9. Advanced thyroid cancers: new era of treatment.

    PubMed

    Mohammed, Amrallah A; El-Shentenawy, Ayman

    2014-07-01

    Since chemotherapy has been shown to be unsuccessful in case of advanced thyroid carcinomas, the research for new therapies is fundamental. Clinical trials of many tyrosine kinase inhibitors as well as anti-angiogenic inhibitors suggest that patients with thyroid cancer could have an advantage with new target therapy. Recently, Food and Drug Administration approved two targeted therapies, vandetanib and cabozantinib for the treatment of metastatic thyroid carcinomas with acceptable outcome. We summarized the results and the toxic effects associated with these treatments reported in clinical trials. Future trials should aim at combinations of targeted agents with or without other treatment modalities to obtain a more effective result in thyroid carcinoma treatment. PMID:24908065

  10. NATO PILOT STUDY ON ADVANCED CANCER RISK ASSESSMENT METHODS

    EPA Science Inventory

    NCEA scientists are participating in a study of advanced cancer risk assessment methods, conducted under the auspices of NATO's Committee on the Challenges of Modern Society. The product will be a book of case studies that illustrate advanced cancer risk assessment methods, avail...

  11. Differences in Parent-Provider Concordance Regarding Prognosis and Goals of Care Among Children With Advanced Cancer

    PubMed Central

    Rosenberg, Abby R.; Orellana, Liliana; Kang, Tammy I.; Geyer, J. Russell; Feudtner, Chris; Dussel, Veronica; Wolfe, Joanne

    2014-01-01

    Purpose Concordance between parents of children with advanced cancer and health care providers has not been described. We aimed to describe parent-provider concordance regarding prognosis and goals of care, including differences by cancer type. Patients and Methods A total of 104 pediatric patients with recurrent or refractory cancer were enrolled at three large children's hospitals. On enrollment, their parents and providers were invited to complete a survey assessing perceived prognosis and goals of care. Patients' survival status was retrospectively abstracted from medical records. Concordance was assessed via discrepancies in perceived prognosis, κ statistics, and McNemar's test. Distribution of categorical variables and survival rates across cancer type were compared with Fisher's exact and log-rank tests, respectively. Results Data were available from 77 dyads (74% of enrolled). Parent-provider agreement regarding prognosis and goals of care was poor (κ, 0.12 to 0.30). Parents were more likely to report cure was likely (P < .001). The frequency of perceived likelihood of cure and the goal of cure varied by cancer type for both parents and providers (P < .001 to .004). Relatively optimistic responses were more common among parents and providers of patients with hematologic malignancies, although there were no differences in survival. Conclusion Parent-provider concordance regarding prognosis and goals in advanced pediatric cancer is generally poor. Perceptions of prognosis and goals of care vary by cancer type. Understanding these differences may inform parent-provider communication and decision making. PMID:25024073

  12. Hematological Practice in India.

    PubMed

    Das, Reena; Ahluwalia, Jasmina; Sachdeva, Man Updesh Singh

    2016-04-01

    This article provides a short summary of hematological practice in India. It focuses particularly on how the patterns of hematologic practice differ from those of countries in the West with particular respect to genetic hematological diseases and a wide range of malignant disorders of hemopoiesis. It also focuses on the difficulties of control and management of hematological disorders set against a background of a relatively poor country. PMID:27040963

  13. Current Role of Genetics in Hematologic Malignancies.

    PubMed

    Prakash, Gaurav; Kaur, Anupriya; Malhotra, Pankaj; Khadwal, Alka; Sharma, Prashant; Suri, Vikas; Varma, Neelam; Varma, Subhash

    2016-03-01

    Rapidly changing field of genetic technology and its application in the management of hematological malignancies has brought significant improvement in treatment and outcome of these disorders. Today, genetics plays pivotal role in diagnosis and prognostication of most hematologic neoplasms. The utilization of genetic tests in deciding specific treatment of various hematologic malignancies as well as for evaluation of depth of treatment response is rapidly advancing. Therefore, it is imperative for practitioners working in the field of hemato-oncology to have sufficient understanding of the basic concepts of genetics in order to comprehend upcoming molecular research in this area and to translate the same for patient care. PMID:26855503

  14. Are Short Telomeres Predictive of Advanced Cancer?

    PubMed Central

    Shay, Jerry W.

    2013-01-01

    Summary The combination of variable telomere length in cancer cells combined with shorter telomere length in cancer-associated stromal cells, strongly correlate with progression to prostate cancer metastasis and cancer death. The implications are that telomere length measurements not only have the potential as a prognostic indicator of prostate cancer outcomes but also as a risk stratification enrichment biomarker for individualized therapeutic interventions. PMID:24124228

  15. Pegylated Interferon Alfa-2a Yields High Rates of Hematologic and Molecular Response in Patients With Advanced Essential Thrombocythemia and Polycythemia Vera

    PubMed Central

    Quintás-Cardama, Alfonso; Kantarjian, Hagop; Manshouri, Taghi; Luthra, Rajyalakshmi; Estrov, Zeev; Pierce, Sherry; Richie, Mary Ann; Borthakur, Gautam; Konopleva, Marina; Cortes, Jorge; Verstovsek, Srdan

    2009-01-01

    Purpose We conducted a phase II study of pegylated interferon alfa-2a (PEG-IFN-α-2a) in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Patients and Methods Seventy-nine patients (40 with PV and 39 with ET) have been treated. Median time from diagnosis to PEG-IFN-α-2a was 54 months in patients with PV and 33 months in patients with ET. Eighty-one percent of patients had received prior therapy. The first three patients received PEG-IFN-α-2a at 450 μg weekly. As a result of poor tolerance, this dose was decreased in a stepwise manner to a current starting dose of 90 μg weekly. Seventy-seven patients are evaluable and have been observed for a median of 21 months. Results The overall hematologic response rate was 80% in PV and 81% in ET (complete in 70% and 76% of patients, respectively). The JAK2V617F mutation was detected in 18 patients with ET and 38 patients with PV; sequential measurements by a pyrosequencing assay were available in 16 patients with ET and 35 patients with PV. The molecular response rate was 38% in ET and 54% in PV, being complete (undetectable JAK2V617F) in 6% and 14%, respectively. The JAK2V617F mutant allele burden continued to decrease with no clear evidence for a plateau. The tolerability of PEG-IFN-α-2a at 90 μg weekly was excellent. Conclusion PEG-IFN-α-2a resulted in remarkable clinical activity, high rates of molecular response, and acceptable toxicity in patients with advanced ET or PV. The ability of PEG-IFN-α-2a to induce complete molecular responses suggests selective targeting of the malignant clone. PMID:19826111

  16. Treatment of advanced thyroid cancer: role of molecularly targeted therapies.

    PubMed

    Covell, Lorinda L; Ganti, Apar Kishor

    2015-09-01

    Advanced thyroid cancer is not amenable to therapy with conventional cytotoxic chemotherapy. However, newer advances in the understanding of the molecular pathogenesis of different subtypes of thyroid cancer have provided new opportunities for the evaluation of molecularly targeted therapies. This has led to multiple clinical trials using various multi-kinase inhibitors and the subsequent US FDA approval of sorafenib for differentiated thyroid cancer and vandetanib and cabozantinib for medullary thyroid carcinoma. This review provides a summary of the current literature for the treatment of advanced thyroid carcinoma and future directions in this disease. PMID:26335853

  17. Advances in genetics: widening our understanding of prostate cancer

    PubMed Central

    Pine, Angela C.; Fioretti, Flavia F.; Brooke, Greg N.; Bevan, Charlotte L.

    2016-01-01

    Prostate cancer is a leading cause of cancer-related death in Western men. Our understanding of the genetic alterations associated with disease predisposition, development, progression, and therapy response is rapidly improving, at least in part, owing to the development of next-generation sequencing technologies. Large advances have been made in our understanding of the genetics of prostate cancer through the application of whole-exome sequencing, and this review summarises recent advances in this field and discusses how exome sequencing could be used clinically to promote personalised medicine for prostate cancer patients. PMID:27408704

  18. Artificial intelligence in hematology.

    PubMed

    Zini, Gina

    2005-10-01

    Artificial intelligence (AI) is a computer based science which aims to simulate human brain faculties using a computational system. A brief history of this new science goes from the creation of the first artificial neuron in 1943 to the first artificial neural network application to genetic algorithms. The potential for a similar technology in medicine has immediately been identified by scientists and researchers. The possibility to store and process all medical knowledge has made this technology very attractive to assist or even surpass clinicians in reaching a diagnosis. Applications of AI in medicine include devices applied to clinical diagnosis in neurology and cardiopulmonary diseases, as well as the use of expert or knowledge-based systems in routine clinical use for diagnosis, therapeutic management and for prognostic evaluation. Biological applications include genome sequencing or DNA gene expression microarrays, modeling gene networks, analysis and clustering of gene expression data, pattern recognition in DNA and proteins, protein structure prediction. In the field of hematology the first devices based on AI have been applied to the routine laboratory data management. New tools concern the differential diagnosis in specific diseases such as anemias, thalassemias and leukemias, based on neural networks trained with data from peripheral blood analysis. A revolution in cancer diagnosis, including the diagnosis of hematological malignancies, has been the introduction of the first microarray based and bioinformatic approach for molecular diagnosis: a systematic approach based on the monitoring of simultaneous expression of thousands of genes using DNA microarray, independently of previous biological knowledge, analysed using AI devices. Using gene profiling, the traditional diagnostic pathways move from clinical to molecular based diagnostic systems. PMID:16203606

  19. Targeting protein-protein interactions in hematologic malignancies: still a challenge or a great opportunity for future therapies?

    PubMed Central

    Cierpicki, Tomasz; Grembecka, Jolanta

    2015-01-01

    Summary Over the past several years, there has been an increasing research effort focused on inhibition of protein-protein interactions (PPIs) to develop novel therapeutic approaches for cancer, including hematologic malignancies. These efforts have led to development of small molecule inhibitors of PPIs, some of which already advanced to the stage of clinical trials while others are at different stages of pre-clinical optimization, emphasizing PPIs as an emerging and attractive class of drug targets. Here, we review several examples of recently developed inhibitors of protein-protein interactions highly relevant to hematologic cancers. We address the existing skepticism about feasibility of targeting PPIs and emphasize potential therapeutic benefit from blocking PPIs in hematologic malignancies. We then use these examples to discuss the approaches for successful identification of PPI inhibitors and provide analysis of the protein-protein interfaces, with the goal to address ‘druggability’ of new PPIs relevant to hematology. We discuss lessons learned to improve the success of targeting new protein-protein interactions and evaluate prospects and limits of the research in this field. We conclude that not all PPIs are equally tractable for blocking by small molecules, and detailed analysis of PPI interfaces is critical for selection of those with the highest chance of success. Together, our analysis uncovers patterns that should help to advance drug discovery in hematologic malignancies by successful targeting of new protein-protein interactions. PMID:25510283

  20. Evaluation of a trastuzumab-containing treatment regimen for patients with unresectable advanced or recurrent gastric cancer

    PubMed Central

    NAMIKAWA, TSUTOMU; MUNEKAGE, ERI; MUNEKAGE, MASAYA; MAEDA, HIROMICHI; YATABE, TOMOAKI; KITAGAWA, HIROYUKI; SAKAMOTO, KOUICHI; OBATAKE, MASAYUKI; KOBAYASHI, MICHIYA; HANAZAKI, KAZUHIRO

    2016-01-01

    The present study aimed to evaluate the efficacy and safety of trastuzumab plus chemotherapy for patients with unresectable advanced or recurrent gastric cancer. A retrospective analysis of 213 patients with unresectable advanced or recurrent gastric cancer who received systemic chemotherapy, including 15 patients who were also administered trastuzumab, at Kochi Medical School between 2007 and 2013 was performed. The overall survival was compared between patients who received trastuzumab plus chemotherapy and patients who received chemotherapy alone, and the safety and efficacy of the trastuzumab-containing regimen was evaluated. Human epidermal growth factor receptor (HER)2 status was examined in 86 patients, of whom 15 (17.4%) exhibited strong positive HER2 expression. The rate of strong positive HER2 expression was significantly higher for intestinal type tumors compared with diffuse type tumors [23.6 (13/55) vs. 6.5% (2/31); P=0.044]. The median overall survival of the patients treated with trastuzumab was significantly longer compared with that for patients who were not treated with trastuzumab (22.9 vs. 11.6 months; P=0.014). The objective response rate and disease control rate for trastuzumab plus chemotherapy were 46.7 and 86.7%, respectively. Frequently encountered grade 3–4 toxicities included neutropenia (26.7%; 4/15), anemia (13.3%; 2/15) and fatigue (13.3%; 2/15). Trastuzumab plus chemotherapy is effective for patients with HER2-positive advanced or recurrent gastric cancer, and the frequencies of hematological and non-hematological toxicities experienced by patients in the present study indicated that it can be safely administered clinically. PMID:27330770

  1. Association Between Bone Marrow Dosimetric Parameters and Acute Hematologic Toxicity in Anal Cancer Patients Treated With Concurrent Chemotherapy and Intensity-Modulated Radiotherapy

    SciTech Connect

    Mell, Loren K. Schomas, David A.; Salama, Joseph K.; Devisetty, Kiran; Aydogan, Bulent; Miller, Robert C.; Jani, Ashesh B.; Kindler, Hedy L.; Roeske, John C.; Chmura, Steven J.

    2008-04-01

    Purpose: To test the hypothesis that the volume of pelvic bone marrow (PBM) receiving 10 and 20 Gy or more (PBM-V{sub 10} and PBM-V{sub 20}) is associated with acute hematologic toxicity (HT) in anal cancer patients treated with concurrent chemoradiotherapy. Methods and Materials: We analyzed 48 consecutive anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiation therapy. The median radiation dose to gross tumor and regional lymph nodes was 50.4 and 45 Gy, respectively. Pelvic bone marrow was defined as the region extending from the iliac crests to the ischial tuberosities, including the os coxae, lumbosacral spine, and proximal femora. Endpoints included the white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin, and platelet count nadirs. Regression models with multiple independent predictors were used to test associations between dosimetric parameters and HT. Results: Twenty patients (42%) had Stage T3-4 disease; 15 patients (31%) were node positive. Overall, 27 (56%), 24 (50%), 4 (8%), and 13 (27%) experienced acute Grade 3-4 leukopenia, neutropenia, anemia, and thrombocytopenia, respectively. On multiple regression analysis, increased PBM-V{sub 5}, V{sub 10}, V{sub 15}, and V{sub 20} were significantly associated with decreased WBC and ANC nadirs, as were female gender, decreased body mass index, and increased lumbosacral bone marrow V{sub 10}, V{sub 15}, and V{sub 20} (p < 0.05 for each association). Lymph node positivity was significantly associated with a decreased WBC nadir on multiple regression analysis (p < 0.05). Conclusion: This analysis supports the hypothesis that increased low-dose radiation to PBM is associated with acute HT during chemoradiotherapy for anal cancer. Techniques to limit bone marrow irradiation may reduce HT in anal cancer patients.

  2. Thyroid hormone autoantibodies: are they a better marker to detect early thyroid damage in patients with hematologic cancers receiving tyrosine kinase inhibitor or immunoregulatory drug treatments?

    PubMed Central

    Mondello, P.; Mian, M.; Pitini, V.; Cuzzocrea, S.; Sindoni, A.; Galletti, M.; Mandolfino, M.; Santoro, D.; Mondello, S.; Aloisi, C.; Altavilla, G.; Benvenga, S.

    2016-01-01

    Background Unlike cytotoxic agents, novel antineoplastic drugs can variably affect thyroid function and so impair patient outcomes. However, the widely used standard thyroid tests have demonstrated low sensitivity for detecting early thyroid damage that leads to dysfunction of the gland. To find a more reliable thyroid marker, we assessed the presence of antibodies binding thyroid hormones (thAbs) in a cancer population undergoing potentially thyrotoxic treatment. Methods From April 2010 to September 2013, 82 patients with hematologic malignancies treated with tyrosine kinase inhibitors or immunoregulatory drugs were recruited. Healthy volunteers (n = 104) served as control subjects. Thyroid function, autoimmunity tests, thAbs, and thyroid sonography were assessed once during treatment. Results Overall, thAb positivity was recorded in 13% of the entire cohort. In most cases, the thAbs were of a single type, with a predominance of T3 immunoglobulin G. More specifically, thAbs were detected in 11 cancer patients; and abnormal levels of thyroid-stimulating hormone, thyroglobulin antibody, and thyroperoxidase antibody were detected in 6 (p = 0.05), 0 (p = 0.0006), and 2 cancer patients (p = 0.001) respectively. Ultrasonographic alterations of the thyroid were observed in 12 cancer patients. In contrast, of the 104 healthy control subjects, only 1 was positive for thAbs (1%). Conclusions We have demonstrated for the first time that thAbs are a reliable marker of early thyroid dysfunction when compared with the widely used standard thyroid tests. A confirmatory prospective trial aiming at evaluating thAbs at various time points during treatment could clarify the incidence and timing of antibody appearance. PMID:27330353

  3. Crizotinib for Advanced Non-Small Cell Lung Cancer

    Cancer.gov

    A summary of results from an international phase III clinical trial that compared crizotinib versus chemotherapy in previously treated patients with advanced lung cancer whose tumors have an EML4-ALK fusion gene.

  4. Combination Therapy Shows Promise for Treating Advanced Breast Cancer

    Cancer.gov

    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.

  5. Refining Preoperative Therapy for Locally Advanced Rectal Cancer

    Cancer.gov

    In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

  6. Bevacizumab improves survival for patients with advanced cervical cancer

    Cancer.gov

    Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug, according to an interim analysis

  7. Some Advanced Kidney Cancer Patients May Postpone Treatment

    MedlinePlus

    ... advanced kidney cancer that has spread require immediate, aggressive treatment, a small new study suggests. "A subset ... them the inconvenience and debilitating side effects of aggressive treatments for about a year, and in some ...

  8. Blocking DNA Repair in Advanced BRCA-Mutated Cancer

    Cancer.gov

    In this trial, patients with relapsed or refractory advanced cancer and confirmed BRCA mutations who have not previously been treated with a PARP inhibitor will be given BMN 673 by mouth once a day in 28-day cycles.

  9. Men with Advanced Prostate Cancer Might Consider Gene Test

    MedlinePlus

    ... html Men With Advanced Prostate Cancer Might Consider Gene Test Detection of genetic flaw could help predict ... suggests. Testing for inherited abnormalities in DNA repair genes could provide patients and family members important information ...

  10. [Concurrent proton therapy and chemotherapy for locally advanced cancers].

    PubMed

    Ishikawa, Hitoshi; Fukumitsu, Nobuyoshi; Ohnishi, Kayoko; Mizumoto, Masashi; Murofushi, Keiko; Numajiri, Haruko; Aihara, Teruhito; Okumura, Toshiyuki; Sakurai, Hideyuki

    2015-02-01

    Charged particles such as protons and carbon-ions offer advantageous physical properties to radiation therapy (RT) for the treatment of various cancers when compared with photons, because they exhibit a spread-out Bragg peak, and may be utilized to achieve a desirable dose distribution to the target volume by using specified beam modulation. Interestingly, the cytocidal effect of protons is almost equal to that of photons, because both protons and photons are considered low-linear energy transfer radiations. Hence, proton beam therapy (PBT) is an attractive RT option, especially in the treatment of locally advanced cancers, as irradiation doses can be safely escalated while sparing the surrounding normal tissues, and because PBT may be concurrently combined with chemotherapy for treating such cancers. Recent advances in PBT techniques including a spot scanning method, as well as an increase in the number of particle therapy institutes are anticipated to yield favorable results through future multi-institutional prospective studies. The University of Tsukuba has carried out several studies to validate the effectiveness of PBT for many types of cancers since 1983. Here, we present our findings on the clinical outcomes of PBT for esophageal cancer, non-small cell lung cancer, intrahepatic biliary tract cancer, pancreas cancer, and bladder cancer; future aspects of PBT concurrently combined with chemotherapy for treating locally advanced cancers are also discussed. PMID:25743133

  11. Hematology in Africa.

    PubMed

    Makani, Julie; Roberts, David J

    2016-04-01

    This review of hematology in Africa highlights areas of current practice and the immediate needs for development and clinical research. Acute hematological practice is dominated by anemia, sickle cell disease, and the need to provide a safe and rapidly available supply of blood. There is a growing need for specialist services for bleeding and coagulation, hematological malignancy, and palliative care. There are many areas of practice where straightforward measures could yield large gains in patient care. There is an urgent need for good clinical research to describe the epidemiology, natural history, and management of hematological diseases in Africa. PMID:27040965

  12. Advances in cancer epidemiology in Japan.

    PubMed

    Tanaka, Hideo

    2014-02-15

    Epidemiologists in Japan have been performing calculations to estimate nationwide cancer incidence rates as well as 5-year survival rates using population-based cancer registry data. There have been remarkable changes in cancer incidence and/or mortality in cancers of the lung, liver and stomach, which were thought to be attributed to the changing impact of exposure to cigarette smoking, chronic hepatitis C virus infection and Helicobacter pylori infection, respectively. In systematic reviews providing evidence in risk/protective factors for cancer sites using case-control and cohort studies of the Japanese population, there were associations between cancer sites (esophagus, stomach, colo-rectum, liver, pancreas, lung and breast) and various lifestyle factors. In the past 10 years, a hospital-based case-control study at Aichi Cancer Center provided valuable evidence of gene-environment interaction on the development of cancer [i.e., the effects of aldehyde dehydrogenase-2 (ALDH2) polymorphism and heavy alcohol drinking on esophageal cancer, ALDH2 polymorphism and smoking on lung cancer, methylenetetrahydrofolate reductase polymorphism and heavy alcohol drinking on pancreatic cancer]. The database with stored DNA was also used and identified seven loci containing significant but low-penetrance polymorphisms associated with the development of breast cancer. These findings together with established risk factors are likely to be useful to predict personalized breast cancer risk in East Asian women. In 2005, the Japan Multi-Institution Collaborative Cohort (J-MICC) study was launched to elucidate gene-environment interactions as well as to confirm preclinical diagnostic biomarkers of cancer. J-MICC, which has recruited 92,000 healthy individuals by the end of 2012, will follow the individuals until 2025. PMID:24105756

  13. A Novel Bioluminescence Orthotopic Mouse Model for Advanced Lung Cancer

    PubMed Central

    Li, Bo; Torossian, Artour; Li, Wenyan; Schleicher, Stephen; Niu, Kathy; Giacalone, Nicholas J.; Kim, Sung June; Chen, Heidi; Gonzalez, Adriana; Moretti, Luigi; Lu, Bo

    2011-01-01

    Lung cancer is the leading cause of cancer-related death in the United States despite recent advances in our understanding of this challenging disease. An animal model for high-throughput screening of therapeutic agents for advanced lung cancer could help promote the development of more successful treatment interventions. To develop our orthotopic lung cancer model, luciferase-expressing A549 cancer cells were injected into the mediastinum of athymic nude mice. To determine whether the model would allow easy monitoring of response to therapeutic interventions, tumors were treated with 30 mg/kg Paclitaxel or were irradiated with 5 fractions of 2 Gy, and tumor burden was monitored using bioluminescence imaging. Evidence of radiation-induced lung injury was assessed using immunohistochemical staining for phospho-Smad2/3 and cleaved caspase-3. We found that tumor implantation recapitulated advanced human lung cancer as evidenced by tumor establishment and proliferation within the mediastinum. The tumor responded to Paclitaxel or radiation as shown by decreased tumor bioluminescence and improved overall survival. Immunohistochemistry revealed increased phospho-Smad2/3 and cleaved caspase-3 in irradiated lungs, consistent with radiation-induced lung injury. This orthotopic lung cancer model may help provide a method to assess therapeutic interventions in a preclinical setting that recapitulates locally advanced lung cancer. PMID:21663394

  14. Music in Reducing Anxiety and Pain in Adult Patients Undergoing Bone Marrow Biopsy for Hematologic Cancers or Other Diseases

    ClinicalTrials.gov

    2012-07-12

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Psychosocial Effects of Cancer and Its Treatment

  15. Advances of Cancer Therapy by Nanotechnology

    PubMed Central

    Wang, Xu; Wang, Yiqing; Chen, Zhuo Georgia

    2009-01-01

    Recent developments in nanotechnology offer researchers opportunities to significantly transform cancer therapeutics. This technology has enabled the manipulation of the biological and physicochemical properties of nanomaterials to facilitate more efficient drug targeting and delivery. Clinical investigations suggest that therapeutic nanoparticles can enhance efficacy and reduced side effects compared with conventional cancer therapeutic drugs. Encouraged by rapid and promising progress in cancer nanotechnology, researchers continue to develop novel and efficacious nanoparticles for drug delivery. The use of therapeutic nanoparticles as unique drug delivery systems will be a significant addition to current cancer therapeutics. PMID:19688065

  16. Pyroxamide in Treating Patients With Advanced Cancer

    ClinicalTrials.gov

    2013-06-04

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous Condition; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  17. Advancing breast cancer survivorship among African-American women.

    PubMed

    Coughlin, Steven S; Yoo, Wonsuk; Whitehead, Mary S; Smith, Selina A

    2015-09-01

    Advances have occurred in breast cancer survivorship but, for many African-American women, challenges and gaps in relevant information remain. This article identifies opportunities to address disparities in breast cancer survival and quality of life, and thereby to increase breast cancer survivorship among African-American women. For breast cancer survivors, common side effects, lasting for long periods after cancer treatment, include fatigue, loss of strength, difficulty sleeping, and sexual dysfunction. For addressing physical and mental health concerns, a variety of interventions have been evaluated, including exercise and weight training, dietary interventions, yoga and mindfulness-based stress reduction, and support groups or group therapy. Obesity has been associated with breast cancer recurrence and poorer survival. Relative to white survivors, African-American breast cancer survivors are more likely to be obese and less likely to engage in physical activity, although exercise improves overall quality of life and cancer-related fatigue. Considerable information exists about the effectiveness of such interventions for alleviating distress and improving quality of life among breast cancer survivors, but few studies have focused specifically on African-American women with a breast cancer diagnosis. Studies have identified a number of personal factors that are associated with resilience, increased quality of life, and positive adaptation to a breast cancer diagnosis. There is a need for a better understanding of breast cancer survivorship among African-American women. Additional evaluations of interventions for improving the quality of life and survival of African-American breast cancer survivors are desirable. PMID:26303657

  18. Advance care planning knowledge and documentation in a hospitalized cancer population

    PubMed Central

    Barakat, Ayman; Barnes, Sunni A.; Casanova, Mark A.; Stone, Marvin J.; Shuey, Kathleen M.

    2013-01-01

    To have a better understanding of our patients’ knowledge of advance directive planning and execution, as well as communication with their oncologists regarding their wishes, we conducted a survey on our inpatient hematology-oncology services. A total of 68 unique hospitalized patients with a diagnosis of cancer completed surveys. Surveys were given to all oncology patients regardless of their reason for admission. Overall, 29% of the patients reported having had a discussion with their oncologist regarding their wishes if they became seriously ill or near death. Of those who did have this conversation, the majority said that they, rather than their physician, initiated it. Although the vast majority of patients (97%) knew what a living will was, only 54% had one in place. Twenty patients had a discussion with their oncologist, and 14 of them (70%) had a living will. This percentage was higher than in the group that did not have a conversation with their physician (48%; 23 of 48 patients), but the difference was not statistically significant. Most cancer patients admitted to an inpatient oncology unit either did not have or did not recall having a discussion with their oncologist regarding end-of-life issues. This study gives us a baseline of information in evaluating future interventions directed to improve the quality of patient-physician communication regarding end-of-life planning. PMID:24082411

  19. Individualized management of advanced bladder cancer: Where do we stand?

    PubMed

    Burgess, Earle F

    2015-04-01

    Despite recent progress in the development of novel targeted therapies in various malignancies, the management of advanced urothelial cancer has changed little over the past 2 decades. Comorbidities inherent to patients with bladder cancer often preclude the use of standard cisplatin-based chemotherapy and underscore the need for individualized treatment recommendations and the development of more effective therapies. This review discusses current issues relevant to the management of patients with locally advanced and metastatic urothelial carcinoma of the bladder and highlights recent advances in defining molecular aberrations that may ultimately lead to personalized therapeutic decision making. PMID:24332641

  20. Survival outcomes and toxicity of intraoperative intraperitoneal chemotherapy in advanced epithelial ovarian cancer

    PubMed Central

    Yoon, Ji-Young; Koo, Yu-Jin; Kim, Mi-Jung; Kim, Tae-Jin; Lim, Kyung-Taek

    2014-01-01

    Objective To assess the effect of single-dose cisplatin intraperitoneally administered during cytoreductive surgery in advanced epithelial ovarian cancer. Methods Data from patients who underwent surgical management followed by intravenous (IV) chemotherapy for stage III epithelial ovarian cancer from 2003 to 2012 were retrospectively reviewed. Subjects were divided into intraperitoneal (IP) and no-intraperitoneal (NIP) groups according to the administration of IP cisplatin 100 mg during the staging surgery. Clinical results such as survival outcomes and chemotherapeutic toxicity were compared between the two groups. Results Thirty-seven patients in the IP group and 26 in the NIP group were identified. There were no significant differences between the two groups in basic characteristics such as age, histology, and surgical procedures. After the surgery with or without IP chemotherapy, there was no difference in the rate of either hematologic or gastrointestinal toxicity or in the rate of incompletion of following IV chemotherapy. Tumor recurrence occurred in 67.6% (25 patients) of IP group and 57.7% (15 patients) of NIP group (P=0.423) during the mean follow-up period of 37 months. The 3-year disease free-survival rate was 39.9% in the IP group and 35.8% in the NIP group, and the relative risk of recurrence was 0.864 (95% confidence interval, 0.447-1.673; P=0.665) in the IP group as compared with the NIP group. Conclusion IP chemotherapy with single-dose cisplatin during cytoreductive surgery is safe and feasible with little chemotherapeutic toxicity in advanced epithelial ovarian cancer, but no distinct improvement in survival could be demonstrated in the present study. PMID:25469337

  1. Clinical utility of ramucirumab in advanced gastric cancer

    PubMed Central

    Chan, Matthew MK; Sjoquist, Katrin M; Zalcberg, John R

    2015-01-01

    Gastric cancer is currently the third most common cause of cancer deaths worldwide. Prognosis remains poor with most patients presenting with advanced or metastatic disease. A better understanding of angiogenesis has led to the investigation of drugs that inhibit the vascular endothelial growth factor (VEGF) pathway including anti-VEGF antibody therapy (eg, bevacizumab), inhibitors of angiogenic receptor tyrosine kinases (eg, sunitinib, sorafenib, apatinib, regorafenib), and inhibitors of vascular endothelial growth factor receptors (VEGFRs) (eg, ramucirumab). Ramucirumab, a VEGFR-2 inhibitor, is the first anti-angiogenic agent approved by the US Food and Drug Administration for use in the treatment of advanced gastric cancers. This review will focus on the clinical utility and potential use of ramucirumab in advanced gastric cancer. PMID:26451083

  2. Recent advances in lung cancer biology

    SciTech Connect

    Lechner, J.

    1995-12-31

    This paper provides an overview of carcinogenesis, especially as related to lung cancers. Various growth factors and their mutated forms as oncogenes are discussed with respect to gene location and their role in the oncogenic process. Finally the data is related to lung cancer induction in uranium miners and exposure to radon.

  3. Prolonged Subcutaneous Administration of 852A, a Novel Systemic Toll-like Receptor 7 Agonist, to Activate Innate Immune Responses in Patients with Advanced Hematologic Malignancies

    PubMed Central

    Weigel, Brenda J.; Cooley, Sarah; DeFor, Todd; Weisdorf, Daniel J.; Panoskaltsis-Mortari, Angela; Chen, Wei; Blazar, Bruce R.; Miller, Jeffrey S.

    2013-01-01

    The toll-like receptor (TLR) 7 agonist 852A, a small-molecule imidazoquinoline, stimulates plasmacytoid dendritic cells to produce multiple cytokines. We conducted a Phase II study of 852A in patients with recurrent hematologic malignancies. The primary objective was assessing the activity of 852A administered subcutaneously twice weekly for 12 weeks. Secondary objectives were assessing the safety of 852A and its ability to activate the immune system with prolonged dosing. Methods Patients with relapsed hematologic malignancies of any age with adequate organ function were eligible. Patients initiated dosing at 0.6 mg/m2 twice weekly and escalated by 0.2 mg/m2 after every 2 doses as tolerated to a target dose of 1.2 mg/m2. Patients with responses or stable disease were eligible for additional cycles. Results Seventeen patients (15 males) entered the study: 6 with AML, 5 ALL, 4 NHL, 1 Hodgkin’s lymphoma, and 1 multiple myeloma. The mean age was 41 years (12–71 years). The median number of prior chemotherapy regimens was 5 (range=1–14). Thirteen patients completed all 24 injections. Grade 3–4 toxicities included nausea, dyspnea, fever, myalgia, malaise, and cough. Responses included 1 complete response (ALL), 1 partial response (AML), 2 stable disease (AML and NHL), and 9 progressive disease. Conclusions This is the first in-human hematologic malignancy trial of a subcutaneously (SC) delivered TLR7 agonist using a prolonged dosing schedule. 852A was safely administered up to 1.2 mg/m2 twice weekly with evidence of sustained tolerability and clinical activity in hematologic malignancies. Systemic TLR agonists for the treatment of hematologic malignancies warrant further study. PMID:22718533

  4. Current advances in T-cell-based cancer immunotherapy

    PubMed Central

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

    2015-01-01

    Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy. PMID:25524383

  5. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer.

    PubMed

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40-60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. PMID:26504848

  6. The adverse effects of sorafenib in patients with advanced cancers.

    PubMed

    Li, Ye; Gao, Zu-Hua; Qu, Xian-Jun

    2015-03-01

    Sorafenib is the first multi-kinase inhibitor (TKI) approved for the treatment of advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC) and is increasingly being used to treat patients with well-differentiated radioiodine-resistant thyroid cancer (DTC). Sorafenib demonstrates targeted activity on several families of receptor and non-receptor tyrosine kinases that are involved in angiogenesis, tumour growth and metastatic progression of cancer. Sorafenib treatment results in long-term efficacy and low incidence of life-threatening toxicities. Although sorafenib has demonstrated many benefits in patients, the adverse effects cannot be ignored. The most common treatment-related toxicities include diarrhoea, fatigue, hand-foot skin reaction and hypertension. Most of these toxicities are considered mild to moderate and manageable to varying degrees; however, cardiovascular events might lead to death. In this MiniReview, we summarize the adverse effects of sorafenib that commonly occur in patients with advanced cancers. PMID:25495944

  7. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

    PubMed Central

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40–60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. PMID:26504848

  8. Conceptualizing prognostic awareness in advanced cancer: A systematic review

    PubMed Central

    Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

    2015-01-01

    This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients’ understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness. PMID:24157936

  9. [Treatment strategies for advanced prostate cancer].

    PubMed

    Küronya, Zsófia; Bíró, Krisztina; Géczi, Lajos; Németh, Hajnalka

    2015-09-01

    There has been dramatic improvement in the diagnosis and treatment of prostate cancer recently. The treatment of localized disease became more successful with the application of new, sophisticated techniques available for urologic surgeons and radiotherapists. Nevertheless a significant proportion of patients relapses after the initial local treatment or is diagnosed with metastatic disease at the beginning. In the past five years, six new drugs became registered for the treatment of metastatic, castration-resistant prostate cancer, such as sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, the α-emitting radionuclide alpharadin and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab. The availability of these new treatment options raises numerous questions. In this review we present the standard of care of metastatic prostate cancer by disease stage (hormone naive/ hormone sensitive metastatic prostate cancer, non-metastatic castration-resistant prostate cancer, oligometastatic/multimetastatic castration-resistant prostate cancer) and the emerging treatment modalities presently assessed in clinical trials. We would also like to give advice on debatable aspects of the management of metastatic prostate cancer. PMID:26339912

  10. Hematologic Disorders: Anemia.

    PubMed

    Baltierra, David; Harper, Tiffany; Jones, Matthew Page; Nau, Konrad C

    2015-06-01

    Anemia occurs in up to 25% of the US population. Normal hemoglobin levels vary by race, sex, and age. Classification of anemia by mean corpuscular volume guides the differential diagnosis and evaluation. Iron studies, reticulocyte count, the red blood cell distribution width index, and blood test results are used to make the diagnosis. Iron deficiency anemia is the most common microcytic anemia and is managed with iron therapy. Parenteral iron is available when the oral route cannot be used. Patients who do not benefit from therapy should be evaluated for adherence, malabsorption, occult bleeding, systemic disease, or less common inherited disorders. A source of gastrointestinal bleeding is found in 60% to 70% of patients with iron deficiency anemia who are referred for endoscopy. Normocytic anemia has a broad differential, including nutritional deficiencies, blood loss, renal disease, malignancy (solid tumors or hematologic cancer), rheumatologic disorders, endocrine disorders, and other systemic diseases. Macrocytic anemias are seen with vitamin B12 and folate deficiency, alcohol use, thyroid disease, hydroxyurea, antiretroviral drugs, myelodysplastic syndromes, and myeloma. Oral vitamin B12 is underused, and can be as effective as intramuscular vitamin B12 in managing anemia due to vitamin B12 deficiency. PMID:26080453

  11. Lapatinib in Treating Patients With Locally Advanced or Metastatic Biliary Tract or Liver Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-12-18

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  12. [Induction chemotherapy for locally advanced cervical cancer].

    PubMed

    Morkhov, K Yu; Nechushkina, V M; Kuznetsov, V V

    2015-01-01

    The main methods of treatment for cervical cancer are surgery, radiotherapy or their combination. During past two decades chemotherapy are increasingly being used not only in patients with disseminated forms of this disease but also in patients undergoing chemoradiotherapy or as induction therapy. Possibilities of adjuvant chemotherapy for cervical cancer are being studied. According to A.D.Kaprin and V.V. Starinskiy in 2013 in Russia, 32% of patients with newly diagnosed cervical cancer underwent only radiation therapy, 32%--combined or complex treatment, 27.3%--only surgery, and just 8.7%--chemoradiotherapy. PMID:26087600

  13. Cancer Cachexia, Recent Advances, and Future Directions

    PubMed Central

    Penet, Marie-France; Bhujwalla, Zaver M.

    2016-01-01

    Cancer cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass with or without loss of fat mass. The syndrome cannot be fully reversed by conventional nutritional support, and despite an increased number of studies related to cancer cachexia, the underlying mechanisms are still poorly defined and therapeutic options are limited. This review focuses on recent studies investigating mechanisms and pathways in cancer cachexia. The role of molecular and functional imaging in identifying cachexia at an earlier stage, in identifying potential metabolic targets and pathways, and in assessing treatment efficacy is also reviewed. PMID:25815852

  14. [Incidence and Risk Assessment of Tumor Lysis Syndrome in Patients with Advanced Germ Cell Cancer].

    PubMed

    Kurobe, Masahiro; Kawai, Koji; Tanaka, Ken; Ichioka, Daishi; Yoshino, Takayuki; Kandori, Shuya; Kawahara, Takashi; Waku, Natsui; Takaoka, Ei-Ichirou; Kojima, Takahiro; Joraku, Akira; Suetomi, Takahiro; Miyazaki, Jun; Nishiyama, Hiroyuki

    2016-05-01

    Tumor lysis syndrome (TLS) is a major oncological emergency. TLS is common in patients with hematological malignancies, but it can occur across a spectrum of cancer types. Germ cell tumors (GCT) have rapid cancer cell turnover and often present with bulky metastasis. The international TLS expert consensus panel has recommended guidelines for a medical decision tree to assign low, intermediate and high risk to patients with cancer at risk for TLS. GCT is classified as intermediate risk for TLS, and the patients who have other TLS risks factors are classified to be at high risk for TLS. In this study, we retrospectively analyzed 67 patients with metastatic GCT who were treated with induction chemotherapy at Tsukuba University Hospital between 2000 and 2013. Thirty-one, 15 and 21 patients were classified with good-, intermediate- and poor-prognosis disease, respectively, according to the International Germ Cell Cancer Collaborative Group criteria. Twelve patients (18%) were classified to be at high risk for TLS, and two patients were treated with allopurinol or rasburicase as prophylaxes for TLS. They did not show progression to laboratory TLS (L-TLS). In the remaining 10 TLS high-risk patients, three (30%) patients developed L-TLS after chemotherapy and started receiving oral allopurinol. As a result, no patients developed clinical TLS (C-TLS). In this study, 30% of TLS-high risk patients developed L-TLS without prophylactic treatment. Therefore, it is important to conduct TLS-risk stratification and consider prophylaxis such as rasburicase for advanced GCT patients at induction chemotherapy. PMID:27320114

  15. Can advanced-stage ovarian cancer be cured?

    PubMed

    Narod, Steven

    2016-04-01

    Approximately 20% of women with advanced-stage ovarian cancer survive beyond 12 years after treatment and are effectively cured. Initial therapy for ovarian cancer comprises surgery and chemotherapy, and is given with the goal of eradicating as many cancer cells as possible. Indeed, the three phases of therapy are as follows: debulking surgery to remove as much of the cancer as possible, preferably to a state of no visible residual disease; chemotherapy to eradicate any microscopic disease that remains present after surgery; and second-line or maintenance therapy, which is given to delay disease progression among patients with tumour recurrence. If no cancer cells remain after initial therapy is completed, a cure is expected. By contrast, if residual cancer cells are present after initial treatment, then disease recurrence is likely. Thus, the probability of cure is contingent on the combination of surgery and chemotherapy effectively eliminating all cancer cells. In this Perspectives article, I present the case that the probability of achieving a cancer-free state is maximized through a combination of maximal debulking surgery and intraperitoneal chemotherapy. I discuss the evidence indicating that by taking this approach, cures could be achieved in up to 50% of women with advanced-stage ovarian cancer. PMID:26787282

  16. Radium-223 for Advanced Prostate Cancer

    Cancer.gov

    A summary of results from a phase III trial that compared radium-223 dichloride plus the best standard of care versus a placebo plus the best standard of care in men with metastatic, castration-resistant prostate cancer.

  17. Olaparib Targets Some Advanced Prostate Cancers.

    PubMed

    2016-01-01

    In the phase II TOPARP-A clinical trial, patients with metastatic castrate-resistant prostate cancer who were treated with the PARP inhibitor olaparib lived nearly three times longer without their cancer worsening if their tumors had mutations in at least one of 12 DNA repair genes. However, physicians say that a larger trial is needed to confirm olaparib's effectiveness against the disease before they start routinely sequencing tumors and prescribing the drug. PMID:26658963

  18. Neoadjuvant chemotherapy in advanced epithelial ovarian cancer: A survival study

    PubMed Central

    Baruah, Upasana; Barmon, Debabrata; Kataki, Amal Chandra; Deka, Pankaj; Hazarika, Munlima; Saikia, Bhargab J.

    2015-01-01

    Context: Patients with advanced ovarian cancer have a poor prognosis in spite of the best possible care. Primary debulking surgery has been the standard of care in advanced ovarian cancer; however, it is associated with high mortality and morbidity rates as shown in various studies. Several studies have discussed the benefit of neoadjuvant chemotherapy in patients with advanced ovarian cancer. Aims: This study aims to evaluate the survival statistics of the patients who have been managed with interval debulking surgery (IDS) from January 2007 to December 2009. Materials and Methods: During the period from January 2007 to December 2009, a retrospective analysis of 104 patients who underwent IDS for stage IIIC or IV advanced epithelial ovarian cancer at our institute were selected for the study. IDS was attempted after three to five courses of chemotherapy with paclitaxal (175 mg/m2 ) and carboplatin (5-6 of area under curve). Overall survival (OS) and progression free survival (PFS) were compared with results of primary debulking study from existing literature. OS and PFS rates were estimated by means of the Kaplan-Meier method. Results were statistically analyzed by IBM SPSS Statistics 19. Results: The median OS was 26 months and the median PFS was 18 months. In multivariate analysis it was found that both OS and PFS was affected by the stage, and extent of debulking. Conclusions: Neoadjuvant chemotherapy, followed by surgical cytoreduction is a promising treatment strategy for the management of advanced epithelial ovarian cancers. PMID:25810573

  19. Surgical adjuvant treatment of locally advanced breast cancer.

    PubMed Central

    Townsend, C M; Abston, S; Fish, J C

    1985-01-01

    The reported incidence of local recurrence after mastectomy for locally advanced breast cancer (TNM Stage III and IV) is between 30% and 50%. The purpose of this study was to evaluate the effect of radiation therapy (XRT) followed by total mastectomy on the incidence of local recurrence in patients with locally advanced breast cancer. Fifty-three patients who presented with locally advanced breast cancer, without distant metastases, were treated with XRT (4500-5000 R) to the breast, chest wall, and regional lymph nodes. Five weeks after completion of XRT, total mastectomy was performed. There were no operative deaths. The complications that occurred in 22 patients after surgery were flap necrosis, wound infection, and seroma. Patients have been followed from 3 to 134 months. Twenty-five patients are alive (3-134 months), 12 free of disease; 28 patients have died with distant metastases (6-67 months). Isolated local recurrence occurred in only two patients. Four patients had local and distant recurrence (total local recurrence is 6/53). The remaining patients all developed distant metastases. We have devised a treatment strategy which significantly decreases the incidence of local recurrence in patients with locally advanced breast cancer. However, the rapid appearance of distant metastases emphasizes the need for systemically active therapy in patients with locally advanced breast cancer. PMID:3994434

  20. Advanced gastric cancer: Current treatment landscape and future perspectives

    PubMed Central

    Digklia, Antonia; Wagner, Anna Dorothea

    2016-01-01

    Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease (locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2 (HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer. PMID:26937129

  1. Myofacial Trigger Points in Advanced Cancer Patients

    PubMed Central

    Hasuo, Hideaki; Ishihara, Tatsuhiko; Kanbara, Kenji; Fukunaga, Mikihiko

    2016-01-01

    Myofascial pain syndrome is started to be recognized as one of important factors of pain in cancer patients. However, no reports on features of myofascial trigger points were found in terminally-ill cancer populations. This time, we encountered 5 patients with myofascial pain syndrome and terminal cancer in whom delirium developed due to increased doses of opioid without a diagnosis of myofascial pain syndrome on initial presentation. The delirium subsided with dose reductions of opioid and treatment of myofascial pain syndrome. The common reason for a delayed diagnosis among the patients included an incomplete palpation of the painful sites, which led to unsuccessful myofascial trigger points identification. The features of myofascial trigger points included single onset in the cancer pain management site with opioid and the contralateral abdominal side muscles of the non-common sites. Withdrawal reflexes associated with cancer pain in the supine position, which are increasingly seen in the terminal cancer patients, were considered to have contributed to this siuation. We consider that careful palpation of the painful site is important, in order to obtain greater knowledge and understanding of the features of myofascial trigger points. PMID:26962285

  2. Intelligent Nanoparticles for Advanced Drug Delivery in Cancer Treatment

    PubMed Central

    Spencer, David S.; Puranik, Amey S.; Peppas, Nicholas A.

