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  1. Harnessing Dendritic Cells for Tumor Antigen Presentation

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    Nierkens, Stefan [Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, Nijmegen 6525 GA (Netherlands); Janssen, Edith M., E-mail: edith.janssen@cchmc.org [Division of Molecular Immunology, Cincinnati Children' s Hospital Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States)

    2011-04-26

    Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8{sup +} and CD4{sup +} T cells; the in vitro loading of DCs with tumor antigens.

  2.  An Uncommon Presentation of Giant Cell Tumor

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    Gopal Malhotra

    2011-09-01

    Full Text Available  Giant Cell Tumors commonly occur at the ends of long bones. However in rare cases, they can occur in the bones of the hands and feet. Tumors in these locations occur in younger patients; in addition, these tumors are more commonly multifocal and are associated with a higher risk for local recurrence than tumors at the ends of long bones. Since lesions in the small bones may be multifocal, a patient with a giant cell tumor of the small bones should undergo a skeletal survey to exclude similar lesions elsewhere. Primary surgical treatment ranges from curettage or excision with or without bone grafting to amputation. The success of surgical treatment depends on the completeness with which the tumor was removed. We are presenting a case report of a 34 year old female, who presented with a swelling in the right hand, following trauma. X-ray of the hand showed an osteolytic expansile lesion at the base of the 1st metacarpal bone. The lesion was initially curetted and then treated by local resection with bone grafting. Histological examination revealed a typical benign giant cell tumor composed of closely packed stromal cells with a variable admixture of giant cells. Follow up at the end of one year did not reveal any recurrence of the tumor.

  3. Multicentric Giant Cell Tumor of Bone: Synchronous and Metachronous Presentation

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    Reiner Wirbel

    2013-01-01

    Full Text Available A 27-year-old man treated 2.5 years ago for synchronous multicentric giant cell tumor of bone located at the right proximal humerus and the right 5th finger presented now with complaints of pain in his right hip and wrist of two-month duration. Radiology and magnetic resonance revealed multicentric giant cell tumor lesions of the right proximal femur, the left ileum, the right distal radius, and the left distal tibia. The patient has an eighteen-year history of a healed osteosarcoma of the right tibia that was treated with chemotherapy, resection, and allograft reconstruction. A literature review establishes this as the first reported case of a patient with synchronous and metachronous multicentric giant cell tumor who also has a history of osteosarcoma.

  4. Spindle cell hemangioma: Unusual presentation of an uncommon tumor

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    Olalere Omoyosola Gbolahan

    2015-01-01

    Full Text Available Spindle cell hemangioma (SCH is an uncommon tumor that usually presents as subcutaneous or deep dermal nodule affecting the extremities and is typically <2 cm in size. A few cases have been reported in the head and neck region. To the best of the authors' knowledge, there are no previous reports of SCH occurring in the orbit in the English literature. We, therefore, report the case of a large SCH involving the right orbit of a healthy 9-year-old Nigerian girl.

  5. UNUSUAL PRESENTATION OF GIANT CELL TUMOR OF PHALANX

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    Ramkumar Reddy

    2015-06-01

    Full Text Available A 13 year old girl presented with a painful and swollen left middle finger with no overlying skin abnormality. There was no history of past trauma. A radiograph showed a radiolucent lesion, within the middle phalanx, with surrounding cortical thinning. No new bone formation. Histological analysis reported benign cartilaginous lesion. With provisional diagnosis of Enchondroma, curettage and cortico - cancellous grafting was done. Over a 4 month duration, the graft absorbed and increase in swelling and brake in cortex. Suspecting a giant cell tumour of bone, amputation of finger through middle phalanx was done . Histology Specimen confirmed giant cell tumour. The patient had excellent hand function and has had no complications . BACKGROUND: Giant cell tumor commonly occurs in upper middle age group females at epiphyses of long bones. Occurrence in children and that of phalanges is a rare condition. Only 2% of all reported GCTs are found in the hand . [1

  6. Forcing Tumor Cells to Present Their Own Tumor Antigens to the Immune System: a Necessary Design for an Efficient Tumor Immunotherapy

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    RobertE.Humphreys; GildaG.Hillman; EricyonHofe; MinzhenXu

    2004-01-01

    The general principle for tumor cells to escape from immune surveillance is to prevent tumor antigens from being recognized by the immune system. Many methods have been developed to increase the immunogenecity of the tumor cells. The most efficient methods are able to force tumor cells to present their own tumor antigens to the immune system. Stimulating Th cells by converting tumor cells into MHC class II+/Ii- antigen presenting cells is one of the most efficient technologies. Using antisense methods, we suppress the expression of the Ii protein that normally co-expresses with MHC class II molecules and blocks the antigenic peptide binding site of MHC class II molecules during synthesis in the endoplasmic reticulum. In such tumor cells, the"unprotected" MHC class II molecules pick up endogenous tumor antigenic peptides, which have been transported into the ER for binding to MHC class I molecules. Simultaneous presentation of tumor antigens by both MHC class I and II molecules generates a robust and long-lasting anti-tumor immune response. MHC class II+/Ii- tumor cells are potent tumor cell vaccines and also cure a significant number of animals with renal and prostate tumors. We have developed analogous human gene vectors that are suitable for most patients and cancers.

  7. Forcing Tumor Cells to Present Their Own Tumor Antigens to the Immune System: a Necessary Design for an Efficient Tumor Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Robert E.Humphreys; Gilda G.Hillman; Eric von Hofe; Minzhen Xu

    2004-01-01

    The general principle for tumor cells to escape from immune surveillance is to prevent tumor antigens from being recognized by the immune system. Many methods have been developed to increase the immunogenecity of the tumor cells. The most efficient methods are able to force tumor cells to present their own tumor antigens to the immune system. Stimulating Th cells by converting tumor cells into MHC class Ⅱ+/Ii- antigen presenting cells is one of the most efficient technologies. Using antisense methods, we suppress the expression of the Ii protein that normally co-expresses with MHC class Ⅱ molecules and blocks the antigenic peptide binding site of MHC class Ⅱ molecules during synthesis in the endoplasmic reticulum. In such tumor cells, the "unprotected" MHC class Ⅱ molecules pick up endogenous tumor antigenic peptides, which have been transported into the ER for binding to MHC class Ⅰ molecules. Simultaneous presentation of tumor antigens by both MHC class Ⅰ and Ⅱ molecules generates a robust and long-lasting anti-tumor immune response. MHC class Ⅱ+/Ii- tumor cells are potent tumor cell vaccines and also cure a significant number of animals with renal and prostate tumors. We have developed analogous human gene vectors that are suitable for most patients and cancers.

  8. Recurrent acute pancreatitis and persistent hyperamylasemia as a presentation of pancreatic osteoclastic giant cell tumor: an unusual presentation of a rare tumor.

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    Rustagi, Tarun; Rampurwala, Murtuza; Rai, Mridula; Golioto, Michael

    2011-01-01

    Giant cell tumors of the pancreas are rare neoplasms divided into three forms: osteoclastic, pleomorphic, and mixed. We report an unusual case of a 62-year-old male presenting with recurrent acute pancreatitis and found to have a mass in the head of the pancreas on routine imaging. Endoscopic retrograde cholangiopancreatography showed a main pancreatic duct stricture, with brush cytology revealing the diagnosis of osteoclastic giant cell tumor of the pancreas. Whipple's procedure was successfully performed for resection of this tumor. and IAP.

  9. Congenital Cerebellar Mixed Germ Cell Tumor Presenting with Hemorrhage in a Newborn

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    Kim, Sung Mok; Kim, Ji Hye; Yoo, So Young; Park, Won Soon; Jang, Yun Sil; Shin, Hyung Jin; Suh, Yeon Lim [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2008-07-15

    We report here on a neonate with congenital cerebellar mixed germ cell tumor, and this initially presented as cerebellar hemorrhage. Postnatal cranial ultrasonography revealed an echogenic cerebellar mass that exhibited the signal characteristics of hemorrhage rather than tumor on MR images. The short-term follow-up images also suggested a resolving cerebellar hemorrhage. One month later, the neonate developed vomiting. A second set of MR images demonstrated an enlarged mass that exhibited changed signal intensity at the same site, which suggested a neoplasm. Histological examination after the surgical resection revealed a mixed germ cell tumor.

  10. Giant cell tumor of the greater wing of the sphenoid: an unusual presentation.

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    Pelaz, Andrés Coca; Llorente Pendás, José L; Rodrigo Tapia, Juan P; Suárez Nieto, Carlos

    2008-05-01

    We report a very unusual presentation of giant cell tumor probably originated on the greater wing of the sphenoid and show a review about the knowledge and the treatment of the lesion in this rare localization. We treated a 48-year-old man with a giant cell tumor of the infratemporal fossa. He presented with a right-side hearing loss and facial pain. The tumor was resected by means of a subtemporal-preauricular approach, and after 12 months of follow-up, the patient is free of recurrence. Giant cell tumors of the skull base are an extremely rare neoplasm, and there is not much information on the literature about the treatment and the prognostic. Wide resection ought to be made, and at the follow-up, the clinician must try to diagnose not only local recurrence but also the possibility of distant metastases to the lung.

  11. Multiple Primary Merkel Cell Carcinomas Presenting as Pruritic, Painful Lower Leg Tumors

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    Laura Blumenthal

    2015-10-01

    Full Text Available Merkel cell carcinoma (MCC is a rare and highly aggressive neuroendocrine tumor of the skin which almost exclusively presents as a solitary tumor. It is most often seen on sun-exposed regions, historically almost exclusively on the head and neck, with only rare case reports on the extremities. Although recent studies have shown increased incidence with up to 20% on the extremities, here we present one of these rare emerging presentations, with the addition of a unique treatment option. Our patient is an 80-year-old male with a 3-month history of multiple raised, rapidly enlarging tumors on the right ankle. Two separate biopsies were performed and demonstrated sheets and clusters of small blue cells filling the dermis with scant cytoplasm, dusty chromatin, and nuclear molding. Subsequent immunohistochemical stains confirmed the diagnosis of multiple primary MCC. Despite the characteristic immunohistochemical profile of primary MCC, the possibility of a metastatic neuroendocrine carcinoma from an alternate primary site was entertained, given his unusual clinical presentation. A complete clinical workup including CT scans of the chest, abdomen, and pelvis showed no evidence of disease elsewhere. Instead of amputation, the patient opted for nonsurgical treatment with radiation therapy alone, resulting in a rapid and complete response. This case represents an unusual presentation of primary MCC and demonstrates further evidence that radiation as monotherapy is an effective local treatment option for inoperable MCC.

  12. Desmoplastic small round cell tumor: Extra abdominal and abdominal presentations and the results of treatment

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    Biswas G

    2005-01-01

    Full Text Available BACKGROUND: Desmoplastic small round cell tumor (DSRCT is a rare malignant neoplasm of adolescent males. Current multimodality treatment prolongs life and rarely achieves cure. Aim: To review the presenting features, histopathology and outcome of 18 patients with DSRCT treated at a single institution. Setting and Design: This is a retrospective observational study of patients with DSRCT who presented at the Tata Memorial Hospital between January 1994 to January 2005. Materials and Methods: Eighteen patients of DSRCT seen during this period were evaluated for their clinical presentation, response to chemotherapy and other multimodality treatment and overall survival. The cohort of 18 patients included 11 males (61% and 7 females (39% with a mean age of 16 years (Range 1½ - 30 years. Majority (83% presented with abdomino-pelvic disease. The others, involving chest wall and extremities. There were 6 patients (33% with metastatic disease at presentation. Results:The treatment primarily included a multimodality approach using a combination of multiagent chemotherapy with adjuvant surgery and radiotherapy as applicable. A response rate of 39% (CR-1, PR-6, with chemotherapy was observed. The overall response rate after multimodality treatment was 39% (CR-5, PR-2. The overall survival was poor except in patients who had complete excision of the tumor. Conclusion: Abdomino-pelvic site was the commonest presentation, the disease can occur at other non-serosal surfaces also. Despite aggressive treatment the outcome was poor. However, complete surgical excision seems to provide a better survival.

  13. Induction of anti-tumor CD8 T cell responses by experimental ECP-induced human dendritic antigen presenting cells.

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    Kibbi, N; Sobolev, O; Girardi, M; Edelson, R L

    2016-08-01

    Extracorporeal photochemotherapy (ECP), or photopheresis, is distinguished by the specificity of the clinically potent immunologic reactions it initiates or regulates. The selectivity of ECP-induced immunoprotection for the malignant clone in cutaneous T cell lymphoma (CTCL), and for the pathogenic clones in allograft rejection and graft-versus-host disease (GVHD), has suggested a central mechanistic role for dendritic antigen presenting cells (DC). Discovery of ECP's induction of monocyte-derived DC, via monocyte signaling by ECP-plate activated platelets, and the absolute dependency of experimental ECP on such induced DC, supports that premise. Herein, we show that ECP-induced DC are capable of stimulating CD8 T cell responses to tumor antigens with which they are loaded. They internalize an antigen-specific melanoma-associated protein then present it onto a class I major histocompatibility, which then stimulates expansion of anti-tumor CD8 T cell populations. We conclude that ECP-induced DC prominently contribute to its initiation of anti-tumor immunity and raise the possibility that the therapy may be applicable to the immunotherapeutic management of a broader spectrum of cancers.

  14. Circulating Tumor Cells: A Review of Present Methods and the Need to Identify Heterogeneous Phenotypes

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    Millner, Lori M.; Linder, Mark W.; Valdes, Roland

    2016-01-01

    The measurement and characterization of circulating tumor cells (CTCs) hold promise for advancing personalized therapeutics. CTCs are the precursor to metastatic cancer and thus have the potential to radically alter patient treatment and outcome. Currently, clinical information provided by the enumeration of CTCs is limited to predicting clinical outcome. Other areas of interest in advancing the practice of pathology include: using CTCs for early detection of potential metastasis, determining and monitoring the efficacy of individualized treatment regimens, and predicting site-specific metastasis. Important hurdles to overcome in obtaining this type of clinical information involve present limitations in defining, detecting, and isolating CTCs. Currently, CTCs are detected using epithelial markers. The definition of what distinguishes a CTC should be expanded to include CTCs with heterogeneous phenotypes, and markers should be identified to enable a more comprehensive capture. Additionally, most methods available for detecting CTCs do not capture functionally viable CTCs. Retaining functional viability would provide a significant advantage in characterizing CTC-subtypes that may predict the site of metastatic invasion and thus assist in selecting effective treatment regimens. In this review we describe areas of clinical interest followed by a summary of current circulating cell-separation technologies and present limitations. Lastly, we provide insight into what is required to overcome these limitations as they relate to applications in advancing the practice of pathology and laboratory medicine. PMID:23884225

  15. Chaperone-rich tumor cell lysate-mediated activation of antigen-presenting cells resists regulatory T cell suppression.

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    Larmonier, Nicolas; Cantrell, Jessica; Lacasse, Collin; Li, Gang; Janikashvili, Nona; Situ, Elaine; Sepassi, Marjan; Andreansky, Samita; Katsanis, Emmanuel

    2008-04-01

    CD4(+)CD25(+) regulatory T lymphocytes (Tregs) critically contribute to the mechanisms of cancer-induced tolerance. These cells suppress anti-tumoral CD8(+) and CD4(+) T lymphocytes and can also restrain the function of APCs. We have previously documented the immunostimulatory effects of a chaperone-rich cell lysate (CRCL) anti-cancer vaccine. Tumor-derived CRCL induces tumor immunity in vivo, partly by promoting dendritic cell (DC) and macrophage activation. In the current study, we evaluated the effects of CD4(+)CD25(+)forkhead box P3(+) Tregs isolated from mice bearing 12B1 bcr-abl(+) leukemia on DC and macrophages that had been activated by 12B1-derived CRCL. CRCL-activated DC and macrophages resisted Treg suppression, as the production of proinflammatory cytokines, the activation of transcription factor NF-kappaB, and their immunostimulatory potential was unaffected by Tregs. Our results thus highlight CRCL as a powerful adjuvant endowed with the capacity to overcome tumor-induced Treg-inhibitory effects on APCs.

  16. Metaphyseal giant cell tumor

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    Pereira, L.F.; Hemais, P.M.P.G.; Aymore, I.L.; Carmo, M.C.R. do; Cunha, M.E.P.R. da; Resende, C.M.C.

    Three cases of metaphyseal giant cell tumor are presented. A review of the literature is done, demostrating the lesion is rare and that there are few articles about it. Age incidence and characteristics of the tumor are discussed.

  17. IgE/FcεRI-Mediated Antigen Cross-Presentation by Dendritic Cells Enhances Anti-Tumor Immune Responses

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    Barbara Platzer

    2015-03-01

    Full Text Available Epidemiologic studies discovered an inverse association between immunoglobulin E (IgE-mediated allergies and cancer, implying tumor-protective properties of IgE. However, the underlying immunologic mechanisms remain poorly understood. Antigen cross-presentation by dendritic cells (DCs is of key importance for anti-tumor immunity because it induces the generation of cytotoxic CD8+ T lymphocytes (CTLs with specificity for tumor antigens. We demonstrate that DCs use IgE and FcεRI, the high-affinity IgE receptor, for cross-presentation and priming of CTLs in response to free soluble antigen at low doses. Importantly, IgE/FcεRI-mediated cross-presentation is a distinct receptor-mediated pathway because it does not require MyD88 signals or IL-12 induction in DCs. Using passive immunization with tumor antigen-specific IgE and DC-based vaccination experiments, we demonstrate that IgE-mediated cross-presentation significantly improves anti-tumor immunity and induces memory responses in vivo. Our findings suggest a cellular mechanism for the tumor-protective features of IgE and expand the known physiological functions of this immunoglobulin.

  18. Localized giant cell tumors in the spinal column radiologic presentation. Tumor de celulas gigantes localizado en la columna dorsal: presentacion radiologica poco frecuente

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    Fernandez Echeverria, M.A.; Parra Blanco, J.A.; Pagola Serrano, M.A.; Mellado Santos, J.M.; Bueno Lopez, J.; Gonzalez Tutor, A. (Hospital Marques Valdecilla. Santander (Spain))

    1994-01-01

    Given the uncommonness of the location of giant cell tumors (GCT) in the spinal column and the limited number of studies published, we present a case of GCT located in the spinal column, which involved both vertebral bodies and partially destroyed the adjacent rib. (Author)

  19. Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines

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    Cleo Goyvaerts

    2015-01-01

    Full Text Available In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. Since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypes in situ. This review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted and finally question the true meaning of targeting antitumor-based vaccines.

  20. Transfection of B7-1 cDNA empowers antigen presentation of blood malignant cells for activation of anti-tumor T cells

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    克晓燕; 贾丽萍; 王晶; 王德炳

    2003-01-01

    Objective To define roles of B7-1 co-stimulation factor expressed in human malignant cell lines in mediating anti-tumor T cell immune responses. Methods Examining human leucocyte antigen (HLA) and B7 expressions on 8 human blood malignancies cell lines by flow cytometry. Transfecting B7-1 gene to B7-1 negative (B7*!-) Raji and B7*!- Jurkat cell lines by liposome, and comparing the potencies of blood malignant cell lines in the induction of T cell activation by examination of T cell cytokine mRNAs before and after transfection using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results High level of HLA Ⅰ and Ⅱ molecules were expressed in most human blood malignant cell lines examined, and the co-stimulatory factor B7-2 was also highly expressed. In contrast, another member of B7 family: B7-1 was either not expressed or very limitedly expressed in most of these hematopoietic malignant cell lines. Most importantly, transfection of B7-1 gene to B7*!-. Raji and B7*!-. Jurkat cell lines made these cell lines better antigen presenting cells for stimulation of anti-tumor T cell activation, which was demonstrated by up regulation of expression of T cell cytokines IL-2, IL-4 and INF-γ mRNAs after incubation of these tumor cells with T cells for 24 h. Conclusions B7 co-stimulation plays an important role in anti-tumor immunity. Transfection of B7-1 gene to the human hematopoietic malignant cell lines that are deficient in the B7-1 expression empowers their antigen presentation potency for activation of anti-tumor T cells. Our results suggested that repairing the deficiency of B7-1 co-stimulatory pathway in tumor cells might be a novel immunotherapeutic approach for human hematopoietic malignancies.

  1. Dentinogenic ghost cell tumor

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    Singhaniya Shikha

    2009-01-01

    Full Text Available Dentinogenic ghost cell tumor (DGCT is a rare tumorous form of calcifying odontogenic cyst and only a small number of cases have been described. It is a locally invasive neoplasm that is characterized by ameloblastoma-like epithelial islands, ghost cells and dentinoid. The present report describes a case of a 21-year-old male with a tumor in the posterior region of the mandible, showing features of DGCT.

  2. Tumor cell metabolism

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    Romero-Garcia, Susana; Lopez-Gonzalez, Jose Sullivan; B´ez-Viveros, José Luis; Aguilar-Cazares, Dolores

    2011-01-01

    Cancer is a genetic disease that is caused by mutations in oncogenes, tumor suppressor genes and stability genes. The fact that the metabolism of tumor cells is altered has been known for many years. However, the mechanisms and consequences of metabolic reprogramming have just begun to be understood. In this review, an integral view of tumor cell metabolism is presented, showing how metabolic pathways are reprogrammed to satisfy tumor cell proliferation and survival requirements. In tumor cells, glycolysis is strongly enhanced to fulfill the high ATP demands of these cells; glucose carbons are the main building blocks in fatty acid and nucleotide biosynthesis. Glutaminolysis is also increased to satisfy NADPH regeneration, whereas glutamine carbons replenish the Krebs cycle, which produces metabolites that are constantly used for macromolecular biosynthesis. A characteristic feature of the tumor microenvironment is acidosis, which results from the local increase in lactic acid production by tumor cells. This phenomenon is attributed to the carbons from glutamine and glucose, which are also used for lactic acid production. Lactic acidosis also directs the metabolic reprogramming of tumor cells and serves as an additional selective pressure. Finally, we also discuss the role of mitochondria in supporting tumor cell metabolism. PMID:22057267

  3. Tumor Destruction and In Situ Delivery of Antigen Presenting Cells Promote Anti-Neoplastic Immune Responses: Implications for the Immunotherapy of Pancreatic Cancer

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    Manfredi AA

    2004-07-01

    Full Text Available Antigen presenting cells (APCs activate helper and cytotoxic T cells specific for antigens expressed by tissue cells, including neoplastic cells. This event occurs after the antigen transfer from tissue cells to APC, and is referred to as "cross-presentation". The number and the state of activation of APC in the tumor control the outcome of cross-presentation, including the establishment of protective immune responses. Cell death favors cross-presentation. Cancer cells normally die, either spontaneously or as a consequence of targeted therapies. The transfer of tumor antigens from dying tumor cells to APCs in vivo, exploiting the cross-presentation pathway, has the potential of yielding novel immunotherapeutic strategies. Their success will depend on at least two factors: the induction of synchronized cell death in the tumor, and the recruitment of activated dendritic cells in the tumor. Under normal conditions, pancreatic cancer represents a privileged environment; its profound chemoresistance reflects limited apoptosis after chemotherapy. Moreover, it usually contains only a few cells endowed with APC function. Endoscopic ultrasonography offers attractive possibilities of circumventing this privilege, including the delivery of ultrasound, radiofrequency or radiation in order to destroy the tumor and the delivery in situ of autologous APC or appropriate chemotactic signals. In general, loco-regional approaches offer the possibility of using the tumor of each patient as a complex antigen source, thus limiting the risk of tumor escape and reducing the need for extensive ex vivo handling of the neoplasm and of the patient APCs.

  4. Microscopic endometrial perivascular epithelioid cell nodules: a case report with the earliest presentation of a uterine perivascular epithelioid cell tumor

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    Fang Chia-Lang

    2012-09-01

    Full Text Available Abstract Perivascular epithelioid cell (PEC tumors (PEComas are a family of related mesenchymal tumors composed of PECs which co-express melanocytic and smooth muscle markers. Although their distinctive histologic, immunohistochemical, ultrastructural, and genetic features have been clearly demonstrated, their histogenesis and normal counterpart remain largely unknown. Precursor lesions of PEComas have rarely been reported. We herein describe a tuberous sclerosis patient with microscopic PEC nodules in the endometrium of adenomyosis, pelvic endometriosis, an ovarian endometriotic cyst, and the endometrium of the uterine cavity. The nodules showed a mixture of spindle-shaped and epithelioid cells concentrically arranged around small arteries. The cells exhibited uniform nuclei, light eosinophilic cytoplasm, and immunoreactivity with HMB-45 and CD10. Some nodules revealed continuity with a PEComa in the myometrium. These findings support microscopic endometrial PEC nodules possibly being precursor lesions of uterine PEComas. The wide distribution of the nodules in the pelvis may be related to the multicentricity of PEComas in tuberous sclerosis patients. Owing to the immunoreactivity with CD10, microscopic endometrial PEC nodules may be misinterpreted as endothelial stromal cells unless melanocytic markers are stained. To the best of our knowledge, this is a case with the earliest manifestation of PEC lesions occurring in the endometrium. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9658280017862643

  5. Tumors Presenting as Multiple Cranial Nerve Palsies

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    Kishore Kumar

    2017-04-01

    Full Text Available Cranial nerve palsy could be one of the presenting features of underlying benign or malignant tumors of the head and neck. The tumor can involve the cranial nerves by local compression, direct infiltration or by paraneoplastic process. Cranial nerve involvement depends on the anatomical course of the cranial nerve and the site of the tumor. Patients may present with single or multiple cranial nerve palsies. Multiple cranial nerve involvement could be sequential or discrete, unilateral or bilateral, painless or painful. The presentation could be acute, subacute or recurrent. Anatomic localization is the first step in the evaluation of these patients. The lesion could be in the brain stem, meninges, base of skull, extracranial or systemic disease itself. We present 3 cases of underlying neoplasms presenting as cranial nerve palsies: a case of glomus tumor presenting as cochlear, glossopharyngeal, vagus and hypoglossal nerve palsies, clivus tumor presenting as abducens nerve palsy, and diffuse large B-cell lymphoma presenting as oculomotor, trochlear, trigeminal and abducens nerve palsies due to paraneoplastic involvement. History and physical examination, imaging, autoantibodies and biopsy if feasible are useful for the diagnosis. Management outcomes depend on the treatment of the underlying tumor.

  6. Immune control of tumors by antigen presentation improvement.

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    Remedi, María Mónica; Bonacci, Gustavo; Vides, Miguel Angel; Donadio, Ana Carolina

    2003-01-01

    Tumor cells cannot activate T lymphocytes, since they do not usually express major histocompatibility complex (MHC) class II molecules. Thus, tumor antigens can only be presented indirectly to T cells through professional antigen-presenting cells (APC). In our laboratory, we have treated a tumor cell line (Tu1-A) - derived from an induced rat mammary sarcoma - in order to increase the expression of MHC class I and class II molecules. In our tumor model, the transference of these induced cells into normal rats generated a tumor mass that exhibited a lower tumor growth rate and an earlier regression as compared to those observed in rats inoculated with wild-type Tu1-A cells. This earlier tumor regression was associated with the development of an antigen-specific immune response. 85-87% of the rats in both groups rejected the tumor and were alive at day 60 after tumor cell inoculation. However, in rats treated with wild-type cells the rejection was delayed and took place after tumor ulceration. Rats that had rejected tumors were rechallenged with wild-type cells in order to assay the presence of a long-lived antitumor immunity. All the animals were resistant to the second tumor challenge. We conclude that the development of a specific immune response could be achieved by the superexpression of MHC molecules on tumor cells or when tumor ulceration promotes APC to take up necrotic cells and tumor antigens are presented to T lymphocytes.

  7. Tenosynovial giant cell tumor presenting as a parotid gland mass: Expanding the differential diagnosis of giant cell-rich lesions in salivary glands

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    Ling Guo

    2014-01-01

    Full Text Available Tenosynovial giant cell tumors (TGCT are rare benign soft tissue tumors affecting mostly young adults. The most common affected sites include the knee, ankle, elbow, shoulder, and fingers. The temporomandibular joint is occasionally affected. Herein, we report a case of a 31-year-old Caucasian male who presented clinically with a parotid gland mass. The initial clinical and radiological work-up failed to reveal any involvement of the adjacent temporomandibular joint. Fine-needle aspiration revealed a cellular tumor composed of mononuclear and multinucleated giant cells with fibrosis and hemosiderin deposition. This was subsequently found to be a TGCT arising from the temporomandibular joint. Giant cell-rich lesions are uncommon in salivary glands. Herein, we describe the cytomorphology and clinico-radiographic features of this tumor with emphasis on the differential diagnosis of giant cell-rich lesions presenting in salivary glands. Despite its rare occurrence, this entity should be considered when giant cells are prominent in specimens acquired from this location.

  8. Gastrointestinal stromal tumor presenting with prominent calcification

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    Naoki Izawa; Takeshi Sawada; Ryuichi Abiko; Daisuke Kumon; Mami Hirakawa; Mika Kobayashi; Nobuyuki Obinata

    2012-01-01

    We present a rare case of a gastrointestinal stromal tumor (GIST) in the stomach with prominent calcification at presentation.A 61-year-old woman visited our hospital because of epigastric discomfort.A spherical calcified lesion with a diameter of about 30 mm was incidentally shown in the left upper quadrant on an abdominal X-ray.Computed tomography demonstrated that the tumor was growing from the upper gastric body,with calcification in the peripheral ring area.A laparoscopic partial gastrectomy was performed,and the resected specimen revealed a well-circumscribed tumor with exophytic growth from the gastric muscularis propria.Microscopic examination revealed spindleshaped tumor cells with calcification and hemorrhage.Additionally,positive immunoreactivity of the tumor to KIT and CD34 and a low mitotic index resulted in the diagnosis of very low risk GIST.There are a few case reports of heavily calcified GIST,although solitary or punctate calcification of primary GIST has been reported in several case series.Dystrophic calcification of necrotic or degenerative tissue is the supposed cause of primary calcified GISTs.In contrast,appearance of calcification after administration of imatinib mesylate,which may be one indicator of disease response,is possibly caused by a different mechanism.

  9. CLEC12A-Mediated Antigen Uptake and Cross-Presentation by Human Dendritic Cell Subsets Efficiently Boost Tumor-Reactive T Cell Responses.

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    Hutten, Tim J A; Thordardottir, Soley; Fredrix, Hanny; Janssen, Lisanne; Woestenenk, Rob; Tel, Jurjen; Joosten, Ben; Cambi, Alessandra; Heemskerk, Mirjam H M; Franssen, Gerben M; Boerman, Otto C; Bakker, Lex B H; Jansen, Joop H; Schaap, Nicolaas; Dolstra, Harry; Hobo, Willemijn

    2016-10-01

    Potent immunotherapies are urgently needed to boost antitumor immunity and control disease in cancer patients. As dendritic cells (DCs) are the most powerful APCs, they are an attractive means to reinvigorate T cell responses. An appealing strategy to use the effective Ag processing and presentation machinery, T cell stimulation and cross-talk capacity of natural DC subsets is in vivo tumor Ag delivery. In this context, endocytic C-type lectin receptors are attractive targeting molecules. In this study, we investigated whether CLEC12A efficiently delivers tumor Ags into human DC subsets, facilitating effective induction of CD4(+) and CD8(+) T cell responses. We confirmed that CLEC12A is selectively expressed by myeloid cells, including the myeloid DC subset (mDCs) and the plasmacytoid DC subset (pDCs). Moreover, we demonstrated that these DC subsets efficiently internalize CLEC12A, whereupon it quickly translocates to the early endosomes and subsequently routes to the lysosomes. Notably, CLEC12A Ab targeting did not negatively affect DC maturation or function. Furthermore, CLEC12A-mediated delivery of keyhole limpet hemocyanin resulted in enhanced proliferation and cytokine secretion by keyhole limpet hemocyanin-experienced CD4(+) T cells. Most importantly, CLEC12A-targeted delivery of HA-1 long peptide resulted in efficient Ag cross-presentation by mDCs and pDCs, leading to strong ex vivo activation of HA-1-specific CD8(+) T cells of patients after allogeneic stem cell transplantation. Collectively, these data indicate that CLEC12A is an effective new candidate with great potential for in vivo Ag delivery into mDCs and pDCs, thereby using the specialized functions and cross-talk capacity of these DC subsets to boost tumor-reactive T cell immunity in cancer patients.

  10. A novel HLA-B18 restricted CD8+ T cell epitope is efficiently cross-presented by dendritic cells from soluble tumor antigen.

    Directory of Open Access Journals (Sweden)

    Rona Y Zhao

    Full Text Available NY-ESO-1 has been a major target of many immunotherapy trials because it is expressed by various cancers and is highly immunogenic. In this study, we have identified a novel HLA-B*1801-restricted CD8(+ T cell epitope, NY-ESO-1(88-96 (LEFYLAMPF and compared its direct- and cross-presentation to that of the reported NY-ESO-1(157-165 epitope restricted to HLA-A*0201. Although both epitopes were readily cross-presented by DCs exposed to various forms of full-length NY-ESO-1 antigen, remarkably NY-ESO-1(88-96 is much more efficiently cross-presented from the soluble form, than NY-ESO-1(157-165. On the other hand, NY-ESO-1(157-165 is efficiently presented by NY-ESO-1-expressing tumor cells and its presentation was not enhanced by IFN-γ treatment, which induced immunoproteasome as demonstrated by Western blots and functionally a decreased presentation of Melan A(26-35; whereas NY-ESO-1(88-96 was very inefficiently presented by the same tumor cell lines, except for one that expressed high level of immunoproteasome. It was only presented when the tumor cells were first IFN-γ treated, followed by infection with recombinant vaccinia virus encoding NY-ESO-1, which dramatically increased NY-ESO-1 expression. These data indicate that the presentation of NY-ESO-1(88-96 is immunoproteasome dependent. Furthermore, a survey was conducted on multiple samples collected from HLA-B18(+ melanoma patients. Surprisingly, all the detectable responses to NY-ESO-1(88-96 from patients, including those who received NY-ESO-1 ISCOMATRIX™ vaccine were induced spontaneously. Taken together, these results imply that some epitopes can be inefficiently presented by tumor cells although the corresponding CD8(+ T cell responses are efficiently primed in vivo by DCs cross-presenting these epitopes. The potential implications for cancer vaccine strategies are further discussed.

  11. [Glomic tumor: presentation of an infrequent case].

    Science.gov (United States)

    Sousa, Vítor; Carvalho, Lina

    2006-01-01

    Glomic tumours are perivascular tumours whose cells resemble modified smooth muscular cells of the glomic body. They are more frequent in the subungueal region and rare in the lung. The authors present a case of a 62 year old women with left thoracic pain and great enforces dyspnoea. She presented a solitary nodule in the external basal segment of the LLL, 1.9 cm diameter, circumscribed, firm and with nodular whitish rose cut surface. Glomic tumours are generally benign. They may origin in ectopic glomic cells or be differentiated from non glomic cells. They should be classified as glomic tumor, glomangioma and glomangiomioma according to the relative abundance of glomic cells and of the vascular and muscular components. Pulmonary metastasis of malignant glomic tumours have been described. In these cases an extra pulmonary primary origin must be excluded. The differential diagnosis of glomic tumours of the lung includes the carcinoid, hemangioperycitoma, smooth muscle tumours (epithelioid leyomioma) and the paraganglioma.

  12. Ghost Cell Tumors.

    Science.gov (United States)

    Sheikh, Jason; Cohen, Molly D; Ramer, Naomi; Payami, Ali

    2017-04-01

    Ghost cell tumors are a family of lesions that range in presentation from cyst to solid neoplasm and in behavior from benign to locally aggressive or metastatic. All are characterized by the presence of ameloblastic epithelium, ghost cells, and calcifications. This report presents the cases of a 14-year-old girl with a calcifying cystic odontogenic tumor (CCOT) and a 65-year-old woman with a peripheral dentinogenic ghost cell tumor (DGCT) with dysplastic changes, a rare locally invasive tumor of odontogenic epithelium. The first patient presented with a 1-year history of slowly progressing pain and swelling at the left body of the mandible. Initial panoramic radiograph displayed a mixed radiolucent and radiopaque lesion. An incisional biopsy yielded a diagnosis of CCOT. Decompression of the mass was completed; after 3 months, it was enucleated and immediately grafted with bone harvested from the anterior iliac crest. The second patient presented with a 3-month history of slowly progressing pain and swelling at the left body of the mandible. Initial panoramic radiograph depicted a mixed radiolucent and radiopaque lesion with saucerization of the buccal mandibular cortex. An incisional biopsy examination suggested a diagnosis of DGCT because of the presence of ghost cells, dentinoid, and islands of ameloblastic epithelium. Excision of the mass with peripheral ostectomy was completed. At 6 and 12 months of follow-up, no evidence of recurrence was noted.

  13. An intramedullary tumor presenting with hyperhidrosis

    Directory of Open Access Journals (Sweden)

    Chatterjee Sandip

    2004-07-01

    Full Text Available A case of a cervical intramedullary tumor is reported whose presentation was with disabling hyperhidrosis. The symptom resolved after surgical debulking of the tumor. Hyperhidrosis as a presenting manifestation of an intramedullary tumor has not been reported earlier.

  14. Acute spontaneous tumor lysis in anaplastic large T-cell lymphoma presenting with hyperuricemic acute renal failure.

    Science.gov (United States)

    Hsu, Hsiang-Hao; Huang, Chiu-Ching

    2004-01-01

    Acute spontaneous tumor lysis (ASTL) syndrome, an extremely rare disease, requires prompt recognition and aggressive management because it is fulminant at its outset, associated with severe metabolic derangement, and potentially reversible. We describe an unusual case in which spontaneous tumor lysis occurred in anaplastic large T-cell lymphoma associated with acute uric acid nephropathy, persistent oliguria, and shock. This case contrasts markedly with previously reported cases of ASTL syndrome, which developed mainly in the pathologic type of Burkitt lymphoma. To our knowledge, this is the first reported occurrence of ASTL syndrome associated with anaplastic large T-cell type lymphoma. This report also chronicles our successful experience with continuous renal replacement therapy in the presence of compromised hemodynamic status.

  15. Glomus Tumor Presenting as Raynaud's Phenomenon

    Directory of Open Access Journals (Sweden)

    M. H. Abdelrahman

    2012-01-01

    Full Text Available Glomus tumors are rare tumors that often include hands and feet; they present characteristically with paroxysmal pain, exquisite point tenderness, and cold sensitivity. Such diagnosis needs to be confirmed by imaging like ultrasound and magnetic resonance imaging (MRI. Surgical excision is the treatment of choice for glomus tumors. There are only few case reports of glomus tumors in association with Raynaud’s phenomenon; this is considered to be the 4th case.

  16. Renaissance in tumor immunotherapy: possible combination with phototherapy (Conference Presentation)

    Science.gov (United States)

    Hamblin, Michael R.

    2016-03-01

    Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce highly toxic reactive oxygen species that destroy tumors. The ideal cancer treatment should target both the primary tumor and the metastases with minimal toxicity. This is best accomplished by educating the body's immune system to recognize the tumor as foreign so that after the primary tumor is destroyed, distant metastases will also be eradicated. PDT may accomplish this feat and stimulate long-term, specific anti-tumor immunity. PDT causes an acute inflammatory response, the rapid induction of large amounts of necrotic and apoptotic tumor cells, induction of damage-associated molecular patterns (DAMPS) including heat-shock proteins, stimulates tumor antigen presentation to naïve T-cells, and generation of cytotoxic T-cells that can destroy distant tumor metastases. By using various syngeneic mouse tumors in immunocompetent mice, we have studied specific PDT regimens related to tumor type as well as mouse genotype and phenotype. We have investigated the role of tumor-associated antigens in PDT-induced immune response by choosing mouse tumors that express: model defined antigen, naturally-occurring cancer testis antigen, and oncogenic virus-derived antigen. We studied the synergistic combination of low-dose cyclophosphamide and PDT that unmasks the PDT-induced immune response by depleting the immunosuppressive T-regulatory cells. PDT combined with immunostimulants (toll-like receptor ligands) can synergistically maximize the generation of anti-tumor immunity by activating dendritic cells and switching immunosuppressive macrophages to a tumor rejection phenotype. Tumors expressing defined tumor-associated antigens with known MHC class I peptides allows anti-tumor immunity to be quantitatively compared.

  17. Extraovarian granulosa cell tumor

    Directory of Open Access Journals (Sweden)

    Paul Prabir

    2009-04-01

    Full Text Available Extraovarian granulosa cell tumor (GCT is a very uncommon tumor, assumed to arise from the ectopic gonadal tissue along the embryonal route of the genital ridge. One such rare case of extraovarian GCT was encountered in a 58-year-old female who presented with a large intraabdominal lump. Computerized tomography revealed one large retroperitoneal mass measuring 15cm x 16cm and another mesenteric mass of 8cm x 5cm size. The patient had a history of hysterectomy with bilateral salpingooophorectomy 20 years ago for uterine leiomyoma. Ultrasonography-guided aspiration smears revealed cytological features suggestive of GCT. Histopathological examination of the excised masses showed features of adult-type GCT. Because metastatic epithelial tumors, particularly from the ovaries, may show identical morphology, immunostains for inhibin and epithelial membrane antigen (EMA were performed. The tumor showed positivity for inhibin while EMA was negative thus confirming the diagnosis of GCT. As this patient had no previous history of GCT and was oophorectomized 20 years ago, the tumor was considered as extraovarian. A diagnosis of extraovarian GCT should be carried out after excluding any previous history of GCT of the ovary. Immunostains help to differentiate GCTs from other neoplasms.

  18. Microvesicle Cargo of Tumor-Associated MUC1 to Dendritic Cells Allows Cross-presentation and Specific Carbohydrate Processing

    DEFF Research Database (Denmark)

    Rughetti, Aurelia; Rahimi, Hassan; Belleudi, Francesca;

    2014-01-01

    Tumor-associated glycoproteins are a group of antigens with high immunogenic interest: The glycoforms generated by the aberrant glycosylation are tumor-specific and the novel glycoepitopes exposed can be targets of tumor-specific immune responses. The MUC1 antigen is one of the most relevant tumo...

  19. Olfactory ensheathing cell tumor

    Directory of Open Access Journals (Sweden)

    Ippili Kaushal

    2009-01-01

    Full Text Available Olfactory ensheathing cells (OECs are found in the olfactory bulb and olfactory nasal mucosa. They resemble Schwann cells on light and electron microscopy, however, immunohistochemical staining can distinguish between the two. There are less than 30 cases of olfactory groove schwannomas reported in the literature while there is only one reported case of OEC tumor. We report an OEC tumor in a 42-year-old male and discuss the pathology and origin of this rare tumor.

  20. Induction of antigen-presenting capacity in tumor cells upon infection with non-replicating recombinant vaccinia virus encoding murine MHC class II and costimulatory molecules.

    Science.gov (United States)

    Marti, W R; Oertli, D; Meko, J B; Norton, J A; Tsung, K

    1997-01-15

    The possibility of inducing antigen-presenting capacity in cells normally lacking such capacity, currently represents a major goal in vaccine research. To address this issue we attempted to generate 'artificial' APC able to stimulate CD4+ T cell responses when tumor cells were infected with a single, recombinant, vaccinia virus (rVV) containing the two genes encoding murine MHC class II I-Ak and a third gene encoding the murine B7-1 (mB7-1) costimulatory molecule. To minimize the cytopathic effect and to improve safety, in view of possible in vivo applications, we made this rVV replication incompetent by Psoralen and long wave UV treatment. Tumor cells infected with rVV encoding I-Ak alone, pulsed with hen egg white lysozyme peptide (HEL46-61), induced IL-2 secretion by an antigen-specific T hybridoma. Tumor cells infected with the rVV encoding mB7-1 provided costimulation for activating resting CD4+ T cells in the presence of ConA. Tumor cells infected with the rVV encoding I-Ak and mB7-1, and pulsed with chicken ovotransferrin peptide (conalbumin133-145), induced a significantly higher response in a specific Th2 cell clone (D10.G4.1) as compared to cells infected with rVV encoding I-Ak molecules only. Thus, this replication incompetent rVV represents a safe, multiple gene, vector system able to confer in one single infection step effective APC capacity to non-professional APCs.

  1. Infantile pericardial round cell tumor

    Directory of Open Access Journals (Sweden)

    K H Sridevi

    2015-01-01

    Full Text Available Cardiac malignancies presenting in infancy are rare. Desmoplastic small round cell tumor (DSRCT is a rare occurrence in this age group. No case of intrapericardial DSRCT has been reported in the literature in infants.

  2. [Femoral osteolytic lesions with soft tissue tumors and hypercalcemia as presentation form of a B-cell lymphoma].

    Science.gov (United States)

    Hernández Hernández, J L; Olmos Martínez, J M; Figols Ladrón de Guevara, J; Riancho Moral, J A; González Macías, J

    2000-05-01

    Hypercalcemia associated with haematological neoplasms account for 15 to 20% of hipercalcemia in malignancy, and occurs usually in patients with multiple myeloma. However, its incidence in patients with linfoma is low, and it is observed usually in T-cell linfomas. Bone affectation is also uncommon in patients with non-Hodgkin linfoma. It usually is seen as a late manifestation of the disease, and its occurrence as the form of presentation is exceptional. We hereby report a patient with a B-cell non-Hodgkin linfoma presenting with hypercalcemia and femoral osteolytic lesions.

  3. ONCOLYTIC VIRUS-MEDIATED REVERSAL OF IMPAIRED TUMOR ANTIGEN PRESENTATION

    Directory of Open Access Journals (Sweden)

    Shashi Ashok Gujar

    2014-04-01

    Full Text Available Anti-tumor immunity can eliminate existing cancer cells and also maintain a constant surveillance against possible relapse. Such an antigen-specific adaptive response begins when tumor-specific T cells become activated. T cell activation requires two signals on antigen presenting cells (APCs: antigen presentation through MHC molecules and co-stimulation. In the absence of one or both of these signals, T cells remain inactivated or can even become tolerized. Cancer cells and their associated microenvironment strategically hinder the processing and presentation of tumor antigens and consequently prevent the development of anti-tumor immunity. Many studies, however, demonstrate that interventions that overturn tumor-associated immune evasion mechanisms can establish anti-tumor immune responses of therapeutic potential. One such intervention is oncolytic virus (OV-based anti-cancer therapy. Here we discuss how OV-induced immunological events override tumor-associated antigen presentation impairment and promote appropriate T cell:APC interaction. Detailed understanding of this phenomenon is pivotal for devising the strategies that will enhance the efficacy of OV-based anti-cancer therapy by complementing its inherent oncolytic

  4. Merkel cell tumor.

    Science.gov (United States)

    Kitazawa, M; Watanabe, H; Kobayashi, H; Ohnishi, Y; Shitara, A; Nitto, H

    1987-06-01

    A Merkel cell tumor appeared on the left cheek of an 83-year-old female was reported. The tumor was located mainly in the dermis and infiltrated to the subcutaneous adipose tissue with an involvement of the blood vessels and lymphatics at the periphery. Electron-microscopically, few of the dense-cored granules and the single globular aggregates of intermediate filaments at the nuclear indentations were observed. Electron-microscopic uranaffin reaction proved positive reaction on the dense-cored granules. Half of the cytoplasmic border was smooth, while the rest had short projections. Desmosomes or junctional complexes were not detected among the tumor cells. Immunohistochemically, the cytoplasm of tumor cell showed positive reaction to both neuron-specific enolase (NSE) and keratin. The single globular positive spots of the latter were localized in accordance with the aggregates of intermediate filaments. These findings suggested a neurogenic origin with double differentiation, epithelial and neuroendocrine, of the Merkel cell tumor.

  5. Sertoli-Leydig cell tumor

    Science.gov (United States)

    Sertoli-stromal cell tumor; Arrhenoblastoma; Androblastoma; Ovarian cancer - Sertoli-Leydig cell tumor ... The Sertoli cells are normally located in the male reproductive glands (the testes). They feed sperm cells. The Leydig cells, also ...

  6. Mouse Leydig Tumor Cells

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    Bo-Syong Pan

    2011-01-01

    Full Text Available Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS. We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR subtype agonists were further used to treat MA-10 cells, showing that A1, A 2A , A 2B , and A3, AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

  7. Krukenberg tumor in a young woman: A rare presentation

    Directory of Open Access Journals (Sweden)

    Deepa Hatwal

    2014-01-01

    Full Text Available Krukenberg tumors mostly occur after 40 years. Metastatic ovarian tumors in young age are very rare and reported to be 2% of all the cases. Thirty percent of all ovarian neoplasms occurring during childhood and adolescence are malignant. A 25-year-old woman, parity- 2, presented with abdominal distension, pain in abdomen and amenorrhea. On examination, 18 weeks lump was palpable, firm to hard in consistency, non-tender and mobile. On ultrasonography bilateral ovarian tumors were reported, without any peritoneal free fluid. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Microscopic examination revealed signet ring cells with glandular differentiation, diffusely invading the ovarian parenchyma. Tumor cells exhibited strong, diffuse immunopositivity for CEA with focal strong immunopositivity for CK7 and CK20 and immunonegativity for SATB2. Diagnosis of Krukenberg tumor was made. Endoscopic biopsy confirmed the diagnosis of adenocarcinoma stomach. This case is reported because of its rarity in younger age group.

  8. Nonislet Cell Tumor Hypoglycemia

    Directory of Open Access Journals (Sweden)

    Johnson Thomas

    2013-01-01

    Full Text Available Nonislet cell tumor hypoglycemia (NICTH is a rare cause of hypoglycemia. It is characterized by increased glucose utilization by tissues mediated by a tumor resulting in hypoglycemia. NICTH is usually seen in large mesenchymal tumors including tumors involving the GI tract. Here we will discuss a case, its pathophysiology, and recent advances in the management of NICTH. Our patient was diagnosed with poorly differentiated squamous cell carcinoma of esophagus. He continued to be hypoglycemic even after starting continuous tube feeds and D5W. General workup for hypoglycemia was negative and insulin-like growth factor II (IGF II was in the normal range. Hypoglycemia secondary to “big” IGF II was considered, and patient was started on steroids. His hypoglycemia resolved within a day of treatment with steroids. Initially patient had hypoglycemia unawareness, which he regained after maintaining euglycemia for 48 hours.

  9. Extraosseous Ewing′s tumor of larynx: A rare presentation

    Directory of Open Access Journals (Sweden)

    Vinod Shinde

    2015-01-01

    Full Text Available Primitive neuroectodermal tumors (PNETs are a group of highly malignant tumors composed of small round cells of neuroectodermal origin that affect soft tissue and bone. PNET of the larynx is extremely rare. We report a case of a 41-year-old male who presented with the complaints of progressively increasing stridor of 3 months duration, which was diagnosed as a case of neuroectodermal tumor in the subglottis. Patient was subjected to microlaryngeal surgery and the tumor was excised. Postoperatively, patient was given three cycles of chemotherapy comprising of ifosfamide, etoposide, and mesna, along with granulocyte colony stimulating factor, with 21 days interval. After chemotherapy repeat computed tomography scan showed no evidence of the tumor and no lymphadenopathy. Patient is symptom free for 18 months following completion of treatment. He is under regular follow-up and is undergoing monthly serial endoscopic evaluation.

  10. An unusual presentation of "silent" disseminated pancreatic neuroendocrine tumor

    Institute of Scientific and Technical Information of China (English)

    Dragomir Marisavljevic; Natasa Petrovic; Nikola Milinic; Vesna Cemerikic; Miodrag Krstic; Olivera Markovic; Dragoljub Bilanovic

    2004-01-01

    To present a patient diagnosed with pancreatic carcinoid that was extremely rare and produced an atypical carcinoid syndrome.We reported a 58-year old male patient who presented with long standing,prominent cervical lymphadenopathy and occasional watery diarrhea.Pathohistological and immunohistochemical examination of lymph node biopsy showed a metastatic neuroendocrine tumor,which was histological type A of carcinoid (EMA+,cytokeratin+,CEA-,NSE+,chromogranin A+,synaptophysin+,insulin-).Bone marrow biopsy showed identical findings.Primary site of the tumor was pancreas and diagnosis was made according to cytological and immunocytochemical analysis of the tumor cells obtained with aspiration biopsy of pancreatic mass (12 mm in diameter) under endoscopic ultrasound guidance.However,serotonin levels in blood and urine samples were normal.It is difficulty to establish the precise diagnosis of a "functionally inactive" pancreatic carcinoid and aspiration biopsy of pancreatic tumor under endoscopic ultrasound guidance can be used as a new potent diagnostic tool.

  11. [Parathyroid cyst presenting as a mediastinal tumor].

    Science.gov (United States)

    Shishido, M; Nagao, M

    1996-08-01

    Mediastinal parathyroid cysts are very rare. Since the first report by DeQuervain, 19 cases have been reported. We encountered a case of mediastinal parathyroid cyst presenting as displacement of the trachea. The cyst originated in the lower portion of the left lobe of the thyroid gland and extended to the mediastinum, displacing the trachea and the esophagus. The monolocular mass was a thin walled cyst, and mognetic imaging indicated that it contained watery fluid. The left lobe of the thyroid gland was found to be displaced upward by the tumor, on thyroid scintigram done with technetium-99, which suggested that the cyst originated in the parathyroid gland.

  12. During twenty years of Cisplatin-based therapy the face of nonseminomatous testicular germ cell tumors is still changing: an evaluation of presentation, management, predictive factors and survival

    Directory of Open Access Journals (Sweden)

    Julia Heinzelbecker

    2013-01-01

    Full Text Available Purpose: To assess the changing presentation and treatment of nonseminomatous testicular germ cell tumors (NSGCT and to investigate predictive factors for the status of metastasis at diagnosis and on relapse and death. Materials and Methods: Retrospective record review of 147 patients that underwent inguinal orchiectomy from 1987-2007. Follow-up data was available for 102 patients (median follow-up: 80 months (0-243; 96 patients alive. Results: Mean patients age increased (p = 0.015 and more patients were diagnosed in clinical stage I (CSI (p = 0.040. The fraction of yolk sac (YS elements inclined (p = 0.030 and pT2 tumors increased (p I showed a declined CSS compared to CSI patients (p = 0.055. The presence of YS elements was associated to an improved RFS (p = 0.038. Conclusions: In our single institution study the face of NSGCT markedly changed over 20 years even after the introduction of Cisplatin-based chemotherapy. These changes were accompanied by an improvement in RFS and CSS. When dealing with NSGCT patients such observations now and in the future should be taken into account.

  13. Pericytes limit tumor cell metastasis

    DEFF Research Database (Denmark)

    Xian, Xiaojie; Håkansson, Joakim; Ståhlberg, Anders

    2006-01-01

    Previously we observed that neural cell adhesion molecule (NCAM) deficiency in beta tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient beta cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions...... and deficient perivascular deposition of ECM components. Conversely, tumor cell expression of NCAM in a fibrosarcoma model (T241) improved pericyte recruitment and increased perivascular deposition of ECM molecules. Together, these findings suggest that NCAM may limit tumor cell metastasis by stabilizing...... the microvessel wall. To directly address whether pericyte dysfunction increases the metastatic potential of solid tumors, we studied beta cell tumorigenesis in primary pericyte-deficient Pdgfb(ret/ret) mice. This resulted in beta tumor cell metastases in distant organs and local lymph nodes, demonstrating a role...

