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Sample records for solid tumor cytogenetics

  1. Cytogenetics of solid tumors Revisión de tema Citogenética de tumores sólidos

    Directory of Open Access Journals (Sweden)

    José Luis Ramírez Castro

    2002-02-01

    Full Text Available Cytogenetic analysis of tumors has provided valuable information on the biology of cancer. It has been established that more than half of solid tumors show chromosomal anomalies; therefore, cytogenetic analysis is of great usefulness for diagnostic and prognostic purposes. Identification of recurrent chromosomal anomalies in numerous tumors has been considered as an indicador of clinical importance. Cytogenetic studies in tissue tumors have revealed near 100,000 clonal chromosome abnormalities belonging to more that 30,000 human neoplasms. However, due to technical difficulties in cell cultures, only one third of solid tumors have been cytogenetically characterized. Conventional cytogenetics has been very useful for molecular characterization of new oncogenes and tumor-suppressor genes involved in human tumorigenesis. In this review, some important issues related with tumors of chromosomal etiology, the diverse types of chromosomal anomalies with their frequencies, modern diagnostic techniques as well as their impact on the diagnosis and prognosis of cancer are presented. EL análisis citogenético de tumores ha proporcionado valiosa información sobre la biología del cáncer. Se ha establecido que más de la mitad de los tumores sólidos presentan alteraciones cromosómicas; por lo tanto, el análisis citogenético es de gran utilidad para el diagnóstico y el pronóstico. La identificación de cambios cromosómicos específicos recurrentes en numerosos tumores se considera un indicador de importancia clínica. Los estudios en este campo han revelado cerca de 100.000 alteraciones cromosómicas en más de 30.000 neoplasias humanas. Sin embargo, los tumores sólidos son los menos caracterizados citogenéticamente, sólo una tercera parte del total de ellos, debido a problemas técnicos en los cultivos celulares. La citogenética convencional ha sido muy útil para la posterior caracterización molecular de nuevos oncogenes y genes supresores de

  2. Contributions of Cytogenetics and Molecular Cytogenetics to the Diagnosis of Adipocytic Tumors

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    Jun Nishio

    2011-01-01

    Full Text Available Over the last 20 years, a number of tumor-specific chromosomal translocations and associated fusion genes have been identified for mesenchymal neoplasms including adipocytic tumors. The addition of molecular cytogenetic techniques, especially fluorescence in situ hybridization (FISH, has further enhanced the sensitivity and accuracy of detecting nonrandom chromosomal translocations and/or other rearrangements in adipocytic tumors. Indeed, most resent molecular cytogenetic analysis has demonstrated a translocation t(11;16(q13;p13 that produces a C11orf95-MKL2 fusion gene in chondroid lipoma. Additionally, it is well recognized that supernumerary ring and/or giant rod chromosomes are characteristic for atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma, and amplification of 12q13–15 involving the MDM2, CDK4, and CPM genes is shown by FISH in these tumors. Moreover, myxoid/round cell liposarcoma is characterized by a translocation t(12;16(q13;p11 that fuses the DDIT3 and FUS genes. This paper provides an overview of the role of conventional cytogenetics and molecular cytogenetics in the diagnosis of adipocytic tumors.

  3. [Familial retinoblastoma: cytogenetic study of the tumor].

    Science.gov (United States)

    Robledo Batanero, M; Manzanal Martínez, A; Ayuso García, C; Benítez Ortiz, J

    1990-05-01

    We report a case of familiar retinoblastoma, in which both mother and daughter show bilateral retinoblastoma. The cytogenetic study, in both peripheral blood lymphocytes and tumoral tissue did not show alterations on the 13 chromosome, although we found a complex kariotype in tumoral tissue defined by three celular lines. In all of them appears a marker in which the 6 chromosome is involved (der 6). The derivated of 6 chromosome are markers highly characteristic of the retinoblastoma cases, and can be related with the aggressivity of tumor and the appearance of the second tumors.

  4. Cytogenetics and molecular genetics of Wilms' tumor of childhood

    NARCIS (Netherlands)

    Slater, R. M.; Mannens, M. M.

    1992-01-01

    We describe the way in which application of cytogenetic and molecular genetic techniques to the study of Wilms' tumor (WT) of the kidney and the associated congenital disorders, such as sporadic aniridia and the Beckwith-Wiedemann syndrome, has led to identification of two regions on the short arm

  5. Interphase fluorescence in situ hybridization analysis detects a much higher rate of thyroid tumors with clonal cytogenetic deviations of the main cytogenetic subgroups than conventional cytogenetics.

    Science.gov (United States)

    Drieschner, Norbert; Rippe, Volkhard; Laabs, Anne; Dittberner, Lea; Nimzyk, Rolf; Junker, Klaus; Rommel, Birgit; Kiefer, Yvonne; Belge, Gazanfer; Bullerdiek, Jörn; Sendt, Wolfgang

    2011-07-01

    In benign thyroid lesions, three main cytogenetic subgroups, characterized by trisomy 7 or structural aberrations involving either chromosomal region 19q13.4 or 2p21, can be distinguished by conventional cytogenetics (CC). As a rule, these aberrations seem to be mutually exclusive. Interphase fluorescence in situ hybridization (I-FISH) analysis on benign as well as malignant thyroid neoplasias has been performed in the past, but rarely in combination with CC. In the present paper, we have analyzed 161 benign thyroid lesions both with CC and I-FISH on touch preparations by using a multi-target, triple-color FISH assay as well as dual-color break-apart probes for detection of the main cytogenetic subgroups. Within the samples, I-FISH detected tumors belonging to either of the subgroups more frequently than CC (23 vs. 11.4%), either due to small subpopulations of aberrant cells or to cryptic chromosomal rearrangements (three cases). Thus, I-FISH seems to be more sensitive than CC, particularly in the detection of subpopulations of cells harboring cytogenetic aberrations that may be overlooked by CC. In summary, I-FISH on touch preparations of benign thyroid lesions seems to be a favorable method for cytogenetic subtyping of thyroid lesions. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Conventional cytogenetic characterization of a new cell line, ACP01, established from a primary human gastric tumor

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    E.M. Lima

    2004-12-01

    Full Text Available Gastric cancer is the second most frequent type of neoplasia and also the second most important cause of death in the world. Virtually all the established cell lines of gastric neoplasia were developed in Asian countries, and western countries have contributed very little to this area. In the present study we describe the establishment of the cell line ACP01 and characterize it cytogenetically by means of in vitro immortalization. Cells were transformed from an intestinal-type gastric adenocarcinoma (T4N2M0 originating from a 48-year-old male patient. This is the first gastric adenocarcinoma cell line established in Brazil. The most powerful application of the cell line ACP01 is in the assessment of cytotoxicity. Solid tumor cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The ACP01 cell line is triploid, grows as a single, non-organized layer, similar to fibroblasts, with focus formation, heterogeneous division, and a cell cycle of approximately 40 h. Chromosome 8 trisomy, present in 60% of the cells, was the most frequent cytogenetic alteration. These data lead us to propose a multifactorial triggering of gastric cancer which evolves over multiple stages involving progressive genetic changes and clonal expansion.

  7. Molecular and cytogenetic characterization of radon-induced lung tumors in the rat

    International Nuclear Information System (INIS)

    Dano, Laurent

    2000-01-01

    Radon is a natural radioactive gas. This radioelement, which is an α-particle emitter, is omnipresent in the environment. Inhalation of atmospheric radon is the major exposure route in man of natural radioactivity which results in respiratory tract contamination. An increased lung cancer risk associated with radon inhalation has been shown both in humans and animals by epidemiological and experimental studies, respectively. In rats, characterization of dose-effect relationships has led to the construction of statistical models that may help theoretically in the prediction of human health involvements of both occupational and domestic chronic exposure to radon. However, little is known about the cellular and molecular mechanisms of radon-induced lung carcinogenesis. In the laboratory, a model of lung cancers induced in rats after radon inhalation is available. This model represents a good tool to identify and characterize the genetic events contributing to the development of radon-induced lung tumors. Carrying out a global approach based on the combined use of classical and molecular cytogenetic methods, the analysis of 17 neoplasms allowed the identification of chromosomal regions frequently altered in these tumors. Numerous similarities have been found between our results and the cytogenetic data for human lung cancers, suggesting common underlying genetic molecular mechanisms for lung cancer development in both species. Moreover, our study has allowed to point to tumor suppressor genes and proto-oncogenes potentially involved in radon-induced lung carcinogenesis. Thus, our results may aid further molecular studies aimed either at confirming the role of these candidate genes or at demonstrating the involvement of yet to be identified genes. (author) [fr

  8. Cross-immunity among allogeneic tumors of rats immunized with solid tumors

    International Nuclear Information System (INIS)

    Ogasawara, Masamichi

    1979-01-01

    Several experiments were done for the study of cross-immunity among allogeneic rat tumors by immunization using gamma-irradiated or non-irradiated solid tumors. Each group of rats which were immunized with gamma-irradiation solid tumor inocula from ascites tumor cell line of tetra-ploid Hirosaki sarcoma, Usubuchi sarcoma or AH 130, showed an apparent resistance against the intraperitoneal challenge with Hirosaki sarcoma. A similar resistance was demonstrated in the case of the challenge with Usubuchi sarcoma into rats immunized with non-irradiated methylcholanthrene (MCA)-induced tumors. In using solid MCA tumors as immunogen and Hirosaki sarcoma as challenge tumor, it was also demonstrated in 2 out of 3 groups immunized with non-irradiated tumors. In the experiment of trying to induce cross-immunity between 2 MCA tumors by immunization with irradiated solid tumor only, the inhibitory effect on the growth was observed in the early stage in the treated groups as compared with the control one. From the above results, it may be considered that the immunization with irradiated solid tumors fromas cites cell lines and non-irradiated solid MCA tumors induced strong cross-immunity in general, but that the immunization with only irradiated solid MCA tumors induced weak cross-immunity commonly. (author)

  9. Cytogenetic study of a pineocytoma

    DEFF Research Database (Denmark)

    Rainho, C A; Rogatto, S R; de Moraes, L C

    1992-01-01

    The cytogenetic findings based on G-banding in a pineocytoma detected in a 29-year-old woman are reported. The chromosomal study showed numerical alterations involving chromosomes X, 5, 8, 11, 14, and 22, structural alterations of chromosomes 1, 3, 12, and 22, as well as various markers. Tumors...... of the pineal region are infrequent, and this is the first report of a pineocytoma studied cytogenetically....

  10. 110 Subfascial lipomatous tumors. MR and CT findings versus histopathological diagnosis and cytogenetic analysis

    International Nuclear Information System (INIS)

    Einarsdottir, H.; Soederlund, V.; Larsson, O.; Mandahl, N.; Bauer, H.C.F.

    1999-01-01

    Purpose: To evaluate whether liposarcoma, atypical lipomatous tumors and lipoma can be differentiated radiologically. Material and Methods: We have retrospectively analyzed CT and/or MR images of 110 subfascial lipomatous lesions. The amount of fat within the tumors was visually graded from the images as: none, 1-75%, 75-95% or 95-100%. The structure of non-fatty tumor components was compared. The images were compared to histopathology and in 37 cases to cytogenetic findings. Results: Only 4 of 20 liposarcomas contained fat. All 4 lesions, histopathologically diagnosed as atypical lipomatous tumors, contained fat but less than 75% of tumor volume. All lesions with more fat than 75% of tumor volume were histologically diagnosed as lipomas. However, one-third of the karyotyped lipomas had ring chromosomes which are considered typical for atypical lipomatous tumors. Conclusion: When a tumor is composed more or less solely of fat, the diagnosis of a lipoma or atypical lipomatous tumor with a phenotype simulating a lipoma can be assumed. When the fat content is less than 75% of the tumor volume or non-fatty nodules are found, biopsies from different tumor components have to be performed to exclude malignancy. When no fat is found, imaging does not help in differentiating lipoma or liposarcoma from other soft tissue tumors. (orig.)

  11. Solid pseudopapillary pancreas tumors. Often neglected

    International Nuclear Information System (INIS)

    Herrmann, K.A.; Reiser, M.F.; Zech, C.J.; Helmberger, T.; Bruns, C.

    2008-01-01

    Solid pseudopapillary tumors of the pancreas (SPTP) are rare tumors of the pancreas with low malignancy potential and a very good prognostic outcome after surgery. They typically occur in young women or adolescents and consist of solid, cystic and cystic-hemorrhagic components. Imaging findings in these tumors are characteristic and include a fibrotic capsule with a clear delineation and exhibit solid and cystic-hemorrhagic signal and density characteristics. Calcifications may be present in the periphery of the tumor. The tumor capsule shows contrast enhancement, the solid components in the periphery enhance in the early phase and gradually and inhomogeneously in late phases. MRI is superior to CT and other imaging modalities for characterization of SPTP. Awareness and knowledge of this tumor entity with an excellent prognosis is crucial to guide the patient towards effective, predominantly organ-sparing surgical treatment. (orig.) [de

  12. Chromosomal differences between acute nonlymphocytic leukemia in patients with prior solid tumors and prior hematologic malignancies. A study of 14 cases with prior breast cancer

    International Nuclear Information System (INIS)

    Mamuris, Z.; Dumont, J.; Dutrillaux, B.; Aurias, A.

    1989-01-01

    A cytogenetic study of 14 patients with secondary acute nonlymphocytic leukemia (S-ANLL) with prior treatment for breast cancer is reported. The chromosomes recurrently involved in numerical or structural anomalies are chromosomes 7, 5, 17, and 11, in decreasing order of frequency. The distribution of the anomalies detected in this sample of patients is similar to that observed in published cases with prior breast or other solid tumors, though anomalies of chromosome 11 were not pointed out, but it significantly differs from that of the S-ANLL with prior hematologic malignancies. This difference is principally due to a higher involvement of chromosome 7 in patients with prior hematologic malignancies and of chromosomes 11 and 17 in patients with prior solid tumors. A genetic determinism involving abnormal recessive alleles located on chromosomes 5, 7, 11, and 17 uncovered by deletions of the normal homologs may be a cause of S-ANLL. The difference between patients with prior hematologic malignancies or solid tumors may be explained by different constitutional mutations of recessive genes in the two groups of patients

  13. Cytogenetic Analysis for Research and Services

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    Sultana MH Faradz

    2017-02-01

    Full Text Available Abstract That the correct chromosome number in man is 46 was first recognized by Tjio and Levan in 1956. Perhaps few Indonesians know that Tjio was an Indonesian scientist studying in Sweden and then living in the US. Cytogenetic analyses are commonly performed to determine both structural and numerical chromosome aberration, whilst changes in chromosomes can lead to birth defects, syndromes, or even cancer.  Several chromosomal aneuploidy syndromes were identified after the establishment of various chromosome banding techniques in late 1960’s.  Specific cell culture media was found to express fragile site in the beginning of 1970’s and since then, inherited Fragile X Mental Retardation syndrome could be diagnosed.  However, some female permutation cases have been often misdiagnosed. Further molecular analysis has resolved this problem by revealing more CGG repeats in the promoter region FMR1 gene, which is related to the expression of fragile site and the severity of the diseases. In Disorder of Sex Development (DSD, early gender assignment and reconstruction surgery has been challenged because of the dilemma of gender identity development in later life. Cytogenetic analysis for the first-line gender assignment is important in newborn with DSD. Proper diagnosis with hormonal and mutation analysis should be elucidated to avoid medical, psychological, and social aspect in adult life. The most frequent genetic cases in our clinical experiences have been Androgen Insensitivity Syndrome and Congenital Adrenal Hyperplasia. Female Complete Androgen Insensitivity Syndrome (CAIS with main symptom primary amenorrhea without cytogenetic analysis has often been diagnosed as inguinal hernia because of testicle location and size. Diagnosis and treatment of several leukemias and lymphomas, as well as some solid tumors, depend on cytogenetic analyses to demonstrate consistent, specific chromosomal aberrations. Chromosome analysis in hematologic

  14. Frequent Chromosome Aberrations Revealed by Molecular Cytogenetic Studies in Patients with Aniridia

    OpenAIRE

    Crolla, John A.; van Heyningen, Veronica

    2002-01-01

    Seventy-seven patients with aniridia, referred for cytogenetic analysis predominantly to assess Wilms tumor risk, were studied by fluorescence in situ hybridization (FISH), through use of a panel of cosmids encompassing the aniridia-associated PAX6 gene, the Wilms tumor predisposition gene WT1, and flanking markers, in distal chromosome 11p13. Thirty patients were found to be chromosomally abnormal. Cytogenetically visible interstitial deletions involving 11p13 were found in 13 patients, 11 o...

  15. Cytogenetic findings in metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Bardi, G; Parada, L A; Bomme, L

    1997-01-01

    Eighteen tumor samples from 11 patients with metastatic colorectal cancer were cytogenetically analyzed after short-term culturing. Of the 13 metastases examined, 11 were from lymph nodes, 1 from the peritoneum and 1 from the lung. In 5 of the 11 patients, matched samples from the primary tumor...... colorectal carcinomas, and del(10)(q22) and add(16)(p13), which so far have not been associated with primary tumors and which may play a particular pathogenetic role in the metastatic process....

  16. Undifferentiated myxoid lipoblastoma with PLAG1-HAS2 fusion in an infant; morphologically mimicking primitive myxoid mesenchymal tumor of infancy (PMMTI)--diagnostic importance of cytogenetic and molecular testing and literature review.

    Science.gov (United States)

    Warren, Mikako; Turpin, Brian K; Mark, Melissa; Smolarek, Teresa A; Li, Xia

    2016-01-01

    Lipoblastoma is a benign myxoid neoplasm arising in young children that typically demonstrates adipose differentiation. It is often morphologically indistinguishable from primitive myxoid mesenchymal tumor of infancy (PMMTI), which is characterized by a well-circumscribed myxoid mass with a proliferation of primitive mesenchymal cells with mild cytologic atypia. PMMTI occurs in the first year of life and is known to have locally aggressive behavior. No specific genetic rearrangements have been reported to date. In contrast, the presence of PLAG1 (Pleomorphic Adenoma Gene 1) rearrangement is diagnostic for lipoblastoma. We hereby demonstrate the combined application of multiple approaches to tackle the diagnostic challenges of a rapidly growing neck tumor in a 3-month-old female. An incisional tumor biopsy had features of an undifferentiated, myxoid mesenchymal neoplasm mimicking PMMTI. However, tumor cells showed diffuse nuclear expression by immunohistochemical (IHC) stain. Conventional cytogenetic and fluorescence in situ hybridization (FISH) analyses as well as next generation sequencing (NGS) demonstrated evidence of PLAG1 rearrangement, confirming the diagnosis of lipoblastoma. This experience warrants that undifferentiated myxoid lipoblastoma can mimic PMMTI, and the combination of cytogenetic and molecular approaches is essential to distinguish these two myxoid neoplasms. Literature on lipoblastomas with relevant molecular and cytogenetic findings is summarized. Our case is the first lipoblastoma diagnosed with a PLAG1 fusion defined by NGS technology. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Solid-pseudo papillary tumor of the pancreas: Frantz's tumor

    International Nuclear Information System (INIS)

    Oliveira, Bruno Righi Rodrigues de; Moreira, Reni Cecilia Lopes; Campos, Marcelo Esteves Chaves

    2010-01-01

    The pseudo papillary solid tumor of the pancreas, also known as Frantz's tumor, is a rare disease, taking place in approximately 0.17% to 2.7% of non-endocrine tumors of the pancreas. Recently, the increase of its incidence has been noted with more than two-thirds of the total cases described in the last 10 years. A possible explanation is a greater knowledge of the disease and a greater uniformity of conceptualization in the last years. Generally, it affects young adult females. In most of the series, the tumor principally attacks the body and tail of the pancreas. The objective of the present report is to present the diagnostic and therapeutic option used in this rare pancreatic tumor of low-grade malignancy. (author)

  18. Therapy-associated Solid Tumors

    International Nuclear Information System (INIS)

    Travis, Lois B.

    2002-01-01

    As survival after a diagnosis of cancer improves, characterization of the late sequelae of treatment becomes critical. The development of second malignant neoplasms represents one of the most serious side effects of treatment with radiation and chemotherapy. Although secondary leukemia was the first reported carcinogenic effect resulting from cancer treatment, solid tumors now comprise the largest second tumor burden in some populations of survivors. It should be recognized, however, that solid cancers do not necessarily represent an adverse effect of therapy, but may also reflect the operation of shared etiologic factors, host determinants, gene-environment interactions, and other influences. Quantification of second cancer risk is important in terms of patient management, enabling clinicians to make informed decisions with regard to optimal treatment of the initial cancer, balancing efficacy against acute and chronic sequelae. This article focuses on selected highlights and recent developments in treatment-associated solid malignancies, with emphasis on radiotherapy and chemotherapy in adults, and summarizes areas for future research. Although cancer therapy represents a double-edged sword, it should always be recognized that it is advances in treatment that are largely responsible for the tremendous improvement in patient survival. Thus, the benefit derived from many cancer therapies far outweighs any risk of developing a second cancer

  19. Secondary myeloid neoplasms: bone marrow cytogenetic and histological features may be relevant to prognosis

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    Roberta Sandra da Silva Tanizawa

    Full Text Available Abstract Background: Secondary myeloid neoplasms comprise a group of diseases arising after chemotherapy, radiation, immunosuppressive therapy or from aplastic anemia. Few studies have addressed prognostic factors in these neoplasms. Method: Forty-two patients diagnosed from 1987 to 2008 with secondary myeloid neoplasms were retrospectively evaluated concerning clinical, biochemical, peripheral blood, bone marrow aspirate, biopsy, and immunohistochemistry and cytogenetic features at diagnosis as prognostic factors. The International Prognostic Scoring System was applied. Statistical analysis employed the Kaplan–Meier method, log-rank and Fisher's exact test. Results: Twenty-three patients (54.8% were male and the median age was 53.5 years (range: 4–88 years at diagnosis of secondary myeloid neoplasms. Previous diseases included hematologic malignancies, solid tumors, aplastic anemia, autoimmune diseases and conditions requiring solid organ transplantations. One third of patients (33% were submitted to chemotherapy alone, 2% to radiotherapy, 26% to both modalities and 28% to immunosuppressive agents. Five patients (11.9% had undergone autologous hematopoietic stem cell transplantation. The median latency between the primary disease and secondary myeloid neoplasms was 85 months (range: 23–221 months. Eight patients were submitted to allogeneic hematopoietic stem cell transplantation to treat secondary myeloid neoplasms. Important changes in bone marrow were detected mainly by biopsy, immunohistochemistry and cytogenetics. The presence of clusters of CD117+ cells and p53+ cells were associated with low survival. p53 was associated to a higher risk according to the International Prognostic Scoring System. High prevalence of clonal abnormalities (84.3% and thrombocytopenia (78.6% were independent factors for poor survival. Conclusion: This study demonstrated that cytogenetics, bone marrow biopsy and immunohistochemistry are very important

  20. Cytogenetic effects induced by radiotherapy of cancer patients

    International Nuclear Information System (INIS)

    Ekhtiar, A.; Al-Achkar, W.

    2008-03-01

    Ionizing radiation plays a key role in the treatment of many neoplasias. But it is well known that ionizing radiation induce wide specter of DNA damages, including SSBs, DSBs, base damage, and DNA-protein cross links. As a consequence, a second tumor may be developed after the primary tumor therapy. Attempts have been made to evaluate the genotoxicity of ionizing radiation in patients undergoing radiotherapy. In the present work, the cytogenetic damage present in peripheral blood lymphocytes of patients (29 donors) treated with fractionated partial-body radiation therapy for Head-and-neck cancer patient was followed before, during and at the end of treatment by means of the cytokinesis-block micronucleus assay. These patients had no previous chemotherapy or radiotherapy. Our results indicate that the level of spontaneous cytogenetic damage in cancer patients and smokers control (3 donors) were higher than in healthy non smoking controls (3 donor). During and after treatment, increased of micronucleus cells frequencies were observed with increasing treatment doses.(author)

  1. Translocation (16;20)(p11.2;q13). sole cytogenetic abnormality in a unicameral bone cyst.

    Science.gov (United States)

    Richkind, Kathleen E; Mortimer, Errol; Mowery-Rushton, Patricia; Fraire, Armando

    2002-09-01

    We report the results of cytogenetic analysis of a case of unicameral bone cyst with a t(16;20(p11.2;q13) present as the sole abnormality. To our knowledge, this is only the second report of a cytogenetically characterized tumor of this type.

  2. Solid tumors are poroelastic solids with a chemo-mechanical feedback on growth.

    Science.gov (United States)

    Ambrosi, D; Pezzuto, S; Riccobelli, D; Stylianopoulos, T; Ciarletta, P

    2017-12-01

    The experimental evidence that a feedback exists between growth and stress in tumors poses challenging questions. First, the rheological properties (the "constitutive equations") of aggregates of malignant cells are still a matter of debate. Secondly, the feedback law (the "growth law") that relates stress and mitotic-apoptotic rate is far to be identified. We address these questions on the basis of a theoretical analysis of in vitro and in vivo experiments that involve the growth of tumor spheroids. We show that solid tumors exhibit several mechanical features of a poroelastic material, where the cellular component behaves like an elastic solid. When the solid component of the spheroid is loaded at the boundary, the cellular aggregate grows up to an asymptotic volume that depends on the exerted compression. Residual stress shows up when solid tumors are radially cut, highlighting a peculiar tensional pattern. By a novel numerical approach we correlate the measured opening angle and the underlying residual stress in a sphere. The features of the mechanobiological system can be explained in terms of a feedback of mechanics on the cell proliferation rate as modulated by the availability of nutrient, that is radially damped by the balance between diffusion and consumption. The volumetric growth profiles and the pattern of residual stress can be theoretically reproduced assuming a dependence of the target stress on the concentration of nutrient which is specific of the malignant tissue.

  3. HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors

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    Andrea Pession

    2011-06-01

    Full Text Available Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing’s sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an eventfree survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemo therapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA-mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results.

  4. [From cytogenetics to cytogenomics of dermatofibrosarcoma protuberans family of tumors].

    Science.gov (United States)

    Bianchini, Laurence; Maire, Georges; Pedeutour, Florence

    2007-02-01

    Dermatofibrosarcoma protuberans (DP) is a rare, slow growing dermal neoplasm of intermediate malignancy. It is made of spindle-shaped tumor cells in a storiform pattern often positive for CD34. The preferred treatment for DP is a surgical wide excision with pathologically sane margins of 3 cm. At the cytogenetic level, DP cells are characterized by either supernumerary ring chromosomes composed of sequences derived from chromosomes 17 and 22 or more rarely of translocations t(17;22). Rings have been mainly observed in adults whereas translocations have been reported in all pediatric cases. These chromosomal rearrangements lead to the formation of a specific fusion gene : COL1A1-PDGFB detected in rings as well as in translocations. DP is therefore a unique example of tumor in which the same molecular event occurs either on rings or linear translocation derivatives and the chromosomal abnormalities display an age-related pattern. So far, the COL1A1-PDGFB fusion gene remains the only fusion gene identified in this tumor. It is also present in variant forms of DP such as giant cell fibroblastoma, Bednar tumor, adult superficial fibrosarcoma and the granular cell variant of DP demonstrating that these tumors are not distinct entities but morphological variants of DP. The breakpoint localization in PDGFB was found to be remarkably constant, placing exon 2 of PDGFB under the control of the COL1A1 promoter. In contrast, the COL1A1 breakpoint was found to be variably located within the exons of the alpha-helical coding region (exons 7-47). No correlation between the breakpoint location in COL1A1 and the age of the patient or any clinical or histological particularity has been established. Moreover, no preferential breakpoint appears to be more particularly linked to one or another variant of DP. The COL1A1-PDGFB fusion gene is detectable either by multiplex RT-PCR with a combination of forward primers designed from a variety of COL1A1 exons and one reverse primer for PDGFB

  5. Targeted radionuclide therapy for solid tumors: An overview

    International Nuclear Information System (INIS)

    De Nardo, Sally J.; De Nardo, Gerald L.

    2006-01-01

    Although radioimmunotherapy (RIT) has been effective in non-Hodgkin's lymphoma (NHL) as a single agent, solid tumors have shown less clinically significant therapeutic response to RIT alone. The clinical impact of RIT or other forms of targeted radionuclide therapy for solid tumors depends on the development of a high therapeutic index (TI) for the tumor vs. normal tissue effect, and the implementation of RIT as part of synergistic combined modality therapy (CMRIT). Preclinical and clinical studies have provided a wealth of information, and new prototypes or paradigms have shed light on future possibilities in many instances. Evidence suggests that combination and sequencing of RIT in CMRIT appropriately can provide effective treatment for many solid tumors. Vascular targets provide RIT enhancement opportunities and nanoparticles may prove to be effective carriers for RIT combined with intracellular drug delivery or alternating magnetic frequency (AMF) induced thermal tumor necrosis. The sequence and timing of combined modality treatments will be of critical importance to achieve synergy for therapy while minimizing toxicity. Fortunately, the radionuclide used for RIT also provides a signal useful for nondestructive quantitation of the influence of sequence and timing of CMRIT on events in animals and patients. This can be readily accomplished clinically using quantitative high-resolution imaging (e.g., positron emission tomography [PET])

  6. New Strategies for the Treatment of Solid Tumors with CAR-T Cells.

    Science.gov (United States)

    Zhang, Hao; Ye, Zhen-Long; Yuan, Zhen-Gang; Luo, Zheng-Qiang; Jin, Hua-Jun; Qian, Qi-Jun

    2016-01-01

    Recent years, we have witnessed significant progresses in both basic and clinical studies regarding novel therapeutic strategies with genetically engineered T cells. Modification with chimeric antigen receptors (CARs) endows T cells with tumor specific cytotoxicity and thus induce anti-tumor immunity against malignancies. However, targeting solid tumors is more challenging than targeting B-cell malignancies with CAR-T cells because of the histopathological structure features, specific antigens shortage and strong immunosuppressive environment of solid tumors. Meanwhile, the on-target/off-tumor toxicity caused by relative expression of target on normal tissues is another issue that should be reckoned. Optimization of the design of CAR vectors, exploration of new targets, addition of safe switches and combination with other treatments bring new vitality to the CAR-T cell based immunotherapy against solid tumors. In this review, we focus on the major obstacles limiting the application of CAR-T cell therapy toward solid tumors and summarize the measures to refine this new cancer therapeutic modality.

  7. Chromosomal Rainbows detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    O' Brien, Benjamin; Jossart, Gregg H.; Ito, Yuko; Greulich-Bode, Karin M.; Weier, Jingly F.; Munne, Santiago; Clark, Orlo H.; Weier, Heinz-Ulrich G.

    2010-08-19

    Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'-end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabase-pair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding

  8. Cancer stem cells in solid tumors: elusive or illusive?

    Directory of Open Access Journals (Sweden)

    Lehrach Hans R

    2010-05-01

    Full Text Available Abstract During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a a stringent definition of cancer stem cells in solid tumors (b specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare. In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.

  9. Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior

    Directory of Open Access Journals (Sweden)

    Abadie Jerome

    2011-05-01

    Full Text Available Abstract Background Histiocytic malignancies in both humans and dogs are rare and poorly understood. While canine histiocytic sarcoma (HS is uncommon in the general domestic dog population, there is a strikingly high incidence in a subset of breeds, suggesting heritable predisposition. Molecular cytogenetic profiling of canine HS in these breeds would serve to reveal recurrent DNA copy number aberrations (CNAs that are breed and/or tumor associated, as well as defining those shared with human HS. This process would identify evolutionarily conserved cytogenetic changes to highlight regions of particular importance to HS biology. Methods Using genome wide array comparative genomic hybridization we assessed CNAs in 104 spontaneously occurring HS from two breeds of dog exhibiting a particularly elevated incidence of this tumor, the Bernese Mountain Dog and Flat-Coated Retriever. Recurrent CNAs were evaluated further by multicolor fluorescence in situ hybridization and loss of heterozygosity analyses. Statistical analyses were performed to identify CNAs associated with tumor location and breed. Results Almost all recurrent CNAs identified in this study were shared between the two breeds, suggesting that they are associated more with the cancer phenotype than with breed. A subset of recurrent genomic imbalances suggested involvement of known cancer associated genes in HS pathogenesis, including deletions of the tumor suppressor genes CDKN2A/B, RB1 and PTEN. A small number of aberrations were unique to each breed, implying that they may contribute to the major differences in tumor location evident in these two breeds. The most highly recurrent canine CNAs revealed in this study are evolutionarily conserved with those reported in human histiocytic proliferations, suggesting that human and dog HS share a conserved pathogenesis. Conclusions The breed associated clinical features and DNA copy number aberrations exhibited by canine HS offer a valuable model

  10. Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior

    International Nuclear Information System (INIS)

    Hedan, Benoit; Thomas, Rachael; Motsinger-Reif, Alison; Abadie, Jerome; Andre, Catherine; Cullen, John; Breen, Matthew

    2011-01-01

    Histiocytic malignancies in both humans and dogs are rare and poorly understood. While canine histiocytic sarcoma (HS) is uncommon in the general domestic dog population, there is a strikingly high incidence in a subset of breeds, suggesting heritable predisposition. Molecular cytogenetic profiling of canine HS in these breeds would serve to reveal recurrent DNA copy number aberrations (CNAs) that are breed and/or tumor associated, as well as defining those shared with human HS. This process would identify evolutionarily conserved cytogenetic changes to highlight regions of particular importance to HS biology. Using genome wide array comparative genomic hybridization we assessed CNAs in 104 spontaneously occurring HS from two breeds of dog exhibiting a particularly elevated incidence of this tumor, the Bernese Mountain Dog and Flat-Coated Retriever. Recurrent CNAs were evaluated further by multicolor fluorescence in situ hybridization and loss of heterozygosity analyses. Statistical analyses were performed to identify CNAs associated with tumor location and breed. Almost all recurrent CNAs identified in this study were shared between the two breeds, suggesting that they are associated more with the cancer phenotype than with breed. A subset of recurrent genomic imbalances suggested involvement of known cancer associated genes in HS pathogenesis, including deletions of the tumor suppressor genes CDKN2A/B, RB1 and PTEN. A small number of aberrations were unique to each breed, implying that they may contribute to the major differences in tumor location evident in these two breeds. The most highly recurrent canine CNAs revealed in this study are evolutionarily conserved with those reported in human histiocytic proliferations, suggesting that human and dog HS share a conserved pathogenesis. The breed associated clinical features and DNA copy number aberrations exhibited by canine HS offer a valuable model for the human counterpart, providing additional evidence towards

  11. Association between tumor-stroma ratio and prognosis in solid tumor patients: a systematic review and meta-analysis.

    Science.gov (United States)

    Wu, Jiayuan; Liang, Caixia; Chen, Manyu; Su, Wenmei

    2016-10-18

    Tumor-related stroma plays an active role in tumor invasion and metastasis. The tumor-stroma ratio (TSR) in the pathologic specimen has drawn increasing attention from the field of predicting tumor prognosis. However, the prognostic value of TSR in solid tumors necessitates further elucidation. We conducted a meta-analysis on 14 studies with 4238 patients through a comprehensive electronic search on databases updated on May 2016 to explore the relationship between TSR and prognosis of solid tumors. The overall hazard ratio showed that rich stroma in tumor tissue was associated with poor overall survival (OS) (14 studies, 4238 patients) and disease-free survival (DFS) (9 studies, 2235 patients) of patients with solid tumors. The effect of low TSR on poor OS was observed among various cancer types, but not in the early stage of cervical caner. A significant relationship between low TSR and poor OS was also observed in the subgroup analyses based on study region, blinding status, and Newcastle-Ottawa Scale (NOS) score. Subgroup analyses indicated that cancer type, clinical stage, study region, blinding status, and NOS score did not affect the prognostic value of TSR for DFS. Moreover, low TSR was significantly correlated with the serious clinical stage, advanced depth of invasion, and positive lymph node metastasis. These findings indicate that a high proportion of stroma in cancer tissue is associated with poor clinical outcomes in cancer patients, and TSR may serve as an independent prognostic factor for solid tumors.

  12. Solid-pseudo papillary tumor of the pancreas: Frantz's tumor

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Bruno Righi Rodrigues de; Moreira, Reni Cecilia Lopes; Campos, Marcelo Esteves Chaves [Instituto Mario Penna, Belo Horizonte, MG (Brazil)], e-mail: brunorighi@yahoo.com.br

    2010-07-01

    The pseudo papillary solid tumor of the pancreas, also known as Frantz's tumor, is a rare disease, taking place in approximately 0.17% to 2.7% of non-endocrine tumors of the pancreas. Recently, the increase of its incidence has been noted with more than two-thirds of the total cases described in the last 10 years. A possible explanation is a greater knowledge of the disease and a greater uniformity of conceptualization in the last years. Generally, it affects young adult females. In most of the series, the tumor principally attacks the body and tail of the pancreas. The objective of the present report is to present the diagnostic and therapeutic option used in this rare pancreatic tumor of low-grade malignancy. (author)

  13. Lymphoma cytogenetics.

    Science.gov (United States)

    Dave, Bhavana J; Nelson, Marilu; Sanger, Warren G

    2011-12-01

    Lymphomas are a heterogeneous group of neoplasms with distinct morphologic, immunologic, and cytogenetic characteristics. Overlapping morphologic and immunophenotypic features often makes accurate diagnosis difficult. Cytogenetics helps simplify the diagnostic complexities presented in transforming and progressive lymphoid malignancies. Genetic studies using technical advances such as fluorescence in situ hybridization and the newer approaches of array comparative genomic hybridization and gene expression profiling play a critical and often defining role in the diagnosis, progression, prognosis, and therapeutic stratification. This article reviews characteristic cytogenetic abnormalities in specific subtypes of lymphomas at diagnosis, disease progression, and prognosis.

  14. Cytogenetically confirmed primary Ewing's sarcoma of the pancreas.

    Science.gov (United States)

    Golhar, Ankush; Ray, Samrat; Haugk, Beate; Singhvi, Suresh Kumar

    2017-05-04

    Ewing's sarcoma is a highly aggressive malignant tumour most commonly affecting long bones in children and adolescents. It is part of the Ewing's sarcoma family of tumours (ESFTs) that also include peripheral primitive neuroectodermal tumour and Askin's tumours. ESFTs share common cytogenetic aberrations, antigenic profiles and proto-oncogene expression with an overall similar clinical course. In 99% of ESFTs, genetic translocation with molecular fusion involves the EWSR1 gene on 22q12. Approximately 30% of ESFTs are extraosseous, most commonly occurring in the soft tissues of extremities, pelvis, retroperitoneum and chest wall. Primary presentation in solid organs is very rare but has been described in multiple sites including the pancreas. Accurate diagnosis of a Ewing's sarcoma in a solid organ is critical in facilitating correct treatment. We report the case of a 17-year-old girl with cytogenetically confirmed primary pancreatic Ewing's sarcoma and provide a brief review of the published literature. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Cytogenetic effects of leachates from tannery solid waste on the somatic cells of Vicia faba.

    Science.gov (United States)

    Chandra, Saurabh; Chauhan, L K S; Pande, P N; Gupta, S K

    2004-04-01

    The contamination of surface- and groundwater by the leaching of solid wastes generated by industrial activities as a result of water runoff and rainfall is a matter of great concern. The leachates from tannery solid waste (TSW), a major environmental pollutant, were examined for their possible genotoxic effects on the somatic cells of Vicia faba. Leachates were prepared from solid wastes procured from leather-tanning industrial sites, and V. faba seedlings were exposed to three test concentrations, 2.5%, 5%, and 10%, through soil and aqueous media for 5 days. The root tips examined for cytogenetic damage revealed that leachate of TSW significantly inhibited the mitotic index and induced significantly frequent chromosomal and mitotic aberrations (CA/MA) in a dose-dependent manner. The chemical analysis of TSW samples revealed that the chief constituents were chromium and nickel, which may cause genetic abnormalities. The frequency of aberrations was found to be higher in the root meristematic cells of Vicia faba exposed through the aqueous medium than those exposed through the soil medium. The results of the present study indicated that contamination of potable water bodies by leachates of TSW may cause genotoxicity. For the biomonitoring of complex mixtures of toxicants with the V. faba bioassay, the use of the aqueous medium seems to be a more promising method than the use of the soil medium. Copyright 2004 Wiley Periodicals, Inc. Environ Toxicol 19: 129-133, 2004.

  16. CT differentiation of solid ovarian tumor and uterine subserosal leiomyoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Rae; Cho, Kyoung Sik [Asan Medical Center, Ulsan Univ. College of Medicine, Seoul (Korea, Republic of); Sohn, Chul Ho [Dongsan Medical Center, Keimyung Univ. College of Medicine, Taegu (Korea, Republic of); Ji, Eun Kyung [Bombit Hospital, Seoul (Korea, Republic of)

    1999-06-01

    On the basis of CT findings, to differentiate between solid ovarian tumor and uterine subserosal myoma. In eight surgically proven cases of solid ovarian tumor and in ten uterine subserosal myoma patients, contrast-enhanced CT images were obtained. Two genitourinary radiologists reviewed the findings with regard to degree of enhancement of the mass as compared with enhancement of uterine myometrium, thickening of round ligaments, visualization of normal ovaries, contour of the mass, and the presence of ascites in the pelvic cavity. Six of eight ovarian tumors but only two of ten uterine myomas were less enhanced than normal uterine myometrium (p<0.05). Pelvic ascites were seen in six of eight ovarian tumors, but in only one of ten uterine myomas (P<0.05). Three of 16 ovaries in ovarian tumor patients, but 12 of 20 ovaries in uterine myoma patients, were normal (p<0.05). Six of 16 round ligaments of the uterus in ovarian tumor patients, were thichened but 11 of 20 round ligaments in uterine myoma patients, were thickened (p>0.05). The contour of the mass was lobulated in two of eight ovarian tumor patients, but in five of ten uterine myoma patients (p>0.05). CT findings suggestive of solid ovarian tumor were less contrast enhancement of the mass than of normal uterine myometrium, pelvic ascites, and nonvisualization of normal ovary.

  17. Cytogenetic and molecular cytogenetic methods in hemato-oncology

    International Nuclear Information System (INIS)

    Novakova, P.; Ilencikova, D.

    2010-01-01

    Cancer, either sporadic or hereditary, is a genetic disease that develops through multiple genetic changes. Specific genetic defects have been found to be associated non randomly with the predisposition, genesis, progression, and metastasis of various kinds of neoplasia. Cytogenetics in haematological malignancy to aid in diagnosis and in identifying recurrent chromosomal rearrangements, an essential prerequisite to identifying genes involved in leukaemia and lymphoma pathogenesis. In the late 1980s, a series of technologies based around fluorescence in situ hybridisation (FISH) revolutionised the field. FISH technology, a combination of molecular and conventional cytogenetic techniques, has brought modern cytogenetics to a new era with significantly higher resolutions and much wider testing spectrum. Since then, numerous new FISH-based technologies have been emerging, from metaphase FISH to interphase FISH, from single-color FISH to multicolor FISH, from comparative gnenomic hybridisation (CGH) to array CGH, and so on. In this review the advantages and limitations of each of the various types of conventional and molecular cytogenetic methodologies are discussed with regard to their application in human neoplasia. (author)

  18. Advanced microtechnologies for cytogenetic analysis

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Vedarethinam, Indumathi; Shah, Pranjul Jaykumar

    2012-01-01

    Cytogenetic and molecular cytogenetic analyses, which aim to detect chromosome abnormalities, are routinely performed in cytogenetic laboratories all over the world. Traditional cytogenetic studies are performed by analyzing the banding pattern of chromosomes, and are complemented by molecular...... cytogenetic techniques such as fluorescent in situ hybridization (FISH). To improve FISH application in cytogenetic analysis the issues with long experimental time, high volumes of expensive reagents and requirement for trained technicians need to be addressed. The protocol has recently evolved towards...... to introduce automation in the cytogenetic laboratories at a microscale. We have developed membrane based micro perfusion systems capable of expansion of lymphocytes in a shorter time and at a smaller scale. The simulated and experimental results show very efficient exchange of the growth medium...

  19. Recurrence of Solid Pseudopapillary Tumor: A Rare Pancreatic Tumor

    Directory of Open Access Journals (Sweden)

    Chandra Punch

    2016-01-01

    Full Text Available Solid pseudopapillary tumor of the pancreas (SPTP is a rare disease of young females that does not usually recur after resection. Here we report a case of an elderly female with history of SPTP ten years ago who presented with anorexia and a palpable left lower quadrant abdominal mass. Imaging revealed metastatic disease and US-guided biopsy of the liver confirmed the diagnosis of SPTP. Due to her advanced age and comorbidities, she elected to undergo hospice care. The objective of this case report is to increase awareness of this tumor and its possibility of recurrence, necessitating further guidelines for follow-up.

  20. Bacteria-mediated in vivo delivery of quantum dots into solid tumor

    International Nuclear Information System (INIS)

    Liu, Ying; Zhou, Mei; Luo, Dan; Wang, Lijun; Hong, Yuankai; Yang, Yepeng; Sha, Yinlin

    2012-01-01

    Highlights: ► New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. ► Bifidobacterium bifidum delivery system has intrinsic biocompatibility. ► The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.

  1. Albumin-bound paclitaxel in solid tumors: clinical development and future directions.

    Science.gov (United States)

    Kundranda, Madappa N; Niu, Jiaxin

    2015-01-01

    Albumin-bound paclitaxel (nab-paclitaxel) is a solvent-free formulation of paclitaxel that was initially developed more than a decade ago to overcome toxicities associated with the solvents used in the formulation of standard paclitaxel and to potentially improve efficacy. Nab-paclitaxel has demonstrated an advantage over solvent-based paclitaxel by being able to deliver a higher dose of paclitaxel to tumors and decrease the incidence of serious toxicities, including severe allergic reactions. To date, nab-paclitaxel has been indicated for the treatment of three solid tumors in the USA. It was first approved for the treatment of metastatic breast cancer in 2005, followed by locally advanced or metastatic non-small-cell lung cancer in 2012, and most recently for metastatic pancreatic cancer in 2013. Nab-paclitaxel is also under investigation for the treatment of a number of other solid tumors. This review highlights key clinical efficacy and safety outcomes of nab-paclitaxel in the solid tumors for which it is currently indicated, discusses ongoing trials that may provide new data for the expansion of nab-paclitaxel's indications into other solid tumors, and provides a clinical perspective on the use of nab-paclitaxel in practice.

  2. Solid and cystic pseudopapillary tumor of the pancreas: A case report

    Directory of Open Access Journals (Sweden)

    Milošević Bojan Z.

    2013-01-01

    Full Text Available Introduction. Solid and cystic pseudopapillary tumor of the pancreas is a rare tumor of the pancreas, for the first time described by Frantz et al. in 1959. The majority of patients are young females and most of them are asymptomatic. Case Outline. We report a case of 25-year old woman who was admitted to our institution with abdominal pain and a palpable mass in the left hypochondrial area. US and CT scan revealed a solid and cystic pseudopapillary tumor in the head of the pancreas. The patient was treated by Whipple procedure, modification Longmire-Traverso. There was no metastatic disease either in the liver or peritoneum. Histologically the tumor was diagnosed as a solid and cystic pseudopapillary tumor of the pancreas. Conclusion. The unclear pre-operative diagnoses, together with incidence of potential malignancy as well as good outcome with resection, suggest that all suspected cystic tumors of the pancreas should be resected. The exact diagnosis is based on histological findings. [Projekat Ministarstva nauke Republike Srbije, br. III41007 i br. III41010

  3. Cytogenetic analysis of a case of myxoid liposarcoma with cartilaginous differentiation

    NARCIS (Netherlands)

    Dijkhuizen, T; Molenaar, WM; Hoekstra, HJ; Wiersema, J; vandenBerg, E

    1996-01-01

    The cytogenetic analysis of a patient with a myxoid liposarcoma exhibiting cartilaginous differentiation is presented. A complex translocation involving chromosome 12, 16, and 19 was found, instead of the t(12;16), specific for myxoid liposarcoma. The involvement of 19q13 in a tumor with

  4. CAR-T cells: the long and winding road to solid tumors.

    Science.gov (United States)

    D'Aloia, Maria Michela; Zizzari, Ilaria Grazia; Sacchetti, Benedetto; Pierelli, Luca; Alimandi, Maurizio

    2018-02-15

    Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles.

  5. Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors

    Directory of Open Access Journals (Sweden)

    Griffiths Gary L

    2009-06-01

    Full Text Available Abstract Background The existence of large pores in the blood-tumor barrier (BTB of malignant solid tumor microvasculature makes the blood-tumor barrier more permeable to macromolecules than the endothelial barrier of most normal tissue microvasculature. The BTB of malignant solid tumors growing outside the brain, in peripheral tissues, is more permeable than that of similar tumors growing inside the brain. This has been previously attributed to the larger anatomic sizes of the pores within the BTB of peripheral tumors. Since in the physiological state in vivo a fibrous glycocalyx layer coats the pores of the BTB, it is possible that the effective physiologic pore size in the BTB of brain tumors and peripheral tumors is similar. If this were the case, then the higher permeability of the BTB of peripheral tumor would be attributable to the presence of a greater number of pores in the BTB of peripheral tumors. In this study, we probed in vivo the upper limit of pore size in the BTB of rodent malignant gliomas grown inside the brain, the orthotopic site, as well as outside the brain in temporalis skeletal muscle, the ectopic site. Methods Generation 5 (G5 through generation 8 (G8 polyamidoamine dendrimers were labeled with gadolinium (Gd-diethyltriaminepentaacetic acid, an anionic MRI contrast agent. The respective Gd-dendrimer generations were visualized in vitro by scanning transmission electron microscopy. Following intravenous infusion of the respective Gd-dendrimer generations (Gd-G5, N = 6; Gd-G6, N = 6; Gd-G7, N = 5; Gd-G8, N = 5 the blood and tumor tissue pharmacokinetics of the Gd-dendrimer generations were visualized in vivo over 600 to 700 minutes by dynamic contrast-enhanced MRI. One additional animal was imaged in each Gd-dendrimer generation group for 175 minutes under continuous anesthesia for the creation of voxel-by-voxel Gd concentration maps. Results The estimated diameters of Gd-G7 dendrimers were 11 ± 1 nm and those of Gd-G8

  6. Bacteria-mediated in vivo delivery of quantum dots into solid tumor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ying [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Zhou, Mei [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Luo, Dan; Wang, Lijun; Hong, Yuankai [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Yang, Yepeng, E-mail: yangyepeng@bjmu.edu.cn [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Sha, Yinlin, E-mail: shyl@hsc.pku.edu.cn [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Biomed-X Center, Peking University, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. Black-Right-Pointing-Pointer Bifidobacterium bifidum delivery system has intrinsic biocompatibility. Black-Right-Pointing-Pointer The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.

  7. Cytogenetic comparisons of synchronous carcinomas and polyps in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Bardi, G; Parada, L A; Bomme, L

    1997-01-01

    Thirty tumorous lesions from seven patients with colorectal cancer were short-term cultured and cytogenetically analysed: 16 non-adenomatous polyps, six adenomas, seven carcinomas, including one in polyp, and one lymph node metastasis. Clonal chromosome aberrations were found in 20 samples in 100...

  8. Obtaining S values for rectangular--solid tumors inside rectangular--solid host organs

    International Nuclear Information System (INIS)

    Stinchcomb, T.G.; Durham, J.S.; Fisher, D.R.

    1991-01-01

    A method is described for obtaining S values between a tumor and its host organ for use with the MIRD formalism. It applies the point-source specific absorbed fractions for an infinite water medium, tabulated by Berger, to a rectangular solid of arbitrary dimensions which contains a rectangular tumor of arbitrary dimensions. Contributions from pairs of source and target volume elements are summed for the S values between the tumor and itself, between the remaining healthy host organ and itself, and between the tumor and the remaining healthy host organ, with the reciprocity theorem assumed for the last. This method labeled MTUMOR, is interfaced with the widely used MIRDOSE program which incorporates the MIRD formalism. An example is calculated

  9. Combination effect of cisplatin and radiation in murine solid tumors

    International Nuclear Information System (INIS)

    Egawa, Shin; Lee, Kan-ei; Ishibashi, Akira; Komiyama, Hiroki; Umezawa, Iwao.

    1986-01-01

    The combination effect of cisplatin and radiation was studied using the two different murine systems of sarcoma 180 and Ehrlich solid tumors. In sarcoma 180 solid tumor the minimal effective doses (MED) of cisplatin and radiation were 19.5 mg/kg and 10375 rad respectively whereas these doses did not show any effective antitumor activity practically. Administration of cisplatin with a doses of 9 mg/kg given 24 hours before radiation (1000 rad), however, showed synergistic antitumor activity. In Ehrlich solid tumor the MED of cisplatin and radiation were 13.8 mg/kg and 2892 rad respectively. Treatment with cisplatin, 3, 6 or 9 mg/kg, given 24 hours before radiation (1000 rad) showed also synergistic antitumor activity also. Sodium thiosulfate (STS) rescue was effective in reducing toxicity of cisplatin on combined use of the drug with radiation. Cell kinetics of sarcoma 180 solid tumor in vivo after the combined treatment was analyzed by computer aided flowcytometry. Accumulation of cells in the radiosensitive G 2 + M phase was observed 18 to 42 hours after a single intraperitoneal administration of 9 mg/kg of cisplatin. It is strongly suggested that this synchronization is one of the mechanisms of the synergism in the combination therapy. (author)

  10. Radio-immunotherapy of solid tumors

    International Nuclear Information System (INIS)

    Chatal, J.F.; Faivre Chauvet, A.; Bardies, M.; Kraeber-Bodere, F.; Barbet, J.

    2001-01-01

    A convincing efficacy of radio-immunotherapy of solid tumors has not been documented yet in clinical studies. Consequently, a methodological optimization is needed within the scope in increasing absorbed doses delivered to tumor targets by amplifying cumulative tumor activity and in the same time in reducing absorbed doses delivered normal organs. Multi-step pre-targeting techniques allow to approach these goals. The most developed technique is based on the high affinity for biotin. In a first step an anti-tumor antibody coupled to avidin or biodin is injected. In a second step, 24 hours later, the circulating residual immuno-conjugate is bound to a molecular complex and eliminated through the reticulo endothelial system of the liver ('chase'phase). A third step, a few hours later, consists in injecting biotin coupled to DOTA chelating agent and labeled with yttrium 90. This small molecule rapidly diffuses to tumor targets and binds to pre-localized immuno-conjugate. Another technique, designed and developed in France, is based on antigen-antibody affinity. In a first step an anti-tumor / anti-hapten bi-specific antibody is injected and, in a second step, a few days later, the small hapten molecule is radiolabeled with I-131 and injected. It diffuses rapidly to the tumor targets and binds to the anti-hapten arm of the pre-localized bi-specific antibody. An alternative way to increase radio-immunotherapy efficacy consists in combining this low-dose rate irradiation to radiosensitizing molecules within the scope of an additive or supra additive effect which has previously documented. (author)

  11. Engineered Breast Cancer Cell Spheroids Reproduce Biologic Properties of Solid Tumors.

    Science.gov (United States)

    Ham, Stephanie L; Joshi, Ramila; Luker, Gary D; Tavana, Hossein

    2016-11-01

    Solid tumors develop as 3D tissue constructs. As tumors grow larger, spatial gradients of nutrients and oxygen and inadequate diffusive supply to cells distant from vasculature develops. Hypoxia initiates signaling and transcriptional alterations to promote survival of cancer cells and generation of cancer stem cells (CSCs) that have self-renewal and tumor-initiation capabilities. Both hypoxia and CSCs are associated with resistance to therapies and tumor relapse. This study demonstrates that 3D cancer cell models, known as tumor spheroids, generated with a polymeric aqueous two-phase system (ATPS) technology capture these important biological processes. Similar to solid tumors, spheroids of triple negative breast cancer cells deposit major extracellular matrix proteins. The molecular analysis establishes presence of hypoxic cells in the core region and expression of CSC gene and protein markers including CD24, CD133, and Nanog. Importantly, these spheroids resist treatment with chemotherapy drugs. A combination treatment approach using a hypoxia-activated prodrug, TH-302, and a chemotherapy drug, doxorubicin, successfully targets drug resistant spheroids. This study demonstrates that ATPS spheroids recapitulate important biological and functional properties of solid tumors and provide a unique model for studies in cancer research. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Endoscopic ultrasound-guided radiofrequency ablation for management of benign solid pancreatic tumors.

    Science.gov (United States)

    Choi, Jun-Ho; Seo, Dong-Wan; Song, Tae Jun; Park, Do Hyun; Lee, Sang Soo; Lee, Sung Koo; Kim, Myung-Hwan

    2018-05-04

     Radiofrequency ablation (RFA) has been increasingly employed in experimental and clinical settings for the management of pancreatic lesions. This study aimed to assess the safety and efficacy of endoscopic ultrasound (EUS)-guided RFA for benign solid pancreatic tumors.  In a single-center, prospective study, 10 patients with benign solid pancreatic tumors underwent EUS-RFA. After the RFA electrode had been inserted into the pancreatic mass, the radiofrequency generator was activated to deliver 50 W of ablation power.  Among the 10 patients, 16 sessions of EUS-RFA were successfully performed. Diagnoses included nonfunctioning neuroendocrine tumor (n = 7), solid pseudopapillary neoplasm (n = 2), and insulinoma (n = 1); the median largest diameter of the tumors was 20 mm (range 8 - 28 mm). During follow-up (median 13 months), radiologic complete response was achieved in seven patients. Two adverse events (12.4 %; 1 moderate and 1 mild) occurred.  EUS-RFA may be a safe and potentially effective treatment option in selected patients with benign solid pancreatic tumors. Multiple sessions may be required if there is a remnant tumor, and adverse events must be carefully monitored. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Chimeric antigen receptor T-cell therapy for solid tumors

    Directory of Open Access Journals (Sweden)

    Kheng Newick

    2016-01-01

    Full Text Available Chimeric antigen receptor (CAR T cells are engineered constructs composed of synthetic receptors that direct T cells to surface antigens for subsequent elimination. Many CAR constructs are also manufactured with elements that augment T-cell persistence and activity. To date, CAR T cells have demonstrated tremendous success in eradicating hematological malignancies (e.g., CD19 CARs in leukemias. This success is not yet extrapolated to solid tumors, and the reasons for this are being actively investigated. Here in this mini-review, we discuss some of the key hurdles encountered by CAR T cells in the solid tumor microenvironment.

  14. Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors.

    Science.gov (United States)

    Zhang, Bing-Lan; Qin, Di-Yuan; Mo, Ze-Ming; Li, Yi; Wei, Wei; Wang, Yong-Sheng; Wang, Wei; Wei, Yu-Quan

    2016-04-01

    Recent reports on the impressive efficacy of chimeric antigen receptor (CAR)-modified T cells against hematologic malignancies have inspired oncologists to extend these efforts for the treatment of solid tumors. Clinical trials of CAR-T-based cancer immunotherapy for solid tumors showed that the efficacies are not as remarkable as in the case of hematologic malignancies. There are several challenges that researchers must face when treating solid cancers with CAR-T cells, these include choosing an ideal target, promoting efficient trafficking and infiltration, overcoming the immunosuppressive microenvironment, and avoiding associated toxicity. In this review, we discuss the obstacles imposed by solid tumors on CAR-T cell-based immunotherapy and strategies adopted to improve the therapeutic potential of this approach. Continued investigations are necessary to improve therapeutic outcomes and decrease the adverse effects of CAR-T cell therapy in patients with solid malignancies in the future.

  15. Potential of epigenetic therapies in the management of solid tumors

    International Nuclear Information System (INIS)

    Valdespino, Victor; Valdespino, Patricia M

    2015-01-01

    Cancer is a complex disease with both genetic and epigenetic origins. The growing field of epigenetics has contributed to our understanding of oncogenesis and tumor progression, and has allowed the development of novel therapeutic drugs. First-generation epigenetic inhibitor drugs have obtained modest clinical results in two types of hematological malignancy. Second-generation epigenetic inhibitors are in development, and have intrinsically greater selectivity for their molecular targets. Solid tumors are more genetic and epigenetically complex than hematological malignancies, but the transcriptome and epigenome biomarkers have been identified for many of these malignancies. This solid tumor molecular aberration profile may be modified using specific or quasi-specific epidrugs together with conventional and innovative anticancer treatments. In this critical review, we briefly analyze the strategies to select the targeted epigenetic changes, enumerate the second-generation epigenetic inhibitors, and describe the main signs indicating the potential of epigenetic therapies in the management of solid tumors. We also highlight the work of consortia or academic organizations that support the undertaking of human epigenetic therapeutic projects as well as some examples of transcriptome/epigenome profile determination in clinical assessment of cancer patients treated with epidrugs. There is a good chance that epigenetic therapies will be able to be used in patients with solid tumors in the future. This may happen soon through collaboration of diverse scientific groups, making the selection of targeted epigenetic aberration(s) more rapid, the design and probe of drug candidates, accelerating in vitro and in vivo assays, and undertaking new cancer epigenetic-therapy clinical trails

  16. Targeting solid tumors with non-pathogenic obligate anaerobic bacteria.

    Science.gov (United States)

    Taniguchi, Shun'ichiro; Fujimori, Minoru; Sasaki, Takayuki; Tsutsui, Hiroko; Shimatani, Yuko; Seki, Keiichi; Amano, Jun

    2010-09-01

    Molecular-targeting drugs with fewer severe adverse effects are attracting great attention as the next wave of cancer treatment. There exist, however, populations of cancer cells resistant to these drugs that stem from the instability of tumor cells and/or the existence of cancer stem cells, and thus specific toxicity is required to destroy them. If such selectivity is not available, these targets may be sought out not by the cancer cell types themselves, but rather in their adjacent cancer microenvironments by means of hypoxia, low pH, and so on. The anaerobic conditions present in malignant tumor tissues have previously been regarded as a source of resistance in cancer cells against conventional therapy. However, there now appears to be a way to make use of these limiting factors as a selective target. In this review, we will refer to several trials, including our own, to direct attention to the utilizable anaerobic conditions present in malignant tumor tissues and the use of bacteria as carriers to target them. Specifically, we have been developing a method to attack solid cancers using the non-pathogenic obligate anaerobic bacterium Bifidobacterium longum as a vehicle to selectively recognize and target the anaerobic conditions in solid cancer tissues. We will also discuss the existence of low oxygen pressure in tumor masses in spite of generally enhanced angiogenesis, overview current cancer therapies, especially the history and present situation of bacterial utility to treat solid tumors, and discuss the rationality and future possibilities of this novel mode of cancer treatment. © 2010 Japanese Cancer Association.

  17. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor.

    Science.gov (United States)

    Boissonnas, Alexandre; Fetler, Luc; Zeelenberg, Ingrid S; Hugues, Stéphanie; Amigorena, Sebastian

    2007-02-19

    Although the immune system evolved to fight infections, it may also attack and destroy solid tumors. In most cases, tumor rejection is initiated by CD8(+) cytotoxic T lymphocytes (CTLs), which infiltrate solid tumors, recognize tumor antigens, and kill tumor cells. We use a combination of two-photon intravital microscopy and immunofluorescence on ordered sequential sections to analyze the infiltration and destruction of solid tumors by CTLs. We show that in the periphery of a thymoma growing subcutaneously, activated CTLs migrate with high instantaneous velocities. The CTLs arrest in close contact to tumor cells expressing their cognate antigen. In regions where most tumor cells are dead, CTLs resume migration, sometimes following collagen fibers or blood vessels. CTLs migrating along blood vessels preferentially adopt an elongated morphology. CTLs also infiltrate tumors in depth, but only when the tumor cells express the cognate CTL antigen. In tumors that do not express the cognate antigen, CTL infiltration is restricted to peripheral regions, and lymphocytes neither stop moving nor kill tumor cells. Antigen expression by tumor cells therefore determines both CTL motility within the tumor and profound tumor infiltration.

  18. Turnover rate of hypoxic cells in solid tumors

    International Nuclear Information System (INIS)

    Ljungkvist, A.S.E.; Bussink, J.; Rijken, P.F.J.W.; Van Der Kogel, A.J.

    2003-01-01

    Most solid tumors contain hypoxic cells, and both the amount and duration of tumor hypoxia has been shown to influence the effect of radiation treatment negatively. It is important to understand the dynamic processes within the hypoxic cell population in non-treated tumors, and the effect of different treatment modalities on the kinetics of hypoxic cells to be able to design optimal combined modality treatments. The turnover rate of hypoxic cells was analyzed in three different solid tumor models with a double bio-reductive hypoxic marker assay with sequential injection of the two hypoxic markers. Previously it was shown that this assay could be used to detect both a decrease and an increase of tumor hypoxia in relation to the tumor vasculature with high spatial resolution. In this study the first hypoxic marker, pimonidazole, was administered at variable times relative to tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. The hypoxic cell turnover rate was calculated as the loss of pimonidazole positive cells relative to CCI-103F. The murine C38 line had the fastest hypoxic turnover rate of 60% /24h and the human xenograft line SCCNij3 had the slowest hypoxic turnover rate of 30% /24 h. The hypoxic turnover rate was most heterogeneous in the SCCNij3 line that even contained viable groups of cells that had been hypoxic for at least 5 days. The human xenograft line MEC82 fell in between with a hypoxic turnover rate of 50% /24 h. The hypoxic cell turnover was related to the potential tumor volume doubling time (Tpot) with a Tpot of 26h in C38 and 103h in SCCNij3. The dynamics of hypoxic cells, quantified with a double hypoxic marker method, showed large differences in hypoxic cell turnover rate and were related to Tpot

  19. Disseminated intravascular coagulation in solid tumors

    International Nuclear Information System (INIS)

    Terzieff, V.; Alonso, I.; Vázquez, A.

    2004-01-01

    It is estimated that 20-25% of cases of disseminated intravascular coagulation (DIC) relate to an underlying neoplasia primarily hematologic. It is estimated that about 5% of patients with solid tumors have CID clinic, although the incidence of subclinical alterations is much higher. The CID is not limited to the activation of the coagulation cascade, which leads to bleeding micro thrombosis and consumption of coagulation factors. Solid tumors are frequently associated adenocarcinomas producers mucin (especially gastric), usually in the context of a disseminated disease. The mucin may act as a promoter of the cascade, but probably it is a multi-event. High levels of TNF to produced by the tumor mass and chemotherapy-induced cell lysis have Also linked. Although the bleeding is usually oriented diagnosis, the most frequent cause of death is thrombosis. There are no specific tests for diagnosis. Elevated levels of D-dimer and products oriented fibrinogen degradation diagnosis. No reduction fibrinogen and almost always, one thrombocytopenia consumption. Treatment is complex and there is no consensus on many points. To recover the lost factors for consumption, it is recommended to use fresh frozen plasma and / or washed red blood cells. the heparin anticoagulation low dose is indicated since the disease causal can not be controlled quickly, but should not be initiated if there thrombocytopenia 50.000.El under profuse bleeding can require the use of tranexamic acid or EACA. Acute DIC, the case of our patient, is rare and very serious

  20. Low-dose-rate high-let radiation cytogenetic effects on mice in vivo as model of space radiation action on mammalian

    Science.gov (United States)

    Sorokina, Svetlana; Zaichkina, Svetlana; Rozanova, Olga; Aptikaeva, Gella; Romanchenko, Sergei; Smirnova, Helene; Dyukina, Alsu; Peleshko, Vladimir

    At present time little is known concerning the biological effects of low-dose-rate high-LET radiation exposure in space. The currently available experimental data on the biological effect of low doses of chronic radiation with high-LET values, which occur under the conditions of aircraft and space flights, have been primarily obtained in the examinations of pilots and astronauts after flights. Another way of obtaining this kind of evidence is the simulation of irradiation conditions during aircraft and space flights on high-energy accelerators and the conduction of large-scale experiments on animals under these conditions on Earth. In the present work, we investigated the cytogenetic effects of low-dose-rate high-LET radiation in the dose ranges of 0.2-30 cGy (1 cGy/day) and 0.5-16 cGy (0.43 cGy/day) in the radiation field behind the concrete shield of the Serpukhov accelerator of 70 GeV protons that simulates the spectral and component composition of radiation fields formed in the conditions of high-altitude flights on SHK mice in vivo. The dose dependence, adaptive response (AR) and the growth of solid tumor were examined. For induction of AR, two groups of mice were exposed to adapting doses of 0.2-30 cGy and the doses of 0.5-16 cGy of high-LET radiation. For comparison, third group of mice from unirradiated males was chronically irradiated with X-rays at adapting doses of 10 cGy (1 cGy/day). After a day, the mice of all groups were exposed to a challenging dose of 1.5 Gy of X-rays (1 Gy/min). After 28 h, the animals of all groups were killed by the method of cervical dislocation. Bone marrow specimens for calculating micronuclei (MN) in polychromatic erythrocytes (PCE) were prepared by a conventional method with minor modifications. The influence of adapting dose of 16 cGy on the growth of solid tumor of Ehrlich ascite carcinoma was estimated by measuring the size of the tumor at different times after the inoculation of ascitic cells s.c. into the femur. It was

  1. Pregnancy following Radical Resection of Solid Pseudopapillary Tumor of the Pancreas

    Directory of Open Access Journals (Sweden)

    James M. O’Brien

    2014-01-01

    Full Text Available Solid pseudopapillary tumor of the pancreas is a rare tumor seen in predominately young women and carries a low malignant potential. We discuss a patient, who presented to our high risk clinic, with a clinical history of solid pseudopapillary tumor of the pancreas, predating her pregnancy. The patient had undergone previous surgery and imaging which had excluded recurrence of disease; however, increased attention was paid to the patient during her pregnancy secondary to elevated hormonal levels of progesterone, which any residual disease would have a heightened sensitivity to. In cases of pregnant patients with a history of pancreatic tumors, a multidisciplinary approach with maternal fetal medicine, medicine, and general surgery is appropriate and can result in a healthy mother and healthy term infant.

  2. Challenges and prospects of chimeric antigen receptor T cell therapy in solid tumors.

    Science.gov (United States)

    Jindal, Vishal; Arora, Ena; Gupta, Sorab

    2018-05-05

    Chimeric antigen receptor (CAR) T cell therapy is a novel and innovative immunotherapy. CAR-T cells are genetically engineered T cells, carrying MHC independent specific antigen receptor and co-stimulatory molecule which can activate an immune response to a cancer specific antigen. This therapy showed great results in hematological malignancies but were unable to prove their worth in solid tumors. Likely reasons for their failure are lack of antigens, poor trafficking, and hostile tumor microenvironment. Excessive amount of research is going on to improve the efficacy of CAR T cell therapy in solid tumors. In this article, we will discuss the challenges faced in improving the outcome of CAR T cell therapy in solid tumors and various strategies adopted to curb them.

  3. Radiotherapy of the most frequent solid tumors in childhood

    International Nuclear Information System (INIS)

    Pfeiffer, J.; Kamprad, F.