    2015-01-01

    Treatment of cancer using nanoparticle-based approaches relies on the rational design of carriers with respect to size, charge, and surface properties. Polymer-based nanomaterials, inorganic materials such as gold, iron oxide, and silica as well as carbon based materials such as carbon nanotubes and graphene are being explored extensively for cancer therapy. The challenges associated with the delivery of these nanoparticles depend greatly on the type of cancer and stage of development. This review highlights design considerations to develop nanoparticle-based approaches for overcoming physiological hurdles in cancer treatment, as well as emerging research in engineering advanced delivery systems for the treatment of primary, metastatic, and multidrug resistant cancers. A growing understanding of cancer biology will continue to foster development of intelligent nanoparticle-based therapeutics that take into account diverse physiological contexts of changing disease states to improve treatment outcomes. PMID:25621200

  3. [Ethics and palliative care in patients with advanced cancer].

    PubMed

    Tenorio-González, Francisco

    2005-01-01

    Recent research in both the biology of cancer and the treatment of patients has increased the life expectancy of cancer patients with recurrence and who have a longer survival rate. Cancer is no longer considered a lethal but a chronic disease. More patients survive, but above all there are more patients with recurrences thus increasing the need for physical or psychological treatment of patients with longer lives. The American Cancer Society reported in 1992 that in the U.S. more than 8 million people survived between 4 and 5 years. This produces both an ethical and medical challenge for treatment of cancer patients. This paper reviews the actual criteria for palliative care: treatment for pain and the ethical and psychological treatment of advanced cancer patients and their families. PMID:16454965

  4. A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies.

    PubMed

    Graux, Carlos; Sonet, Anne; Maertens, Johan; Duyster, Justus; Greiner, Jochen; Chalandon, Yves; Martinelli, Giovanni; Hess, Dagmar; Heim, Dominik; Giles, Francis J; Kelly, Kevin R; Gianella-Borradori, Athos; Longerey, Blandine; Asatiani, Ekaterine; Rejeb, Narmyn; Ottmann, Oliver G

    2013-09-01

    A phase I dose-escalation study of MSC1992371A, an oral aurora kinase inhibitor, was carried out in patients with hematologic malignancies. Patients received escalating doses either on days 1-3 and 8-10 (n=36) or on days 1-6 (n=39) of a 21-day cycle. The maximum tolerated doses were 37 and 28 mg/m(2)/day, respectively. Dose-limiting toxicities included severe neutropenia with infection and sepsis, mucositis/stomatitis, and diarrhea. Complete responses occurred in 3 patients. Four disease-specific expansion cohorts then received the dose and schedule dictated by the escalation phase but the study was prematurely discontinued due to hematologic and gastrointestinal toxicity at clinically effective doses. PMID:23746966

  5. Photodynamic Cancer Therapy—Recent Advances

    NASA Astrophysics Data System (ADS)

    Abrahamse, Heidi

    2011-09-01

    The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when "photoradiation therapy" was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first or second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular

  6. Major clinical research advances in gynecologic cancer in 2014

    PubMed Central

    Lee, Kyung-Hun; Kim, Kidong; Kang, Sokbom

    2015-01-01

    In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review. PMID:25872896

  7. Advanced Imaging Among Health Maintenance Organization Enrollees With Cancer

    PubMed Central

    Loggers, Elizabeth T.; Fishman, Paul A.; Peterson, Do; O'Keeffe-Rosetti, Maureen; Greenberg, Caprice; Hornbrook, Mark C.; Kushi, Lawrence H.; Lowry, Sarah; Ramaprasan, Arvind; Wagner, Edward H.; Weeks, Jane C.; Ritzwoller, Debra P.

    2014-01-01

    Purpose: Fee-for-service (FFS) Medicare expenditures for advanced imaging studies (defined as computed tomography [CT], magnetic resonance imaging [MRI], positron emission tomography [PET] scans, and nuclear medicine studies [NM]) rapidly increased in the past two decades for patients with cancer. Imaging rates are unknown for patients with cancer, whether under or over age 65 years, in health maintenance organizations (HMOs), where incentives may differ. Materials and Methods: Incident cases of breast, colorectal, lung, prostate, leukemia, and non-Hodgkin lymphoma (NHL) cancers diagnosed in 2003 and 2006 from four HMOs in the Cancer Research Network were used to determine 2-year overall mean imaging counts and average total imaging costs per HMO enrollee by cancer type for those under and over age 65. Results: There were 44,446 incident cancer patient cases, with a median age of 75 (interquartile range, 71-81), and 454,029 imaging procedures were performed. The mean number of images per patient increased from 7.4 in 2003 to 12.9 in 2006. Rates of imaging were similar across age groups, with the exception of greater use of echocardiograms and NM studies in younger patients with breast cancer and greater use of PET among younger patients with lung cancer. Advanced imaging accounted for approximately 41% of all imaging, or approximately 85% of the $8.7 million in imaging expenditures. Costs were nearly $2,000 per HMO enrollee; costs for younger patients with NHL, leukemia, and lung cancer were nearly $1,000 more in 2003. Conclusion: Rates of advanced imaging appear comparable among FFS and HMO participants of any age with these six cancers. PMID:24844241

  8. Colorectal cancer development and advances in screening.

    PubMed

    Simon, Karen

    2016-01-01

    Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known benefits of early screening, CRC remains the second leading cause of cancer-related deaths in the United States. Hence, it is important for health care providers to have an understanding of the risk factors for CRC and various stages of disease development in order to recommend appropriate screening strategies. This article provides an overview of the histological/molecular changes that characterize the development of CRC. It describes the available CRC screening methods and their advantages and limitations and highlights the stages of CRC development in which each screening method is most effective. PMID:27486317

  9. Colorectal cancer development and advances in screening

    PubMed Central

    Simon, Karen

    2016-01-01

    Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known benefits of early screening, CRC remains the second leading cause of cancer-related deaths in the United States. Hence, it is important for health care providers to have an understanding of the risk factors for CRC and various stages of disease development in order to recommend appropriate screening strategies. This article provides an overview of the histological/molecular changes that characterize the development of CRC. It describes the available CRC screening methods and their advantages and limitations and highlights the stages of CRC development in which each screening method is most effective. PMID:27486317

  10. Advances in immunotherapy for non-small cell lung cancer.

    PubMed

    Reckamp, Karen L

    2015-12-01

    In most patients, lung cancer presents as advanced disease with metastases to lymph nodes and/or distant organs, and survival is poor. Lung cancer is also a highly immune-suppressing malignancy with numerous methods to evade antitumor immune responses, including deficiencies in antigen processing and presentation, release of immunomodulatory cytokines, and inhibition of T-cell activation. Advances in understanding the complex interactions of the immune system and cancer have led to novel therapies that promote T-cell activation at the tumor site, resulting in prolonged clinical benefit. Immune checkpoint inhibitors, specifically programmed death receptor 1 pathway antibodies, have demonstrated impressively durable responses and improved survival in patients with non-small cell lung cancer. This article will review the recent progress made in immunotherapy for lung cancer with data from trials evaluating programmed death receptor 1 and cytotoxic T-lymphocyte-associated protein 4 monoclonal antibodies in addition to cancer vaccines. The review will focus on studies that have been published and the latest randomized trials exploring immune therapy in lung cancer. These results form the framework for a new direction in the treatment of lung cancer toward immunotherapy. PMID:27058851

  11. [A Case of Locally Advanced Gastric Cancer after Neoadjuvant Chemotherapy].

    PubMed

    Okamoto, Tatsuya; Tanaka, Keita; Yonemitsu, Kimihiro; Munechika, Taro; Nomi, Masako; Maeno, Hiroshi; Nagao, Shuji; Kawamoto, Shunji; Sasaguri, Takakazu; Sueishi, Katsuo

    2015-11-01

    A 60s male was admitted to our hospital because of appetite loss and nausea. After examination, he was diagnosed with type 3 advanced gastric cancer in the antrum. Abdominal computed tomography showed gastric cancer invasion to the left liver lobe. We initiated neoadjuvant chemotherapy using S-1 plus CDDP after laparoscopic gastrojejunostomy. S-1 was orally administered for 3 weeks followed by a 2-week drug-free period. CDDP was administered intravenously on day 8 of each course. After 5 courses of chemotherapy, the gastric cancer was reduced in size. We therefore performed total gastrectomy with D2-affiliated left liver resection. S-1 plus CDDP is expected to improve outcomes in unresectable or locally advanced gastric cancer. PMID:26805257

  12. Advances in cancer research. Volume 41

    SciTech Connect

    Klein, G.; Weinhouse, S.

    1984-01-01

    This book contains seven chapters. They are: The Epidemiology of Diet and Cancer; Molecular Aspects of Immunoglobin Expression by Human B Cell Leukemias and Lymphomas; Mouse Mammary Tumor Virus: Transcriptional Control and Involvement in Tumorigenesis; Dominant Susceptibility to Cancer in Man; Multiple Myeloma; Waldenstreom's Macroglobulinemia, and Benign Monoclonal Gammopathy: Characteristics of the B Cell Clone, Immunoregulatory Cell Populations and Clinical Implications; Idiotype Network Interactions in Tumor Immunity; and Chromosomal Location of Immunoglobulin Genes: Partial Mapping of these Genes in the Rabbit and Comparison with Ig Genes Carrying Chromosomes of Man and Mouse.

  13. Advancement in treatment and diagnosis of pancreatic cancer with radiopharmaceuticals

    PubMed Central

    Xu, Yu-Ping; Yang, Min

    2016-01-01

    Pancreatic cancer (PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition, radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC. PMID:26909131

  14. Profile of olaparib in the treatment of advanced ovarian cancer

    PubMed Central

    Chase, Dana M; Patel, Shreya; Shields, Kristin

    2016-01-01

    Olaparib is a poly(ADP-ribose) polymerase inhibitor that received accelerated approval from the US Food and Drug Administration as monotherapy for patients with germline BRCA mutations and ovarian cancer treated with three or more prior lines of chemotherapy. This article summarizes the mechanism of poly(ADP-ribose) polymerase inhibition, therapeutic profile and uses of olaparib, and current and ongoing literature pertaining to olaparib in advanced ovarian cancer. PMID:27186080

  15. Intraarterial pelvic infusion chemotherapy in advanced gynecologic cancer.

    PubMed

    Lifshitz, S; Railsback, L D; Buchsbaum, H J

    1978-10-01

    Fourteen patients with advanced localized gynecologic cancer were treated with 44 courses of intraarterial pelvic infusion chemotherapy. All patients received methotrexate with folinic acid rescue; 9 patients also received vincristine. Tumor regression was observed in 3 of 14 patients (21.4%). In 5 patients there were major complications related to 28 intraarterial catheter placements. Two patients developed leukopenia following chemotherapy. The value of intraarterial infusion chemotherapy in gynecologic cancer is limited. Its use in gynecologic oncology is discussed. PMID:309571

  16. Immunotherapy and complexity: overcoming barriers to control of advanced cancer.

    PubMed

    Lage, Agustin

    2014-01-01

    Recent advances in fundamental immunology are changing paradigms for management of advanced cancer, now acknowledged as a chronic disease whose prevalence will increase, and one whose complexity makes it difficult to control. Immunotherapy is emerging as an alternative, with new monoclonal antibodies, therapeutic vaccines and deeper understanding of fundamental phenomena in the interaction between tumor and immune system. These novel insights concern mechanisms of programmed contraction of the immune response, characterization of molecular and cellular markers of immunosenescence, the dual role of inflammation, characterization of myeloid-derived suppressor cells and cancer stem cells, and the phenomena of immunogenic apoptosis and oncogene addiction. Additionally, new data drive a deeper understanding of four barriers to overcome in control of advanced cancer: the complexity of biological systems, tumor heterogeneity, tumor mutation rates, and human genome-environment mismatch. The new landscape points to six main strategies: manage advanced cancer as a chronic disease, find relevant molecular markers for patient stratification, develop a rationale for therapeutic combinations, target regulatory control loops in the immune system, expand mathematical modeling capacity, and evaluate complex health intervention packages in real-world conditions. These transitions in cancer immunotherapy research are illustrated in this paper through description of ongoing projects at Cuba's Molecular Immunology Center. PMID:25208123

  17. Combination anti-CD137 and anti-CD40 antibody therapy in murine myc-driven hematological cancers.

    PubMed

    Westwood, Jennifer A; Matthews, Geoffrey M; Shortt, Jake; Faulkner, David; Pegram, Hollie J; Duong, Connie P M; Chesi, Marta; Bergsagel, P Leif; Sharp, Leslie L; Huhn, Richard D; Darcy, Phillip K; Johnstone, Ricky W; Kershaw, Michael H

    2014-08-01

    In order to stimulate antigen presentation and T cell activity against cancer, we treated three different tumor models in mice with the monoclonal antibodies anti-CD40 plus anti-CD137 (BiMab). In a subcutaneous transplantable MC38 colon cancer model, there was significant enhancement in the survival of mice following BiMab treatment. Anti-CD40 has shown considerable success against lymphoma in previous studies by other investigators, and we also showed in this study that, in a model of Eμ-Myc lymphoma, there was a statistically significant enhancement of survival of mice following BiMab treatment. Following the success of the BiMab treatment in the previous two models, we wished to determine if it would be successful in a mouse model of multiple myeloma. Firstly, we tested a transplantable model of disease in which multiple myeloma cells derived from Vk*MYC mice were injected intravenously. A minor proportion of anti-CD137 and BiMab treated mice experienced prolongation of life beyond 250 days. Then we tested the therapy in a spontaneously occurring multiple myeloma model, in Vk*MYC transgenic mice. The majority of mice treated survived longer than control mice, although statistical significance was not demonstrated. PMID:24934848

  18. Integrative clinical genomics of advanced prostate cancer.

    PubMed

    Robinson, Dan; Van Allen, Eliezer M; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim; Bradley, Robert K; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P; Hussain, Maha; Feng, Felix Y; Tomlins, Scott A; Cooney, Kathleen A; Smith, David C; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E; Morris, Michael J; Solomon, Stephen B; Durack, Jeremy C; Reuter, Victor E; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T; Bowden, Michaela; Balk, Stephen P; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y; Mostaghel, Elahe A; Cheng, Heather H; Mulcahy, Hyojeong; True, Lawrence D; Plymate, Stephen R; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Perez-Lopez, Raquel; Demichelis, Francesca; Robinson, Brian D; Schiffman, Marc; Nanus, David M; Tagawa, Scott T; Sigaras, Alexandros; Eng, Kenneth W; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I; Scher, Howard I; Pienta, Kenneth J; Kantoff, Philip; de Bono, Johann S; Rubin, Mark A; Nelson, Peter S; Garraway, Levi A; Sawyers, Charles L; Chinnaiyan, Arul M

    2015-05-21

    Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals. PMID:26000489

  19. Advances in cancer research. Volume 48

    SciTech Connect

    Klein, G.; Weinhouse, S.

    1987-01-01

    This book contains the following five selections: Oncotrophoblast Gene Expression: Placental Alkaline Phosphatase; Cellular Events during Hepatocarcinogenesis in Rats and the Questions of Premalignancy; Human Papillomaviruses and Genital Cancer; Herpes Simplex Type 2 Virus and Cervical Neoplasia; and Transforming Genes and Target Cells of Murine Spleen Focus-Forming Viruses.

  20. Integrative clinical genomics of advanced prostate cancer

    PubMed Central

    Dan, Robinson; Van Allen, Eliezer M.; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J.; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim M.; Bradley, Robert K.; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P.; Hussain, Maha; Feng, Felix Y.; Tomlins, Scott A.; Cooney, Kathleen A.; Smith, David C.; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E.; Morris, Michael J.; Solomon, Stephen B.; Durack, Jeremy C.; Reuter, Victor E.; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T.; Bowden, Michaela; Balk, Stephen P.; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y.; Mostaghel, Elahe A.; Cheng, Heather H.; Mulcahy, Hyojeong; True, Lawrence D.; Plymate, Stephen R.; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Lopez, Raquel Perez; Demichelis, Francesca; Robinson, Brian D.; Schiffman, Marc A.; Nanus, David M.; Tagawa, Scott T.; Sigaras, Alexandros; Eng, Kenneth W.; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I.; Scher, Howard I.; Pienta, Kenneth J.; Kantoff, Philip; de Bono, Johann S.; Rubin, Mark A.; Nelson, Peter S.; Garraway, Levi A.; Sawyers, Charles L.; Chinnaiyan, Arul M.

    2015-01-01

    SUMMARY Toward development of a precision medicine framework for metastatic, castration resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53 and PTEN were frequent (40–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified novel genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin and ZBTB16/PLZF. Aberrations of BRCA2, BRCA1 and ATM were observed at substantially higher frequencies (19.3% overall) than seen in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides evidence that clinical sequencing in mCRPC is feasible and could impact treatment decisions in significant numbers of affected individuals. PMID:26000489

  1. Advances in cancer research: Volume 47

    SciTech Connect

    Klein, G.; Weinhouse, S.

    1986-01-01

    This book contains eight chapters. Some of the titles are: Genetic Epidemiology of Familial Aggregation of Cancer; Terminal Transferase in Normal and Leukemic Cells; Malignant Metamorphosis: Developmental Genes as Culprits for Oncogenesis in Xiphophorus; and Transcription Activation by Viral and Cellular Oncogenes.

  2. American Society of Hematology

    MedlinePlus

    Main Navigation Account Navigation Main Content American Society of Hematology ASH Store ASH Job Center ASH Apps Share Your Idea Donate My Account Search Show Main Menu + About Awards Membership ASH ...

  3. Microarrays in hematology.

    PubMed

    Walker, Josef; Flower, Darren; Rigley, Kevin

    2002-01-01

    Microarrays are fast becoming routine tools for the high-throughput analysis of gene expression in a wide range of biologic systems, including hematology. Although a number of approaches can be taken when implementing microarray-based studies, all are capable of providing important insights into biologic function. Although some technical issues have not been resolved, microarrays will continue to make a significant impact on hematologically important research. PMID:11753074

  4. Ixabepilone and Liposomal Doxorubicin in Advanced Ovarian Cancer

    ClinicalTrials.gov

    2016-02-11

    Fallopian Tube Cancer; Female Reproductive Cancer; Recurrent Breast Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer

  5. Early Gastric Cancer: Current Advances of Endoscopic Diagnosis and Treatment.

    PubMed

    Zhu, Linlin; Qin, Jinyu; Wang, Jin; Guo, Tianjiao; Wang, Zijing; Yang, Jinlin

    2016-01-01

    Endoscopy is a major method for early gastric cancer screening because of its high detection rate, but its diagnostic accuracy depends heavily on the availability of endoscopic instruments. Many novel endoscopic techniques have been shown to increase the diagnostic yield of early gastric cancer. With the improved detection rate of EGC, the endoscopic treatment has become widespread due to advances in the instruments available and endoscopist's experience. The aim of this review is to summarize frequently-used endoscopic diagnosis and treatment in early gastric cancer (EGC). PMID:26884753

  6. Early Gastric Cancer: Current Advances of Endoscopic Diagnosis and Treatment

    PubMed Central

    Zhu, Linlin; Qin, Jinyu; Wang, Jin; Guo, Tianjiao; Wang, Zijing; Yang, Jinlin

    2016-01-01

    Endoscopy is a major method for early gastric cancer screening because of its high detection rate, but its diagnostic accuracy depends heavily on the availability of endoscopic instruments. Many novel endoscopic techniques have been shown to increase the diagnostic yield of early gastric cancer. With the improved detection rate of EGC, the endoscopic treatment has become widespread due to advances in the instruments available and endoscopist's experience. The aim of this review is to summarize frequently-used endoscopic diagnosis and treatment in early gastric cancer (EGC). PMID:26884753

  7. Recent advances in the field of anti-cancer immunotherapy

    PubMed Central

    Neves, Henrique; Kwok, Hang Fai

    2015-01-01

    Background The main goal of anti-cancer therapy is to specifically inhibit the malignant activity of cancer cells, while leaving healthy cells unaffected. As such, for every proposed therapy, it is important to keep in mind the therapeutic index — the ratio of the toxic dose over the therapeutic dose. The use of immunotherapy has allowed a means to both specifically block protein–protein interaction and deliver cytotoxic events to a tumor-specific antigen. Review scope It is the objective of this review to give an overview on current immunotherapy treatment for cancers using monoclonal antibodies. We demonstrate three exciting targets for immunotherapy, TNF-α Converting Enzyme (TACE), Cathepsin S and Urokinase Plasmogen Activator and go over the advances made with one of the most used monoclonal antibodies in cancer therapy, Rituximab; as well as Herceptin, which is used for breast cancer therapy. Furthermore, we touch on other venues of immunotherapy, such as adaptive cell transfer, the use of nucleic acids and the use of dendritic cells. Finally, we summarize some ongoing studies that spell tentative advancements for anti-cancer immunotherapy. General significance Immunotherapy is at the forefront of anti-cancer therapies, allying both a high degree of specificity to general high effectiveness and fewer side-effects. PMID:26673349

  8. Fear of recurrence and its impact on quality of life in patients with hematological cancers in the course of allogeneic hematopoietic SCT.

    PubMed

    Sarkar, S; Scherwath, A; Schirmer, L; Schulz-Kindermann, F; Neumann, K; Kruse, M; Dinkel, A; Kunze, S; Balck, F; Kröger, N; Koch, U; Mehnert, A

    2014-09-01

    We examined the course and the prevalence of a high fear of cancer recurrence (FCR) in patients undergoing allogeneic PBSC transplantation (hematopoietic SCT (HSCT)) before HSCT (N=239), 100 days after (n=150, and 12 months after allogeneic HSCT (n=102). The Fear of Progression Questionnaire-Short Form (FoP-Q-SF), the EORTC Quality of Life Questionnaire, and the Hospital Anxiety and Depression Scale were used. Pre-HSCT 36% of patients, 100 days after HSCT 24% of patients, and 1 year after HSCT 23% of patients fulfilled the criteria for high FCR (FoP-Q-SF cutoff=34). Being married (b=2.76, P=0.026), female gender (b=4.45, P<0.001) and depression (b=4.44, P<0.001) were significantly associated with FCR at baseline. One hundred days after HSCT, depression significantly predicted FCR (b=6.46, P<0.001). One year following HSCT, female gender (b=6.61, P=0.008) and higher depression were (b=4.88, P=0.004) significant predictors for FCR. Over the three assessment points, patients with high FCR had a significantly lower quality of life compared to patients with low FCR in physical functioning (P=0.019), role functioning (P=0.003), emotional functioning (P<0.001), cognitive functioning (P=0.003), social functioning (P<0.001) and global quality of life (P<0.001). Our data provide evidence that FCR is a prevalent problem in patients with hematological malignancies and has a significant adverse impact on health-related quality of life. PMID:25000458

  9. [Recent advances in diagnosis of prostate cancer].

    PubMed

    Hara, Isao

    2016-01-01

    Most valuable tool for diagnosis of prostate cancer is PSA. Although PSA is highly specific for organ, it is not so specific for disease. Therefore, about 70% of patients whose PSA value is 4-10 ng/mL are forced to undergo unnecessary prostate biopsy. In order to discriminate the unnecessary biopsies, several markers such as free/total PSA ratio, PSA density, and PSA velocity have been developed. However, none of these markers were widely approved in daily clinical settings. Prostate cancer antigen 3 (PCA3) is thought to be a useful marker for necessity of repeat biopsy. Functional MR imaging such as dynamic contrast enhancement (DCE), diffusion weighted imaging(DWI), MR spectroscopy (MRS) have been developed. Recently MRI-TRUS fusion biopsy is gathering attention. In terms of pathology, atypical glands but not high grade PIN require repeat biopsy after 3 to 6 months from initial biopsy. PMID:26793874

  10. Advances in the understanding of cancer immunotherapy.

    PubMed

    Shore, Neal D

    2015-09-01

    The principal role of the immune system is to prevent and eradicate pathogens and infections. The key characteristics or features of an effective immune response include specificity, trafficking, antigen spread and durability (memory). The immune system is recognised to have a critical role in controlling cancer through a dynamic relationship with tumour cells. Normally, at the early stages of tumour development, the immune system is capable of eliminating tumour cells or keeping tumour growth abated; however, tumour cells may evolve multiple pathways over time to evade immune control. Immunotherapy may be viewed as a treatment designed to boost or restore the ability of the immune system to fight cancer, infections and other diseases. Immunotherapy manifests differently from traditional cancer treatments, eliciting delayed response kinetics and thus may be more effective in patients with lower tumour burden, in whom disease progression may be less rapid, thereby allowing ample time for the immunotherapy to evolve. Because immunotherapies may have a different mechanism of action from traditional cytotoxic or targeted biological agents, immunotherapy techniques have the potential to combine synergistically with traditional therapies. PMID:24612369

  11. Hormonal therapy in advanced or recurrent endometrial cancer

    PubMed Central

    Kokka, Fani; Brockbank, Elly; Oram, David; Gallagher, Chris; Bryant, Andrew

    2014-01-01

    Background Endometrial cancer is a cancer of the lining of the womb and worldwide is the seventh most common cancer in women. Treatment with hormones is thought to be beneficial in patients with endometrial cancer. Objectives To assess the indications, effectiveness and safety of hormone therapy for advanced or recurrent epithelial endometrial cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE up to May 2009 and and CENTRAL (Issue 2, 2009). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies, and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that studied hormonal therapy in adult women diagnosed with advanced or recurrent endometrial cancer. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Comparisons were restricted to single-trial analyses so we did not synthesise data in meta-analyses. Main results We found six trials (542 participants) that met our inclusion criteria. These trials assessed the effectiveness of hormonal therapy in women with advanced or recurrent endometrial cancer as a single agent, as part of combination therapy and as low versus high dose. All comparisons were restricted to single-trial analyses, where we found no evidence that hormonal therapy as a single agent or as a combination treatment prolonged overall or five-year disease-free survival of women with advanced or recurrent endometrial cancer. However, low-dose hormonal therapy may have had a benefit in terms of overall and progression-free survival (PFS) compared to high-dose hormonal therapy (HR 1.31, 95% CI 1.04 to 1.66 and HR 1.35, 95% CI 1.07 to 1.71 for overall and PFS, respectively). Authors’ conclusions We found insufficient evidence that hormonal treatment in any form, dose or as part of combination therapy improves the survival of patients with advanced or

  12. Radical Prostatectomy for Locally Advanced Prostate Cancer: Current Status.

    PubMed

    Faria, Eliney F; Chapin, Brian F; Muller, Roberto L; Machado, Roberto D; Reis, Rodolfo B; Matin, Surena F

    2015-07-01

    In the past, prostate cancer (PC) could only be detected clinically, and delayed diagnosis of locally advanced or metastatic disease at presentation was common. Prostate-specific antigen testing and magnetic resonance imaging led to PC detection in a much earlier stage. However, controversy about the best treatment for locally advanced PC remains. Recent refinements in surgery and radiation therapy have improved outcomes, but no comparative study has yet conclusively determined superiority of one option over the other. In this review, we present the most recent evidence about the role of radical prostatectomy for locally advanced PC treatment from a surgeon's perspective. PMID:26048432

  13. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.

    PubMed

    Pérez-Herrero, Edgar; Fernández-Medarde, Alberto

    2015-06-01

    Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vascularization and, in time, acquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastatic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, such as the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic drugs, as well as the development of multidrug resistance, support the need to find new effective targeted treatments based on the changes in the molecular biology of the tumor cells. These novel targeted therapies, of increasing interest as evidenced by FDA-approved targeted cancer drugs in recent years, block biologic transduction pathways and/or specific cancer proteins to induce the death of cancer cells by means of apoptosis and stimulation of the immune system, or specifically deliver chemotherapeutic agents to cancer cells, minimizing the undesirable side effects. Although targeted therapies can be achieved directly by altering specific cell signaling by means of monoclonal antibodies or small molecules inhibitors, this review focuses on indirect targeted approaches that

  14. Treatment of advanced medullary thyroid cancer.

    PubMed

    Smit, Johannes

    2013-03-14

    Therapy decisions in advanced medullary thyroid carcinoma should be guided by a critical appraisal of the natural disease course (slowly progressive vs. aggressive) and benefits and side effects of therapy. Therapy goals should be distinguished between curative and palliative. Local treatments are mainly palliative and may add to quality of life. The advent of novel systemic therapies opens promising perspectives but its place in the therapeutic arsenal must be further determined. PMID:23514632

  15. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2016-06-17

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

  16. Motolimod effectively drives immune activation in advanced cancer patients

    PubMed Central

    Dietsch, Gregory N.

    2016-01-01

    ABSTRACT A novel approach to immunotherapy is the activation of toll-like receptor 8 (TLR8). Motolimod, a selective TLR8 agonist can act in concert with approved immunotherapies to sensitize T cells and augment natural killer (NK) cell function. Despite treatment with chemotherapeutic agents and advance disease, cancer patients remain sensitive to motolimod.

  17. Advances take stage - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Regulatory advances in proteomics will be taking center stage at a Symposia scheduled to occur at the 2011 American Association for Clinical Chemistry (AACC) Annual Meeting. The symposium entitled "Enabling Translational Proteomics with NCI's Clinical Proteomic Technologies for Cancer" is scheduled for July 25, 2011 at AACC's annual Meeting.

  18. Recent Advances and Prospects for Multimodality Therapy in Pancreatic Cancer.

    PubMed

    Chadha, Awalpreet S; Khoo, Allison; Aliru, Maureen L; Arora, Harpreet K; Gunther, Jillian R; Krishnan, Sunil

    2016-10-01

    The outcomes for treatment of pancreatic cancer have not improved dramatically in many decades. However, the recent promising results with combination chemotherapy regimens for metastatic disease increase optimism for future treatments. With greater control of overt or occult metastatic disease, there will likely be an expanding role for local treatment modalities, especially given that nearly a third of pancreatic cancer patients have locally destructive disease without distant metastatic disease at the time of death. Technical advances have allowed for the safe delivery of dose-escalated radiation therapy, which can then be combined with chemotherapy, targeted agents, immunotherapy, and nanoparticulate drug delivery techniques to produce novel and improved synergistic effects. Here we discuss recent advances and future directions for multimodality therapy in pancreatic cancer. PMID:27619253

  19. Annual Advances in Cancer Prevention Lecture | Division of Cancer Prevention

    Cancer.gov

    2016 Keynote Lecture Polyvalent Vaccines Targeting Oncogenic Driver Pathways A special keynote lecture became part of the NCI Summer Curriculum in Cancer Prevention in 2000. This lecture will be held on Thursday, July 21, 2016 at 1:30pm at Masur Auditorium, Building 10, NIH Main Campus, Bethesda, MD. This year’s keynote speaker is Dr. Mary L. (Nora) Disis, MD. |

  20. Annual Advances in Cancer Prevention Lecture | Division of Cancer Prevention

    Cancer.gov

    2015 Keynote Lecture HPV Vaccination: Preventing More with Less A special keynote lecture became part of the NCI summer Curriculum in Cancer Prevention in 2000. This lecture will be held on Thursday, July 23, 2015 at 3:00pm at Masur Auditorium, Building 10, NIH Main Campus, Bethesda, MD. This year’s keynote speaker is Dr. Douglas Lowy, NCI Acting Director. |

  1. [Treatment strategy for advanced prostate cancer with bone metastases].

    PubMed

    Sugimoto, Mikio; Kakehi, Yoshiyuki

    2006-08-01

    The introduction of PSA screening has led to confirming a shift towards an earlier pathological stage in the diagnosis of prostate cancer. Consequently, the proportion of detecting early stage prostate cancer has clearly been increasing. On the other hand, progressive cancers in the form of distant metastases and locally advanced ones that have been confirmed at the initial diagnosis exhibit a constant rate. In addition, there have been a lot of cases where hormonal resistance was acquired during hormonal therapy which resulted in advanced metastases of the prostate. Prostate cancer has a tendency to be metastatic to bones. Combining the fact that the survival period of patients undergoing treatment is prolonged after metastases, the length of suffering caused by complications, such as ostealgia, pathological fracture and myelopathy, becomes an issue in which QOL and ADL of the patient are sacrificed for a long time. As for treatment of prostate cancer with metastases, a palliative treatment is common in the clinical scene. However, we can extend a life prognosis with use of radiotherapy and surgical treatment in addition to the palliative treatment at an appropriate time. It appears that a combination of new chemotherapy and hormonal therapy will be promising. In the future, we believe that the appearance of new anticancer drugs, endocrine therapies, bisphosphonates and strontium treatment could be used as a part of the treatment strategy for prostate cancer with bone metastases. PMID:16912523

  2. Advanced imaging techniques for the detection of breast cancer.

    PubMed

    Jochelson, Maxine

    2012-01-01

    Mammography is the only breast imaging examination that has been shown to reduce breast cancer mortality. Population-based sensitivity is 75% to 80%, but sensitivity in high-risk women with dense breasts is only in the range of 50%. Breast ultrasound and contrast-enhanced breast magnetic resonance imaging (MRI) have become additional standard modalities used in the diagnosis of breast cancer. In high-risk women, ultrasound is known to detect approximately four additional cancers per 1,000 women. MRI is exquisitely sensitive for the detection of breast cancer. In high-risk women, it finds an additional four to five cancers per 100 women. However, both ultrasound and MRI are also known to lead to a large number of additional benign biopsies and short-term follow-up examinations. Many new breast imaging tools have improved and are being developed to improve on our current ability to diagnose early-stage breast cancer. These can be divided into two groups. The first group is those that are advances in current techniques, which include digital breast tomosynthesis and contrast-enhanced mammography and ultrasound with elastography or microbubbles. The other group includes new breast imaging platforms such as breast computed tomography (CT) scanning and radionuclide breast imaging. These are exciting advances. However, in this era of cost and radiation containment, it is imperative to look at all of them objectively to see which will provide clinically relevant additional information. PMID:24451711

  3. [Treatment outcome of peptide vaccination for advanced colorectal cancer].

    PubMed

    Sugiura, Fumiaki; Inoue, Keisuke; Kogita, Akihiro; Yoshioka, Yasumasa; Hida, Jinichi; Okuno, Kiyotaka; Sukegawa, Yasushi

    2013-11-01

    Complementary DNA( cDNA) microarray technology coupled with laser microdissection has been used to identify human leukocyte antigen (HLA)-A24-restricted epitope peptides as potential targets for cancer vaccination in colorectal cancer patients. These antigenic peptides were derived from 2 different cancer-testis antigens, ring finger protein 43 (RNF43) and translocase of outer mitochondrial membrane 34( TOMM34). We conducted a clinical trial of colorectal cancer-specific peptide( RNF43, TOMM34) vaccines with uracil/tegafur( UFT)+Leucovorin( LV) for the treatment of advanced or recurrent colorectal cancer. The vaccinations were well tolerated without any serious adverse events. There were long-term survivors in the group showing cytotoxic T lymphocyte (CTL) responses against both RNF43 and TOMM34, as well as in the group showing CTL responses against either RNF43 or TOMM34. A new study has been planned to obtain more immunological responses. We started a clinical trial of vaccines against multiple peptides (RNF43, TOMM34, forkhead box protein M1 [FOXM1], maternal embryonic leucine zipper kinase [MELK], holliday junction recognition protein[HJURP], vascular endothelial growth factor receptor 1[VEGFR1], and VEGFR2) for the treatment of advanced or recurrent colorectal cancer. PMID:24393856

  4. The safety profile of vorinostat (suberoylanilide hydroxamic acid) in hematologic malignancies: A review of clinical studies.

    PubMed

    Duvic, Madeleine; Dimopoulos, Meletios

    2016-02-01

    Histone acetyltransferases and histone deacetylases (HDACs) are multifunctional enzymes that posttranslationally modify both histone and nonhistone acetylation sites, affecting a broad range of cellular processes (e.g., cell cycle, apoptosis, and protein folding) often dysregulated in cancer. HDAC inhibitors are small molecules that directly interact with HDAC catalytic sites preventing the removal of acetyl groups, thereby counteracting the effects of HDACs. Since the first HDAC inhibitor, valproic acid, was investigated as a potential antitumor agent, there have been a number of other HDAC inhibitors developed to improve efficacy and safety. Despite significant progress in the management of patients with hematologic malignancies, overall survival is still poor. The discovery that HDACs may play a role in hematologic malignancies and preclinical studies showing promising activity with HDAC inhibitors in various tumor types, led to clinical evaluation of HDAC inhibitors as potential treatment options for patients with advanced hematologic malignancies. The Food and Drug Administration has approved two HDAC inhibitors, vorinostat (2006) and romidepsin (2009), for the treatment of cutaneous T-cell lymphoma. This review highlights the safety of HDAC inhibitors currently approved or being investigated for the treatment of hematologic malignancies, with a specific focus on the safety experience with vorinostat in cutaneous T-cell lymphoma. PMID:26827693

  5. Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancer

    PubMed Central

    Ratosa, Ivica; Oblak, Irena; Anderluh, Franc; Velenik, Vaneja; But-Hadzic, Jasna; Ermenc, Ajra Secerov; Jeromen, Ana

    2015-01-01

    Background. To purpose of the study was to analyze the results of preoperative radiochemotherapy in patients with unresectable gastric or locoregionally advanced gastroesophageal junction (GEJ) cancer treated at a single institution. Patients and methods. Between 1/2004 and 6/2012, 90 patients with locoregionally advanced GEJ or unresectable gastric cancer were treated with preoperative radiochemotherapy at the Institute of Oncology Ljubljana. Planned treatment schedule consisted of induction chemotherapy with 5-fluorouracil and cisplatin, followed by concomitant radiochemotherapy four weeks later. Three-dimensional conformal external beam radiotherapy was delivered by dual energy (6 and 15 MV) linear accelerator in 25 daily fractions of 1.8 Gy in 5 weeks with two additional cycles of chemotherapy repeated every 28 days. Surgery was performed 4–6 weeks after completing radiochemotherapy. Following the surgery, multidisciplinary advisory team reassessed patients for the need of adjuvant chemotherapy. The primary endpoints were histopathological R0 resection rate and pathological response rate. The secondary endpoints were toxicity of preoperative radiochemotherapy and survival. Results. Treatment with preoperative radiochemotherapy was completed according to the protocol in 84 of 90 patients (93.3%). Twenty patients (22.2%) did not undergo the surgery because of the disease progression, serious comorbidity, poor performance status or still unresectable tumour. In 13 patients (14.4%) only exploration was performed because the tumour was assessed as unresectable or diffuse peritoneal carcinomatosis was established. Fifty-seven patients (63.4%) underwent surgery with the aim of complete removal of the tumour. Radical resection was achieved in 50 (55.6%) patients and the remaining seven (7.8%) patients underwent non-radical surgery (R1 in five and R2 in two patients). In this group of patients (n = 57), pathological complete response of tumour was achieved in five

  6. Improving Goals of Care Discussion in Advanced Cancer Patients

    ClinicalTrials.gov

    2016-06-30

    Primary Stage IV Hepatobiliary; Esophageal; Colorectal Cancer; Glioblastoma; Cancer of Stomach; Cancer of Pancreas; Melanoma; Head or Neck Cancer; Stage III; Stage IV; Lung Cancers; Pancreatic Cancers

  7. Advances in target therapy in lung cancer.

    PubMed

    Sculier, Jean-Paul; Berghmans, Thierry; Meert, Anne-Pascale

    2015-03-01

    Herein, we have reviewed and analysed recent literature, published in 2013 and early 2014, in the context of pre-existing data. Considered target therapies were tyrosine kinase inhibitors of active epidermal growth factor receptor mutations (e.g. erlotinib, gefinitib and afatinib), anaplastic lymphoma kinase rearrangements (e.g. crizotinib) or angiogenesis (drugs under development), or monoclonal antibodies against vascular endothelial growth factor (e.g. bevacizumab) or epidermal growth factor receptors (e.g. cetuximab). The therapeutic project has to consider tyrosine kinase inhibitors in the case of nonsmall cell lung cancer with active epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangement. However, these drugs should not be used in the absence of the targeted genetic abnormalities. PMID:25726551

  8. Psychological distress in parents of children with advanced cancer

    PubMed Central

    Rosenberg, Abby R; Dussel, Veronica; Kang, Tammy; Geyer, J. Russel; Gerhardt, Cynthia A; Feudtner, Chris; Wolfe, Joanne

    2014-01-01

    Objectives To describe the prevalence and factors of psychological distress (PD) among parents of children with advanced cancer. Design Cohort study embedded within a randomized clinical trial (Pediatric Quality of Life and Evaluation of Symptoms Technology [PediQUEST] study). Setting Multicenter study conducted at three children’s hospitals (Boston Children’s Hospital, Children’s Hospital of Philadelphia, Seattle Children’s Hospital). Participants Parents of children with advanced (progressive, recurrent, or refractory) cancer Outcome Measure Parental PD, as measured by the Kessler-6 (K6) general psychological distress scale. Results 86 of 104 parents completed the Survey about Caring for Children with Cancer (SCCC, 83% participation); 81 parents had complete K6 data. Over 50% of parents reported high PD and 16% met criteria for serious PD (compared to US prevalence of 2–3%). Parent perceptions of prognosis, goals of therapy, child symptoms/suffering, and financial hardship were associated with PD. In multivariate analyses, average parent K6 scores were higher among parents who believed their child was suffering highly and who reported great economic hardship. Conversely, PD was significantly lower among parents whose prognostic understanding was aligned with concrete goals of care. Conclusions Parenting a child with advanced cancer is strongly associated with high to severe levels of PD. Interventions aimed at aligning prognostic understanding with concrete care goals, and easing child suffering and financial hardship may mitigate parental PD. PMID:23545569

  9. Economic Impact of Advanced Pediatric Cancer on Families

    PubMed Central

    Bona, Kira; Dussel, Veronica; Orellana, Liliana; Kang, Tammy; Geyer, Russ; Feudtner, Chris; Wolfe, Joanne

    2013-01-01

    Context Despite emerging evidence of substantial financial distress in families of children with complex illness, little is known about economic hardship in families of children with advanced cancer. Objectives To describe perceived financial hardship, work disruptions, income losses and associated economic impact in families of children with advanced cancer stratified by federal poverty level (FPL). Methods This is a cross-sectional survey of 86 parents of children with progressive, recurrent or non-responsive cancer at three children’s hospitals. Seventy-one families with complete income data (82%) are included in this analysis. Results Parental work disruptions were prevalent across all income levels, with 67 (94%) families reporting some disruption. At least one parent quit a job because of the child’s illness in 29 (42%) families. Nineteen (27%) families described their child’s illness as a great economic hardship. Income losses due to work disruptions were substantial for all families; families at or below 200% FPL, however, were disproportionately affected. Six (50%) of the poorest families lost more than 40% of their annual income as compared with two (5%) of the wealthiest families (P=0.006). As a result of income losses, nine (15%) previously non-poor families fell from above to below the 200% FPL. Conclusion The economic impact of pediatric advanced cancer on families is significant at all income levels, although poorer families suffer disproportionate losses. Development of ameliorative intervention strategies is warranted. PMID:23870843

  10. Advances in Breast Cancer: Pathways to Personalized Medicine

    PubMed Central

    Olopade, Olufunmilayo I.; Grushko, Tatyana A.; Nanda, Rita; Huo, Dezheng

    2015-01-01

    Breast cancer is a complex disease caused by the progressive accumulation of multiple gene mutations combined with epigenetic dysregulation of critical genes and protein pathways. There is substantial interindividual variability in both the age at diagnosis and phenotypic expression of the disease. With an estimated 1,152,161 new breast cancer cases diagnosed worldwide per year, cancer control efforts in the postgenome era should be focused at both population and individual levels to develop novel risk assessment and treatment strategies that will further reduce the morbidity and mortality associated with the disease. The discovery that mutations in the BRCA1 and BRCA2 genes increase the risk of breast and ovarian cancers has radically transformed our understanding of the genetic basis of breast cancer, leading to improved management of high-risk women. A better understanding of tumor host biology has led to improvements in the multidisciplinary management of breast cancer, and traditional pathologic evaluation is being complemented by more sophisticated genomic approaches. A number of genomic biomarkers have been developed for clinical use, and increasingly, pharmacogenetic end points are being incorporated into clinical trial design. For women diagnosed with breast cancer, prognostic or predictive information is most useful when coupled with targeted therapeutic approaches, very few of which exist for women with triple-negative breast cancer or those with tumors resistant to chemotherapy. The immediate challenge is to learn how to use the molecular characteristics of an individual and their tumor to improve detection and treatment, and ultimately to prevent the development of breast cancer. The five articles in this edition of CCR Focus highlight recent advances and future directions on the pathway to individualized approaches for the early detection, treatment, and prevention of breast cancer. PMID:19088015

  11. Phase II Trial of Neoadjuvant Bevacizumab, Capecitabine, and Radiotherapy for Locally Advanced Rectal Cancer

    SciTech Connect

    Crane, Christopher H.; Eng, Cathy; Feig, Barry W.; Das, Prajnan; Skibber, John M.; Chang, George J.; Wolff, Robert A.; Krishnan, Sunil; Hamilton, Stanley; Janjan, Nora A.; Maru, Dipen M.; Ellis, Lee M.; Rodriguez-Bigas, Miguel A.

    2010-03-01

    Purpose: We designed this Phase II trial to assess the efficacy and safety of the addition of bevacizumab to concurrent neoadjuvant capecitabine-based chemoradiation in locally advanced rectal cancer. Methods: Between April 2004 and December 2007, 25 patients with clinically staged T3N1 (n = 20) or T3N0 (n = 5) rectal cancer received neoadjuvant therapy with radiotherapy (50.4 Gy in 28 fractions over 5.5 weeks), bevacizumab every 2 weeks (3 doses of 5 mg/kg), and capecitabine (900 mg/m{sup 2} orally twice daily only on days of radiation), followed by surgical resection a median of 7.3 weeks later. Results: Procedures included abdominoperineal resection (APR; 6 patients), proctectomy with coloanal anastamosis (8 patients), low anterior resection (10 patients), and local excision (1 patient). Eight (32%) of 25 patients had a pathologic complete response, and 6 (24%) of 25 had <10% viable tumor cells in the specimen. No patient had Grade 3 hand-foot syndrome, gastrointestinal toxicity, or significant hematologic toxicity. Three wound complications required surgical intervention (one coloanal anastamostic dehiscence requiring completion APR and two perineal wound dehiscences after initial APR). Five minor complications occurred that resolved without operative intervention. With a median follow-up of 22.7 months (range, 4.5-32.4 months), all patients were alive; one patient has had a recurrence in the pelvis (2-year actuarial rate, 6.2%) and 3 had distant recurrences. Conclusions: The addition of bevacizumab to neoadjuvant chemoradiation resulted in encouraging pathologic complete response without an increase in acute toxicity. The impact of bevacizumab on perineal wound and anastamotic healing due to concurrent bevacizumab requires further study.