  14. Supratentorial cortical ependymoma: An unusual presentation of a rare tumor

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Mohaghegh

    2015-01-01

    Full Text Available Ependymomas are glial tumors derived from ependymal cells lining the ventricles and the central canal of the spinal cord. Two thirds of ependymomas arise in the infratentorial or intraventricles, whereas one-third are located in supratentorial space. But supratentorial "cortical" ependymomas are very rare. We report a case of a cortical ependymoma in a 17-year-old boy. The patient presented with transient recurrent right weakness and diplopia. This tumor was located in the left parieto-occipital region and he had gross total excision. Microscopy and immunohistochemistry showed grade III differentiation ependymoma.

  15. Supratentorial cortical ependymoma: An unusual presentation of a rare tumor.

    Science.gov (United States)

    Mohaghegh, Mohammad Reza; Chitsaz, Ahmad; Okhovat, Ali Asghar; Pour, Elnaz Babaei

    2015-01-01

    Ependymomas are glial tumors derived from ependymal cells lining the ventricles and the central canal of the spinal cord. Two thirds of ependymomas arise in the infratentorial or intraventricles, whereas one-third are located in supratentorial space. But supratentorial "cortical" ependymomas are very rare. We report a case of a cortical ependymoma in a 17-year-old boy. The patient presented with transient recurrent right weakness and diplopia. This tumor was located in the left parieto-occipital region and he had gross total excision. Microscopy and immunohistochemistry showed grade III differentiation ependymoma.

  16. Peripheral dentinogenic ghost cell tumor

    Directory of Open Access Journals (Sweden)

    Sushant S Kamat

    2013-01-01

    Full Text Available Dentinogenic ghost cell tumors (DGCT are uncommon lesions mainly with rare peripheral types. This report presents a case of peripheral DGCT on the left side of the mandibular alveolar ridge of a heavy smoker, a 68-year-old man, with main presenting feature as a mild pain. Submandibular lymphadenopathy and radiological "saucerization" were evident. Differential diagnosis included fibroma, neurofibroma, peripheral ameloblastoma, peripheral odontogenic fibroma, and peripheral giant cell granuloma. Histologically, ameloblastoma-like epithelial elements were seen in association with grouped ghost cells. Proliferating polyhedral cells and stellate reticulum-like cells with various densities were spread over a wide range of the field. The lesion was curetted and after 2 years of follow up, it did not recur.

  17. SYNOVIAL GIANT CELL TUMOR OF THE KNEE.

    Science.gov (United States)

    Abdalla, Rene Jorge; Cohen, Moisés; Nóbrega, Jezimar; Forgas, Andrea

    2009-01-01

    Synovial giant cell tumor is a benign neoplasm, rarely reported in the form of malignant metastasis. Synovial giant cell tumor most frequently occurs on the hand, and, most uncommon, on the ankle and knee. In the present study, the authors describe a rare case of synovial giant cell tumor on the knee as well as the treatment approach. Arthroscopy has been shown, in this case, to be the optimal method for treating this kind of lesion, once it allowed a less aggressive approach, while providing good visualization of all compartments of knee joint and full tumor resection.

  18. Whole tumor antigen vaccination using dendritic cells: Comparison of RNA electroporation and pulsing with UV-irradiated tumor cells

    Directory of Open Access Journals (Sweden)

    Benencia Fabian

    2008-04-01

    Full Text Available Abstract Because of the lack of full characterization of tumor associated antigens for solid tumors, whole antigen use is a convenient approach to tumor vaccination. Tumor RNA and apoptotic tumor cells have been used as a source of whole tumor antigen to prepare dendritic cell (DC based tumor vaccines, but their efficacy has not been directly compared. Here we compare directly RNA electroporation and pulsing of DCs with whole tumor cells killed by ultraviolet (UV B radiation using a convenient tumor model expressing human papilloma virus (HPV E6 and E7 oncogenes. Although both approaches led to DCs presenting tumor antigen, electroporation with tumor cell total RNA induced a significantly higher frequency of tumor-reactive IFN-gamma secreting T cells, and E7-specific CD8+ lymphocytes compared to pulsing with UV-irradiated tumor cells. DCs electroporated with tumor cell RNA induced a larger tumor infiltration by T cells and produced a significantly stronger delay in tumor growth compared to DCs pulsed with UV-irradiated tumor cells. We conclude that electroporation with whole tumor cell RNA and pulsing with UV-irradiated tumor cells are both effective in eliciting antitumor immune response, but RNA electroporation results in more potent tumor vaccination under the examined experimental conditions.

  19. Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

    Directory of Open Access Journals (Sweden)

    Tozeren Aydin

    2006-11-01

    phosphorylation. Signaling pathways involved in adhesion and communication of cultured cancer cells were downregulated. The three way pathways comparison presented in this study brings light into the differences in the use of cellular pathways by tumor cells and cancer cell lines.

  20. Giant cell tumor in adipose package Hoffa

    Science.gov (United States)

    Etcheto, H. Rivarola; Escobar, G.; Blanchod, C. Collazo; Palanconi, M.; Zordan, J.; Salinas, E. Alvarez; Autorino₁, Carlos

    2017-01-01

    Tumors of adipose Hoffa package are very uncommon, with isolated cases reported in the literature. His presentation in pediatric patients knee is exceptional. The most frequently described tumors are benign including vellonodular synovitis. The extra-articular localized variant there of is known as giant cell tumor of the tendon sheath. It is characterized by locally aggressive nature, and has been described in reports of isolated cases. Objective: A case of giant cell tumor of the tendon sheath in adipose presentation package Hoffa in pediatric patients is presented in this paper. Methods: male patient eleven years with right knee pain after sports practice was evaluated. Physical examination, showed limited extension -30º, joint effusion, stable negative Lachman maneuver without peripheral knee laxity. MRI hyperintense on tumor is observed in T2 and hypointense on T1 homogeneous and defined edges content displayed prior to LCA related to adipose Hoffa package. Results: The tumor specimen was obtained and histopathology is defined as densely cellular tissue accumulation of xantomisados fibrocollagenous with histiocytes and multinucleated giant cells, compatible with giant cell tumor of tendon sheath. Conclusion: The presentation of giant cell tumors of the tendon sheath in Hoffa fat pad is exceptional. However, his suspicion allows adequate preoperative surgical planning, as a whole resection is the only procedure that has been shown to decrease the rate of recurrence of this disease.

  1. Ovarian Germ Cell Tumors Treatment

    Science.gov (United States)

    ... ovarian germ cell tumor are swelling of the abdomen or vaginal bleeding after menopause. Ovarian germ cell ... if you have either of the following: Swollen abdomen without weight gain in other parts of the ...

  2. Tumor Evasion from T Cell Surveillance

    Directory of Open Access Journals (Sweden)

    Katrin Töpfer

    2011-01-01

    Full Text Available An intact immune system is essential to prevent the development and progression of neoplastic cells in a process termed immune surveillance. During this process the innate and the adaptive immune systems closely cooperate and especially T cells play an important role to detect and eliminate tumor cells. Due to the mechanism of central tolerance the frequency of T cells displaying appropriate arranged tumor-peptide-specific-T-cell receptors is very low and their activation by professional antigen-presenting cells, such as dendritic cells, is frequently hampered by insufficient costimulation resulting in peripheral tolerance. In addition, inhibitory immune circuits can impair an efficient antitumoral response of reactive T cells. It also has been demonstrated that large tumor burden can promote a state of immunosuppression that in turn can facilitate neoplastic progression. Moreover, tumor cells, which mostly are genetically instable, can gain rescue mechanisms which further impair immune surveillance by T cells. Herein, we summarize the data on how tumor cells evade T-cell immune surveillance with the focus on solid tumors and describe approaches to improve anticancer capacity of T cells.

  3. Intramedullary spinal cord primitive neuroectodermal tumor presenting with hydrocephalus.

    Science.gov (United States)

    Alexiou, George A; Siozos, George; Stefanaki, Kalliopi; Moschovi, Maria; Prodromou, Neofytos

    2013-02-01

    Spinal primitive neuroectodermal tumors are exceedingly rare. Herewith, we present the first case of an intramedullary spinal cord tumor associated with hydrocephalus in a 2-month-old boy that presented with left hemiparesis. The patient had been diagnosed on prenatal ultrasound with enlarged ventricular system. At his current admission, a brain magnetic resonance imaging (MRI) revealed hydrocephalus and an intramedullary lesion extending from the second cervical to the first thoracic vertebrae. Dissemination of the tumor was revealed intracranially and in the spinal canal. After a ventriculoperitoneal shunt placement a radical resection of the tumor was performed, however some small tumor remnants could not be safely removed. Postoperative there was no neurologic deterioration. The tumor was diagnosed as a central nervous system primitive neuroectodermal tumor (World Health Organization grade IV). Spinal intramedullary primitive neuroectodermal tumors are extremely rare. In such rare tumors, multiinstitutional studies are needed for treatment guidelines to be established.

  4. Primary renal primitive neuroectodermal tumor: A rare presentation

    Directory of Open Access Journals (Sweden)

    V Goel

    2015-01-01

    Full Text Available Primitive Neuroectodermal Tumor of the kidney is a rare entity. Very few cases of primary renal PNET have been reported to date. Most literature about rPNET is isolated case reports. We report a case of rPNET in a 39-year-old male with a pre-operative diagnosis of renal cell carcinoma with renal vein thrombosis. The patient underwent radical nephrectomy with thrombolectomy, and histopathological examination revealed a highly aggressive tumor composed of monotonous sheets of round cells. Tumor cells were positive for CD 99 and FLI-1, hence confirming the diagnosis of Primitive Neuroectodermal Tumor. Post-surgery, patient was given VAC/IE-based adjuvant chemotherapy. In view of highly aggressive nature of this tumor, prompt diagnosis and imparting effective chemotherapy regimen to the patient is required, and it is important to differentiate PNET from other small round-cell tumors because of different therapeutic approach.

  5. Pituitary macroadenoma presenting as a nasal tumor: case report

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    Nivaldo Adolfo Silva Junior

    Full Text Available CONTEXT: Pituitary macroadenomas are rare intracranial tumors. In a few cases, they may present aggressive behavior and invade the sphenoid sinus and nasal cavity, causing unusual symptoms. In this paper, we report an atypical case of pituitary adenoma presenting as a nasal mass.CASE REPORT: The patient was a 44-year-old woman who had had amenorrhea and galactorrhea for ten months, with associated nasal obstruction, macroglossia and acromegaly. Both growth hormone and prolactin levels were increased. Magnetic resonance imaging showed a large mass originating from the lower surface of the pituitary gland, associated with sella turcica erosion and tumor extension through the sphenoid sinus and nasal cavity. Histopathological analysis demonstrated a chromophobe pituitary adenoma with densely packed rounded epithelial cells, with some atypias and rare mitotic figures. There was no evidence of metastases.CONCLUSION: Macroadenoma invading the nasal cavity is a rare condition and few similar cases have been reported in the literature. This study contributes towards showing that tumor extension to the sphenoid sinus and nasopharynx needs to be considered and investigated in order to make an early diagnosis when atypical symptoms like nasal obstruction are present.

  6. Lung metastasis of benign giant cell tumor: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Bosi, Thiago Carneiro da Cunha; Andrade, Fernando Coelho Goulart de; Turtelli, Celso Montenegro; Ribeiro Junior, Helio Antonio [Universidade Federal do Triangulo Mineiro (UFMT), Uberaba, MG (Brazil). Dept. of Radiology and Imaging Diagnosis]. E-mail: tccbosi@yahoo.com.br; Fatureto, Marcelo Cunha [Universidade Federal do Triangulo Mineiro (UFMT), Uberaba, MG (Brazil). Dept. of Thoracic Surgery; Etchebehere, Renata Margarida [Universidade Federal do Triangulo Mineiro (UFMT), Uberaba, MG (Brazil). Dept. of Pathology

    2008-05-15

    Giant cell tumor is the sixth most frequent primary bone neoplasm, affecting long bone metaphysis, most frequently in young adults. On radiological images, this tumor appears as a lytic, well-defined, eccentric lesion. The authors report a case of benign giant cell tumor in a patient who presented with lung metastases five years after undergoing resection of the primary tumor. (author)

  7. Clear-cell variant of calcifying epithelial odontogenic tumor (Pindborg tumor) in the mandible

    Institute of Scientific and Technical Information of China (English)

    Ching-Yi Chen; Chung-Wei Wu; Wen-Chen Wang; Li-Min Lin; Yuk-Kwan Chen

    2013-01-01

    We present an uncommon case (female patient aged 59 years) of the clear-cell variant of calcifying epithelial odontogenic tumor (CEOT) (also known as Pindborg tumor) in the mandible. The clinical characteristics and probable origins of the clear tumor cells of previously reported cases of clear-cell variant of intraosseous CEOT are also summarized and discussed.

  8. Destruction of solid tumors by immune cells

    Science.gov (United States)

    López, Álvaro G.; Seoane, Jesús M.; Sanjuán, Miguel A. F.

    2017-03-01

    The fractional cell kill is a mathematical expression describing the rate at which a certain population of cells is reduced to a fraction of itself. In order to investigate the fractional cell kill that governs the rate at which a solid tumor is lysed by a cell population of cytotoxic CD8+ T cells (CTLs), we present several in silico simulations and mathematical analyses. When the CTLs eradicate efficiently the tumor cells, the models predict a correlation between the morphology of the tumors and the rate at which they are lysed. However, when the effectiveness of the immune cells is decreased, the mathematical function fails to reproduce the process of lysis. This limit is thoroughly discussed and a new fractional cell kill is proposed.

  9. [Sertoli cell tumor of the testis].

    Science.gov (United States)

    Hita Rosino, E; López Hidalgo, J; Mellado Mesa, P; Olivar Buera, M

    2001-01-01

    Sertoli cell tumors (TCS) derivated from sex-cord estroma cells, are an uncommon variety of testicles neoplasms. A 66 year-old patient that came to the consultation for an increased scrotum of size present. Ultrasound viewed a hipoecoic nodule capable with testicular tumor, more secondary hidrocele. After undergoing the standard treatment, by means of groin radical orchiectomy, its pathologic analysis identified the lesion as Sertoli cell tumor conventional. The pathologic features that best correlate with a clinically benign course are as follows: a lower size tumor to 5 cm, mild nuclear atypia, a mitotic rate of less than 5 mitosis per 10 high power fields, and absent necrosis. Our case presented with these features. Follow-up of these neoplasms should be prolonged by the unusual of its presentation and a small percentage of cases are clinically malignant.

  10. CD8+ Tumor-Infiltrating T Cells Are Trapped in the Tumor-Dendritic Cell Network

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    Alexandre Boissonnas

    2013-01-01

    Full Text Available Chemotherapy enhances the antitumor adaptive immune T cell response, but the immunosuppressive tumor environment often dominates, resulting in cancer relapse. Antigen-presenting cells such as tumor-associated macrophages (TAMs and tumor dendritic cells (TuDCs are the main protagonists of tumor-infiltrating lymphocyte (TIL immuno-suppression. TAMs have been widely investigated and are associated with poor prognosis, but the immuno-suppressive activity of TuDCs is less well understood. We performed two-photon imaging of the tumor tissue to examine the spatiotemporal interactions between TILs and TuDCs after chemotherapy. In a strongly immuno-suppressive murine tumor model, cyclophosphamide-mediated chemotherapy transiently enhanced the antitumor activity of adoptively transferred ovalbumin-specific CD8+ T cell receptor transgenic T cells (OTI but barely affected TuDC compartment within the tumor. Time lapse imaging of living tumor tissue showed that TuDCs are organized as a mesh with dynamic interconnections. Once infiltrated into the tumor parenchyma, OTI T cells make antigen-specific and long-lasting contacts with TuDCs. Extensive analysis of TIL infiltration on histologic section revealed that after chemotherapy the majority of OTI T cells interact with TuDCs and that infiltration is restricted to TuDC-rich areas. We propose that the TuDC network exerts antigen-dependent unproductive retention that trap T cells and limit their antitumor effectiveness.

  11. Primitive neuroectodermal tumor of adrenal: clinical presentation and outcomes.

    Science.gov (United States)

    Dutta, Deep; Shivaprasad, K S; Das, Ram Narayan; Ghosh, Sujoy; Chowdhury, Subhankar

    2013-01-01

    Primitive neuroectodermal tumor (PNET) of adrenal is an extremely rare tumor of neural crest origin. A nonfunctional left adrenal mass (14.6 × 10.5 × 10.0 cm) on computed tomography (CT) was detected in a 40-year-old lady with abdominal pain, swelling, and left pleural effusion. She underwent left adrenalectomy and left nephrectomy with retroperitoneal resection. Histopathology revealed sheets and nest of oval tumor cells with hyperchromatic nuclei, prominent nucleoli, scanty cytoplasm, brisk mitotic activity, necrosis, lymphovascular invasion, capsular invasion, and extension to the surrounding muscles; staining positive for Mic-2 (CD-99 antigen), vimentin, synaptophysin, and Melan-A. Thoracocentesis, pleural fluid study, and pleural biopsy did not show metastasis. She responded well to vincristine, adriamycin, and cyclophosphamide followed by ifosfamide and etoposide (IE). This is the first report of adrenal peripheral PNET (pPNET) from India. This report intends to highlight that pPNET should be suspected in a patient presenting with huge nonfunctional adrenal mass which may be confused with adrenocortical carcinoma.

  12. Primitive neuroectodermal tumor of adrenal: Clinical presentation and outcomes

    Directory of Open Access Journals (Sweden)

    Deep Dutta

    2013-01-01

    Full Text Available Primitive neuroectodermal tumor (PNET of adrenal is an extremely rare tumor of neural crest origin. A nonfunctional left adrenal mass (14.6 × 10.5 × 10.0 cm on computed tomography (CT was detected in a 40-year-old lady with abdominal pain, swelling, and left pleural effusion. She underwent left adrenalectomy and left nephrectomy with retroperitoneal resection. Histopathology revealed sheets and nest of oval tumor cells with hyperchromatic nuclei, prominent nucleoli, scanty cytoplasm, brisk mitotic activity, necrosis, lymphovascular invasion, capsular invasion, and extension to the surrounding muscles; staining positive for Mic-2 (CD-99 antigen, vimentin, synaptophysin, and Melan-A. Thoracocentesis, pleural fluid study, and pleural biopsy did not show metastasis. She responded well to vincristine, adriamycin, and cyclophosphamide followed by ifosfamide and etoposide (IE. This is the first report of adrenal peripheral PNET (pPNET from India. This report intends to highlight that pPNET should be suspected in a patient presenting with huge nonfunctional adrenal mass which may be confused with adrenocortical carcinoma.

  13. MESOTHELIOMA PRESENTING WITH PNEUMOTHORAX AND INTERLOBAR TUMOR

    NARCIS (Netherlands)

    MANNES, GPM; GOUW, ASH; BERENDSEN, HH; VERHOEFF, AJ; POSTMUS, PE

    1991-01-01

    A patient presented with a pneumothorax, a parahilar mass and a pleural effusion on the left side. Histology proved that this was caused by a malignant mesothelioma, epithelial type. The pneumothorax persisted, even after chest drainage and pleurodesis with talc powder and tetracycline.

  14. Neuroendocrine tumor presenting like lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Vincenzi Bruno

    2011-10-01

    Full Text Available Abstract Introduction Neuroendocrine tumors are a rare but diverse group of malignancies that arise in a wide range of organ systems, including the mediastinum. Differential diagnosis includes other masses arising in the middle mediastinum such as lymphoma, pericardial, bronchogenic and enteric cysts, metastatic tumors, xanthogranuloma, systemic granuloma, diaphragmatic hernia, meningocele and paravertebral abscess. Case presentation We present a case of 42-year-old Caucasian man with a neuroendocrine tumor of the middle-posterior mediastinum and liver metastases, which resembled a lymphoma on magnetic resonance imaging. Conclusion The differential diagnosis in patients with mediastinal masses and liver lesions should include neuroendocrine tumor.

  15. Energy and Redox Homeostasis in Tumor Cells

    Directory of Open Access Journals (Sweden)

    Marcus Fernandes de Oliveira

    2012-01-01

    Full Text Available Cancer cells display abnormal morphology, chromosomes, and metabolism. This review will focus on the metabolism of tumor cells integrating the available data by way of a functional approach. The first part contains a comprehensive introduction to bioenergetics, mitochondria, and the mechanisms of production and degradation of reactive oxygen species. This will be followed by a discussion on the oxidative metabolism of tumor cells including the morphology, biogenesis, and networking of mitochondria. Tumor cells overexpress proteins that favor fission, such as GTPase dynamin-related protein 1 (Drp1. The interplay between proapoptotic members of the Bcl-2 family that promotes Drp 1-dependent mitochondrial fragmentation and fusogenic antiapoptotic proteins such as Opa-1 will be presented. It will be argued that contrary to the widespread belief that in cancer cells, aerobic glycolysis completely replaces oxidative metabolism, a misrepresentation of Warburg’s original results, mitochondria of tumor cells are fully viable and functional. Cancer cells also carry out oxidative metabolism and generally conform to the orthodox model of ATP production maintaining as well an intact electron transport system. Finally, data will be presented indicating that the key to tumor cell survival in an ROS rich environment depends on the overexpression of antioxidant enzymes and high levels of the nonenzymatic antioxidant scavengers.

  16. In Vitro Efficient Expansion of Tumor Cells Deriving from Different Types of Human Tumor Samples

    Directory of Open Access Journals (Sweden)

    Ilaria Turin

    2014-03-01

    Full Text Available Obtaining human tumor cell lines from fresh tumors is essential to advance our understanding of antitumor immune surveillance mechanisms and to develop new ex vivo strategies to generate an efficient anti-tumor response. The present study delineates a simple and rapid method for efficiently establishing primary cultures starting from tumor samples of different types, while maintaining the immuno-histochemical characteristics of the original tumor. We compared two different strategies to disaggregate tumor specimens. After short or long term in vitro expansion, cells analyzed for the presence of malignant cells demonstrated their neoplastic origin. Considering that tumor cells may be isolated in a closed system with high efficiency, we propose this methodology for the ex vivo expansion of tumor cells to be used to evaluate suitable new drugs or to generate tumor-specific cytotoxic T lymphocytes or vaccines.

  17. A GIANT CONGENITAL ORBITAL TUMOR - AN UNUSUAL PRESENTATION OF RETINOBLASTOMA

    NARCIS (Netherlands)

    ZWAAN, CM; DEWAAL, FC; KOOLE, FD; MENKO, FH; VANDERVALK, P; SLATER, RM; SCHEFFER, H; VANWAVEREN, G; MOLL, AC; SCHOUTENVANMEETEREN, AYN; TAN, KEWP

    1994-01-01

    We report a case of an unusual giant congential tumor presenting in a newborn infant as a large exophytic mass emerging from the left orbit. After enucleation orbital recurrence developed within 14 days. No anti-tumor treatment was given and the child died at the age of 4 weeks. The histopathologica

  18. Malignant peripheral nerve sheath tumor of facial nerve: Presenting as parotid mass

    Directory of Open Access Journals (Sweden)

    Bageshri P Gogate

    2013-01-01

    Full Text Available Malignant peripheral nerve sheath tumor (MPNST is very uncommon tumor of parotid gland and it is an uncommon spindle cell sarcoma accounting for approximately 5% of all soft-tissue sarcoma. There is strong association between MPNSTs and neurofibromatosis (NF-1 and previous irradiation. Structural abnormality of chromosome 17 is associated with NF-1 and so MPNST. We present a case of a 78-year-old male presenting with slowly growing parotid mass who underwent tumor resection.

  19. Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses.

    Science.gov (United States)

    Joshi, Nikhil S; Akama-Garren, Elliot H; Lu, Yisi; Lee, Da-Yae; Chang, Gregory P; Li, Amy; DuPage, Michel; Tammela, Tuomas; Kerper, Natanya R; Farago, Anna F; Robbins, Rebecca; Crowley, Denise M; Bronson, Roderick T; Jacks, Tyler

    2015-09-15

    Infiltration of regulatory T (Treg) cells into many tumor types correlates with poor patient prognoses. However, mechanisms of intratumoral Treg cell function remain to be elucidated. We investigated Treg cell function in a genetically engineered mouse model of lung adenocarcinoma and found that Treg cells suppressed anti-tumor responses in tumor-associated tertiary lymphoid structures (TA-TLSs). TA-TLSs have been described in human lung cancers, but their function remains to be determined. TLSs in this model were spatially associated with >90% of tumors and facilitated interactions between T cells and tumor-antigen-presenting dendritic cells (DCs). Costimulatory ligand expression by DCs and T cell proliferation rates increased in TA-TLSs upon Treg cell depletion, leading to tumor destruction. Thus, we propose that Treg cells in TA-TLSs can inhibit endogenous immune responses against tumors, and targeting these cells might provide therapeutic benefit for cancer patients.

  20. Peripheral primitive neuroectodermal tumor of the kidney presenting with pulmonary tumor embolism: A case report

    Institute of Scientific and Technical Information of China (English)

    Sathya; Chinnaa; Chandan; J; Das; Sanjay; Sharma; Prabhjot; Singh; Amlesh; Seth; Suvendu; Purkait; Sandeep; R; Mathur

    2014-01-01

    Peripheral primitive neuroectodermal tumor(PNET) of the kidney is a rare, aggressive tumor known for its recurrence and metastatic potential. Despite the frequency of venous extension to the renal veins and inferior vena cava, pulmonary tumor embolism at the initial presentation is not common. We report a case of 22-year-old female with PNET of the kidney who presented with tumor embolism in the inferior vena cava(IVC) and bilateral pulmonary artery. The patient underwent surgical resection and histopathological analysis confirmed the presence of tumor within the IVC and pulmonary arteries. The patient received adjuvant chemotherapy and is currently doing well on follow-up.

  1. Molecular biology of testicular germ cell tumors.

    Science.gov (United States)

    Gonzalez-Exposito, R; Merino, M; Aguayo, C

    2016-06-01

    Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies.

  2. GRANULAR CELL TUMOR OF BREAST (CYTOLOGICAL DIAGNOSIS CONFIRMED BY HISTOPATHOLOGY

    Directory of Open Access Journals (Sweden)

    Divvya

    2014-10-01

    Full Text Available Granular cell tumor is a tumor derived from Schwann cells of peripheral nerves and it can occur throughout the body. About 5% of granular cell tumors occur in breast and are mostly benign in nature. We report a case of 30 year old female who presented with a swelling in right breast which on histo pathological examination revealed features consistent with granular cell tumor. This case is highlighted to reveal the importance of histopathology in differentiating granular cell tumor from carcinoma breast which is difficult based on clinical, radiological and cytological examination alone.

  3. BM-12CEREBRAL INFARCTION SECONDARY TO PULMONARY VEIN COMPRESSION AND LEFT ATRIAL APPENDAGE TUMOR INFILTRATION AS THE PRESENTING SIGN OF METASTATIC SQUAMOUS CELL CARCINOMA OF THE BASE OF THE TONGUE

    Science.gov (United States)

    Dredla, Brynn; Siegel, Jason; Jaeckle, Kurt

    2014-01-01

    BACKGROUND: Squamous cell carcinoma of the tongue has been documented to metastasize to the lungs and rarely involve the heart. The majority of documented cases of cardiac metastases are from postmortem analysis. Cases of sudden death, syncope, and dyspnea have been reported. However, stroke and tumor embolization to the brain as the initial clinical presentation has not been documented in the English literature. METHODS: Case Report. RESULTS: This case addresses a 61-year-old male with Stage IVA squamous cell carcinoma of the left tongue base, believed to be in remission after systemic chemotherapy and local radiation, who presented with acute cerebral infarctions involving multiple vascular territories. Cardiac CT obtained during stroke etiology evaluation displayed metastatic disease compressing the pulmonary vein resulting in virtual pulmonary vein thrombus. Transthoracic echocardiogram was negative for cardiac valvular pathology. Anticoagulation was initiated. Twelve days later he returned with recurrent strokes and suspected tumor embolization to the brain. Imaging displayed left atrial appendage structural abnormality highly suggestive of tumor infiltration. CONCLUSION: Cardiac metastases are rare and non-myxomatous tumor embolization to the brain even rarer especially in the setting of cerebral infarction due to pulmonary vein thrombus. Here we describe a case of multiple acute cerebral infarctions appearing from a proximal source refractory to anticoagulation. Thromboembolism from the pulmonary vein and tumor embolization from cardiac metastases are the likely mechanisms for his clinical presentation and radiographic findings. This case demonstrates the complexity of multiple stroke etiologies in one patient and the importance of cardiac imaging in stroke evaluation, particularly in the setting of a patient with a history of cancer.

  4. Esophageal Gastrointestinal Stromal Tumors Presenting as Mediastinal Mass

    Directory of Open Access Journals (Sweden)

    M. Kafeel

    2013-11-01

    Full Text Available Gastrointestinal stromal tumors (GISTs are the most common mesenchymal tumors of the gastrointestinal tract and are predominant in the stomach and intestine but rare in the esophagus. Here, we report a case of esophageal GIST which presented as a mediastinal mass on chest X-ray and dyspnea. The case was initially diagnosed as leiomyosarcoma, which could create a diagnostic dilemma. Therefore, recognizing this uncommon presentation as a mediastinal mass with esophageal GIST is important in the differential diagnosis.

  5. Desmoid tumor in Gardner's Syndrome presented as acute abdomen

    Directory of Open Access Journals (Sweden)

    Rizos Spiros

    2006-03-01

    Full Text Available Abstract Background Gardner's syndrome can occasionally be complicated with intra-abdominal desmoid tumor. These tumors usually remain asymptomatic but can exhibit symptoms due to intestinal, vascular and ureteral compression and obstruction. Case presentation A rare case of a 41-year-old male patient with Gardner's syndrome complicated with intra-abdominal desmoid tumor, which first presented as acute abdomen, is presented. Conclusion Extra-abdominal manifestations of Gardner's syndrome along with a palpable abdominal mass would raise suspicion for the presence of a desmoid tumor in the majority of cases. In life-threatening cases, surgical treatment should be considered as a palliative approach, though the extent of excision remains debatable

  6. ADAM12 produced by tumor cells rather than stromal cells accelerates breast tumor progression

    DEFF Research Database (Denmark)

    Frohlich, Camilla; Nehammer, Camilla; Albrechtsen, Reidar;

    2011-01-01

    hypothesized, however, that the tumor-associated stroma may stimulate ADAM12 expression in tumor cells, based on the fact that TGF-ß1 stimulates ADAM12 expression and is a well-known growth factor released from tumor-associated stroma. TGF-ß1 stimulation of ADAM12-negative Lewis lung tumor cells induced ADAM12...... synthesis, and growth of these cells in vivo induced a >200-fold increase in ADAM12 expression. Our observation that ADAM12 expression is significantly higher in the terminal duct lobular units (TDLUs) adjacent to human breast carcinoma compared with TDLUs found in normal breast tissue supports our......Expression of ADAM12 is low in most normal tissues, but is markedly increased in numerous human cancers, including breast carcinomas. We have previously shown that overexpression of ADAM12 accelerates tumor progression in a mouse model of breast cancer (PyMT). In the present study, we found...

  7. Neoplastic meningitis as the presentation of occult primitive neuroectodermal tumors.

    Science.gov (United States)

    Jennings, M T; Slatkin, N; D'Angelo, M; Ketonen, L; Johnson, M D; Rosenblum, M; Creasy, J; Tulipan, N; Walker, R

    1993-10-01

    Seven children and young adults initially presented with subacute meningitis and/or increased intracranial pressure. The diagnosis of neoplastic meningitis secondary to a primitive neuroectodermal neoplasm was delayed by the absence of an obvious primary tumor. The neuroradiologic appearance was that of a basimeningeal infiltrative process, complicated by communicating hydrocephalus or "pseudotumor cerebri." Myelography was important in the diagnosis of disseminated meningeal malignancy in four cases. Cerebrospinal fluid cytologic diagnosis was insensitive but ultimately confirmed in five cases. All seven patients experienced progressive disease despite neuraxis radiotherapy and intensive chemotherapy; six have died. Systemic dissemination to bone and/or peritoneum occurred in three patients while on therapy. In two, a primary parenchymal brain or spinal cord tumor could not be identified at postmortem examination. The presentation of a primitive neuroectodermal tumor as subacute meningitis without an evident primary tumor heralds an aggressive and refractory neoplasm.

  8. Ultrasound features of orbital granular cell tumor.

    Science.gov (United States)

    Ayres, Bernadete; Miller, Neil R; Eberhart, Charles G; Dibernardo, Cathy W

    2009-01-01

    The authors report the echographic characteristics of a rare orbital granular cell tumor and correlate these findings with histopathology. A 56-year-old woman presented with proptosis. Complete ophthalmic and ultrasound examinations were performed. Ultrasound revealed an oval, well-outlined orbital mass in the intraconal space with low-medium reflectivity and regular internal structure. An orbitotomy with complete excision of the tumor was performed. Histopathologic evaluation showed sheets and nests of cells with abundant eosinophilic and granular cytoplasm in a uniform distribution throughout the lesion. The echographic characteristics correlated well with the morphologic surgical findings and the histologic architecture. This is the first report describing the echographic characteristics of orbital granular cell tumor.

  9. Severe acute tumor lysis syndrome in patients with germ-cell tumors

    Directory of Open Access Journals (Sweden)

    Guilherme Alvarenga Feres

    2008-01-01

    Full Text Available Germ-cell tumors are a high-proliferative type of cancer that may evolve to significant bulky disease. Tumor lysis syndrome is rarely reported in this setting. The reports of three patients with germ-cell tumors who developed severe acute tumor lysis syndrome following the start of their anticancer therapy are presented. All patients developed renal dysfunction and multiorgan failure. Patients with extensive germ-cell tumors should be kept on close clinical and laboratory monitoring. Physicians should be aware of this uncommon but severe complication and consider early admission to the intensive care unit for the institution of measures to prevent acute renal failure.

  10. Mechanisms of tumor cell necrosis.

    Science.gov (United States)

    Proskuryakov, Sergey Y; Gabai, Vladimir L

    2010-01-01

    Until recently, necrosis, unlike apoptosis, was considered as passive and unregulated form of cell death. However, during the last decade a number of experimental data demonstrated that, except under extreme conditions, necrosis may be a well-regulated process activated by rather specific physiological and pathological stimuli. In this review, we consider mechanisms and the role of necrosis in tumor cells. It became recently clear that the major player in necrotic cascade is a protein kinase RIP1, which can be activated by number of stumuli including TNF, TRAIL, and LPS, oxidative stress, or DNA damage (via poly-ADP-ribose polymerase). RIP1 kinase directly (or indirectly via another kinase JNK) transduces signal to mitochondria and causes specific damage (mitochondrial permeability transition). Mitochondrial collapse activates various proteases (e.g., calpains, cathepsin) and phospholipases, and eventually leads to plasma membrane destruction, a hallmark of necrotic cell death. Necrosis, in contrast to apoptosis, usually evokes powerful inflammatory response, which may participate in tumor regression during anticancer therapy. On the other hand, excessive spontaneous necrosis during tumor development may lead to more aggressive tumors due to stimulatory role of necrosis-induced inflammation on their growth.

  11. Multiparametric classification links tumor microenvironments with tumor cell phenotype.

    Directory of Open Access Journals (Sweden)

    Bojana Gligorijevic

    2014-11-01

    Full Text Available While it has been established that a number of microenvironment components can affect the likelihood of metastasis, the link between microenvironment and tumor cell phenotypes is poorly understood. Here we have examined microenvironment control over two different tumor cell motility phenotypes required for metastasis. By high-resolution multiphoton microscopy of mammary carcinoma in mice, we detected two phenotypes of motile tumor cells, different in locomotion speed. Only slower tumor cells exhibited protrusions with molecular, morphological, and functional characteristics associated with invadopodia. Each region in the primary tumor exhibited either fast- or slow-locomotion. To understand how the tumor microenvironment controls invadopodium formation and tumor cell locomotion, we systematically analyzed components of the microenvironment previously associated with cell invasion and migration. No single microenvironmental property was able to predict the locations of tumor cell phenotypes in the tumor if used in isolation or combined linearly. To solve this, we utilized the support vector machine (SVM algorithm to classify phenotypes in a nonlinear fashion. This approach identified conditions that promoted either motility phenotype. We then demonstrated that varying one of the conditions may change tumor cell behavior only in a context-dependent manner. In addition, to establish the link between phenotypes and cell fates, we photoconverted and monitored the fate of tumor cells in different microenvironments, finding that only tumor cells in the invadopodium-rich microenvironments degraded extracellular matrix (ECM and disseminated. The number of invadopodia positively correlated with degradation, while the inhibiting metalloproteases eliminated degradation and lung metastasis, consistent with a direct link among invadopodia, ECM degradation, and metastasis. We have detected and characterized two phenotypes of motile tumor cells in vivo, which

  12. Redefining circulating tumor cells by image processing

    NARCIS (Netherlands)

    Ligthart, S.T.

    2012-01-01

    Circulating tumor cells (CTC) in the blood of patients with metastatic carcinomas are associated with poor survival and can be used to guide therapy. However, CTC are very heterogeneous in size and shape, and are present at very low frequencies. Missing or misjudging a few events may have great cons

  13. Primary Testicular Carcinoid Tumor presenting as Carcinoid Heart Disease

    Directory of Open Access Journals (Sweden)

    Manjunath L Chikkaraddi

    2015-01-01

    Full Text Available Primary carcinoid tumors of the testis are very rare, and they seldom present with carcinoid syndrome. We report a hereto unreported instance, where a patient with a long-standing testicular mass presented with carcinoid heart disease, an uncommon form of carcinoid syndrome. He presented with symptoms of right heart failure, episodic facial flushing and was found to have severe right-sided valvular heart disease. His urinary 5-hydroxy indole acetic acid level was elevated. He underwent orchidectomy and the histopathology confirmed a testicular carcinoid tumor.

  14. Atypical teratoid/rhabdoid tumor: an unusual presentation

    Energy Technology Data Exchange (ETDEWEB)

    Gandhi, Chirag D. [Mount Sinai School of Medicine, Department of Neurosurgery, One Gustave L. Levy Place, Box 1136, Annenberg 8-06, New York, NY (United States); Krieger, Mark D.; McComb, J. Gordon [Children' s Hospital of Los Angeles, Division of Neurosurgery, Los Angeles, CA (United States)

    2004-10-01

    Atypical teratoid/ rhabdoid tumor (AT/RT) of the central nervous system is a rare, highly aggressive malignancy of infancy. Although it is reported infrequently in the literature, it has often been histologically confused with a primitive neuroectodermal tumor (PNET)/medulloblastoma (MB) but has a much worse prognosis. We present an infant with two AT/RT tumors, one suprasellar in location and the other within the vermis without evidence of tumor elsewhere. What makes this case unusual is that there were two separate lesions in different cranial compartments, with no evidence of subarachnoid seeding. In addition, the lesions had different magnetic resonance imaging (MRI) characteristics even though they were histologically the same. (orig.)

  15. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

    An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

  16. Dendritic cells are stressed out in tumor.

    Science.gov (United States)

    Maj, Tomasz; Zou, Weiping

    2015-09-01

    A recently paper published in Cell reports that dendritic cells (DCs) are dysfunctional in the tumor environment. Tumor impairs DC function through induction of endoplasmic reticulum stress response and subsequent disruption of lipid metabolic homeostasis.

  17. Treatment Option Overview (Extragonadal Germ Cell Tumors)

    Science.gov (United States)

    ... Germ Cell Tumors Treatment Extragonadal Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Extragonadal Germ ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  18. The ruthenium complex cis-(dichloro)tetraammineruthenium(III) chloride presents selective cytotoxicity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) tumor cell lines.

    Science.gov (United States)

    Silveira-Lacerda, Elisângela de Paula; Vilanova-Costa, Cesar Augusto Sam Tiago; Hamaguchi, Amélia; Pavanin, Luiz Alfredo; Goulart, Luiz Ricardo; Homsi-Brandenburgo, Maria Inês; Dos Santos, Wagner Batista; Soares, Andreimar Martins; Nomizo, Auro

    2010-06-01

    The aim of present study was to verify the in vitro antitumor activity of a ruthenium complex, cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) toward different tumor cell lines. The antitumor studies showed that ruthenium(III) complex presents a relevant cytotoxic activity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) cell lines and a very low cytotoxicity toward human peripheral blood mononuclear cells. The ruthenium(III) complex decreased the fraction of tumor cells in G0/G1 and/or G2-M phases, indicating that this compound may act on resting/early entering G0/G1 cells and/or precycling G2-M cells. The cytotoxic activity of a high concentration (2 mg mL(-1)) of cis-[RuCl(2)(NH(3))(4)]Cl toward Jurkat cells correlated with an increased number of annexin V-positive cells and also the presence of DNA fragmentation, suggesting that this compound induces apoptosis in tumor cells. The development of new antineoplastic medications demands adequate knowledge in order to avoid inefficient or toxic treatments. Thus, a mechanistic understanding of how metal complexes achieve their activities is crucial to their clinical success and to the rational design of new compounds with improved potency.

  19. Incidentally Discovered Extensive Squamous Metaplasia within Borderline Phyllodes Tumor: Presentation of a Rare Tumor.

    Science.gov (United States)

    Uğraş, Nesrin; Tolunay, Şahsine; Öz Atalay, Fatma; Gökgöz, Şehsuvar

    2016-01-01

    Phyllodes tumors are uncommon biphasic fibroepithelial neoplasms of breast, comprising less than 1% of all breast neoplasms. We therefore aimed to present the case with its microscopic findings. In this article, we report a 59-year-old female admitted to the general surgery department with a rapidly, enlarging, palpable mass in right breast. After histopathological examination, it was diagnosed as borderline phyllodes tumor with extensive squamous metaplasia. Metaplastic changes are infrequent in the stromal and epithelial component of these tumors. Extensive squamous metaplasia within phyllodes tumor is rare and may occur in benign, borderline and malign subtypes.

  20. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  1. Dendritic cell-tumor cell hybrids and immunotherapy

    DEFF Research Database (Denmark)

    Cathelin, Dominique; Nicolas, Alexandra; Bouchot, André

    2011-01-01

    Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation...

  2. Cyberknife radiosurgery for cranial plasma cell tumor.

    Science.gov (United States)

    Alafaci, Cetty; Grasso, Giovanni; Conti, Alfredo; Caffo, Mariella; Salpietro, Francesco Maria; Tomasello, Francesco

    2014-01-01

    Cranial and intracranial involvement by myelomatous disease is relatively uncommon. Furthermore, systemic manifestations of multiple myeloma are present in the majority of these cases at the time of symptom onset. The authors report the case of a patient with serial appearance of multiple intracranial plasma cell tumor localizations as the first manifestations of a multiple myeloma. The patient was treated with CyberKnife radiosurgery for a lesion localized at the clivus and sella turcica with complete local control. With such a technique, based on high-dose conformality, the tumor was centered with an ablative dose of radiation and, at the same time, with a low dose spreading to the surrounding critical structures. The radiosensitivity of plasma cell tumors renders this treatment modality particularly advantageous for their localized manifestation. A technical description of this case is provided. To our knowledge, this is the first case of successful Cyberknife radiosurgery of multifocal intracranial plasmacytoma.

  3. Delayed menopause due to granulosa cell tumor of the ovary

    Directory of Open Access Journals (Sweden)

    Bhushan Murkey

    2011-01-01

    Full Text Available A 52-year-old patient presented with complaints of menorrhagia. Endometrial biopsy revealed simple hyperplasia of the endometrium. Total abdominal hysterectomy with bilateral oophorectomy was carried out. The ovaries looked grossly normal, but histopathology reported granulosa cell tumor of the right ovary. Granulosa cell tumors belong to the sexcord stromal category and account for approximately 2% of all ovarian tumors. We review the features and treatment of granulosa cell tumors and the importance of screening for ovarian tumors in a case of endometrial hyperplasia and delayed menopause.

  4. SCA-1 Identifies the Tumor-Initiating Cells in Mammary Tumors of BALB-neuT Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Cristina Grange

    2008-12-01

    Full Text Available Cancer stem cells, initiating and sustaining the tumor process, have been isolated in human and murine breast cancer using different cell markers. In the present study, we aimed to evaluate the presence and characteristics of stem/tumor-initiating cells in the model of the mouse mammary neoplasia driven by the activated form of rat Her-2/neu oncogene (BALB-neuT mice. For this purpose, we generated tumor spheres from primary spontaneous BALB-neuT tumors. Tumor sphere cultures were characterized for clonogenicity, self-renewal, and ability to differentiate in epithelial/myoepithelial cells of the mammary gland expressing basal and luminal cytokeratins and alpha-smooth muscle actin. In addition, tumor spheres were more resistant to doxorubicin compared with parental tumor cells. In the attempt to identify a selected marker for the sphere-generating cells, we found that Sca-1+ cells, present in tumors or enriched in mammospheres, and not CD24+ or CD29+ cells, were responsible for the sphere generation in vitro. Moreover, cells from the tumor spheres showed an increased tumor-generating ability in respect to the epithelial tumor cells. Sca-1+ sorted cells or clonal mammospheres derived from a Sca-1+ cell showed a superimposable tumor-initiating ability. The data of the present study indicate that a Sca-1+ population derived from mammary BALB-neuT tumors is responsible for sphere generation in culture and for initiating tumors in vivo.

  5. 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.

  6. [Predictive value of Hodgkin's lymphoma tumor burden in present].

    Science.gov (United States)

    Kulyova, S A; Karitsky, A P

    2014-01-01

    Today approximately 70% of patients with Hodgkin lymphoma can be cured with the combined-modality therapy. Tumor burden, the importance of which was demonstrated 15 years ago for the first time, is a powerful prognostic factor. Data of literature of representations on predictive value of Hodgkin's lymphoma tumor burden are shown in the article. The difficult immunological relations between tumor cells and reactive ones lead to development of the main symptoms. Nevertheless, the collective sign of tumor burden shows the greatest influence on survival and on probability of resistance, which relative risk can be predicted on this variable and treatment program. Patients with bulky disease need escalated therapy with high-dose chemotherapy. Integration into predictive models of the variable will change an expected contribution of clinical and laboratory parameters in the regression analyses constructed on patients with Hodgkin's lymphoma. Today the role of diagnostic functional methods, in particular a positron emission tomography, for metabolic active measurement is conducted which allows excluding a reactive component.

  7. Dendritic-tumor fusion cells in cancer immunotherapy.

    Science.gov (United States)

    Takakura, Kazuki; Kajihara, Mikio; Ito, Zensho; Ohkusa, Toshifumi; Gong, Jianlin; Koido, Shigeo

    2015-03-01

    A promising area of clinical investigation is the use of cancer immunotherapy to treat cancer patients. Dendritic cells (DCs) operate as professional antigen-presenting cells (APCs) and play a critical role in the induction of antitumor immune responses. Thus, DC-based cancer immunotherapy represents a powerful strategy. One DC-based cancer immunotherapy strategy that has been investigated is the administration of fusion cells generated with DCs and whole tumor cells (DC-tumor fusion cells). The DC-tumor fusion cells can process a broad array of tumor-associated antigens (TAAs), including unidentified molecules, and present them through major histocompatibility complex (MHC) class I and II pathways in the context of co-stimulatory signals. Improving the therapeutic efficacy of DC-tumor fusion cell-based cancer immunotherapy requires increased immunogenicity of DCs and whole tumor cells. We discuss the potential ability of DC-tumor fusion cells to activate antigen-specific T cells and strategies to improve the immunogenicity of DC-tumor fusion cells as anticancer vaccines.

  8. Exophthalmos Revealing a Krukenberg Tumor: A Case Presentation and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Mohamed Fetohi

    2016-07-01

    Full Text Available Background: Krukenberg tumor is a well-known ovarian metastasis, usually of signet ring cell carcinoma in female patients. In the literature, there are a few documented cases of ocular metastasis in patients with Krukenberg tumor. Case Presentation: We report the case of a 35-year-old single Moroccan woman. She presented chronic pelvic pain, hematemesis and blurring of vision in the left eye. Clinical examination showed a pelvic mass and an exophthalmos with a divergent strabismus in the left eye. Pelvic and abdominal ultrasound showed a right tissular ovarian mass. Computed tomography (CT scan of the abdomen and pelvis revealed an ovarian tumor and bone metastasis. Orbital magnetic resonance imaging (MRI showed a hypertrophy of the left inferior rectus muscle behind the exophthalmos. Stomach endoscopy revealed an ulcerated and protruded mass of the antro-fundic junction. Histopathology and immunohistochemistry showed an infiltration of the gastric mucosa by atypically isolated signet ring cells similar to the tumor cells found in the ovarian histopathological exams. Discussion: Krukenberg tumor is an uncommon metastatic tumor of the ovary. This article provides an overview of the major pathological manifestations of Krukenberg tumor, patient characteristics, clinical and laboratory features of the disease, prognostic factors, and current knowledge about its pathogenesis.

  9. Exophthalmos Revealing a Krukenberg Tumor: A Case Presentation and Review of the Literature

    Science.gov (United States)

    Fetohi, Mohamed; Errarhay, Sanaa; Bazine, Aziz; Namad, Tarikq

    2016-01-01

    Background Krukenberg tumor is a well-known ovarian metastasis, usually of signet ring cell carcinoma in female patients. In the literature, there are a few documented cases of ocular metastasis in patients with Krukenberg tumor. Case Presentation We report the case of a 35-year-old single Moroccan woman. She presented chronic pelvic pain, hematemesis and blurring of vision in the left eye. Clinical examination showed a pelvic mass and an exophthalmos with a divergent strabismus in the left eye. Pelvic and abdominal ultrasound showed a right tissular ovarian mass. Computed tomography (CT) scan of the abdomen and pelvis revealed an ovarian tumor and bone metastasis. Orbital magnetic resonance imaging (MRI) showed a hypertrophy of the left inferior rectus muscle behind the exophthalmos. Stomach endoscopy revealed an ulcerated and protruded mass of the antro-fundic junction. Histopathology and immunohistochemistry showed an infiltration of the gastric mucosa by atypically isolated signet ring cells similar to the tumor cells found in the ovarian histopathological exams. Discussion Krukenberg tumor is an uncommon metastatic tumor of the ovary. This article provides an overview of the major pathological manifestations of Krukenberg tumor, patient characteristics, clinical and laboratory features of the disease, prognostic factors, and current knowledge about its pathogenesis. PMID:27721760

  10. Imaging Tumor Cell Movement In Vivo

    OpenAIRE

    Entenberg, David; Kedrin, Dmitriy; Wyckoff, Jeffrey; Sahai, Erik; Condeelis, John; Segall, Jeffrey E

    2013-01-01

    This unit describes the methods that we have been developing for analyzing tumor cell motility in mouse and rat models of breast cancer metastasis. Rodents are commonly used both to provide a mammalian system for studying human tumor cells (as xenografts in immunocompromised mice) as well as for following the development of tumors from a specific tissue type in transgenic lines. The Basic Protocol in this unit describes the standard methods used for generation of mammary tumors and imaging th...

  11. Large mid-esophageal granular cell tumor: benign versus malignant

    Directory of Open Access Journals (Sweden)

    Prarthana Roselil Christopher

    2015-06-01

    Full Text Available Granular cell tumors are rare soft tissue neoplasms, among which only 2% are malignant, arising from nervous tissue. Here we present a case of a large esophageal granular cell tumor with benign histopathological features which metastasized to the liver, but showing on positron emission tomography-computerized tomography standardized uptake value suggestive of a benign lesion.

  12. "Flagellated" cancer cells propel anti-tumor immunity.

    Science.gov (United States)

    Garaude, Johan; Blander, J Magarian

    2012-09-01

    The use of innate immune receptor agonists in cancer therapies has suffered from many drawbacks. Our recent observations suggest that some of these hurdles can be overcome by introducing flagellin into tumor cells to promote tumor antigen presentation by dendritic cells (DCs) and simultaneously trigger two types of pattern recognition receptors (PRRs).

  13. NMR exposure sensitizes tumor cells to apoptosis.

    Science.gov (United States)

    Ghibelli, L; Cerella, C; Cordisco, S; Clavarino, G; Marazzi, S; De Nicola, M; Nuccitelli, S; D'Alessio, M; Magrini, A; Bergamaschi, A; Guerrisi, V; Porfiri, L M

    2006-03-01

    NMR technology has dramatically contributed to the revolution of image diagnostic. NMR apparatuses use combinations of microwaves over a homogeneous strong (1 Tesla) static magnetic field. We had previously shown that low intensity (0.3-66 mT) static magnetic fields deeply affect apoptosis in a Ca2+ dependent fashion (Fanelli et al., 1999 FASEBJ., 13;95-102). The rationale of the present study is to examine whether exposure to the static magnetic fields of NMR can affect apoptosis induced on reporter tumor cells of haematopoietic origin. The impressive result was the strong increase (1.8-2.5 fold) of damage-induced apoptosis by NMR. This potentiation is due to cytosolic Ca2+ overload consequent to NMR-promoted Ca2+ influx, since it is prevented by intracellular (BAPTA-AM) and extracellular (EGTA) Ca2+ chelation or by inhibition of plasma membrane L-type Ca2+ channels. Three-days follow up of treated cultures shows that NMR decrease long term cell survival, thus increasing the efficiency of cytocidal treatments. Importantly, mononuclear white blood cells are not sensitised to apoptosis by NMR, showing that NMR may increase the differential cytotoxicity of antitumor drugs on tumor vs normal cells. This strong, differential potentiating effect of NMR on tumor cell apoptosis may have important implications, being in fact a possible adjuvant for antitumor therapies.

  14. Rare Renal Incidentaloma in Pregnancy: An Unusual Primitive Neuroectodermal Tumor Presentation

    OpenAIRE

    2015-01-01

    Peripheral Primitive Neuroectodermal Tumors (PNETs) are rare lesions that arise from outside the central nervous system and normally do not affect the genitourinary system. Primary renal presentations are extremely rare but given their aggressive behavior and characteristic cytomorphologic and genetic features should be considered well-defined distinct clinical entities in order to distinguish them from other primary tumors featuring round cells in the kidney. We report one case of PNET invol...

  15. T cell avidity and tumor recognition: implications and therapeutic strategies

    Directory of Open Access Journals (Sweden)

    Roszkowski Jeffrey J

    2005-09-01

    Full Text Available Abstract In the last two decades, great advances have been made studying the immune response to human tumors. The identification of protein antigens from cancer cells and better techniques for eliciting antigen specific T cell responses in vitro and in vivo have led to improved understanding of tumor recognition by T cells. Yet, much remains to be learned about the intricate details of T celltumor cell interactions. Though the strength of interaction between T cell and target is thought to be a key factor influencing the T cell response, investigations of T cell avidity, T cell receptor (TCR affinity for peptide-MHC complex, and the recognition of peptide on antigen presenting targets or tumor cells reveal complex relationships. Coincident with these investigations, therapeutic strategies have been developed to enhance tumor recognition using antigens with altered peptide structures and T cells modified by the introduction of new antigen binding receptor molecules. The profound effects of these strategies on T celltumor interactions and the clinical implications of these effects are of interest to both scientists and clinicians. In recent years, the focus of much of our work has been the avidity and effector characteristics of tumor reactive T cells. Here we review concepts and current results in the field, and the implications of therapeutic strategies using altered antigens and altered effector T cells.