    1980-01-01

    During the past decade the prognosis of malignant tumors in childhood could be clearly improved, realized by combining surgery, radiation therapy and chemotherapy. Recommendations for the use of radiotherapy for the most frequent solid tumors in childhood are represented basing on the experience of the study groups 'Pediatric Hematology and Oncology' of the Society for Pediatrics of the GDR and 'Tumors in Childhood' of the Section of Children's Surgery of the GDR. Besides general problems which have to be taken into consideration in the treatment of infantile tumors the radiotherapeutical measures for Wilms' tumors, neuroblastomas, cerebral tumors, embryonal sarcomas of the soft parts and bone tumors are discussed. The necessary close cooperation of the attending branches is pointed out and both the regional centralization of patients' care and a superregional cooperation are required. (author)

  4. Frequency of USP6 rearrangements in myositis ossificans, brown tumor, and cherubism: molecular cytogenetic evidence that a subset of ''myositis ossificans-like lesions'' are the early phases in the formation of soft-tissue aneurysmal bone cyst

    International Nuclear Information System (INIS)

    Sukov, William R.; Erickson-Johnson, Michele; Unni, K.K.; Wang, Xiaoke; Oliveira, Andre M.; Franco, Marcello F.; Chou, Margaret M.; Wenger, Doris E.

    2008-01-01

    USP6 rearrangements with several partner genes have been identified recently in primary but not in secondary aneurysmal bone cysts (ABCs). Several lesions show histologic features that may overlap with ABC, including myositis ossificans (MO), brown tumor, and cherubism. The objective of this study was to assess whether these lesions harbored USP6 rearrangements. Twelve patients with classic radiologic and histologic features of MO, 6 with brown tumors, and 5 with cherubism diagnosed at our institution were studied for the presence of USP6 rearrangements using fluorescence in situ hybridization with probes flanking the USP6 locus on chromosome 17p13. In addition, conventional cytogenetic analysis was performed in 2 patients with cherubism. USP6 rearrangements were identified in 2 patients with radiologic and histologic features consistent with MO. None of the patients with brown tumor or cherubism demonstrated USP6 rearrangements. Cytogenetic analysis of the cherubism patients demonstrated normal karyotypes. These findings indicate that a subset of cases with apparent classic histologic and imaging features of MO are rather better classified as being soft-tissue ABC with clonal USP6 rearrangements. In contrast, no USP6 rearrangements were found in patients with cherubism or brown tumor, supporting the prevailing view that these lesions are distinct biologic entities. (orig.)

  5. Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

    Science.gov (United States)

    Riaz, Muhammad Kashif; Riaz, Muhammad Adil; Zhang, Xue; Lin, Congcong; Wong, Ka Hong; Chen, Xiaoyu; Lu, Aiping

    2018-01-01

    Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed. PMID:29315231

  6. Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

    Directory of Open Access Journals (Sweden)

    Muhammad Kashif Riaz

    2018-01-01

    Full Text Available Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed.

  7. Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Hamid R. Mirzaei

    2017-12-01

    Full Text Available Adoptive cellular immunotherapy (ACT employing engineered T lymphocytes expressing chimeric antigen receptors (CARs has demonstrated promising antitumor effects in advanced hematologic cancers, such as relapsed or refractory acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, supporting the translation of ACT to non-hematological malignancies. Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in solid tumors success has been limited likely due to heterogeneous antigen expression, immunosuppressive networks in the tumor microenvironment limiting CAR T cell function and persistence, and suboptimal trafficking to solid tumors. Here, we outline specific approaches to overcome barriers to CAR T cell effectiveness in the context of the tumor microenvironment and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell design. We anticipate these modifications will further expand CAR T cell therapy in clinical practice.

  8. Recent advances of bispecific antibodies in solid tumors

    Directory of Open Access Journals (Sweden)

    Shengnan Yu

    2017-09-01

    Full Text Available Abstract Cancer immunotherapy is the most exciting advancement in cancer therapy. Similar to immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T, bispecific antibody (BsAb is attracting more and more attention as a novel strategy of antitumor immunotherapy. BsAb not only offers an effective linkage between therapeutics (e.g., immune effector cells, radionuclides and targets (e.g., tumor cells but also simultaneously blocks two different oncogenic mediators. In recent decades, a variety of BsAb formats have been generated. According to the structure of Fc domain, BsAb can be classified into two types: IgG-like format and Fc-free format. Among these formats, bispecific T cell engagers (BiTEs and triomabs are commonly investigated. BsAb has achieved an exciting breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. In this review, we focus on the preclinical experiments and clinical studies of epithelial cell adhesion molecule (EpCAM, human epidermal growth factor receptor (HER family, carcinoembryonic antigen (CEA, and prostate-specific membrane antigen (PSMA related BsAbs in solid tumors, as well as discuss the challenges and corresponding approaches in clinical application.

  9. New Chimeric Antigen Receptor Design for Solid Tumors

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    Yuedi Wang

    2017-12-01

    Full Text Available In recent years, chimeric antigen receptor (CAR T-cell therapy has become popular in immunotherapy, particularly after its tremendous success in the treatment of lineage-restricted hematologic cancers. However, the application of CAR T-cell therapy for solid tumors has not reached its full potential because of the lack of specific tumor antigens and inhibitory factors in suppressive tumor microenvironment (TME (e.g., programmed death ligand-1, myeloid-derived suppressor cells, and transforming growth factor-β. In this review, we include some limitations in CAR design, such as tumor heterogeneity, indefinite spatial distance between CAR T-cell and its target cell, and suppressive TME. We also summarize some new approaches to overcome these hurdles, including targeting neoantigens and/or multiple antigens at once and depleting some inhibitory factors.

  10. Analysis of the value of imaging in diagnosing pancreatic solid-pseudopapillary tumor

    International Nuclear Information System (INIS)

    Sun Canhui; Li Ziping; Meng Quanfei; Feng Shiting; Fan Miao; Peng Zhenpeng

    2007-01-01

    Objective: To describe the imaging features of solid-pseudopapillary tumor of the pancreas(SPTP) and evaluate the value of imaging in diagnosing SPTP. Methods: The imaging appearances in seven cases of SPTP confirmed by surgery and pathology were analyzed retrospectively. The un-enhanced and biphasic enhanced CT scanning were per- formed on all seven cases, including gastrointestinal barium meal series on three cases, endoscopic ultrasonography (EUS) on three cases, and MRI on one case. Results All tumors presented well-encapsulated heterogeneous soft tissue mass with varying degrees of solid and cystic components. Barium meal examination showed displaced gastrointestinal wall due to the tumoral compression. EUS demonstrated hyper-echoic mass with scattered small anechoic areas within the tumor. The tumor capsules were hyper-echoic. On un-enhanced CT, the mass appeared hypo-dense with mixed solid and cystic portions in six cases, and with predominantly cystic portion in one case. Calcification appeared in two cases. On biphasic enhanced CT, the mass showed peripheral and heterogeneous enhancement. Three tumors showed marked enhancement, and four tumors showed mild enhancement. Multiple small vessels within the tumor revealed on the arterial phase scanning in one case. The tumor capsules showed discontinuous enhancement in three cases. On T 1 WI, the mass appeared heterogeneous and predominantly isodense. On T 2 WI, the mass appeared heterogeneous and predominantly hyper-dense. The tumor capsule was hypo-dense on T 1 WI and T 2 WI. The mild dilatation of the biliary tract and pancreatic duct was revealed in two cases, respectively. Conclusion: Both CT and MRI can describe characteristic features of SPTP well, and should be used as the main diagnostic methods for SPTP before operation. (authors)

  11. Chimeric-antigen receptor T (CAR-T) cell therapy for solid tumors: challenges and opportunities.

    Science.gov (United States)

    Xia, An-Liang; Wang, Xiao-Chen; Lu, Yi-Jun; Lu, Xiao-Jie; Sun, Beicheng

    2017-10-27

    Chimeric antigen receptor (CAR)-engineered T cells (CAR-T cells) have been shown to have unprecedented efficacy in B cell malignancies, most notably in B cell acute lymphoblastic leukemia (B-ALL) with up to a 90% complete remission rate using anti-CD19 CAR-T cells. However, CAR T-cell therapy for solid tumors currently is faced with numerous challenges such as physical barriers, the immunosuppressive tumor microenvironment and the specificity and safety. The clinical results in solid tumors have been much less encouraging, with multiple cases of toxicity and a lack of therapeutic response. In this review, we will discuss the current stats and challenges of CAR-T cell therapy for solid tumors, and propose possibl e solutions and future perspectives.

  12. Photoirradiation system for solid tumors in photodynamic therapy

    International Nuclear Information System (INIS)

    Pacheco, L.; Stolik, S.; Rosa, J.M. de la

    2012-01-01

    Photodynamic therapy (PDT) is a clinical procedure which induces cell death for destroying cancerous tissues mostly. This is accomplished by photochemical reaction produced by the combined action of three elements: photo sensitizer, light and oxygen. One aspect of the development of PDT is focused on the treatment of solid and deep tumors, where a set of delivering-light probes are placed into the tumor mass. However, this technique still has several challenges, for although certain parameters involved in the procedure may be adjusted, the complex geometry and non-homogeneity of a tumor difficult to establish the appropriate treatment planning. This paper addresses an overview of interstitial PDT and presents our proposal of photo irradiation system. (Author)

  13. The cytogenetic damage in gynaecological cancer patients during radiotherapy. The variability of cytogenetic response to irradiation

    International Nuclear Information System (INIS)

    Vyinnyikov, V.A.; Maznik, N.A.; Sipko, T.C.; Pshenyichna, N.D.

    2013-01-01

    The limits of cytogenetic changes in blood lymphocytes of gynecological cancer patients undergoing radiotherapy and assessment the individual variability of the kinetics of chromosome aberration yields depending on treatment schemes was evaluated. Cytogenetic study was carried out in 53 female patients with uterine cancer. For the first time in vivo aberration yields were compared in the representational groups of gynecological cancer patients undergoing telegammatherapy, intracavitary brachytherapy or their combination; the limits of cytogenetic changes were evaluated and the magnitude of the individual variability of kinetics of cytogenetic damage yield was assessed depending on the scheme of therapeutic irradiation

  14. Solid pancreatic pseudopapillary tumor managed laparoscopically: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    D. Cuccurullo

    Full Text Available Background: Solid pancreatic pseudopapillary tumors are a rare neoplasms, about 1–3% of all pancreatic neoplasms. This cancer mainly affects women between the third and fourth decade of life.They are not well known; the molecular origins represent a low degree of malignancy, in which the complete resection is curative. We report our experience with a case report of SPT in a young man. Presentation of case: Thirty-six years old male patient with a mass about 10 cm in the pancreatic tail and splenic ilum. After following CT and MR, the patient was subjected to surgery. Histophatological result was solid tumor pseudopapillary of pancreas with no pathological lymph nodes. Discussion and conclusion: Solid pseudopapillary neoplasm shows histological characteristic solid and pseudopapillary proliferation. Immunohistochemistry detects, among the causes of tumor development, a correlation between the Beta-catenin mutations, alteration of the E-cadherin. In the most cases, therapy is surgical treatment with laparoscopic. Keywords: Pancreatic pseudopapillary neoplasm, Pancreatic tumor, Laparoscopic surgery

  15. Solid tissue culture for cytogenetic analysis: a collaborative survey for the Association of Clinical Cytogeneticists.

    Science.gov (United States)

    Rodgers, C S; Creasy, M R; Fitchett, M; Maliszewska, C T; Pratt, N R; Waters, J J

    1996-01-01

    AIMS: To survey the diagnostic service provided by UK laboratories for the culture of solid tissue samples (excluding tumours) and in particular to examine the variation in culture success rates and the problems of maternal cell overgrowth. METHODS: Twenty seven laboratories took part in a collaborative survey during 1992. Each laboratory submitted data on up to a maximum of 60 consecutive specimens (n = 1361) over a six month period. RESULTS: Skin specimens, the largest category received (n = 520), were the most problematic (51% success rate). Culture success rates were significantly lower (43%) when skin specimens (n = 140) were transported dry to the laboratory. Success rates for skin specimens also varied, depending on the origin of the specimen, from 18% for intra-uterine deaths (IUD) (n = 94) to 85% for neonatal deaths (n = 33) and 83% for live patients (n = 54). Culture of selected extra-fetal tissues from IUD, stillbirths and following elective termination of pregnancy (TOP) gave comparable success rates to those achieved for skin samples from neonatal deaths and live births. Skewed sex ratios, female > male, were identified for products of conception (POC) (n = 298) and placental biopsy specimens (n = 97). CONCLUSIONS: By appropriate selection, transport and processing of tissues, and in particular by avoiding relying solely on skin samples from IUD, stillbirths and TOP, an increase in culture success rates for solid tissue samples submitted for cytogenetic analysis could be achieved. The high risk of maternal cell contamination from POC and placental biopsy specimens was also identified in this survey. PMID:8881913

  16. Cytogenetic biodosimetry: what it is and how we do it.

    Science.gov (United States)

    Wong, K F; Siu, Lisa L P; Ainsbury, E; Moquet, J

    2013-04-01

    Dicentric assay is the international gold standard for cytogenetic biodosimetry after radiation exposure, despite being very labour-intensive, time-consuming, and highly expertise-dependent. It involves the identification of centromeres and structure of solid-stained chromosomes and the enumeration of dicentric chromosomes in a large number of first-division metaphases of cultured T lymphocytes. The dicentric yield is used to estimate the radiation exposure dosage according to a statistically derived and predetermined dose-response curve. It can be used for population triage after large-scale accidental over-exposure to ionising radiation or with a view to making clinical decisions for individual patients receiving substantial radiation. In this report, we describe our experience in the establishment of a cytogenetic biodosimetry laboratory in Queen Elizabeth Hospital, Hong Kong. This was part of the contingency plan for emergency measures against radiation accidents at nuclear power stations.

  17. Some epidemiological and clinical characteristics of solid malignant tumors in children from Las Tunas

    Directory of Open Access Journals (Sweden)

    Silvio Laffita Estévez

    2015-11-01

    Full Text Available Background: cancer has kept up as the second cause of death in Las Tunas pediatric population.Objective: to characterize clinical and epidemiological variables of the cases diagnosed with solid malignant tumors in children seen and treated in the onco-pediatric consultation of “Mártires de Las Tunas” Pediatric Hospital from 2010 to 2014.Methods: a descriptive and retrospective study was carried out in 62 patients with solid malignant tumors in the pediatric population of Las Tunas province, from January, 2010 to December, 2014. The variables considered were: presumptive diagnosis, age, family history of tumors, clinical signs of alarm related to the tumor at the moment of diagnosis and investigations to confirm the diagnosis.  Results: non-Hodgkin lymphoma was the most frequently diagnosed tumor, with a 19, 35% of the patients. The most affected age group was between 11 and 14 years old, with a 33, 87%. The 16, 13% of the patients had family history of solid malignant tumors. The most frequent form of presentation was the abdominal tumor, with 29, 03 %. Abdominal ultrasound and computerized axial tomography were the most used complementary diagnostic means, both in the 17, 74% of the patients. Biopsy was used to confirm the 96, 77% of the cases.Conclusions: the clinical and epidemiological variables were characterized in pediatric patients diagnosed with solid malignant tumors in Las Tunas. Children between 11 and 14 years old and family history of malignant tumors were the most significant findings.

  18. Angiogenesis and anti-angiogenesis: Perspectives for the treatment of solid tumors

    NARCIS (Netherlands)

    Hinsbergh, V.W.M. van; Collen, A.; Koolwijk, P.

    1999-01-01

    Angiogenesis is the formation of new blood vessels from preexisting ones. Many solid tumors depend on an extensive newly formed vascular network to become nourished and to expand. Tumor cells induce the formation of an extensive but aberrant vascular network by the secretion of angiogenic factors. A

  19. Nutritional status changes in children with malignant solid tumor before and after chemotherapy

    OpenAIRE

    Boris Januar; Sri S Nasar; Rulina Suradi; Maria Abdulsalam

    2016-01-01

    Background Although aggressive multimodal treatment programs in childhood cancer have significantly increased survival rates, the morbidity caused by protein energy malnutrition related to therapy is still high. Objective To describe nutritional status changes in children with malignant solid tumors after 21 days of chemotherapy. Methods A descriptive prospective study with pre- and post-test design in children with malignant solid tumors was conducted in the Departmen...

  20. Using a 3-d model system to screen for drugs effective on solid tumors

    OpenAIRE

    Fayad, Walid

    2011-01-01

    There is a large medical need for the development of effective anticancer agents with minimal side effects. The present thesis represents an attempt to identify potent drugs for treatment of solid tumors. We used a strategy where 3-D multicellular tumor spheroids (cancer cells grown in three dimensional culture) were utilized as in vitro models for solid tumors. Drug libraries were screened using spheroids as targets and using apoptosis induction and loss of cell viability as endpoints. The h...

  1. Chimeric antigen receptor T cell (CAR-T) immunotherapy for solid tumors: lessons learned and strategies for moving forward.

    Science.gov (United States)

    Li, Jian; Li, Wenwen; Huang, Kejia; Zhang, Yang; Kupfer, Gary; Zhao, Qi

    2018-02-13

    Recently, the US Food and Drug Administration (FDA) approved the first chimeric antigen receptor T cell (CAR-T) therapy for the treatment CD19-positive B cell acute lymphoblastic leukemia. While CAR-T has achieved remarkable success in the treatment of hematopoietic malignancies, whether it can benefit solid tumor patients to the same extent is still uncertain. Even though hundreds of clinical trials are undergoing exploring a variety of tumor-associated antigens (TAA), no such antigen with comparable properties like CD19 has yet been identified regarding solid tumors CAR-T immunotherapy. Inefficient T cell trafficking, immunosuppressive tumor microenvironment, suboptimal antigen recognition specificity, and lack of safety control are currently considered as the main obstacles in solid tumor CAR-T therapy. Here, we reviewed the solid tumor CAR-T clinical trials, emphasizing the studies with published results. We further discussed the challenges that CAR-T is facing for solid tumor treatment and proposed potential strategies to improve the efficacy of CAR-T as promising immunotherapy.

  2. AKT Inhibition in Solid Tumors With AKT1 Mutations.

    Science.gov (United States)

    Hyman, David M; Smyth, Lillian M; Donoghue, Mark T A; Westin, Shannon N; Bedard, Philippe L; Dean, Emma J; Bando, Hideaki; El-Khoueiry, Anthony B; Pérez-Fidalgo, José A; Mita, Alain; Schellens, Jan H M; Chang, Matthew T; Reichel, Jonathan B; Bouvier, Nancy; Selcuklu, S Duygu; Soumerai, Tara E; Torrisi, Jean; Erinjeri, Joseph P; Ambrose, Helen; Barrett, J Carl; Dougherty, Brian; Foxley, Andrew; Lindemann, Justin P O; McEwen, Robert; Pass, Martin; Schiavon, Gaia; Berger, Michael F; Chandarlapaty, Sarat; Solit, David B; Banerji, Udai; Baselga, José; Taylor, Barry S

    2017-07-10

    Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity of AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary end points were progression-free survival (PFS) and response according to Response Evaluation Criteria in Solid Tumors (RECIST). Tumor biopsies and plasma cell-free DNA (cfDNA) were collected in the majority of patients to identify predictive biomarkers of response. Results In patients with AKT1 E17K-mutant tumors (n = 52) and a median of five lines of prior therapy, the median PFS was 5.5 months (95% CI, 2.9 to 6.9 months), 6.6 months (95% CI, 1.5 to 8.3 months), and 4.2 months (95% CI, 2.1 to 12.8 months) in patients with estrogen receptor-positive breast, gynecologic, and other solid tumors, respectively. In an exploratory biomarker analysis, imbalance of the AKT1 E17K-mutant allele, most frequently caused by copy-neutral loss-of-heterozygosity targeting the wild-type allele, was associated with longer PFS (hazard ratio [HR], 0.41; P = .04), as was the presence of coincident PI3K pathway hotspot mutations (HR, 0.21; P = .045). Persistent declines in AKT1 E17K in cfDNA were associated with improved PFS (HR, 0.18; P = .004) and response ( P = .025). Responses were not restricted to patients with detectable AKT1 E17K in pretreatment cfDNA. The most common grade ≥ 3 adverse events were hyperglycemia (24%), diarrhea (17%), and rash (15.5%). Conclusion This study provides the first clinical data that AKT1 E17K is a therapeutic target in human cancer. The genomic context of the AKT1 E17K mutation further conditioned response to AZD5363.

  3. Study of arsenic trioxide-induced vascular shutdown and enhancement with radiation in solid tumor

    International Nuclear Information System (INIS)

    Monzen, Hajime; Griffin, R.J.; Williams, B.W.; Amamo, Morikazu; Ando, Satoshi; Hasegawa, Takeo

    2004-01-01

    Arsenic trioxide (ATO) has been reported to be an effective chemotherapeutic agent for acute promyelocytic leukemia (APL), and, recently, anti-tumor effect has been demonstrated in solid tumors. However, little is known about the mechanism of action of the ATO effect on solid tumor. We investigated the anti-vascular effect of ATO and the potential of combining ATO with radiation therapy. We studied the anti-vascular effect of ATO and radiosensitization of squamous cell carcinoma (SCC) VII murine tumors of C3H mice. The anti-vascular effect was examined using magnetic resonance imaging (MRI), and radiosensitivity was studied by clonogenic assay and tumor growth delay. Histopathological changes of the tumors after various treatments were also observed with hematoxylin and eosin (H and E) staining. Necrosis and blood flow changes in the central region of tumors in the hind limbs of the animals were observed on T2-weighted imaging after an intraperitoneal (i.p.) injection of 8 mg/kg of ATO alone. ATO exposure followed by radiation decreased the clonogenic survival of SCC VII cells compared with either treatment alone. Tumor growth delay after 10-20 Gy of radiation alone was increased slightly compared with control tumors, but the combination of ATO injection 2 hours before exposure to 20 Gy of radiation significantly prolonged tumor growth delay by almost 20 days. The results suggest that ATO and radiation can enhance the radiosensitivity of solid tumor. (author)

  4. Mathematical Based Calculation of Drug Penetration Depth in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Hamidreza Namazi

    2016-01-01

    Full Text Available Cancer is a class of diseases characterized by out-of-control cells’ growth which affect cells and make them damaged. Many treatment options for cancer exist. Chemotherapy as an important treatment option is the use of drugs to treat cancer. The anticancer drug travels to the tumor and then diffuses in it through capillaries. The diffusion of drugs in the solid tumor is limited by penetration depth which is different in case of different drugs and cancers. The computation of this depth is important as it helps physicians to investigate about treatment of infected tissue. Although many efforts have been made on studying and measuring drug penetration depth, less works have been done on computing this length from a mathematical point of view. In this paper, first we propose phase lagging model for diffusion of drug in the tumor. Then, using this model on one side and considering the classic diffusion on the other side, we compute the drug penetration depth in the solid tumor. This computed value of drug penetration depth is corroborated by comparison with the values measured by experiments.

  5. Strategies for enhancing adoptive T-cell immunotherapy against solid tumors using engineered cytokine signaling and other modalities.

    Science.gov (United States)

    Shum, Thomas; Kruse, Robert L; Rooney, Cliona M

    2018-05-04

    Cancer therapy has been transformed by the demonstration that tumor-specific T-cells can eliminate tumor cells in a clinical setting with minimal long-term toxicity. However, significant success in the treatment of leukemia and lymphoma with T-cells using native receptors or redirected with chimeric antigen receptors (CARs) has not been recapitulated in the treatment of solid tumors. This lack of success is likely related to the paucity of costimulatory and cytokine signaling available in solid tumors, in addition to a range of inhibitory mechanisms. Areas covered: We summarize the latest developments in engineered T-cell immunotherapy, describe the limitations of these approaches in treating solid tumors, and finally highlight several strategies that may be useful in mediating solid tumor responses in the future, while also ensuring safety of engineered cells. Expert opinion: CAR-T therapies require further engineering to achieve their potential against solid tumors. Facilitating cytokine signaling in CAR T-cells appears to be essential in achieving better responses. However, the engineering of T-cells with potentially unchecked proliferation and potency raises the question of whether the simultaneous combination of enhancements will prove safe, necessitating continued advancements in regulating CAR-T activity at the tumor site and methods to safely switch off these engineered cells.

  6. Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

    Science.gov (United States)

    Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

    2016-02-01

    Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

  7. Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials

    OpenAIRE

    Kelly, K; Infante, JR; Taylor, MH; Patel, MR; Wong, DJ; Iannotti, N; Mehnert, JM; Loos, AH; Koch, H; Speit, I; Gulley, JL

    2018-01-01

    © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. BACKGROUND: Antibodies targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy. METHODS: Patients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patient...

  8. Uptake of labelled tallysomycin by solid Ehrlich ascites tumors in mice

    International Nuclear Information System (INIS)

    Liniecki, J.; Rembelska, M.; Koniarek, B.

    1983-01-01

    Tumor and normal tissue uptake of 51 Cr- or 57 Co-labelled bleomycin (BLEO) and tallysomycin (TLM) was compared in female solid Ehrlich ascites tumor mice of Swiss strain. The complexes were administered intraperitoneally: 30-50 μg of each complex with an activity of 40-120 μCi. Activity distribution factors (ADF) and tumor/non-tumor ratios for blood, bone, skeletal muscles, kidneys and liver were determined. The ratios were generally higher for complexes labelled with 57 Co than for the 51 Cr-labelled ones; bleomycin appears equivalent or superior to tallysomycin. (orig.) [de

  9. Frequency of USP6 rearrangements in myositis ossificans, brown tumor, and cherubism: molecular cytogenetic evidence that a subset of ''myositis ossificans-like lesions'' are the early phases in the formation of soft-tissue aneurysmal bone cyst

    Energy Technology Data Exchange (ETDEWEB)

    Sukov, William R.; Erickson-Johnson, Michele; Unni, K.K.; Wang, Xiaoke; Oliveira, Andre M. [Mayo Clinic, Department of Laboratory Medicine and Pathology, Rochester, MN (United States); Franco, Marcello F. [Universidade Federal do Estado de Sao Paulo (UNEFESP), Departamento de Patologia, Sao Paulo (Brazil); Chou, Margaret M. [University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Wenger, Doris E. [Mayo Clinic, Department of Radiology, Rochester, MN (United States)

    2008-04-15

    USP6 rearrangements with several partner genes have been identified recently in primary but not in secondary aneurysmal bone cysts (ABCs). Several lesions show histologic features that may overlap with ABC, including myositis ossificans (MO), brown tumor, and cherubism. The objective of this study was to assess whether these lesions harbored USP6 rearrangements. Twelve patients with classic radiologic and histologic features of MO, 6 with brown tumors, and 5 with cherubism diagnosed at our institution were studied for the presence of USP6 rearrangements using fluorescence in situ hybridization with probes flanking the USP6 locus on chromosome 17p13. In addition, conventional cytogenetic analysis was performed in 2 patients with cherubism. USP6 rearrangements were identified in 2 patients with radiologic and histologic features consistent with MO. None of the patients with brown tumor or cherubism demonstrated USP6 rearrangements. Cytogenetic analysis of the cherubism patients demonstrated normal karyotypes. These findings indicate that a subset of cases with apparent classic histologic and imaging features of MO are rather better classified as being soft-tissue ABC with clonal USP6 rearrangements. In contrast, no USP6 rearrangements were found in patients with cherubism or brown tumor, supporting the prevailing view that these lesions are distinct biologic entities. (orig.)

  10. Advances in Cancer Immunotherapy in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Smitha Menon

    2016-11-01

    Full Text Available Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses. Drugs which block the immune regulatory checkpoints namely the PD-1/PDL1 and CTLA 4 pathway have shown tremendous promise in a wide spectrum of solid and hematological malignancies, significantly improving overall survival in newly diagnosed and heavily pretreated patients alike. Hence there is renewed enthusiasm in the field of immune oncology with current research focused on augmenting responses to checkpoint inhibitors by combination therapy as well as studies looking at other immune modulators and adoptive T cell therapy. In this article, we highlight the key clinical advances and concepts in immunotherapy with particular emphasis on checkpoint inhibition as well as the future direction in this field.

  11. Characterization of cell suspensions from solid tumors

    International Nuclear Information System (INIS)

    Pallavicini, M.

    1985-01-01

    The desirable features of cells in suspension will necessarily be dependent upon the use for which the cells were prepared. Adequate cell yield or recovery is defined by the measurement to be performed. Retention of cellular morphology is important for microscopic identification of cell types in a heterogenous cell suspension, and may be used to determine whether the cells in suspension are representative of those in the tumor in situ. Different dispersal protocols may yield cells with different degrees of clonogenicity, as well as altered biochemical features, such as loss of cellular proteins, surface antigens, nucleotide pools, etc. The quality of the cell suspension can be judged by the degree of cell clumping and level of cellular debris, both of which impact on flow cytometric measurements and studies in which the number of cells be known accurately. Finally, if the data measured on the cells in suspension are to be extrapolated to phenomena occurring in the tumor in situ, it is desirable that the cells in suspension are representative of those in the solid tumor in vivo. This report compares characteristics of tumor cell suspensions obtained by different types of selected disaggregation methods. 33 refs., 2 figs., 4 tabs

  12. Evaluation of malignant solid tumor in childhood with FDG-PET

    International Nuclear Information System (INIS)

    Ishida, Amane; Goto, Hiroaki; Kuroki, Fumiko

    2006-01-01

    Usefulness of FDG-PET (18F-deoxyglucose PET) was examined in evaluation of diagnosis and therapeutic efficacy of childhood malignant solid tumors. Subjects were 32 patients (16 males) of the median age of 7 y (1 - 27 y), involving those with neuroblastoma (9 cases), hepatoblastoma (4), chronic granulomatous disorder (4) and others (each ≤2). They underwent 75 FDG-PET examinations for diagnosis before and during treatment in authors' hospital in the period from May 2001 to December 2003. Standard uptake value (SUV), 1 x 1 cm region of interest (ROI) of abnormally high distribution area of radioactivity in the lesion/FDG dose/kg body wt., was used for evaluation: SUV>1.5 was defined positive. In neuroblastoma, FDG was found to be highly distributed and kinetics of SUV, to be useful for evaluation of therapeutic efficacy and early metastasis detection. In some cases of hepatoblastoma, the therapeutic effectiveness and recurrence were not satisfactorily evaluative. The distribution of FDG was not satisfactory in Wilms' tumor relative to other tumors. The PET was thought to be useful, despite their small case number examined, for those evaluations of Ewing's tumor, dysgerminoma and Langerhans cell histiocytosis. Thus FDG-PET was found useful for detection, evaluation of therapeutic efficacy and early metastasis detection of pediatric malignant solid tumors. (T.I.)

  13. Recombinant Immunotoxin Therapy of Solid Tumors: Challenges and Strategies.

    Science.gov (United States)

    Shan, Liang; Liu, Yuanyi; Wang, Paul

    2013-01-01

    Immunotoxins are a group of protein-based therapeutics, basically comprising two functional moieties: one is the antibody or antibody Fv fragment that allows the immunotoxin to bind specifically to target cells; another is the plant or bacterial toxin that kills the cells upon internalization. Immunotoxins have several unique features which are superior to conventional chemotherapeutics, including high specificity, extraordinary potency, and no known drug resistance. Development of immunotoxins evolves with time and technology, but significant progress has been achieved in the past 20 years after introduction of recombinant DNA technique and generation of the first single-chain variable fragment of monoclonal antibodies. Since then, more than 1,000 recombinant immunotoxins have been generated against cancer. However, most success in immunotoxin therapy has been achieved against hematological malignancies, several issues persist to be significant barriers for effective therapy of human solid tumors. Further development of immunotoxins will largely focus on the improvement of penetration capability to solid tumor mass and elimination of immunogenicity occurred when given repeatedly to patients. Promising strategies may include construction of recombinant antibody fragments with higher binding affinity and stability, elimination of immunodominant T- and B-cell epitopes of toxins, modification of immunotoxins with macromolecules like poly(ethylene glycol) and liposomes, and generation of immunotoxins with humanized antibody fragments and human endogenous cytotoxic enzymes. In this paper, we briefly reviewed the evolution of immunotoxin development and then discussed the challenges of immunotoxin therapy for human solid tumors and the potential strategies we may seek to overcome the challenges.

  14. L-Asparaginase delivered by Salmonella typhimurium suppresses solid tumors

    Directory of Open Access Journals (Sweden)

    Kwangsoo Kim

    Full Text Available Bacteria can be engineered to deliver anticancer proteins to tumors via a controlled expression system that maximizes the concentration of the therapeutic agent in the tumor. L-asparaginase (L-ASNase, which primarily converts asparagine to aspartate, is an anticancer protein used to treat acute lymphoblastic leukemia. In this study, Salmonellae were engineered to express L-ASNase selectively within tumor tissues using the inducible araBAD promoter system of Escherichia coli. Antitumor efficacy of the engineered bacteria was demonstrated in vivo in solid malignancies. This result demonstrates the merit of bacteria as cancer drug delivery vehicles to administer cancer-starving proteins such as L-ASNase to be effective selectively within the microenvironment of cancer tissue.

  15. Approaches to drug resistance in solid tumors : with emphasis on lung cancer

    NARCIS (Netherlands)

    Bakker, Marleen

    2005-01-01

    De novo or acquired resistance of tumor cells to anticancer agents remains a major problem for the therapeutic efficacy of chemotherapeutic drugs. Most solid tumors are intrinsically insensitive or acquire resistance after initial response to chemotherapy. Different mechanisms seem to play a role in

  16. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review.

    Science.gov (United States)

    Shrotriya, Shiva; Walsh, Declan; Bennani-Baiti, Nabila; Thomas, Shirley; Lorton, Cliona

    2015-01-01

    A systematic literature review was done to determine the relationship between elevated CRP and prognosis in people with solid tumors. C-reactive protein (CRP) is a serum acute phase reactant and a well-established inflammatory marker. We also examined the role of CRP to predict treatment response and tumor recurrence. MeSH (Medical Subject Heading) terms were used to search multiple electronic databases (PubMed, EMBASE, Web of Science, SCOPUS, EBM-Cochrane). Two independent reviewers selected research papers. We also included a quality Assessment (QA) score. Reports with QA scores <50% were excluded. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) methodology was utilized for this review (S1 PRISMA Checklist). 271 articles were identified for final review. There were 45% prospective studies and 52% retrospective. 264 had intermediate QA score (≥50% but <80%); Seven were adequate (80% -100%); A high CRP was predictive of prognosis in 90% (245/271) of studies-80% of the 245 studies by multivariate analysis, 20% by univariate analysis. Many (52%) of the articles were about gastrointestinal malignancies (GI) or kidney malignancies. A high CRP was prognostic in 90% (127 of 141) of the reports in those groups of tumors. CRP was also prognostic in most reports in other solid tumors primary sites. A high CRP was associated with higher mortality in 90% of reports in people with solid tumors primary sites. This was particularly notable in GI malignancies and kidney malignancies. In other solid tumors (lung, pancreas, hepatocellular cancer, and bladder) an elevated CRP also predicted prognosis. In addition there is also evidence to support the use of CRP to help decide treatment response and identify tumor recurrence. Better designed large scale studies should be conducted to examine these issues more comprehensively.

  17. Molecular cytogenetic anomalies and phenotype alterations in a newly established cell line from Wilms tumor with diffuse anaplasia.

    Science.gov (United States)

    Faussillon, Marine; Murakami, Ichiro; Bichat, Magalie; Telvi, Louise; Jeanpierre, Cécile; Nezelof, Christian; Jaubert, Francis; Gogusev, Jean

    2008-07-01

    The novel continuous cell line WT-Pe.1 was established in vitro from Wilms tumor with histological features of diffuse anaplasia. The cultures grew as poorly differentiated epithelial-like cells with pleomorphic polygonal shapes and formation of typical monolayers. WT-Pe.1 cells were immunoreactive for cytokeratin, vimentin, laminin, villin, CD10, and CD24 proteins. Conventional cytogenetic analysis by RHG-banding revealed a hypotriploid karyotype with numerous abnormalities including ring chromosomes, double-minutes, homogeneous staining regions, radial structures, dicentrics, and several marker chromosomes. Comparative genomic hybridization analysis revealed DNA copy numbers losses on chromosome segments 1p, 3p, 6q, 9q34.1 approximately q34.3, 11q24 approximately q25, 14q12 approximately qter, 16q, 18q, and 22q11 approximately q13; gain of genomic material was localized on chromosome arms 1q, 4p, 6q, and 7p and the entire chromosome 12. With DNA from the original tumor, copy number losses were detected on chromosomes 1p, 14q, 16q, 17q, and 22q and gains were observed on 1q, 4p, 8q, 12p, 12q, and chromosome 14p. Copy number amplifications of distinct loci were found on 1q21.1 and 4p15.3, as well as an elevated copy number of cyclin D2 (CCND2) and cyclin D associated kinase (CDK4) genes on chromosome 12 (confirmed by fluorescence in situ hybridization).

  18. Chromosome abnormalities in colorectal adenomas: two cytogenetic subgroups characterized by deletion of 1p and numerical aberrations

    DEFF Research Database (Denmark)

    Bomme, L; Bardi, G; Pandis, N

    1996-01-01

    Cytogenetic analysis of short-term cultures from 34 benign colorectal polyps, all histologically verified as adenomas, revealed clonal chromosome aberrations in 21 of them. Eight polyps had structural rearrangements, whereas only numerical changes were found in 13. A combination of structural...... and another with a small 1p deletion. In three adenomas, del(1)(p36) was the only cytogenetic aberration, supporting the authors' previous conclusion that loss of one or more gene loci in band 1p36 is a common early change in colorectal tumorigenesis. Chromosome 8 was involved in structural changes in two...... adenomas; in one this led to loss of 8p and in the other to gain of 8q. The cytogenetic findings did not correlate in a statistically significant manner with clinicopathologic parameters, such as grade of dysplasia, macroscopic or microscopic adenoma structure, tumor size and location, or the patients' sex...

  19. Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors.

    Science.gov (United States)

    Yu, Man; Lee, Carol; Wang, Marina; Tannock, Ian F

    2015-10-01

    Cellular causes of resistance and limited drug distribution within solid tumors limit therapeutic efficacy of anticancer drugs. Acidic endosomes in cancer cells mediate autophagy, which facilitates survival of stressed cells, and may contribute to drug resistance. Basic drugs (e.g. doxorubicin) are sequestered in acidic endosomes, thereby diverting drugs from their target DNA and decreasing penetration to distal cells. Proton pump inhibitors (PPIs) may raise endosomal pH, with potential to improve drug efficacy and distribution in solid tumors. We determined the effects of the PPI lansoprazole to modify the activity of doxorubicin. To gain insight into its mechanisms, we studied the effects of lansoprazole on endosomal pH, and on the spatial distribution of doxorubicin, and of biomarkers reflecting its activity, using in vitro and murine models. Lansoprazole showed concentration-dependent effects to raise endosomal pH and to inhibit endosomal sequestration of doxorubicin in cultured tumor cells. Lansoprazole was not toxic to cancer cells but potentiated the cytotoxicity of doxorubicin and enhanced its penetration through multilayered cell cultures. In solid tumors, lansoprazole improved the distribution of doxorubicin but also increased expression of biomarkers of drug activity throughout the tumor. Combined treatment with lansoprazole and doxorubicin was more effective in delaying tumor growth as compared to either agent alone. Together, lansoprazole enhances the therapeutic effects of doxorubicin both by improving its distribution and increasing its activity in solid tumors. Use of PPIs to improve drug distribution and to inhibit autophagy represents a promising strategy to enhance the effectiveness of anticancer drugs in solid tumors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  20. Immunoconjugates against solid tumors: mind the gap.

    Science.gov (United States)

    Ricart, A D

    2011-04-01

    The objective of immunoconjugate development is to combine the specificity of immunoglobulins with the efficacy of cytotoxic molecules. This therapeutic approach has been validated in hematologic malignancies; however, several obstacles to achieving efficacy in treating solid tumors have been identified. These include insufficient specificity of targets and poor antibody delivery, most specifically to the tumor core. Heterogeneous antigen expression, imperfect vascular supply, and elevated interstitial fluid pressure have been suggested as the factors responsible for the poor delivery of antibodies. Promising immunoconjugates are in development: immunoconjugates targeting the prostate-specific membrane antigen, trastuzumab-DM1, lorvotuzumab mertansine, and SS1P. Advances in cancer biology and antibody engineering may overcome some of the challenges. New small antibody formats, such as single-chain Fv, Fab, and diabodies, may improve penetration within tumor masses. Nevertheless, the cost of treatment might require justification in terms of demonstrable improvement in quality of life in addition to efficacy; further economic evaluation might be necessary before this approach can replace the current standards of care in clinical practice.

  1. Effect of fluid friction on interstitial fluid flow coupled with blood flow through solid tumor microvascular network.

    Science.gov (United States)

    Sefidgar, Mostafa; Soltani, M; Raahemifar, Kaamran; Bazmara, Hossein

    2015-01-01

    A solid tumor is investigated as porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multiscale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. The mathematical method involves processes such as blood flow through vessels and solute and fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model predicts.

  2. Four cases of solid pseudopapillary tumors of pancreas: Imaging findings and pathological correlations

    International Nuclear Information System (INIS)

    Vargas-Serrano, Blanca; Dominguez-Ferreras, Esther; Chinchon-Espino, David

    2006-01-01

    Objective: Solid pseudopapillary tumor of the pancreas (SPTP tumor) is a rare pancreatic neoplasm with low malignant potential, which usually affects female patients in the second or third decades of life. It is a non-functional, slow-growing neoplasm that very often reaches considerable size before the first symptoms appear. Symptomatology is frequently related to tumor size. Surgical excision is usually curative in most cases. Infrequently the tumor can appear in male patients or in aged women, which can make the diagnosis more difficult. Some patients develop liver metastases in the follow-up that can be resected. Our purpose is to review the radiological and pathological findings of SPTP with emphasis on these infrequent cases. Subjects and methods: The medical records and radiological findings of patients who underwent surgery for SPTP between 2000 and 2005 were retrospectively reviewed. Study eligibility required that patients had undergone surgical resection and that a SPTP had been pathologically proved. Results: Four cases of solid pseudopapillary tumor of the pancreas were diagnosed and treated in our institution in the study period. Two of the patients, developed on follow-up liver metastases, and peritoneal, hepatic, and nodal metastases, respectively. Conclusion: Solid pseudopapillary tumors are well-encapsulated neoplasms that usually have a good prognosis after surgical excision. A malignant behavior is uncommon and in this case lymph node involvement, hepatic metastases and occasionally peritoneal invasion may also occur. Resection of liver metastases can prolong the long-term survival of the patients

  3. Cytogenetics in animal production

    Directory of Open Access Journals (Sweden)

    L. Iannuzzi

    2010-04-01

    Full Text Available Cytogenetics applied to domestic animals is a useful biotechnology to be applied in the genetic improvement of livestock. Indeed, it can be used to select reproducers free chromosome abnormalities which are responsible for abnormal body conformation (aneuploidy, lower fertility (balanced chromosome abnormalities or sterility (sex chromosome abnormalities. Cytogenetics may also be applied to assess environmental pollution by studying animals living in hazardous areas and using them as biological indicators (sentinels. Chromosomes also represent optimal biological structures to study the evolution among related (bovids and unrelated (bovidshumans species, especially using comparative FISH-mapping which is one of the most powerful tools to establish the correct order of loci along chromosomes. These comparisons allow us to transfer useful information from richer genomes (human to those of domestic animals. Moreover, the use of specific molecular markers and the FISH-technique on both mitotic and extended (fiber-FISH chromosomes, has heralded a new era of cytogenetics, allowing swift extension of genetic physical maps, better anchoring of both linkage and RH-maps to specific chromosome regions, and use in a variety of applications (clinical cases, embryo and sperm analyses, evolution. In this study a brief review of these fields of the animal cytogenetics is presented.

  4. The history of human cytogenetics in India-A review.

    Science.gov (United States)

    Dutta, Usha R

    2016-09-10

    It is 60years since the discovery of the correct number of chromosomes in 1956; the field of cytogenetics had evolved. The late evolution of this field with respect to other fields is primarily due to the underdevelopment of lenses and imaging techniques. With the advent of the new technologies, especially automation and evolution of advanced compound microscopes, cytogenetics drastically leaped further to greater heights. This review describes the historic events that had led to the development of human cytogenetics with a special attention about the history of cytogenetics in India, its present status, and future. Apparently, this review provides a brief account into the insights of the early laboratory establishments, funding, and the German collaborations. The details of the Indian cytogeneticists establishing their labs, promoting the field, and offering the chromosomal diagnostic services are described. The detailed study of chromosomes helps in increasing the knowledge of the chromosome structure and function. The delineation of the chromosomal rearrangements using cytogenetics and molecular cytogenetic techniques pays way in identifying the molecular mechanisms involved in the chromosomal rearrangement. Although molecular cytogenetics is greatly developing, the conventional cytogenetics still remains the gold standard in the diagnosis of various numerical chromosomal aberrations and a few structural aberrations. The history of cytogenetics and its importance even in the era of molecular cytogenetics are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Recent advances in the design of drug-loaded polymeric implants for the treatment of solid tumors.

    Science.gov (United States)

    Wadee, Ameena; Pillay, Viness; Choonara, Yahya E; du Toit, Lisa C; Penny, Clement; Ndesendo, Valence M K; Kumar, Pradeep; Murphy, Caragh S

    2011-10-01

    The effective treatment of solid tumors continues to be a great challenge to clinicians, despite the development of novel drugs. In order to improve the clinical efficacy of existing chemotherapeutic agents, researchers have considered the possibility of site-specific solid tumor treatment. The greatest advantage of localized delivery is the significantly fewer side effects experienced by patients. Recently, in situ forming implants have attracted considerable interest. These polymeric systems are injected as solutions into tumor sites and the injected solution forms an implant as a result of local environmental stimuli and hence removes the need for surgical implantation. This review summarizes the attempts that have been made to date in the development of polymeric implants for the treatment of solid tumors. Both in situ forming implants and preformed implants, fabricated using natural and synthetic polymers, are described. In addition, the peri- or intra-tumoral delivery of chemotherapeutic agents based on implants inserted surgically into the affected region is also discussed along with a short coverage of implants having an undesirable initial burst release effect. Although these implants have been shown to improve the treatment of various solid tumors, the ideal implant that is able to deliver high doses of chemotherapeutics to the tumor site, over prolonged periods with relatively few side effects on normal tissue, is yet to be formulated.

  6. Tenascin-W is a better cancer biomarker than tenascin-C for most human solid tumors

    Directory of Open Access Journals (Sweden)

    Brellier Florence

    2012-09-01

    Full Text Available Abstract Background Tenascins are large glycoproteins found in the extracellular matrix of many embryonic and adult tissues. Tenascin-C is a well-studied biomarker known for its high overexpression in the stroma of most solid cancers. Tenascin-W, the least studied member of the family, is highly expressed in the stroma of colon and breast tumors and in gliomas, but not in the corresponding normal tissues. Other solid tumors have not been analyzed. The present study was undertaken to determine whether tenascin-W could serve as a cancer-specific extracellular matrix protein in a broad range of solid tumors. Methods We analyzed the expression of tenascin-W and tenascin-C by immunoblotting and by immunohistochemistry on multiple frozen tissue microarrays of carcinomas of the pancreas, kidney and lung as well as melanomas and compared them to healthy tissues. Results From all healthy adult organs tested, only liver and spleen showed detectable levels of tenascin-W, suggesting that tenascin-W is absent from most human adult organs under normal, non-pathological conditions. In contrast, tenascin-W was detectable in the majority of melanomas and their metastases, as well as in pancreas, kidney, and lung carcinomas. Comparing lung tumor samples and matching control tissues for each patient revealed a clear overexpression of tenascin-W in tumor tissues. Although the number of samples examined is too small to draw statistically significant conclusions, there seems to be a tendency for increased tenascin-W expression in higher grade tumors. Interestingly, in most tumor types, tenascin-W is also expressed in close proximity to blood vessels, as shown by CD31 co-staining of the samples. Conclusions The present study extends the tumor biomarker potential of tenascin-W to a broad range of solid tumors and shows its accessibility from the blood stream for potential therapeutic strategies.

  7. Chimeric antigen receptor-modified T cells for the treatment of solid tumors: Defining the challenges and next steps☆

    OpenAIRE

    Beatty, Gregory L.; O’Hara, Mark

    2016-01-01

    Chimeric antigen receptor (CAR) T cell therapy has shown promise in CD19 expressing hematologic malignancies, but how to translate this success to solid malignancies remains elusive. Effective translation of CAR T cells to solid tumors will require an understanding of potential therapeutic barriers, including factors that regulate CAR T cells expansion, persistence, trafficking, and fate within tumors. Herein, we describe the current state of CAR T cells in solid tumors; define key barriers t...

  8. Targeting the PD-1 pathway in pediatric solid tumors and brain tumors

    Directory of Open Access Journals (Sweden)

    Wagner LM

    2017-04-01

    Full Text Available Lars M Wagner,1 Val R Adams2 1Division of Pediatric Hematology/Oncology, 2Department of Pharmacy Practice and Science, University of Kentucky, Lexington, KY, USA Abstract: While remarkable advances have been made in the treatment of pediatric leukemia over the past decades, new therapies are needed for children with advanced solid tumors and high-grade brain tumors who fail standard chemotherapy regimens. Immunotherapy with immune checkpoint inhibitors acting through the programmed cell death-1 (PD-1 pathway has shown efficacy in some chemotherapy-resistant adult cancers, generating interest that these agents may also be helpful to treat certain refractory pediatric malignancies. In this manuscript we review current strategies for targeting the PD-1 pathway, highlighting putative biomarkers and the rationale for investigation of these drugs to treat common pediatric tumors such as sarcoma, neuroblastoma, and high-grade glioma. We summarize the completed and ongoing clinical trial data available, and suggest potential applications for further study. Keywords: PD-1, nivolumab, pembrolizumab, pediatric, sarcoma, neuroblastoma, glioma

  9. CBT-501 Study for Select Advanced or Relapsed/Recurrent Solid Tumors

    Science.gov (United States)

    2018-02-07

    Solid Tumor; Advanced Cancer; ColoRectal Cancer; Endometrial Cancer; Gastric Cancer; Hepatocellular Cancer; Nonsmall Cell Lung Cancer; Mesothelioma; Ovarian Cancer; Renal Cancer; Nasopharyngeal Cancer; Esophageal Cancer; Gastroesophageal Junction Adenocarcinoma

  10. Cytogenetics of Legumes in the Phaseoloid Clade

    Directory of Open Access Journals (Sweden)

    Aiko Iwata

    2013-11-01

    Full Text Available Cytogenetics played an essential role in studies of chromosome structure, behavior, and evolution in numerous plant species. The advent of molecular cytogenetics combined with recent development of genomic resources has ushered in a new era of chromosome studies that have greatly advanced our knowledge of karyotypic diversity, genome and chromosome organization, and chromosomal evolution in legumes. This review summarizes some of the achievements of cytogenetic studies in legumes in the Phaseoloid clade, which includes several important legume crops such as common bean ( L., cowpea [ (L. Walp.], soybean [ (L. Merr.], and pigeonpea [ (L. Huth]. In the Phaseoloid clade, karyotypes are mostly stable. There are, however, several species with extensive chromosomal changes. Fluorescence in situ hybridization has been useful to reveal chromosomal structure by physically mapping transposons, satellite repeats, ribosomal DNA genes, and bacterial artificial chromosome clones onto chromosomes. Polytene chromosomes, which are much longer than the mitotic chromosomes, have been successfully found and used in cytogenetic studies in some and species. Molecular cytogenetics will continue to be an important tool in legume genetics and genomics, and we discuss future applications of molecular cytogenetics to better understand chromosome and genome structure and evolution in legumes.

  11. [Progress of cytogenetic detection in myelodysplastic syndromes].

    Science.gov (United States)

    Zhou, Qing-Bing; Hu, Xiao-Mei; Liu, -Feng; Ma, Rou

    2011-12-01

    In recent years, significant progresses have been got in study on pathogenesis, treatment and prognosis of myelodysplastic syndromes (MDS), especially on use of new technology, that has great importance for cytogenetics of MDS. Recently, the progress of cytogenetic detection in MDS is very remarkable. Based on the metaphase cytogenetics (MC) method, prognostic significance of cytogenetics in MDS was clarified gradually. For example, people have known the prognostic significance of 12 p-, 11 q-, +21, t(11(q23)), although these genetic abnormalities are rare in the MDS. In addition, chromosome mutation emerged in the process of MDS may indicate the poor prognosis. On the other hand, with the use of SNP-A and aCGH in the study of genetics, MDS cytogenetic abnormality detection rate has been further improved and can reach to 78%. At the same time, some of MDS patients with the "normal karyotype" detected by MC have new hidden aberrations through the SNP or CGH detection, and these patients have a poorer prognosis. In this review, the advances of study on cytogenetic detection for MDS based on MC and SNP-A or aCGH methods are summarized.

  12. The Cerrado (Brazil) plant cytogenetics database.

    Science.gov (United States)

    Roa, Fernando; Telles, Mariana Pires de Campos

    2017-01-01

    Cerrado is a biodiversity hotspot that has lost ca. 50% of its original vegetation cover and hosts ca. 11,000 species belonging to 1,423 genera of phanerogams. For a fraction of those species some cytogenetic characteristics like chromosome numbers and C-value were available in databases, while other valuable information such as karyotype formula and banding patterns are missing. In order to integrate and share all cytogenetic information published for Cerrado species, including frequency of cytogenetic attributes and scientometrics aspects, Cerrado plant species were searched in bibliographic sources, including the 50 richest genera (with more than 45 taxa) and 273 genera with only one species in Cerrado. Determination of frequencies and the database website (http://cyto.shinyapps.io/cerrado) were developed in R. Studies were pooled by employed technique and decade, showing a rise in non-conventional cytogenetics since 2000. However, C-value estimation, heterochromatin staining and molecular cytogenetics are still not common for any family. For the richest and best sampled families, the following modal 2n counts were observed: Oxalidaceae 2n = 12, Lythraceae 2n = 30, Sapindaceae 2n = 24, Solanaceae 2n = 24, Cyperaceae 2n = 10, Poaceae 2n = 20, Asteraceae 2n = 18 and Fabaceae 2n = 26. Chromosome number information is available for only 16.1% of species, while there are genome size data for only 1.25%, being lower than the global percentages. In general, genome sizes were small, ranging from 2C = ca. 1.5 to ca. 3.5 pg. Intra-specific 2n number variation and higher 2n counts were mainly related to polyploidy, which relates to the prevalence of even haploid numbers above the mode of 2n in most major plant clades. Several orphan genera with almost no cytogenetic studies for Cerrado were identified. This effort represents a complete diagnosis for cytogenetic attributes of plants of Cerrado.

  13. Genetic instability in nerve sheath cell tumors

    DEFF Research Database (Denmark)

    Rogatto, Silvia Regina; Casartelli, Cacilda; Rainho, Claudia Aparecida

    1995-01-01

    After in vitro culture, we analyzed cytogenetically four acoustic nerve neurinomas, one intraspinal neurinoma and one neurofibroma obtainedfrom unrelated patients. Monosomy of chromosomes 22 and 16 was an abnormality common to all cases, followed in frequency by loss of chromosomes 18 (three cases...... by the presence of polyploid cells with inconsistent abnormalities, endoreduplications and telomeric associations resulting in dicentric chromosomes. It is probable that these cytogenetic abnormalities represent some kind of evolutionary advantage for the in vitro progression of nerve sheath tumors....

  14. Solid and Cystic Tumor (SCT of the Pancreas in an Adult Man

    Directory of Open Access Journals (Sweden)

    K. Ohiwa

    1997-01-01

    Full Text Available Solid and cystic tumor (SCT of the pancreas predominantly Occurs in women, and the occurrence in men is extremely rare. We experienced a male case of SCT. A 38-year-old man was admitted with the complaint of upper abdominal pain. CT scan showed the presence of a mass in the head of the pancreas. The mass was composed of high density areas and low density areas. Ultrasonograms revealed the mass being composed of high echoic areas and low echoic areas. The mass .was hypovascular on angiography. SCT was suspected and pancreaticoduodenectomy was performed. The cut surface of the tumor showed mainly cystic degenerative areas containing dark red hemorrhagic materials. Microscopically, there were solid areas in the periphery and pseudopapillary areas in the center. No metastasis was found in the removed lymph nodes. The tumor cells were not stained by Grimelius' silver stain. The tumor cells were positive for alpha-l-antitrypsin (AAT and neuron-specific enolase (NSE. Pancreatic hormones such as insulin, glucagon, and somatostatin were all negative. Electron micrograph showed that tumor cells were rich in mitochondria. Zymogen granules and neurosecretory granules were not detected. Estrogen receptor (ER and progesterone receptor (PR were both negative.

  15. Differentiation between benign and malignant solid pseudopapillary tumor of the pancreas by MDCT

    International Nuclear Information System (INIS)

    Yin, Qihua; Wang, Mingliang; Wang, Chengsheng; Wu, Zhiyuan; Yuan, Fei; Chen, Kun; Tang, Yonghua; Zhao, Xuesong; Miao, Fei

    2012-01-01

    Purpose: The purpose of this study was to determine if characteristic features on computed tomographic and (or) magnetic resonance imaging can differentiate benign and malignant solid pseudopapillary neoplasms (SPN). Materials and methods: A total of 82 pathologically diagnosed SPN patients were included. CT and MRI were reviewed by 3 radiologists. Each tumor was analyzed through the clinical and imaging features. Results: The highest occurrence of malignant SPN was observed in the group of patients (11–19 years old) followed by the group of patients (50–65 years old). When the tumor was located in the tail and the size was equal or larger than 6.0 cm, the positive and predictive value, the predictive value, sensitivity and specificity for a malignant SPN were 61.5%, 100%, 100% and 78.6%, respectively. Presence of complete encapsulation was more frequent in benign SPNs, but focal discontinuity in the malignant SPNs. Amorphous or scattered calcifications, all near-solid tumors and presence of upstream pancreatic ductal was found in the benign SPNs. Conclusion: A focal discontinuity of the capsule, large tumor size (>6.0 cm) and a pancreatic tail location may suggest malignancy of SPN. In contrast, tumors with amorphous or scattered calcifications, and all near-solid tumors may be indicative of benignancy. Age (less than 20 or more than 50 years old) is a possible risk factor of SPN. In comparison to other pancreatic neoplasms, such as ductal adenocarcinoma, a complete/incomplete pseudo-capsule, without upstream pancreatic duct dilatation and lymph nodes metastasis, and the presence of internal calcification and hemorrhage are more likely SPN.

  16. The Cerrado (Brazil plant cytogenetics database

    Directory of Open Access Journals (Sweden)

    Fernando Roa

    2017-04-01

    Full Text Available Cerrado is a biodiversity hotspot that has lost ca. 50% of its original vegetation cover and hosts ca. 11,000 species belonging to 1,423 genera of phanerogams. For a fraction of those species some cytogenetic characteristics like chromosome numbers and C-value were available in databases, while other valuable information such as karyotype formula and banding patterns are missing. In order to integrate and share all cytogenetic information published for Cerrado species, including frequency of cytogenetic attributes and scientometrics aspects, Cerrado plant species were searched in bibliographic sources, including the 50 richest genera (with more than 45 taxa and 273 genera with only one species in Cerrado. Determination of frequencies and the database website (http://cyto.shinyapps.io/cerrado were developed in R. Studies were pooled by employed technique and decade, showing a rise in non-conventional cytogenetics since 2000. However, C-value estimation, heterochromatin staining and molecular cytogenetics are still not common for any family. For the richest and best sampled families, the following modal 2n counts were observed: Oxalidaceae 2n = 12, Lythraceae 2n = 30, Sapindaceae 2n = 24, Solanaceae 2n = 24, Cyperaceae 2n = 10, Poaceae 2n = 20, Asteraceae 2n = 18 and Fabaceae 2n = 26. Chromosome number information is available for only 16.1% of species, while there are genome size data for only 1.25%, being lower than the global percentages. In general, genome sizes were small, ranging from 2C = ca. 1.5 to ca. 3.5 pg. Intra-specific 2n number variation and higher 2n counts were mainly related to polyploidy, which relates to the prevalence of even haploid numbers above the mode of 2n in most major plant clades. Several orphan genera with almost no cytogenetic studies for Cerrado were identified. This effort represents a complete diagnosis for cytogenetic attributes of plants of Cerrado.

  17. Cytogenetic and molecular-genetic aberrations in malignant primary bone tumors

    International Nuclear Information System (INIS)

    Zoubek, A.; Kovar, H.; Gadner, H.

    1998-01-01

    Osteosarcoma, chondrosarcoma and tumors of the Ewing group are the most frequently observed primary malignant bone tumors. In an Internet homepage recently constructed for the Orthopedic Hospital Rizzoli Bologna, Italy, these tumors have represented the majority of 4423 malignant bone tumors in the archives of this institution since 1920 (http://www.tizeta.it/rizzoli). Malignant fibrous histiocytoma, fibrosarcoma, hemangioendothelioma, malignant hemangiopericytoma and giant-cell tumors are diagnosed less frequently. Since the introduction of modern molecular and cytogenic techniques, knowledge of genetic aberrations in malginant bone tumors has steadily increased. However, so far only for the group of Ewing tumors has a recurrent chromosomal marker, the translocation t(11; 22)(q24; q12), been identified. (orig.) [de

  18. Molecular mechanisms for synergistic effect of proteasome inhibitors with platinum-based therapy in solid tumors.

    Science.gov (United States)

    Chao, Angel; Wang, Tzu-Hao

    2016-02-01

    The successful development of the proteasome inhibitor bortezomib as an anticancer drug has improved survival in patients with multiple myeloma. With the emergence of the newly US Food and Drug Administration-approved proteasome inhibitor carfilzomib, ongoing trials are investigating this compound and other proteasome inhibitors either alone or in combination with other chemotherapy drugs. However, in solid tumors, the efficacy of proteasome inhibitors has not lived up to expectations. Results regarding the potential clinical efficacy of bortezomib combined with other agents in the treatment of solid tumors are eagerly awaited. Recent identification of the molecular mechanisms (involving apoptosis and autophagy) by which bortezomib and cisplatin can overcome chemotherapy resistance and sensitize tumor cells to anticancer therapy can provide insights into the development of novel therapeutic strategies for patients with solid malignancies. Copyright © 2016. Published by Elsevier B.V.

  19. RHOEO SPATHACEA: A CYTOGENETICAL REVIEW

    OpenAIRE

    Datta Animesh K.; Mandal Aninda; Bhattacharya Arnab; Saha Aditi; Paul Rita

    2012-01-01

    A cytogenetical review is conducted on Rhoeo spathacea (Swartz) Stearn (monotypic genus of the family Commelinaceae) including conventional heterozygote (var. bicolor) form (2n=12) and a rare bivalent forming clone of var. concolor (2n=12) with an objective to provide cytological configurations explaining some of the important cytogenetical aspects, which is rather difficult in sexually propagated plant species due to sterility barriers. Cytological configurations documented may generate inte...

  20. Prospective Clinical Study of Precision Oncology in Solid Tumors.

    Science.gov (United States)

    Sohal, Davendra P S; Rini, Brian I; Khorana, Alok A; Dreicer, Robert; Abraham, Jame; Procop, Gary W; Saunthararajah, Yogen; Pennell, Nathan A; Stevenson, James P; Pelley, Robert; Estfan, Bassam; Shepard, Dale; Funchain, Pauline; Elson, Paul; Adelstein, David J; Bolwell, Brian J

    2015-11-09

    Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact. Colorectal (25%), breast (18%), lung (13%), and pancreatobiliary (13%) cancers were the most common diagnoses. Median time from consent to result was 25 days (range = 3-140). Of 223 evaluable samples, 49% (n = 109) of patients were recommended a specific therapy, but only 11% (n = 24) received such therapy: 12 on clinical trials, nine off-label, three on-label. Lack of clinical trial access (n = 49) and clinical deterioration (n = 29) were the most common reasons for nonrecommendation/nonreceipt of genomics-driven therapy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Effect of Arrabidaea chica extracts on the Ehrlich solid tumor development

    Directory of Open Access Journals (Sweden)

    Ana Flávia C. Ribeiro

    2012-04-01

    Full Text Available The aim of this study was to investigate the effect of Arrabidaea chica (Humb. & Bonpl. B. Verl., Bignoniaceae, extracts on Ehrlich solid tumor development in Swiss mice. Leaves of A. chica were extracted with two distinct solvents, ethanol and water. The phytochemical analysis of the extracts indicated different classes of secondary metabolites like as anthocyanidins, flavonoids, tannins and saponins. Ethanol (EE and aqueous (AE extracts at 30 mg/kg reduced the development of Ehrlich solid tumor after ten days of oral treatment. The EE group presented increase in neutrophil count, α1 and β globulin values, and decrease of α2 globulin values. Furthermore, EE reduced the percentage of CD4+ T cells in blood but did not alter the percentage of inflammatory mononuclear cells associated with tumor suggesting a direct action of EE on tumor cells. Reduced tumor development observed in AE group was accompanied by a lower percentage of CD4+ T lymphocytes in blood. At the tumor microenvironment, this treatment decreased the percentage of CD3+ T cells, especially due to a reduction of CD8+ T subpopulation and NK cells. The antitumor activity presented by the AE is possibly related to an anti-inflammatory activity. None of the extracts produced toxic effects in animals. In conclusion, the ethanol and aqueous extracts of A. chica have immunomodulatory and antitumor activities attributed to the presence of flavonoids, such as kaempferol. These effects appear to be related to different mechanisms of action for each extract. This study demonstrates the potential of A. chica as an antitumor agent confirming its use in traditional popular medicine.

  2. The prognostic role of controlling nutritional status scores in patients with solid tumors.

    Science.gov (United States)

    Liang, Ruo-Fei; Li, Jun-Hong; Li, Mao; Yang, Yuan; Liu, Yan-Hui

    2017-11-01

    We conducted a meta-analysis to investigate the association between preoperative controlling nutritional status (CONUT) scores in various solid tumors and clinical outcomes. Relevant studies published up to August 12, 2017 were identified using electronic databases, including PubMed, Embase, and Web of Science. The pooled hazard ratios (HR) and their corresponding 95% confidence intervals (CI) for overall survival (OS) and event-free survival (EFS) were calculated to explore the relationship between preoperative CONUT score and prognosis. In total, 674 patients with solid tumors from four published studies were included in this meta-analysis. The pooled HR for OS was 1.98 (95% CI, 1.34-2.91, p=0.001), indicating that patients with high CONUT scores had worse OS. The pooled HR for EFS was 1.98 (95% CI, 1.34-2.93, p=0.001), revealing that high CONUT scores were significantly associated with short EFS. Our data suggest that high preoperative CONUT scores indicate poor prognosis for patients with solid tumors. Further studies are needed to verify the significance of CONUT scores in clinical practice. Copyright © 2017. Published by Elsevier B.V.

  3. Cytogenetic Resources and Information.

    Science.gov (United States)

    De Braekeleer, Etienne; Huret, Jean-Loup; Mossafa, Hossain; Dessen, Philippe

    2017-01-01

    The main databases devoted stricto sensu to cancer cytogenetics are the "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer" ( http://cgap.nci.nih.gov/Chromosomes/Mitelman ), the "Atlas of Genetics and Cytogenetics in Oncology and Haematology" ( http://atlasgeneticsoncology.org ), and COSMIC ( http://cancer.sanger.ac.uk/cosmic ).However, being a complex multistep process, cancer cytogenetics are broadened to "cytogenomics," with complementary resources on: general databases (nucleic acid and protein sequences databases; cartography browsers: GenBank, RefSeq, UCSC, Ensembl, UniProtKB, and Entrez Gene), cancer genomic portals associated with recent international integrated programs, such as TCGA or ICGC, other fusion genes databases, array CGH databases, copy number variation databases, and mutation databases. Other resources such as the International System for Human Cytogenomic Nomenclature (ISCN), the International Classification of Diseases for Oncology (ICD-O), and the Human Gene Nomenclature Database (HGNC) allow a common language.Data within the scientific/medical community should be freely available. However, most of the institutional stakeholders are now gradually disengaging, and well-known databases are forced to beg or to disappear (which may happen!).

  4. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review.

    LENUS (Irish Health Repository)

    Shrotriya, Shiva

    2015-01-01

    A systematic literature review was done to determine the relationship between elevated CRP and prognosis in people with solid tumors. C-reactive protein (CRP) is a serum acute phase reactant and a well-established inflammatory marker. We also examined the role of CRP to predict treatment response and tumor recurrence.

  5. Eosinophilia in routine blood samples as a biomarker for solid tumor development

    DEFF Research Database (Denmark)

    Andersen, Christen Bertel L; Siersma, V.D.; Hasselbalch, H.C.

    2014-01-01

    eosinophilia in routine blood samples as a potential biomarker of solid tumor development in a prospective design. MATERIAL AND METHODS: From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356 196 individuals with at least one differential cell count (DIFF) encompassing...... was increased with mild eosinophilia [OR 1.93 (CI 1.29-2.89), p = 0.0013]. No associations with eosinophilia were observed for the remaining solid cancers. CONCLUSION: We demonstrate that eosinophilia in routine blood samples associates with an increased risk of bladder cancer. Our data emphasize...... that additional preclinical studies are needed in order to shed further light on the role of eosinophils in carcinogenesis, where it is still unknown whether the cells contribute to tumor immune surveillance or neoplastic evolution....

  6. Solid pseudopapillary tumor of pancreas with sickle cell trait: A rare case report

    Directory of Open Access Journals (Sweden)

    Harish S Permi

    2013-01-01

    Full Text Available Solid pseudopapillary tumor of pancreas is a rare pancreatic neoplasm affecting young women, has low malignant potential and amenable for surgical excision with good long-term survival. Sickle cell trait is benign condition, which involves one normal beta-globin chain and one HbS chain. Although it is a benign condition, individuals are prone to have rare complications that may predispose to death under certain circumstances. We report a rare coexistence of solid pseudopapillary tumor of pancreas with sickle cell trait in an 18-year-old female who underwent distal pancreatectomy with splenectomy. Histopathological examination and haemoglobin electrophoresis confirmed the diagnosis.

  7. Bone marrow transplantation in aplastic anemia, acute leukemia and solid tumors

    International Nuclear Information System (INIS)

    Champlin, R.; Feig, S.; Gale, R.P.

    1980-01-01

    Results of bone marrow transplantation for the treatment of aplastic anemia, acute leukemia and solid tumors in the first 141 patients treated between September 1973 and January 1980 are reviewed. Preparation for transplantation with total body irradiation is described. (Auth.)