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

    ClinicalTrials.gov

    2016-04-18

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

  13. Proton beam therapy for locally advanced lung cancer: A review

    PubMed Central

    Schild, Steven E; Rule, William G; Ashman, Jonathan B; Vora, Sujay A; Keole, Sameer; Anand, Aman; Liu, Wei; Bues, Martin

    2014-01-01

    Protons interact with human tissue differently than do photons and these differences can be exploited in an attempt to improve the care of lung cancer patients. This review examines proton beam therapy (PBT) as a component of a combined modality program for locally advanced lung cancers. It was specifically written for the non-radiation oncologist who desires greater understanding of this newer treatment modality. This review describes and compares photon (X-ray) radiotherapy (XRT) to PBT. The physical differences of these beams are described and the clinical literature is reviewed. Protons can be used to create treatment plans delivering significantly lower doses of radiation to the adjacent organs at risk (lungs, esophagus, and bone marrow) than photons. Clinically, PBT combined with chemotherapy has resulted in low rates of toxicity compared to XRT. Early results suggest a possible improvement in survival. The clinical results of proton therapy in lung cancer patients reveal relatively low rates of toxicity and possible survival benefits. One randomized study is being performed and another is planned to clarify the clinical differences in patient outcome for PBT compared to XRT. Along with the development of better systemic therapy, newer forms of radiotherapy such as PBT should positively impact the care of lung cancer patients. This review provides the reader with the current status of this new technology in treating locally advanced lung cancer. PMID:25302161

  14. Inverse Planned High-Dose-Rate Brachytherapy for Locoregionally Advanced Cervical Cancer: 4-Year Outcomes

    SciTech Connect

    Tinkle, Christopher L.; Weinberg, Vivian; Chen, Lee-May; Littell, Ramey; Cunha, J. Adam M.; Sethi, Rajni A.; Chan, John K.; Hsu, I-Chow

    2015-08-01

    Purpose: Evaluate the efficacy and toxicity of image guided brachytherapy using inverse planning simulated annealing (IPSA) high-dose-rate brachytherapy (HDRB) boost for locoregionally advanced cervical cancer. Methods and Materials: From December 2003 through September 2009, 111 patients with primary cervical cancer were treated definitively with IPSA-planned HDRB boost (28 Gy in 4 fractions) after external radiation at our institution. We performed a retrospective review of our experience using image guided brachytherapy. Of the patients, 70% had a tumor size >4 cm, 38% had regional nodal disease, and 15% had clinically evident distant metastasis, including nonregional nodal disease, at the time of diagnosis. Surgical staging involving pelvic lymph node dissection was performed in 15% of patients, and 93% received concurrent cisplatin-based chemotherapy. Toxicities are reported according to the Common Terminology Criteria for Adverse Events version 4.0 guidelines. Results: With a median follow-up time of 42 months (range, 3-84 months), no acute or late toxicities of grade 4 or higher were observed, and grade 3 toxicities (both acute and late) developed in 8 patients (1 constitutional, 1 hematologic, 2 genitourinary, 4 gastrointestinal). The 4-year Kaplan-Meier estimate of late grade 3 toxicity was 8%. Local recurrence developed in 5 patients (4 to 9 months after HDRB), regional recurrence in 3 (6, 16, and 72 months after HDRB), and locoregional recurrence in 1 (4 months after HDR boost). The 4-year estimates of local, locoregional, and distant control of disease were 94.0%, 91.9%, and 69.1%, respectively. The overall and disease-free survival rates at 4 years were 64.3% (95% confidence interval [CI] of 54%-73%) and 61.0% (95% CI, 51%-70%), respectively. Conclusions: Definitive radiation by use of inverse planned HDRB boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease. However, overall

  15. Advancing cancer control research in an emerging news media environment.

    PubMed

    Smith, Katherine C; Niederdeppe, Jeff; Blake, Kelly D; Cappella, Joseph N

    2013-12-01

    Cancer is both highly feared and highly newsworthy, and there is a robust body of research documenting the content and effects of cancer news coverage on health behaviors and policy. Recent years have witnessed ongoing, transformative shifts in American journalism alongside rapid advances in communication technology and the public information environment. These changes create a pressing need to consider a new set of research questions, sampling strategies, measurement techniques, and theories of media effects to ensure continued relevance and adaptation of communication research to address critical cancer control concerns. This paper begins by briefly reviewing what we know about the role of cancer news in shaping cancer-related beliefs, attitudes, behaviors, and policies. We then outline challenges and opportunities, both theoretical and methodological, posed by the rapidly changing news media environment and the nature of audience engagement. We organize our discussion around three major shifts associated with the emerging news media environment as it relates to health communication: 1) speed and dynamism of news diffusion, 2) increased narrowcasting of media content for specialized audiences, and 3) broadened participation in shaping media content. In so doing, we articulate a set of questions for future theory and research, in an effort to catalyze innovative communication scholarship to improve cancer prevention and control. PMID:24395988

  16. Recent Advances in Metabolic Profiling And Imaging of Prostate Cancer

    PubMed Central

    Thapar, Roopa; Titus, Mark A

    2015-01-01

    Cancer is a metabolic disease. Cancer cells, being highly proliferative, show significant alterations in metabolic pathways such as glycolysis, respiration, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, lipid metabolism, and amino acid metabolism. Metabolites like peptides, nucleotides, products of glycolysis, the TCA cycle, fatty acids, and steroids can be an important read out of disease when characterized in biological samples such as tissues and body fluids like urine, serum, etc. The cancer metabolome has been studied since the 1960s by analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Current research is focused on the identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients and distinguish between benign and advanced metastatic forms of the disease. In this review, we discuss the current state of prostate cancer metabolomics, the biomarkers that show promise in distinguishing indolent from aggressive forms of the disease, the strengths and limitations of the analytical techniques being employed, and future applications of metabolomics in diagnostic imaging and personalized medicine of prostate cancer. PMID:25632377

  17. Molecular Targets of Isothiocyanates in Cancer: Recent Advances

    PubMed Central

    Gupta, Parul; Kim, Bonglee; Kim, Sung-Hoon; Srivastava, Sanjay K.

    2014-01-01

    Cancer is a multistep process resulting in uncontrolled cell division. It results from aberrant signaling pathways that lead to uninhibited cell division and growth. Various recent epidemiological studies have indicated that consumption of cruciferous vegetables such as garden cress, broccoli, etc., reduces the risk of cancer. Isothiocyanates (ITC) have been identified as major active constituents of cruciferous vegetables. ITCs occur in plants as glucosinolate and can readily be derived by hydrolysis. Numerous mechanistic studies have demonstrated the anti-cancer effects of ITCs in various cancer types. ITCs suppress tumor growth by generating reactive oxygen species or by inducing cycle arrest leading to apoptosis. Based on the exciting outcomes of pre-clinical studies, few ITCs have advanced to the clinical phase. Available data from pre-clinical as well as available clinical studies suggests ITCs to be one of the promising anti-cancer agents available from natural sources. This is an up-to-date exhaustive review on the preventive and therapeutic effects of ITCs in cancer. PMID:24510468

  18. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    PubMed

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research. PMID:26925962

  19. Hematologic complications of pregnancy.

    PubMed

    Townsley, Danielle M

    2013-07-01

    Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This review discusses specifically the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations; however, care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist, and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy, and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. PMID:23953339

  20. Hematologic Complications of Pregnancy

    PubMed Central

    Townsley, Danielle M.

    2013-01-01

    Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This paper specifically reviews the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations,; however care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome, or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters in order to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. PMID:23953339

  1. Cisplatin/gemcitabine or oxaliplatin/gemcitabine in the treatment of advanced biliary tract cancer: a systematic review

    PubMed Central

    Fiteni, Frédéric; Nguyen, Thierry; Vernerey, Dewi; Paillard, Marie-Justine; Kim, Stefano; Demarchi, Martin; Fein, Francine; Borg, Christophe; Bonnetain, Franck; Pivot, Xavier

    2014-01-01

    Cisplatin/gemcitabine association has been a standard of care for first-line regimen in advanced biliary tract cancer nevertheless oxaliplatin/gemcitabine regimen is frequently preferred. Because comparative effectiveness in clinical outcomes of cisplatin- versus oxaliplatin-containing chemotherapy is not available, a systematic review of studies assessing cisplatin/gemcitabine or oxaliplatin/gemcitabine chemotherapies in advanced biliary tract cancer was performed. Published studies evaluating cisplatin/gemcitabine or oxaliplatin/gemcitabine in advanced biliary tract cancer were included. Each study was weighted according to the number of patients included. The primary objective was to assess weighted median of medians overall survival (mOS) reported for both regimens. Secondary goals were to assess weighted median of medians progression-free survival (mPFS) and toxic effects were pooled and compared within each arm. Thirty-three studies involving 1470 patients were analyzed. In total, 771 and 699 patients were treated by cisplatin/gemcitabine and oxaliplatin/gemcitabine, respectively. Weighted median of mOS was 9.7 months in cisplatin group and 9.5 months in oxaliplatin group. Cisplatin-based chemotherapy was significantly associated with more grade 3 and 4 asthenia, diarrhea, liver toxicity, and hematological toxicity. Sensitivity analysis including only the studies with the standard regimen of cisplatin (25–35 mg/m2 administered on days 1 and 8) showed that the weighted median of mOS increased from 9.7 to 11.7 months but Gem/CDDP regimen remained more toxic than Gemox regimen. These results suggest that the Gem/CDDP regimen with cisplatin (25–35 mg/m2) administered on days 1 and 8 is associated with survival advantage than Gemox regimen but with addition of toxicity. PMID:25111859

  2. Sequences and Combinations of Multifaceted Therapy In Advanced Prostate Cancer

    PubMed Central

    Vaishampayan, Ulka

    2015-01-01

    Purpose of Review Multiple agents with very distinct mechanisms of actions and unique toxicities and efficacies have become available for use in advanced prostate cancer. The next wave of investigations is focused on development of combinations and optimal sequences of the currently available agents. The focus of this review paper is to provide an update on clinical developments in advanced prostate cancer occurring within the past year, and to highlight the ongoing investigations of promising novel targets and compounds. Recent Findings The clinical use of enzalutamide prior to chemotherapy, demonstrated improvement in progression free survival (PFS) and overall survival (OS) as compared to placebo in metastatic castrate resistant prostate cancer (CRPC). This report of the PREVAIL trial led to the FDA approval of this agent. Novel agents such as cabozantinib and custirsen that had shown promising results in phase II trials, revealed disappointing results in the phase III setting. The breakthrough report, of the ability of the ARV-7 mutation, detected in circulating tumor cells, to predict lack of response to abiraterone or enzalutamide, and the remarkable responses of poly ADP ribose polymerase (PARP) inhibitors in prostate cancer with BRCA1/2 mutations, have elevated hopes of a bright future in the biomarker driven therapeutic arena. Summary As the clinical application of the recently approved multifaceted therapies widens, trials addressing optimal sequences and combinations are gaining importance. In addition, exploring the utility of therapies in the hormone naïve or non-metastatic settings is an area of active investigation. Early use of available agents, optimal sequencing and aid of biomarkers to guide therapeutic choices will make the achievement of lifetime remissions in advanced prostate cancer a reachable goal. PMID:25811344

  3. Stereotactic Body Radiation Therapy Boost in Locally Advanced Pancreatic Cancer

    SciTech Connect

    Seo, Young Seok; Kim, Mi-Sook; Yoo, Sung Yul; Cho, Chul Koo; Yang, Kwang Mo; Yoo, Hyung Jun; Choi, Chul Won; Lee, Dong Han; Kim, Jin; Kim, Min Suk; Kang, Hye Jin; Kim, YoungHan

    2009-12-01

    Purpose: To investigate the clinical application of a stereotactic body radiation therapy (SBRT) boost in locally advanced pancreatic cancer patients with a focus on local efficacy and toxicity. Methods and Materials: We retrospectively reviewed 30 patients with locally advanced and nonmetastatic pancreatic cancer who had been treated between 2004 and 2006. Follow-up duration ranged from 4 to 41 months (median, 14.5 months). A total dose of 40 Gy was delivered in 20 fractions using a conventional three-field technique, and then a single fraction of 14, 15, 16, or 17 Gy SBRT was administered as a boost without a break. Twenty-one patients received chemotherapy. Overall and local progression-free survival were calculated and prognostic factors were evaluated. Results: One-year overall survival and local progression-free survival rates were 60.0% and 70.2%, respectively. One patient (3%) developed Grade 4 toxicity. Carbohydrate antigen 19-9 response was found to be an independent prognostic factor for survival. Conclusions: Our findings indicate that a SBRT boost provides a safe means of increasing radiation dose. Based on the results of this study, we recommend that a well controlled Phase II study be conducted on locally advanced pancreatic cancer.

  4. Locally advanced pancreatic cancer. Looking beyond traditional chemotherapy and radiation.

    PubMed

    Savir, Guy; Huber, Kathryn E; Saif, Muhammad Wasif

    2013-07-01

    About a third of all pancreatic cancer is found to be locally advanced at the time of diagnosis, where the tumor is inoperable but remains localized to the pancreas and regional lymphatics. Sadly, this remains a universally deadly disease with progression to distant disease being the predominant mode of failure and average survival under one year. Optimal treatment of these patients continues to be an area of controversy, with chemotherapy alone being the treatment preference in Europe, and chemotherapy followed by chemoradiation in selected patients, preferred in the USA. The aim of this paper is to summarize the key abstracts presented at the 2013 ASCO Annual Meeting that address evolving approaches to the management of locally advanced pancreatic cancer. The late breaking abstract (#LBA4003) provided additional European data showing non-superiority of chemoradiation compared to chemotherapy in locally advanced pancreatic cancer patients without distant progression following 4 months of chemotherapy. Another late breaking abstract, (#LBA4004), unfortunately showed a promising new complement to gemcitabine and capecitabine using immunotherapy in the form of a T-helper vaccine did not translate to improved survival in the phase III setting. PMID:23846922

  5. Role of primary surgery in advanced ovarian cancer

    PubMed Central

    Münstedt, Karsten; Franke, Folker E

    2004-01-01

    Background Major issues in surgery for advanced ovarian cancer remain unresolved. Existing treatment guidelines are supported by a few published reports and fewer prospective randomized clinical trials. Methods We reviewed published reports on primary surgical treatment, surgical expertise, inadequate primary surgery/quality assurance, neoadjuvant chemotherapy, interval debulking, and surgical prognostic factors in advanced ovarian cancer to help resolve outstanding issues. Results The aim of primary surgery is a well-planned and complete intervention with optimal staging and surgery. Surgical debulking is worthwhile as there are further effective treatments available to control unresectable residual disease. Patients of gynecologic oncology specialist surgeons have better survival rates. This may reflect a working 'culture' rather than better technical skills. One major problem though, is that despite pleas to restrict surgery to experienced surgeons, specialist centers are often left to cope with the results of inadequate primary surgical resections. Patients with primary chemotherapy or those who have had suboptimal debulking may benefit from interval debulking. A proposal for a better classification of residual tumor is given. Conclusions Optimal surgical interventions have definite role to play in advanced ovarian cancers. Improvements in surgical treatment in the general population will probably improve patients' survival when coupled with improvements in current chemotherapeutic approaches. PMID:15461788

  6. High-Intensity Focused Ultrasound Treatment for Advanced Pancreatic Cancer

    PubMed Central

    Zhou, Yufeng

    2014-01-01

    Pancreatic cancer is under high mortality but has few effective treatment modalities. High-intensity focused ultrasound (HIFU) is becoming an emerging approach of noninvasively ablating solid tumor in clinics. A variety of solid tumors have been tried on thousands of patients in the last fifteen years with great success. The principle, mechanism, and clinical outcome of HIFU were introduced first. All 3022 clinical cases of HIFU treatment for the advanced pancreatic cancer alone or in combination with chemotherapy or radiotherapy in 241 published papers were reviewed and summarized for its efficacy, pain relief, clinical benefit rate, survival, Karnofsky performance scale (KPS) score, changes in tumor size, occurrence of echogenicity, serum level, diagnostic assessment of outcome, and associated complications. Immune response induced by HIFU ablation may become an effective way of cancer treatment. Comments for a better outcome and current challenges of HIFU technology are also covered. PMID:25053938

  7. [A Case of Isolated Leptomeningeal Carcinomatosis from Advanced Gastric Cancer].

    PubMed

    Ji, Jung Geun; Chung, Joo Won; Nam, Seung Woo; Choi, Seung Kyu; Lee, Dong Won; Kim, Dae In; Jeon, Byung Gwan; Shin, Yun Jae

    2016-08-25

    Leptomeningeal carcinomatosis (LMC) is rare metastatic form of gastric cancer. Most cases are diagnosed in the final stage after multiple distant metastasis. An 84-year-old woman was admitted with melena, headache and vomiting. Esophagogastroduodenoscopy showed an ulceroinfiltrating lesion at the stomach (Borrmann class III), and biopsy revealed a signet ring cell carcinoma. The abdominal-pelvic CT showed no evidence of metastasis. A sudden decrease of consciousness was noted, but the brain CT showed no active lesion while the brain MRI revealed enhancement of leptomeninges. A lumbar puncture was performed and the cerebrospinal fluid study revealed malignant neoplastic cells. With family consent, no further evaluation and treatment were administered and she died six weeks after the diagnosis of gastric cancer. We report an extremely rare case of a patient who initially presented with neurologic symptoms, and was diagnosed LMC from advanced gastric cancer without any evidence of metastasis in abdomen and pelvis. PMID:27554216

  8. A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

    PubMed Central

    Li, Yi; Wang, Ji; Ma, Xiaowei; Tan, Li; Yan, Yanli; Xue, Chaofan; Hui, Beina; Liu, Rui; Ma, Hailin; Ren, Juan

    2016-01-01

    Neoadjuvant chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy not only can reduce tumor size and recurrence, but also increase the tumor resection rate and anus retention rate with very slight side effect. Comparing with preoperative chemotherapy, preoperative chemoradiotherapy can further reduce the local recurrence rate and downstage. Middle and low rectal cancers can benefit more from neoadjuvant chemradiotherapy than high rectal cancer. It needs to refine the selection of appropriate patients and irradiation modes for neoadjuvant chemoradiotherapy. Different therapeutic reactions to neoadjuvant chemoradiotherapy affect the type of surgical techniques, hence calling for the need of much attention. Furthermore, many problems such as accurate staging before surgery, selection of suitable neoadjuvant chemoradiotherapy method, and sensitivity prediction to preoperative radiotherapy need to be well settled. PMID:27489505

  9. Quality of life and the treatment of advanced lung cancer.

    PubMed

    Plunkett, Tim A; Chrystal, Kathryn F; Harper, Peter G

    2003-07-01

    Lung cancer is the leading cause of cancer deaths worldwide, with the majority of patients presenting with advanced disease. Despite the introduction of newer therapeutic agents and modest survival improvement, the overall prognosis for these patients is poor. The goals of therapy should therefore include improvement in quality of life (QOL), palliation of symptoms, and prolongation of survival. Quality of life has now become recognized as an important outcome measure for cancer therapy. Quality-of-life endpoints are being increasingly incorporated into clinical trials of newer agents to further define meaningful response. The assessment of QOL involves comprehensive measurement tools that address the physical, social, functional, and emotional well-being of the patient. Such measurements should be easy to use, meaningful, and relevant to the patients and clinician. Although these measures assess the longitudinal impact of treatment on QOL, pretreatment QOL scores may also be an important prognostic factor for survival in patients with lung carcinoma. This article reviews QOL measures and the data for QOL benefits from therapy in patients with advanced small-cell and non-small-cell lung cancer. PMID:14596700

  10. Advances in epigenetic biomarker research in colorectal cancer

    PubMed Central

    Wang, Xi; Kuang, Ye-Ye; Hu, Xiao-Tong

    2014-01-01

    Colorectal cancer (CRC) causes approximately 600000 deaths annually and is the third leading cause of cancer mortality worldwide. Despite significant advancements in treatment options, CRC patient survival is still poor owing to a lack of effective tools for early diagnosis and a limited capacity for optimal therapeutic decision making. Since there exists a need to find new biomarkers to improve diagnosis of CRC, the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to clinical practice. Epigenetic alterations are thought to hold great promise as tumor biomarkers. In this review, we will primarily focus on recent advances in the study of epigenetic biomarkers for colorectal cancer and discuss epigenetic biomarkers, including DNA methylation, microRNA expression and histone modification, in cancer tissue, stool, plasma, serum, cell lines and xenografts. These studies have improved the chances that epigenetic biomarkers will find a place in the clinical practices of screening, early diagnosis, prognosis, therapy choice and recurrence surveillance for CRC patients. However, these studies have typically been small in size, and evaluation at a larger scale of well-controlled randomized clinical trials is the next step that is necessary to increase the quality of epigenetic biomarkers and ensure their widespread clinical use. PMID:24764665

  11. Requirement for a standardised definition of advanced gastric cancer

    PubMed Central

    DE SOL, ANGELO; TRASTULLI, STEFANO; GRASSI, VERONICA; CORSI, ALESSIA; BARILLARO, IVAN; BOCCOLINI, ANDREA; DI PATRIZI, MICOL SOLE; DI ROCCO, GIORGIO; SANTORO, ALBERTO; CIROCCHI, ROBERTO; BOSELLI, CARLO; REDLER, ADRIANO; NOYA, GIUSEPPE; KONG, SEONG-HO

    2014-01-01

    Each year, ~988,000 new cases of stomach cancer are reported worldwide. Uniformity for the definition of advanced gastric cancer (AGC) is required to ensure the improved management of patients. Various classifications do actually exist for gastric cancer, but the classification determined by lesion depth is extremely important, as it has been shown to correlate with patient prognosis; for example, early gastric cancer (EGC) has a favourable prognosis when compared with AGC. In the literature, the definition of EGC is clear, however, there is heterogeneity in the definition of AGC. In the current study, all parameters of the TNM classification for AGC reported in each previous study were individually analysed. It was necessary to perform a comprehensive systematic literature search of all previous studies that have reported a definition of ACG to guarantee homogeneity in the assessment of surgical outcome. It must be understood that the term ‘advanced gastric cancer’ may implicate a number of stages of disease, and studies must highlight the exact clinical TNM stages used for evaluation of the study. PMID:24348842

  12. Rhus verniciflua Stokes against Advanced Cancer: A Perspective from the Korean Integrative Cancer Center

    PubMed Central

    Choi, Woncheol; Jung, Hyunsik; Kim, Kyungsuk; Lee, Sookyung; Yoon, Seongwoo; Park, Jaehyun; Kim, Sehyun; Cheon, Seongha; Eo, Wankyo; Lee, Sanghun

    2012-01-01

    Active anticancer molecules have been searched from natural products; many drugs were developed from either natural products or their derivatives following the conventional pharmaceutical paradigm of drug discovery. However, the advances in the knowledge of cancer biology have led to personalized medicine using molecular-targeted agents which create new paradigm. Clinical benefit is dependent on individual biomarker and overall survival is prolonged through cytostatic rather than cytotoxic effects to cancer cell. Therefore, a different approach is needed from the single lead compound screening model based on cytotoxicity. In our experience, the Rhus verniciflua stoke (RVS) extract traditionally used for cancer treatment is beneficial to some advanced cancer patients though it is herbal extract not single compound, and low cytotoxic in vitro. The standardized RVS extract's action mechanisms as well as clinical outcomes are reviewed here. We hope that these preliminary results would stimulate different investigation in natural products from conventional chemicals. PMID:22174564

  13. Overcoming Drug Resistance and Treating Advanced Prostate Cancer

    PubMed Central

    Semenas, Julius; Allegrucci, Cinzia; Boorjian, Stephen A; Mongan, Nigel P; Persson, Jenny Liao

    2012-01-01

    Most of the prostate cancers (PCa) in advanced stage will progress to castration-resistant prostate cancer (CRPC). Within CRPC group, 50-70% of the patients will develop bone metastasis in axial and other regions of the skeleton. Once PCa cells spread to the bone, currently, no treatment regimens are available to eradicate the metastasis, and cancer-related death becomes inevitable. In 2012, it is estimated that there will be 28,170 PCa deaths in the United States. Thus, PCa bone metastasis-associated clinical complications and treatment resistance pose major clinical challenges. In this review, we will present recent findings on the molecular and cellular pathways that are responsible for bone metastasis of PCa. We will address several novel mechanisms with a focus on the role of bone and bone marrow microenvironment in promoting PCa metastasis, and will further discuss why prostate cancer cells preferentially metastasize to the bone. Additionally, we will discuss novel roles of several key pathways, including angiogenesis and extracellular matrix remodeling in bone marrow and stem cell niches with their relationship to PCa bone metastasis and poor treatment response. We will evaluate how various chemotherapeutic drugs and radiation therapies may allow aggressive PCa cells to gain advantageous mutations leading to increased survival and rendering the cancer cells to become resistant to treatment. The novel concept relating several key survival and invasion signaling pathways to stem cell niches and treatment resistance will be reviewed. Lastly, we will provide an update of several recently developed novel drug candidates that target metastatic cancer microenvironments or niches, and discuss the advantages and significance provided by such therapeutic approaches in pursuit of overcoming drug resistance and treating advanced PCa. PMID:22746994

  14. Hematologic malignancies during pregnancy: A review.

    PubMed

    Mahmoud, Hossam K; Samra, Mohamed A; Fathy, Gamal M

    2016-07-01

    Malignancy is the second most common cause of mortality in the reproductive period and it complicates up to one out of every 1000 pregnancies. When cancer is diagnosed during pregnancy, the management approach must take into consideration both the mother and her fetus. Hematologic cancers diagnosed in pregnancy are not common, resulting in paucity of randomized controlled trials. Diagnosis of such malignancies may be missed or delayed, as their symptoms are similar to those encountered during normal pregnancy. Also, many imaging studies may be hazardous during pregnancy. Management of these malignancies during pregnancy induces many treatment-related risks for mother and baby and should consider patient's preferences for pregnancy continuation. In this article, hematologic malignancies diagnosed in pregnant patients including acute leukemias, chronic myeloid leukemia, lymphomas, multiple myeloma and myeloproliferative neoplasms, will be reviewed, including diagnostic and management strategies and their impact on the pregnant patient and the developing fetus. PMID:27408762

  15. Advancing Techniques of Radiation Therapy for Rectal Cancer.

    PubMed

    Patel, Sagar A; Wo, Jennifer Y; Hong, Theodore S

    2016-07-01

    Since the advent of radiation therapy for rectal cancer, there has been continual investigation of advancing technologies and techniques that allow for improved dose conformality to target structures while limiting irradiation of surrounding normal tissue. For locally advanced disease, intensity modulated and proton beam radiation therapy both provide more highly conformal treatment volumes that reduce dose to organs at risk, though the clinical benefit in terms of toxicity reduction is unclear. For early stage disease, endorectal contact therapy and high-dose rate brachytherapy may be a definitive treatment option for patients who are poor operative candidates or those with low-lying tumors that desire sphincter-preservation. Finally, there has been growing evidence that supports stereotactic body radiotherapy as a safe and effective salvage treatment for the minority of patients that locally recur following trimodality therapy for locally advanced disease. This review addresses these topics that remain areas of active clinical investigation. PMID:27238474

  16. Confocal microscopy of skin cancers: Translational advances toward clinical utility

    PubMed Central

    Rajadhyaksha, Milind

    2014-01-01

    Recent advances in translational research in and technology for confocal microscopy of skin cancers, toward clinical applications, are described. Advances in translational research are in diagnosis of melanoma in vivo, pre-operative mapping of lentigo maligna melanoma margins to guide surgery and intra-operative imaging of residual basal cell carcinomas to guide shave-biopsy. Advances in technology include mosaicing microscopy for detection of basal cell carcinomas in large areas of excised tissue, toward rapid pathology-at-the-bedside, and development of small, simple and low-cost line-scanning confocal microscopes for worldwide use in diverse primary healthcare settings. Current limitations and future opportunities and challenges for both clinicians and technologists are discussed. PMID:19964286

  17. Advances in Genetic Testing for Hereditary Cancer Syndromes.

    PubMed

    Thomas, Ellen; Mohammed, Shehla

    2016-01-01

    The ability to identify genetic mutations causing an increased risk of cancer represents the first widespread example of personalised medicine, in which genetic information is used to inform patients of their cancer risks and direct an appropriate strategy to minimise those risks. Increasingly, an understanding of the genetic basis of many cancers also facilitates selection of the most effective therapeutic options. The technology underlying genetic testing has been revolutionised in the years since the completion of the Human Genome Project in 2001. This has advanced knowledge of the genetic factors underlying familial cancer risk, and has also improved genetic testing capacity allowing a larger number of patients to be tested for a constitutional cancer predisposition. To use these tests safely and effectively, they must be assessed for their ability to provide accurate and useful results, and be requested and interpreted by health professionals with an understanding of their strengths and limitations. Genetic testing is increasing in its scope and ambition with each year that passes, requiring a greater proportion of the healthcare workforce to acquire a working knowledge of genetics and genetic testing to manage their patients safely and sensitively. PMID:27075345

  18. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015.

    PubMed

    Gillessen, S; Omlin, A; Attard, G; de Bono, J S; Efstathiou, E; Fizazi, K; Halabi, S; Nelson, P S; Sartor, O; Smith, M R; Soule, H R; Akaza, H; Beer, T M; Beltran, H; Chinnaiyan, A M; Daugaard, G; Davis, I D; De Santis, M; Drake, C G; Eeles, R A; Fanti, S; Gleave, M E; Heidenreich, A; Hussain, M; James, N D; Lecouvet, F E; Logothetis, C J; Mastris, K; Nilsson, S; Oh, W K; Olmos, D; Padhani, A R; Parker, C; Rubin, M A; Schalken, J A; Scher, H I; Sella, A; Shore, N D; Small, E J; Sternberg, C N; Suzuki, H; Sweeney, C J; Tannock, I F; Tombal, B

    2015-08-01

    The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged. PMID:26041764

  19. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015

    PubMed Central

    Gillessen, S.; Omlin, A.; Attard, G.; de Bono, J. S.; Efstathiou, E.; Fizazi, K.; Halabi, S.; Nelson, P. S.; Sartor, O.; Smith, M. R.; Soule, H. R.; Akaza, H.; Beer, T. M.; Beltran, H.; Chinnaiyan, A. M.; Daugaard, G.; Davis, I. D.; De Santis, M.; Drake, C. G.; Eeles, R. A.; Fanti, S.; Gleave, M. E.; Heidenreich, A.; Hussain, M.; James, N. D.; Lecouvet, F. E.; Logothetis, C. J.; Mastris, K.; Nilsson, S.; Oh, W. K.; Olmos, D.; Padhani, A. R.; Parker, C.; Rubin, M. A.; Schalken, J. A.; Scher, H. I.; Sella, A.; Shore, N. D.; Small, E. J.; Sternberg, C. N.; Suzuki, H.; Sweeney, C. J.; Tannock, I. F.; Tombal, B.

    2015-01-01

    The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged. PMID:26041764

  20. Carboplatin and gemcitabine in first-line treatment of elderly patients with advanced non-small cell lung cancer: data from a retrospective study.

    PubMed

    Genestreti, G; Giovannini, N; Frizziero, M; Maglie, M; Sanna, S; Cingarlini, S; Molino, A M; Piciucchi, S; Cetto, G L; Santo, A

    2011-08-01

    We retrospectively evaluated elderly patients with advanced non-small cell lung cancer (NSCLC) treated with carboplatin (AUC 4-5) and gemcitabine (1,000-1,200 mg/m²). Thirty-six patients with performance Status (pS) 0-1 and median age 73 (range 70-78 years) were considered. Histology was squamous cell carcinoma (8 patients), adenocarcinoma (22) and NSCLC not otherwise specified (6). 149 cycles of chemotherapy were administered with a median of 3 per patient (range 3-6). Grade 3 non-hematologic toxicities were dyspnea (1 patient) and fever (1). Grade 3/4 hematologic toxicities were anemia (6), neutropenia (6) and thrombocytopenia (10), with dose reduction required in 13 patients. The overall disease control rate was 44.4%. We recorded no complete response, 8 partial response, 8 stable disease and 20 progressive disease. After a medium follow-up of 11 months, median progression- free survival and median survival were 5 and 11 months, respectively. Carboplatin and gemcitabine is a safe and active regimen in elderly advanced NSCLC patients with good PS. PMID:21803702

  1. Causal Attributions for Fatigue by Older Adults with Advanced Cancer

    PubMed Central

    Siegel, Karolynn; Lekas, Helen-Maria; Maheshwari, Deepali

    2012-01-01

    Context Fatigue is a prevalent, debilitating and often disruptive symptom for cancer patients. Yet, it remains inadequately understood and managed, especially among late middle- aged and older patients with advanced disease. Few studies have explored fatigue qualitatively and almost none have focused on patients’ attributions for this subjective and multidimensional symptom. Objectives Our objectives were to: 1) examine the attributions patients 55 or older with advanced cancer made for their fatigue and how they arrived at these attributions; and 2) understand how patients’ attributions affect how they contend with fatigue, including communication with health care providers. Methods We conducted qualitative in-depth interviews with 35 patients 55 years of age or older on their experiences with fatigue. Patients had a variety of cancers and were at stages IV or late III of the disease. Interviews were thematically coded and analyzed. Results Two main themes emerged: 1) Cancer-related treatment was the master and often the sole attribution patients made for their fatigue. Patients making this attribution expressed certainty about its accuracy and seemed less distressed about the symptom. 2) Multiple causes of fatigue, typically a combination of cancer, treatment and non-threatening causes (e.g., older age, overexertion, or anemia), were also offered by some. Patients seemed to resist identifying disease severity as a cause and appeared motivated to normalize and minimize the symptom, thus decreasing its threatening impact. Conclusion Patients’ causal attributions for fatigue had a profound effect on their physical and psychological well-being, their communication with providers, and their integration of the symptom into their lives. PMID:22652133

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

    ClinicalTrials.gov

    2015-09-30

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

  3. Hematological Problems of Pregnancy

    PubMed Central

    Ballem, P.J.

    1988-01-01

    Hematologic complications are relatively common in pregnancy. Furthermore, many chronic hematologic disorders require special surveillance and intervention in pregnancy. In this brief review, the author discusses common nutritional anemias in pregnancy. She reviews the disorders of hemoglobin synthesis and the need for early genetic counselling and prenatal diagnosis, as well as the special requirements and problems affected patients encounter in pregnancy. An overview of the frequent causes of thrombocytopenia in pregnancy is given and an approach suggested to the management of both the mother and the fetus. An approach is also presented to the management of women at risk for thrombosis in pregnancy, a particularly vexing and controversial problem. The risks of the various forms of anticoagulation are reviewed. Finally, a brief review of obstetrical hemorrhage is presented along with some guidelines useful in its management. PMID:21253125

  4. Hematology and immunology studies

    NASA Technical Reports Server (NTRS)

    Kimzey, S. L.; Fischer, C. L.; Johnson, P. C.; Ritzmann, S. E.; Mengel, C. E.

    1975-01-01

    The hematology and immunology program conducted in support of the Apollo missions was designed to acquire specific laboratory data relative to the assessment of the health status of the astronauts prior to their commitment to space flight. A second objective was to detect and identify any alterations in the normal functions of the immunohematologic systems which could be attributed to space flight exposure, and to evaluate the significance of these changes relative to man's continuing participation in space flight missions. Specific changes observed during the Gemini Program formed the basis for the major portion of the hematology-immunology test schedule. Additional measurements were included when their contribution to the overall interpretation of the flight data base became apparent.

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

    PubMed Central

    Simpson, Guy R; Relph, Kate; Harrington, Kevin; Melcher, Alan; Pandha, Hardev

    2016-01-01

    Oncolytic viruses are multifunctional anticancer agents with huge clinical potential, and have recently passed the randomized Phase III clinical trial hurdle. Both wild-type and engineered viruses have been selected for targeting of specific cancers, to elicit cytotoxicity, and also to generate antitumor immunity. Single-agent oncolytic virotherapy treatments have resulted in modest effects in the clinic. There is increasing interest in their combination with cytotoxic agents, radiotherapy and immune-checkpoint inhibitors. Similarly to oncolytic viruses, the benefits of chemotherapeutic agents may be that they induce systemic antitumor immunity through the induction of immunogenic cell death of cancer cells. Combining these two treatment modalities has to date resulted in significant potential in vitro and in vivo synergies through various mechanisms without any apparent additional toxicities. Chemotherapy has been and will continue to be integral to the management of advanced cancers. This review therefore focuses on the potential for a number of common cytotoxic agents to be combined with clinically relevant oncolytic viruses. In many cases, this combined approach has already advanced to the clinical trial arena.

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

    PubMed

    Simpson, Guy R; Relph, Kate; Harrington, Kevin; Melcher, Alan; Pandha, Hardev

    2016-01-01

    Oncolytic viruses are multifunctional anticancer agents with huge clinical potential, and have recently passed the randomized Phase III clinical trial hurdle. Both wild-type and engineered viruses have been selected for targeting of specific cancers, to elicit cytotoxicity, and also to generate antitumor immunity. Single-agent oncolytic virotherapy treatments have resulted in modest effects in the clinic. There is increasing interest in their combination with cytotoxic agents, radiotherapy and immune-checkpoint inhibitors. Similarly to oncolytic viruses, the benefits of chemotherapeutic agents may be that they induce systemic antitumor immunity through the induction of immunogenic cell death of cancer cells. Combining these two treatment modalities has to date resulted in significant potential in vitro and in vivo synergies through various mechanisms without any apparent additional toxicities. Chemotherapy has been and will continue to be integral to the management of advanced cancers. This review therefore focuses on the potential for a number of common cytotoxic agents to be combined with clinically relevant oncolytic viruses. In many cases, this combined approach has already advanced to the clinical trial arena. PMID:27579292

  7. Efficacy and safety analysis of chemotherapy for advanced colitis-associated colorectal cancer in Japan.

    PubMed

    Nio, Kenta; Higashi, Daijiro; Kumagai, Hozumi; Arita, Shuji; Shirakawa, Tsuyoshi; Nakashima, Koji; Shibata, Yoshihiro; Esaki, Motohiro; Manabe, Tatsuya; Nagai, Shuntaro; Ueki, Takashi; Nakano, Michitaka; Ariyama, Hiroshi; Kusaba, Hitoshi; Hirahashi, Minako; Oda, Yoshinao; Esaki, Taito; Mitsugi, Kenji; Futami, Kitaro; Akashi, Koichi; Baba, Eishi

    2016-06-01

    Chemotherapy for advanced colitis-associated colorectal cancer (CAC) has been insufficiently evaluated. The goal of this study was to clarify the efficacy and safety of chemotherapy for CAC in Japan. CAC patients who were treated with chemotherapy between 2005 and 2015 were retrospectively examined. Twenty-nine patients (median age, 48 years; 23 men) were assessed. Eighteen patients had ulcerative colitis, and 11 had Crohn's disease. Three ulcerative colitis and four Crohn's disease patients were in the active disease phase. Primary tumors were located in the rectum/anus (n=16), the left colon (n=9), or the right colon (n=4). Palliative or adjuvant chemotherapy was performed in 13 and 16 patients, respectively. First-line palliative chemotherapy regimens were as follows: fluorouracil, leucovorin, and oxaliplatin (FOLFOX; n=6), FOLFOX+bevacizumab (n=3), and others (n=4). Adjuvant chemotherapy regimens were S-1 (n=7), oxaliplatin-based (n=4) and others (n=5). In palliative chemotherapy, the objective response rate was 15%, and the median progression-free survival and overall survival were 182 and 315 days, respectively. In adjuvant chemotherapy, the 5-year relapse-free survival rate was 78%. Grade 3/4 adverse events (AEs) were observed in 16 patients (55%). Active and remission inflammatory bowel disease patients suffered grade 3/4 nonhematological AEs at an incidence of 71 and 23%, respectively (P<0.01). Dose reduction was required in 11 patients (38%), eight of whom required it for hematological AEs. Adjuvant chemotherapy for CAC exhibited sufficient efficacy, whereas modest efficacy was shown for palliative chemotherapy for CAC. AEs, particularly nonhematological AEs, were closely associated with disease activity of colitis. PMID:26771865

  8. Hemi body irradiation: An economical way of palliation of pain in bone metastasis in advanced cancer

    PubMed Central

    Pal, Santanu; Dutta, Samrat; Adhikary, Shyam Sundar; Bhattacharya, Biswamit; Ghosh, Balaram; Patra, Niladri B.

    2014-01-01

    Test (P < 0.05) was significant in VAS score changes, VRS score changes, PPR score changes, and GPS score changes. Along with the decrease in morphine tablets, the Linear Correlation of various scales for pain reduction like VAS, VRS, PPR, and GPS were significant. As such, the quality of life was better due to decreased pain and also, a decrease in the dose of analgesics. Grade 1 and 2 hematological toxicity and grade 1 diarrhea were observed as common side-effects. The average total cost of treatment including hospital stay, medicines, and radiation charges was around INR 400.00. Conclusion: This study shows that hemibody irradiation is not only an effective modality for palliation of severe bone pain in advanced cancer cases but also economical, involves short hospital stay, with acceptable side-effects, utilizes the simple Telecobalt machine, and is less cumbersome in comparison to other currently available pain palliation methods like oral morphine and radiopharmaceuticals. PMID:24665443

  9. A Trial for Patients With Advanced/Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2009-11-13

    Neoplasms; Neoplasms by Site; Urogenital Neoplasms; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms; Cancer of Endometrium; Endometrial Cancer; Cancer of the Endometrium; Endometrium Cancer; Neoplasms, Endometrial

  10. Current perspectives in the treatment of advanced prostate cancer.

    PubMed

    Valdespino, Victor; Tsagozis, Panagiotis; Pisa, Pavel

    2007-01-01

    Prostate cancer (PC) continues to be an important world health problem for men. Patients with locally confined PC are treated with either radiotherapy or surgery. However, treatment of more advanced stages of the disease is problematic. Initially, androgen deprivation offers a period of clinical stability, which is however invariably followed by progression to non-responsiveness to hormonal manipulation. Current management of patients with androgen-independent prostate cancer (AIPC) displays modest response rates and achieves only short-term benefit. Recently, knowledge in the complex pathophysiology of advanced PC has led to the identification of mechanisms and target molecules permitting the introduction of new therapies. Consequently, many investigational treatments are ongoing for AIPC in Phase-II and Phase-III trials aiming at the combination of chemotherapeutic regimens along with immunotherapy targeting PC-associated antigens. Other attractive options are gene therapy, as well as the targeting of survival signaling, differentiation, and apoptosis of the malignant PC cells. Further treatment modalities are directed against the tumor microenvironment, bone metastasis, or both. Collectively, the aforementioned efforts introduce a new era in the management of advanced PC. Novel pharmaceutical compounds and innovative approaches, integrated into the concept of individualized therapy will hopefully, during the next decade, improve the outcome and survival for hundreds of thousands of men worldwide. PMID:17873302

  11. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    NASA Astrophysics Data System (ADS)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  12. A Phase I Study of the First-in-Class Anti-Mitochondrial Metabolism Agent, CPI-613, in Patients with Advanced Hematologic Malignancies

    PubMed Central

    Pardee, Timothy S.; Lee, King; Luddy, John; Maturo, Claudia; Rodriguez, Robert; Isom, Scott; Miller, Lance D.; Stadelman, Kristin M.; Levitan, Denise; Hurd, David; Ellis, Leslie R.; Harrelson, Robin; Manuel, Megan; Dralle, Sarah; Lyerly, Susan; Powell, Bayard L

    2014-01-01

    Purpose The lipoate derivative CPI-613 is a first-in-class agent that targets mitochondrial metabolism. This study determined the effects of CPI-613 on mitochondrial function and defined the maximally tolerated dose (MTD), pharmacokinetics (PKs), and safety in patients with relapsed or refractory hematologic malignancies. Experimental Design Human leukemia cell lines were exposed to CPI-613 and mitochondrial function was assayed. A phase I trial was conducted in which CPI-613 was given as a 2-hour infusion on days 1 and 4 for 3 weeks every 28 days. Results CPI-613 inhibited mitochondrial respiration of human leukemia cells consistent with the proposed mechanism of action. In the phase I trial, 26 patients were enrolled. CPI-613 was well tolerated with no marrow suppression observed. When the infusion time was shortened to 1 hour renal failure occurred in 2 patients. At 3780 mg/m2, there were 2 dose-limiting toxicities (DLTs). At a dose of 2940 mg/m2 over 2 hours, no DLTs were observed, establishing this as the MTD. Renal failure occurred in a total of 4 patients and resolved in all but 1, who chose hospice care. CPI-613 has a triphasic elimination with an alpha half-life of ~1.34 hours. Of 21 evaluable, heavily pretreated, patients, 4 achieved an objective response and 2 achieved prolonged stabilization of disease for a clinical benefit rate of 29%. Following drug exposure, gene expression profiles of peripheral blood mononuclear cells from responders demonstrated immune activation. Conclusion CPI-613 inhibits mitochondrial function and demonstrates activity in a heavily pretreated cohort of patients. PMID:25165100

  13. Recent advances in active specific cancer vaccine treatment for colorectal cancer.

    PubMed

    Okuno, Kiyotaka; Sugiura, Fumiaki; Itoh, Kyogo; Yoshida, Koji; Tsunoda, Takuya; Nakamura, Yusuke

    2012-06-01

    Cloning techniques to identify genes and peptides of tumor-associated antigens have created new possibilities for the immunotherapy of patients with advanced cancer. Here, we review recent clinical trials of specific cancer vaccines, mainly HLA-restricted peptides, and epitope-encoding vectors for advanced colorectal cancer (CRC). Many researchers initially focused on carcinoembryonic antigen (CEA) as an immunologic target antigen that is overexpressed on virtually all CRCs. A recombinant vaccine containing the CEA gene and dendritic cells (DCs) loaded with CEA peptide was administered to patients with CEA-elevated CRC. Although CEA-specific responses were detected, the clinical responses were limited. Recently, new types of clinical trials--namely, a personalized protocol to take into account the immunological diversity of cytotoxic T cell responses among patients and a novel cancer-testis antigen protocol that uses multiple peptides derived from genes identified by the cDNA array method--have been introduced. The personalized protocol seemed to be better than the classical (non-personalized) protocol in terms of clinical response and survival. Novel cancer-testis antigen protocols that use multiple CRC-derived peptides were recently conducted in patients with advanced CRC. The preliminary study yielded promising results regarding specific T cell responses to peptides and survival benefits. In this review, we summarize these results and discuss future perspectives. PMID:22339221

  14. Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies: posttransplantation CD8-depleted donor lymphocyte infusions contribute to improve T-cell recovery.