  16. Ovarian metastasis in patient with endometrial carcinoma or synchronous tumors: Presentation of a case

    Directory of Open Access Journals (Sweden)

    Đorđević Momčilo

    2010-01-01

    Full Text Available Introduction. Synchronous, independent tumors are two or more tumors which appear independently from each other at the same moment. Metastatic tumors originate by disseminating malignant cells from other organs. Synchronous, primary malignities make 1.7% of all genitals malignities. Joined endometrial and ovarian carcinomas are found in 5% of cases. Presentation of a case. In this research, we present the case of an obese woman, 37 years old, who had associated endometrial tumors of uterus and ovary, without malign cells in peritoneal dilution, positive estrogen, negative progestine and focal expression of p53 receptors present in about 10-15% tumor cells. Discussion. This patient underwent the classic hysterectomy with reciprocal adnexectomy. After the operation, complete radial and hemiotheraphy was performed. The patient was without recurrence of the disease 30 months after the operation. The differentiation of primary independent synchronous and metastatic tumors is important not only for the prognosis, but also for the choice of the therapy. Conclusion. There are no reliable clinical and histological criteria for diagnoses. Most cases are most frequently regarded as higher stages.

  17. Granular cell tumors of the urinary bladder

    Directory of Open Access Journals (Sweden)

    Kayani Naila

    2007-03-01

    Full Text Available Abstract Background Granular cell tumors (GCTs are extremely rare lesions of the urinary bladder with only nine cases being reported in world literature of which one was malignant. Generally believed to be of neural origin based on histochemical, immunohistochemical, and ultrastructural studies; they mostly follow a clinically benign course but are commonly mistaken for malignant tumors since they are solid looking, ulcerated tumors with ill-defined margins. Materials and methods We herein report two cases of GCTs, one benign and one malignant, presenting with gross hematuria in a 14- and a 47-year-old female, respectively. Results Histopathology revealed characteristic GCTs with positive immunostaining for neural marker (S-100 and negative immunostaining for epithelial (cytokeratin, Cam 5.2, AE/A13, neuroendocrine (neuron specific enolase, chromogranin A, and synaptophysin and sarcoma (desmin, vimentin markers. The benign tumor was successfully managed conservatively with transurethral resection alone while for the malignant tumor, radical cystectomy, hysterectomy with bilateral salpingo-oophorectomy, anterior vaginectomy, plus lymph node dissection was done. Both cases show long-term disease free survival. Conclusion We recommend careful pathologic assessment for establishing the appropriate diagnosis and either a conservative or aggressive surgical treatment for benign or localized malignant GCT of the urinary bladder, respectively.

  18. Brain congenital tumors of atypical presentation. Tumores cerebrales congenitos de presentacion atipica

    Energy Technology Data Exchange (ETDEWEB)

    Borden Ferre, F.; Menor Serrano, F.; Martinez Fernandez, M.; Moreno Flores, A.; Poyatos, C. (Hospital La Fe. Valencia (Spain))

    1994-01-01

    We present four cases of brain tumor within the first year of life, with atypical clinical and radiological onset. Two astrocytomas of the visual pathway presented with visual changes without involving the ventricular system. The other two, not histologically confirmed, were located in the medial portion of the temporal lobe, the first sign of which was a cyanotic crisis.

  19. Tumor-infiltrating B lymphocytes as an efficient source of highly specific immunoglobulins recognizing tumor cells

    Directory of Open Access Journals (Sweden)

    Pelliccia Angela

    2007-10-01

    Full Text Available Abstract Background There is much evidence that tumor cells elicit a humoral immune response in patients. In most cases, the presence of antibodies in peripheral blood is detected only in small proportion of patients with tumors overexpressing the corresponding antigen. In the present study, we analyzed the significance of local humoral response provided by tumor-infiltrating lymphocytes in breast cancer patients. Methods The ability of a patient's immune system to produce specific antibodies inside tumor tissue, capable of recognizing tumor cells, was explored through analysis of the oligoclonality of antibodies derived from tumor-infiltrating lymphocytes and construction of a series of recombinant antibody libraries in scFv format, derived from breast tumor-infiltrating B lymphocytes. These libraries and one from peripheral blood lymphocytes of a single breast cancer patient were panned against three purified surface tumor antigens, such as CEA, MUC1 and ED-B domain, and against intact MCF7 breast carcinoma cells. Results Application of novel display vector, pKM19, allowed isolation of a large panel of breast cancer-specific antibodies against known tumor antigens, as well as against breast carcinoma cells. Reactivity of novel scFvs was confirmed by ELISA, immunohistochemistry, fluorescence staining and flow cytometry. We demonstrated that seven of ten primary breast tumor specimens, obtained using discarded surgical material, could be exploited as an appropriate source for generation of phage display libraries, giving highly specific antitumor antibodies which recognize heterologous tumor cells. Conclusion Local humoral immune response within tumor tissue in breast cancer patients frequently has an oligoclonal character. Efficient selection of specific antitumor antibodies from recombinant antibody libraries, derived from such oligoclonal tumor-infiltrated B lymphocytes, indicates the presence of natural immune response against tumor antigens

  20. Atypical Presentation of Atypical Teratoid Rhabdoid Tumor in a Child

    Directory of Open Access Journals (Sweden)

    Y. T. Udaka

    2013-01-01

    Full Text Available Atypical Teratoid Rhabdoid Tumor (ATRT is a rare malignant intracranial neoplasm more commonly diagnosed in young children. The authors report the case of an 11-year-old boy with a long standing history of slowly progressive weight loss, fatigue, and weakness over 1.5 years whose magnetic resonance imaging revealed a large heterogeneous enhancing dorsally exophytic lower brainstem mass. Examination revealed extreme cachexia, gaze-evoked nystagmus, dysphagia, dysarthria, bilateral dysmetria, and global weakness without ambulation. The protracted history and neuroimaging features were most suggestive of a low grade glioma. However, pathology revealed a hypercellular tumor with large hyperchromatic nucleoli and loss of INI-1 staining on immunohistochemistry consistent with a diagnosis of an ATRT. The child died shortly after surgery due to complications from his brainstem infiltrative disease. This case illustrates the diverse presentation of ATRT in childhood that can clinically and radiographically mimic that of low grade glioma.

  1. CARCINO I D TUMOR PRESENTING AS A PRIMARY MESENTERIC MASS

    Directory of Open Access Journals (Sweden)

    Nidhi

    2015-06-01

    Full Text Available We report a case of large primary mesenteric carcinoid tum or which was 7x7x4 cm. The 60 yr s old patient presented with the complaint of an abdominal mass since 1 yr. On radiology she was found to have a complex density mass surrounded by mesenteric fat with clear planes. On histopathology it was confirmed to be a carcinoid tumour of benign natur e. Primary mesenteric carcinoid tumor is very rare. 90% of them are found in GI tract with secondary involvement of mesentry in 40 - 80% cases when the size is larger than 2 cm. In this case it was a primary mesenteric tumour as there was no evidence of any o ther tumor. And second distant metastasis rate reported as 80% to 90% when they are larger than 2cm. The large size, primary mesenteric location and no metastasis despite large size make our case unique and rare.

  2. Robo-Enabled Tumor Cell Extrusion.

    Science.gov (United States)

    Richardson, Helena E; Portela, Marta

    2016-12-19

    How aberrant cells are removed from a tissue to prevent tumor formation is a key question in cancer biology. Reporting in this issue of Developmental Cell, Vaughen and Igaki (2016) show that a pathway with an important role in neural guidance also directs extrusion of tumor cells from epithelial tissues.

  3. Evolution of cooperation among tumor cells.

    Science.gov (United States)

    Axelrod, Robert; Axelrod, David E; Pienta, Kenneth J

    2006-09-01

    The evolution of cooperation has a well established theoretical framework based on game theory. This approach has made valuable contributions to a wide variety of disciplines, including political science, economics, and evolutionary biology. Existing cancer theory suggests that individual clones of cancer cells evolve independently from one another, acquiring all of the genetic traits or hallmarks necessary to form a malignant tumor. It is also now recognized that tumors are heterotypic, with cancer cells interacting with normal stromal cells within the tissue microenvironment, including endothelial, stromal, and nerve cells. This tumor cell-stromal cell interaction in itself is a form of commensalism, because it has been demonstrated that these nonmalignant cells support and even enable tumor growth. Here, we add to this theory by regarding tumor cells as game players whose interactions help to determine their Darwinian fitness. We marshal evidence that tumor cells overcome certain host defenses by means of diffusible products. Our original contribution is to raise the possibility that two nearby cells can protect each other from a set of host defenses that neither could survive alone. Cooperation can evolve as by-product mutualism among genetically diverse tumor cells. Our hypothesis supplements, but does not supplant, the traditional view of carcinogenesis in which one clonal population of cells develops all of the necessary genetic traits independently to form a tumor. Cooperation through the sharing of diffusible products raises new questions about tumorigenesis and has implications for understanding observed phenomena, designing new experiments, and developing new therapeutic approaches.

  4. Effect of tumor cells and tumor microenvironment on NK-cell function.

    Science.gov (United States)

    Vitale, Massimo; Cantoni, Claudia; Pietra, Gabriella; Mingari, Maria Cristina; Moretta, Lorenzo

    2014-06-01

    The ability of tumors to manage an immune-mediated attack has been recently included in the "next generation" of cancer hallmarks. In solid tumors, the microenvironment that is generated during the first steps of tumor development has a pivotal role in immune regulation. An intricate net of cross-interactions occurring between tumor components, stromal cells, and resident or recruited immune cells skews the possible acute inflammatory response toward an aberrant ineffective chronic inflammatory status that favors the evasion from the host's defenses. Natural killer (NK) cells have powerful cytotoxic activity, but their activity may be eluded by the tumor microenvironment. Immunosubversion, immunoediting or immunoselection of poorly immunogenic tumor cells and interference with tumor infiltration play a major role in evading NK-cell responses to tumors. Tumor cells, tumor-associated fibroblasts and tumor-induced aberrant immune cells (i.e. tolerogenic or suppressive macrophages, dendritic cells (DCs) and T cells) can interfere with NK-cell activation pathways or the complex receptor array that regulate NK-cell activation and antitumor activity. Thus, the definition of tumor microenvironment-related immunosuppressive factors, along with the identification of new classes of tissue-residing NK-like innate lymphoid cells, represent key issues to design effective NK-cell-based therapies of solid tumors.

  5. Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors

    Science.gov (United States)

    2016-08-25

    Desmoplastic Small Round Cell Tumor; Ewing Sarcoma of Bone or Soft Tissue; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

  6. Cancer Stem Cells and Pediatric Solid Tumors

    Directory of Open Access Journals (Sweden)

    Gregory K. Friedman

    2011-01-01

    Full Text Available Recently, a subpopulation of cells, termed tumor-initiating cells or tumor stem cells (TSC, has been identified in many different types of solid tumors. These TSC, which are typically more resistant to chemotherapy and radiation compared to other tumor cells, have properties similar to normal stem cells including multipotency and the ability to self-renew, proliferate, and maintain the neoplastic clone. Much of the research on TSC has focused on adult cancers. With considerable differences in tumor biology between adult and pediatric cancers, there may be significant differences in the presence, function and behavior of TSC in pediatric malignancies. We discuss what is currently known about pediatric solid TSC with specific focus on TSC markers, tumor microenvironment, signaling pathways, therapeutic resistance and potential future therapies to target pediatric TSC.

  7. Pulmonary tumor thrombotic microangiopathy with cor pulmonale due to desmoplastic small round cell tumor.

    Science.gov (United States)

    Sadimin, Evita T; Collier, Adrienne G; Gaffney, Joseph W; Fyfe, Billie

    2012-04-01

    A 12-year-old boy presented acutely after an episode of syncope with perioral cyanosis. He died 19 hours after admission due to cor pulmonale as a complication of metastatic desmoplastic small round cell tumor in the lungs with associated tumor thrombotic microangiopathy.

  8. Supratentorial primitive neuroectodermal tumor presenting with intracranial hemorrhage in adult

    Directory of Open Access Journals (Sweden)

    Bashar Abuzayed

    2014-01-01

    Full Text Available A 24-year-old female patient presented with complaints of nausea, vomiting and of loss of consciousness lasted for 15 minutes with left sided weakness. Neuroradiological evaluation revealed a hemorrhagic mass lesion in the right frontal lobe. The patient was operated and intraoperative findings showed a cortical-subcortical hematoma including hemorrhagic and disrupted tissue with a pathologic purple tissue on the periphery of the hematoma. Postoperative course was uneventful and postoperative histopathological examination revealed primitive neuroectodermal tumor. The patient was then referred to medical and radiation oncology clinics for further evaluation and treatment.

  9. Metastasis and circulating tumor cells

    NARCIS (Netherlands)

    Dalum, van G.; Holland, L.; Terstappen, L.W.M.M.

    2012-01-01

    Cancer is a prominent cause of death worldwide. In most cases, it is not the primary tumor which causes death, but the metastases. Metastatic tumors are spread over the entire human body and are more difficult to remove or treat than the primary tumor. In a patient with metastatic disease, circulati

  10. [Granular cell tumor of the larynx].

    Science.gov (United States)

    Modrzyński, M; Wróbel, B; Zawisza, E; Drozd, K

    1999-09-01

    Granular cell tumor is an unusual growth of probably neuroectodermal histogenesis, first reported by Abrikossoff in 1926 with the name of myoblastenmyoma. Authors described a case of a 54 year man with laryngeal seat of granular-cell myoblastoma. In this case Abrikossoff tumor was located in the right vocal chord. The tumor was treated successfully surgically by microlaryngoscopy. The etiology, clinical features and diagnostic difficulties are discussed.

  11. Malignant phyllodes tumor of the breast presenting with hypoglycemia: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Pacioles T

    2014-12-01

    Full Text Available Toni Pacioles,1 Rahul Seth,2,3 Cesar Orellana,3 Ivy John,4 Veera Panuganty,3 Ruban Dhaliwal3,5 1Department of Hematology and Oncology, Edwards Comprehensive Cancer Center, Marshall University, Huntington, WV, USA; 2Division of Hematology and Oncology, 3Department of Medicine, 4Department of Pathology, 5Division of Endocrinology, SUNY Upstate Medical University, Syracuse, NY, USA Abstract: Phyllodes tumors are rare fibroepithelial neoplasms that account for less than 1% of all breast tumors and are typically found in middle-aged women. Phyllodes tumors that present with hypoglycemia are even rarer. No one morphologic finding is reliable in predicting the clinical behavior of this tumor. Surgery has been the primary mode of treatment to date. However, the extent of resection and the role of adjuvant radiotherapy or chemotherapy are still controversial. Here, we present a challenging case of malignant phyllodes tumor of the breast associated with hypoglycemia, and review the literature regarding clinical findings, pathologic risk factors for recurrence, and treatment recommendations. Keywords: breast cancer, fibroepithelial neoplasm, neuroendocrine tumor, adjuvant treatment, non-islet cell tumor-induced hypoglycemia

  12. Granular cell tumors of the tracheobronchial tree.

    NARCIS (Netherlands)

    Maten, van der J; Blaauwgeers, JL; Sutedja, G.; Kwa, HB; Postmus, P.E.; Wagenaar, SS

    2003-01-01

    OBJECTIVE: To describe the population-based incidence and clinical characteristics of granular cell tumors of the tracheobronchial tree. METHODS: All newly registered tracheobronchial granular cell tumors in the Dutch Network and National Database for Pathology for 10 consecutive years (1990-1999) w

  13. Treatment Option Overview (Ovarian Germ Cell Tumors)

    Science.gov (United States)

    ... ovarian germ cell tumor are swelling of the abdomen or vaginal bleeding after menopause. Ovarian germ cell ... if you have either of the following: Swollen abdomen without weight gain in other parts of the ...

  14. General Information about Ovarian Germ Cell Tumors

    Science.gov (United States)

    ... ovarian germ cell tumor are swelling of the abdomen or vaginal bleeding after menopause. Ovarian germ cell ... if you have either of the following: Swollen abdomen without weight gain in other parts of the ...

  15. Immune Cells in Blood Recognize Tumors

    Science.gov (United States)

    NCI scientists have developed a novel strategy for identifying immune cells circulating in the blood that recognize specific proteins on tumor cells, a finding they believe may have potential implications for immune-based therapies.

  16. [Precocious pseudopuberty secondary to granulosa cell tumor].

    Science.gov (United States)

    Fernández, F; Jordán, J; Carmona, M; Oliver, A; Gracia, R; González, M; Peralta, A

    1984-12-01

    A case report of pseudoprecocity secondary to a unilateral ovarian tumor of granulosa cells is presented in a 13 month old female. Clinical manifestations appeared at two months of age as unilateral enlargement of the breast, development of pubic hair and vaginal discharge. Plasma estrogen levels were elevated, whereas there was no response of FSH and LH to LH-RH stimulation. The absence of a palpable abdominal mass and a normal ultrasound examination of the abdomen must be pointed out in our case. The suspected clinical and laboratory diagnosis was later confirmed by surgical abdominal examination and ovarian histopathology study. With the exception of a minimal breast enlargement which persists at two years of age, all other signs of pseudoprecocity have disappeared after the surgical removal of the neoplasm. The importance of surgical abdominal examination must be pointed out as a diagnostic method when clinical and laboratory findings suggest an ovarian tumor inspite of normal abdominal palpation, ultrasound and roentgenology.

  17. Tumor Seeding With Renal Cell Carcinoma After Renal Biopsy

    OpenAIRE

    M.F.B. Andersen; Norus, T.P.

    2016-01-01

    Tumor seeding following biopsy of renal cell carcinoma is extremely rare with an incidence of 1:10.000. In this paper two cases with multiple recurrent RRC metastasis in the biopsy tract following biopsy of renal tumor is presented and the current literature is shortly discussed.

  18. Androgen - secreting steroid cell tumor of the ovary

    Directory of Open Access Journals (Sweden)

    Paras Ratilal Udhreja

    2014-01-01

    Full Text Available Steroid cell tumors (SCTs, not otherwise specified of the ovary are rare subgroup of sex cord tumors, which account for less than 0.1% of all ovarian tumors and also that will present at any age. The majority of these tumors produce steroids with testosterone being the most common. A case of a 28-year-old woman who presented with symptoms of virilization is reported. Although SCTs are generally benign, there is a risk for malignant transformation. Surgery is the most important and hallmark treatment.

  19. Left inguinal lymphadenopathy as the solitary metastatic presentation of primitive neuroectodermal tumor of unknown origin

    Directory of Open Access Journals (Sweden)

    Tamojit Chaudhuri

    2013-01-01

    Full Text Available Primitive neuroectodermal tumor (PNET/ewing′s sarcoma is a rare neural crest tumor of central nervous system, thoracopulmonary regions, pelvis, and lower extremities. Visceral involvement by PNET is a rare phenomenon, with kidney being the most commonly involved organ. We report a 35-year-old Asian female presenting with left inguinal swelling, with computed tomography scan evidence of conglomerate lymph nodal mass in the left external iliac and inguinal region. A clinico-radiological diagnosis of lymphoproliferative disorder was made. She subsequently underwent excision biopsy. Histopathology of the biopsy specimen revealed completely effaced lymph nodal architecture, which was replaced by a tumor composed of nests of small, round, blue cells. On immunohistochemistry, the tumor cells were positive for CD99 and negative for CD3, CD20, leucocyte common antigen, epithelial membrane antigen, cytokeratin, desmin, vimentin, synaptophysin, and chromogranin A. Extensive search regarding any possible different site of involvement by the tumor was negative. The clinical presentation and histological, cytological, and immunohistochemical pattern, lead to the diagnosis of metastatic PNET of the left external iliac and inguinal lymph node with unknown primary origin. To the best of our knowledge, it is the first ever reported case of inguinal lymphadenopathy as the solitary metastatic presentation of PNET of unknown origin.

  20. Isolation of Circulating Tumor Cells by Dielectrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Gascoyne, Peter R. C., E-mail: pgascoyn@mdanderson.org [Department of Imaging Physics Research, The University of Texas M.D. Anderson Cancer Center Unit 951, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Shim, Sangjo [Department of Imaging Physics Research, The University of Texas M.D. Anderson Cancer Center Unit 951, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Department of Biomedical Engineering, The University of Texas at Austin, 1 University Station, C0800, Austin, TX 78712 (United States); Present address: Micro & Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, 208 North Wright Street, Urbana, IL 61801 (United States)

    2014-03-12

    Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a) the principles of DEP; (b) the biological basis for the dielectric differences between CTCs and blood cells; (c) why such differences are expected to be present for all types of tumors; and (d) instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF) is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies.

  1. Isolation of Circulating Tumor Cells by Dielectrophoresis

    Directory of Open Access Journals (Sweden)

    Peter R. C. Gascoyne

    2014-03-01

    Full Text Available Dielectrophoresis (DEP is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a the principles of DEP; (b the biological basis for the dielectric differences between CTCs and blood cells; (c why such differences are expected to be present for all types of tumors; and (d instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies.

  2. Adenovirus-mediated gene transfer to tumor cells.

    Science.gov (United States)

    Cascalló, Manel; Alemany, Ramon

    2004-01-01

    Cell transduction in vitro is only the first step toward proving that a genetherapy vector can be useful to treat tumors. However, tumor targeting in vivo is now the milestone for gene therapy to succeed against disseminated cancer. Therefore, most valuable information is obtained from studies of vector biodistribution. Owing to the hepatotropism of adenoviral vectors, a particularly important parameter is the tumor/liver ratio. This ratio can be given at the level of gene expression if the amount of transgene expression is measured. To optimize the targeting, however, the levels of viral particles that reach the tumor compared to other organs must be studied. Most of this chapter deals with methods to quantify the virus fate in tumor-bearing animals. We present a radioactive labeling method that can be used to study biodistribution. After a small section dealing with tumor models, we describe methods to quantify different parameters related to adenovirus-mediated tumor targeting.

  3. Circulating tumor cells in oral squamous cell carcinoma: An insight

    Directory of Open Access Journals (Sweden)

    B V Prakruthi

    2015-01-01

    Full Text Available Circulating tumor cells (CTCs are those cells present in the blood and have antigenic and/or genetic characteristics of a specific tumor type. CTCs can be detected in the peripheral blood of cancer patients. Various techniques are available for detection of CTCs, which provide evidence for future metastasis. CTCs may provide new insight into the biology of cancer and process of metastasis in oral squamous cell carcinoma (OSCC. The detection of CTCs may represent a new diagnostic tool for predicting the occurrence of metastatic disease in OSCC and endow with the treatment strategies to efficiently treat and prevent cancer metastasis. This review gives an insight into the significance of CTCs and different techniques for detection of CTCs.

  4. CellTracks cytometer for detection of circulating tumor cells

    NARCIS (Netherlands)

    Tibbe, A.G.J.; Kooi, van der A.; Groot, de M.R.; Vermes, I.

    2003-01-01

    Introduction: In patients with carcinomas, tumor cells are shed into the circulation. The number of the circulating tumor cells is low and technology is needed that has sufficient sensitivity and specificity to enumerate and characterize these cells. The CellTracks system was developed to provide an

  5. Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

    Institute of Scientific and Technical Information of China (English)

    Guanqun Qiao; Qingquan Li; Gang Peng; Jun Ma; Hongwei Fan; Yingbin Li

    2013-01-01

    Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are stil unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cel s and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cel s were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibril ary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibril ary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibril ary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cel s. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.

  6. Herceptin conjugates linked by EDC boost direct tumor cell death via programmed tumor cell necrosis.

    Directory of Open Access Journals (Sweden)

    Jiemiao Hu

    Full Text Available Tumor-targeted antibody therapy is one of the safest biological therapeutics for cancer patients, but it is often ineffective at inducing direct tumor cell death and is ineffective against resistant tumor cells. Currently, the antitumor efficacy of antibody therapy is primarily achieved by inducing indirect tumor cell death, such as antibody-dependent cell cytotoxicity. Our study reveals that Herceptin conjugates, if generated via the crosslinker EDC (1-ethyl-3-(3-dimethylaminopropyl carbodiimide hydrochloride, are capable of engendering human epidermal growth factor receptor 2 (Her2 positive tumor cells death. Using a high-performance liquid chromatography (HPLC system, three peaks with estimated molecular weights of antibody monomer, dimer, and trimer were isolated. Both Herceptin trimer and dimer separated by HPLC induced significant levels of necrotic tumor cell death, although the trimer was more effective than the dimer. Notably, the Herceptin trimer also induced Herceptin-resistant tumor cell death. Surprisingly different from the known cell death mechanism that often results from antibody treatment, the Herceptin trimer elicited effective and direct tumor cell death via a novel mechanism: programmed cell necrosis. In Her2-positive cells, inhibition of necrosis pathways significantly reversed Herceptin trimer-induced cell death. In summary, the Herceptin trimer reported herein harbors great potential for overcoming tumor cell resistance to Herceptin treatment.

  7. Dentinogenic Ghost Cell Tumor of the Peripheral Variant Mimicking Epulis

    Directory of Open Access Journals (Sweden)

    Uddipan Kumar

    2010-01-01

    Full Text Available Dentinogenic ghost cell tumor (DGCT is an uncommon locally invasive odontogenic tumor regarded by many as a variant of calcifying odontogenic cyst. The peripheral variant of this clinical rarity appears as a well-circumscribed mass mimicking a nonspecific gingival enlargement. Microscopic appearance of odontogenic epithelium admixed with focal areas of dentinoid formation and sheets of ghost cells giving the definitive diagnosis of dentinogenic ghost cell tumor imply that microscopic examination is compulsory for any gingival mass. Van Gieson histochemical stain further confirmed the nature of dentinoid-like material. A complete workup of a case of peripheral dentinogenic ghost cell tumor is presented in this paper and the current concept as well as the appraisal of literature is presented.

  8. Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis in Prostate Cancer Cells after Treatment with Xanthohumol-A Natural Compound Present in Humulus lupulus L.

    Science.gov (United States)

    Kłósek, Małgorzata; Mertas, Anna; Król, Wojciech; Jaworska, Dagmara; Szymszal, Jan; Szliszka, Ewelina

    2016-06-22

    TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is an endogenous ligand, which plays role in immune surveillance and anti-tumor immunity. It has ability to selectively kill tumor cells showing no toxicity to normal cells. We tested the apoptotic and cytotoxic activities of xanthohumol, a prenylated chalcone found in Humulus lupulus on androgen-sensitive human prostate adenocarcinoma cells (LNCaP) in combination with TRAIL. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium reduction assay (MTT) and lactate dehydrogenase assay (LDH). The expression of death receptors (DR4/TRAIL-R1 and DR5/TRAIL-R2) and apoptosis were detected using flow cytometry. We examined mitochondrial membrane potential (ΔΨm) by DePsipher reagent using fluorescence microscopy. The intracellular expression of proteins was evaluated by Western blotting. Our study showed that xanthohumol enhanced cytotoxic and apoptotic effects of TRAIL. The tested compounds activated caspases-3, -8, -9, Bid, and increased the expression of Bax. They also decreased expression of Bcl-xL and decreased mitochondrial membrane potential, while the expression of death receptors was not changed. The findings suggest that xanthohumol is a compound of potential use in chemoprevention of prostate cancer due to its sensitization of cancer cells to TRAIL-mediated apoptosis.

  9. Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis in Prostate Cancer Cells after Treatment with Xanthohumol—A Natural Compound Present in Humulus lupulus L.

    Directory of Open Access Journals (Sweden)

    Małgorzata Kłósek

    2016-06-01

    Full Text Available TRAIL (tumor necrosis factor-related apoptosis-inducing ligand is an endogenous ligand, which plays role in immune surveillance and anti-tumor immunity. It has ability to selectively kill tumor cells showing no toxicity to normal cells. We tested the apoptotic and cytotoxic activities of xanthohumol, a prenylated chalcone found in Humulus lupulus on androgen-sensitive human prostate adenocarcinoma cells (LNCaP in combination with TRAIL. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide tetrazolium reduction assay (MTT and lactate dehydrogenase assay (LDH. The expression of death receptors (DR4/TRAIL-R1 and DR5/TRAIL-R2 and apoptosis were detected using flow cytometry. We examined mitochondrial membrane potential (ΔΨm by DePsipher reagent using fluorescence microscopy. The intracellular expression of proteins was evaluated by Western blotting. Our study showed that xanthohumol enhanced cytotoxic and apoptotic effects of TRAIL. The tested compounds activated caspases-3, -8, -9, Bid, and increased the expression of Bax. They also decreased expression of Bcl-xL and decreased mitochondrial membrane potential, while the expression of death receptors was not changed. The findings suggest that xanthohumol is a compound of potential use in chemoprevention of prostate cancer due to its sensitization of cancer cells to TRAIL-mediated apoptosis.

  10. Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis in Prostate Cancer Cells after Treatment with Xanthohumol—A Natural Compound Present in Humulus lupulus L.

    Science.gov (United States)

    Kłósek, Małgorzata; Mertas, Anna; Król, Wojciech; Jaworska, Dagmara; Szymszal, Jan; Szliszka, Ewelina

    2016-01-01

    TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is an endogenous ligand, which plays role in immune surveillance and anti-tumor immunity. It has ability to selectively kill tumor cells showing no toxicity to normal cells. We tested the apoptotic and cytotoxic activities of xanthohumol, a prenylated chalcone found in Humulus lupulus on androgen-sensitive human prostate adenocarcinoma cells (LNCaP) in combination with TRAIL. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium reduction assay (MTT) and lactate dehydrogenase assay (LDH). The expression of death receptors (DR4/TRAIL-R1 and DR5/TRAIL-R2) and apoptosis were detected using flow cytometry. We examined mitochondrial membrane potential (ΔΨm) by DePsipher reagent using fluorescence microscopy. The intracellular expression of proteins was evaluated by Western blotting. Our study showed that xanthohumol enhanced cytotoxic and apoptotic effects of TRAIL. The tested compounds activated caspases-3, -8, -9, Bid, and increased the expression of Bax. They also decreased expression of Bcl-xL and decreased mitochondrial membrane potential, while the expression of death receptors was not changed. The findings suggest that xanthohumol is a compound of potential use in chemoprevention of prostate cancer due to its sensitization of cancer cells to TRAIL-mediated apoptosis. PMID:27338375

  11. Characterization of cell suspensions from solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pallavicini, M.

    1985-07-10

    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. Stages of Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... tumors include the following: Having certain genetic syndromes : Klinefelter syndrome may increase the risk of germ cell ... and procedures may be used: Physical exam and history : An exam of the body to check general ...

  13. Expressional patterns of chaperones in ten human tumor cell lines

    Directory of Open Access Journals (Sweden)

    Slavc Irene

    2004-12-01

    Full Text Available Abstract Background Chaperones (CH play an important role in tumor biology but no systematic work on expressional patterns has been reported so far. The aim of the study was therefore to present an analytical method for the concomitant determination of several CH in human tumor cell lines, to generate expressional patterns in the individual cell lines and to search for tumor and non-tumor cell line specific CH expression. Human tumor cell lines of neuroblastoma, colorectal and adenocarcinoma of the ovary, osteosarcoma, rhabdomyosarcoma, malignant melanoma, lung, cervical and breast cancer, promyelocytic leukaemia were homogenised, proteins were separated on two-dimensional gel electrophoresis with in-gel digestion of proteins and MALDI-TOF/TOF analysis was carried out for the identification of CH. Results A series of CH was identified including the main CH groups as HSP90/HATPas_C, HSP70, Cpn60_TCP1, DnaJ, Thioredoxin, TPR, Pro_isomerase, HSP20, ERP29_C, KE2, Prefoldin, DUF704, BAG, GrpE and DcpS. Conclusions The ten individual tumor cell lines showed different expression patterns, which are important for the design of CH studies in tumor cell lines. The results can serve as a reference map and form the basis of a concomitant determination of CH by a protein chemical rather than an immunochemical method, independent of antibody availability or specificity.

  14. Targeting tumor-associated antigens to the MHC class I presentation pathway.

    Science.gov (United States)

    Gross, G; Margalit, A

    2007-06-01

    There is little doubt that cytotoxic T lymphocytes (CTLs) can kill tumor cells in-vivo. However, most CTL-inducing immunization protocols examined so far in cancer patients have yielded only limited clinical benefits, underscoring the urge to improve current approaches for the effective induction of tumor-reactive CTLs. The tumor side of the immunological frontline is armed with large masses, high mutability and an arsenal of immune evasion and suppression mechanisms. Accordingly, the confronting CTLs should come in large numbers, recognize an assortment of MHC class I (MHC-I) bound tumor-associated peptides and be brought into action under effective immunostimulatory conditions. Naïve CTLs are activated to become effector cells in secondary lymphoid organs, following their productive encounter with MHC-I-bound peptides at the surface of dendritic cells (DCs). Therefore, many cancer vaccines under development focus on the optimization of peptide presentation by DCs at this critical stage. The elucidation of discrete steps and the subsequent identification of inherent bottlenecks in the MHC-I antigen presentation pathway have fueled elaborate efforts to enhance vaccine efficacy by the rational targeting of proteins or peptides, formulated into these vaccines, to this pathway. Protein- and gene-based strategies are accordingly devised to deliver tumor-associated peptides to selected cellular compartments, which are essential for the generation of functional CTL ligands. Many of these strategies target the conventional, endogenous route, while others harness the unique pathways that enable DCs to present exogenous antigens, known as cross-presentation. Here we dissect the intricate machinery that produces CTL ligands and examine how knowledge-based cancer vaccines can target the sequence of workstations, biochemical utensils and molecular intermediates comprising this production line.

  15. The glycan profile of endothelial cells in the present of tumor-conditioned medium and potential roles of beta-1,6-GlcNAc branching on HUVEC conformation.

    Science.gov (United States)

    Peng, Yunli; Li, Jing; Geng, Meiyu

    2010-07-01

    Endothelium plays a vital role in the logistics of the immune system, as well as the maintenance of the homeostasis. The major objective of this study is to unravel the relationship between expression changes of carbohydrate structures and the dysfunction of human umbilical vein endothelial cells (HUVEC) stimulated with tumor-conditioned medium (TCM), which is involved in tumor cell extravasation. Using flow cytometry (FCM) assay, the expression profiles of a selected group of 9 carbohydrate structures have been determined in HUVEC under control conditions and TCM-treated conditions, six of which increased significantly in expression after induction. Particularly, the expression level of beta-1,6-GlcNAc branching glycan was extremely higher after the stimulation. In parallel, the conformation change of HUVEC monolayer has been detected with inverted phase contrast microscopy and confocal microscopy. Under TCM stimulation, the actin cytoskeleton underwent rearrangement and formed abundant stress fiber within cells; therefore cell contraction was induced, which resulted in paracellular gap formation and barrier dysfunction. We furthered our study to investigate the mechanism underlying the conformation change of HUVEC. The results demonstrated that TCM induced the increase in beta-1,6-GlcNAc branching expression of PECAM-1, accompanied by the tyrosine phosphorylation of PECAM-1. The downstream effector RhoA was activated in consequence of the activation of PECAM-1. In conclusion, our results strongly suggested that the carbohydrate composition of endothelial cell surface is very important for the cells to exert their physiological effects correlated with cancer extravasation.

  16. Dysfunction of Murine Dendritic Cells Induced by Incubation with Tumor Cells

    Institute of Scientific and Technical Information of China (English)

    Fengguang Gao; Xin Hui; Xianghuo He; Dafang Wan; Jianren Gu

    2008-01-01

    In vivo studies showed that dendritic cell (DC) dysfunction occurred in tumor microcnvironment. As tumors were composed of many kinds of cells, the direct effects of tumor cells on immature DCs (imDCs) are needed for further studies in vitro. In the present study, bone marrow-derived imDCs were incubated with lymphoma, hepatoma and menaloma cells in vitro and surface molecules in imDCs were determined by flow cytometry. Then, imDCs incubated with tumor cells or control imDCs were further pulsed with tumor lysates and then incubated with splenocytes to perform mixed lymphocyte reaction. The DC-dependent tumor antigen-specific T cell proliferation,and IL-12 secretion were determined by flow cytometry, and enzyme-linked immunosorbent assay respectively.Finally, the DC-dependent tumor-associated antigen-specific CTL was determined by enzyme-linked immunospot assay. The results showed that tumor cell-DC incubation down-regulated the surface molecules in imDCs, such as CD80, CD54, CDllb, CD11a and MHC class Ⅱ molecules. The abilities of DC-dependent antigen-specific T cell proliferation and IL-12 secretion were also decreased by tumor cell incubation in vitro. Most importantly, the ability for antigenic-specific CTL priming of DCs was also decreased by incubation with tumor cells. In the present in vitro study demonstrated that the defective abilities of DCs induced by tumor cell co-incubation and the co-incubation system might be useful for future study of tumor-immune cells direct interaction and for drug screen of immune-modulation.

  17. Tumor-derived death receptor 6 modulates dendritic cell development.

    Science.gov (United States)

    DeRosa, David C; Ryan, Paul J; Okragly, Angela; Witcher, Derrick R; Benschop, Robert J

    2008-06-01

    Studies in murine models of cancer as well as in cancer patients have demonstrated that the immune response to cancer is often compromised. This paradigm is viewed as one of the major mechanisms of tumor escape. Many therapies focus on employing the professional antigen presenting dendritic cells (DC) as a strategy to overcome immune inhibition in cancer patients. Death receptor 6 (DR6) is an orphan member of the tumor necrosis factor receptor superfamily (TNFRSF21). It is overexpressed on many tumor cells and DR6(-/-) mice display altered immunity. We investigated whether DR6 plays a role in tumorigenesis by negatively affecting the generation of anti-tumor activity. We show that DR6 is uniquely cleaved from the cell surface of tumor cell lines by the membrane-associated matrix metalloproteinase (MMP)-14, which is often overexpressed on tumor cells and is associated with malignancy. We also demonstrate that >50% of monocytes differentiating into DC die when the extracellular domain of DR6 is present. In addition, DR6 affects the cell surface phenotype of the resulting immature DC and changes their cytokine production upon stimulation with LPS/IFN-gamma. The effects of DR6 are mostly amended when these immature DC are matured with IL-1beta/TNF-alpha, as measured by cell surface phenotype and their ability to present antigen. These results implicate MMP-14 and DR6 as a mechanism tumor cells can employ to actively escape detection by the immune system by affecting the generation of antigen presenting cells.

  18. Pindborg tumor of maxilla: Unusual presentation with review

    Directory of Open Access Journals (Sweden)

    Suresh Kumar Sachdeva

    2014-01-01

    Full Text Available The calcifying epithelial odontogenic tumor (CEOT, also known as the Pindborg tumor, is a rare benign odontogenic neoplasm, accounts for 0.4-3% of all odontogenic tumors. The CEOT is a benign, locally invasive, slow growing neoplasm occurring as intraosseous and extraosseous forms. The extraosseous variant is diagnosed slightly earlier (mean age 34.4 years than the intraosseous type (mean age 38.9 years, with equal gender predilection. The most frequent location is the mandibular premolar and molar area; less frequently the lesion is found in the maxilla. This case report is a peculiar case of Pindborg tumor characterized by a rare localization of the lesion extending from anterior to the posterior of the maxilla in a 76-year-old female.

  19. Large-cell Neuroendocrine Carcinoma of the Lung: Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Serra Valdés

    2014-11-01

    Full Text Available Lung cancer is the leading cause of death among malignant tumors. Pulmonary neuroendocrine tumors encompass a broad spectrum of tumors including the large-cell neuroendocrine carcinoma. The case of a 57-year-old white housewife with a history of smoking, diabetes, hypothyroidism and hypertension who sought medical attention because of headache, vomiting, weight loss, neuropsychiatric symptoms and metastatic inguinal lymphadenopathy is presented. The symptoms resulted from the extrapulmonary metastases found. Imaging studies, histology and immunohistochemistry confirmed the diagnosis of large-cell carcinoma of the lung with neuroendocrine pattern. This type of highly aggressive tumor is usually diagnosed when there are already multiple metastases, which affects the short-term prognosis. The aim of this paper is to inform the medical community of this case due to the scarce reports in the literature.

  20. Antitumor Cell-Complex Vaccines Employing Genetically Modified Tumor Cells and Fibroblasts

    Directory of Open Access Journals (Sweden)

    Antonio Miguel

    2014-02-01

    Full Text Available The present study evaluates the immune response mediated by vaccination with cell complexes composed of irradiated B16 tumor cells and mouse fibroblasts genetically modified to produce GM-CSF. The animals were vaccinated with free B16 cells or cell complexes. We employed two gene plasmid constructions: one high producer (pMok and a low producer (p2F. Tumor transplant was performed by injection of B16 tumor cells. Plasma levels of total IgG and its subtypes were measured by ELISA. Tumor volumes were measured and survival curves were obtained. The study resulted in a cell complex vaccine able to stimulate the immune system to produce specific anti-tumor membrane proteins (TMP IgG. In the groups vaccinated with cells transfected with the low producer plasmid, IgG production was higher when we used free B16 cell rather than cell complexes. Nonspecific autoimmune response caused by cell complex was not greater than that induced by the tumor cells alone. Groups vaccinated with B16 transfected with low producer plasmid reached a tumor growth delay of 92% (p ≤ 0.01. When vaccinated with cell complex, the best group was that transfected with high producer plasmid, reaching a tumor growth inhibition of 56% (p ≤ 0.05. Significant survival (40% was only observed in the groups vaccinated with free transfected B16 cells.

  1. Langerhans cell histiocytosis presenting as hypothyroid goitre: a unique presentation.

    Science.gov (United States)

    Marupudi, Krishna Chaitanya; Karanth, Suman S; Thomas, Joseph

    2014-12-02

    Langerhans cell histiocytosis (LCH) is a disease involving the antigen presenting cells, which can range from a single system involvement with an indolent course to a multisystem disease with increased morbidity. We present a rare case of LCH presenting as hypothyroid goitre that was successfully treated as per the LCH III trial protocol with a combination of vinblastine and oral prednisolone. We highlight the need for awareness of this rare presentation of LCH as a painless goitre which is often misdiagnosed as poorly differentiated thyroid carcinoma or overlooked as a benign disease.

  2. Klinefelter Syndrome with Poor Risk Extragonadal Germ Cell Tumor

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    Jeremy A. Konheim

    2017-01-01

    Full Text Available Germ cell tumors are the most common malignancy in men aged 15-35 years old, with a small percentage presenting in an extragonadal location. These tumors are seldom identified in the gastrointestinal tract. There is increased risk of extragonadal germ cell tumors (EGCT in men with Klinefelter syndrome (KS. We report a rare case of a 37-year-old male with KS and EGCT discovered in the duodenum and pelvis. After treatment with Bleomycin-Etoposide-Cisplatin (BEP, he developed growing teratoma syndrome (GTS and myelodysplasia. Despite surgical excision of the pelvic growing teratoma, he unfortunately died secondary to complications of severe bone marrow suppression.

  3. Klinefelter Syndrome with Poor Risk Extragonadal Germ Cell Tumor.

    Science.gov (United States)

    Konheim, Jeremy A; Israel, Jonathan A; Delacroix, Scott E

    2017-01-01

    Germ cell tumors are the most common malignancy in men aged 15-35 years old, with a small percentage presenting in an extragonadal location. These tumors are seldom identified in the gastrointestinal tract. There is increased risk of extragonadal germ cell tumors (EGCT) in men with Klinefelter syndrome (KS). We report a rare case of a 37-year-old male with KS and EGCT discovered in the duodenum and pelvis. After treatment with Bleomycin-Etoposide-Cisplatin (BEP), he developed growing teratoma syndrome (GTS) and myelodysplasia. Despite surgical excision of the pelvic growing teratoma, he unfortunately died secondary to complications of severe bone marrow suppression.

  4. Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells.

    Science.gov (United States)

    Hippen, Keli L; Harker-Murray, Paul; Porter, Stephen B; Merkel, Sarah C; Londer, Aryel; Taylor, Dawn K; Bina, Megan; Panoskaltsis-Mortari, Angela; Rubinstein, Pablo; Van Rooijen, Nico; Golovina, Tatiana N; Suhoski, Megan M; Miller, Jeffrey S; Wagner, John E; June, Carl H; Riley, James L; Blazar, Bruce R

    2008-10-01

    Previously, we showed that human umbilical cord blood (UCB) regulatory T cells (Tregs) could be expanded approximately 100-fold using anti-CD3/28 monoclonal antibody (mAb)-coated beads to provide T-cell receptor and costimulatory signals. Because Treg numbers from a single UCB unit are limited, we explored the use of cell-based artificial antigen-presenting cells (aAPCs) preloaded with anti-CD3/28 mAbs to achieve higher levels of Treg expansion. Compared with beads, aAPCs had similar expansion properties while significantly increasing transforming growth factor beta (TGF-beta) secretion and the potency of Treg suppressor function. aAPCs modified to coexpress OX40L or 4-1BBL expanded UCB Tregs to a significantly greater extent than bead- or nonmodified aAPC cultures, reaching mean expansion levels exceeding 1250-fold. Despite the high expansion and in contrast to studies using other Treg sources, neither OX40 nor 4-1BB signaling of UCB Tregs reduced in vitro suppression. UCB Tregs expanded with 4-1BBL expressing aAPCs had decreased levels of proapoptotic bim. UCB Tregs expanded with nonmodified or modified aAPCs versus beads resulted in higher survival associated with increased Treg persistence in a xeno-geneic graft-versus-host disease lethality model. These data offer a novel approach for UCB Treg expansion using aAPCs, including those coexpressing OX40L or 4-1BBL.

  5. Mediastinal germ cell tumors: a radiologic-pathologic review

    Energy Technology Data Exchange (ETDEWEB)

    Drevelegas, A. [Dept. of Radiology, Aristoteles Univ., Thessaloniki (Greece); Palladas, P. [Dept. of Radiology, G. Papanicolaou Hospital, Thessaloniki (Greece); Scordalaki, A. [Dept. of Pathology, G. Papanicolaou Hospital, Thessaloniki (Greece)

    2001-10-01

    Germ cell tumors of the mediastinum are histologically identical to those found in the testes and ovaries. Early diagnosis and treatment improve the survival rate. Imaging studies of teratoma demonstrate a rounded, often lobulated heterogeneous mass containing soft tissue elements with fluid and fat attenuation. Calcification is present in 20-43% of cases. Seminomas are large masses of homogeneous soft tissue attenuation. Malignant nonseminomatous germ cell tumors are heterogeneous tumors with irregular borders due to invasion of adjacent structures. CT shows the location and extent of the tumors as well as intrinsic elements including soft tissue, fat, fluid, and calcification. CT is the modality of choice for the diagnostic evaluation of these tumors. MRI reveals masses of heterogeneous signal intensity, is more sensitive in depicting infiltration of the adjacent structures by fat plane obliteration, and is performed as an ancillary study. (orig.)

  6. Myeloid cells contribute to tumor lymphangiogenesis.

    Science.gov (United States)

    Zumsteg, Adrian; Baeriswyl, Vanessa; Imaizumi, Natsuko; Schwendener, Reto; Rüegg, Curzio; Christofori, Gerhard

    2009-09-17

    The formation of new blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis) promotes tumor outgrowth and metastasis. Previously, it has been demonstrated that bone marrow-derived cells (BMDC) can contribute to tumor angiogenesis. However, the role of BMDC in lymphangiogenesis has largely remained elusive. Here, we demonstrate by bone marrow transplantation/reconstitution and genetic lineage-tracing experiments that BMDC integrate into tumor-associated lymphatic vessels in the Rip1Tag2 mouse model of insulinoma and in the TRAMP-C1 prostate cancer transplantation model, and that the integrated BMDC originate from the myelomonocytic lineage. Conversely, pharmacological depletion of tumor-associated macrophages reduces lymphangiogenesis. No cell fusion events are detected by genetic tracing experiments. Rather, the phenotypical conversion of myeloid cells into lymphatic endothelial cells and their integration into lymphatic structures is recapitulated in two in vitro tube formation assays and is dependent on fibroblast growth factor-mediated signaling. Together, the results reveal that myeloid cells can contribute to tumor-associated lymphatic vessels, thus extending the findings on the previously reported role of hematopoietic cells in lymphatic vessel formation.

  7. Myeloid cells contribute to tumor lymphangiogenesis.

    Directory of Open Access Journals (Sweden)

    Adrian Zumsteg

    Full Text Available The formation of new blood vessels (angiogenesis and lymphatic vessels (lymphangiogenesis promotes tumor outgrowth and metastasis. Previously, it has been demonstrated that bone marrow-derived cells (BMDC can contribute to tumor angiogenesis. However, the role of BMDC in lymphangiogenesis has largely remained elusive. Here, we demonstrate by bone marrow transplantation/reconstitution and genetic lineage-tracing experiments that BMDC integrate into tumor-associated lymphatic vessels in the Rip1Tag2 mouse model of insulinoma and in the TRAMP-C1 prostate cancer transplantation model, and that the integrated BMDC originate from the myelomonocytic lineage. Conversely, pharmacological depletion of tumor-associated macrophages reduces lymphangiogenesis. No cell fusion events are detected by genetic tracing experiments. Rather, the phenotypical conversion of myeloid cells into lymphatic endothelial cells and their integration into lymphatic structures is recapitulated in two in vitro tube formation assays and is dependent on fibroblast growth factor-mediated signaling. Together, the results reveal that myeloid cells can contribute to tumor-associated lymphatic vessels, thus extending the findings on the previously reported role of hematopoietic cells in lymphatic vessel formation.

  8. Acute effect of lactic acid on tumor-endothelial cell metabolic coupling in the tumor microenvironment

    Science.gov (United States)

    Zhu, Guanqun; Wang, Degui; Li, Shenqian; Yang, Xuecheng; Cao, Yanwei; Wang, Yonghua; Niu, Haitao

    2016-01-01

    The present study aimed to systematically analyze alterations in the expression of mitochondrial-associated proteins in human bladder cancer T24 cells co-cultured with tumor-associated human umbilical vein endothelial cells (HUVECs), and to investigate the characteristics of bladder cancer cell energy metabolism. The present study used the following techniques: A co-culture system of T24 cells and HUVECs was constructed using a microfluidic chip as a 3D co-culture system; the concentration of lactic acid in the medium of the cells was determined using an automatic microplate reader; a qualitative analysis of mitochondria-associated protein expression was performed by immunofluorescent staining; and a quantitative analysis of mitochondrial-associated protein expression was conducted using western blotting. The present results revealed that between the control groups (monoculture of T24 cells or HUVECs), the mitochondrial-associated protein fluorescence intensity was increased in the HUVECs compared with the T24 cells. The fluorescence intensity of mitochondrial-associated proteins in the HUVEC control group was increased compared with the HUVECs in the experimental co-culture group. In the T24 cells, the protein fluorescence intensity was increased in the experimental co-culture group compared with the control group. In addition, the expression of mitochondria-associated proteins was increased in HUVECs compared with T24 cells in the control groups, while T24 cells in the experimental co-culture group had an increased expression compared with HUVECs in the experimental group (P<0.05). For T24 cells, the expression of mitochondrial-associated proteins was increased in the experimental group compared with the control group, and contrasting results were observed for the HUVECs (P<0.05). Determination of lactic acid concentration demonstrated that lactic acid concentration was highest in the experimental co-culture group, followed by the T24 control group and the HUVEC

  9. Primitive neuroectodermal tumor in a mixed germ cell tumor - A rare case report

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    Khushboo Dewan

    2015-01-01

    Full Text Available A rare case of testicular tumor in a 20-year-old male with Primitive Neuroectodermal Tumor (PNET was reported. Imaging studies showed a large heterogenous mass in the right scrotal sac and a large retroperitoneal mass with metastasis in the lung and liver. Serum alpha fetoprotein (AFP was markedly elevated with moderate increase in serum β-human chorionic gonadotropin (hCG levels. After orchidectomy, a histological diagnosis of mixed germ cell tumor-teratoma with primitive neuroectodermal, embryonal, and yolk sac components was made. Some scattered embryoid bodies representative of primitive germ cell tumor were also present. Morphological diversity including PNET prompted the authors to report this case as PNET points toward a poor prognosis.

  10. [Sarcomatoid pleural mesothelioma presenting as posterior mediastinal tumor with dysphagia].

    Science.gov (United States)

    Togashi, K; Hosaka, Y; Sato, K

    2007-01-01

    Case 1: A 46-year-old man with dysphagia, chest pain and cough admitted to our department. Radiological studies demonstrated a solid mass with a maximal diameter of 5cm at the posterior mediastinum. The tumor was resected, then postoperative radiotherapy (60Gy) and chemotherapy were performed. Results of histological and immunohistochemical study showed that the tumor consisted of sarcomatoid mesothelioma. The patient died of recurrence with bone metastasis 6 months after surgery. Case 2: A 76-year-old man with dysphagia, chest pain and cough admitted to our department Radiological studies demonstrated a solid mass with a maximal diameter of 12cm in the posterior mediastinum. accompanied by abundant effusion in the bilateral pleural cavities. The patient underwent open biopsy and histological and immunohistochemical study showed that the tumor consisted of sarcomatoid mesothelioma. The patient died of multiple organ failure on the 1st postoperative day. We report extremely rare cases of sarcomatoid mesothelioma that appeared to be posterior mediastinal tumor before surgery, and discuss the difficulty of diagnosing sarcomatoid mesothelioma with atypical clinical manifestations.

  11. Cancer stem cell plasticity and tumor hierarchy

    Institute of Scientific and Technical Information of China (English)

    Marina Carla Cabrera; Robert E Hollingsworth; Elaine M Hurt

    2015-01-01

    The origins of the complex process of intratumoralheterogeneity have been highly debated and differentcellular mechanisms have been hypothesized to accountfor the diversity within a tumor. The clonal evolution andcancer stem cell (CSC) models have been proposed asdrivers of this heterogeneity. However, the concept ofcancer stem cell plasticity and bidirectional conversionbetween stem and non-stem cells has added additionalcomplexity to these highly studied paradigms and may helpexplain the tumor heterogeneity observed in solid tumors.The process of cancer stem cell plasticity in which cancercells harbor the dynamic ability of shifting from a non-CSCstate to a CSC state and vice versa may be modulated byspecific microenvironmental signals and cellular interactionsarising in the tumor niche. In addition to promoting CSCplasticity, these interactions may contribute to the cellulartransformation of tumor cells and affect response tochemotherapeutic and radiation treatments by providingCSCs protection from these agents. Herein, we review theliterature in support of this dynamic CSC state, discussthe effectors of plasticity, and examine their role in thedevelopment and treatment of cancer.

  12. Present and future of allogeneic natural killer cell therapy

    Directory of Open Access Journals (Sweden)

    Okjae eLim

    2015-06-01

    Full Text Available Natural killer (NK cells are innate lymphocytes that are capable of eliminating tumor cells and are therefore used for cancer therapy. Although many early investigators used autologous NK cells, including lymphokine-activated killer cells, the clinical efficacies were not satisfactory. Meanwhile, human leukocyte antigen (HLA-haploidentical hematopoietic stem cell transplantation revealed the anti-tumor effect of allogeneic NK cells, and HLA-haploidentical, killer cell immunoglobulin-like receptor (KIR ligand-mismatched allogeneic NK cells are currently used for many protocols requiring NK cells. Moreover, allogeneic NK cells from non-HLA-related healthy donors have been recently used in cancer therapy. The use of allogeneic NK cells from non-HLA-related healthy donors allows the selection of donor NK cells with higher flexibility and to prepare expanded, cryopreserved NK cells for instant administration without delay for ex vivo expansion. In cancer therapy with allogeneic NK cells, optimal matching of donors and recipients is important to maximize the efficacy of the therapy. In this review, we summarize the present state of allogeneic NK cell therapy and its future directions.