  8. Hypoxic cell turnover in different solid tumor lines

    International Nuclear Information System (INIS)

    Ljungkvist, Anna S.E.; Bussink, Johan; Kaanders, Johannes H.A.M.; Rijken, Paulus F.J.W.; Begg, Adrian C.; Raleigh, James A.; Kogel, Albert J. van der

    2005-01-01

    Purpose: Most solid tumors contain hypoxic cells, and the amount of tumor hypoxia has been shown to have a negative impact on the outcome of radiotherapy. The efficacy of combined modality treatments depends both on the sequence and timing of the treatments. Hypoxic cell turnover in tumors may be important for optimal scheduling of combined modality treatments, especially when hypoxic cell targeting is involved. Methods and Materials: Previously we have shown that a double bioreductive hypoxic marker assay could be used to detect changes of tumor hypoxia in relation to the tumor vasculature after carbogen and hydralazine treatments. This assay was used in the current study to establish the turnover rate of hypoxic cells in three different tumor models. The first hypoxic marker, pimonidazole, was administered at variable times before tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. Hypoxic cell turnover was defined as loss of pimonidazole (first marker) relative to CCI-103F (second marker). Results: The half-life of hypoxic cell turnover was 17 h in the murine C38 colon carcinoma line, 23 h and 49 h in the human xenograft lines MEC82 and SCCNij3, respectively. Within 24 h, loss of pimonidazole-stained areas in C38 and MEC82 occurred concurrent with the appearance of pimonidazole positive cell debris in necrotic regions. In C38 and MEC82, most of the hypoxic cells had disappeared after 48 h, whereas in SCCNij3, viable cells that had been labeled with pimonidazole were still observed after 5 days. Conclusions: The present study demonstrates that the double hypoxia marker assay can be used to study changes in both the proportion of hypoxic tumor cells and their lifespan at the same time. The present study shows that large differences in hypoxic cell turnover rates may exist among tumor lines, with half-lives ranging from 17-49 h

  9. Onconase-induced changes in radiation response and physiological parameters in solid tumors

    International Nuclear Information System (INIS)

    Lee, I.; Shui, C.; Shogen, K.; Mikulski, S.M.; Nunno, M.; Wallner, P.E.

    1996-01-01

    Purpose: Onconase (ONC), previously known as P-30 protein, is a novel basic amphibian protein isolated from eggs of the leopard frog. The original study conducted by Darzynkiewicz et al. (Cell Tissue Kinetics, 1988) demonstrated that ONC shows anti-proliferative and cytotoxic activities against several tumor cell lines in vitro. Since then, to our knowledge, no studies regarding the inhibitory effect of ONC in solid tumor models were performed. ONC is also known to inhibit cell-cycle progression from the radiation-sensitive G 1 phase to the radiation-resistant S phase. Thus, we examined the effect of ONC as a potential radiation sensitizer. The radiation response and physiological parameters were evaluated in C3H mice and/or nude mice bearing various (murine and/or human) tumor models. Materials and Method: First, we examined the effect of ONC on the cellular proliferative, as well as the clonogenic, response of various cell lines (i.e., H4IIE rat hepatoma, AsPC-1 human pancreas adenocarcinoma, DU145 human prostate carcinoma, LS174T human colon adenocarcinoma, A549 human lung carcinoma, MCaIV murine adenocarcinoma, FSaII murine fibrosarcoma, and CCL-209 bovine artery pulmonary endothelial cells) by using the MTT and clonogenic cell survival assays. Second, we determined the enhancement of radiation response before, during, and after treatment with ONC in several cell lines. Third, we determined whether ONC can inhibit the growth of solid tumors in vivo (i.e., FSaII and MCaIV in C3H mice, LS174T in nude mice). Fourth, we examined whether minocycline, an antiangiogenic agent, could amplify the tumoricidal efficacy of ONC in solid tumors. To test our hypothesis: if ONC could eradicate the outgrowth of tumor cells in confined spaces, it could lower the elevated pressure in solid tumors, we measured tumor interstitial fluid pressure (TIFP) using the wick-in-needle method, and systemic pressure using the right carotid artery cannulation method after treatment with ONC

  10. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    International Nuclear Information System (INIS)

    Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

    2014-01-01

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

  11. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

  12. Unmet needs in automated cytogenetics

    International Nuclear Information System (INIS)

    Bender, M.A.

    1976-01-01

    Though some, at least, of the goals of automation systems for analysis of clinical cytogenetic material seem either at hand, like automatic metaphase finding, or at least likely to be met in the near future, like operator-assisted semi-automatic analysis of banded metaphase spreads, important areas of cytogenetic analsis, most importantly the determination of chromosomal aberration frequencies in populations of cells or in samples of cells from people exposed to environmental mutagens, await practical methods of automation. Important as are the clinical diagnostic applications, it is apparent that increasing concern over the clastogenic effects of the multitude of potentially clastogenic chemical and physical agents to which human populations are being increasingly exposed, and the resulting emergence of extensive cytogenetic testing protocols, makes the development of automation not only economically feasible but almost mandatory. The nature of the problems involved, and acutal of possible approaches to their solution, are discussed

  13. Antibody or Antibody Fragments: Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

    Directory of Open Access Journals (Sweden)

    Katerina T. Xenaki

    2017-10-01

    Full Text Available The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody–drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are clearly still necessary. A major factor limiting the efficacy of antibody-targeted cancer therapies may be the incomplete penetration of the antibody or antibody–drug conjugate into the tumor. Incomplete tumor penetration also affects the outcome of molecular imaging, when using such targeting agents. From the injection site until they arrive inside the tumor, targeting molecules are faced with several barriers that impact intratumoral distribution. The primary means of antibody transport inside tumors is based on diffusion. The diffusive penetration inside the tumor is influenced by both antibody properties, such as size and binding affinity, as well as tumor properties, such as microenvironment, vascularization, and targeted antigen availability. Engineering smaller antibody fragments has shown to improve the rate of tumor uptake and intratumoral distribution. However, it is often accompanied by more rapid clearance from the body and in several cases also by inherent destabilization and reduction of the binding affinity of the antibody. In this perspective, we discuss different cancer targeting approaches based on antibodies or their fragments. We carefully consider how their size and binding properties influence their intratumoral uptake and distribution, and how this may affect cancer imaging and therapy of solid tumors.

  14. Impact of baseline cytogenetic findings and cytogenetic response on outcome of high-risk myelodysplastic syndromes and low blast count AML treated with azacitidine.

    Science.gov (United States)

    Sébert, Marie; Komrokji, Rami S; Sekeres, Mikkael A; Prebet, Thomas; Cluzeau, Thomas; Santini, Valeria; Gyan, Emmanuel; Sanna, Alessandro; Ali, Najla HAl; Hobson, Sean; Eclache, Virginie; List, Alan; Fenaux, Pierre; Adès, Lionel

    2017-12-01

    Karyotype according to the revised IPSS is a strong independent prognostic factor for overall survival (OS) in myelodysplastic syndromes (MDS), however established in untreated patients. The prognostic impact of cytogenetics and cytogenetic response (CyR) in MDS patients receiving azacitidine (AZA) remains uncertain. We examined the prognostic value of baseline cytogenetics and CyR for overall response rate (ORR) and OS in 702 AZA-treated higher risk MDS and low blast count acute myeloid leukemia (AML), including 493 (70%) with abnormal karyotype. None of the cytogenetic abnormalities had significant impact on ORR (43.9%) or complete response (15.35%), except 3q abnormalities and complex karyotypes, which were associated with a lower ORR. OS differed significantly across all R-IPSS cytogenetic subgroups (pcytogenetics. CyR was achieved in 32% of the 281 evaluable patients with abnormal cytogenetics, was complete (CCyR) in 71 (25.3%) patients. We found no correlation between hematological response and cytogenetic response and 21% of the patients with CCyR did not achieve morphological response. In the 281 patients, we found no impact of CyR on survival, but when restricting to MDS (ie: <20% marrow blasts) achievement of CCyR was associated with better OS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Chimeric antigen receptor T cells: a novel therapy for solid tumors

    Directory of Open Access Journals (Sweden)

    Shengnan Yu

    2017-03-01

    Full Text Available Abstract The chimeric antigen receptor T (CAR-T cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. The third generation of CAR-T demonstrates increased antitumor cytotoxicity and persistence through modification of CAR structure. In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2, and mesothelin (MSLN, as well as the challenges for CAR-T cell therapy.

  16. Cytogenetic Alterations in Multiple Myeloma: Prognostic Significance and the Choice of Frontline Therapy.

    Science.gov (United States)

    Stella, Flavia; Pedrazzini, Estela; Agazzoni, Mara; Ballester, Oscar; Slavutsky, Irma

    2015-01-01

    Multiple myeloma tumor cells demonstrate multiple and often complex genetic lesions as evaluated by standard cytogenetic/FISH studies. Over the past decade, specific abnormalities have been associated with standard or high-risk clinical behavior and they have become strong prognostic indicators. Further, as evidenced by recent randomized clinical trials, the choice of front-line therapy (transplant vs. no transplant, inclusion of novel drugs such as bortezomib, thalidomide, and lenalidomide) may be able to overcome the adverse effect of high-risk genetic lesions.

  17. Strategies for improving chemotherapeutic delivery to solid tumors mediated by vascular permeability modulation

    Science.gov (United States)

    Roy Chaudhuri, Tista

    An essential mode of distribution of blood-borne chemotherapeutic agents within a solid tumor is via the micro-circulation. Poor tumor perfusion, because of a lack of functional vasculature or a lack of microvessels, as well as low tumor vascular permeability, can prevent adequate deposition of even low molecular-weight agents into the tumor. The modulation of tumor vascular function and density can provides numerous strategies for improving intratumor deposition of chemotherapeutic agents. Here we investigated strategies to improve drug delivery to two tumor types that share in common poor drug delivery, but differ in the underlying cause. First, in an angiogenesis-driven brain tumor model of Glioblastoma, the vascular permeability barrier, along with poorly-functional vasculature, hinders drug delivery. A strategy of nanoparticle-based tumor 'priming' to attack the vascular permeability barrier, employing sterically stabilized liposomal doxorubicin (SSL-DXR), was investigated. Functional and histological evaluation of tumor vasculature revealed that after an initial period of depressed vascular permeability and vascular pruning 3--4 days after SSL-DXR administration, vascular permeability and perfusion were restored and then elevated after 5--7 days. As a result of tumor priming, deposition of subsequently-administered nanoparticles was enhanced, and the efficacy of temozolomide (TMZ), if administered during the window of elevated permeability, was increased. The sequenced regimen resulted in a persistent reduction of the tumor proliferative index and a 40% suppression of tumor volume, compared to animals that received both agents simultaneously. Second, in a hypovascular, pancreatic ductal adenocarcinoma model, disruption of tumor-stromal communication via sonic hedgehog (sHH) signaling pathway inhibition mediated an indirect vascular proliferation and a more than 2-fold increase in intratumor nanoparticle deposition. Enhanced delivery of SSL-DXR in tumors pre

  18. A quantitative theory of solid tumor growth, metabolic rate and vascularization.

    Directory of Open Access Journals (Sweden)

    Alexander B Herman

    Full Text Available The relationships between cellular, structural and dynamical properties of tumors have traditionally been studied separately. Here, we construct a quantitative, predictive theory of solid tumor growth, metabolic rate, vascularization and necrosis that integrates the relationships between these properties. To accomplish this, we develop a comprehensive theory that describes the interface and integration of the tumor vascular network and resource supply with the cardiovascular system of the host. Our theory enables a quantitative understanding of how cells, tissues, and vascular networks act together across multiple scales by building on recent theoretical advances in modeling both healthy vasculature and the detailed processes of angiogenesis and tumor growth. The theory explicitly relates tumor vascularization and growth to metabolic rate, and yields extensive predictions for tumor properties, including growth rates, metabolic rates, degree of necrosis, blood flow rates and vessel sizes. Besides these quantitative predictions, we explain how growth rates depend on capillary density and metabolic rate, and why similar tumors grow slower and occur less frequently in larger animals, shedding light on Peto's paradox. Various implications for potential therapeutic strategies and further research are discussed.

  19. Solid KHT tumor dispersal for flow cytometric cell kinetic analysis

    International Nuclear Information System (INIS)

    Pallavicini, M.G.; Folstad, L.J.; Dunbar, C.

    1981-01-01

    A bacterial neutral protease was used to disperse KHT solid tumors into single cell suspensions suitable for routine cell kinetic analysis by flow cytometry and for clonogenic cell survival. Neutral protease disaggregation under conditions which would be suitable for routine tumor dispersal was compared with a trypsin/DNase procedure. Cell yield, clonogenic cell survival, DNA distributions of untreated and drug-perturbed tumors, rates of radioactive precursor incorporation during the cell cycle, and preferential cell cycle phase-specific cell loss were investigated. Tumors dispersed with neutral protease yielded approximately four times more cells than those dispersed with trypsin/DNase and approximately a 1.5-fold higher plating efficiency in a semisolid agar system. Quantitative analysis of DNA distributions obtained from untreated and cytosine-arabinoside-perturbed tumors produced similar results with both dispersal procedures. The rates of incorporation of tritiated thymidine during the cell cycle were also similar with neutral protease and trypsin/DNase dispersal. Preferential phase-specific cell loss was not obseved with either technique. We find that neutral protease provides good single cell suspensions of the KHT tumor for cell survival measurements and for cell kinetic analysis of drug-induced perturbations by flow cytometry. In addition, the high cell yields facilitate electronic cell sorting where large numbers of cells are often required

  20. Development and Application of Camelid Molecular Cytogenetic Tools

    Science.gov (United States)

    Avila, Felipe; Das, Pranab J.; Kutzler, Michelle; Owens, Elaine; Perelman, Polina; Rubes, Jiri; Hornak, Miroslav; Johnson, Warren E.

    2014-01-01

    Cytogenetic chromosome maps offer molecular tools for genome analysis and clinical cytogenetics and are of particular importance for species with difficult karyotypes, such as camelids (2n = 74). Building on the available human–camel zoo-fluorescence in situ hybridization (FISH) data, we developed the first cytogenetic map for the alpaca (Lama pacos, LPA) genome by isolating and identifying 151 alpaca bacterial artificial chromosome (BAC) clones corresponding to 44 specific genes. The genes were mapped by FISH to 31 alpaca autosomes and the sex chromosomes; 11 chromosomes had 2 markers, which were ordered by dual-color FISH. The STS gene mapped to Xpter/Ypter, demarcating the pseudoautosomal region, whereas no markers were assigned to chromosomes 14, 21, 22, 28, and 36. The chromosome-specific markers were applied in clinical cytogenetics to identify LPA20, the major histocompatibility complex (MHC)-carrying chromosome, as a part of an autosomal translocation in a sterile male llama (Lama glama, LGL; 2n = 73,XY). FISH with LPAX BACs and LPA36 paints, as well as comparative genomic hybridization, were also used to investigate the origin of the minute chromosome, an abnormally small LPA36 in infertile female alpacas. This collection of cytogenetically mapped markers represents a new tool for camelid clinical cytogenetics and has applications for the improvement of the alpaca genome map and sequence assembly. PMID:23109720

  1. Effect of Au-dextran NPs as anti-tumor agent against EAC and solid tumor in mice by biochemical evaluations and histopathological investigations.

    Science.gov (United States)

    Medhat, Dalia; Hussein, Jihan; El-Naggar, Mehrez E; Attia, Mohamed F; Anwar, Mona; Latif, Yasmine Abdel; Booles, Hoda F; Morsy, Safaa; Farrag, Abdel Razik; Khalil, Wagdy K B; El-Khayat, Zakaria

    2017-07-01

    Dextran-capped gold nanoparticles (Au-dextran NPs) were prepared exploiting the natural polysaccharide polymer as both reducing and stabilizing agent in the synthesis process, aiming at studying their antitumor effect on solid carcinoma and EAC-bearing mice. To this end, Au-dextran NPs were designed via simple eco-friendly chemical reaction and they were characterized revealing the monodispersed particles with narrow distributed size of around 49nm with high negative charge. In vivo experiments were performed on mice. Biochemical analysis of liver and kidney functions and oxidation stress ratio in addition to histopathological investigations of such tumor tissues were done demonstrating the potentiality of Au-dextran NPs as antitumor agent. The obtained results revealed that EAC and solid tumors caused significant increase in liver and kidney functions, liver oxidant parameters, alpha feto protein levels and diminished liver antioxidant accompanied by positive expression of tumor protein p53 of liver while the treatment with Au-dextran NPs for both types caused improvement in liver and kidney functions, increased liver antioxidant, increased the expression level of B-cell lymphoma 2 gene and subsequently suppressed the apoptotic pathway. As a result, the obtained data provides significant antitumor effects of the Au-dextran NPs in both Ehrlich ascites and solid tumor in mice models. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Solid tumors after chemotherapy or surgery for testicular nonseminoma: a population-based study.

    Science.gov (United States)

    Fung, Chunkit; Fossa, Sophie D; Milano, Michael T; Oldenburg, Jan; Travis, Lois B

    2013-10-20

    Increased risks of solid tumors after older radiotherapy strategies for testicular cancer (TC) are well established. Few population-based studies, however, focus on solid cancer risk among survivors of TC managed with nonradiotherapy approaches. We quantified the site-specific risk of solid cancers among testicular nonseminoma patients treated in the modern era of cisplatin-based chemotherapy, without radiotherapy. Standardized incidence ratios (SIRs) for solid tumors were calculated for 12,691 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2008) and treated initially with either chemotherapy (n = 6,013) or surgery (n = 6,678) without radiotherapy. Patients accrued 116,073 person-years of follow-up. Two hundred ten second solid cancers were observed. No increased risk followed surgery alone (SIR, 0.93; 95% CI, 0.76 to 1.14; n = 99 solid cancers), whereas significantly increased 40% excesses (SIR, 1.43; 95% CI, 1.18 to 1.73; n = 111 solid cancers) occurred after chemotherapy. Increased risks of solid cancers after chemotherapy were observed in most follow-up periods (median latency, 12.5 years), including more than 20 years after treatment (SIR, 1.54; 95% CI, 0.96 to 2.33); significantly increased three- to seven-fold risks occurred for cancers of the kidney (SIR, 3.37; 95% CI, 1.79 to 5.77), thyroid (SIR, 4.40; 95% CI, 2.19 to 7.88), and soft tissue (SIR, 7.49; 95% CI, 3.59 to 13.78). To our knowledge, this is the first large population-based series reporting significantly increased risks of solid cancers among patients with testicular nonseminoma treated in the modern era of cisplatin-based chemotherapy. Subsequent analytic studies should focus on the evaluation of dose-response relationships, types of solid cancers, latency patterns, and interactions with other possible factors, including genetic susceptibility.

  3. Factors associated with abandonment of therapy by children diagnosed with solid tumors in Peru.

    Science.gov (United States)

    Vasquez, Liliana; Diaz, Rosdali; Chavez, Sharon; Tarrillo, Fanny; Maza, Ivan; Hernandez, Eddy; Oscanoa, Monica; García, Juan; Geronimo, Jenny; Rossell, Nuria

    2018-06-01

    Abandonment of treatment is a major cause of treatment failure and poor survival in children with cancer in low- and middle-income countries. The incidence of treatment abandonment in Peru has not been reported. The aim of this study was to examine the prevalence of and factors associated with treatment abandonment by pediatric patients with solid tumors in Peru. We retrospectively reviewed the sociodemographic and clinical data of children referred between January 2012 and December 2014 to the two main tertiary centers for childhood cancer in Peru. The definition of treatment abandonment followed the International Society of Paediatric Oncology, Paediatric Oncology in Developing Countries, Abandonment of Treatment recommendation. Data from 1135 children diagnosed with malignant solid tumors were analyzed, of which 209 (18.4%) abandoned treatment. Bivariate logistic regression analysis showed significantly higher abandonment rates in children living outside the capital city, Lima (forest; odds ratio [OR] 3.25; P < 0.001), those living in a rural setting (OR 3.44; P < 0.001), and those whose parent(s) lacked formal employment (OR 4.39; P = 0.001). According to cancer diagnosis, children with retinoblastoma were more likely to abandon treatment compared to children with other solid tumors (OR 1.79; P = 0.02). In multivariate regression analyses, rural origin (OR 2.02; P = 0.001) and lack of formal parental employment (OR 2.88; P = 0.001) were independently predictive of abandonment. Treatment abandonment prevalence of solid tumors in Peru is high and closely related to sociodemographical factors. Treatment outcomes could be substantially improved by strategies that help prevent abandonment of therapy based on these results. © 2018 Wiley Periodicals, Inc.

  4. Molecular cytogenetics for acute megakaryocytic leukemia diagnosis

    Directory of Open Access Journals (Sweden)

    E. A. Matveeva

    2014-07-01

    Full Text Available Acute megakaryocytic leukemia (AML M7 – a rare disease characterized by poor treatment response, except for t(1;22 variant in infants. Cytogenetic abnormalities in AML M7 are highly heterogeneous. We collected samples from children with AML M7 to analyze the disease cytogenetic profile. During September 2009 to March 2012 20 AML M7 patients was studied using fluorescence in situ hybridization. Complex and heterogeneous chromosomal abnormalities were revealed. It was found that no recurring abnormalities and cytogenetic markers unique to each patients. Also, the 19p13 amplification described previously only in myeloid cell lines was detected.

  5. Molecular cytogenetics for acute megakaryocytic leukemia diagnosis

    Directory of Open Access Journals (Sweden)

    E. A. Matveeva

    2012-01-01

    Full Text Available Acute megakaryocytic leukemia (AML M7 – a rare disease characterized by poor treatment response, except for t(1;22 variant in infants. Cytogenetic abnormalities in AML M7 are highly heterogeneous. We collected samples from children with AML M7 to analyze the disease cytogenetic profile. During September 2009 to March 2012 20 AML M7 patients was studied using fluorescence in situ hybridization. Complex and heterogeneous chromosomal abnormalities were revealed. It was found that no recurring abnormalities and cytogenetic markers unique to each patients. Also, the 19p13 amplification described previously only in myeloid cell lines was detected.

  6. Investigation of particle accumulation, chemosensitivity and thermosensitivity for effective solid tumor therapy using thermosensitive liposomes and hyperthermia

    NARCIS (Netherlands)

    W.J.M. Lokerse (Wouter); M. Bolkestein (Michiel); T.L.M. ten Hagen (Timo); M. de Jong (Marcel); A.M.M. Eggermont (Alexander); Grüll, H. (Holger); G.A. Koning (Gerben)

    2016-01-01

    textabstractDoxorubicin (Dox) loaded thermosensitive liposomes (TSLs) have shown promising results for hyperthermia-induced local drug delivery to solid tumors. Typically, the tumor is heated to hyperthermic temperatures (41-42 °C), which induced intravascular drug release from TSLs within the tumor

  7. Cytogenetic abnormalities in acute leukaemia of ambiguous lineage: an overview.

    Science.gov (United States)

    Manola, Kalliopi N

    2013-10-01

    Acute leukaemia of ambiguous lineage (ALAL) is a rare complex entity with heterogeneous clinical, immunophenotypic, cytogenetic and molecular genetic features and adverse outcome. According to World Health Organization 2008 classification, ALAL encompasses those leukaemias that show no clear evidence of differentiation along a single lineage. The rarity of ALAL and the lack of uniform diagnostic criteria have made it difficult to establish its cytogenetic features, although cytogenetic analysis reveals clonal chromosomal abnormalities in 59-91% of patients. This article focuses on the significance of cytogenetic analysis in ALAL supporting the importance of cytogenetic analysis in the pathogenesis, diagnosis, prognosis, follow up and treatment selection of ALAL. It reviews in detail the types of chromosomal aberrations, their molecular background, their correlation with immunophenotype and age distribution and their prognostic relevance. It also summarizes some novel chromosome aberrations that have been observed only once. Furthermore, it highlights the ongoing and future research on ALAL in the field of cytogenetics. © 2013 John Wiley & Sons Ltd.

  8. Anti-m antibody in solid tumors-two case reports.

    Science.gov (United States)

    Soni, Shiv Kumar; Goyal, Hari; Sood, S K; Setia, Rasika

    2014-09-01

    Anti-M antibodies are usually of IgM, appear as cold agglutinins and are clinically insignificant. We are reporting two cases of anti-M in cases of solid tumors where the anti-M caused discrepancy in blood grouping, reacted in coombs phase of crossmatching. Anti-M in first case showed dosage effect. These antibodies can be clinical significant when detected in coombs phase, making M antigen negative coombs compatible unit transfusion imperative.

  9. Characterization of a switchable chimeric antigen receptor platform in a pre-clinical solid tumor model.

    Science.gov (United States)

    Pishali Bejestani, Elham; Cartellieri, Marc; Bergmann, Ralf; Ehninger, Armin; Loff, Simon; Kramer, Michael; Spehr, Johannes; Dietrich, Antje; Feldmann, Anja; Albert, Susann; Wermke, Martin; Baumann, Michael; Krause, Mechthild; Bornhäuser, Martin; Ehninger, Gerhard; Bachmann, Michael; von Bonin, Malte

    2017-01-01

    The universal modular chimeric antigen receptor (UniCAR) platform redirects CAR-T cells using a separated, soluble targeting module with a short half-life. This segregation allows precise controllability and flexibility. Herein we show that the UniCAR platform can be used to efficiently target solid cancers in vitro and in vivo using a pre-clinical prostate cancer model which overexpresses prostate stem cell antigen (PSCA). Short-term administration of the targeting module to tumor bearing immunocompromised mice engrafted with human UniCAR-T cells significantly delayed tumor growth and prolonged survival of recipient mice both in a low and high tumor burden model. In addition, we analyzed phenotypic and functional changes of cancer cells and UniCAR-T cells in association with the administration of the targeting module to reveal potential immunoevasive mechanisms. Most notably, UniCAR-T cell activation induced upregulation of immune-inhibitory molecules such as programmed death ligands. In conclusion, this work illustrates that the UniCAR platform mediates potent anti-tumor activity in a relevant in vitro and in vivo solid tumor model.

  10. Induction of oncogene addiction shift to NF-κB by camptothecin in solid tumor cells

    International Nuclear Information System (INIS)

    Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko; Nakashima, Makoto; Tsuruo, Takashi; Umezawa, Kazuo; Higashihara, Masaaki; Watanabe, Toshiki; Horie, Ryouichi

    2009-01-01

    The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-κB activity driven by IκB kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in this study present an example of the shift in signals that support the survival of solid tumor cells to NF-κB during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-κB inhibitors.

  11. Induction of oncogene addiction shift to NF-{kappa}B by camptothecin in solid tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko; Nakashima, Makoto [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan); Tsuruo, Takashi [Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Umezawa, Kazuo [Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-0061 (Japan); Higashihara, Masaaki [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan); Watanabe, Toshiki [Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Horie, Ryouichi, E-mail: rhorie@med.kitasato-u.ac.jp [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan)

    2009-12-04

    The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-{kappa}B activity driven by I{kappa}B kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-{kappa}B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in this study present an example of the shift in signals that support the survival of solid tumor cells to NF-{kappa}B during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-{kappa}B inhibitors.

  12. In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

    International Nuclear Information System (INIS)

    Mylonaki, Effie; Manika, Katerina; Zarogoulidis, Paul; Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas; Mourelatos, Dionysios

    2012-01-01

    Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer

  13. Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice

    Directory of Open Access Journals (Sweden)

    C.M. Souza

    2014-10-01

    Full Text Available Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106 cells in 0.05mL. After tumor inoculation, the animals were separated into two groups (n = 10. The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker and for CD31 (blood vessel marker. Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy.

  14. Cytogenetics of jaw cysts - a pilot study.

    Science.gov (United States)

    Manor, Esther; Brennan, Peter A; Bodner, Lipa

    2012-07-01

    The pathogenesis of cysts that arise in the jaws is still not certain, and the underlying mechanisms of epithelial proliferation are not fully understood. Cysts of the jaw may involve a reactive, inflammatory, or neoplastic process. Cytogenetics, the study of the number and structure of chromosomes, has provided valuable information about the diagnosis, prognosis, and targeted treatment in many cancers, including oral squamous cell carcinoma. Cytogenetics can also provide information about the possible aetiology or neoplastic potential of a lesion, though to our knowledge no studies of this technique have been used for cysts in the jaws. In this pilot study we used cytogenetics in a series of 10 cysts (3 radicular, 4 dentigerous, 2 of the nasopalatine duct, and 1 dermoid). In all cases we found normal karyotypes. Further work and larger numbers are needed for a definitive study, but we can hypothesise from this pilot study that these cysts do not have cytogenetic aberrations and so have no neoplastic potential. Copyright © 2011 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  15. Evaluating the Needs of Patients Living With Solid Tumor Cancer: A Survey Design.

    Science.gov (United States)

    Schmidt, April L; Lorenz, Rebecca A; Buchanan, Paula M; McLaughlin, Laura

    2018-03-01

    To describe the unmet needs of adult patients living with solid tumor cancer. Survey design. Adult patients living with solid tumor cancer from two outpatient clinics were mailed the Sheffield Profile for Assessment and Referral to Care, a holistic screening questionnaire for assessing palliative care needs, and a demographics questionnaire. One hundred fifteen patients returned the instruments, corresponding to a 62% response rate. There were no significant differences by cancer type (breast, non-breast) or gender. However, Caucasians reported significantly more psychological issues, such as anxiety, than non-Caucasians ([ n = 101 (87.8%)] and [ n = 14 (12.2%)], respectively, p = .032). Older patients reported more concerns about loss of independence/activity ( p = .012) compared with younger age groups. Patients living with Stage III/IV cancer reported more distressed about independence/activity ( p = .034), family/social issues ( p = .007), and treatment side effects ( p = .027) than patients living with Stage I/II cancer. Patients living with solid tumor cancer have a myriad of unmet needs regardless of age, gender, cancer type, or cancer stage. There appears to be important differences by cancer stage. The Sheffield Profile for Assessment and Referral to Care questionnaire provides a holistic approach for nurses to identify unmet needs and concerns. Future research should explore the preferred methods of receiving support and information.

  16. Phase I study of single-agent ribociclib in Japanese patients with advanced solid tumors.

    Science.gov (United States)

    Doi, Toshihiko; Hewes, Becker; Kakizume, Tomoyuki; Tajima, Takeshi; Ishikawa, Norifumi; Yamada, Yasuhide

    2018-01-01

    The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in cancers. Ribociclib, an orally available, selective CDK4/6 inhibitor, showed preliminary clinical activity in a phase I study in the USA and Europe for patients with solid tumors and lymphomas. The present study aimed to determine the single-agent maximum tolerated dose (MTD) and recommended dose for expansion (RDE) in Japanese patients with advanced solid tumors. Ribociclib safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity were also assessed. Japanese patients with solid tumors that had progressed on prior therapies received escalating doses of single-agent ribociclib on a 3-weeks-on/1-week-off schedule. Treatment continued until the development of toxicity or disease progression. A dose escalation was planned for patients with esophageal cancer. In the dose-escalation phase, 4 patients received 400 mg ribociclib and 13 patients received 600 mg ribociclib. Four patients experienced dose-limiting toxicities, 3 of whom were in the 600 mg group. The RDE was declared to be 600 mg, and the MTD was not determined. The most frequent adverse events were hematologic and gastrointestinal. Four patients achieved stable disease at the 600 mg dose; no patients achieved complete or partial response. All patients discontinued the study, the majority due to disease progression. No patients discontinued due to adverse events. Dose escalation was not pursued due to lack of observed efficacy in esophageal cancer. At the RDE of 600 mg/d on a 3-weeks-on/1-week-off schedule, ribociclib showed acceptable safety and tolerability profiles in Japanese patients with advanced solid tumors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  17. Cytogenetic prognostication within medulloblastoma subgroups.

    Science.gov (United States)

    Shih, David J H; Northcott, Paul A; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M; Garzia, Livia; Peacock, John; Mack, Stephen C; Wu, Xiaochong; Rolider, Adi; Morrissy, A Sorana; Cavalli, Florence M G; Jones, David T W; Zitterbart, Karel; Faria, Claudia C; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G; Liau, Linda M; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K; Thompson, Reid C; Bailey, Simon; Lindsey, Janet C; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M C; Scherer, Stephen W; Phillips, Joanna J; Gupta, Nalin; Fan, Xing; Muraszko, Karin M; Vibhakar, Rajeev; Eberhart, Charles G; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F; Weiss, William A; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R; Rubin, Joshua B; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M; Gajjar, Amar; Packer, Roger J; Rutkowski, Stefan; Pomeroy, Scott L; French, Pim J; Kloosterhof, Nanne K; Kros, Johan M; Van Meir, Erwin G; Clifford, Steven C; Bourdeaut, Franck; Delattre, Olivier; Doz, François F; Hawkins, Cynthia E; Malkin, David; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T; Pfister, Stefan M; Taylor, Michael D

    2014-03-20

    Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.

  18. Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors.

    Science.gov (United States)

    Milowsky, Matthew I; Nanus, David M; Kostakoglu, Lale; Sheehan, Christine E; Vallabhajosula, Shankar; Goldsmith, Stanley J; Ross, Jeffrey S; Bander, Neil H

    2007-02-10

    Based on prostate-specific membrane antigen (PSMA) expression on the vasculature of solid tumors, we performed a phase I trial of antibody J591, targeting the extracellular domain of PSMA, in patients with advanced solid tumor malignancies. This was a proof-of-principle evaluation of PSMA as a potential neovascular target. The primary end points were targeting,toxicity, maximum-tolerated dose, pharmacokinetics (PK), and human antihuman antibody (HAHA) response. Patients had advanced solid tumors previously shown to express PSMA on the neovasculature. They received 111Indium (111ln)-J591 for scintigraphy and PK, followed 2 weeks later by J591 with a reduced amount of 111In for additional PK measurements. J591 dose levels were 5, 10, 20, 40, and 80 mg. The protocol was amended for six weekly administrations of unchelated J591. Patients with a response or stable disease were eligible for re-treatment. Immunohistochemistry assessed PSMA expression in tumor tissues. Twenty-seven patients received monoclonal antibody (mAb) J591. Treatment was well tolerated. Twenty (74%) of 27 patients had at least one area of known metastatic disease targeted by 111In-J591, with positive imaging seen in patients with kidney, bladder, lung, breast, colorectal, and pancreatic cancers, and melanoma. Seven of 10 patient specimens available for immunohistochemical assessment of PSMA expression in tumor-associated vasculature demonstrated PSMA staining. No HAHA response was seen. Three patients of 27 with stable disease received re-treatment. Acceptable toxicity and excellent targeting of known sites of metastases were demonstrated in patients with multiple solid tumor types, highlighting a potential role for the anti-PSMA antibody J591 as a vascular-targeting agent.

  19. Role of DNA repair in repair of cytogenetic damages. Slowly repaired DNA injuries involved in cytogenetic damages repair

    International Nuclear Information System (INIS)

    Zaichkina, S.I.; Rozanova, O.M.; Aptikaev, G.F.; Ganassi, E.Eh.

    1989-01-01

    Caffeine was used to study the kinetics of cytogenetic damages repair in Chinese hamster fibroblasts. Its half-time (90 min) was shown to correlate with that of repair of slowly repaired DNA damages. The caffeine-induced increase in the number of irreparable DNA damages, attributed to inhibition of double-strand break repair, is in a quantitative correlation with the effect of the cytogenetic damage modification

  20. Biochemical parameters of bone metabolism in bone metastases of solid tumors (Review)

    NARCIS (Netherlands)

    Meijer, Wilhelmus; van der Veer, E; Willemse, P H

    1998-01-01

    The role of biochemical markers of bone metabolism in the diagnosis and monitoring of bone metastases in solid tumors is reviewed. Emphasis is on the recently developed markers, which may provide a more accurate quantitation of bone metabolism. In metastatic bone disease, bone formation and

  1. Cytogenetic techniques as biological indicator and dosimeter of radiation damage

    International Nuclear Information System (INIS)

    Hadjidekova, V.; Hristova, R.

    2006-01-01

    Full text: The cytogenetic methods are established techniques for bio monitoring and bio dosimetry of professionally and accidentally exposed to ionizing radiation subjects. They are applied to continue the evaluation of the physical dosimetry and to consider the individual radiosensitivity. The results of cytogenetic monitoring and dosimetry of radiation exposed subjects carried out during the last 5 years in laboratory of Radiation Genetics, NCRRP is reported. Laboratory of Radiation genetics performs cytogenetic monitoring of low dose radiation professionally or medically exposed subjects: workers in Kozloduy NPP, radioactive waste repository workers, X-rays diagnostically exposed patients, and radiotherapy exposed as well. Three cytogenetic indicators are applied as the most sensitive indicators for human radiation exposure: analysis of micronuclei (MN), chromosomal aberrations (CA) and stable translocations (FISH). The optimized methodology for application of different cytogenetic techniques for radiation estimation is discussed

  2. Serum cross-linked n-telopeptides of type 1 collagen (NTx in patients with solid tumors

    Directory of Open Access Journals (Sweden)

    Fernando Jablonka

    Full Text Available CONTEXT AND OBJECTIVE: Cross-linked N-telopeptides of type I collagen (NTx increase in concentration in situations in which bone resorption is increased, such as osteoporosis and bone metastasis (BM. We aimed to evaluate the serum concentrations of NTx in a sample of patients with several types of solid tumors. DESIGN AND SETTING: Cross-sectional analytical study with a control group in a tertiary public hospital. METHODS: We performed the quantitative enzyme-linked immunosorbent assay (ELISA on serum NTx levels in 19 subjects without a history of cancer and 62 patients with various solid tumors who had been referred for a bone scan. Three experienced analysts read all bone scans. RESULTS: The serum NTx levels in patients with cancer and BM, with cancer but without BM and without cancer were 46.77 ± 2.58, 32.85 ± 2.05 and 22.32 ± 2.90 respectively (P < 0.0001. We did not find any significant correlations of serum NTx with age, gender, history of bone pain, tumor type and bone alkaline phosphatase levels. We found a significant correlation between serum NTx and alkaline phosphatase levels (R² = 0.08; P = 0.022. CONCLUSIONS: Serum NTx levels are significantly higher in patients with solid tumors and bone metastases than they are in patients without bone metastases and in normal controls.

  3. Cytogenetic and autoradiographic investigations in gonadal dysgenesis

    International Nuclear Information System (INIS)

    Baron, J.; Warenik-Szymankiewicz, A.; Medical Academy, Poznan

    1977-01-01

    Cytogenetic analysis in 23 patients with Turner's syndrome and in 33 women with pure gonadal dysgenesis consisted of sex chromatin determination and karyotype studies employing autoradiography in questionable cases. Here autoradiography is used as an indispensable complement to cytogenetic techniques. The labelling behaviour of aberrant chromosomes is described. After treatment of the autoradiographic films for more differentiation in results is employed

  4. Physical location of SSR regions and cytogenetic instabilities in ...

    Indian Academy of Sciences (India)

    2014-08-18

    Aug 18, 2014 ... RESEARCH NOTE. Physical location of SSR regions and cytogenetic instabilities in Pinus ... first cytogenetic study in Scots pine using SSRs in FISH experiments. ... Science, Mannheim, Germany) according to manufacturer's.

  5. Cytogenetic and morphological assessment of bone marrow in therapeutic irradiation

    International Nuclear Information System (INIS)

    Sharma, U.; Das, B.P.; Singhal, R.M.; Radhakrishnaiah, Y.; Rath, G.K.; Padmaraju, I.; Bhargava, V.L.

    1978-01-01

    Morphological and cytogenetic study from the irradiated bone marrow, in 59 cases of radically irradiated carcinoma cervix was done. Regeneration of a marrow adjudged on cellular morphology was after 12 months whereas cytogenetic studies revealed it at the end of three months. It is concluded that cytogenetic study is a more sensitive parameter in assessing the recovery of bone marrow. (author)

  6. Genetic changes of two Wilms tumors with anaplasia and a review of the literature suggesting a marker profile for therapy resistance.

    Science.gov (United States)

    Stock, Cornelia; Ambros, Inge M; Lion, Thomas; Zoubek, Andreas; Amann, Gabriele; Gadner, Helmut; Ambros, Peter F

    2002-06-01

    Cytogenetic data on Wilms tumors (WT) with anaplasia frequently associated with an unfavorable outcome are scarce. We present cytogenetic changes of two WT with anaplasia (primary tumor material) from nonresponders with a synopsis of the literature. The WT were investigated by cytogenetic analysis, comparative genomic hybridization, fluorescence in situ hybridization, immunofluorescence, and flow cytometric analyses. Both tumors exhibited characteristic genetic changes. One tumor was hypodiploid due to loss of entire chromosome 11; losses of 16p, 16q, 17p, chromosome 19 material, and loss of 22q12-qter. The other tumor was hyperdiploid and triploid, and displayed gain of 1q12-q23 and chromosome 9 material. Moreover, two morphological and genetically distinct cell lines have been established from both tumors, demonstrating underrepresentation of chromosomes 13, 14, 16, and 19. Karyotype descriptions of 120 WT with known clinical data together with data of this report confirm: (1) inter- and intratumor heterogeneity exists; (2) loss or underrepresentation of chromosome material at 11, 13, 14, 16, 17p, 19, and 22q in various combinations presents a new marker profile of resistance to cytotoxic agents regardless of the histological types; and (3) the prognostic impact of gain at 1q12-q23 sequences warrants further validation.

  7. Outcome for children with metastatic solid tumors over the last four decades.

    Directory of Open Access Journals (Sweden)

    Stephanie M Perkins

    Full Text Available Outcomes for pediatric solid tumors have significantly improved over the last 30 years. However, much of this improvement is due to improved outcome for patients with localized disease. Here we evaluate overall survival (OS for pediatric patients with metastatic disease over the last 40 years.The United States Surveillance, Epidemiology, and End Results (SEER database was used to conduct this study. Patients diagnosed between 0 and 18 years of age with metastatic Ewings sarcoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma or Wilms tumor were included in the analysis.3,009 patients diagnosed between 1973-2010 met inclusion criteria for analysis. OS at 10 years for patients diagnosed between 1973-1979, 1980-1989, 1990-1999 and 2000-2010 was 28.3%, 37.2%, 44.7% and 49.3%, respectively (p<0.001. For patients diagnosed between 2000-2010, 10-year OS for patients with Ewing sarcoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma and Wilms tumor was 30.6%, 54.4%, 29.3%, 27.5%, and 76.6%, respectively, as compared to 13.8%, 25.1%, 13.6%, 17.9% and 57.1%, respectively, for patients diagnosed between 1973-1979. OS for neuroblastoma significantly increased with each decade. For patients with osteosarcoma and Ewing sarcoma, there was no improvement in OS over the last two decades. There was no improvement in outcome for patients with rhabdomyosarcoma or Wilms tumor over the last 30 years.OS for pediatric patients with metastatic solid tumors has significantly improved since the 1970s. However, outcome has changed little for some malignancies in the last 20-30 years. These data underscore the importance of continued collaboration and studies to improve outcome for these patients.

  8. Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.

    Directory of Open Access Journals (Sweden)

    Maciej H Swat

    Full Text Available Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution. Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

  9. Cytogenetic profile of aplastic anaemia in Indian children.

    Science.gov (United States)

    Gupta, Vineeta; Kumar, Akash; Saini, Isha; Saxena, Ajit Kumar

    2013-03-01

    Aplastic anaemia is a rare haematological disorder characterized by pancytopenia with a hypocellular bone marrow. It may be inherited/genetic or acquired. Acquired aplastic anaemia has been linked to many drugs, chemicals and viruses. Cytogenetic abnormalities have been reported infrequently with acquired aplastic anaemia. Majority of the studies are in adult patients from the West. We report here cytogenetic studies on paediatric patients with acquired aplastic anaemia seen in a tertiary care hospital in north India. Patients (n=71, age 4-14 yr) were diagnosed according to the guidelines of International Agranulocytosis and Aplastic Anaemia Study. Conventional cytogenetics with Giemsa Trypsin Giemsa (GTG) banding was performed. Karyotyping was done according to the International System for Human Cytogenetics Nomenclature (ISCN). Of the 71 patients, 42 had successful karyotyping where median age was 9 yr; of these 42, 27 (64.3%) patients had severe, nine (21.4%) had very severe and six (14.3%) had non severe aplastic anaemia. Five patients had karyotypic abnormalities with trisomy 12 (1), trisomy 8 (1) and monosomy 7 (1). Two patients had non numerical abnormalities with del 7 q - and t (5:12) in one each. Twenty nine patients had uninformative results. There was no difference in the clinical and haematological profile of patients with normal versus abnormal cytogenetics although the number of patients was small in the two groups. Five (11.9%) patients with acquired aplastic anaemia had chromosomal abnormalities. Trisomy was found to be the commonest abnormality. Cytogenetic abnormalities may be significant in acquired aplastic anaemia although further studies on a large sample are required to confirm the findings.

  10. Molecular cytogenetic in the familial cancers

    International Nuclear Information System (INIS)

    Cermak, M.

    2015-01-01

    The development of cancer diseases is accompanied by number of genetic changes at different levels of the genome. Some of these changes are still subject of research but others are already known in such an extent that they are associated with a specific type of malignity, the development, or treatment possibilities. The cancer genetics dispose of wide range of techniques, with reliable detection of the causal changes. Starting the molecular cytogenetics has launched a new era in diagnostics of genetic aberrations. Fluorescence in situ hybridization (FISH) definitely changed cytogenetic world from black and white to color one and set the foundation of modern investigative methods such as M-FISH, CGH, array CGH and many others. Successively all these methodologies have become a part of routine cancer diagnostics thorough the world. Actually, when much attention is given mostly to submicroscopic changes in DNA supposed as predispositions to various malignancies, the molecular cytogenetics is trying to success in competition of modern highly sensitive molecular biology methods. (author)

  11. Genetic and modifying factors that determine the risk of brain tumors

    DEFF Research Database (Denmark)

    Montelli, Terezinha de Cresci Braga; Peraçoli, Maria Terezinha Serrão; Rogatto, Silvia Regina

    2011-01-01

    of tumor escape, CNS tumor immunology, immune defects that impair anti-tumor systemic immunity in brain tumor patients and local immuno-suppressive factors within CNS are also reviewed. New hope to treatment perspectives, as dendritic-cell-based vaccines is summarized too. Concluding, it seems well...... responses can alert immune system. However, it is necessary to clarify if individuals with both constitutional defects in immune functions and genetic instability have higher risk of developing brain tumors. Cytogenetic prospective studies and gene copy number variations analysis also must be performed...

  12. Quest: A New Approach to Molecular Staging of Tumors

    Science.gov (United States)

    2004-08-01

    nerve sheath tumors. Cancer Investigation 21:901-918, 2003. "* Book Chapter. Stephens K. Neurofibromatosis. In Molecular Pathology in Clinical Practice...sheath tumors. Cancer Investigation 21:901-918, 2003. (a preprint is provided for your review). 2. Book Chapter. Stephens K. Neurofibromatosis. In...neurofibromatosis. Cancer Res 2002, 62, 1573-1577. 49. Molenaar , W.M., Dijkhuizen, T., van Echten, J., Hoekstra, H.J., van den Berg, E. Cytogenetic support

  13. Cytogenetic analysis of colorectal adenomas: karyotypic comparisons of synchronous tumors

    DEFF Research Database (Denmark)

    Bomme, L; Bardi, G; Pandis, N

    1998-01-01

    The phenotypic progression of colorectal tumors is driven by their step-by-step acquisition of genomic alterations. These pathogenetically important mutations are at the same time markers of tumor clonality. The aim of this study was to describe the clonal relation among synchronous colorectal ad...

  14. Role of DNA repair in repair of cytogenetic damages. Contribution of repair of single-strand DNA breaks to cytogenetic damages repair

    International Nuclear Information System (INIS)

    Rozanova, O.M.; Zaichkina, S.I.; Aptikaev, G.F.; Ganassi, E.Eh.

    1989-01-01

    The comparison was made between the results of the effect of poly(ADP-ribosylation) ingibitors (e.g. nicotinamide and 3-aminobenzamide) and a chromatin proteinase ingibitor, phenylmethylsulfonylfluoride, on the cytogenetic damages repair, by a micronuclear test, and DNA repair in Chinese hamster fibroblasts. The values of the repair half-periods (5-7 min for the cytogenetic damages and 5 min for the rapidly repaired DNA damages) and a similar modyfying effect with regard to radiation cytogenetic damages and kynetics of DNA damages repair were found to be close. This confirms the contribution of repair of DNA single-strand breaks in the initiation of structural damages to chromosomes

  15. Anxiety, depression in patients receiving chemotherapy for solid tumors

    International Nuclear Information System (INIS)

    Mansoor, S.; Jehangir, S.

    2015-01-01

    To determine the frequency of anxiety and depression in patients undergoing chemotherapy for solid tumors using Hospital Anxiety Depression Scale (HADS). Study Design: Cross sectional descriptive study. Place and Duration of Study: Out-patient department of Armed Forces Institute of Mental Health, Rawalpindi from June 2011 to December 2011. Methodology: Consecutive non probability sampling technique was used to select patients of age (25-70 years), male or female, who had received atleast 03 cycles of chemotherapy for solid tumors. Those with history of prior psychiatric illness, current use of psychotropic medication or psychoactive substance use, and any major bereavement in past one year were excluded from the study. After taking informed consent, relevant socio- demographic data was collected and HADS was administered. HADS-A cut off score of 7 was taken as significant anxiety while a HADS-D cut off score of 7 was taken as significant depression. Results: The total number of participants was 209. The mean age of patients was 42.9 years, with 55.5% males and 44.5% females. Overall 33/209 (15.8%) patients had anxiety while 56/209 (26.8%) were found to have depression. There was a higher frequency of anxiety and depression in younger patients (less than age 40 years), females, patients who were single or divorced, and patients receiving chemotherapy for pancreatic carcinoma. Conclusion: Patients undergoing chemotherapy suffer from considerable levels of anxiety and depression, thus highlighting the need for specialized interventions. (author)

  16. Targeting doxorubicin encapsulated in stealth liposomes to solid tumors by non thermal diode laser.

    Science.gov (United States)

    Ghannam, Magdy M; El Gebaly, Reem; Fadel, Maha

    2016-04-05

    The use of liposomes as drug delivery systems is the most promising technique for targeting drug especially for anticancer therapy. In this study sterically stabilized liposomes was prepared from DPPC/Cholesterol/PEG-PE encapsulated doxorubicin. The effect of lyophilization on liposomal stability and hence expiration date were studied. Moreover, the effect of diode laser on the drug released from liposomesin vitro and in vivo in mice carrying implanted solid tumor were also studied. The results indicated that lyophilization of the prepared liposomes encapsulating doxorubicin led to marked stability when stored at 5 °C and it is possible to use the re-hydrated lyophilized liposomes within 12 days post reconstitution. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells is a promising method in cancer therapy. We can conclude that lyophilization of the liposomes encapsulating doxorubicin lead to marked stability for the liposomes when stored at 5 °C. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells through the use of photosensitive sterically stabilized liposomes loaded with doxorubicin is a promising method. It proved to be applicable and successful for treatment of Ehrlich solid tumors implanted in mice and eliminated toxic side effects of doxorubicin.

  17. Identification of recurrent chromosomal aberrations in germ cell tumors of neonates and infants using genomewide array-based comparative genomic hybridization.

    NARCIS (Netherlands)

    Veltman, I.M.; Veltman, J.; Janssen, I.M.; Hulsbergen-van de Kaa, C.A.; Oosterhuis, W.; Schneider, D.; Stoop, H.; Gillis, A.J.M.; Zahn, S.; Looijenga, L.H.J.; Gobel, U.; Geurts van Kessel, A.H.M.

    2005-01-01

    Human germ cell tumors (GCTs) of neonates and infants comprise a heterogeneous group of neoplasms, including teratomas and yolk sac tumors with distinct clinical and epidemiologic features. As yet, little is known about the cytogenetic constitution of these tumors. We applied the recently developed

  18. Cytogenetic analysis after evaluation of 750 fetal deaths : proposal for diagnostic workup

    NARCIS (Netherlands)

    Korteweg, Fleurisca J.; Bouman, Katelijne; Erwich, Jan Jaap H. M.; Timmer, Albertus; Veeger, Nic J. G. M.; Ravise, Joke M.; Nijman, Thomas H.; Holm, Andjozien P.

    OBJECTIVE: To estimate success rates for cytogenetic analysis in different tissues after intrauterine fetal death, and study selection criteria and value of cytogenetic testing in determining cause of death. METHODS: Cytogenetic analyses and the value of this test in determining cause by a

  19. Smart thermosensitive liposomes for effective solid tumor therapy and in vivo imaging.

    Directory of Open Access Journals (Sweden)

    Kevin Affram

    Full Text Available In numerous studies, liposomes have been used to deliver anticancer drugs such as doxorubicin to local heat-triggered tumor. Here, we investigate: (i the ability of thermosensitive liposomal nanoparticle (TSLnp as a delivery system to deliver poorly membrane-permeable anticancer drug, gemcitabine (Gem to solid pancreatic tumor with the aid of local mild hyperthermia and, (ii the possibility of using gadolinium (Magnevist® loaded-TSLnps (Gd-TSLnps to increase magnetic resonance imaging (MRI contrast in solid tumor. In this study, we developed and tested gemcitabine-loaded thermosensitive liposomal nanoparticles (Gem-TSLnps and gadolinium-loaded thermosensitive liposomal nanoparticles (Gd-TSLnps both in in-vitro and in-vivo. The TSLnps exhibited temperature-dependent release of Gem, at 40-42°C, 65% of Gem was released within 10 min, whereas < 23% Gem leakage occurred at 37°C after a period of 2 h. The pharmacokinetic parameters and tissue distribution of both Gem-TSLnps and Gd-TSLnps were significantly greater compared with free Gem and Gd, while Gem-TSLnps plasma clearance was reduced by 17-fold and that of Gd-TSLpns was decreased by 2-fold. Area under the plasma concentration time curve (AUC of Gem-TSLnps (35.17± 0.04 μghr/mL was significantly higher than that of free Gem (2.09 ± 0.01 μghr/mL whereas, AUC of Gd-TSLnps was higher than free Gd by 3.9 fold high. TSLnps showed significant Gem accumulation in heated tumor relative to free Gem. Similar trend of increased Gd-TSLnps accumulation was observed in non-heated tumor compared to that of free Gd; however, no significant difference in MRI contrast enhancement between free Gd and Gd-TSLnps ex-vivo tumor images was observed. Despite Gem-TSLnps dose being half of free Gem dose, antitumor efficacy of Gem-TSLnps was comparable to that of free Gem(Gem-TSLnps 10 mg Gem/kg compared with free Gem 20 mg/kg. Overall, the findings suggest that TSLnps may be used to improve Gem delivery and enhance

  20. An overview of viral oncology in Italy - report from the Pavia meeting on solid tumors

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    Perfetti Vittorio

    2012-09-01

    Full Text Available Abstract This is a report on some of the research activities currently ongoing in Italy as outlined at the “Viruses and solid tumors” meeting jointly organized by the Oncology Sections of IRCCS Policlinico “San Matteo” (Pavia and IRCCS National Cancer Institute (Aviano, held in Pavia, Italy, on October 2011. Experts from the various disciplines involved in the study of the complex relationships between solid tumors and viruses met to discuss recent developments in the field and to report their personal contributions to the specified topics. Secondary end point was to establish a multidisciplinary work group specifically devoted to solid tumors and infectious agents, aimed to identify areas of common interest, promoting and establishing collaborative projects and programs, and to coordinate clinical and research activities. The group, which will be named IVOG (Italian Viral Oncology Group, will operate under the patronage of the various scientific societies of interest.

  1. Human interphase chromosomes: a review of available molecular cytogenetic technologies

    Directory of Open Access Journals (Sweden)

    Yurov Yuri B

    2010-01-01

    Full Text Available Abstract Human karyotype is usually studied by classical cytogenetic (banding techniques. To perform it, one has to obtain metaphase chromosomes of mitotic cells. This leads to the impossibility of analyzing all the cell types, to moderate cell scoring, and to the extrapolation of cytogenetic data retrieved from a couple of tens of mitotic cells to the whole organism, suggesting that all the remaining cells possess these genomes. However, this is far from being the case inasmuch as chromosome abnormalities can occur in any cell along ontogeny. Since somatic cells of eukaryotes are more likely to be in interphase, the solution of the problem concerning studying postmitotic cells and larger cell populations is interphase cytogenetics, which has become more or less applicable for specific biomedical tasks due to achievements in molecular cytogenetics (i.e. developments of fluorescence in situ hybridization -- FISH, and multicolor banding -- MCB. Numerous interphase molecular cytogenetic approaches are restricted to studying specific genomic loci (regions being, however, useful for identification of chromosome abnormalities (aneuploidy, polyploidy, deletions, inversions, duplications, translocations. Moreover, these techniques are the unique possibility to establish biological role and patterns of nuclear genome organization at suprachromosomal level in a given cell. Here, it is to note that this issue is incompletely worked out due to technical limitations. Nonetheless, a number of state-of-the-art molecular cytogenetic techniques (i.e multicolor interphase FISH or interpahase chromosome-specific MCB allow visualization of interphase chromosomes in their integrity at molecular resolutions. Thus, regardless numerous difficulties encountered during studying human interphase chromosomes, molecular cytogenetics does provide for high-resolution single-cell analysis of genome organization, structure and behavior at all stages of cell cycle.

  2. MRI after magnetic drug targeting in patients with advanced solid malignant tumors

    International Nuclear Information System (INIS)

    Lemke, A.-J.; Senfft von Pilsach, M.-I.; Felix, R.; Luebbe, A.; Bergemann, C.; Riess, H.

    2004-01-01

    The purpose of this study was to evaluate the ability of MRI to detect magnetic particle uptake into advanced solid malignant tumors and to document the extension of these tumors, carried out in the context of magnetic drug targeting. In a prospective phase I trial, 11 patients were examined with MRI before and after magnetic drug targeting. The sequence protocol included T1-WI and T2-WI in several planes, followed by quantitative and qualitative evaluation of the signal intensities and tumor extensions. In nine patients, a signal decrease was observed in the early follow-up (2-7 days after therapy) on the T2-weighted images; two patients did not show a signal change. The signal changes in T1-WI were less distinct. In late follow-up (4-6 weeks after therapy), signal within nine tumors reached their initially normal level on both T1-WI and T2-WI; two tumors showed a slight signal decrease on T2-WI and a slight signal increase on T1-WI. Within the surveillance period, tumor remission in 3 out of 11 patients was observed, and in 5 patients tumor growth had stopped. The remaining three patients showed significant tumor growth. There was no statistically significant correlation between signal change and response. MRI is a suitable method to detect magnetite particles, deposited at the tumor site via magnetic drug targeting. MRI is therefore eligible to control the success of MDT and to assess the tumor size after the end of therapy. (orig.)

  3. In vitro anti-proliferative effect of interferon alpha in solid tumors: A potential predicative test

    International Nuclear Information System (INIS)

    Fuchsberger, N.; Kubes, M.; Kontsek, P.; Borecky, L.; Hornak, M.; Silvanova; Godal, A.; Svec, J.

    1993-01-01

    An in vitro test for the anti-proliferative effect of human leukocyte interferon (IFN-alpha) was performed in primary cultures of tumor cells obtained from 32 patients with either malignant melanoma (13), renal carcinoma (4) or bladder carcinoma (15). Our results demonstrated activity of IFN in all three groups of solid tumors. However, appreciable differences in sensitivity to anti-proliferative effect of IFN between individual tumors of the same type were found. The potential of this anti-proliferative test for prediction of treatment response in IFN-therapy is discussed. (author)

  4. Whole-body magnetic resonance imaging for detection of skeletal metastases in children and young people with primary solid tumors - systematic review

    International Nuclear Information System (INIS)

    Smets, A.M.; Deurloo, E.E.; Slager, T.J.E.; Stoker, J.; Bipat, S.

    2018-01-01

    Many solid neoplasms have a propensity for osteomedullary metastases of which detection is important for staging and subsequent treatment. Whole-body magnetic resonance imaging (WB-MRI) has been shown to accurately detect osteomedullary metastases in adults, but these findings cannot be unconditionally extrapolated to staging of children with malignant solid tumors. To conduct a literature review on the sensitivity of WB-MRI for detecting skeletal metastases in children with solid tumors. Searches in MEDLINE and EMBASE databases up to 15 May 2017 were performed to identify studies on the diagnostic value of WB-MRI. Inclusion criteria were children and adolescents (age <21 years) with a primary solid tumor who were evaluated for skeletal metastases by WB-MRI and compared to any type of reference standard. The number of included patients had to be at least five and data on true positives, true negatives, false-positives and false-negatives had to be extractable. Five studies including 132 patients (96 patients with solid tumors) were eligible. Patient groups and used reference tests were heterogeneous, producing unclear or high risk of bias. Sensitivity of WB-MRI ranged between 82% and 100%. The positive predictive value of WB-MRI was variable among the studies and influenced by the used reference standard. Although WB-MRI may seem a promising radiation-free technique for the detection of skeletal metastases in children with solid tumors, published studies are small and too heterogeneous to provide conclusive evidence that WB-MRI can be an alternative to currently used imaging techniques. (orig.)

  5. Whole-body magnetic resonance imaging for detection of skeletal metastases in children and young people with primary solid tumors - systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Smets, A.M.; Deurloo, E.E.; Slager, T.J.E.; Stoker, J.; Bipat, S. [Academic Medical Center (AMC), Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands)

    2018-02-15

    Many solid neoplasms have a propensity for osteomedullary metastases of which detection is important for staging and subsequent treatment. Whole-body magnetic resonance imaging (WB-MRI) has been shown to accurately detect osteomedullary metastases in adults, but these findings cannot be unconditionally extrapolated to staging of children with malignant solid tumors. To conduct a literature review on the sensitivity of WB-MRI for detecting skeletal metastases in children with solid tumors. Searches in MEDLINE and EMBASE databases up to 15 May 2017 were performed to identify studies on the diagnostic value of WB-MRI. Inclusion criteria were children and adolescents (age <21 years) with a primary solid tumor who were evaluated for skeletal metastases by WB-MRI and compared to any type of reference standard. The number of included patients had to be at least five and data on true positives, true negatives, false-positives and false-negatives had to be extractable. Five studies including 132 patients (96 patients with solid tumors) were eligible. Patient groups and used reference tests were heterogeneous, producing unclear or high risk of bias. Sensitivity of WB-MRI ranged between 82% and 100%. The positive predictive value of WB-MRI was variable among the studies and influenced by the used reference standard. Although WB-MRI may seem a promising radiation-free technique for the detection of skeletal metastases in children with solid tumors, published studies are small and too heterogeneous to provide conclusive evidence that WB-MRI can be an alternative to currently used imaging techniques. (orig.)

  6. Inflammatory myofibroblastic tumor

    Directory of Open Access Journals (Sweden)

    Sangeeta Palaskar

    2011-01-01

    Full Text Available Inflammatory myofibroblastic tumor is an uncommon lesion of unknown cause. It encompasses a spectrum of myofibroblastic proliferation along with varying amount of inflammatory infiltrate. A number of terms have been applied to the lesion, namely, inflammatory pseudotumor, fibrous xanthoma, plasma cell granuloma, pseudosarcoma, lymphoid hamartoma, myxoid hamartoma, inflammatory myofibrohistiocytic proliferation, benign myofibroblatoma, and most recently, inflammatory myofibroblastic tumor. The diverse nomenclature is mostly descriptive and reflects the uncertainty regarding true biologic nature of these lesions. Recently, the concept of this lesion being reactive has been challenged based on the clinical demonstration of recurrences and metastasis and cytogenetic evidence of acquired clonal chromosomal abnormalities. We hereby report a case of inflammatory pseudotumor and review its inflammatory versus neoplastic behavior.

  7. Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents.

    Science.gov (United States)

    Ma, Brigette B Y; Bristow, Robert G; Kim, John; Siu, Lillian L

    2003-07-15

    Molecular targeted agents have been combined with radiotherapy (RT) in recent clinical trials in an effort to optimize the therapeutic index of RT. The appeal of this strategy lies in their potential target specificity and clinically acceptable toxicity. This article integrates the salient, published research findings into the underlying molecular mechanisms, preclinical efficacy, and clinical applicability of combining RT with molecular targeted agents. These agents include inhibitors of intracellular signal transduction molecules, modulators of apoptosis, inhibitors of cell cycle checkpoints control, antiangiogenic agents, and cyclo-oxygenase-2 inhibitors. Molecular targeted agents can have direct effects on the cytoprotective and cytotoxic pathways implicated in the cellular response to ionizing radiation (IR). These pathways involve cellular proliferation, DNA repair, cell cycle progression, nuclear transcription, tumor angiogenesis, and prostanoid-associated inflammation. These pathways can also converge to alter RT-induced apoptosis, terminal growth arrest, and reproductive cell death. Pharmacologic modulation of these pathways may potentially enhance tumor response to RT though inhibition of tumor repopulation, improvement of tumor oxygenation, redistribution during the cell cycle, and alteration of intrinsic tumor radiosensitivity. Combining RT and molecular targeted agents is a rational approach in the treatment of solid tumors. Translation of this approach from promising preclinical data to clinical trials is actively underway.

  8. Ultrasonic enhancement of drug penetration in solid tumors

    Directory of Open Access Journals (Sweden)

    Chun-yen eLai

    2013-08-01

    Full Text Available Increasing the penetration of drugs within solid tumors can be accomplished through multiple ultrasound-mediated mechanisms. The application of ultrasound can directly change the structure or physiology of tissues or can induce changes in a drug or vehicle in order to enhance delivery and efficacy. With each ultrasonic pulse, a fraction of the energy in the propagating wave is absorbed by tissue and results in local heating. When ultrasound is applied to achieve mild hyperthermia, the thermal effects are associated with an increase in perfusion or the release of a drug from a temperature-sensitive vehicle. Higher ultrasound intensities locally ablate tissue and result in increased drug accumulation surrounding the ablated region of interest. Further, the mechanical displacement induced by the ultrasound pulse can result in the nucleation, growth and collapse of gas bubbles. As a result of such cavitation, the permeability of a vessel wall or cell membrane can be increased. Finally, the radiation pressure of the propagating pulse can translate particles or tissues. In this perspective, we will review recent progress in ultrasound-mediated tumor delivery and the opportunities for clinical translation.

  9. Anti-leukemic therapies induce cytogenetic changes of human bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Yeh, Su-Peng; Lo, Wen-Jyi; Lin, Chiao-Lin; Liao, Yu-Min; Lin, Chen-Yuan; Bai, Li-Yuan; Liang, Ji-An; Chiu, Chang-Fang

    2012-02-01

    Both bone marrow hematopoietic cells (BM-HCs) and mesenchymal stem cells (BM-MSCs) may have cytogenetic aberrations in leukemic patients, and anti-leukemic therapy may induce cytogenetic remission of BM-HCs. The impact of anti-leukemic therapy on BM-MSCs remains unknown. Cytogenetic studies of BM-MSCs from 15 leukemic patients with documented cytogenetic abnormalities of BM-HCs were investigated. To see the influence of anti-leukemic therapy on BM-MSCs, cytogenetic studies were carried out in seven of them after the completion of anti-leukemic therapy, including anthracycline/Ara-C-based chemotherapy in two patients, high-dose busulfan/cyclophosphamide-based allogeneic transplantation in two patients, and total body irradiation (TBI)-based allogeneic transplantation in three patients. To simulate the effect of TBI in vitro, three BM-MSCs from one leukemic patient and two normal adults were irradiated using the same dosage and dosing schedule of TBI and cytogenetics were re-examined after irradiation. At the diagnosis of leukemia, two BM-MSCs had cytogenetic aberration, which were completely different to their BM-HCs counterpart. After the completion of anti-leukemic therapy, cytogenetic aberration was no longer detectable in one patient. Unexpectedly, BM-MSCs from three patients receiving TBI-based allogeneic transplantation acquired new, clonal cytogenetic abnormalities after transplantation. Similarly, complex cytogenetic abnormalities were found in all the three BM-MSCs exposed to in vitro irradiation. In conclusion, anti-leukemic treatments induce not only "cytogenetic remission" but also new cytogenetic abnormalities of BM-MSCs. TBI especially exerts detrimental effect on the chromosomal integrity of BM-MSCs and highlights the equal importance of investigating long-term adverse effect of anti-leukemic therapy on BM-MSCs as opposed to beneficial effect on BM-HCs.

  10. Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network.

    Science.gov (United States)

    Soltani, M; Chen, P

    2013-01-01

    Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor's surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy's law for tissue, and simplified Navier-Stokes equation for blood flow through capillaries) are used for simulating interstitial and intravascular flows and Starling's law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.

  11. Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network.

    Directory of Open Access Journals (Sweden)

    M Soltani

    Full Text Available Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor's surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy's law for tissue, and simplified Navier-Stokes equation for blood flow through capillaries are used for simulating interstitial and intravascular flows and Starling's law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.

  12. Integrin α5β1, the Fibronectin Receptor, as a Pertinent Therapeutic Target in Solid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schaffner, Florence; Ray, Anne Marie; Dontenwill, Monique, E-mail: monique.dontenwill@unistra.fr [UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Tumoral signaling and therapeutic targets, Université de Strasbourg, Faculté de Pharmacie, 67401 Illkirch (France)

    2013-01-15

    Integrins are transmembrane heterodimeric proteins sensing the cell microenvironment and modulating numerous signalling pathways. Changes in integrin expression between normal and tumoral cells support involvement of specific integrins in tumor progression and aggressiveness. This review highlights the current knowledge about α5β1 integrin, also called the fibronectin receptor, in solid tumors. We summarize data showing that α5β1 integrin is a pertinent therapeutic target expressed by tumoral neovessels and tumoral cells. Although mainly evaluated in preclinical models, α5β1 integrin merits interest in particular in colon, breast, ovarian, lung and brain tumors where its overexpression is associated with a poor prognosis for patients. Specific α5β1 integrin antagonists will be listed that may represent new potential therapeutic agents to fight defined subpopulations of particularly aggressive tumors.

  13. Antibody or Antibody Fragments : Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

    NARCIS (Netherlands)

    Xenaki, Katerina T; Oliveira, Sabrina; van Bergen En Henegouwen, Paul M P

    2017-01-01

    The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody-drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are

  14. Treatment With JAK Inhibitors in Myelofibrosis Patients Nullifies the Prognostic Impact of Unfavorable Cytogenetics.

    Science.gov (United States)

    Ma, Vincent T; Boonstra, Philip S; Menghrajani, Kamal; Perkins, Cecelia; Gowin, Krisstina L; Mesa, Ruben A; Gotlib, Jason R; Talpaz, Moshe

    2018-05-01

    In the era before Janus kinase (JAK) inhibitors, cytogenetic information was used to predict survival in myelofibrosis patients. However, the prognostic value of cytogenetics in the setting of JAK inhibitor therapy remains unknown. We performed a retrospective analysis of 180 patients with bone marrow biopsy-proven myelofibrosis from 3 US academic medical centers. We fit Cox proportional hazards models for overall survival and transformation-free survival on the bases of 3 factors: JAK inhibitor therapy as a time-dependent covariate, dichotomized cytogenetic status (favorable vs. unfavorable), and statistical interaction between the two. The median follow-up time was 37.1 months. Among patients treated with best available therapy, unfavorable cytogenetic status was associated with decreased survival (hazard ratio = 2.31; P = .025). At initiation of JAK inhibitor therapy, unfavorable cytogenetics was (nonsignificantly) associated with increased survival compared to favorable cytogenetics (hazard ratio = 0.292; P = .172). The ratio of hazard ratios was 0.126 (P = .034). These findings were similar after adjusting for standard clinical prognostic factors as well as when measured against transformation-free survival. The initiation of JAK inhibitor therapy appears to change the association between cytogenetics and overall survival. There was little difference in survival between treatment types in patients with favorable cytogenetics. However, the use of JAK inhibitor therapy among patients with unfavorable cytogenetics was not associated with worse survival compared to favorable cytogenetics. Our analyses suggest that initiation of JAK inhibitor therapy nullifies the negative prognostic implication of unfavorable cytogenetics established in the pre-JAK inhibitor therapy era. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  15. CD 99 immunocytochemistry in solid pseudopapillary tumor of pancreas: A study on fine-needle aspiration cytology smears.