    PubMed

    Dodero, Anna; Carniti, Cristiana; Raganato, Anna; Vendramin, Antonio; Farina, Lucia; Spina, Francesco; Carlo-Stella, Carmelo; Di Terlizzi, Simona; Milanesi, Marco; Longoni, Paolo; Gandola, Lorenza; Lombardo, Claudia; Corradini, Paolo

    2009-05-01

    Haploidentical hematopoietic stem cell transplantation provides an option for patients with advanced hematologic malignancies lacking a compatible donor. In this prospective phase 1/2 trial, we evaluated the role of reduced-intensity conditioning (RIC) followed by early add-backs of CD8-depleted donor lymphocyte infusions (DLIs). The RIC regimen consisted of thiotepa, fludarabine, cyclophosphamide, and 2 Gy total body irradiation. Twenty-eight patients with advanced lymphoproliferative diseases (n = 24) or acute myeloid leukemia (n = 4) were enrolled. Ex vivo and in vivo T-cell depletion was carried out by CD34(+) cell selection and alemtuzumab treatment. The 2-year cumulative incidence of nonrelapse mortality was 26% and the 2-year overall survival (OS) was 44%, with a better outcome for patients with chemosensitive disease (OS, 75%). Overall, 54 CD8-depleted DLIs were administered to 23 patients (82%) at 3 different dose levels without loss of engraftment or acute toxicities. Overall, 6 of 23 patients (26%) developed grade II-IV graft-versus-host disease, mainly at dose level 2. In conclusion, our RIC regimen allowed a stable engraftment with a rather low nonrelapse mortality in poor-risk patients; OS is encouraging with some long-term remissions in lymphoid malignancies. CD8-depleted DLIs are feasible and promote the immune reconstitution. PMID:19211934

  15. Integrative and complementary therapies for patients with advanced cancer.

    PubMed

    Marchand, Lucille

    2014-07-01

    In integrative medicine, well-being is emphasized, and in palliative care, quality of life (QOL) is a similar concept or goal. Both can occur despite advanced cancer. Integrative medicine serves to combine the best of alternative, complementary and conventional therapies to optimize well-being and QOL, whether or not a person is at the end of their life. When integrative medicine is combined with palliative care modalities, the toolbox to provide symptom control and well-being or QOL is increased or broadened. Palliative care and integrative medicine are best provided early in the trajectory of illness such as cancer, and increase in amount as the illness progresses toward end of life. In cancer care, symptoms of the cancer, as well as symptoms produced by cancer therapies, are addressed with conventional and integrative therapies. Goals of care change as the disease progresses, and a patient's unique situation creates a different balance of integrative and conventional therapies. Integrative therapies such as music, aromatherapy, and massage might appeal to more patients than more specific, less common integrative therapies that might be more expensive, or seem more unusual such as Ayurvedic medicine and energy modalities. Each person may be drawn to different integrative modalities depending on factors such as cultural traditions, beliefs, lifestyle, internet information, advice from family and friends, books, etc. This review focuses on how integrative and complementary modalities can be included in comprehensive palliative care for patients with advanced malignancies. Nutrition and movement, often neglected in conventional treatment strategies, will also be included in the larger context of integrative and palliative modalities. Both conventional and integrative modalities in palliative care help patients live with empowerment, hope, and well-being no matter how long their lives last. A comprehensive review of all integrative and complementary therapies is

  16. Matrine promotes the efficacy and safety of platinum-based doublet chemotherapy for advanced non-small cell lung cancer

    PubMed Central

    Rong, Biaoxue; Zhao, Chongchong; Gao, Wenlong; Yang, Shuanying

    2015-01-01

    Purpose: Many studies have investigated the efficacy of matrine combined with platinum-based doublet chemotherapy (PBDC) versus PBDC alone for treating advanced non-small cell lung cancer (NSCLC). This study is an analytic value of available evidence. Methods: twenty-two studies reporting matrine combined with PBDC versus PBDC alone for treating advanced NSCLC were reviewed. Pooled odds ratios and hazard ratio with 95% confidence intervals were calculated using either the fixed effects model or random effects model. Results: The overall response rate (ORR) and disease control rate (DCR) of matrine combined with PBDC for treating NSCLC were significantly higher than those of PBDC alone, with 15.1% and 19.7% improvement, respectively (P < 0.00001). In addition, the mean survival time (MST) and quality of life (QOL) were improved after the treatment of matrine combined with PBDC (P < 0.00001). The main adverse effects found in this review were hematological reactions, nausea and vomiting. Matrine combined with PBDC had a lower incidence of adverse reactions compared with PBDC alone (P < 0.05). Conclusions: Matrine combined with PBDC was associated with higher RR, DCR, and MST as well as superior QOL profiles compared with PBDC alone. Matrine combined with PBDC decrease the incidence of adverse reactions compared with PBDC alone. PMID:26628952

  17. Identification and characterization of RET fusions in advanced colorectal cancer

    PubMed Central

    Garrett, Christopher R.; Seery, Tara; Sanford, Eric M.; Balasubramanian, Sohail; Ross, Jeffrey S.; Stephens, Philip J.; Miller, Vincent A.; Ali, Siraj M.; Chiu, Vi K.

    2015-01-01

    There is an unmet clinical need for molecularly directed therapies available for metastatic colorectal cancer. Comprehensive genomic profiling has the potential to identify actionable genomic alterations in colorectal cancer. Through comprehensive genomic profiling we prospectively identified 6 RET fusion kinases, including two novel fusions of CCDC6-RET and NCOA4-RET, in metastatic colorectal cancer (CRC) patients. RET fusion kinases represent a novel class of oncogenic driver in CRC and occurred at a 0.2% frequency without concurrent driver mutations, including KRAS, NRAS, BRAF, PIK3CA or other fusion tyrosine kinases. Multiple RET kinase inhibitors were cytotoxic to RET fusion kinase positive cancer cells and not RET fusion kinase negative CRC cells. The presence of a RET fusion kinase may identify a subset of metastatic CRC patients with a high response rate to RET kinase inhibition. This is the first characterization of RET fusions in CRC patients and highlights the therapeutic significance of prospective comprehensive genomic profiling in advanced CRC. PMID:26078337

  18. Identification and characterization of RET fusions in advanced colorectal cancer.

    PubMed

    Le Rolle, Anne-France; Klempner, Samuel J; Garrett, Christopher R; Seery, Tara; Sanford, Eric M; Balasubramanian, Sohail; Ross, Jeffrey S; Stephens, Philip J; Miller, Vincent A; Ali, Siraj M; Chiu, Vi K

    2015-10-01

    There is an unmet clinical need for molecularly directed therapies available for metastatic colorectal cancer. Comprehensive genomic profiling has the potential to identify actionable genomic alterations in colorectal cancer. Through comprehensive genomic profiling we prospectively identified 6 RET fusion kinases, including two novel fusions of CCDC6-RET and NCOA4-RET, in metastatic colorectal cancer (CRC) patients. RET fusion kinases represent a novel class of oncogenic driver in CRC and occurred at a 0.2% frequency without concurrent driver mutations, including KRAS, NRAS, BRAF, PIK3CA or other fusion tyrosine kinases. Multiple RET kinase inhibitors were cytotoxic to RET fusion kinase positive cancer cells and not RET fusion kinase negative CRC cells. The presence of a RET fusion kinase may identify a subset of metastatic CRC patients with a high response rate to RET kinase inhibition. This is the first characterization of RET fusions in CRC patients and highlights the therapeutic significance of prospective comprehensive genomic profiling in advanced CRC. PMID:26078337

  19. Advanced Cell Culture Techniques for Cancer Drug Discovery

    PubMed Central

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

    2014-01-01

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

  20. Spinal analgesia for advanced cancer patients: an update.

    PubMed

    Mercadante, Sebastiano; Porzio, Giampiero; Gebbia, Vittorio

    2012-05-01

    In the nineties, spinal analgesia has been described as an useful means to control pain in advanced cancer patients. The aim of this review was to update this information with a systematic analysis of studies performed in the last 10 years. 27 papers pertinent with the topic selected for review were collected according to selection criteria. Few studies added further information on spinal analgesia in last decade. Despite a lack of a clinical evidence, spinal analgesia with a combination of opioids, principally morphine, and local anesthetics may allow to achieve analgesia in patients who had been intensively treated unsuccessfully with different trials of opioids. Some adjuvant drugs such as clonidine, ketamine, betamethasone, meperidine, and ziconotide may be promising agents, but several problems have to be solved before they can be used in the daily practice. In complex pain situations, spinal analgesia should not be negated to cancer patients, and oncologists should address this group of patients to other specialists. PMID:21684173

  1. Can S-1 replace fluorouracil for advanced gastric cancer? A PRISMA-compliant systematic review and meta-analysis.

    PubMed

    Chen, Xiao-Dong; He, Fu-Qian; Chen, Mi; Tang, Ling-Chao; Tang, Xiao-Li

    2016-06-01

    It remains to be seen whether S-1 can be a replacement for infusional fluorouracil (5-FU) for advanced gastric cancer (AGC). The aim of this study was to compare the efficacy and safety of S-1 with 5-FU in AGC.PubMed and Cochrane Library were searched. Randomized controlled trials and meta-analyses comparing S-1 with 5-FU for AGC were eligible. Meta-analysis was performed using RevMan 5.2.Seven trials involving 2443 patients were included. Compared with 5-FU, S-1 showed no significant prolongation of overall survival (OS) (hazard ratio [HR] = 0.91, 95% confidence interval [CI] [0.83-1.01], P = 0.07) and progression-free survival (HR = 0.89, 95% CI [0.70-1.13], P = 0.35), but longer time to treatment failure (HR = 0.74, 95% CI [0.56-0.97], P = 0.03). The objective response rates were comparable (risk ratio [RR] = 1.36, 95% CI [0.95, 1.96], P = 0.10). Regarding treatment-related deaths and hematological toxicities, there was significant heterogeneity between Asian and non-Asian trials, and subgroup analysis was applied. In Asian patients, there was a significant increase in hematological toxicities such as leukopenia (grade 1-4: RR = 1.22, 95% CI [1.08, 1.37], P = 0.001; grade 3-4: RR = 2.21, 95% CI [1.52, 3.21], P < 0.0001), neutropenia (grade 1-4: RR = 1.29, 95% CI [1.11, 1.48], P = 0.0005; grade 3-4: RR = 1.87, 95% CI [1.11, 3.17], P = 0.02), and thrombocytopenia (grade 1-4: RR = 1.71, 95% CI [1.22, 2.41], P = 0.002) in S-1-containing regimens compared with 5-FU-containing regimens, but without significant difference in treatment-related mortality rate (risk difference [RD] = 0.00, 95% CI [-0.01, 0.01], P = 0.68). In non-Asian patients, S-1-containing regimens were, however, associated with significantly fewer treatment-related deaths (RD = -0.02, 95% CI [-0.05, -0.00], P = 0.04), as well as less all grade 1-4 and grade 3-4 hematological toxicities except anemia. There was no significant heterogeneity in nonhematologic toxicities between Asian and non

  2. Stereotactic Body Radiotherapy and Gemcitabine for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Mahadevan, Anand; Jain, Sanjay; Goldstein, Michael; Miksad, Rebecca; Pleskow, Douglas; Sawhney, Mandeep; Brennan, Darren M.D.; Callery, Mark; Vollmer, Charles

    2010-11-01

    Purpose: Patients with nonmetastatic locally advanced unresectable pancreatic cancer have a dismal prognosis. Conventional concurrent chemoradiotherapy requires 6 weeks of daily treatment and can be arduous. We explored the safety and effectiveness of a 3-day course of hypofractionated stereotactic body radiotherapy (SBRT) followed by gemcitabine in this population. Patients and Methods: A total of 36 patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with {>=}12 months of follow-up were included. They received three fractions of 8, 10, or 12 Gy (total dose, 24-36 Gy) of SBRT according to the tumor location in relation to the stomach and duodenum, using fiducial-based respiratory motion tracking on a robotic radiosurgery system. The patients were then offered gemcitabine for 6 months or until tolerance or disease progression. Results: With an overall median follow-up of 24 months (range, 12-33), the local control rate was 78%, the median overall survival time was 14.3 months, the median carbohydrate antigen 19-9-determined progression-free survival time was 7.9 months, and the median computed tomography-determined progression-free survival time was 9.6 months. Of the 36 patients, 28 (78%) eventually developed distant metastases. Six patients (17%) were free of progression at the last follow-up visit (range, 13-30 months) as determined by normalized tumor markers with stable computed tomography findings. Nine Grade 2 (25%) and five Grade 3 (14%) toxicities attributable to SBRT occurred. Conclusion: Hypofractionated SBRT can be delivered quickly and effectively in patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with acceptable side effects and minimal interference with gemcitabine chemotherapy.

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

    ClinicalTrials.gov

    2013-01-24

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

  4. [Certain aspects of neoadjuvant therapy of locally advanced breast cancer].

    PubMed

    Voznyĭ, E K; Gurov, S N; Dobrovol'skaia, N Iu

    2001-01-01

    The paper presents the results of a complex investigation of patients with locally-advanced breast cancer who received neoadjuvant chemotherapy or chemoradiation at initial stage. The clinical and pathomorphological effects, nature of neoadjuvant therapy and number of courses were followed up for 5- and 10-year periods. A direct correlation was found between number of courses for chemotherapy-sensitive patients, on the one hand, and greater effect, more intensive medicinal pathomorphism and longer recurrence-free survival, particularly, at later stages, on the other. PMID:11826490

  5. Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis

    PubMed Central

    Wang, Yuan; Hu, Guo-fang; Zhang, Qian-qian; Tang, Ning; Guo, Jun; Liu, Li-yan; Han, Xiao; Wang, Xia; Wang, Zhe-hai

    2016-01-01

    Background Pancreatic cancer is considered as a chemoresistant neoplasm with extremely dismal prognosis. Gemcitabine is recommended as the standard agent for locally advanced or metastatic pancreatic cancer. A series of trials have been conducted to improve the outcome of advanced pancreatic cancer with other anticancer drugs in combination with gemcitabine. Unfortunately, the designers of the clinical trials failed to improve the poor prognosis of patients with advanced pancreatic cancer. Erlotinib was the first additional drug that improved the overall survival of patients with advanced pancreatic cancer with gemcitabine. We performed this systematic review and meta-analysis to explore the efficacy and safety of the combination of gemcitabine with erlotinib (GemErlo) for patients with advanced pancreatic cancer using the currently available evidence. Methods PubMed/MEDLINE, EMBASE, the Cochrane Library, and relevant abstracts of major conferences were comprehensively searched. Data results on objective response rate, disease control rate, and 1-year survival were pooled by using MetaAnalyst with a random-effects model. Results on progression-free survival and overall survival were only summarized descriptively. Results A total of 24 studies with 1,742 patients with locally advanced or metastatic pancreatic cancer treated with GemErlo were included. Combined objective response rate was 14.4% (95% CI: 11.6%–17.7%), disease control rate was 55.0% (95% CI: 51.5%–58.5%), and 1-year survival rate was 28.5% (95% CI: 24.0%–33.4%). Progression-free survival ranged from 2.63 to 9.6 months, and overall survival varied from 6 to 10 months. As for the toxicity profile, the most common adverse events (AEs) were hematologic reactions, skin rash, and gastrointestinal reactions. Other severe AEs, which had low incidence, included treatment-induced death and interstitial lung disease. Conclusion Our study showed that GemErlo is associated with reasonable activity in treating

  6. [Maintenance therapy for advanced non-small-cell lung cancer].

    PubMed

    Saruwatari, Koichi; Yoh, Kiyotaka

    2014-08-01

    Maintenance therapy is a new treatment strategy for advanced non-small-cell lung cancer(NSCLC), and it consists of switch maintenance and continuation maintenance.Switch maintenance is the introduction of a different drug, not included as part of the induction therapy, immediately after completion of 4 cycles of first-line platinum-based chemotherapy.Continuation maintenance is a continuation of at least one of the drugs used in the induction therapy in the absence of disease progression.Several phase III trials have reported survival benefits with continuation maintenance of pemetrexed and switch maintenance of pemetrexed or erlotinib.Therefore, maintenance therapy has become a part of the standard first-line treatment for advanced NSCLC.However, further research is needed to elucidate the selection criteria of patients who may benefit the most from maintenance therapy. PMID:25132023

  7. Drug-Induced Hematologic Syndromes

    PubMed Central

    Mintzer, David M.; Billet, Shira N.; Chmielewski, Lauren

    2009-01-01

    Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications. PMID:19960059

  8. Improvements in diagnosis have changed the incidence of histological types in advanced gastric cancer.

    PubMed Central

    Ikeda, Y.; Mori, M.; Kamakura, T.; Haraguchi, Y.; Saku, M.; Sugimachi, K.

    1995-01-01

    The data on 912 patients with early cancer and 1245 with advanced cancer who were seen between 1971 and 1990 were compared. The incidence of undifferentiated-type cancer increased significantly in patients with advanced gastric cancer, but not in patients with early gastric cancer. When the histological types were compared with regard to sex, age and location in patients with early gastric cancer the undifferentiated type was found to increase only in males, while in patients with advanced gastric cancer the undifferentiated type increased in both sexes as well as in younger patients and in both the upper and middle third of the stomach. These differences in the trends between early and advanced cancers are probably due to the different degrees of diagnostic accuracy for the early detection of histological types. PMID:7640228

  9. Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer

    MedlinePlus

    ... Prevention Lung Cancer Screening Research Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer ( ... starting treatment without their disease getting worse (progression-free survival), as assessed by radiologic review. Results Progression- ...

  10. Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer

    PubMed Central

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Matsumoto, Yoshihiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients. PMID:27182156

  11. Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer.

    PubMed

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Matsumoto, Yoshihiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-05-14

    The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients. PMID:27182156

  12. Pretargeted Radioimmunotherapy for Hematologic and Other Malignancies

    PubMed Central

    Press, Oliver W.; Pagel, John M.

    2010-01-01

    Summation Radioimmunotherapy (RIT) has emerged as one of the most promising treatment options, particularly for hematologic malignancies. However, this approach has generally been limited by a suboptimal therapeutic index (target-to-nontarget ratio) and an inability to deliver sufficient radiation doses to tumors selectively. Pretargeted RIT (PRIT) circumvents these limitations by separating the targeting vehicle from the subsequently administered therapeutic radioisotope, which binds to the tumor-localized antibody or is quickly excreted if unbound. A growing number of preclinical proof-of-principle studies demonstrate that PRIT is feasible and safe and provides improved directed radionuclide delivery to malignant cells compared with conventional RIT while sparing normal cells from nonspecific radiotoxicity. Early phase clinical studies corroborate these preclinical findings and suggest better efficacy and lesser toxicities in patients with hematologic and other malignancies. With continued research, PRIT-based treatment strategies promise to become cornerstones to improved outcomes for cancer patients despite their complexities. PMID:20423225

  13. Advances of stereotactic body radiotherapy in pancreatic cancer

    PubMed Central

    Wei, Qichun; Yu, Wei; Rosati, Lauren M.

    2015-01-01

    Pancreatic cancer (PCA) is one of the most aggressive tumors with few effective treatment modalities. It is the 4th and 7th leading cause of cancer death in the United States and China, respectively. At the time of diagnosis, only 20% of cases present with a resectable tumor, and about 40% with a locally advanced tumor that is considered unresectable. Even resected patients still have a poor prognosis, with an incidence of local recurrence ranging from 20% to 60%. It is also reported that up to 30% of PCA patients die from locally obstructive disease with few or no distant metastases. These findings have highlighted the importance of local radiation therapy in the treatment of PCA. As the role of conventional chemoradiotherapy remains controversial, the dawn of the pancreas stereotactic body radiation therapy (SBRT) era represents a potential paradigm shift in the management of PCA. SBRT delivers a higher biological effective dose to the tumor with sharp dose escalation in a shorter treatment time course. Pancreas SBRT is a novel therapeutic option to achieve local tumor control with minimal toxicity. Herein, we review the advancement of SBRT for PCA patients with different stages of pancreatic adenocarcinoma. PMID:26361404

  14. Targeted therapy in Advanced Bladder cancer- what have we learned?

    PubMed Central

    Jordan, Emmet; Iyer, Gopa

    2016-01-01

    Synopsis Urothelial carcinoma (UC) is the second most common genitourinary malignancy in the United States. In the metastatic setting, cisplatin-based chemotherapy results in a median overall survival (OS) of 12–15 months and remains the only standard of care for this disease. Despite advances in the treatment of other genitourinary malignancies, no novel therapies have been FDA-approved for UC in the last 20 years. To date, no clinical trials of targeted agents in UC have led to improvements in survival compared to cytotoxic therapy. The Cancer Genome Atlas (TCGA) has detected numerous potentially actionable genetic alterations in bladder cancer, providing a roadmap for the use of small molecule inhibitors in this disease. Additionally, the advancement of Next Generation sequencing technologies within the past five years has allowed for rapid, deep sequencing to define the molecular profile of tumors in real time. In this chapter, we outline representative trials of targeted therapies in UC and discuss the significance of genetic pre-selection in trial design as a method to optimize responses to these agents, thus hopefully expanding the armamentarium of treatment options against this lethal disease. PMID:25882566

  15. The role of surgery in advanced epithelial ovarian cancer

    PubMed Central

    Martín-Cameán, María; Delgado-Sánchez, Elsa; Piñera, Antonio; Diestro, Maria Dolores; De Santiago, Javier; Zapardiel, Ignacio

    2016-01-01

    Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3–17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer. PMID:27594911

  16. The role of surgery in advanced epithelial ovarian cancer.

    PubMed

    Martín-Cameán, María; Delgado-Sánchez, Elsa; Piñera, Antonio; Diestro, Maria Dolores; De Santiago, Javier; Zapardiel, Ignacio

    2016-01-01

    Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3-17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer. PMID:27594911

  17. CC-486 (Oral Azacitidine) Bioequivalence Study in Patients With Solid Tumor or Hematologic Malignancies

    ClinicalTrials.gov

    2016-08-10

    Hematological Neoplasms; Non-Hodgkin's Lymphoma; Hodgkin's Lymphoma; Lymphoma; Multiple Myeloma; Acute Myeloid Leukemia; Leukemia; Myelodysplastic Syndromes; Neoplasms; Melanoma; Breast Cancer; Metastatic Breast Cancer; Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Renal Cell Carcinoma; Glioblastoma Multiforme; Osteosarcoma; Sarcoma; Thyroid Cancer; Genitourinary

  18. FOREWORD: Conference on Advanced Metrology for Cancer Therapy 2011 Conference on Advanced Metrology for Cancer Therapy 2011

    NASA Astrophysics Data System (ADS)

    Ankerhold, Ulrike

    2012-10-01

    Although physical treatments play a central role in cancer therapy, SI-traceable metrology has only been established for some of them. Several forms of treatment currently used (particularly intensity-modulated radiation therapy (IMRT), hadron therapy, high-intensity therapeutic ultrasound (HITU) and brachytherapy) suffer from the limited metrological support, which restricts the success of these techniques. Recognizing this deficit, the European Union identified metrology for health as one of the first four Targeted Programmes in the framework of the European Metrology Research Programme (EMRP) running from 2008 to 2011. This programme included two EMRP projects addressing metrology for cancer therapy: project T2.J06 dealing with brachytherapy project T2.J07 dealing with external beam cancer therapy using ionizing radiation and high-intensity therapeutic ultrasound. Primary measurement standards applicable to modern treatment conditions were developed under both projects, together with measurement techniques which are meant as a basis for future protocols for dosimetry, treatment planning and monitoring. In order to provide a platform for the presentation of current developments in clinical measurement techniques for cancer therapy, together with the achievements of both projects, an international Conference on Advanced Metrology for Cancer Therapy (CAMCT) was held from 29 November to 1 December 2011 at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Germany. The main sessions of the conference: Primary and secondary standards of absorbed dose to water for IMRT and brachytherapy, 3D dose distributions and treatment planning for IMRT and brachytherapy, Hadron therapy (protons and carbon ions), High-intensity therapeutic ultrasound (HITU), were geared to the main foci of the projects. Metrologists and medical physicists from countries all over the world attended the conference and made it into a forum for the exchange of information and expertise

  19. Chemotherapy advances in small-cell lung cancer.

    PubMed

    Chan, Bryan A; Coward, Jermaine I G

    2013-10-01

    Although chemotherapeutic advances have recently been heralded in lung adenocarcinomas, such success with small-cell lung cancer (SCLC) has been ominously absent. Indeed, the dismal outlook of this disease is exemplified by the failure of any significant advances in first line therapy since the introduction of the current standard platinum-etoposide doublet over 30 years ago. Moreover, such sluggish progress is compounded by the dearth of FDA-approved agents for patients with relapsed disease. However, over the past decade, novel formulations of drug classes commonly used in SCLC (e.g. topoisomerase inhibitors, anthracyclines, alkylating and platinum agents) are emerging as potential alternatives that could effectively add to the armamentarium of agents currently at our disposal. This review is introduced with an overview on the historical development of chemotherapeutic regimens used in this disease and followed by the recent encouraging advances witnessed in clinical trials with drugs such as amrubicin and belotecan which are forging new horizons for future treatment algorithms. PMID:24163749

  20. Targeting oncogenic Ras signaling in hematologic malignancies

    PubMed Central

    Ward, Ashley F.; Braun, Benjamin S.

    2012-01-01

    Ras proteins are critical nodes in cellular signaling that integrate inputs from activated cell surface receptors and other stimuli to modulate cell fate through a complex network of effector pathways. Oncogenic RAS mutations are found in ∼ 25% of human cancers and are highly prevalent in hematopoietic malignancies. Because of their structural and biochemical properties, oncogenic Ras proteins are exceedingly difficult targets for rational drug discovery, and no mechanism-based therapies exist for cancers with RAS mutations. This article reviews the properties of normal and oncogenic Ras proteins, the prevalence and likely pathogenic role of NRAS, KRAS, and NF1 mutations in hematopoietic malignancies, relevant animal models of these cancers, and implications for drug discovery. Because hematologic malignancies are experimentally tractable, they are especially valuable platforms for addressing the fundamental question of how to reverse the adverse biochemical output of oncogenic Ras in cancer. PMID:22898602

  1. Phase I Study of Axitinib in Combination with Cisplatin and Capecitabine in Patients with Previously Untreated Advanced Gastric Cancer

    PubMed Central

    Oh, Do-Youn; Doi, Toshihiko; Shirao, Kuniaki; Lee, Keun-Wook; Park, Sook Ryun; Chen, Ying; Yang, Liqiang; Valota, Olga; Bang, Yung-Jue

    2015-01-01

    Purpose This phase I trial evaluated the question of whether the standard starting dose of axitinib could be administered in combination with therapeutic doses of cisplatin/capecitabine in patients with previously untreated advanced gastric cancer, and assessed overall safety, pharmacokinetics, and preliminary antitumor activity of this combination. Materials and Methods Patients in dose level (DL) 1 received axitinib 5 mg twice a day (days 1 to 21) with cisplatin 80 mg/m2 (day 1) and capecitabine 1,000 mg/m2 twice a day (days 1 to 14) in 21-day cycles. Maximum tolerated dose (MTD) was the highest dose at which ≤ 30% of the first 12 patients experienced a dose-limiting toxicity (DLT) during cycle 1. Ten additional patients were enrolled and treated at the MTD in order to obtain additional safety and pharmacokinetic data. Results Three DLTs occurred during cycle 1 in three (25%) of the first 12 patients: ruptured abdominal aortic aneurysm, acute renal failure, and > 5 consecutive days of missed axitinib due to thrombocytopenia. DL1 was established as the MTD, since higher DL cohorts were not planned. Common grade 3/4 non-hematologic adverse events in 22 patients treated at DL1 included hypertension (36.4%) and decreased appetite and stomatitis (18.2% each). Cisplatin/capecitabine slightly increased axitinib exposure; axitinib decreased capecitabine and 5-fluorouracil exposure. Eight patients (36.4%) each had partial response or stable disease. Median response duration was 9.1 months; median progression-free survival was 3.8 months. Conclusion In patients with advanced gastric cancer, standard doses of axitinib plus therapeutic doses of cisplatin and capecitabine could be administered in combination. Adverse events were manageable. PMID:25687867

  2. Optimal Number of Endoscopic Biopsies in Diagnosis of Advanced Gastric and Colorectal Cancer

    PubMed Central

    Choi, Yeowon; Choi, Hyo Sun; Jeon, Woo Kyu; Kim, Byung Ik; Park, Dong Il; Cho, Yong Kyun; Kim, Hong Joo; Park, Jung Ho

    2012-01-01

    Endoscopic biopsy is necessary to confirm a histopathologic diagnosis. Currently, 6 to 8 biopsies are recommended for diagnosis of a suspected malignant lesion. However, multiple biopsies may result in several problems, such as an increased risk of bleeding, procedure prolongation, and increased workload to pathologists. The aim of this study was to clarify the optimal number of endoscopic biopsy specimens required in diagnosis of advanced gastrointestinal cancer. Patients who were diagnosed with advanced gastrointestinal cancer during endoscopy were included. Five specimens were obtained sequentially from viable tissue of the cancer margin. Experienced pathologists evaluated each specimen and provided diagnoses. A total of 91 patients were enrolled. Fifty-nine subjects had advanced gastric cancer, and 32 had advanced colon cancer. Positive diagnosis rates of the first, second, and third advanced gastric cancer specimens were 81.3%, 94.9%, and 98.3%, respectively, while positive diagnosis rates of advanced colon cancer specimens were 78.1%, 87.5%, and 93.8%. Further biopsies did not increase positive diagnosis cumulative rates. This study demonstrated that three specimens were sufficient to make correct pathologic diagnoses in advanced gastrointestinal cancer. Therefore, we recommend 3 or 4 biopsies from viable tissue in advanced gastrointestinal cancer to make a pathologic diagnosis during endoscopy. PMID:22219611

  3. Cancer Related Fatigue and Quality of Life in Patients with Advanced Prostate Cancer Undergoing Chemotherapy

    PubMed Central

    Charalambous, Andreas; Kouta, Christiana

    2016-01-01

    Cancer related fatigue (CRF) is a common and debilitating symptom that can influence quality of life (QoL) in cancer patients. The increase in survival times stresses for a better understanding of how CRF affects patients' QoL. This was a cross-sectional descriptive study with 148 randomly recruited prostate cancer patients aiming to explore CRF and its impact on QoL. Assessments included the Cancer Fatigue Scale, EORTC QLQ-C30, and EORTC QLQ-PR25. Additionally, 15 in-depth structured interviews were performed. Quantitative data were analyzed with simple and multiple regression analysis and independent samples t-test. Qualitative data were analyzed with the use of thematic content analysis. The 66.9% of the patients experienced CRF with higher levels being recorded for the affective subscale. Statistically significant differences were found between the patients reporting CRF and lower levels of QoL (mean = 49.1) and those that did not report fatigue and had higher levels of QoL (mean = 72.1). The interviews emphasized CRF's profound impact on the patients' lives that was reflected on the following themes: “dependency on others,” “loss of power over decision making,” and “daily living disruption.” Cancer related fatigue is a significant problem for patients with advanced prostate cancer and one that affects their QoL in various ways. PMID:26981530

  4. Borrmann Type 4 Advanced Gastric Cancer: Focus on the Development of Scirrhous Gastric Cancer

    PubMed Central

    Jung, Kyoungwon; Park, Moo In; Kim, Sung Eun; Park, Seun Ja

    2016-01-01

    Early diagnosis of Borrmann type 4 advanced gastric cancer (AGC) is very important for improving the prognosis of AGC patients. Because there is no definite mass in most cases of Borrmann type 4 AGC, its accurate diagnosis via endoscopy requires an understanding of its pathogenesis and developmental process. Moreover, many people confuse linitis plastica (LP) type gastric cancer (GC), scirrhous GC, and Borrmann type 4 AGC. To distinguish each of these cancers, knowledge of their endoscopic and pathological differences is necessary, especially for LP type GCs in the developmental stage. In conclusion, diagnosis of pre-stage or latent LP type GC before progression to typical LP type GC requires the detection of IIc-like lesions in the fundic gland area. It is also crucial to identify any abnormalities such as sclerosis of the gastric wall and hypertrophy of the mucosal folds during endoscopy. PMID:27456608

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

    ClinicalTrials.gov

    2015-09-28

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

  6. Advances in Breast Cancer – Looking Back over the Year

    PubMed Central

    Lüftner, D.; Lux, M. P.; Maass, N.; Schütz, F.; Schwidde, I.; Fasching, P. A.; Fehm, T.; Janni, W.; Kümmel, S.; Kolberg, H.-C.

    2012-01-01

    Treatment options as well as the characteristics for therapeutic decisions in patients with primary and advanced breast cancer are increasing in number and variety. New targeted therapies in combination with established chemotherapy schemes are broadening the spectrum, yet not every new, promising combination achieves a better result. New data from the field of pharmacogenomics point to prognostic and predictive factors that take not only the properties of the tumour but also the genetic disposition of the patient into consideration. Current therapeutic decision-making is thus based on a combination of classical clinical and modern molecular biomarkers. Health-economic concerns are also being taken into consideration more frequently, meaning political decisions may also become a factor. This review presents the trends over the past year. PMID:26640285

  7. Hematologic manifestations of Helicobacter pylori infection

    PubMed Central

    Campuzano-Maya, Germán

    2014-01-01

    Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases. PMID:25278680

  8. Novel immunotherapies for hematological malignancies

    PubMed Central

    Nelson, Michelle H.; Paulos, Chrystal M.

    2014-01-01

    Summary The immune system is designed to discriminate between self and tumor tissue. Through genetic recombination, there is fundamentally no limit to the number of tumor antigens that immune cells can recognize. Yet, tumors use a variety of immunosuppressive mechanisms to evade immunity. Insight into how the immune system interacts with tumors is expanding rapidly and has accelerated the translation of immunotherapies into medical breakthroughs. Herein, we appraise the state of the art in immunotherapy with a focus on strategies that exploit the patient’s immune system to kill cancer. We review various forms of immune-based therapies, which have shown significant promise in patients with hematological malignancies, including (i) conventional monoclonal therapies like rituximab, (ii) engineered monoclonal antibodies called bispecific T cell engagers (BiTEs), (iii) monoclonal antibodies and pharmaceutical drugs that block inhibitory T-cell pathways (i.e. PD-1, CTLA-4 and IDO), and (iv) adoptive cell transfer (ACT) therapy with T cells engineered to express chimeric antigen receptors (CARs) or T-cell receptors (TCRs). We also assess the idea of using these therapies in combination and conclude by suggesting multi-prong approaches to improve treatment outcomes and curative responses in patients. PMID:25510273

  9. Novel immunotherapies for hematologic malignancies.

    PubMed

    Nelson, Michelle H; Paulos, Chrystal M

    2015-01-01

    The immune system is designed to discriminate between self and tumor tissue. Through genetic recombination, there is fundamentally no limit to the number of tumor antigens that immune cells can recognize. Yet, tumors use a variety of immunosuppressive mechanisms to evade immunity. Insight into how the immune system interacts with tumors is expanding rapidly and has accelerated the translation of immunotherapies into medical breakthroughs. Herein, we appraise novel strategies that exploit the patient's immune system to kill cancer. We review various forms of immune-based therapies, which have shown significant promise in patients with hematologic malignancies, including (i) conventional monoclonal therapies like rituximab; (ii) engineered monoclonal antibodies called bispecific T-cell engagers; (iii) monoclonal antibodies and pharmaceutical drugs that block inhibitory T-cell pathways (i.e. PD-1, CTLA-4, and IDO); and (iv) adoptive cell transfer therapy with T cells engineered to express chimeric antigen receptors or T-cell receptors. We also assess the idea of using these therapies in combination and conclude by suggesting multi-prong approaches to improve treatment outcomes and curative responses in patients. PMID:25510273

  10. Evaluation of Instrumental Activities of Daily Living in Greek Patients with Advanced Cancer

    ERIC Educational Resources Information Center

    Mystakidou, Kyriaki; Parpa, Efi; Tsilika, Eleni; Panagiotoua, Irene; Roumeliotou, Anna; Symeonidi, Matina; Galanos, Antonis; Kouvaris, Ioannis

    2013-01-01

    Translation of the instrumental activities of daily living (IADL) was carried out and its psychometric properties were assessed in a Greek sample of patients with advanced cancer. The scale was translated with the forward-backward procedure into the Greek language. It was initially administered to 136 advanced cancer patients. To assess…

  11. Aggressive chemosurgical debulking in patients with advanced ovarian cancer.

    PubMed

    Ng, L W; Rubin, S C; Hoskins, W J; Jones, W B; Hakes, T B; Markman, M; Reichman, B; Almadrones, L; Lewis, J L

    1990-09-01

    From July 1986 to June 1989, 43 evaluable patients with advanced ovarian cancer were treated on protocol with initial cytoreductive surgery, two courses of high-intensity intravenous Cytoxan (1000 mg/m2) and cisplatin (120-200 mg/m2) chemotherapy, and repeat debulking laparotomy in an effort to maximize response to a subsequent four cycles of intraperitoneal platinum-based chemotherapy. Two patients were stage IIIA, 2 stage IIIB, 28 stage IIIC, and 11 stage IV. Five tumors were grade 1, 9 grade 2, and 29 grade 3. Thirty-eight (88%) patients had bulky tumor (5-25 cm) found at first laparotomy; 25 of these had greater than 1-cm residual after initial debulking. Following two cycles of intensive intravenous chemotherapy 18 of these 25 had greater than 1-cm disease found at second laparotomy; 12 of 18 underwent secondary cytoreduction to less than 1 cm. Thus, 30 of these 38 (79%) patients entered the intraperitoneal phase of the protocol with less than 1-cm disease. Four patients had 2- to 5-cm tumor at initial laparotomy; two of four were debulked to less than 1-cm residual. All four were found to have less than 1-cm disease at second laparotomy. This combination regimen was well tolerated. There was one treatment-related death. In sum, 42 of 43 patients had tumor greater than 2 cm at staging laparotomy and 38 (88%) had large, bulky disease (5-25 cm); 34 of 43 (79%) entered the intraperitoneal phase of the protocol with optimal (less than 1-cm) disease. Aggressive chemosurgical cytoreduction in patients with bulky advanced ovarian cancer can leave a large proportion of patients with minimal residual disease and maximize their chances of responding to subsequent intraperitoneal chemotherapy. PMID:2227548

  12. Neoadjuvant chemotherapy for high-grade advanced gastric cancer.

    PubMed

    Yonemura, Y; Sawa, T; Kinoshita, K; Matsuki, N; Fushida, S; Tanaka, S; Ohoyama, S; Takashima, T; Kimura, H; Kamata, T

    1993-01-01

    Fifty-five patients with high-grade advanced gastric cancer in whom the presence of stage IV was confirmed by preoperative diagnostic imaging were treated with PMUE therapy by a combined use of cisplatin (CDDP) 75 mg/m2, mitomycin C (MMC) 10 mg/body, etoposide 150 mg/body, and UFT (a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil in a molar ratio of 1:4) 400 mg/day. CDDP and MMC was administered intravenously on the first day, followed by etoposide 50 mg/day on the 3rd, 4th, and 5th days. All the patients had measurable lesions that were evaluated by computed tomography scanning before and after the treatments. These patients were allocated randomly to two groups. Of these cases, 29 belonged to the neoadjuvant chemotherapy (NAC) group to whom PMUE therapy was given preoperatively; the remaining 26 patients underwent operation first and received PMUE thereafter (control group). Background factors did not differ significantly between the two groups. The response rate was higher in the NAC group than in the control group (62% in the former versus 35% in the latter). The resectability rates were 79% and 88% in the NAC and control groups, respectively. However, the rate of potentially curable cases was higher in the NAC group than in the control group (38% in the former versus 15% in the latter). Among the nonresection cases, the prognosis was highly unfavorable in both groups. In the resection cases, however, the survival rate was significantly better in the NAC group than in the control group. These results may indicate that in patients with high-grade, advanced gastric cancer initial chemotherapy (neoadjuvant chemotherapy) and then surgery should be considered. PMID:8511923

  13. Orphan symptoms in advanced cancer patients followed at home.

    PubMed

    Mercadante, Sebastiano; Porzio, Giampiero; Valle, Alessandro; Fusco, Flavio; Aielli, Federica; Adile, Claudio; Casuccio, Alessandra

    2013-12-01

    Orphan symptoms are rarely assessed, particularly at home. The aim of this multicenter prospective study was to assess the prevalence of these symptoms and eventual factors possibly associated in advanced cancer patients at admission of a home care program. A prospective study was performed at three home care programs in Italy. Patients' data were collected, including age, sex, diagnosis, and Karnofsky status. Possible contributing factors were analyzed; preexisting neurological diseases, cerebral metastases, hyperthermia, diabetes, a state of dehydration clinically evident and/or oliguria, possible biochemical parameters when available, data regarding recent chemotherapy, opioids and doses, use of neuroleptics, benzodiazepine or anticonvulsants, corticosteroids, anti-inflammatory, and antibiotics were collected. Myoclonus, hiccup, sweating, pruritus, and tenesmus, either rectal or vesical, were assessed, according to a preliminary definition, at time of home care program admission. Three hundred sixty-two patients were surveyed at the three home care programs. Globally, 48 patients presented one or more orphan symptoms in the period taken into consideration, and 7 patients presented more than 1 symptom. One patient presented occasional and diffuse myoclonus. Nineteen patients presented sweating, 13 patients presented pruritus, and 14 patients presented hiccup. Finally, nine patients presented rectal or vesical tenesmus. There was a significant correlation between sweating and transdermal fentanyl use (P = 0.044), fever (P = 0.001), hiccup (P < 0.0005), and vesical tenesmus (P = 0.028). Pruritus was not associated to any factor. Hiccup was associated with gender (males, P = 0.006) and sweating (P < 0.0005). Vesical tenesmus was associated with fever (P = 0.019) and sweating (P = 0.028). Although the symptoms examined have a low prevalence in advanced cancer patients admitted to home care, the distress for patients may be high and

  14. Integrating Palliative Care Into the Care of Patients With Advanced Lung Cancer.

    PubMed

    Kapo, Jennifer M; Akgün, Kathleen M

    2015-01-01

    Lung cancer is the leading cause of death due to malignancy. Although lung cancer mortality has been decreasing in recent years, it remains substantially higher than other causes of cancer death. Median survival for patients with locally advanced non-small cell lung cancer, defined as lung cancer involving regional lymph nodes, is estimated to be approximately 10 to 17 months, and median survival for patients with metastatic disease is only 6 to 9 months. In addition, patients with advanced lung cancer often experience debilitating symptoms and poor quality of life. Pain, dyspnea, and fatigue are most frequently reported and affect at least 65% of patients with advanced lung cancer. Given this burden of symptoms and high mortality, patients and their families facing a diagnosis of advanced lung cancer are in need of support. Palliative care, with its focus on addressing the emotional, physical, and spiritual sources of suffering utilizing the expertise of an interdisciplinary team, can provide this comprehensive support. This review describes the role of supportive and palliative care integrated into the treatment of patients with a diagnosis of advanced lung cancer with sections focused on the evaluation and treatment of pain and dyspnea, approaches to challenging communication tasks, and the support of caregivers who care for patients with advanced lung cancer. PMID:26389769

  15. War and peace? The oncologic and the palliative care perspective on personalized cancer treatment in a patient with advanced cancer.

    PubMed

    Masel, Eva K; Schur, Sophie; Posch, Doris; Weixler, Dietmar; Meran, Johannes G; Schmidinger, Manuela; Watzke, Herbert H

    2015-08-01

    Personalized cancer treatment utilizing targeted therapies in a tailored approach is based on tumor and/or patient-specific molecular profiles. Recent clinical trials continue to look for new potential targets in heavily pretreated patients or rare disease entities. Careful selection of patients who may derive benefit from such therapies constitutes a challenge. This case report presents an experimental personalized cancer treatment in an advanced cancer patient and provides a list of issues for discussion: How can we combine treatment goals and simultaneously meet the individual needs in advanced cancer reconciling both perspectives: oncology and palliative care? PMID:25986998

  16. [{sup 18}F]FDG-PET Standard Uptake Value as a Metabolic Predictor of Bone Marrow Response to Radiation: Impact on Acute and Late Hematological Toxicity in Cervical Cancer Patients Treated With Chemoradiation Therapy

    SciTech Connect

    Elicin, Olgun; Callaway, Sharon; Prior, John O.; Bourhis, Jean; Ozsahin, Mahmut; Herrera, Fernanda G.