  13. Cytomorphology of Circulating Colorectal Tumor Cells: A Small Case Series

    Directory of Open Access Journals (Sweden)

    Dena Marrinucci

    2010-01-01

    Full Text Available Several methodologies exist to enumerate circulating tumor cells (CTCs from the blood of cancer patients; however, most methodologies lack high-resolution imaging, and thus, little is known about the cytomorphologic features of these cells. In this study of metastatic colorectal cancer patients, we used immunofluorescent staining with fiber-optic array scanning technology to identify CTCs, with subsequent Wright-Giemsa and Papanicolau staining. The CTCs were compared to the corresponding primary and metastatic tumors. The colorectal CTCs showed marked intrapatient pleomorphism. In comparison to the corresponding tissue biopsies, cells from all sites showed similar pleomorphism, demonstrating that colorectal CTCs retain the pleomorphism present in regions of solid growth. They also often retain particular cytomorphologic features present in the patient's primary and/or metastatic tumor tissue. This study provides an initial analysis of the cytomorphologic features of circulating colon cancer cells, providing a foundation for further investigation into the significance and metastatic potential of CTCs.

  14. Testicular germ cell tumors: Molecular genetic and clinicomorphological aspects

    Directory of Open Access Journals (Sweden)

    M. V. Nemtsova

    2015-03-01

    Full Text Available Testicular tumors are the most common form of solid cancer in young men. According to the 2004 WHO classification, testicular germ cell tumors (TGCT may present with different histological types. Embryonic cells of varying grade may be a source of TGCT and the occurrence of this type of tumors is directly related to the formation of a pool of male sex cells and gametogenesis. The paper gives information on mo- lecular stages for the process of formation of male sex cells in health, as well as ways of their impairments leading to TGCT. An investigation of the profiles of gene expression and the spectrum of molecular damages revealed genes responsible for a predisposition to the sporadic and hereditary forms of TGCT. The paper presents the current molecular genetic and clinicomorphological characteristics of TGCT. 

  15. Recent advances in molecular and cell biology of testicular germ-cell tumors.

    Science.gov (United States)

    Chieffi, Paolo

    2014-01-01

    Testicular germ-cell tumors (TGCTs) are the most frequent solid malignant tumors in men 20-40 years of age and the most frequent cause of death from solid tumors in this age group. TGCTs comprise two major histologic groups: seminomas and nonseminomas germ-cell tumors (NSGCTs). NSGCTs can be further divided into embryonal, carcinoma, Teratoma, yolk sac tumor, and choriocarcinoma. Seminomas and NSGCTs present significant differences in clinical features, therapy, and prognosis, and both show characteristics of the primordial germ cells. Many discovered biomarkers including OCT3/4, SOX2, SOX17, HMGA1, Nek2, GPR30, Aurora-B, estrogen receptor β, and others have given further advantages to discriminate between histological subgroups and could represent useful novel molecular targets for antineoplastic strategies. More insight into the pathogenesis of TGCTs is likely to improve disease management not only to better treatment of these tumors but also to a better understanding of stem cells and oncogenesis.

  16. Highlights on FOX03 and tumor-associated dendritic cells in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Kwong Y Tsang; James L Gulley

    2011-01-01

    @@ Cancer immunotherapy sometimes fails to provoke effective immune responses because of immunosuppressive mechanisms present in the tumor-bearing host.Dendritic cells (DCs) are the most potent antigenpresenting cells.After internalizing tumorassociated antigens (TAAs) at the tumor site,CCR7+ DCs traffic to the tumor-draining lymph nodes,where they influence the maturation of T cells.DCs may also be present at the tumor site.These tumor-associated DCs (TADCs) cross-present TAAs to recruited CD8+ T cells,which develop into TAA-specific effector cells.When activated,TADCs can mediate the sensitization of naive T cells that have been recruited into the tumor site.For this reason,interaction between tumor-infiltrating T cells and TADCs is essential for activating and maintaining specific antitumor immune responses.

  17. Gangliosides regulate tumor cell adhesion to collagen.

    Science.gov (United States)

    Kazarian, Tamara; Jabbar, Adnan A; Wen, Fei-Qui; Patel, Dharmesh A; Valentino, Leonard A

    2003-01-01

    The ability of tumor cells to adhere to extracellular matrix proteins is critical for migration and invasion. The factors that regulate tumor cell adhesion are poorly characterized. Gangliosides promote platelet adhesion and may also play a role in the adhesion of other cell types. We hypothesized that pharmacological depletion of membrane gangliosides from adherent cells would abrogate adhesion to collagen and promote migration and invasion. To test these hypotheses, LA-N1 neuroblastoma cells, which avidly adhere to collagen and are rich with membrane gangliosides (43.69 nmol/10(8) cells), were cultured in the presence of D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol-HCl. Endogenous gangliosides were reduced by 98% (0.76 nmol/10(8) cells) and adhesion to collagen decreased by 67%. There were no changes in cell morphology, viability, proliferation rate or apoptosis. Pre-incubation of ganglioside-depleted cells in conditioned medium from control cells restored adhesion to collagen (0.45 +/- 0.002), comparable to that of control cells (0.49 +/- 0.035). Similarly, pre-incubation of ganglioside-depleted cells with purified GD2 completely restored adhesion in a concentration-dependent manner. When LA-N1 cells were cultured with retinoic acid, a biological response modifier known to increase endogenous gangliosides, adhesion to collagen increased. Next, we questioned whether changes in adhesion would be reflected as changes in migration and invasion. Cells depleted of endogenous cellular gangliosides migrated more than control cells. Finally, control cells replete with their endogenous gangliosides demonstrated less invasive potential than control cells. The data demonstrate that endogenous tumor gangliosides increase neuroblastoma cell adhesion to collagen and reduce migration and invasion in vitro.

  18. Giant cell tumor of tendon sheath: Spectrum of radiologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Karasick, D.; Karasick, S. (Jefferson Medical Coll., Philadelphia, PA (United States) Thomas Jefferson Univ. Hospital, Philadelphia, PA (United States))

    1992-05-01

    Giant cell tumor of tendon sheath is the second most common tumor of the hand. It can also occur in larger joints. Radiologic features include a soft-tissue mass with or without osseous erosion. Less commonly, it can cause periostitis or permeative osseous invasion; it may rarely calcify. The entire imaging spectrum of this lesion is presented, with emphasis on atypical appearances which can mimic other lesions. (orig.).

  19. Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung Carcinoma

    Directory of Open Access Journals (Sweden)

    Teizo eYoshimura

    2015-06-01

    Full Text Available The chemokine MCP-1/CCL2 is produced by a variety of tumors and plays an important role in cancer progression. We and others previously demonstrated that the primary source of MCP-1 in several mouse tumors, including 4T1 breast cancer, M5076 sarcoma and B16 melanoma, was stromal cells. In the present study, we identified that tumor cells were the primary source of MCP-1 in Lewis lung carcinoma (LLC, because MCP-1 mRNA was highly expressed in tumors grown in both WT and MCP-1-/- mice with elevated serum MCP-1 levels. Since LLC cells isolated from tumors expressed low levels of MCP-1 in vitro, it appeared that the tumor-stromal cell interaction in a tumor microenvironment increased MCP-1 expression in LLC cells. In fact, co-culture of LLC cells with normal mouse peritoneal macrophages or normal lung cells containing macrophages increased MCP-1 expression by LLC cells. Macrophages from TNFα-/- mice failed to activate LLC cells and anti-TNFα neutralizing antibody abolished the effect of WT macrophages on LLC cells. When LLC cells were transplanted into TNFα-/- mice, the levels of MCP-1 mRNA in tumors and serum MCP-1 levels were markedly lower as compared to WT mice, and importantly tumors grew more slowly. Taken together, our results indicate that TNFα released by tumor cell-activated macrophages is critical for increased MCP-1 production by tumors cells. Thus, disruption of tumor-stromal cell interaction may inhibit tumor progression by reducing the production of tumor-promoting proinflammatory mediators, such as MCP-1.

  20. Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung Carcinoma.

    Science.gov (United States)

    Yoshimura, Teizo; Liu, Mingyong; Chen, Xin; Li, Liangzhu; Wang, Ji Ming

    2015-01-01

    The chemokine MCP-1/CCL2 is produced by a variety of tumors and plays an important role in cancer progression. We and others previously demonstrated that the primary source of MCP-1 in several mouse tumors, including 4T1 breast cancer, M5076 sarcoma, and B16 melanoma, was stromal cells. In the present study, we identified that tumor cells were the primary source of MCP-1 in Lewis lung carcinoma (LLC), because MCP-1 mRNA was highly expressed in tumors grown in both wild type (WT) and MCP-1(-/-) mice with elevated serum MCP-1 levels. Since LLC cells isolated from tumors expressed low levels of MCP-1 in vitro, it appeared that the tumor-stromal cell interaction in a tumor microenvironment increased MCP-1 expression in LLC cells. In fact, co-culture of LLC cells with normal mouse peritoneal macrophages or normal lung cells containing macrophages increased MCP-1 expression by LLC cells. Macrophages from TNFα(-/-) mice failed to activate LLC cells and anti-TNFα neutralizing antibody abolished the effect of WT macrophages on LLC cells. When LLC cells were transplanted into TNFα(-/-) mice, the levels of MCP-1 mRNA in tumors and serum MCP-1 levels were markedly lower as compared to WT mice, and importantly, tumors grew more slowly. Taken together, our results indicate that TNFα released by tumor cell-activated macrophages is critical for increased MCP-1 production by tumors cells. Thus, disruption of tumor-stromal cell interaction may inhibit tumor progression by reducing the production of tumor-promoting proinflammatory mediators, such as MCP-1.

  1. Giant cell tumor of bone: Multimodal approach

    Directory of Open Access Journals (Sweden)

    Gupta A

    2007-01-01

    Full Text Available Background: The clinical behavior and treatment of giant cell tumor of bone is still perplexing. The aim of this study is to clarify the clinico-pathological correlation of tumor and its relevance in treatment and prognosis. Materials and Methods: Ninety -three cases of giant cell tumor were treated during 1980-1990 by different methods. The age of the patients varied from 18-58 yrs with male and female ratio as 5:4. The upper end of the tibia was most commonly involved (n=31, followed by the lower end of the femur(n=21, distal end of radius(n=14,upper end of fibula (n=9,proximal end of femur(n=5, upper end of the humerus(n=3, iliac bone(n=2,phalanx (n=2 and spine(n=1. The tumors were also encountered on uncommon sites like metacarpals (n=4 and metatarsal(n=1. Fifty four cases were treated by curettage and bone grafting. Wide excision and reconstruction was performed in twenty two cases . Nine cases were treated by wide excision while primary amputation was performed in four cases. One case required only curettage. Three inaccessible lesions of ilium and spine were treated by radiotherapy. Results: 19 of 54 treated by curettage and bone grafting showed a recurrence. The repeat curettage and bone grafting was performed in 18 cases while amputation was done in one. One each out of the cases treated by wide excision and reconstruction and wide excision alone recurred. In this study we observed that though curettage and bone grafting is still the most commonly adopted treatment, wide excision of tumor with reconstruction has shown lesser recurrence. Conclusion: For radiologically well-contained and histologically typical tumor, curettage and autogenous bone grafting is the treatment of choice . The typical tumors with radiologically deficient cortex, clinically aggressive tumors and tumors with histological Grade III should be treated by wide excision and reconstruction.

  2. Immunosuppressive cells in tumor immune escape and metastasis.

    Science.gov (United States)

    Liu, Yang; Cao, Xuetao

    2016-05-01

    Tumor immune escape and the initiation of metastasis are critical steps in malignant progression of tumors and have been implicated in the failure of some clinical cancer immunotherapy. Tumors develop numerous strategies to escape immune surveillance or metastasize: Tumors not only modulate the recruitment and expansion of immunosuppressive cell populations to develop the tumor microenvironment or pre-metastatic niche but also switch the phenotype and function of normal immune cells from a potentially tumor-reactive state to a tumor-promoting state. Immunosuppressive cells facilitate tumor immune escape by inhibiting antitumor immune responses and furthermore promote tumor metastasis by inducing immunosuppression, promoting tumor cell invasion and intravasation, establishing a pre-metastatic niche, facilitating epithelial-mesenchymal transition, and inducing angiogenesis at primary tumor or metastatic sites. Numerous translational studies indicate that it is possible to inhibit tumor immune escape and prevent tumor metastasis by blocking immunosuppressive cells and eliminating immunosuppressive mechanisms that are induced by either immunosuppressive cells or tumor cells. Furthermore, many clinical trials targeting immunosuppressive cells have also achieved good outcome. In this review, we focus on the underlying mechanisms of immunosuppressive cells in promoting tumor immune escape and metastasis, discuss our current understanding of the interactions between immunosuppressive cells and tumor cells in the tumor microenvironment, and suggest future research directions as well as potential clinical strategies in cancer immunotherapy.

  3. Unusual Radiologic Finding of Intracranial Inflammatory Myofibroblastic Tumor Presenting a Cyst with Mural Nodule.

    Science.gov (United States)

    Park, Jong-Heok; Yoon, Wan-Soo; Chung, Dong-Sup

    2015-10-01

    An intracranial cyst tumor with a mural nodule can be representative of some types of brain tumors, but is a rare presentation of intracranial inflammatory myofibroblastic tumor (IMT). Herein, we report the case of an intracranial IMT in a 48-year-old woman presenting with the extremely unusual radiologic findings of a cyst with a mural nodule.

  4. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors.

    Science.gov (United States)

    Wyckoff, Jeffrey B; Wang, Yarong; Lin, Elaine Y; Li, Jiu-feng; Goswami, Sumanta; Stanley, E Richard; Segall, Jeffrey E; Pollard, Jeffrey W; Condeelis, John

    2007-03-15

    Although the presence of macrophages in tumors has been correlated with poor prognosis, until now there was no direct observation of how macrophages are involved in hematogenous metastasis. In this study, we use multiphoton microscopy to show, for the first time, that tumor cell intravasation occurs in association with perivascular macrophages in mammary tumors. Furthermore, we show that perivascular macrophages of the mammary tumor are associated with tumor cell intravasation in the absence of local angiogenesis. These results show that the interaction between macrophages and tumor cells lying in close proximity defines a microenvironment that is directly involved in the intravasation of cancer cells in mammary tumors.

  5. Oriented collagen fibers direct tumor cell intravasation

    KAUST Repository

    Han, Weijing

    2016-09-24

    In this work, we constructed a Collagen I-Matrigel composite extracellular matrix (ECM). The composite ECM was used to determine the influence of the local collagen fiber orientation on the collective intravasation ability of tumor cells. We found that the local fiber alignment enhanced cell-ECM interactions. Specifically, metastatic MDA-MB-231 breast cancer cells followed the local fiber alignment direction during the intravasation into rigid Matrigel (∼10 mg/mL protein concentration).

  6. T and NK cells: two sides of tumor immunoevasion.

    Science.gov (United States)

    Fruci, Doriana; Lo Monaco, Elisa; Cifaldi, Loredana; Locatelli, Franco; Tremante, Elisa; Benevolo, Maria; Giacomini, Patrizio

    2013-02-04

    Natural Killer (NK) cells are known to reject several experimental murine tumors, but their antineoplastic activity in humans is not generally agreed upon, as exemplified by an interesting correspondence recently appeared in Cancer Research. In the present commentary, we join the discussion and bring to the attention of the readers of the Journal of Translational Medicine a set of recent, related reports. These studies demonstrate that effectors of the adaptive and innate immunity need to actively cooperate in order to reject tumors and, conversely, tumors protect themselves by dampening both T and NK cell responses. The recently reported ability of indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2) expressed by melanoma cells to down-regulate activating NK receptors is yet another piece of evidence supporting combined and highly effective T/NK cell disabling. Major Histocompatibility Complex class I (MHC-I) molecules, including Human Leukocyte Antigen E (HLA-E), represent another class of shared activating/inhibitory ligands. Ongoing clinical trials with small molecules interfering with IDO and PGE2 may be exploiting an immune bonus to control cancer. Conversely, failure to simultaneously engage effectors of both the innate and the adaptive immunity may contribute to explain the limited clinical efficacy of T cell-only vaccination trials. Shared (T/NK cells) natural immunosuppressants and activating/inhibitory ligands expressed by tumor cells may provide mechanistic insight into impaired gathering and function of immune effectors at the tumor site.

  7. Myelin Basic Protein-Induced Production of Tumor Necrosis Factor-α and Interleukin-6, and Presentation of the Immunodominant Peptide MBP85-99 by B Cells from Patients with Relapsing-Remitting Multiple Sclerosis

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Börnsen, Lars; Sellebjerg, Finn

    2016-01-01

    to study cytokine production by B cells, but here we used the physiologically relevant self-antigen myelin basic protein (MBP) to stimulate B cells from untreated patients with RRMS and healthy donors. Moreover, we took advantage of the unique ability of the monoclonal antibody MK16 to recognize...... the immunodominant peptide MBP85-99 presented on HLA-DR15, and used it as a probe to directly study B-cell presentation of self-antigenic peptide. The proportions of B cells producing TNF-α or IL-6 after stimulation with MBP were higher in RRMS patients than in healthy donors, indicating a pro-inflammatory profile...... with reduced ability of B cells to produce IL-10 after stimulation with MBP, indicative of diminished B-cell immune regulatory function in patients with the most severe disease. Moreover, EDSS correlated positively with the frequencies of TNF-α, IL-6 and IL-10 producing B cells after polyclonal stimulation...

  8. Solitary fibrous tumor of the orbit presenting in pregnancy

    Directory of Open Access Journals (Sweden)

    Das Jayanta

    2009-01-01

    Full Text Available A 32-year-old woman, three months pregnant, reported with the complaint of protrusion of the right eye for six months. She gave history of rapid protrusion of eyeball for the last two months along with the history of double vision for the last one month. Computer tomography (CT scan revealed a well-defined mass lesion in the intraconal space of the right orbit which was excised through a lateral orbitotomy approach. Histological examination and immunohistochemistry revealed a solitary fibrous tumor, which showed a rapid progression in pregnancy.

  9. Management of nonfunctioning islet cell tumors

    Institute of Scientific and Technical Information of China (English)

    Han Liang; Pu Wang; Xiao-Na Wang; Jia-Cang Wang; Xi-Shan Hao

    2004-01-01

    AIM: To more clearly define the clinical and pathological characteristics and appropriate diagnosis and treatment of nonfunctioning (NFICTs) islet cell tumors, and to review our institutional experience over the last 30 years.METHODS: The records of 43 patients confirmed to have nonfunctioning islet cell tumors of pancreas were retrospectively reviewed. Survival was estimated by the Kaplan-Meier methods and potential risk factors for survival were compared with the log-rank tests.RESULTS: The mean age was 31.63 years (range, 8 to 67 years). There were 7 men and 36 women. Twentyeight patients had a confirmed diagnosis of nonfunctioning islet cell carcinoma (NFICC) and benign islet cell tumors were found in 15 patients. The most common symptoms in patients with NFICTs were abdominal pain (55.8%),nausea and/or vomiting (32.6%), fatigue (25.6%) and abdominal mass (23.3%). Preoperative ultrasonic and computed tomography localized the tumors in all patients.Forty-three NFICTs were distributed throughout the pancreas, with 21 located to the right of the superior mesenteric vessels, 10 in the body of the pancreas, 6 in the tail of the pancreas, and multiple tumors were found in one patient. Thirty-nine of 43 patients (91%) underwent surgical resection. Surgical treatment was curative in 30patients (70%) and palliative in 9(21%). The resectability and curative resection rate in patients with NFICC of pancreas were 89% and 61%, respectively. The overall cumulative 5- and 10-year survival rates for patients with NFICC were 58.05% and 29.03%, respectively. Radical operation and diameter of cancer small than :10 cm were positive prognostic factors in females younger than 30years old. Multivariate Cox regression analysis indicated that radical operation was the only independent prognostic factor, P=0.007.CONCLUSION: Nonfunctioning islet cell tumors of pancreas are found mainly in young women. The long-term results for patients undergone surgery, especially curative resection are

  10. Central granular cell odontogenic tumor: Report of an unusual case

    Directory of Open Access Journals (Sweden)

    Mani Madan

    2016-01-01

    Full Text Available Central granular cell odontogenic tumor (CGCOT is an unusual benign odontogenic neoplasm characterized by the presence of granular cells associated with apparently inactive odontogenic epithelium. These tumors tend to occur in the posterior mandible and usually present as well-defined unilocular or multilocular radiolucent lesions. So far, only <40 cases of CGCOT have been described in the literature under various terminologies. Though these tumors were not considered as distinct entity in the recent WHO classification of odontogenic tumors, long-term follow-up is recommended as malignant counterpart of CGCOT has already been reported. The main aim of this article is to report an additional case of CGCOT to the literature, occurring in a 73-year-old male.

  11. Primary cerebellar extramedullary myeloid cell tumor mimicking oligodendroglioma.

    Science.gov (United States)

    Ho, D M; Wong, T T; Guo, W Y; Chang, K P; Yen, S H

    1997-10-01

    Extramedullary myeloid cell tumors (EMCTs) are tumors consisting of immature cells of the myeloid series that occur outside the bone marrow. Most of them are associated with acute myelogenous leukemia or other myeloproliferative disorders, and a small number occur as primary lesions, i.e., are not associated with hematological disorders. Occurrence inside the cranium is rare, and there has been only one case of primary EMCT involving the cerebellum reported in the literature. The case we report here is a blastic EMCT occurring in the cerebellum of a 3-year-old boy who had no signs of leukemia or any hematological disorder throughout the entire course. The cerebellar tumor was at first misdiagnosed as an "oligodendroglioma" because of the uniformity and "fried egg" artifact of the tumor cells. The tumor disappeared during chemotherapy consisting of 12 treatments. However, it recurred and metastasized to the cerebrospinal fluid (CSF) shortly after the therapy was completed. A diagnosis of EMCT was suspected because of the presence of immature myeloid cells in the CSF, and was confirmed by anti-myeloperoxidase and anti-lysozyme immunoreactivity of the cerebellar tumor. The patient succumbed 1 year and 3 months after the first presentation of the disease.

  12. Dynamic visualization the whole process of cytotoxic T lymphocytes killing the B16 tumor cells in vitro

    Science.gov (United States)

    Qi, Shuhong; Zhang, Zhihong

    2016-03-01

    Cytotoxic T lymphocytes (CTLs) played a key role in the immune system to destroy the tumor cells. Although some mechanisms of CTLs killing the tumor cells are revealed already, the dynamic information of CTLs interaction with tumor cells are still not known very clearly. Here we used confocal microscopy to visualize the whole process of CTLs killing the tumor cells in vitro. The imaging data showed that CTLs destroyed the target tumor cells rapidly and efficiently. Several CTLs surrounded one or some tumor cells and the average time for CTLs destroying one tumor cell is just a few minutes in vitro. The study displayed the temporal events of CTLs interacting with tumor cells at the beginning and finally killing them and directly presented the efficient tumor cell cytotoxicity of the CTLs. The results helped us to deeply understand the mechanism of the CTLs destroying the tumor cells and to develop the cancer immunotherapy.

  13. T Cells as Antigen Carriers for Anti-tumor Vaccination.

    Science.gov (United States)

    Traversari, Catia; Russo, Vincenzo

    2016-01-01

    The exploitation of the physiologic processing and presenting machinery of dendritic cells (DCs) by in vivo loading of tumor-associated antigens may improve the immunogenic potential and clinical efficacy of DC-based cancer vaccines. The approach developed by our group was based on the clinical observation that some patients treated with the infusion of donor lymphocytes transduced to express the HSV-TK suicide gene for relapse of hematologic malignancies, after allogeneic hematopoietic stem cell transplantation, developed a T cell-mediated immune response specifically directed against the HSV-TK gene product.We demonstrated that lymphocytes genetically modified to express HSV-TK as well as self/tumor antigens, acting as antigen carriers, efficiently target DCs in vivo in tumor-bearing mice. The infusion of TRP-2-transduced lymphocytes induced the establishment of protective immunity and long-term memory in tumor-bearing mice by cross-presentation of the antigen mediated by the CD11c(+)CD8a(+) DCs subset. A similar approach was applied in a clinical setting. Ten patients affected by MAGE-3(+) metastatic melanoma were treated with autologous lymphocytes retrovirally transduced to express the MAGE-3 tumor antigen. In three patients, the treatment led to the increase of MAGE-3 specific CD8+ and CD4+ effectors and the development of long-term memory, which ultimately correlated with a favorable clinical outcome. Transduced lymphocytes represent an efficient way for in vivo loading of tumor-associated antigens of DCs.

  14. Circulating Tumor Cells in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Brian [Institute of Urology, University of Southern California, 1441 Eastlake Avenue, Suite 7416, Los Angeles, CA 90033 (United States); Rochefort, Holly [Department of Surgery, University of Southern California, 1520 San Pablo Street, HCT 4300, Los Angeles, CA 90033 (United States); Goldkorn, Amir, E-mail: agoldkor@usc.edu [Department of Internal Medicine and Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Suite 3440, Los Angeles, CA 90033 (United States)

    2013-12-04

    Circulating tumor cells (CTCs) can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management.

  15. Circulating Tumor Cells in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Brian Hu

    2013-12-01

    Full Text Available Circulating tumor cells (CTCs can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management.

  16. Circulating tumor cells: utopia or reality?

    Science.gov (United States)

    Conteduca, Vincenza; Zamarchi, Rita; Rossi, Elisabetta; Condelli, Valentina; Troiani, Laura; Aieta, Michele

    2013-09-01

    Circulating tumor cells (CTCs) could be considered a sign of tumor aggressiveness, but highly sensitive and specific methods of CTC detection are necessary owing to the rarity and heterogeneity of CTCs in peripheral blood. This review summarizes recent studies on tumor biology, with particular attention to the metastatic cascade, and the molecular characterization and clinical significance of CTCs. Recent technological approaches to enrich and detect these cells and challenges of CTCs for individualized cancer treatment are also discussed. This review also provides an insight into the positive and negative features of the future potential applications of CTC detection, which sometimes remains still a 'utopia', but its actual utility remains among the fastest growing research fields in oncology.

  17. Desmoplastic small round cell tumor of the kidney mimicking Wilms tumor: a case report and review of the literature.

    Science.gov (United States)

    da Silva, Rogério Cardoso; Medeiros Filho, Plínio; Chioato, Lucimara; Silva, Tácio R B; Ribeiro, Sérgio M; Bacchi, Carlos E

    2009-12-01

    Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive, malignant neoplasm usually present with the widespread abdominal serosal involvement and affects mainly adolescents and young adults. When presenting within visceral organs, as kidney, the diagnosis of DSRCT imposes significant difficulties. We present a case of primary DSRCT of the kidney in a 10-year-old boy mimicking clinically and pathologically Wilms tumor. The tumor showed morphologic and immunohistochemical features of DSRCT and the presence of the Ewing sarcoma and Wilm tumor 1 fusion transcripts resulting from the t(11;22) (p13;q12) reciprocal translocation. DSRCT should be considered in the differential diagnosis of Wilm tumor and other small blue-round cell tumors of the kidney.

  18. Syndecans in tumor cell adhesion and signaling

    Directory of Open Access Journals (Sweden)

    Rapraeger Alan C

    2004-01-01

    Full Text Available Abstract Anchorage of cells to "heparin" – binding domains that are prevalent in extracellular matrix (ECM components is thought to occur primarily through the syndecans, a four-member family of transmembrane heparan sulfate proteoglycans that communicate environmental cues from the ECM to the cytoskeleton and the signaling apparatus of the cell. Known activities of the syndecans trace to their highly conserved cytoplasmic domains and to their heparan sulfate chains, which can serve to regulate the signaling of growth factors and morphogens. However, several emerging studies point to critical roles for the syndecans' extracellular protein domains in tumor cell behavior to include cell adhesion and invasion. Although the mechanisms of these activities remain largely unknown, one possibility involves "co-receptor" interactions with integrins that may regulate integrin function and the cell adhesion-signaling phenotype. Thus, alterations in syndecan expression, leading to either overexpression or loss of expression, both of which take place in tumor cells, may have dramatic effects on tumor cell invasion.

  19. Determining Outdoor CPV Cell Temperature (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Muller, M.

    2011-04-01

    An accurate method is needed for determining cell temperature when measuring CPV modules outdoors. It has been suggested that cell temperature can be calculated though a procedure that shutters sunlight to the cells while measuring the transients in open-circuit voltage (Voc) and heat sink temperature. This presentation documents application of this shutter procedure to multiple CPV modules at NREL. The challenges and limitations are presented along with an alternate approach to measuring CPV cell operating temperature.

  20. Metabolic Hallmarks of Tumor and Immune Cells in the Tumor Microenvironment

    Science.gov (United States)

    Renner, Kathrin; Singer, Katrin; Koehl, Gudrun E.; Geissler, Edward K.; Peter, Katrin; Siska, Peter J.; Kreutz, Marina

    2017-01-01

    Cytotoxic T lymphocytes and NK cells play an important role in eliminating malignant tumor cells and the number and activity of tumor-infiltrating T cells represent a good marker for tumor prognosis. Based on these findings, immunotherapy, e.g., checkpoint blockade, has received considerable attention during the last couple of years. However, for the majority of patients, immune control of their tumors is gray theory as malignant cells use effective mechanisms to outsmart the immune system. Increasing evidence suggests that changes in tumor metabolism not only ensure an effective energy supply and generation of building blocks for tumor growth but also contribute to inhibition of the antitumor response. Immunosuppression in the tumor microenvironment is often based on the mutual metabolic requirements of immune cells and tumor cells. Cytotoxic T and NK cell activation leads to an increased demand for glucose and amino acids, a well-known feature shown by tumor cells. These close metabolic interdependencies result in metabolic competition, limiting the proliferation, and effector functions of tumor-specific immune cells. Moreover, not only nutrient restriction but also tumor-driven shifts in metabolite abundance and accumulation of metabolic waste products (e.g., lactate) lead to local immunosuppression, thereby facilitating tumor progression and metastasis. In this review, we describe the metabolic interplay between immune cells and tumor cells and discuss tumor cell metabolism as a target structure for cancer therapy. Metabolic (re)education of tumor cells is not only an approach to kill tumor cells directly but could overcome metabolic immunosuppression in the tumor microenvironment and thereby facilitate immunotherapy. PMID:28337200

  1. The critical role of the tumor microenvironment in shaping natural killer cell-mediated anti-tumor immunity

    Directory of Open Access Journals (Sweden)

    Joanna eBaginska

    2013-12-01

    Full Text Available Considerable evidence has been gathered over the last 10 years showing that the tumor microenvironment (TME is not simply a passive recipient of immune cells, but an active participant in the establishment of immunosuppressive conditions. It is now well documented that hypoxia, within the TME, affects the functions of immune effectors including natural killer (NK cells by multiple overlapping mechanisms. Indeed, each cell in the TME, irrespective of its transformation status, has the capacity to adapt to the hostile TME and produce immune modulatory signals or mediators affecting the function of immune cells either directly or through the stimulation of other cells present in the tumor site. This observation has led to intense research efforts focused mainly on tumor-derived factors. Notably, it has become increasingly clear that tumor cells secrete a number of environmental factors such as cytokines, growth factors, exosomes, and microRNAs impacting the immune cell response. Moreover, tumor cells in hostile microenvironments may activate their own intrinsic resistance mechanisms, such as autophagy, to escape the effective immune response. Such adaptive mechanisms may also include the ability of tumor cells to modify their metabolism and release several metabolites to impair the function of immune cells. In this review, we summarize the different mechanisms involved in the TME that affect the anti-tumor immune function of NK cells.

  2. Somatostatin receptor subtypes in neuroendocrine tumor cell lines and tumor tissues.

    Science.gov (United States)

    Jonas, S; John, M; Boese-Landgraf, J; Häring, R; Prevost, G; Thomas, F; Rosewicz, S; Riecken, E O; Wiedenmann, B; Neuhaus, P

    1995-01-01

    Somatostatin receptor scintigraphy (SRS) is positive in approximately 80% of all patients who have been found to have neuroendocrine (NE) gastroenteropancreatic (GEP) tumors. The reasons for negative results are unclear. The aim of the present study was identification of the specific somatostatin receptor (SSTR) subtypes that are responsible for the in vivo binding of the widely used somatostatin (SST) analogues octreotide and lanreotide in human neuroendocrine gastroenteropancreatic tumors. Ten patients were subjected to SRS with radiolabeled octreotide. Following surgical resection, tumor tissues were analyzed for SSTR subtype mRNA expression by the reverse transcription-polymerase chain reaction (RT-PCR). In addition, SSTR subtype transcripts were investigated by Northern blot analysis and RT-PCR in neuroendocrine tumor cell lines. Expression of SSTR at the protein level was studied by chemical cross-linking experiments. Three patients were negative by SRS. However, RT-PCR revealed most prominently SSTR 2 expression in all tumor specimens. In addition, all tumor tissues analyzed by chemical crosslinking exhibited SST-14 binding sites, indicating that at least some NE tumors were false-negative on SRS.

  3. Cerebral infratentorial large B-cell lymphoma presenting as Parkinsonism.

    Science.gov (United States)

    Lin, Chih-Ming; Hong, Kelvin

    2010-03-01

    Though rare, primary intracranial tumors can present with Parkinsonian symptoms, and diagnosis can be delayed unless there is a high index of suspicion. We herein present an 81-year-old man who was seen in our neurology clinic due to acute onset of unsteady gait and altered consciousness. Parkinsonism was initially diagnosed because of the typical manifestations. Levodopa was prescribed; however, there was a limited effect on his symptoms. Upon detail history and neurological examination, left sided hemiparesis was disclosed. Cerebral imaging studies revealed a solid mass over the right infratentorial para-midbrain area leading to reactive obstructive hydrocephalus. Work-up including chest and abdominal CT scanning, upper and lower GI endoscopy, and tumor marker studies failed to uncover any abnormalities. A neurosurgeon was consulted and a shunt procedure and biopsy of the infratentorial mass were performed. Histopathological examination of the biopsy tissue revealed tumor diffusely intermixed with large cells consistent with large B-cell lymphoma. The patient and his family declined further treatment. Though rare, cerebral tumors can present with Parkinsonian features and represent a diagnostic challenge. Clinicians should be aware of the possibility of cerebral neoplasms causing Parkinsonism, and include them in the differential diagnosis, especially for patients presenting with atypical Parkinsonian features, or those not responsive to initial therapy.

  4. How do CD4+ T cells detect and eliminate tumor cells that either lack or express MHC class II molecules?

    Directory of Open Access Journals (Sweden)

    Ole Audun Werner Haabeth

    2014-04-01

    Full Text Available CD4+ T cells contribute to tumor eradication, even in the absence of CD8+ T cells. Cytotoxic CD4+ T cells can directly kill MHC class II positive tumor cells. More surprisingly, CD4+ T cells can indirectly eliminate tumor cells that lack MHC class II expression. Here, we review the mechanisms of direct and indirect CD4+ T cell-mediated elimination of tumor cells. An emphasis is put on T cell receptor (TCR transgenic models, where anti-tumor responses of naïve CD4+ T cells of defined specificity can be tracked. Some generalizations can tentatively be made. For both MHCIIPOS and MHCIINEG tumors, presentation of tumor specific antigen by host antigen presenting cells (APCs appears to be required for CD4+ T cell priming. This has been extensively studied in a myeloma model (MOPC315, where host APCs in tumor-draining lymph nodes are primed with secreted tumor antigen. Upon antigen recognition, naïve CD4+ T cells differentiate into Th1 cells and migrate to the tumor. At the tumor site, the mechanisms for elimination of MHCIIPOS and MHCIINEG tumor cells differ. In a TCR transgenic B16 melanoma model, MHCIIPOS melanoma cells are directly killed by cytotoxic CD4+ T cells in a perforin/granzyme B-dependent manner. By contrast, MHCIINEG myeloma cells are killed by IFN-g stimulated M1-like macrophages. In summary, while the priming phase of CD4+ T cells appears similar for MHCIIPOS and MHCIINEG tumors, the killing mechanisms are different. Unresolved issues and directions for future research are addressed.

  5. Escape from Tumor Cell Dormancy

    Science.gov (United States)

    2012-10-01

    with embryogenesis and wound repair (onco-fetal-wound connection). In normal physiological TN-C establishes interactions between the epithelium and the...cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res, 53(7), 1690-5 (1993) 185. B. Saha, B...Villette and N. J. Maitland: Prostate epithelial cell lines form spheroids with evidence of glandular differentiation in three-dimensional Matrigel

  6. Renal cell carcinoma with areas mimicking renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma.

    Science.gov (United States)

    Petersson, Fredrik; Grossmann, Petr; Hora, Milan; Sperga, Maris; Montiel, Delia Perez; Martinek, Petr; Gutierrez, Maria Evelyn Cortes; Bulimbasic, Stela; Michal, Michal; Branzovsky, Jindrich; Hes, Ondrej

    2013-07-01

    We present a cohort of 8 renal carcinomas that displayed a variable (5%-95% extent) light microscopic appearance of renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma (RAT/CCPRCC) without fulfilling the criteria for these tumors. All but 1 case predominantly (75%-95% extent) showed histopathologic features of conventional clear cell renal cell carcinoma. In 5 of 7 cases with mostly conventional clear renal cell carcinoma (CRCC) morphology, a diagnosis of CRCC was supported by the molecular genetic findings (presence of von Hippel-Lindau tumor suppressor [VHL] mutation and/or VHL promoter methylation and/or loss of heterozygosity [LOH] for 3p). Of the other 2 cases with predominantly characteristic CRCC morphology, 1 tumor did not reveal any VHL mutation, VHL promoter methylation, or LOH for 3p, and both chromosomes 7 and 17 were disomic, whereas the other tumor displayed polysomy for chromosomes 7 and 17 and no VHL mutation, VHL promoter methylation, or LOH for 3p. One tumor was composed primarily (95%) of distinctly RAT/CCPRCC-like morphology, and this tumor harbored a VHL mutation and displayed polysomy for chromosomes 7 and 17. Of the 5 cases with both histomorphologic features and molecular genetic findings of CRCC, we detected significant immunoreactivity for α-methylacyl-CoA racemase in 2 cases and strong diffuse immunopositivity for cytokeratin 7 in 3 cases. Despite the combination of positivity for α-methylacyl-CoA racemase and cytokeratin 7 in 2 cases, there was nothing to suggest of the possibility of a conventional papillary renal cell carcinoma with a predominance of clear cells.

  7. The cytology of a thyroid granular cell tumor.

    Science.gov (United States)

    Chang, Shu-Mei; Wei, Chang-Kuo; Tseng, Chih-En

    2009-01-01

    Granular cell tumor (GCT) of the thyroid is rare. Before this report, only four cases of thyroid GCT have been reported, none of which presented a cytopathological examination. In this paper, we report the fine needle aspiration cytology and pathological analysis of a thyroid GCT from a 12-year-old girl who presented with a painless neck mass. The tumor cells were single, in syncytial clusters, or pseudofollicles, contained small round, oval, or spindle nuclei, indistinct nucleoli, and a large amount of grayish, granular fragile cytoplasm. The background contained granular debris and naked nuclei. A differential diagnosis of thyroid GCT with more frequent thyroid lesions containing cytoplasmic granules, including Hurthle cells, macrophages, follicular cells, and cells of black thyroid syndrome, was also performed.

  8. Detection of circulating tumor cells in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Annkathrin eHanssen

    2015-09-01

    Full Text Available Lung Cancer is the most common cause of cancer related deaths that frequently metastasizes prior to disease diagnosis. Circulating tumor cells (CTCs are found in many different types of epithelial tumors and are of great clinical interest in terms of prognosis and therapy intervention. Here, we present and discuss EpCAM-dependent and -independent capture of CTCs in non-small cell lung cancer (NSCLC and the clinical relevance of CTC detection and characterization. Taking blood samples and analyzing CTCs as liquid biopsy might be a far less invasive diagnostic strategy than biopsies of lung tumors or metastases. Moreover, sequential blood sampling allows to study the dynamic changes of tumor cells during therapy, in particular the development of resistant tumor cell clones.

  9. Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Kazumasa [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Hiroi, Miki [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Shimada, Jun [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Ohmori, Yoshihiro, E-mail: ohmori@dent.meikai.ac.jp [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan)

    2011-09-28

    Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163{sup +} cells were significantly increased based on the pathological grade. CD163{sup +} cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163{sup +} cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4{sup +} and CD8{sup +} T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163{sup +} TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC.

  10. The biology of circulating tumor cells.

    Science.gov (United States)

    Pantel, K; Speicher, M R

    2016-03-10

    Metastasis is a biologically complex process consisting of numerous stochastic events which may tremendously differ across various cancer types. Circulating tumor cells (CTCs) are cells that are shed from primary tumors and metastatic deposits into the blood stream. CTCs bear a tremendous potential to improve our understanding of steps involved in the metastatic cascade, starting from intravasation of tumor cells into the circulation until the formation of clinically detectable metastasis. These efforts were propelled by novel high-resolution approaches to dissect the genomes and transcriptomes of CTCs. Furthermore, capturing of viable CTCs has paved the way for innovative culturing technologies to study fundamental characteristics of CTCs such as invasiveness, their kinetics and responses to selection barriers, such as given therapies. Hence the study of CTCs is not only instrumental as a basic research tool, but also allows the serial monitoring of tumor genotypes and may therefore provide predictive and prognostic biomarkers for clinicians. Here, we review how CTCs have contributed to significant insights into the metastatic process and how they may be utilized in clinical practice.

  11. Giant cell tumor of the temporal bone – a case report

    Directory of Open Access Journals (Sweden)

    Rao Saraswathi G

    2005-09-01

    Full Text Available Abstract Background Giant cell tumor is a benign but locally aggressive bone neoplasm which uncommonly involves the skull. The petrous portion of the temporal bone forms a rare location for this tumor. Case presentation The authors report a case of a large giant cell tumor involving the petrous and squamous portions of the temporal bone in a 26 year old male patient. He presented with right side severe hearing loss and facial paresis. Radical excision of the tumor was achieved but facial palsy could not be avoided. Conclusion Radical excision of skull base giant cell tumor may be hazardous but if achieved is the optimal treatment and may be curative.

  12. Tumoral calcinosis presenting as an extradural mass: MR findings and pathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    Iglesias, A.; Arias, M.; Brasa, J. [Unidad de Resonancia Magnetica (MEDTEC), Hospital Xeral-Cies, 36204 Vigo (Spain); Gonzalez, A. [Servicio de Anatomia Patologica, Hospital Xeral-Cies, 36204 Vigo (Spain); Conde, C. [Servicio de Neurocirugia, Hospital Xeral-Cies, 36204 Vigo (Spain)

    2002-09-01

    Two cases of idiopathic tumoral calcinosis presenting as an extradural mass are reported. There are few reports in the literature of this pathological process presenting as extradural masses, so both cases represent very unusual locations for tumoral calcinosis. Magnetic resonance imaging features and pathological correlation of these two cases are presented. Tumoral calcinosis might be considered as a rare but possible cause of extradural mass. (orig.)

  13. Granular cell tumor with orbital involvement in a child

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Fabiano [Universidade Estadual de Campinas (FCM/UNICAMP), SP (Brazil). Fac. de Ciencias Medicas. Dept. de Radiologia; Iyeyasu, Josie Naomi; Carvalho, Keila Monteiro de [Universidade Estadual de Campinas (FCM/UNICAMP), SP (Brazil). Fac. de Ciencias Medicas. Dept. de Oftalmo-Otorrinolaringologia; Altemani, Albina Messias [Universidade Estadual de Campinas (FCM/UNICAMP), SP (Brazil). Fac. de Ciencias Medicas. Dept. de Anatomia Patologica

    2011-09-15

    The authors report a rare case of granular cell tumor in the left medial rectus muscle of a seven-year-old boy. Clinical, pathologic and radiologic findings of the present case are described and a brief literature review is undertaken. (author)

  14. In Vivo Imaging of Natural Killer Cell Trafficking in Tumors

    NARCIS (Netherlands)

    Galli, Filippo; Rapisarda, Anna Serafina; Stabile, Helena; Malviya, Gaurav; Manni, Isabella; Bonanno, Elena; Piaggio, Giulia; Gismondi, Angela; Santoni, Angela; Signore, Alberto

    2015-01-01

    Natural killer cells (NKs) are important effectors of the innate immune system, with marked antitumor activity. Imaging NK trafficking in vivo may be relevant to following up the efficacy of new therapeutic approaches aiming at increasing tumor-infiltrating NKs (TINKs). The specific aims of present

  15. Clear cell variant of calcifying epithelial odontogenic tumor of maxilla: Report of a rare case.

    Science.gov (United States)

    Badrashetty, Dinesh; Rangaswamy, Shruthi; Belgode, Niranjan

    2013-09-01

    The calcifying epithelial odontogenic tumor (CEOT) is a rare benign tumor of the jaws. Pindborg's tumor having clear cells is extremely rare. Twelve central lesions have been reported of which only three cases have occurred in maxilla. Clear cell variant is a distinct entity, has more aggressive biological behavior and higher chances of recurrence. Hence it is important that presence of clear cells be included in histopathological diagnosis. Here we present a rare case of clear cell CEOT having aggressive behavior.

  16. Malignant transformation and treatment of cystic mixed germ cell tumor

    Institute of Scientific and Technical Information of China (English)

    Yapeng Zhao; Hongyu Duan; Qinghui Zhang; Bingxin Shi; Hui Liang; Yuqi Zhang

    2016-01-01

    Objective: The authors report an extremely unusual presentation and management of a children pineal mixed germ cell tumor mainly composed of immature teratoma, aiming to summarize main theraptic points by literature review. Methods: A cystic lesion located in the rear of third ventricle in a child was detected 3 years ago with no other therapy performed except for a ventriculo-peritoneal shunt. During the following 3 years, intermitted regular brain MRI demonstrated no evidence of lesion aggrandizement. However from 20 days before admission to our institute the patient began to present acutely with exacerbating clinical symptoms meanwhile brain MRI showed signs of abrupt revulsions of initial lesion without any incentive cause. Neurological examination revealed a significant rising of serum tumor marker level. Then surgical resection was performed immediately after admission which was followed by correlative two-course chemotherapy. Results: Postoperative brain MRI demonstrated totally removing of the lesion in rear of third ventricle. Serum tumor marker level decreased remarkably after surgery and declined to normal level after two-course chemotherapy. No obvious neurological deficit occurred except for short-term memory difficulty which gradually recovered within two weeks. Soon after the second course chemotherapy the patient was currently asymptomatic and returned to school. Conclusions: (1) To ensure definitive diagnosis and proper therapecutic protocols benefit from grasping clinical features of mixed germ cell tumor. (2) Overall preoperative investigation including serum tumor marker level is as critical as neurological imaging examination. (3) Surgical excision is confirmed to be the key modality of treatment. With the regarding of mixed germ cell tumor, never highlight total resection too much. (4) Postoperative adjuvant chemotherapy is recommended as further intensive treatment to improve the prognosis of mix germ cell tumor.

  17. Cell cycle regulatory factors in juxta-tumoral renal parenchyma.

    Science.gov (United States)

    Petruşcă, Daniela Nicoleta; Petrescu, Amelia; Vrabie, Camelia; Niculescu, L; Jinga, V; Diaconu, Carmen; Braşoveanu, Lorelei

    2005-01-01

    The aim of this study was to evaluate regulatory cell cycle factors in juxta-tumoral renal parenchyma in order to obtain information regarding early primary changes occurred in normal renal cells. Specimens of juxta-tumoral renal parenchyma were harvested from the tumoral kidney in 10 patients with no history of treatment before surgery. The expression of p53, Bcl-2, Rb and PCNA was studied by immunohistochemical methods in paraffin-embedded tissues. The apoptotic status was evaluated by flow-cytometry analysis following propidium iodide incorporation. The p53 protein expression was recognized in most of the cases (80%) with different intensities. High intensity apoptotic process detected in juxta-tumoral parenchyma seemed to be p53 dependent and well correlated with the low Bcl-2 expression. 70% of cases were Rb positive. In this type of tissue Rb has only an anti-proliferative and anti-tumoral role. PCNA was present in half of the cases being low expressed due to the tissue regenerating mechanism. Our data suggest that the high intensity of programmed cell death in this type of tissue is supported by the status of cell regulatory factors that control this process. Previous studies have demonstrated that healthy renal tissue has neither apoptosis nor mitotic activity. Juxta-tumoral renal tissue is also displaying normal morphology and DNA content (diploidy) but the microenvironmental status induced by the tumor presence prompts cells to choose death rather than malignant transformation. Further studies are necessary to emphasize if these results have a clinical relevance for the outcome of therapeutical approaches in renal carcinomas.

  18. Investigation on the effect of peptides mixture from tumor cells inducing anti-tumor specific immune response

    Institute of Scientific and Technical Information of China (English)

    冯作化; 黄波; 张桂梅; 李东; 王洪涛

    2002-01-01

    The peptides mixture was prepared from tumor cells by freezing-thawing cells, precipitation by heating, followed by acidification of the solution. The activation and proliferation of mouse splenocytes by HSP70-peptide complex, formed by the binding of HSP70 and peptides in vitro, were observed, so was the specific cytotoxicity of the proliferative lymphocytes to tumor cells. The phenotypes of the proliferative lymphocytes were analyzed by a flow cytometer. BALB/c mice inoculated with H22 hepatocarcinoma cells in peritoneal cavity or hind thigh were immunized by injection with HSP70-peptides complex to observe the inhibitory effect of the immunization on tumor and lifetime of tumor-bearing mice. On the other hand, blood samples were collected from the immunized mice to check the functions of liver and kidney. The results showed that the peptides mixture from tumor cells contained tumor-specific antigen peptides which could be presented by HSP70 to activate lymphocytes in vitro, the proliferative lymphocytes were T cells which were specifically cytotoxic to tumor cells, the in vivo growth of both ascitic and solid carcinoma could be suppressed by immunization with HSP70-peptides and the lifetime of tumor-bearing mice was prolonged, the in vivo immunization with HSP70-H22-peptides had no impact on the function of mouse liver and kidney, suggesting that there was no occurrence of autoimmunity in vivo after immunization.

  19. Primary desmoplastic small round cell tumor of the femur

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Akihiko; Garcia, Joaquin [Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, NY (United States); Edgar, Mark A. [Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States); Meyers, Paul A. [Weill Medical College of Cornell University, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Pediatrics, New York, NY (United States); Morris, Carol D. [Weill Medical College of Cornell University, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Surgery, Orthopaedic Service, New York, NY (United States); Panicek, David M. [Weill Medical College of Cornell University, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States)

    2008-09-15

    Desmoplastic small round cell tumor (DSRCT) is a rare malignant neoplasm typically involving the abdominal cavity of a young male. Extra-abdominal occurrence of this tumor is very rare. We report a 10-year-old girl with primary DSRCT arising within the left femur. The patient presented with knee pain, and radiological findings were strongly suggestive of osteogenic sarcoma. In addition to the typical microscopic appearance and immunophenotype, RT-PCR demonstrated the chimeric transcript of EWS-WT1, which is diagnostic of DSRCT. Pulmonary metastases were present at initial staging studies, but no abdominal or pelvic lesion was present. Despite chemotherapy and complete tumor excision, the patient developed progressive lung and bone metastases and died 3 years after initial presentation. This is the second reported case of primary DSRCT of bone with genetic confirmation. (orig.)

  20. MHC class II antigen presentation by B cells in health and disease

    NARCIS (Netherlands)

    Souwer, Yuri

    2009-01-01

    MHC class II antigen presentation by B cells is important to activate CD4+ T cells that stimulate the B cell to produce antibodies. Besides this, disruption of MHC class II antigen presentation could play a role in immune escape by tumor cells. This thesis describes MHC class II antigen presentation

  1. A novel splice mutation in the TP53 gene associated with Leydig cell tumor and primitive neuroectodermal tumor

    DEFF Research Database (Denmark)

    Stecher, C.W.; Hasle, H.; Grønbæk, Kirsten

    2008-01-01

    A 20-month-old boy presented with precocious puberty due to a Leydig cell tumor, and at the age of 6 years with a primitive neuroectodermal brain-tumor (PNET). A novel splice site mutation of the TP53-gene, likely to be associated with a nonfunctional protein, was found in the proband, his father...

  2. Multifunctional Nucleic Acids for Tumor Cell Treatment

    DEFF Research Database (Denmark)

    Pofahl, Monika; Wengel, Jesper; Mayer, Günter

    2014-01-01

    We report on a multifunctional nucleic acid, termed AptamiR, composed of an aptamer domain and an antimiR domain. This composition mediates cell specific delivery of antimiR molecules for silencing of endogenous micro RNA. The introduced multifunctional molecule preserves cell targeting, anti......-proliferative and antimiR function in one 37-nucleotide nucleic acid molecule. It inhibits cancer cell growth and induces gene expression that is pathologically damped by an oncomir. These findings will have a strong impact on future developments regarding aptamer- and antimiR-related applications for tumor targeting...

  3. Epigenetics, Nervous System Tumors, and Cancer Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Qureshi, Irfan A. [Rosyln and Leslie Goldstein Laboratory for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Institute for Brain Disorders and Neural Regeneration, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Rose F. Kennedy Center for Research on Intellectual and Developmental Disabilities, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Mehler, Mark F., E-mail: mark.mehler@einstein.yu.edu [Rosyln and Leslie Goldstein Laboratory for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Institute for Brain Disorders and Neural Regeneration, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Rose F. Kennedy Center for Research on Intellectual and Developmental Disabilities, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States)

    2011-09-13

    Recent advances have begun to elucidate how epigenetic regulatory mechanisms are responsible for establishing and maintaining cell identity during development and adult life and how the disruption of these processes is, not surprisingly, one of the hallmarks of cancer. In this review, we describe the major epigenetic mechanisms (i.e., DNA methylation, histone and chromatin modification, non-coding RNA deployment, RNA editing, and nuclear reorganization) and discuss the broad spectrum of epigenetic alterations that have been uncovered in pediatric and adult nervous system tumors. We also highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells (CSCs), which are thought to be present in a range of nervous system tumors and responsible for tumor maintenance, progression, treatment resistance, and recurrence. We believe that better understanding how epigenetic mechanisms operate in neural cells and identifying the etiologies and consequences of epigenetic deregulation in tumor cells and CSCs, in particular, are likely to promote the development of enhanced molecular diagnostics and more targeted and effective therapeutic agents for treating recalcitrant nervous system tumors.

  4. Epigenetics, Nervous System Tumors, and Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Mark F. Mehler

    2011-09-01

    Full Text Available Recent advances have begun to elucidate how epigenetic regulatory mechanisms are responsible for establishing and maintaining cell identity during development and adult life and how the disruption of these processes is, not surprisingly, one of the hallmarks of cancer. In this review, we describe the major epigenetic mechanisms (i.e., DNA methylation, histone and chromatin modification, non-coding RNA deployment, RNA editing, and nuclear reorganization and discuss the broad spectrum of epigenetic alterations that have been uncovered in pediatric and adult nervous system tumors. We also highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells (CSCs, which are thought to be present in a range of nervous system tumors and responsible for tumor maintenance, progression, treatment resistance, and recurrence. We believe that better understanding how epigenetic mechanisms operate in neural cells and identifying the etiologies and consequences of epigenetic deregulation in tumor cells and CSCs, in particular, are likely to promote the development of enhanced molecular diagnostics and more targeted and effective therapeutic agents for treating recalcitrant nervous system tumors.