    Science.gov (United States)

    Ghosh, Ranajoy; Mallik, Saumya R; Mathur, Sandeep R; Iyer, Venkateswaran K

    2013-07-01

    Solid pseudopapillary tumor of pancreas (SPTP) is a rare pancreatic tumor of uncertain histogenesis usually affecting young women. Though these tumors have characteristic cytomorphology, it is sometimes difficult to differentiate them from neuroendocrine tumors of the pancreas. We reviewed cases of SPTP to delineate the diagnostic cytological features and also observed utility of CD 99 (MIC 2) immunostaining to aid in the diagnosis of this tumor. This study was designed to demonstrate the utility of CD 99 immunostaining along with cytological features for making a pre-operative diagnosis and delineating it from the neuroendocrine tumor of pancreas which is a close mimic. Cytomorphological features of 11 cases of solid pseudopapillary neoplasm diagnosed by pre-operative fine-needle aspiration cytology (FNAC) at our institute were reviewed. Immunocytochemistry for CD 99 was also performed on the smears. All the cases had cellular smears with monomorphic cells lying singly, as loosely cohesive clusters as well as forming delicate pseudopapillae. Presence of intra and extra-cellular basement membrane material, background foamy macrophages and nuclear grooves were the other salient features. Immunocytochemistry for CD 99 could be performed on eight cases and demonstrated typical paranuclear dot-like positivity. Pre-operative early diagnosis of SPTP can be made by FNAC which can further be aided by CD 99 immunocytochemistry.

  16. Antibody-Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review.

    Science.gov (United States)

    Lambert, John M; Morris, Charles Q

    2017-05-01

    Attaching a cytotoxic "payload" to an antibody to form an antibody-drug conjugate (ADC) provides a mechanism for selective delivery of the cytotoxic agent to cancer cells via the specific binding of the antibody to cancer-selective cell surface molecules. The first ADC to receive marketing authorization was gemtuzumab ozogamicin, which comprises an anti-CD33 antibody conjugated to a highly potent DNA-targeting antibiotic, calicheamicin, approved in 2000 for treating acute myeloid leukemia. It was withdrawn from the US market in 2010 following an unsuccessful confirmatory trial. The development of two classes of highly potent microtubule-disrupting agents, maytansinoids and auristatins, as payloads for ADCs resulted in approval of brentuximab vedotin in 2011 for treating Hodgkin lymphoma and anaplastic large cell lymphoma, and approval of ado-trastuzumab emtansine in 2013 for treating HER2-positive breast cancer. Their success stimulated much research into the ADC approach, with >60 ADCs currently in clinical evaluation, mostly targeting solid tumors. Five ADCs have advanced into pivotal clinical trials for treating various solid tumors-platinum-resistant ovarian cancer, mesothelioma, triple-negative breast cancer, glioblastoma, and small cell lung cancer. The level of target expression is a key parameter in predicting the likelihood of patient benefit for all these ADCs, as well as for the approved compound, ado-trastuzumab emtansine. The development of a patient selection strategy linked to target expression on the tumor is thus critically important for identifying the population appropriate for receiving treatment.

  17. Comparison of F-18-FDG PET/CT findings between pancreatic solid pseudopapillary tumor and pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Kim, Yong-il; Kim, Seok-ki; Paeng, Jin Chul; Lee, Ho-Young

    2014-01-01

    Objective: Pancreatic solid pseudopapillary tumor (SPT) is a rare benign tumor. Little data are available on positron emission tomographic/computed tomographic (PET/CT) characteristics of this tumor. Therefore, we analyzed the metabolic characteristics of SPT using F-18-FDG PET/CT and compared the results with those of pancreatic ductal adenocarcinoma. Methods: We retrospectively reviewed the records of 11 SPT patients and 46 patients with ductal adenocarcinoma. Ten SPT patients had primary tumors and 1 patient had metastatic SPT. Maximum standardized uptake value (max SUV), mean SUV, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor-to-background ratio (TBR) were evaluated. Mann–Whitney U test between pancreatic SPT and ductal adenocarcinoma was performed. In addition, age, gender and tumor size-adjusted analysis of covariance (ANCOVA) was done between pancreatic SPT and ductal adenocarcinoma. Results: Compared with pancreatic ductal adenocarcinomas, SPTs had significantly higher tumor size-adjusted MTV and TLG. MTV and TLG values were significantly correlated with T-stage of the SPTs. In 1 SPT patient, metastases in the liver and mesentery were revealed by intense uptake of FDG on F-18-FDG PET/CT, and after PET/CT had suggested the presence of pancreatic SPT. Conclusion: We recommend that SPT be considered when a solid pancreatic mass with increased FDG metabolism is encountered on PET/CT. F-18-FDG PET/CT may be useful in detecting subtle metastases of SPT

  18. Bifidobacterial recombinant thymidine kinase-ganciclovir gene therapy system induces FasL and TNFR2 mediated antitumor apoptosis in solid tumors

    International Nuclear Information System (INIS)

    Wang, Changdong; Ma, Yongping; Hu, Qiongwen; Xie, Tingting; Wu, Jiayan; Zeng, Fan; Song, Fangzhou

    2016-01-01

    Directly targeting therapeutic suicide gene to a solid tumor is a hopeful approach for cancer gene therapy. Treatment of a solid tumor by an effective vector for a suicide gene remains a challenge. Given the lack of effective treatments, we constructed a bifidobacterial recombinant thymidine kinase (BF-rTK) -ganciclovir (GCV) targeting system (BKV) to meet this requirement and to explore antitumor mechanisms. Bifidobacterium (BF) or BF-rTK was injected intratumorally with or without ganciclovir in a human colo320 intestinal xenograft tumor model. The tumor tissues were analyzed using apoptosis antibody arrays, real time PCR and western blot. The colo320 cell was analyzed by the gene silencing method. Autophagy and necroptosis were also detected in colo320 cell. Meanwhile, three human digestive system xenograft tumor models (colorectal cancer colo320, gastric cancer MKN-45 and liver cancer SSMC-7721) and a breast cancer (MDA-MB-231) model were employed to validate the universality of BF-rTK + GCV in solid tumor gene therapy. The survival rate was evaluated in three human cancer models after the BF-rTK + GCV intratumor treatment. The analysis of inflammatory markers (TNF-α) in tumor indicated that BF-rTK + GCV significantly inhibited TNF-α expression. The results suggested that BF-rTK + GCV induced tumor apoptosis without autophagy and necroptosis occurrence. The apoptosis was transduced by multiple signaling pathways mediated by FasL and TNFR2 and mainly activated the mitochondrial control of apoptosis via Bid and Bim, which was rescued by silencing Bid or/and Bim. However, BF + GCV only induced apoptosis via Fas/FasL signal pathway accompanied with increased P53 expression. We further found that BF-rTK + GCV inhibited the expression of the inflammatory maker of TNF-α. However, BF-rTK + GCV did not result in necroptosis and autophagy. BF-rTK + GCV induced tumor apoptosis mediated by FasL and TNFR2 through the mitochondrial control of apoptosis via Bid and Bim

  19. Occurrence and prognostic significance of cytogenetic evolution in patients with multiple myeloma

    Science.gov (United States)

    Binder, M; Rajkumar, S V; Ketterling, R P; Dispenzieri, A; Lacy, M Q; Gertz, M A; Buadi, F K; Hayman, S R; Hwa, Y L; Zeldenrust, S R; Lust, J A; Russell, S J; Leung, N; Kapoor, P; Go, R S; Gonsalves, W I; Kyle, R A; Kumar, S K

    2016-01-01

    Cytogenetic evaluation at the time of diagnosis is essential for risk stratification in multiple myeloma, however little is known about the occurrence and prognostic significance of cytogenetic evolution during follow-up. We studied 989 patients with multiple myeloma, including 304 patients with at least two cytogenetic evaluations. Multivariable-adjusted regression models were used to assess the associations between the parameters of interest and cytogenetic evolution as well as overall survival. The prognostic significance of baseline cytogenetic abnormalities was most pronounced at the time of diagnosis and attenuated over time. In the patients with serial cytogenetic evaluations, the presence of t(11;14) at the time of diagnosis was associated with decreased odds of cytogenetic evolution during follow-up (odds ratio (OR)=0.22, 95% confidence interval (CI)=0.09–0.56, P=0.001), while the presence of at least one trisomy or tetrasomy was associated with increased odds (OR=2.96, 95% CI=1.37–6.42, P=0.006). The development of additional abnormalities during the 3 years following diagnosis was associated with increased subsequent mortality (hazard ratio=3.31, 95% CI=1.73–6.30, P<0.001). These findings emphasize the importance of the underlying clonal disease process for risk assessment and suggest that selected patients may benefit from repeated risk stratification. PMID:26967818

  20. Cytogenetic heterogeneity and their serial dynamic changes during acquisition of cytogenetic aberrations in cultured mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung-Ah [Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Im, Kyong Ok; Park, Si Nae; Kwon, Ji Seok [Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Seon Young [Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Oh, Keunhee; Lee, Dong-Sup [Laboratory of Immunology and Cancer Biology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul (Korea, Republic of); Transplantation Research Institute, Seoul National University College of Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Min Kyung; Kim, Seong Who [Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jang, Mi; Lee, Gene [Lab of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul (Korea, Republic of); Oh, Yeon-Mok; Lee, Sang Do [Department of Pulmonary and Critical Care Medicine, Asthma Center and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Lee, Dong Soon, E-mail: soonlee@snu.ac.kr [Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-07-15

    Highlights: • We evaluated cytogenetic aberrations of MSC during culture using G-banding and FISH. • We tracked the quantitative changes of each clone among heterogeneity upon passages. • The changes of cytogenetic profile upon passages were similar to cancer stem cell. - Abstract: To minimize the risk of tumorigenesis in mesenchymal stem cells (MSCs), G-banding analysis is widely used to detect chromosomal aberrations in MSCs. However, a critical limitation of G-banding is that it only reflects the status of metaphase cells, which can represent as few as 0.01% of tested cells. During routine cytogenetic testing in MSCs, we often detect chromosomal aberrations in minor cell populations. Therefore, we aimed to investigate whether such a minority of cells can expand over time or if they ultimately disappear during MSC passaging. We passaged MSCs serially while monitoring quantitative changes for each aberrant clone among heterogeneous MSCs. To investigate the cytogenetic status of interphase cells, which represent the main population, we also performed interphase FISH analysis, in combination with G-banding and telomere length determination. In human adipose tissue-derived MSCs, 4 types of chromosomal aberrations were found during culturing, and in umbilical cord MSCs, 2 types of chromosomal aberrations were observed. Sequential dynamic changes among heterogeneous aberrant clones during passaging were similar to the dynamic changes observed in cancer stem cells during disease progression. Throughout all passages, the quantitative G-banding results were inconsistent with those of the interphase FISH analysis. Interphase FISH revealed hidden aberrations in stem cell populations with normal karyotypes by G-banding analysis. We found that telomere length gradually decreased during passaging until the point at which cytogenetic aberrations appeared. The present study demonstrates that rare aberrant clones at earlier passages can become predominant clones during

  1. Cytogenetic heterogeneity and their serial dynamic changes during acquisition of cytogenetic aberrations in cultured mesenchymal stem cells

    International Nuclear Information System (INIS)

    Kim, Jung-Ah; Im, Kyong Ok; Park, Si Nae; Kwon, Ji Seok; Kim, Seon Young; Oh, Keunhee; Lee, Dong-Sup; Kim, Min Kyung; Kim, Seong Who; Jang, Mi; Lee, Gene; Oh, Yeon-Mok; Lee, Sang Do; Lee, Dong Soon

    2015-01-01

    Highlights: • We evaluated cytogenetic aberrations of MSC during culture using G-banding and FISH. • We tracked the quantitative changes of each clone among heterogeneity upon passages. • The changes of cytogenetic profile upon passages were similar to cancer stem cell. - Abstract: To minimize the risk of tumorigenesis in mesenchymal stem cells (MSCs), G-banding analysis is widely used to detect chromosomal aberrations in MSCs. However, a critical limitation of G-banding is that it only reflects the status of metaphase cells, which can represent as few as 0.01% of tested cells. During routine cytogenetic testing in MSCs, we often detect chromosomal aberrations in minor cell populations. Therefore, we aimed to investigate whether such a minority of cells can expand over time or if they ultimately disappear during MSC passaging. We passaged MSCs serially while monitoring quantitative changes for each aberrant clone among heterogeneous MSCs. To investigate the cytogenetic status of interphase cells, which represent the main population, we also performed interphase FISH analysis, in combination with G-banding and telomere length determination. In human adipose tissue-derived MSCs, 4 types of chromosomal aberrations were found during culturing, and in umbilical cord MSCs, 2 types of chromosomal aberrations were observed. Sequential dynamic changes among heterogeneous aberrant clones during passaging were similar to the dynamic changes observed in cancer stem cells during disease progression. Throughout all passages, the quantitative G-banding results were inconsistent with those of the interphase FISH analysis. Interphase FISH revealed hidden aberrations in stem cell populations with normal karyotypes by G-banding analysis. We found that telomere length gradually decreased during passaging until the point at which cytogenetic aberrations appeared. The present study demonstrates that rare aberrant clones at earlier passages can become predominant clones during

  2. Flow cytogenetics and chromosome sorting.

    Science.gov (United States)

    Cram, L S

    1990-06-01

    This review of flow cytogenetics and chromosome sorting provides an overview of general information in the field and describes recent developments in more detail. From the early developments of chromosome analysis involving single parameter or one color analysis to the latest developments in slit scanning of single chromosomes in a flow stream, the field has progressed rapidly and most importantly has served as an important enabling technology for the human genome project. Technological innovations that advanced flow cytogenetics are described and referenced. Applications in basic cell biology, molecular biology, and clinical investigations are presented. The necessary characteristics for large number chromosome sorting are highlighted. References to recent review articles are provided as a starting point for locating individual references that provide more detail. Specific references are provided for recent developments.

  3. FLAG-tagged CD19-specific CAR-T cells eliminate CD19-bearing solid tumor cells in vitro and in vivo.

    Science.gov (United States)

    Berahovich, Robert; Xu, Shirley; Zhou, Hua; Harto, Hizkia; Xu, Qumiao; Garcia, Andres; Liu, Fenyong; Golubovskaya, Vita M; Wu, Lijun

    2017-06-01

    Autologous T cells expressing chimeric antigen receptors (CARs) specific for CD19 have demonstrated remarkable efficacy as therapeutics for B cell malignancies. In the present study, we generated FLAG-tagged CD19-specific CAR-T cells (CD19-FLAG) and compared them to their non-tagged counterparts for their effects on solid and hematological cancer cells in vitro and in vivo . For solid tumors, we used HeLa cervical carcinoma cells engineered to overexpress CD19 (HeLa-CD19), and for hematological cancer we used Raji Burkitt's lymphoma cells, which endogenously express CD19. Like non-tagged CD19 CAR-T cells, CD19-FLAG CAR-T cells expanded in culture >100-fold and exhibited potent cytolytic activity against both HeLa-CD19 and Raji cells in vitro . CD19-FLAG CAR-T cells also secreted significantly more IFN-gamma and IL-2 than the control T cells. In vivo , CD19-FLAG CAR-T cells significantly blocked the growth of HeLa-CD19 solid tumors, increased tumor cleaved caspase-3 levels, and expanded systemically. CD19-FLAG CAR-T cells also significantly reduced Raji tumor burden and extended mouse survival. These results demonstrate the strong efficacy of FLAG-tagged CD19 CAR-T cells in solid and hematological cancer models.

  4. Applications of lipid nanocarriers for solid tumors therapy: literature review

    International Nuclear Information System (INIS)

    Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury; Taveira, Eliseu Jose Fleury

    2012-01-01

    Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed R database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

  5. Allelic imbalance and cytogenetic deletion of 1p in colorectal adenomas: a target region identified between DIS199 and DIS234

    DEFF Research Database (Denmark)

    Bomme, L; Heim, S; Bardi, G

    1998-01-01

    short-term cultured and karyotyped colorectal adenomas for allelic imbalance at eight microsatellite loci in 1p. Allelic imbalances were detected in seven of the 12 adenomas that had cytogenetically visible abnormalities of chromosome 1, as well as in four adenomas that either had a normal karyotype...... region. This genomic area contains the human homologue of the tumor modifier gene Mom1 (1p35-36.1), which, in mice, modifies the number of intestinal tumors in multiple intestinal neoplasia (Min)-mutated animals. To evaluate whether the imbalances corresponded to interstitial deletions of 1p material, we...

  6. [Cytogenetic Abnormalities and Outcomes of 117 Patients with Multiple Myeloma Detected by FISH].

    Science.gov (United States)

    Zhai, Bing; Zou, Dan-Dan; Yan, Jian-Jun; Wang, Nan; Wang, Li-Li; Zhu, Hong-Li; Huang, Wen-Rong; Yu, Li

    2016-02-01

    To analyze the cytogenetic abnormalities and prognostic outcomes of patients with multiple myeloma (MM) detected by fluorescence in situ hybridization (FISH). The clinical record of 117 newly-diagnosed patients with MM treated in department of hematology and geriatric hematology of our hospital for 7 years were collected, and their molecular cytogenetic abnormalities detected by FISH and the clinical outcome were analyzed retrospectively. The detected rate of cytogenetic abnormality was 76.9%(90/117), the most common abnormality deteted by FISH was 1q21+ (71.1%), followed by 13q- (56.6%). The cross comparison method showed that 13q- and 17p13-, t(11;14) and t(4;14) were related respectively. All the patients with cytogenetic abnormalities showed no significant difference in the overall survival from cytogenetic normal patients. The positive rate of molecular cytogenetic abnormalities detected by FISH in MM patients is high, but data from larger and longer studies are needed to evaluate the prognostic outcomes.

  7. Cytogenetic and molecular abnormalities in chronic myelomonocytic leukemia

    International Nuclear Information System (INIS)

    Patnaik, M M; Tefferi, A

    2016-01-01

    Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder associated with peripheral blood monocytosis and an inherent tendency to transform to acute myeloid leukemia. CMML has overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Clonal cytogenetic changes are seen in ~30%, whereas gene mutations are seen in >90% of patients. Common cytogenetic abnormalities include; trisomy 8, -Y, -7/del(7q), trisomy 21 and del(20q), with the Mayo–French risk stratification effectively risk stratifying patients based on cytogenetic abnormalities. Gene mutations frequently involve epigenetic regulators (TET2 ~60%), modulators of chromatin (ASXL1 ~40%), spliceosome components (SRSF2 ~50%), transcription factors (RUNX1 ~15%) and signal pathways (RAS ~30%, CBL ~15%). Of these, thus far, only nonsense and frameshift ASXL1 mutations have been shown to negatively impact overall survival. This has resulted in the development of contemporary, molecularly integrated (inclusive of ASXL1 mutations) CMML prognostic models, including Molecular Mayo Model and the Groupe Français des Myélodysplasies model. Better understanding of the prevalent genetic and epigenetic dysregulation has resulted in emerging targeted treatment options for some patients. The development of an integrated (cytogenetic and molecular) prognostic model along with CMML-specific response assessment criteria are much needed future goals

  8. A comprehensive cytogenetic classification of 1466 Chinese patients with de novo acute lymphoblastic leukemia.

    Science.gov (United States)

    Li, Xin; Li, Juan; Hu, Yanjie; Xie, Wei; Du, Wen; Liu, Wei; Li, Xiaoqing; Chen, Xiangjun; Li, Hongrui; Wang, Junfeng; Zhang, Lannan; Huang, Shiang

    2012-06-01

    Cytogenetics and molecular cytogenetics of 1466 Chinese patients with de novo acute lymphoblastic leukemia (ALL) were studied. Cytogenetic results were available in 1175 patients. Cross-correlations of 23 subclasses of cytogenetic abnormalities were described. Childhood cases had higher incidences of normal karyotype, t(1;19), +8, 12q-, +21, +22 and high hyperdiploidy with 51-65 chromosomes, and lower incidences of t(9;22) and -5/5q- than adult ones (all pcytogenetic subclasses with immunophenotyping subgroups of ALL were studied. Our study presents the cytogenetic characteristics of a large series of Chinese ALL patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. The combined effect of interferon synthesis inductors, radiosensitizing and antitumoral agents on solid tumors

    International Nuclear Information System (INIS)

    Leonidze, D.L.

    1987-01-01

    In experiments with mice bearing solid sarcoma 37 a study was conducted on the combined effect of radiation and inductors of endogenous inerferon synthesis (IEIS), together with hyperthermia or together with an alkylating and carbomoilating agent, dimethinur. The effect was estimated by the tumor growth coefficient and by the number of animals with the regressed tumors. Poly I; polyC was not shiown to influence the efficiency of hyperthermia combined with radiation with radiation; dextransulphate and tiloron increased the radiosensitizing effect of hyperthermia. Dimethinur aggravated the effect of radiation, but with IEIS used together with dimethynur and radiation, the response of the tumor increased insignificantly as compared to the effect of IEIS together with radiation

  10. Cancer stem cells in solid tumors: is 'evading apoptosis' a hallmark of cancer?

    Science.gov (United States)

    Enderling, Heiko; Hahnfeldt, Philip

    2011-08-01

    Conventional wisdom has long held that once a cancer cell has developed it will inevitably progress to clinical disease. Updating this paradigm, it has more recently become apparent that the tumor interacts with its microenvironment and that some environmental bottlenecks, such as the angiogenic switch, must be overcome for the tumor to progress. In parallel, attraction has been drawn to the concept that there is a minority population of cells - the cancer stem cells - bestowed with the exclusive ability to self-renew and regenerate the tumor. With therapeutic targeting issues at stake, much attention has shifted to the identification of cancer stem cells, the thinking being that the remaining non-stem population, already fated to die, will play a negligible role in tumor development. In fact, the newly appreciated importance of intercellular interactions in cancer development also extends in a unique and unexpected way to interactions between the stem and non-stem compartments of the tumor. Here we discuss recent findings drawn from a hybrid mathematical-cellular automaton model that simulates growth of a heterogeneous solid tumor comprised of cancer stem cells and non-stem cancer cells. The model shows how the introduction of cell fate heterogeneity paradoxically influences the tumor growth dynamic in response to apoptosis, to reveal yet another bottleneck to tumor progression potentially exploitable for disease control. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Prognostic implications of genetic aberrations in acute myelogenous leukemia with normal cytogenetics.

    Science.gov (United States)

    Ghanem, Hady; Tank, Niki; Tabbara, Imad A

    2012-01-01

    Acute myelogenous leukemia (AML) is a genetically heterogeneous disease in which somatic mutations, that disturb cellular growth, proliferation, and differentiation, accumulate in hematopoietic progenitor cells. Cytogenetic findings, at diagnosis, have been proven to be one of the most important prognostic indicators in AML. About half of the patients with AML are found to have "normal" cytogenetic analysis by standard culture techniques. These patients are considered as an intermediate risk group. Cytogenetically normal AML (CN-AML) is the largest cytogenetic risk group, and the variation in clinical outcome of patients in this group is greater than in any other cytogenetic group. Besides mutation testing, age and presenting white blood cell count are important predictors of overall survival, suggesting that other factors independent of cytogenetic abnormalities, contribute to the outcome of patients with AML. The expanding knowledge at the genetic and molecular levels is helping define several subgroups of patients with CN-AML with variable prognosis. In this review, we describe the clinical and prognostic characteristics of CN-AML patients as a group, as well as the various molecular and genetic aberrations detected in these patients and their clinical and prognostic implications. Copyright © 2011 Wiley Periodicals, Inc.

  12. Cytogenetic dosimetry in suspected cases of ionizing radiation occupational exposure

    International Nuclear Information System (INIS)

    Ramalho, Adriana T.; Costa, Maria Lucia P.; Oliveira, Monica S.; Silva, Francisco Cesar A. da

    2001-01-01

    Cytogenetic dosimetry is very useful in routine as well as in serious accident situations in which exposed individuals do not wear physical dosimeters. Since 1984, the technique of cytogenetic dosimetry has been used as a routine in our laboratory at IRD/CNEN to complement the data of physical dosimetry. In the period from 1984 to 2000, 138 cases of occupational overexposure of individual dosimeters were investigated by us. In total, only in 36 of the 138 cases investigated the overexposure was confirmed by cytogenetic dosimetry. The data indicates a total confirmation index of just 26% of the suspected cases.(author)

  13. Magnetite nanoparticles inhibit tumor growth and upregulate the expression of p53/p16 in Ehrlich solid carcinoma bearing mice.

    Directory of Open Access Journals (Sweden)

    Heba Bassiony

    Full Text Available BACKGROUND: Magnetite nanoparticles (MNPs have been widely used as contrast agents and have promising approaches in cancer treatment. In the present study we used Ehrlich solid carcinoma (ESC bearing mice as a model to investigate MNPs antitumor activity, their effect on expression of p53 and p16 genes as an indicator for apoptotic induction in tumor tissues. METHOD: MNPs coated with ascorbic acid (size: 25.0±5.0 nm were synthesized by co-precipitation method and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day by day for 14 injections; intratumorally (IT or intraperitoneally (IP. Tumor size, pathological changes and iron content in tumor and normal muscle tissues were assessed. We also assessed changes in expression levels of p53 and p16 genes in addition to p53 protein level by immunohistochemistry. RESULTS: Our results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor. A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor. This increase was accompanied with increase in p53 protein expression. It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group. CONCLUSION: MNPs might be more effective in breast cancer treatment if injected intratumorally to be directed to the tumor tissues.

  14. Improving CART-Cell Therapy of Solid Tumors with Oncolytic Virus-Driven Production of a Bispecific T-cell Engager.

    Science.gov (United States)

    Wing, Anna; Fajardo, Carlos Alberto; Posey, Avery D; Shaw, Carolyn; Da, Tong; Young, Regina M; Alemany, Ramon; June, Carl H; Guedan, Sonia

    2018-05-01

    T cells expressing chimeric antigen receptors (CART) have shown significant promise in clinical trials to treat hematologic malignancies, but their efficacy in solid tumors has been limited. Oncolytic viruses have the potential to act in synergy with immunotherapies due to their immunogenic oncolytic properties and the opportunity of incorporating therapeutic transgenes in their genomes. Here, we hypothesized that an oncolytic adenovirus armed with an EGFR-targeting, bispecific T-cell engager (OAd-BiTE) would improve the outcome of CART-cell therapy in solid tumors. We report that CART cells targeting the folate receptor alpha (FR-α) successfully infiltrated preestablished xenograft tumors but failed to induce complete responses, presumably due to the presence of antigen-negative cancer cells. We demonstrated that OAd-BiTE-mediated oncolysis significantly improved CART-cell activation and proliferation, while increasing cytokine production and cytotoxicity, and showed an in vitro favorable safety profile compared with EGFR-targeting CARTs. BiTEs secreted from infected cells redirected CART cells toward EGFR in the absence of FR-α, thereby addressing tumor heterogeneity. BiTE secretion also redirected CAR-negative, nonspecific T cells found in CART-cell preparations toward tumor cells. The combinatorial approach improved antitumor efficacy and prolonged survival in mouse models of cancer when compared with the monotherapies, and this was the result of an increased BiTE-mediated T-cell activation in tumors. Overall, these results demonstrated that the combination of a BiTE-expressing oncolytic virus with adoptive CART-cell therapy overcomes key limitations of CART cells and BiTEs as monotherapies in solid tumors and encourage its further evaluation in human trials. Cancer Immunol Res; 6(5); 605-16. ©2018 AACR . ©2018 American Association for Cancer Research.

  15. Monoclonal antibodies and Fc fragments for treating solid tumors

    Directory of Open Access Journals (Sweden)

    Eisenbeis AM

    2012-01-01

    Full Text Available Andrea M Eisenbeis, Stefan J GrauDepartment of Neurosurgery, University Hospital of Cologne, Cologne, GermanyAbstract: Advances in biotechnology, better understanding of pathophysiological processes, as well as the identification of an increasing number of molecular markers have facilitated the use of monoclonal antibodies and Fc fragments in various fields in medicine. In this context, a rapidly growing number of these substances have also emerged in the field of oncology. This review will summarize the currently approved monoclonal antibodies used for the treatment of solid tumors with a focus on their clinical application, biological background, and currently ongoing trials.Keywords: targeted therapy, monoclonal antibodies, cancer, biological therapy

  16. Imaging of solid tumor using near-infrared emitting purple bacteria

    International Nuclear Information System (INIS)

    Moon, Sung Min; Min, Jung Joon; Kim, Sun A; Choy, Hyon E.; Bom, Hee Seung

    2005-01-01

    Rhodobacter sphaeroides 2.4.1 is α-3 purple nonsulfur eubacterium with an extensive metabolism. Under anaerobic conditions, it is able to grow by photosynthesis, respiration and fermentation. When grown photosynthetically, it uses wavelengths of light in the near-infrared and contains a reaction center that is the peripheral light-harvesting (LH2) complex. These molecules absorb and emit near-infrared light. Using this near-infrared fluorescent bacterial we investigated its targeting capacity of solid tumor in small animals. R. sphaeroides 2.4.1 strains were cultured in sistrons minimal medium A (SIS) at 32 C. Xenograft tumor model has been established by subcutaneous injection of CT26 mouse colon cancer cell line. 1X10 8 Rhodobacter sphaeroides cells suspended in 100 ul of PBS were injected via tail vein with 1-cc insulin syringe into tumor bearing mouse. In vivo fluorescence imaging has been done after 20 min to 30 days of purple bacteria using indocyanine (ICG) emission filter (Em=810∼835 nm). Near-infrared imaging signal from Rhodobacter sphaeroides was initially detected at liver for 3 days but at the necrotic region of tumor mass thereafter. Total photon flux measured 5.5X10 8 (p/s/cm 2 /sr) at Day 1. Also it was increased to 7.8X10 8 (p/s/cm 2 /sr) at 12 day. One of important characteristic is that the signal appeared only at central necrosis area. It has been monitored for 36 day. We successfully imaged cancer with near-infrared fluorescence bacteria. Our result indicate that near-infrared fluorescence purple bacteria are able to be used to monitor bacterial trafficking in living tumor models

  17. Mathematical operations in cytogenetic dosimetry: Dosgen

    International Nuclear Information System (INIS)

    Garcia L, O.; Zequera J, T.

    1996-01-01

    Handling of formulas and mathematical procedures for fitting and using of dose-response relationships in cytogenetic dosimetry is often difficulted by the absence of collaborators specialized in mathematics and computation. DOSGEN program contains the main mathematical operations which are used in cytogenetic dosimetry. It is able to run in IBM compatible Pc's by non-specialized personnel.The program possibilities are: Poisson distribution fitting test for the number of aberration per cell, dose assessment for whole body irradiation, dose assessment for partial irradiation and determination of irradiated fraction. The program allows on screen visualization and printing of results. DOSGEN has been developed in turbo pascal and is 33Kb of size. (authors). 4 refs

  18. Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

    Directory of Open Access Journals (Sweden)

    Millard M

    2017-10-01

    Full Text Available Marie Millard,1,2 Ilya Yakavets,1–3 Vladimir Zorin,3,4 Aigul Kulmukhamedova,1,2,5 Sophie Marchal,1,2 Lina Bezdetnaya1,2 1Centre de Recherche en Automatique de Nancy, Centre National de la Recherche Scientifique UMR 7039, Université de Lorraine, 2Research Department, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France; 3Laboratory of Biophysics and Biotechnology, 4International Sakharov Environmental Institute, Belarusian State University, Minsk, Belarus; 5Department of Radiology, Medical Company Sunkar, Almaty, Kazakhstan Abstract: The increasing number of publications on the subject shows that nanomedicine is an attractive field for investigations aiming to considerably improve anticancer chemotherapy. Based on selective tumor targeting while sparing healthy tissue, carrier-mediated drug delivery has been expected to provide significant benefits to patients. However, despite reduced systemic toxicity, most nanodrugs approved for clinical use have been less effective than previously anticipated. The gap between experimental results and clinical outcomes demonstrates the necessity to perform comprehensive drug screening by using powerful preclinical models. In this context, in vitro three-dimensional models can provide key information on drug behavior inside the tumor tissue. The multicellular tumor spheroid (MCTS model closely mimics a small avascular tumor with the presence of proliferative cells surrounding quiescent cells and a necrotic core. Oxygen, pH and nutrient gradients are similar to those of solid tumor. Furthermore, extracellular matrix (ECM components and stromal cells can be embedded in the most sophisticated spheroid design. All these elements together with the physicochemical properties of nanoparticles (NPs play a key role in drug transport, and therefore, the MCTS model is appropriate to assess the ability of NP to penetrate the tumor tissue. This review presents recent developments in MCTS models for a

  19. Cytogenetics And Its Relevance to the Practice of Modern Medicine ...

    African Journals Online (AJOL)

    This review outlines the importance of cytogenetics in modern medicine, the need to develop the application to the level of a full discipline in Nigeria to prevent and control these disorders and reawaken the interest of scientists and postgraduate students in this all-important discipline. Keywords: Human cytogenetics ...

  20. Leveraging Hypoxia-Activated Prodrugs to Prevent Drug Resistance in Solid Tumors.

    Directory of Open Access Journals (Sweden)

    Danika Lindsay

    2016-08-01

    Full Text Available Experimental studies have shown that one key factor in driving the emergence of drug resistance in solid tumors is tumor hypoxia, which leads to the formation of localized environmental niches where drug-resistant cell populations can evolve and survive. Hypoxia-activated prodrugs (HAPs are compounds designed to penetrate to hypoxic regions of a tumor and release cytotoxic or cytostatic agents; several of these HAPs are currently in clinical trial. However, preliminary results have not shown a survival benefit in several of these trials. We hypothesize that the efficacy of treatments involving these prodrugs depends heavily on identifying the correct treatment schedule, and that mathematical modeling can be used to help design potential therapeutic strategies combining HAPs with standard therapies to achieve long-term tumor control or eradication. We develop this framework in the specific context of EGFR-driven non-small cell lung cancer, which is commonly treated with the tyrosine kinase inhibitor erlotinib. We develop a stochastic mathematical model, parametrized using clinical and experimental data, to explore a spectrum of treatment regimens combining a HAP, evofosfamide, with erlotinib. We design combination toxicity constraint models and optimize treatment strategies over the space of tolerated schedules to identify specific combination schedules that lead to optimal tumor control. We find that (i combining these therapies delays resistance longer than any monotherapy schedule with either evofosfamide or erlotinib alone, (ii sequentially alternating single doses of each drug leads to minimal tumor burden and maximal reduction in probability of developing resistance, and (iii strategies minimizing the length of time after an evofosfamide dose and before erlotinib confer further benefits in reduction of tumor burden. These results provide insights into how hypoxia-activated prodrugs may be used to enhance therapeutic effectiveness in the

  1. Cytogenetic study is not essential in patients with aplastic anemia

    Science.gov (United States)

    Dutta, Atreyee; De, Rajib; Dolai, Tuphan K; Mitra, Pradip K; Halder, Ajanta

    2017-01-01

    Depending on contemporary treatment approach of aggressive immunosuppression, Aplastic Anemia (AA) is caused by immunological destruction of otherwise normal hematopoietic stem cells. The aim was to summarize the cytogenetic abnormalities in AA patients and the frequency of Fanconi Anemia (FA) in morphologically normal AA patients in eastern India. Ethical clearances were obtained from both institutions involved in this study. Out of 72800 patients attending the outpatient department, 520 pancytopenia patients were screened for AA after Bone marrow (BM) aspiration and biopsy. Samples were collected from 117 cases in 3 phases. 51 peripheral venous blood (PVB) samples in the first phase, 19 BM & PVB paired samples in the second phase and 47 BM samples in third phase were collected followed by leukocyte and/or BM stem cell culture. Next GTG banding and karyotyping were performed. PVB was collected from 63 (< 50 years) AA patients and stress cytogenetics was done to diagnose FA. In the first phase of the study, out of 51 PVB samples, 1 (1.96%) showed a unique chromosomal abnormality, i.e. 45,XY,rob(14:21)(p10:q10)[20]. In the second phase of study, among 19 BM & PVB paired samples, 1 (5.26%) showed abnormal karyotype i.e. 45,X,-Y[3]/46,XY[47]. In the third phase of the study, 47 BM samples showed normal karyotype. Only 6 (9.52%) cases were found positive for stress cytogenetics. A negligible percentage showing cytogenetic abnormality in such a considerable number of AA cases indicates that routine cytogenetic analysis of AA patient is not essential. A significant percentage was positive for stress cytogenetics; suggestive for FA, even the patients were morphologically normal. PMID:29181263

  2. Cytogenetic profile in 1,921 cases of trisomy 21 syndrome.

    Science.gov (United States)

    Flores-Ramírez, Francisco; Palacios-Guerrero, Claudia; García-Delgado, Constanza; Morales-Jiménez, Ariadna Berenice; Arias-Villegas, Christian Martín; Cervantes, Alicia; Morán-Barroso, Verónica Fabiola

    2015-08-01

    Trisomy 21 is the most frequent genetic cause of intellectual disability. It is caused by different cytogenetic aberrations: free trisomy, Robertsonian translocations, mosaicism, duplication of the critical region and other structural rearrangements of chromosome 21. The aim of the study was to identify in Mexican trisomy 21 patients who attended Hospital Infantil de México Federico Gómez from 1992-2011 the type and frequency of the cytogenetic aberration and to evaluate the effect of maternal age. A retrospective analysis of epidemiological data and karyotype reports were carried out; type and frequency of the cytogenetic variants were determined. We identified 2,018 cases referred with a clinical diagnosis of trisomy 21. In 1,921 analyses (95.2%) a cytogenetic variant of trisomy 21 was identified: free trisomy 21 in 1,787 cases (93.02%), four cases (0.21%) had an additional non-contributory aberration; Robertsonian translocations in 92 cases (4.79%); mosaicism in 31 cases (1.61%) and seven cases (0.36%) had other chromosomal abnormalities, five (0.26%) had other contributory structural rearrangements and two corresponded to double aneuploidies (0.10%). Gender distribution was 1,048 (54.56%) males and 873 (45.44%) females. A maternal age effect was observed in patients with free trisomy 21 with mothers >36 years of age. The present work reports the experience of a Mexican referral center regarding the karyotype diagnosis of patients with trisomy 21 and is one of the most extensive studies published so far. Percentages of the cytogenetic abnormalities present in our population reflect the ones previously reported for these cytogenetic alterations worldwide. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  3. Cytogenetic study is not essential in patients with aplastic anemia.

    Science.gov (United States)

    Dutta, Atreyee; De, Rajib; Dolai, Tuphan K; Mitra, Pradip K; Halder, Ajanta

    2017-01-01

    Depending on contemporary treatment approach of aggressive immunosuppression, Aplastic Anemia (AA) is caused by immunological destruction of otherwise normal hematopoietic stem cells. The aim was to summarize the cytogenetic abnormalities in AA patients and the frequency of Fanconi Anemia (FA) in morphologically normal AA patients in eastern India. Ethical clearances were obtained from both institutions involved in this study. Out of 72800 patients attending the outpatient department, 520 pancytopenia patients were screened for AA after Bone marrow (BM) aspiration and biopsy. Samples were collected from 117 cases in 3 phases. 51 peripheral venous blood (PVB) samples in the first phase, 19 BM & PVB paired samples in the second phase and 47 BM samples in third phase were collected followed by leukocyte and/or BM stem cell culture. Next GTG banding and karyotyping were performed. PVB was collected from 63 (cytogenetics was done to diagnose FA. In the first phase of the study, out of 51 PVB samples, 1 (1.96%) showed a unique chromosomal abnormality, i.e. 45,XY,rob(14:21)(p10:q10)[20]. In the second phase of study, among 19 BM & PVB paired samples, 1 (5.26%) showed abnormal karyotype i.e. 45,X,-Y[3]/46,XY[47]. In the third phase of the study, 47 BM samples showed normal karyotype. Only 6 (9.52%) cases were found positive for stress cytogenetics. A negligible percentage showing cytogenetic abnormality in such a considerable number of AA cases indicates that routine cytogenetic analysis of AA patient is not essential. A significant percentage was positive for stress cytogenetics; suggestive for FA, even the patients were morphologically normal.

  4. Cytogenetics of Festulolium (Festuca x Lolium hybrids).

    Science.gov (United States)

    Kopecký, D; Lukaszewski, A J; Dolezel, J

    2008-01-01

    Grasses are the most important and widely cultivated crops. Among them, ryegrasses (Lolium spp.) and fescues (Festuca spp.) provide high quality fodder for livestock, are used for turf and amenity purposes, and play a fundamental role in environment protection. Species from the two genera display complementary agronomic characteristics and are often grown in mixtures. Breeding efforts to combine desired features in single entities culminated with the production of Festuca x Lolium hybrids. The so called Festuloliums enjoy a considerable commercial success with numerous cultivars registered all over the world. They are also very intriguing from a strictly cytogenetic point of view as the parental chromosomes recombine freely in hybrids. Until a decade ago this phenomenon was only known in general quantitative terms. The introduction of molecular cytogenetic tools such as FISH and GISH permitted detailed studies of intergeneric chromosome recombination and karyotyping of Festulolium cultivars. These tools were also invaluable in revealing the origin of polyploid fescues, and facilitated the development of chromosome substitution and introgression lines and physical mapping of traits of interest. Further progress in this area will require the development of a larger set of cytogenetic markers and high-resolution cytogenetic maps. It is expected that the Lolium-Festuca complex will continue providing opportunities for breeding superior grass cultivars and the complex will remain an attractive platform for fundamental research of the early steps of hybrid speciation and interaction of parental genomes, as well as the processes of chromosome pairing, elimination and recombination. 2008 S. Karger AG, Basel

  5. Secondary solid tumors following radiation in Hodgkin's disease: experience of the Institut Gustave-Roussy

    International Nuclear Information System (INIS)

    Cosset, J.M.; Henry-Amar, M.; Dietrich, P.Y.; Socie, G.; Girinsky, T.; Hayat, M.; Tubiana, M.

    1992-01-01

    From 1961 to 1984, in the Institut Gustave-Roussy, 893 patients have been treated in Hodgkin's disease. The authors study the solid tumors that they have observed after exclusive radiotherapy and chemo-radiotherapy in order to know the radiation effect in the birth of this type of cancer

  6. Filter Paper-based Nucleic Acid Storage in High-throughput Solid Tumor Genotyping.

    Science.gov (United States)

    Stachler, Matthew; Jia, Yonghui; Sharaf, Nematullah; Wade, Jacqueline; Longtine, Janina; Garcia, Elizabeth; Sholl, Lynette M

    2015-01-01

    Molecular testing of tumors from formalin-fixed paraffin-embedded (FFPE) tissue blocks is central to clinical practice; however, it requires histology support and increases test turnaround time. Prospective fresh frozen tissue collection requires special handling, additional storage space, and may not be feasible for small specimens. Filter paper-based collection of tumor DNA reduces the need for histology support, requires little storage space, and preserves high-quality nucleic acid. We investigated the performance of tumor smears on filter paper in solid tumor genotyping, as compared with paired FFPE samples. Whatman FTA Micro Card (FTA preps) smears were prepared from 21 fresh tumor samples. A corresponding cytology smear was used to assess tumor cellularity and necrosis. DNA was isolated from FTA preps and FFPE core samples using automated methods and quantified using SYBR green dsDNA detection. Samples were genotyped for 471 mutations on a mass spectrophotometry-based platform (Sequenom). DNA concentrations from FTA preps and FFPE correlated for untreated carcinomas but not for mesenchymal tumors (Spearman σ=0.39 and σ=-0.1, respectively). Average DNA concentrations were lower from FTA preps as compared with FFPE, but DNA quality was higher with less fragmentation. Seventy-six percent of FTA preps and 86% of FFPE samples generated adequate DNA for genotyping. FTA preps tended to perform poorly for collection of DNA from pretreated carcinomas and mesenchymal neoplasms. Of the 16 paired DNA samples that were genotyped, 15 (94%) gave entirely concordant results. Filter paper-based sample preservation is a feasible alternative to FFPE for use in automated, high-throughput genotyping of carcinomas.

  7. Echinococcus cysticus of the liver - sonographic pattern suggestive of solid tumor

    International Nuclear Information System (INIS)

    Grosser, G.; Hauenstein, K.H.; Henke, W.

    1985-01-01

    In a patient with Hodgkin's disease, an intrahepatic echodense mass was diagnosed incidentally by ultrasonography. The sonographic pattern suggested a solid tumor. Despite negative or borderline serology, computed tomography establised the diagnosis of echinococcus cysticus by documentation of one ''daughter'' cyst; this diagnosis was confirmed by surgery. The criteria of echinococcus cysticus in modern imaging methods like sonography and computed tomography are summarized and the diagnostic value of various procedures including diagnostic procedure in seronegative cases are discussed. (orig.) [de

  8. Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts

    DEFF Research Database (Denmark)

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini

    2013-01-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome pr...

  9. 75 FR 32484 - Array-Based Cytogenetic Tests: Questions on Performance Evaluation, Result Reporting and...

    Science.gov (United States)

    2010-06-08

    ...] Array-Based Cytogenetic Tests: Questions on Performance Evaluation, Result Reporting and Interpretation... public meeting: Array-Based Cytogenetic Tests: Questions on Performance Evaluation, Result Reporting and... cytogenetic tests. Date and Time: The meeting will be held on June 30, 2010, from 1:30 p.m. to 5 p.m. Location...

  10. Cytogenetic effects of the action of ionizing radiations on human populations

    International Nuclear Information System (INIS)

    Shevchenko, V.A.; Snigiryova, G.P.

    1998-01-01

    The objective of the present work is the analysis of available materials on practical application of the cytogenetic method for dose assessment in people participating in the post-accidental rescue and clean-up operations in Chernobyl (so-called 'liquidators'). These materials will be compared with the results of cytogenetic investigations performed in other regions of Russia exposed to radiation (the village Muslyumovo in the Chelyabinsk region, several localities of the Altai Territory in the vicinity of the Semipalatinsk nuclear test site) as well as with the results of cytogenetic monitoring in the population living around the Three Mile Island (TMI) nuclear power plant (Pennsylvania, USA) where a nuclear accident occurred in 1979. The work presents the results of cytogenetic investigations obtained by the traditional method of analysis of the frequency of unstable chromosome aberrations and by the FISH method based on the frequency of stable chromosome aberrations. (J.P.N.)

  11. Clinical and cytogenetic features of a Brazilian sample of patients with phenotype of oculo-auriculo-vertebral spectrum: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Alessandra Pawelec da Silva

    Full Text Available CONTEXT AND OBJECTIVE: Oculo-auriculo-vertebral spectrum (OAVS is considered to be a defect of embryogenesis involving structures originating from the first branchial arches. Our objective was to describe the clinical and cytogenetic findings from a sample of patients with the phenotype of OAVS.DESIGN AND SETTING: Cross-sectional study in a referral hospital in southern Brazil.METHODS: The sample consisted of 23 patients who presented clinical findings in at least two of these four areas: orocraniofacial, ocular, auricular and vertebral. The patients underwent a clinical protocol and cytogenetic evaluation through high-resolution karyotyping, fluorescence in situ hybridization for 5p and 22q11 microdeletions and investigation of chromosomal instability for Fanconi anemia.RESULTS: Cytogenetic abnormalities were observed in three cases (13% and consisted of: 47,XX,+mar; mos 47,XX,+mar/46,XX; and 46,XX,t(6;10(q13; q24. We observed cases of OAVS with histories of gestational exposition to fluoxetine, retinoic acid and crack. One of our patients was a discordant monozygotic twin who had shown asymmetrical growth restriction during pregnancy. Our patients with OAVS were characterized by a broad clinical spectrum and some presented atypical findings such as lower-limb reduction defect and a tumor in the right arm, suggestive of hemangioma/lymphangioma.CONCLUSIONS: We found a wide range of clinical characteristics among the patients with OAVS. Different chromosomal abnormalities and gestational expositions were also observed. Thus, our findings highlight the heterogeneity of the etiology of OAVS and the importance of these factors in the clinical and cytogenetic evaluation of these patients.

  12. Quick cytogenetic screening of breeding bulls using flow cytometric sperm DNA histogram analysis.

    Science.gov (United States)

    Nagy, Szabolcs; Polgár, Péter J; Andersson, Magnus; Kovács, András

    2016-09-01

    The aim of the present study was to test the FXCycle PI/RNase kit for routine DNA analyses in order to detect breeding bulls and/or insemination doses carrying cytogenetic aberrations. In a series of experiments we first established basic DNA histogram parameters of cytogenetically healthy breeding bulls by measuring the intraspecific genome size variation of three animals, then we compared the histogram profiles of bulls carrying cytogenetic defects to the baseline values. With the exception of one case the test was able to identify bulls with cytogenetic defects. Therefore, we conclude that the assay could be incorporated into the laboratory routine where flow cytometry is applied for semen quality control.

  13. Echinococcus cysticus of the liver - sonographic pattern suggestive of solid tumor

    Energy Technology Data Exchange (ETDEWEB)

    Grosser, G.; Hauenstein, K.H.; Henke, W.

    1985-09-01

    In a patient with Hodgkin's disease, an intrahepatic echodense mass was diagnosed incidentally by ultrasonography. The sonographic pattern suggested a solid tumor. Despite negative or borderline serology, computed tomography establised the diagnosis of echinococcus cysticus by documentation of one ''daughter'' cyst; this diagnosis was confirmed by surgery. The criteria of echinococcus cysticus in modern imaging methods like sonography and computed tomography are summarized and the diagnostic value of various procedures including diagnostic procedure in seronegative cases are discussed.

  14. Comprehensive 5-Year Study of Cytogenetic Aberrations in 668 Infertile Men

    Science.gov (United States)

    Yatsenko, Alexander N.; Yatsenko, Svetlana A.; Weedin, John W.; Lawrence, Amy E.; Patel, Ankita; Peacock, Sandra; Matzuk, Martin M.; Lamb, Dolores J.; Cheung, Sau Wai; Lipshultz, Larry I.

    2010-01-01

    Purpose The causes of male infertility are heterogeneous but more than 50% of cases have a genetic basis. Specific genetic defects have been identified in less than 20% of infertile males and, thus, most causes remain to be elucidated. The most common cytogenetic defects associated with nonobstructive azoospermia are numerical and structural chromosome abnormalities, including Klinefelter syndrome (47,XXY) and Y chromosome microdeletions. To refine the incidence and nature of chromosomal aberrations in males with infertility we reviewed cytogenetic results in 668 infertile men with oligozoospermia and azoospermia. Materials and Methods High resolution Giemsa banding chromosome analysis and/or fluorescence in situ hybridization were done in 668 infertile males referred for routine cytogenetic analysis between January 2004 and March 2009. Results The overall incidence of chromosomal abnormalities was about 8.2%. Of the 55 patients with abnormal cytogenetic findings sex chromosome aneuploidies were observed in 29 (53%), including Klinefelter syndrome in 27 (49%). Structural chromosome abnormalities involving autosomes (29%) and sex chromosomes (18%) were detected in 26 infertile men. Abnormal cytogenetic findings were observed in 35 of 264 patients (13.3%) with azoospermia and 19 of 365 (5.2%) with oligozoospermia. Conclusions Structural chromosomal defects and low level sex chromosome mosaicism are common in oligozoospermia cases. Extensive cytogenetic assessment and fluorescence in situ hybridization may improve the detection rate in males with oligozoospermia. These findings highlight the need for efficient genetic testing in infertile men so that couples may make informed decisions on assisted reproductive technologies to achieve parenthood. PMID:20172548

  15. Omitting cytogenetic assessment from routine treatment response monitoring in chronic myeloid leukemia is safe.

    Science.gov (United States)

    Geelen, Inge G P; Thielen, Noortje; Janssen, Jeroen J W M; Hoogendoorn, Mels; Roosma, Tanja J A; Valk, Peter J M; Visser, Otto; Cornelissen, Jan J; Westerweel, Peter E

    2018-04-01

    The monitoring of response in chronic myeloid leukemia (CML) is of great importance to identify patients failing their treatment in order to adjust TKI choice and thereby prevent progression to advanced stage disease. Cytogenetic monitoring has a lower sensitivity, is expensive, and requires invasive bone marrow sampling. Nevertheless, chronic myeloid leukemia guidelines continue to recommend performing routine cytogenetic response assessments, even when adequate molecular diagnostics are available. In a population-based registry of newly diagnosed CML patients in the Netherlands, all simultaneous cytogenetic and molecular assessments performed at 3, 6, and 12 months were identified and response of these matched assessments was classified according to European Leukemia Net (ELN) recommendations. The impact of discrepant cytogenetic and molecular response classifications and course of patients with additional chromosomal abnormalities were evaluated. The overall agreement of 200 matched assessments was 78%. In case of discordant responses, response at 24 months was consistently better predicted by the molecular outcome. Cytogenetic response assessments provided relevant additional clinical information only in some cases of molecular "warning." The development of additional cytogenetic abnormalities was always accompanied with molecular failure. We conclude that it is safe to omit routine cytogenetics for response assessment during treatment and to only use molecular monitoring, in order to prevent ambiguous classifications, reduce costs, and reduce the need for invasive bone marrow sampling. Cytogenetic re-assessment should still be performed when molecular response is suboptimal. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Monitoring the effect of belinostat in solid tumors by H4 acetylation

    DEFF Research Database (Denmark)

    Marquard, L.; Petersen, K.D.; Persson, M.

    2008-01-01

    after treatment with HDAC inhibitors, and could thus be used as a marker for monitoring cellular response to HDAC inhibitor treatment. Here we describe the utility of a newly described monoclonal antibody against acetylated H4 for immunohistochemistry on paraffin-embedded fine needle biopsies from nude...... acetylation in fine needle biopsies using the T25 antibody may prove useful in monitoring HDAC inhibitor efficacy in clinical trials involving humans with solid tumors Udgivelsesdato: 2008/5...

  17. Maternal and Birth Characteristics and Childhood Embryonal Solid Tumors: A Population-Based Report from Brazil.

    Science.gov (United States)

    de Paula Silva, Neimar; de Souza Reis, Rejane; Garcia Cunha, Rafael; Pinto Oliveira, Júlio Fernando; Santos, Marceli de Oliveira; Pombo-de-Oliveira, Maria S; de Camargo, Beatriz

    2016-01-01

    Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics. A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS) or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma). Children aged birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS) was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67-1.01)). Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma. This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes.

  18. Solid tumor models for the assessment of different treatment modalities. XIV. The evaluation of host and tumor response to cyclophosphamide and radiation

    International Nuclear Information System (INIS)

    Looney, W.B.; Hopkins, H.A.; MacLeod, M.S.; Ritenour, E.R.

    1979-01-01

    The effect of increasing doses of cyclophosphamide (50 to 250 mg/kg) on the time of occurrence of maximal and minimal tumor growth rates, tumor volume reduction, and linear doubling times (LDT) on the solid tumor model H-4-II-E has been determined. Tumor response to cyclophosphamide was classified as class I, tumor regression; class II, pseudo-regression; and class III, slow-down. The overall treatment efficiency (OTE) has been used to assess the magnitude of tumor volume changes after treatment. The maximum OTE occurred after 150 mg/kg of cyclophosphamide. Increasing the dose to 200 and 250 mg/kg of cyclophosphamide resulted in a decrease in OTE. Similar parameters were utilized to measure the effectiveness of increasing doses of local tumor radiation (750, 1500, 2000, 2500, 3000 and 3500R). The major increase in OTE occurs when the radiation dose is increased from 750R to 2000R. Increasing the dose further to 3500R results in smaller incremental increases in the OTE. Results of the study indicate that increasing the cyclophosphamide dose beyond a certain level (i.e., 150 mg/kg) increases mortality and morbidity without concomitant therapeutic benefit. The effects of increasing the dose of local tumor radiation on life span have given results which suggest that increasing the total radiation dose beyond a certain limit is less effective in increasing life span

  19. Birth weight and risk of childhood solid tumors in Brazil: a record linkage between population-based data sets.

    Science.gov (United States)

    de Paula Silva, Neimar; de Souza Reis, Rejane; Cunha, Rafael Garcia; Oliveira, Julio Fernando; da Silva de Lima, Fernanda Cristina; Pombo-de-Oliveira, Maria Socorro; Santos, Marceli Oliveira; de Camargo, Beatriz

    2017-04-20

    To analyze the relationship between the development of childhood solid tumors and 1) birth weight and 2) fetal growth, using two Brazilian population-based data sets. A case-cohort study was performed using two population-based data sets, and linkage between the Live Birth Information System (Sistema de Informação sobre Nascidos Vivos, SINASC) and 14 population-based cancer registries (PBCRs) was established. Four controls per case were chosen randomly from the SINASC data set. Tumors were classified as central nervous system (CNS), non-CNS embryonal, and other tumors ("miscellaneous"). Adjustments were made for potential confounders (maternal age, mode of delivery, maternal education, birth order, gestational age, sex, and geographic region). Odds ratios (ORs) with 95% confidence intervals (CIs) were computed using unconditional logistic regression analysis. In a trend analysis, for every 500 g of additional birth weight, the crude OR was 1.12 (CI: 1.00-1.24) and the adjusted OR was 1.02 (CI: 0.90-1.16) for all tumors. For every 1 000 g of additional birth weight, the crude OR was 1.25 (CI: 1.00-1.55) and the adjusted OR was 1.04 (CI: 0.82-1.34) for all tumors. Among children diagnosed after reaching the age of 3 years, in the miscellaneous tumor category, the OR was significantly increased for every additional 500 g and 1 000 g of birth weight. The study data suggested that increased birth weight was associated with childhood solid tumor development, especially among children more than 3 years old with "miscellaneous" tumors.

  20. Cytogenetics of Post-Irradiation Mouse Leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Wald, N.; Pan, S.; Upton, A.; Brown, R. [Graduate School of Public Health, University of Pittsburgh, PA (United States); Oak Ridge National Laboratory, Oak Ridge, TN (United States)

    1969-11-15

    The interrelationship between radiation, cytogenetic abnormalities, and viruses in leukaemogenesis has been studied in the RF/Un mouse which develops a high incidence of granulocytic leukaemia on radiation exposure. A virus-like agent has been demonstrated in such leukaemic animals and the disease has been transmitted by passage of apparently acellular materials from irradiated primary animals to normal recipients. Pilot cytogenetic studies revealed consistent abnormal chromosome markers and modal shifts in both irradiated leukaemic animals and in non-irradiated animals developing leukaemia after passage injection. To define better the relationship between consistent bone-marrow chromosome aberrations and postirradiation primary and passaged leukaemia, 100 RF/Un mice were studied which were irradiated with 300 R of 250-kVp X-rays at 100 weeks of age and subsequently developed leukaemia. Eighty-seven had granulocytic leukaemia and in 72 of these, bone-marrow cytogenetic abnormalities were found. The distribution of-numerical and structural chromosome aberrations in 3225 cells studied are reviewed in derail. The correlation of specific aberrations to clinical and histopathologic findings has been attempted: Sequential passages of apparently cell-free material from the post-irradiation leukaemic mice into unirradiated RE/Un recipients and subsequent passages from leukaemic recipients were performed to observe the evolution of any initial chromosome markers and shifts in modal chromosome number in the passage generations. Two-hundred-thirty-six mice were inoculated with the material obtained either from primary post-irradiation leukaemic mice or from serially-passaged leukaemia cases. In the most extensive passaged line, 22 transfer generations containing 129 leukaemic mice were examined by clinical, histopathologic, -haematologic and cytogenetic procedures. Evolution of abnormal chromosome modes from 41 in the early passages to 39 chromosomes consistently after the 4

  1. Solitary fibrous tumor arising in an intrathoracic goiter

    DEFF Research Database (Denmark)

    Larsen, Stine Rosenkilde; Godballe, Christian; Krogdahl, Annelise

    2010-01-01

    . CONCLUSION: The histological appearance and immunohistochemical reaction pattern of SFT is characteristic. The entity should be considered when dealing with a spindle cell lesion in the thyroid gland. All cases of this site of origin reported have had a benign clinical course. As only a small number of cases......BACKGROUND: Solitary fibrous tumor (SFT) is a rare spindle cell tumor most often found in the mediastinal pleura. Nineteen cases of SFT arising in the thyroid gland have been reported. We report a case of SFT of the thyroid gland with immunohistochemical and cytogenetic investigation. SUMMARY: A 58...

  2. Array comparative genomic hybridization and cytogenetic analysis in pediatric acute leukemias

    Science.gov (United States)

    Dawson, A.J.; Yanofsky, R.; Vallente, R.; Bal, S.; Schroedter, I.; Liang, L.; Mai, S.

    2011-01-01

    Most patients with acute lymphocytic leukemia (all) are reported to have acquired chromosomal abnormalities in their leukemic bone marrow cells. Many established chromosome rearrangements have been described, and their associations with specific clinical, biologic, and prognostic features are well defined. However, approximately 30% of pediatric and 50% of adult patients with all do not have cytogenetic abnormalities of clinical significance. Despite significant improvements in outcome for pediatric all, therapy fails in approximately 25% of patients, and these failures often occur unpredictably in patients with a favorable prognosis and “good” cytogenetics at diagnosis. It is well known that karyotype analysis in hematologic malignancies, although genome-wide, is limited because of altered cell kinetics (mitotic rate), a propensity of leukemic blasts to undergo apoptosis in culture, overgrowth by normal cells, and chromosomes of poor quality in the abnormal clone. Array comparative genomic hybridization (acgh—“microarray”) has a greatly increased genomic resolution over classical cytogenetics. Cytogenetic microarray, which uses genomic dna, is a powerful tool in the analysis of unbalanced chromosome rearrangements, such as copy number gains and losses, and it is the method of choice when the mitotic index is low and the quality of metaphases is suboptimal. The copy number profile obtained by microarray is often called a “molecular karyotype.” In the present study, microarray was applied to 9 retrospective cases of pediatric all either with initial high-risk features or with at least 1 relapse. The conventional karyotype was compared to the “molecular karyotype” to assess abnormalities as interpreted by classical cytogenetics. Not only were previously undetected chromosome losses and gains identified by microarray, but several karyotypes interpreted by classical cytogenetics were shown to be discordant with the microarray results. The

  3. Strategy of diagnosis and treatment for pediatric solid tumor patients using FDG-PET

    International Nuclear Information System (INIS)

    Hosono, Ako; Watanabe, Atsuko; Tsuji, Naoko; Kawamoto, Hiroshi; Makimoto, Atsushi; Tateishi, Ukihide; Terauthi, Takashi

    2006-01-01

    Usefulness of FDG-PET (18F-deoxyglucose PET) was investigated in diagnosis and therapeutic planning of childhood and adolescence malignant solid tumors. Evidence was based on 46 patients (25 males) of ages 5-30 y, involving those with rhabdomyosarcoma (17 cases), Ewing's sarcoma (13), osteosarcoma (5), neuroblastoma (4), Wilms' tumor (2), germinoma (2), and each 1 case of ganglioblastoma, retinoblastoma and hepatoblastoma. In total, they underwent 104 FDG-PET examinations for diagnosis before and during treatment in authors' hospital in the period from January 2005 to February 2006. Evaluations were done with the standard uptake value (SUV, 1 x 1 cm ROI of abnormally high distribution area of radioactivity in the lesion/FDG dose/kg body wt.), by recurrence, by early detection of exacerbation and by follow up of residual tumors, of which typical image findings were herein presented. From the aspects of the present purposes, it was concluded that FDG-PET had advantages of high resolution, short imaging time, quantitative diagnosis (SUV) as well as the tumor detection, and had defects of difficulty of detection of tumors of <1 cm size, of distribution to normal or benign tissues and of difficulty of central nervous system (CNS) imaging. (T.I.)

  4. Cytogenetic, clinical, and cytologic characteristics of radiotherapy-related leukemias

    International Nuclear Information System (INIS)

    Philip, P.; Pedersen-Bjergaard, J.

    1988-01-01

    From 1978 to 1985, we observed eight cases of acute nonlymphocytic leukemia or preleukemia, three cases of acute lymphoblastic leukemia, and three cases of chronic myeloid leukemia in patients previously treated exclusively with radiotherapy for other tumor types. The latent period from administration of radiotherapy to development of leukemia varied between 12 and 243 months. Clonal chromosome aberrations reported previously as characteristic of acute nonlymphocytic leukemia following therapy with alkylating agents were observed in three of the eight patients with acute nonlymphocytic leukemia (5q- and -7) and in two of the three patients with acute lymphoblastic leukemia (-7 and 12p-). All three patients with radiotherapy-related chronic myeloid leukemia presented a t(9;22)(q34;q11). The results suggest that cytogenetic characteristics may reflect the etiology in radiation-induced acute leukemias, whereas radiation-related chronic myeloid leukemia does not seem to differ chromosomally from de novo cases of the disease

  5. Pneumothorax as a complication of combination antiangiogenic therapy in children and young adults with refractory/recurrent solid tumors.

    Science.gov (United States)

    Interiano, Rodrigo B; McCarville, M Beth; Wu, Jianrong; Davidoff, Andrew M; Sandoval, John; Navid, Fariba

    2015-09-01

    Antiangiogenic agents show significant antitumor activity against various tumor types. In a study evaluating the combination of sorafenib, bevacizumab, and low-dose cyclophosphamide in children with solid tumors, an unexpectedly high incidence of pneumothorax was observed. We evaluated patient characteristics and risk factors for the development of pneumothorax in patients receiving this therapy. Demographics, clinical course, and radiographic data of 44 patients treated with sorafenib, bevacizumab and cyclophosphamide were reviewed. Risk factors associated with the development of pneumothorax were analyzed. Pneumothorax likely related to study therapy developed in 11 of 44 (25%) patients of whom 33 had pulmonary abnormalities. Median age of patients was 14.7 years (range, 1.08-24.5). Histologies associated with pneumothorax included rhabdoid tumor, synovial sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, and renal cell carcinoma. Cavitation of pulmonary nodules in response to therapy was associated with pneumothorax development (Ppneumothorax was 5.7 weeks (range, 2.4-31). The development of cavitary pulmonary nodules in response to therapy is a risk factor for pneumothorax. As pneumothorax is a potentially life-threatening complication of antiangiogenic therapy in children with solid tumors, its risk needs to be evaluated when considering this therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

    Directory of Open Access Journals (Sweden)

    Hyun-Kyoung Kim

    Full Text Available BACKGROUND: The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs, which are abundant in solid tumors, can be utilized for identification of rearranged ends. METHOD: As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP microarray method entailing CNB-region refinement by competitor DNA. RESULT: Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9% were identified, and two polymerase chain reaction (PCR-amplifiable rearrangements were obtained in six cases (66.7%. And significantly, TNGS-CNB, with its high positive identification rate (82.6% of PCR-amplifiable rearrangements at candidate sites (19/23, just from filtering of aligned sequences, requires little effort for validation. CONCLUSION: Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

  7. Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

    Science.gov (United States)

    Kim, Hyun-Kyoung; Park, Won Cheol; Lee, Kwang Man; Hwang, Hai-Li; Park, Seong-Yeol; Sorn, Sungbin; Chandra, Vishal; Kim, Kwang Gi; Yoon, Woong-Bae; Bae, Joon Seol; Shin, Hyoung Doo; Shin, Jong-Yeon; Seoh, Ju-Young; Kim, Jong-Il; Hong, Kyeong-Man

    2014-01-01

    The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS) for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs), which are abundant in solid tumors, can be utilized for identification of rearranged ends. As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB) in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP) microarray method entailing CNB-region refinement by competitor DNA. Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9%) were identified, and two polymerase chain reaction (PCR)-amplifiable rearrangements were obtained in six cases (66.7%). And significantly, TNGS-CNB, with its high positive identification rate (82.6%) of PCR-amplifiable rearrangements at candidate sites (19/23), just from filtering of aligned sequences, requires little effort for validation. Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

  8. Oral mucositis in patients treated with chemotherapy for solid tumors: a retrospective analysis of 150 cases

    NARCIS (Netherlands)

    Raber-Durlacher, J. E.; Weijl, N. I.; Abu Saris, M.; de Koning, B.; Zwinderman, A. H.; Osanto, S.

    2000-01-01

    The incidence and the severity of chemotherapy-associated oral mucositis were determined in a retrospective analysis of 150 patients with various solid tumors. In addition, possible risk factors for the development of mucositis were identified. Patients were treated with chemotherapeutic regimens

  9. New cytogenetically visible copy number variant in region 8q21.2

    Directory of Open Access Journals (Sweden)

    Ewers Elisabeth

    2011-01-01

    Full Text Available Abstract Background Cytogenetically visible unbalanced chromosomal abnormalities (UBCA, reported for >50 euchromatic regions of almost all human autosomes, are comprised of a few megabases of DNA, and carriers are in many cases clinically healthy. It may be speculated, that some of the UBCA may be similar or identical to copy number variants (CNV of the human genome. Results Here we report on a yet unreported cytogenetically visible copy number variant (CNV in the long arm of chromosome 8, region 8q21.2, detected in three unrelated clinically healthy carriers. Conclusion The first description of a cytogenetically visible CNV/UBCA in 8q21.2 shows that banding cytogenetics is far from being outdated. It is a cost efficient, up-to-date method for a single cell specific overview on the whole genome, still prepared to deliver unexpected findings.

  10. Cytogenetic abnormalities in Tunisian women with premature ovarian failure.

    Science.gov (United States)

    Ayed, Wiem; Amouri, Ahlem; Hammami, Wajih; Kilani, Olfa; Turki, Zinet; Harzallah, Fatma; Bouayed-Abdelmoula, Nouha; Chemkhi, Imen; Zhioua, Fethi; Slama, Claude Ben

    2014-12-01

    To identify the distribution of chromosome abnormalities among Tunisian women with premature ovarian failure (POF) referred to the department of Cytogenetic at the Pasteur Institute of Tunis (Tunisia), standard cytogenetic analysis was carried out in a total of 100 women younger than 40 affected with premature ovarian failure. We identified 18 chromosomal abnormalities, including seven X-numerical anomalies in mosaic and non-mosaic state (45,X; 47,XXX), four sex reversal, three X-structural abnormalities (terminal deletion and isochromosomes), one autosomal translocation and one supernumerary marker. The overall prevalence of chromosomal abnormalities was 18% in our cohort. X chromosome aneuploidy was the most frequent aberration. This finding confirms the essential role of X chromosome in ovarian function and underlies the importance of cytogenetic investigations in the routine management of POF. Copyright © 2014 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  11. Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.