    2014-12-01

    Purpose: To quantify the relationship between bone marrow (BM) response to radiation and radiation dose by using {sup 18}F-labeled fluorodeoxyglucose positron emission tomography [{sup 18}F]FDG-PET standard uptake values (SUV) and to correlate these findings with hematological toxicity (HT) in cervical cancer (CC) patients treated with chemoradiation therapy (CRT). Methods and Materials: Seventeen women with a diagnosis of CC were treated with standard doses of CRT. All patients underwent pre- and post-therapy [{sup 18}F]FDG-PET/computed tomography (CT). Hemograms were obtained before and during treatment and 3 months after treatment and at last follow-up. Pelvic bone was autosegmented as total bone marrow (BM{sub TOT}). Active bone marrow (BM{sub ACT}) was contoured based on SUV greater than the mean SUV of BM{sub TOT}. The volumes (V) of each region receiving 10, 20, 30, and 40 Gy (V{sub 10}, V{sub 20}, V{sub 30}, and V{sub 40}, respectively) were calculated. Metabolic volume histograms and voxel SUV map response graphs were created. Relative changes in SUV before and after therapy were calculated by separating SUV voxels into radiation therapy dose ranges of 5 Gy. The relationships among SUV decrease, radiation dose, and HT were investigated using multiple regression models. Results: Mean relative pre-post-therapy SUV reductions in BM{sub TOT} and BM{sub ACT} were 27% and 38%, respectively. BM{sub ACT} volume was significantly reduced after treatment (from 651.5 to 231.6 cm{sup 3}, respectively; P<.0001). BM{sub ACT} V{sub 30} was significantly correlated with a reduction in BM{sub ACT} SUV (R{sup 2}, 0.14; P<.001). The reduction in BM{sub ACT} SUV significantly correlated with reduction in white blood cells (WBCs) at 3 months post-treatment (R{sup 2}, 0.27; P=.04) and at last follow-up (R{sup 2}, 0.25; P=.04). Different dosimetric parameters of BM{sub TOT} and BM{sub ACT} correlated with long-term hematological outcome. Conclusions: The volumes of BM

  17. Pulmonary disease in patients with hematologic malignancies.

    PubMed

    Poletti, Venerino; Trisolini, Rocco; Tura, Sante

    2002-03-01

    Patients with hematologic neoplasms frequently experience pulmonary disease. The possibility of a malignant involvement of the lung parenchyma is a well recognized and not unusual event, secondary spread due to lymphoproliferative disorders being the most common situation. Furthermore, the development and the advances in treatment options such as hematopoietic stem cell transplantation, radiation therapy and/or combined drug regimen use have significantly widened the spectrum of non-neoplastic pulmonary complications that can crop up in these patients. Infections, drug/radiation-induced toxicity, and graft-versus-host disease (GVHD)-related complications account by now for most pulmonary problems in hematologic patients and represent a difficult challenge both in diagnostic and in therapeutic terms for the clinician. The aim of this review is to highlight the clinicopathologic spectrum of lung diseases which can occur in the setting of hematologic malignancies. A particular emphasis is devoted to the diagnostic approach, high-resolution computed tomography (HRCT) assuming a key role since different patterns of CT abnormalities are associated with a different yield of the available diagnostic tools and may help in narrowing the differential diagnosis. PMID:12002382

  18. Nanopharmacology in translational hematology and oncology

    PubMed Central

    Tomuleasa, Ciprian; Braicu, Cornelia; Irimie, Alexandra; Craciun, Lucian; Berindan-Neagoe, Ioana

    2014-01-01

    Nanoparticles have displayed considerable promise for safely delivering therapeutic agents with miscellaneous therapeutic properties. Current progress in nanotechnology has put forward, in the last few years, several therapeutic strategies that could be integrated into clinical use by using constructs for molecular diagnosis, disease detection, cytostatic drug delivery, and nanoscale immunotherapy. In the hope of bringing the concept of nanopharmacology toward a viable and feasible clinical reality in a cancer center, the present report attempts to present the grounds for the use of cell-free nanoscale structures for molecular therapy in experimental hematology and oncology. PMID:25092977

  19. Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-07-01

    Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Bladder Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Pancreatic Cancer; Transitional Cell Carcinoma of the Bladder; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  20. Does Multidisciplinary Care Enhance the Management of Advanced Breast Cancer?: Evaluation of Advanced Breast Cancer Multidisciplinary Team Meetings

    PubMed Central

    Chirgwin, Jacquie; Craike, Melinda; Gray, Christine; Watty, Kathy; Mileshkin, Linda; Livingston, Patricia M.

    2010-01-01

    Purpose: To assess the contribution of the advanced breast cancer (ABC) multidisciplinary team meetings (MDMs) to patient care and clinical outcomes. Methods: Members of ABC MDMs at two health services completed questionnaires in November 2007. The questionnaire asked about the performance of the MDMs and their contribution to improvement in patient care in five domains: medical management, psychosocial care, palliative care, care in the community, and benefits for team members. A final section covered the perceived value and importance of the MDM in patient management. Descriptive statistics (frequencies, mean, and standard deviation) were used to summarize the performance, improvement, and importance scores. Results: A total of 27 multidisciplinary team members (73%) completed the questionnaire. The MDM performed best in medical management (mean performance score out of 5 [M] = 3.78) and palliative care (M = 3.77). These were also the areas that were most improved through the MDM. Benefits to team members and care in the community (both M = 3.05) ranked lowest by both measures. The MDM provided the most benefit for patient management in the areas of “awareness of services available” (M = 4.32), “efficiency of referrals” (M = 4.27) and “supportive care for patients” (M = 4.27). “Awareness of services available,” “psychological care for patients,” and “continuity of care” were considered the most important (M = 4.64). Conclusion: The study provides evidence that MDMs make an important contribution to the logistical and medical management of patients with advanced breast cancer. PMID:21358959

  1. Palliative Surgical Approach in Advanced Nonresponsive Mucinous Ovarian Cancer: A Rare Case Report

    PubMed Central

    Agarwal, Manika; Kumar, Ritesh; Topno, Noor; Mishra, Shweta; Dhirasaria, Ashish; Singh, A Santa

    2016-01-01

    Advanced mucinous ovarian cancer is a separate entity and has different biological behaviour. There is a wide range of therapeutic challenges and dilemmas in the management of these patients. The authors present a case of advanced ovarian mucinous cystadenocarcinoma with pseudomyxoma peritonei who had poor response to standard neoadjuvant chemotherapy. This case is highlighted to emphasize the challenges in the decision making for the management of advanced mucinous ovarian cancer. PMID:27162429

  2. High-Dose Chemotherapy, Total-Body Irradiation, and Autologous Stem Cell Transplantation or Bone Marrow Transplantation in Treating Patients With Hematologic Cancer or Solid Tumors

    ClinicalTrials.gov

    2013-05-07

    Breast Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  3. CPI-613 in Treating Patients With Advanced or Metastatic Bile Duct Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2015-12-28

    Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Unresectable Extrahepatic Bile Duct Cancer

  4. Planes, Trains, and Automobiles: Perspectives on CAR T Cells and Other Cellular Therapies for Hematologic Malignancies.

    PubMed

    Gill, Saar

    2016-08-01

    Hematologic oncologists now have at their disposal (or a referral away) a myriad of new options to get from point A (a patient with relapsed or poor-risk disease) to point B (potential tumor eradication and long-term disease-free survival). In this perspective piece, we discuss the putative mechanisms of action and the relative strengths and weaknesses of currently available cellular therapy approaches. Notably, while many of these approaches have been published in high impact journals, with the exception of allogeneic stem cell transplantation and of checkpoint inhibitors (PD1/PDL1 or CTLA4 blockade), the published clinical trials have mostly been early phase, uncontrolled studies. Therefore, many of the new cellular therapy approaches have yet to demonstrate incontrovertible evidence of enhanced overall survival compared with controls. Nonetheless, the science behind these is sure to advance our understanding of cancer immunology and ultimately to bring us closer to our goal of curing cancer. PMID:27136938

  5. Cross-sectional study on comorbidities and adverse events in patients with advanced and recurrent ovarian cancer in France

    PubMed Central

    Le Saux, Olivia; Taylor, Aliki; Chia, Victoria; Pillas, Demetris; Kaur, Moninder; Freyer, Gilles

    2015-01-01

    Purpose The purpose of this study was to evaluate the prevalence of comorbidities and adverse events (AEs), and determine the treatment patterns according to platinum-sensitivity status in patients with advanced (stage IIIB–IV) or recurrent epithelial ovarian cancer (EOC). Methods A cross-sectional study was carried out in France with patients over 18 years, diagnosed with advanced (stage IIIB–IV) or recurrent EOC between 2009 and 2012. A total of 23 physicians (oncologists and gynecologists) participated, contributing 127 patients. Data were abstracted by participating physicians into a case report form. Results Of the 127 patients included, 92 (72.4%) had advanced EOC and 35 (27.6%) had recurrent EOC. A total of 73 comorbidities were reported in 44 patients (34.6%). Vascular (10.2%), metabolic (7.1%), respiratory (5.5%), and psychiatric disorders (5.5%) were the most common types of comorbidities reported. Prevalence of AEs was 74.8%, of which 12.6% were classified as serious. The most common AEs were anemia (16.5%), hematologic events (12.6%), taste change (11.8%), and headache (7.1%). Throughout the follow-up period, twelve patient deaths were reported (six due to disease progression). Of 35 patients with recurrent disease, 16 were highly platinum sensitive (recurrence >12 months after stopping platinum-based therapy), eleven were partially platinum sensitive (recurrence 6–12 months after stopping platinum-based therapy), seven were platinum resistant (recurrence within 6 months of stopping platinum-based therapy or progression while receiving second- or later-line platinum-based therapy), and one was platinum refractory (recurrence within 6 months from the start of first-line platinum-based therapy). Conclusion In this cross-sectional study of advanced and metastatic ovarian cancer patients, approximately one-third of patients were diagnosed with comorbidities, and approximately three-quarters were diagnosed with AEs (12.6% with severe AEs). PMID

  6. [Advances in Surgical Treatment of Early Stage Non-small Cell Lung Cancer].

    PubMed

    Hu, Jian; Bao, Feichao

    2016-06-20

    Lung cancer is the leading cause of cancer-related deaths worldwide, computed tomography screening has made the disease spectrum of lung cancer shift from the previously predominating central local advanced squamous cell carcinoma to early stage lung adenocarcinoma represented by solitary pulmonary nodule, ground-glass opacity (GGO) and sub-centimeter nodule. This paper reviewed the recent proceeding in the surgical management of early stage lung cancer. PMID:27335305

  7. Cancer of the Pancreas: Molecular Pathways and Current Advancement in Treatment

    PubMed Central

    Polireddy, Kishore; Chen, Qi

    2016-01-01

    Pancreatic cancer is one of the most lethal cancers among all malignances, with a median overall survival of <1 year and a 5-year survival of ~5%. The dismal survival rate and prognosis are likely due to lack of early diagnosis, fulminant disease course, high metastasis rate, and disappointing treatment outcome. Pancreatic cancers harbor a variety of genetic alternations that render it difficult to treat even with targeted therapy. Recent studies revealed that pancreatic cancers are highly enriched with a cancer stem cell (CSC) population, which is resistant to chemotherapeutic drugs, and therefore escapes chemotherapy and promotes tumor recurrence. Cancer cell epithelial to mesenchymal transition (EMT) is highly associated with metastasis, generation of CSCs, and treatment resistance in pancreatic cancer. Reviewed here are the molecular biology of pancreatic cancer, the major signaling pathways regulating pancreatic cancer EMT and CSCs, and the advancement in current clinical and experimental treatments for pancreatic cancer. PMID:27471566

  8. [A Case of Advanced Esophageal Cancer and Tongue Cancer Treated with Induction DCF Chemotherapy Followed by Radical Surgery].

    PubMed

    Tanaka, Motomu; Koyanagi, Kazuo; Sugiura, Hitoshi; Kakefuda, Toshihiro

    2015-11-01

    A man in his 60s was admitted for the treatment of advanced cervical esophageal cancer with metastasis to the lymph nodes and advanced tongue cancer with metastasis to the lymph nodes. Esophageal cancer was suspected to have invaded the trachea. The tongue cancer was located on the left side and had invaded beyond the median line of the tongue. Both cancers were pathologically diagnosed as squamous cell carcinomas. Therefore, it was determined that pharyngo-laryngo- esophagectomy and total glossectomy were required prior to the treatment. However, after 2 courses of docetaxel/cisplatin/ 5-FU combined induction chemotherapy, both cancers remarkably decreased; consequently, an esophagectomy to preserve laryngeal function and partial glossectomy could be performed simultaneously. The patient is well without recurrence 1 year post-surgery. PMID:26602401

  9. Phase 1 Pharmacogenetic and Pharmacodynamic Study of Sorafenib With Concurrent Radiation Therapy and Gemcitabine in Locally Advanced Unresectable Pancreatic Cancer

    SciTech Connect

    Chiorean, E. Gabriela; Schneider, Bryan P.; Akisik, Fatih M.; Perkins, Susan M.; Anderson, Stephen; Johnson, Cynthia S.; DeWitt, John; Helft, Paul; Clark, Romnee; Johnston, Erica L.; Spittler, A. John; Deluca, Jill; Bu, Guixue; Shahda, Safi; Loehrer, Patrick J.; Sandrasegaran, Kumar; Cardenes, Higinia R.

    2014-06-01

    Purpose: To define the safety, efficacy, and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy (CRT) in locally advanced pancreatic cancer. Methods and Materials: Patients received gemcitabine 1000 mg/m{sup 2} intravenously weekly × 3 every 4 weeks per cycle for 1 cycle before CRT and continued for up to 4 cycles after CRT. Weekly gemcitabine 600 mg/m{sup 2} intravenously was given during concurrent intensity modulated radiation therapy of 50 Gy to gross tumor volume in 25 fractions. Sorafenib was dosed orally 400 mg twice daily until progression, except during CRT when it was escalated from 200 mg to 400 mg daily, and 400 mg twice daily. The maximum tolerated dose cohort was expanded to 15 patients. Correlative studies included dynamic contrast-enhanced MRI and angiogenesis genes polymorphisms (VEGF-A and VEGF-R2 single nucleotide polymorphisms). Results: Twenty-seven patients were enrolled. No dose-limiting toxicity occurred during induction gemcitabine/sorafenib followed by concurrent CRT. The most common grade 3/4 toxicities were fatigue, hematologic, and gastrointestinal. The maximum tolerated dose was sorafenib 400 mg twice daily. The median progression-free survival and overall survival for 25 evaluable patients were 10.6 and 12.6 months, respectively. The median overall survival for patients with VEGF-A -2578 AA, -1498 CC, and -1154 AA versus alternate genotypes was 21.6 versus 14.7 months. Dynamic contrast-enhanced MRI demonstrated higher baseline K{sup trans} in responding patients. Conclusions: Concurrent sorafenib with CRT had modest clinical activity with increased gastrointestinal toxicity in localized unresectable pancreatic cancer. Select VEGF-A/VEGF-R2 genotypes were associated with favorable survival.

  10. Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

    ClinicalTrials.gov

    2016-07-05

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; Endometrial Serous Adenocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Lung Carcinoid Tumor; Malignant Pancreatic Gastrinoma; Malignant Pancreatic Glucagonoma; Malignant Pancreatic Insulinoma; Malignant Pancreatic Somatostatinoma; Metastatic Digestive System Neuroendocrine Tumor G1; Ovarian Carcinosarcoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Pancreatic Alpha Cell Adenoma; Pancreatic Beta Cell Adenoma; Pancreatic Delta Cell Adenoma; Pancreatic G-Cell Adenoma; Pancreatic Polypeptide Tumor; Recurrent Adult Liver Carcinoma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Corpus Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

  11. Clinical cancer advances 2007: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

    PubMed

    Gralow, Julie; Ozols, Robert F; Bajorin, Dean F; Cheson, Bruce D; Sandler, Howard M; Winer, Eric P; Bonner, James; Demetri, George D; Curran, Walter; Ganz, Patricia A; Kramer, Barnett S; Kris, Mark G; Markman, Maurie; Mayer, Robert J; Raghavan, Derek; Ramsey, Scott; Reaman, Gregory H; Sawaya, Raymond; Schuchter, Lynn M; Sweetenham, John W; Vahdat, Linda T; Davidson, Nancy E; Schilsky, Richard L; Lichter, Allen S

    2008-01-10

    A MESSAGE FROM ASCO'S PRESIDENT: For the third year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO publishes this report to demonstrate the important progress being made on the front lines of clinical cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and organizations, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on the use of magnetic resonance imaging for breast cancer screening, the association between hormone replacement therapy and breast cancer incidence, the link between human papillomavirus and head and neck cancers, and the use of radiation therapy to prevent lung cancer from spreading. They also report on effective new targeted therapies for cancers that have been historically difficult to treat, such as liver cancer and kidney cancer, among many others. A total of 24 advances are featured in this year's report. These advances and many more over the past several years show that the nation's long-term investment in cancer research is paying off. But there are disturbing signs that progress could slow. We are now in the midst of the longest sustained period of flat government funding for cancer research in history. The budgets for the National Institutes of Health and the National Cancer Institute (NCI) have been unchanged for four years. When adjusted for inflation, cancer research funding has actually declined 12% since 2004. These budget constraints limit the NCI's ability to fund promising cancer research. In the past several years the number of grants that the NCI has been able to fund has significantly decreased; this year, in response to just the

  12. New Players for Advanced Prostate Cancer and the Rationalisation of Insulin-Sensitising Medication

    PubMed Central

    Gunter, Jennifer H.; Sarkar, Phoebe L.; Lubik, Amy A.; Nelson, Colleen C.

    2013-01-01

    Obesity and type 2 diabetes are recognised risk factors for the development of some cancers and, increasingly, predict more aggressive disease, treatment failure, and cancer-specific mortality. Many factors may contribute to this clinical observation. Hyperinsulinaemia, dyslipidaemia, hypoxia, ER stress, and inflammation associated with expanded adipose tissue are thought to be among the main culprits driving malignant growth and cancer advancement. This observation has led to the proposal of the potential utility of “old players” for the treatment of type 2 diabetes and metabolic syndrome as new cancer adjuvant therapeutics. Androgen-regulated pathways drive proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen deprivation therapy (ADT) exploits this dependence to systemically treat advanced prostate cancer resulting in anticancer response and improvement of cancer symptoms. However, the initial therapeutic response from ADT eventually progresses to castrate resistant prostate cancer (CRPC) which is currently incurable. ADT rapidly induces hyperinsulinaemia which is associated with more rapid treatment failure. We discuss current observations of cancer in the context of obesity, diabetes, and insulin-lowering medication. We provide an update on current treatments for advanced prostate cancer and discuss whether metabolic dysfunction, developed during ADT, provides a unique therapeutic window for rapid translation of insulin-sensitising medication as combination therapy with antiandrogen targeting agents for the management of advanced prostate cancer. PMID:23573093

  13. Outcomes of advanced and recurrent cervical cancer treated with cisplatin and generic topotecan: retrospective analysis in a tertiary care hospital in Thailand

    PubMed Central

    Charoenkwan, Kittipat; Cheewakriangkrai, Chalong

    2010-01-01

    Objective Retrospective evaluation of the outcome of stage IVB, recurrent or persistent cervical cancer treated with cisplatin and generic topotecan (CT) in a tertiary care hospital in Thailand. Methods The medical records of patients treated with CT regimen at Chiang Mai University Hospital between January 2005 and December 2007 were reviewed and analyzed. The treatment protocol consisted of IV topotecan 0.75 mg/m2 on days 1, 2, and 3; combined with cisplatin 50 mg/m2 IV on day 1 and repeated every 21 days until progression or unacceptable toxicity for a maximum of 6 cycles. The outcomes were evaluated based on the response rate, progression free survival (PFS), and overall survival (OS) by using the World Health Organization criteria. The adverse effects of the treatments were also determined. Results Twenty-one cervical cancer patients received the CT regimen. The tumor response rate was 28.6%. The median PFS and OS was 4 and 11 months, respectively. With 87 cycles of chemotherapy, the most common grade 3 & 4 hematologic toxicity was neutropenia (57.9%). Conclusion Advanced and recurrent cervical cancer patients treated with cisplatin and generic topotecan had a favorable outcome with manageable toxicity. PMID:21278885

  14. Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant For Hematological Cancer

    ClinicalTrials.gov

    2014-09-03

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

  15. Living Fully in the Shadow of Mortal Time: Psychosocial Assets in Advanced Cancer

    PubMed Central

    Wise, Meg; Marchand, Lucille

    2013-01-01

    Objective To characterize the strategies and psychosocial conditions that influence how resilient people live in the face of advanced cancer. Methods Grounded theory interviews and surveys of ten resilient people with advanced cancer were collected and analyzed. Findings Personal assets including positive relationships, purpose in life, faith, and a sense of mastery contributed to living fully in “mortal time.” Strategies included embracing paradox, reframing time, deepening connections, and aligning actions with priorities. Open-ended interviews yielded rich illness and life stories; many participants requested a copy of the transcript. Conclusions Resilient people use a range of strategies to thrive in the face of advanced cancer. PMID:23923470

  16. Hypofractionated ablative radiotherapy for locally advanced pancreatic cancer

    PubMed Central

    Crane, Christopher H.

    2016-01-01

    The role of radiation in locally advanced unresectable pancreatic cancer (LAPC) is controversial. Randomized trials evaluating standard doses of chemoradiation have not shown a significant benefit from the use of consolidative radiation. Results from non-randomized studies of 3–5-fraction stereotactic body radiotherapy (SBRT) have been similar to standard chemoradiation, but with less toxicity and a shorter treatment time. Doses of SBRT have been reduced to subablative levels for the sake of tolerability. The benefit of both options is unclear. In contrast, ablative doses can be delivered using an SBRT technique in 15–28 fractions. The keys to the delivery of ablative doses are computed tomography (CT) image guidance and respiratory gating. Higher doses have resulted in encouraging long-term survival results. In this review, we present a comprehensive solution to achieving ablative doses for selected patients with pancreatic tumors by using a combination of classical, modern and novel concepts of radiotherapy: fractionation, CT image guidance, respiratory gating, intentional dose heterogeneity, and simultaneous integrated protection. PMID:27029741

  17. [Complications of radical surgery for advanced ovarian cancer].

    PubMed

    Chéreau, E; Ballester, M; Lesieur, B; Selle, F; Coutant, C; Rouzier, R; Daraï, E

    2011-01-01

    Treatment of advanced ovarian cancer should include surgery with optimal cytoreduction, which is the first prognosis factor. This surgery usually requires extensive resection (pelvic surgery, extensive lymphadenectomy, upper abdominal surgery and sometimes multiple intestinal resection). The complete surgery usually requires a resection of the diaphragm peritoneum in 10 to 100% of cases, intestinal resection in 20 to 100% of cases, splenectomy in 1 to 33% of cases, pancreatectomy in 0 11% of cases, resection of liver metastases in 0 to 16% of cases and cholecystectomy in 2 to 20% of cases. The main complications reported were digestive fistula (1.4 to 8.2%), lymphocyst (0.6 to 32%), septic complications (3.7 to 41.4%) and pulmonary complications (0 to 59%) in case of diaphragmatic surgery. The postoperative mortality ranges from 0.3 to 5.7%. Radical surgery increases the rate of complete cytoreduction with significant morbidity and postoperative mortality. Because these complications decrease survival, it is essential to assess the risk of occurrence of these events to inform patients. PMID:21183387

  18. Managing addiction in advanced cancer patients: why bother?

    PubMed

    Passik, S D; Theobald, D E

    2000-03-01

    The management of addiction in patients with advanced cancer can be time-consuming, labor-intensive, and difficult. Some clinicians believe that it is not worth the effort, due in part to a failure to appreciate the deleterious impact of addiction on palliative care efforts and a view of addiction as intractable in any case. Indeed, it is possible that some clinicians perceive addiction not only fatalistically but, because of common misconceptions, believe that managing or attempting to decrease the patient's use of alcohol or illicit substances would be tantamount to depriving a dying patient of a source of pleasure. In this paper, we argue that managing addiction is an essential aspect of palliative care for chemically-dependent and alcoholic patients. The goal of such efforts is not complete abstinence, but exerting enough control over illicit drug and alcohol use to allow palliative care interventions to decrease suffering. To illustrate this view, we describe two patients with chemical-dependency. We highlight the impact of unchecked substance abuse on patients' perpetuation of their own suffering, the complication of symptom management, the diagnosis and treatment of mood/anxiety disorders, and the effect on the patients' family and caregivers. PMID:10760628

  19. Intraoperative and external beam irradiation for locally advanced colorectal cancer.

    PubMed Central

    Gunderson, L L; Martin, J K; Bèart, R W; Nagorney, D M; Fieck, J M; Wieand, H S; Martinez, A; O'Connell, M J; Martenson, J A; McIlrath, D C

    1988-01-01

    In view of poor local control rates obtained with standard treatment, intraoperative radiation (IORT) using electrons was combined with external beam irradiation and surgical resection, with or without 5-fluorouracil (5FU), in 51 patients with locally advanced colorectal cancer (recurrent, 36 patients; primary, 15 patients). Patients received 4500-5500 cGy (rad) of fractionated, multiple field external beam irradiation and an IORT dose of 1000-2000 cGy. Thirty of 51 patients (59%) are alive and 22 patients (43%) are free of disease. In 44 patients at risk greater than or equal to 1 year, local progression within the IORT field has occurred in 1 of 44 (2%) and within the external beam field in 8 of 44 (18%). All local failures have occurred in patients with recurrence or with gross residual after partial resection, and the risk was less in patients who received 5FU during external irradiation (1 of 11, 9% vs. 6 of 31, 19%). The incidence of distant metastases is high in patients with recurrence, but subsequent peritoneal failures are infrequent. Acute and chronic tolerance have been acceptable, but peripheral nerve appears to be a dose-limiting structure. Randomized trials are needed to determine whether potential gains with IORT are real. PMID:3337561

  20. Postmastectomy radiotherapy for locally advanced breast cancer receiving neoadjuvant chemotherapy.

    PubMed

    Meattini, Icro; Cecchini, Sara; Di Cataldo, Vanessa; Saieva, Calogero; Francolini, Giulio; Scotti, Vieri; Bonomo, Pierluigi; Mangoni, Monica; Greto, Daniela; Nori, Jacopo; Orzalesi, Lorenzo; Casella, Donato; Simoncini, Roberta; Fambrini, Massimiliano; Bianchi, Simonetta; Livi, Lorenzo

    2014-01-01

    Neoadjuvant chemotherapy (NAC) is widely used in locally advanced breast cancer (BC) treatment. The role of postmastectomy radiotherapy (PMRT) after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated with NAC and mastectomy at our center; 98 cases (57.6%) underwent PMRT and 72 cases (42.4%) did not receive radiation. At a median follow-up period of 7.7 years (range 2-16) for the whole cohort, median time to locoregional recurrence (LRR) was 3.3 years (range 0.7-12.4). The 5-year and 10-year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate analysis the factors that significantly correlated with survival outcome were ≥ 4 positive nodes (HR 5.0, 1.51-16.52; P = 0.035), extracapsular extension (HR 2.18, 1.37-3.46; P = 0.009), and estrogen receptor positive disease (HR 0.57, 0.36-0.90; P = 0.003). Concerning LRR according to use of radiation, PMRT reduced LRR for patient with clinical T3 staged disease (P = 0.015). Our experience confirmed the impact of pathological nodal involvement on survival outcome. PMRT was found to improve local control in patients presenting with clinical T3 tumors, regardless of the response to chemotherapy. PMID:25045694

  1. Advances in the care of patients with mucinous colorectal cancer.

    PubMed

    Hugen, Niek; Brown, Gina; Glynne-Jones, Robert; de Wilt, Johannes H W; Nagtegaal, Iris D

    2016-06-01

    The majority of colorectal cancers (CRCs) are classified as adenocarcinoma not otherwise specified (AC). Mucinous carcinoma (MC) is a distinct form of CRC and is found in 10-15% of patients with CRC. MC differs from AC in terms of both clinical and histopathological characteristics, and has long been associated with an inferior response to treatment compared with AC. The debate concerning the prognostic implications of MC in patients with CRC is ongoing and MC is still considered an unfavourable and unfamiliar subtype of the disease. Nevertheless, in the past few years epidemiological and clinical studies have shed new light on the treatment and management of patients with MC. Use of a multidisciplinary approach, including input from surgeons, pathologists, oncologists and radiologists, is beginning to lead to more-tailored approaches to patient management, on an individualized basis. In this Review, the authors provide insight into advances that have been made in the care of patients with MC. The prognostic implications for patients with colon or rectal MC are described separately; moreover, the predictive implications of MC regarding responses to commonly used therapies for CRC, such as chemotherapy, radiotherapy and chemoradiotherapy, and the potential for, and severity of, metastasis are also described. PMID:26323388

  2. Selective Mastectomy in the Management of Locally Advanced Breast Cancer

    SciTech Connect

    Ahern, Verity . E-mail: verity.ahern@swahs.healthnsw.gov.au; Boyages, John; Gebski, Val M. Stat; Moon, Dominic; Wilcken, Nicholas

    2007-07-15

    Purpose: To evaluate local control for patients with locally advanced noninflammatory breast cancer (LABC) managed by selective mastectomy. Methods and Materials: Between 1979 and 1996, 176 patients with LABC were prospectively managed by chemotherapy (CT)-irradiation (RT)-CT without routine mastectomy. All surviving patients were followed for a minimum of 5 years. Results: A total of 132 patients (75%) had a T4 tumor and 22 (12.5%) supraclavicular nodal disease. The clinical complete response rate was 91% (160/176), which included 13 patients who underwent mastectomy and 2 an iridium wire implant. The first site of failure was local for 43 patients (breast {+-} axilla for 38); 27 of these patients underwent salvage mastectomy and 11 did not for an overall mastectomy rate of 23% (40/176). If all 176 patients had undergone routine mastectomy (136 extra mastectomies), 11 additional patients may have avoided an unsalvageable first local relapse. The others would have either have not had a local relapse or would have suffered local relapse after distant disease. No tumor or treatment related factor was found to predict local disease at death. Median disease-free and overall survival for all patients was 26 and 52 months, respectively. Conclusions: Selective mastectomy in LABC may not jeopardize local control or survival.

  3. [Resection for advanced pancreatic cancer following multimodal therapy].

    PubMed

    Kleeff, J; Stöß, C; Yip, V; Knoefel, W T

    2016-05-01

    Pancreatic cancer patients presenting with borderline resectable or locally advanced unresectable tumors remain a therapeutic challenge. Despite the lack of high quality randomized controlled trials, perioperative neoadjuvant treatment strategies are often employed for this group of patients. At present the FOLFIRINOX regimen, which was established in the palliative setting, is the backbone of neoadjuvant therapy, whereas local ablative treatment, such as stereotactic irradiation and irreversible electroporation are currently under investigation. Resection after modern multimodal neoadjuvant therapy follows the same principles and guidelines as upfront surgery specifically regarding the extent of resection, e.g. lymphadenectomy, vascular resection and multivisceral resection. Because it is still exceedingly difficult to predict tumor response after neoadjuvant therapy, a special treatment approach is necessary. In the case of localized stable disease following neoadjuvant therapy, aggressive surgical exploration with serial frozen sections at critical (vascular) margins might be necessary to minimize the risk of debulking procedures and maximize the chance of a curative resection. A multidisciplinary and individualized approach is mandatory in this challenging group of patients. PMID:27138271

  4. Hospitalists caring for patients with advanced cancer: An experience-based guide.

    PubMed

    Koo, Douglas J; Tonorezos, Emily S; Kumar, Chhavi B; Goring, Tabitha N; Salvit, Cori; Egan, Barbara C

    2016-04-01

    Every year, nearly 5 million adults with cancer are hospitalized. Limited evidence suggests that hospitalization of the cancer patient is associated with adverse morbidity and mortality. Hospitalization of the patient with advanced cancer allows for an intense examination of health status in the face of terminal illness and an opportunity for defining goals of care. This experience-based guide reports what is currently known about the topic and outlines a systematic approach to maximizing opportunities, improving quality, and enhancing the well-being of the hospitalized patient with advanced cancer. Journal of Hospital Medicine 2016;11:292-296. © 2015 Society of Hospital Medicine. PMID:26588430

  5. Recent Advances in Molecular Biology of Thyroid Cancer and Their Clinical Implications

    PubMed Central

    Xing, Mingzhao

    2009-01-01

    Synopsis Thyroid cancer is the most common endocrine malignancy with a rapid rising incidence in recent years. Novel efficient management strategies are increasingly needed for this cancer. Remarkable advances have occurred in recent years in understanding the molecular biology of thyroid cancer. This is reflected in several major biological areas of thyroid cancer, including the molecular alterations for the loss of radioiodine avidity of thyroid cancer, the pathogenic role of the MAP kinase and PI3K/Akt pathways and their related genetic alterations, and the aberrant methylation of functionally important genes in thyroid tumorigenesis and pathogenesis. These exciting advances in molecular biology of thyroid cancer provide unprecedented opportunities for the development of molecular-based novel diagnostic, prognostic, and therapeutic strategies for this cancer. PMID:19040974

  6. Cap-Independent Translation in Hematological Malignancies

    PubMed Central

    Horvilleur, Emilie; Wilson, Lindsay A.; Bastide, Amandine; Piñeiro, David; Pöyry, Tuija A. A.; Willis, Anne E.

    2015-01-01

    Hematological malignancies are a heterogeneous group of diseases deriving from blood cells progenitors. Although many genes involved in blood cancers contain internal ribosome entry sites (IRESes), there has been only few studies focusing on the role of cap-independent translation in leukemia and lymphomas. Expression of IRES trans-acting factors can also be altered, and interestingly, BCL-ABL1 fusion protein expressed from “Philadelphia” chromosome, found in some types of leukemia, regulates several of them. A mechanism involving c-Myc IRES and cap-independent translation and leading to resistance to chemotherapy in multiple myeloma emphasize the contribution of cap-independent translation in blood cancers and the need for more work to be done to clarify the roles of known IRESes in pathology and response to chemotherapeutics. PMID:26734574

  7. BMI1: A Biomarker of Hematologic Malignancies

    PubMed Central

    Sahasrabuddhe, Anagh A.

    2016-01-01

    BMI1 oncogene is a catalytic member of epigenetic repressor polycomb group proteins. It plays a critical role in the regulation of gene expression pattern and consequently several cellular processes during development, including cell cycle progression, senescence, aging, apoptosis, angiogenesis, and importantly self-renewal of adult stem cells of several lineages. Preponderance of evidences indicates that deregulated expression of PcG protein BMI1 is associated with several human malignancies, cancer stem cell maintenance, and propagation. Importantly, overexpression of BMI1 correlates with therapy failure in cancer patients and tumor relapse. This review discusses the diverse mode of BMI1 regulation at transcriptional, posttranscriptional, and posttranslational levels as well as at various critical signaling pathways regulated by BMI1 activity. Furthermore, this review highlights the role of BMI1 as a biomarker and therapeutic target for several subtypes of hematologic malignancies and the importance to target this biomarker for therapeutic applications. PMID:27168727

  8. Aluminum toxicity. Hematological effects.

    PubMed

    Mahieu, S; del Carmen Contini, M; Gonzalez, M; Millen, N; Elias, M M

    2000-01-01

    Sequential effects of intoxication with aluminum hydroxide (Al) (80 mg/Kg body weight, i.p., three times a week), were studied on rats from weaning and up to 28 weeks. The study was carried out on hematological and iron metabolism-related parameters on peripheral blood, at the end of the 1st, 2nd, 3rd, 4th, 5th and 6th months of exposure. As it was described that hematotoxic effects of Al are mainly seen together with high levels of uremia, renal function was measured at the same periods. The animals treated developed a microcytosis and was accompanied by a decrease in mean corpuscular hemoglobin (MCH). Significantly lower red blood cell counts (RBC million/microl) were found in rats treated during the 1st month. These values matched those obtained for control rats during the 2nd month. From the 3rd month onwards, a significant increase was observed as compared to control groups, and the following values were obtained by the 6th month: (T) 10.0 +/- 0.3 versus (C) 8.7 +/- 0.2 (million/microl). Both MCH and mean corpuscular volume (MCV) were found to be significantly lower in groups treated from the 2nd month. At the end of the 6th month the following values were found: MCH (T) 13.3 +/- 0.1 versus (C) 16.9 +/- 0.3 (pg); MCV (T) 42.1 +/- 0.7 versus (C) 51.8 +/- 0.9 (fl). Al was found responsible for lower serum iron concentration levels and in the percentage of transferrin saturation. Thus, although microcytic anemia constitutes an evidence of chronic aluminum exposure, prolonged exposure could lead to a recovery of hematocrit and hemoglobin concentration values with an increase in red cell number. Nevertheless, both microcytosis and the decrease of MCH would persist. These modifications took place without changes being observed in the renal function during the observation period. PMID:10643868

  9. A Phase II study of acute toxicity for Celebrex{sup TM} (celecoxib) and chemoradiation in patients with locally advanced cervical cancer: Primary endpoint analysis of RTOG 0128

    SciTech Connect

    Gaffney, David K. . E-mail: david.gaffney@hci.utah.edu; Winter, Kathryn M.S.; Dicker, Adam P.; Miller, Brigitte; Eifel, Patricia J.; Ryu, Janice; Avizonis, Vilija; Fromm, Mitch; Greven, Kathryn

    2007-01-01

    Purpose: To determine treatment-related acute toxicity rates in patients with locally advanced cervical cancer treated by oral celecoxib, i.v. cisplatin and 5-FU, and concurrent pelvic radiation therapy. Methods and Materials: Eligible patients on this RTOG Phase I-II study for advanced cervix cancer included FIGO Stage IIB-IVA or patients with FIGO Stage IB through IIA with biopsy proven pelvic node metastases or tumor size {>=}5 cm. Patients were treated with pelvic radiotherapy and brachytherapy. Celecoxib was prescribed at 400 mg twice daily beginning on day 1 for 1 year. Cisplatin (75 mg/m2) and 5-FU (1g/m2 for 4 days) were administered every 3 weeks times 3. The primary end point of the study was treatment related toxicity. Results: Between August 2001 and March 2004, 84 patients were accrued to the study and 77 patients were evaluable for toxicity. Regarding the primary end point, toxicities were observed in the following areas: blood/bone marrow (16), gastrointestinal (14), pain (7), renal/genitourinary (6), cardiovascular (3), hemorrhage (1), and neurologic (1). For the first 75 evaluable patients, a toxicity failure was identified in 36 patients for a rate of 48%. Conclusions: Celecoxib at 400 mg twice daily together with concurrent cisplatin and 5-FU and pelvic radiotherapy has a high incidence of acute toxicities. The most frequent toxicities were hematologic. Albeit, the toxicity was deemed excessive in this trial, the rate of toxicities was not too different compared to other recent experiences with concurrent chemoradiation for advanced cervix cancer.

  10. Azacitidine and Entinostat in Treating Patients With Advanced Breast Cancer

    ClinicalTrials.gov

    2016-05-26

    Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  11. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Cancer.gov

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  12. p53 mutations and overexpression in locally advanced breast cancers.

    PubMed Central

    Faille, A.; De Cremoux, P.; Extra, J. M.; Linares, G.; Espie, M.; Bourstyn, E.; De Rocquancourt, A.; Giacchetti, S.; Marty, M.; Calvo, F.

    1994-01-01

    Alterations in the p53 gene were analysed in 39 patients with locally advanced breast cancers (LABCs) (stage III-IV) with inflammatory signs in most cases (UICC stage T4d = 32 patients) by molecular and immunohistochemical (IHC) approaches. All patients were included in the same therapy protocol. Using polymerase chain reaction (PCR) and a single-strand conformational polymorphism migration technique (SSCP), the presence of mutations in exons 2-11, covering the entire coding sequence of the p53 gene, was evaluated. Using the mouse specific anti-human p53 monoclonal antibody (PAb 1801), we also looked for overexpression of the p53 protein in tissue sections. In 16 cases shifted bands were reproducibly identified by PCR-SSCP, and all but one (localised to exon 10) were in exons 5-8, the usual mutational hotspots. Fifteen of these 16 samples were sequenced and 14 of the suspected mutations (36%) were confirmed. Most of them (12) were single nucleotide substitutions, and transitions were more frequent (eight cases) than transversions (four cases). Fourteen of the tumour samples were positively stained with the monoclonal antibody PAb 1801, 11 with nuclear staining only, two with mixed cytoplasmic and nuclear staining and one with cytoplasmic staining only. Staining patterns were very heterogeneous in terms of the percentage of positive cells (10-75%) and their distribution in the tissue section (isolated foci or dispersed cells). In 11 of the 14 mutated cases a positive immunostaining was observed. The presence of a p53 mutation was significantly associated with larger tumour diameter (chi 2 = 7.490, P = 0.0062) and the presence of clinical metastases (stage IV) (chi 2 = 10.113, P = 0.0015). A non-statistically significant trend of association was observed between p53 mutation, negative oestrogen receptors and lower response rate to therapy. Our results in this group of patients and the heterogeneity of the staining of tumour cells in tissue sections suggest that p53

  13. 1st International consensus guidelines for advanced breast cancer (ABC 1).

    PubMed

    Cardoso, F; Costa, A; Norton, L; Cameron, D; Cufer, T; Fallowfield, L; Francis, P; Gligorov, J; Kyriakides, S; Lin, N; Pagani, O; Senkus, E; Thomssen, C; Aapro, M; Bergh, J; Di Leo, A; El Saghir, N; Ganz, P A; Gelmon, K; Goldhirsch, A; Harbeck, N; Houssami, N; Hudis, C; Kaufman, B; Leadbeater, M; Mayer, M; Rodger, A; Rugo, H; Sacchini, V; Sledge, G; van't Veer, L; Viale, G; Krop, I; Winer, E

    2012-06-01

    The 1st international Consensus Conference for Advanced Breast Cancer (ABC 1) took place on November 2011, in Lisbon. Consensus guidelines for the management of this disease were developed. This manuscript summarizes these international consensus guidelines. PMID:22425534

  14. Polypharmacy in patients with advanced cancer and the role of medication discontinuation.

    PubMed

    LeBlanc, Thomas W; McNeil, Michael J; Kamal, Arif H; Currow, David C; Abernethy, Amy P

    2015-07-01

    Polypharmacy is a well known problem in elderly patients in general, but its prevalence and effects in patients with cancer are less clear, particularly in end-of-life settings. This Review examines the existing literature on polypharmacy in advanced cancer and end-of-life settings by reviewing evidence-based approaches to reduce polypharmacy, and outlining the potential benefits of decreasing the number of drugs that patients with cancer can take, with emphasis on the need for thoughtful discontinuation initiatives in the context of life-limiting malignant disease. In view of the apparent burden of polypharmacy in patients with advanced cancer, we expect that greater attention to polypharmacy could lead to improvements in adverse drug events, cost, and possibly quality of life. However, few data for specific interventions in the advanced cancer population are available, and thus more research is warranted. PMID:26149885

  15. Advanced gastric cancer: What we know and what we still have to learn

    PubMed Central

    Coccolini, Federico; Montori, Giulia; Ceresoli, Marco; Cima, Simona; Valli, Maria Carla; Nita, Gabriela E; Heyer, Arianna; Catena, Fausto; Ansaloni, Luca

    2016-01-01

    Gastric cancer is a common neoplastic disease and, more precisely, is the third leading cause of cancer death in the world, with differences amongst geographic areas. The definition of advanced gastric cancer is still debated. Different stadiating systems lead to slightly different stadiation of the disease, thus leading to variations between the single countries in the treatment and outcomes. In the present review all the possibilities of treatment for advanced gastric cancer have been analyzed. Surgery, the cornerstone of treatment for advanced gastric cancer, is analyzed first, followed by an investigation of the different forms and drugs of chemotherapy and radiotherapy. New frontiers in treatment suggest the growing consideration for intraperitoneal administration of chemotherapeutics and combination of traditional drugs with new ones. Moreover, the necessity to prevent the relapse of the disease leads to the consideration of administering intraperitoneal chemotherapy earlier in the therapeutical algorithm. PMID:26811653

  16. [Effect of Jinshuibao capsule on the immunological function of 36 patients with advanced cancer].

    PubMed

    Zhou, D H; Lin, L Z

    1995-08-01

    Jinshuibao Capsule (JSBC), produced by Jiangxi Jinshuibao pharmaceutical Company Limited, possesses the similar active principles and pharmacological activity with those of Cordyceps sinensis. The effect of JSBC on the immunological function of 36 patients with advanced cancer showed that it could restore cellular immunological function, improve quality of life, but had no significant effect on humoral immunological function. The results suggested that JSBC could be used as adjuvant drug in advanced cancer. PMID:8580695

  17. [Clinical study of recombinant interferon alpha-2 (Sch 30500) in advanced gynecological cancers].