  5. HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.

    Science.gov (United States)

    Aits, Sonja; Gustafsson, Lotta; Hallgren, Oskar; Brest, Patrick; Gustafsson, Mattias; Trulsson, Maria; Mossberg, Ann-Kristin; Simon, Hans-Uwe; Mograbi, Baharia; Svanborg, Catharina

    2009-03-01

    HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.

  6. Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Franck Chiappini

    2012-01-01

    Full Text Available Liver cancer is the fifth most common cancer in men and the seventh in women. During the past 20 years, the incidence of HCC has tripled while the 5-year survival rate has remained below 12%. The presence of circulating tumor cells (CTC reflects the aggressiveness nature of a tumor. Many attempts have been made to develop assays that reliably detect and enumerate the CTC during the development of the HCC. In this case, the challenges are (1 there are few markers specific to the HCC (tumor cells versus nontumor cells and (2 they can be used to quantify the number of CTC in the bloodstream. Another technical challenge consists of finding few CTC mixed with million leukocytes and billion erythrocytes. CTC detection and identification can be used to estimate prognosis and may serve as an early marker to assess antitumor activity of treatment. CTC can also be used to predict progression-free survival and overall survival. CTC are an interesting source of biological information in order to understand dissemination, drug resistance, and treatment-induced cell death. Our aim is to review and analyze the different new methods existing to detect, enumerate, and characterize the CTC in the peripheral circulation of patients with HCC.

  7. Antigen presentation by MHC-dressed cells

    Directory of Open Access Journals (Sweden)

    Masafumi eNakayama

    2015-01-01

    Full Text Available Professional antigen presenting cells (APCs such as conventional dendritic cells (DCs process protein antigens to MHC-bound peptides and then present the peptide-MHC complexes to T cells. In addition to this canonical antigen presentation pathway, recent studies have revealed that DCs and non-APCs can acquire MHC class I (MHCI and/or MHC class II (MHCII from neighboring cells through a process of cell-cell contact-dependent membrane transfer called trogocytosis. These MHC-dressed cells subsequently activate or regulate T cells via the preformed antigen peptide-MHC complexes without requiring any further processing. In addition to trogocytosis, intercellular transfer of MHCI and MHCII can be mediated by secretion of membrane vesicles such as exosomes from APCs, generating MHC-dressed cells. This review focuses on the physiological role of antigen presentation by MHCI- or MHCII-dressed cells, and also discusses differences and similarities between trogocytosis and exosome-mediated transfer of MHC.

  8. Challenges in circulating tumor cell detection by the CellSearch system

    NARCIS (Netherlands)

    Andree, K.C.; Dalum, van G.; Terstappen, L.W.M.M.

    2016-01-01

    Enumeration and characterization of circulating tumor cells (CTC) hold the promise of a real time liquid biopsy. They are however present in a large background of hematopoietic cells making their isolation technically challenging. In 2004, the CellSearch system was introduced as the first and only F

  9. Stem Cells and the Origin and Propagation of Brain Tumors

    OpenAIRE

    2008-01-01

    In recent years there has been a flood of interest in the relationship between brain tumors and stem cells. Some investigators have focused on the sensitivity of normal stem cells to transformation, others have described phenotypic or functional similarities between tumor cells and stem cells, and still others have suggested that tumors contain a subpopulation of “cancer stem cells” that is crucial for tumor maintenance or propagation. While all these concepts are interesting and provide insi...

  10. Amplification of tumor inducing putative cancer stem cells (CSCs) by vitamin A/retinol from mammary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Rohit B. [Department of Microbiology and Molecular Genetics, University of Pittsburgh, PA 15261 (United States); Wang, Qingde [Department of Surgery, University of Pittsburgh, PA 15261 (United States); Khillan, Jaspal S., E-mail: khillan@pitt.edu [Department of Microbiology and Molecular Genetics, University of Pittsburgh, PA 15261 (United States)

    2013-07-12

    Highlights: •Vitamin A supports self renewal of putative CSCs from mammary tumors. •These cells exhibit impaired retinol metabolism into retinoic acid. •CSCs from mammary tumors differentiate into mammary specific cell lineages. •The cells express mammary stem cell specific CD29 and CD49f markers. •Putative CSCs form highly metastatic tumors in NOD SCID mouse. -- Abstract: Solid tumors contain a rare population of cancer stem cells (CSCs) that are responsible for relapse and metastasis. The existence of CSC however, remains highly controversial issue. Here we present the evidence for putative CSCs from mammary tumors amplified by vitamin A/retinol signaling. The cells exhibit mammary stem cell specific CD29{sup hi}/CD49f{sup hi}/CD24{sup hi} markers, resistance to radiation and chemo therapeutic agents and form highly metastatic tumors in NOD/SCID mice. The cells exhibit indefinite self renewal as cell lines. Furthermore, the cells exhibit impaired retinol metabolism and do not express enzymes that metabolize retinol into retinoic acid. Vitamin A/retinol also amplified putative CSCs from breast cancer cell lines that form highly aggressive tumors in NOD SCID mice. The studies suggest that high purity putative CSCs can be isolated from solid tumors to establish patient specific cell lines for personalized therapeutics for pre-clinical translational applications. Characterization of CSCs will allow understanding of basic cellular and molecular pathways that are deregulated, mechanisms of tumor metastasis and evasion of therapies that has direct clinical relevance.

  11. Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles

    Science.gov (United States)

    Balivada, Sivasai

    Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V

  12. Lymphovascular invasion in testicular germ cell tumors: clinicopathological correlates

    Directory of Open Access Journals (Sweden)

    Yaron Ehrlich

    2013-08-01

    Full Text Available Introduction. We assessed clinical–pathological correlates of lymphovascular invasion in testicular germ–cell tumors.Material and methods. Archived pathology specimens from 145 patients treated by radical orchiectomy for testicular germ cell tumors at our institution in 1995–2006 were reanalyzed by a dedicated urologic pathologist, and the corresponding medical records were reviewed. The association of lymphovascular invasion with clinical and pathological parameters was tested using stepwise logistic regression analysis.Results. Lymphovascular invasion was identified in 38 (26% patients and was associated with younger age, testicular pain at presentation, elevated serum tumor markers, nonseminoma histology, and advanced clinical stage. Orchalgia was indicated as the impetus for referral in 67 (46% patients and characterized as a dull aching sensation, persistent or intermittent in nature. Among the 98 men diagnosed with clinical stage I, those presenting with testicular pain had a 1.8X–higher likelihood of lymphovascular invasion than those without pain (95% CI 1.13–14.9, p = 0.02, and patients with elevated serum tumor markers had an 8.5–fold increased probability of lymphovascular invasion than those presenting with normal tumor markers (CI 1.1–54.2, p = 0.05. Among men with nonseminoma histology, elevated tumor markers was the strongest predictor of lymphovascular invasion in both univariate and multivariate analyses (OR 5.05, 95% CI 1.16–21.8, p = 0.03.Conclusion. Providing pathologists with information on pre–orchiectomy tumor marker levels and, possibly, testicular pain at presentation may increase their vigilance in searching for lymphovascular invasion, potentially improving their diagnostic accuracy. Whether it may also translate into improved oncological outcomes needs further evaluation.

  13. Mast cell activation syndromes presenting as anaphylaxis.

    Science.gov (United States)

    Akin, Cem

    2015-05-01

    Anaphylaxis results from severe systemic mast cell activation. In addition to IgE-mediated and physical triggers, it may occur with a clonal mast cell disease and in an idiopathic fashion without clear provoking factors. Disorders of mast cell activation are classified into primary (clonal), secondary, and idiopathic. Mast cell activation syndrome (MCAS) is a multisystem disorder characterized by objective documentation of elevated mast cell mediators during attacks and a favorable response to antimediator therapy. It should be considered in the differential diagnosis of patients presenting with recurrent anaphylaxis without a clear cause. This article discusses the diagnosis of MCAS.

  14. Salivary duct carcinoma with striking neutrophil-tumor cell cannibalism

    OpenAIRE

    Payam Arya; Khalbuss, Walid E.; Monaco, Sara E.; Liron Pantanowitz

    2011-01-01

    Cannibalism of neutrophils by tumor cells has previously been reported in certain carcinomas, lymphoma and melanoma. Tumor cannibalism is believed to serve as a tumor-immune escape mechanism, associated with high-grade aggressive cancers with a significantly increased metastatic potential. This interesting phenomenon has not been previously documented in association with salivary gland tumors. We report, for the first time, striking neutrophil-tumor cell cannibalism associated with a high gra...

  15. Synergistic effects of host B7-H4 deficiency and gemcitabine treatment on tumor regression and anti-tumor T cell immunity in a mouse model.

    Science.gov (United States)

    Leung, Joanne; St-Onge, Philippe; Stagg, John; Suh, Woong-Kyung

    2017-04-01

    B7-H4 (B7x/B7S1), a B7 family inhibitor of T cell activity, is expressed in multiple human cancers and correlates with decreased infiltrating lymphocytes and poor prognosis. In murine models, tumor-expressed B7-H4 enhances tumor growth and reduces T cell immunity, and blockade of tumor-B7-H4 rescues T cell activity and lowers tumor burden. This implicates B7-H4 as a target for cancer immunotherapy, yet limits the efficacy of B7-H4 blockade exclusively to patients with B7-H4+ tumors. Given the expression of B7-H4 on host immune cells, we have previously shown that BALB/c mice lacking host B7-H4 have enhanced anti-tumor profiles, yet similar 4T1 tumor growth relative to control. Given that T cell-mediated immunotherapies work best for tumors presenting tumor-associated neoantigens, we further investigated the function of host B7-H4 in the growth of a more immunogenic derivative, 4T1-12B, which is known to elicit strong anti-tumor CD8 T cell responses due to expression of a surrogate tumor-specific antigen, firefly luciferase. Notably, B7-H4 knockout hosts not only mounted greater tumor-associated anti-tumor T cell responses, but also displayed reduced tumors. Additionally, B7-H4-deficiency synergized with gemcitabine to further inhibit tumor growth, often leading to tumor eradication and the generation of protective T cell immunity. These findings imply that inhibition of host B7-H4 can enhance anti-tumor T cell immunity in immunogenic cancers, and can be combined with other anti-cancer therapies to further reduce tumor burden regardless of tumor-B7-H4 positivity.

  16. Favorable alteration of tumor microenvironment by immunomodulatory cytokines for efficient T-cell therapy in solid tumors.

    Science.gov (United States)

    Tähtinen, Siri; Kaikkonen, Saija; Merisalo-Soikkeli, Maiju; Grönberg-Vähä-Koskela, Susanna; Kanerva, Anna; Parviainen, Suvi; Vähä-Koskela, Markus; Hemminki, Akseli

    2015-01-01

    Unfavorable ratios between the number and activation status of effector and suppressor immune cells infiltrating the tumor contribute to resistance of solid tumors to T-cell based therapies. Here, we studied the capacity of FDA and EMA approved recombinant cytokines to manipulate this balance in favor of efficient anti-tumor responses in B16.OVA melanoma bearing C57BL/6 mice. Intratumoral administration of IFN-α2, IFN-γ, TNF-α, and IL-2 significantly enhanced the anti-tumor effect of ovalbumin-specific CD8+ T-cell (OT-I) therapy, whereas GM-CSF increased tumor growth in association with an increase in immunosuppressive cell populations. None of the cytokines augmented tumor trafficking of OT-I cells significantly, but injections of IFN-α2, IFN-γ and IL-2 increased intratumoral cytokine secretion and recruitment of endogenous immune cells capable of stimulating T-cells, such as natural killer and maturated CD11c+ antigen-presenting cells. Moreover, IFN-α2 and IL-2 increased the levels of activated tumor-infiltrating CD8+ T-cells concomitant with reduction in the CD8+ T-cell expression of anergy markers CTLA-4 and PD-1. In conclusion, intratumoral administration of IFN-α2, IFN-γ and IL-2 can lead to immune sensitization of the established tumor, whereas GM-CSF may contribute to tumor-associated immunosuppression. The results described here provide rationale for including local administration of immunostimulatory cytokines into T-cell therapy regimens. One appealing embodiment of this would be vectored delivery which could be advantageous over direct injection of recombinant molecules with regard to efficacy, cost, persistence and convenience.

  17. Favorable alteration of tumor microenvironment by immunomodulatory cytokines for efficient T-cell therapy in solid tumors.

    Directory of Open Access Journals (Sweden)

    Siri Tähtinen

    Full Text Available Unfavorable ratios between the number and activation status of effector and suppressor immune cells infiltrating the tumor contribute to resistance of solid tumors to T-cell based therapies. Here, we studied the capacity of FDA and EMA approved recombinant cytokines to manipulate this balance in favor of efficient anti-tumor responses in B16.OVA melanoma bearing C57BL/6 mice. Intratumoral administration of IFN-α2, IFN-γ, TNF-α, and IL-2 significantly enhanced the anti-tumor effect of ovalbumin-specific CD8+ T-cell (OT-I therapy, whereas GM-CSF increased tumor growth in association with an increase in immunosuppressive cell populations. None of the cytokines augmented tumor trafficking of OT-I cells significantly, but injections of IFN-α2, IFN-γ and IL-2 increased intratumoral cytokine secretion and recruitment of endogenous immune cells capable of stimulating T-cells, such as natural killer and maturated CD11c+ antigen-presenting cells. Moreover, IFN-α2 and IL-2 increased the levels of activated tumor-infiltrating CD8+ T-cells concomitant with reduction in the CD8+ T-cell expression of anergy markers CTLA-4 and PD-1. In conclusion, intratumoral administration of IFN-α2, IFN-γ and IL-2 can lead to immune sensitization of the established tumor, whereas GM-CSF may contribute to tumor-associated immunosuppression. The results described here provide rationale for including local administration of immunostimulatory cytokines into T-cell therapy regimens. One appealing embodiment of this would be vectored delivery which could be advantageous over direct injection of recombinant molecules with regard to efficacy, cost, persistence and convenience.

  18. Malignant peripheral nerve sheath tumor of the anterior mediastinum: a rare presentation

    Directory of Open Access Journals (Sweden)

    Babusha Kalra

    2014-12-01

    Full Text Available Malignant peripheral nerve sheath tumor (MPNST is a rare tumor that accounts for 5% of all thoracic neoplasm usually located in the posterior mediastinum and is generally associated with a poor outcome. We present a case of MPNST of the anterior mediastinum presenting in a rare location leading to diagnostic dilemmas and treated primarily by surgical resection.

  19. Single-cell analyses of circulating tumor cells

    Institute of Scientific and Technical Information of China (English)

    Xi-Xi Chen; Fan Bai

    2015-01-01

    Circulating tumor cells (CTCs) are a population of tumor cells mediating metastasis, which results in most of the cancer related deaths. hTe number of CTCs in the peripheral blood of patients is rare, and many platforms have been launched for detection and enrichment of CTCs. Enumeration of CTCs has already been used as a prognosis marker predicting the survival rate of cancer patients. Yet CTCs should be more potential. Studies on CTCs at single cell level may help revealing the underlying mechanism of tumorigenesis and metastasis. Though far from developed, this area of study holds much promise in providing new clinical application and deep understanding towards metastasis and cancer development.

  20. Review: Biological relevance of disseminated tumor cells in cancer patients.

    Science.gov (United States)

    Riethdorf, Sabine; Wikman, Harriet; Pantel, Klaus

    2008-11-01

    The prognosis of cancer patients is largely determined by the occurrence of distant metastases. In patients with primary tumors, this relapse is mainly due to clinically occult micrometastasis present in secondary organs at primary diagnosis but not detectable even with high resolution imaging procedures. Sensitive and specific immunocytochemical and molecular assays enable the detection and characterization of disseminated tumor cells (DTC) at the single cell level in bone marrow (BM) as the common homing site of DTC and circulating tumor cells (CTC) in peripheral blood. Because of the high variability of results in DTC and CTC detection, there is an urgent need for standardized methods. In this review, we will focus on BM and present currently available methods for the detection and characterization of DTC. Furthermore, we will discuss data on the biology of DTC and the clinical relevance of DTC detection. While the prognostic impact of DTC in BM has clearly been shown for primary breast cancer patients, less is known about the clinical relevance of DTC in patients with other carcinomas. Current findings suggest that DTC are capable to survive chemotherapy and persist in a dormant nonproliferating state over years. To what extent these DTC have stem cell properties is subject of ongoing investigations. Further characterization is required to understand the biology of DTC and to identify new targets for improved risk prevention and tailoring of therapy. Our review will focus on breast, colon, lung, and prostate cancer as the main tumor entities in Europe and the United States.

  1. Pro-Tumor and Anti-Tumor Functions of IL-17 and of TH17 Cells in Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Gulubova M.

    2016-10-01

    Full Text Available The current review reveals the seven subclasses of CD4+ T helper cells, i.e. Th1, Th2, Th9, Th17, Th22, regulatory T cells and Tfh, the cytokines produced by them and their role in tumor microenvironment. Main attention was paid to IL-17 and Th17 cells. IL-17-producing cells were described, among which were Treg17 cells and Tc17 cells. The transcription factors, engaged in the activation of Th17 cell differentiation were reviewed. It was shown that Th17 cells might possess regulatory functions in tumor microenvironments that directs toward immunosuppression. The reciprocity between Treg and Th17 cells is realized when the production of a large amount of TGF-β in tumors causes Treg cell differentiation, and the addition of IL-6 shifts the differentiation of naïve T cells to Th17 cells. The main pro-tumor role of IL-17 is the promotion of tumor angiogenesis through stimulation of fibroblasts and endothelial cells. The antitumor functions of IL-17 are associated with enhancement of cytotoxic activity of tumor specific CTL cells and with angiogenesis that provide channels through which immune cells might invade tumor and promote antitumor immunity.

  2. AIDS-associated plasmablastic lymphoma presenting as a poorly differentiated esophageal tumor: A diagnostic dilemma

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Plasmablastic lymphoma (PBL) is a rare form of diffuse large B-cell lymphoma characterized by weak/absent expression of conventional B-cell markers and strong expression of plasma cell markers. It is strongly associated with human immunodeficiency virus (HIV) and Epstein Barr virus infection, and shows an unusual tropism to the oral cavity. Herein we describe a patient with AIDS who presented with weight loss and dysphagia owing to a large gastroesophageal mass. His radiographic and endoscopic findings and long history of cigarette consumption suggested carcinoma. Biopsy demonstrated a poorly differentiated tumor stained negatively to routine lymphoid markers including CD20. However, gene rearrangement studies confirmed a B-cell process and a more detailed immunohistochemical analysis revealed the cells stained positively for CD138 (plasma cell antigen). These findings were diagnostic of PBL. Our report reviews the wide differential diagnosis of PBL and underscores the importance of a broad array of viral and molecular studies needed to establish this diagnosis.

  3. Photobiomodulation on tumor cells in vitro and tumor tissue in vivo

    Science.gov (United States)

    Rong, Dong-Liang; Liu, Timon Cheng-Yi; Jin, Hua

    2006-01-01

    Background and Objective: There are many kinds of photobiomodulation (PBM) on tumor cells whereas PBM induced oncogenic transformation has not been found. These will be discussed in view of the anti-cancer efficacy of PBM. Study Design/Materials and Methods: The biological information model of PBM (BIMP) will be used to study PBM on tumor cells. Results: The PBM on tumor cells includes cell proliferation, cell cycle modulation, cell adhesion, cell differentiation and so on. The PBM on small tumor tissue in vivo may include the inhibition or promotion of tumor growth. The PBM can be designed to play an important role in anti-cancer treatments in terms of BIMP. Conclusions and discussion: PBM on tumor cells may develop into a novel anti-cancer therapeutic approach.

  4. Angiogenesis-independent tumor growth mediated by stem-like cancer cells.

    NARCIS (Netherlands)

    Sakariassen, P.; Prestegarden, L.; Wang, J.; Skaftnesmo, K.O.; Mahesparan, R.; Molthoff, C.F.M.; Sminia, P.; Sundlisaeter, E.; Misra, A.; Tysnes, B.B.; Chekenya, M.; Peters, H.; Lende, G.; Kalland, K.H.; Oyan, A.M.; Petersen, K.; Jonassen, I.; Kogel, A.J. van der; Feuerstein, B.G.; Terzis, A.J.; Bjerkvig, R.; Enger, P.O.

    2006-01-01

    In this work, highly infiltrative brain tumors with a stem-like phenotype were established by xenotransplantation of human brain tumors in immunodeficient nude rats. These tumors coopted the host vasculature and presented as an aggressive disease without signs of angiogenesis. The malignant cells ex

  5. Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer

    Directory of Open Access Journals (Sweden)

    Catherine Oakman

    2010-06-01

    Full Text Available Adjuvant systemic therapy targets minimal residual disease. Our current clinical approach in the adjuvant setting is to presume, rather than confirm, the presence of minimal residual disease. Based on assessment of the primary tumor, we estimate an individual’s recurrence risk. Subsequent treatment decisions are based on characteristics of the primary tumor, with the presumption of consistent biology and treatment sensitivity between micrometastases and the primary lesion. An alternative approach is to identify micrometastatic disease. Detection of disseminated tumor cells (DTC in the bone marrow and circulating tumor cells (CTC from peripheral blood collection may offer quantification and biocharacterization of residual disease. This paper will review the prognostic and predictive potential of micrometastatic disease in early breast cancer.

  6. Giant cell tumor of the spine.

    Science.gov (United States)

    Ozaki, Toshifumi; Liljenqvist, Ulf; Halm, Henry; Hillmann, Axel; Gosheger, Georg; Winkelmann, Winfried

    2002-08-01

    Six patients with giant cell tumor of the spine had surgery between 1981 and 1995. Three lesions were located in the scrum, two lesions were in the thoracic spine, and one lesion was in the lumbar spine. Preoperatively, all patients had local pain and neurologic symptoms. Two patients had cement implanted after curettage or intralesional excision of the sacral tumor; one patient had a local relapse. After the second curettage and cement implantation, the tumor was controlled. One patient with a sacral lesion had marginal excision and spondylodesis; no relapse developed. Two patients with thoracic lesions had planned marginal excision and spondylodesis; the margins finally became intralesional, but no relapse developed. One patient with a lumbar lesion had incomplete removal of the tumor and received postoperative irradiation. At the final followup (median, 69 months), five of six patients were disease-free and one patient died of disease progression. Two of the five surviving patients had pain after standing or neurologic problems. Although some contamination occurred, planning a marginal excision of the lesion seems beneficial for vertebral lesions above the sacrum. Total sacrectomy of a sacral lesion seems to be too invasive when cement implantation can control the lesion.

  7. OUR EXPERIENCE WITH RARE PRESENTATION OF GASTROINTESTINAL STROMAL TUMORS IN A RURAL MEDICAL COLLEGE HOSPITAL

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    Jigar Vipul

    2013-10-01

    Full Text Available ABSTRACT : Gastrointestinal stromal tumors (GIST - are one of the most common mesenchymal tumors of the gastrointestinal tract [1 - 3% of all gastrointestinal malignancies]. Their behaviour is driven by mutations in the kit gene or PDGFRA gene and may or may not positively stain for kit. We report fo ur additional cases of a GIST presenting as an abdominal mass along with a pertinent review of the literature. All four patients received surgical resection. The mean tumor size was 10.5 with an average mitotic index of 6.25 per 50 high power fields. Three patients were disease free and one patient came with recurrence. In conclusion, symptomatic patents have an increased incidence of high - risk tumors and metastases at presentation. Adjuvant therapy with imatinib improves disease - free survival in patients w ith large abdominal GIST tumors, but no change in overall survival was noted. KEY WORD: Gastrointestinal stromal tumors; Imatinib; mitotic index;Meckel’s Diverticulum

  8. Snail levels control the migration mechanism of mesenchymal tumor cells.

    Science.gov (United States)

    Belgiovine, Cristina; Chiesa, Giulio; Chiodi, Ilaria; Frapolli, Roberta; Bonezzi, Katiuscia; Taraboletti, Giulia; D'Incalci, Maurizio; Mondello, Chiara

    2016-07-01

    Cancer cells use two major types of movement: Mesenchymal, which is typical of cells of mesenchymal origin and depends on matrix metalloproteinase (MMP) activity, and amoeboid, which is characteristic of cells with a rounded shape and relies on the activity of Rho-associated kinase (ROCK). The present authors previously demonstrated that, during neoplastic transformation, telomerase-immortalized human fibroblasts (cen3tel cells) acquired a ROCK-dependent/MMP independent mechanism of invasion, mediated by the downregulation of the ROCK cellular inhibitor Round (Rnd)3/RhoE. In the present study, cen3tel transformation was also demonstrated to be paralleled by downregulation of Snail, a major determinant of the mesenchymal movement. To test whether Snail levels could determine the type of movement adopted by mesenchymal tumor cells, Snail was ectopically expressed in tumorigenic cells. It was observed that ectopic Snail did not increase the levels of typical mesenchymal markers, but induced cells to adopt an MMP-dependent mechanism of invasion. In cells expressing ectopic Snail, invasion became sensitive to the MMP inhibitor Ro 28-2653 and insensitive to the ROCK inhibitor Y27632, suggesting that, once induced by Snail, the mesenchymal movement prevails over the amoeboid one. Snail-expressing cells had a more aggressive behavior in vivo, and exhibited increased tumor growth rate and metastatic ability. These results confirm the high plasticity of cancer cells, which can adopt different types of movement in response to changes in the expression of specific genes. Furthermore, the present findings indicate that Rnd3 and Snail are possible regulators of the type of invasion mechanism adopted by mesenchymal tumor cells.

  9. Spatial organization and correlations of cell nuclei in brain tumors.

    Directory of Open Access Journals (Sweden)

    Yang Jiao

    Full Text Available Accepting the hypothesis that cancers are self-organizing, opportunistic systems, it is crucial to understand the collective behavior of cancer cells in their tumorous heterogeneous environment. In the present paper, we ask the following basic question: Is this self-organization of tumor evolution reflected in the manner in which malignant cells are spatially distributed in their heterogeneous environment? We employ a variety of nontrivial statistical microstructural descriptors that arise in the theory of heterogeneous media to characterize the spatial distributions of the nuclei of both benign brain white matter cells and brain glioma cells as obtained from histological images. These descriptors, which include the pair correlation function, structure factor and various nearest neighbor functions, quantify how pairs of cell nuclei are correlated in space in various ways. We map the centroids of the cell nuclei into point distributions to show that while commonly used local spatial statistics (e.g., cell areas and number of neighboring cells cannot clearly distinguish spatial correlations in distributions of normal and abnormal cell nuclei, their salient structural features are captured very well by the aforementioned microstructural descriptors. We show that the tumorous cells pack more densely than normal cells and exhibit stronger effective repulsions between any pair of cells. Moreover, we demonstrate that brain gliomas are organized in a collective way rather than randomly on intermediate and large length scales. The existence of nontrivial spatial correlations between the abnormal cells strongly supports the view that cancer is not an unorganized collection of malignant cells but rather a complex emergent integrated system.

  10. Paradoxical dependencies of tumor dormancy and progression on basic cell kinetics.

    Science.gov (United States)

    Enderling, Heiko; Anderson, Alexander R A; Chaplain, Mark A J; Beheshti, Afshin; Hlatky, Lynn; Hahnfeldt, Philip

    2009-11-15

    Even after a tumor is established, it can early on enter a state of dormancy marked by balanced cell proliferation and cell death. Disturbances to this equilibrium may affect cancer risk, as they may cause the eventual lifetime clinical presentation of a tumor that might otherwise have remained asymptomatic. Previously, we showed that cell death, proliferation, and migration can play a role in shifting this dynamic, making the understanding of their combined influence on tumor development essential. We developed an individual cell-based computer model of the interaction of cancer stem cells and their nonstem progeny to study early tumor dynamics. Simulations of tumor growth show that three basic components of tumor growth--cell proliferation, migration, and death--combine in unexpected ways to control tumor progression and, thus, clinical cancer risk. We show that increased proliferation capacity in nonstem tumor cells and limited cell migration overall lead to space constraints that inhibit proliferation and tumor growth. By contrast, increasing the rate of cell death produces the expected tumor size reduction in the short term, but results ultimately in paradoxical accelerated long-term growth owing to the liberation of cancer stem cells and formation of self-metastases.

  11. Tumor-altered dendritic cell function: implications for anti-tumor immunity

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    Kristian Michael Hargadon

    2013-07-01

    Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti-tumor

  12. The thrombotic potential of circulating tumor microemboli: computational modeling of circulating tumor cell-induced coagulation

    OpenAIRE

    Phillips, Kevin G.; Lee, Angela M.; Tormoen, Garth W.; Rigg, Rachel A.; Kolatkar, Anand; Luttgen, Madelyn; Bethel, Kelly; Bazhenova, Lyudmila; Kuhn, Peter; Newton, Paul; McCarty, Owen J.T.

    2014-01-01

    Thrombotic events can herald the diagnosis of cancer, preceding any cancer-related clinical symptoms. Patients with cancer are at a 4- to 7-fold increased risk of suffering from venous thromboembolism (VTE), with ∼7,000 patients with lung cancer presenting from VTEs. However, the physical biology underlying cancer-associated VTE remains poorly understood. Several lines of evidence suggest that the shedding of tissue factor (TF)-positive circulating tumor cells (CTCs) and microparticles from p...

  13. Tetrathiomolybdate inhibits head and neck cancer metastasis by decreasing tumor cell motility, invasiveness and by promoting tumor cell anoikis

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    Merajver Sofia D

    2010-08-01

    Full Text Available Abstract Background The metastatic spread of solid tumors is directly or indirectly responsible for most cancer-related deaths. Tumor metastasis is very complex and this process requires a tumor cell to acquire enhanced motility, invasiveness and anoikis resistance to successfully establish a tumor at a distal site. Metastatic potential of tumor cells is directly correlated with the expression levels of several angiogenic cytokines. Copper is a mandatory cofactor for the function of many of these angiogenic mediators as well as other proteins that play an important role in tumor cell motility and invasiveness. We have previously shown that tetrathiomolybdate (TM is a potent chelator of copper and it mediates its anti-tumor effects by suppressing tumor angiogenesis. However, very little is known about the effect of TM on tumor cell function and tumor metastasis. In this study, we explored the mechanisms underlying TM-mediated inhibition of tumor metastasis. Results We used two in vivo models to examine the effects of TM on tumor metastasis. Animals treated with TM showed a significant decrease in lung metastasis in both in vivo models as compared to the control group. In addition, tumor cells from the lungs of TM treated animals developed significantly smaller colonies and these colonies had significantly fewer tumor cells. TM treatment significantly decreased tumor cell motility and invasiveness by inhibiting lysyl oxidase (LOX activity, FAK activation and MMP2 levels. Furthermore, TM treatment significantly enhanced tumor cell anoikis by activating p38 MAPK cell death pathway and by downregulating XIAP survival protein expression. Conclusions Taken together, these results suggest that TM is a potent suppressor of head and neck tumor metastasis by modulating key regulators of tumor cell motility, invasiveness and anoikis resistance.

  14. HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53.

    Science.gov (United States)

    Hallgren, O; Gustafsson, L; Irjala, H; Selivanova, G; Orrenius, S; Svanborg, C

    2006-02-01

    HAMLET (Human alpha-lactalbumin Made Lethal to Tumor cells) triggers selective tumor cell death in vitro and limits tumor progression in vivo. Dying cells show features of apoptosis but it is not clear if the apoptotic response explains tumor cell death. This study examined the contribution of apoptosis to cell death in response to HAMLET. Apoptotic changes like caspase activation, phosphatidyl serine externalization, chromatin condensation were detected in HAMLET-treated tumor cells, but caspase inhibition or Bcl-2 over-expression did not prolong cell survival and the caspase response was Bcl-2 independent. HAMLET translocates to the nuclei and binds directly to chromatin, but the death response was unrelated to the p53 status of the tumor cells. p53 deletions or gain of function mutations did not influence the HAMLET sensitivity of tumor cells. Chromatin condensation was partly caspase dependent, but apoptosis-like marginalization of chromatin was also observed. The results show that tumor cell death in response to HAMLET is independent of caspases, p53 and Bcl-2 even though HAMLET activates an apoptotic response. The use of other cell death pathways allows HAMLET to successfully circumvent fundamental anti-apoptotic strategies that are present in many tumor cells.

  15. 3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood.

    Science.gov (United States)

    Zheng, Siyang; Lin, Henry K; Lu, Bo; Williams, Anthony; Datar, Ram; Cote, Richard J; Tai, Yu-Chong

    2011-02-01

    Detection of circulating tumor cells has emerged as a promising minimally invasive diagnostic and prognostic tool for patients with metastatic cancers. We report a novel three dimensional microfilter device that can enrich viable circulating tumor cells from blood. This device consists of two layers of parylene membrane with pores and gap precisely defined with photolithography. The positions of the pores are shifted between the top and bottom membranes. The bottom membrane supports captured cells and minimize the stress concentration on cell membrane and sustain cell viability during filtration. Viable cell capture on device was investigated with scanning electron microscopy, confocal microscopy, and immunofluorescent staining using model systems of cultured tumor cells spiked in blood or saline. The paper presents and validates this new 3D microfiltration concept for circulation tumor cell enrichment application. The device provides a highly valuable tool for assessing and characterizing viable enriched circulating tumor cells in both research and clinical settings.

  16. Circulating Tumor Cells, Enumeration and Beyond

    Directory of Open Access Journals (Sweden)

    Jian-Mei Hou

    2010-06-01

    Full Text Available The detection and enumeration of circulating tumor cells (CTCs has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology.

  17. Tumor cells prevent mouse dendritic cell maturation induced by TLR ligands.

    Science.gov (United States)

    Idoyaga, Juliana; Moreno, José; Bonifaz, Laura

    2007-08-01

    Tumor cells can evade the immune system through several mechanisms, one of which is to block DC maturation. It has been suggested that signaling via Toll-like receptors (TLR) may be involved in the induction of prophylactic anti-cancer immunity and in the treatment of established tumors. In the present study we found that high numbers of tumor cells interfere with BMDC activation induced by the TLR ligands LPS and poly IC. Tumor cells blocked TLR3- and TLR4-mediated induction of MHCII and the co-stimulatory molecules CD40 and CD86, as well as the cytokines IL-12, TNF-alpha and IL-6. Importantly, tumor cells induced inhibitory molecules (B7-DC, B7-H1 and CD80) on spleen DC in vivo and on BMDC, even in the presence of TLR ligands. Moreover, after a long exposure with tumor cells, purified BMDC were unable to respond to a second challenge with TLR ligands. The failure of tumor exposed-BMDC to express co-stimulatory molecules and cytokines in the presence of TLR ligands has implications for the future development of DC-based cancer immune therapies using TLR ligands as adjuvants for the activation of DC.

  18. The Challenges of Detecting Circulating Tumor Cells in Sarcoma

    Science.gov (United States)

    Tellez-Gabriel, Marta; Brown, Hannah K.; Young, Robin; Heymann, Marie-Françoise; Heymann, Dominique

    2016-01-01

    Sarcomas are a heterogeneous group of malignant neoplasms of mesenchymal origin, many of which have a propensity to develop distant metastases. Cancer cells that have escaped from the primary tumor are able to invade into surrounding tissues, to intravasate into the bloodstream to become circulating tumor cells (CTCs), and are responsible for the generation of distant metastases. Due to the rarity of these tumors and the absence of specific markers expressed by sarcoma tumor cells, the characterization of sarcoma CTCs has to date been relatively limited. Current techniques for isolating sarcoma CTCs are based on size criteria, the identification of circulating cells that express either common mesenchymal markers, sarcoma-specific markers, such as CD99, CD81, or PAX3, and chromosomal translocations found in certain sarcoma subtypes, such as EWS-FLI1 in Ewing’s sarcoma, detection of osteoblast-related genes, or measurement of the activity of specific metabolic enzymes. Further studies are needed to improve the isolation and characterization of sarcoma CTCs, to demonstrate their clinical significance as predictive and/or prognostic biomarkers, and to utilize CTCs as a tool for investigating the metastatic process in sarcoma and to identify novel therapeutic targets. The present review provides a short overview of the most recent literature on CTCs in sarcoma. PMID:27656422

  19. Mutational analysis of circulating tumor cells from colorectal cancer patients and correlation with primary tumor tissue.

    Directory of Open Access Journals (Sweden)

    Anna Lyberopoulou

    Full Text Available Circulating tumor cells (CTCs provide a non-invasive accessible source of tumor material from patients with cancer. The cellular heterogeneity within CTC populations is of great clinical importance regarding the increasing number of adjuvant treatment options for patients with metastatic carcinomas, in order to eliminate residual disease. Moreover, the molecular profiling of these rare cells might lead to insight on disease progression and therapeutic strategies than simple CTCs counting. In the present study we investigated the feasibility to detect KRAS, BRAF, CD133 and Plastin3 (PLS3 mutations in an enriched CTCs cell suspension from patients with colorectal cancer, with the hypothesis that these genes` mutations are of great importance regarding the generation of CTCs subpopulations. Subsequently, we compared CTCs mutational status with that of the corresponding primary tumor, in order to access the possibility of tumor cells characterization without biopsy. CTCs were detected and isolated from blood drawn from 52 colorectal cancer (CRC patients using a quantum-dot-labelled magnetic immunoassay method. Mutations were detected by PCR-RFLP or allele-specific PCR and confirmed by direct sequencing. In 52 patients, discordance between primary tumor and CTCs was 5.77% for KRAS, 3.85% for BRAF, 11.54% for CD133 rs3130, 7.69% for CD133 rs2286455 and 11.54% for PLS3 rs6643869 mutations. Our results support that DNA mutational analysis of CTCs may enable non-invasive, specific biomarker diagnostics and expand the scope of personalized medicine for cancer patients.

  20. Porous Silicon Microparticle Potentiates Anti-Tumor Immunity by Enhancing Cross-Presentation and Inducing Type I Interferon Response

    Directory of Open Access Journals (Sweden)

    Xiaojun Xia

    2015-05-01

    Full Text Available Micro- and nanometer-size particles have become popular candidates for cancer vaccine adjuvants. However, the mechanism by which such particles enhance immune responses remains unclear. Here, we report a porous silicon microparticle (PSM-based cancer vaccine that greatly enhances cross-presentation and activates type I interferon (IFN-I response in dendritic cells (DCs. PSM-loaded antigen exhibited prolonged early endosome localization and enhanced cross-presentation through both proteasome- and lysosome-dependent pathways. Phagocytosis of PSM by DCs induced IFN-I responses through a TRIF- and MAVS-dependent pathway. DCs primed with PSM-loaded HER2 antigen produced robust CD8 T cell-dependent anti-tumor immunity in mice bearing HER2+ mammary gland tumors. Importantly, this vaccination activated the tumor immune microenvironment with elevated levels of intra-tumor IFN-I and MHCII expression, abundant CD11c+ DC infiltration, and tumor-specific cytotoxic T cell responses. These findings highlight the potential of PSM as an immune adjuvant to potentiate DC-based cancer immunotherapy.

  1. Gastrointestinal Stromal Tumor. A Case Presentation Tumor del estroma gastrointestinal. Presentación de un caso

    Directory of Open Access Journals (Sweden)

    Carlos Manuel Ramírez Pérez

    2012-06-01

    Full Text Available

    The terms gastrointestinal stromal tumor refers to tumors of the connective tissue that can be located from the mouth to the anus. The case of a male patient, 64 years old, who attended consultation because of upper gastrointestinal bleeding in the form of melena with a slight decrease in hemoglobin, good general condition and records of previous good health is presented. Gastrointestinal stromal tumor was suspected from the initial examination through video-assisted endoscopy, a diagnosis confirmed later through immunohistochemical examination. The patient underwent surgery with wedge resection of the tumor mass and conservation of gastric and esophageal sphincter. The biopsy results coincided before and after surgery.

    Los términos tumor del estroma gastrointestinal hacen referencia a tumores del tejido conectivo que pueden estar situados desde la boca hasta el ano. Se presenta el caso de un paciente masculino, de 64 años de edad, que acudió a consulta por presentar sangrado digestivo alto en forma de melena, con leve disminución de las cifras de hemoglobina, relativo buen estado general y antecedentes de buena salud. Se tuvo sospecha de tumor del estroma gastrointestinal desde el examen inicial mediante endoscopia asistida por video, diagnóstico confirmado después por el examen inmunohistoquímico. El paciente fue sometido a cirugía con resección en cuña de la masa tumoral y con conservación de los esfínteres gástrico y esofágico, el resultado de la biopsia pre y posoperatoria fue coincidente

  2. Painful scoliosis due to superposed giant cell bone tumor and aneurysmal bone cyst in a child.

    Science.gov (United States)

    Togral, Guray; Arikan, Murat; Hasturk, Askin E; Gungor, Safak

    2014-07-01

    Giant cell bone tumors are the most common precursor lesions of aneurysmal bone cysts (ABCs) developing secondarily. In giant cell bone tumors containing an explicit ABC component, the observation of the solid component of the giant cell bone tumor plays a critical role in the separation of the primary ABC. In general, ABC cases together with giant cell tumors in the bone are diagnosed histopathologically. The combination of giant cell bone tumor with superposed ABC and that of painful scoliosis with backache is rarely seen in children. In this case study, we discussed the diagnosis and the treatment of a giant cell tumor and superposed an ABC present in the fifth lumbar spine in a pediatric patient admitted to our clinic with a complaint of acute scoliotic back pain.

  3. Birt-Hogg-Dube syndrome presenting as multiple oncocytic parotid tumors

    Directory of Open Access Journals (Sweden)

    Lindor Noralane M

    2012-10-01

    Full Text Available Abstract Mutations in FLCN cause Birt-Hogg-Dubé syndrome, an autosomal dominant disorder notable for development of cutaneous fibrofolliculomas or trichodiscomas, a variety of renal tumors, and spontaneous pneumothorax due to cystic lung changes. We present a woman referred for genetic evaluation due to bilateral parotid gland tumors, who was subsequently diagnosed with Birt-Hogg-Dubé syndrome.

  4. Mixed germ cell tumors: Report of two cases

    Directory of Open Access Journals (Sweden)

    Pradhan M Pagaro

    2013-01-01

    Full Text Available Germ cell tumors arise in the ovaries and testis and rarely in other tissues. Mixed germ cell tumors are rare. We report two cases of mixed germ cell tumors, one consisting of seminoma and immature teratoma in the testis of a 30-year-old male and second consisting of a yolk sac tumor and immature teratoma in the ovary of a 17-year-old female. Many combinations of mixed germ cell tumors have been reported but very few cases of the above-mentioned combinations have been reported in literature.

  5. PIM kinase inhibition presents a novel targeted therapy against triple-negative breast tumors with elevated MYC expression

    Science.gov (United States)

    Horiuchi, Dai; Camarda, Roman; Zhou, Alicia Y.; Yau, Christina; Momcilovic, Olga; Balakrishnan, Sanjeev; Corella, Alexandra N.; Eyob, Henok; Kessenbrock, Kai; Lawson, Devon A.; Marsh, Lindsey A.; Anderton, Brittany N.; Rohrberg, Julia; Kunder, Ratika; Bazarov, Alexey V.; Yaswen, Paul; McManus, Michael T.; Rugo, Hope S.; Werb, Zena; Goga, Andrei

    2017-01-01

    Triple-negative breast cancer (TNBC), which lacks the expression of the estrogen, progesterone, and HER2 receptors, represents the breast cancer subtype with the poorest outcome1. No targeted therapy is available against this subtype due to lack of validated molecular targets. We previously reported that MYC signaling is disproportionally elevated in triple-negative (TN) tumors compared to receptor-positive (RP) tumors2. MYC is an essential, pleiotropic transcription factor that regulates the expression of hundreds of genes3. Direct inhibition of oncogenic MYC transcriptional activity has remained challenging4,5. The present study conducted an shRNA screen against all kinases to uncover novel MYC-dependent synthetic lethal combinations, and identified PIM1, a non-essential kinase. Here we demonstrate that PIM1 expression was elevated in TN tumors and was associated with poor prognosis in patients with hormone and HER2 receptor-negative tumors. Small molecule PIM kinase inhibitors halted the growth of human TN tumors with elevated MYC expression in patient-derived tumor xenograft (PDX) and MYC-driven transgenic breast cancer models by inhibiting oncogenic transcriptional activity of MYC while simultaneously restoring the function of the endogenous cell cycle inhibitor, p27. Our findings warrant clinical evaluation of PIM kinase inhibitors in patients with TN tumors that exhibit elevated MYC expression. PMID:27775705

  6. Circulating tumor cells: highlight on practical implications.

    Science.gov (United States)

    Gazzaniga, Paola; Raimondi, Cristina; Gradilone, Angela; Naso, Giuseppe; Cortesi, Enrico; Frati, Luigi

    2012-02-01

    Circulating tumor cells (CTCs) are cells of presumed epithelial origin, whose prognostic and predictive value in metastatic cancer patients has recently been demonstrated. To date, the count of CTCs through the CellSearch® system represents a valid approach for monitoring disease status in patients with metastatic colorectal, breast, and prostate cancer; in these cancer types, a rise in the CTC count at any time during treatment predicts a poor outcome. Nevertheless, the clinical utility of monitoring CTC counts remains controversial, and what to do when CTC counts rise during therapy still remains an unanswered question. In this report, we suggest how to integrate CTC counts with their molecular characterization to better translate biologic information obtained on CTCs into daily clinical practice.

  7. Enhancing whole-tumor cell vaccination by engaging innate immune system through NY-ESO-1/dendritic cell interactions.

    Science.gov (United States)

    Xu, Le; Zheng, Junying; Nguyen, David H; Luong, Quang T; Zeng, Gang

    2013-10-01

    NY-ESO-1 is a cancer/germline antigen (Ag) with distinctively strong immunogenicity. We have previously demonstrated that NY-ESO-1 serves as an endogenous adjuvant by engaging dendritic cell (DC)-surface receptors of calreticulin (CRT) and toll-like receptor (TLR) 4. In the present study, NY-ESO-1 was investigated for its immunomodulatory roles as a molecular adjuvant in whole-tumor cell vaccines using the Renca kidney cancer model. Renca cells were genetically engineered to express NY-ESO-1 on the cell surface to enhance direct interactions with DC. The effect of ectopic cell-surface expression of NY-ESO-1 was investigated on tumor immunogenicity, DC activation, cytotoxic T lymphocytes against model tumor-associated Ags, and the effectiveness of the modified tumor cells as a therapeutic whole-cell vaccine. Cell-surface expression of NY-ESO-1 was able to reduce the tumor growth of Renca cells in BALB/c mice, although the modification did not alter cell proliferation rate in vitro. Directly engaging the innate immune system through NY-ESO-1 facilitated the interaction of tumor cells with DC, leading to enhanced DC activation and subsequent tumor-specific T-cell priming. When used as a therapeutic whole-cell vaccine, Renca cells with NY-ESO-1 on the surface mediated stronger inhibitory effects on tumor growth and metastasis compared with parental Renca or Renca cells expressing a control protein GFP on the surface. Augmented antitumor efficacy correlated with increased CD8 T-cell infiltration into tumors and decreased myeloid-derived suppressor cells and regulatory T cells in the spleen. As a cancer/germline Ag and as an immunomodulatory adjuvant through engaging innate immune receptors, NY-ESO-1 offers a unique opportunity for improved whole-tumor cell vaccinations upon the classic GM-CSF-engineered cell vaccines.

  8. Tumor cell culture on collagen–chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies

    Directory of Open Access Journals (Sweden)

    Aziz Mahmoudzadeh

    2016-07-01

    Full Text Available Tumor cells naturally live in three-dimensional (3D microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen–chitosan scaffold compared with 2D plate cultures. Collagen–chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen–chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies.

  9. Uncommon of the uncommon: Malignant Perivascular epithelioid cell tumor of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyun Ju; Lee, Ho Yun; Han, Joung Ho; Choi, Yong Soo; Lee, Kyung Soo [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2013-08-15

    A perivascular epithelioid cell (PEC) tumor is a rare mesenchymal tumor characterized by abundant cytoplasmic Periodic acid-Schiff positive glycogen (also called sugar tumor or clear cell tumor of the lung for this characteristic) and is mostly benign. We report a case of a 63-year-old man who presented with an enlarging mass on chest radiograph. After a thorough workup, diagnosis of malignant pulmonary PEC tumor with lung to lung metastases was established. Herein, the difficulties of diagnosis and management we confronted are described.

  10. Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor

    DEFF Research Database (Denmark)

    Paiva, Carlos Eduardo; Moraes Neto, Francisco Alves; Agaimy, Abbas;

    2008-01-01

    Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms, either synchronously or metachronously. In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman...

  11. Plexin D1 is ubiquitously expressed on tumor vessels and tumor cells in solid malignancies.

    NARCIS (Netherlands)

    Roodink, I.; Verrijp, K.; Raats, J.; Leenders, W.P.J.

    2009-01-01

    BACKGROUND: Plexin D1 is expressed on both tumor-associated endothelium and malignant cells in a number of clinical brain tumors. Recently we demonstrated that Plexin D1 expression is correlated with tumor invasion level and metastasis in a human melanoma progression series. The objective of this st

  12. Circulating tumor cells: exploring intratumor heterogeneity of colorectal cancer.

    Science.gov (United States)

    Raimondi, Cristina; Nicolazzo, Chiara; Gradilone, Angela; Giannini, Giuseppe; De Falco, Elena; Chimenti, Isotta; Varriale, Elisa; Hauch, Siegfried; Plappert, Linda; Cortesi, Enrico; Gazzaniga, Paola

    2014-05-01

    The hypothesis of the "liquid biopsy" using circulating tumor cells (CTCs) emerged as a minimally invasive alternative to traditional tissue biopsy to determine cancer therapy. Discordance for biomarkers expression between primary tumor tissue and circulating tumor cells (CTCs) has been widely reported, thus rendering the biological characterization of CTCs an attractive tool for biomarkers assessment and treatment selection. Studies performed in metastatic colorectal cancer (mCRC) patients using CellSearch, the only FDA-cleared test for CTCs assessment, demonstrated a much lower yield of CTCs in this tumor type compared with breast and prostate cancer, both at baseline and during the course of treatment. Thus, although attractive, the possibility to use CTCs as therapy-related biomarker for colorectal cancer patients is still limited by a number of technical issues mainly due to the low sensitivity of the CellSearch method. In the present study we found a significant discordance between CellSearch and AdnaTest in the detection of CTCs from mCRC patients. We then investigated KRAS pathway activating mutations in CTCs and determined the degree of heterogeneity for KRAS oncogenic mutations between CTCs and tumor tissues. Whether KRAS gene amplification may represent an alternative pathway responsible for KRAS activation was further explored. KRAS gene amplification emerged as a functionally equivalent and mutually exclusive mechanism of KRAS pathway activation in CTCs, possibly related to transcriptional activation. The serial assessment of CTCs may represent an early biomarker of treatment response, able to overcome the intrinsic limit of current molecular biomarkers represented by intratumor heterogeneity.

  13. Deleted in Malignant Brain Tumors 1 is Present in the Vascular Extracellular Matrix and Promotes Angiogenesis

    DEFF Research Database (Denmark)

    Müller-Enbergs, Helmut; Hu, Jiong; Popp, Rüdiger;

    2012-01-01

    OBJECTIVE: Deleted in malignant brain tumors 1 (DMBT1) belongs to the scavenger receptor cysteine-rich superfamily of proteins and is implicated in innate immunity, cell polarity, and differentiation. Here we studied the role of DMBT1 in endothelial cells. METHODS AND RESULTS: DMBT1 was secreted...

  14. A think tank of TINK/TANKs: tumor-infiltrating/tumor-associated natural killer cells in tumor progression and angiogenesis.

    Science.gov (United States)

    Bruno, Antonino; Ferlazzo, Guido; Albini, Adriana; Noonan, Douglas M

    2014-08-01

    Tumor-infiltrating leukocytes are often induced by the cancer microenvironment to display a protumor, proangiogenic phenotype. This "polarization" has been described for several myeloid cells, in particular macrophages. Natural killer (NK) cells represent another population of innate immune cells able to infiltrate tumors. The role of NK in tumor progression and angiogenesis has not yet been fully investigated. Several studies have shown that tumor-infiltrating NK (here referred to as "TINKs") and tumor-associated NK (altered peripheral NK cells, which here we call "TANKs") are compromised in their ability to lysew tumor cells. Recent data have suggested that they are potentially protumorigenic and can also acquire a proangiogenic phenotype. Here we review the properties of TINKs and TANKs and compare their activities to that of NK cells endowed with a physiological proangiogenic phenotype, in particular decidual NK cells. We speculate on the potential origins of TINKs and TANKs and on the immune signals involved in their differentiation and polarization. The TINK and TANK phenotype has broad implications in the immune response to tumors, ranging from a deficient control of cancer and cancer stem cells to an altered crosstalk with other relevant players of the immune response, such as dendritic cells, to induction of cancer angiogenesis. With this recently acquired knowledge that has not yet been put into perspective, we point out new potential avenues for therapeutic intervention involving NK cells as a target or an ally in oncology.

  15. Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes

    Science.gov (United States)

    Johnson, Eric D.; Gulbahce, Evin; McNally, Joseph; Buys, Saundra S.

    2016-01-01

    Introduction Phyllodes tumors (PTs) are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported. PMID:28203179

  16. A Case of Large Phyllodes Tumor Causing “Rupture” of the Breast: A Unique Presentation

    Directory of Open Access Journals (Sweden)

    Junaid Nabi

    2013-01-01

    Full Text Available Introduction. Phyllodes tumors are rare fibroepithelial tumors which constitute less than 1% of all known breast neoplasms. The importance of recognizing these tumors lies in the need to differentiate them from fibroadenomas and other benign breast lesions to avoid inappropriate surgical management. We report a case of large phyllodes tumor which caused rupture of the breast and presented as an external fungating breast mass, a presentation which is exceedingly rare. Case Presentation. A 32-year-old female presented with a 1-year history of a mass in her right breast and eruption of the mass through the skin for the last 3 months. On physical examination, an ulcerated, irregular, and nodular mass measuring  cms was found hanging in the lower and outer quadrant of the right breast. Ultrasonography revealed an exophytic mass with heterogeneous echotexture and vascularity. Under general anesthesia, the tumor was excised. The resected specimen was  cm in size and the tumor was not invasive to the surrounding tissues. Histological examination confirmed a benign case of Phyllodes tumor. Conclusion. Clinicians should be aware of the myriad ways in which Phyllodes can present. A rapidly growing breast mass in a female should raise strong suspicion for Phyllodes. It is necessary to differentiate it from fibroadenomas to avoid inappropriate surgical management which may lead to local recurrence.

  17. Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes

    Directory of Open Access Journals (Sweden)

    Eric D. Johnson

    2016-12-01

    Full Text Available Introduction: Phyllodes tumors (PTs are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for <1% of malignant breast tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case: A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion: PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion: We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported.