    Science.gov (United States)

    Sun, Jihong; Zhang, Shizheng; Jiang, Shaojie; Bai, Weixian; Liu, Fei; Yuan, Hong; Ji, Jiansong; Luo, Jingfeng; Han, Guocan; Chen, Lumin; Jin, Yin; Hu, Peng; Yu, Lei; Yang, Xiaoming

    2016-09-01

    Magnetic resonance (MR) contrast agents focusing on special functions are required to improve cancer diagnosis, particularly in the early stages. Here, we designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a tumor-absorbable nanoparticle contrast agent for the histological confirmation of MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo via direct uptake of this contrast agent, which displayed reasonable T1 relaxivity and no significant cytotoxicity at the experimental concentrations in human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In vitro cell uptake experiments demonstrated that contrast agent absorption by the two types of cancer cells was concentration-dependent in the safe concentration range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more significant enhancement at the tumor site compared with the infusion of Gd-DTPA in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots distributed from the tumor capsule into the tumor. This study establishes the "proof-of-principle" of a new MRI technique wherein colorectal tumors are enhanced via direct absorption or uptake of the nanoparticle contrast agent.

  12. Prenatal cytogenetic diagnosis after transabdominal chorionic villus sampling in the first trimester

    DEFF Research Database (Denmark)

    Therkelsen, A J; Jensen, P K; Hertz, Jens Michael

    1988-01-01

    First trimester prenatal cytogenetic diagnosis was attempted in 350 pregnancies after transabdominal chorionic villus sampling. The cytogenetic investigation was performed using both a short-term method (24 h incubation) and cell culture. Adequate samples were obtained in 99.1 per cent and in all...... of 181 cases where the 24 h incubation revealed a male karyotype. Studies of culture morphology showed that colonies of convoluted cells may serve as a marker for contamination with maternal cells in culture. For the present, we recommend using a short-term method as well as cell culture for cytogenetic...

  13. MOLECULAR CYTOGENETICS OF LYMPHOMA. WHERE DO WE STAND IN 2010?

    OpenAIRE

    2011-01-01

    Abstract Since approximately 20 years most malignant lymphomas are classified by the recognition of clinico-pathologic entities, each with its own combination of clinical, morphologic, immunophenotypic and molecular genetic characteristics. Obviously, in many instances molecular cytogenetics is of great help for classification and in some lymphomas it is even a prerequisite. Molecular cytogenetic alterations can be detected by a large variety of techniques, ranging from conventiona...

  14. Cytogenetic and molecular profile of endometrial stromal sarcoma.

    Science.gov (United States)

    Micci, Francesca; Gorunova, Ludmila; Agostini, Antonio; Johannessen, Lene E; Brunetti, Marta; Davidson, Ben; Heim, Sverre; Panagopoulos, Ioannis

    2016-11-01

    Recent cytogenetic and molecular investigations have improved our understanding of endometrial stromal tumors, including sarcomas (ESS), and helped redefine their classification into more pathogenetically meaningful categories. Because much more can be gained through such studies, we add information on another 22 ESS examined by karyotyping, PCR analysis, expression array analysis, and transcriptome sequencing. In spite of the known preference for certain pathogenetic pathways, we found considerable genetic heterogeneity in high-grade (HG) as well as in low-grade (LG) ESS. Not all HG tumors showed a YWHAE-NUTM chimeric transcript and as many as six LGESS showed no hitherto known ESS-related fusions. Among the transcripts identified by transcriptome sequencing and verified by Sanger sequencing, new variants of ZC3H7-BCOR and its reciprocal BCOR-ZC3H7 were identified as was involvement of the CREBBP and MLLT4 genes (both well known leukemia-related genes) in two new fusions. FISH analysis identified a known EPC1-PHF1 fusion which led to the identification of a new variant at the molecular level. The fact that around 70 genes were found differentially expressed, by microarray analysis, when comparing LGESS showing ESS-related fusions with LGESS without such transcripts, underscores the biochemical importance of the observed genetic heterogeneity and hints that new subgroups/entities in LGESS still remain undiscovered. © 2016 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc. © 2016 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.

  15. Polymodification. Short-term hyperglycemia and local hyperthermia in hypoxiradiotherapy of transplantable solid tumors

    International Nuclear Information System (INIS)

    Kozin, S.V.; Krimker, V.M.; Yarmonenko, S.P.

    1984-01-01

    Application possibilities of hyperglycemia and local hyperthermia in combination with hypoxiradiotherapy of solid tumors, have been evaluated. The experiments conducted have shown the great possibilities of combined use of radiation, hyperglycemia, hyperthermia, for selective affection of tumours, and application of gaseous hypoxia during irradiation - for simultaneous principal protection of normal tissues. Interaction of all the agents will undoubtedly require a versatile study to develop the optimum regimes of action

  16. Birth weight and risk of childhood solid tumors in Brazil: a record linkage between population-based data sets

    Directory of Open Access Journals (Sweden)

    Neimar de Paula Silva

    2017-04-01

    Full Text Available ABSTRACT Objective To analyze the relationship between the development of childhood solid tumors and 1 birth weight and 2 fetal growth, using two Brazilian population-based data sets. Methods A case–cohort study was performed using two population-based data sets, and linkage between the Live Birth Information System (Sistema de Informação sobre Nascidos Vivos, SINASC and 14 population-based cancer registries (PBCRs was established. Four controls per case were chosen randomly from the SINASC data set. Tumors were classified as central nervous system (CNS, non-CNS embryonal, and other tumors (“miscellaneous”. Adjustments were made for potential confounders (maternal age, mode of delivery, maternal education, birth order, gestational age, sex, and geographic region. Odds ratios (ORs with 95% confidence intervals (CIs were computed using unconditional logistic regression analysis. Results In a trend analysis, for every 500 g of additional birth weight, the crude OR was 1.12 (CI: 1.00–1.24 and the adjusted OR was 1.02 (CI: 0.90–1.16 for all tumors. For every 1 000 g of additional birth weight, the crude OR was 1.25 (CI: 1.00–1.55 and the adjusted OR was 1.04 (CI: 0.82–1.34 for all tumors. Among children diagnosed after reaching the age of 3 years, in the miscellaneous tumor category, the OR was significantly increased for every additional 500 g and 1 000 g of birth weight. Conclusions The study data suggested that increased birth weight was associated with childhood solid tumor development, especially among children more than 3 years old with “miscellaneous” tumors.

  17. A short introduction to cytogenetic studies in mammals with reference to the present volume.

    Science.gov (United States)

    Graphodatsky, A; Ferguson-Smith, M A; Stanyon, R

    2012-01-01

    Genome diversity has long been studied from the comparative cytogenetic perspective. Early workers documented differences between species in diploid chromosome number and fundamental number. Banding methods allowed more detailed descriptions of between-species rearrangements and classes of differentially staining chromosome material. The infusion of molecular methods into cytogenetics provided a third revolution, which is still not exhausted. Chromosome painting has provided a global view of the translocation history of mammalian genome evolution, well summarized in the contributions to this special volume. More recently, FISH of cloned DNA has provided details on defining breakpoint and intrachromosomal marker order, which have helped to document inversions and centromere repositioning. The most recent trend in comparative molecular cytogenetics is to integrate sequencing information in order to formulate and test reconstructions of ancestral genomes and phylogenomic hypotheses derived from comparative cytogenetics. The integration of comparative cytogenetics and sequencing promises to provide an understanding of what drives chromosome rearrangements and genome evolution in general. We believe that the contributions in this volume, in no small way, point the way to the next phase in cytogenetic studies. Copyright © 2012 S. Karger AG, Basel.

  18. Value of amniocentesis versus fetal tissue for cytogenetic analysis in cases of fetal demise.

    Science.gov (United States)

    Bryant Borders, Ann E; Greenberg, Jessica; Plaga, Stacey; Shepard-Hinton, Megan; Yates, Carin; Elias, Sherman; Shulman, Lee P

    2009-01-01

    Use of fetal tissue for cytogenetic analysis in cases of second- and third-trimester fetal demise frequently results in unacceptably high failure rates. We reviewed our ongoing use of amniocentesis prior to uterine evacuation to determine if this provided a better source of cells for cytogenetic analysis. We compared cytogenetic results using fetal tissues obtained following uterine evacuation to our ongoing use of amniotic fluid cell obtained by transabdominal amniocentesis prior to uterine evacuation from 2003 to 2008. In 49 of the 63 cases evaluated by fetal tissue biopsies performed after uterine evacuation, a karyotypic analysis was obtained (77.8%). Among the 38 cases evaluated by amniocentesis, an amniotic fluid sample and fetal cytogenetic results were obtained in all 38 (100%) cases. Our findings indicate that amniocentesis is a more reliable source of cytogenetic information than fetal tissue in cases of second- and third-trimester fetal demise.

  19. Cytogenetic characterization of Encyclia caximboensis cultivated in vitro (Orchidaceae)

    OpenAIRE

    Gizelly Mendes Silva; Tatiane Lemos Varella; Kaliane Maximiliano Cruz; Ilio Fealho Carvalho; Isane Vera Karsburg; Maurecilne Lemes Silva

    2015-01-01

    Encyclia caximboensis is an Amazonian species endemic to the Serra do Cachimbo, which is located between the northern of the Mato Grosso state and the southern part of Para state. Studies reporting in vitro cultivation and cytogenetic characterization of this species are still scarce. Therefore, the objective of this work was to determine the cytogenetic characteristics and to identify the nucleolar organizer regions (NORs) of the species E. Caximboensis, cultivated in vitro. Seeds of E. caxi...

  20. Cytogenetic Nomenclature: Changes in the ISCN 2013 Compared to the 2009 Edition.

    Science.gov (United States)

    Simons, A; Shaffer, L G; Hastings, R J

    2013-01-01

    The latest edition of the International System for Human Cytogenetic Nomenclature, ISCN 2013, has recently been published following a thorough revision of the 2009 issue and the incorporation of suggestions from the community by the current standing committee. This review will highlight the multiple nomenclature changes in the respective chapters of the 2013 version compared to the previous version of the ISCN published in 2009. These highlights are meant as a guide for the cytogeneticist to assist in the transition in the use of this updated nomenclature for describing cytogenetic and molecular cytogenetic findings in both clinical and research reports.

  1. Acute myeloid leukaemia: expression of MYC protein and its association with cytogenetic risk profile and overall survival.

    Science.gov (United States)

    Mughal, Muhammad Kashif; Akhter, Ariz; Street, Lesley; Pournazari, Payam; Shabani-Rad, Meer-Taher; Mansoor, Adnan

    2017-09-01

    Acute myeloid leukaemia (AML) is a clinically aggressive disease with marked genetic heterogeneity. Cytogenetic abnormalities provide the basis for risk stratification into clinically favourable, intermediate, and unfavourable groups. There are additional genetic mutations, which further influence the prognosis of patients with AML. Most of these result in molecular aberrations whose downstream target is MYC. It is therefore logical to study the relationship between MYC protein expression and cytogenetic risk groups. We studied MYC expression by immunohistochemistry in a large cohort (n = 199) of AML patients and correlated these results with cytogenetic risk profile and overall survival (OS). We illustrated differential expression of MYC protein across various cytogenetic risk groups (p = 0.03). Highest expression of MYC was noted in AML patients with favourable cytogenetic risk group. In univariate analysis, MYC expression showed significant negative influence of OS in favourable and intermediate cytogenetic risk group (p = 0.001). Interestingly, MYC expression had a protective effect in the unfavourable cytogenetic risk group. In multivariate analysis, while age and cytogenetic risk group were significant factors influencing survival, MYC expression by immunohistochemistry methods also showed some marginal impact (p = 0.069). In conclusion, we have identified differential expression of MYC protein in relation to cytogenetic risk groups in AML patients and documented its possible impact on OS in favourable and intermediate cytogenetic risk groups. These preliminary observations mandate additional studies to further investigate the routine clinical use of MYC protein expression in AML risk stratification. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors: A Randomized Clinical Trial.

    Science.gov (United States)

    Pramanik, Raja; Agarwala, Sandeep; Gupta, Yogendra Kumar; Thulkar, Sanjay; Vishnubhatla, Sreenivas; Batra, Atul; Dhawan, Deepa; Bakhshi, Sameer

    2017-09-01

    Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence. To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy. A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options. One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression. The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points. A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than

  3. Investigation of the effects of long-term infusion of 125I-iododeoxyuridine on tumor growth in mice (solid mouse tumor sarcoma-180)

    International Nuclear Information System (INIS)

    Wirtz, F.

    1987-05-01

    The present experiments were designed to test the therapeutic qualification of 125 I incorporated in DNA of tumor cells. The tumor-host system used was the solid mouse tumor sarcoma-180 growing on female albino mice (NMRI). A device was built which makes it possible to intravenously infuse tumor bearing mice with solutions of 125 IUdR for several weeks. Three or, respectively, 5 days before the onset of the infusions the mice were inocculated into the right hind leg with 3x10 5 tumor cells in 0.1 ml physiological salt solution. The total activity administered per mouse was 100 μCi infused during a period of 10 days. After termination of the infusions tumor sizes and retained radioactivities were measured every 5 days until death of the animals occured. In comparison with tumors of control animals tumors of mice infused with 125 IUdR showed a mean retardation in growth of about 27% of the volumes of control tumors during the total period of post-infusion observation (25 days). Extension of life expectancy and an increase of the rate of final tumor regression did not occur. Likewise, no significant differences were observed between tumors which were 3 or 5 days old on the first day of infusion. After termination of the infusions the residual whole-body radioactivity per mouse was about 1% of the total activity infused per animal. This was in good agreement with calculations considering rates of incorporation and excretion and confirmed earlier assumptions that only about 5% of the administered IUdR is incorporated initially. The number further confirmed that, during the first 10 days after incorporation, the daily loss of activity - due to cell death - is about 30%. Control animals without tumors showed a faster decrease of incorporated activity or, respectively, loss of cells than tumor bearing mice. This difference could in part be explained by an exhaution of the short-lived cell populations of the reticulo-endothelial system of tumor bearing animals. (orig

  4. Antitumor Effect of Selenium and Modified Pectin Nano Particles and Gamma Radiation on Ehrilch Solid Tumor in Female Mice

    International Nuclear Information System (INIS)

    Mansour, S. Z.; Anis, L.M.; EI- Batal, A.I.

    2010-01-01

    Selenium nano particle (Nano- Se) is a novel Se species with novel biological activities with low toxicity. The aim of the present work was to evaluate the antitumor activity of a novel Nano- Se compound with or without gamma irradiation of female mice. Selenium size- controlled Nano-Se was prepared by a simple method by adding modified pectin to the selenious acid and ascorbic acid. The antitumor activity of Selenium and Modified Pectin Nano Particles (Se-Mp- NPs) were evaluated against Ehrilch ascites carcinoma (In vitro) and Ehrilch solid tumor model (In vivo). The antioxidant states of the novel compound were assessed measuring parameters in blood and tumor tissue of female mice. Malonaldehydoyl (MDA) end product of lipid peroxidation was evaluated in plasma and tumor tissue. Glutathione -S- transferase (GST) and cytochrome P450 (Cyto P450) were determined in tumor tissue homogenate. Tumor necrosis factor alpha (TNF- a) concentration and interleukin 10 (IL- 10) concentrations was evaluated in plasma of female mice. The effect of tumor inoculation and different treatments on liver enzymes (ALT and AST) and kidney Function (urea and creatinine) were detected in the plasma of animals. Apoptosis was shown and estimated in tumor tissue of animals histopathological of tumor in different groups of mice were examined. Ehrilch solid tumor induced a significant increase in MDA content, GSH-Px and GST activities level and in the amount of metabolites of CYP 450. Moreover, a significant decrease was observed in GSH content, SOD activity level in the tumor tissue, INF- a concentration, IL- 10 concentration in the plasma. Also, a significant alteration in kidney and liver functions was occurred as compared to control group. The results showed a significant antitumor activity of selenium and Modified Pectin Nano Particles (Se-Mp- NPs) at the concentration 2.25 μg / ml was 70%

  5. Roberts syndrome: clinical and cytogenetic aspects

    OpenAIRE

    Mann, N P; Fitzsimmons, J; Fitzsimmons, E; Cooke, P

    1982-01-01

    Roberts syndrome is reported in two sibs of consanguineous parents. Both infants had severe tetraphocomelia, facial clefting, and other serious malformations. In addition they were found to have an unusual cytogenetic abnormality with distortion of the normal sister chromatid relationship in many chromosomes.

  6. Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman.

    Science.gov (United States)

    Lestelle, Valentin; de Coster, Claire; Sarran, Anthony; Poizat, Flora; Delpero, Jean-Robert; Raoul, Jean-Luc

    2015-01-01

    We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare.

  7. Calculations in cytogenetic dosimetry by means of the dosgen program

    International Nuclear Information System (INIS)

    Garcia Lima, O.; Zerquera, J.T.

    1996-01-01

    The DOSGEN program sums up the different calculations routing that are more often used in cytogenetic dosimetry. It can be implemented in a compatible IBM PC by cytogenetic experts having a basic knowledge of computing. The programs has been successfully applied using experimental data and its advantages have been acknowledge by Latin American and Asian Laboratories dealing with this medical branch. The program is written in Pascal Language and requires 42 K bytes

  8. Transient mild hyperthermia induces E-selectin mediated localization of mesoporous silicon vectors in solid tumors.

    Directory of Open Access Journals (Sweden)

    Dickson K Kirui

    Full Text Available BACKGROUND: Hyperthermia treatment has been explored as a strategy to overcome biological barriers that hinder effective drug delivery in solid tumors. Most studies have used mild hyperthermia treatment (MHT to target the delivery of thermo-sensitive liposomes carriers. Others have studied its application to permeabilize tumor vessels and improve tumor interstitial transport. However, the role of MHT in altering tumor vessel interfacial and adhesion properties and its relationship to improved delivery has not been established. In the present study, we evaluated effects of MHT treatment on tumor vessel flow dynamics and expression of adhesion molecules and assessed enhancement in particle localization using mesoporous silicon vectors (MSVs. We also determined the optimal time window at which maximal accumulation occur. RESULTS: In this study, using intravital microscopy analyses, we showed that temporal mild hyperthermia (∼1 W/cm(2 amplified delivery and accumulation of MSVs in orthotopic breast cancer tumors. The number of discoidal MSVs (1000×400 nm adhering to tumor vasculature increased 6-fold for SUM159 tumors and 3-fold for MCF-7 breast cancer tumors. By flow chamber experiments and Western blotting, we established that a temporal increase in E-selectin expression correlated with enhanced particle accumulation. Furthermore, MHT treatment was shown to increase tumor perfusion in a time-dependent fashion. CONCLUSIONS: Our findings reveal that well-timed mild hyperthermia treatment can transiently elevate tumor transport and alter vascular adhesion properties and thereby provides a means to enhance tumor localization of non-thermally sensitive particles such as MSVs. Such enhancement in accumulation could be leveraged to increase therapeutic efficacy and reduce drug dosing in cancer therapy.

  9. Cellular Biochemistry and Cytogenetics in a Rat Lung Tumor Model

    Science.gov (United States)

    1984-10-01

    lung tumor system the specific aims are: 1. To conduct studies of the effect of 3-methylchlanthrene (MCA) on DNA synthesis and cell proliferation in...alkylation of nucleic acids of the rat by N-methyl-N- nitrosourea , dimethylnitrosamine, dimethylsulfate, and methylmethanesulfonate. Biochem. J. 110:39-47

  10. Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Xiaonan Zhang

    2015-11-01

    Full Text Available The disorganized nature of tumor vasculature results in the generation of microenvironments characterized by nutrient starvation, hypoxia and accumulation of acidic metabolites. Tumor cell populations in such areas are often slowly proliferating and thus refractory to chemotherapeutical drugs that are dependent on an active cell cycle. There is an urgent need for alternative therapeutic interventions that circumvent growth dependency. The screening of drug libraries using multicellular tumor spheroids (MCTS or glucose-starved tumor cells has led to the identification of several compounds with promising therapeutic potential and that display activity on quiescent tumor cells. Interestingly, a common theme of these drug screens is the recurrent identification of agents that affect mitochondrial function. Such data suggest that, contrary to the classical Warburg view, tumor cells in nutritionally-compromised microenvironments are dependent on mitochondrial function for energy metabolism and survival. These findings suggest that mitochondria may represent an “Achilles heel” for the survival of slowly-proliferating tumor cells and suggest strategies for the development of therapy to target these cell populations.

  11. Specific genomic regions are differentially affected by copy number alterations across distinct cancer types, in aggregated cytogenetic data.

    Science.gov (United States)

    Kumar, Nitin; Cai, Haoyang; von Mering, Christian; Baudis, Michael

    2012-01-01

    Regional genomic copy number alterations (CNA) are observed in the vast majority of cancers. Besides specifically targeting well-known, canonical oncogenes, CNAs may also play more subtle roles in terms of modulating genetic potential and broad gene expression patterns of developing tumors. Any significant differences in the overall CNA patterns between different cancer types may thus point towards specific biological mechanisms acting in those cancers. In addition, differences among CNA profiles may prove valuable for cancer classifications beyond existing annotation systems. We have analyzed molecular-cytogenetic data from 25579 tumors samples, which were classified into 160 cancer types according to the International Classification of Disease (ICD) coding system. When correcting for differences in the overall CNA frequencies between cancer types, related cancers were often found to cluster together according to similarities in their CNA profiles. Based on a randomization approach, distance measures from the cluster dendrograms were used to identify those specific genomic regions that contributed significantly to this signal. This approach identified 43 non-neutral genomic regions whose propensity for the occurrence of copy number alterations varied with the type of cancer at hand. Only a subset of these identified loci overlapped with previously implied, highly recurrent (hot-spot) cytogenetic imbalance regions. Thus, for many genomic regions, a simple null-hypothesis of independence between cancer type and relative copy number alteration frequency can be rejected. Since a subset of these regions display relatively low overall CNA frequencies, they may point towards second-tier genomic targets that are adaptively relevant but not necessarily essential for cancer development.

  12. Neoplastic Meningitis from Solid Tumors: A Prospective Clinical Study in Lombardia and a Literature Review on Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    A. Silvani

    2013-01-01

    Full Text Available Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC and liposomal antitumor agents (liposomal AraC. Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported.

  13. A Case of Recurrent Solid Pseudopapillary Tumor of the Pancreas with Involvement of the Spleen and Kidney

    OpenAIRE

    Park, Sang Eun; Park, Nam Sook; Chun, Jae Min; Park, Nam Whan; Yang, Young Joon; Yun, Gak Won; Lee, Hyo Jin; Yun, Hwan Jung; Jo, Deog Yeon; Song, Kyu Sang; Kim, Samyong

    2006-01-01

    Solid pseudopapillary tumor of the pancreas (SPTP) is a rare primary pancreatic tumor of an unknown etiology that is usually diagnosed in adolescent girls and young women. Most SPTPs are considered to be benign and only rarely metastasize. We report here on a 27-year old woman with recurrent SPTP with involvement of both the spleen and left kidney at the time of the initial diagnosis, and with aggressive behavior. In July 1995, she was admitted with abdominal discomfort and mass. She underwen...

  14. Review of bayesian statistical analysis methods for cytogenetic radiation biodosimetry, with a practical example

    International Nuclear Information System (INIS)

    Ainsbury, Elizabeth A.; Lloyd, David C.; Rothkamm, Kai; Vinnikov, Volodymyr A.; Maznyk, Nataliya A.; Puig, Pedro; Higueras, Manuel

    2014-01-01

    Classical methods of assessing the uncertainty associated with radiation doses estimated using cytogenetic techniques are now extremely well defined. However, several authors have suggested that a Bayesian approach to uncertainty estimation may be more suitable for cytogenetic data, which are inherently stochastic in nature. The Bayesian analysis framework focuses on identification of probability distributions (for yield of aberrations or estimated dose), which also means that uncertainty is an intrinsic part of the analysis, rather than an 'afterthought'. In this paper Bayesian, as well as some more advanced classical, data analysis methods for radiation cytogenetics are reviewed that have been proposed in the literature. A practical overview of Bayesian cytogenetic dose estimation is also presented, with worked examples from the literature. (authors)

  15. CLASSICAL AND MOLECULAR CYTOGENETIC STUDIES FOR BREEDING AND SELECTION OF TULIPS

    Directory of Open Access Journals (Sweden)

    Aurel Popescu

    2012-12-01

    Full Text Available Due to their extreme popularity as fresh cut flowers and garden plants, and being used extensively for landscaping, tulips undergone a continuous process of selective breeding. For almost nine decades, classical cytogenetic studies, mainly the chromosome counts, have been an important part in the breeding programme for polyploid tulips. The efficiency of breeding is greatly aided by a thorough knowledge of the occurrence of polyploidy in the plant material. While the traditional cytogenetic approaches are still highly useful in selecting polyploids and aneuploids arising from crosses involving (most often parents of different ploidy or from the material subjected to ploidy manipulation, the new strategies for inducing polyploidy in tulips, either in vivo or in vitro, and advances in molecular cytogenetics are expected to allow a significant increase in breeding efficiency. Together with the shortening of breeding cycle, major genetic improvements could be made for specific traits. In this we review the development of cytogenetic studies in tulips, and the most relevant achievements so far, providing an overview of what we consider to be valuable tools for the processes of selective breeding .

  16. Maternal and Birth Characteristics and Childhood Embryonal Solid Tumors: A Population-Based Report from Brazil.

    Directory of Open Access Journals (Sweden)

    Neimar de Paula Silva

    Full Text Available Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics.A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma. Children aged <6 years were selected. Adjustments were made for potential confounders. Odds ratios (OR with 95% confidence intervals (CI were computed by unconditional logistic regression analysis using SPSS.Males, high maternal education level, and birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67-1.01. Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma.This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes.

  17. Clinical, Histopathological and Cytogenetic Prognosticators in Uveal Melanoma - A Comprehensive Review.

    Science.gov (United States)

    Berus, Tomasz; Halon, Agnieszka; Markiewicz, Anna; Orlowska-Heitzman, Jolanta; Romanowska-Dixon, Bozena; Donizy, Piotr

    2017-12-01

    Uveal melanoma is the most prevalent primary intraocular cancer in adults. Although it accounts for only 5% of all melanomas, it is responsible for 13% of deaths due to this type of cancer. A wide variety of therapeutic options of primary tumor is available and progress in its management is noticeable. The fact still remains, however, that almost half of patients develop metastases which may be due to practically undetectable cancer spread present as early as at diagnosis of the primary focus. Metastatic disease is uniformly fatal despite systemic therapy. Prediction of metastasis is crucial for prognosis. It also allows targeting of emerging new therapeutic methods to the appropriate group of patients. The Authors reviewed literature concerning epidemiology and etiopathogenesis of uveal melanoma, and its clinical, histopathological and cytogenetic prognosticators. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Application of 10BSH entrapped transferrin-PEG-liposome to boron neutron-capture therapy (BNCT) for solid tumor

    International Nuclear Information System (INIS)

    Maruyama, K.; Ishida, O.; Iwatsuru, M.; Yanagie, H.; Eriguchi, M.; Kobayashi, H.

    2000-01-01

    The successful treatment of cancer by BNCT requires the selective concentration of 10 B within malignant tumor cells. Intracellular targeting ability and cytotoxic effects of 10 B entrapped TF-PEG-liposomes, in which TF is covalently linked to the distal terminal of PEG chains on the external surface of PEG-liposomes, were examined in Colon 26 tumor-bearing mice. TF-PEG-liposomes readily bound to tumor cells in vivo, and were internalized by receptor-mediated endocytosis. 10 B-PEG-liposomes and 10 B-TF-PEG-liposomes showed prolonged residence time in the circulation and low RES uptake in tumor-bearing mice, resulting in enhanced extravasation of the liposomes into the solid tumor tissue and reached high level of 10 B content in tumor. After thermal neutron irradiation of mice injected with 10 B-PEG-liposomes or 10 B-TF-PEG-liposome, tumor growth was suppressed relative to controls. These results suggest that intravenous injection of 10 B TF-PEG-liposome can increase the intracellular retention of 10 B atoms, which were introduced by receptor mediated endocytosis after binding, causing tumor growth suppression in vivo upon thermal neutron irradiation. (author)

  19. Cytogenetic examination of cosmonauts for space radiation exposure estimation

    Science.gov (United States)

    Snigiryova, G. P.; Novitskaya, N. N.; Fedorenko, B. S.

    2012-08-01

    PurposeTo evaluate radiation induced chromosome aberration frequency in peripheral blood lymphocytes of cosmonauts who participated in flights on Mir Orbital Station and ISS (International Space Station). Materials and methodsCytogenetic examination which has been performed in the period 1992-2008 included the analysis of chromosome aberrations using conventional Giemsa staining method in 202 blood samples from 48 cosmonauts who participated in flights on Mir Orbital Station and ISS. ResultsSpace flights led to an increase of chromosome aberration frequency. Frequency of dicentrics plus centric rings (Dic+Rc) depend on the space flight duration and accumulated dose value. After the change of space stations (from Mir Orbital Station to ISS) the radiation load of cosmonauts based on data of cytogenetic examination decreased. Extravehicular activity also adds to chromosome aberration frequency in cosmonauts' blood lymphocytes. Average doses after the first flight, estimated by the frequency of Dic+Rc, were 227 and 113 mGy Eq for long-term flights (LTF) and 107 and 53 mGy Eq for short-term flights (STF). ConclusionCytogenetic examination of cosmonauts can be applied to assess equivalent doses.

  20. Differentiation of Solid Renal Tumors with Multiparametric MR Imaging.

    Science.gov (United States)

    Lopes Vendrami, Camila; Parada Villavicencio, Carolina; DeJulio, Todd J; Chatterjee, Argha; Casalino, David D; Horowitz, Jeanne M; Oberlin, Daniel T; Yang, Guang-Yu; Nikolaidis, Paul; Miller, Frank H

    2017-01-01

    Characterization of renal tumors is critical to determine the best therapeutic approach and improve overall patient survival. Because of increased use of high-resolution cross-sectional imaging in clinical practice, renal masses are being discovered with increased frequency. As a result, accurate imaging characterization of these lesions is more important than ever. However, because of the wide array of imaging features encountered as well as overlapping characteristics, identifying reliable imaging criteria for differentiating malignant from benign renal masses remains a challenge. Multiparametric magnetic resonance (MR) imaging based on various anatomic and functional parameters has an important role and adds diagnostic value in detection and characterization of renal masses. MR imaging may allow distinction of benign solid renal masses from several renal cell carcinoma (RCC) subtypes, potentially suggest the histologic grade of a neoplasm, and play an important role in ensuring appropriate patient management to avoid unnecessary surgery or other interventions. It is also a useful noninvasive imaging tool for patients who undergo active surveillance of renal masses and for follow-up after treatment of a renal mass. The purpose of this article is to review the characteristic MR imaging features of RCC and common benign renal masses and propose a diagnostic imaging approach to evaluation of solid renal masses using multiparametric MR imaging. © RSNA, 2017.

  1. Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman

    Directory of Open Access Journals (Sweden)

    Valentin Lestelle

    2015-10-01

    Full Text Available We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare.

  2. Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Dai, Wei; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Cheng, Yue; Zheng, Hong; Ngan, Roger Kai Cheong; Ng, Wai Tong; Lee, Anne Wing Mui; Yau, Chun Chung; Lee, Victor Ho Fu; Lung, Maria Li

    2015-01-01

    Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10 −9 ), but was less obvious in other types of solid tumors except for prostate and Epstein–Barr virus (EBV)-positive gastric cancer (FDR<10 −3 ). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection

  3. Cytogenetic diagnosis of Roberts SC phocomelia syndrome: First report from Kashmir

    Directory of Open Access Journals (Sweden)

    Tahir M. Malla

    2016-01-01

    Full Text Available There are several syndromes in which specific mitotic chromosomal abnormalities can be seen, like premature centromere separation, premature (sister chromatid separation, and somatic aneuploidies. Identifications of such specific cytogenetic findings can be the key factor that leads towards the diagnosis of syndromes like Roberts SC phocomelia. The case presented here as Roberts SC phocomelia syndrome was identified as a child with multiple congenital anomalies and dysmorphic features. Conventional cytogenetic analysis of the case revealed premature sister chromatid separation. The premature centromeric separation was also confirmed by C banding analysis of the child. It is the first and the only case of Roberts SC phocomelia diagnosed from this part of the world. The present case report emphasizes the importance of conventional cytogenetics in the diagnosis of such syndromes.

  4. Epidemiology and Outcomes of Bloodstream Infections in Patients With Solid Tumors in a Central American Population at Mexico Hospital, San Jose, Costa Rica

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    Jorge Calvo-Lon

    2017-12-01

    Full Text Available Purpose: Bloodstream infections (BSIs are an important cause of mortality in patients with solid tumors. We conducted a retrospective study to evaluate the epidemiologic profile and mortality of patients with solid tumors who have BSIs and were admitted to Mexico Hospital. This is the first study in Costa Rica and Central America describing the current epidemiologic situation. Methods: We analyzed the infectious disease database for BSIs in patients with solid tumors admitted to Mexico Hospital from January 2012 to December 2014. Epidemiology and mortality were obtained according to microorganism, antibiotic sensitivity, tumor type, and presence of central venous catheter (CVC. Descriptive statistics were used. Results: A total of 164 BSIs were recorded, the median age was 58 years, 103 patients (63% were males, and 128 cases of infection (78% were the result of gram-negative bacilli (GNB. Klebsiella pneumoniae (21%, Escherichia coli (21%, and Pseudomonas aeruginosa (15% were the most common microorganisms isolated. Gram-positive cocci (GPC were found in 36 patients, with the most frequent microorganisms being Staphylococcus aureus (10% and Staphyloccocus epidermidis (6%. With respect to tumor type, BSIs were more frequent in the GI tract (57% followed by head and neck (9% and genitourinary tract (8%. Regarding antibiotic susceptibility, only 17% (GNB expressed extended-spectrum beta-lactamase and 12% (GPC had methicillin resistance. Patients with CVCs (n = 59 were colonized mainly by GNB (78%. Overall the mortality rate at 30 days was about 30%. Conclusion: GNB are the most frequent cause of BSIs in solid tumors and in patients with CVCs. GI cancers had more BSIs than other sites. Mortality and antibiotic sensitivity remained stable and acceptable during this observational period in this Latin American population.

  5. Molecular cytogenetic characterization of a human thyroid cancercell line

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich G.; Tuton, Tiffany B.; Ito, Yuko; Chu, LisaW.; Lu, Chung-Mei; Baumgartner, Adolf; Zitzelsberger, Horst F.; Weier,Jingly F.

    2006-01-04

    The incidence of papillary thyroid carcinoma (PTC) increases significantly after exposure of the head and neck region to ionizing radiation, yet we know neither the steps involved in malignant transformation of thyroid epithelium nor the specific carcinogenic mode of action of radiation. Such increased tumor frequency became most evident in children after the 1986 nuclear accident in Chernobyl, Ukraine. In the twelve years following the accident, the average incidence of childhood PTCs (chPTC) increased over one hundred-fold compared to the rate of about 1 tumor incidence per 10{sup 6} children per year prior to 1986. To study the etiology of radiation-induced thyroid cancer, we formed an international consortium to investigate chromosomal changes and altered gene expression in cases of post-Chernobyl chPTC. Our approach is based on karyotyping of primary cultures established from chPTC specimens, establishment of cell lines and studies of genotype-phenotype relationships through high resolution chromosome analysis, DNA/cDNA micro-array studies, and mouse xenografts that test for tumorigenicity. Here, we report the application of fluorescence in situ hybridization (FISH)-based techniques for the molecular cytogenetic characterization of a highly tumorigenic chPTC cell line, S48TK, and its subclones. Using chromosome 9 rearrangements as an example, we describe a new approach termed ''BAC-FISH'' to rapidly delineate chromosomal breakpoints, an important step towards a better understanding of the formation of translocations and their functional consequences.

  6. 40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

    Science.gov (United States)

    2010-07-01

    ... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis. (a... chosen for the test. Slides shall be coded before microscopic analysis. (f) Data and report—(1) Treatment... cytogenetics tests: Chromosomal analysis. 798.5385 Section 798.5385 Protection of Environment ENVIRONMENTAL...

  7. Pattern of malignant solid tumors and lymphomas in children in the east delta of Egypt: A five-year study.

    Science.gov (United States)

    Hesham, Mervat; Atfy, Mervat; Hassan, Tamer; Abdo, Mohamed; Morsy, Saed; El Malky, Mohamed; Latif, Dalia Abdel

    2014-11-01

    Worldwide, the incidence and mortality rates of childhood cancers differ. The study of incidence patterns and survival rates in childhood malignancies is important in aiding in the planning of treatment centers and in obtaining further information with regard to the etiology. Few studies have investigated the survival in cases of childhood solid tumors in Egypt. The aim of the current study was to evaluate the patterns, frequency and outcome of solid tumors and lymphomas in children admitted to and followed up at the Pediatric Oncology Department of Zagazig University Hospital (Zagazig, Egypt) over a duration of 5 years (January 2004 to December 2008). A retrospective study was conducted, which included 155 children with solid tumors and lymphomas. The medical records were reviewed and the relevant data collected, in particular, those concerning demographic, clinical, histopathological, laboratory and imaging data as well as the treatment plans and outcomes. The mean age of patients was 5.6±3.04 years at diagnosis. The patients comprised 94 males and 61 females. Non-Hodgkin lymphoma (NHL) was the most common tumor type, followed by neuroblastoma (31.0 and 29.0%, respectively). When patients were stratified in terms of age (<5, ≥5 but <10, and ≥10 years), the <5-years-of-age group exhibited the greatest number of patients. Fever, pallor and pain were the most frequent initial clinical presentations among the patients and stage II was the most common stage (39.1%) followed by stage IV, III and I (35.0, 20.3 and 5.6% respectively). The overall 5-year survival rate in the study group was 66.7%. The survival rate was significantly higher in patients with Wilm's tumor and Hodgkin lymphoma, followed by NHL (92.0, 88.0 and 72.0%, respectively; P<0.001), while the mortality rate was significantly higher in patients with neuroblastoma (P<0.001). In conclusion, NHL and neuroblastoma were the most common tumors; the survival rates were higher in patients with Wilm's tumor

  8. Cytogenetic studies in workers with chronic occupational radiation exposure

    International Nuclear Information System (INIS)

    Grynszpan, D.

    1989-01-01

    The technique of chromosomal aberration detection on peripheral lymphocytes blood samples from monazite industry workers was used to study the cytogenetic effect of low chronic radiation doses. Cells from 51 workers and 21 controls were analysed. Cytogenetic data from individuals from different working areas were statistically compared among themselves and with the control group. The possible correlations between chromosomal aberration frequencies and cumulative external dose and working time were investigated. The influence of smoking was also tested. The link to the wives spontaneous abortions was analysed. Our results indicate possible biological effects on this sample of workers. (author)

  9. Solid pseudopapillary tumors of the pancreas: 27 cases from a single institution

    Directory of Open Access Journals (Sweden)

    ZHOU Haiyang

    2013-01-01

    Full Text Available ObjectiveTo summarize the clinicopathologic features and treatment outcomes of solid pseudopapillary tumors (SPTs of the pancreas. MethodsTwenty-seven cases of SPT of the pancreas admitted for treatment to the Peking University Cancer Hospital between September 2008 and September 2012 were retrospectively analyzed. ResultsThe majority of the pancreatic SPT patients were young adults (median age: 29 years old and females (85.2%. All 27 patients were treated with surgical resection using pancreaticoduodenectomy (n=4, duodenum preserving pancreatic tumor resection (n=6, middle pancreatectomy (n=5, distal pancreatectomy (n=5, or distal pancreatectomy plus splenectomy (n=7. The minimum tumor diameter was 1.5 cm, the maximum diameter was 12.0 cm, and the average diameter was 5.4 cm. Twelve patients developed pancreatic leakage and pyrexia following the operation. One patient suffered splenic artery hemorrhage. All 27 patients survived and completed follow-up. Only one patient developed recurrence, which was treated by a second surgical resection, and all other patients showed no clinical signs of recurrence or metastasis. ConclusionSPT of the pancreas has uncertain malignant potential with good prognosis. Radical resection with preservation of the surrounding tissues is an effective and safe treatment for SPT.

  10. A new Bayesian model applied to cytogenetic partial body irradiation estimation

    International Nuclear Information System (INIS)

    Higueras, Manuel; Puig, Pedro; Ainsbury, Elizabeth A.; Vinnikov, Volodymyr A.; Rothkamm, Kai

    2016-01-01

    A new zero-inflated Poisson model is introduced for the estimation of partial body irradiation dose and fraction of body irradiated. The Bayes factors are introduced as tools to help determine whether a data set of chromosomal aberrations obtained from a blood sample reflects partial or whole body irradiation. Two examples of simulated cytogenetic radiation exposure data are presented to demonstrate the usefulness of this methodology in cytogenetic biological dosimetry. (authors)

  11. Role of cytogenetic techniques in biological dosimetry of absorbed radiation

    International Nuclear Information System (INIS)

    Rao, B.S.

    2016-01-01

    In most of the radiation accidents, physical dosimetric information is rarely available. Further, most of the accidental exposures are non-uniform involving either partial body or localized exposure to significant doses. In such situations, physical dosimetry does not provide reliable dose estimate. It has now been realized that biological dosimetric techniques can play an important role in the assessment of absorbed dose. In recent years, a number of biological indicators of radiation have been identified. These include the kinetics of onset and persistence of prodromal syndromes (radiation sickness), cytogenetic changes in peripheral blood lymphocytes, hematological changes, biochemical indicators, ESR spectroscopy of biological samples, induction of gene mutations in red blood cells, cytogenetic and physiological changes in skin and neurophysiological changes. In general, dosimetric information is derived by a combination of several different methods, as they have potential to serve as prognostic indicators. The role of cytogenetic techniques in peripheral blood lymphocytes (PBL) as biological indicators of absorbed radiation is reviewed here

  12. [EVALUATION OF THE CYTOGENETIC AND MUTAGEN-MODIFYING ACTIVITY OF CAFFEINE IN MOUSE BONE MARROW CELLS].

    Science.gov (United States)

    Durnev, A D; Kulakova, A V; Zhanataev, A K; Oganesiants, L A

    2015-01-01

    The cytogenetic and mutagen-modifying activity of caffeine was studied with the method of chromosomal aberrations in bone marrow cells of mice hybrids F1 CBAxC57BL/6. Caffeine per se was administered intragastrically or intraperitoneally, and in combination with mutagens--intragastrically. Mutagens injected intraperitoneally. Caffeine at doses of 10 and 100 mg/kg (single dose) and 10 mg/kg (five days) in parenteral administration and oral introduction failed to possess cytogenetic activity. In combination with mutagens caffeine (1, 10 and 100 mg/kg) had no effect on the cytogenetic activity of dioxydine (200 mg/kg/intraperitoneally) for a single coadministration, five-day pre or five-day coadministration. In combination with other mutagens under the same processing conditions caffeine at doses of 10 and 100 mg/kg significantly increased cytogenetic effects of cyclophosphamide (20 mg/kg) in the pretreatment of the animals and at the dose of 100 mg/kg significantly attenuated the cytogenetic effect of cisplatin (5 mg/kg) in single and repeated co-administration. Thus we have shown the absence of caffeine cytogenetic activity in vivo and showed the multidirectional effect of caffeine in doses far exceeding its daily consumption, to the manifestation ofcytogenetic effects of certain chemical mutagens in some modes of processing animals.

  13. Somatic Genetic Variation in Solid Pseudopapillary Tumor of the Pancreas by Whole Exome Sequencing

    Directory of Open Access Journals (Sweden)

    Meng Guo

    2017-01-01

    Full Text Available Solid pseudopapillary tumor of the pancreas (SPT is a rare pancreatic disease with a unique clinical manifestation. Although CTNNB1 gene mutations had been universally reported, genetic variation profiles of SPT are largely unidentified. We conducted whole exome sequencing in nine SPT patients to probe the SPT-specific insertions and deletions (indels and single nucleotide polymorphisms (SNPs. In total, 54 SNPs and 41 indels of prominent variations were demonstrated through parallel exome sequencing. We detected that CTNNB1 mutations presented throughout all patients studied (100%, and a higher count of SNPs was particularly detected in patients with older age, larger tumor, and metastatic disease. By aggregating 95 detected variation events and viewing the interconnections among each of the genes with variations, CTNNB1 was identified as the core portion in the network, which might collaborate with other events such as variations of USP9X, EP400, HTT, MED12, and PKD1 to regulate tumorigenesis. Pathway analysis showed that the events involved in other cancers had the potential to influence the progression of the SNPs count. Our study revealed an insight into the variation of the gene encoding region underlying solid-pseudopapillary neoplasm tumorigenesis. The detection of these variations might partly reflect the potential molecular mechanism.

  14. Comparison of new nitrosoureas esters with modified steroidal nucleus for cytogenetic and antineoplastic activity.

    Science.gov (United States)

    Hussein, A; Mioglou-Kalouptsi, E; Papageorgiou, A; Karapidaki, I; Iakovidou-Kritsi, Z; Lialiaris, T; Xrysogelou, E; Camoutsis, C; Mourelatos, D

    2007-01-01

    Nitrosourea is decomposed under physiological conditions to react with biological macromolecules by two mechanisms: alkylation (with proteins and nucleic acids) and carbamoylation (with proteins but not nucleic acids). It has been suggested that the alkylating action is responsible for the therapeutic effects of nitrosoureas, and that the carbamoylation activity leads to toxicity effects. In order to reduce systemic toxicity and improve specificity and distribution for cancer therapy, 2-haloethyl nitrosourea has been esterified with modified steroids, which are used as biological platforms for transporting the alkylating agent to the tumor site in a specific manner. The cytogenetic and antineoplastic effect were studied of seven newly synthesized esters of N,N-bis(2-chloroethyl)alanyl carboxyl derivatives with a modified steroidal nucleus (compounds 1-7). As a very sensitive indicator of genotoxicity the Sister Chromatid Exchange (SCE) assay was used and as a valuable marker of cytostatic activity the cell Proliferation Rate Index (PRI) in cultures of normal human lymphocytes was used. The order of magnitude of the cytogenetic activity on a molar basis (15, 30, 120 microM) of the compounds was 7>6>3>5>2>4>1. The most active compound 7 has an enlarged (seven carbon atoms) A ring modified with a lactam group (-NHCO-) with the nitrosourea moiety esterified at position 17 In the group of seven substances a correlation was observed between the magnitude of SCE response and the depression in PRI (r=-O, 65, p6>2>5>4>3>1 and on lympocytic P388 leukemia cells is 7>2>6>5>4>3>1. The present results are in agreement with previous suggestions that the effectiveness in cytogenetic activity may well be correlated with antitumor effects [T/C: 248% for the compound 7 in 250 mg/kg b.w.; T/C: mean survival time of drug-treated animals (T) (excluding long term survivals) vs. corn-oil-treated controls (C)].

  15. Radiation-induced tumors of the nervous system

    International Nuclear Information System (INIS)

    Bernstein, M.; Laperriere, N.

    1991-01-01

    Therapeutic and nontherapeutic ionizing radiation has long been recognized as a putative carcinogenic agent, but the evidence that radiation causes tumors is circumstantial at worst and statistically significant at best. There are no distinct histological, biochemical, cytogenetic, or clinical criteria that can be used to determine if an individual tumor was caused directly by previous irradiation of the anatomic area. Additional supportive evidence for radiation-induced tumors includes a position correlation between radiation dose and tumor incidence (usually in the low dose range) and experimental induction of the same neoplasm in appropriate animal models. even if these criteria are fulfilled, coincidental development of a second tumor can never be discounted in an individual patient, particularly if there is an underlying diathesis to develop multiple tumors of different histology, such as in Recklinghausen's disease, or if there is an strong family history for the development of neoplastic disease. In this paper, the authors critically evaluate the available evidence to support the hypothesis that radiation induces tumors in the nervous system. The current concepts of radiation carcinogenesis are discussed and are followed by a discussion of animal data and clinical experience in humans. Finally, a brief discussion on treatment of radiation-induced nervous system tumors is presented

  16. Use of magnetic resonance imaging to detect neoplastic meningitis: Limited use in leukemia and lymphoma but convincing results in solid tumors

    International Nuclear Information System (INIS)

    Pauls, Sandra; Fischer, Ann-Cathrin; Brambs, Hans-Jürgen; Fetscher, Sebastian; Höche, Wolfram; Bommer, Martin

    2012-01-01

    Background: An early diagnosis of meningitis is important to improve patients’ survival. Data about a direct comparison of cerebrospinal fluid cytology (CSF-cytology) and MRI are very limited. Therefore, the aim of this study was to compare these two diagnostic modalities in diagnosing meningitis in patients with hematopoietic and solid malignancies. Methods: In 68 patients suspicious for neoplastic meningitis, cytology and MRI (1.5 T) was performed. The meningeal, pial or intraparenchymal hyperintense signal or contrast enhancement was correlated to the final CNS diagnosis and to cytology. Results: 44 patients (64.7%) had neoplastic meningitis, 21 patients (30.9%) had non-neoplastic meningitis. The sensitivity to diagnose meningeal disease was 49.2% for MRI and 95.4% for cytology (p < 0.001). In patients with neoplastic meningitis, sensitivity was 45.5% for MRI and 93.2% for cytology (p < 0.001). In patients with infectious meningitis, sensitivity was 57.1% for MRI and 100% for cytology (p = 0.0013). In patients with solid tumors, the sensitivity was 84.6% for both diagnostic methods. The sensitivity for MRI was low in patients with leukemia (20.0%) and lymphoma (37.5%). The positive predictive value (PPV) for MRI to differentiate infectious from neoplastic meningitis was high in patients with infectious meningitis (75.0%), in patients with lymphoma (83.3%), and in patients with solid tumors (72.7%). Ppv was low in patients with leukemia (33.3%). Conclusion: Diagnostic value of MRI for diagnosing meningitis is especially limited in patients with hematopoietic malignancies. MRI better detected leptomeningeal involvement caused by solid tumors than by leukemia or lymphoma. The ppv to specify neoplastic meningitis depends on tumor subtype.

  17. Conventional and molecular cytogenetics of human non-medullary thyroid carcinoma: characterization of eight cell line models and review of the literature on clinical samples

    International Nuclear Information System (INIS)

    Ribeiro, Franclim Ricardo; Meireles, Ana Margarida; Rocha, Ana Sofia; Teixeira, Manuel Rodrigues

    2008-01-01

    Cell lines are often poorly characterized from a genetic point of view, reducing their usefulness as tumor models. Our purpose was to assess the genetic background of eight commonly used human thyroid carcinoma models and to compare the findings with those reported for primary tumors of the gland. We used chromosome banding analysis and comparative genomic hybridization to profile eight non-medullary thyroid carcinoma cell lines of papillary (TPC-1, FB2, K1 and B-CPAP), follicular (XTC-1) or anaplastic origin (8505C, C643 and HTH74). To assess the representativeness of the findings, we additionally performed a thorough review of cytogenetic (n = 125) and DNA copy number information (n = 270) available in the literature on clinical samples of thyroid carcinoma. The detailed characterization of chromosomal markers specific for each cell line revealed two cases of mistaken identities: FB2 was shown to derive from TPC-1 cells, whereas K1 cells have their origin in cell line GLAG-66. All cellular models displayed genomic aberrations of varying complexity, and recurrent gains at 5p, 5q, 8q, and 20q (6/7 cell lines) and losses at 8p, 13q, 18q, and Xp (4/7 cell lines) were seen. Importantly, the genomic profiles were compatible with those of the respective primary tumors, as seen in the meta-analysis of the existing literature data. We provide the genomic background of seven independent thyroid carcinoma models representative of the clinical tumors of the corresponding histotypes, and highlight regions of recurrent aberrations that may guide future studies aimed at identifying target genes. Our findings further support the importance of routinely performing cytogenetic studies on cell lines, to detect cross-contamination mishaps such as those identified here

  18. 42 CFR 493.1276 - Standard: Clinical cytogenetics.

    Science.gov (United States)

    2010-10-01

    ... SERVICES (CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Quality System for Nonwaived Testing Analytic Systems § 493.1276 Standard: Clinical cytogenetics. (a) The laboratory must have policies and procedures for ensuring accurate and reliable patient specimen identification during the process...

  19. Whole-body MRI in comparison to skeletal scintigraphy for detection of skeletal metastases in patients with solid tumors

    International Nuclear Information System (INIS)

    Ghanem, N.; Altehoefer, C.; Winterer, J.; Schaefer, O.; Bley, T.A.; Langer, M.; Kelly, T.; Moser, E.

    2004-01-01

    The aim of this study was to compare the diagnostic efficacy of whole-body magnetic resonance imaging (WB-MRI) as a new and rapid examination technique with skeletal scintigraphy for detection of skeletal metastases from solid tumors. In 129 patients with solid malignant tumors, WB-MRI was performed for individual comparison with skeletal scintigraphy. Examinations were performed with the innovative AngioSURF trademark rolling table with integrated phased array surface coil and coronary TIRM sequences for different body regions. The results for WB-MRI and skeletal scintigraphy were concordant in 81% of the cases, whereby both procedures excluded skeletal metastases in 43%. WB-MRI and skeletal scintigraphy demonstrated skeletal metastases in 38% of the cases, whereby WB-MRI provided more comprehensive findings in 45%. In 12% of the cases, skeletal scintigraphy was superior to WB-MRI and in 19% the findings were discordant, whereby WB-MRI detected skeletal metastases in 15 cases which had not been found on skeletal scintigraphy. In nine cases, skeletal scintigraphy was positive when the WB-MRI was negative. In 60% of the cases, WB-MRI evidenced tumor-associated findings. WB-MRI represents a promising new staging technique for detection of skeletal metastases, which is more sensitive in many cases than skeletal scintigraphy in detecting and assessing the extent of skeletal metastases - and tumor-associated findings that are relevant for treatment strategy. (orig.) [de

  20. Characterization of Compounds with Tumor-Cell Proliferation Inhibition Activity from Mushroom (Phellinus baumii) Mycelia Produced by Solid-State Fermentation.

    Science.gov (United States)

    Zhang, Henan; Shao, Qian; Wang, Wenhan; Zhang, Jingsong; Zhang, Zhong; Liu, Yanfang; Yang, Yan

    2017-04-27

    The inhibition of tumor-cell proliferationbyan organicsolvent extract from the solid-state fermentation of Phellinus baumii mycelia inoculated in rice medium was investigated in vitro. The active compounds inhibiting tumor-cell proliferation were characterized. Results revealed that all (petroleum ether, chloroform, ethyl acetate, and butanol) fractions inhibited tumor-cell proliferation in a dose-dependent fashion. The ethyl acetate extract had the highest inhibitory effecton tumor-cell proliferation, and the butanol fraction had the lowest. Six compounds were isolated and purified from the ethyl acetate extract of P. baumii mycelia by the tandem application of silica-gel column chromatography (SGCC), high-speed countercurrent chromatography (HSCCC), and preparative HPLC. These compounds were identified by NMR and electrospray ionization-mass spectrometry (ESI-MS) spectroscopic methods as ergosterol (RF1), ergosta-7,22-dien-3β-yl pentadecanoate (RF3), 3,4-dihydroxy benzaldehyde(RF6), inoscavinA (RF7), baicalein(RF10), and 24-ethylcholesta-5,22-dien-3β-ol (RF13). To further clarify the activity of these compounds, the cell-proliferation-inhibition tests of these compounds on various tumor cells were carried out and evaluatedin vitro. Results suggested that compounds RF6, RF7, and RF10 had potent inhibition effects on the proliferation of a series of tumor cell lines, including K562, L1210, SW620, HepG2, LNCaP, and MCF-7cells. These findings indicated that P. baumii mycelia produced by solid-state fermentation in rice canbe used to obtain active compounds with the ability to inhibittumor-cell proliferation.

  1. The distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab within solid tumors

    International Nuclear Information System (INIS)

    Lee, Carol M; Tannock, Ian F

    2010-01-01

    Poor distribution of some anticancer drugs in solid tumors may limit their anti-tumor activity. Here we used immunohistochemistry to quantify the distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab in relation to blood vessels and to regions of hypoxia in human tumor xenografts. The antibodies were injected into mice implanted with human epidermoid carcinoma A431 or human breast carcinoma MDA-MB-231 transfected with ERBB2 (231-H2N) that express high levels of ErbB1 and ErbB2 respectively, or wild-type MDA-MB-231, which expresses intermediate levels of ErbB1 and low levels of ErbB2. The distribution of cetuximab in A431 xenografts and trastuzumab in 231-H2N xenografts was time and dose dependent. At early intervals after injection of 1 mg cetuximab into A431 xenografts, the concentration of cetuximab decreased with increasing distance from blood vessels, but became more uniformly distributed at later times; there remained however limited distribution and binding in hypoxic regions of tumors. Injection of lower doses of cetuximab led to heterogeneous distributions. Similar results were observed with trastuzumab in 231-H2N xenografts. In MDA-MB-231 xenografts, which express lower levels of ErbB1, homogeneity of distribution of cetuximab was achieved more rapidly. Cetuximab and trastuzumab distribute slowly, but at higher doses achieve a relatively uniform distribution after about 24 hours, most likely due to their long half-lives in the circulation. There remains poor distribution within hypoxic regions of tumors

  2. MR imaging of malignant ovarian tumors

    International Nuclear Information System (INIS)

    Kim, Jun Ho; Kang, Heoung Keun; Moon, Woong Jae; Seo, Jeong Jin; Kim, Jae Kyu; Choi, Ho Sun

    1994-01-01

    To evaluate MRI findings of malignant ovarian tumors. MRI findings were retrospectively reviewed in 25 patients with surgically confirmed 30 malignant ovarian tumors(common epithelial tumor; 23, sex cord stromal tumor; 2, endo dermal sinus tumor; 1, metastatic tumor; 4). The findings evaluated were the lesion size, solid and/or cystic component, wall thickness, septal thickness, necrosis, invasion of adjacent organ, ascites, and adenopathy. MRI findings of the malignant ovarian tumors were as follow: Size of lesion was 5-35cm(mean 14cm); solid component was present in 80%(24/30); wall thickness was more than 3mm in 90%(27/30); septal thickness was more than 3mm in 70%(21/30); tumor necrosis was present in 40%(12/30%); invasion of adjacent organ was present in 76%(19/25); ascites was present in 56%(14/25); lymphadenopathy was present in 24% (6/25). MRI findings of absence of solid component(6/6), even wall and septal thickness(7/7, 19/19) were found only in epithelial tumors. Uneven septal thickness more than 3mm(7/11) was a predominant MRI findings of non-epithelial tumors. Well-defined cystic lesion within solid component was seen in Krukenberg tumors. Evaluation of the lesion size, internal architecture, invasion of adjacent organ, ascites, and lymphadenopathy in MRI would enable diagnosis of malignant ovarian tumors and could lead to possible differential diagnosis of epithelial tumors from non-epithelial tumors

  3. Comparative cytogenetics of Auchenorrhyncha (Hemiptera, Homoptera): a review

    Science.gov (United States)

    Kuznetsova, Valentina; Aguin-Pombo, Dora

    2015-01-01

    Abstract A comprehensive review of cytogenetic features is provided for the large hemipteran suborder Auchenorrhyncha, which currently contains approximately 42,000 valid species. This review is based on the analysis of 819 species, 483 genera, and 31 families representing all presently recognized Auchenorrhyncha superfamilies, e.i. Cicadoidea (cicadas), Cercopoidea (spittle bugs), Membracoidea (leafhoppers and treehoppers), Myerslopioidea (ground-dwelling leafhoppers), and Fulgoroidea (planthoppers). History and present status of chromosome studies are described, as well as the structure of chromosomes, chromosome counts, trends and mechanisms of evolution of karyotypes and sex determining systems, their variation at different taxonomic levels and most characteristic (modal) states, occurrence of parthenogenesis, polyploidy, B-chromosomes and chromosome rearrangements, and methods used for cytogenetic analysis of Auchenorrhyncha. PMID:26807037

  4. Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country.

    Science.gov (United States)

    Velloso, E D R P; Chauffaille, M L; Peliçario, L M; Tanizawa, R S S; Toledo, S R C; Gaiolla, R D; Lopes, L F

    2013-01-01

    Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome). Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

  5. Sex chromosome aneuploidy in cytogenetic findings of referral patients from south of Iran

    Directory of Open Access Journals (Sweden)

    Najmeh Jouyan

    2012-01-01

    Full Text Available Background: Chromosome abnormality (CA including Sex chromosomes abnormality (SCAs is one of the most important causes of disordered sexual development and infertility. SCAs formed by numerical or structural alteration in X and Y chromosomes, are the most frequently CA encountered at both prenatal diagnosis and at birth. Objective: This study describes cytogenetic findings of cases suspected with CA referred for cytogenetic study. Materials and Methods: Blood samples of 4151 patients referred for cytogenetic analysis were cultured for chromosome preparation. Karyotypes were prepared for all samples and G-Banded chromosomes were analyzed using x100 objective lens. Sex chromosome aneuploidy cases were analyzed and categorized in two groups of Turners and Klinefelter’s syndrome (KFS. Results: Out of 230 (5.54% cases with chromosomally abnormal karyotype, 122 (30% cases suspected of sexual disorder showed SCA including 46% Turner’s syndrome, 46% KFS and the remaining other sex chromosome abnormalities. The frequency of classic and mosaic form of Turner’s syndrome was 33% and 67%, this was 55% and 45% for KFS, respectively. Conclusion: This study shows a relatively high sex chromosome abnormality in this region and provides cytogenetic data to assist clinicians and genetic counselors to determine the priority of requesting cytogenetic study. Differences between results from various reports can be due to different genetic background or ethnicity.

  6. The Use of Linezolid in Children with Malignant Solid Tumors

    Directory of Open Access Journals (Sweden)

    H.I. Klymniuk

    2015-09-01

    Full Text Available In recent decades, in the treatment of cancer there has been achieved a significant success not only by the introduction of cancer treatment protocol, but mostly due to the planned combination concomitant treatment of infectious complications. The need for antimicrobial agents against resistant Gram-positive bacteria, such as methicillin-resistant staphylococci, penicillin-resistant pneumococci, vancomycin-resistant enterococci, has significantly increased. In the department of pediatric oncology of the National cancer institute (Kyiv, linezolid preparations were used in children with infection of soft tissues and bones, febrile neutropenia and for the treatment of severe cases of sepsis. Experience of Linelid® use in the department of pediatric oncology of the National cancer institute indicates its effectiveness, safety and good tolerance in children with malignant solid tumors.

  7. Cytogenetic Profile and Gene Mutations of Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Nawaf Alkhayat

    2017-07-01

    Full Text Available Background: Childhood acute lymphoblastic leukemia (ALL is characterized by recurrent genetic aberrations. The identification of those abnormalities is clinically important because they are considered significant risk-stratifying markers. Aims: There are insufficient data of cytogenetic profiles in Saudi Arabian patients with childhood ALL leukemia. We have examined a cohort of 110 cases of ALL to determine the cytogenetic profiles and prevalence of FLT3 mutations and analysis of the more frequently observed abnormalities and its correlations to other biologic factors and patient outcomes and to compare our results with previously published results. Materials and methods: Patients —We reviewed all cases from 2007 to 2016 with an established diagnosis of childhood ALL. Of the 110 patients, 98 were B-lineage ALL and 12 T-cell ALL. All the patients were treated by UKALL 2003 protocol and risk stratified according previously published criteria. Cytogenetic analysis —Chromosome banding analysis and fluorescence in situ hybridization were used to detect genetic aberrations. Analysis of FLT3 mutations —Bone marrow or blood samples were screened for FLT3 mutations (internal tandem duplications, and point mutations, D835 using polymerase chain reaction methods. Result: Cytogenetic analysis showed chromosomal anomalies in 68 out of 102 cases with an overall incidence 66.7%. The most frequent chromosomal anomalies in ALL were hyperdiploidy, t(9;22, t(12;21, and MLL gene rearrangements. Our data are in accordance with those published previously and showed that FLT3 mutations are not common in patients with ALL (4.7% and have no prognostic relevance in pediatric patients with ALL. On the contrary, t(9;22, MLL gene rearrangements and hypodiploidy were signs of a bad prognosis in childhood ALL with high rate of relapse and shorter overall survival compared with the standard-risk group ( P  = .031.The event-free survival was also found to be worse ( P

  8. In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mylonaki, Effie; Manika, Katerina [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Zarogoulidis, Paul, E-mail: pzarog@hotmail.com [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Mourelatos, Dionysios [Biology and Genetics, Medical School, Aristotle University of Thessaloniki (Greece)

    2012-12-15

    Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p < 0.001). The in vivo administration of AM after chemotherapy increased SCEs in both cancer types (SCLC: p < 0.001, NSCLC: p = 0.003) and this increase was synergistic, the rates of SCEs in the presence of AM were higher than the expected SCE values if the increases above background for chemotherapy and AM were independent and additive (SCLC: p < 0.001, NSCLC: p = 0.008). Although in both groups of patients cell division delays were observed after the combined chemotherapy plus in vivo AM treatment, the correlation between the magnitude of the SCE response and the PRI depression was not statistically significant (p > 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer.

  9. CAR T Cells Releasing IL-18 Convert to T-Bethigh FoxO1low Effectors that Exhibit Augmented Activity against Advanced Solid Tumors

    Directory of Open Access Journals (Sweden)

    Markus Chmielewski

    2017-12-01

    Full Text Available Adoptive therapy with chimeric antigen receptor (CAR-redirected T cells has achieved remarkable efficacy in the treatment of hematopoietic malignancies. However, eradicating large solid tumors in advanced stages of the disease remains challenging. We explored augmentation of the anti-tumor immune reaction by establishing an acute inflammatory reaction. Systematic screening indicates that IL-18 polarizes CAR T cells toward T-bethigh FoxO1low effectors with an acute inflammatory response. CAR T cells engineered with inducible IL-18 release exhibited superior activity against large pancreatic and lung tumors that were refractory to CAR T cells without cytokines. IL-18 CAR T cell treatment was accompanied by an overall change in the immune cell landscape associated with the tumor. More specifically, CD206− M1 macrophages and NKG2D+ NK cells increased in number, whereas Tregs, suppressive CD103+ DCs, and M2 macrophages decreased, suggesting that “iIL18 TRUCKs” can be used to sensitize large solid tumor lesions for successful immune destruction.

  10. Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors

    Science.gov (United States)

    2018-05-15

    Ewing's Sarcoma; Osteosarcoma; Astrocytoma; Atypical Teratoid/Rhabdoid Tumor; Ependymoma; Germ Cell Tumor; Glioma; Medulloblastoma; Rhabdoid Tumor; Retinoblastoma; Clear Cell Sarcoma; Renal Cell Carcinoma; Wilms Tumor; Hepatoblastoma; Neuroblastoma; Rhabdomyosarcoma

  11. Clinicopathologic and prognostic significance of C-reactive protein/albumin ratio in patients with solid tumors: an updated systemic review and meta-analysis.

    Science.gov (United States)

    Wu, Jiayuan; Tan, Wenkai; Chen, Lin; Huang, Zhe; Mai, Shao

    2018-03-02

    C-reactive protein/albumin ratio (CAR) was originally used as a novel inflammation-based prognostic score in predicting outcomes in septic patients. Recently, more and more studies have reported the prognostic value of pretreatment CAR in solid tumors. However, the results remain controversial rather than conclusive. We conducted a meta-analysis based on 24 studies with 10203 patients to explore the relationship between CAR and survival outcomes in patients with solid tumors. The correlation between CAR and clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was applied to be the effect size estimate. The overall results showed that elevated CAR was associated with shorter overall survival (OS) (including 23 studies and 10067 patients) and poorer disease-free survival (DFS) (including 6 studies and 2904 patients). Significant associations between high CAR level and poor OS were also found in the subgroup analyses of study region, cancer type, primary treatment, clinical stage, cut-off selection, sample size, and cut-off value. Moreover, subgroup analyses demonstrated that study region, primary treatment, clinical stage, sample size, and cut-off value did not alter the prognostic value of CAR for DFS. Furthermore, elevated CAR was correlated with certain phenotypes of tumor aggressiveness, such as poor histological grade, serious clinical stage, advanced tumor depth, positive lymph node metastasis, and positive distant metastasis. Together, our meta-analysis suggests that elevated level of serum CAR predicts worse survival and unfavorable clinical characteristics in cancer patients, and CAR may serve as an effective prognostic factor for solid tumors.

  12. Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country

    Directory of Open Access Journals (Sweden)

    E.D.R.P. Velloso

    2013-01-01

    Full Text Available Myelodysplastic syndromes (MDS and juvenile myelomonocytic leukemia (JMML are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED. We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome. Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

  13. Characterization of Soft Tissue Tumors by Diffusion-Weighted Imaging

    International Nuclear Information System (INIS)

    Pekcevik, Yeliz; Kahya, Mehmet Onur; Kaya, Ahmet

    2015-01-01

    Diffusion-weighted imaging (DWI) is a noninvasive method for investigation of tumor histological content. It has been applied for some musculoskeletal tumors and reported to be useful. The aim of the present study was to prospectively evaluate the apparent diffusion coefficient (ADC) values of benign and malignant soft tissue tumors and to determine if ADC can help differentiate these tumors. DWI was performed on 25 histologically proven soft tissue masses. It was obtained with a single-shot echo-planar imaging technique using a 1.5T magnetic resonance (MR) machine. The mean ADC values were calculated. We grouped soft tissue tumors as benign cystic, benign solid or mixed, malignant cystic and malignant solid or mixed tumors and compared mean ADC values between these groups. There was only one patient with a malignant cystic tumor and was not included in the statistical analysis. The median ADC values of benign and malignant tumors were 2.31 ± 1.29 and 0.90 ± 0.70 (median ± interquartile range), respectively. The mean ADC values were different between benign and malignant tumors (P = 0.031). Benign cystic tumors had significantly higher ADC values than benign solid or mixed tumors and malignant solid or mixed tumors (p values were < 0.001 and 0.003, respectively). Malignant solid or mixed tumors had lower ADC values than benign solid or mixed tumors (P = 0.02). Our preliminary results have shown that although there is some overlap between benign and malignant tumors, adding DWI, MR imaging to routine soft tissue tumor protocols may improve diagnostic accuracy

  14. Palliative Care Use Among Patients With Solid Cancer Tumors: A National Cancer Data Base Study.

    Science.gov (United States)

    Osagiede, Osayande; Colibaseanu, Dorin T; Spaulding, Aaron C; Frank, Ryan D; Merchea, Amit; Kelley, Scott R; Uitti, Ryan J; Ailawadhi, Sikander

    2018-01-01

    Palliative care has been increasingly recognized as an important part of cancer care but remains underutilized in patients with solid cancers. There is a current gap in knowledge regarding why palliative care is underutilized nationwide. To identify the factors associated with palliative care use among deceased patients with solid cancer tumors. Using the 2016 National Cancer Data Base, we identified deceased patients (2004-2013) with breast, colon, lung, melanoma, and prostate cancer. Data were described as percentages. Associations between palliative care use and patient, facility, and geographic characteristics were evaluated through multivariate logistic regression. A total of 1 840 111 patients were analyzed; 9.6% received palliative care. Palliative care use was higher in the following patient groups: survival >24 months (17% vs 2%), male (54% vs 46%), higher Charlson-Deyo comorbidity score (16% vs 8%), treatment at designated cancer programs (74% vs 71%), lung cancer (76% vs 28%), higher grade cancer (53% vs 24%), and stage IV cancer (59% vs 13%). Patients who lived in communities with a greater percentage of high school degrees had higher odds of receiving palliative care; Central and Pacific regions of the United States had lower odds of palliative care use than the East Coast. Patients with colon, melanoma, or prostate cancer had lower odds of palliative care than patients with breast cancer, whereas those with lung cancer had higher odds. Palliative care use in solid cancer tumors is variable, with a preference for patients with lung cancer, younger age, known insurance status, and higher educational level.