    PubMed

    Kasamatsu, T; Ohmi, K; Takeuchi, S; Takamizawa, H; Matsuzawa, M; Kawana, T; Ueda, K; Kubo, H; Tsumuji, Y; Kawashima, Y

    1985-08-01

    Recombinant interferon alpha-2 (Sch 30500) was administered to 29 patients with advanced gynecological cancers (14 patients with cancer of the cervix, 8 with ovarian cancer, 4 with uterine sarcoma, 2 with endometrial cancer and 1 with unclassified cancer). No antitumor effects (CR and PR) were noted in 23 evaluable patients. Side effects observed were fever, tachycardia, diarrhea, chills, general fatigue, anorexia, nausea and vomiting. In some patients, leukopenia, decrease of hemoglobin and elevation of SGOT and SGPT were observed. No production of antibody for Sch 30500 was noted. PMID:3896157

  18. Postmastectomy Radiotherapy for Locally Advanced Breast Cancer Receiving Neoadjuvant Chemotherapy

    PubMed Central

    Meattini, Icro; Di Cataldo, Vanessa; Saieva, Calogero; Francolini, Giulio; Scotti, Vieri; Bonomo, Pierluigi; Mangoni, Monica; Greto, Daniela; Nori, Jacopo; Orzalesi, Lorenzo; Casella, Donato; Simoncini, Roberta; Fambrini, Massimiliano; Bianchi, Simonetta; Livi, Lorenzo

    2014-01-01

    Neoadjuvant chemotherapy (NAC) is widely used in locally advanced breast cancer (BC) treatment. The role of postmastectomy radiotherapy (PMRT) after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated with NAC and mastectomy at our center; 98 cases (57.6%) underwent PMRT and 72 cases (42.4%) did not receive radiation. At a median follow-up period of 7.7 years (range 2–16) for the whole cohort, median time to locoregional recurrence (LRR) was 3.3 years (range 0.7–12.4). The 5-year and 10-year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate analysis the factors that significantly correlated with survival outcome were ≥4 positive nodes (HR 5.0, 1.51–16.52; P = 0.035), extracapsular extension (HR 2.18, 1.37–3.46; P = 0.009), and estrogen receptor positive disease (HR 0.57, 0.36–0.90; P = 0.003). Concerning LRR according to use of radiation, PMRT reduced LRR for patient with clinical T3 staged disease (P = 0.015). Our experience confirmed the impact of pathological nodal involvement on survival outcome. PMRT was found to improve local control in patients presenting with clinical T3 tumors, regardless of the response to chemotherapy. PMID:25045694

  19. Locally Advanced Breast Cancer: Autologous Versus Implant-based Reconstruction

    PubMed Central

    Prousskaia, Elena; Chow, Whitney; Angelaki, Anna; Cirwan, Cleona; Hamed, Hisham; Farhadi, Jian

    2016-01-01

    Background: Recent papers and guidelines agree that patients with locally advanced breast cancer (LABC) should be offered breast reconstruction. Yet, the type of reconstruction in this group of patients is still a point of controversy. Methods: One hundred fourteen patients, treated for LABC from 2007 to 2013, were divided into 3 groups based on the reconstructive option: no reconstruction (NR), implant-based/expander-based reconstruction (IBR), and autologous tissue reconstruction (ATR). We analyzed demographics and compared delay in adjuvant therapy, length of hospitalization, surgical complications, failure of reconstruction, local recurrence, and disease-free survival. Results: Twenty-six patients had NR, 38 had IBR, and 50 had ATR. No significant difference was found in the percentage of patients who had their adjuvant treatment delayed [16% (NR) vs 22% (IBR) vs 14% (ATR)]. Mean length of hospitalization for the NR, IBR, and ATR groups was 2.7, 6, and 7.5 days, respectively. Complication rates requiring readmission were 36% (NR), 42% (IBR), and 32% (ATR). In the IBR group, 37% of implants were removed because of complications. Failure of reconstruction was 37% and 0% for the IBR and ATR groups, respectively. Local recurrence rates in the NR and Reconstruction (groups IBR and ATR combined) groups were 7% and 2%, respectively. Mean survival times in patients were 18 (NR), 10.3 (IBR), and 12.2 (ATR) months. Conclusions: No significant difference was found in the hospital stay length, adjuvant treatment delay, and complication rates between IBR and ATR. High rates of failed reconstruction suggest that the use of implants should be considered very carefully in patients with LABC. PMID:27014551

  20. The association between metabolic syndrome and the risk of prostate cancer, high-grade prostate cancer, advanced prostate cancer, prostate cancer-specific mortality and biochemical recurrence

    PubMed Central

    2013-01-01

    Background Although a previous meta-analysis reported no association between metabolic syndrome (MetS) and prostate cancer risk, a number of studies suggest that MetS may be associated with the aggressiveness and progression of prostate cancer. However, these results have been inconsistent. This systematic review and meta-analysis investigated the nature of this association. Methods We systematically searched MEDLINE, EMBASE and bibliographies of retrieved studies up to January 2013 using the keywords “metabolic syndrome” and “prostate cancer”. We assessed relative risks (RRs) of the prostate cancer, several parameters of prostate cancer aggressiveness and progression associated with MetS using 95% confidence intervals (95% CIs). Results The literature search produced 547 hits from which 19 papers were extracted for the meta-analysis. In cancer-free population with and without MetS, the combined adjusted RR (95% CI) of prostate cancer risk and prostate cancer-specific mortality in longitudinal cohort studies is 0.96 (0.85 ~ 1.09) and 1.12 (1.02 ~ 1.23) respectively. In the prostate cancer patients with and without MetS, the combined unadjusted OR (95% CI) of high grade Gleason prostate cancer is 1.44 (1.20 ~ 1.72), the OR of advanced prostate cancer is 1.37 (1.12 ~ 1.68) and the OR of biochemical recurrence is 2.06 (1.43 ~ 2.96). Conclusions The overall analyses revealed no association between MetS and prostate cancer risk, although men with MetS appear more likely to have high-grade prostate cancer and more advanced disease, were at greater risk of progression after radical prostatectomy and were more likely to suffer prostate cancer-specific death. Further primary studies with adjustment for appropriate confounders and larger, prospective, multicenter investigations are required. PMID:23406686

  1. Secondary pulmonary alveolar proteinosis in hematologic malignancies.

    PubMed

    Chaulagain, Chakra P; Pilichowska, Monika; Brinckerhoff, Laurence; Tabba, Maher; Erban, John K

    2014-12-01

    Pulmonary alveolar proteinosis (PAP), characterized by deposition of intra-alveolar PAS positive protein and lipid rich material, is a rare cause of progressive respiratory failure first described by Rosen et al. in 1958. The intra-alveolar lipoproteinaceous material was subsequently proven to have been derived from pulmonary surfactant in 1980 by Singh et al. Levinson et al. also reported in 1958 the case of 19-year-old female with panmyelosis afflicted with a diffuse pulmonary disease characterized by filling of the alveoli with amorphous material described as "intra-alveolar coagulum". This is probably the first reported case of PAP in relation to hematologic malignancy. Much progress has been made on PAP first described by Rosen which is currently classified as idiopathic or primary or autoimmune PAP. Idiopathic PAP occurs as a result of auto-antibodies directed against granulocyte-macrophage colony stimulating factor (GM-CSF) impeding the surfactant clearing function of alveolar macrophages leading to progressive respiratory failure. Whole lung lavage and GM-CSF therapy has improved outcomes in patients with idiopathic PAP. Despite major advancement in the management of hematologic malignancy and its complications, little is known about the type of PAP first described by Levinson and now known as secondary PAP; a term also used when PAP occurs due to other causes such as occupational dusts. In this article we review and analyze the limited literature available in secondary PAP due to hematologic malignancies and present a case of PAP associated with chronic lymphocytic leukemia successfully treated with bendamustine and rituximab. PMID:25300566

  2. Targeting cell cycle regulators in hematologic malignancies

    PubMed Central

    Aleem, Eiman; Arceci, Robert J.

    2015-01-01

    Hematologic malignancies represent the fourth most frequently diagnosed cancer in economically developed countries. In hematologic malignancies normal hematopoiesis is interrupted by uncontrolled growth of a genetically altered stem or progenitor cell (HSPC) that maintains its ability of self-renewal. Cyclin-dependent kinases (CDKs) not only regulate the mammalian cell cycle, but also influence other vital cellular processes, such as stem cell renewal, differentiation, transcription, epigenetic regulation, apoptosis, and DNA repair. Chromosomal translocations, amplification, overexpression and altered CDK activities have been described in different types of human cancer, which have made them attractive targets for pharmacological inhibition. Mouse models deficient for one or more CDKs have significantly contributed to our current understanding of the physiological functions of CDKs, as well as their roles in human cancer. The present review focuses on selected cell cycle kinases with recent emerging key functions in hematopoiesis and in hematopoietic malignancies, such as CDK6 and its role in MLL-rearranged leukemia and acute lymphocytic leukemia, CDK1 and its regulator WEE-1 in acute myeloid leukemia (AML), and cyclin C/CDK8/CDK19 complexes in T-cell acute lymphocytic leukemia. The knowledge gained from gene knockout experiments in mice of these kinases is also summarized. An overview of compounds targeting these kinases, which are currently in clinical development in various solid tumors and hematopoietic malignances, is presented. These include the CDK4/CDK6 inhibitors (palbociclib, LEE011, LY2835219), pan-CDK inhibitors that target CDK1 (dinaciclib, flavopiridol, AT7519, TG02, P276-00, terampeprocol and RGB 286638) as well as the WEE-1 kinase inhibitor, MK-1775. The advantage of combination therapy of cell cycle inhibitors with conventional chemotherapeutic agents used in the treatment of AML, such as cytarabine, is discussed. PMID:25914884

  3. Distinguishing Symptoms of Grief and Depression in a Cohort of Advanced Cancer Patients

    ERIC Educational Resources Information Center

    Jacobsen, Juliet C.; Zhang, Baohui; Block, Susan D.; Maciejewski, Paul K.; Prigerson, Holly G.

    2010-01-01

    Several studies have shown that the symptoms of grief are different from symptoms of depression among bereaved family members. This study is an attempt to replicate this finding among advanced cancer patients and examine clinical correlates of patient grief and depression. Analyses were conducted on data from interviews with 123 advanced cancer…

  4. Advances in the management of differentiated thyroid cancer with follicular cell strain.

    PubMed

    Ben Slimène, Faouzi; Mhiri, Aida; Ben Ali, Moez; Slimène, Hédia; Ben Raies, Nouzha; Karboua, Esma; Schlumberger, Martin

    2016-03-01

    The management of nodules and thyroid cancer is evolving. The aim is to individualize the treatment, decreasing aggression in the forms low risk and instead seeking new therapeutic options in advanced disease. This update shows the main recent advances in this field. PMID:27575497

  5. Fish hematology and associated disorders.

    PubMed

    Grant, Krystan R

    2015-01-01

    Fish health is a growing concern as pets, education, and aquaculture evolves. For the veterinary staff, fish handling, diagnostics, medicine, and surgery may require specialized training and equipment in comparison with terrestrial and arboreal animals, simply because of their aquatic nature and diversity. Fish hematology is one diagnostic tool that may not require additional equipment, may be inexpensive, and provide useful information in guiding treatment options. Challenges involving hematology may include handling and restraint, venipuncture, evaluation, and interpretation. In this article, strategies for these challenges are discussed for teleost (bony fish) and elasmobranch (cartilaginous fish) fish types. PMID:25421028

  6. Fish Hematology and Associated Disorders.

    PubMed

    Grant, Krystan R

    2015-09-01

    Fish health is a growing concern as pets, education, and aquaculture evolves. For the veterinary staff, fish handling, diagnostics, medicine, and surgery may require specialized training and equipment in comparison with terrestrial and arboreal animals, simply because of their aquatic nature and diversity. Fish hematology is one diagnostic tool that may not require additional equipment, may be inexpensive, and provide useful information in guiding treatment options. Challenges involving hematology may include handling and restraint, venipuncture, evaluation, and interpretation. In this article, strategies for these challenges are discussed for teleost (bony fish) and elasmobranch (cartilaginous fish) fish types. PMID:26297413

  7. Therapeutic vaccines for prostate cancer: recent advances and future directions.

    PubMed

    Strauss, Julius; Madan, Ravi A

    2016-07-01

    In recent years, therapeutic cancer vaccines have emerged as a viable and promising treatment for prostate cancer. Beyond sipuleucel-T, phase III trials are evaluating multiple vaccine platforms in men with this disease. Growing data evaluating vaccine therapies suggests that these agents are more effective in patients with more indolent and possibly also earlier stages of disease. In addition, a wealth of preclinical data has shown that traditional prostate cancer treatments including anti androgens, cytotoxic and radiation therapies may provide immunologic synergy when given in combination with vaccine platforms. Building off this data, numerous clinical trials are evaluating therapeutic cancer vaccines in early stage prostate cancer and also in combination with traditional prostate cancer therapies. In addition, in order to optimize immune responses, ongoing trials are evaluating vaccines in combination with immune checkpoint inhibitors. Preliminary data from these trials have been promising and are offering an exciting glimpse at the future of immunotherapy for this disease. PMID:26889831

  8. Advanced Gold Nanomaterials for Photothermal Therapy of Cancer.

    PubMed

    Ahmad, Rasheed; Fu, Juan; He, Nongyue; Li, Song

    2016-01-01

    Photothermal therapy represents a non-invasive therapeutic tool to eradicate cancer tumor with minimum toxic effects. In this ablative therapy, accurate delivery of efficient photothermal conversion agents followed by laser irradiation results in tumor ablation with lower toxicity compared to other cancer therapies. Gold nanomaterials are efficient to passively target and deliver photothermal agents to the cancer tumor. Through surface plasma resonance, gold nanomaterials including nanorods, nanostars, nanoflowers, nanocages and nanoshells exhibited strong NIR absorption and are widely utilized during photothermal ablative therapy of cancer. Currently, researchers have devoted their attention to minimize toxicity of photothermal agents using modified probe design. By developing this noninvasive cancer therapy, expectations to minimize toxicity of cancer treatment may become reality sooner. PMID:27398434

  9. Clinical Management of Pain in Advanced Lung Cancer

    PubMed Central

    Simmons, Claribel P.L.; MacLeod, Nicholas; Laird, Barry J.A.

    2012-01-01

    Lung cancer is the most common cancer in the world and pain is its most common symptom. Pain can be brought about by several different causes including local effects of the tumor, regional or distant spread of the tumor, or from anti-cancer treatment. Patients with lung cancer experience more symptom distress than patients with other types of cancer. Symptoms such as pain may be associated with worsening of other symptoms and may affect quality of life. Pain management adheres to the principles set out by the World Health Organization’s analgesic ladder along with adjuvant analgesics. As pain can be caused by multiple factors, its treatment requires pharmacological and non-pharmacological measures from a multidisciplinary team linked in with specialist palliative pain management. This review article examines pain management in lung cancer. PMID:23115483

  10. Approval summary: pemetrexed maintenance therapy of advanced/metastatic nonsquamous, non-small cell lung cancer (NSCLC).

    PubMed

    Cohen, Martin H; Cortazar, Patricia; Justice, Robert; Pazdur, Richard

    2010-01-01

    On July 2, 2009, the U.S. Food and Drug Administration approved pemetrexed injection (Alimta® Injection; Eli Lilly and Company, Indianapolis, IN) for maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based doublet induction chemotherapy. A double-blind study of pemetrexed plus best supportive care versus placebo plus best supportive care was conducted. Pemetrexed, 500 mg/m(2) i.v., was administered every 21 days until disease progression. Folic acid, vitamin B(12), and a corticosteroid were given to all study patients. There were 663 randomized patients (pemetrexed, 441; placebo, 222). Treatments were well balanced with respect to baseline disease characteristics and stratification factors. The median overall survival (OS) time for intent-to-treat (ITT) patients was 13.4 months for patients receiving pemetrexed and 10.6 months for those receiving placebo (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.65-0.95; p = .012). Median OS times were 15.5 months versus 10.3 months for patients with nonsquamous histologies receiving pemetrexed and placebo, respectively (HR, 0.70; 95% CI, 0.56-0.88). The median OS time in patients with squamous histology receiving pemetrexed was 9.9 months, versus 10.8 months for those receiving placebo (HR, 1.07; 95% CI, 0.77-1.50). A significantly longer progression-free survival interval for both the ITT and nonsquamous patient populations receiving pemetrexed maintenance therapy was also observed. The most common (>5%) adverse reactions in patients receiving pemetrexed were hematologic toxicity, an increase in hepatic enzymes, fatigue, gastrointestinal toxicity, sensory neuropathy, and skin rash. PMID:21148615

  11. Treatment for Chronic Pain in Patients With Advanced Cancer

    ClinicalTrials.gov

    2010-11-07

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Pain; Precancerous/Nonmalignant Condition; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  12. Treatment of Locally Advanced Pancreatic Cancer: The Role of Radiation Therapy

    SciTech Connect

    Johung, Kimberly; Saif, Muhammad Wasif; Chang, Bryan W.

    2012-02-01

    Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

  13. Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers.

    PubMed

    Mimeault, M; Hauke, R; Mehta, P P; Batra, S K

    2007-01-01

    Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. This review summarizes recent advances in our understanding of the cellular origin and molecular mechanisms at the basis of cancer initiation and progression as well as the heterogeneity of cancers arising from the malignant transformation of adult stem/progenitor cells. We describe the critical functions provided by several growth factor cascades, including epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF) receptor (KIT), hedgehog and Wnt/beta-catenin signalling pathways that are frequently activated in cancer progenitor cells and are involved in their sustained growth, survival, invasion and drug resistance. Of therapeutic interest, we also discuss recent progress in the development of new drug combinations to treat the highly aggressive and metastatic cancers including refractory/relapsed leukaemias, melanoma and head and neck, brain, lung, breast, ovary, prostate, pancreas and gastrointestinal cancers which remain incurable in the clinics. The emphasis is on new therapeutic strategies consisting of molecular targeting of distinct oncogenic signalling elements activated in the cancer progenitor cells and their local microenvironment during cancer progression. These new targeted therapies should improve the efficacy of current therapeutic treatments against aggressive cancers, and thereby preventing disease relapse and enhancing patient survival. PMID:17979879

  14. miR-29s: a family of epi-miRNAs with therapeutic implications in hematologic malignancies

    PubMed Central

    Amodio, Nicola; Rossi, Marco; Raimondi, Lavinia; Pitari, Maria Rita; Botta, Cirino; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2015-01-01

    A wealth of studies has highlighted the biological complexity of hematologic malignancies and the role of dysregulated signal transduction pathways. Along with the crucial role of genetic abnormalities, epigenetic aberrations are nowadays emerging as relevant players in cancer development, and significant research efforts are currently focusing on mechanisms by which histone post-translational modifications, DNA methylation and noncoding RNAs contribute to the pathobiology of cancer. As a consequence, these studies have provided the rationale for the development of epigenetic drugs, such as histone deacetylase inhibitors and demethylating compounds, some of which are currently in advanced phase of pre-clinical investigation or in clinical trials. In addition, a more recent body of evidence indicates that microRNAs (miRNAs) might target effectors of the epigenetic machinery, which are aberrantly expressed or active in cancers, thus reverting those epigenetic abnormalities driving tumor initiation and progression. This review will focus on the broad epigenetic activity triggered by members of the miR-29 family, which underlines the potential of miR-29s as candidate epi-therapeutics for the treatment of hematologic malignancies. PMID:25968566

  15. miR-29s: a family of epi-miRNAs with therapeutic implications in hematologic malignancies.

    PubMed

    Amodio, Nicola; Rossi, Marco; Raimondi, Lavinia; Pitari, Maria Rita; Botta, Cirino; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2015-05-30

    A wealth of studies has highlighted the biological complexity of hematologic malignancies and the role of dysregulated signal transduction pathways. Along with the crucial role of genetic abnormalities, epigenetic aberrations are nowadays emerging as relevant players in cancer development, and significant research efforts are currently focusing on mechanisms by which histone post-translational modifications, DNA methylation and noncoding RNAs contribute to the pathobiology of cancer. As a consequence, these studies have provided the rationale for the development of epigenetic drugs, such as histone deacetylase inhibitors and demethylating compounds, some of which are currently in advanced phase of pre-clinical investigation or in clinical trials. In addition, a more recent body of evidence indicates that microRNAs (miRNAs) might target effectors of the epigenetic machinery, which are aberrantly expressed or active in cancers, thus reverting those epigenetic abnormalities driving tumor initiation and progression. This review will focus on the broad epigenetic activity triggered by members of the miR-29 family, which underlines the potential of miR-29s as candidate epi-therapeutics for the treatment of hematologic malignancies. PMID:25968566

  16. Targeted therapy for advanced urothelial cancer of the bladder: where do we stand?

    PubMed

    Zhu, Zhaowei; Shen, Zhoujun; Xu, Chen

    2012-11-01

    The treatment of advanced urothelial cancer of the bladder has evolved substantially during recent years. Chemotherapy has been the mainstay of treatment and confers survival advantage. Despite such advances, the chemotherapy of bladder cancer is far from satisfactory due to severe side effects. Targeted therapy with novel drugs directed at specific molecular pathways opens promising new avenues to improve patient outcome. A systematic review examined the clinical data for novel targeted agents in 10 phase II trials, with a focus on bevacizumab, aflibercept, sunitinib, sorafenib, gefitinib, lapatinib and trastuzumab. Besides, we present studies on other novel, promising targeted agents, including pazopanib, cetuximab and everolimus. Although bevacizumab and trastuzumab have shown promising results for patients with advanced bladder cancer, other targeted agents have not achieved the same clinical benefit in this disease as seen in other common epithelial cancers. Ultimately, combination targeted therapy, sequential therapy, adjuvant and neoadjuvant therapy may yield the best outcomes. PMID:22583418

  17. Serum cytokeratin 19 fragment in advanced lung cancer: could we eventually have a serum tumor marker?

    PubMed Central

    Bastawisy, Ahmed El; azzouny, Mahmoud El; Mohammed, Gamal; allah, Ahmad Awad; Behiry, Eman

    2014-01-01

    Introduction: Lung cancer is one of the most lethal malignancies; however, no serum marker has been routinely recommended until now. Methods: This is a prospective case control study including two groups of patients: Group I—patients with advanced lung cancer and Group II—patients with benign lung disease as control. Serum cytokeratin 19 (CK19) fragment levels were measured at baseline by real-time polymerase chain reaction before first-line chemotherapy. The CK19 cut-off taken was 15-cycle threshold. The primary end point was the comparison of high CK19 in cases and controls. The secondary end point was the correlation between high CK19 and progressive disease (PD), progression-free survival, and overall survival (OS) in advanced lung cancer patients. Results: A total of 30 patients with advanced lung cancer (16 non-small and 14 small cell lung cancer) and 15 patients with benign lung disease were included and followed up during the period from October 2008 to October 2011 with median follow-up of one and half years. High CK19 was found in 90% of lung cancer cases as compared with 7% in controls (p < 0.001). High CK19 was found in all cases showing PD (p = 0.04). One-year OS in high CK was 61% as compared with 33% in normal CK (p = 0.1). Conclusion: Serum CK19 fragment is a potential diagnostic and prognostic marker for advanced lung cancer. PMID:24567753

  18. Targeting the Apoptosis Pathway in Hematologic Malignancies

    PubMed Central

    Zaman, Shadia; Wang, Rui; Gandhi, Varsha

    2014-01-01

    Apoptosis is a cell death program that is well-orchestrated for normal tissue homeostasis and for removal of damaged, old, or infected cells. It is regulated by intrinsic and extrinsic pathways. The intrinsic pathway responds to signals such as ultraviolet radiation or DNA damage and activates “executioner” caspases through a mitochondria-dependent pathway. The extrinsic pathway is activated by death signals induced, for example, by an infection that activates the immune system or receptor-mediated pathways. The extrinsic pathway signals also cascade down to executioner caspases that cleave target proteins and lead to cell death. Strict control of cellular apoptosis is important for the hematopoietic system as it has a high turnover rate. However, the apoptosis program is often deregulated in hematologic malignancies leading to the accumulation of malignant cells. Therefore, apoptosis pathways have been identified for development of anticancer therapeutics. We review here the proteins that have been targeted for anticancer drug development in hematologic malignancies. These include BCL-2 family proteins, death ligands and receptors, inhibitor of apoptosis family proteins, and caspases. Except for caspase activators, drugs that target each of these classes of proteins have advanced into clinical trials. PMID:24295132

  19. 42 CFR 493.941 - Hematology (including routine hematology and coagulation).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Hematology (including routine hematology and coagulation). 493.941 Section 493.941 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF....941 Hematology (including routine hematology and coagulation). (a) Program content and frequency...

  20. 42 CFR 493.941 - Hematology (including routine hematology and coagulation).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Hematology (including routine hematology and coagulation). 493.941 Section 493.941 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF....941 Hematology (including routine hematology and coagulation). (a) Program content and frequency...

  1. 42 CFR 493.941 - Hematology (including routine hematology and coagulation).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Hematology (including routine hematology and coagulation). 493.941 Section 493.941 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF....941 Hematology (including routine hematology and coagulation). (a) Program content and frequency...

  2. 42 CFR 493.941 - Hematology (including routine hematology and coagulation).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Hematology (including routine hematology and coagulation). 493.941 Section 493.941 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF....941 Hematology (including routine hematology and coagulation). (a) Program content and frequency...

  3. Advances in cancer research using gold nanoparticles mediated photothermal ablation

    PubMed Central

    MOCAN, LUCIAN; MATEA, CRISTIAN T.; BARTOS, DANA; MOSTEANU, OFELIA; POP, TEODORA; MOCAN, TEODORA; IANCU, CORNEL

    2016-01-01

    Recent research suggests that nanotechnologies may lead to the development of novel cancer treatment. Gold nanoparticles with their unique physical and chemical properties hold great hopes for the development of thermal-based therapies against human malignancies. This review will focus on various strategies that have been developed to use gold nanoparticles as photothermal agents against human cancers. PMID:27152068

  4. The next steps in improving the outcomes of advanced ovarian cancer.

    PubMed

    Openshaw, Mark R; Fotopoulou, Christina; Blagden, Sarah; Gabra, Hani

    2015-06-01

    Worldwide ovarian cancer affects over 200,000 women per year. Overall survival rates are poor due to two predominate reasons. First, the majority of patients present with advanced disease creating significant difficulty with effecting disease eradication. Second, acquisition of chemotherapy resistance results in untreatable progressive disease. Advances in treatment of advanced ovarian cancer involve a spectrum of interventions including improvements in frontline debulking surgery and combination chemotherapy. Anti-angiogenic factors have been shown to have activity in frontline and recurrent disease while novel chemotherapeutic agents and targeted treatments are in development particularly for disease that is resistant to platinum-based chemotherapy. These developments aim to improve the progression-free and overall survival of women with advanced ovarian cancer. PMID:26102473

  5. Surgery for Locally Advanced T4 Rectal Cancer: Strategies and Techniques.

    PubMed

    Helewa, Ramzi M; Park, Jason

    2016-06-01

    Locally advanced T4 rectal cancer represents a complex clinical condition that requires a well thought-out treatment plan and expertise from multiple specialists. Paramount in the management of patients with locally advanced rectal cancer are accurate preoperative staging, appropriate application of neoadjuvant and adjuvant treatments, and, above all, the provision of high-quality, complete surgical resection in potentially curable cases. Despite the advanced nature of this disease, extended and multivisceral resections with clear margins have been shown to result in good oncological outcomes and offer patients a real chance of cure. In this article, we describe the assessment, classification, and multimodality treatment of primary locally advanced T4 rectal cancer, with a focus on surgical planning, approaches, and outcomes. PMID:27247535

  6. Targeting p53 by small molecules in hematological malignancies.

    PubMed

    Saha, Manujendra N; Qiu, Lugui; Chang, Hong

    2013-01-01

    p53 is a powerful tumor suppressor and is an attractive cancer therapeutic target. A breakthrough in cancer research came from the discovery of the drugs which are capable of reactivating p53 function. Most anti-cancer agents, from traditional chemo- and radiation therapies to more recently developed non-peptide small molecules exert their effects by enhancing the anti-proliferative activities of p53. Small molecules such as nutlin, RITA, and PRIMA-1 that can activate p53 have shown their anti-tumor effects in different types of hematological malignancies. Importantly, nutlin and PRIMA-1 have successfully reached the stage of phase I/II clinical trials in at least one type of hematological cancer. Thus, the pharmacological activation of p53 by these small molecules has a major clinical impact on prognostic use and targeted drug design. In the current review, we present the recent achievements in p53 research using small molecules in hematological malignancies. Anticancer activity of different classes of compounds targeting the p53 signaling pathway and their mechanism of action are discussed. In addition, we discuss how p53 tumor suppressor protein holds promise as a drug target for recent and future novel therapies in these diseases. PMID:23531342

  7. Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Osti, Mattia Falchetto; Agolli, Linda; Valeriani, Maurizio; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Enrici, Riccardo Maurizi

    2013-03-01

    Purpose: Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Methods and Materials: Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. Results: The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Conclusions: Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized

  8. Androgen Receptor as a Driver of Therapeutic Resistance in Advanced Prostate Cancer

    PubMed Central

    Kahn, Barbara; Collazo, Joanne; Kyprianou, Natasha

    2014-01-01

    The role of the androgen receptor (AR) signaling axis in the progression of prostate cancer is a cornerstone to our understanding of the molecular mechanisms causing castration-resistant prostate cancer (CRPC). Resistance of advanced prostate cancer to available treatment options makes it a clinical challenge that results in approximately 30,000 deaths of American men every year. Since the historic discovery by Dr. Huggins more than 70 years ago, androgen deprivation therapy (ADT) has been the principal treatment for advanced prostate cancer. Initially, ADT induces apoptosis of androgen-dependent prostate cancer epithelial cells and regression of androgen-dependent tumors. However, the majority of patients with advanced prostate cancer progress and become refractory to ADT due to emergence of androgen-independent prostate cancer cells driven by aberrant AR activation. Microtubule-targeting agents such as taxanes, docetaxel and paclitaxel, have enjoyed success in the treatment of metastatic prostate cancer; although new, recently designed mitosis-specific agents, such as the polo-kinase and kinesin-inhibitors, have yielded clinically disappointing results. Docetaxel, as a first-line chemotherapy, improves prostate cancer patient survival by months, but tumor resistance to these therapeutic agents inevitably develops. On a molecular level, progression to CRPC is characterized by aberrant AR expression, de novo intraprostatic androgen production, and cross talk with other oncogenic pathways. Emerging evidence suggests that reactivation of epithelial-mesenchymal-transition (EMT) processes may facilitate the development of not only prostate cancer but also prostate cancer metastases. EMT is characterized by gain of mesenchymal characteristics and invasiveness accompanied by loss of cell polarity, with an increasing number of studies focusing on the direct involvement of androgen-AR signaling axis in EMT, tumor progression, and therapeutic resistance. In this article, we

  9. 42 CFR 493.849 - Condition: Hematology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Hematology. 493.849 Section 493.849 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.849 Condition: Hematology. The specialty of hematology, for the purpose of...

  10. 42 CFR 493.1215 - Condition: Hematology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Hematology. 493.1215 Section 493.1215 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1215 Condition: Hematology. If the laboratory provides services in the specialty of Hematology,...

  11. Physical Activity in Patients With Advanced-Stage Cancer: A Systematic Review of the Literature

    PubMed Central

    Albrecht, Tara A.; Taylor, Ann Gill

    2014-01-01

    The importance of physical activity for chronic disease prevention and management has become generally well accepted. The number of research interventions and publications examining the benefits of physical activity for patients with cancer has been rising steadily. However, much of that research has focused on the impact of physical activity either prior to or early in the cancer diagnosis, treatment, and survivorship process. Research focusing on the effects of physical activity, specifically for patients with advanced-stage cancer and poorer prognostic outcomes, has been addressed only recently. The purpose of this article is to examine the state of the science for physical activity in the advanced-stage disease subset of the cancer population. Exercise in a variety of intensities and forms, including yoga, walking, biking, and swimming, has many health benefits for people, including those diagnosed with cancer. Research has shown that, for people with cancer (including advanced-stage cancer), exercise can decrease anxiety, stress, and depression while improving levels of pain, fatigue, shortness of breath, constipation, and insomnia. People diagnosed with cancer should discuss with their oncologist safe, easy ways they can incorporate exercise into their daily lives. PMID:22641322

  12. Physical activity in patients with advanced-stage cancer: a systematic review of the literature.

    PubMed

    Albrecht, Tara A; Taylor, Ann Gill

    2012-06-01

    The importance of physical activity for chronic disease prevention and management has become generally well accepted. The number of research interventions and publications examining the benefits of physical activity for patients with cancer has been rising steadily. However, much of that research has focused on the impact of physical activity either prior to or early in the cancer diagnosis, treatment, and survivorship process. Research focusing on the effects of physical activity, specifically for patients with advanced-stage cancer and poorer prognostic outcomes, has been addressed only recently. The purpose of this article is to examine the state of the science for physical activity in the advanced-stage disease subset of the cancer population. Exercise in a variety of intensities and forms, including yoga, walking, biking, and swimming, has many health benefits for people, including those diagnosed with cancer. Research has shown that, for people with cancer (including advanced-stage cancer), exercise can decrease anxiety, stress, and depression while improving levels of pain, fatigue, shortness of breath, constipation, and insomnia. People diagnosed with cancer should discuss with their oncologist safe, easy ways they can incorporate exercise into their daily lives. PMID:22641322

  13. A profile of enzalutamide for the treatment of advanced castration resistant prostate cancer

    PubMed Central

    Greasley, Rosa; Khabazhaitajer, Mohammad; Rosario, Derek J

    2015-01-01

    Recent advances in understanding the mechanisms underlying the development and progression of castration resistant prostate cancer from androgen-sensitive prostate cancer have provided new avenues exploring efficacious therapies in a disease which is the second leading cause of cancer deaths among men in the western world. In the evolution of second generation anti-androgens, enzalutamide, a novel androgen-receptor signaling inhibitor, has emerged targeting multiple steps within the androgenic stimulation pathway. This review discusses what is currently known of the mechanisms surrounding castration resistant prostate cancer development and the current human clinical trials to determine whether enzalutamide presents a new hope for men with advanced prostate cancer. The issues of therapy resistance, withdrawal effects and cross-resistance are briefly touched upon. PMID:26109877

  14. Selumetinib and Akt Inhibitor MK-2206 in Treating Patients With Refractory or Advanced Gallbladder or Bile Duct Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-09-08

    Adenocarcinoma of the Gallbladder; Adenocarcinoma With Squamous Metaplasia of the Gallbladder; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage II Gallbladder Cancer; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer

  15. Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

    PubMed Central

    2013-01-01

    Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

  16. Major clinical research advances in gynecologic cancer in 2012.

    PubMed

    Suh, Dong Hoon; Kim, Jae-Weon; Kim, Kidong; Kim, Hak Jae; Lee, Kyung-Hun

    2013-01-01

    Ten topics were chosen among major clinical research achievements in gynecologic oncology in 2012. For ovarian cancer, comprehensive review of the history of bevacizumab studies was followed by poly adenosine diphosphate [ADP]-ribose polymerase (PARP) inhibitors and other molecular targeted agents such as epidermal growth factor receptor tyrosine kinase inhibitor and AMG 386. For the development of genomic study in gynecologic cancers, BRCA and DICER1 mutations were covered in epithelial and nonepithelial ovarian cancer, respectively. For endometrial cancer, targeted agents including mammalian target of rapamycin (mTOR) inhibitors and bevacizumab were discussed. Radiation therapy "sandwiched" between combination chemotherapy schedules for the treatment of uterine papillary serous carcinoma was also reviewed. Preoperative prediction of lymph node metastasis, definition of low-risk group, and recurrence and survival outcomes of laparoscopic approaches were addressed. For cervical cancer, we reviewed long-term benefit of human papillomavirus test and efficacy of paclitaxel/carboplatin versus paclitaxel/cisplatin in stage IVB, persistent or recurrent disease. In addition, the effect of three dimensional image-based high-dose rate brachytherapy was also reviewed. For vulvar cancer, the diagnostic value of sentinel lymph node biopsy was discussed. For breast cancer, positive results of three outstanding phase III randomized clinical trials, CLEOPATRA, EMILIA, and BOLERO-2 were introduced. Lastly, updates of major practice guidelines were summarized. PMID:23346316

  17. Major clinical research advances in gynecologic cancer in 2012

    PubMed Central

    Suh, Dong Hoon; Kim, Kidong; Kim, Hak Jae; Lee, Kyung-Hun

    2013-01-01

    Ten topics were chosen among major clinical research achievements in gynecologic oncology in 2012. For ovarian cancer, comprehensive review of the history of bevacizumab studies was followed by poly adenosine diphosphate [ADP]-ribose polymerase (PARP) inhibitors and other molecular targeted agents such as epidermal growth factor receptor tyrosine kinase inhibitor and AMG 386. For the development of genomic study in gynecologic cancers, BRCA and DICER1 mutations were covered in epithelial and nonepithelial ovarian cancer, respectively. For endometrial cancer, targeted agents including mammalian target of rapamycin (mTOR) inhibitors and bevacizumab were discussed. Radiation therapy "sandwiched" between combination chemotherapy schedules for the treatment of uterine papillary serous carcinoma was also reviewed. Preoperative prediction of lymph node metastasis, definition of low-risk group, and recurrence and survival outcomes of laparoscopic approaches were addressed. For cervical cancer, we reviewed long-term benefit of human papillomavirus test and efficacy of paclitaxel/carboplatin versus paclitaxel/cisplatin in stage IVB, persistent or recurrent disease. In addition, the effect of three dimensional image-based high-dose rate brachytherapy was also reviewed. For vulvar cancer, the diagnostic value of sentinel lymph node biopsy was discussed. For breast cancer, positive results of three outstanding phase III randomized clinical trials, CLEOPATRA, EMILIA, and BOLERO-2 were introduced. Lastly, updates of major practice guidelines were summarized. PMID:23346316

  18. Prognostic significance of hematological profiles in melanoma patients.

    PubMed

    Gandini, Sara; Ferrucci, Pier Francesco; Botteri, Edoardo; Tosti, Giulio; Barberis, Massimo; Pala, Laura; Battaglia, Angelo; Clerici, Alessandra; Spadola, Giuseppe; Cocorocchio, Emilia; Martinoli, Chiara

    2016-10-01

    Cancer-related inflammation may play an important role in disease progression and patient outcome, and could be easily monitored through indirect parameters routinely evaluated at diagnosis. Here, we investigated if peripheral blood cells and the ratios of neutrophils to lymphocytes (NLR) and of lymphocytes to monocytes (LMR) as surrogate markers of cancer related inflammation are associated with disease progression and survival of melanoma patients at any stage of the disease. Records of 1,182 melanoma patients included in an Institutional tumor registry in the period 2000-2010, were reviewed. Among them, 584 patients with a cutaneous or unknown primary melanoma and available pre-operative blood tests were analyzed. Survival was estimated with the Kaplan-Meier method, and analyzed using Log-rank test, Cox regression and multivariate Cox proportional hazard models. We found that patients presenting with distant metastases had higher leukocytes, neutrophils and monocytes, and lower lymphocytes compared to Stage I-III patients. Furthermore, at a single-patient level, hematological profiles changed on disease progression from regional to distant metastatic, with significantly increased circulating leukocytes, neutrophils and monocytes, and decreased lymphocytes. Peripheral blood cell counts were not associated with survival of patients with a localized or regionally metastasized melanoma. Instead, in Stage IV patients, leukocytes (p = 0.001), neutrophils (p = 0.0002), monocytes (p = 0.002), NLR (p < 0.0001) and LMR (p = 0.005) were all significantly associated with survival, independently of other known prognostic factors. These results suggest that cellular components of peripheral blood do count for survival of patients with advanced melanoma. PMID:27252119

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

    ClinicalTrials.gov

    2015-12-14

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

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

    ClinicalTrials.gov

    2015-10-13

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

  1. Clinical cancer advances 2011: Annual Report on Progress Against Cancer from the American Society of Clinical Oncology.

    PubMed

    Vogelzang, Nicholas J; Benowitz, Steven I; Adams, Sylvia; Aghajanian, Carol; Chang, Susan Marina; Dreyer, Zoann Eckert; Janne, Pasi A; Ko, Andrew H; Masters, Greg A; Odenike, Olatoyosi; Patel, Jyoti D; Roth, Bruce J; Samlowski, Wolfram E; Seidman, Andrew D; Tap, William D; Temel, Jennifer S; Von Roenn, Jamie H; Kris, Mark G

    2012-01-01

    A message from ASCO'S President. It has been forty years since President Richard Nixon signed the National Cancer Act of 1971, which many view as the nation's declaration of the "War on Cancer." The bill has led to major investments in cancer research and significant increases in cancer survival. Today, two-thirds of patients survive at least five years after being diagnosed with cancer compared with just half of all diagnosed patients surviving five years after diagnosis in 1975. The research advances detailed in this year's Clinical Cancer Advances demonstrate that improvements in cancer screening, treatment, and prevention save and improve lives. But although much progress has been made, cancer remains one of the world's most serious health problems. In the United States, the disease is expected to become the nation's leading cause of death in the years ahead as our population ages. I believe we can accelerate the pace of progress, provided that everyone involved in cancer care works together to achieve this goal. It is this viewpoint that has shaped the theme for my presidential term: Collaborating to Conquer Cancer. In practice, this means that physicians and researchers must learn from every patient's experience, ensure greater collaboration between members of a patient's medical team, and involve more patients in the search for cures through clinical trials. Cancer advocates, insurers, and government agencies also have important roles to play. Today, we have an incredible opportunity to improve the quality of cancer care by drawing lessons from the real-world experiences of patients. The American Society of Clinical Oncology (ASCO) is taking the lead in this area, in part through innovative use of health information technology. In addition to our existing quality initiatives, ASCO is working with partners to develop a comprehensive rapid-learning system for cancer care. When complete, this system will provide physicians with personalized, real

  2. Selection Criteria for the Radical Treatment of Locally Advanced Rectal Cancer

    PubMed Central

    Davies, Mansel Leigh; Harris, Dean; Davies, Mark; Lucas, Malcolm; Drew, Peter; Beynon, John

    2011-01-01

    There are over 14,000 newly diagnosed rectal cancers per year in the United Kingdom of which between 50 and 64 percent are locally advanced (T3/T4) at presentation. Pelvic exenterative surgery was first described by Brunschwig in 1948 for advanced cervical cancer, but early series reported high morbidity and mortality. This approach was later applied to advanced primary rectal carcinomas with contemporary series reporting 5-year survival rates between 32 and 66 percent and to recurrent rectal carcinoma with survival rates of 22–42%. The Swansea Pelvic Oncology Group was established in 1999 and is involved in the assessment and management of advanced pelvic malignancies referred both regionally and UK wide. This paper will set out the selection, assessment, preparation, surgery, and outcomes from pelvic exenterative surgery for locally advanced primary rectal carcinomas. PMID:22312517

  3. Nanomedicine strategies for hematological malignancies: what is next?

    PubMed

    Visani, Giuseppe; Loscocco, Federica; Isidori, Alessandro

    2014-10-01

    The major obstacle in treating cancer depends on the low therapeutic index of most anticancer drugs. The lack of specificity, coupled with the large volumes of distribution, translates into a nonpreferential distribution of anticancer drugs to the tumor. Accordingly, the dose of the anticancer drug that is achievable within tumor is limited, resulting in suboptimal treatment and unwanted toxicity. Nanoparticles applied as drug-delivery systems are submicron-sized (3-200 nm) particles, that can enhance the selectivity of the active drug to cancer cells through a change of its pharmacokinetic profile, while avoiding toxicity in normal cells. This review will discuss the current uses of nanodrugs in hematology, with a focus on the most promising nanoparticles in development for the treatment of hematologic tumors. PMID:25413858

  4. Stromal Expression of MicroRNA-21 in Advanced Colorectal Cancer Patients with Distant Metastases

    PubMed Central

    Lee, Kyu Sang; Nam, Soo Kyung; Koh, Jiwon; Kim, Duck-Woo; Kang, Sung-Bum; Choe, Gheeyoung; Kim, Woo Ho; Lee, Hye Seung

    2016-01-01

    Background: The aim of this study was to determine the regional heterogeneity and clinicopathological significance of microRNA-21 (miR-21) in advanced colorectal cancer (CRC) patients with distant metastasis. Methods: miR-21 expression was investigated by using locked nucleic acid– fluorescence in situ hybridization in the center and periphery of the primary cancer and in distant metastasis from 170 patients with advanced CRC. In addition, α-smooth muscle actin and desmin were evaluated to identify cancer-associated fibroblasts (CAFs) by using immunohistochemistry. Results: The miR-21 signal was observed in the cancer stroma. The expression of miR-21 (a score of 1–4) in the center and periphery of the primary cancer and in distant metastasis was observed in specimens from 133 (78.2%), 105 (61.8%), and 91 (53.5%) patients, respectively. miR-21 expression was heterogeneous in advanced CRC. Discordance between miR-21 expression in the center of the primary cancer and either the periphery of the primary cancer or distant metastasis was 31.7% or 44.7%, respectively. miR-21 stromal expression in the periphery of the primary cancer was significantly associated with a better prognosis (p=.004). miR-21 expression was significantly associated with CAFs in the center of the primary cancer (p=.001) and distant metastases (p=.041). Conclusions: miR-21 expression is observed in cancer stroma related to the CAF quantity and frequently presents regional heterogeneity in CRC. Our findings indicate that the role of miR-21 in predicting prognosis may be controversial but provide a new perspective of miR-21 level measurement in cancer specimens. PMID:27240857

  5. Same Chemotherapy Regimen Leads to Different Myelotoxicity in Different Malignancies: A Comparison of Chemotherapy-Associated Myelotoxicity in Patients With Advanced Ovarian and Non-Small-Cell Lung Cancer.

    PubMed

    Tas, Faruk; Yildiz, Ibrahim; Kilic, Leyla; Ciftci, Rumeysa; Keskin, Serkan; Sen, Fatma

    2016-01-01

    Carboplatin-paclitaxel chemotherapy combination is the standard first-line treatment of advanced ovarian cancer and is the most commonly used treatment combination shown to be effective in advanced non-small-cell lung cancer (NSCLC). The most important dose-limiting side effect is hematologic toxicity. In this study, the severity of treatment-related myelotoxicity is compared in patients with advanced ovarian and lung cancers who received same schedule of carboplatin-paclitaxel. The study was prospectively performed from February 2009 to July 2011 and involved 103 patients with stages Ic-IV ovarian (n = 51) and advanced NSCLC (n = 52) who were administered a maximum of 6 cycles of carboplatin-paclitaxel as a first-line treatment. Full blood counts were measured before treatment, before each chemotherapy cycle during therapy, and at the first and sixth month after therapy. The median ages were 59 years (range, 35-77 years) for patients with NSCLC and 56 years (range, 38-75 years) for patients with ovarian cancer. The frequencies of anemia were 17% and 28.6% before the initiation of chemotherapy, 39.2% and 68.0% at the third cycle of treatment, and 44.2% and 45.2% at the sixth cycle of treatment in patients with NSCLC and ovarian cancer, respectively. Initial leukopenia rates were 3.4% and 0%; at the third cycle 46.0% and 41.2%; and at the sixth cycle 41.9% and 48.8% in patients with NSCLC and ovarian cancer, respectively. At the third cycle, 2.5% of the patients with NSCLC and 10.4% of the patients with ovarian cancer had thrombocytopenia, and at the sixth cycle, 23.3% of the patients with NSCLC and 25% of the patients with ovarian cancer had thrombocytopenia. Hemoglobin, leukocyte, and platelet values at the third cycle were significantly lower than those at admission in both cancer groups. Declines in hemoglobin levels in patients with NSCLC and in platelets in patients with ovarian cancer at the sixth cycle were statistically significant compared with the third

  6. [Advances in studies on metabolic syndrome and breast cancer].