  18. Syphilis presenting as inflammatory tumors of the liver in HIV-positive homosexual men.

    Science.gov (United States)

    Hagen, Catherine E; Kamionek, Michal; McKinsey, David S; Misdraji, Joseph

    2014-12-01

    Syphilis, a sexually transmitted infection caused by the spirochete Treponema pallidum, has seen a resurgence since 2001, particularly in men who have sex with men. Syphilis can affect the liver during the secondary stage as syphilitic hepatitis and during the tertiary stage as gummas. We describe 3 cases of syphilis in human immunodeficiency virus-positive homosexual men that presented as hepatic mass lesions clinically suspected of being malignant tumors. Histologically, 2 of the 3 cases showed a plump spindle cell proliferation, mixed inflammatory infiltrate with numerous neutrophils, and abscesses, whereas the third case showed granulomas and pericholangitis/cholangitis. Immunohistochemical staining for T. pallidum showed innumerable organisms in 2 of the cases. Pathologists must be aware of the possibility of syphilis causing hepatic inflammatory masses in human immunodeficiency virus-positive men who have sex with men in order to avoid misdiagnosis or delayed treatment.

  19. 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.

  20. Tumor cell "dead or alive": caspase and survivin regulate cell death, cell cycle and cell survival.

    Science.gov (United States)

    Suzuki, A; Shiraki, K

    2001-04-01

    Cell death and cell cycle progression are two sides of the same coin, and these two different phenomenons are regulated moderately to maintain the cellular homeostasis. Tumor is one of the disease states produced as a result of the disintegrated regulation and is characterized as cells showing an irreversible progression of cell cycle and a resistance to cell death signaling. Several investigations have been performed for the understanding of cell death or cell cycle, and cell death research has remarkably progressed in these 10 years. Caspase is a nomenclature referring to ICE/CED-3 cysteine proteinase family and plays a central role during cell death. Recently, several investigations raised some possible hypotheses that caspase is also involved in cell cycle regulation. In this issue, therefore, we review the molecular basis of cell death and cell cycle regulated by caspase in tumor, especially hepatocellular carcinoma cells.

  1. Semiallogenic fusions of MSI+ tumor cells and activated B cells induce MSI-specific T cell responses

    Directory of Open Access Journals (Sweden)

    Klier Ulrike

    2011-09-01

    Full Text Available Abstract Background Various strategies have been developed to transfer tumor-specific antigens into antigen presenting cells in order to induce cytotoxic T cell responses against tumor cells. One approach uses cellular vaccines based on fusions of autologous antigen presenting cells and allogeneic tumor cells. The fusion cells combine antigenicity of the tumor cell with optimal immunostimulatory capacity of the antigen presenting cells. Microsatellite instability caused by mutational inactivation of DNA mismatch repair genes results in translational frameshifts when affecting coding regions. It has been shown by us and others that these mutant proteins lead to the presentation of immunogenic frameshift peptides that are - in principle - recognized by a multiplicity of effector T cells. Methods We chose microsatellite instability-induced frameshift antigens as ideal to test for induction of tumor specific T cell responses by semiallogenic fusions of microsatellite instable carcinoma cells with CD40-activated B cells. Two fusion clones of HCT116 with activated B cells were selected for stimulation of T cells autologous to the B cell fusion partner. Outgrowing T cells were phenotyped and tested in functional assays. Results The fusion clones expressed frameshift antigens as well as high amounts of MHC and costimulatory molecules. Autologous T cells stimulated with these fusions were predominantly CD4+, activated, and reacted specifically against the fusion clones and also against the tumor cell fusion partner. Interestingly, a response toward 6 frameshift-derived peptides (of 14 tested could be observed. Conclusion Cellular fusions of MSI+ carcinoma cells and activated B cells combine the antigen-presenting capacity of the B cell with the antigenic repertoire of the carcinoma cell. They present frameshift-derived peptides and can induce specific and fully functional T cells recognizing not only fusion cells but also the carcinoma cells. These

  2. Primitive neuroectodermal tumor (PNET) as somatic-type malignancy arising from an extragonadal germ-cell tumor: clinical, pathological and molecular features of a case.

    Science.gov (United States)

    Garg, Amit; Nahal, Ayoub; Turcotte, Robert; Tabah, Roger; Alcindor, Thierry

    2013-01-01

    We report a rare case of a 34-year-old man with a right axillary mass. Ten years previously, he had been diagnosed with a right scapular nonseminomatous germ-cell tumor consisting of teratoma, completely resected without any further treatment. Presently he was found to have a metastatic malignant small round cell tumor consistent with a secondary somatic malignancy arising in the background of nonseminomatous germ-cell tumor, teratoma, yolk sac tumor, and primitive neuroectodermal tumor with distinct chromosome 22 translocation. Although the patient initially responded well to chemotherapy with etoposide, cisplatin, ifosfamide and mesna, he relapsed shortly after.

  3. Rare giant cell tumor involvement of the olecranon bone.

    Science.gov (United States)

    Yang, Chen; Gong, Yubao; Liu, Jianguo; Qi, Xin

    2014-06-01

    Giant cell tumor (GCT) of bone is a relatively common benign bone lesion and is usually located in long bones, but involvement of the olecranon is extremely rare. Here, we present a case of solitary GCT of bone in the olecranon that was confirmed by preoperative needle biopsy and postoperative histological examination. The treatment included intralesional curettage, allogeneic bone grafting, and plating. At 26 months follow-up, the patient had no local recurrence.

  4. Rare giant cell tumor involvement of the olecranon bone

    Directory of Open Access Journals (Sweden)

    Chen Yang

    2014-01-01

    Full Text Available Giant cell tumor (GCT of bone is a relatively common benign bone lesion and is usually located in long bones, but involvement of the olecranon is extremely rare. Here, we present a case of solitary GCT of bone in the olecranon that was confirmed by preoperative needle biopsy and postoperative histological examination. The treatment included intralesional curettage, allogeneic bone grafting, and plating. At 26 months follow-up, the patient had no local recurrence.

  5. Towards Optimal Diagnosis of Type II Germ Cell Tumors

    OpenAIRE

    Stoop, Hans

    2011-01-01

    textabstractThe aim of the work described in this thesis is to improve the understanding of the pathobiology of testicular cancer (type II Germ Cell Tumors) to create possibilities for optimalization of diagnosis for this type of malignancy in routine pathology laboratories. The different studies presented here show valuable additional information on the microscopic diagnostics in daily practice. This enables proper and complete diagnosis of this relative rare variant of cancer ensuring the b...

  6. Congenital Gingival Granular Cell Tumor: A Case Report

    Science.gov (United States)

    Yıldırım, Ceren; Zerener, Tamer; Şençimen, Metin; Akgün, Özlem Martı; Altuğ, Hasan Ayberk; ÇİÇEK, Ali Fuat

    2017-01-01

    The congenital gingival granular cell tumor (CGCT), also as known as congenital epulis, is an unusual benign oral mucosal lesion in newborns. A two-day-old female patient was admitted to the Department of Pediatric Dentistry at Gulhane Medical Academy, Ankara, Turkey with her family, and an intraoral examination showed a CGCT located in the buccal region of the maxillary right first primary molar. In this report, we present a case of CGCT in a newborn. PMID:28293667

  7. Btryoid Wilm's tumor in a child presenting with gross hematuria: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chae Jung; Im, Young Jae; Shin, Hyun Joo; Kim, Myung Joon; Lee, Mi Jung [Severance Children' s Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-09-15

    We report a unique case of botryoid Wilms' tumor with its characteristic imaging findings in a 5-month-old boy presenting with gross hematuria. In our case, ultrasonography revealed lobulated hyperechoic lesions filling the pelvicalyceal system without parenchymal invasion, mimicking a blood clot. However, magnetic resonance imaging (MRI) demonstrated the exact extent of the lesion with diffusion restriction and delayed enhancement suggestive of a tumor. Despite their rarity, botryoid Wilms' tumors should be included in the differential diagnosis of lobulated renal pelvic lesions presenting as gross hematuria in children, and MRI can suggest the diagnosis.

  8. Tumor-Induced Myeloid-Derived Suppressor Cells.

    Science.gov (United States)

    De Sanctis, Francesco; Bronte, Vincenzo; Ugel, Stefano

    2016-06-01

    Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous, immune-suppressive leukocyte population that develops systemically and infiltrates tumors. MDSCs can restrain the immune response through different mechanisms including essential metabolite consumption, reactive oxygen and nitrogen species production, as well as display of inhibitory surface molecules that alter T-cell trafficking and viability. Moreover, MDSCs play a role in tumor progression, acting directly on tumor cells and promoting cancer stemness, angiogenesis, stroma deposition, epithelial-to-mesenchymal transition, and metastasis formation. Many biological and pharmaceutical drugs affect MDSC expansion and functions in preclinical tumor models and patients, often reversing host immune dysfunctions and allowing a more effective tumor immunotherapy.

  9. Circulating Tumor Cell and Cell-free Circulating Tumor DNA in Lung Cancer.

    Science.gov (United States)

    Nurwidya, Fariz; Zaini, Jamal; Putra, Andika Chandra; Andarini, Sita; Hudoyo, Achmad; Syahruddin, Elisna; Yunus, Faisal

    2016-09-01

    Circulating tumor cells (CTCs) are tumor cells that are separated from the primary site or metastatic lesion and disseminate in blood circulation. CTCs are considered to be part of the long process of cancer metastasis. As a 'liquid biopsy', CTC molecular examination and investigation of single cancer cells create an important opportunity for providing an understanding of cancer biology and the process of metastasis. In the last decade, we have seen dramatic development in defining the role of CTCs in lung cancer in terms of diagnosis, genomic alteration determination, treatment response and, finally, prognosis prediction. The aims of this review are to understand the basic biology and to review methods of detection of CTCs that apply to the various types of solid tumor. Furthermore, we explored clinical applications, including treatment monitoring to anticipate therapy resistance as well as biomarker analysis, in the context of lung cancer. We also explored the potential use of cell-free circulating tumor DNA (ctDNA) in the genomic alteration analysis of lung cancer.

  10. Peripheral facial palsy, the only presentation of a primitive neuroectodermal tumor of the skull base

    OpenAIRE

    Kim, Hyung Jin; Kang, Ben; Joo, Eun Young; Kim, Eun Young; Kwon, Young Se

    2015-01-01

    Introduction Peripheral facial palsy is rarely caused by primary neoplasms, which are mostly constituted of tumors of the central nervous system, head and neck, and leukemia. Presentation of case A 2-month-old male infant presented with asymmetric facial expression for 3 weeks. Physical examination revealed suspicious findings of right peripheral facial palsy. Computed tomography of the temporal bone revealed a suspicious bone tumor centered in the right petrous bone involving surrounding bon...

  11. Fatty acid synthase - Modern tumor cell biology insights into a classical oncology target.

    Science.gov (United States)

    Buckley, Douglas; Duke, Gregory; Heuer, Timothy S; O'Farrell, Marie; Wagman, Allan S; McCulloch, William; Kemble, George

    2017-02-12

    Decades of preclinical and natural history studies have highlighted the potential of fatty acid synthase (FASN) as a bona fide drug target for oncology. This review will highlight the foundational concepts upon which this perspective is built. Published studies have shown that high levels of FASN in patient tumor tissues are present at later stages of disease and this overexpression predicts poor prognosis. Preclinical studies have shown that experimental overexpression of FASN in previously normal cells leads to changes that are critical for establishing a tumor phenotype. Once the tumor phenotype is established, FASN elicits several changes to the tumor cell and becomes intertwined with its survival. The product of FASN, palmitate, changes the biophysical nature of the tumor cell membrane; membrane microdomains enable the efficient assembly of signaling complexes required for continued tumor cell proliferation and survival. Membranes densely packed with phospholipids containing saturated fatty acids become resistant to the action of other chemotherapeutic agents. Inhibiting FASN leads to tumor cell death while sparing normal cells, which do not have the dependence of this enzyme for normal functions, and restores membrane architecture to more normal properties thereby resensitizing tumors to killing by chemotherapies. One compound has recently reached clinical studies in solid tumor patients and highlights the need for continued evaluation of the role of FASN in tumor cell biology. Significant advances have been made and much remains to be done to optimally apply this class of pharmacological agents for the treatment of specific cancers.

  12. Pharmacogenomics of Scopoletin in Tumor Cells

    Directory of Open Access Journals (Sweden)

    Ean-Jeong Seo

    2016-04-01

    Full Text Available Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based RNA expression profiling of the NCI cell line panel showed that cellular response of scopoletin did not correlate to the expression of ATP-binding cassette (ABC transporters as classical drug resistance mechanisms (ABCB1, ABCB5, ABCC1, ABCG2. This was also true for the expression of the oncogene EGFR and the mutational status of the tumor suppressor gene, TP53. However, mutations in the RAS oncogenes and the slow proliferative activity in terms of cell doubling times significantly correlated with scopoletin resistance. COMPARE and hierarchical cluster analyses of transcriptome-wide mRNA expression resulted in a set of 40 genes, which all harbored binding motifs in their promoter sequences for the transcription factor, NF-κB, which is known to be associated with drug resistance. RAS mutations, slow proliferative activity, and NF-κB may hamper its effectiveness. By in silico molecular docking studies, we found that scopoletin bound to NF-κB and its regulator IκB. Scopoletin activated NF-κB in a SEAP-driven NF-κB reporter cell line, indicating that NF-κB might be a resistance factor for scopoletin. In conclusion, scopoletin might serve as lead compound for drug development because of its favorable activity against tumor cells with ABC-transporter expression, although NF-κB activation may be considered as resistance factor for this compound. Further investigations are warranted to explore the full therapeutic potential of this natural product.

  13. Effect of immunomodulation on the fate of tumor cells in the central nervous system and systemic organs of mice. Distribution of (/sup 125/I)5-iodo-2'-deoxyuridine-labeled KHT tumor cells after left intracardial injection

    Energy Technology Data Exchange (ETDEWEB)

    Conley, F.K.

    1982-08-01

    The effect of systemic immunomodulation on tumor cell arrest and retention in the central nervous system was studied by following radioactively labeled tumor cells. KHT mouse sarcoma tumor cells were labeled in vitro with (/sup 125/I)IdUrd, and 1x10/sup 5/ tumor cells were injected into the left side of the hearts of syngeneic C3H mice. Experimental groups consisted of untreated normal mice, mice pretreated iv with Corynebacterium parvum, and mice chronically infected with Toxoplasma gondii; in this model both groups of immunomodulated mice are protected from developing systemic metastatic tumor, but only Toxoplasma-infected mice have protection against metastatic brain tumor. At time intervals from 1 to 96 hours, groups of mice from each experimental group were killed, and the brain and other organs were monitored for radioactivity to determine the number of viable tumor cells that had been present at the time of death. Normal mice demonstrated significant retention of tumor cells in the brain and kidneys plus adrenals at 96 hours. By contrast, in both groups of immunomodulated mice tumor cells were rapidly eliminated from systemic organs, but tumor cells were significantly retained in the central nervous system even at 96 hours after tumor cell injections. The results indicated that generalized immunomodulation had more effect in elimination of tumor cells from systemic organs than from the brain and that the elimination of tumor cells from the brain in Toxoplasma-infected mice was a delayed phenomenon.

  14. Tumor infiltrating immune cells in gliomas and meningiomas.

    Science.gov (United States)

    Domingues, Patrícia; González-Tablas, María; Otero, Álvaro; Pascual, Daniel; Miranda, David; Ruiz, Laura; Sousa, Pablo; Ciudad, Juana; Gonçalves, Jesús María; Lopes, María Celeste; Orfao, Alberto; Tabernero, María Dolores

    2016-03-01

    Tumor-infiltrating immune cells are part of a complex microenvironment that promotes and/or regulates tumor development and growth. Depending on the type of cells and their functional interactions, immune cells may play a key role in suppressing the tumor or in providing support for tumor growth, with relevant effects on patient behavior. In recent years, important advances have been achieved in the characterization of immune cell infiltrates in central nervous system (CNS) tumors, but their role in tumorigenesis and patient behavior still remain poorly understood. Overall, these studies have shown significant but variable levels of infiltration of CNS tumors by macrophage/microglial cells (TAM) and to a less extent also lymphocytes (particularly T-cells and NK cells, and less frequently also B-cells). Of note, TAM infiltrate gliomas at moderate numbers where they frequently show an immune suppressive phenotype and functional behavior; in contrast, infiltration by TAM may be very pronounced in meningiomas, particularly in cases that carry isolated monosomy 22, where the immune infiltrates also contain greater numbers of cytotoxic T and NK-cells associated with an enhanced anti-tumoral immune response. In line with this, the presence of regulatory T cells, is usually limited to a small fraction of all meningiomas, while frequently found in gliomas. Despite these differences between gliomas and meningiomas, both tumors show heterogeneous levels of infiltration by immune cells with variable functionality. In this review we summarize current knowledge about tumor-infiltrating immune cells in the two most common types of CNS tumors-gliomas and meningiomas-, as well as the role that such immune cells may play in the tumor microenvironment in controlling and/or promoting tumor development, growth and control.

  15. Langerhans Cell Histiocytosis Presenting as Uncontrolled Asthma

    Directory of Open Access Journals (Sweden)

    Frederic A. Rawlins

    2013-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is an uncommon disorder affecting primarily young adult smokers. It is characterized by abnormal proliferation of Langerhans cells, specialized monocyte-macrophage lineage antigen-presenting cells. LCH can affect the lungs in isolation or as part of a systemic disease. Most commonly, the disease presents in the third or fourth decade without gender predominance. Symptoms typically include dyspnea and cough. Commonly, physical examination is unremarkable but cor pulmonale may be observed in advanced disease. The chest radiograph is typically abnormal with nodular or interstitial infiltrates and cystic changes. High-resolution computed tomography of the chest with these findings in the middle and upper lobes of an adult smoker is virtually diagnostic of LCH. Pulmonary function assessment is variable. Asthma has rarely been reported in association with this disorder. There are only three reported cases of the diagnosis of concomitant asthma which have been made in association with the diagnosis of LCH. We present a case in which our patient presented with signs and symptoms of asthma to include confirmatory findings of airway hyperresponsiveness. The diagnosis of LCH was established after the patient failed to respond to conventional treatment for asthma, and further evaluation was completed.

  16. Giant cell tumor of the humeral head treated by denosumab: Implication to shoulder surgeons

    Directory of Open Access Journals (Sweden)

    Ka Hei Leung

    2015-01-01

    Full Text Available Giant cell tumor is a benign bone tumor that is commonly encountered. The optimal treatment of a giant cell tumor which causes extensive bony destruction is controversial. Recent studies on the receptor activator of nuclear factor κB ligand antagonist denosumab may offer a new treatment option for these patients. We presented a patient with giant cell tumor of the humeral head. He was initially treated with denosumab and subsequently with the operation. The shoulder joint was successfully salvaged. But there are potential difficulties that surgeons may face in patients treated with denosumab.

  17. The role of dendritic cells in graft-versus-tumor effect

    Directory of Open Access Journals (Sweden)

    Pavan eReddy

    2014-02-01

    Full Text Available Dendritic cells (DCs are the most potent antigen presenting cells (APCs. DCs play a pivotal role in determining the character and magnitude of immune responses to tumors. Host and donor hematopoietic derived DCs play a critical role in the development of graft-versus host disease (GVHD following allogeneic hematopoietic cell transplantation (allo-HCT. GVHD is tightly linked with the graft-versus-tumor (GVT effect. Although both host and donor DCs are important regulators of GVHD, the role of DCs in GVT is poorly understood. GVT is caused by donor T cells that attack recipient tumor cells. The donor T cells recognize alloantigens and tumor specific antigens (TSAs are mediating GVHD. The process of presentation of these antigens, especially TSAs remains unknown. Recent data suggested that DC may be essential role for inducing GVT. The mechanisms that DCs possess may include direct presentation, cross-presentation, cross-dressing. . The role they play in GVT will be reviewed.

  18. Tumor Heterogeneity, Single-Cell Sequencing, and Drug Resistance

    Directory of Open Access Journals (Sweden)

    Felix Schmidt

    2016-06-01

    Full Text Available Tumor heterogeneity has been compared with Darwinian evolution and survival of the fittest. The evolutionary ecosystem of tumors consisting of heterogeneous tumor cell populations represents a considerable challenge to tumor therapy, since all genetically and phenotypically different subpopulations have to be efficiently killed by therapy. Otherwise, even small surviving subpopulations may cause repopulation and refractory tumors. Single-cell sequencing allows for a better understanding of the genomic principles of tumor heterogeneity and represents the basis for more successful tumor treatments. The isolation and sequencing of single tumor cells still represents a considerable technical challenge and consists of three major steps: (1 single cell isolation (e.g., by laser-capture microdissection, fluorescence-activated cell sorting, micromanipulation, whole genome amplification (e.g., with the help of Phi29 DNA polymerase, and transcriptome-wide next generation sequencing technologies (e.g., 454 pyrosequencing, Illumina sequencing, and other systems. Data demonstrating the feasibility of single-cell sequencing for monitoring the emergence of drug-resistant cell clones in patient samples are discussed herein. It is envisioned that single-cell sequencing will be a valuable asset to assist the design of regimens for personalized tumor therapies based on tumor subpopulation-specific genetic alterations in individual patients.

  19. HPV16-associated tumors control myeloid cell homeostasis in lymphoid organs, generating a suppressor environment for T cells.

    Science.gov (United States)

    Stone, Simone Cardozo; Rossetti, Renata Ariza Marques; Bolpetti, Aline; Boccardo, Enrique; Souza, Patricia Savio de Araujo; Lepique, Ana Paula

    2014-10-01

    Tumors are complex structures containing different types of cells and molecules. The importance of the tumor microenvironment in tumor progression, growth, and maintenance is well-established. However, tumor effects are not restricted to the tumor microenvironment. Molecules secreted by, as well as cells that migrate from tumors, may circulate and reach other tissues. This may cause a series of systemic effects, including modulation of immune responses, and in some cases, leukocytosis and metastasis promotion. Leukocytosis has been described as a poor prognostic factor in patients with cervical cancer. The main etiological factor for cervical cancer development is persistent infection with high oncogenic risk HPV. Our laboratory has been exploring the effects of high oncogenic risk, HPV-associated tumors on lymphoid organs of the host. In the present study, we observed an increase in myeloid cell proliferation and alteration in cell signaling in APCs in the spleen of tumor-bearing mice. In parallel, we characterized the cytokines secreted in the inflammatory and tumor cell compartments in the tumor microenvironment and in the spleen of tumor-bearing mice. We show evidence of constitutive activation of the IL-6/STAT3 signaling pathway in the tumor, including TAMs, and in APCs in the spleen. We also observed that IL-10 is a central molecule in the tolerance toward tumor antigens through control of NF-κB activation, costimulatory molecule expression, and T cell proliferation. These systemic effects over myeloid cells are robust and likely an important problem to be addressed when considering strategies to improve anti-tumor T cell responses.

  20. Ovarian tumor-initiating cells display a flexible metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Angela S. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Roberts, Paul C. [Biomedical Science and Pathobiology, Virginia Tech, Blacksburg, VA (United States); Frisard, Madlyn I. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Hulver, Matthew W., E-mail: hulvermw@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Schmelz, Eva M., E-mail: eschmelz@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States)

    2014-10-15

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

  1. Prognostic value of CD66b positive tumor-infiltrating neutrophils in testicular germ cell tumor

    OpenAIRE

    2016-01-01

    Background Prognostic value of immune cells is not clear in testicular germ cell tumors (TGCTs). We aimed to investigate the prognostic value of tumor-infiltrating neutrophils in TGCTs. Methods A total of 102 patients who underwent orchiectomy for TGCT were investigated for CD66b positive tumor-infiltrating neutrophils (CD66b + TINs). Immmunostaining for CD66b was performed in 102 sections as described. Clinicopathological parameters as well as cancer specific survival and overall survival we...

  2. Pancreatic Extra-Gastrointestinal Stromal Tumor: An Unusual Presentation of a Rare Diagnosis

    Science.gov (United States)

    Joshi, Jitesh; Rustagi, Tarun

    2010-01-01

    Background: Gastrointestinal stromal tumors (GISTs) rarely develop outside the digestive tract and such tumors are designated extra-GISTs (EGISTs). The majority of EGISTs are located in the mesentery, omentum, and retroperitoneum, and the primary localization in the pancreas has been reported in only about six cases. We describe a patient with a large metastatic pancreatic EGIST that had metastasized to the liver at time of presentation. Case: An 84-year-old male presented with worsening confusion and agitation for the past few days. He also reported progressively increasing abdominal distension for the past 3 years, more so in the past few months. He denied any abdominal pain, nausea, or vomiting. He mentioned one episode of melena 2 months ago. There was a history of unintentional weight loss of 30 pounds over the past few months. Review of systems was otherwise negative. Past medical history was significant for diabetes mellitus and lactose intolerance. Pertinent examination findings included a cachectic appearance, altered mentation without any focal neurologic deficit, and marked abdominal distension with dullness on percussion. Investigations were significant for elevated ammonia level (168 ug/dL), AST/ALT/Alk. phosphatase (424/153/102 U/L), and total bilirubin of 1.7 mg/dL. CEA and CA19-9 were within normal limits. Computed tomography (CT) scan of the abdomen showed an extremely large central heterogeneous mass of 34 × 24 × 27 cm replacing the entire pancreatic tissue and multiple hepatic metastases. Subsequently, a CT-guided liver biopsy demonstrated a spindle cell neoplasm with CD117 (c-kit), CD34, and vimentin-positive cells, consistent with liver metastasis from an EGIST. On day 3, he had massive hematemesis, for which he was transferred to the intensive care unit. His condition rapidly deteriorated with hemodynamic instability and further worsening of mental status. After a thorough discussion about treatment options and prognosis, his family

  3. Malignant gastrointestinal stromal tumor presenting with hemoperitoneum in puerperium: report of a case with review of the literature

    Directory of Open Access Journals (Sweden)

    Vasilakaki Thivi

    2010-11-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GISTs are mesenchymal tumors that develop in the wall of the gastrointestinal tract and their diagnosis during pregnancy or puerperium is extremely rare. Case A 28-year old patient presented with acute abdomen due to hemoperitoneum from a large mass arising of the small intestine with distended vessels on its top and a ruptured superficial vessel bleeding into the peritoneal cavity. The patient was at the tenth postpartum day of her first pregnancy. The preoperative diagnosis was a possible ovarian or uterine mass. After an emergency exploratory laparotomy a segmental bowel resection was performed, removing the tumor with a part of 3-cm of the small intestine. Histology revealed GIST with maximum diameter of 13 cm and mitotic rates more than 5 mitoses per 50 high power fields with some atypical forms, indicating a high risk malignancy. Immunohistochemical staining of the tumor tissue demonstrated strongly positive reactivity to CD 117 (c-kit and CD34 in almost all the tumor cells. The patient was treated with oral imatinib mesylate (Gleevec 400 mg daily for one year. Three years after surgery, the patient was alive without evidence of metastases or local recurrence. Conclusion Considering that only few patients with gastrointestinal stromal tumors have been reported in the obstetrical and gynecological literature, the awareness of such an entity by the obstetricians-gynecologists is necessary in order to facilitate coordinated approach with the general surgeons and oncologists for the optimal care of the patients.

  4. In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell - endothelial cell interaction

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    Mees Soeren T

    2010-04-01

    Full Text Available Abstract Background Metastasis formation is the leading cause of death among colon cancer patients. We established a new in-situ model of in vivo microscopy of the lung to analyse initiating events of metastatic tumor cell adhesion within this typical metastatic target of colon cancer. Methods Anaesthetized CD rats were mechanically ventilated and 106 human HT-29LMM and T84 colon cancer cells were injected intracardially as single cell suspensions. Quantitative in vivo microscopy of the lung was performed in 10 minute intervals for a total of 40 minutes beginning with the time of injection. Results After vehicle treatment of HT-29LMM controls 15.2 ± 5.3; 14.2 ± 7.5; 11.4 ± 5.5; and 15.4 ± 6.5 cells/20 microscopic fields were found adherent within the pulmonary microvasculature in each 10 minute interval. Similar numbers were found after injection of the lung metastasis derived T84 cell line and after treatment of HT-29LMM with unspecific mouse control-IgG. Subsequently, HT-29LMM cells were treated with function blocking antibodies against β1-, β4-, and αv-integrins wich also did not impair tumor cell adhesion in the lung. In contrast, after hydrolization of sialylated glycoproteins on the cells' surface by neuraminidase, we observed impairment of tumor cell adhesion by more than 50% (p Conclusions These results demonstrate that the initial colon cancer cell adhesion in the capillaries of the lung is predominantly mediated by tumor cell - endothelial cell interactions, possibly supported by platelets. In contrast to reports of earlier studies that metastatic tumor cell adhesion occurs through integrin mediated binding of extracellular matrix proteins in liver, in the lung, the continuously lined endothelium appears to be specifically targeted by circulating tumor cells.

  5. The use of bispecific antibodies in tumor cell and tumor vasculature directed immunotherapy

    NARCIS (Netherlands)

    Molema, G; Kroesen, BJ; Helfrich, W; Meijer, DKF; de Leij, LFMH

    2000-01-01

    To overcome dose limiting toxicities and to increase efficacy of immunotherapy of cancer, a number of strategies are under development for selectively redirecting effector cells/molecules towards tumor cells. Many of these strategies exploit the specificity of tumor associated antigen recognition by

  6. The metabolic advantage of tumor cells

    Directory of Open Access Journals (Sweden)

    Schwartz Laurent

    2011-06-01

    Full Text Available Abstract 1- Oncogenes express proteins of "Tyrosine kinase receptor pathways", a receptor family including insulin or IGF-Growth Hormone receptors. Other oncogenes alter the PP2A phosphatase brake over these kinases. 2- Experiments on pancreatectomized animals; treated with pure insulin or total pancreatic extracts, showed that choline in the extract, preserved them from hepatomas. Since choline is a methyle donor, and since methylation regulates PP2A, the choline protection may result from PP2A methylation, which then attenuates kinases. 3- Moreover, kinases activated by the boosted signaling pathway inactivate pyruvate kinase and pyruvate dehydrogenase. In addition, demethylated PP2A would no longer dephosphorylate these enzymes. A "bottleneck" between glycolysis and the oxidative-citrate cycle interrupts the glycolytic pyruvate supply now provided via proteolysis and alanine transamination. This pyruvate forms lactate (Warburg effect and NAD+ for glycolysis. Lipolysis and fatty acids provide acetyl CoA; the citrate condensation increases, unusual oxaloacetate sources are available. ATP citrate lyase follows, supporting aberrant transaminations with glutaminolysis and tumor lipogenesis. Truncated urea cycles, increased polyamine synthesis, consume the methyl donor SAM favoring carcinogenesis. 4- The decrease of butyrate, a histone deacetylase inhibitor, elicits epigenic changes (PETEN, P53, IGFBP decrease; hexokinase, fetal-genes-M2, increase 5- IGFBP stops binding the IGF - IGFR complex, it is perhaps no longer inherited by a single mitotic daughter cell; leading to two daughter cells with a mitotic capability. 6- An excess of IGF induces a decrease of the major histocompatibility complex MHC1, Natural killer lymphocytes should eliminate such cells that start the tumor, unless the fever prostaglandin PGE2 or inflammation, inhibit them...

  7. Anal phyllodes tumor in a male patient: a unique case presentation and literature review

    OpenAIRE

    Ho, Szu-pei; Tseng, Hui-Hwa; King, TM; Chow, Philip-C

    2013-01-01

    Abstract Lesions of anogenital mammary-like glands are rare, and only 44 female cases have been reported. Herein, we describe a particularly rare case of phyllodes tumor of anogenital mammary-like glands in a 41-year-old male presenting anal bleeding. Papillectomy was performed. The excised tumor was circumscribed in shape, and after it was sliced into sections, it was noted that there were leaf-like slits on the surface of cut side. Under the microscope, the tumor was found to be biphasic, w...

  8. Flow cytometric DNA ploidy analysis of ovarian granulosa cell tumors

    NARCIS (Netherlands)

    D. Chadha; C.J. Cornelisse; A. Schabert (A.)

    1990-01-01

    textabstractAbstract The nuclear DNA content of 50 ovarian tumors initially diagnosed as granulosa cell tumors was measured by flow cytometry using paraffin-embedded archival material. The follow-up period of the patients ranged from 4 months to 19 years. Thirty-eight tumors were diploid or near-dip

  9. Prostatic stromal tumor with fatal outcome in a young man: histopathological and immunohistochemical case presentation

    Directory of Open Access Journals (Sweden)

    Massimo Roncalli

    2010-12-01

    Full Text Available Stromal tumors of the prostate are rare and only a few cases have been described in the literature, including exceptional cases of stromal tumors with unknown malignant potential (STUMP and a fatal outcome in young patients. Morphologically distinguishing a STUMP from a stromal sarcoma of the prostate (PSS is still a challenge. We describe the histopathological and immunohistochemical findings in a 34-year-old man with a malignant specialized cell stromal tumor of the prostate that was diagnosed initially as STUMP, and he developed lung metastases within a few months. The patient attended our hospital because of lower urinary tract symptoms, after having excreted tissue through the urethra a few months before. Ultrasonography and urethrocystoscopy examinations showed a mass arising from the verumontanum, and a transurethral resection (TUR revealed a high-grade spindle cell sarcoma reminiscent of a phyllode tumor of the breast. The tumor cells were immunoreactive for vimentin, progesterone receptor and, focally, CD34. The preliminary histo­logical findings were subsequently confirmed after radical prostatectomy. The patient developed bilateral lung metastases and died 25 months after the initial diagnosis. Although rare in young patients, the challenging differential diagnosis of STUMP and PSS means that a prostate STUMP diagnosis made on the basis of biopsy or TUR specimens also requires urethrocystoscopic monitoring for the early detection of any progression to PSS. Radical prostatectomy should also be carefully considered.

  10. Tumor-derived circulating endothelial cell clusters in colorectal cancer.

    KAUST Repository

    Cima, Igor

    2016-06-29

    Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor-derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease.

  11. A Rare Case of Phyllodes Tumor Metastasis to the Stomach Presenting as Anemia.

    Science.gov (United States)

    Choi, Do Il; Chi, Ho Seok; Lee, Sang Ho; Kwon, Youngmee; Park, Seog Yun; Sim, Sung Hoon; Park, In Hae; Lee, Keun Seok

    2016-09-01

    Metastasis of a phyllodes tumor to the stomach is an extremely rare condition with important clinical implications. A 44-year-old woman was initially diagnosed with a phyllodes tumor in her right breast in 2008, and subsequently presented to an out-patient clinic with dizziness on December 16, 2013. We found that she had severe anemia (hemoglobin levels: 6.7 g/dL), and we quickly performed esophagogastroduodenoscopy to identify the cause. This procedure revealed large ulcerofungating masses with active bleeding in the stomach. Histopathological examination revealed that the masses were consistent with phyllodes tumor metastases. In patients with a metastatic phyllodes tumor presenting as anemia, gastric metastasis should be considered as one of the differential diagnoses because overlooking the possibility might have dire consequences if cytotoxic chemotherapy were administered.

  12. Newcastle disease virus selectively kills human tumor cells.

    Science.gov (United States)

    Reichard, K W; Lorence, R M; Cascino, C J; Peeples, M E; Walter, R J; Fernando, M B; Reyes, H M; Greager, J A

    1992-05-01

    Newcastle disease virus (NDV), strain 73-T, has previously been shown to be cytolytic to mouse tumor cells. In this study, we have evaluated the ability of NDV to replicate in and kill human tumor cells in culture and in athymic mice. Plaque assays were used to determine the cytolytic activity of NDV on six human tumor cell lines, fibrosarcoma (HT1080), osteosarcoma (KHOS), cervical carcinoma (KB8-5-11), bladder carcinoma (HCV29T), neuroblastoma (IMR32), and Wilm's tumor (G104), and on nine different normal human fibroblast lines. NDV formed plaques on all tumor cells tested as well as on chick embryo cells (CEC), the native host for NDV. Plaques did not form on any of the normal fibroblast lines. To detect NDV replication, virus yield assays were performed which measured virus particles in infected cell culture supernatants. Virus yield increased 10,000-fold within 24 hr in tumor and CEC supernatants. Titers remained near zero in normal fibroblast supernatants. In vivo tumoricidal activity was evaluated in athymic nude Balb-c mice by subcutaneous injection of 9 x 10(6) tumor cells followed by intralesional injection of either live or heat-killed NDV (1.0 x 10(6) plaque forming units [PFU]), or medium. After live NDV treatment, tumor regression occurred in 10 out of 11 mice bearing KB8-5-11 tumors, 8 out of 8 with HT-1080 tumors, and 6 out of 7 with IMR-32 tumors. After treatment with heat-killed NDV no regression occurred (P less than 0.01, Fisher's exact test). Nontumor-bearing mice injected with 1.0 x 10(8) PFU of NDV remained healthy. These results indicate that NDV efficiently and selectively replicates in and kills tumor cells, but not normal cells, and that intralesional NDV causes complete tumor regression in athymic mice with a high therapeutic index.

  13. Congenital granular cell lesion: A rare tumor of new born

    Directory of Open Access Journals (Sweden)

    Rajesh Kumar

    2013-01-01

    Full Text Available Congenital granular cell tumor (CGCT, or congenital epulis, is an uncommon benign soft tissue lesion that usually arises from the alveolar mucosa of neonates and may cause respiratory and feeding problems. The histogenesis and clinical history of the lesion remains obscure. Treatment involves surgical excision and recurrences are rare. The present report describes a case of congenital granular cell lesion (CGCL in the anterior segment of maxillary alveolar ridge of a 2-month-old female. This lesion was causing feeding problem and was excised under local anesthesia, with no recurrence even after 3 years.

  14. Androgen Secreting Steroid Cell Tumor of the Ovary Represented with Postmenopasal Bleeding and Extensive Hirsutism

    OpenAIRE

    Jadranka Georgievska; Vesna Antovska; Neli Basheska; Natasha Aleksioska

    2013-01-01

    Introduction: Steroid cell tumors of the ovary present less than 0.1% of all ovarian tumors and belong in the group of sex cord-stromal tumors. Case description: We present a case of 69-year-old woman investigated because of postmenopausal bleeding, a 5-year history of excessive hirsutism, baldness and acne. The evaluation revealed elevated serum testosterone, but ultrasound detected a 2 cm-mass of the left ovary. The patient underwent hysterectomy and bilateral adnexectomy. The histopath...

  15. Past, present and future of fuel cells

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Though the fuel cell was invented by Grove in 1839,there are no commercially viable products at present.The development of fuel cells can be conveniently divided into three phases-exploratory phase(1839-1967).The main emphasis of the work is to increase the area of the three-phase interface at the electrode.The problem was solved by Bacon who invented the dual porosity,biporous nickel electrode.He demonstrated the first H2/O2 fuel cell(180℃,20atm).This cell was later improved and scaled up to power the Apollo lunar mission.However,the cost is too high for civilian applications and we come to the development phase (1967-2001).The main emphasis has been on the use of Teflon bonded electrodes and novel catalysts(PtRu,Pt/WO3 and Pt-Ru/WO3 anode catalyst for the anodic oxidation of impure H2 and methanol.In addition,the recent discovery of gadolinium doped ceria has reduced the operating temperature of solid oxide electrolytes to ~500℃ instead of 1 000℃.From 2001 onwards,we may be entering the breakthrough phase where the most favourable candidates are direct methanol vapor fuel cells and solid oxide electrolyte fuel cells.In the former case,there is a need to reduce the cross-over of methanol to the cathode compartment and the development of air cathode catalyst which are less affected by methanol and in the latter case,there is a need to improve the activity of the anode and cathode catalysts.

  16. The Antigen Presenting Cells Instruct Plasma Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Wei eXu

    2014-01-01

    Full Text Available The professional antigen presenting cells (APCs, including many subsets of dendritic cells and macrophages, not only mediate prompt but nonspecific response against microbes, but also bridge the antigen-specific adaptive immune response through antigen presentation. In the latter, typically activated B cells acquire cognate signals from T helper cells in the germinal center of lymphoid follicles to differentiate into plasma cells, which generate protective antibodies. Recent advances have revealed that many APC subsets provide not only signal 1 (the antigen, but also signal 2 to directly instruct the differentiation process of plasma cells in a T cell-independent manner. Herein, the different signals provided by these APC subsets to direct B cell proliferation, survival, class switching and terminal differentiation are discussed. We furthermore propose that the next generation of vaccines for boosting antibody response could be designed by targeting APCs.

  17. Tumor endothelial cells express high pentraxin 3 levels.

    Science.gov (United States)

    Hida, Kyoko; Maishi, Nako; Kawamoto, Taisuke; Akiyama, Kosuke; Ohga, Noritaka; Hida, Yasuhiro; Yamada, Kenji; Hojo, Takayuki; Kikuchi, Hiroshi; Sato, Masumi; Torii, Chisaho; Shinohara, Nobuo; Shindoh, Masanobu

    2016-12-01

    It has been described that tumor progression has many similarities to inflammation and wound healing in terms of the signaling processes involved. Among biological responses, angiogenesis, which is necessary for tumor progression and metastasis, is a common hallmark; therefore, tumor blood vessels have been considered as important therapeutic targets in anticancer therapy. We focused on pentraxin 3 (PTX3), which is a marker of cancer-related inflammation, but we found no reports on its expression and function in tumor blood vessels. Here we showed that PTX3 is expressed in mouse and human tumor blood vessels based on immunohistochemical analysis. We found that PTX3 is upregulated in primary mouse and human tumor endothelial cells compared to normal endothelial cells. We also showed that PTX3 plays an important role in the proliferation of the tumor endothelial cells. These results suggest that PTX3 is an important target for antiangiogenic therapy.

  18. Immunohistochemical characterization of feline mast cell tumors.

    Science.gov (United States)

    Mallett, C L; Northrup, N C; Saba, C F; Rodriguez, C O; Rassnick, K M; Gieger, T L; Childress, M O; Howerth, E W

    2013-01-01

    Expression of histamine, serotonin, and KIT was evaluated in 61 archived feline mast cell tumors (MCTs) from the skin (n = 29), spleen (n = 17), and gastrointestinal (GI) tract (n = 15) using immunohistochemistry. Twenty-eight percent of cutaneous MCTs, 18% of splenic MCTs, and 53% of GI MCTs displayed histamine immunoreactivity. Serotonin immunoreactivity was detected in 3 GI and 1 cutaneous MCT. Sixty-nine percent of cutaneous MCTs, 35% of splenic MCTs, and 33% of GI MCTs were positive for KIT. Expression of these biogenic amines and KIT was less common than expected. Results of this study suggest heterogeneity in feline MCTs based on anatomic location. Further studies are needed to explain the significance of these differences.

  19. Dielectrophoretic capture and genetic analysis of single neuroblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Erica L Carpenter

    2014-07-01

    Full Text Available Our understanding of the diversity of cells that escape the primary tumor and seed micrometastases remains rudimentary, and approaches for studying circulating and disseminated tumor cells have been limited by low throughput and sensitivity, reliance on single parameter sorting, and a focus on enumeration rather than phenotypic and genetic characterization. Here we utilize a highly sensitive microfluidic and dielectrophoretic approach for the isolation and genetic analysis of individual tumor cells. We employed fluorescence labeling to isolate 208 single cells from spiking experiments conducted with 11 cell lines, including 8 neuroblastoma cell lines, and achieved a capture sensitivity of 1 tumor cell per 106 white blood cells. Sample fixation or freezing had no detectable effect on cell capture. Point mutations were accurately detected in the whole genome amplification product of captured single tumor cells but not in negative control white blood cells. We applied this approach to capture 144 single tumor cells from 10 bone marrow samples from patients suffering from neuroblastoma. In this pediatric malignancy, high-risk patients often exhibit wide-spread hematogenous metastasis, but access to primary tumor can be difficult or impossible. Here we used flow-based sorting to pre-enrich samples with tumor involvement below 0.02%. For all patients for whom a mutation in the Anaplastic Lymphoma Kinase gene had already been detected in their primary tumor, the same mutation was detected in single cells from their marrow. These findings demonstrate a novel, non-invasive, and adaptable method for the capture and genetic analysis of single tumor cells from cancer patients.

  20. Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes.

    Science.gov (United States)

    Thompson, Camilla A; Purushothaman, Anurag; Ramani, Vishnu C; Vlodavsky, Israel; Sanderson, Ralph D

    2013-04-05

    Emerging evidence indicates that exosomes play a key role in tumor-host cross-talk and that exosome secretion, composition, and functional capacity are altered as tumors progress to an aggressive phenotype. However, little is known regarding the mechanisms that regulate these changes. Heparanase is an enzyme whose expression is up-regulated as tumors become more aggressive and is associated with enhanced tumor growth, angiogenesis, and metastasis. We have discovered that in human cancer cells (myeloma, lymphoblastoid, and breast cancer), when expression of heparanase is enhanced or when tumor cells are exposed to exogenous heparanase, exosome secretion is dramatically increased. Heparanase enzyme activity is required for robust enhancement of exosome secretion because enzymatically inactive forms of heparanase, even when present in high amounts, do not dramatically increase exosome secretion. Heparanase also impacts exosome protein cargo as reflected by higher levels of syndecan-1, VEGF, and hepatocyte growth factor in exosomes secreted by heparanase-high expressing cells as compared with heparanase-low expressing cells. In functional assays, exosomes from heparanase-high cells stimulated spreading of tumor cells on fibronectin and invasion of endothelial cells through extracellular matrix better than did exosomes secreted by heparanase-low cells. These studies reveal that heparanase helps drive exosome secretion, alters exosome composition, and facilitates production of exosomes that impact both tumor and host cell behavior, thereby promoting tumor progression.

  1. [The problems of yolk sac tumor morphogenesis in a light of the tumor stem cell theory].

    Science.gov (United States)

    Karseladze, A I

    2011-01-01

    The analysis of possible morphogenesis of the different structures in human yolk sac tumor has been considered. The author has supposed that features of blood vessel microarchitecture formation and perpetual differentiation of tumor cells or theirs functional modification play a crucial role in the morphogenesis of YST. The immunohistochemical investigation of some stem cells markers has showed the necessity of accounting of their distribution pattern in various cellular structures for the differential diagnosis of morphogenetical steps of YST. The growth of tumor cells differentiation rate correlates with increasing of stem cells markers expression as well c-kit > OCT4 > CD30 > PLAP.

  2. Tumor-derived IL-35 promotes tumor growth by enhancing myeloid cell accumulation and angiogenesis.

    Science.gov (United States)

    Wang, Zhihui; Liu, Jin-Qing; Liu, Zhenzhen; Shen, Rulong; Zhang, Guoqiang; Xu, Jianping; Basu, Sujit; Feng, Youmei; Bai, Xue-Feng

    2013-03-01

    IL-35 is a member of the IL-12 family of cytokines that is comprised of an IL-12 p35 subunit and an IL-12 p40-related protein subunit, EBV-induced gene 3 (EBI3). IL-35 functions through IL-35R and has a potent immune-suppressive activity. Although IL-35 was demonstrated to be produced by regulatory T cells, gene-expression analysis revealed that it is likely to have a wider distribution, including expression in cancer cells. In this study, we demonstrated that IL-35 is produced in human cancer tissues, such as large B cell lymphoma, nasopharyngeal carcinoma, and melanoma. To determine the roles of tumor-derived IL-35 in tumorigenesis and tumor immunity, we generated IL-35-producing plasmacytoma J558 and B16 melanoma cells and observed that the expression of IL-35 in cancer cells does not affect their growth and survival in vitro, but it stimulates tumorigenesis in both immune-competent and Rag1/2-deficient mice. Tumor-derived IL-35 increases CD11b(+)Gr1(+) myeloid cell accumulation in the tumor microenvironment and, thereby, promotes tumor angiogenesis. In immune-competent mice, spontaneous CTL responses to tumors are diminished. IL-35 does not directly inhibit tumor Ag-specific CD8(+) T cell activation, differentiation, and effector functions. However, IL-35-treated cancer cells had increased expression of gp130 and reduced sensitivity to CTL destruction. Thus, our study indicates novel functions for IL-35 in promoting tumor growth via the enhancement of myeloid cell accumulation, tumor angiogenesis, and suppression of tumor immunity.

  3. Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation

    Directory of Open Access Journals (Sweden)

    Moen Ingrid

    2012-01-01

    Full Text Available Abstract Background The tumor microenvironment is pivotal in tumor progression. Thus, we aimed to develop a mammary tumor model to elucidate molecular characteristics in the stroma versus the tumor cell compartment by global gene expression. Secondly, since tumor hypoxia influences several aspects of tumor pathophysiology, we hypothesized that hyperoxia might have an inhibitory effect on tumor growth per se. Finally, we aimed to identify differences in gene expression and key molecular mechanisms, both in the native state and following treatment. Methods 4T1 dsRed breast cancer cells were injected into eGFP expressing NOD/SCID mice. Group 1 was exposed to 3 intermittent HBO treatments (Day 1, 4 and 7, Group 2 to 7 daily HBO treatments (both 2.5bar, 100% O2, à 90 min, whereas the controls were exposed to a normal atmosphere. Tumor growth, histology, vascularisation, cell proliferation, cell death and metastasis were assessed. Fluorescence-activated cell sorting was used to separate tumor cells from stromal cells prior to gene expression analysis. Results The purity of sorted cells was verified by fluorescence microscopy. Gene expression profiling demonstrated that highly expressed genes in the untreated tumor stroma included constituents of the extracellular matrix and matrix metalloproteinases. Tumor growth was significantly inhibited by HBO, and the MAPK pathway was found to be significantly reduced. Immunohistochemistry indicated a significantly reduced microvessel density after intermittent HBO, whereas daily HBO did not show a similar effect. The anti-angiogenic response was reflected in the expression trends of angiogenic factors. Conclusions The present in vivo mammary tumor model enabled us to separate tumor and stromal cells, and demonstrated that the two compartments are characterized by distinct gene expressions, both in the native state and following HBO treatments. Furthermore, hyperoxia induced a significant tumor growth

  4. Targeted delivery of let-7b to reprogramme tumor-associated macrophages and tumor infiltrating dendritic cells for tumor rejection.

    Science.gov (United States)

    Huang, Zhen; Gan, Jingjing; Long, Ziyan; Guo, Guangxing; Shi, Xiafei; Wang, Chunming; Zang, Yuhui; Ding, Zhi; Chen, Jiangning; Zhang, Junfeng; Dong, Lei

    2016-06-01

    Both tumor associated macrophages (TAMs) and tumor infiltrating dendritic cells (TIDCs) are important components in the tumor microenvironment that mediate tumor immunosuppression and promote cancer progression. Targeting these cells and altering their phenotypes may become a new strategy to recover their anti-tumor activities and thereby restore the local immune surveillance against tumor. In this study, we constructed a nucleic acid delivery system for the delivery of let-7b, a synthetic microRNA mimic. Our carrier has an affinity for the mannose receptors on TAMs/TIDCs and is responsive to the low-pH tumor microenvironment. The delivery of let-7b could reactivate TAMs/TIDCs by acting as a TLR-7 agonist and suppressing IL-10 production in vitro. In a breast cancer mouse model, let-7b delivered by this system efficiently reprogrammed the functions of TAMs/TIDCs, reversed the suppressive tumor microenvironment, and inhibited tumor growth. Taken together, this strategy, designed based upon TAMs/TIDCs-targeting delivery and the dual biological functions of let-7b (TLR-7 ligand and IL-10 inhibitor), may provide a new approach for cancer immunotherapy.

  5. Cell-extrinsic effects of tumor ER stress imprint myeloid dendritic cells and impair CD8⁺ T cell priming.

    Science.gov (United States)

    Mahadevan, Navin R; Anufreichik, Veronika; Rodvold, Jeffrey J; Chiu, Kevin T; Sepulveda, Homero; Zanetti, Maurizio

    2012-01-01

    Tumor-infiltrating myeloid cells, such as dendritic cells (BMDC), are key regulators of tumor growth. However, the tumor-derived signals polarizing BMDC to a phenotype that subverts cell-mediated anti-tumor immunity have yet to be fully elucidated. Addressing this unresolved problem we show that the tumor unfolded protein response (UPR) can function in a cell-extrinsic manner via the transmission of ER stress (TERS) to BMDC. TERS-imprinted BMDC upregulate the production of pro-inflammatory, tumorigenic cytokines but also the immunosuppressive enzyme arginase. Importantly, they downregulate cross-presentation of high-affinity antigen and fail to effectively cross-prime CD8(+) T cells, causing T cell activation without proliferation and similarly dominantly suppress cross-priming by bystander BMDC. Lastly, TERS-imprinted BMDC facilitate tumor growth in vivo with fewer tumor-infiltrating CD8(+) T cells. In sum, we demonstrate that tumor-borne ER stress imprints ab initio BMDC to a phenotype that recapitulates several of the inflammatory/suppressive characteristics ascribed to tumor-infiltrating myeloid cells, highlighting the tumor UPR as a critical controller of anti-tumor immunity and a new target for immune modulation in cancer.

  6. Cell-extrinsic effects of tumor ER stress imprint myeloid dendritic cells and impair CD8⁺ T cell priming.

    Directory of Open Access Journals (Sweden)

    Navin R Mahadevan

    Full Text Available Tumor-infiltrating myeloid cells, such as dendritic cells (BMDC, are key regulators of tumor growth. However, the tumor-derived signals polarizing BMDC to a phenotype that subverts cell-mediated anti-tumor immunity have yet to be fully elucidated. Addressing this unresolved problem we show that the tumor unfolded protein response (UPR can function in a cell-extrinsic manner via the transmission of ER stress (TERS to BMDC. TERS-imprinted BMDC upregulate the production of pro-inflammatory, tumorigenic cytokines but also the immunosuppressive enzyme arginase. Importantly, they downregulate cross-presentation of high-affinity antigen and fail to effectively cross-prime CD8(+ T cells, causing T cell activation without proliferation and similarly dominantly suppress cross-priming by bystander BMDC. Lastly, TERS-imprinted BMDC facilitate tumor growth in vivo with fewer tumor-infiltrating CD8(+ T cells. In sum, we demonstrate that tumor-borne ER stress imprints ab initio BMDC to a phenotype that recapitulates several of the inflammatory/suppressive characteristics ascribed to tumor-infiltrating myeloid cells, highlighting the tumor UPR as a critical controller of anti-tumor immunity and a new target for immune modulation in cancer.

  7. T Cell-Tumor Interaction Directs the Development of Immunotherapies in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    A. E. Albers

    2010-01-01

    Full Text Available The competent immune system controls disease effectively due to induction, function, and regulation of effector lymphocytes. Immunosurveillance is exerted mostly by cytotoxic T-lymphocytes (CTLs while specific immune suppression is associated with tumor malignancy and progression. In squamous cell carcinoma of the head and neck, the presence, activity, but also suppression of tumor-specific CTL have been demonstrated. Functional CTL may exert a selection pressure on the tumor cells that consecutively escape by a combination of molecular and cellular evasion mechanisms. Certain of these mechanisms target antitumor effector cells directly or indirectly by affecting cells that regulate CTL function. This results in the dysfunction or apoptosis of lymphocytes and dysregulated lymphocyte homeostasis. Another important tumor-escape mechanism is to avoid recognition by dysregulation of antigen processing and presentation. Thus, both induction of functional CTL and susceptibility of the tumor and its microenvironment to become T cell targets should be considered in CTL-based immunotherapy.