  15. Cytogenetic Profile of de novo Acute Myeloid Leukemia Patients in Malaysia.

    Science.gov (United States)

    Meng, Chin Yuet; Noor, Puteri J; Ismail, Azli; Ahid, Mohd Fadly Md; Zakaria, Zubaidah

    2013-03-01

    Acute myeloid leukemia (AML) is a heterogeneous disease in terms of cytogenetics and molecular genetics. AML is the most common acute leukemia in adults and its incidence increases with age. Diagnostic cytogenetics is an important prognostic indicator for predicting outcome of AML. We examined the karyotypic patterns of 480 patients with de novo AML seen at government hospitals throughout the country and evaluated the association of chromosome aberrations with the age of patient. Chromosome abnormalities were detected in 146 (30.4%) patients. The most common cytogenetic abnormality was balanced translocation t (8; 21), followed by trisomy 8 (as sole abnormality) and t (15; 17). The age of our Malaysian patients at diagnosis ranged from four months to 81 years, with a median age of 39 years. The normal karyotype was found mainly in patients aged 15-30 years. About 75% of patients with t (8; 21) were below 40 years of age, and the complex karyotype was found with the highest frequently (34.3%) in elderly patients (age above 60 years). More than half of the patients with complex karyotype were above 50 years of age. The deletion 5q was detected only in patients aged above 50 years. Different cytogenetic abnormalities in AML show different frequencies with increasing age. Probably different genetic mechanisms are involved in the pathogenesis of AML and these mechanisms might occur at different frequencies over lifetime.

  16. Fluorescence-based codetection with protein markers reveals distinct cellular compartments for altered MicroRNA expression in solid tumors

    DEFF Research Database (Denmark)

    Sempere, Lorenzo F; Preis, Meir; Yezefski, Todd

    2010-01-01

    of altered miRNA expression in solid tumors, we developed a sensitive fluorescence-based in situ hybridization (ISH) method to visualize miRNA accumulation within individual cells in formalin-fixed, paraffin-embedded tissue specimens. This ISH method was implemented to be compatible with routine clinical...

  17. PNU-145156E, a novel angiogenesis inhibitor, in patients with solid tumors : A phase I and pharmacokinetic study

    NARCIS (Netherlands)

    Groen, HJM; de Vries, EGE; Wynendaele, W; van der Graaf, WTA; Lechuga, EFMJ; Poggesi, [No Value; Dirix, LY; van Oosterom, AT

    2001-01-01

    Our aim was to establish, in patients with solid tumors, the dose-limiting toxicity, maximum tolerated dose (MTD), and pharmacology of PNU-145156E, a new sulfonated distamycin A derivative that blocked circulating angiogenesis-promoting growth factors in animal studies and exhibited an antitumor

  18. Liver Tumors (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Liver Tumors KidsHealth / For Parents / Liver Tumors What's in this article? Types of Tumors ... Cancerous) Tumors Symptoms Diagnosis Treatment Coping Print The liver is the body's largest solid organ. Lying next ...

  19. Comparison between cytogenetic damage induced in human lymphocytes by environmental chemicals or radiation

    Energy Technology Data Exchange (ETDEWEB)

    Cebulska-Wasilewska, A. [Institute of Nuclear Physics, Cracow (Poland)

    1997-12-31

    Author compared cytogenetic effects of chemicals (benzene and the member at benzene related compounds) and ionizing radiation on the human lymphocytes. Levels of various types of cytogenetic damage observed among people from petroleum plants workers groups are similar to the levels of damages detected in the blood of people suspected of the accidental exposure to a radiation source

  20. Comparison between cytogenetic damage induced in human lymphocytes by environmental chemicals or radiation

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.

    1997-01-01

    Author compared cytogenetic effects of chemicals (benzene and the member at benzene related compounds) and ionizing radiation on the human lymphocytes. Levels of various types of cytogenetic damage observed among people from petroleum plants workers groups are similar to the levels of damages detected in the blood of people suspected of the accidental exposure to a radiation source

  1. Pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Poussaint, Tina Y. [Department of Radiology, Boston, MA (United States); Panigrahy, Ashok [Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States); Huisman, Thierry A.G.M. [Charlotte R. Bloomberg Children' s Center, Johns Hopkins Hospital, Division of Pediatric Radiology and Pediatric Neuroradiology, Baltimore, MD (United States)

    2015-09-15

    Among all causes of death in children from solid tumors, pediatric brain tumors are the most common. This article includes an overview of a subset of infratentorial and supratentorial tumors with a focus on tumor imaging features and molecular advances and treatments of these tumors. Key to understanding the imaging features of brain tumors is a firm grasp of other disease processes that can mimic tumor on imaging. We also review imaging features of a common subset of tumor mimics. (orig.)

  2. Cytogenetic biological dosimetry. Dose estimative in accidental exposure

    International Nuclear Information System (INIS)

    Santos, O.R. dos; Campos, I.M.A. de.

    1988-01-01

    The methodology of cytogenetic biological dosimetry is studied. The application in estimation of dose in five cases of accidental exposure is reported. An hematological study and culture of lymphocytes is presented. (M.A.C.) [pt

  3. Cytogenetic, genomic in situ hybridization (GISH) and agronomic ...

    African Journals Online (AJOL)

    F3 generations of a wheat-Psathyrostachys huashanica intergeneric cross. Their agronomic traits were evaluated in the field and their meiotic behaviors and chromosome composition were analyzed by cytogenetic and GISH (genomic in situ ...

  4. Primary cutaneous follicle center lymphoma associated with an extracutaneous dissemination: a cytogenetic finding of potential prognostic value.

    Science.gov (United States)

    Subramaniyam, Shivakumar; Magro, Cynthia M; Gogineni, Swarna; Tam, Wayne; Mathew, Susan

    2015-11-01

    Cytogenetic studies on cutaneous lymphomas are rare, and very little is known about their prognostic value. We present a rare case of primary cutaneous follicle center lymphoma (PCFCL) with a complex translocation presenting with cutaneous and extracutaneous dissemination in the lymph node. Morphologic, immunohistochemical, conventional cytogenetic, and fluorescence in situ hybridization (FISH) studies were performed on this patient. A combination of cytogenetic and FISH analysis identified a complex novel four-way t(2;14;9;3) (p11.2;q32;p13;q27) translocation involving rearrangements of BCL6, immunoglobulin light and heavy chain genes, and an unknown gene on 9p. Our report elaborates the morphologic and immunohistochemical features in combination with cytogenetic and molecular cytogenetic analysis of PCFCL, which provide additional insight into the clinical and biologic behavior of this lesion. Copyright© by the American Society for Clinical Pathology.

  5. A cytogenetic analysis of 2 cases of phosphaturic mesenchymal tumor of mixed connective tissue type.

    Science.gov (United States)

    Graham, Rondell P; Hodge, Jennelle C; Folpe, Andrew L; Oliveira, Andre M; Meyer, Kevin J; Jenkins, Robert B; Sim, Franklin H; Sukov, William R

    2012-08-01

    Phosphaturic mesenchymal tumor of mixed connective tissue type is a rare, histologically distinctive mesenchymal neoplasm associated with tumor-induced osteomalacia resulting from production of the phosphaturic hormone fibroblast growth factor 23. Because of its rarity, specific genetic alterations that contribute to the pathogenesis of these tumors have yet to be elucidated. Herein, we report the abnormal karyotypes from 2 cases of confirmed phosphaturic mesenchymal tumor of mixed connective tissue type. G-banded analysis demonstrated the first tumor to have a karyotype of 46,Y,t(X;3;14)(q13;p25;q21)[15]/46XY[5], and the second tumor to have a karyotype of 46, XY,add(2)(q31),add(4)(q31.1)[2]/92,slx2[3]/46,sl,der(2)t(2;4)(q14.2;p14),der(4)t(2;4)(q14.2;p14),add(4)(q31.1)[10]/46,sdl,add(13)(q34)[4]/92,sdl2x2[1]. These represent what is, to our knowledge, the first examples of abnormal karyotypes obtained from phosphaturic mesenchymal tumor of mixed connective tissue type. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Cytogenetic analysis in couples with recurrent miscarriages: a ...

    Indian Academy of Sciences (India)

    Journal of Genetics, DOI 10.1007/s12041-016-0713-3, Vol. 95, No. ... After taking the written informed consent; clinical and med- ical history was .... Cytogenetic investigations in ..... outcomes have been reported after surgical interventions.

  7. Optimizing the dosing schedule of l-asparaginase improves its anti-tumor activity in breast tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Shoya Shiromizu

    2018-04-01

    Full Text Available Proliferation of acute lymphoblastic leukemic cells is nutritionally dependent on the external supply of asparagine. l-asparaginase, an enzyme hydrolyzing l-asparagine in blood, is used for treatment of acute lymphoblastic leukemic and other related blood cancers. Although previous studies demonstrated that l-asparaginase suppresses the proliferation of cultured solid tumor cells, it remains unclear whether this enzyme prevents the growth of solid tumors in vivo. In this study, we demonstrated the importance of optimizing dosing schedules for the anti-tumor activity of l-asparaginase in 4T1 breast tumor-bearing mice. Cultures of several types of murine solid tumor cells were dependent on the external supply of asparagine. Among them, we selected murine 4T1 breast cancer cells and implanted them into BALB/c female mice kept under standardized light/dark cycle conditions. The growth of 4T1 tumor cells implanted in mice was significantly suppressed by intravenous administration of l-asparaginase during the light phase, whereas its administration during the dark phase failed to show significant anti-tumor activity. Decreases in plasma asparagine levels due to the administration of l-asparaginase were closely related to the dosing time-dependency of its anti-tumor effects. These results suggest that the anti-tumor efficacy of l-asparaginase in breast tumor-bearing mice is improved by optimizing the dosing schedule. Keywords: l-asparaginase, Asparagine, Solid tumor, Chrono-pharmacotherapy

  8. A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy

    Directory of Open Access Journals (Sweden)

    Han LQ

    2016-11-01

    Full Text Available Leiqiang Han, Tianqi Wang, Jingliang Wu, Xiaolan Yin, Hao Fang, Na Zhang School of Pharmaceutical Science, Shandong University, Ji’nan, Shandong, People’s Republic of China Abstract: Small molecule-based nanodrugs with nanoparticles (NPs that are mainly composed of small molecules, have been considered as a promising candidate for a next-generation nanodrug, owing to their unique properties. Vorinostat (SAHA is a canonical US Food and Drug Administration-approved histone deacetylase (HDAC inhibitor for the treatment of cutaneous T-cell lymphoma. However, the lack of efficacy against solid tumors hinders its progress in clinical use. Herein, a novel nanodrug of SAHA was developed based on disulfide-linked prodrug SAHA-S-S-VE. SAHA-S-S-VE could self-assemble into 148 nm NPs by disulfide-induced mechanisms, which were validated by molecular dynamics simulations. Under reduced conditions, the redox-responsive behavior of SAHA-S-S-VE was investigated, and the HDAC inhibition results verified the efficient release of free SAHA. With a biocompatible d-a-tocopheryl polyethylene glycol succinate (TPGS functionalization, the SAHA-S-S-VE/TPGS NPs exhibited low critical aggregation concentration of 4.5 µM and outstanding stability in vitro with drug-loading capacity of 24%. In vitro biological assessment indicated that SAHA-S-S-VE/TPGS NPs had significant anticancer activity against HepG2. Further in vivo evaluation demonstrated that the resulting NPs could be accumulated in the tumor region and inhibit the tumor growth effectively. This approach, which turned SAHA into a self-assembled redox-responsive nanodrug, provided a new channel for the use of HDAC inhibitor in solid tumor therapy. Keywords: SAHA, HDAC, small molecule, nanoparticles, self-assemble, disulfide bond

  9. Cytogenetic consequence of radiation in epithelial kidney cells of a monkey

    International Nuclear Information System (INIS)

    Kosichenko, L.P.; Trots, A.A.

    1980-01-01

    The cytogenetic consequence of radiation in kidney epithelial cells of monkeys are studied 3.5-9 years after the cessation of everyday irradiation in small doses (2.99-4.9 R daily) and 6.0-12.5 years after single 550-652 R irradiation. The increased amount of reconstructed chromosomes is mainly conditioned by stable chromosome exchange; reconstructions of the non-stable type are also preserved. The cytogenetic consequence of irradiation is determined by various factors, radiation conditions and the total dose of radiation, in particular

  10. Cytogenetic methods for the detection of radiation-induced chromosome damage in aquatic organisms

    International Nuclear Information System (INIS)

    Kligerman, A.D.

    1979-01-01

    One means of evaluating the genetic effects of radiation on the genomes of aquatic organisms is to screen radiation-exposed cells for chromosome aberrations. A brief literature review of studies dealing with radiation-induced chromosome damage in aquatic organisms is presented, and reasons are given detailing why most previous studies are of little quantitative value. Suggestions are made for obtaining adequate qualitative and quantitative data through the use of modern cytogenetic methods and a model systems approach to the study of cytogenetic radiation damage in aquatic organisms. Detailed procedures for both in vivo and in vitro cytogenetic methods are described, and experimental considerations are discussed. Finally, suggestions for studies that could be of value in establishing protective guidelines for aquatic ecosystems are presented. (author)

  11. The occurrence of recruitment supported from the finding of an increase in radiosensitivity of quiescent cells in solid tumors after fractionated irradiation with X-rays

    International Nuclear Information System (INIS)

    Masunaga, Shinichiro; Ono, Koji; Kinashi, Yuko; Suzuki, Minoru; Akaboshi, Mitsuhiko

    1998-01-01

    We examined the behavior of quiescent cells in solid tumors irradiated twice at various intervals with X-rays, using our recently developed method for selectively detecting the response of quiescent cells in solid tumors. To determine the labeling indices of tumors at the second irradiation, each mouse group included mice that were continuously administered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted before the first irradiation. Radiosensitivity of total tumor cells at the second irradiation decreased in proportion to the increase in interval time. However, radiosensitivity of quiescent cells was raised with increase in the interval time. In addition, the labeling index at the second irradiation was higher than that at the first irradiation. These findings supported the occurrence of recruitment from quiescent to proliferating state during fractionated irradiation. (author)

  12. A novel gene therapy-based approach that selectively targets hypoxic regions within solid tumors

    International Nuclear Information System (INIS)

    Dougherty, S.T.; Dougherty, G.J.; Davis, P.D.

    2003-01-01

    There is compelling evidence that malignant cells present within the hypoxic regions that are commonly found within solid tumors contribute significantly to local recurrence following radiation therapy. We describe now a novel strategy designed to target such cells that exploits the differential production within hypoxic regions of the pro-angiogenic cytokine vascular endothelial cell growth factor (VEGF). Specifically, we have generated cDNA constructs that encode two distinct chimeric cell surface proteins that incorporate, respectively, the extracellular domains of the VEGF receptors Flk-1 or Flt-1, fused in frame to the membrane spanning and cytoplasmic domains of the pro-apoptotic protein Fas. Both chimeric proteins (Flk/Fas and Flt/Fas) appear stable and can be readily detected on the surface of transfected cells by Western blot and/or FACS analysis. Importantly, tumor cells expressing the chimeric proteins were rapidly killed in a dose-dependent fashion upon the addition of exogenous recombinant VEGF. Adenoviral vectors encoding Flk/Fas have been generated and shown to induce tumor cells to undergo apoptosis upon transfer to hypoxic conditions in vitro. This activity is dependent upon the endogenous production of VEGF. Studies are currently underway to test the ability of adenoviral Flk/Fas (Ad.Flk/Fas) to reduce tumor recurrence in vivo when used as an adjuvant therapy in conjunction with clinically relevant doses of ionizing radiation

  13. State-of-the-art cytogenetic techniques to detect radiation damage induced by low doses bin human lymphocytes

    International Nuclear Information System (INIS)

    Hadjidekova, V.

    2004-01-01

    Cytogenetic techniques are the most sensitive and reliable tools for bio-monitoring and bio-dosimetry of people professionally or accidentally exposed to ionizing radiation. They are applied in addition to the evaluations of the physical dosimetry and they consider the individual radiosensitivity. The main potential risk for humans from exposure to low doses of ionizing radiations is the enhanced incidence of stochastic effects, i.e. carcinogenesis and heritable genetic effects. This report presents a comparative evaluation of the cytogenetic markers for radiation damage of humans and general conclusions of cytogenetic studies of chromosomal aberrations and micronuclei formation in individuals occupationally exposed to action of ionizing radiation. The sensitivity of the methods is compared and their great development and mastering during the last years, as well as the basis of their application - the relation between the frequency of cytogenetic markers observed in lymphocytes in peripheral blood and the risk of malignant disease. The advantages and disadvantages of different cytogenetic techniques are discussed. (author)

  14. Photodynamic therapy of solid tumors

    Science.gov (United States)

    Jori, Giulio

    Some porphyrin compounds, which are characterized by a relatively large degree of hydrophobicity (n-octanol/water partition coefficient above 8), are accumulated in greater amounts and retained for longer periods of time by neoplastic as compared with normal tissues. The affinity of these dyes for tumors is partially a consequence of their in vivo transport by low-density lipoproteins, which are preferentially endocytosized by hyperproliferating tissues in a receptor-mediated process. In general, at 24-48 h after the systematic administration of porphyrin doses in the range of 2.5 mg/kg body weight, the ratio of drug concentration between the neoplastic and the surrounding tissues is sufficiently large to guarantee a selective photoexcitation of the porphyrin. Toward this aim, the porphyrin-containing tumor tissues are irradiated with light wavelengths longer than 600 nm, since the transmittance of biological tissues is maximal in this spectral region. The electronically excited porphyrin transfers its excitation energy to oxygen, thus generating activated oxygen species (mainly, singlet oxygen): as a consequence, the photooxidative modification of subcellular targets (e.g. the plasma membrane and mitochondria) is readily obtained leading to an irreversible necrosis of the cell. With the most frequently used porphyrins for clinical phototherapy (including hematoporphyrin and its derivatives HpD and Photofrin II), one observes the preferential photosensitized destruction of endothelial cells, hence the vascular damage is a major process involved in the necrosis of tumors. The optimization of the phototherapy of tumors is presently pursued by the definition of clinical protocols tailored to the optical properties of specific neoplastic tissues as well as by the use of porphyrin analogs, such as chlorins and phthalocyanines, having an extinction coefficient in the red spectral region larger than that typical of hematoporphyrin and HpD.

  15. Molecular cytogenetic identification of a wheat– Thinopyrum ...

    Indian Academy of Sciences (India)

    Thinopyrum ponticum (2n = 70) serves as a valuable gene pool for wheat improvement. Line SN0224, derived from crosses between Th. ponticum and the common wheat cultivar Yannong15, was identified in the present study. Cytogenetic observations showed that SN0224 contains 42 chromosomes in the root-tip cells ...

  16. Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics.

    Science.gov (United States)

    Magliacane, Gilda; Grassini, Greta; Bartocci, Paola; Francaviglia, Ilaria; Dal Cin, Elena; Barbieri, Gianluca; Arrigoni, Gianluigi; Pecciarini, Lorenza; Doglioni, Claudio; Cangi, Maria Giulia

    2015-10-13

    Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance, we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies.

  17. An overview of cytogenetics of the tribe Meliponini (Hymenoptera: Apidae).

    Science.gov (United States)

    Tavares, Mara Garcia; Lopes, Denilce Meneses; Campos, L A O

    2017-06-01

    The present study provides a comprehensive review of cytogenetic data on Meliponini and their chromosomal evolution. The compiled data show that only 104 species of stingless bees, representing 32 of the 54 living genera have been studied cytogenetically and that among these species, it is possible to recognize three main groups with n = 9, 15 and 17, respectively. The first group comprises the species of the genus Melipona, whereas karyotypes with n = 15 and n = 17 have been detected in species from different genera. Karyotypes with n = 17 are the most common among the Meliponini studied to date. Cytogenetic information on Meliponini also shows that although chromosome number, in general, is conserved among species of a certain genus, other aspects, such as chromosome morphology, quantity, distribution and composition of heterochromatin, may vary between them. This reinforces the fact that the variations observed in the karyotypes of different Meliponini groups cannot be explained by a single theory or a single type of structural change. In addition, we present a discussion about how these karyotype variations are related to the phylogenetic relationships among the different genera of this tribe.

  18. Therapeutic potential and challenges of Natural killer cells in treatment of solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea eGras Navarro

    2015-04-01

    Full Text Available Natural killer (NK cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing requiring one–to-one target engagement and site directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME and augment adaptive immune responses by promoting differentiation, activation and/ or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach.

  19. An informative constitutional cytogenetic marker found in a patient post bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Zaslav, A.L.; Graziano, J.; Ebert, R. [Albert Einstein College of Medicine, New Hyde Park, NY (United States)] [and others

    1994-09-01

    It is cytogenetically difficult to distinguish between host and donor cells in allogeneic bone marrow transplantation (BMT) individuals of the same sex. Here we describe a patient with a cytogenetic marker found after BMT. A 7-month-old male presented with leukemia which was CD7+, CD33+, HLADR+, and CD4-, CD8-, indicating a diagnosis of acute stem cell leukemia (ASCL). Cytogenetic analysis revealed an abnormal clone in all of the cells analyzed: 46,XY,t(2;8)(p11.2;q24),inv(9)(p13p24). This translocation is associated with B-cell acute lymphoblastic leukemia (ALL); thus, it was possible for this patient to develop B-cell ALL. The abnormal clone persisted along with normal 46,XY cells, and evolved in several of seven additional analyses. The patient was treated with two courses of chemotherapy and failed to attain cytogenetic remission. While in relapse, the patient received a BMT from his 3-year-old brother. Two weeks later, a different translocation was seen in all cells: 46,XY,t(3;12)(p21;q21). This result could be interpreted in two ways: (1) the structural abnormality was indicative of a newly evolved clone related to the patient`s disease; or (2) the donor was a balanced translocation carrier. Cytogenetic analysis of peripheral blood from the donor revealed the same translocation seen in the patient. Parental blood chromosomes were normal indicating that the donor carried a de novo balanced translocation. Subsequent chromosome analysis of both peripheral blood and BM from the patient revealed the presence of the translocation in all cells. De novo balanced translocations are rare and occur with a frequency of 1/2,000 live borns. The family received genetic counseling and was informed of the possible reproductive risks to translocation carriers. This unusual finding will serve as a useful cytogenetic marker to assist in monitoring the patient`s clinical course, i.e., chimerism and remission status.

  20. Computed tomographic findings of ovarian tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Kwi Ryeon; Lee, Ki Man; Woo, Seong Ku; Suh, Soo Jhi [Keimyung University School of Medicine, Seoul (Korea, Republic of); Kang, Duk Sik [Kyungpook National University College of Medicine, Taegu (Korea, Republic of)

    1986-08-15

    The diagnosis of ovarian tumor has been mainly dependent on manual pelvic examination and ultrasonography. But in case of malignant ovarian tumor, CT has more advantages over ultrasonography in assessing anatomic details, relationships to bowel loops, precise extents of tumors and follow-up examinations after surgery. Authors analyzed CT features of 46 cases of pathologically proven ovarian tumors for recent 4 years at Keimyung University Dongsan Hospital. The results were as follows: 1. The most common tumor was serous cyst adenocarcinoma (9 cases: 20%), followed by metastases (8 cases: 17%), mucinous cyst adenocarcinoma (7 cases: 15%), mucinous cyst adenocarcinoma (5 cases: 11%), teratoma (5 cases: 11%), lymphoma (3 cases: 7%) and dysgerminoma (2 cases: 4%). 2. The ovarian tumors were variable in size from 2.5 cm to 33 cm in diameter. Most of the solid tumors were smaller than 10 cm in diameter and most of the cystic tumors were larger than 10 cm in diameter. Usually mucinous tumors were much larger than serous tumors. Mucinous cyst adenomas were the largest tumors. 3. Unilateral tumors (left 19, right 13 cases) were more common than bilateral tumors (12 cases). Bilateral tumors were seen in serous and mucinous cyst adenocarcinoma, metastases and lymphoma. 4. CT features of mucinous cyst adenomas were smooth margins and thin wall of the tumor masses and multifaceted cysts with internal septa in all 7 cases. 5. In contrast, CT demonstration of bilaterally, irregular margin, thick wall, enhancing solid lesion, septal irregularity, adhesion to adjacent structures, peritoneal/omental implantation, ascites and hydronephrosis were signs suggesting malignancy. CT features of the serous cyst adenocarcinoma were mostly solid to mixed nature (83%), irregular margin (75%), enhancing solid lesion (67%), papillary growth (75%), internal septa (58%), multilocularity (58%) and calcification (25%) in descending order of frequency. 6. On CT, mucinous cystadenocarcinoma were

  1. BRAFV600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study

    Directory of Open Access Journals (Sweden)

    Cohn AL

    2017-02-01

    Full Text Available Allen L Cohn,1 Bann-Mo Day,2 Sarang Abhyankar,3 Edward McKenna,2 Todd Riehl,4 Igor Puzanov5 1Medical Research, Rocky Mountain Cancer Centers, Denver, CO, 2US Medical Affairs, 3Global Safety and Risk Management, 4Product Development Oncology, Genentech, Inc., South San Francisco, CA, 5Melanoma Section, Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Background: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer or multiple myeloma harboring activating BRAFV600 mutations for enrollment in a vemurafenib clinical study.Methods: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAFV600 mutations by bidirectional direct Sanger sequencing.Results: Overall incidence of BRAFV600E mutation in evaluable patients (n=548 was 3% (95% confidence interval [CI], 1.7–4.7: 11% in colorectal tumors (n=75, 6% in biliary tract tumors (n=16, 3% in non-small cell lung cancers (n=71, 2% in other types of solid tumors (n=180, and 3% in multiple myeloma (n=31. There were no BRAFV600 mutations in this cohort of patients with ovarian tumors (n=68, breast cancer (n=86, or prostate cancer (n=21.Conclusion: This multicenter, national screening study confirms previously reported incidences of BRAFV600 mutations from single-center studies. Patients identified with BRAFV600 mutations were potentially eligible for enrollment in the VE-BASKET study. Keywords: genetic testing, proto-oncogene proteins B-raf, PLX4032

  2. Applications of lipid nanocarriers for solid tumors therapy: literature review; Aplicacoes das nanoparticulas lipidicas no tratamento de tumores solidos: revisao de literatura

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Fac. de Farmacia; Taveira, Eliseu Jose Fleury, E-mail: stephaniafleury@gmail.com [Hospital Erasto Gaertner, Curitiba, PR (Brazil). Oncologia Clinica

    2012-07-01

    Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed{sup R} database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

  3. Molecular cytogenetic analyses of Epinephelus bruneus and Epinephelus moara (Perciformes, Epinephelidae

    Directory of Open Access Journals (Sweden)

    Minglan Guo

    2014-06-01

    Full Text Available Genus Epinephelus (Perciformes, Epinephelidae, commonly known as groupers, are usually difficult in species identification for the lack and/or change of morphological specialization. In this study, molecular cytogenetic analyses were firstly performed to identify the closely related species Epinephelus bruneus and E. moara in this genus. The species-specific differences of both fish species showed in karyotype, chromosomal distribution of nucleolar organizer regions (NORs and localization of 18S rDNA. The heterochromatin (interstitial C-bands and distribution pattern of telomere (TTAGGGn in E. bruneus revealed the chromosomal rearrangements and different karyotypic evolutionary characteristics compared to those in E. moara. The cytogenetic data suggested that the lineages of E. bruneus and E. moara were recently derived within the genus Epinephelus, and E. moara exhibited more plesiomorphic features than E. bruneus. All results confirmed that E. moara, which has long been considered a synonym of E. bruneus, is a distinct species in the family Epinephelidae. In addition, molecular cytogenetic analyses are useful in species differentiation and phylogenetic reconstruction in groupers.

  4. PET/CT evaluation of response to chemotherapy in non-small cell lung cancer: PET response criteria in solid tumors (PERCIST) versus response evaluation criteria in solid tumors (RECIST).

    Science.gov (United States)

    Ding, Qiyong; Cheng, Xu; Yang, Lu; Zhang, Qingbo; Chen, Jianwei; Li, Tiannv; Shi, Haibin

    2014-06-01

    (18)F-FDG PET/CT is increasingly used in evaluation of treatment response for patients with non-small cell lung cancer (NSCLC). There is a need for an accurate criterion to evaluate the effect and predict the prognosis. The aim of this study is to evaluate therapeutic response in NSCLC with comparing PET response criteria in solid tumors (PERCIST) to response evaluation criteria in solid tumors (RECIST) criteria on PET/CT. Forty-four NSCLC patients who received chemotherapy but no surgery were studied. Chemotherapeutic responses were evaluated using (18)F-FDG PET and CT according to the RECIST and PERCIST methodologies. PET/CT scans were obtained before chemotherapy and after 2 or 4-6 cycles' chemotherapy. The percentage changes of tumor longest diameters and standardized uptake value (SUV) (corrected for lean body mass, SUL) before and after treatment were compared using paired t-test. The response was categorized into 4 levels according to RECIST and PERCIST: CR (CMR) =1, PR (PMR) =2, SD (SMD) =3, PD (PMD) =4. Pearson chi-square test was used to compare the proportion of four levels in RECIST and PERCIST. Finally the relationship between progression-free survival (PFS) and clinicopathologic parameters (such as TNM staging, percentage changes in diameters and SUL, RECIST and PERCIST results etc.) were evaluated using univariate and multivariate Cox proportional hazards regression method. The difference of percentage changes between diameters and SUL was not significant using paired t-test (t=-1.69, P=0.098). However the difference was statistically significant in the 40 cases without increasing SUL (t=-3.31, P=0.002). The difference of evaluation results between RECIST and PERCIST was not significant by chi-square test (χ(2)=5.008, P=0.171). If RECIST evaluation excluded the new lesions which could not be found or identified on CT images the difference between RECIST and PERCIST was significant (χ(2)=11.759, P=0.007). Reduction rate of SULpeak (%), RECIST and

  5. Cytogenetic profile of aplastic anaemia in Indian children

    Directory of Open Access Journals (Sweden)

    Vineeta Gupta

    2013-01-01

    Interpretation & conclusions: Five (11.9% patients with acquired aplastic anaemia had chromosomal abnormalities. Trisomy was found to be the commonest abnormality. Cytogenetic abnormalities may be significant in acquired aplastic anaemia although further studies on a large sample are required to confirm the findings.

  6. A molecular cytogenetic analysis of introgression in Alstroemeria

    NARCIS (Netherlands)

    Kamstra, S.A.

    1999-01-01

    This thesis describes the results of a molecular cytogenetic investigation of the process of introgression in Alstroemeria . The aim of this study was to transfer chromosomes or genes from one Alstroemeria species into another. For this, two

  7. Radiation-induced malignant tumours: a specific cytogenetic profile?

    International Nuclear Information System (INIS)

    Chauveinc, L.; Gaboriaux, G.; Dutrillaux, A. M.; Dutrillaux, B.; Chauveinc, L.; Ricoul, M.; Sabatier, L.; Dutrillaux, B.

    1997-01-01

    To date, there is no criterion enabling to determine the spontaneous or radio-induced origin of malignant tumour occurring in a previously irradiated patient. Biological studies are rare. The cytogenetic data which could be found in the literature for eleven radio-induced tumours suggest that aneuploidies and polyclonality are frequent events. We studied, by R-Banding cytogenetic technique, five patients with short-term cultures (3 cases), short and long-term cultures (1 case) and xeno-grafting on nude pattern a high rate of balanced translocations, numerous random break points and a polyclonal evolution (10 clones). All other tumours, including the xeno-grafting sarcoma, had a monoclonal profile with complex karyotypes, hypo-diploid formulas and many deletions. These results show that the mechanism of radiation-induced tumours frequently involves chromosomes losses and deletions. The most likely explanation is that these alterations unmask radiation induced recessive mutations of tumour suppressor genes. (authors)

  8. A 1.7-Mb YAC contig around the human BDNF gene (11p13): integration of the physical, genetic, and cytogenetic maps in relation to WAGR syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Rosier, M.F.; Martin, A.; Houlgatte, R. [Genetique Moleculaire et Biologie du Development, Villejuif (France)] [and others

    1994-11-01

    WAGR (Wilms tumor, aniridia, genito-urinary abnormalities, mental retardation) syndrome in humans is associated with deletions of the 11p13 region. The brain-derived neurotrophic factor (BDNF) gene maps to this region, and its deletion seems to contribute to the severity of the patient`s mental retardation. Yeast artificial chromosomes (YACs) carrying the BDNF gene have been isolated and characterized. Localization of two known exons of this gene leads to a minimal estimation of its size of about 40 kb. Chimerism of the BDNF YACs has been investigated by fluorescence in situ hybridization and chromosome assignment on somatic cell hybrids. Using the BDNF gene, YAC end sequence tagged sites (STS), and Genethon microsatellite markers, the authors constructed a 1.7-Mb contig and refined the cytogenetic map at 11p13. The resulting integrated physical, genetic, and cytogenetic map constitutes a resource for the characterization of genes that may be involved in the WAGR syndrome. 42 refs., 2 figs., 3 tabs.

  9. Development of cell-cycle checkpoint therapy for solid tumors.

    Science.gov (United States)

    Tamura, Kenji

    2015-12-01

    Cellular proliferation is tightly controlled by several cell-cycle checkpoint proteins. In cancer, the genes encoding these proteins are often disrupted and cause unrestrained cancer growth. The proteins are over-expressed in many malignancies; thus, they are potential targets for anti-cancer therapies. These proteins include cyclin-dependent kinase, checkpoint kinase, WEE1 kinase, aurora kinase and polo-like kinase. Cyclin-dependent kinase inhibitors are the most advanced cell-cycle checkpoint therapeutics available. For instance, palbociclib (PD0332991) is a first-in-class, oral, highly selective inhibitor of CDK4/6 and, in combination with letrozole (Phase II; PALOMA-1) or with fulvestrant (Phase III; PALOMA-3), it has significantly prolonged progression-free survival, in patients with metastatic estrogen receptor-positive, HER2-negative breast cancer, in comparison with that observed in patients using letrozole, or fulvestrant alone, respectively. In this review, we provide an overview of the current compounds available for cell-cycle checkpoint protein-directed therapy for solid tumors. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Clinical characteristics of patient selection and imaging predictors of outcome in solid tumors treated with checkpoint-inhibitors

    International Nuclear Information System (INIS)

    Rossi, Sabrina; Toschi, Luca; Castello, Angelo; Grizzi, Fabio; Mansi, Luigi; Lopci, Egesta

    2017-01-01

    The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types. However, not all patients respond to immune checkpoint inhibitors, hence, specific biomarkers are necessary to guide and monitor therapy. The utility of PD-L1 expression as a biomarker has varied in different clinical trials, but, to date, no consensus has been reached on whether PD-L1 expression is an ideal marker for response and patient selection; approximately 20-25% of patients will respond to immunotherapy with checkpoint inhibitors despite a negative PD-L1 staining. On the other hand, major issues concern the evaluation of objective response in patients treated with immunotherapy. Pure morphological criteria as commonly used in solid tumors (i.e. RECIST) are not sufficient because change in size is not an early and reliable marker of tumor response to biological therapies. Thus, the scientific community has required a continuous adaptation of immune-related response criteria (irRC) to overcome the problem. In this context, metabolic information and antibody-based imaging with positron emission tomography (PET) have been investigated, providing a powerful approach for an optimal stratification of patients at staging and during the evaluation of the response to therapy. In the present review we provide an overview on the clinical characteristics of patient selection when using imaging

  11. Clinical characteristics of patient selection and imaging predictors of outcome in solid tumors treated with checkpoint-inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, Sabrina; Toschi, Luca [Humanitas Clinical and Research Hospital, Medical Oncology, Rozzano (Italy); Castello, Angelo [Humanitas Clinical and Research Hospital, Nuclear Medicine, Rozzano (Italy); Grizzi, Fabio [Humanitas Clinical and Research Hospital, Immunology and Inflammation, Rozzano (Italy); Mansi, Luigi [Seconda Universita di Napoli, Nuclear Medicine, Naples (Italy); Lopci, Egesta [Humanitas Clinical and Research Hospital, Nuclear Medicine, Rozzano (Italy); Humanitas Cancer Center, Humanitas Clinical and Research Hospital, Nuclear Medicine, Rozzano, MI (Italy)

    2017-12-15

    The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types. However, not all patients respond to immune checkpoint inhibitors, hence, specific biomarkers are necessary to guide and monitor therapy. The utility of PD-L1 expression as a biomarker has varied in different clinical trials, but, to date, no consensus has been reached on whether PD-L1 expression is an ideal marker for response and patient selection; approximately 20-25% of patients will respond to immunotherapy with checkpoint inhibitors despite a negative PD-L1 staining. On the other hand, major issues concern the evaluation of objective response in patients treated with immunotherapy. Pure morphological criteria as commonly used in solid tumors (i.e. RECIST) are not sufficient because change in size is not an early and reliable marker of tumor response to biological therapies. Thus, the scientific community has required a continuous adaptation of immune-related response criteria (irRC) to overcome the problem. In this context, metabolic information and antibody-based imaging with positron emission tomography (PET) have been investigated, providing a powerful approach for an optimal stratification of patients at staging and during the evaluation of the response to therapy. In the present review we provide an overview on the clinical characteristics of patient selection when using imaging

  12. Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.

    Directory of Open Access Journals (Sweden)

    Hamid R Molavian

    Full Text Available Hypoxia and acidity are two main microenvironmental factors intimately associated with solid tumors and play critical roles in tumor growth and metastasis. The experimental results of Helmlinger and colleagues (Nature Medicine 3, 177, 1997 provide evidence of a lack of correlation between these factors on the micrometer scale in vivo and further show that the distribution of pH and pO(2 are heterogeneous. Here, using computational simulations, grounded in these experimental results, we show that the lack of correlation between pH and pO(2 and the heterogeneity in their shapes are related to the heterogeneous concentration of buffers and oxygen in the blood vessels, further amplified by the network of blood vessels and the cell metabolism. We also demonstrate that, although the judicious administration of anti-angiogenesis agents (normalization process in tumors may lead to recovery of the correlation between hypoxia and acidity, it may not normalize the pH throughout the whole tumor. However, an increase in the buffering capacity inside the blood vessels does appear to increase the extracellular pH throughout the whole tumor. Based on these results, we propose that the application of anti-angiogenic agents and at the same time increasing the buffering capacity of the tumor extracellular environment may be the most efficient way of normalizing the tumor microenvironment. As a by-product of our simulation we show that the recently observed lack of correlation between glucose consumption and hypoxia in cells which rely on respiration is related to the inhomogeneous consumption of glucose to oxygen concentration. We also demonstrate that this lack of correlation in cells which rely on glycolysis could be related to the heterogeneous concentration of oxygen inside the blood vessels.

  13. Radiobiologic significance of apoptosis and micronucleation in quiescent cells within solid tumors following γ-ray irradiation

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Suzuki, Minoru; Kinashi, Yuko; Takagaki, Masao

    2001-01-01

    Purpose: To determine the frequency of apoptosis in quiescent (Q) cells within solid tumors following γ-ray irradiation, using four different tumor cell lines. In addition, to assess the significance of detecting apoptosis in these cell lines. Methods and Materials: C3H/He mice bearing SCC VII or FM3A tumors, Balb/c mice bearing EMT6/KU tumors, and C57BL mice bearing EL4 tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received γ-ray irradiation at a dose of 4-25 Gy while alive or after tumor clamping. Immediately after irradiation, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 hours after irradiation, tumor cell suspensions obtained in the same manner were fixed. The apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Results: In total cells, SCC VII, FM3A, and EMT6/KU cells showed reasonable relationships between MN frequency and surviving fraction (SF). However, fewer micronuclei were induced in EL4 cells than the other cell lines. In contrast, a comparatively close relationship between apoptosis frequency and SF was found in total cells of EL4 cell line. Less apoptosis was observed in the other cell lines. Quiescent tumor cells exhibited significantly lower values of MN and apoptosis frequency probably due to their large hypoxic fraction, similar to total tumor cells on clamped irradiation. Conclusion: γ-ray irradiation induced MN formation in SCC VII, FM3A, and EMT6/KU tumor cells, and the apoptosis was marked in EL4 cells compared with

  14. Cancer predictive value of cytogenetic markers used in occupational health surveillance programs. A report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health

    Energy Technology Data Exchange (ETDEWEB)

    Hagmar, Lars; Stroemberg, Ulf; Mikoczy, Zoli; Tinnerberg, Hakan; Skerfving, Staffan [Department of Occupational and Environmental Medicine, Lund University, S-221 85 Lund (Sweden); Bonassi, Stefano; Lando, Cecilia [Department of Environmental Epidemiology, Istituto Nazionale per la Ricerca sul Cancro, Viale Benedetto XV, I-1016132 Genoa (Italy); Hansteen, Inger-Lise [Department of Occupational Medicine, Telemark Central Hospital, N-3710 Skien (Norway); Montagud, Alicia Huici [Centro Nacional de Condiciones de Trabajo, Instituto Nacional de Seguridad e Higiene en el Trabajo, Dulcet 2-10, ES-08034 Barcelona (Spain); Knudsen, Lisbeth [National Institute of Occupational Health, Lersoe Parkalle 105, DK-2100 Copenhagen (Denmark); Norppa, Hannu [Finnish Institute of Occupational Health, Topeliuksekatu 41 aA, FIN-00250 Helsinki (Finland); Reuterwall, Christina [National Institute of Work Life, S-171 84 Solna (Sweden); Broegger, Anton [Norwegian Radium Hospital, Oslo (Norway); Forni, Alessandra [Istituto di Medicina del Lavoro Clinica del Lavoro `L. Devoto`, Milan (Italy); Hoegstedt, Benkt [Department of Occupational Medicine, Central Hospital, Halmstad (Sweden); Lambert, Bo [Department of Environmental Medicine, Centre for Nutrition and Toxicology, Karolinska Institute, Stockholm (Sweden); Mitelman, Felix [Department of Clinical Genetics, Lund University, Lund (Sweden); Nordenson, Ingrid [National Institute of Work Life, Umea (Sweden); Salomaa, Sisko [Finnish Center for Radiation and Nuclear Safety, Helsinki (Finland)

    1998-09-20

    The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base

  15. Cancer predictive value of cytogenetic markers used in occupational health surveillance programs. A report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health

    International Nuclear Information System (INIS)

    Hagmar, Lars; Stroemberg, Ulf; Mikoczy, Zoli; Tinnerberg, Hakan; Skerfving, Staffan; Bonassi, Stefano; Lando, Cecilia; Hansteen, Inger-Lise; Montagud, Alicia Huici; Knudsen, Lisbeth; Norppa, Hannu; Reuterwall, Christina; Broegger, Anton; Forni, Alessandra; Hoegstedt, Benkt; Lambert, Bo; Mitelman, Felix; Nordenson, Ingrid; Salomaa, Sisko

    1998-01-01

    The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base

  16. Cytogenetic variability in pinus sylvestris L. populations experiencing anthropogenic influence

    International Nuclear Information System (INIS)

    Oudalova, A.; Geras'kin, S.; Vasiliev, D.; Dikarev, V.

    2004-01-01

    Techno-genic pollution has become one of the most significant ecological factors determining biosphere existence and development. An analysis of genetic consequences of the radiation accidents in the South Urals and Chernobyl has shown that mutation and recombination processes are considerably accelerated in plant and animal's populations experiencing techno-genic influence. This implies that there are complicated adaptation processes leading to changes in genetic structure of populations and increasing genetic load. Pinus sylvestris L. populations growing at the territory of the 'radon' Leningrad regional radioactive waste reprocessing enterprise and Sosnovy Bor town were monitored 6 years (1997-2002) by a set of cyto-genetical and morphological tests. Cytogenetic damage levels within intercalary meristem of needle as well as in root meristem of seedlings were found to significantly exceed corresponding controls. A higher radioresistance of the Scots pine seeds analyzed was demonstrated with an acute γ-radiation that also revealed a selection process directed at an enhancement of repair efficiency and resulting in a shift of mean values of radioresistance in populations towards higher values. An enlargement of variance of studied cytogenetic parameters was found in the populations experiencing techno-genic influence. This indicates, with an account of phenomenon of the enhanced radioresistance, that there are processes of cyto-genetical adaptation in the investigated regions. An analysis of the structure of ecological-genetical variability was carried out with the purpose of separating two components in the inter-population variability - the first is engaged to the genetically determined variability of biological characteristics intrinsic for this species, and the second is responsible for the variability originating from anthropogenic contamination of the natural habitat. Changes of these two types of variability were studied in dependence on time and techno

  17. Cytogenetic variability in pinus sylvestris L. populations experiencing anthropogenic influence

    Energy Technology Data Exchange (ETDEWEB)

    Oudalova, A.; Geras' kin, S.; Vasiliev, D.; Dikarev, V. [Russian Institute of Agricultural Radiology and Agroecology, Obninsk (Russian Federation)

    2004-07-01

    Techno-genic pollution has become one of the most significant ecological factors determining biosphere existence and development. An analysis of genetic consequences of the radiation accidents in the South Urals and Chernobyl has shown that mutation and recombination processes are considerably accelerated in plant and animal's populations experiencing techno-genic influence. This implies that there are complicated adaptation processes leading to changes in genetic structure of populations and increasing genetic load. Pinus sylvestris L. populations growing at the territory of the 'radon' Leningrad regional radioactive waste reprocessing enterprise and Sosnovy Bor town were monitored 6 years (1997-2002) by a set of cyto-genetical and morphological tests. Cytogenetic damage levels within intercalary meristem of needle as well as in root meristem of seedlings were found to significantly exceed corresponding controls. A higher radioresistance of the Scots pine seeds analyzed was demonstrated with an acute {gamma}-radiation that also revealed a selection process directed at an enhancement of repair efficiency and resulting in a shift of mean values of radioresistance in populations towards higher values. An enlargement of variance of studied cytogenetic parameters was found in the populations experiencing techno-genic influence. This indicates, with an account of phenomenon of the enhanced radioresistance, that there are processes of cyto-genetical adaptation in the investigated regions. An analysis of the structure of ecological-genetical variability was carried out with the purpose of separating two components in the inter-population variability - the first is engaged to the genetically determined variability of biological characteristics intrinsic for this species, and the second is responsible for the variability originating from anthropogenic contamination of the natural habitat. Changes of these two types of variability were studied in dependence on

  18. Cytogenetic techniques for biological indications and dosimetry of of radiation damages in humans

    International Nuclear Information System (INIS)

    Hadjidekova, V.

    2003-01-01

    The cytogenetic methods present a proved way for bio-monitoring and bio-dosimetry for persons, submitted to ionising radiation in occupational and emergency conditions. Their application complement and assist the evaluation of the physical dosimetry and takes in account the individual radiosensitivity of the organism. A comparative assessment is made of the cytogenetic markers for radiation damage of humans applied in Bulgaria. It is discussed the sensitivity of the methods and their development in the last years, as well as the basic concept for their application - the causal relationship between the frequency of the observation of cytogenetic markers in peripheral blood lymphocytes and the risk of oncological disease. The conventional analysis of dicentrics is recognised as a 'golden standard' for the quantitative assessment of the radiation damage. The long term persisting translocations reflect properly the cumulative dose burden from chronic exposure. The micronucleus test allows a quick screening of large groups of persons, working in ionising radiation environment. The combined application with centromeric DNA probe improves the sensitivity and presents a modern alternative of the bio-monitoring and bio-dosimetry. It is discussed the advantages of the different cytogenetic techniques and their optimised application for the assessment of the radiation impact on humans

  19. Cytogenetic Profile of Down Syndrome Cases Seen by a General Genetics Outpatient Service in Brazil

    Science.gov (United States)

    Biselli, Joice; Goloni-Bertollo, Eny; Ruiz, Mariangela; Pavarino-Bertelli, Erika

    2009-01-01

    Down syndrome or trisomy 21 can be caused by three types of chromosomal abnormalities: free trisomy 21, translocation or mosaicism. The cytogenetic diagnosis, made through karyotypic examination, is important mainly to determine recurrence risks to assist genetic counselling. The object of this work was to carry out a cytogenetic profile of…

  20. Customized laboratory information management system for a clinical and research leukemia cytogenetics laboratory.

    Science.gov (United States)

    Bakshi, Sonal R; Shukla, Shilin N; Shah, Pankaj M

    2009-01-01

    We developed a Microsoft Access-based laboratory management system to facilitate database management of leukemia patients referred for cytogenetic tests in regards to karyotyping and fluorescence in situ hybridization (FISH). The database is custom-made for entry of patient data, clinical details, sample details, cytogenetics test results, and data mining for various ongoing research areas. A number of clinical research laboratoryrelated tasks are carried out faster using specific "queries." The tasks include tracking clinical progression of a particular patient for multiple visits, treatment response, morphological and cytogenetics response, survival time, automatic grouping of patient inclusion criteria in a research project, tracking various processing steps of samples, turn-around time, and revenue generated. Since 2005 we have collected of over 5,000 samples. The database is easily updated and is being adapted for various data maintenance and mining needs.

  1. CT of abdominal tumor

    International Nuclear Information System (INIS)

    Endo, Satoshi; Yamada, Kenji; Ito, Masatoshi; Ito, Hisao; Yamaura, Harutsugu

    1981-01-01

    CT findings in 33 patients who had an abdominal tumor were evaluated. CT revealed a tumor in 31 cases. The organ from which the tumor originated was correctly diagnosed in 18 patients. Whether the tumor was solid or cystic was correctly predicted in 28 patients. The diagnosis malignant or benign nature of tumor was correct, incorrect and impossible, in 23, 3, and five patiens, respectively. (Kondo, M.)

  2. Marcadores de proliferação celular na avaliação do crescimento do tumor sólido e ascítico de Ehrlich Cell proliferation markers for evaluating the growth of solid and ascitic forms of Ehrlich tumor

    Directory of Open Access Journals (Sweden)

    A.E. Silva

    2006-08-01

    Full Text Available Twenty BALB/c mice were inoculated with cell suspension of Ehrlich tumor. Ten mice were inoculated in the cushion plant (solid form and the other 10 in the peritoneum (ascitic form. Animals were euthanized on different times (7 and 14 days. Cytological and histological slides, immunohistochemical (PCNA analysis and NORs silver impregnation technique were performed. The results showed more proliferation on the 7th day in the ascitic form and on 14th day in the solid form, using both analyses (PCNA and AgNORs. The alterations observed in the Ehrlich tumor’s proliferation activity suggested that the growth curve is different between ascitic and solid forms. In the first one, the proliferation peak occurs on the seventh day and in the solid tumor the growth curve was more delayed, showing increased proliferative potential after seven days.

  3. Cytogenetic studies of 1232 patients with different sexual development abnormalities from the Sultanate of Oman.

    Science.gov (United States)

    Al-Alawi, Intisar; Goud, Tadakal Mallana; Al-Harasi, Salma; Rajab, Anna

    2016-02-01

    The aim of this study was to evaluate cytogenetic findings in Omani patients who had been referred for suspicion of sex chromosome abnormalities that resulted in different clinical disorders. Furthermore, it sought to examine the frequency of chromosomal anomalies in these patients and to compare the obtained results with those reported elsewhere. Cytogenetic analysis was performed on 1232 cases with variant characteristics of sexual development disorders who had been referred to the cytogenetic department, National Genetic Centre, Ministry of Health, from different hospitals in the Sultanate of Oman between 1999 and 2014. The karyotype results demonstrated chromosomal anomalies in 24.2% of the cases, where 67.5% of abnormalities were identified in referral females, whereas only 32.6% were in referral males. Of all sex chromosome anomalies detected, Turner syndrome was the most frequent (38.2%) followed by Klinefelter syndrome (24.9%) and XY phenotypic females (16%). XXX syndrome and XX phenotypic males represented 6.8% and 3.8% of all sex chromosome anomalies, respectively. Cytogenetic analysis of patients referred with various clinical suspicions of chromosomal abnormalities revealed a high rate of chromosomal anomalies. This is the first broad cytogenetic study reporting combined frequencies of sex chromosome anomalies in sex development disorders in Oman. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  4. Cytogenetic activity of the coumarin glucoside seseloside

    International Nuclear Information System (INIS)

    Arshava, E.A.

    1986-01-01

    The cytogenetic effect of the coumarin glucoside seseloside on plant objects was studied. It was established that low concentrations of the preparation (from 1 x 10 -5 to 1 x 10 -3 μg/ml) inhibit both spontaneous and radiation-induced mutagenesis. The effect of high concentrations (10 and 100 μg/ml) causes a mutagenic effect

  5. Cytogenetic highlights and transitions.

    Science.gov (United States)

    Spinner, Nancy B

    2016-06-01

    Medical cytogenetics, genetic diagnostics, and medical genetics had their origins in the late 1950's, as evaluation of human chromosomes became possible, and it was recognized that chromosomal abnormalities could cause a variety of clinical phenotypes. Dr. Laird Jackson began his medical and scientific career just as this field was emerging and he was an early adopter and driver of several key trends in the development of these fields, notably in the area of prenatal diagnostics. Laird's greatest impact was in his work to demonstrate the clinical utility of amniocentesis, chorionic villous sampling, and chromosomal microarray analysis for prenatal diagnosis. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. A cytogenetic model predicts relapse risk and survival in patients with acute myeloid leukemia undergoing hematopoietic stem cell transplantation in morphologic complete remission.

    Science.gov (United States)

    Rashidi, Armin; Cashen, Amanda F

    2015-01-01

    Up to 30% of patients with acute myeloid leukemia (AML) and abnormal cytogenetics have persistent cytogenetic abnormalities (pCytAbnl) at morphologic complete remission (mCR). We hypothesized that the prognostic significance of pCytAbnl in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) in mCR varies with cytogenetic risk group. We analyzed the data on 118 patients with AML and abnormal cytogenetics who underwent HSCT in mCR, and developed a risk stratification model based on pCytAbnl and cytogenetic risk group. The model distinguished three groups of patients (Pcytogenetics (n=25) had the shortest median time to relapse (TTR; 5 months), relapse-free survival (RFS; 3 months), and overall survival (OS; 7 months). The group with favorable/intermediate risk cytogenetics and without pCytAbnl (n=43) had the longest median TTR (not reached), RFS (57 months), and OS (57 months). The group with pCytAbnl and favorable/intermediate risk cytogenetics, or, without pCytAbnl but with unfavorable risk cytogenetics (n=50) experienced intermediate TTR (18 months), RFS (9 months), and OS (18 months). In conclusion, a cytogenetic risk model identifies patients with AML in mCR with distinct rates of relapse and survival following HSCT. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. Introduction of a multiinstitutional research project

    International Nuclear Information System (INIS)

    Zips, D.; Petersen, C.; Adam, M.; Molls, M.; Philbrook, C.; Flentje, M.; Haase, A.; Schmitt, P.; Mueller-Klieser, W.; Thews, O.; Walenta, S.; Baumann, M.

    2004-01-01

    Background: recent developments in imaging technology and tumor biology have led to new techniques to detect hypoxia and related alterations of the metabolic microenvironment in tumors. However, whether these new methods can predict radiobiological hypoxia and outcome after fractionated radiotherapy still awaits experimental evaluation. Material and methods: the present article will introduce a multiinstitutional research project addressing the impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. The four laboratories involved are situated at the universities of Dresden, Mainz, Munich and Wuerzburg, Germany. Results: the joint scientific project started to collect data obtained on a set of ten different human tumor xenografts growing in nude mice by applying various imaging techniques to detect tumor hypoxia and related parameters of the metabolic microenvironment. These techniques include magnetic resonance imaging and spectroscopy, metabolic mapping with quantitative bioluminescence and single-photon imaging, histological multiparameter analysis of biochemical hypoxia, perfusion and vasculature, and immunohistochemistry of factors related to angiogenesis, invasion and metastasis. To evaluate the different methods, baseline functional radiobiological data including radiobiological hypoxic fraction and outcome after fractionated irradiation will be determined. Conclusion: besides increasing our understanding of tumor biology, the project will focus on new, clinically applicable strategies for microenvironment profiling and will help to identify those patients that might benefit from targeted interventions to improve tumor oxygenation. (orig.)

  8. Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications

    Directory of Open Access Journals (Sweden)

    George D. Cresswell

    2016-07-01

    Full Text Available The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA are proposed as prognostic biomarkers to stratify patients, for example 1q+ in Wilms tumor (WT; current clinical trials use only one sample per tumor to profile this genetic biomarker. We multisampled 20 WT cases and assessed genome-wide allele-specific CNA and loss of heterozygosity, and inferred tumor evolution, using Illumina CytoSNP12v2.1 arrays, a custom analysis pipeline, and the MEDICC algorithm. We found remarkable diversity of ITGH and evolutionary trajectories in WT. 1q+ is heterogeneous in the majority of tumors with this change, with variable evolutionary timing. We estimate that at least three samples per tumor are needed to detect >95% of cases with 1q+. In contrast, somatic 11p15 LOH is uniformly an early event in WT development. We find evidence of two separate tumor origins in unilateral disease with divergent histology, and in bilateral WT. We also show subclonal changes related to differential response to chemotherapy. Rational trial design to include biomarkers in risk stratification requires tumor multisampling and reliable delineation of ITGH and tumor evolution.

  9. Targeted drug delivery and penetration into solid tumors.

    Science.gov (United States)

    Corti, Angelo; Pastorino, Fabio; Curnis, Flavio; Arap, Wadih; Ponzoni, Mirco; Pasqualini, Renata

    2012-09-01

    Delivery and penetration of chemotherapeutic drugs into tumors are limited by a number of factors related to abnormal vasculature and altered stroma composition in neoplastic tissues. Coupling of chemotherapeutic drugs with tumor vasculature-homing peptides or administration of drugs in combination with biological agents that affect the integrity of the endothelial lining of tumor vasculature is an appealing strategy to improve drug delivery to tumor cells. Promising approaches to achieve this goal are based on the use of Asn-Gly-Arg (NGR)-containing peptides as ligands for drug delivery and of NGR-TNF, a peptide-tumor necrosis factor-α fusion protein that selectively alters drug penetration barriers and that is currently tested in a randomized Phase III trial in patients with malignant pleural mesothelioma. © 2011 Wiley Periodicals, Inc.

  10. CCCT - NCTN Steering Committees - Pediatric and Adolescent Tumor

    Science.gov (United States)

    The Pediatric and Adolescent Solid Tumor Steering Committee addresses the design, prioritization and evaluation of concepts for large phase 2 and phase 3 clinical trials in extracranial solid tumors of children and youth.

  11. Cytogenetic and Molecular Findings in Children with Acute Lymphoblastic Leukemia: Experience of a Single Institution in Argentina

    Science.gov (United States)

    Coccé, Mariela C.; Alonso, Cristina N.; Rossi, Jorge G.; Bernasconi, Andrea R.; Rampazzi, Maria A.; Felice, Maria S.; Rubio, Patricia L.; Eandi Eberle, Silvia; Medina, Adriana; Gallego, Marta S.

    2015-01-01

    The purpose of the current study was to evaluate the cytogenetic findings in 1,057 children with acute lymphoblastic leukemia (ALL) referred to the cytogenetics laboratory at the Hospital de Pediatría Dr. Juan P. Garrahan, between 1991 and 2014. Chromosomal abnormalities were evaluated by G-banding and FISH. Since December 2002, RT-PCR determinations were systematically carried out for BCR-ABL1, KMT2A-AFF1, ETV6-RUNX1, and TCF3-PBX1 rearrangements in children, adding KMT2A-MLLT3 and KMT2A-MLLT1 in infants. The percentage of abnormalities detected by cytogenetics was 70.1%. Four novel abnormalities, t(2;8)(p11.2;p22), inv(4)(p16q25), t(1;7)(q25;q32), and t(5;6)(q21;q21), were found in this cohort. We compared cytogenetic and RT-PCR results for BCR-ABL1, KMT2A-AFF1 and TCF3-PBX1 rearrangements in 497 children evaluated by both methods. The results were highly concordant (p cytogenetic findings in children with ALL reported in Argentina. PMID:26648836

  12. Molecular cytogenetic characterization of a new wheat Secale ...

    Indian Academy of Sciences (India)

    A stable, highly fertile wheat Secale africanum substitution line LF24, derived from the F7 generation of a cross between Mianyang11 (MY11) and Triticum durum, S. africanum amphiploid (YF) was identified through molecular cytogenetic analysis. Application of C-banding, in situ hybridization and molecular markers ...

  13. Cytogenetics in medical practice | Nelson | South African Medical ...

    African Journals Online (AJOL)

    A cytogenetics and tissue culture laboratory is an essential component of a medical genetics department. Chromosome analysis provides a definite answer in many cases where clinical diagnosis is in doubt, and supplies information on which counselling may be based. Cultured cells from different body tissues may be the ...

  14. Cytogenetic effects in adolescents from different areas of Kemerovskaya oblast'

    International Nuclear Information System (INIS)

    Druzhinin, V.G.; Lifanov, A.Y.; Golovina, T.A.

    1995-01-01

    Considerable variations in the frequency of spontaneous chromosomal aberrations were revealed during a cytogenetic study of two groups of adolescents from ecologically different areas of Kemerovskaya oblast'. In a sample of adolescents living in an industrial center (the Kemerovo city), this parameter (1.4±0.37%) did not exceed the population average value, whereas adolescents of the same age from a mountain region with sparse industry (the town of Tashtagol) exhibited, on average, a frequency of 5.87±0.62%. An increased proportion of chromosomal-type aberrations in the qualitative spectrum of cytogenetic damage, which was observed for the group of adolescents from Tashtagol, suggests that this population was exposed to radiation. 13 refS., 1 fig., 3 tabs

  15. Effect of veliparib (ABT-888) on cardiac repolarization in patients with advanced solid tumors : a randomized, placebo-controlled crossover study

    NARCIS (Netherlands)

    Munasinghe, Wijith; Stodtmann, Sven; Tolcher, Anthony; Calvo, Emiliano; Gordon, Michael; Jalving, Mathilde; de Vos-Geelen, Judith; Medina, Diane; Bergau, Dennis; Nuthalapati, Silpa; Hoffman, David; Shepherd, Stacie; Xiong, Hao

    2016-01-01

    Veliparib (ABT-888) is an orally bioavailable potent inhibitor of poly(ADP-ribose) polymerase (PARP)-1 and PARP-2. This phase 1 study evaluated the effect of veliparib on corrected QT interval using Fridericia's formula (QTcF). Eligible patients with advanced solid tumors received single-dose oral

  16. Radiologic findings of granulosa cell tumor of the ovary

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Jung Eun; Kim, Kie Hwan; Yoo, Ji Young; Lee, Eun Chun; Lee, Tae Hyun; Chin, Soo Il [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1997-08-01

    To evaluate the radiologic findings of granulosa cell tumor of the ovary. Fourteen cases(fifteen tumors) of pathologically confirmed ovarian granulosa cell tumor were retrospectively analyzed on the basis of CT(n=10), MR imaging(n=4), and ultrasound(n=7) findings. The patients' mean age was 44.3(range, 5-71)years. The mean diameter of the tumors was 12.1(range, 5-26.5)cm. Thirteen cases were unilateral, and one was bilateral. Eleven tumors(ten cases) were mainly solid and eight of these had focal cystic components. Multilocular cysts accounted for three cases, and in two of these, mural nodules were present. One case was a unilocular cyst with no mural nodule. Ten cases were well demarcated. All the solid tumors were enhanced on postcontrast CT and MR imaging. Endometrial thickening was seen in five cases, ascites in six, and peritoneal implants or omental fat infiltration in five. One was associated with lymph node metastasis. All the postmenopausal patients had solid tumors, whereas 66.7%(4 of 6 cases) of young adults and children had cystic tumors. Granulosa cell tumors of the ovary were solid or cystic;the former were more common. There were no characteristic findings which permitted definitive differentiation from other ovarian tumors.

  17. Cytogenetic analysis and occupational health in the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Šrám, Radim; Rössner, P.; Šmerhovský, Zdeněk

    2004-01-01

    Roč. 566, č. 1 (2004), s. 21-48 ISSN 1383-5742 Institutional research plan: CEZ:AV0Z5039906 Keywords : cytogenetic analysis * occupational exposure Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 3.667, year: 2004

  18. Delayed repair of DNA single-strand breaks does not increase cytogenetic damage

    International Nuclear Information System (INIS)

    Morgan, W.F.; Djordjevic, M.C.; Jostes, R.F.; Pantelias, G.E.

    1985-01-01

    DNA damage and cytogenetic effects of ionizing radiation were investigated in Chinese hamster ovary (CHO) cells and unstimulated human peripheral blood lymphocytes. DNA damage and repair were analysed by alkaline elution under conditions that predominantly measured DNA single-strand breaks (ssb). X-radiation (2.5 Gy) induced ssb in both CHO cells and unstimulated lymphocytes, and the breaks were repaired within 30 and 90 min, respectively. This rapid repair was delayed by the poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide (3AB). The cytogenetic effects of the 3AB-induced delay in DNA repair were examined by analysing sister chromatid exchange (SCE) frequency in CHO cells and fragmentation of prematurely condensed chromosomes (PCC) in unstimulated human lymphocytes after 2.5 Gy of X-rays. Although 3AB delayed the rejoining of DNA ssb, this delay did not result in increased cytogenetic damage manifested as either SCE or fragmentation of PCC. These results indicate that the rapidly rejoining DNA ssb are not important in the production of chromosome damage. (author)

  19. Clinicopathologic features and surgical outcome of solid pseudopapillary tumor of the pancreas: analysis of 17 cases

    Directory of Open Access Journals (Sweden)

    Wang Xiao-Guang

    2013-02-01

    Full Text Available Abstract Background We summarize our experience of the diagnosis, surgical treatment, and prognosis of solid pseudopapillary tumors (SPTs. Methods We carried out a retrospective study of clinical data from a series of 17 patients with SPT managed in two hospitals between October 2001 and November 2011. Results All of the 17 patients were female and the average age at diagnosis was 26.6 years (range 11 years to 55 years. The tumor was located in the body or tail in ten patients, the head in five patients, and the neck in two patients. The median tumor size was 5.5 cm (range 2 cm to 10 cm. All 17 patients had curative resections, including seven distal pancreatectomies, five local resections, four pancreaticoduodenectomies, and one central pancreatectomy. Two patients required concomitant splenic vein resection due to local tumor invasion. All patients were alive and disease-free at a median follow-up of 48.2 months (range 2 to 90 months. There were no significant associations between clinicopathologic factors and malignant potential of SPT. Ki-67 was detected in three patients with pancreatic parenchyma invasion. Conclusions The SPT is an infrequent tumor, typically affecting young women without notable symptoms. Surgical resection is justified even in the presence of local invasion or metastases, as patients demonstrate excellent long-term survival. Positive immunoreactivity for Ki-67 may predict the malignant potential of SPTs.

  20. Polyphenon-E encapsulated into chitosan nanoparticles inhibited proliferation and growth of Ehrlich solid tumor in mice

    Directory of Open Access Journals (Sweden)

    Azza I. Othman

    2018-03-01

    Full Text Available Limited bioavailability of green tea polyphenols hampered their delivery to tumor and hence therapeutic effectiveness. This study investigated the antitumor activity of polyphenon-E (PE encapsulated into chitosan nanoparticles (CSNPs in Ehrlich solid tumor in mice. CSNPs-PE, with a particle size of 53–69 nm showed 83% entrapment efficiency and a sustained release of PE in pH = 7.4 at 37 °C. The data demonstrated a higher percentage of released drug in case of less crosslinked formulations. Ehrlich ascites carcinoma (EAC cells (2.5 × 106/0.2 ml/mouse were injected subcutaneously in the back of mice. Oral administration of CSNPs-PE for 30 days produced a significant decrease in tumor volume (53% and weight (60% compared with free PE and voids CSNPs (72%. Compared with free PE and control, cell cycle revealed G0/G1 arrest associated with decrease in proliferating cell nuclear antigen (PCNA. In tumor tissue of CSNPs-PE treated mice, compared with free PE, there were; 1 induction of Bax and p53, 2 activation of caspases-3,-8 and -9, and CD95, 3 decrease in Bcl-2 expression of 4 inhibition of VEGF and CD31 expressions in tumor tissue. In conclusion, encapsulation of PE into CSNPs provided a good platform for cancer chemotherapy and raised existing application of different polyphenols for nanochemotherapy/prevention.

  1. Cytogenetical effects of low doses: results obtained by N.N.Luchik and present-day problems

    International Nuclear Information System (INIS)

    Geras'kin, S.A.; Sevan'kaev, A.V.

    1996-01-01

    The analysis of present status of the problem of quantitative assessment of cytogenetic effects low is presented. The importance of works of N.V. Luchik is demonstrated for the development of this field of radiobiology. The results of the author's own experimental and theoretical research on the regularities of induction of cytogenetical damage by low doses of ionising radiation are presented

  2. Long Term Storage of cytogenetic changes in liquidators of Chernobyl

    International Nuclear Information System (INIS)

    Karpov, V. B.

    2004-01-01

    At present chromosome aberration analysis in lymphocytes as well as micronucleus assay are most reliable methods of bio indication of radiation effects. The problem of persistent of cytogenetic changes during the long term after exposure is very important. The cytogenetic studies of liquidators residents of St. Petersburg and region revealed that the average chromosome aberration rate 4-5 years after the accident constitutes 4.94±0.38, number of aberrant cells was 4.82±0.36, dicentrics -0.23±0.10 per 100 cells, micronucleus number -46.1±2.1 per 100 cells that is significantly higher than in control group. dispersion analysis confirms the reported level of external exposure effects on chromosome aberration rate (?=0.04) in this group of liquidators. In 73 persons from the group of high risk participants of nuclear tests, nuclear submarine personnel 8-45 years after average number of chromosome aberrations was 6.5±0.32; dicentrics - 0.64±0.10, centric rings- 0.04±0.02 per 100 cells, for micronuclei -51.4±2.82 per thousand cells, that is significantly higher than in control group (p<0.01). In 45.2% cases the aberration markers (disentrics and centric rings) were found. The late cytogenetic effects were observed after decades and possibility to use these indicators for long term diagnosis is now under consideration. (Author)

  3. Nanoscaled biological gated field effect transistors for cytogenetic analysis

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Andersen, Karsten Brandt

    2014-01-01

    Cytogenetic analysis is the study of chromosome structure and function, and is often used in cancer diagnosis, as many chromosome abnormalities are linked to the onset of cancer. A novel label free detection method for chromosomal translocation analysis using nanoscaled field effect transistors...