    PubMed

    Cao, Li; Yao, Guangyu; Hu, Xiaolei; Chen, Lujia; Ye, Changsheng

    2015-12-01

    Breast cancer is one of the most common malignancies in women. Over these years, the morbidity of metabolic syndrome (MS) has also been increasing in China, probably due to changes in economies and lifestyles. As a result, the association to between these two diseases has at tracted much attention. Results demonstrated the presence of MS was associated with breast cancer risk, and the risk became higher when more MS components were present compared to no components. Moreover, a specific association was indicated between MS and breast cancer recurrence and metastasis to some extent as well. Further, for breast cancer patients, being diagnosed with MS can increase the mortality and lead to poor prognosis. The mechanisms underlying the association is not clear yet, but several factors are speculated to be the possible causes, including the elevated level of insulin, insulin like growth factor-1, leptin and pro-inflammatory cytokines, the decreased level of adiponectin as well as the interaction between DBC1 and SIRT1. The prognosis of patients with breast cancer combined MS can be improved by means of changing diet habits, increasing physical activities and drug-intervention. Although the specific mechanisms underlying the association are still need to be elucidated, better understanding of the association must help us with new strategies for the prevention and treatment of breast cancer. PMID:26850671

  7. Advances in diagnosis and treatment of metastatic cervical cancer

    PubMed Central

    2016-01-01

    Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases. PMID:27171673

  8. Advances in cancer therapeutics and patient access to new drugs.

    PubMed

    Dranitsaris, George; Truter, Ilse; Lubbe, Martie S; Amir, Eitan; Evans, William

    2011-03-01

    Globally, there are approximately 7.4 million cancer deaths annually, approximately 13% of deaths from all causes. Cancer is a disease of older people and, as the population ages over the next 10-20 years, we can expect an increase in the cancer incidence. Encouragingly, cancer mortality has stabilized in many countries. Part of this success may be attributed to the development of new cancer agents, collectively called 'targeted therapies', that are more specific to key components of tumour growth. Worldwide, however, one of the main factors that limit patient access to these important new drugs is their cost, which is higher than traditional chemotherapy. In this review, the clinical and pharmacoeconomic data of selected targeted agents are discussed. In the second part of this article, the challenges faced by healthcare systems in making such drugs available to patients is reviewed. Current strategies used by many countries around the world to manage cancer drug budgets are presented, along with a proposed approach using pharmacoeconomic methodology that may increase patient access. PMID:21184619

  9. Advances in diagnosis and treatment of metastatic cervical cancer.

    PubMed

    Li, Haoran; Wu, Xiaohua; Cheng, Xi

    2016-07-01

    Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases. PMID:27171673

  10. Antibody-based immunotherapy of solid cancers: progress and possibilities.

    PubMed

    Nicodemus, Christopher F

    2015-01-01

    Monoclonal antibodies remain a primary product option for novel cancer treatment. The properties of an antibody are a function of the antigen specificity and constant region incorporated. The rapid advance in molecular understanding of cancer biology and the host-tumor interaction has defined a new range of targets for antibody development. The clinical success of the checkpoint inhibitors has validated immune modulation and mobilization as a therapeutic approach. Solid cancers are distinguished from hematologic malignancies because the solid tumor stroma contains significant tumor promoting and immune dampening elements less prominent in hematologic cancer. This review highlights how engineered monoclonal antibody products are emerging as potential cornerstones of new more personalized cancer treatment paradigms that target both tumor and the stromal environment. PMID:26314410

  11. Antibody-based immunotherapy of solid cancers: progress and possibilities

    PubMed Central

    Nicodemus, Christopher F

    2015-01-01

    Monoclonal antibodies remain a primary product option for novel cancer treatment. The properties of an antibody are a function of the antigen specificity and constant region incorporated. The rapid advance in molecular understanding of cancer biology and the host–tumor interaction has defined a new range of targets for antibody development. The clinical success of the checkpoint inhibitors has validated immune modulation and mobilization as a therapeutic approach. Solid cancers are distinguished from hematologic malignancies because the solid tumor stroma contains significant tumor promoting and immune dampening elements less prominent in hematologic cancer. This review highlights how engineered monoclonal antibody products are emerging as potential cornerstones of new more personalized cancer treatment paradigms that target both tumor and the stromal environment. PMID:26314410

  12. Phase I study of a new cancer vaccine of ten mixed peptides for advanced cancer patients.

    PubMed

    Iwasa, Satoru; Yamada, Yasuhide; Heike, Yuji; Shoji, Hirokazu; Honma, Yoshitaka; Komatsu, Nobukazu; Matsueda, Satoko; Yamada, Akira; Morita, Michi; Yamaguchi, Rin; Tanaka, Natsuki; Kawahara, Akihiko; Kage, Masayoshi; Shichijo, Shigeki; Sasada, Tetsuro; Itoh, Kyogo

    2016-05-01

    A phase I study of a new cancer vaccine (KRM-10), consisting of a mixture of 10 different short peptides, was conducted for patients with advanced gastrointestinal cancers. Primary or secondary endpoints included the dose-limiting toxicity (DLT), or safety and immune responses, respectively. Peptide-specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG), together with soluble inflammatory factors, were measured before and after vaccination. Twenty-one patients were vaccinated with KRM-10 at dose levels of 10 (n = 6), 20 (n = 8) or 30 mg (n = 7) of peptides every week for 6 weeks. No DLT were observed in the dose range evaluated. Common treatment-related adverse events were a grade 1 injection site reaction in 15 patients, and fever in three patients (grade 1 in two patients and grade 2 in one patient). CTL activity to at least one peptide at the time of the third and sixth vaccination increased in 2 and 3 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 2 and 1 of 6 (30 mg) patients, respectively. IgG levels, at the third and sixth vaccination, were also increased in 1 and 1 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 1 and 3 of 6 (30 mg) patients, respectively. The KRM-10 vaccine consisting of 20 mg of peptides was determined as the optimal dose for a coming phase II trial because of its safety, and also for demonstrating the most potent activity for augmenting the immune response of the three doses tested. This trial was registered at the UMIN Clinical Trials Registry as UMIN000008820. PMID:26920496

  13. Hematologic malignancies: at the forefront of immunotherapeutic innovation

    PubMed Central

    Bachireddy, Pavan; Burkhardt, Ute E.; Rajasagi, Mohini; Wu, Catherine J.

    2015-01-01

    The recent successes of cancer immunotherapy have stimulated interest for the potential widespread application of these approaches; hematologic malignancies have provided both initial proofs-of-concept and an informative testing ground for a variety of immune-based therapeutics. The immune-cell origin of many of the blood malignancies provides a unique opportunity to both understand the mechanisms of human immune-responsiveness and immune-evasion as well as to exploit the unique therapeutic opportunities they provide. PMID:25786696

  14. Recent evidence, advances, and current practices in surgical treatment of lung cancer.

    PubMed

    Suda, Kenichi; Sato, Katsuaki; Mizuuchi, Hiroshi; Kobayashi, Yoshihisa; Shimoji, Masaki; Tomizawa, Kenji; Takemoto, Toshiki; Iwasaki, Takuya; Sakaguchi, Masahiro; Mitsudomi, Tetsuya

    2014-11-01

    In the last 10-15 years, strategies and modalities of lung cancer treatment have changed dramatically. Meanwhile, the treatment objectives, the lung cancers themselves, have also changed, probably owing to early detection by computed tomography and aging of the population. In particular, the proportions of smaller lung cancers, lung adenocarcinomas with ground-glass opacity, and lung cancers in older patients are increasing. Along with these changes, surgeons have innovated and evaluated novel procedures for pulmonary resection. These include the application of minimally invasive surgical techniques, such as video-assisted thoracoscopic surgery (VATS) and robotic surgery, and sub-lobar resection, such as wedge resection and segmentectomy, for small peripheral lung cancers. Currently, VATS has gained wide acceptance and several institutions in Japan have started using robotic surgery for lung cancers. Two important clinical trials of sub-lobar resection for small peripheral lung cancers are now underway in Japan. In addition, surgery itself is of growing importance in lung cancer treatment. In particular, recent evidence supports the use of surgery in strictly selected patients with locally advanced disease, lung cancers with N2 lymph node metastases, small cell lung cancers, recurrent oligo-metastasis after pulmonary resection, or relapsed tumors after drug treatment. Surgical treatment also provides abundant tumor samples for molecular analysis, which can be used for drug selection in the adjuvant setting or after disease relapse. In the era of personalized treatment, surgery is still one of the most important treatment modalities to combat lung cancer. PMID:25453375

  15. PI-3 kinase p110β: a therapeutic target in advanced prostate cancers

    PubMed Central

    Li, Benyi; Sun, Aijing; Jiang, Wencong; Thrasher, J Brantley; Terranova, Paul

    2014-01-01

    Prostate cancers in the castration-resistant stage are life-threatening because they are not curable in clinic. The novel androgen receptor inhibitor Xandi (Enzalutamide) and the new CYP17 inhibitor Zytiga (Abiraterone) prolonged patient survival only a few months in advanced prostate cancers. Therefore, novel therapeutic agents for advanced prostate cancers are urgently needed. PI-3 kinases are major intracellular signaling molecules that regulate multiple signal pathways related to cellular metabolism, cytokinesis, growth and survival. Accumulating evidence in the literature indicates that some isoforms of this kinase family are oncogenic and abnormally expressed in various human cancers, including prostate cancers. Recent extensive studies from our group and others showed that PI-3 kinase p110β is aberrantly overexpressed in advanced prostate cancers and is critical for prostate cancer development and progression as demonstrated in cell-based and animal models. Importantly, novel p110β-specific inhibitors have been developed and are currently been testing in clinical trials. In this article, we will briefly summarize recent developments in this regard. PMID:25374921

  16. Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management.

    PubMed

    Mulshine, James L; Avila, Rick; Yankelevitz, David; Baer, Thomas M; Estépar, Raul San Jose; Ambrose, Laurie Fenton; Aldigé, Carolyn R

    2015-05-01

    The Prevent Cancer Foundation Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management was held in New York, NY on May 16 and 17, 2014. The two goals of the Workshop were to define strategies to drive innovation in precompetitive quantitative research on the use of imaging to assess new therapies for management of early lung cancer and to discuss a process to implement a national program to provide high quality computed tomography imaging for lung cancer and other tobacco-induced disease. With the central importance of computed tomography imaging for both early detection and volumetric lung cancer assessment, strategic issues around the development of imaging and ensuring its quality are critical to ensure continued progress against this most lethal cancer. PMID:25898957

  17. Dose to specific subregions of pelvic bone marrow defined with FDG-PET as a predictor of hematologic nadirs during concomitant chemoradiation in anal cancer patients.

    PubMed

    Franco, Pierfrancesco; Arcadipane, Francesca; Ragona, Riccardo; Lesca, Adriana; Gallio, Elena; Mistrangelo, Massimiliano; Cassoni, Paola; Arena, Vincenzo; Bustreo, Sara; Faletti, Riccardo; Rondi, Nadia; Morino, Mario; Ricardi, Umberto

    2016-07-01

    To test the hypothesis that irradiated volume of specific subregions of pelvic active bone marrow as detected by (18)FDG-PET may be a predictor of decreased blood cells nadirs in anal cancer patients undergoing concurrent chemoradiation, we analyzed 44 patients submitted to IMRT and concurrent chemotherapy. Several bony structures were defined: pelvic and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. Active BM was characterized employing (18)FDG-PET and characterized in all subregions as the volume having standard uptake values (SUVs) higher than SUVmean. All other regions were defined as inactive BM. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin (Hb) and platelet (Plt) nadirs. Generalized linear modeling was used to find correlations between dosimetric variables and blood cells nadirs. WBC nadir was significantly correlated with LSBM mean dose (β = -1.852; 95 % CI -3.205/-0.500; p = 0.009), V10 (β = -2.153; 95 % CI -4.263/-0.721; p = 0.002), V20 (β = -2.081; 95 % CI -4.880/-0.112; p = 0.003), V30 (β = -1.971; 95 % CI -4.748/-0.090; p = 0.023) and IBM V10 (β = -0.073; 95 % CI -0.106/-0.023; p = 0.016). ANC nadir found to be significantly associated with LSBM V10 (β = -1.878; 95 % CI -4.799/-0.643; p = 0.025), V20 (β = -1.765; 95 % CI -4.050/-0.613; p = 0.030) and IBM V10 (β = -0.039; 95 % CI -0.066/-0.010; p = 0.027). Borderline significance was found for correlation between Plt nadir and LSBM V30 (β = -0.056; 95 % CI -2.748/-0.187; p = 0.060), V40 (β = -0.059; 95 % CI -3.112/-0.150; p = 0.060) and IBM V30 (β = -0.028; 95 % CI -0.074/-0.023; p = 0.056). No inactive BM subsites were found to be correlated with any blood cell nadir. (18)FDG-PET is able to define active bone marrow within pelvic osseous structures. LSBM is the strongest predictor of decreased blood cells

  18. Recent advances in robotic surgery for rectal cancer.

    PubMed

    Ishihara, Soichiro; Otani, Kensuke; Yasuda, Koji; Nishikawa, Takeshi; Tanaka, Junichiro; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Nozawa, Hiroaki; Kazama, Shinsuke; Yamaguchi, Hironori; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2015-08-01

    Robotic technology, which has recently been introduced to the field of surgery, is expected to be useful, particularly in treating rectal cancer where precise manipulation is necessary in the confined pelvic cavity. Robotic surgery overcomes the technical drawbacks inherent to laparoscopic surgery for rectal cancer through the use of multi-articulated flexible tools, three-dimensional stable camera platforms, tremor filtering and motion scaling functions, and greater ergonomic and intuitive device manipulation. Assessments of the feasibility and safety of robotic surgery for rectal cancer have reported similar operation times, blood loss during surgery, rates of postoperative morbidity, and circumferential resection margin involvement when compared with laparoscopic surgery. Furthermore, rates of conversion to open surgery are reportedly lower with increased urinary and male sexual functions in the early postoperative period compared with laparoscopic surgery, demonstrating the technical advantages of robotic surgery for rectal cancer. However, long-term outcomes and the cost-effectiveness of robotic surgery for rectal cancer have not been fully evaluated yet; therefore, large-scale clinical studies are required to evaluate the efficacy of this new technology. PMID:26059248

  19. Using implementation science to advance cancer prevention in India.

    PubMed

    Krishnan, Suneeta; Sivaram, Sudha; Anderson, Benjamin O; Basu, Partha; Belinson, Jerome L; Bhatla, Neerja; D'Cruz, Anil; Dhillon, Preet K; Gupta, Prakash C; Joshi, Niranjan; Jhulka, P K; Kailash, Uma; Kapambwe, Sharon; Katoch, Vishwa Mohan; Kaur, Prabhdeep; Kaur, Tanvir; Mathur, Prashant; Prakash, Anshu; Sankaranarayanan, R; Selvam, Jerard M; Seth, Tulika; Shah, Keerti V; Shastri, Surendra; Siddiqi, Maqsood; Srivastava, Anurag; Trimble, Edward; Rajaraman, Preetha; Mehrotra, Ravi

    2015-01-01

    Oral, cervical and breast cancers, which are either preventable and/or amenable to early detection and treatment, are the leading causes of cancer-related morbidity and mortality in India. In this paper, we describe implementation science research priorities to catalyze the prevention and control of these cancers in India. Research priorities were organized using a framework based on the implementation science literature and the World Health Organization's definition of health systems. They addressed both community-level as well as health systems-level issues. Community-level or "pull" priorities included the need to identify effective strategies to raise public awareness and understanding of cancer prevention, monitor knowledge levels, and address fear and stigma. Health systems-level or "push" and "infrastructure" priorities included dissemination of evidence- based practices, testing of point-of-care technologies for screening and diagnosis, identification of appropriate service delivery and financing models, and assessment of strategies to enhance the health workforce. Given the extent of available evidence, it is critical that cancer prevention and treatment efforts in India are accelerated. Implementation science research can generate critical insights and evidence to inform this acceleration. PMID:25987015

  20. Role of Helicobacter pylori in gastric cancer: advances and controversies.

    PubMed

    Meng, Wenbo; Bai, Bing; Sheng, Liang; Li, Yan; Yue, Ping; Li, Xun; Qiao, Liang

    2015-11-01

    Gastric cancer is one of the most common cancers of digestive system globally and Helicobacter pylori (HP) infection is believed to be a major risk factor. HP can be classified into different types based on the presence and expression level of CagA and VacA, and, when exposed to adverse environment, HP changes its phenotype from helical type to coccoid type, with each having different pathogenicity. The mechanisms of HP-induced gastric carcinogenesis and progression are complicated, including DNA nitration and oxidation induced by mutagenic factors, HP-induced epigenetic modifications, HP-induced disruption of the balance between cell proliferation and apoptosis, and HP-induced cancer cell invasion and metastasis. HP may also affect the biological function of cancer stem cells and induction of cell autophagy. The lipopolysaccharide produced by HP can act through toll-like receptor-4 (TLR-4) to induce gastric mucosal inflammation and is thereby linked to the development of gastric cancer. PMID:26645900

  1. Advances in immunotherapy for treatment of lung cancer

    PubMed Central

    Bustamante Alvarez, Jean G.; González-Cao, María; Karachaliou, Niki; Santarpia, Mariacarmela; Viteri, Santiago; Teixidó, Cristina; Rosell, Rafael

    2015-01-01

    Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 (PD-1) and its ligand (PD-L1), on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab, another anti PD-1 antibody, has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer (NSCLC), supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months. PMID:26487966

  2. The Emerging Role of Extracellular Vesicle-Mediated Drug Resistance in Cancers: Implications in Advanced Prostate Cancer

    PubMed Central

    Soekmadji, Carolina; Nelson, Colleen C.

    2015-01-01

    Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs. PMID:26587537

  3. Feasibility of intensity-modulated and image-guided radiotherapy for locally advanced esophageal cancer

    PubMed Central

    2014-01-01

    Background In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed. Methods A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70 Gy (62.4-75 Gy). Results At a median follow-up of 14 months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications. Conclusions IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications. PMID:24742268

  4. Imaging heterogeneous absorption distribution of advanced breast cancer by optical tomography

    NASA Astrophysics Data System (ADS)

    Xu, Yan; Zhu, Quing

    2010-11-01

    Tumor vascular patterns of advanced breast cancers are complex and heterogeneous. Two typical light absorption patterns of periphery enhancement and posterior shadowing have been observed when imaging these advanced cancers using optical tomography guided by ultrasound. We perform a series simulation and phantom experiments to systemically evaluate the effects of target parameters, target locations, and target optical properties on imaging periphery enhancement absorption distribution using reflection geometry. Large tumors are modeled as concentric semiellipsoidal targets of different outer shell and inner core optical properties. We show that larger targets of more than 3 to 4 cm diameter with outer shell thicknesses less than 1 cm can be resolved at a depth less than 3 cm. A clinical example is given to show the complex vasculature distributions seen from an advanced cancer.

  5. Recent advances in the pharmacogenetics of cancer chemotherapy.

    PubMed

    Watters, James W; McLeod, Howard L

    2002-12-01

    Patient response to chemotherapy varies widely between individuals. Pharmacogenetics is the study of inherited DNA polymorphisms that influence drug disposition and effects, the goal of which is the individualization of drug treatment. As unpredictable efficacy and high levels of systemic toxicity are common in cancer chemotherapy, pharmacogenetics is particularly appealing for oncology. Recent studies have shown that polymorphisms in genes involved in drug metabolism, nucleotide synthesis and DNA repair contribute to inter-patient variability in the efficacy and toxicity of many chemotherapy agents. This review will discuss recent developments in the most clinically relevant examples of cancer pharmacogenetics, and how genetic differences among individuals are shaping the future of cancer chemotherapy. PMID:12596358

  6. Role of STAT3 in Cancer Metastasis and Translational Advances

    PubMed Central

    Patil, Prachi; Gude, Rajiv P.

    2013-01-01

    Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. It is activated by tyrosine phosphorylation at position 705 leading to its dimerization, nuclear translocation, DNA binding, and activation of gene transcription. Under normal physiological conditions, STAT3 activation is tightly regulated. However, compelling evidence suggests that STAT3 is constitutively activated in many cancers and plays a pivotal role in tumor growth and metastasis. It regulates cellular proliferation, invasion, migration, and angiogenesis that are critical for cancer metastasis. In this paper, we first describe the mechanism of STAT3 regulation followed by how STAT3 is involved in cancer metastasis, then we summarize the various small molecule inhibitors that inhibit STAT3 signaling. PMID:24199193

  7. The ex vivo purge of cancer cells using oncolytic viruses: recent advances and clinical implications

    PubMed Central

    Tsang, Jovian J; Atkins, Harold L

    2015-01-01

    Hematological malignancies are treated with intensive high-dose chemotherapy, with or without radiation. This is followed by hematopoietic stem cell (HSC) transplantation (HSCT) to rescue or reconstitute hematopoiesis damaged by the anticancer therapy. Autologous HSC grafts may contain cancer cells and purging could further improve treatment outcomes. Similarly, allogeneic HSCT may be improved by selectively purging alloreactive effector cells from the graft rather than wholesale immune cell depletion. Viral agents that selectively replicate in specific cell populations are being studied in experimental models of cancer and immunological diseases and have potential applications in the context of HSC graft engineering. This review describes preclinical studies involving oncolytic virus strains of adenovirus, herpes simplex virus type 1, myxoma virus, and reovirus as ex vivo purging agents for HSC grafts, as well as in vitro and in vivo experimental studies using oncolytic coxsackievirus, measles virus, parvovirus, vaccinia virus, and vesicular stomatitis virus to eradicate hematopoietic malignancies. Alternative ex vivo oncolytic virus strategies are also outlined that aim to reduce the risk of relapse following autologous HSCT and mitigate morbidity and mortality due to graft-versus-host disease in allogeneic HSCT. PMID:27512666

  8. Advances in the diagnosis and treatment of non-small cell lung cancer.

    PubMed

    Pillai, Rathi N; Ramalingam, Suresh S

    2014-03-01

    The diagnostic and therapeutic landscape of non-small cell lung cancer (NSCLC) has changed dramatically in the past 50 years since the Surgeon General's report on smoking and lung cancer. Early detection is now a reality for lung cancer. The use of low-dose computed tomography scans for early detection decreases mortality and is beginning to be used in routine clinical practice. Technological advances such as positron emission tomography and endobronchial ultrasound have improved the accuracy of NSCLC staging. The cure rate for early-stage NSCLC has improved as a result of multimodality treatment approaches. The role of systemic therapy has also expanded to earlier stages of the disease. In recent years, the initial steps toward personalized medicine by utilization of targeted treatments based on tumor genotype have been undertaken. Emerging technological advances and greater insights into tumor biology are poised to greatly reduce the burden of lung cancer in the years to come. PMID:24516099

  9. Connecting Prognostic Ligand Receptor Signaling Loops in Advanced Ovarian Cancer

    PubMed Central

    Eng, Kevin H.; Ruggeri, Christina

    2014-01-01

    Understanding cancer cell signal transduction is a promising lead for uncovering therapeutic targets and building treatment-specific markers for epithelial ovarian cancer. To brodaly assay the many known transmembrane receptor systems, previous studies have employed gene expression data measured on high-throughput microarrays. Starting with the knowledge of validated ligand-receptor pairs (LRPs), these studies postulate that correlation of the two genes implies functional autocrine signaling. It is our goal to consider the additional weight of evidence that prognosis (progression-free survival) can bring to prioritize ovarian cancer specific signaling mechanism. We survey three large studies of epithelial ovarian cancers, with gene expression measurements and clinical information, by modeling survival times both categorically (long/short survival) and continuously. We use differential correlation and proportional hazards regression to identify sets of LRPs that are both prognostic and correlated. Of 475 candidate LRPs, 77 show reproducible evidence of correlation; 55 show differential correlation. Survival models identify 16 LRPs with reproduced, significant interactions. Only two pairs show both interactions and correlation (PDGFAPDGFRA and COL1A1CD44) suggesting that the majority of prognostically useful LRPs act without positive feedback. We further assess the connectivity of receptors using a Gaussian graphical model finding one large graph and a number of smaller disconnected networks. These LRPs can be organized into mutually exclusive signaling clusters suggesting different mechanisms apply to different patients. We conclude that a mix of autocrine and endocrine LRPs influence prognosis in ovarian cancer, there exists a heterogenous mix of signaling themes across patients, and we point to a number of novel applications of existing targeted therapies which may benefit ovarian cancer. PMID:25244152

  10. Advances in glucose metabolism research in colorectal cancer

    PubMed Central

    Fang, Sitian; Fang, Xiao

    2016-01-01

    Cancer cells uptake glucose at a higher rate and produce lactic acid rather than metabolizing pyruvate through the tricarboxylic acid cycle. This adaptive metabolic shift is termed the Warburg effect. Recently progress had been made regarding the mechanistic understanding of glucose metabolism and associated diagnostic and therapeutic methods, which have been investigated in colorectal cancer. The majority of novel mechanisms involve important glucose metabolism associated genes and miRNA regulation. The present review discusses the contribution of these research results to facilitate with the development of novel diagnosis and anticancer treatment options. PMID:27602209

  11. Advances in the surgical treatment of breast cancer.

    PubMed

    Xing, Lei; He, Qiang; Wang, Yuan-Yuan; Li, Hong-Yuan; Ren, Guo-Sheng

    2016-06-01

    Breast cancer has become the top malignant neoplasm in Chinese women with an increasing risk of morbidity and mortality. As a crucial part of comprehensive treatment of breast cancer, breast surgical technique is ceaselessly ameliorating and enriching its features. With the purpose of achieving minimal surgical intervention and satisfactory cosmetic results, the trend of mammary surgery is focusing on minimally invasive treatment and aesthetics in the 21st century. This article gives an overview of the most representative surgical procedures, such as breast conservative surgery, sentinel lymph node dissection, oncoplastic technique and breast reconstructive surgery. PMID:27265302

  12. Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

    NASA Astrophysics Data System (ADS)

    Subramaniam, Prasad

    Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused on the use of several kinds of nanomaterials for cancer and stem cell imaging and also for the delivery of anticancer therapeutics to tumor cells. However, the proper diagnosis and treatment of aggressive tumors such as brain and breast cancer requires highly sensitive diagnostic agents, in addition to the ability to deliver multiple therapeutics using a single platform to the target cells. Addressing these challenges, novel multifunctional nanomaterial-based platforms that incorporate multiple therapeutic and diagnostic agents, with superior molecular imaging and targeting capabilities, has been presented in this work. The initial part of this work presents the development of novel nanomaterials with superior optical properties for efficiently delivering soluble cues such as small interfering RNA (siRNA) into brain cancer cells with minimal toxicity. Specifically, this section details the development of non-toxic quantums dots for the imaging and delivery of siRNA into brain cancer and mesenchymal stem cells, with the hope of using these quantum dots as multiplexed imaging and delivery vehicles. The use of these quantum dots could overcome the toxicity issues associated with the use of conventional quantum dots, enabled the imaging of brain cancer and stem cells with high efficiency and allowed for the delivery of siRNA to knockdown the target oncogene in brain cancer cells. The latter part of this thesis details the development of nanomaterial-based drug delivery platforms for the co-delivery of multiple anticancer drugs to brain tumor cells. In particular, this part of the thesis focuses on

  13. Hematologic manifestations of celiac disease

    PubMed Central

    Halfdanarson, Thorvardur R.; Litzow, Mark R.; Murray, Joseph A.

    2007-01-01

    Celiac disease is a common systemic disorder that can have multiple hematologic manifestations. Patients with celiac disease may present to hematologists for evaluation of various hematologic problems prior to receiving a diagnosis of celiac disease. Anemia secondary to malabsorption of iron, folic acid, and/or vitamin B12 is a common complication of celiac disease and many patients have anemia at the time of diagnosis. Celiac disease may also be associated with thrombocytosis, thrombocytopenia, leukopenia, venous thromboembolism, hyposplenism, and IgA deficiency. Patients with celiac disease are at increased risk of being diagnosed with lymphoma, especially of the T-cell type. The risk is highest for enteropathy-type T-cell lymphoma (ETL) and B-cell lymphoma of the gut, but extraintestinal lymphomas can also be seen. ETL is an aggressive disease with poor prognosis, but strict adherence to a gluten-free diet may prevent its occurrence. PMID:16973955

  14. Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant

    ClinicalTrials.gov

    2016-03-01

    Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Renal Cell Cancer; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia

  15. Ramucirumab for advanced gastric cancer or gastro-oesophageal junction adenocarcinoma

    PubMed Central

    Young, Kate; Smyth, Elizabeth; Chau, Ian

    2015-01-01

    Ramucirumab, a fully humanized monoclonal antibody directed against vascular endothelial growth factor receptor 2, is the first targeted agent to have demonstrated an improvement in survival, as a single agent or in combination, in a molecularly unselected population in gastro-oesophageal cancer. Now that second-line treatment is routinely considered for patients with advanced gastro-oesophageal cancer, ramucirumab, with its favourable toxicity profile compared with cytotoxic treatment, provides a valuable additional treatment option. PMID:26557893

  16. Interleukin-6 and leptin as markers of energy metabolic changes in advanced ovarian cancer patients.

    PubMed

    Macciò, Antonio; Madeddu, Clelia; Massa, Daniela; Astara, Giorgio; Farci, Daniele; Melis, Gian Benedetto; Mantovani, Giovanni

    2009-09-01

    The progression of the neoplastic disease is characterized by specific alterations of energy metabolism and by symptoms like fatigue, anorexia, nausea, anaemia, immunodepression and poor performance status (PS). The main cause of these symptoms and metabolic abnormalities is the chronic action of proinflammatory cytokines released both by tumour and immune cells. The present study aimed to assess the relationship between markers of inflammation (C-Reactive Protein, Fibrinogen, proinflammatory cytokines) and energy metabolic status (BMI, leptin, oxidative stress) according to clinical parameters in 104 ovarian cancer patients at different stage and, moreover, to evaluate prospectively the changes of these parameters in accordance to tumour response in a subgroup of 70 advanced stage ovarian cancer patients. Advanced stage and poor PS were associated to high-grade inflammation and impaired energy metabolism. Among inflammatory mediators, interleukin (IL)-6 had a central role as predictive factor of leptin, reactive oxygen species and glutathione peroxidase. In turn, leptin considered the key marker of the nutritional status and energy metabolism, was independently determined from stage and IL-6, not only from BMI. Moreover, the evaluation of the changes of these parameters during the course of the neoplastic disease in the subgroup of advanced ovarian cancer patients clearly unveils the central role of IL-6 and leptin as early markers of the metabolic alterations and symptoms associated to disease progression in advanced stage ovarian cancer. Their assessment should be included in monitoring disease outcome, especially when cancer is no longer curable and quality of life becomes the primary endpoint. PMID:18624749

  17. Independent contributors to overall quality of life in people with advanced cancer

    PubMed Central

    M Rodríguez, A; Mayo, N E; Gagnon, B

    2013-01-01

    Background: The definition of health for people with cancer is not focused solely on the physiology of illness and the length of life remaining, but is also concerned with improving the well-being and the quality of the life (QOL) remaining to be lived. This study aimed to identify the constructs most associated with QOL in people with advanced cancer. Methods: Two hundred three persons with recent diagnoses of different advanced cancers were evaluated with 65 variables representing individual and environmental factors, biological factors, symptoms, function, general health perceptions and overall QOL at diagnosis. Three independent stepwise multiple linear regressions identified the most important contributors to overall QOL. R2 ranking and effect sizes were estimated and averaged by construct. Results: The most important contributor of overall QOL for people recently diagnosed with advanced cancer was social support. It was followed by general health perceptions, energy, social function, psychological function and physical function. Conclusions: We used effect sizes to summarise multiple multivariate linear regressions for a more manageable and clinically interpretable picture. The findings emphasise the importance of incorporating the assessment and treatment of relevant symptoms, functions and social support in people recently diagnosed with advanced cancer as part of their clinical care. PMID:23591199

  18. Endoscopic therapy for early gastric cancer: Standard techniques and recent advances in ESD

    PubMed Central

    Kume, Keiichiro

    2014-01-01

    The technique of endoscopic submucosal dissection (ESD) is now a well-known endoscopic therapy for early gastric cancer. ESD was introduced to resect large specimens of early gastric cancer in a single piece. ESD can provide precision of histologic diagnosis and can also reduce the recurrence rate. However, the drawback of ESD is its technical difficulty, and, consequently, it is associated with a high rate of complications, the need for advanced endoscopic techniques, and a lengthy procedure time. Various advances in the devices and techniques used for ESD have contributed to overcoming these drawbacks. PMID:24914364

  19. Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

    PubMed

    Aguiar, Pedro Nazareth; Muniz, Thiago Pimentel; Miranda, Raelson Rodrigues; Tadokoro, Hakaru; Forones, Nora Manoukian; Monteiro, Ines-de-Paula; Castelo-Branco, Pedro; Janjigian, Yelena Y; de Mello, Ramon Andrade

    2016-03-01

    In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs. PMID:26838766

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

    PubMed

    Yin, Huijing; Deng, Jiong

    2015-10-20

    Cancer stem cells (CSCs) are emerging as a hot topic for cancer research. Lung CSCs share many characteristics with normal lung stem cells (SCs), including self-renewal and multi-potency for differentiation. Many molecular markers expressed in various types of CSCs were also found in lung CSCs, such as CD133, CD44, aldehyde dehydrogenase (ALDH) and ATP-binding cassette sub-family G member 2 (ABCG2). Similarly, proliferation and expansion of lung CSCs are regulated not only by signal transduction pathways functioning in normal lung SCs, such as Notch, Hedgehog and Wnt pathways, but also by those acting in tumor cells, such as epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K) pathways. As CSC plays an critical role in tumor recurrence, metastasis and drug-resistance, understanding the difference between lung CSCs and normal lung SCs, identifying and targeting CSC markers or related signaling pathways may increase the efficacy of therapy on lung cancer and improved survival of lung cancer patients. PMID:26483336

  1. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances

    PubMed Central

    Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

    2016-01-01

    Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments. PMID:26855534

  2. Fludarabine Phosphate, Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, Total-Body Irradiation, and Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancer

    ClinicalTrials.gov

    2014-02-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hematopoietic/Lymphoid Cancer; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma

  3. Beclomethasone Dipropionate in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer

    ClinicalTrials.gov

    2015-03-05

    Hematopoietic/Lymphoid Cancer; Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Graft Versus Host Disease; Isolated Plasmacytoma of Bone; Juvenile Myelomonocytic Leukemia; Meningeal Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Disease, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small

  4. The Awakening of an Advanced Malignant Cancer: An Insult to the Mitochondrial Genome

    PubMed Central

    Cook, Cody C.; Higuchi, Masahiro

    2011-01-01

    Background In only months-to-years a primary cancer can progress to an advanced phenotype that is metastatic and resistant to clinical treatments. As early as the 1900s, it was discovered that the progression of a cancer to the advanced phenotype is often associated with a shift in the metabolic profile of the disease from a state of respiration to anaerobic fermentation – a phenomenon denoted as the Warburg Effect. Scope of Review Reports in the literature strongly suggest that the Warburg Effect is generated as a response to a loss in the integrity of the sequence and/or copy number of the mitochondrial genome content within a cancer. Multiple studies regarding the progression of cancer indicate that mutation, and/or, a flux in the copy number, of the mitochondrial genome content can support the early development of a cancer, until; the mutational load and/or the reduction-to-depletion of the copy number of the mitochondrial genome content induces the progression of the disease to an advanced phenotype. General Significance Collectively, evidence has revealed that the human cell has incorporated the mitochondrial genome content into a cellular mechanism that, when pathologically actuated, can de (un)differentiate a cancer from the parental tissue of origin into an autonomous disease that disrupts the hierarchical structure-and-function of the human body. PMID:21920409

  5. Prolonged complete response following gemcitabine-erlotinib combined therapy in advanced pancreatic cancer

    PubMed Central

    CZARNECKA, ANNA M.; KORZEŃ, PIOTR; NOWAK-DEMENT, ANNA; KUKWA, WOJCIECH; KORNILUK, JAN; SZCZYLIK, CEZARY

    2016-01-01

    Pancreatic cancer is one of the most lethal types of malignant solid tumor and is typically associated with a poor prognosis. The majority of patients are diagnosed with advanced-stage disease, therefore, the median survival period is <6 months. Recently, a number of basic research projects and clinical trials were undertaken with the aim of improving treatment outcomes in pancreatic cancer; however, only one agent, erlotinib, passed the clinical trials. Erlotinib is an inhibitor of epidermal growth factor receptor, which when overexpressed in cancer, promotes angiogenesis, cell proliferation and inhibits apoptosis. The US Food and Drug Administration and European Medicines Agency approved erlotinib in combination with gemcitabine for the first-line treatment of advanced pancreatic cancer. To the best of our knowledge, the current study is the first to report a case of pancreatic cancer treated with this regimen alone to achieve a complete response (CR). A 40-year-old male with a medical history of chronic pancreatitis and hypertension was diagnosed with medically inoperable adenocarcinoma of the pancreas. Following palliative surgery, the patient began palliative gemcitabine and erlotinib chemotherapy. After three months, this treatment strategy resulted in a CR, as determined by imaging studies. Therapy was discontinued after 14 months due to the development of peritoneal metastases and the patient was referred for treatment with the folinic acid, 5-fluorouracil, irinotecan and oxaliplatin regimen. A CR is rarely reported in pancreatic cancer, however, a treatment strategy of gemcitabine and erlotinib may induce rapid regression of advanced-stage disease. PMID:26893699

  6. Review of systemic therapies for locally advanced and metastatic rectal cancer

    PubMed Central

    Osipov, Arsen; Tan, Carlyn; Tuli, Richard; Hendifar, Andrew

    2015-01-01

    Rectal cancer, along with colon cancer, is the second leading cause of cancer-related deaths in the U.S. Up to a quarter of patients have metastatic disease at diagnosis and 40% will develop metastatic disease. The past 10 years have been extremely exciting in the treatment of both locally advanced and metastatic rectal cancer (mRC). With the advent of neoadjuvant chemoradiation, increased numbers of patients with locally advanced rectal cancer (LARC) are surviving longer and some are seeing their tumors shrink to sizes that allow for resection. The advent of biologics and monoclonal antibodies has propelled the treatment of mRC further than many could have hoped. Combined with regimens such as FOLFOX or FOLFIRI, median survival rates have been increased to an average of 23 months. However, the combinations of chemotherapy regimens seem endless for rectal cancer. We will review the major chemotherapies available for locally advanced and mRC as well as regimens currently under investigation such as FOLFOXIRI. We will also review vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitors as single agents and in combination with traditional chemotherapy regimens. PMID:25830038

  7. Management of locally advanced and metastatic colon cancer in elderly patients

    PubMed Central

    Kurniali, Peter C; Hrinczenko, Borys; Al-Janadi, Anas

    2014-01-01

    Colon cancer is the second leading cause of cancer mortality in the United States with a median age at diagnosis of 69 years. Sixty percent are diagnosed over the age of 65 years and 36% are 75 years or older. At diagnosis, approximately 58% of patients will have locally advanced and metastatic disease, for which systemic chemotherapy has been shown to improve survival. Treatment of cancer in elderly patients is more challenging due to multiple factors, including disabling co-morbidities as well as a decline in organ function. Cancer treatment of elderly patients is often associated with more toxicities that may lead to frequent hospitalizations. In locally advanced disease, fewer older patients receive adjuvant chemotherapy despite survival benefit and similar toxicity when compared to their younger counterparts. A survival benefit is also observed in the palliative chemotherapy setting for elderly patients with metastatic disease. When treating elderly patients with colon cancer, one has to consider drug pharmacokinetics and pharmacodynamics. Since chronological age is a poor marker of a patient’s functional status, several methods of functional assessment including performance status and activities of daily living (ADL) or instrumental ADL, or even a comprehensive geriatric assessment, may be used. There is no ideal chemotherapy regimen that fits all elderly patients and so a regimen needs to be tailored for each individual. Important considerations when treating elderly patients include convenience and tolerability. This review will discuss approaches to the management of elderly patients with locally advanced and metastatic colon cancer. PMID:24616568

  8. Advances in molecular imaging: targeted optical contrast agents for cancer diagnostics

    PubMed Central

    Hellebust, Anne; Richards-Kortum, Rebecca

    2012-01-01

    Over the last three decades, our understanding of the molecular changes associated with cancer development and progression has advanced greatly. This has led to new cancer therapeutics targeted against specific molecular pathways; such therapies show great promise to reduce mortality, in part by enabling physicians to tailor therapy for patients based on a molecular profile of their tumor. Unfortunately, the tools for definitive cancer diagnosis – light microscopic examination of biopsied tissue stained with nonspecific dyes – remain focused on the analysis of tissue ex vivo. There is an important need for new clinical tools to support the molecular diagnosis of cancer. Optical molecular imaging is emerging as a technique to help meet this need. Targeted, optically active contrast agents can specifically label extra-and intracellular biomarkers of cancer. Optical images can be acquired in real time with high spatial resolution to image-specific molecular targets, while still providing morphologic context. This article reviews recent advances in optical molecular imaging, highlighting the advances in technology required to improve early cancer detection, guide selection of targeted therapy and rapidly evaluate therapeutic efficacy. PMID:22385200

  9. Novel therapy for locally advanced triple-negative breast cancer

    PubMed Central

    YAMADA, ATSUKO; OSADA, SHINJI; TANAHASHI, TOSHIYUKI; MATSUI, SATOSHI; SASAKI, YOSHIYUKI; TANAKA, YOSHIHIRO; OKUMURA, NAOKI; MATSUHASHI, NOBUHISA; TAKAHASHI, TAKAO; YAMAGUCHI, KAZUYA; YOSHIDA, KAZUHIRO

    2015-01-01

    To evaluate a novel therapy for triple-negative breast cancer (TNBC), the biological responses to vitamin K3 (VK3) should be considered with the understanding of the features of breast cancer. In human breast cancer cell lines, the effects of VK3 on cell growth inhibition and the cellular signaling pathway were determined by MTT assay and western blotting. In the in vivo study, a subcutaneous tumor model of breast cancer was created, VK3 was injected into the subcutaneous tumors, and tumor size was measured. The IC50 of VK3 for breast cancer cells was calculated to be 11.3–25.1 μM. VK3 induced phosphorylation of whole tyrosine and epidermal growth factor receptor. VK3 mediated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) for 30 min. ERK but not JNK phosphorylation was maintained for at least 6 h. In contrast, another antioxidant agent, catalase, showed no effect on either ERK phosphorylation or growth inhibition. On built-up tumors under the skin of mice, local treatment with VK3 was effective in a time- and dose-dependent manner, and the experiments for total tumor volume also showed a dose-dependent effect of VK3. The expression of phosphorylated ERK was clearly detected at 10.9 times the control in tumor tissue, whereas ethanol itself showed no effect. In conclusion, ERK plays a critical role in VK3-induced growth inhibition, and it will be the focus of next steps in the development of molecular therapy for TNBC. PMID:26252842

  10. New sources of drugs for hematologic malignancies

    PubMed Central

    Sukhai, Mahadeo A.; Spagnuolo, Paul A.; Weir, Scott; Kasper, James; Patton, Lavonne

    2011-01-01

    Advancing novel therapeutic agents for the treatment of malignancy into the marketplace is an increasingly costly and lengthy process. As such, new strategies for drug discovery are needed. Drug repurposing represents an opportunity to rapidly advance new therapeutic strategies into clinical trials at a relatively low cost. Known on-patent or off-patent drugs with unrecognized anticancer activity can be rapidly advanced into clinical testing for this new indication by leveraging their known pharmacology, pharmacokinetics, and toxicology. Using this approach, academic groups can participate in the drug discovery field and smaller biotechnology companies can “de-risk” early-stage drug discovery projects. Here, several scientific approaches used to identify drug repurposing opportunities are highlighted, with a focus on hematologic malignancies. In addition, a discussion of the regulatory issues that are unique to drug repurposing and how they impact developing old drugs for new indications is included. Finally, the mechanisms to enhance drug repurposing through increased collaborations between academia, industry, and nonprofit charitable organizations are discussed. PMID:21511957

  11. Inhibition of CXCR4 by LY2624587, a Fully Humanized Anti-CXCR4 Antibody Induces Apoptosis of Hematologic Malignancies

    PubMed Central

    Peng, Sheng-Bin; Zhang, Xiaoyi; Paul, Donald; Kays, Lisa M.; Ye, Ming; Vaillancourt, Peter; Dowless, Michele; Stancato, Louis F.; Stewart, Julie; Uhlik, Mark T.; Long, Haiyan; Chu, Shaoyou; Obungu, Victor H.