  8. An unusual mixed germ cell tumor of the testis consisting of rhabdomyosarcoma, mature teratoma and yolk sac tumor

    Institute of Scientific and Technical Information of China (English)

    Eva Lovri(c); Dubravka Bobonj Hi(z)ak; Melita Peri(c) Balja; Tanja Leni(c)ek; Bo(z)o Kru(s)lin

    2010-01-01

    @@ Dear Editor, We recently encountered a rare case of testicular mixed germ cell tumor (MGCT) in a 32-year-old man. The tumor was composed of a combination of a yolk sac tumor, teratoma and rhabdomyosarcomatous somatic type malignancy.

  9. An unusual presentation of Langerhans cell histiocytosis

    Directory of Open Access Journals (Sweden)

    Palak Agarwal

    2014-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a relatively rare and unique disease. An incidence of 7.9% in the jaws is reported. We report a case of 9-year-old male child referred to us from dental outpatient department, who presented with a firm swelling in right lower jaw along with bilateral submandibular lymphadenopathy for 1-month. Fine-needle aspiration was done from lytic lesion in the body of mandible and multiple smears were prepared. On the basis of the clinical and cytomorphological findings, a diagnosis of LCH was suggested. The diagnosis was confirmed on histology. Thus, a high possibility of LCH should be considered in children presenting with lytic lesions in head and neck region.

  10. An unusual presentation of Langerhans cell histiocytosis

    Science.gov (United States)

    Agarwal, Palak; Kaushal, Manju

    2014-01-01

    Langerhans cell histiocytosis (LCH) is a relatively rare and unique disease. An incidence of 7.9% in the jaws is reported. We report a case of 9-year-old male child referred to us from dental outpatient department, who presented with a firm swelling in right lower jaw along with bilateral submandibular lymphadenopathy for 1-month. Fine-needle aspiration was done from lytic lesion in the body of mandible and multiple smears were prepared. On the basis of the clinical and cytomorphological findings, a diagnosis of LCH was suggested. The diagnosis was confirmed on histology. Thus, a high possibility of LCH should be considered in children presenting with lytic lesions in head and neck region. PMID:25745295

  11. Basal Cell Nevus Syndrome. A Case Presentation

    Directory of Open Access Journals (Sweden)

    Ángel Luis Cruz Leiva

    2007-12-01

    Full Text Available Basal Cell Nevus Syndrome is an infrequent entity of very low incidence according to reports in medical literature. It is characterized by considerable groups of alterations which are presented in the organism in a variable way, and with localized lesions in the maxillofacial area. A 61 year-old white male patient who lives in the urban area of Cienfuegos city is presented. He has family references of numerous physical deformities since he was born such as mental retardation, presence of moles since the first decade of his life and augmentation of the mandibular body volume. The diagnosis was keratocysts based on the clinical and radiological examinations as well as histopathological studies.

  12. Mast Cell Tumor in Dogs – Incidence and Histopathological Characterization

    OpenAIRE

    Grabarević, Željko; Bubić Špoljar, Jadranka; Gudan Kurilj, Andrea; Šoštarić-Zuckermann, Ivan-Conrado; Artuković, Branka; Hohšteter, Marko; Beck, Ana; Džaja, Petar; Maltar Strmečki, Nadica

    2009-01-01

    Incidence of mast cell tumors, their distribution according to sex, breed, age and localisation in Croatia is not established yet. Also, the statistical significance of the various histopathological parameters according to Patnaik’s scheme, in the diagnostics of the tumor grade was not performed. Investigation analysed mast cell tumors histopathologicaly characterized at the Department of General Pathology and Pathological Morphology of the Veterinary Faculty Zagreb from January 1st 2002 to D...

  13. Direct Liver Invasion from a Gastric Adenocarcinoma as an Initial Presentation of Extranodal Tumor Spread

    Directory of Open Access Journals (Sweden)

    Mitanshu Shah

    2012-01-01

    Full Text Available Gastric cancer often carries a poor prognosis, with an estimated 740,000 deaths from the malignancy occurring yearly worldwide (Dicken et al., 2005. The mortality of disease is largely dependent on the extent of tumor spread, as gastric cancer has a predilection to metastasize to other visceral secondaries via hematogenous and lymphatic dissemination. Direct invasion of a gastric adenocarcinoma to adjacent organs secondary to gastric wall perforation does occur; however, it is often present in the setting of advanced disease. Rarely does direct tumor invasion to adjacent organs from a gastric adenocarcinoma present as the initial manifestation of extranodal tumor spread. We present a case of a 40-year-old male with direct tumor extension to the liver as an initial presentation of extranodal tumor spread from a gastric adenocarcinoma. Clinicians should be aware of such an occurrence, as treatment modalities in direct liver extension from a gastric adenocarcinoma vary and may be directed towards palliation rather than curative intent.

  14. Dynamic Behavior and Function of Foxp3+ Regulatory T Cells in Tumor Bearing Host

    Institute of Scientific and Technical Information of China (English)

    F. Xiao-Feng Qin

    2009-01-01

    Regulatory T cells (Tregs) expressing forkhead/winged-helix transcription factor Foxp3 represent a distinct lineage of lymphocytes which play a central role in protecting the host from autoimmune diseases. However, Tregs also pose a major problem to anti-tumor immunity. Growing body of evidence from both laboratory and clinical investigations has demonstrated that expansion and accumulation of these immunosuppressive cells correlates with advanced tumor growth and predicts poor disease prognosis. How tumor development subverts normal self-tolerance function of Tregs thereby thwarts host anti-tumor immunity remains elusive. This review will discuss our current knowledge in understanding the dynamics and plasticity of Foxp3+ Treg activation and induction in tumor bearing hosts and their interaction with various antigen presenting cells (APCs) in tumor microenvironment leading to the establishment of active local and systemic immune suppression.

  15. Primary Dural Spinal Lymphoma Presentation of a Rare Spinal Tumor Case

    Directory of Open Access Journals (Sweden)

    Dilber Ayçiçek Çeçen

    2015-01-01

    Full Text Available Background. Primary spinal dural lymphomas (PSDL are tumors with characteristic histopathology of a lymphoma, which are completely in the spinal epidural space without any other systemic involvement. Extranodal primary lymphoma involving nervous system prefers thalamus/basal ganglia, periventricular region, cerebellum, eyes, meninges/dura, and cranial nerves or spinal cord. Rare spinal localization with acute spinal cord compression is worth attention. Case Presentation. A 48-year-old male presented with a several-month-long history of upper back pain. Lately, he had numbness and weakness at both lower extremities and was unable to walk for one week. A spinal MRI showed a thoracic lesion with cord compression at T2–T4 levels. The patient underwent surgical decompression, with his final histopathology showing diffuse large B-cell lymphoma. Systemic work-up was negative for nodal disease. Following surgery, he received radiotherapy combined with chemotherapy. He experienced a good outcome after four years. Conclusion. The upper thoracic cord is a rare location for primary spinal lesions/metastases, both of which prefer the lower thoracic and upper lumbar regions. In cases of progressive paraparesis, there should be immediate surgical intervention in the case of denovo disease, followed by combined radiotherapy and chemotherapy procedures.

  16. A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas

    Science.gov (United States)

    2016-10-18

    Ewing Sarcoma; Gastrointestinal Tumor; Germ Cell Tumor; Hepatic Tumor; Lymphoma; Wilms Tumor; Rhabdoid Tumor; Clear Cell Carcinoma; Renal Cell Carcinoma; Melanoma; Neuroblastoma; Rhabdomyosarcoma; Non-rhabdomyosarcoma

  17. 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.

  18. Clear cell variant of calcifying epithelial odontogenic tumor of maxilla: Report of a rare case

    Directory of Open Access Journals (Sweden)

    Dinesh Badrashetty

    2013-01-01

    Full Text Available The calcifying epithelial odontogenic tumor (CEOT is a rare benign tumor of the jaws. Pindborg′s tumor having clear cells is extremely rare. Twelve central lesions have been reported of which only three cases have occurred in maxilla. Clear cell variant is a distinct entity, has more aggressive biological behavior and higher chances of recurrence. Hence it is important that presence of clear cells be included in histopathological diagnosis. Here we present a rare case of clear cell CEOT having aggressive behavior.

  19. Cell Mediated Photothermal Therapy of Brain Tumors.

    Science.gov (United States)

    Hirschberg, Henry; Madsen, Steen J

    2017-03-01

    Gold based nanoparticles with strong near infra-red (NIR) absorption are ideally suited for photothermal therapy (PTT) of brain tumors. The goal of PTT is to induce rapid heating in tumor tissues while minimizing thermal diffusion to normal brain. PTT efficacy is sensitively dependent on both nanoparticle concentration and distribution in tumor tissues. Nanoparticle delivery via passive approaches such as the enhanced permeability and retention (EPR) effect is unlikely to achieve sufficient nanoparticle concentrations throughout tumor volumes required for effective PTT. A simple approach for improving tumor biodsitribution of nanoparticles is the use of cellular delivery vehicles. Specifically, this review focuses on the use of monocytes/macrophages (Mo/Ma) as gold nanoparticle delivery vectors for PTT of brain tumors. Although the efficacy of this delivery approach has been demonstrated in both in vitro and animal PTT studies, its clinical potential for the treatment of brain tumors remains uncertain.

  20. Cancer stem cells: a new approach to tumor development

    Directory of Open Access Journals (Sweden)

    Natália Cristina Ciufa Kobayashi

    2015-02-01

    Full Text Available Many theories have been proposed to explain the origins of cancer. Currently, evidences show that not every tumor cell is capable of initiating a tumor. Only a small part of the cancer cells, called cancer stem cells (CSCs, can generate a tumor identical to the original one, when removed from human tumors and transplanted into immunosuppressed mice. The name given to these cells comes from the resemblance to normal stem cells, except for the fact that their ability to divide is infinite. These cells are also affected by their microenvironment. Many of the signaling pathways, such as Wnt, Notch and Hedgehog, are altered in this tumoral subpopulation, which also contributes to abnormal proliferation. Researchers have found several markers for CSCs; however, much remains to be studied, or perhaps a universal marker does not even exist, since they vary among tumor types and even from patient to patient. It was also found that cancer stem cells are resistant to radiotherapy and chemotherapy. This may explain the re-emergence of the disease, since they are not completely eliminated and minimal amounts of CSCs can repopulate a tumor. Once the diagnosis in the early stages greatly increases the chances of curing cancer, identifying CSCs in tumors is a goal for the development of more effective treatments. The objective of this article is to discuss the origin of cancer according to the theory of stem cell cancer, as well as its markers and therapies used for treatment.

  1. Multiple skin tumors of indeterminate cells in an adult.

    Science.gov (United States)

    Kolde, G; Bröcker, E B

    1986-10-01

    An adult patient with multiple unusual histiocytic tumors of the skin is described. As shown by immunohistologic study, electron microscopy, and immunoelectron microscopy, the tumors represent circumscribed proliferations of the Langerhans cell-related indeterminate dendritic cells of the skin. This distinct cutaneous histiocytosis may represent a paraneoplastic syndrome.

  2. Intracellular particle tracking as a tool for tumor cell characterization

    NARCIS (Netherlands)

    Li, Yixuan; Duits, Michel H.G.; Schnekenburger, Jürgen

    2009-01-01

    We studied the dynamics of two types of intracellular probe particles, ballistically injected latex spheres and endogenous granules, in tumor cell lines of differerent metastatic potential: breast tumor cells (MCF-7 malignant, MCF-10A benign) and pancreas adenocarcinoma (PaTu8988T malignant, PaTu898

  3. Induction of Tumor Cell Apoptosis via Fas/DR5

    Institute of Scientific and Technical Information of China (English)

    Wenzhu Li; Shengyu Wang; Caixia Chen; Guohong Zhuang

    2006-01-01

    The apoptosis inducing effects on tumor cell lines MGC803, BEL7402 and HL60 by Fas ligand and anti-human DR5 monoclonal antibodies (anti-DR5 mAb) and the underlying mechanism was studied, Fas/DR5 mRNA was detected by RT-PCR. Cytotoxicity exerted by FasL/anti-DR5 mAb on tumor cell lines was measured by MTT assay and the induced apoptosis was determined by agarose gel electrophoresis. Flow cytometry was employed to analyze the mode of cell death. The mRNA expression of DR5 in MGC803 and BEL7402 cells after giving anti-DR5 mAb was up-regulated compared with control group, while it was down-regulated in HL60 cells in the same condition.The mRNA expression of Fas in HL60 was higher after giving FasL compared with control group, while it was lower in MGC803 and BEL7402. MGC803 and BEL7402 were sensitive to anti-DR5 mAb but partially to FasL,and HL60 was sensitive to FasL but less sensitive to anti-DR5 mAb. Apoptosis induced by Fas ligand and anti-DR5 mAb vary among tumor cell lines. The underlying mechanism may be relevant to Fas/DR5 mRNA expression,which was presented as the release of caspase-8 and Bcl-2.

  4. Inguinal lymph node metastases from germ cell testicular tumors.

    Science.gov (United States)

    Klein, F A; Whitmore, W F; Sogani, P C; Batata, M; Fisher, H; Herr, H W

    1984-03-01

    Between 1948 and 1982, 22 patients were seen with metastasis to the inguinal nodes from testicular germ cell tumors: 8 had a history of unilateral or bilateral orchiopexy with or without herniorrhaphy, 4 had nonsurgically corrected or uncorrected cryptorchidism, 9 had a history of herniorrhaphy, hydrocelectomy or transscrotal orchiectomy and 1 had no history of scrotal, iliac or inguinal surgery, or of tunica vaginalis or scrotal wall involvement by tumor. The histological type was pure seminoma in 5 patients, embryonal carcinoma in 7 and mixed tumor in 10. Treatment was individualized for tumor type and mode of presentation, and varied during the years according to the modalities available. At the time of this report 8 of 22 patients (36 per cent) are alive without evidence of disease from 2 to 29.5 years, 3 (16 per cent) have died without evidence of disease 10 to 17 years after treatment, 10 (45 per cent) have died of metastases 10 months to 6 years after treatment and 1 has been lost to followup. The over-all incidence of groin metastases from testicular carcinoma is low, even with a history of scrotal or inguinal surgery.

  5. Treatment Options By Stage (Ovarian Germ Cell Tumors)

    Science.gov (United States)

    ... ovarian germ cell tumor are swelling of the abdomen or vaginal bleeding after menopause. Ovarian germ cell ... if you have either of the following: Swollen abdomen without weight gain in other parts of the ...

  6. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Suhail Mahmoud M

    2011-12-01

    Full Text Available Abstract Background Gum resins obtained from trees of the Burseraceae family (Boswellia sp. are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to optimize conditions for preparing Boswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells. Methods Boswellia sacra essential oil was prepared from Omani Hougari grade resins through hydrodistillation at 78 or 100 oC for 12 hours. Chemical compositions were identified by gas chromatography-mass spectrometry; and total boswellic acids contents were quantified by high-performance liquid chromatography. Boswellia sacra essential oil-mediated cell viability and death were studied in established human breast cancer cell lines (T47D, MCF7, MDA-MB-231 and an immortalized normal human breast cell line (MCF10-2A. Apoptosis was assayed by genomic DNA fragmentation. Anti-invasive and anti-multicellular tumor properties were evaluated by cellular network and spheroid formation models, respectively. Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation. Results More abundant high molecular weight compounds, including boswellic acids, were present in Boswellia sacra essential oil prepared at 100 oC hydrodistillation. All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death, whereas the immortalized normal human breast cell line was more resistant to essential oil

  7. Biodegradable polymeric micelle-encapsulated doxorubicin suppresses tumor metastasis by killing circulating tumor cells

    Science.gov (United States)

    Deng, Senyi; Wu, Qinjie; Zhao, Yuwei; Zheng, Xin; Wu, Ni; Pang, Jing; Li, Xuejing; Bi, Cheng; Liu, Xinyu; Yang, Li; Liu, Lei; Su, Weijun; Wei, Yuquan; Gong, Changyang

    2015-03-01

    Circulating tumor cells (CTCs) play a crucial role in tumor metastasis, but it is rare for any chemotherapy regimen to focus on killing CTCs. Herein, we describe doxorubicin (Dox) micelles that showed anti-metastatic activity by killing CTCs. Dox micelles with a small particle size and high encapsulation efficiency were obtained using a pH-induced self-assembly method. Compared with free Dox, Dox micelles exhibited improved cytotoxicity, apoptosis induction, and cellular uptake. In addition, Dox micelles showed a sustained release behavior in vitro, and in a transgenic zebrafish model, Dox micelles exhibited a longer circulation time and lower extravasation from blood vessels into surrounding tissues. Anti-tumor and anti-metastatic activities of Dox micelles were investigated in transgenic zebrafish and mouse models. In transgenic zebrafish, Dox micelles inhibited tumor growth and prolonged the survival of tumor-bearing zebrafish. Furthermore, Dox micelles suppressed tumor metastasis by killing CTCs. In addition, improved anti-tumor and anti-metastatic activities were also confirmed in mouse tumor models, where immunofluorescent staining of tumors indicated that Dox micelles induced more apoptosis and showed fewer proliferation-positive cells. There were decreased side effects in transgenic zebrafish and mice after administration of Dox micelles. In conclusion, Dox micelles showed stronger anti-tumor and anti-metastatic activities and decreased side effects both in vitro and in vivo, which may have potential applications in cancer therapy.

  8. Internalization of NK cells into tumor cells requires ezrin and leads to programmed cell-in-cell death

    Institute of Scientific and Technical Information of China (English)

    Shan Wang; Zhen Guo; Peng Xia; Tingting Liu; Jufang Wang; Shan Li; Lihua Sun; Jianxin Lu; Qian Wen; Mingqian Zhou; Li Ma; Xia Ding; Xiaoning Wang; Xuebiao Yao

    2009-01-01

    Cytotoxic lymphocytes are key players in the orchestration of immune response and elimination of defective cells. We have previously reported that natural killer (NK) cells enter target tumor cells, leading to either target cell death or self-destruction within tumor cells. However, it has remained elusive as to the fate of NK cells after internaliza-tion and whether the heterotypic cell-in-cell process is different from that of the homotypic cell-in-cell event recently named entosis. Here, we show that NK cells undergo a cell-in-cell process with the ultimate fate of apoptosis within tumor cells and reveal that the internalization process requires the actin cytoskeletal regulator, ezrin. To visualize how NK cells enter into tumor cells, we carried out real-time dual color imaging analyses of NK cell internalization into tumor cells. Surprisingly, most NK cells commit to programmed cell death after their entry into tumor cells, which is distinctively different from entosis observed in the homotypic cell-in-cell process. The apoptotic cell death of the internalized NK cells was evident by activation of caspase 3 and DNA fragmentation. Furthermore, NK cell death after internalization is attenuated by the caspase inhibitor, Z-VAD-FMK, confirming apoptosis as the mode of NK cell death within tumor cells. To determine protein factors essential for the entry of NK cells into tumor cells, we car-ried out siRNA-based knockdown analysis and discovered a critical role of ezrin in NK cell internalization. Impor-tantly, PKA-mediated phosphorylation of ezrin promotes the NK cell internalization process. Our findings suggest a novel regulatory mechanism by which ezrin governs NK cell internalization into tumor cells.

  9. An unusual presentation of tumor lysis syndrome in a patient with advanced gastric adenocarcinoma: case report and literature review.

    Science.gov (United States)

    Vodopivec, Danica Maria; Rubio, Jose Enrique; Fornoni, Alessia; Lenz, Oliver

    2012-01-01

    Tumor lysis syndrome (TLS) is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia in patients with a malignancy. When these laboratory abnormalities develop rapidly, clinical complications such as cardiac arrhythmias, acute renal failure, seizures, or death may occur. TLS is caused by rapid release of intracellular contents by dying tumor cells, a condition that is expected to be common in hematologic malignancies. However, TLS rarely occurs with solid tumors, and here we present the second chemotherapy-induced TLS in a patient with advanced gastric adenocarcinoma to be reported in the literature. We also provide information regarding the total cases of TLS in solid tumors reported from 1977 to present day. Our methodology involved identifying key articles from existing reviews of the literature and then using search terms from these citations in MEDLINE to find additional publications. We relied on a literature review published in 2003 by Baeksgaard et al., where they gathered all total 45 cases reported from 1977 to 2003. Then, we looked for new reported cases from 2004 to present day. All reports (case reports, brief reports, letters to editor, correspondence, reviews, journals, and short communications) identified through these searches were reviewed and included.

  10. An Unusual Presentation of Tumor Lysis Syndrome in a Patient with Advanced Gastric Adenocarcinoma: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Danica Maria Vodopivec

    2012-01-01

    Full Text Available Tumor lysis syndrome (TLS is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia in patients with a malignancy. When these laboratory abnormalities develop rapidly, clinical complications such as cardiac arrhythmias, acute renal failure, seizures, or death may occur. TLS is caused by rapid release of intracellular contents by dying tumor cells, a condition that is expected to be common in hematologic malignancies. However, TLS rarely occurs with solid tumors, and here we present the second chemotherapy-induced TLS in a patient with advanced gastric adenocarcinoma to be reported in the literature. We also provide information regarding the total cases of TLS in solid tumors reported from 1977 to present day. Our methodology involved identifying key articles from existing reviews of the literature and then using search terms from these citations in MEDLINE to find additional publications. We relied on a literature review published in 2003 by Baeksgaard et al., where they gathered all total 45 cases reported from 1977 to 2003. Then, we looked for new reported cases from 2004 to present day. All reports (case reports, brief reports, letters to editor, correspondence, reviews, journals, and short communications identified through these searches were reviewed and included.

  11. Nonepiphyseal Giant Cell Tumor of the Rib: A Case Report

    Directory of Open Access Journals (Sweden)

    Hippocrates Moschouris

    2012-01-01

    Full Text Available A case of a 32-year-old female patient with a giant cell tumor originating in the middle part of the left 10th rib is presented. On X-rays and CT, the tumor caused a well-defined osteolysis with nonsclerotic borders. On MRI, it exhibited intermediate signal intensity on T1 sequences and central high signal and peripheral intermediate signal on T2 sequences. On contrast-enhanced MR images both central and peripheral-periosteal enhancement was noted. Thanks to its small size ( cm, the lesion was easily resected en bloc with a part of the affected rib. The patient is free of recurrence for 3 years after the operation.

  12. Tumor-stem cells interactions by fluorescence imaging

    Science.gov (United States)

    Meleshina, Aleksandra V.; Cherkasova, Elena I.; Sergeeva, Ekaterina; Turchin, Ilya V.; Kiseleva, Ekaterina V.; Dashinimaev, Erdem B.; Shirmanova, Marina V.; Zagaynova, Elena V.

    2013-02-01

    Recently, great deal of interest is investigation the function of the stem cells (SC) in tumors. In this study, we studied «recipient-tumor- fluorescent stem cells » system using the methods of in vivo imaging and laser scanning microscopy (LSM). We used adipose-derived adult stem (ADAS) cells of human lentiviral transfected with the gene of fluorescent protein Turbo FP635. ADAS cells were administrated into nude mice with transplanted tumor HeLa Kyoto (human cervical carcinoma) at different stages of tumor growth (0-8 days) intravenously or into tumor. In vivo imaging was performed on the experimental setup for epi - luminescence bioimaging (IAP RAS, Nizhny Novgorod). The results of the imaging showed localization of fluorophore tagged stem cells in the spleen on day 5-9 after injection. The sensitivity of the technique may be improved by spectral separation autofluorescence and fluorescence of stem cells. We compared the results of in vivo imaging and confocal laser scanning microscopy (LSM 510 META, Carl Zeiss, Germany). Internal organs of the animals and tumor tissue were investigated. It was shown that with i.v. injection of ADAS, bright fluorescent structures with spectral characteristics corresponding to TurboFP635 protein are locally accumulated in the marrow, lungs and tumors of animals. These findings indicate that ADAS cells integrate in the animal body with transplanted tumor and can be identified by fluorescence bioimaging techniques in vivo and ex vivo.

  13. Tumor antigen-specific CD4+ T cells in cancer immunity: from antigen identification to tumor prognosis and development of therapeutic strategies.

    Science.gov (United States)

    Protti, M P; De Monte, L; Monte, L D; Di Lullo, G; Lullo, G D

    2014-04-01

    CD4(+) T cells comprise a large fraction of tumor infiltrating lymphocytes and it is now established that they may exert an important role in tumor immune-surveillance. Several CD4(+) T cell subsets [i.e. T helper (Th)1, Th2, T regulatory (Treg), Th17, Th22 and follicular T helper (Tfh)] have been described and differentiation of each subset depends on both the antigen presenting cells responsible for its activation and the cytokine environment present at the site of priming. Tumor antigen-specific CD4(+) T cells with different functional activity have been found in the blood of cancer patients and different CD4(+) T cell subsets have been identified at the tumor site by the expression of specific transcription factors and the profile of secreted cytokines. Importantly, depending on the subset, CD4(+) T cells may exert antitumor versus pro-tumor functions. Here we review the studies that first identified the presence of tumor-specific CD4(+) T cells in cancer patients, the techniques used to identify the tumor antigens recognized, the role of the different CD4(+) T cell subsets in tumor immunity and in cancer prognosis and the development of therapeutic strategies aimed at activating efficient antitumor CD4(+) T cell effectors.

  14. Giant cell tumor of the tendon sheath: a rare periungual location simulating myxoid cyst*

    Science.gov (United States)

    Minotto, Renan; Rodrigues, Camila Britto; Grill, Aline Barcellos; Furian, Roque

    2017-01-01

    Giant cell tumor of the tendon sheath is a benign soft tissue tumor most frequent between the third and fifth decades of life. It can mimic and make differential diagnoses with several hand tumors. Definitive diagnosis and the treatment of choice are reached with complete resection and histopathological examination. Here we describe a case with clinical presentation similar to that of a myxoid cyst. PMID:28225971

  15. Identification of a population of epidermal squamous cell carcinoma cells with enhanced potential for tumor formation.

    Directory of Open Access Journals (Sweden)

    Gautam Adhikary

    Full Text Available Epidermal squamous cell carcinoma is among the most common cancers in humans. These tumors are comprised of phenotypically diverse populations of cells that display varying potential for proliferation and differentiation. An important goal is identifying cells from this population that drive tumor formation. To enrich for tumor-forming cells, cancer cells were grown as spheroids in non-attached conditions. We show that spheroid-selected cells form faster growing and larger tumors in immune-compromised mice as compared to non-selected cells. Moreover, spheroid-selected cells gave rise to tumors following injection of as few as one hundred cells, suggesting these cells have enhanced tumor-forming potential. Cells isolated from spheroid-selected tumors retain an enhanced ability to grow as spheroids when grown in non-attached culture conditions. Thus, these tumor-forming cells retain their phenotype following in vivo passage as tumors. Detailed analysis reveals that spheroid-selected cultures are highly enriched for expression of epidermal stem cell and embryonic stem cell markers, including aldehyde dehydrogenase 1, keratin 15, CD200, keratin 19, Oct4, Bmi-1, Ezh2 and trimethylated histone H3. These studies indicate that a subpopulation of cells that possess stem cell-like properties and express stem cell markers can be derived from human epidermal cancer cells and that these cells display enhanced ability to drive tumor formation.

  16. Primary Cervical Placental Site Trophoblastic Tumor: A Rare Entity with an Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Kanthilatha Pai

    2013-10-01

    Full Text Available Placental site trophoblastic tumour (PSTT is the least common form of gestational trophoblastic neoplasia accounting for only 1-2% of trophoblastic tumors. Approximately 200 cases are reported in English literature. PSTT presenting as a cervical growth is even less common. Differentiation of PSTT from other types of GTN, non-neoplastic gestational trophoblastic disease and non-trophoblastic tumors is important clinically due to differences in their therapeutic approaches.Appreciation of the morphologic features and immunophenotype allows their accurate diagnosis.Although most of the cases of PSTT behave in a benign fashion,the clinical behavior of PSTT can sometimes be variable and several prognostic factors can help to predict the biological behavior of this condition. We report a rare case of placental site trophoblastic tumor, presenting as a cervical mass, in a 38 year old female, and review the literature. [J Interdiscipl Histopathol 2013; 1(5.000: 286-289

  17. Germ Cell Tumor Targeting Chemotherapy in Gastric Adenocarcinoma with an Endodermal Sinus Tumor Component: A Case Report.

    Science.gov (United States)

    Choi, Jung Eun; Choe, A Reum; Yoon, Sang Eun; Nam, Eun Mi; Park, Heejung; Lee, Kyoung Eun

    2017-01-01

    The most common sites for extragonadal germ cell tumors are the midline mediastinum, retroperitoneum and, much less frequently, the stomach. The stomach-originated primary germ cell tumor carries a poor prognosis, especially when metastasis occurs to the liver, with a mean survival time of 1 month. We describe the case of a 77-year-old male who presented with usual symptoms of gastric malignancy. Gastrectomy was performed. Histopathology of surgically resected tissue revealed a mixture of adenocarcinoma and endodermal sinus tumor components with α-fetoprotein production. After liver metastasis was identified, oxaliplatin and capecitabine were administered as palliative chemotherapy. The response was poor. For the second-line therapy, bleomycin, etoposide, and cisplatin (BEP) therapy was initiated. The overall response to these drugs was a partial response and the residual liver lesion was considered to be resectable. The patient died of pneumonia 11 months following the BEP session, representing an overall survival time of 22 months. Gastric adenocarcinoma with a germ cell tumor component is uncommon and an effective combination of chemotherapeutic agents is not yet clear. In this case, the patient received germ cell tumor-targeting chemotherapy and showed a durable response. Hence, germ cell-targeting cytotoxic agents have potential as the 'front-line regimen'.

  18. Extra-tongue oral granular cell tumor: Histological and immunohistochemical aspect

    Science.gov (United States)

    Pigatti, Fernanda-Mombrini; Martins-Mussi, Maria-Carolina; Sedassari, Bruno-Tavares; Orsini-Machado de Sousa, Suzana-Cantanhede

    2017-01-01

    Background Granular cell tumor (GCT) is an uncommon benign tumor founded in any part of the body but mainly in the tongue. Extra-tongue oral granular cell tumor (ETOGCT) is rare with few cases reported. Here we describe seven cases of oral GCT located in sites other then the tongue and discuss histopathological and immunohistochemical differences between differential diagnoses. Material and Methods We retrieved all cases diagnosed with oral granular cell tumor, from the Oral Pathology Service at the School of Dentistry/ University of São Paulo, and excluded the ones sited in the tongue. Immunohistochemical staining anti-S100 was also performed. Results The presented cases of Extra-tongue Oral Granular Cell Tumor (ETOGT) are composed by granular cells with intimately association with the adjacent tissue. Atypia and mitoses were not seen, and in most cases, the typical pseudoepitheliomatous hyperplasia was not observed. Conclusions The importance of an adequate attention is to avoid misdiagnoses, since ETOGT is rare and the tricking histopathological findings could induce to it. All the cases can be differentiated from the tumors that has a granular cell proliferation through a morphological analysis and when needed, immunohistochemistry stain. Key words:Abrikossoff`s tumor, granular cell tumor, oral cavity. PMID:27918739

  19. High interstitial fluid pressure promotes tumor cell proliferation and invasion in oral squamous cell carcinoma.

    Science.gov (United States)

    Yu, Tao; Liu, Kun; Wu, Yingying; Fan, Jinchuan; Chen, Jianchao; Li, Chao; Zhu, Guiquan; Wang, Zhaohui; Li, Longjiang

    2013-11-01

    It has been shown that interstitial fluid pressure (IFP) is elevated in many solid tumors. The elevated IFP in tumors is responsible, at least in part, for the poor blood supply, inadequate delivery of therapeutic agents to solid tumors and poor treatment response in patients. The present study was carried out to examine alterations in malignant phenotypes in oral squamous cell carcinoma cells subjected to conditions mimicking IFP and to identify the relevant molecular mechanisms. We investigated tumor cell proliferation and invasion using SCC-4 and SCC-9 cells subjected to an increased extracellular pressure of 0, 15 and 30 mmHg in vitro. The results revealed that the increased IFP resulted in a marked increase in cancer cell proliferation, survival and invasion in vitro and altered the expression of >1,800 genes involved in invasion and metastasis, the heat shock pathway, the p38 and JNK signaling pathway, apoptosis and the cell growth and differentiation signaling pathway. These results suggest the important potential clinical application of measuring IFP, which can be used as a generic marker of prognosis and response to therapy.

  20. Goblet Cell Carcinoid Tumor of the Appendix with Small Bowel Obstruction: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Su Yeon; Jang, Kyung Mi; Kim, Min Jeong; Koh, Sung Hye; Jeon, Eui Yong; Min, Kwang Seon; Seo, Jin Won; Park, Hyoung Chul [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2009-09-15

    Goblet cell carcinoid tumor of the appendix (GCTA) is a tumor with histological features of both adenocarcinoma and carcinoid tumors. The most common clinical presentation of GCTA is acute appendicitis, although small bowel obstruction has been reported as a rare clinical symptom of GCTA. However, to the best of our knowledge, the CT feature of small bowel obstructions in patients with GCTA has not been reported to date. Here, we present a case of small bowel obstruction in a patient with GCTA caused by extensive tumor infiltration at the terminal ileum and distal ileum.

  1. The Klatskin Tumor That Wasn't: An Unusual Presentation of Sarcoidosis.

    Science.gov (United States)

    Farooq, Priya D; Potosky, Darryn R

    2016-08-01

    We present the case of a patient who presented with signs and symptoms associated with a Klatskin tumor. After endoscopic retrograde cholangiopancreatography (ERCP) and biopsy, she was found instead to have granulomatous infiltration of the extrahepatic biliary tree consistent with biliary sarcoidosis. The patient was treated successfully with systemic corticosteroids and azathioprine. She later developed cutaneous, lymphatic, and pulmonary granulomatous disease. Isolated biliary disease is a rare initial presentation of systemic sarcoidosis.

  2. The Klatskin Tumor That Wasn’t: An Unusual Presentation of Sarcoidosis

    Science.gov (United States)

    Potosky, Darryn R.

    2016-01-01

    We present the case of a patient who presented with signs and symptoms associated with a Klatskin tumor. After endoscopic retrograde cholangiopancreatography (ERCP) and biopsy, she was found instead to have granulomatous infiltration of the extrahepatic biliary tree consistent with biliary sarcoidosis. The patient was treated successfully with systemic corticosteroids and azathioprine. She later developed cutaneous, lymphatic, and pulmonary granulomatous disease. Isolated biliary disease is a rare initial presentation of systemic sarcoidosis. PMID:27761479

  3. Circulating Tumor Cells in Breast Cancer Patients: An Evolving Role in Patient Prognosis and Disease Progression

    Directory of Open Access Journals (Sweden)

    Holly Graves

    2011-01-01

    Full Text Available In this paper, we examine the role of circulating tumor cells (CTCs in breast cancer. CTCs are tumor cells present in the peripheral blood. They are found in many different carcinomas but are not present in patients with benign disease. Recent advances in theories regarding metastasis support the role of early release of tumor cells in the neoplastic process. Furthermore, it has been found that phenotypic variation exists between the primary tumor and CTCs. Of particular interest is the incongruency found between primary tumor and CTC HER2 status in both metastatic and early breast cancer. Overall, CTCs have been shown to be a poor prognostic marker in metastatic breast cancer. CTCs in early breast cancer are not as well studied, however, several studies suggest that the presence of CTCs in early breast cancer may also suggest a poorer prognosis. Studies are currently underway looking at the use of CTC level monitoring in order to guide changes in therapy.

  4. From Tumor Immunosuppression to Eradication: Targeting Homing and Activity of Immune Effector Cells to Tumors

    Directory of Open Access Journals (Sweden)

    Oana Draghiciu

    2011-01-01

    Full Text Available Unraveling the mechanisms used by the immune system to fight cancer development is one of the most ambitious undertakings in immunology. Detailed knowledge regarding the mechanisms of induction of tolerance and immunosuppression within the tumor microenvironment will contribute to the development of highly effective tumor eradication strategies. Research within the last few decades has shed more light on the matter. This paper aims to give an overview on the current knowledge of the main tolerance and immunosuppression mechanisms elicited within the tumor microenvironment, with the focus on development of effective immunotherapeutic strategies to improve homing and activity of immune effector cells to tumors.

  5. [Frequent allelic losses in tumor-associated stromal cells and tumor epitelium of prostate cancer].

    Science.gov (United States)

    Kekeeva, T V; Popova, O P; Shegaĭ, P V; Zavalishina, L E; Andreeva, Iu Iu; Zaletaev, D V; Nemtsova, M V

    2008-01-01

    It has become increasingly clear that tumor microenvironment plays a critical role in carcinogenesis. Accumulation of genetic alterations is typical not only for cancer epithelial cells but tumor-associated fibroblasts as well. Tumor epithelia, tumor-associated stroma from prostatectomy specimens of patients with prostate cancer and cells from prostatic intraepithelial neoplasia (PIN) and adjacent stroma from males with PIN were isolated by using laser capture microdissection. Microsatellite allelotyping was evaluated using 4 highly polymorphic markers for chromosomal regions 8p22, 16q23-24 and 13q14. Incidences of alterations (loss of heterozygosity or allelic imbalance) were 48% for region 8p22, 72% for 16q23 and 37% for 13q14. The LOH frequencies in tumor-associated stroma cells were very similar. Alterations at chromosome 13q were significantly associated with advanced tumor stage, whereas AI at 16q was also associated with high Gleason score and lymph node metastasis. We find some incidences of allelic imbalance in premalignant lesions in epithelial (16-27%) and stromal (7-22%) components. Our results show that the frequencies of genetic aberrations are as high in stromal cells as in tumor cells.

  6. Tumor Irradiation Increases the Recruitment of Circulating Mesenchymal Stem Cells into the Tumor Microenvironment

    Science.gov (United States)

    Klopp, Ann H.; Spaeth, Erika L.; Dembinski, Jennifer L.; Woodward, Wendy A.; Munshi, Anupama; Meyn, Raymond E.; Cox, James D.; Andreeff, Michael; Marini, Frank C.

    2011-01-01

    Mesenchymal stem cells (MSC) migrate to and proliferate within sites of inflammation and tumors as part of the tissue remodeling process. Radiation increases the expression of inflammatory mediators that could enhance the recruitment of MSC into the tumor microenvironment. To investigate this, bilateral murine 4T1 breast carcinomas (expressing renilla luciferase) were irradiated unilaterally (1 or 2 Gy). Twenty-four hours later, 2 × 105 MSC-expressing firefly luciferase were injected i.v. Mice were then monitored with bioluminescent imaging for expression of both renilla (tumor) and firefly (MSC) luciferase. Forty-eight hours postirradiation, levels of MSC engraftment were 34% higher in tumors receiving 2 Gy (P = 0.004) than in the contralateral unirradiated limb. Immunohistochemical staining of tumor sections from mice treated unilaterally with 2 Gy revealed higher levels of MSC in the parenchyma of radiated tumors, whereas a higher proportion of MSC remained vasculature-associated in unirradiated tumors. To discern the potential mediators involved in MSC attraction, in vitro migration assays showed a 50% to 80% increase in MSC migration towards conditioned media from 1 to 5 Gy-irradiated 4T1 cells compared with unirradiated 4T1 cells. Irradiated 4T1 cells had increased expression of the cytokines, transforming growth factor-β1, vascular endothelial growth factor, and platelet-derived growth factor-BB, and this up-regulation was confirmed by immunohistochemistry in tumors irradiated in vivo. Interestingly, the chemokine receptor CCR2 was found to be up-regulated in MSC exposed to irradiated tumor cells and inhibition of CCR2 led to a marked decrease of MSC migration in vitro. In conclusion, clinically relevant low doses of irradiation increase the tropism for and engraftment of MSC in the tumor microenvironment. PMID:18089798

  7. Endothelial cell tumor growth is Ape/ref-1 dependent.

    Science.gov (United States)

    Biswas, Ayan; Khanna, Savita; Roy, Sashwati; Pan, Xueliang; Sen, Chandan K; Gordillo, Gayle M

    2015-09-01

    Tumor-forming endothelial cells have highly elevated levels of Nox-4 that release H2O2 into the nucleus, which is generally not compatible with cell survival. We sought to identify compensatory mechanisms that enable tumor-forming endothelial cells to survive and proliferate under these conditions. Ape-1/ref-1 (Apex-1) is a multifunctional protein that promotes DNA binding of redox-sensitive transcription factors, such as AP-1, and repairs oxidative DNA damage. A validated mouse endothelial cell (EOMA) tumor model was used to demonstrate that Nox-4-derived H2O2 causes DNA oxidation that induces Apex-1 expression. Apex-1 functions as a chaperone to keep transcription factors in a reduced state. In EOMA cells Apex-1 enables AP-1 binding to the monocyte chemoattractant protein-1 (mcp-1) promoter and expression of that protein is required for endothelial cell tumor formation. Intraperitoneal injection of the small molecule inhibitor E3330, which specifically targets Apex-1 redox-sensitive functions, resulted in a 50% decrease in tumor volume compared with mice injected with vehicle control (n = 6 per group), indicating that endothelial cell tumor proliferation is dependent on Apex-1 expression. These are the first reported results to establish Nox-4 induction of Apex-1 as a mechanism promoting endothelial cell tumor formation.

  8. INTERNALIZATION OF ANTIMICROBIAL PEPTIDE ACIPENSIN 1 INTO HUMAN TUMOR CELLS

    Directory of Open Access Journals (Sweden)

    E. S. Umnyakova

    2016-01-01

    Full Text Available Search for new compounds providing delivery of drugs into infected or neoplastic cells, is an important direction of biomedical research. Cell-penetrating peptides are among those compounds, due to their ability to translocate through membranes of eukaryotic cells, serving as potential carriers of various therapeutic agents to the target cells. The aim of present work was to investigate the ability of acipensin 1, an antimicrobial peptide of innate immune system, for in vitro penetration into human tumor cells. Acipensin 1 is a cationic peptide that we have previously isolated from leukocytes of the Russian sturgeon, Acipenser gueldenstaedtii. Capability of acipensin 1 to enter the human erytroleukemia K-562 cells has been investigated for the first time. A biotechnological procedure for producing a recombinant acipensin 1 peptide has been developed. The obtained peptide was conjugated with a fluorescent probe BODIPY FL. By means of confocal microscopy, we have shown that the tagged acipensin 1 rapidly enters into K-562 cells and can be detected in the intracellular space within 5 min after its addition to the cell culture. Using flow cytometry technique, penetration kinetics of the labeled peptide into K-562 cells (at nontoxic micromolar concentrations has been studied. We have observed a rapid internalization of the peptide to the target cells, thus confirming the results of microscopic analysis, i.e, the labeled acipensin was detectable in K-562 cells as soon as wihin 2-3 seconds after its addition to the incubation medium. The maximum of fluorescence was reached within a period of approx. 45 seconds, with further “plateau” at the terms of >100 seconds following cell stimulation with the test compound. These data support the concept, that the antimicrobial peptides of innate immunity system possess the features of cell-penetrating peptides, and allow us to consider the studied sturgeon peptide a promising template for development of new

  9. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  10. Collagen-rich stroma in aggressive colon tumors induces mesenchymal gene expression and tumor cell invasion

    NARCIS (Netherlands)

    Vellinga, T T; den Uil, S; Rinkes, IHB; Marvin, D; Ponsioen, B; Alvarez-Varela, A; Fatrai, S; Scheele, C; Zwijnenburg, D A; Snippert, H; Vermeulen, L; Medema, J P; Stockmann, H B; Koster, J; Fijneman, R J A; de Rooij, J; Kranenburg, O

    2016-01-01

    Gene expression-based classification systems have identified an aggressive colon cancer subtype with mesenchymal features, possibly reflecting epithelial-to-mesenchymal transition (EMT) of tumor cells. However, stromal fibroblasts contribute extensively to the mesenchymal phenotype of aggressive col

  11. Uncommon Case of Intrapericardial Nontyphoidal Salmonella Infection in a Preterm Baby Presenting As a Cardiac Tumor.

    Science.gov (United States)

    Bobylev, Dmitry; Sarikouch, Samir; Meschenmoser, Luitgard; Hohmann, Dagmar; Beerbaum, Philipp; Horke, Alexander

    2016-04-01

    We report a case of an intrapericardial infection resulting from Salmonella Tennessee in a 2-month-old baby, which, upon initial presentation, was masked by a cardiac tumor. The diagnosis was confirmed after successful surgical resection of the mass. Transmission of the infection may have occurred between mother and child in utero, rendering this case extremely unusual.

  12. Klatskin tumor presented with melena and jaundice: interesting case with hemobilia

    OpenAIRE

    ETİK, Diğdem ÖZER; YÜREKLİ, Öykü Tayfur; ÖDEMİŞ, Bülent; DİŞİBEYAZ, Selçuk; Parlak, Erkan

    2015-01-01

    Hemobilia bleeding into the biliary tree is an unusual cause of upper gastrointestinal bleeding. Generally, etiologies of hemobilia are iatrogenic or traumatic in origin. Cholangiocarcinoma is a rare gastrointestinal tumor that can become evident with hemobilia. We present a 77-year-old female with a history of warfarin use, who suffered from a protracted course of melena and jaundice.

  13. Salivary gland anlage tumor in a neonate presenting with respiratory distress: radiographic and pathologic correlation.

    Science.gov (United States)

    Mogensen, M A; Lin, A C; Chang, K W; Berry, G J; Barnes, P D; Fischbein, N J

    2009-05-01

    We present a case of congenital salivary gland anlage tumor (SGAT) of the nasal septum in a 2-week-old infant who had difficulty breathing through her nose since birth. CT and MR imaging demonstrated a circumscribed mass within the nasal cavity that did not communicate with the intracranial compartment. Differential diagnosis and clinical significance of recognizing this rare lesion are reviewed.

  14. Galectin-3 Determines Tumor Cell Adaptive Strategies in Stressed Tumor Microenvironments

    Science.gov (United States)

    Cardoso, Ana Carolina Ferreira; Andrade, Luciana Nogueira de Sousa; Bustos, Silvina Odete; Chammas, Roger

    2016-01-01

    Galectin-3 is a member of the β-galactoside-binding lectin family, whose expression is often dysregulated in cancers. While galectin-3 is usually an intracellular protein found in the nucleus and in the cytoplasm, under certain conditions, galectin-3 can be secreted by an yet unknown mechanism. Under stressing conditions (e.g., hypoxia and nutrient deprivation) galectin-3 is upregulated, through the activity of transcription factors, such as HIF-1α and NF-κB. Here, we review evidence that indicates a positive role for galectin-3 in MAPK family signal transduction, leading to cell proliferation and cell survival. Galectin-3 serves as a scaffold protein, which favors the spatial organization of signaling proteins as K-RAS. Upon secretion, extracellular galectin-3 interacts with a variety of cell surface glycoproteins, such as growth factor receptors, integrins, cadherins, and members of the Notch family, among other glycoproteins, besides different extracellular matrix molecules. Through its ability to oligomerize, galectin-3 forms lectin lattices that act as scaffolds that sustain the spatial organization of signaling receptors on the cell surface, dictating its maintenance on the plasma membrane or their endocytosis. Galectin-3 induces tumor cell, endothelial cell, and leukocyte migration, favoring either the exit of tumor cells from a stressed microenvironment or the entry of endothelial cells and leukocytes, such as monocytes/macrophages into the tumor organoid. Therefore, galectin-3 plays homeostatic roles in tumors, as (i) it favors tumor cell adaptation for survival in stressed conditions; (ii) upon secretion, galectin-3 induces tumor cell detachment and migration; and (iii) it attracts monocyte/macrophage and endothelial cells to the tumor mass, inducing both directly and indirectly the process of angiogenesis. The two latter activities are potentially targetable, and specific interventions may be designed to counteract the protumoral role of extracellular

  15. Using polarization-sensitive optical coherence tomography to identify tumor stromal fibrosis and increase tumor biopsy yield (Conference Presentation)

    Science.gov (United States)

    Hariri, Lida P.; Adams, David C.; Miller, Alyssa J.; Mino-Kenudson, Mari; Suter, Melissa J.

    2016-03-01

    Tissue biopsy is the principal method used to diagnose tumors in a variety of organ systems. It is essential to maximize tumor yield in biopsy specimens for both clinical diagnostic and research purposes. This is particularly important in tumors where additional tissue is needed for molecular analysis to identify patients who would benefit from mutation-specific targeted therapy, such as in lung carcinomas. Inadvertent sampling of fibrotic stroma within tumor nodules contaminates biopsies, decreases tumor yield, and can impede diagnosis. The ability to assess tumor composition and guide biopsy site selection in real time is likely to improve diagnostic yield. Polarization sensitive OCT (PS-OCT) measures birefringence in organized tissues, such as collagen, and could be used to distinguish tumor from fibrosis. In this study, PS-OCT was obtained in 65 lung nodule samples from surgical resection specimens containing varying ratios of tumor and fibrosis. PS-OCT was obtained with either a custom-built helical scanning catheter (0.8 or 1.6mm in diameter) or a dual-axis bench top scanner. Strong birefringence was observed in nodules containing dense fibrosis, with no birefringence in adjacent regions of tumor. Tumors admixed with early, loosely-organized collagen demonstrated mild-to-moderate birefringence, and tumors with little collagen content showed little to no birefringent signal. PS-OCT provides significant insights into tumor nodule composition, and has potential to differentiate tumor from stromal fibrosis during biopsy site selection to increase diagnostic tumor yield.

  16. Increased initiation and growth of tumor cell lines, cancer stem cells and biopsy material in mice using basement membrane matrix protein (Cultrex or Matrigel) co-injection.

    Science.gov (United States)

    Fridman, Rafael; Benton, Gabriel; Aranoutova, Irina; Kleinman, Hynda K; Bonfil, R Daniel

    2012-05-17

    This protocol requires 2-4 h and presents a method for injecting tumor cells, cancer stem cells or dispersed biopsy material into subcutaneous or orthotopic locations within recipient mice. The tumor cells or biopsy are mixed with basement membrane matrix proteins (CultrexBME or Matrigel) at 4 °C and then injected into recipient animals at preferred anatomical sites. Tumor cells can also be co-injected with additional cell types, such as fibroblasts, stromal cells, endothelial cells and so on. Details are given on appropriate cell numbers, handling and concentration of the basement membrane proteins, recipient animals, injection location and techniques. This procedure enables the growth of tumors from cells or biopsy material (tumor graft) with greater efficiency of take and growth, and with retention of the primary tumor phenotype based on histology. Co-injection with additional cell types provides more physiological models of human cancers for use in drug screening and studying cancer biology.

  17. Augmentation of anti-tumor activity by immunization with Mycobacterium tuberculosis (Tbc and tuberculin-coupled tumor cells.

    Directory of Open Access Journals (Sweden)

    Yada,Yoshihiko

    1985-04-01

    Full Text Available The anti-tumor effect of immunization with heat-killed Mycobacterium tuberculosis (Tbc and Tuberculin (PPD-coupled syngeneic tumor cells was examined in vivo. Three tumor cell lines were employed. Immunization of Tbc-primed BALB/c mice with PPD-coupled syngeneic Meth-A tumor cells displayed a potent anti-tumor effect on viable Meth-A cells inoculated subcutaneously. Neither PPD-coupled LLC (Lewis Lung Carcinoma cells nor sonicated PPD-coupled Meth-A cells were capable of immunizing these mice. PPD-coupled syngeneic whole tumor cells were indispensable for induction of this tumor-specific resistance. Immunization of Tbc-primed C3H/He mice with PPD-coupled syngeneic MH134 tumor cells did not elicit anti-tumor activity against MH134, but additional pretreatment of mice with cyclophosphamide brought on an anti-tumor effect. Antimetastatic reactivity was investigated in C57BL/6 mice bearing LLC, with a reduction in metastases noted. This antimetastatic effect was observed even when the mice were immunized with PPD-coupled LLC cells three days after removal of the initial tumor. Immunization with Tbc and PPD-coupled Meth-A cells together with intraperitoneal administration of murine or rat interleukin 2 (IL 2 further augmented anti-Meth-A resistance. Murine IL 2 further inhibited tumor growth during the early stage, while rat IL 2 showed an anti-tumor effect throughout the course of tumor growth.

  18. Haematopoietic stem cells: past, present and future

    Science.gov (United States)

    Ng, Ashley P; Alexander, Warren S

    2017-01-01

    The discovery and characterisation of haematopoietic stem cells has required decades of research. The identification of adult bone marrow as a source of haematopoietic cells capable of protecting an organism from otherwise lethal irradiation led to the intense search for their identity and characteristics. Using functional assays along with evolving techniques for isolation of haematopoietic cells, haematopoietic stem cell populations were able to be enriched and their characteristics analysed. The key haematopoietic stem cell characteristics of pluripotentiality and the ability for self-renewal have emerged as characteristics of several haematopoietic stem cell populations, including those that have recently challenged the conventional concepts of the haematopoietic hierarchy. Human allogeneic stem cell therapy relies on these functional characteristics of haematopoietic stem cells that can be isolated from peripheral blood, bone marrow or cord blood, with the additional requirement that immunological barriers need to be overcome to allow sustained engraftment while minimising risk of graft-versus-host disease developing in the recipient of transplanted stem cells. Current and future research will continue to focus on the identification of haematopoietic stem cell regulators and methods for in vitro and in vivo stem cell manipulation, including genome editing, to expand the scope, potential and safety of therapy using haematopoietic stem cells. PMID:28180000

  19. Development of PIN and Prostate Adenocarcinoma Cell Lines: A Model System for Multistage Tumor Progression

    Directory of Open Access Journals (Sweden)

    Colin R. Soares

    2002-01-01

    Full Text Available Existing prostate cancer cell lines have been derived from late stages of human prostate cancer. In this paper, we present two cell lines generated from prostatic intraepithelial neoplasia (PIN, the precursor lesion for prostate adenocarcinoma. Pr-111 and Pr-117 were established from PIN lesions that developed in the C3(1/Tag transgenic model of prostate cancer. Pr-111 and Pr-117 cells express simian virus 40 large T antigen (SV40 Tag and are immortalized in culture, distinguishing them from normal prostate cells. The growth rates of these two cell lines are quite different; with Pr-111 cells growing much more slowly (doubling time approximately 40 hours compared to Pr-117 cells (doubling time approximately 22 hours, and also show significantly different growth rates in different media. Both prostate cell lines express cytokeratin and androgen receptor (AR with Pr-111 cells demonstrating androgen-dependent growth and Pr-117 cells exhibiting androgen-responsive growth characteristics. Athymic nude mice injected with Pr-111 cells either do not develop tumors or develop tumors after a long latency period of 14 weeks. Pr-117 cells, however, develop tumors by 3 to 6 weeks, suggesting that Pr-117 cells represent a later stage of tumor progression. These two novel cell lines will be useful for studying early stages of prostate tumor development and androgen responsiveness.