  4. Significance of molecular-cytogenetic aberrations for the achievement of first remission in de novo acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Boriana M. Zaharieva

    2008-12-01

    Full Text Available OBJECTIVE: The majority of adults diagnosed with acute myeloid leukemia (AML display acquired cytogenetic aberrations at presentation. In this article, we present the major cytogenetic findings regarding AML and review their clinical significance for achievement of the first complete remission.METHODS: We studied 71 adult patients with de novo AML, without previous myelodysplasia or alkylating therapy. Conventional cytogenetics and FISH were performed on bone marrow cells. The patients with AML were assigned to 12 subgroups according to established data for cytogenetic, molecular and general laboratory results. The selection of the analyzed parameters is consistent with internationally accepted “prognostic factors” in adult AML.RESULTS: Complete remission upon induction therapy was achieved in 40% of cases (in a mean period of 2.3 months from therapy initiation. The patients with t(15;17 PML-RARA and inv(16/CBFbeta-MYH11ë demonstrated the highest frequency of complete remission. Patients with hypodiploidy, t(9;22/bcr-abl and complex karyotypes were therapy-resistant or died within the first three months after AML diagnosis. CONCLUSION: Molecular-cytogenetic findings have an important significance for achievement of first complete remission. However, laboratory and biologic features (age, WBC and LDH and type of AML have a large influence on the disease outcome.

  5. Therapeutic efficacy and microSPECT/CT imaging of {sup 188}Re-DXR-liposome in a C26 murine colon carcinoma solid tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Y.-J.; Chang, C.-H.; Yu, C.-Y.; Chang, T.-J.; Chen, L.-C. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chen, M.-H. [National Health Research Institutes, Miaoli, Taiwan (China); Lee, T.-W. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Ting Gann [National Health Research Institutes, Miaoli, Taiwan (China)], E-mail: gann.ting@msa.hinet.net

    2010-01-15

    Nanocarriers can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. The objective of this study was to investigate the therapeutic efficacy of a new co-delivery radiochemotherapeutics of {sup 188}Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (DXR) ({sup 188}Re-DXR-liposome) in a C26 murine colon carcinoma solid tumor model. To evaluate the targeting and localization of {sup 188}Re-DXR-liposome in C26 murine tumor-bearing mice, biodistribution, microSPECT/CT imaging and pharmacokinetic studies were performed. The antitumor effect of {sup 188}Re-DXR-liposome was assessed by tumor growth inhibition, survival ratio and histopathological hematoxylin-eosin staining. The tumor target and localization of the nanoliposome delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome were demonstrated in the biodistribution, pharmacokinetics and in vivo nuclear imaging studies. In the study on therapeutic efficacy, the tumor-bearing mice treated with bimodality radiochemotherapeutics of {sup 188}Re-DXR-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI=0.048; 74 days) than those treated with radiotherapeutics of {sup 188}Re-liposome (MGI=0.134; 60 days) and chemotherapeutics of Lipo-Dox (MGI=0.413; 38 days). The synergistic tumor regression effect was observed with the combination index (CI) exceeding 1 (CI=1.145) for co-delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome. Two (25%) of the mice treated with radiochemotherapeutics were completely cured after 120 days. The therapeutic efficacy of radiotherapeutics of {sup 188}Re-liposome and the synergistic effect of the combination radiochemotherapeutics of {sup 188}Re-DXR-liposome have been demonstrated in a C26 murine solid tumor animal model, which pointed to the potential benefit and promise of the co-delivery of

  6. Current concepts in non-gastrointestinal stromal tumor soft tissue sarcomas: A primer for radiologists

    Energy Technology Data Exchange (ETDEWEB)

    Baheti, Akahay D. [Dept. of Radiology, Tata Memorial Centre, Mumbai (India); Tirumani, Harika [Dept. of Radiology, University of Arkansas for Medical Sciences, Little Rock (United States); O' Neill, Alibhe; Jagannathan, Jyothi P. [Dept. of Imaging, Dana-Farber Cancer Institute, Boston (United States)

    2017-01-15

    Non-gastrointestinal stromal tumor (GIST) soft tissue sarcomas (STSs) are a heterogeneous group of neoplasms whose classification and management continues to evolve with better understanding of their biologic behavior. The 2013 World Health Organization (WHO) has revised their classification based on new immunohistochemical and cytogenetic data. In this article, we will provide a brief overview of the revised WHO classification of soft tissue tumors, discuss in detail the radiology and management of the two most common adult non-GIST STS, namely liposarcoma and leiomyosarcoma, and review some of the emerging histology-driven targeted therapies in non-GIST STS, focusing on the role of the radiologist.

  7. Current concepts in non-gastrointestinal stromal tumor soft tissue sarcomas: A primer for radiologists

    International Nuclear Information System (INIS)

    Baheti, Akahay D.; Tirumani, Harika; O'Neill, Alibhe; Jagannathan, Jyothi P.

    2017-01-01

    Non-gastrointestinal stromal tumor (GIST) soft tissue sarcomas (STSs) are a heterogeneous group of neoplasms whose classification and management continues to evolve with better understanding of their biologic behavior. The 2013 World Health Organization (WHO) has revised their classification based on new immunohistochemical and cytogenetic data. In this article, we will provide a brief overview of the revised WHO classification of soft tissue tumors, discuss in detail the radiology and management of the two most common adult non-GIST STS, namely liposarcoma and leiomyosarcoma, and review some of the emerging histology-driven targeted therapies in non-GIST STS, focusing on the role of the radiologist

  8. CT morphology of benign median nerve tumors

    International Nuclear Information System (INIS)

    Feyerabend, T.; Schmitt, R.; Lanz, U.; Warmuth-Metz, M.; Wuerzburg Univ.

    1990-01-01

    Computed tomography (CT) was performed in 3 patients with benign tumors of the median nerve, histologically confirmed as neurilemmoma, fibrolipoma and hemangioma. The neurilemmoma showed a ring-shaped contrast enhancement. The fibrolipoma presented with areas of solid soft tissue and areas of fat. The hemangioma was a solid tumor with a lacunar, vascular contrast enhancement. According to our experience and to the previous literature CT gives useful information regarding the anatomic location, size, and relationship of peripheral nerve sheath tumors to surrounding structures, and may help to differentiate between various tumor types. (orig.)

  9. Optimizing the dosing schedule of l-asparaginase improves its anti-tumor activity in breast tumor-bearing mice.

    Science.gov (United States)

    Shiromizu, Shoya; Kusunose, Naoki; Matsunaga, Naoya; Koyanagi, Satoru; Ohdo, Shigehiro

    2018-04-01

    Proliferation of acute lymphoblastic leukemic cells is nutritionally dependent on the external supply of asparagine. l-asparaginase, an enzyme hydrolyzing l-asparagine in blood, is used for treatment of acute lymphoblastic leukemic and other related blood cancers. Although previous studies demonstrated that l-asparaginase suppresses the proliferation of cultured solid tumor cells, it remains unclear whether this enzyme prevents the growth of solid tumors in vivo. In this study, we demonstrated the importance of optimizing dosing schedules for the anti-tumor activity of l-asparaginase in 4T1 breast tumor-bearing mice. Cultures of several types of murine solid tumor cells were dependent on the external supply of asparagine. Among them, we selected murine 4T1 breast cancer cells and implanted them into BALB/c female mice kept under standardized light/dark cycle conditions. The growth of 4T1 tumor cells implanted in mice was significantly suppressed by intravenous administration of l-asparaginase during the light phase, whereas its administration during the dark phase failed to show significant anti-tumor activity. Decreases in plasma asparagine levels due to the administration of l-asparaginase were closely related to the dosing time-dependency of its anti-tumor effects. These results suggest that the anti-tumor efficacy of l-asparaginase in breast tumor-bearing mice is improved by optimizing the dosing schedule. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  10. How cytogenetical methods help victims prove radiation exposure and claim right for social support: NCERM experience

    International Nuclear Information System (INIS)

    Aleksanin, S.; Slozina, N.; Neronova, E.; Smoliakov, E.

    2011-01-01

    Russian citizens who were irradiated because of radiation disasters, nuclear weapons testing and some other sources have a right to some social support and financial compensation. In order to get this compensation people have to prove that they were irradiated. As it is, not all victims for a variety of reasons have formal documents. Thus they apply for cytogenetic investigation to prove irradiation months, years and even decades after irradiation. Since 1992 the cytogenetic investigations related to radiation exposure were performed in NRCERM for more than 700 people. At the beginning of this investigation FISH method was not certified as a biodosimenty test in Russia. Only dicentric analysis was approved as a proof of irradiation. It is known that the rate of dicentrics decrease in time, but the residual level of cytogenetical markers could be revealed a long time after a radiation accident. Thus the dicentric analysis was performed for the people who applied for biological indication of radiation exposure at that time. Rates of dicentrics exceeding control levels were revealed in half the people who applied for radiation conformation. Now FISH method is certified in Russia and both cytogenetic tests of biodosimetry (dicentrics and FISH) are available for all comers. Increased levels of translocations were found in 8 cases (the dose rate from 0.16 to 0.64 Gy). On the basis of the results of cytogenetic tests official documents were supplied to these people and they were entitled to apply for radiation exposure compensation. Thus cytogenetic tests are very effective and in some cases the only possible way for the victims to prove irradiation exposure and to apply for radiation exposure compensation a long time after an accident.

  11. How cytogenetical methods help victims prove radiation exposure and claim right for social support: NCERM experience

    Energy Technology Data Exchange (ETDEWEB)

    Aleksanin, S., E-mail: Aleksanin@arcerm.spb.ru [Nikiforov Russian Center of Emergency and Radiation Medicine EMERCOM of Russia, (NRCERM) ul. Akademika Lebedeva 4/2, 194044 St. Petersburg (Russian Federation); Slozina, N., E-mail: NataliaSlozina@peterlink.ru [Nikiforov Russian Center of Emergency and Radiation Medicine EMERCOM of Russia, (NRCERM) ul. Akademika Lebedeva 4/2, 194044 St. Petersburg (Russian Federation); Neronova, E.; Smoliakov, E. [Nikiforov Russian Center of Emergency and Radiation Medicine EMERCOM of Russia, (NRCERM) ul. Akademika Lebedeva 4/2, 194044 St. Petersburg (Russian Federation)

    2011-09-15

    Russian citizens who were irradiated because of radiation disasters, nuclear weapons testing and some other sources have a right to some social support and financial compensation. In order to get this compensation people have to prove that they were irradiated. As it is, not all victims for a variety of reasons have formal documents. Thus they apply for cytogenetic investigation to prove irradiation months, years and even decades after irradiation. Since 1992 the cytogenetic investigations related to radiation exposure were performed in NRCERM for more than 700 people. At the beginning of this investigation FISH method was not certified as a biodosimenty test in Russia. Only dicentric analysis was approved as a proof of irradiation. It is known that the rate of dicentrics decrease in time, but the residual level of cytogenetical markers could be revealed a long time after a radiation accident. Thus the dicentric analysis was performed for the people who applied for biological indication of radiation exposure at that time. Rates of dicentrics exceeding control levels were revealed in half the people who applied for radiation conformation. Now FISH method is certified in Russia and both cytogenetic tests of biodosimetry (dicentrics and FISH) are available for all comers. Increased levels of translocations were found in 8 cases (the dose rate from 0.16 to 0.64 Gy). On the basis of the results of cytogenetic tests official documents were supplied to these people and they were entitled to apply for radiation exposure compensation. Thus cytogenetic tests are very effective and in some cases the only possible way for the victims to prove irradiation exposure and to apply for radiation exposure compensation a long time after an accident.

  12. Cytogenetic characterization of Encyclia caximboensis cultivated in vitro (Orchidaceae

    Directory of Open Access Journals (Sweden)

    Gizelly Mendes Silva

    2015-12-01

    Full Text Available Encyclia caximboensis is an Amazonian species endemic to the Serra do Cachimbo, which is located between the northern of the Mato Grosso state and the southern part of Para state. Studies reporting in vitro cultivation and cytogenetic characterization of this species are still scarce. Therefore, the objective of this work was to determine the cytogenetic characteristics and to identify the nucleolar organizer regions (NORs of the species E. Caximboensis, cultivated in vitro. Seeds of E. caximboensis were disinfected using a syringe and subsequently cultivated in MS medium without growth regulators. The germination started after 20 days of culture, with the development of protocorm and 40,500 seedlings were obtained after 90 days of culture. To perform the cytogenetic characterization, root tips of 180-day-old seedlings were submitted to blocking treatment using 3 µM trifiuralin and then fixed in methanol-acetic acid solution, 3:1 (v/v. The meristems were submitted to enzymatic digestion, fixed in methanol-acetic acid solution, 3:1 (v/v and the slides were stained using 5% Giemsa solution. Ag-NOR banding was carried out on 20-day-old slides by incubation in 50% silver nitrate solution (AgNO3 for 19 hours. The results indicated that E. caximboensis has 2n=2x=24 with all metacentric type chromosomes, ranging from 1.88 to 0.66 pm in length, with simple NORs in small blocks localized in the proximal region of the third chromosome pair.

  13. Not All Next Generation Sequencing Diagnostics are Created Equal: Understanding the Nuances of Solid Tumor Assay Design for Somatic Mutation Detection

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Phillip N., E-mail: pgray@ambrygen.com; Dunlop, Charles L.M.; Elliott, Aaron M. [Ambry Genetics, 15 Argonaut, Aliso Viejo, CA 92656 (United States)

    2015-07-17

    The molecular characterization of tumors using next generation sequencing (NGS) is an emerging diagnostic tool that is quickly becoming an integral part of clinical decision making. Cancer genomic profiling involves significant challenges including DNA quality and quantity, tumor heterogeneity, and the need to detect a wide variety of complex genetic mutations. Most available comprehensive diagnostic tests rely on primer based amplification or probe based capture methods coupled with NGS to detect hotspot mutation sites or whole regions implicated in disease. These tumor panels utilize highly customized bioinformatics pipelines to perform the difficult task of accurately calling cancer relevant alterations such as single nucleotide variations, small indels or large genomic alterations from the NGS data. In this review, we will discuss the challenges of solid tumor assay design/analysis and report a case study that highlights the need to include complementary technologies (i.e., arrays) and germline analysis in tumor testing to reliably identify copy number alterations and actionable variants.

  14. Reporting of Diagnostic Cytogenetic Results.

    Science.gov (United States)

    Giersch, Anne B S; Bieber, Frederick R; Dubuc, Adrian M; Fletcher, Jonathan A; Ligon, Azra H; Mason-Suares, Heather; Morton, Cynthia C; Weremowicz, Stanislawa; Xiao, Sheng; Dal Cin, Paola

    2016-04-01

    This appendix, developed by the staff at the Center for Advanced Molecular Diagnostics in the Department of Pathology at the Brigham and Women's Hospital, includes a comprehensive list of current "macros" or standardized statements used to facilitate reporting of cytogenetic results. These are provided as a useful reference for other laboratories. The statements are organized under the general categories of constitutional or acquired abnormalities and subdivided into analysis type (GTG-banding, FISH, or chromosomal microarray). Multi-specimen usage macros are included that can be applied to two or more specimen types. Copyright © 2016 John Wiley & Sons, Inc.

  15. Molecular cytogenetic identification of a wheat–Thinopyrum ...

    Indian Academy of Sciences (India)

    FANG HE

    ... have supported the development of several wheat germplasms that are in use ... Li, formerly of the Northwest Institute of Botany, Chinese. Academy of Sciences ... Cytogenetic analysis. Seeds were germinated in Petri dishes maintained at 4.

  16. Molecular cytogenetic characterization of two Turner syndrome patients with mosaic ring X chromosome.

    Science.gov (United States)

    Chauhan, Pooja; Jaiswal, Sushil Kumar; Lakhotia, Anjali Rani; Rai, Amit Kumar

    2016-09-01

    In the present study, we reported two cases of TS with mosaic ring X chromosome showing common clinical characteristics of TS like growth retardation and ovarian dysfunction. The purpose of the present study was to cytogenetically characterize both cases. Whole blood culture and G-banding were performed for karyotyping the cases following standard protocol. Origin of the ring chromosome and degree of mosaicism were further determined by fluorescence in situ hybridization (FISH). Breakpoints and loss of genetic material in formation of different ring X chromosomes r (X) in cases were determined with the help of cytogenetic microarray. Cases 1 and 2 with ring chromosome were cytogenetically characterized as 45, X [114]/46Xr (X) (p22.11q21.32) [116] and 45, X [170]/46, Xr (X) (p22.2q21.33) [92], respectively. Sizes of these ring X chromosomes were found to be ~75 and ~95 Mb in cases 1 and 2, respectively, using visual estimation as part of cytogenetic observation. In both cases, we observed breakpoints on Xq chromosome were within relatively narrow region between Xq21.33 and Xq22.1 compared to regions in previously reported cases associated with ovarian dysgenesis. Our observation agrees with the fact that despite of large heterogeneity, severity of the cases with intact X-inactive specific transcript (XIST) is dependent on degree of mosaicism and extent of Xq deletion having crucial genes involved directly or indirectly in various physiological involving ovarian cyclicity.

  17. A phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors.

    Science.gov (United States)

    Lin, Jianqing; Gilbert, Jill; Rudek, Michelle A; Zwiebel, James A; Gore, Steve; Jiemjit, Anchalee; Zhao, Ming; Baker, Sharyn D; Ambinder, Richard F; Herman, James G; Donehower, Ross C; Carducci, Michael A

    2009-10-01

    This was a phase I trial to determine the minimal effective dose and optimal dose schedule for 5-azacytidine (5-AC) in combination with sodium phenylbutyrate in patients with refractory solid tumors. The pharmacokinetics, pharmacodynamics, and antineoplastic effects were also studied. Three dosing regimens were studied in 27 patients with advanced solid tumors, and toxicity was recorded. The pharmacokinetics of the combination of drugs was evaluated. Repeat tumor biopsies and peripheral blood mononuclear cells (PBMC) were analyzed to evaluate epigenetic changes in response to therapy. EBV titers were evaluated as a surrogate measure for gene re-expression of epigenetic modulation in PBMC. The three dose regimens of 5-AC and phenylbutyrate were generally well tolerated and safe. A total of 48 cycles was administrated to 27 patients. The most common toxicities were bone marrow suppression-related neutropenia and anemia, which were minor. The clinical response rate was disappointing for the combination of agents. One patient showed stable disease for 5 months whereas 26 patients showed progressive disease as the best tumor response. The administration of phenylbutyrate and 5-AC did not seem to alter the pharmacokinetics of either drug. Although there were individual cases of targeted DNA methyltransferase activity and histone H3/4 acetylation changes from paired biopsy or PBMC, no conclusive statement can be made based on these limited correlative studies. The combination of 5-AC and phenylbutyrate across three dose schedules was generally well tolerated and safe, yet lacked any real evidence for clinical benefit.

  18. Cytogenetics of the Brazilian Bolitoglossa paraensis (Unterstein, 1930 salamanders (Caudata, Plethodontidae

    Directory of Open Access Journals (Sweden)

    Jéssica Barata da Silva

    2014-09-01

    Full Text Available Plethodontid salamanders of genus Bolitoglossa constitute the largest and most diverse group of salamanders, including around 20% of living caudate species. Recent studies have indicated the occurrence of five recognized species in the Brazilian Amazon Rainforest. We present here the first cytogenetic data of a Brazilian salamander, which may prove to be a useful by contribution to the cytotaxonomy of the genus. Specimens were collected near the "type" locality (Utinga, Belém, PA, Brazil. Chromosomal preparations from duodenal epithelial cells and testes were subjected to Giemsa staining, C-banding and DAPI/CMA3 fluorochrome staining. All specimens showed a karyotype with 13 bi-armed chromosome pairs (2n = 26. Nucleolar Organizer Regions, evidenced by CMA3, were located distally on the long arm of pair 7 (7q. DAPI+ heterochromatin was predominantly centromeric, with some small pericentromeric bands. Although the C-banding patterns of other Bolitoglossa species are so far unknown, cytogenetic studies conducted in other Plethodontid salamanders have demonstrated that pericentromeric heterochromatin is a useful cytological marker for identifying interspecific homeologies. Species diversification is usually accompanied by chromosomal changes. Therefore, the cytogenetic characterization of Bolitoglossa populations from the middle and western Brazilian Amazon Basin could identify differences which may lead to the identification of new species.

  19. Diagnosis and treatment of solid pseudopapillary tumor of the pancreas: experience of one single institution from Turkey

    Science.gov (United States)

    2013-01-01

    Background Solid pseudopapillary neoplasia (SPN) of the pancreas is an extremely rare epithelial tumor of low malignant potential. SPN accounts for less than 1% to 2% of exocrine pancreatic tumors. The aim of this study is to report our experience with SPN of the pancreas. It includes a summary of the current literature to provide a reference for the management of this rare clinical entity. Methods A retrospective analysis was performed of all patients diagnosed and treated for SPN in our hospital over the past 15 years (1998 to 2013). A database of the characteristics of these patients was developed, including age, gender, tumor location and size, treatment, and histopathological and immunohistochemical features. Results During this time period, 255 patients with pancreatic malignancy (which does not include ampulla vateri, distal choledocal and duodenal tumor) were admitted to our department, only 10 of whom were diagnosed as having SPN (2.5%). Nine patients were women (90%) and one patient was a man (10%). Their median age was 38.8 years (range 18 to 71). The most common symptoms were abdominal pain and dullness. Seven patients (70%) presented with abdominal pain or abdominal dullness and three patient (30%) were asymptomatic with the diagnosis made by an incidental finding on routine examination. Abdominal computed tomography and/or magnetic resonance imaging showed the typical features of solid pseudopapillary neoplasm in six (60%) of the patients. Four patients underwent distal pancreatectomy with splenectomy, one patient underwent a total mass excision, and one patient underwent total pancreatic resection. Two required extended distal pancreatectomy with splenectomy. Two underwent spleen-preserving distal pancreatectomy. Conclusions SPN is a rare neoplasm that primarily affects young women. The prognosis is favorable even in the presence of distant metastasis. Although surgical resection is generally curative, a close follow-up is advised in order to

  20. Cytogenetic effects of radiation from Chernobyl nuclear accident on humans and animals in the contaminated area of Belarus

    International Nuclear Information System (INIS)

    Yeliseeva, K.; Mikhalevich, L.; Kartel, N.

    1995-01-01

    Cytogenetic monitoring of amphibian and rodent populations, and children from the radio contaminated regions of the Republic of Belarus was conducted as a follow up to Chernobyl nuclear accident. A statistically significant increase in the levels of cytogenetic damage in bone marrow cells of amphibians and rodent and in peripheral blood lymphocytes of children was found. The presence of chromosome-type aberrations supports the conclusion that radiation is the causative agent. However, no direct relationship between the level of radionuclide contamination and the degree of the cytogenetic damage was found. (Author)

  1. Dynamics of cytogenetic indexes of agriculture animals dwelling on the Semipalatinsk test site territory

    International Nuclear Information System (INIS)

    Mukusheva, M.K.; Sejsebaev, A.T.; Karabalin, B.K.; Tusupbaev, V.I.; Zhapbasov, R.Zh.

    2001-01-01

    Aim of the work is analysis of genetic processes taking place in the agricultural animal populations exposed to constant radiation due to increased radiation background in their dwelling places. By the cytogenetic methods the sheep, cattle and horses were examined. It was revealed cytogenetic effect manifested in form of a high genome genetic instability level for studied animals. It is suggested, that the effect is caused with low chronic ionizing radiation doses exposure on the agricultural animals somatic cells

  2. Longitudinal fluorescence in situ hybridization reveals cytogenetic evolution in myeloma relapsing after autologous transplantation

    Science.gov (United States)

    Merz, Maximilian; Jauch, Anna; Hielscher, Thomas; Mai, Elias K.; Seckinger, Anja; Hose, Dirk; Bertsch, Uta; Neben, Kai; Raab, Marc S.; Salwender, Hans; Blau, Igor W.; Lindemann, Hans-Walter; Schmidt-Wolf, Ingo; Scheid, Christof; Haenel, Mathias; Weisel, Katja; Goldschmidt, Hartmut; Hillengass, Jens

    2017-01-01

    To investigate cytogenetic evolution after upfront autologous stem cell transplantation for newly diagnosed myeloma we retrospectively analyzed fluorescence in situ hybridization results of 128 patients with paired bone marrow samples from the time of primary diagnosis and at relapse. High-risk cytogenetic abnormalities (deletion 17p and/or gain 1q21) occurred more frequently after relapse (odds ratio: 6.33; 95% confidence interval: 1.86–33.42; P<0.001). No significant changes were observed for defined IGH translocations [t(4;14); t(11;14); t(14;16)] or hyperdiploid karyotypes between primary diagnosis and relapse. IGH translocations with unknown partners occurred more frequently at relapse. New deletion 17p and/or gain 1q21 were associated with cytogenetic heterogeneity, since some de novo lesions with different copy numbers were present only in subclones. No distinct baseline characteristics were associated with the occurrence of new high-risk cytogenetic abnormalities after progression. Patients who relapsed after novel agent-based induction therapy had an increased risk of developing high-risk aberrations (odds ratio 10.82; 95% confidence interval: 1.65–127.66; P=0.03) compared to those who were treated with conventional chemotherapy. Survival analysis revealed dismal outcomes regardless of whether high-risk aberrations were present at baseline (hazard ratio, 3.53; 95% confidence interval: 1.53–8.14; P=0.003) or developed at relapse only (hazard ratio, 3.06; 95% confidence interval: 1.09–8.59; P=0.03). Our results demonstrate cytogenetic evolution towards high-risk disease after autologous transplantation and underline the importance of repeated genetic testing in relapsed myeloma (EudraCT number of the HD4 trial: 2004-000944-26). PMID:28495913

  3. Sample tracking in an automated cytogenetic biodosimetry laboratory for radiation mass casualties

    International Nuclear Information System (INIS)

    Martin, P.R.; Berdychevski, R.E.; Subramanian, U.; Blakely, W.F.; Prasanna, P.G.S.

    2007-01-01

    Chromosome-aberration-based dicentric assay is expected to be used after mass-casualty life-threatening radiation exposures to assess radiation dose to individuals. This will require processing of a large number of samples for individual dose assessment and clinical triage to aid treatment decisions. We have established an automated, high-throughput, cytogenetic biodosimetry laboratory to process a large number of samples for conducting the dicentric assay using peripheral blood from exposed individuals according to internationally accepted laboratory protocols (i.e., within days following radiation exposures). The components of an automated cytogenetic biodosimetry laboratory include blood collection kits for sample shipment, a cell viability analyzer, a robotic liquid handler, an automated metaphase harvester, a metaphase spreader, high-throughput slide stainer and coverslipper, a high-throughput metaphase finder, multiple satellite chromosome-aberration analysis systems, and a computerized sample-tracking system. Laboratory automation using commercially available, off-the-shelf technologies, customized technology integration, and implementation of a laboratory information management system (LIMS) for cytogenetic analysis will significantly increase throughput. This paper focuses on our efforts to eliminate data-transcription errors, increase efficiency, and maintain samples' positive chain-of-custody by sample tracking during sample processing and data analysis. This sample-tracking system represents a 'beta' version, which can be modeled elsewhere in a cytogenetic biodosimetry laboratory, and includes a customized LIMS with a central server, personal computer workstations, barcode printers, fixed station and wireless hand-held devices to scan barcodes at various critical steps, and data transmission over a private intra-laboratory computer network. Our studies will improve diagnostic biodosimetry response, aid confirmation of clinical triage, and medical

  4. Sample tracking in an automated cytogenetic biodosimetry laboratory for radiation mass casualties

    Energy Technology Data Exchange (ETDEWEB)

    Martin, P.R.; Berdychevski, R.E.; Subramanian, U.; Blakely, W.F. [Armed Forces Radiobiology Research Institute, Uniformed Services University of Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States); Prasanna, P.G.S. [Armed Forces Radiobiology Research Institute, Uniformed Services University of Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: prasanna@afrri.usuhs.mil

    2007-07-15

    Chromosome-aberration-based dicentric assay is expected to be used after mass-casualty life-threatening radiation exposures to assess radiation dose to individuals. This will require processing of a large number of samples for individual dose assessment and clinical triage to aid treatment decisions. We have established an automated, high-throughput, cytogenetic biodosimetry laboratory to process a large number of samples for conducting the dicentric assay using peripheral blood from exposed individuals according to internationally accepted laboratory protocols (i.e., within days following radiation exposures). The components of an automated cytogenetic biodosimetry laboratory include blood collection kits for sample shipment, a cell viability analyzer, a robotic liquid handler, an automated metaphase harvester, a metaphase spreader, high-throughput slide stainer and coverslipper, a high-throughput metaphase finder, multiple satellite chromosome-aberration analysis systems, and a computerized sample-tracking system. Laboratory automation using commercially available, off-the-shelf technologies, customized technology integration, and implementation of a laboratory information management system (LIMS) for cytogenetic analysis will significantly increase throughput. This paper focuses on our efforts to eliminate data-transcription errors, increase efficiency, and maintain samples' positive chain-of-custody by sample tracking during sample processing and data analysis. This sample-tracking system represents a 'beta' version, which can be modeled elsewhere in a cytogenetic biodosimetry laboratory, and includes a customized LIMS with a central server, personal computer workstations, barcode printers, fixed station and wireless hand-held devices to scan barcodes at various critical steps, and data transmission over a private intra-laboratory computer network. Our studies will improve diagnostic biodosimetry response, aid confirmation of clinical triage, and

  5. Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors

    International Nuclear Information System (INIS)

    Valous, Nektarios A.; Lahrmann, Bernd; Halama, Niels; Grabe, Niels; Bergmann, Frank; Jäger, Dirk

    2016-01-01

    not only on percentage content of proliferation phase but also on how the phase fills the space. Lacunarity curves demonstrate variations in the sampled image sections. Since the spatial distribution of proliferation in each case is different, the width of the curves changes too. Image sections that have smaller numerical variations in the computed features correspond to neoplasms with spatially homogeneous proliferation, while larger variations correspond to cases where proliferation shows various degrees of clumping. Grade 1 (uniform/nonuniform: 74%/26%) and grade 3 (uniform: 100%) pNENs demonstrate a more homogeneous proliferation with grade 1 neoplasms being more variant, while grade 2 tumor regions render a more diverse landscape (50%/50%). Hence, some cases show an increased degree of spatial heterogeneity comparing to others with similar grade. Whether this is a sign of different tumor biology and an association with a more benign/malignant clinical course needs to be investigated further. The extent and range of spatial heterogeneity has the potential to be evaluated as a prognostic marker. Conclusions: The association with tumor grade as well as the rationale that the methodology reflects true tumor architecture supports the technical soundness of the method. This reflects a general approach which is relevant to other solid tumors and biomarkers. Drawing upon the merits of computational biomedicine, the approach uncovers salient features for use in future studies of clinical relevance.

  6. Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors.

    Science.gov (United States)

    Valous, Nektarios A; Lahrmann, Bernd; Halama, Niels; Bergmann, Frank; Jäger, Dirk; Grabe, Niels

    2016-06-01

    content of proliferation phase but also on how the phase fills the space. Lacunarity curves demonstrate variations in the sampled image sections. Since the spatial distribution of proliferation in each case is different, the width of the curves changes too. Image sections that have smaller numerical variations in the computed features correspond to neoplasms with spatially homogeneous proliferation, while larger variations correspond to cases where proliferation shows various degrees of clumping. Grade 1 (uniform/nonuniform: 74%/26%) and grade 3 (uniform: 100%) pNENs demonstrate a more homogeneous proliferation with grade 1 neoplasms being more variant, while grade 2 tumor regions render a more diverse landscape (50%/50%). Hence, some cases show an increased degree of spatial heterogeneity comparing to others with similar grade. Whether this is a sign of different tumor biology and an association with a more benign/malignant clinical course needs to be investigated further. The extent and range of spatial heterogeneity has the potential to be evaluated as a prognostic marker. The association with tumor grade as well as the rationale that the methodology reflects true tumor architecture supports the technical soundness of the method. This reflects a general approach which is relevant to other solid tumors and biomarkers. Drawing upon the merits of computational biomedicine, the approach uncovers salient features for use in future studies of clinical relevance.

  7. Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Valous, Nektarios A. [Applied Tumor Immunity Clinical Cooperation Unit, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg 69120 (Germany); Lahrmann, Bernd; Halama, Niels; Grabe, Niels [Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg 69120 (Germany); Bergmann, Frank [Institute of Pathology, Heidelberg University Hospital, Heidelberg 69120 (Germany); Jäger, Dirk [Department of Medical Oncology, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg 69120, Germany and National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg 69120 (Germany)

    2016-06-15

    not only on percentage content of proliferation phase but also on how the phase fills the space. Lacunarity curves demonstrate variations in the sampled image sections. Since the spatial distribution of proliferation in each case is different, the width of the curves changes too. Image sections that have smaller numerical variations in the computed features correspond to neoplasms with spatially homogeneous proliferation, while larger variations correspond to cases where proliferation shows various degrees of clumping. Grade 1 (uniform/nonuniform: 74%/26%) and grade 3 (uniform: 100%) pNENs demonstrate a more homogeneous proliferation with grade 1 neoplasms being more variant, while grade 2 tumor regions render a more diverse landscape (50%/50%). Hence, some cases show an increased degree of spatial heterogeneity comparing to others with similar grade. Whether this is a sign of different tumor biology and an association with a more benign/malignant clinical course needs to be investigated further. The extent and range of spatial heterogeneity has the potential to be evaluated as a prognostic marker. Conclusions: The association with tumor grade as well as the rationale that the methodology reflects true tumor architecture supports the technical soundness of the method. This reflects a general approach which is relevant to other solid tumors and biomarkers. Drawing upon the merits of computational biomedicine, the approach uncovers salient features for use in future studies of clinical relevance.

  8. Establishment of a new human pleomorphic malignant fibrous histiocytoma cell line, FU-MFH-2: molecular cytogenetic characterization by multicolor fluorescence in situ hybridization and comparative genomic hybridization

    Directory of Open Access Journals (Sweden)

    Isayama Teruto

    2010-11-01

    Full Text Available Abstract Background Pleomorphic malignant fibrous histiocytoma (MFH is one of the most frequent malignant soft tissue tumors in adults. Despite the considerable amount of research on MFH cell lines, their characterization at a molecular cytogenetic level has not been extensively analyzed. Methods and results We established a new permanent human cell line, FU-MFH-2, from a metastatic pleomorphic MFH of a 72-year-old Japanese man, and applied multicolor fluorescence in situ hybridization (M-FISH, Urovysion™ FISH, and comparative genomic hybridization (CGH for the characterization of chromosomal aberrations. FU-MFH-2 cells were spindle or polygonal in shape with oval nuclei, and were successfully maintained in vitro for over 80 passages. The histological features of heterotransplanted tumors in severe combined immunodeficiency mice were essentially the same as those of the original tumor. Cytogenetic and M-FISH analyses displayed a hypotriploid karyotype with numerous structural aberrations. Urovysion™ FISH revealed a homozygous deletion of the p16INK4A locus on chromosome band 9p21. CGH analysis showed a high-level amplification of 9q31-q34, gains of 1p12-p34.3, 2p21, 2q11.2-q21, 3p, 4p, 6q22-qter, 8p11.2, 8q11.2-q21.1, 9q21-qter, 11q13, 12q24, 15q21-qter, 16p13, 17, 20, and X, and losses of 1q43-qter, 4q32-qter, 5q14-q23, 7q32-qter, 8p21-pter, 8q23, 9p21-pter, 10p11.2-p13, and 10q11.2-q22. Conclusion The FU-MFH-2 cell line will be a particularly useful model for studying molecular pathogenesis of human pleomorphic MFH.

  9. Cytogenetic effects of in vitro irradiation of human spermatozoa

    International Nuclear Information System (INIS)

    Miro, R.; Genesca, A.; Alvarez, R.; Tusell, L.; Ponsa, I.

    1997-01-01

    The effects of human mutagens, clastogens and aneugens have been studied almost exclusively in somatic tissues. However, currently there is a considerable discussion about the potential of ionizing radiation to induce heritable germ cell mutations. While the various viewpoints remain controversial. One of the aims of germ cell cytogenetic studies must be to improve the ability to identify and estimate the actual genetic risk in humans. One way to assess the risk of transmission of genetic anomalies by men occupationally or accidentally exposed to ionizing radiation is to determine whether there is a dose-related genetic damage in human spermatozoa. Cytogenetic analysis of human spermatozoa is possible after interspecific in vitro fertilization between zona pellucida-free hamster oocytes and human spermatozoa. Using this assay system we have analyzed the radiation induction of structural chromosome abnormalities in sperm derived complements at the first embryo cleavage, as well as the radiation induction of micronuclei and aneuploidy in two-cell hybrid embryos. (author)

  10. Cytogenetic Analysis of 65 Women with Premature Ovarian Insufficiency

    Directory of Open Access Journals (Sweden)

    Seda Ates

    2016-09-01

    Full Text Available Aim: Premature ovarian insufficiency (POI is characterized as amenorrhea for more than 6 months, occurring before the age of 40, with an increased follicle-stimulating hormone and low estrogen concentrations. The aim of our study is to determine the types and distribution of cytogenetic abnormalities among women with POI. Material and Method: The study is based on the retrospective karyotype analysis of 65 women with idiopathic POI referred to the Medical Genetics Department at the Bezmialem Vakif University Hospital. Results: Chromosomal abnormalities were present in 12 of 65 cases (18.4%. All of them had numerical abnormalities of the X chromosome. The most frequently detected abnormalities were X chromosome mosaicisms. Two cases had fragile X premutation carriers. Eight (12.3% women were considered as familial POI. Discussion: Our results underline the essential role of the X chromosome in the etiology of POI. Therefore, regardless of clinical features and woman%u2019s age, cytogenetic investigations should be routinely performed in cases with POI.

  11. In situ hybridization (ISH) in a cytogenetic; Hybrydyzacja in situ w genetyce

    Energy Technology Data Exchange (ETDEWEB)

    Zawada, M. [Polska Akademia Nauk, Poznan (Poland). Zaklad Genetyki Czlowieka; Latos-Bielenska, A. [Akademia Medyczna, Poznan (Poland)

    1993-12-31

    Nucleic acids contain genetic information for structure and function of cell organism. The information bearing sequences of DNA, know as genes, are spread along DNA molecule. ISH is one of the best and the most-direct techniques available for studies on gene localization, structure and expression. It combines technical achievements of molecular biology and cytogenetic. Application of ISH provides an opportunity to visualize specific DNA or RNA sequences in preparations of chromosomes, cells or tissue sections. It has been used widely both in research (genes mapping and expression, genome evolution, nuclear topography, mitosis, meiosis) as well as in clinical studies (clinical cytogenetic, prenatal diagnostics, cancer diagnostics). (author). 46 refs.

  12. Some implications of Scale Relativity theory in avascular stages of growth of solid tumors in the presence of an immune system response.

    Science.gov (United States)

    Buzea, C Gh; Agop, M; Moraru, Evelina; Stana, Bogdan A; Gîrţu, Manuela; Iancu, D

    2011-08-07

    We present a traveling-wave analysis of a reduced mathematical model describing the growth of a solid tumor in the presence of an immune system response in the framework of Scale Relativity theory. Attention is focused upon the attack of tumor cells by tumor-infiltrating cytotoxic lymphocytes (TICLs), in a small multicellular tumor, without necrosis and at some stage prior to (tumor-induced) angiogenesis. For a particular choice of parameters, the underlying system of partial differential equations is able to simulate the well-documented phenomenon of cancer dormancy and propagation of a perturbation in the tumor cell concentration by cnoidal modes, by depicting spatially heterogeneous tumor cell distributions that are characterized by a relatively small total number of tumor cells. This behavior is consistent with several immunomorphological investigations. Moreover, the alteration of certain parameters of the model is enough to induce soliton like modes and soliton packets into the system, which in turn result in tumor invasion in the form of a standard traveling wave. In the same framework of Scale Relativity theory, a very important feature of malignant tumors also results, that even in avascular stages they might propagate and invade healthy tissues, by means of a diffusion on a Newtonian fluid. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Results of six years of cytogenetic studies in amniotic fluid

    Directory of Open Access Journals (Sweden)

    Enelis Reyes Reyes

    2015-10-01

    Full Text Available Background: research into different genetic diseases is one of the preventive programs of paramount importance at public health level. The early detection of chromosomopathies and the establishment of an appropriate strategy reduce the morbidity-morality rate and improve the patients’ quality of life.Objective: to describe the behavior of the results of the cytogenetic studies in the amniotic fluid of pregnant women from Las Tunas province during six years: from 2008 to 2014.Methods: a retrospective and descriptive study was carried out to assess the results of cytogenetic studies in amniotic liquid during six years: from 2008 to 2014. The statistical records were checked and the results, the indication criteria, the behavior of the age groups in women advanced in age and the diagnosed chromosomopathies were assessed.Results: the samples with results that exceeded the non-conclusive and positive women prevailed; 2, 3 positive cases of chromosomopathies were diagnosed out of 100 studied women at risk; pregnant women of advanced gestational years prevailed as indication criterion, being the 37 to 40 years old age group the predominant one; in the positive cases, numeric chromosomopathies of the type trisomy 21 or Down’s syndrome prevailed, with a frequency of 1, 2 out of 100 pregnant women at risk.Conclusions: the program of the cytogenetic diagnosis in the amniotic fluid has been an effective tool to detect congenital prenatal defects by chromosomopathies, very useful in the process of genetic advice.

  14. Mild hyperthermia can induce adaptation to cytogenetic damage caused by subsequent X irradiation

    International Nuclear Information System (INIS)

    Cai, Lu.; Jiang, Jie.

    1995-01-01

    Many low-level environmental agents are able to induce an increased resistance to subsequent mutagenic effects induced by ionizing radiation. In this paper, an induced cytogenetic adaptation to radiation in human lymphocytes was studied with mild hyperthermia as the adaptive treatment and compared with that induced by low-dose radiation. We found that this adaptation could be induced not only in PHA-stimulated human lymphocytes (at 14, 38 and 42 h after addition of PHA), but also in unstimulated G 0 -phase cells (before addition of PHA) by mild hyperthermia (41 degrees C for 1 h) as well as 50 mGy X rays. When the two adaptive treatments were combined, no additive effects on the magnitude of the adaptation induced were observed, suggesting that low-dose radiation and hyperthermia may share one mechanism of induction of adaptation to cytogenetic damage. Some mechanisms which may be involved in the induction of adaptation to cytogenetic damage by low-dose radiation are discussed and compared with the effects of mild hyperthermia in inducing thermotolerance and radioresistance. 56 refs., 4 figs., 3 tabs

  15. Cytogenetic Examination of South American Tapirs, Tapirus Terrestris (Perissodactyla, Tapiridae, from the Wroclaw Zoological Garden

    Directory of Open Access Journals (Sweden)

    Kosowska B.

    2015-12-01

    Full Text Available Cytogenetic Examination of South American Tapirs, Tapirus terrestris (Perissodactyla, Tapiridae from the Wroclaw Zoological Garden. Kosowska, B., Strzała, T., Moska, M., Ratajszczak, R., Dobosz, T. - Seven lowland tapirs (Tapirus terrestris from Wrocław ZOO (three females and four males, differing from each other with exterior and sexual behaviour were verified with cytogenetic analysis in order to check their taxonomic status. Cytogenetic analysis was done using two alternative methods of blood collection: 1 conventionally with venepuncture, and 2 with blood sucking bugs from the Reduviidae family. Lymphocytes capable of growing were obtained only with conventional method of blood sampling. Karyotypes and karyograms of all analyzed tapirs were created using classical cytogenetic methods of chromosomes staining. All possessed karyograms had diploid chromosome number equal 80 (2n = 80. Homologous chromosomes did not differ between each other with quantity, size, centromeres location, length of arms, G bands and all were classified as proper karyograms of Tapirus terrestris species representatives. The X chromosomes as well as the first pair of chromosomes (both metacentric, were the largest among all analyzed, respectively. All remaining 38 pairs of chromosomes were acrocentric with Y chromosome as the smallest one (in males’ karyograms. Blood collected with blood sucking bugs proved to be unsuitable for cell culture. None of the seven established cultures was effective as lymphocytes obtained with this method did not show growth potential in prepared media. Thus, blood collected from the tapirs via Dipetalogaster maxima species did not show usefulness for cytogenetic studies due to the inability of cells to proliferation, even after a relatively short period of time elapsed since the blood sampling (1 to 2 hours.

  16. Cytogenetic studies on some Nigerian species of Solanum L ...

    African Journals Online (AJOL)

    Cytogenetic studies to determine the chromosome number, structure and behaviour of some species of Solanum in Nigeria were carried out. Attempt was also made to induce polyploidy in the species. Comparative analysis of the cytological behaviour of the diploid and polyploid cytotypes was made. The studies show that ...

  17. Advances in the role of cytogenetic analysis in the molecular diagnosis of B-cell lymphomas.

    Science.gov (United States)

    Grange, Béatrice; Callet-Bauchu, Evelyne; Salles, Gilles; Sujobert, Pierre

    2017-06-01

    Cytogenetic abnormalities represent essential determinants of diagnosis and prognosis in B-cell lymphomas. Their theranostic value is increasingly significant with the development of targeted therapies, in order to adapt the treatment at diagnosis as well as when relapse occurs. Areas covered: As the significance of these biomarkers is influenced by the technology used to detect them, an overview describing the strength and weakness of conventional and emerging technologies is provided. This review also updates the diverse cytogenetic abnormalities found in B-cell lymphomas, emphasizing their value in treatment decision. Expert commentary: Cytogenetics remains an essential analysis for the diagnostic work-up of lymphomas. As whole genome sequencing becomes more and more affordable routinely, the next challenge will be to recover all the information conveyed by conventional karyotype, including the analysis of the clonal architecture at the single cell level, in whole genome data.

  18. Cytogenetic studies on recipients of allogeneic bone marrow transplants after fractionated total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, N; Goedde-Salz, E; Loeffler, H [Christian-Albrechts-Univ., Kiel (Germany, F.R.)

    1985-06-01

    Cytogenetic findings from the bone marrow (BM) and the peripheral blood (PB) of nine consecutive patients after allogeneic bone marrow transplantation (BMT) for acute or chronic myelogenous leukaemia are reported. After a conditioning regimen consisting of cyclophosphamide and fractionated total body irradiation (TBI) given in five or six fractions of 2 Gy, persistence of host cells was detected in four out of seven cases with permanent engraftment. While one of these patients relapsed 4 months after host cells had been found in BM and PB, the other patients stayed relapse-free 124, 257 and 347 d after grafting. Before transplantation, the leukaemic cells in all three cases carried unique cytogenetic abnormalities giving the opportunity to distinguish the leukaemic population from chromosomally non-aberrant cells thought to represent residual normal host cells. As the persisting host cells after BMT lacked any cytogenetic abnormalities, it is suggested that they were members of residual normal clones not involved in the leukaemic process.

  19. Cytogenetic studies on recipients of allogeneic bone marrow transplants after fractionated total body irradiation

    International Nuclear Information System (INIS)

    Schmitz, N.; Goedde-Salz, E.; Loeffler, H.

    1985-01-01

    Cytogenetic findings from the bone marrow (BM) and the peripheral blood (PB) of nine consecutive patients after allogeneic bone marrow transplantation (BMT) for acute or chronic myelogenous leukaemia are reported. After a conditioning regimen consisting of cyclophosphamide and fractionated total body irradiation (TBI) given in five or six fractions of 2 Gy, persistence of host cells was detected in four out of seven cases with permanent engraftment. While one of these patients relapsed 4 months after host cells had been found in BM and PB, the other patients stayed relapse-free 124, 257 and 347 d after grafting. Before transplantation, the leukaemic cells in all three cases carried unique cytogenetic abnormalities giving the opportunity to distinguish the leukaemic population from chromosomally non-aberrant cells thought to represent residual normal host cells. As the persisting host cells after BMT lacked any cytogenetic abnormalities, it is suggested that they were members of residual normal clones not involved in the leukaemic process. (author)

  20. Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study.

    Science.gov (United States)

    Ito, Yoshinori; Suenaga, Mitsukuni; Hatake, Kiyohiko; Takahashi, Shunji; Yokoyama, Masahiro; Onozawa, Yusuke; Yamazaki, Kentaro; Hironaka, Shuichi; Hashigami, Kiyoshi; Hasegawa, Hirotaka; Takenaka, Nobuko; Boku, Narikazu

    2012-04-01

    Neratinib (HKI-272), a potent, irreversible, small-molecule, orally administered, pan-ErbB inhibitor that blocks signal transduction via inhibition of three epidermal growth factor receptors [ErbB1, ErbB2 (Her2) and ErbB4], is being developed for the treatment of solid tumors, including breast cancer. This Phase 1 dose-escalation study assessed the safety, tolerability, maximum-tolerated dose, antitumor activity and pharmacokinetics of neratinib in Japanese patients with advanced solid tumors. Patients received neratinib 80, 160, 240 or 320 mg orally; each patient enrolled in only one dose cohort. Patients received a single dose in week 1, followed by daily continuous doses. Blood samples collected were on days 1 and 21 for pharmacokinetic analyses. Twenty-one patients were enrolled (3 breast cancer; 17 colorectal cancer; 1 gastric cancer). Neratinib-related adverse events (all grades) included diarrhea (20 patients), fatigue (14 patients), nausea and abdominal pain (9 patients each) and anorexia (8 patients). Grade ≥3 neratinib-related adverse events in two or more patients were diarrhea and anorexia (two patients each). Dose-limiting toxicities were diarrhea and anorexia (two patients, 320 mg dose). The maximum-tolerated dose and recommended dose was neratinib 240 mg once daily. Of 21 evaluable patients, 2 with breast cancer had partial response, 3 had stable disease ≥24 weeks, 7 had stable disease ≥16 weeks and 9 had progressive disease. Pharmacokinetic analyses indicated that neratinib exposures increased with dose. The safety, efficacy and pharmacokinetic profiles of neratinib are consistent with those reported for non-Japanese patients and warrant further investigation of neratinib in Japanese patients with solid tumors.

  1. The results of selective cytogenetic monitoring of Chernobyl accident victims in the Ukraine

    International Nuclear Information System (INIS)

    Pilinskaya, M.A.

    1996-01-01

    Selective cytogenetic monitoring of the highest priority groups of Chernobyl disaster victims has been carried out since 1987. In 1992-1993, 125 liquidators (irradiated mainly in 1986) and 42 persons recovering from acute radiation sickness of the second and third degrees of severity were examined. Cytogenetic effects (an elevated level of unstable as well as stable markers of radiation exposure) were found in all groups, which showed a positive correlation with the initial degree of irradiation severity even 6-7 y after the accident. Comparative scoring of conventional staining vs. G-banding in 10 liquidators showed the identical rate of unstable aberrations. At the same time, the yield of stable aberrations for G-banded slides exceeded the frequency for conventional staining. In order to study possible mutagenic activity of chronic low levels of irradiation, the cytogenetic monitoring of some critical groups of the population (especially children and occupational groups-tractor drivers and foresters) living in areas of the Ukraine contaminated by radionuclides was carried out. In all the examined groups, a significant increase in the frequency of aberrant metaphases, chromosome aberrations (both unstable and stable), an chromatid aberrations was observed. Data gathered from groups of children reflect the intensity of mutagenic impact on the studied populations and demonstrate a positive correlation with the duration of exposure. Results of cytogenetic examination of adults confirmed the importance of considering the contribution of occupational radiation exposure to genetic effects of Chernobyl accident factors on the population of contaminated areas. 17 refs., 3 tabs

  2. Further improvement of genetic and cytogenetic test pattern with increased relevance predicting carcinogenic and pharmacological effects

    Energy Technology Data Exchange (ETDEWEB)

    Siebert, D.

    1982-08-01

    Testing of chemicals for their genetic activity by applying only one method has the disadvantage, that the results are of limited value. However, a combination of several test systems in such a manner that the apparent difference between the results allows additional conclusions about the pharmacokinetic properties of the substances tested, the correlation between molecular mutations and cytogenetic effects and the possible carcinogenic activity. Three nitrofuran derivatives (nitrofurantoin, carofur and FANFT) tested in six different in vitro and in vivo mutagenicity tests partly showed strong genetic activity without metabolic activation and weak cytogenetic effects. However, polycyclic hydrocarbons needed mammalian metabolism to display their mutagenicity: Dimethylbenzoanthracene and benzo(a)pyrene could be activated by liver microsomes and showed also cytogenetic effects, but phenanthrene was only active in the SCE-test. Out of nine heavy metal salts potassium chromate, potassium dichromate, calcium chromate and cis-dichloro diammine-Pt(II) were effective in at least one genetic and one cytogenetic test. The correlation between mutagenic and the known carcinogenic activity of all test substances was good in the case of the hydrocarbons and the nitrofuran derivatives; the heavy metal salts, however, are of low relevance for the carcinogenicity of the metals itself.

  3. The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition

    International Nuclear Information System (INIS)

    Peddaboina, Chander; Smythe, W Roy; Cao, Xiaobo; Jupiter, Daniel; Fletcher, Steven; Yap, Jeremy L; Rai, Arun; Tobin, Richard P; Jiang, Weihua; Rascoe, Philip; Rogers, M Karen Newell

    2012-01-01

    It has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. Mcl-1 is a critical survival protein in a variety of cell lineages and is critically regulated via ubiquitination. The Mcl-1, Bcl-xL and USP9X expression patterns in human lung and colon adenocarcinomas were evaluated via immunohistochemistry. Interaction between USP9X and Mcl-1 was demonstrated by immunoprecipitation-western blotting. The protein expression profiles of Mcl-1, Bcl-xL and USP9X in multiple cancer cell lines were determined by western blotting. Annexin-V staining and cleaved PARP western blotting were used to assay for apoptosis. The cellular toxicities after various treatments were measured via the XTT assay. In our current analysis of colon and lung cancer samples, we demonstrate that Mcl-1 and Bcl-xL are overexpressed and also co-exist in many tumors and that the expression levels of both genes correlate with the clinical staging. The downregulation of Mcl-1 or Bcl-xL via RNAi was found to increase the sensitivity of the tumor cells to chemotherapy. Furthermore, our analyses revealed that USP9X expression correlates with that of Mcl-1 in human cancer tissue samples. We additionally found that the USP9X inhibitor WP1130 promotes Mcl-1 degradation and increases tumor cell sensitivity to chemotherapies. Moreover, the combination of WP1130 and ABT-737, a well-documented Bcl-xL inhibitor, demonstrated a chemotherapeutic synergy and promoted apoptosis in different tumor cells. Mcl-1, Bcl-xL and USP9X overexpression are tumor survival mechanisms protective against chemotherapy. USP9X inhibition increases tumor cell sensitivity to various chemotherapeutic agents including Bcl-2/Bcl-xL inhibitors

  4. Radiation Therapy Intensification for Solid Tumors: A Systematic Review of Randomized Trials

    Energy Technology Data Exchange (ETDEWEB)

    Yamoah, Kosj [Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (United States); Showalter, Timothy N. [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

    2015-11-15

    Purpose: To systematically review the outcomes of randomized trials testing radiation therapy (RT) intensification, including both dose escalation and/or the use of altered fractionation, as a strategy to improve disease control for a number of malignancies. Methods and Materials: We performed a literature search to identify randomized trials testing RT intensification for cancers of the central nervous system, head and neck, breast, lung, esophagus, rectum, and prostate. Findings were described qualitatively. Where adequate data were available, pooled estimates for the effect of RT intensification on local control (LC) or overall survival (OS) were obtained using the inverse variance method. Results: In primary central nervous system tumors, esophageal cancer, and rectal cancer, randomized trials have not demonstrated that RT intensification improves clinical outcomes. In breast cancer and prostate cancer, dose escalation has been shown to improve LC or biochemical disease control but not OS. Radiation therapy intensification may improve LC and OS in head and neck and lung cancers, but these benefits have generally been limited to studies that did not incorporate concurrent chemotherapy. Conclusions: In randomized trials, the benefits of RT intensification have largely been restricted to trials in which concurrent chemotherapy was not used. Novel strategies to optimize the incorporation of RT in the multimodality treatment of solid tumors should be explored.

  5. Cytogenetic studies of three triazine herbicides. I. In vitro studies

    Science.gov (United States)

    Atrazine, simazine, and cyanazine are widely used pre-emergence and post-emergence triazine herbicides that have made their way into the potable water supply of many agricultural communities. Because of this and the prevalence of contradictory cytogenetic studies in the literatur...

  6. On the mechanism of cytogenetic effect of electromagnetic radiation: role of oxidation homeostasis

    International Nuclear Information System (INIS)

    Brezitskaya, N.V.; Timchenko, O.I.

    2000-01-01

    The evaluation of the role of changes in oxidation homeostasis in developing the cytogenetic effects arising by the electromagnetic irradiation impact is carried out. The experiments were performed on white male rats. The animals were subjected to impact of the nonionizing radiations in the microwave range during 40 days by 7 hours a day. It is established that changes in the free-radical oxidation by the impact of nonionizing radiation of the electromagnetic fields have a wave-like character. It is established that changes in the oxidation homeostasis proceed the development of cytogenetic effects and may be the cause thereof [ru

  7. CYTOGENETIC STUDY OF FOUR SPECIES OF LAND SNAILS OF ...

    African Journals Online (AJOL)

    The chromosomal study of the four species of achatinid snails was carried out with the aim of determining their chromosome numbers as part of a preliminary attempt to understand the cytogenetics of land snails of Nigeria. The haploid chromosomes of various species of snails studied were obtained from their ovotestis ...

  8. Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location.

    Science.gov (United States)

    Maranchie, Jodi K; Afonso, Anoushka; Albert, Paul S; Kalyandrug, Sivaram; Phillips, John L; Zhou, Shubo; Peterson, James; Ghadimi, Bijan M; Hurley, Katheen; Riss, Joseph; Vasselli, James R; Ried, Thomas; Zbar, Berton; Choyke, Peter; Walther, McClellan M; Klausner, Richard D; Linehan, W Marston

    2004-01-01

    von Hippel Lindau disease (VHL) is an autosomal dominant familial cancer syndrome linked to alteration of the VHL tumor suppressor gene. Affected patients are predisposed to develop pheochromocytomas and cystic and solid tumors of the kidney, CNS, pancreas, retina, and epididymis. However, organ involvement varies considerably among families and has been shown to correlate with the underlying germline alteration. Clinically, we observed a paradoxically lower prevalence of renal cell carcinoma (RCC) in patients with complete germline deletion of VHL. To determine if a relationship existed between the type of VHL deletion and disease, we retrospectively evaluated 123 patients from 55 families with large germline VHL deletions, including 42 intragenic partial deletions and 13 complete VHL deletions, by history and radiographic imaging. Each individual and family was scored for cystic or solid involvement of CNS, pancreas, and kidney, and for pheochromocytoma. Germline deletions were mapped using a combination of fluorescent in situ hybridization (FISH) and quantitative Southern and Southern blot analysis. An age-adjusted comparison demonstrated a higher prevalence of RCC in patients with partial germline VHL deletions relative to complete deletions (48.9 vs. 22.6%, p=0.007). This striking phenotypic dichotomy was not seen for cystic renal lesions or for CNS (p=0.22), pancreas (p=0.72), or pheochromocytoma (p=0.34). Deletion mapping revealed that development of RCC had an even greater correlation with retention of HSPC300 (C3orf10), located within the 30-kb region of chromosome 3p, immediately telomeric to VHL (52.3 vs. 18.9%, p <0.001), suggesting the presence of a neighboring gene or genes critical to the development and maintenance of RCC. Careful correlation of genotypic data with objective phenotypic measures will provide further insight into the mechanisms of tumor formation. Copyright 2003 Wiley-Liss, Inc.

  9. Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.

    Science.gov (United States)

    Lassau, Nathalie; Bonastre, Julia; Kind, Michèle; Vilgrain, Valérie; Lacroix, Joëlle; Cuinet, Marie; Taieb, Sophie; Aziza, Richard; Sarran, Antony; Labbe-Devilliers, Catherine; Gallix, Benoit; Lucidarme, Olivier; Ptak, Yvette; Rocher, Laurence; Caquot, Louis-Michel; Chagnon, Sophie; Marion, Denis; Luciani, Alain; Feutray, Sylvaine; Uzan-Augui, Joëlle; Coiffier, Benedicte; Benastou, Baya; Koscielny, Serge

    2014-12-01

    Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate. Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it

  10. Field distribution and DNA transport in solid tumors during electric field-mediated gene delivery.

    Science.gov (United States)

    Henshaw, Joshua W; Yuan, Fan

    2008-02-01

    Gene therapy has a great potential in cancer treatment. However, the efficacy of cancer gene therapy is currently limited by the lack of a safe and efficient means to deliver therapeutic genes into the nucleus of tumor cells. One method under investigation for improving local gene delivery is based on the use of pulsed electric field. Despite repeated demonstration of its effectiveness in vivo, the underlying mechanisms behind electric field-mediated gene delivery remain largely unknown. Without a thorough understanding of these mechanisms, it will be difficult to further advance the gene delivery. In this review, the electric field-mediated gene delivery in solid tumors will be examined by following individual transport processes that must occur in vivo for a successful gene transfer. The topics of examination include: (i) major barriers for gene delivery in the body, (ii) distribution of electric fields at both cell and tissue levels during the application of external fields, and (iii) electric field-induced transport of genes across each of the barriers. Through this approach, the review summarizes what is known about the mechanisms behind electric field-mediated gene delivery and what require further investigations in future studies.

  11. Computed Tomography Imaging of Solid Tumors Using a Liposomal-Iodine Contrast Agent in Companion Dogs with Naturally Occurring Cancer.

    Science.gov (United States)

    Ghaghada, Ketan B; Sato, Amy F; Starosolski, Zbigniew A; Berg, John; Vail, David M

    2016-01-01

    Companion dogs with naturally occurring cancer serve as an important large animal model in translational research because they share strong similarities with human cancers. In this study, we investigated a long circulating liposomal-iodine contrast agent (Liposomal-I) for computed tomography (CT) imaging of solid tumors in companion dogs with naturally occurring cancer. The institutional animal ethics committees approved the study and written informed consent was obtained from all owners. Thirteen dogs (mean age 10.1 years) with a variety of masses including primary and metastatic liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after intravenous administration of Liposomal-I (275 mg/kg iodine dose). Conventional contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained for each dog prior to admission into the study. Liposomal-I resulted in significant (p contrast agent was demonstrated. Liposomal-I enabled visualization of primary and metastatic liver tumors. Sub-cm sized liver lesions grossly appeared as hypo-enhanced compared to the surrounding normal parenchyma with improved lesion conspicuity in the post-24 hour scan. Large liver tumors (> 1 cm) demonstrated a heterogeneous pattern of intra-tumoral signal with visibly higher signal enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors, including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung tumors, were visualized with a heterogeneous enhancement pattern in the post-24 hour scan. The long circulating liposomal-iodine contrast agent enabled prolonged visualization of small and large tumors in companion dogs with naturally occurring cancer. The study warrants future work to assess the sensitivity and specificity of the Liposomal-I agent in various types of

  12. Molecular and cytogenetic assessment of Dipterygium glaucum genotoxicity

    Directory of Open Access Journals (Sweden)

    NADA H. ALTWATY

    2016-01-01

    Full Text Available ABSTRACT The aim of the present study is to assess the genotoxicity of Dipterygium glaucum grows widely in Saudi Arabia desert to produce safety herbal products. This work is considered the first and pioneer report so far due to the lack and poor evaluated reports of the plant species for their mutagensity, genotoxicity and cytogenetics effects. Cytogenetic effects of D. glaucum on mitotic in roots of Vicia faba showed reduction in mitotic activity using three extracts; water, ethanol and ethyl acetate. Chromosomal abnormalities were recorded that included stickiness of chromosomes, chromatin bridge, fragments, lagging chromosome and micronuclei. Protein bands and RAPD analyses of V. faba treated with three D. glaucum extracts revealed some newly induced proteins and DNA fragments and other disappeared. Chemical constitution of the plant species should be identified with their biological activities against human and animal cells like HeLa cancer cell line. We are recommending using additional genotoxicity tests and other toxicity tests on animal culture with different concentrations and also utilizing several drought and heat tolerant genes of the plant species in gene cloning to develop and improve other economical crop plants instead of using the species as oral herbal remedy

  13. Transmitted cytogenetic abnormalities in patients with mental retardation: pathogenic or normal variants?

    DEFF Research Database (Denmark)

    Bisgaard, Anne-Marie; Kirchhoff, Maria; Nielsen, Jens Erik

    2007-01-01

    Knowing the origin of cytogenetic abnormalities detected in individuals with mental retardation and dysmorphic features is essential to genetic counselling of affected families. To illustrate this, we report on six families with transmitted cytogenetic abnormalities and discuss the genotype...... generations and included interstitial deletions of 1p31.3-p32.1, 2q13, 10q11.21-q11.23, and 13q31.1; a duplication of 1p34.1-p34.2; and in one family both a deletion of 18q21.1 and a duplication of 4q35.1-q35.2. The probands were mentally retarded and had nonspecific dysmorphic features except for one patient...

  14. Comparative data in the radiation-induced yields of cytogenetic alterations

    International Nuclear Information System (INIS)

    Koeteles, G.J.

    1993-01-01

    The need of biological indicators of radiation injuries is growing for various conditions of exposures like external or internal, acute or chronic. The search for such indicators did not result in techniques fulfilling yet all these requirements. So far, the dielectric chromosome aberration analysis can be used as the most reliable assay in radiation accidents. In the recent years several laboratories including ours have initiated research to apply a more simple cytogenetic technique, i.e. the detection of micronuclei in lymphocytes. The fairly consequent dose-effect relationships obtained by several laboratories made the technique rather promising, especially after the modification recommended to recognize interphase cells after their first mitotic divisions. In this presentation dose-effect relationships of formations of various cytogenetic abnormalities are compared with special emphasis on their applicabilities in dose assessments in radiation accidents. Basically, the materials and methods were as published earlier

  15. Pyruvate kinase M2 overexpression and poor prognosis in solid tumors of digestive system: evidence from 16 cohort studies.

    Science.gov (United States)

    Wu, Jiayuan; Hu, Liren; Chen, Manyu; Cao, Wenjun; Chen, Haicong; He, Taiping

    2016-01-01

    The expression of pyruvate kinase M2 (PKM2) has been linked to tumor formation and invasion. Specifically, the relationship between high PKM2 expression and prognosis has been evaluated in solid tumors of digestive system. However, the prognostic value of PKM2 remains controversial. A literature search of PubMed, Embase, and Cochrane databases was conducted until October 2015. The end point focused on overall survival (OS). The pooled hazard ratio (HR) or odds ratio and the 95% confidence intervals were calculated to correlate PKM2 overexpression with OS and clinicopathological characteristics by employing fixed- or random-effects models, depending on the heterogeneity of the included studies. We identified 18 cohorts in 16 studies involving 2,812 patients for this meta-analysis. Overall, the combined HR for OS in all tumor types was 1.74 (1.44-2.11; Pdigestive system, thereby suggesting that PKM2 might be an indicator of poor prognosis in digestive system cancers.

  16. Two-photon excited fluorescence imaging of the pancreatic solid pseudopapillary tumor without hematoxylin and eosin stains.

    Science.gov (United States)

    Xu, Yahao; Liao, Chenxi; Chen, Jing; Chen, Youting; Zhu, Xiaoqin; Chen, Jianxin

    2016-05-01

    Solid pseudopapillary tumor (SPT) of the pancreas is an epithelial tumor with low-grade malignant potential and present more common in females. At present, the gold standard for accurate diagnosis of pancreatic tumor was mostly depending on the pathological and/or cytological evaluation. In this work, TPEF microscopy was applied to obtain the images of human normal pancreas and SPT of the pancreas without hematoxylin and eosin (H&E) staining, for the purpose of identifying the organization structural, cell morphological, and cytoplasm changing, which were then compared to their corresponding H&E stained histopathological results. Our results showed that high-resolution TPEF imaging of the pancreatic SPT can clearly distinguish the pathological features from normal pancreas in unstained histological sections, and the results are consistent with the histological results. Moreover, we measured the nuclear-cytoplasmic ratios of the pancreatic SPT and normal pancreas to characterize their difference in the cytomorphological feature. It indicated that this technique can achieve the consistent information of pathological diagnosis, and has the potential to substantially improve the optical diagnosis and treatment of the pancreatic SPT without H&E staining in the future. SCANNING 38:245-250, 2016. © 2015 Wiley Periodicals, Inc. © Wiley Periodicals, Inc.

  17. Cytogenetic analysis in 61 couples with spontaneous abortions

    Institute of Scientific and Technical Information of China (English)

    江静; 傅曼芬; 王德芬

    2001-01-01

    Objective To examine the relationship between spontaneous abortion and chromosomal abnormalities. Methods Couples who had one or more consecutive spontaneous abortions and had normal genitals were enrolled for cytogenetic karyotype analysis. Results In the 61 couples, the detected incidence was 11.5%, with five Robertsonian translocations, one reciprocal translocation, and one pericentric inversion of chromosome 7. Conclusion Chromosomal abnormalities may play an important role in fetal wastage.

  18. Hydrothermally synthesized PEGylated calcium phosphate nanoparticles incorporating Gd-DTPA for contrast enhanced MRI diagnosis of solid tumors.

    Science.gov (United States)

    Mi, Peng; Kokuryo, Daisuke; Cabral, Horacio; Kumagai, Michiaki; Nomoto, Takahiro; Aoki, Ichio; Terada, Yasuko; Kishimura, Akihiro; Nishiyama, Nobuhiro; Kataoka, Kazunori

    2014-01-28

    Organic-inorganic hybrid nanoparticles with calcium phosphate (CaP) core and PEGylated shell were developed to incorporate magnetic resonance imaging (MRI) contrast agent diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) for noninvasive diagnosis of solid tumors. A two-step preparation method was applied to elaborate hybrid nanoparticles with a z-average hydrodynamic diameter about 80nm, neutral surface ξ-potential and high colloidal stability in physiological environments by self-assembly of poly(ethylene glycol)-b-poly(aspartic acid) block copolymer, Gd-DTPA, and CaP in aqueous solution, followed with hydrothermal treatment. Incorporation into the hybrid nanoparticles allowed Gd-DTPA to show significant enhanced retention ratio in blood circulation, leading to high accumulation in tumor positions due to enhanced permeability and retention (EPR) effect. Moreover, Gd-DTPA revealed above 6 times increase of relaxivity in the nanoparticle system compared to free form, and eventually, selective and elevated contrast enhancements in the tumor positions were observed. These results indicate the high potential of Gd-DTPA-loaded PEGylated CaP nanoparticles as a novel contrast agent for noninvasive cancer diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Infektion mit Epstein-Barr-Virus und Tumor-Entstehung beim Menschen

    Science.gov (United States)

    Kirchner, H.