    2016-01-01

    SDF-1 and CXCR4 are a chemokine and chemokine receptor pair playing critical roles in tumorigenesis. Overexpression of CXCR4 is a hallmark of many hematological malignancies including acute myeloid leukemia, chronic lymphocytic leukemia and non-Hodgkin’s lymphoma, and generally correlates with a poor prognosis. In this study, we developed a humanized anti-CXCR4 monoclonal antibody, LY2624587 as a potent CXCR4 antagonist that was advanced into clinical study for cancer. LY2624587 blocked SDF-1 binding to CXCR4 with an IC50 of 0.26 nM, and inhibited SDF-1-induced GTP binding with a Kb of 0.66 nM. In human lymphoma U937 and leukemia CCRF-CEM cells expressing endogenous CXCR4, LY2624587 inhibited SDF-1-induced cell migration with IC50 values of 3.7 and 0.26 nM, respectively. This antibody also inhibited CXCR4 and SDF-1 mediated cell signaling including activation of MAPK and AKT in tumor cells expressing CXCR4. Bifocal microscopic and flow cytometry analyses revealed that LY2624587 mediated receptor internalization and caused CXCR4 down-regulation on the cell surface. In human hematologic cancer cells, LY2624587 caused dose dependent apoptosis in vitro and in vivo. In mouse xenograft models developed with human leukemia and lymphoma cells expressing high levels of CXCR4, LY2624587 exhibited dose-dependent tumor growth inhibition and provided significant survival benefit in a disseminated lymphoma model. Collectively, we have demonstrated that CXCR4 inhibition by LY2624587 has the potential for the treatment of human hematological malignancies. PMID:26954567

  12. A decision exercise to engage cancer patients and families in Deliberation about Medicare Coverage for advanced Cancer Care

    PubMed Central

    2014-01-01

    Background Concerns about unsustainable costs in the US Medicare program loom as the number of retirees increase and experiences serious and costly illnesses like cancer. Engagement of stakeholders, particularly cancer patients and their families, in prioritizing insured services offers a valuable strategy for informing Medicare coverage policy. We designed and evaluated a decision exercise that allowed cancer patients and family members to choose Medicare benefits for advanced cancer patients. Methods The decision tool, Choosing Health plans All Together (CHAT) was modified to select services for advanced cancer patients. Patients with a cancer history (N = 246) and their family members (N = 194) from North Carolina participated in 70 CHAT sessions. Variables including participants’ socio-demographic characteristics, health status, assessments of the exercise and results of group benefit selections were collected. Routine descriptive statistics summarized participant characteristics and Fisher’s exact test compared group differences. Qualitative analysis of group discussions were used to ascertain reasons for or against selecting benefits. Results Patients and family members (N = 440) participated in 70 CHAT exercises. Many groups opted for such services as palliative care, nursing facilities, and services not currently covered by the Medicare program. In choosing among four levels of cancer treatment coverage, no groups chose basic coverage, 27 groups (39%) selected intermediate coverage, 39 groups (56%) selected high coverage, and 4 groups (6%) chose the most comprehensive cancer coverage. Reasons for or against benefit selection included fairness, necessity, need for prioritizing, personal experience, attention to family needs, holistic health outlook, preference for comfort, freedom of choice, and beliefs about the proper role of government. Participants found the exercise very easy (59%) or fairly easy (39%) to understand and very informative (66%) or

  13. Advances in the use of nanocarriers for cancer diagnosis and treatment

    PubMed Central

    Vieira, Débora Braga; Gamarra, Lionel Fernel

    2016-01-01

    ABSTRACT The use of nanocarriers as drug delivery systems for therapeutic or imaging agents can improve the pharmacological properties of commonly used compounds in cancer diagnosis and treatment. Advances in the surface engineering of nanoparticles to accommodate targeting ligands turned nanocarriers attractive candidates for future work involving targeted drug delivery. Although not targeted, several nanocarriers have been approved for clinical use and they are currently used to treat and/or diagnosis various types of cancers. Furthermore, there are several formulations, which are now in various stages of clinical trials. This review examined some approved formulations and discussed the advantages of using nanocarriers in cancer therapy. PMID:27074238

  14. New and emerging targeted treatments in advanced non-small-cell lung cancer.

    PubMed

    Hirsch, Fred R; Suda, Kenichi; Wiens, Jacinta; Bunn, Paul A

    2016-09-01

    Targeted therapies are substantially changing the management of lung cancers. These treatments include drugs that target driver mutations, those that target presumed important molecules in cancer cell proliferation and survival, and those that inhibit immune checkpoint molecules. This area of research progresses day by day, with novel target discoveries, novel drug development, and use of novel combination treatments. Researchers and clinicians have also extensively investigated the predictive biomarkers and the molecular mechanisms underlying inherent or acquired resistance to these targeted therapies. We review recent progress in the development of targeted treatments for patients with advanced non-small-cell lung cancer, especially focusing on data from published clinical trials. PMID:27598681

  15. Advances in the use of nanocarriers for cancer diagnosis and treatment.

    PubMed

    Vieira, Débora Braga; Gamarra, Lionel Fernel

    2016-03-01

    The use of nanocarriers as drug delivery systems for therapeutic or imaging agents can improve the pharmacological properties of commonly used compounds in cancer diagnosis and treatment. Advances in the surface engineering of nanoparticles to accommodate targeting ligands turned nanocarriers attractive candidates for future work involving targeted drug delivery. Although not targeted, several nanocarriers have been approved for clinical use and they are currently used to treat and/or diagnosis various types of cancers. Furthermore, there are several formulations, which are now in various stages of clinical trials. This review examined some approved formulations and discussed the advantages of using nanocarriers in cancer therapy. PMID:27074238

  16. Vorinostat in solid and hematologic malignancies

    PubMed Central

    Siegel, David; Hussein, Mohamad; Belani, Chandra; Robert, Francisco; Galanis, Evanthia; Richon, Victoria M; Garcia-Vargas, José; Sanz-Rodriguez, Cesar; Rizvi, Syed

    2009-01-01

    Vorinostat (Zolinza®), a histone deacetylase inhibitor, was approved by the US Food and Drug Administration in October 2006 for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. This review summarizes evidence on the use of vorinostat in solid and hematologic malignancies and collated tolerability data from the vorinostat clinical trial program. Pooled vorinostat clinical trial data from 498 patients with solid or hematologic malignancies show that vorinostat was well tolerated as monotherapy or combination therapy. The most commonly reported drug-related adverse events (AEs) associated with monotherapy (n = 341) were fatigue (61.9%), nausea (55.7%), diarrhea (49.3%), anorexia (48.1%), and vomiting (32.8%), and Grade 3/4 drug-related AEs included fatigue (12.0%), thrombocytopenia (10.6%), dehydration (7.3%), and decreased platelet count (5.3%). The most common drug-related AEs observed with vorinostat in combination therapy (n = 157, most of whom received vorinostat 400 mg qd for 14 days) were nausea (48.4%), diarrhea (40.8%), fatigue (34.4%), vomiting (31.2%), and anorexia (20.4%), with the majority of AEs being Grade 2 or less. In Phase I trials, combinations with vorinostat were generally well tolerated and preliminary evidence of anticancer activity as monotherapy or in combination with other systemic therapies has been observed across a range of malignancies. Ongoing and planned studies will further evaluate the potential of vorinostat in combination therapy, including combinations with radiation, in patients with diverse malignancy types, including non-small-cell lung cancer, glioblastoma multiforme, multiple myeloma, and myelodysplastic syndrome. PMID:19635146

  17. Exercise and relaxation intervention for patients with advanced lung cancer: a qualitative feasibility study.

    PubMed

    Adamsen, L; Stage, M; Laursen, J; Rørth, M; Quist, M

    2012-12-01

    Lung cancer patients experience loss of physical capacity, dyspnea, pain, reduced energy and psychological distress. The aim of this study was to explore feasibility, health benefits and barriers of exercise in former sedentary patients with advanced stage lung cancer, non-small cell lung cancer (NSCLC) (III-IV) and small cell lung cancer (SCLC) (ED), undergoing chemotherapy. The intervention consisted of a hospital-based, supervised, group exercise and relaxation program comprising resistance-, cardiovascular- and relaxation training 4 h weekly, 6 weeks, and a concurrent unsupervised home-based exercise program. An explorative study using individual semi-structured interviews (n=15) and one focus group interview (n=8) was conducted among the participants. Throughout the intervention the patients experienced increased muscle strength, improvement in wellbeing, breathlessness and energy. The group exercise and relaxation intervention showed an adherence rate of 76%, whereas the patients failed to comply with the home-based exercise. The hospital-based intervention initiated at time of diagnosis encouraged former sedentary lung cancer patients to participation and was undertaken safely by cancer patients with advanced stages of disease, during treatment. The patients experienced physical, functional and emotional benefits. This study confirmed that supervised training in peer-groups was beneficial, even in a cancer population with full-blown symptom burden and poor prognosis. PMID:21599754

  18. Non-small cell lung cancer: current treatment and future advances

    PubMed Central

    Zappa, Cecilia

    2016-01-01

    Lung cancer has a poor prognosis; over half of people diagnosed with lung cancer die within one year of diagnosis and the 5-year survival is less than 18%. Non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancer cases. Risk factors for developing NSCLC have been identified, with cigarette smoking being a major factor along with other environmental and genetic risk factors. Depending on the staging of lung cancer, patients are eligible for certain treatments ranging from surgery to radiation to chemotherapy as well as targeted therapy. With the advancement of genetics and biomarkers testing, specific mutations have been identified to better target treatment for individual patients. This review discusses current treatments including surgery, chemotherapy, radiotherapy, and immunotherapy as well as how biomarker testing has helped improve survival in patients with NSCLC. PMID:27413711

  19. Recent advancements in toxicity prediction following prostate cancer radiotherapy.

    PubMed

    Ospina, J D; Fargeas, A; Dréan, G; Simon, A; Acosta, O; de Crevoisier, R

    2015-01-01

    In external beam radiotherapy for prostate cancer limiting toxicities for dose escalation are bladder and rectum toxicities. Normal tissue complication probability models aim at quantifying the risk of developping adverse events following radiotherapy. These models, originally proposed in the context of uniform irradiation, have evolved to implementations based on the state-of-the-art classification methods which are trained using empirical data. Recently, the use of image processing techniques combined with population analysis methods has led to a new generation of models to understand the risk of normal tissue complications following radiotherapy. This paper overviews those methods in the case of prostate cancer radiation therapy and propose some lines of future research. PMID:26737471

  20. Personalizing Therapy in Advanced Non–Small Cell Lung Cancer

    PubMed Central

    Villaruz, Liza C.; Burns, Timothy F.; Ramfidis, Vasilis S.; Socinski, Mark A.

    2016-01-01

    The recognition that non–small cell lung cancer (NSCLC) is not a single disease entity, but rather a collection of distinct molecularly driven neoplasms, has permanently shifted the therapeutic landscape of NSCLC to a personalized approach. This personalization of NSCLC therapy is typified by the dramatic response rates seen in EGFR mutant NSCLC when treated with targeted tyrosine kinase inhibitor therapy and in ALK translocation–driven NSCLC when treated with ALK inhibitors. Targeted therapeutic approaches in NSCLC necessitate consideration of more invasive biopsy techniques aimed at providing sufficient tissue for both histological determination and molecular profiling in all patients with stage IV disease both at the time of diagnosis and at the time of disease progression. Comprehensive genotyping efforts have identified oncogenic drivers in 62% lung adenocarcinomas and an increasing proportion of squamous cell carcinomas of the lung. The identification of these oncogenic drivers and the triage of patients to clinical trials evaluating novel targeted therapeutic approaches will increasingly mold a landscape of personalized lung cancer therapy where each genotype has an associated targeted therapy. This review outlines the state of personalized lung cancer therapy as it pertains to individual NSCLC genotypes. PMID:24258572

  1. A Phase II Study of Fixed-Dose Rate Gemcitabine Plus Low-Dose Cisplatin Followed by Consolidative Chemoradiation for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Ko, Andrew H.; Venook, Alan P.

    2007-07-01

    Purpose: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population. Methods and Materials: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m{sup 2} at 10 mg/m{sup 2}/min) plus cisplatin 20 mg/m{sup 2} on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800 mg/m{sup 2} orally twice daily on the day of radiation) as a radiosensitizer. Results: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months. Conclusions: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation.

  2. [Research Progress on Co-stimulating Molecule B7-H3 in Hematological Malignancies].

    PubMed

    Zhang, Wei; Wang, Jing; Ke, Xiao-Yan

    2015-12-01

    Costimulatory molecule B7-H3 is a new member of the B7 immunoregulatory family identified in 2001. Although B7-H3 mRNA is widely detected in a variety of lymphoid and nonlymphoid organs, but the B7-H3 protein is distributed limitedly, generally absent or low expressed in normal tissues. The triggering receptor expressed on myeloid cell (TREM)-like transcript 2 (TLT-2) is a possible receptor for B7-H3, but it is not confirmed. B7-H3 has an important immunologic function having costimulatory or coinhibitory immunoregulatory effects in adaptive immune responses, but its exact mechanism remains contentious. The recent studies reported that aberrant overexpression of B7-H3 was found in a wide range of solid cancer tissues and cells, and associated with more advanced disease and poor prognosis, and directly performed nonimmunological functions in oncogenesis. However, more and more studies demonstrate that B7-H3 also plays an important role in progression of hematologic malignancies. The overexpression of B7-H3 is significantly associated with the malignant degree, relapse, progression and prognosis in haematological malignancies. Thus, B7-H3 represents a novel diagnostic marker and potential therapeutic target for cancers. The immunotherapy targeting to B7-H3 become one of the hotspots of recent researches, and some monoclonal antibodies have already entered into clinical trials. This review summarizes the available data on the relationship between B7-H3 and hematologic malignancies, and further focusing on B7-H3 as a potential therapeutic target in these tumors. PMID:26708906

  3. Effect of pravastatin on the survival of patients with advanced gastric cancer

    PubMed Central

    Bujanda, Luis; Rodríguez-González, Araceli; Sarasqueta, Cristina; Eizaguirre, Emma; Hijona, Elizabeth; Marín, José J.G.; Perugorria, María J.; Banales, Jesús M.; Cosme, Angel

    2016-01-01

    Objectives A fluoropyrimidine plus cisplatin combined with surgery is standard first-line treatment for advanced gastric cancer. We evaluated the effect of pravastatin on overall survival in patients with advanced gastric cancer in a prospective cohort study. Methods At the time of surgery, we assigned 60 patients with advanced gastric cancer (stage III or IV) to receive standard first-line treatment (control group) or standard first-line treatment plus pravastatin at a dose of 40 mg once daily (pravastatin group). The minimum follow-up period was 4 years and the maximum of 6 years. Results The mean of age was 66 years and the TNM stage was III and IV in 65% and 35% of patients, respectively. There was no significant difference between the two groups (control vs pravastatin) in median overall survival (15 vs 14 months; P = 0.8). Predictors of survival were the stage (hazard ratio of death stage IV (III stage as reference): 4.4; 95% CI: 2–9.7; p < 0.05) and older age (hazard ratio of death ≥ 65 years (< 65 years as reference): 2.8; 95% CI: 1.3–6; p < 0.05). Conclusions Pravastatin did not improve outcome in patients with advanced gastric cancer. PMID:26735890

  4. Effectiveness of the Mindfulness Art Therapy Short Version for Japanese Patients with Advanced Cancer

    ERIC Educational Resources Information Center

    Ando, Michiyo; Kira, Haruko; Hayashida, Shigeru; Ito, Sayoko

    2016-01-01

    The aim of this study was to investigate the feasibility of the Mindfulness Art Therapy Short Version for Japanese patients with advanced cancer. Patients learned mindfulness practices and then made art to express their feelings in the first session. After receiving instruction on practicing mindfulness 2 weeks later, they participated in a second…

  5. New strategies in advanced cervical cancer: from angiogenesis blockade to immunotherapy.

    PubMed

    Tewari, Krishnansu S; Monk, Bradley J

    2014-11-01

    Cervical cancer remains unique among solid tumor malignancies. Persistent infection with oncogenic subtypes of the human papillomavirus (HPV) results in carcinogenesis, predominantly occurring at the cervical transformation zone where endocervical columnar cells undergo metaplasia to a stratified squamous epithelium. The molecular cascade involving viral oncoproteins, E6 and E7 and their degradative interactions with cellular tumor suppressor gene products, p53 and pRb, respectively, has been precisely delineated. The precursor state of cervical neoplasia may last for years allowing for ready detection through successful screening programs in developed countries using cervical cytology and/or high-risk HPV DNA testing. Prophylactic HPV L1 capsid protein vaccines using virus-like-particle technology have been developed to prevent primary infection by the most common high-risk HPVs (16 and 18). Women who lack access to health care and those who undergo sporadic screening remain at risk. Although radical surgery (including fertility-sparing surgery) is available for patients with early-stage cancers, and chemoradiation plus high-dose-rate brachytherapy can cure the majority of those with locally advanced disease, patients with metastatic and nonoperable recurrent cervical cancer constitute a high-risk population with an unmet clinical need. On August 14, 2014, the FDA approved the antiangiogenesis drug bevacizumab for women with advanced cervical cancer. This review will highlight advances in translational science, antiangiogenesis therapy and immunotherapy for advanced disease. PMID:25104084

  6. Negative religious coping as a correlate of suicidal ideation in patients with advanced cancer

    PubMed Central

    Trevino, K. M.; Balboni, M.; Zollfrank, A.; Balboni, T.; Prigerson, H. G.

    2016-01-01

    Objective The purpose of this study is to examine the relationship between negative religious coping (NRC) and suicidal ideation in patients with advanced cancer, controlling for demographic and disease characteristics and risk and protective factors for suicidal ideation. Methods Adult patients with advanced cancer (life expectancy ≤6 months) were recruited from seven medical centers in the northeastern and southwestern USA (n = 603). Trained raters verbally administered the examined measures to patients upon study entry. Multivariable logistic regression analyses regressed suicidal ideation on NRC controlling for significant demographic, disease, risk, and protective factors. Results Negative religious coping was associated with an increased risk for suicidal ideation (OR, 2.65 [95% CI, 1.22, 5.74], p = 0.01) after controlling for demographic and disease characteristics, mental and physical health, self-efficacy, secular coping, social support, spiritual care received, global religiousness and spirituality, and positive religious coping. Conclusions Negative religious coping is a robust correlate of suicidal ideation. Assessment of NRC in patients with advanced cancer may identify patients experiencing spiritual distress and those at risk for suicidal ideation. Confirmation of these results in future studies would suggest the need for interventions targeting the reduction of NRC to reduce suicidal ideation among advanced cancer patients. PMID:24577802

  7. Ropidoxuridine in Treating Patients With Advanced Gastrointestinal Cancer Undergoing Radiation Therapy

    ClinicalTrials.gov

    2016-06-17

    Bile Duct Carcinoma; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIA Small Intestinal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIB Small Intestinal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Small Intestinal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  8. Symptoms and problems in a nationally representative sample of advanced cancer patients.

    PubMed

    Johnsen, A T; Petersen, M A; Pedersen, L; Groenvold, M

    2009-09-01

    Little is known about the need for palliative care among advanced cancer patients who are not in specialist palliative care. The purpose was to identify prevalence and predictors of symptoms and problems in a nationally representative sample of Danish advanced cancer patients. Patients with cancer stage 3 or 4 from 54 hospital departments (n = 1630) received the EORTC QLQ-C30 questionnaire. Mean scores were calculated according to the scoring manual and in addition a 'symptom/problem' and a 'severe symptom/problem' was defined and calculated. Multiple logistic regression was used to identify predictors. In total, 977 (60%) patients participated. The most frequent symptoms/problems were fatigue (57%; severe 22%) followed by reduced role function, insomnia and pain. Age, cancer stage, primary tumour, type of department, marital status and whether the patient had recently been hospitalized or not were associated with several symptoms and problems. This is probably the first nationally representative study of its kind. It shows that advanced cancer patients in Denmark have symptoms and problems that deserve attention and that some patient groups are especially at risk. PMID:19443525

  9. Anterior-only Partial Sacrectomy for en bloc Resection of Locally Advanced Rectal Cancer

    PubMed Central

    Roldan, Hector; Perez-Orribo, Luis F.; Plata-Bello, Julio M.; Martin-Malagon, Antonio I.; Garcia-Marin, Victor M.

    2014-01-01

    Study Design Case report. Objective The usual procedure for partial sacrectomies in locally advanced rectal cancer combines a transabdominal and a posterior sacral route. The posterior approach is flawed with a high rate of complications, especially infections and wound-healing problems. Anterior-only approaches have indirectly been mentioned within long series of rectal cancer surgery. We describe a case of partial sacrectomy for en bloc resection of a locally advanced rectal cancer with invasion of the low sacrum through a combined transabdominal and perineal approach without any posterior incision. Methods Through a midline laparotomy, the tumor was dissected and the sacral osteotomy was performed. Once the sacrum was mobile, the muscular attachments to its posterior wall were cut through the perineal approach. This latter route was also used to remove the whole specimen. Results The postoperative period was uneventful in terms of infection and wound healing, but the patient developed right foot dorsiflexion paresis that completely disappeared in 1 month. Resection margins were negative. After a follow-up of 18 months, the patient has no local recurrence but presented lung and liver metastases. Conclusion In cases of rectal cancer involving the low sacrum, the combination of a transabdominal and a perineal route to carry out the partial sacrectomy is a feasible approach that avoids changes of surgical positioning and the morbidity related to posterior incisions. This strategy should be considered when deciding on undertaking partial sacrectomy in locally advanced rectal cancer. PMID:25396109

  10. Recent technological advances in using mouse models to study ovarian cancer.

    PubMed

    House, Carrie Danielle; Hernandez, Lidia; Annunziata, Christina Messineo

    2014-01-01

    Serous epithelial ovarian cancer (SEOC) is the most lethal gynecological cancer in the United States with disease recurrence being the major cause of morbidity and mortality. Despite recent advances in our understanding of the molecular mechanisms responsible for the development of SEOC, the survival rate for women with this disease has remained relatively unchanged in the last two decades. Preclinical mouse models of ovarian cancer, including xenograft, syngeneic, and genetically engineered mice, have been developed to provide a mechanism for studying the development and progression of SEOC. Such models strive to increase our understanding of the etiology and dissemination of ovarian cancer in order to overcome barriers to early detection and resistance to standard chemotherapy. Although there is not a single model that is most suitable for studying ovarian cancer, improvements have led to current models that more closely mimic human disease in their genotype and phenotype. Other advances in the field, such as live animal imaging techniques, allow effective monitoring of the microenvironment and therapeutic efficacy. New and improved preclinical mouse models, combined with technological advances to study such models, will undoubtedly render success of future human clinical trials for patients with SEOC. PMID:24592355

  11. Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer.

    PubMed

    Gollins, S; Sebag-Montefiore, D

    2016-02-01

    Improved surgical technique plus selective preoperative radiotherapy have decreased rectal cancer pelvic local recurrence from, historically, 25% down to about 5-10%. However, this improvement has not reduced distant metastatic relapse, which is the main cause of death and a key issue in rectal cancer management. The current standard is local pelvic treatment (surgery ± preoperative radiotherapy) followed by adjuvant chemotherapy, depending on resection histology. For circumferential resection margin (CRM)-threatened cancer on baseline magnetic resonance imaging, downstaging long-course preoperative chemoradiation (LCPCRT) is generally used. However, for non-CRM-threatened disease, varying approaches are currently adopted in the UK, including straight to surgery, short-course preoperative radiotherapy and LCPCRT. Clinical trials are investigating intensification of concurrent chemoradiation. There is also increasing interest in investigating preoperative neoadjuvant chemotherapy (NAC) as a way of exposing micro-metastatic disease to full-dose systemic chemotherapy as early as possible and potentially reducing metastatic relapse. Phase II trials suggest that this strategy is feasible, with promising histological response and low rates of tumour progression during NAC. Phase III trials are needed to determine the benefit of NAC when added to standard therapy and also to determine if it can be used instead of neoadjuvant radiotherapy-based schedules. Although several measures of neoadjuvant treatment response assessment based on imaging or pathology are promising predictive biomarkers for long-term survival, none has been validated in prospective phase III studies. The phase III setting will enable this, also providing translational opportunities to examine molecular predictors of response and survival. PMID:26645661

  12. [Recent Advances in Systemic Chemotherapy for Metastatic Colorectal Cancer].

    PubMed

    Miyamoto, Yuji; Oki, Eiji; Saeki, Hiroshi; Maehara, Yoshihiko; Baba, Hideo

    2016-01-01

    The recent development of chemotherapeutic agents and biomarkers have remarkably improved treatment outcomes of metastatic colorectal cancer (mCRC). However, decision making regarding the choice of therapy for mCRC has been complicated by the availability of many different treatment options. In this review, we will discuss the clinical evidence for current systemic treatment, including the key roles of 3 cytotoxic drugs and oral fluoropyrimidines, the appropriate use of anti-VEGF and anti-EGFR therapy, the significance of RAS mutation status as a predictive marker for anti-EGFR therapy, and new agents for salvage therapy (regorafenib and TAS-102 [TFTD]). PMID:26809522

  13. Advanced Vulvar Cancers: What are the Best Options for Treatment?

    PubMed

    Soderini, Alejandro; Aragona, Alejandro; Reed, Nicholas

    2016-10-01

    The treatment of patients with vulvar cancer remains challenging for gynecologic oncologists. Up to 30 % of the cases are diagnosed in a clinical condition of irresectability, and some kind of strategy has to be taken into account beyond surgery. In this regard, a common and standard definition is critical to maximize oncological results and minimize complications after treatments. Each patient treatment must be tailored individually according to their clinical and biological features and to the setting in which they are dealing with. PMID:27586378

  14. [Recent advance in adjuvant therapy for breast cancer].

    PubMed

    Shimizu, Chikako; Watanabe, Toru

    2002-12-01

    Adjuvant systemic therapy has contributed to a significant improvement of disease-free and overall survival in addition to surgery and irradiation to the local disease. The adjuvant therapy to a patient is determined integrating the information on estimated risk of recurrence, benefit and harm of the therapy and the patient's value. In this review, the state of the art of adjuvant therapy is discussed from several aspects, such as interpretation and evaluation of risk, the best available evidences on adjuvant systemic therapy, the future direction of primary therapy for breast cancer, and patient-oriented decision making. PMID:12506467

  15. Cancer drug development in China: recent advances and future challenges.

    PubMed

    Wu, Yi-Long; Zhang, Helena; Yang, Yumei

    2015-06-01

    Over the past 10 years, the Chinese Government, academic organizations, and biopharmaceutical companies have tried to transition the nation from a consumer of generic drugs into a developer of innovative therapies. Here, we present a timeline of recent innovative cancer drug development, with a particular focus on four case studies that have reshaped perceptions of what can be done in China. We present metrics comparing China with other countries alongside analysis of what national authorities are doing to close the gap in areas where China still lags behind the West. PMID:25463037

  16. B-Cell Hematologic Malignancy Vaccination Registry

    ClinicalTrials.gov

    2015-09-15

    Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

  17. Target Therapy in Hematological Malignances: New Monoclonal Antibodies

    PubMed Central

    Szymczyk, Agnieszka; Pawlowski, Johannes

    2014-01-01

    Apart from radio- and chemotherapy, monoclonal antibodies (MoAbs) represent a new, more selective tool in the treatment of hematological malignancies. MoAbs bind with the specific antigens of the tumors. This interaction is a basis for targeted therapies which exhibit few side effects and significant antitumor activity. This review provides an overview of the functional characteristics of MoAbs, with some examples of their clinical application. The promising results in the treatment of hematological malignancies have led to the more frequent usage of MoAbs in the therapy. Development of MoAbs is a subject of extensive research. They are a promising method of cancer treatment in the future.

  18. Advanced gastric cancer and a concomitant pregnancy associated with disseminated intravascular coagulation.

    PubMed

    Kurabayashi, Takumi; Isii, Keisuke; Suzuki, Mina; Takakuwa, Koichi; Shibazaki, Yasuhiko; Ozawa, Tsunenori; Narisawa, Rintaro; Sekizuka, Naoto; Tanaka, Kenichi

    2004-07-01

    Gastric cancer associated with pregnancy is extremely rare and the prognosis is generally grave. A 31-year-old Japanese women, 41 weeks pregnant, displayed disseminated intravascular coagulation (DIC), although clinical symptoms and diagnostic examinations did not indicate an obstetrical cause. She went into labor spontaneously and vaginally delivered a 3248-g normal female infant, after receiving a blood transfusion. On the day 5 postpartum, a gastroduodenal fiberscope examination indicated advanced gastric cancer. She was also diagnosed with bilateral chronic subdural hematoma and underwent an operation to allow drainage. It was not possible to treat her curatively, so she was treated conservatively for DIC. She died on day 13 postpartum. Necropsy of the iliac bone indicated bone marrow metastasis of adenocarcinoma. This is the first known case of a pregnant woman with DIC occurring as the first manifestation of advanced gastric cancer. PMID:15232763

  19. Technical advances in endoscopic ultrasound-guided fiducial placement for the treatment of pancreatic cancer

    PubMed Central

    Chavalitdhamrong, Disaya; DiMaio, Christopher J.; Siersema, Peter D.; Wagh, Mihir S.

    2015-01-01

    Radiation therapy has an important role in the treatment of locally advanced or metastatic pancreatic cancer and can be used alone or in conjunction with surgery and/or systemic chemotherapy. Because of the challenge of delivering an accurate and optimal radiation dose, image-guided radiation therapy can be used to improve targeting. Fiducial markers can be placed in the tumor and used for localization in patients undergoing image-guided radiation therapy. The safety and feasibility of endoscopic ultrasound (EUS)-guided placement of fiducials has been assessed and reported for the management of pancreatic cancer. We herein review the technique, efficacy, and safety profile of EUS-guided fiducial placement. In addition, we highlight recent advances and technological upgrades in EUS-guided fiducial delivery systems for pancreatic cancer most relevant to practicing gastroenterologists and interventional endoscopists. PMID:26355267

  20. Technical advances in endoscopic ultrasound-guided fiducial placement for the treatment of pancreatic cancer.

    PubMed

    Chavalitdhamrong, Disaya; DiMaio, Christopher J; Siersema, Peter D; Wagh, Mihir S

    2015-08-01

    Radiation therapy has an important role in the treatment of locally advanced or metastatic pancreatic cancer and can be used alone or in conjunction with surgery and/or systemic chemotherapy. Because of the challenge of delivering an accurate and optimal radiation dose, image-guided radiation therapy can be used to improve targeting. Fiducial markers can be placed in the tumor and used for localization in patients undergoing image-guided radiation therapy. The safety and feasibility of endoscopic ultrasound (EUS)-guided placement of fiducials has been assessed and reported for the management of pancreatic cancer. We herein review the technique, efficacy, and safety profile of EUS-guided fiducial placement. In addition, we highlight recent advances and technological upgrades in EUS-guided fiducial delivery systems for pancreatic cancer most relevant to practicing gastroenterologists and interventional endoscopists. PMID:26355267

  1. New molecular targeted therapies for advanced non-small-cell lung cancer

    PubMed Central

    Méndez, Míriam; Custodio, Ana; Provencio, Mariano

    2011-01-01

    Non-small-cell lung cancer (NSCLC) is a uniformly fatal disease and most patients will present with advanced stage. Treatment outcomes remain unsatisfactory, with low long-term survival rates. Standard treatment, such as palliative chemotherapy and radiotherapy, offers a median survival not exceeding 1 year. Hence, considerable efforts have started to be made in order to identify new biological agents which may safely and effectively be administered to advanced NSCLC patients. Two cancer cell pathways in particular have been exploited, the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) pathways. However, novel targeted therapies that interfere with other dysregulated pathways in lung cancer are already in the clinic. This review outlines the most promising research approaches to the treatment of NSCLC, discussed according to the specific molecular pathway targeted. PMID:22263060

  2. Epidemiological overview, advances in diagnosis, prevention, treatment and management of epithelial ovarian cancer in Mexico.

    PubMed

    Gallardo-Rincón, Dolores; Espinosa-Romero, Raquel; Muñoz, Wendy Rosemary; Mendoza-Martínez, Roberto; Villar-Álvarez, Susana Del; Oñate-Ocaña, Luis; Isla-Ortiz, David; Márquez-Manríquez, Juan Pablo; Apodaca-Cruz, Ángel; Meneses-García, Abelardo

    2016-04-01

    The epithelial ovarian cancer (EOC) has been underdiagnosed because it does not have a specific clinical presentation, and the signs and symptoms are similar to the irritable bowel syndrome and pelvic inflammatory disease. EOC is less common than breast and cervical cancer, but it is more lethal. On the whole, EOC has an early dissemination to peritoneal cavity, which delays a timely diagnosis and increases the rate of advanced diagnosed disease. The diagnosis usually surprises the women and the primary care physician. Therefore, it is necessary to count on prevention and early diagnosis programs. EOC has 80% response to surgical treatment, but nearly 70% of the patients may relapse in five years. The objectives of this document are presenting a summary of the EOC epidemiology and comment about advancements in prevention, diagnosis, and treatment of this cancer. That will raise awareness about the importance of this disease. PMID:27557390

  3. Continuous subcutaneous infusion of lidocaine for persistent hiccup in advanced cancer.

    PubMed

    Kaneishi, Keisuke; Kawabata, Masahiro

    2013-03-01

    Persistent hiccup can cause anorexia, weight loss, disabling sleep deprivation, anxiety, and depression. Therefore, relief of persistent hiccup is important for advanced cancer patients and their family. Most reports on this condition are case series reports advocating the use of baclofen, haloperidol, gabapentin, and midazolam. However, these medications are occasionally ineffective or accompanied by intolerable side effects. The sodium channel blocker lidocaine has been shown to be effective in treating a variety of disorders thought to involve neuropathic mechanisms. Intravenous administration of lidocaine is common but efficacy has also been reported for subcutaneous infusion. In advanced cancer patients, subcutaneous infusion is easy, advantageous, and accompanied by less discomfort. We report a case of severe and sustained hiccup caused by gastric cancer that was successfully treated with a continuous subcutaneous infusion of lidocaine (480 mg (24 ml)/day) without severe side effects. PMID:22661318

  4. Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

    PubMed Central

    Brahmer, Julie R.; Tykodi, Scott S.; Chow, Laura Q.M.; Hwu, Wen-Jen; Topalian, Suzanne L.; Hwu, Patrick; Drake, Charles G.; Camacho, Luis H.; Kauh, John; Odunsi, Kunle; Pitot, Henry C.; Hamid, Omid; Bhatia, Shailender; Martins, Renato; Eaton, Keith; Chen, Shuming; Salay, Theresa M.; Alaparthy, Suresh; Grosso, Joseph F.; Korman, Alan J.; Parker, Susan M.; Agrawal, Shruti; Goldberg, Stacie M.; Pardoll, Drew M.; Gupta, Ashok; Wigginton, Jon M.

    2013-01-01

    BACKGROUND Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host’s immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. METHODS In this multicenter phase 1 trial, we administered intravenous anti–PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti–PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. RESULTS As of February 24, 2012, a total of 207 patients — 75 with non–small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer — had received anti–PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non–small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non–small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.) PMID:22658128

  5. Stereotactic body radiotherapy using CyberKnife for locally advanced unresectable and metastatic pancreatic cancer

    PubMed Central

    Su, Ting-Shi; Liang, Ping; Lu, Huan-Zhen; Liang, Jian-Ning; Liu, Jian-Min; Zhou, Ying; Gao, Ying-Chuan; Tang, Min-Yang

    2015-01-01

    AIM: To evaluate the efficacy and toxicity of stereotactic body radiotherapy using CyberKnife for locally advanced unresectable and metastatic pancreatic cancer. METHODS: From June 2010 to May 2014, 25 patients with locally advanced unresectable and metastatic pancreatic cancer underwent stereotactic body radiotherapy. Nine patients presented with unresectable locally advanced disease and 16 had metastatic disease. Primary end-points of this study were overall survival, relief of abdominal pain, and toxicity. RESULTS: Fourteen patients were treated with a total dose of 30-36 Gy in three fractions and the remainder with 40-48 Gy in four fractions. Median follow-up was 11 mo (range: 2-25 mo). The median survival duration calculated from the time of stereotactic body radiotherapy for the entire group, the locally advanced group, and the metastatic group was 9.0 mo, 13.5 mo, and 8.5 mo, respectively. Overall survival was 37% and 18% at one and two years, respectively. Abdominal pain relief was achieved within 2 wk of completing radiotherapy in the patients who received successful palliation (13 of 20 patients had significant pain). Five patients (20%) had grade 1 nausea, and one (4%) had grade 2 nausea. No acute grade 3+ toxicity was seen. CONCLUSION: Stereotactic body radiotherapy using the CyberKnife system is a promising, noninvasive, palliative treatment with acceptable toxicity for locally advanced unresectable and metastatic pancreatic cancer. PMID:26185389

  6. Combination Chemotherapy With or Without Vismodegib in Treating Patients With Advanced Stomach Cancer or Gastroesophageal Junction Cancer

    ClinicalTrials.gov

    2015-12-16

    Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

  7. Irinotecan, Fluorouracil, and Leucovorin in Treating Patients With Advanced Gastrointestinal Cancer

    ClinicalTrials.gov

    2016-04-19

    Anal Cancer; Carcinoma of the Appendix; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Gastrointestinal Carcinoid Tumor; Gastrointestinal Stromal Tumor; Liver Cancer; Pancreatic Cancer; Small Intestine Cancer

  8. Personalized cancer medicine—advances and socio-economic challenges

    PubMed Central

    Jackson, David B.; Sood, Anil K.

    2012-01-01

    It was Hippocrates, the father of Western medicine, who first emphasized the patient as the most important determinant of therapeutic efficacy. Although the principle of adjusting treatment to specific patient characteristics has since been the strategy of physicians, this is undermined by a population-biased approach to drug development. Therefore, it is generally true to say that our current evidential approach to cancer treatment is driven more by drug-regulation requirements and market considerations than the specific needs of an individual patient. But, with cancer drug costs now spiraling out of control and the modest efficacy typically seen in patients, the community is again turning to Hippocrates’ ancient paradigm—this time with emphasis on molecular considerations. Rapidly evolving technologies are empowering us to describe the molecular ‘nature’ of a patient and/or tumor and with this has come the beginning of truly personalized medicine, with maximized efficacy, cost effectiveness and hopefully improved survival for the patient. PMID:21989071

  9. Recent advances in the molecular diagnostics of gastric cancer

    PubMed Central

    Kanda, Mitsuro; Kodera, Yasuhiro

    2015-01-01

    Gastric cancer (GC) is the third most common cause of cancer-related death in the world, representing a major global health issue. Although the incidence of GC is declining, the outcomes for GC patients remain dismal because of the lack of effective biomarkers to detect early GC and predict both recurrence and chemosensitivity. Current tumor markers for GC, including serum carcinoembryonic antigen and carbohydrate antigen 19-9, are not ideal due to their relatively low sensitivity and specificity. Recent improvements in molecular techniques are better able to identify aberrant expression of GC-related molecules, including oncogenes, tumor suppressor genes, microRNAs and long non-coding RNAs, and DNA methylation, as novel molecular markers, although the molecular pathogenesis of GC is complicated by tumor heterogeneity. Detection of genetic and epigenetic alterations from gastric tissue or blood samples has diagnostic value in the management of GC. There are high expectations for molecular markers that can be used as new screening tools for early detection of GC as well as for patient stratification towards personalized treatment of GC through prediction of prognosis and drug-sensitivity. In this review, the studies of potential molecular biomarkers for GC that have been reported in the publicly available literature between 2012 and 2015 are reviewed and summarized, and certain highlighted papers are examined. PMID:26379391

  10. Advances in prostate cancer chemoprevention: a translational perspective.

    PubMed

    Nambiar, Dhanya; Singh, Rana P

    2013-01-01

    Chemopreventive interventions are steadily emerging as an important aspect of cancer management and control. Herein, we have discussed the major epidemiological and clinical studies advocating the role of androgen inhibitors, flavonoids and antioxidants in preventing prostate cancer (PCa). Androgen inhibitors have lately been discussed not only in treatment of PCa, but also as preventive agents especially after trials with Finasteride and Dutasteride. Flavonoids such as silibinin, green tea polyphenols, genistein, curcumin have shown great promise, but avenues to improve their bioavailability are requisite. Agents with antioxidant potentials like lycopene, selenium, and vitamin E have also been explored. Antioxidant trials have yielded mixed results or benefitted only a subgroup of population, although further studies are needed to establish them as preventive agent. Although a majority of the trials resulted in positive outcomes supporting their role as preventive agents; one should be cautious of neutral or negative results as well. For clinical applicability of these agents, we need to identify the ideal target population, time of intervention, appropriate dosage, and extent of intervention required. Incoherency of data with these agents urges for a stringent study design and thorough interpretation to accurately judge the necessity and feasibility of the preventive measures. PMID:23682779

  11. Recent advances in prostate cancer pathology: Gleason grading and beyond.

    PubMed

    Shah, Rajal B; Zhou, Ming

    2016-05-01

    Since its initial description in 1966 by Dr Donald Gleason, Gleason grading has become the cornerstone in the management of prostate cancer (PCa). With widespread use of Prostate Specific Antigen (PSA) screening and needle core biopsy, the diagnosis and management of PCa have dramatically evolved. In addition, better understanding of the morphological spectrum of prostate cancer and its clinical significance have prompted the refinement of the grading criteria and reporting guidelines commensurate to contemporary practice. The modification of the Gleason grading system implemented by the International Society of Urological Pathology in 2005 and subsequent revision in 2014 has profoundly impacted how PCa is graded and managed. This review aims to provide a concise update on the refinement of the histological criteria for various Gleason patterns and problem areas of Gleason grading, and provide recommendations on how to improve the grading reproducibility. The new proposal to group Gleason scores into clinically meaningful "grade groups" will also be discussed. Finally, we will discuss how magnetic resonance imaging (MRI)-targeted biopsy and emerging genetic markers may help improve the Gleason grading accuracy and risk stratification currently based on clinicopathological parameters. PMID:26991008

  12. Locally Advanced Lung Cancer: An Optimal Setting for Vaccines and Other Immunotherapies

    PubMed Central

    Iyengar, Puneeth; Gerber, David E.

    2013-01-01

    Lung cancer has traditionally been considered relatively resistant to immunotherapies. However, recent advances in the understanding of tumor-associated antigens, anti-tumor immune responses, and tumor immunosuppression mechanisms have resulted in a number of promising immunomodulatory therapies such as vaccines and checkpoint inhibitors. Locally advanced non-small cell lung cancer (NSCLC) is an optimal setting for these treatments because standard therapies such as surgery, radiation, and chemotherapy may enhance anti-tumor immune effects by debulking the tumor, increasing tumor antigen presentation, and promoting T-cell response and trafficking. Clinical trials incorporating immunomodulatory agents into combined modality therapy of locally advanced NSCLC have shown promising results. Future challenges include identifying biomarkers to predict those patients most likely to benefit from this approach, radiographic assessment of treatment effects, the timing and dosing of combined modality treatment including immunotherapies, and avoidance of potentially overlapping toxicities. PMID:23708072

  13. Strategies and Advancements in Harnessing the Immune System for Gastric Cancer Immunotherapy

    PubMed Central

    Subhash, Vinod Vijay; Yeo, Mei Shi; Tan, Woei Loon; Yong, Wei Peng

    2015-01-01

    In cancer biology, cells and molecules that form the fundamental components of the tumor microenvironment play a major role in tumor initiation, and progression as well as responses to therapy. Therapeutic approaches that would enable and harness the immune system to target tumor cells mark the future of anticancer therapy as it could induce an immunological memory specific to the tumor type and further enhance tumor regression and relapse-free survival in cancer patients. Gastric cancer is one of the leading causes of cancer-related mortalities that has a modest survival benefit from existing treatment options. The advent of immunotherapy presents us with new approaches in gastric cancer treatment where adaptive cell therapies, cancer vaccines, and antibody therapies have all been used with promising outcomes. In this paper, we review the current advances and prospects in the gastric cancer immunotherapy. Special focus is laid on new strategies and clinical trials that attempt to enhance the efficacy of various immunotherapeutic modalities in gastric cancer. PMID:26579545

  14. Recent advances from the National Cancer Institute Alliance for Nanotechnology in Cancer.

    PubMed

    Farrell, Dorothy; Alper, Joe; Ptak, Krzystof; Panaro, Nicholas J; Grodzinski, Piotr; Barker, Anna D

    2010-02-23

    Nanotechnology will have great impact on how cancer is diagnosed and treated in the future. New technologies to detect and image cancerous changes and materials that enable new methods of cancer treatment will radically alter patient outcomes. The National Cancer Institute (NCI) Alliance for Nanotechnology in Cancer sponsors research in cancer prevention, diagnosis, and therapy and promotes translation of basic science discoveries into clinical practice. The Fourth Annual NCI Alliance Principal Investigator Meeting was held in Manhattan Beach, California October 20-22, 2009. Presented here are highlights from the research presentations at the meeting, in the areas of in vitro diagnostics, targeted delivery of anticancer and contrast enhancement agents, and nanotherapeutics and therapeutic monitoring. PMID:20175564

  15. [Clinical study of Peptide-cocktail vaccination with tegafur-uracil/leucovorin for advanced colorectal cancer].

    PubMed

    Sugiura, Fumiaki; Inoue, Keisuke; Okuno, Kiyotaka; Sukegawa, Yasushi

    2012-11-01

    cDNA microarray technology coupled with laser microdissection has been used to identify human leukocyte antigen(HLA)-A24-restricted epitope peptides as potential targets for cancer vaccination in colorectal cancer patients. These antigenic peptides were derived from 2 different testis cancer antigens, ring finger protein 43(RNF43) and translocase of outer mitochondrial membrane 34(TOMM34). We conducted a clinical trial of vaccines against colorectal cancer specific peptides(RNF43 and TOMM34) with tegafur-uracil/Leucovorin( UFT/LV) for the treatment of advanced or recurrent colorectal cancer. The vaccinations were well tolerated without any adverse events. The highest long-term survival was observed in the group showing cytolytic T-lymphocyte (CTL) responses against both RNF43 and TOMM34, followed by the group showing CTL responses against only RNF43 or only TOMM34. A new study has been planned in order to obtain more immunological responses, and we have started a clinical trial of vaccines against multiple peptides[RNF43, TOMM34, forkhead box protein M1(FOXM1), maternal embryonic leucine zipper kinase(MELK), holliday junction recognition protein(HJURP), vascular endothelial growth factor receptor (VEGFR)1, and VEGFR2]by using UFT/LV for the treatment of advanced or recurrent colorectal cancer. PMID:23267878

  16. Serum Matrix Metalloproteinase-7 is an independent prognostic biomarker in advanced bladder cancer

    PubMed Central

    2014-01-01

    Background Urine markers have been studied extensively but there is a lack of blood prognostic markers in bladder cancer. MMP-7 is produced by stromal cells and by tumor cells and is overexpressed in a variety of epithelial and mesenchymal tumors. In this study, we assessed with an immunoassay we developed, the prognostic value of serum MMP-7 in a series of patients with advanced bladder cancer. Methods Serum samples were collected from 56 patients with advanced bladder cancer who were treated at the Montpellier Cancer Institute between March 2003 and December 2004. MMP-7 was quantified in serum samples by using a homogeneous sandwich fluoroimmunoassay we developed based on the time resolved amplified cryptate emission (TRACE) technology. Results The median overall survival of the study population was 2.2 years (95% CI, 1.4 to 3.0) with 1- and 5-year survival rates of 73% (95% CI, 59% to 82%) and 25% (95% CI, 14% to 37%), respectively. High MMP-7 serum levels were associated with poor survival. Using a cut-off value of 11.5 ng/mL, the median overall survival was 3.0 years (95% CI, 1.5 to 5.1) for patients with MMP-7 serum level <11.5 ng/mL and 1.3 years (95% CI, 0.8 to 2.5) for patients with serum level ?11.5 ng/mL. Multivariate analysis identified high MMP-7 serum concentration as an independent prognostic factor for survival in patients with advanced bladder cancer (R?=?2.1, 95% CI, 1.1 to 4.4). Conclusions Our results show that the MMP-7 serum concentration is an independent prognostic factor in patients with locally advanced and or metastatic bladder cancer. PMID:25984271

  17. Clinical hematology of rodent species.

    PubMed

    Pilny, Anthony A

    2008-09-01

    Pet rodents, such as rats, guinea pigs, and chinchillas, differ from more traditional companion animal species in many aspects of their hematologic parameters. Animals within this order have much diversity in size, anatomy, methods of restraint, and blood collection technique. Appropriate sample collection is often the most challenging aspect of the diagnostic protocol, and inappropriate restraint may cause a stress response that interferes with blood test results. For many of these patients, sedation is required and can also affect results as well. In most cases, however, obtaining a standard database is necessary and very possible when providing medical care for this popular group of pets. PMID:18675732

  18. Epigenetics in the hematologic malignancies

    PubMed Central

    Fong, Chun Yew; Morison, Jessica; Dawson, Mark A.

    2014-01-01

    A wealth of genomic and epigenomic data has identified abnormal regulation of epigenetic processes as a prominent theme in hematologic malignancies. Recurrent somatic alterations in myeloid malignancies of key proteins involved in DNA methylation, post-translational histone modification and chromatin remodeling have highlighted the importance of epigenetic regulation of gene expression in the initiation and maintenance of various malignancies. The rational use of targeted epigenetic therapies requires a thorough understanding of the underlying mechanisms of malignant transformation driven by aberrant epigenetic regulators. In this review we provide an overview of the major protagonists in epigenetic regulation, their aberrant role in myeloid malignancies, prognostic significance and potential for therapeutic targeting. PMID:25472952

  19. Targeted therapy in advanced bladder cancer: what have we learned?

    PubMed

    Jordan, Emmet J; Iyer, Gopa

    2015-05-01

    Despite advances in the treatment of other genitourinary malignancies, no novel therapies have been approved by the US Food and Drug Administration for urothelial carcinoma (UC) in the last 20 years. To date, no clinical trials of targeted agents in UC have led to improvements in survival compared with cytotoxic therapy. This article outlines representative trials of targeted therapies in UC and discusses the significance of genetic preselection in trial design as a method to optimize responses to these agents, thus, hopefully expanding the armamentarium of treatment options against this lethal disease. PMID:25882566

  20. Chromatin signatures of cancer

    PubMed Central

    Morgan, Marc A.; Shilatifard, Ali

    2015-01-01

    Changes in the pattern of gene expression play an important role in allowing cancer cells to acquire their hallmark characteristics, while genomic instability enables cells to acquire genetic alterations that promote oncogenesis. Chromatin plays central roles in both transcriptional regulation and the maintenance of genomic stability. Studies by cancer genome consortiums have identified frequent mutations in genes encoding chromatin regulatory factors and histone proteins in human cancer, implicating them as major mediators in the pathogenesis of both hematological malignancies and solid tumors. Here, we review recent advances in our understanding of the role of chromatin in cancer, focusing on transcriptional regulatory complexes, enhancer-associated factors, histone point mutations, and alterations in heterochromatin-interacting factors. PMID:25644600