    1981-08-01

    The Epstein-Barr Virus (EBV) is the only infectious agent for which a close association with human malignant tumors has been clearly demonstrated. These tumors are one type of nasopharyngeal carcinoma which is frequent in parts of East Asia and the Burkitt lymphoma which predominantly occurs in parts of Africa and New Guinea. Nonetheless, the EBV is the causative agent of infectious mononucleosis (IM), a benign, self-limiting lymphoproliferative disease of adolescents. The major difference between the countries in which the EBV-induced tumors occur and those in which IM occurs is the late primary EBV infection in the latter, whereas primary infection with EBV occurs in the first year of life in the former. All theories of viral carcinogenesis have to explain the long latency period between primary infection and tumor growth and how an ubiquitous virus may be oncogenic. Thus, invariably, one has to assume a role of cofactors, which may be of cytogenetic nature or may be represented by additional infections or by chemical agents. Since most modern theories of carcinogenesis consider a multi-step development of tumors, the theory that infection with an ubiquitous virus at the right time of life represents one step to carcinogenesis seems to be tenable.

  20. Cytogenetic damage in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients undergoing radiotherapy

    International Nuclear Information System (INIS)

    Minicucci, E.M.; Ribeiro, L.R.; Camargo, J.L.V. de; Salvadori, D.M.F.

    2005-01-01

    This study evaluated cytogenetic damage by measuring the frequency of micronucleated cells (MNC) in peripheral blood and buccal mucosa of head-and-neck cancer patients undergoing radiotherapy. MNC frequencies were assessed in 31 patients before, during, and after radiotherapy, and in 17 healthy controls matched for gender, age, and smoking habits. Results showed no statistically significant difference between patients and controls prior to radiotherapy in cytokinesis-blocked lymphocytes or buccal mucosa cells. During treatment, increased MNC frequencies were observed in both cell types. Micronucleated lymphocyte levels remained high in samples collected 30 to 140 days after the end of treatment, while MNC frequency in buccal mucosa decreased to values statistically similar to baseline values. There is controversy over the effects of age, smoking habit, tumor stage, and/or metastasis on MNC frequency. However, increased frequency of micronucleated buccal mucosa cells was seen in patients under 60 years old and in those with tumors >4 cm. In conclusion, the data show that radiotherapy has a potent clastogenic effect in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients, and that the baseline MNC frequency in these two tissues is not a sensitive marker for head-and neck neoplasm. (author)

  1. First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors

    DEFF Research Database (Denmark)

    Abdul Razak, Albiruni R; Mau-Sørensen, Morten; Gabrail, Nashat Y

    2016-01-01

    PURPOSE: This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of selinexor (KPT-330), a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1), and determined the recommended phase II dose. PATIENTS AND METHODS: In total, 189 patients with advanced solid tumors...

  2. Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting

    Energy Technology Data Exchange (ETDEWEB)

    Kharya, Parul; Jain, Ashish; Gulbake, Arvind; Shilpi, Satish; Jain, Ankit; Hurkat, Pooja [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India); Majumdar, Subrata [Bose Institute, Division of Molecular Medicine (India); Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2013-11-15

    The purpose of this study is to investigate the targeting potential of amino acid (phenylalanine)-coupled solid lipid nanoparticles (SLN) loaded with ionically complexed doxorubicin HCl (Dox). Ionic complexation was used to enhance the loading efficiency and release characteristics of water soluble form of Dox. l-Type amino acid transporters (LAT1) are highly expressed on blood brain barrier as well as on many brain cancer cells, thus targeting LAT1 using phenylalanine improved anticancer activity of prepared nanocarrier. The phenylalanine-coupled SLN were characterized by fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, particle size, zeta potential, entrapment efficiency and in vitro release. The particle size of the resulting SLN was found to be in the range of 163.3 ± 5.2 to 113.0 ± 2.6 nm, with a slightly negative surface charge. In ex vivo study on C6 glioma cell lines, the cellular cytotoxicity of the SLN was highly increased when coupled with phenylalanine. In addition, stealthing sheath of PEG present on the surface of the SLN enhanced the cellular uptake of the SLN on C6 glioma cell line. Results of biodistribution and fluorescence studies clearly revealed that phenylalanine-coupled SLN could deliver high amount of drug into the brain tumor cells and showed the brain-targeting potential.

  3. Tenosynovial Giant Cell Tumor: Better molecular understanding revolutionizes treatment outcome

    Directory of Open Access Journals (Sweden)

    Emad Shash

    2016-01-01

    Full Text Available Tenosynovial giant cell tumors (TGCTs are rare tumors, which are primarily treated via surgery with a low likelihood of metastasis. Although wide excision is an excellent choice for local control, tumors located within or close to major joints, along with the benign nature of the disease, make such resection impractical. An increase in local recurrences and the need for multiple surgical procedures promoted the interest in targeted-therapies for this disease. TGCTs contain a mixture of giant cells, mononuclear cells and inflammatory cells, with clonal cytogenetic abnormalities through rearrangements involving 1p11–13. Colony stimulating factor (CSF1 gene encodes for the ligand of CSF1 receptor (CSF1R. The CSF1 gene is located at the chromosome 1p13 breakpoint and is found to be translocated in 63%–77% of patients with TGCTs. Selective CSF1R inhibitors yield high response rate and disease control, demonstrating the integration of a new drug development technology that could revolutionize treatment outcomes.

  4. Meiosis in hematological malignancies. In situ cytogenetic morphology

    OpenAIRE

    Logothetou-Rella, H.

    1996-01-01

    This is the first study on the in situ cytogenetic morphology and analysis of malignant bone marrow cells, growing attached on a culture vessel surface. It was documented that bone marrow cells, in different types of hematological malignancies, divide by meiosis giving rise to a non-repetitive aneuploidy. Male and female gametes are formed by meiosis and fertilization occurs in a life cycle of: Fertilization Meiosis Gametes - Embryo - Gametes Immature a...

  5. Plant centromeric retrotransposons: a structural and cytogenetic perspective

    Czech Academy of Sciences Publication Activity Database

    Neumann, Pavel; Navrátilová, Alice; Koblížková, Andrea; Kejnovský, Eduard; Hřibová, Eva; Hobza, Roman; Widmer, A.; Doležel, Jaroslav; Macas, Jiří

    2011-01-01

    Roč. 2, č. 4 (2011), s. 1-16 ISSN 1759-8753 R&D Projects: GA AV ČR KJB500960802; GA MŠk(CZ) LC06004; GA ČR GA522/09/0083 Institutional research plan: CEZ:AV0Z50510513; CEZ:AV0Z50040507; CEZ:AV0Z50040702; CEZ:AV0Z50380511 Keywords : plant chromosomes * retrotransposons * cytogenetic perspective Subject RIV: EB - Genetics ; Molecular Biology

  6. Intra-Abdominal Desmoplastic Small Round Cell Tumor with Elevated Serum CA 125: A Case Report

    Directory of Open Access Journals (Sweden)

    Sheau-Fang Yang

    2003-10-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT is a rare and highly aggressive tumor usually involving the peritoneum. It occurs more commonly in young males and is characterized by distinctive clinical, histologic, and immunophenotypic features. The histogenesis of DSRCT remains unknown. Coexpression of epithelial, mesenchymal, and neural antigens in the same cell provides evidence that DSRCT may arise from a primitive pluripotent stem cell with divergent differentiation. Recently, according to cytogenetic studies, some authors have proposed that the divergent differentiation of DSRCT may be the result of the fusion of Ewing's sarcoma gene and Wilms' tumor suppressor gene. Clinically, an elevated serum CA 125 concentration is found in some patients with DSRCT. We present the case of a 29-year-old man with diffuse intra-abdominal DSRCT and elevated serum CA 125 concentration and briefly review the relevant literature.

  7. Prognostic impact of the integration of volumetric quantification of the solid part of the tumor on 3DCT and FDG-PET imaging in clinical stage IA adenocarcinoma of the lung.

    Science.gov (United States)

    Furumoto, Hideyuki; Shimada, Yoshihisa; Imai, Kentaro; Maehara, Sachio; Maeda, Junichi; Hagiwara, Masaru; Okano, Tetsuya; Masuno, Ryuhei; Kakihana, Masatoshi; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

    2018-07-01

    The aim of this study was to conduct comparative analyses of the biological malignant potential of clinical stage IA adenocarcinoma using positron emission tomography/computed tomography (PET/CT), high-resolution CT (HRCT), and three-dimensional CT (3DCT). The predictive performance of these parameters was evaluated in terms of clinical outcomes and pathological invasiveness (positive lymphatic permeation, blood-vessel invasion, pleural invasion, and lymph-node metastasis). We enrolled 170 patients with c-IA adenocarcinoma who underwent PET/CT, HRCT, and 3D reconstruction of lung structures using the Synapse Vincent system (Fujifilm Corporation, Tokyo, Japan) followed by complete resection. Maximum standardized uptake values (SUV max ) of F 18 -fluorodeoxyglucose and the size and volume of the solid part of the tumor were quantified and analyzed in relation to surgical outcomes. Univariate analysis demonstrated that all the three parameters and whole-tumor volume were associated with unfavorable disease-free survival (DFS), while the volume of the solid part was the independent predictor on multivariate analysis (p  2.4 and solid-part volume > 779 mm 3 versus those with SUV max  ≤ 2.4 or solid-part volume ≤779 mm 3 were 81.2% versus 98.3% (p IA adenocarcinoma, the volume of the solid part of the tumor was the independent predictor for unfavorable DFS, and the integration of the volume of the solid part and SUV max was highly beneficial for the prediction of survival and pathological invasiveness. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors12

    Science.gov (United States)

    Hovelson, Daniel H.; McDaniel, Andrew S.; Cani, Andi K.; Johnson, Bryan; Rhodes, Kate; Williams, Paul D.; Bandla, Santhoshi; Bien, Geoffrey; Choppa, Paul; Hyland, Fiona; Gottimukkala, Rajesh; Liu, Guoying; Manivannan, Manimozhi; Schageman, Jeoffrey; Ballesteros-Villagrana, Efren; Grasso, Catherine S.; Quist, Michael J.; Yadati, Venkata; Amin, Anmol; Siddiqui, Javed; Betz, Bryan L.; Knudsen, Karen E.; Cooney, Kathleen A.; Feng, Felix Y.; Roh, Michael H.; Nelson, Peter S.; Liu, Chia-Jen; Beer, David G.; Wyngaard, Peter; Chinnaiyan, Arul M.; Sadis, Seth; Rhodes, Daniel R.; Tomlins, Scott A.

    2015-01-01

    Next-generation sequencing (NGS) has enabled genome-wide personalized oncology efforts at centers and companies with the specialty expertise and infrastructure required to identify and prioritize actionable variants. Such approaches are not scalable, preventing widespread adoption. Likewise, most targeted NGS approaches fail to assess key relevant genomic alteration classes. To address these challenges, we predefined the catalog of relevant solid tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions) through comprehensive bioinformatics analysis of >700,000 samples. To detect these variants, we developed the Oncomine Comprehensive Panel (OCP), an integrative NGS-based assay [compatible with 95% accuracy for KRAS, epidermal growth factor receptor, and BRAF mutation detection as well as for ALK and TMPRSS2:ERG gene fusions. Associating positive variants with potential targeted treatments demonstrated that 6% to 42% of profiled samples (depending on cancer type) harbored alterations beyond routine molecular testing that were associated with approved or guideline-referenced therapies. As a translational research tool, OCP identified adaptive CTNNB1 amplifications/mutations in treated prostate cancers. Through predefining somatic variants in solid tumors and compiling associated potential treatment strategies, OCP represents a simplified, broadly applicable targeted NGS system with the potential to advance precision oncology efforts. PMID:25925381

  9. Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

    Science.gov (United States)

    2018-05-15

    Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

  10. Cytogenetic damage at low doses and the problem of bioindication of chronic low level radiation exposure

    International Nuclear Information System (INIS)

    Geras'kin, S.A.; Dikarev, V.G.; Nesterov, E.B.; Vasiliev, D.V.; Dikareva, N.S.

    2000-01-01

    The analysis undertaken by us of the experimentally observed cellular responses to low dose irradiation has shown that the relationship between the yield of induced cytogenetic damage and radiation dose within low dose range is non-linear and universal in character. Because of the relationship between the yield of cytogenetic damage and dose within low dose range is non-linear, the aberration frequency cannot be used in biological dosimetry in the most important in terms of practical application case. The cytogenetic damage frequency cannot be used in biological dosimetry also because of the probability of synergistic and antagonistic interaction effects of the different nature factors simultaneously acting on test-object in real conditions is high within low dose (concentration) range. In our experimental study of the regularities in the yield of structural mutations in conditions of combined influence of ionizing radiation, heavy metals and pesticides it was found that synergistic and antagonistic effects are mainly induced in conditions of combined action of low exposure injuring agents. Experiments on agricultural plants were carried out in 1986-1989 at the 30-km zone around Chernobyl NPP. It was shown that chronic low dose exposure could cause an inheritable destabilization of genetic structures expressing in increase of cytogenetic damage and yield karyotypic variability in offspring's of irradiated organisms. Obviously exactly this circumstance is the reason of the phenomenon found in our researches of significant time delay of cytogenetic damage reduction rate from radioactive pollution reduction rate from time past from the accident moment. Research of cytogenetic damage of reproductive (seeds) and vegetative (needles) plant organs of the Pinus sylvestris tree micropopulations growing in contrast by radioactive pollution level sites of the 30-km ChNPP zone and also in the vicinity of the industrial plant > for processing and temporary storage of

  11. Molecular cytogenetics of cutaneous melanocytic lesions - diagnostic, prognostic and therapeutic aspects

    NARCIS (Netherlands)

    Blokx, Willeke Am M.; van Dijk, Marcory C. R. F.; Ruiter, Dirk J.

    This review intends to update current knowledge regarding molecular cytogenetics in melanocytic tumours with a focus on cutaneous melanocytic lesions. Advantages and limitations of diverse, already established methods, such as (fluorescence) in situ hybridization and mutation analysis, to detect

  12. Molecular cytogenetics of cutaneous melanocytic lesions - diagnostic, prognostic and therapeutic aspects.

    NARCIS (Netherlands)

    Blokx, W.A.M.; Dijk, M.C.R.F. van; Ruiter, D.J.

    2010-01-01

    This review intends to update current knowledge regarding molecular cytogenetics in melanocytic tumours with a focus on cutaneous melanocytic lesions. Advantages and limitations of diverse, already established methods, such as (fluorescence) in situ hybridization and mutation analysis, to detect

  13. Cytogenetic studies of 11 meningiomas and their clinical significance. II

    DEFF Research Database (Denmark)

    Poulsgård, L; Schrøder, H D; Rønne, M

    1990-01-01

    Cytogenetic analyses of 11 consecutive cases of meningiomas from 7 female and 4 male patients are reported. Chromosomal abnormalities were found in all cases. Only two of the cases showed cells with normal karyotype in addition to the abnormal stemline. Two of the cases displayed a more aggressive...

  14. A comparative analysis of molecular genetic and conventional cytogenetic detection of diagnostically important translocations in more than 400 cases of acute leukemia, highlighting the frequency of false-negative conventional cytogenetics.

    Science.gov (United States)

    King, Rebecca L; Naghashpour, Mojdeh; Watt, Christopher D; Morrissette, Jennifer J D; Bagg, Adam

    2011-06-01

    In this study, we correlated the results of concurrent molecular and cytogenetic detection of entity-defining translocations in adults with acute leukemia to determine the frequency of cryptic translocations missed by conventional cytogenetics (CC) and of recurrent, prognostically relevant translocations not detectable by multiplex reverse transcriptase-polymerase chain reaction (MRP). During a 5.5-year period, 442 diagnostic acute leukemia specimens were submitted for MRP-based detection of 7 common recurrent translocations: t(8;21), t(15;17), inv(16), t(9;22), t(12;21), t(4;11), and t(1;19), with a detection rate of 15.2% (67/442). CC was performed in 330 (74.7%) of 442 cases. In 7 of these 330 cases, CC missed the translocation detected by MRP. In 50 additional cases, CC revealed 1 of the MRP-detectable translocations (all were also MRP positive), yielding a false-negative rate of 12% (7/57) for the CC assay. The remaining 140 of 190 cases with clonal cytogenetic changes harbored abnormalities that were not targeted by the MRP assay, including 8 that define specific acute myeloid leukemia entities. This study revealed the frequent occurrence of false-negative, entity-defining CC analysis and highlighted the complementary nature of MRP and CC approaches in detecting genetic abnormalities in acute leukemia.

  15. Monitoring of DNA and cytogenetic damage in lymphocytes from persons with skin cancer diseases

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.; Dyga, W.; Krasnowolski, S.; Wierzewska, A.; Budzanowska, E.

    1999-01-01

    There is a lot of interest in the studies that would help to understand whether there is a casual association between cancer and various types of molecular or cytogenetic damage detected in human cells. One major oncogenesis process is activation of proto-oncogenes by point mutations or chromosomal translocation. There are substantial evidence that indicates that the loss of heterozygosity of certain chromosomes is involved in human cancerogenesis. Our study aimed to elicit the possible association between cancer and DNA and cytogenetic abnormalities induced in lymphocytes of people bearing various categories of skin cancer cells. Fresh blood was collected by venipuncture from 25 individuals (including nine prior to cancer treatment). All patients were nonsmoking males, however 42.3 % of them were former smokers. Blood samples were divided into two parts and in the first part of samples cytogenetic studies were performed immediately, while from the second part lymphocytes were isolated and stored at -70 o C for further studies in vitro. In the later one a single cell gel electrophoresis assay (SCGE) known as a Comet assay was performed to study individual susceptibility to the induction of DNA damage by UV or radiation and to estimate variability in cellular repair capabilities. An average of 220 per sample of good metaphase spreads in the first mitotic division, and 100 per sample in the second division, were accepted for analysis of cytogenetic damage. Chromosome and chromatid type aberrations were scored in the cells in the first mitosis and expressed as total aberration frequency including gaps and excluding gaps. Sister chromatid exchanges, high frequency cells and proliferative rate index were screened and evaluated in the second mitosis. Each of the patient revealed exceeding in at least one of the cytogenetic biomarkers level from the biomarker's level detected in a reference group. In order to estimate susceptibility of people to environmentally induced

  16. CGH and SNP array using DNA extracted from fixed cytogenetic preparations and long-term refrigerated bone marrow specimens

    Directory of Open Access Journals (Sweden)

    MacKinnon Ruth N

    2012-02-01

    Full Text Available Abstract Background The analysis of nucleic acids is limited by the availability of archival specimens and the quality and amount of the extracted material. Archived cytogenetic preparations are stored in many laboratories and are a potential source of total genomic DNA for array karyotyping and other applications. Array CGH using DNA from fixed cytogenetic preparations has been described, but it is not known whether it can be used for SNP arrays. Diagnostic bone marrow specimens taken during the assessment of hematological malignancies are also a potential source of DNA, but it is generally assumed that DNA must be extracted, or the specimen frozen, within a day or two of collection, to obtain DNA suitable for further analysis. We have assessed DNA extracted from these materials for both SNP array and array CGH. Results We show that both SNP array and array CGH can be performed on genomic DNA extracted from cytogenetic specimens stored in Carnoy's fixative, and from bone marrow which has been stored unfrozen, at 4°C, for at least 36 days. We describe a procedure for extracting a usable concentration of total genomic DNA from cytogenetic suspensions of low cellularity. Conclusions The ability to use these archival specimens for DNA-based analysis increases the potential for retrospective genetic analysis of clinical specimens. Fixed cytogenetic preparations and long-term refrigerated bone marrow both provide DNA suitable for array karyotyping, and may be suitable for a wider range of analytical procedures.

  17. Imaging of pancreatic tumors

    International Nuclear Information System (INIS)

    Brambs, Hans-Juergen; Juchems, Markus

    2010-01-01

    Ductal adenocarcinoma is the most frequent solid tumor of the pancreas. This tumor has distinct features including early obstruction of the pancreatic duct, diminished enhancement after administration of contrast material due to desmoplastic growth, high propensity to infiltrate adjacent structures and to metastasize into the liver and the peritoneum. Hormone active endocrine tumors cause specific clinical symptoms. Imaging is aimed at localization of these hypervascular tumors. Non hormone active tumors are most frequently malignant and demonstrate very varying features. Cystic pancreatic tumors are increasingly detected by means of cross sectional imaging. Exact classification can be achieved with knowledge of the macropathology and considering clinical presentation as well as age and gender of the patients. (orig.)

  18. Phenotypic and Genetic Characterization of Circulating Tumor Cells by Combining Immunomagnetic Selection and FICTION Techniques

    Science.gov (United States)

    Campos, María; Prior, Celia; Warleta, Fernando; Zudaire, Isabel; Ruíz-Mora, Jesús; Catena, Raúl; Calvo, Alfonso; Gaforio, José J.

    2008-01-01

    The presence of circulating tumor cells (CTCs) in breast cancer patients has been proven to have clinical relevance. Cytogenetic characterization of these cells could have crucial relevance for targeted cancer therapies. We developed a method that combines an immunomagnetic selection of CTCs from peripheral blood with the fluorescence immunophenotyping and interphase cytogenetics as a tool for investigation of neoplasm (FICTION) technique. Briefly, peripheral blood (10 ml) from healthy donors was spiked with a predetermined number of human breast cancer cells. Nucleated cells were separated by double density gradient centrifugation of blood samples. Tumor cells (TCs) were immunomagnetically isolated with an anti-cytokeratin antibody and placed onto slides for FICTION analysis. For immunophenotyping and genetic characterization of TCs, a mixture of primary monoclonal anti-pancytokeratin antibodies was used, followed by fluorescent secondary antibodies, and finally hybridized with a TOP2A/HER-2/CEP17 multicolor probe. Our results show that TCs can be efficiently isolated from peripheral blood and characterized by FICTION. Because genetic amplification of TOP2A and ErbB2 (HER-2) in breast cancer correlates with response to anthracyclines and herceptin therapies, respectively, this novel methodology could be useful for a better classification of patients according to the genetic alterations of CTCs and for the application of targeted therapies. (J Histochem Cytochem 56:667–675, 2008) PMID:18413646

  19. Estimation of absorbed doses on the basis of cytogenetic methods

    International Nuclear Information System (INIS)

    Shevchenko, V.A.; Rubanovich, A.V.; Snigiryova, G.P.

    1998-01-01

    Long-term studies in the field of radiation cytogenetics have resulted in the discovery of relationship between induction of chromosome aberrations and the type of ionizing radiation, their intensity and dose. This has served as a basis of biological dosimetry as an area of application of the revealed relationship, and has been used in the practice to estimate absorbed doses in people exposed to emergency irradiation. The necessity of using the methods of biological dosimetry became most pressing in connection with the Chernobyl accident in 1986, as well as in connection with other radiation situations that occurred in nuclear industry of the former USSR. The materials presented in our works demonstrate the possibility of applying cytogenetic methods for assessing absorbed doses in populations of different regions exposed to radiation as a result of accidents at nuclear facilities (Chernobyl, the village Muslymovo on the Techa river, the Three Mile Island nuclear power station in the USA where an accident occurred in 1979). Fundamentally, new possibilities for retrospective dose assessment are provided by the FISH-method that permits the assessment of absorbed doses after several decades since the exposure occurred. In addition, the application of this method makes it possible to restore the dynamics of unstable chromosome aberrations (dicentrics and centric rings), which is important for further improvement of the method of biological dosimetry based on the analysis of unstable chromosome aberrations. The purpose of our presentation is a brief description of the cytogenetic methods used in biological dosimetry, consideration of statistical methods of data analysis and a description of concrete examples of their application. (J.P.N.)

  20. Transcriptional response to hypoxia in human tumors.

    NARCIS (Netherlands)

    Lal, A.; Peters, H.; Croix, B. St.; Haroon, Z.A.; Dewhirst, M.W.; Strausberg, R.L.; Kaanders, J.H.A.M.; Kogel, A.J. van der; Riggins, G.J.

    2001-01-01

    BACKGROUND: The presence of hypoxic regions within solid tumors is associated with a more malignant tumor phenotype and worse prognosis. To obtain a blood supply and protect against cellular damage and death, oxygen-deprived cells in tumors alter gene expression, resulting in resistance to therapy.

  1. Cytogenetic characterization and H-ras associated transformation of immortalized human mammary epithelial cells

    Directory of Open Access Journals (Sweden)

    Larivee Siobhan

    2006-05-01

    Full Text Available Abstract Introduction Immortalization is a key step in malignant transformation, but immortalization alone is insufficient for transformation. Human mammary epithelial cell (HMEC transformation is a complex process that requires additional genetic changes beyond immortalization and can be accomplished in vitro by accumulation of genetic changes and expression of H-ras. Methods HMEC were immortalized by serial passaging and transduction with the catalytic subunit of the human telomerase gene (hTERT. The immortalized cells were passaged in vitro and studied by a combination of G- banding and Spectral Karyotyping (SKY. H-ras transduced, hTERT immortalized cells were cloned in soft agar and injected into nude mice. Extensive analysis was performed on the tumors that developed in nude mice, including immunohistochemistry and western blotting. Results Immortal HMEC alone were not tumorigenic in γ-irradiated nude mice and could not grow in soft agar. Late passage hTERT immortalized HMEC from a donor transduced with a retroviral vector containing the mutant, autoactive, human H-ras61L gene acquired anchorage independent growth properties and the capacity for tumorigenic growth in vivo. The tumors that developed in the nude mice were poorly differentiated epithelial carcinomas that continued to overexpress ras. These cells were resistant to doxorubicin mediated G1/S phase arrest but were sensitive to treatment with a farnesyltransferase inhibitor. Conclusion Some of the cytogenetic changes are similar to what is observed in premalignant and malignant breast lesions. Despite these changes, late passage immortal HMEC are not tumorigenic and could only be transformed with overexpression of a mutant H-ras oncogene.

  2. Ewing’s sarcoma: an uncommon breast tumor

    Directory of Open Access Journals (Sweden)

    Sawsen Meddeb

    2014-10-01

    Full Text Available Ewing’s sarcoma/primitive neuroectodermal tumors (EWS/PNET are rare malignant and aggressive tumors, usually seen in the trunk and lower limbs of children and young adults. They are uncommon in the breast. We report a case of a 43-year-old woman who developed a painless breast mass. An initial core needle biopsy concluded to a fibrocystic dystrophy contrasting with a rapidly growing mass; thus a large lumpectomy was done. Diagnosis of primary PNET of the breast was established, based on both histopathological examination and immunohistochemical findings. Surgical margins were positive, therefore, left modified radical mastectomy with axillary lymph nodes dissection was performed. The patient was given 6 cycles of adjuvant chemotherapy containing cyclophosphamide, adriamycin and vincristine. Twenty months later, she is in life without recurrence or metastasis. EWS/PNET may impose a diagnostic challenge. Indeed, mammography and ultrasonography features are non specific. The histopathological pattern is variable depending on the degree of neuroectodermal differentiation. Immuno-phenotyping is necessary and genetic study is the only confirmatory tool of diagnosis showing a characteristic cytogenetic anomaly; t (11; 22 translocation.

  3. Novel anti-c-Mpl monoclonal antibodies identified multiple differentially glycosylated human c-Mpl proteins in megakaryocytic cells but not in human solid tumors.

    Science.gov (United States)

    Zhan, Jinghui; Felder, Barbara; Ellison, Aaron R; Winters, Aaron; Salimi-Moosavi, Hossein; Scully, Sheila; Turk, James R; Wei, Ping

    2013-06-01

    Thrombopoietin and its cognate receptor, c-Mpl, are the primary molecular regulators of megakaryocytopoiesis and platelet production. To date the pattern of c-Mpl expression in human solid tumors and the distribution and biochemical properties of c-Mpl proteins in hematopoietic tissues are largely unknown. We have recently developed highly specific mouse monoclonal antibodies (MAb) against human c-Mpl. In this study we used these antibodies to demonstrate the presence of full-length and truncated human c-Mpl proteins in various megakaryocytic cell types, and their absence in over 100 solid tumor cell lines and in the 12 most common primary human tumor types. Quantitative assays showed a cell context-dependent distribution of full-length and truncated c-Mpl proteins. All forms of human c-Mpl protein were found to be modified with extensive N-linked glycosylation but different degrees of sialylation and O-linked glycosylation. Of note, different variants of full-length c-Mpl protein exhibiting differential glycosylation were expressed in erythromegakaryocytic leukemic cell lines and in platelets from healthy human donors. This work provides a comprehensive analysis of human c-Mpl mRNA and protein expression on normal and malignant hematopoietic and non-hematopoietic cells and demonstrates the multiple applications of several novel anti-c-Mpl antibodies.

  4. Remodeling of Tumor Stroma and Response to Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, Anna; Ganss, Ruth, E-mail: ganss@waimr.uwa.edu.au [Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000 (Australia)

    2012-03-27

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy.

  5. Remodeling of Tumor Stroma and Response to Therapy

    International Nuclear Information System (INIS)

    Johansson, Anna; Ganss, Ruth

    2012-01-01

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy

  6. Safety, pharmacokinetics, and antitumor activity of AMG 386, a selective angiopoietin inhibitor, in adult patients with advanced solid tumors.

    Science.gov (United States)

    Herbst, Roy S; Hong, David; Chap, Linnea; Kurzrock, Razelle; Jackson, Edward; Silverman, Jeffrey M; Rasmussen, Erik; Sun, Yu-Nien; Zhong, Don; Hwang, Yuying C; Evelhoch, Jeffrey L; Oliner, Jonathan D; Le, Ngocdiep; Rosen, Lee S

    2009-07-20

    PURPOSE AMG 386 is an investigational peptide-Fc fusion protein (ie, peptibody) that inhibits angiogenesis by preventing the interaction of angiopoietin-1 and angiopoietin-2 with their receptor, Tie2. This first-in-human study evaluated the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of AMG 386 in adults with advanced solid tumors. PATIENTS AND METHODS Patients in sequential cohorts received weekly intravenous AMG 386 doses of 0.3, 1, 3, 10, or 30 mg/kg. Results Thirty-two patients were enrolled on the study and received AMG 386. One occurrence of dose-limiting toxicity was seen at 30 mg/kg: respiratory arrest, which likely was caused by tumor burden that was possibly related to AMG 386. The most common toxicities were fatigue and peripheral edema. Proteinuria (n = 11) was observed without clinical sequelae. Only four patients (12%) experienced treatment-related toxicities greater than grade 1. A maximum-tolerated dose was not reached. PK was dose-linear and the mean terminal-phase elimination half-life values ranged from 3.1 to 6.3 days. Serum AMG 386 levels appeared to reach steady-state after four weekly doses, and there was minimal accumulation. No anti-AMG 386 neutralizing antibodies were detected. Reductions in volume transfer constant (K(trans); measured by dynamic contrast-enhanced magnetic resonance imaging) were observed in 10 patients (13 lesions) 48 hours to 8 weeks after treatment. One patient with refractory ovarian cancer achieved a confirmed partial response (ie, 32.5% reduction by Response Evaluation Criteria in Solid Tumors) and withdrew from the study with a partial response after 156 weeks of treatment; four patients experienced stable disease for at least 16 weeks. CONCLUSION Weekly AMG 386 appeared well tolerated, and its safety profile appeared distinct from that of vascular endothelial growth factor-axis inhibitors. AMG 386 also appeared to impact tumor vascularity and showed antitumor activity in this patient

  7. Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors

    International Nuclear Information System (INIS)

    Bonde, Anne-Katrine; Tischler, Verena; Kumar, Sushil; Soltermann, Alex; Schwendener, Reto A

    2012-01-01

    Several stromal cell subtypes including macrophages contribute to tumor progression by inducing epithelial-mesenchymal transition (EMT) at the invasive front, a mechanism also linked to metastasis. Tumor associated macrophages (TAM) reside mainly at the invasive front but they also infiltrate tumors and in this process they mainly assume a tumor promoting phenotype. In this study, we asked if TAMs also regulate EMT intratumorally. We found that TAMs through TGF-β signaling and activation of the β-catenin pathway can induce EMT in intratumoral cancer cells. We depleted macrophages in F9-teratocarcinoma bearing mice using clodronate-liposomes and analyzed the tumors for correlations between gene and protein expression of EMT-associated and macrophage markers. The functional relationship between TAMs and EMT was characterized in vitro in the murine F9 and mammary gland NMuMG cells, using a conditioned medium culture approach. The clinical relevance of our findings was evaluated on a tissue microarray cohort representing 491 patients with non-small cell lung cancer (NSCLC). Gene expression analysis of F9-teratocarcinomas revealed a positive correlation between TAM-densities and mesenchymal marker expression. Moreover, immunohistochemistry showed that TAMs cluster with EMT phenotype cells in the tumors. In vitro, long term exposure of F9-and NMuMG-cells to macrophage-conditioned medium led to decreased expression of the epithelial adhesion protein E-cadherin, activation of the EMT-mediating β-catenin pathway, increased expression of mesenchymal markers and an invasive phenotype. In a candidate based screen, macrophage-derived TGF-β was identified as the main inducer of this EMT-associated phenotype. Lastly, immunohistochemical analysis of NSCLC patient samples identified a positive correlation between intratumoral macrophage densities, EMT markers, intraepithelial TGF-β levels and tumor grade. Data presented here identify a novel role for macrophages in EMT

  8. Trends in cytogenetic testing and identification of chromosomal abnormalities among pregnancies and children with birth defects, metropolitan Atlanta, 1968-2005.

    Science.gov (United States)

    Jackson, Jodi M; Crider, Krista S; Rasmussen, Sonja A; Cragan, Janet D; Olney, Richard S

    2012-01-01

    The purpose of this study was to examine changes in the use of cytogenetic testing and identification of chromosomal abnormalities among pregnancies and children with birth defects. Utilizing data from 1968 to 2005 from the Metropolitan Atlanta Congenital Defects Program, we analyzed trends in the frequency and timing (prenatal or postnatal) of cytogenetic testing and the prevalence of recognized chromosome abnormalities among pregnancies and children with birth defects (n = 51,424). Cytogenetic testing of pregnancies and children with birth defects increased from 7.2% in 1968 to 25.0% in 2005, as did the identification of chromosomal abnormalities (2.2% in 1968 to 6.8% in 2005). The use of prenatal cytogenetic testing decreased from 1996 to 2005 among women aged ≥35 years. Identification of chromosomal abnormalities in pregnancies and children with birth defects increased from 1968 to 2005, possibly due to increased testing, improved diagnostic techniques, or increasing maternal age. The decline in prenatal cytogenetic testing observed among mothers aged ≥35 years may be related to the availability of improved prenatal screening techniques, resulting in a reduction in the utilization of invasive diagnostic tests. Published 2011 Wiley Periodicals, Inc. This article is a U.S. Government work and is in the public domain in the USA.

  9. Notes on the cytogenetics of some South African Xiphinema species ...

    African Journals Online (AJOL)

    The cytogenetics of several South African species of Xiphinemawere studied and compared with the existing data for this genus from Europe. The process of oogenesis appears to be very similar in all species studied, with little interspecific and intraspecific differences. The ovaries of the South African specimens are larger, ...

  10. Cytogenetic studies of the blood (M111), part A

    Science.gov (United States)

    Lockhart, L. H.

    1973-01-01

    The cytogenetic study of the crew appears to indicate that Skylab-type environmental conditions have no deleterious effect upon chromosomal material. The findings are, however, less clear-cut than might be desired, due in large measure to confounding of the experimental design by the administration of isotope injections for the purposes of other experiments and to the lack of control subjects.

  11. Chronic Lymphocytic Leukemia with t(14;18(q32;q21 as a Sole Cytogenetic Abnormality

    Directory of Open Access Journals (Sweden)

    Ghaleb Elyamany

    2014-01-01

    Full Text Available Background Chronic lymphocytic leukemia (CLL is the most common leukemia in adults. The chromosomal abnormality t(14;18(q32;q21 is most commonly associated with neoplasms of a follicular center cell origin. However, t(14;18 has also been reported in rare cases of CLL. Objective We describe the clinicopathologic, immunophenotypic, conventional, and molecular cytogenetic features of two rare cases proven to be CLL morphologically and immunologically in which t(14;18 was found as the sole cytogenetic abnormality. Methods Morphologic, flow cytometric analysis and molecular cytogenetic of peripheral blood and/or bone marrow samples were analyzed. Results Cytomorphologically, the cells were small mature lymphocytes without any findings that had characteristics of follicular lymphoma (FL such as indented or clefted nuclei. Immunologic findings were characteristic of typical CLL without expression of CD10. A cytogenetic study revealed the two cases of CLL carrying t(14;18(q32;q21. Conclusion We concluded that CLL with t(14;18 is rare and should be differentiated from FL as the therapy is highly diverse between both diseases. Using immunoglobulin heavy chain gene ( IGH probes are important in the workup of patients with suspected CLL and suggest that the IGH probe should be used routinely in all CLL fluorescence in situ hybridization (FISH panels.

  12. Validation and Application of a Custom-Designed Targeted Next-Generation Sequencing Panel for the Diagnostic Mutational Profiling of Solid Tumors.

    Directory of Open Access Journals (Sweden)

    Guy Froyen

    Full Text Available The inevitable switch from standard molecular methods to next-generation sequencing for the molecular profiling of tumors is challenging for most diagnostic laboratories. However, fixed validation criteria for diagnostic accreditation are not in place because of the great variability in methods and aims. Here, we describe the validation of a custom panel of hotspots in 24 genes for the detection of somatic mutations in non-small cell lung carcinoma, colorectal carcinoma and malignant melanoma starting from FFPE sections, using 14, 36 and 5 cases, respectively. The targeted hotspots were selected for their present or future clinical relevance in solid tumor types. The target regions were enriched with the TruSeq approach starting from limited amounts of DNA. Cost effective sequencing of 12 pooled libraries was done using a micro flow cell on the MiSeq and subsequent data analysis with MiSeqReporter and VariantStudio. The entire workflow was diagnostically validated showing a robust performance with maximal sensitivity and specificity using as thresholds a variant allele frequency >5% and a minimal amplicon coverage of 300. We implemented this method through the analysis of 150 routine diagnostic samples and identified clinically relevant mutations in 16 genes including KRAS (32%, TP53 (32%, BRAF (12%, APC (11%, EGFR (8% and NRAS (5%. Importantly, the highest success rate was obtained when using also the low quality DNA samples. In conclusion, we provide a workflow for the validation of targeted NGS by a custom-designed pan-solid tumor panel in a molecular diagnostic lab and demonstrate its robustness in a clinical setting.

  13. Prenatal BoBs TM in the cytogenetic analysis of products of ...

    African Journals Online (AJOL)

    Background. Fifty percent of spontaneous miscarriages (SMs) are attributed to chromosomal abnormalities. Cytogenetic analysis is an important tool for patient counselling and assessment of the risk of recurrence in future pregnancies. Conventional karyotyping has been the gold standard for chromosomal investigation of ...

  14. Application of molecular cytogenetic techniques to clarify apparently balanced complex chromosomal rearrangements in two patients with an abnormal phenotype: Case report

    NARCIS (Netherlands)

    P.J.P. de Vree (Paula); M.E.H. Simon (Marleen); M.F. van Dooren (Marieke); G.H.T. Stoevelaar (Gerda); J.T.W. Hilkmann (José); M.A. Rongen (Michel); G.C.M. Huijbregts (Gido); A.J.H.M. Verkerk (Annemieke); P. Poddighe (Pino)

    2009-01-01

    textabstractBackground. Complex chromosomal rearrangements (CCR) are rare cytogenetic findings that are difficult to karyotype by conventional cytogenetic analysis partially because of the relative low resolution of this technique. High resolution genotyping is necessary in order to identify cryptic

  15. Dose escalation to high-risk sub-volumes based on non-invasive imaging of hypoxia and glycolytic activity in canine solid tumors

    DEFF Research Database (Denmark)

    Clausen, Malene M.; Hansen, Anders Elias; af Rosenschold, Per Munck

    2013-01-01

    : Positron emission tomography/computed tomography (PET/CT) scans of five spontaneous canine solid tumors were included. FDG-PET/CT was obtained at day 1, 64Cu-ATSM at day 2 and 3 (3 and 24 h pi.). GTV was delineated and CT images were co-registered. Sub-volumes for 3 h and 24 h 64Cu-ATSM (Cu3 and Cu24) were...

  16. In Vivo Monitoring of pH, Redox Status, and Glutathione Using L-Band EPR for Assessment of Therapeutic Effectiveness in Solid Tumors

    Science.gov (United States)

    Bobko, Andrey A.; Eubank, Timothy D.; Voorhees, Jeffrey L.; Efimova, Olga V.; Kirilyuk, Igor A.; Petryakov, Sergey; Trofimiov, Dmitrii G.; Marsh, Clay B.; Zweier, Jay L.; Grigor’ev, Igor A.; Samouilov, Alexandre; Khramtsov, Valery V.

    2011-01-01

    Approach for in vivo real-time assessment of tumor tissue extracellular pH (pHe), redox, and intracellular glutathione based on L-band EPR spectroscopy using dual function pH and redox nitroxide probe and disulfide nitroxide biradical, is described. These parameters were monitored in PyMT mice bearing breast cancer tumors during treatment with granulocyte macrophage colony-stimulating factor. It was observed that tumor pHe is about 0.4 pH units lower than that in normal mammary gland tissue. Treatment with granulocyte macrophage colony-stimulating factor decreased the value of pHe by 0.3 units compared with PBS control treatment. Tumor tissue reducing capacity and intracellular glutathione were elevated compared with normal mammary gland tissue. Granulocyte macrophage colony-stimulating factor treatment resulted in a decrease of the tumor tissue reducing capacity and intracellular glutathione content. In addition to spectroscopic studies, pHe mapping was performed using recently proposed variable frequency proton–electron double-resonance imaging. The pH mapping superimposed with MRI image supports probe localization in mammary gland/tumor tissue, shows high heterogeneity of tumor tissue pHe and a difference of about 0.4 pH units between average pHe values in tumor and normal mammary gland. In summary, the developed multifunctional approach allows for in vivo, noninvasive pHe, extracellular redox, and intracellular glutathione content monitoring during investigation of various therapeutic strategies for solid tumors. Magn Reson Med 000:000–000, 2011. PMID:22113626

  17. Promotion of Tumor Invasion by Cooperation of Granulocytes and Macrophages Activated by Anti-tumor Antibodies

    Directory of Open Access Journals (Sweden)

    Emilio Barbera-Guillem

    1999-11-01

    Full Text Available We investigated the potential role of anti-tumor antibodies and tumor antigens in the formation of immune complexes which promote matrix degradation and angiogenesis. B-cell deficient or B-cell depleted mice showed a reduction in tumor invasion and metastasis. In vitro invasion assays and in vivo models of metastasis showed that anti-sTn antibodies and sTn tumor antigens form complexes which induce granulocytes and macrophages together to mediate tumor invasion and metastasis by processes including extracellular matrix degradation and angiogenesis. These results suggest the existence of a tumor promoting role of a B-cell immune response induced by shed tumor associated antigens of solid, nonlymphoid tumors.

  18. Role for the Wilms tumor gene in genital development?

    International Nuclear Information System (INIS)

    van Heyningen, V.; Bickmore, W.A.; Seawright, A.; Fletcher, J.M.; Maule, J.; Hastie, N.D.; Fekete, G.; Gessler, M.; Bruns, G.A.P.; Huerre-Jeanpierre, C.; Junien, C.; Williams, B.R.G.

    1990-01-01

    Detailed molecular definition of the WAGR region at chromosome 11p13 has been achieved by chromosome breakpoint analysis and long-range restriction mapping. Here the authors describe the molecular detection of a cytogenetically invisible 1-megabase deletion in an individual with aniridia, cryptorchidism, and hypospadias but no Wilms tumor (WT). The region of overlap between this deletion and one associated with WT and similar genital anomalies but no aniridia covers a region of 350-400 kilobases, which is coincident with the extent of homozygous deletion detected in tumor tissue from a sporadic WT. A candidate WT gene located within this region has recently been isolated, suggesting nonpenetrance for tumor expression in the first individual. The inclusion within the overlap region of a gene for WT predisposition and a gene for the best-documented WT-associated genitourinary malformations leads to suggest that both of these anomalies result from a loss-of-function mutation at the same locus. This in turn implies that the WT gene exerts pleiotropic effect on both kidney and genitourinary development, a possibility supported by the observed expression pattern of the WT candidate gene in developing kidney and gonads

  19. Cytogenetic studies in persons, professionally exposed to low doses ionizing radiation

    International Nuclear Information System (INIS)

    Bulanova, M.; Ivanov, B.; Khristova, M.; Praskova, L.; Mikhajlov, M.; Dovev, I.

    1981-01-01

    Cytogenetic techniques were used to examine peripheral lymphocytes taken from 33 subjects employed at the IRT-2000-Sofia Nuclear Reactor and exposed to mixed gamma and neutron radiation in its Zone A. Physical dosimetry data (from pen and film personnel dosimeters) showed the exposures to be below maximum permissible levels, in complience with Radiation Safety Norms in the P.R. of Bulgaria (1972). The subjects were distributed into three groups according to the length of their occupational experience as radiation workers. Comparisons were made with cytogenetic findings in the lymphocyte cultures taken from 30 subjects with no occupational radiation exposure. Radiation workers exhibited a significant increase in chromosomal damage of the chromosome and chromatid type. Subjects with 5-10 years of occupational experience had a higher degree of chromosomal damage than the less-than-5-years group. For persons with more than 10 years of occupational experience, however, no increase over controls could be ascertained in percentage of chromosomal damage. When radiation workers were re-distributed in accord with the exposures received, it was evident that the effect increased with the accumulated dose, the group with about 0.02 Sievert having nearly twice the aberrant cell percentage for the 0.01 Sievert group. In the group of up to 0.05 Sievert, the percentage of aberrant cells was in the order of that observed after exposure to 0.02 Sievert. From the findings in the analysis, radiation quality seemed to play no part in enliciting the cytogenetic response of peripheral lymphocytes. (A.B.)

  20. Definition of the zebrafish genome using flow cytometry and cytogenetic mapping

    Directory of Open Access Journals (Sweden)

    Zhou Yi

    2007-06-01

    Full Text Available Abstract Background The zebrafish (Danio rerio is an important vertebrate model organism system for biomedical research. The syntenic conservation between the zebrafish and human genome allows one to investigate the function of human genes using the zebrafish model. To facilitate analysis of the zebrafish genome, genetic maps have been constructed and sequence annotation of a reference zebrafish genome is ongoing. However, the duplicative nature of teleost genomes, including the zebrafish, complicates accurate assembly and annotation of a representative genome sequence. Cytogenetic approaches provide "anchors" that can be integrated with accumulating genomic data. Results Here, we cytogenetically define the zebrafish genome by first estimating the size of each linkage group (LG chromosome using flow cytometry, followed by the cytogenetic mapping of 575 bacterial artificial chromosome (BAC clones onto metaphase chromosomes. Of the 575 BAC clones, 544 clones localized to apparently unique chromosomal locations. 93.8% of these clones were assigned to a specific LG chromosome location using fluorescence in situ hybridization (FISH and compared to the LG chromosome assignment reported in the zebrafish genome databases. Thirty-one BAC clones localized to multiple chromosomal locations in several different hybridization patterns. From these data, a refined second generation probe panel for each LG chromosome was also constructed. Conclusion The chromosomal mapping of the 575 large-insert DNA clones allows for these clones to be integrated into existing zebrafish mapping data. An accurately annotated zebrafish reference genome serves as a valuable resource for investigating the molecular basis of human diseases using zebrafish mutant models.

  1. The impact of the depth of field on cytogenetic image quality in scanning microscopy

    Science.gov (United States)

    Qiu, Yuchen; Chen, Xiaodong; Li, Yuhua; Zheng, Bin; Li, Shibo; Zhang, Roy R.; Chen, Wei R.; Liu, Hong

    2011-03-01

    The purpose of this study is to investigate the impact of the depth of field (DOF) of microscopic systems on cytogenetic image qualities. Due to the narrow DOF of high magnification, large numerical aperture (N.A.) objective lenses, random vibrations of even high precision scanning stages may result in large amount of off focused images. In this study, the DOF of microscopic systems with various objective magnifications/numerical apertures (N.A.) is first measured using standard resolution targets. The impact of DOF on cytogenetic image qualities is then subjectively evaluated with clinical samples, by comparing the band shape and sharpness of analyzable chromosomes. For a specific digital microscopic system with 100× objective lens (N.A. = 1.25), the results of observational studies revealed that chromosomal bands are still recognizable when the images are obtained approximately +/- 1 μm from the focusing plane. The chromosomal bands become fuzzy and unrecognizable when the system is 1.5 μm away from the focusing position. The results of this preliminary experimental study may provide useful design trade-off parameters for developing optimal scanning microscopic systems for cytogenetic applications.

  2. A phase I pharmacokinetic study of ursolic acid nanoliposomes in healthy volunteers and patients with advanced solid tumors

    Directory of Open Access Journals (Sweden)

    Ying G

    2013-01-01

    Full Text Available Zhongling Zhu,1,4 Zhengzi Qian,2,4 Zhao Yan,1,4 Cuicui Zhao,2,4 Huaqing Wang,2,4 Guoguang Ying3,41Department of Clinical Pharmacology, 2Department of Lymphoma, 3Laboratory of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China; 4Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of ChinaBackground: Ursolic acid is a promising anticancer agent. The current study aims to evaluate the single- and multiple-dose pharmacokinetics (PK as well as the safety of ursolic acid nanoliposomes (UANL in healthy volunteers and in patients with advanced solid tumors.Methods: Twenty-four healthy volunteers in the single-dose PK study were divided into three different groups, which received 37, 74, and 98 mg/m2 of UANL. Eight patients in the multiple-dose PK study were administered with 74 mg/m2 of UANL daily for 14 days. The UA plasma concentrations were determined using ultra-performance liquid chromatograph-tandem mass spectrometry.Results: The plasma concentration profiles of all subjects were characterized by a biexponential decline after infusion. The mean peak plasma concentration (Cmax increased linearly as a function of the dose (r = 0.999. The mean area under the plasma concentration-time curve (AUC from 0 to 16 hours also increased proportionally with dose escalation (r = 0.998. However, the clearance was constant over the specific dose interval. In the multiple-dose PK study, the trough and average concentrations remained low. The mean AUC, half-life, Cmax, time to Cmax, and the volume of distribution on the first day were similar to those on the last day. All subjects tolerated the treatments well. Most UANL-associated adverse events varied from mild to moderate.Conclusions: UANL exhibits relatively linear PK behavior with dose levels from 37 mg/m2 to 98 mg/m2. No drug accumulation was observed with repeated doses of UANL. The intravenous infusion of UANL was well

  3. Tumor stem cells: A new approach for tumor therapy (Review)

    Science.gov (United States)

    MENG, MIN; ZHAO, XIN-HAN; NING, QIAN; HOU, LEI; XIN, GUO-HONG; LIU, LI-FENG

    2012-01-01

    Recent studies have demonstrated the existence of a minority of tumor cells possessing the stem cell properties of self-renewal and differentiation in leukemia and several solid tumors. However, these cells do not possess the normal regulatory mechanisms of stem cells. Following transplantation, they are capable of initiating tumorigenesis and are therefore known as ‘tumor stem cells’. Cellular origin analysis of tumor stem cells has resulted in three hypotheses: Embryonal rest hypothesis, anaplasia and maturation arrest. Several signaling pathways which are involved in carcinogenesis, including Wnt/β-catenin, Notch and Oct-4 signaling pathways are crucial in normal stem cell self-renewal decisions, suggesting that breakdown in the regulation of self-renewal may be a key event in the development of tumors. Thus, tumors can be regarded as an abnormal organ in which stem cells have escaped from the normal constraints on self-renewal, thus, leading to abnormally differentiated tumor cells that lose the ability to form tumors. This new model for maligancies has significance for clinical research and treatment. PMID:22844351

  4. Cytogenetic abnormalities in a series of 1,029 patients with primary myelodysplastic syndromes: a report from the US with a focus on some undefined single chromosomal abnormalities.

    Science.gov (United States)

    Pozdnyakova, Olga; Miron, Patricia M; Tang, Guilin; Walter, Otto; Raza, Azra; Woda, Bruce; Wang, Sa A

    2008-12-15

    Conventional karyotype has an established role in myelodysplastic syndrome (MDS) and is included in the International Prognostic Scoring System (IPSS) for patient risk stratification and treatment selection. Although some chromosomal abnormalities have been well characterized, the significance of several miscellaneous, infrequent, single chromosomal abnormalities remains to be defined. In addition, the emerging therapeutic agents may change the natural course of disease in patients with MDS and the cytogenetic impact on risk stratification. Clinicopathologic data were retrieved on 1029 patients who had a diagnosis of primary MDS and had available cytogenetic data (karyotype) on file. Cytogenetic abnormalities were identified in 458 patients (45%) and occurred most frequently in patients who had refractory anemia with excess blasts (62%). Overall, the 3 cytogenetic risk groups defined by the IPSS -- good, intermediate, and poor -- effectively stratified the patients' overall survival (OS) (64 months, 31 months, and 12 months, respectively; P < .001). With the exception of gain of chromosome 8, single cytogenetic abnormalities within the intermediate group were extremely infrequent in the series but demonstrated variable OS ranging from 10 months for patients who had isochromosome (17q) to 69 months for patients who had deletion of 12p [del(12p)], suggesting different prognostic significance. In the poor cytogenetic risk group, patients with isolated del(7q) and derivative (1;7)(q10;p10) had a significantly better median OS than patients who had either loss of chromosome 7 or a complex karyotype (P < .05). The current data generated from a large cohort of patients with primary MDS indicated that some specific cytogenetic abnormalities carry different risk than their IPSS cytogenetic risk-group assignment, especially in the new treatment era. Because of the extreme low frequency, additional combined studies are needed to better categorize some rare single cytogenetic

  5. Cancer predictive value of cytogenetic markers used in occupational health surveillance programs: a report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health

    DEFF Research Database (Denmark)

    Hagmar, L; Bonassi, S; Strömberg, U

    1998-01-01

    cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each...... as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed...... country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers...

  6. Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors

    Directory of Open Access Journals (Sweden)

    Yongkun Sun

    2016-10-01

    Full Text Available Abstract Background Anlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of anlotinib in patients with advanced refractory solid tumors. Methods Anlotinib (5–16 mg was orally administered in patients with solid tumor once a day on two schedules: (1 four consecutive weeks (4/0 or (2 2-week on/1-week off (2/1. Pharmacokinetic sampling was performed in all patients. Twenty-one patients were further enrolled in an expanded cohort study on the recommended dose and schedule. Preliminary tumor response was also assessed. Results On the 4/0 schedule, dose-limiting toxicity (DLT was grade 3 hypertension at 10 mg. On the 2/1 schedule, DLT was grade 3 hypertension and grade 3 fatigue at 16 mg. Pharmacokinetic assessment indicated that anlotinib had long elimination half-lives and significant accumulation during multiple oral doses. The 2/1 schedule was selected, with 12 mg once daily as the maximum tolerated dose for the expanding study. Twenty of the 21 patients (with colon adenocarcinoma, non-small cell lung cancer, renal clear cell cancer, medullary thyroid carcinoma, and soft tissue sarcoma were assessable for antitumor activity of anlotinib: 3 patients had partial response, 14 patients had stable disease including 12 tumor burden shrinkage, and 3 had disease progression. The main serious adverse effects were hypertension, triglyceride elevation, hand-foot skin reaction, and lipase elevation. Conclusions At the dose of 12 mg once daily at the 2/1 schedule, anlotinib displayed manageable toxicity, long circulation, and broad-spectrum antitumor potential, justifying the conduct of further studies.

  7. Cytogenetic report of a male breast cancer

    DEFF Research Database (Denmark)

    Cavalli, L R; Rogatto, S R; Rainho, C A

    1995-01-01

    of chromosome 8 in the characterization of the subtype of ductal breast carcinomas and demonstrate that chromosome 17, which is frequently involved in female breast cancers, is also responsible for the development or progression of primary breast cancers in males.......The cytogenetic findings on G-banding in an infiltrating ductal breast carcinoma in a 69-year-old man are reported. The main abnormalities observed were trisomy of chromosomes 8 and 9 and structural rearrangement in the long arm of chromosome 17 (add(17)(q25)). Our results confirm the trisomy...

  8. CAR-T cell therapy in gastrointestinal tumors and hepatic carcinoma: From bench to bedside.

    Science.gov (United States)

    Zhang, Qi; Zhang, Zimu; Peng, Meiyu; Fu, Shuyu; Xue, Zhenyi; Zhang, Rongxin

    2016-01-01

    The chimeric antigen receptor (CAR) is a genetically engineered receptor that combines a scFv domain, which specifically recognizes the tumor-specific antigen, with T cell activation domains. CAR-T cell therapies have demonstrated tremendous efficacy against hematologic malignancies in many clinical trials. Recent studies have extended these efforts to the treatment of solid tumors. However, the outcomes of CAR-T cell therapy for solid tumors are not as remarkable as the outcomes have been for hematologic malignancies. A series of hurdles has arisen with respect to CAR-T cell-based immunotherapy, which needs to be overcome to target solid tumors. The major challenge for CAR-T cell therapy in solid tumors is the selection of the appropriate specific antigen to demarcate the tumor from normal tissue. In this review, we discuss the application of CAR-T cells to gastrointestinal and hepatic carcinomas in preclinical and clinical research. Furthermore, we analyze the usefulness of several specific markers in the study of gastrointestinal tumors and hepatic carcinoma.

  9. Cytogenetic Monitoring of Mammals of Semipalatinsk Test Site

    International Nuclear Information System (INIS)

    Zhapbasov, R.Zh.; Tusupbaev, V.I.; Karimbaeva, K.S.; Seisebaev, A.T.; Nurgalieva, K.G.; Chenal, C.

    1998-01-01

    The cytogenetic monitoring of the natural populations of mammals living under conditions of environment radioactive contamination is the simplest method to study the genetic consequences of nuclear tests. This work presents the preliminary results of the cytogenetic monitoring of the natural populations of rodents (Allactaga maior Kerr., Allactaga saltafor Eversm., Citellus erytrogenus Brandt) and domestic sheep (Ovis aries). The exposure of gonads is considered to be the most hazardous among the consequences of the chronic ionizing exposure since the exposure of gonads can cause not only somatic damages but also hereditary ones transferring to the farther generations, The genetic damage assessment of rodent reproductive cells was performed using the morphological test for abnormal form of the sperm head. It is generally accepted, that spermatogenesis disorders, which result in abnormal spermatozoa, are bound to the genetic disturbances during mitotic and meiotic division stages of male sex cells. The analysis of data obtained shows that the rodent males living on the radioactive contaminated sites (Balapan, Degelen) have the higher numbers of abnormal spermatozoa. So, the Allactaga maior taken from the sites with the gamma background of 250 μr/h showed the frequency of abnormal spermatozoa within 48.27 - 62.73 %. This value for the control animals from the gamma background of 11 - 16 μr/h did not exceed 5.8 %. The most objective and sensitive method for assessment of environmental contamination genetic consequences for the natural populations is to determine the damages of the cell genetic apparatus, e. g. the frequency of the visible changes in chromosome number and structure. The cytogenetic study of animals showed that the significant number of marrow cells of rodents and sheep living on the technical fields of the Test Site are the metaphase cells with polyploid (0.98 - 3.50 %) and aneuploidy (11.03 -19.72 %) chromosomal sets. There were also found the

  10. BRAF mutation testing in solid tumors: a methodological comparison.

    Science.gov (United States)

    Weyant, Grace W; Wisotzkey, Jeffrey D; Benko, Floyd A; Donaldson, Keri J

    2014-09-01

    Solid tumor genotyping has become standard of care for the characterization of proto-oncogene mutational status, which has traditionally been accomplished with Sanger sequencing. However, companion diagnostic assays and comparable laboratory-developed tests are becoming increasingly popular, such as the cobas 4800 BRAF V600 Mutation Test and the INFINITI KRAS-BRAF assay, respectively. This study evaluates and validates the analytical performance of the INFINITI KRAS-BRAF assay and compares concordance of BRAF status with two reference assays, the cobas test and Sanger sequencing. DNA extraction from FFPE tissue specimens was performed followed by multiplex PCR amplification and fluorescent label incorporation using allele-specific primer extension. Hybridization to a microarray, signal detection, and analysis were then performed. The limits of detection were determined by testing dilutions of mutant BRAF alleles within wild-type background DNA, and accuracy was calculated based on these results. The INFINITI KRAS-BRAF assay produced 100% concordance with the cobas test and Sanger sequencing and had sensitivity equivalent to the cobas assay. The INFINITI assay is repeatable with at least 95% accuracy in the detection of mutant and wild-type BRAF alleles. These results confirm that the INFINITI KRAS-BRAF assay is comparable to traditional sequencing and the Food and Drug Administration-approved companion diagnostic assay for the detection of BRAF mutations. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  11. Kinetics of the absorbed dose formation and the effect of chronic β-irradiation on the cytogenetic characteristics and harvest of barley plants

    International Nuclear Information System (INIS)

    Zyablitskaya, E.Ya.; Kal'chenko, V.A.; Aleksakhin, R.M.; Zuev, N.D.

    1984-01-01

    A study was made of the kinetics of the absorbed dose formation, of the cytogenetic effects and the yield of barley plants growing in the experimental fields artificially contaminated with 90 Sr- 90 Y. It was shown that 70% of the dose absorbed during the vegetation period fall on the 1st and the and stages of organogenesis. The dose absorbed was shown to increase the cytogenetic effects. As calculated per 1 Gy the cytogenetic effects had an inverse relation to the dose rate

  12. Molecular cytogenetic of the Amoy croaker, Argyrosomus amoyensis (Teleostei, Sciaenidae)

    Science.gov (United States)

    Liao, Mengxiang; Zheng, Jiao; Wang, Zhiyong; Wang, Yilei; Zhang, Jing; Cai, Mingyi

    2017-08-01

    The family Sciaenidae is remarkable for its species richness and economic importance. However, the cytogenetic data available in this fish group are still limited, especially those obtained using fluorescence in situ hybridization (FISH). In the present study, the chromosome characteristics of a sciaenid species, Argyrosomus amoyensis, were examined with several cytogenetic methods, including dual-FISH with 18S and 5S rDNA probes, and a self-genomic in situ hybridization procedure (Self-GISH). The karyotype of A. amoyensis comprised 2n=48 acrocentric chromosomes. A single pair of nucleolar organizer regions (NORs) was located at the proximal position of chromosome 1, which was positive for silver nitrate impregnation (AgNO3) staining and denaturation-propidium iodide (DPI) staining but negative for Giemsa staining and 4',6-diamidino-2-phenylindole (DAPI) staining, and was confirmed by FISH with 18S rDNA probes. The 5S rDNA sites were located at the centromeric region of chromosome 3. Telomeric FISH signals were detected at all chromosome ends with different intensities, but internal telomeric sequences (ITSs) were not found. Self-GISH resulted in strong signals distributed at the centromeric regions of all chromosomes. C-banding revealed not only centromeric heterochromatin, but also heterochromatin that located on NORs, in interstitial and distal telomeric regions of specific chromosomes. These results suggest that the karyotype of Amoy croaker was relatively conserved and primitive. By comparison with the reported cytogenetic data of other sciaenids, it can be deduced that although the karyotypic macrostructure and chromosomal localization of 18S rDNA are conserved, the distribution of 5S rDNA varies dynamically among sciaenid species. Thus, the 5S rDNA sites may have different evolutionary dynamics in relation to other chromosomal regions, and have the potential to be effective cytotaxonomic markers in Sciaenidae.

  13. Cytogenetic studies of 19 meningiomas and their clinical significance. I

    DEFF Research Database (Denmark)

    Poulsgård, L; Rønne, M; Schrøder, H D

    1989-01-01

    Cytogenetic analysis of 19 meningiomas from 10 female and 9 male patients are reported. Chromosomal abnormalities were found in all cases with a stemline karyotype 45, XY, -22 or 45, XX, -22. Three of these had additional sidelines: (a) 44, XX, -1, -4, -6, -8, -22, +19, +del(1) (:p33----q43), +dup...

  14. Impact of cytogenetic abnormalities in adults with Ph-negative B-cell precursor acute lymphoblastic leukemia.

    Science.gov (United States)

    Lafage-Pochitaloff, Marina; Baranger, Laurence; Hunault, Mathilde; Cuccuini, Wendy; Lefebvre, Christine; Bidet, Audrey; Tigaud, Isabelle; Eclache, Virginie; Delabesse, Eric; Bilhou-Nabéra, Chrystèle; Terré, Christine; Chapiro, Elise; Gachard, Nathalie; Mozziconacci, Marie-Joelle; Ameye, Geneviève; Porter, Sarah; Grardel, Nathalie; Béné, Marie C; Chalandon, Yves; Graux, Carlos; Huguet, Françoise; Lhéritier, Véronique; Ifrah, Norbert; Dombret, Hervé

    2017-10-19

    Multiple cytogenetic subgroups have been described in adult Philadelphia chromosome (Ph)-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), often comprising small numbers of patients. In this study, we aimed to reassess the prognostic value of cytogenetic abnormalities in a large series of 617 adult patients with Ph-negative BCP-ALL (median age, 38 years), treated in the intensified Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/2005 trials. Combined data from karyotype, DNA index, fluorescence in situ hybridization, and polymerase chain reaction screening for relevant abnormalities were centrally reviewed and were informative in 542 cases (88%), allowing classification in 10 exclusive primary cytogenetic subgroups and in secondary subgroups, including complex and monosomal karyotypes. Prognostic analyses focused on cumulative incidence of failure (including primary refractoriness and relapse), event-free survival, and overall survival. Only 2 subgroups, namely t(4;11)/ KMT2A-AFF1 and 14q32/ IGH translocations, displayed a significantly worse outcome in this context, still observed after adjustment for age and after censoring patients who received allogeneic stem cell transplantation (SCT) in first remission at SCT time. A worse outcome was also observed in patients with low hypodiploidy/near triploidy, but this was likely related to their higher age and worse tolerance to therapy. The other cytogenetic abnormalities, including complex and monosomal karyotypes, had no prognostic value in these intensive protocols designed for adult patients up to the age of 60 years. © 2017 by The American Society of Hematology.

  15. Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors.

    Science.gov (United States)

    Smith, Tyrel T; Moffett, Howell F; Stephan, Sirkka B; Opel, Cary F; Dumigan, Amy G; Jiang, Xiuyun; Pillarisetty, Venu G; Pillai, Smitha P S; Wittrup, K Dane; Stephan, Matthias T

    2017-06-01

    Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting. Here, we have tested implantable biopolymer devices that deliver CAR T cells directly to the surfaces of solid tumors, thereby exposing them to high concentrations of immune cells for a substantial time period. In immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we found that CAR T cells can migrate from biopolymer scaffolds and eradicate tumors more effectively than does systemic delivery of the same cells. We have also demonstrated that codelivery of stimulator of IFN genes (STING) agonists stimulates immune responses to eliminate tumor cells that are not recognized by the adoptively transferred lymphocytes. Thus, these devices may improve the effectiveness of CAR T cell therapy in solid tumors and help protect against the emergence of escape variants.

  16. Evaluation of apoptosis and micronucleation induced by reactor neutron beams with two different cadmium ratios in total and quiescent cell populations within solid tumors

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Sakurai, Yoshinori; Takagaki, Masao; Kobayashi, Tooru; Kinashi, Yuko; Suzuki, Minoru

    2001-01-01

    Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to reactor neutron beam irradiation with two different cadmium (Cd) ratios was examined in terms of micronucleus (MN) frequency and apoptosis frequency, using four different tumor cell lines. Methods and Materials: C57BL mice bearing EL4 tumors, C3H/He mice bearing SCC VII or FM3A tumors, and Balb/c mice bearing EMT6/KU tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty min after i.p. injection of sodium borocaptate- 10 B (BSH), or 3 h after oral administration of p-boronophenylalanine- 10 B (BPA), the tumors were irradiated with neutron beams. The tumors without 10 B-compound administration were irradiated with neutron beams or γ-rays. This neutron beam irradiation was performed using neutrons with two different Cd ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the MN frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, for apoptosis assay, 6 h after irradiation, tumor cell suspensions obtained in the same manner were fixed, and the apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequencies in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Results: Without 10 B-compounds, the sensitivity difference between total and Q cells was reduced by neutron beam irradiation. Under our particular neutron beam irradiation condition, relative biological effectiveness (RBE) of neutrons was larger in Q cells than in total cells, and the RBE values were larger for low Cd-ratio than high Cd-ratio neutrons. With 10 B-compounds, both frequencies were increased for each cell population, especially for total cells. BPA

  17. Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors.

    Science.gov (United States)

    Trigos, Anna S; Pearson, Richard B; Papenfuss, Anthony T; Goode, David L

    2017-06-13

    Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers. Genes conserved with unicellular organisms were strongly up-regulated, whereas genes of metazoan origin were primarily inactivated. These patterns were most consistent for processes known to be important in cancer, implicating both selection and active regulation during malignant transformation. The coordinated expression of strongly interacting multicellularity and unicellularity processes was lost in tumors. This separation of unicellular and multicellular functions appeared to be mediated by 12 highly connected genes, marking them as important general drivers of tumorigenesis. Our findings suggest common principles closely tied to the evolutionary history of genes underlie convergent changes at the cellular process level across a range of solid cancers. We propose altered activity of genes at the interfaces between multicellular and unicellular regions of human gene regulatory networks activate primitive transcriptional programs, driving common hallmark features of cancer. Manipulation of cross-talk between biological processes of different evolutionary origins may thus present powerful and broadly applicable treatment strategies for cancer.

  18. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

    OpenAIRE

    Dirix, Luc Y.; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E.; Somer, Robert; Smakal, Martin; Emens, Leisha A.; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja

    2017-01-01

    Purpose Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. Methods In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 week...

  19. Current status, new frontiers and challenges in radiation biodosimetry using cytogenetic, transcriptomic and proteomic technologies

    Energy Technology Data Exchange (ETDEWEB)

    Fenech, Michael, E-mail: michael.fenech@csiro.au [Commonwealth Scientific and Industrial Research Organisation, Gate 13 Kintore Avenue, Adelaide, SA 5000 (Australia)

    2011-09-15

    Biodosimetric methods for determining exposure dose in individuals following a radiation accident are important for the health management of the exposed cohort and prioritisation of high dose exposure cases to receive emergency medical treatment. This brief review provides a succinct outline of (i) the current status of standard cytogenetic methods used in radiation biodosimetry; (ii) development of high-throughput systems for current standard cytogenetic methods; (iii) emerging minimally invasive methods; (iv) the impact of nutrition and genotype on observed dose-response relationships and (v) new frontiers in biodosimetry using molecular biology techniques such as transcriptomics and proteomics.

  20. Molecular and cytogenetic analysis of the giant genomes of Fritillaria lilies

    Czech Academy of Sciences Publication Activity Database

    Ambrožová, K.; Macas, Jiří; Neumann, Pavel; Leitch, I. J.; Lysák, M.

    2009-01-01

    Roč. 17, č. 4 (2009), s. 558-559 ISSN 0967-3849. [International Chromosome Conference (ICC) /17./. 23.6.2009-26.6.2009, Boone] Institutional research plan: CEZ:AV0Z50510513 Keywords : giant genomes of Fritillaria lilies * cytogenetic analysis Subject RIV: EB - Genetics ; Molecular Biology