  20. Primary de novo malignant giant cell tumor of kidney: a case report

    Directory of Open Access Journals (Sweden)

    Torkian Bahman

    2004-06-01

    Full Text Available Abstract Background Osteoclast-like giant cell tumors are usually observed in osseous tissue or as tumors of tendon sheath, characterized by the presence of multinucleated giant cells and mononuclear stromal cells. It has been reported in various extraosseous sites including breast, skin, soft tissue, salivary glands, lung, pancreas, female genital tract, thyroid, larynx and heart. However, extraosseus occurrence of such giant cell tumors in the kidney is extremely rare and is usually found in combination with a conventional malignancy. De-novo primary malignant giant cell tumors of the kidney are unusual lesions and to our knowledge this is the second such case. Case Presentation We report a rare case of extraosseous primary denovo malignant giant cell tumor of the renal parenchyma in a 39-year-old Caucasian female to determine the histogenesis of this neoplasm with a detailed literature review. Conclusion Primary denovo malignant giant cell tumor of the kidney is extremely rare. The cellular origin of this tumor is favored to be a pluripotential mesenchymal stromal cell of the mononuclear/phagocytic cellular lineage. Awareness of this neoplasm is important in the pathological interpretation of unusual findings at either fine needle aspiration or frozen section of solid renal masses.

  1. Diffuse thyroid metastases and bilateral internal jugular vein tumor thrombus from renal cell cancer

    OpenAIRE

    Jha, Priyanka; Shekhar, Mallika; Wan, Jennifer; Mari-Aparici, Carina

    2016-01-01

    Renal cell cancer rarely metastasizes to the thyroid gland, and it has been reported to present as a solitary mass. We present a case of diffuse thyroid cancer metastases from renal cell cancer. Bilateral internal jugular vein tumor thrombi were also present. To the best of our knowledge, this is the first description of diffuse thyroid metastases from renal cell cancer in the English literature. Renal cell cancer metastases should be considered in the differential of thyroid imaging abnormal...

  2. Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After Therapy

    Science.gov (United States)

    2015-10-01

    AD_________________ (Leave blank) Award Number: W81XWH-14-1-0350 TITLE: Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After...30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTILE Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After Therapy 5a. CONTRACT NUMBER...Innovative reporter gene systems are designed to mark quiescent or proliferating lung cancer cells (Aim 1) and then used to track and trace the dynamics of

  3. S-100 Negative Granular Cell Tumor of the Oral Cavity.

    Science.gov (United States)

    Solomon, Lynn W; Velez, Ines

    2016-09-01

    Classic granular cell tumor is a mesenchymal neoplasm that commonly occurs on the skin, but is not infrequently found in the oral cavity, primarily on the dorsal tongue. Diagnosis is usually straightforward with hematoxylin and eosin stained slides. Immunohistochemical studies on classic granular cell tumor shows positive immunostaining for S-100 and vimentin, while CD68 is variably positive. We report a case of otherwise unremarkable oral granular cell tumor that was immunohistochemically negative for S-100, and positive for vimentin and CD68, and discuss the differential diagnosis. The results of the immunohistochemical studies in our case are compared with those of classic S-100 positive oral granular cell tumors, as well as cutaneous and oral S-100 negative granular cell tumors. Classic S-100 positive granular cell tumors and S-100 negative granular cell tumors of the oral cavity can only be distinguished by immunohistochemical studies; however, the necessity of this distinction is unclear, as both are benign lesions in which recurrence is unlikely.

  4. Pindborg Tumor Presenting as a Nasal Polyp: Immunohistology and Ultrastructural Features of a Rare Case, With Review of the Literature.

    Science.gov (United States)

    Mitra, Suvradeep; Kaur, Gurwinder; Nada, Ritambhra; Mohindra, Satyawati

    2016-09-01

    Calcifying epithelial odontogenic tumor, also known as Pindborg tumor, is a rare benign odontogenic tumor. This tumor predominantly involves the mandible, though the maxilla can also be involved in some cases. The involvement of maxillary sinuses, however, has been previously reported in only 8 case reports English literature. These patients chiefly presented with nasal obstruction along with epistaxis or proptosis in rare cases. However, a primary presentation as nasal polyp is unheard of. We present a rare case of calcifying epithelial odontogenic tumor presenting as a nasal polyp, posing a diagnostic difficulty.

  5. Ex vivo expansion protocol for human tumor specific T cells for adoptive T cell therapy.

    Science.gov (United States)

    Rasmussen, Anne-Marie; Borelli, Gabriel; Hoel, Hanna Julie; Lislerud, Kari; Gaudernack, Gustav; Kvalheim, Gunnar; Aarvak, Tanja

    2010-04-15

    Adoptive T cell therapy is a promising treatment strategy for patients with different types of cancer. The methods used for generation of high numbers of tumor specific T cells usually require long-term ex vivo culture, which frequently lead to generation of terminally differentiated effector cells, demonstrating low persistence in vivo. Therefore, optimization of protocols for generation of T cells for adoptive cell therapy is warranted. The aim of this work was to develop a protocol for expansion of antigen-specific T cells using Dynabeads CD3/CD28 to obtain T cells expressing markers important for in vivo persistence and survival. To achieve high numbers of antigen-specific T cells following expansion, we have tested the effect of depleting regulatory T cells using Dynabeads CD25 and including a pre-stimulation step with peptide prior to the non-specific expansion with Dynabeads. Our data demonstrate that virus- and tumor specific T cells can be expanded to high numbers using Dynabeads CD3/CD28 following optimization of the culture conditions. The expansion protocol presented here results in enrichment of antigen-specific CD8(+) T cells with an early/intermediate memory phenotype. This is observed even when the antigen-specific CD8(+) T cells demonstrated a terminal effector phenotype prior to expansion. This protocol thus results in expanded T cells with a phenotypic profile which may increase the chance of retaining long-term persistence following adoptive transfer. Based on these data we have developed a cGMP protocol for expansion of tumor specific T cells for adoptive T cell therapy.

  6. Malignant gastrointestinal stromal tumor of the ampulla of Vater presenting with obstructive jaundice

    Directory of Open Access Journals (Sweden)

    Filippou Dimitrios

    2006-01-01

    Full Text Available Malignant gastrointestinal stromal tumor (GIST consists a rare neoplasm, developing in small intestine and stomach. The presenting manifastations include weakness, weight loss, nausea, melena and anaemia. The present case refers to a 65 years old female patient with a GIST of the ampulla of Vater presenting with obstructive jaundice. Diagnosis was achieved pre-operatively by biopsies collected through diagnostic ERCP. The tumour was locally excised, with preservation of the ampulla. The histological analysis suggested low grade GIST positive for both CD 117 (c-kit and CD34. Two years after the surgery the patient remains free of disease. Malignant GIST of the ampulla of the Vater is extremely rare as only few similar cases have been described in the literature. This is the first time a GIST being presented as obstructive jaundice ever reported. Despite the unavailability of EUS-FNA, the diagnosis was set preoperatively and the tumor was resected.

  7. Ovarian steroid cell tumor in women with polycystic ovarian syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Yarandi F

    2013-04-01

    Full Text Available Background: Steroid cell tumor is one of the rare ovarian tumors and forms 0.1% of all ovarian tumors, divided to three subgroups. Steroid cell tumor that are not otherwise specified (NOS are the most common type and represent 60% of steroid cell tumors. One of the most known signs of this tumor is hormonal function, especially androgenic effects of it. Primary treatment consists of eradication of tumor via surgery.Case presentation: The patient is a 29 years old female with history of poly cystic ovarian syndrome since 10 years ago, who attended to the clinic of General Women Hospital of Tehran in January 2011. In pelvic ultrasonography, there was a 6449mm mass in the right adnexa consisting of homogeneous component. She underwent laparotomy and unilateral salpingoophorectomy was done. Pathological report was steroid cell tumor of ovary.Conclusion: The aim of this study is reporting one of the rare tumors of ovary and assessment of the correct way of diagnosis and treatment of it.

  8. Sporadic Multifocal Malignant Peripheral Nerve Sheath Tumor-A Rare Presentation: Multifocal MPNST.

    Science.gov (United States)

    Leena, J B; Fernandes, Hilda; Swethadri, G K

    2013-06-01

    Malignant peripheral nerve sheath tumors(MPNST) are uncommon neoplasms with an incidence of 0.001% in general population. Multifocality is a rare manifestation of MPNST . A case of a 65 year old patient who presented with multiple swellings involving the neck, extremity and back without associated neurofibromatosis is reported for its rarity of presentation.. Diagnosis was made by FNAC and confirmed by peroperative findings and histopathology.

  9. SPECTRUM OF FUNCTIONING ISLET CELL TUMOR ON MULTISLICE COMPUTED TOMOGRAPHY: EXPERIENCE ON 70 PATIENTS

    Institute of Scientific and Technical Information of China (English)

    Hua-dan Xue; Zheng-yu Jin; Wei Liu; Hao Sun; Reto Merges; Xuan Wang; Xiao-na Zhang; Yun Wang; Wen-min Zhao; Jiu-hong Chen

    2008-01-01

    Objective To review experience in preoperative detection of islet cell tumors using multislice computed tomo-graphy (MSCT) and summarize various imaging features of functioning islet cell tumors on enhanced MSCT.Methods Seventy patients with clinical or pathological diagnosis of functioning pancreatic islet cell tumor between October 2003 and February 2007 were included in this retrospective study. Seventy-four enhanced MSCT scans in these patients were identified. All MSCT scans were interpreted by two experienced radiologists by consensus interpretation.Surgery and pathology reports were used to confirm the diagnosis, localization, and size of tumors.Results Totally, 73 functioning islet cell tumors including 65 benign insulinomas, 2 benign giucagnnomas, 3 ma-lignant insulinomas, and 3 malignant glucagonomas were pathologically diagnosed. Tumors in only two cases were not found by MSCT. In 67 benign lesions, 32 showed typical enhancement style, 21 showed prolonged enhancement in por-tal venous phase, 4 showed delayed enhancement, 4 had iso-dense enhancement with normal pancreatic parenchyma, 2 had no enhancement at all in arterial phase and portal venous phase, and 4 had inhomogeneous enhancement with necro-sis or cyst-formation. Patchy or spotty calcifications were found in 3 of the 67 tumors. In 6 malignant islet cell tumors,vessel invasion (2/6) and bowel invasion (1/6) were seen. Different enhancement patterns were shown. All hepatic metastases showed hyper-enhancement during their arterial phase.Conelusions Pancreatic islet cell tumor may display a wide spectrum of presentations in MSCT. Umors with unu-sual appearances often present as diagunstie challenges. Non-contrast and post-contrast multiphase scans are recommen-ded for the localization of functioning islet cell tumors.

  10. TAP-independent self-peptides enhance T cell recognition of immune-escaped tumors

    Science.gov (United States)

    Doorduijn, Elien M.; Sluijter, Marjolein; Querido, Bianca J.; Oliveira, Cláudia C.; Achour, Adnane; Ossendorp, Ferry; van der Burg, Sjoerd H.; van Hall, Thorbald

    2016-01-01

    Tumor cells frequently escape from CD8+ T cell recognition by abrogating MHC-I antigen presentation. Deficiency in processing components, like the transporter associated with antigen processing (TAP), results in strongly decreased surface display of peptide/MHC-I complexes. We previously identified a class of hidden self-antigens known as T cell epitopes associated with impaired peptide processing (TEIPP), which emerge on tumor cells with such processing defects. In the present study, we analyzed thymus selection and peripheral behavior of T cells with specificity for the prototypic TEIPP antigen, the “self” TRH4 peptide/Db complex. TEIPP T cells were efficiently selected in the thymus, egressed with a naive phenotype, and could be exploited for immunotherapy against immune-escaped, TAP-deficient tumor cells expressing low levels of MHC-I (MHC-Ilo). In contrast, overt thymus deletion and functionally impaired TEIPP T cells were observed in mice deficient for TAP1 due to TEIPP antigen presentation on all body cells in these mice. Our results strongly support the concept that TEIPPs derive from ubiquitous, nonmutated self-antigens and constitute a class of immunogenic neoantigens that are unmasked during tumor immune evasion. These data suggest that TEIPP-specific CD8+ T cells are promising candidates in the treatment of tumors that have escaped from conventional immunotherapies. PMID:26784543

  11. The Role and Clinical Relevance of Disseminated Tumor Cells in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Banys, Malgorzata, E-mail: maggybanys@yahoo.de [Department of Obstetrics and Gynecology, University of Duesseldorf, Duesseldorf D-40225 (Germany); Department of Obstetrics and Gynecology, Marienkrankenhaus Hamburg, Hamburg D-22087 (Germany); Krawczyk, Natalia; Fehm, Tanja [Department of Obstetrics and Gynecology, University of Duesseldorf, Duesseldorf D-40225 (Germany)

    2014-01-15

    Tumor cell dissemination is a common phenomenon observed in most cancers of epithelial origin. One-third of breast cancer patients present with disseminated tumor cells (DTCs) in bone marrow at time of diagnosis; these patients, as well as patients with persistent DTCs, have significantly worse clinical outcome than DTC-negative patients. Since DTC phenotype may differ from the primary tumor with regard to ER and HER2 status, reevaluation of predictive markers on DTCs may optimize treatment choices. In the present review, we report on the clinical relevance of DTC detection in breast cancer.

  12. The Role and Clinical Relevance of Disseminated Tumor Cells in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Malgorzata Banys

    2014-01-01

    Full Text Available Tumor cell dissemination is a common phenomenon observed in most cancers of epithelial origin. One-third of breast cancer patients present with disseminated tumor cells (DTCs in bone marrow at time of diagnosis; these patients, as well as patients with persistent DTCs, have significantly worse clinical outcome than DTC-negative patients. Since DTC phenotype may differ from the primary tumor with regard to ER and HER2 status, reevaluation of predictive markers on DTCs may optimize treatment choices. In the present review, we report on the clinical relevance of DTC detection in breast cancer.

  13. Apoptosis and tumor cell death in response to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

    Science.gov (United States)

    Hallgren, Oskar; Aits, Sonja; Brest, Patrick; Gustafsson, Lotta; Mossberg, Ann-Kristin; Wullt, Björn; Svanborg, Catharina

    2008-01-01

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a molecular complex derived from human milk that kills tumor cells by a process resembling programmed cell death. The complex consists of partially unfolded alpha-lactalbumin and oleic acid, and both the protein and the fatty acid are required for cell death. HAMLET has broad antitumor activity in vitro, and its therapeutic effect has been confirmed in vivo in a human glioblastoma rat xenograft model, in patients with skin papillomas and in patients with bladder cancer. The mechanisms of tumor cell death remain unclear, however. Immediately after the encounter with tumor cells, HAMLET invades the cells and causes mitochondrial membrane depolarization, cytochrome c release, phosphatidyl serine exposure, and a low caspase response. A fraction of the cells undergoes morphological changes characteristic of apoptosis, but caspase inhibition does not rescue the cells and Bcl-2 overexpression or altered p53 status does not influence the sensitivity of tumor cells to HAMLET. HAMLET also creates a state of unfolded protein overload and activates 20S proteasomes, which contributes to cell death. In parallel, HAMLET translocates to tumor cell nuclei, where high-affinity interactions with histones cause chromatin disruption, loss of transcription, and nuclear condensation. The dying cells also show morphological changes compatible with macroautophagy, and recent studies indicate that macroautophagy is involved in the cell death response to HAMLET. The results suggest that HAMLET, like a hydra with many heads, may interact with several crucial cellular organelles, thereby activating several forms of cell death, in parallel. This complexity might underlie the rapid death response of tumor cells and the broad antitumor activity of HAMLET.

  14. Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor progression.

    Science.gov (United States)

    Behnan, Jinan; Isakson, Pauline; Joel, Mrinal; Cilio, Corrado; Langmoen, Iver A; Vik-Mo, Einar O; Badn, Wiaam

    2014-05-01

    The identity of the cells that contribute to brain tumor structure and progression remains unclear. Mesenchymal stem cells (MSCs) have recently been isolated from normal mouse brain. Here, we report the infiltration of MSC-like cells into the GL261 murine glioma model. These brain tumor-derived mesenchymal stem cells (BT-MSCs) are defined with the phenotype (Lin-Sca-1+CD9+CD44+CD166+/-) and have multipotent differentiation capacity. We show that the infiltration of BT-MSCs correlates to tumor progression; furthermore, BT-MSCs increased the proliferation rate of GL261 cells in vitro. For the first time, we report that the majority of GL261 cells expressed mesenchymal phenotype under both adherent and sphere culture conditions in vitro and that the non-MSC population is nontumorigenic in vivo. Although the GL261 cell line expressed mesenchymal phenotype markers in vitro, most BT-MSCs are recruited cells from host origin in both wild-type GL261 inoculated into green fluorescent protein (GFP)-transgenic mice and GL261-GFP cells inoculated into wild-type mice. We show the expression of chemokine receptors CXCR4 and CXCR6 on different recruited cell populations. In vivo, the GL261 cells change marker profile and acquire a phenotype that is more similar to cells growing in sphere culture conditions. Finally, we identify a BT-MSC population in human glioblastoma that is CD44+CD9+CD166+ both in freshly isolated and culture-expanded cells. Our data indicate that cells with MSC-like phenotype infiltrate into the tumor stroma and play an important role in tumor cell growth in vitro and in vivo. Thus, we suggest that targeting BT-MSCs could be a possible strategy for treating glioblastoma patients.

  15. Metachronous bilateral testicular germ cell tumors: Report of two cases

    Directory of Open Access Journals (Sweden)

    James Francis

    2009-01-01

    Full Text Available Metachronous bilateral testicular germ cell tumors is a rare known problem. However, no report of metachronus bilateralism was identified in the PubMed database published from India so far, where testicular cancer is relatively rare. We report the cases of two gentlemen. One had stage 1 nonseminomatous germ cell tumor (NSGCT at the age of 32 in 1990 and developed marker relapse on surveillance and had chemotherapy using cisplatin and etoposide for four cycles. He developed contralateral seminoma in the testis 13 years later. Another patient had left orchidectomy in 2003 for NSGCT, had adjuvant BEP for two cycles, and developed a contralateral testicular tumor 5 years later, which was also seminoma. As more patients with germ cell tumors are cured with chemotherapy, long-term problems become important. Contralateral testicular tumor is one of them. As it can be very late, many years of continued follow-up examination and patients′ awareness are necessary.

  16. Stromal Cell-Derived Factor-1 Promotes Cell Migration, Tumor Growth of Colorectal Metastasis

    Directory of Open Access Journals (Sweden)

    Otto Kollmar

    2007-10-01

    Full Text Available In a mouse model of established extrahepatic colorectal metastasis, we analyzed whether stromal cellderived factor (SDF 1 stimulates tumor cell migration in vitro, angiogenesis, tumor growth in vivo. METHODS: Using chemotaxis chambers, CT26.WT colorectal tumor cell migration was studied under stimulation with different concentrations of SDF-1. To evaluate angiogenesis, tumor growth in vivo, green fluorescent protein-transfected CT26.WT cells were implanted in dorsal skinfold chambers of syngeneic BALB/c mice. After 5 days, tumors were locally exposed to SDF-1. Cell proliferation, tumor microvascularization, growth were studied during a further 9-day period using intravital fluorescence microscopy, histology, immunohistochemistry. Tumors exposed to PBS only served as controls. RESULTS:In vitro, > 30% of unstimulated CT26.WT cells showed expression of the SDF-1 receptor CXCR4. On chemotaxis assay, SDF-1 provoked a dose-dependent increase in cell migration. In vivo, SDF-1 accelerated neovascularization, induced a significant increase in tumor growth. Capillaries of SDF-1-treated tumors showed significant dilation. Of interest, SDF-1 treatment was associated with a significantly increased expression of proliferating cell nuclear antigen, a downregulation of cleaved caspase-3. CONCLUSION: Our study indicates that the CXC chemokine SDF-1 promotes tumor cell migration in vitro, tumor growth of established extrahepatic metastasis in vivo due to angiogenesis-dependent induction of tumor cell proliferation, inhibition of apoptotic cell death.

  17. Induction of tumor necrosis factor expression and resistance in a human breast tumor cell line.

    OpenAIRE

    Spriggs, D; Imamura, K; Rodriguez, C; Horiguchi, J; Kufe, D W

    1987-01-01

    Tumor necrosis factor (TNF) is a polypeptide cytokine that is cytotoxic to some but not all tumor cells. The basis for resistance to the cytotoxic effects of this agent remains unclear. We have studied the development of TNF resistance in human ZR-75-1 breast carcinoma cells. ZR-75-1 cells have undetectable levels of TNF RNA and protein. However, TNF transcripts are transiently induced in these cells by exposure to recombinant human TNF. This induction of TNF RNA is associated with production...

  18. Delayed cardiac metastasis from phyllodes breast tumor presenting as cardiogenic shock.

    Science.gov (United States)

    Garg, Naveen; Moorthy, Nagaraja; Agrawal, Surendra K; Pandey, Santanu; Kumari, Niraj

    2011-01-01

    Malignant metastases to the heart and pericardium, which occur far more often than do primary cardiac neoplasms, typically lead to fatal outcomes. The phyllodes tumor is a rare, predominantly benign fibroepithelial breast neoplasm with variable malignancy potential. Herein, we describe the case of a 35-year-old woman who, 3 years after undergoing a simple mastectomy for a rapidly enlarging breast neoplasm, presented with cardiogenic shock and was found to have a large right ventricular tumor that obstructed the right ventricular outflow tract. Despite successful resection of the ventricular mass and a right atrial mass of organized thrombus, the patient died 8 days postoperatively of multiorgan failure due to severe right ventricular dysfunction. Histopathologic analysis determined that the right ventricular mass was a malignant, metastatic phyllodes tumor. To our knowledge, this is only the 2nd reported case of a phyllodes tumor that metastasized to the heart and presented as an intracavitary mass with cardiogenic shock. In addition to discussing our patient's case, we review the pertinent medical literature.

  19. Detection and Isolation of Circulating Tumor Cells in Urologic Cancers: A Review

    Directory of Open Access Journals (Sweden)

    Robert D. Loberg

    2004-07-01

    Full Text Available The American Cancer Society has estimated that in 2003, there will be approximately 239,600 new cases of urologic cancer diagnosed and 54,600 urologic cancer-related deaths in the United States. To date, the majority of research and therapy design have focused on the microenvironment of the primary tumor site, as well as the microenvironment of the metastatic or secondary (target tumor site. Little attention has been placed on the interactions of the circulating tumor cells and the microenvironment of the circulation (i.e., the third microenvironment. The purpose of this review is to present the methods for the detection and isolation of circulating tumor cells and to discuss the importance of circulating tumor cells in the biology and treatment of urologic cancers.

  20. Perivascular epithelioid cell tumor (PEComa) of abdominal cavity from falciform ligament: a case report.

    Science.gov (United States)

    Choi, Cheol Woong; Kim, Tae Oh; Kim, Kyung Yeob; Lee, Sun Mi; Kim, Gwang Ha; Kang, Dae Hwan; Song, Geun Am; Kim, Suk; Kim, Dae Hwan

    2009-04-01

    We present a case of perivascular epithelioid cell tumors (PEComas) in the abdominal cavity at the falciform ligament. A 30-yr-old Korean man visited to hospital for the evaluation of a growing, palpable abdominal mass. He had felt the mass growing over 6 months. There was no family or personal history of tuberous sclerosis. The resected specimen showed a mass of 8.0x7.0x5.5 cm in size. Histological examination showed sheets of spindle-to-epithelioid cells with clear-to-eosinophilic cytoplasm. Immunohistochemically, tumor cells were positive for HMB-4 (gp100) and smooth muscle actin. They were also positive for the S-100, which is a marker of neurogenic and melanocytic tumors. Patient was treated with radical resection of tumor without any adjuvant therapy. He is well and on follow-up visits without tumor recurrence.

  1. Infantile and adult testicular germ cell tumors : a different pathogenesis?

    NARCIS (Netherlands)

    van Echten, J; Timmer, A; van der Veen, AY; Molenaar, WM; de Jong, B

    2002-01-01

    Most adult testicular germ cell tumors have a characteristic chromosomal abnormality that is an isochromosome 12p [i(12p)]. Furthermore. these tumors are characterized by a chromosome number in the triploid range and gains and losses of (parts of) specific chromosomes. Cytogenetic investigation of t

  2. Towards intraoperative assessment of tumor margins in breast surgery using optical coherence elastography (Conference Presentation)

    Science.gov (United States)

    Kennedy, Brendan F.; Wijesinghe, Philip; Allen, Wes M.; Chin, Lixin; Latham, Bruce; Saunders, Christobel M.; Sampson, David D.

    2016-03-01

    Surgical excision of tumor is a critical factor in the management of breast cancer. The most common surgical procedure is breast-conserving surgery. The surgeon's goal is to remove the tumor and a rim of healthy tissue surrounding the tumor: the surgical margin. A major issue in breast-conserving surgery is the absence of a reliable tool to guide the surgeon in intraoperatively assessing the margin. A number of techniques have been proposed; however, the re-excision rate remains high and has been reported to be in the range 30-60%. New tools are needed to address this issue. Optical coherence elastography (OCE) shows promise as a tool for intraoperative tumor margin assessment in breast-conserving surgery. Further advances towards clinical translation are limited by long scan times and small fields of view. In particular, scanning over sufficient areas to assess the entire margin in an intraoperative timeframe has not been shown to be feasible. Here, we present a protocol allowing ~75% of the surgical margins to be assessed within 30 minutes. To achieve this, we have incorporated a 65 mm-diameter (internal), wide-aperture annular piezoelectric transducer, allowing the entire surface of the excised tumor mass to be automatically imaged in an OCT mosaic comprised of 10 × 10 mm tiles. As OCT is effective in identifying adipose tissue, our protocol uses the wide-field OCT to selectively guide subsequent local OCE scanning to regions of solid tissue which often present low contrast in OCT images. We present promising examples from freshly excised human breast tissue.

  3. Unique presentation of a giant mediastinal tumor as kyphosis: a case report

    Directory of Open Access Journals (Sweden)

    Spartalis Eleftherios D

    2012-04-01

    Full Text Available Abstract Introduction Although posture distortion is a common problem in elderly patients, spinal deformity caused by a thymoma has not been previously reported. Thymomas are slowly growing tumors that predominantly cause respiratory symptoms. Case presentation We report the case of an 83-year-old woman who was admitted with a giant mediastinal mass that had caused progressive spinal distortion and weight loss to our department. The clinical and laboratory investigations that followed revealed one of the largest thymomas ever reported in the medical literature, presenting as a mass lesion placed at the left hemithorax. She underwent complete surgical excision of the tumor via a median sternotomy. Two years after the operation, she showed significant improvement in her posture, no pulmonary discomfort, and a gain of 20 kg; she remains disease free based on radiographic investigations. Conclusions In this case, a chronic asymmetric load on the spine resulted in an abnormal vertebral curvature deformity that presented as kyphosis.

  4. Malignant Tumor Derived from Skin Melanocytes of a Bovine of Unusual Presentation: A Case Study

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Chaves Velásquez

    2015-05-01

    Full Text Available Melanocytic tumors and melanomas in domestic animals include neoplasms composed of melanin-producing cells. In cattle, these tumors are rare and mostly benign, while malignant tumors are almost non-existent. The article reports the case of a female crossbred cow 38 months of age with a fluctuating mass located between the mandibular border and the left parotid region, about three months duration, with evident growth in the last thirty days. After surgical excision, a sample preserved in buffered formalin (10% was sent to the Laboratory of Pathology (University of Nariño—consisting of a fragment of 7.0 × 10.5 × 8.0 cm, ellipsoid, with skin and hair on one side, irregular surface, blackish brown, semi-soft consistency, and presence of shear translucent slimy content—for processing and inclusion in paraffin, cut to 5 μm thickness and stained with hematoxylin-eosin coloration. The forwarded tissue was classified as a neoplasm of malignant behavior derived from melanocytes, due to its cellular characteristics: growth pattern, pattern of distribution, severe cellular pleomorphism, anisocytosis, megalocytosis, nuclear pleomorphism, anisokaryosis, megalokaryosis, and involvement of blood vessel walls; additionally, the paraffin block was cut for immunohistochemical processing using monoclonal markers (S-100 DAKO® and Melan A DAKO®, contrasted with Mayer’s hematoxylin. Strong immunostaining of neoplastic cells is evident, and it constitutes the first reported case of this disease in Nariño (Colombia.

  5. Specific Antitumor Effects of Tumor Vaccine Produced by Electrofusion between Osteosarcoma Cell and Dendritic Cell in Rats

    Institute of Scientific and Technical Information of China (English)

    ZheYu; QingyuFan; XinbaoHao; HuaLong

    2004-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells capable of inducing primary T-cell responses. Several immunotherapy treatment strategies involve manipulation of DCs, both in vivo and ex vivo, to promote the immunogenic presentation of tumor-associated antigens. In this study, an electrofusion protocol was developed to induce fusion between osteosarcoma cells and allogeneic bone marrow-derived DCs. Preimmunization with irradiated electrofusion products was found to provide partial or complete protection from tumor challenge in the UMR106 tumor model. Vaccinated survivors developed long immunological memory. The therapeutic potential of this type of approach was suggested by the ability of UMR106-DC electrofusion products which could induce tumor rejection in a substantial percentage (60%) of hosts bearing pre-established tumor cells.These results tended to indicate that treatment with electrofused tumor cells and allogeneic DCs might be capable of inducing a potent antitumor response and could conceivably be applied to a wide range of cancer indications for which tumor-associated antigens have not been identified. Cellular & Molecular Immunology.2004;1(6):454-460.

  6. Increased IMP dehydrogenase gene expression in solid tumor tissues and tumor cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Collart, F.R.; Chubb, C.B.; Mirkin, B.L.; Huberman, E.

    1992-07-10

    IMP dehydrogenase, a regulatory enzyme of guanine nucleotide biosynthesis, may play a role in cell proliferation and malignancy. To assess this possibility, we examined IMP dehydrogenase expression in a series of human solid tumor tissues and tumor cell lines in comparison with their normal counterparts. Increased IMP dehydrogenase gene expression was observed in brain tumors relative to normal brain tissue and in sarcoma cells relative to normal fibroblasts. Similarly, in several B- and T-lymphoid leukemia cell lines, elevated levels of IMP dehydrogenase mRNA and cellular enzyme were observed in comparison with the levels in peripheral blood lymphocytes. These results are consistent with an association between increased IMP dehydrogenase expression and either enhanced cell proliferation or malignant transformation.

  7. An unusual presentation of a malignant jejunal tumor and a different management strategy.

    Science.gov (United States)

    Samaiya, Atul; Deo, Sv Suryanarayana; Thulkar, Sanjay; Hazarika, Sidhartha; Kumar, Sunil; Parida, Dillip K; Shukla, Nootan K

    2005-01-09

    BACKGROUND: Malignant small bowel tumors are very rare and leiomyosarcoma accounts for less than 15% of the cases. Management of these tumors is challenging in view of nonspecific symptoms, unusual presentation and high incidence of metastasis. In this case report, an unusual presentation of jejunal sarcoma and management of liver metastasis with radiofrequency ablation (RFA) is discussed. CASE PRESENTATION: A 45-year-old male presented with anemia and features of small bowel obstruction. Operative findings revealed a mass lesion in jejunum with intussusception of proximal loop. Resection of bowel mass was performed. Histopathological findings were suggestive of leiomyosarcoma. After 3-years of follow-up, the patient developed recurrence in infracolic omentum and a liver metastasis. The omental mass was resected and liver lesion was managed with radiofrequency ablation. CONCLUSION: Jejunal leiomyosarcoma is a rare variety of malignant small bowel tumor and a clinical presentation with intussusception is unusual. We suggest that an aggressive management approach using a combination of surgery and a newer technique like RFA can be attempted in patients with limited metastatic spread to liver to prolong the long-term survival in a subset of patients.

  8. VEGF-C Promotes Immune Tolerance in B16 Melanomas and Cross-Presentation of Tumor Antigen by Lymph Node Lymphatics

    Directory of Open Access Journals (Sweden)

    Amanda W. Lund

    2012-03-01

    Full Text Available Tumor expression of the lymphangiogenic factor VEGF-C is correlated with metastasis and poor prognosis, and although VEGF-C enhances transport to the draining lymph node (dLN and antigen exposure to the adaptive immune system, its role in tumor immunity remains unexplored. Here, we demonstrate that VEGF-C promotes immune tolerance in murine melanoma. In B16 F10 melanomas expressing a foreign antigen (OVA, VEGF-C protected tumors against preexisting antitumor immunity and promoted local deletion of OVA-specific CD8+ T cells. Naive OVA-specific CD8+ T cells, transferred into tumor-bearing mice, were dysfunctionally activated and apoptotic. Lymphatic endothelial cells (LECs in dLNs cross-presented OVA, and naive LECs scavenge and cross-present OVA in vitro. Cross-presenting LECs drove the proliferation and apoptosis of OVA-specific CD8+ T cells ex vivo. Our findings introduce a tumor-promoting role for lymphatics in the tumor and dLN and suggest that lymphatic endothelium in the local microenvironment may be a target for immunomodulation.

  9. Differential gene expression in stromal cells of human giant cell tumor of bone.

    Science.gov (United States)

    Wuelling, M; Delling, G; Kaiser, E

    2004-12-01

    Giant cell tumor (GCT) offers a unique model for the hematopoietic-stromal cell interaction in human bone marrow. Evidence has been presented that GCT stromal cells (GCTSCs) promote accumulation, size and activity of the giant cells. Although GCTSCs are considered the neoplastic component of GCT, little is known about their genetic basis and, to date, a tumor-specific gene expression pattern has not been characterized. Mesenchymal stem cells (MSCs) have been identified as the origin of the GCT neoplastic stromal cell. Using state of the art array technology, expression profiling was applied to enriched stromal cell populations from five different GCTs and two primary MSCs as controls. Of the 29 differentially expressed genes found, 25 showed an increased expression. Differential mRNA expression was verified by real-time polymerase chain reaction analysis of 10 selected genes, supporting the validity of cDNA arrays as a tool to identify tumor-related genes in GCTSCs. Increased expression of two oncogenes, JUN and NME2, was substantiated at the protein level, utilizing immunohistochemical evaluation of GCT sections and Western-blot analysis. Increased phosphorylation of JUN Ser-63 was also found.

  10. Low p21(Waf1/Cip1) protein level sensitizes testicular germ cell tumor cells to Fas-mediated apoptosis

    NARCIS (Netherlands)

    Spierings, DCJ; de Vries, EGE; Stel, AJ; Rietstap, NT; Vellenga, E; de Jong, S

    2004-01-01

    In the present study, we investigated the relation between p21 expression and the sensitivity of testicular germ cell tumor (TGCT) cells to apoptotic stimuli. Despite similar cisplatin-induced wild-type p53 accumulation, the TGCT cell lines Tera and Scha expressed low p21 protein and mRNA levels in

  11. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

    Directory of Open Access Journals (Sweden)

    Matthias Edinger

    1999-10-01

    Full Text Available Revealing the mechanisms of neoplastic disease and enhancing our ability to intervene in these processes requires an increased understanding of cellular and molecular changes as they occur in intact living animal models. We have begun to address these needs by developing a method of labeling tumor cells through constitutive expression of an optical reporter gene, noninvasively monitoring cellular proliferation in vivo using a sensitive photon detection system. A stable line of HeLa cells that expressed a modified firefly luciferase gene was generated, proliferation of these cells in irradiated severe combined immunodeficiency (SCID mice was monitored. Tumor cells were introduced into animals via subcutaneous, intraperitoneal and intravenous inoculation and whole body images, that revealed tumor location and growth kinetics, were obtained. The number of photons that were emitted from the labeled tumor cells and transmitted through murine tissues was sufficient to detect 1×103 cells in the peritoneal cavity, 1×104 cells at subcutaneous sites and 1×106 circulating cells immediately following injection. The kinetics of cell proliferation, as measured by photon emission, was exponential in the peritoneal cavity and at subcutaneous sites. Intravenous inoculation resulted in detectable colonies of tumor cells in animals receiving more than 1×103 cells. Our demonstrated ability to detect small numbers of tumor cells in living animals noninvasively suggests that therapies designed to treat minimal disease states, as occur early in the disease course and after elimination of the tumor mass, may be monitored using this approach. Moreover, it may be possible to monitor micrometastases and evaluate the molecular steps in the metastatic process. Spatiotemporal analyses of neoplasia will improve the predictability of animal models of human disease as study groups can be followed over time, this method will accelerate development of novel therapeutic

  12. Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer

    OpenAIRE

    Friel, Anne M.; Corcoran, Claire; Crown, John; O'Driscoll, Lorraine

    2010-01-01

    Abstract Early detection of cancer is vital to improved overall survival rates. At present, evidence is accumulating for the clinical value of detecting occult tumor cells in peripheral blood, plasma, and serum specimens from cancer patients. Both molecular and cellular approaches, which differ in sensitivity and specificity, have been used for such means. Circulating tumor cells and extracellular nucleic acids have been detected within blood, plasma, and sera of cancer patients. A...

  13. Cholecystokinin expression in tumors

    DEFF Research Database (Denmark)

    Rehfeld, Jens F

    2016-01-01

    in different neuroendocrine tumors; cerebral gliomas and astrocytomas and specific pediatric tumors. Tumor hypersecretion of CCK was recently reported in a patient with a metastatic islet cell tumor and hypercholecystokininemia resulting in a novel tumor syndrome, the cholecystokininoma syndrome. This review...... presents an overview of the cell-specific biogenesis of CCK peptides, and a description of the CCK expression in tumors and of the cholecystokininoma syndrome. Finally, assays for the diagnosis of CCK-producing tumors are reviewed....

  14. Cell cycle-arrested tumor cells exhibit increased sensitivity towards TRAIL-induced apoptosis

    OpenAIRE

    Ehrhardt, H.; Wachter, F; Grunert, M.; Jeremias, I

    2013-01-01

    Resting tumor cells represent a huge challenge during anticancer therapy due to their increased treatment resistance. TNF-related apoptosis-inducing ligand (TRAIL) is a putative future anticancer drug, currently in phases I and II clinical studies. We recently showed that TRAIL is able to target leukemia stem cell surrogates. Here, we tested the ability of TRAIL to target cell cycle-arrested tumor cells. Cell cycle arrest was induced in tumor cell lines and xenografted tumor cells in G0, G1 o...

  15. Flow cytometric applications of tumor biology: prospects and pitfalls. [Applications in study of spontaneous dog tumors and in drug and radiation effects on cultured V79 cells

    Energy Technology Data Exchange (ETDEWEB)

    Raju, M.R.; Johnson, T.S.; Tokita, N.; Gillette, E.L.

    1979-01-01

    A brief review of cytometry instrumentation and its potential applications in tumor biology is presented using our recent data. Age-distribution measurements of cells from spontaneous dog tumors and cultured cells after exposure to x rays, alpha particles, or adriamycin are shown. The data show that DNA fluorescence measurements have application in the study of cell kinetics after either radiation or drug treatment. Extensive and careful experimentation is needed to utilize the sophisticated developments in flow cytometry instrumentation.

  16. Phenotypic characterization of drug resistance and tumor initiating cancer stem cells from human bone tumor osteosarcoma cell line OS-77

    Directory of Open Access Journals (Sweden)

    Yue Zhang

    2014-08-01

    Full Text Available The cancer stem cell theory suggest that presence of small subpopulation of cancer stem cells are the major implication in the cancer treatment and also responsible for tumor recurrence. Based on Hoechst 33342 dye exclusion technique, we have identified about 3.3% of cancer stem like side population (SP cells from human osteosarcoma OS-77 cell line whose prevalence is significantly reduced to 0.3% after treatment with verapamil. The sphere formation assay revealed that osteosarcoma SP cells are highly capable to form tumor spheres (sarcospheres. Further by immunocytochemistry and RT-PCR, we show that OS-77 SP cells have enhanced expression of stem cell surface markers such as CD44, Nanog and ATP-binding cassette (ABC transporter gene (ABCG2 which contributes to self-renewal and drug resistance, respectively. Our findings help to designing a novel therapeutic drug which could effectively target the cancer stem cells and prevent the tumor relapse.

  17. Functional significance of erythropoietin receptor on tumor cells

    Institute of Scientific and Technical Information of China (English)

    Kodetthoor B Udupa

    2006-01-01

    Erythropoietin (Epo) is the regulator of red blood cell formation. Its receptor (EpoR) is now found in many cells and tissues of the body. EpoR is also shown to occur in tumor cells and Epo enhances the proliferation of these cells through cell signaling. EpoR antagonist can reduce the growth of the tumor in vivo. In view of our current knowledge of Epo, its recombinant forms and receptor,use of Epo in cancer patients to enhance the recovery of hematocrit after chemotherapy treatment has to be carefully evaluated.

  18. Childhood Central Nervous System Germ Cell Tumors Treatment

    Science.gov (United States)

    ... germ cell tumors to form is near the pineal gland and in an area of the brain ... of the inside of the brain, showing the pineal and pituitary glands, optic nerve, ventricles (with cerebrospinal ...

  19. General Information about Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... tumors include the following: Having certain genetic syndromes : Klinefelter syndrome may increase the risk of germ cell ... and procedures may be used: Physical exam and history : An exam of the body to check general ...

  20. Treatment Options for Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... tumors include the following: Having certain genetic syndromes : Klinefelter syndrome may increase the risk of germ cell ... and procedures may be used: Physical exam and history : An exam of the body to check general ...

  1. The Role of Tumor Cell-Derived Connective Tissue Growth Factor (CTGF/CCN2) in Pancreatic Tumor Growth

    Science.gov (United States)

    Bennewith, Kevin L.; Huang, Xin; Ham, Christine M.; Graves, Edward E.; Erler, Janine T.; Kambham, Neeraja; Feazell, Jonathan; Yang, George P.; Koong, Albert

    2009-01-01

    Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CCN2 derived from either tumor cells or stromal cells as it affects the growth of pancreatic tumors is unknown. Using genetic inhibition of CCN2, we have discovered that CCN2 derived from tumor cells is a critical regulator of pancreatic tumor growth. Pancreatic tumor cells derived from CCN2 shRNA-expressing clones showed dramatically reduced growth in soft agar and when implanted subcutaneously. We also observed a role for CCN2 in the growth of pancreatic tumors implanted orthotopically, with tumor volume measurements obtained by PET imaging. Mechanistically, CCN2 protects cells from hypoxia-mediated apoptosis, providing an in vivo selection for tumor cells that express high levels of CCN2. We found that CCN2 expression and secretion was increased in hypoxic pancreatic tumor cells in vitro, and we observed co-localization of CCN2 and hypoxia in pancreatic tumor xenografts and clinical pancreatic adenocarcinomas. Furthermore, we found increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal cells surrounding the tumor, supporting our assertion that tumor cell-derived CCN2 is important for pancreatic tumor growth. Taken together, these data improve our understanding of the mechanisms responsible for pancreatic tumor growth and progression, and also indicate that CCN2 produced by tumor cells represents a viable therapeutic target for the treatment of pancreatic cancer. PMID:19179545

  2. Training stem cells for treatment of malignant brain tumors

    Institute of Scientific and Technical Information of China (English)

    Shengwen; Calvin; Li; Mustafa; H; Kabeer; Long; T; Vu; Vic; Keschrumrus; Hong; Zhen; Yin; Brent; A; Dethlefs; Jiang; F; Zhong; John; H; Weiss; William; G; Loudon

    2014-01-01

    The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for pa-tients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution(i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system.

  3. Doege-Potter syndrome presenting with hypoinsulinemic hypoglycemia in a patient with a malignant extrapleural solitary fibrous tumor: a case report

    Directory of Open Access Journals (Sweden)

    Schutt Robert C

    2013-01-01

    Full Text Available Abstract Introduction Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor. This tumor causes hypoglycemia by the secretion of a prohormone form of insulin-like growth factor II. We describe the diagnosis and management of Doege-Potter syndrome and the use of transarterial chemoembolization in a patient with a malignant extrapleural solitary fibrous tumor. Case presentation Our patient was a 64-year-old Caucasian woman who initially presented with urinary incontinence and was found to have a 14.5×9.0×9.0cm retroperitoneal solitary fibrous tumor compressing her bladder. Her tumor was surgically resected but recurred with multiple hepatic metastatic lesions. The hepatic metastases progressed despite systemic chemotherapy and treatment with doxorubicin transarterial chemoembolization. Her course was complicated by the development of recurrent fasting hypoglycemia, most likely secondary to Doege-Potter syndrome. Her hypoglycemia was managed with corticosteroid therapy and frequent scheduled nutrient intake overnight. Conclusions The rarity of hepatic solitary fibrous tumors and consequent lack of controlled trials make this report significant in that it describes the diagnostic approach to Doege-Potter syndrome, describes our experience with the use of doxorubicin transarterial chemoembolization, and presents management options for tumor-associated hypoglycemia in the case of extensive disease not amenable to surgical resection.

  4. An in vivo-like tumor stem cell-related glioblastoma in vitro model for drug discovery

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Aaberg-Jessen, Charlotte; Nørregaard, Annette

    the effects of new drugs on tumor cells including tumor stem cells. Implantation of glioblastoma cells into organotypic brain slice cultures has previously been published as a model system, but not using a stem cell favourable environment. Organotypic corticostriatal rat brain slice cultures were prepared......The discovery of tumor stem cells being highly resistant against therapy makes new demands to model systems suitable for evaluation of the effects of new drugs on tumor stem cells. The aim of the present study was therefore to develop an in vivo-like in vitro glioblastoma model for testing...... and cultured in a serum containing medium replaced after three days with a serum-free stem cell medium. Thereafter fluorescent DiI labelled glioblastoma spheroids from the cell line U87 and the tumor stem cell line SJ-1 established in our laboratory were implanted into the brain slices between cortex...

  5. Active targeting of tumor cells using light emitting bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Sung Min; Min, Jung Joon; Hong, Yeong Jin; Kim, Hyun Ju; Le, Uuenchi N.; Rhee, Joon Haeng; Song, Ho Chun; Heo, Young Jun; Bom, Hee Seung; Choy, Hyon E [School of Medicine, Chonnam National University, Gwangju (Korea, Republic of)

    2004-07-01

    The presence of bacteria and viruses in human tumors has been recognized for more than 50 years. Today, with the discovery of bacterial strains that specifically target tumors, and aided by genomic sequencing and genetic engineering, there is new interest in the use of bacteria as tumor vectors. Here, we show that bacteria injected intravenously into live animals entered and replicated in solid tumors and metastases using the novel imaging technology of biophotonics. Bioluminescence operon (LuxCDABE) or fluorescence protein, GFP) has been cloned into pUC19 plasmid to engineer pUC19lux or pUC19gfp. Engineered plasmid was transformed into different kinds of wild type (MG1655) or mutant E. coli (DH5, ppGpp, fnr, purE, crpA, flagella, etc.) strains to construct light emitting bacteria. Xenograft tumor model has been established using CT26 colon cancer cell line. Light emitting bacteria was injected via tail vein into tumor bearing mouse. In vivo bioluminescence imaging has been done after 20 min to 14 days of bacterial injection. We observed localization of tumors by light-emitting E. coli in tumor (CT-26) bearing mice. We confirmed the presence of light-emitting bacteria under the fluorescence microscope with E. coli expressing GFP. Althoug varying mutants strain with deficient invading function has been found in tumor tissues, mutant strains of movement (flagella) couldn't show any light signal from the tumor tissue under the cooled CCD camera, indicating bacteria may actively target the tumor cells. Based on their 'tumor-finding' nature, bacteria may be designed to carry multiple genes or drugs for detection and treatment of cancer, such as prodrug-converting enzymes, toxins, angiogenesis inhibitors and cytokines.

  6. 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......) and chromosomes 8, 17 and 19 (two cases). Trisomy of chromosome 20 was also detected in two cases. Structural rearrangements were detected at low frequencies, with del(10)(p12) being present in two cases. In addition, we observed cell subpopulations showing a certain degree of genetic instability, reflected...

  7. Intracranial germ cell tumor mimicking anorexia nervosa.

    Science.gov (United States)

    Andreu Martínez, F J; Martínez Mateu, J M

    2006-12-01

    We report on a case of a 23 year-old female diagnosed as having a germ-cell tumour located in the sellar region. The patient referred anorexia, psychic disorders, weight loss of 15 kilograms and secondary amenorrhea during the previous three years. This is the reason why the patient was diagnosed as having anorexia nervosa. Subsequently, the patient presented some endocrine dysfunction. MRI revealed the existence of a lesion located in suprasellar and hypothalamic regions. This case shows that the presence of intracranial tumours next to the hypothalamus must be borne in mind as a rare but real possibility in cases of anorexia nervosa, specially in those non-typical cases.

  8. DNA Analysis in Samples From Younger Patients With Germ Cell Tumors and Their Parents or Siblings

    Science.gov (United States)

    2016-10-05

    Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Embryonal Carcinoma; Testicular Seminoma; Testicular Teratoma; Testicular Yolk Sac Tumor

  9. Review of juxtaglomerular cell tumor with focus on pathobiological aspect

    Directory of Open Access Journals (Sweden)

    Pan Chin-Chen

    2011-08-01

    Full Text Available Abstract Juxtaglomerular cell tumor (JGCT generally affects adolescents and young adults. The patients experience symptoms related to hypertension and hypokalemia due to renin-secretion by the tumor. Grossly, the tumor is well circumscribed with fibrous capsule and the cut surface shows yellow or gray-tan color with frequent hemorrhage. Histologically, the tumor is composed of monotonous polygonal cells with entrapped normal tubules. Immunohistochemically, tumor cells exhibit a positive reactivity for renin, vimentin and CD34. Ultrastructurally, neoplastic cells contain rhomboid-shaped renin protogranules. Genetically, losses of chromosomes 9 and 11 were frequently observed. Clinically, the majority of tumors showed a benign course, but rare tumors with vascular invasion or metastasis were reported. JGCT is a curable cause of hypertensive disease if it is discovered early and surgically removed, but may cause a fatal outcome usually by a cerebrovascular attack or may cause fetal demise in pregnancy. Additionally, pathologists and urologists need to recognize that this neoplasm in most cases pursues a benign course, but aggressive forms may develop in some cases.

  10. A novel splice mutation in the TP53 gene associated with Leydig cell tumor and primitive neuroectodermal tumor

    DEFF Research Database (Denmark)

    Stecher, Chalotte Willemann; Grønbaek, Kirsten; Hasle, Henrik

    2008-01-01

    A 20-month-old boy presented with precocious puberty due to a Leydig cell tumor, and at the age of 6 years with a primitive neuroectodermal brain-tumor (PNET). A novel splice site mutation of the TP53-gene, likely to be associated with a nonfunctional protein, was found in the proband, his father...... and younger sister, but only the proband has so far developed malignancy. The clinical phenotype in the boy is suggestive of Li-Fraumeni syndrome, but the family does not strictly conform to the canonical definition. Udgivelsesdato: 2008-Mar...

  11. Cell jamming: Collective invasion of mesenchymal tumor cells imposed by tissue confinement

    NARCIS (Netherlands)

    Haeger, A.; Krause, M.; Wolf, K. van der; Friedl, P.

    2014-01-01

    BACKGROUND: Cancer invasion is a multi-step process which coordinates interactions between tumor cells with mechanotransduction towards the surrounding matrix, resulting in distinct cancer invasion strategies. Defined by context, mesenchymal tumors, including melanoma and fibrosarcoma, develop eithe

  12. Starved and asphyxiated: how can CD8+T cells within a tumor microenvironment prevent tumor progression

    Directory of Open Access Journals (Sweden)

    Ying eZhang

    2016-02-01

    Full Text Available Although cancer immunotherapy has achieved significant breakthroughs in recent years, its overall efficacy remains limited in the majority of patients. One major barrier is exhaustion of tumor antigen (TA-specific CD8+ tumor-infiltrating lymphocytes (TILs, which conventionally has been attributed to persistent stimulation with antigen within the tumor microenvironment (TME. A series of recent studies have highlighted that the TME poses significant metabolic challenges to TILs, which may contribute to their functional exhaustion. Hypoxia increases the expression of co-inhibitors on activated CD8+T cells, which in general reduces the T cells’ effector functions. It also impairs the cells’ ability to gain energy through oxidative phosphorylation (OXPHOS. Glucose limitation increases expression of programmed cell death protein (PD-1 and reduces functions of activated CD8+T cells. A combination of hypoxia and hypoglycemia, as is common in solid tumors, places CD8+TILs at dual metabolic jeopardy by affecting both major pathways of energy production. Recently, a number of studies addressed the effects of metabolic stress on modulating CD8+T cell metabolism, differentiation and functions. Here we discuss recent findings on how different types of metabolic stress within the TME shape the tumor-killing capacity of CD8+T cells. We propose that manipulating the metabolism of TILs to more efficiently utilize nutrients especially during intermittent periods of hypoxia could maximize their performance, prolong their survival and improve the efficacy of active cancer immunotherapy.

  13. Tumor senescence and radioresistant tumor-initiating cells (TICs): let sleeping dogs lie!

    Science.gov (United States)

    Zafarana, Gaetano; Bristow, Robert G

    2010-01-01

    Preclinical data from cell lines and experimental tumors support the concept that breast cancer-derived tumor-initiating cells (TICs) are relatively resistant to ionizing radiation and chemotherapy. This could be a major determinant of tumor recurrence following treatment. Increased clonogenic survival is observed in CD24-/low/CD44+ TICs derived from mammosphere cultures and is associated with (a) reduced production of reactive oxygen species, (b) attenuated activation of γH2AX and CHK2-p53 DNA damage signaling pathways, (c) reduced propensity for ionizing radiation-induced apoptosis, and (d) altered DNA double-strand or DNA single-strand break repair. However, recent data have shed further light on TIC radioresistance as irradiated TICs are resistant to tumor cell senescence following DNA damage. Taken together, the cumulative data support a model in which DNA damage signaling and repair pathways are altered in TICs and lead to an altered mode of cell death with unique consequences for long-term clonogen survival. The study of TIC senescence lays the foundation for future experiments in isogenic models designed to directly test the capacity for senescence and local control (that is, not solely local regression) and spontaneous metastases following treatment in vivo. The study also supports the targeting of tumor cell senescence pathways to increase TIC clonogen kill if the targeting also maintains the therapeutic ratio.

  14. Conditions for NIR fluorescence-guided tumor resectioning in preclinical lung cancer model (Conference Presentation)

    Science.gov (United States)

    Kim, Minji; Quan, Yuhua; Choi, Byeong Hyun; Choi, Yeonho; Kim, Hyun Koo; Kim, Beop-Min

    2016-03-01

    Pulmonary nodule could be identified by intraoperative fluorescence imaging system from systemic injection of indocyanine green (ICG) which achieves enhanced permeability and retention (EPR) effects. This study was performed to evaluate optimal injection time of ICG for detecting cancer during surgery in rabbit lung cancer model. VX2 carcinoma cell was injected in rabbit lung under fluoroscopic computed tomography-guidance. Solitary lung cancer was confirmed on positron emitting tomography with CT (PET/CT) 2 weeks after inoculation. ICG was administered intravenously and fluorescent intensity of lung tumor was measured using the custom-built intraoperative color and fluorescence merged imaging system (ICFIS) for 15 hours. Solitary lung cancer was resected through thoracoscopic version of ICFIS. ICG was observed in all animals. Because Lung has fast blood pulmonary circulation, Fluorescent signal showed maximum intensity earlier than previous studies in other organs. Fluorescent intensity showed maximum intensity within 6-9 hours in rabbit lung cancer. Overall, Fluorescent intensity decreased with increasing time, however, all tumors were detectable using fluorescent images until 12 hours. In conclusion, while there had been studies in other organs showed that optimal injection time was at least 24 hours before operation, this study showed shorter optimal injection time at lung cancer. Since fluorescent signal showed the maximum intensity within 6-9 hours, cancer resection could be performed during this time. This data informed us that optimal injection time of ICG should be evaluated in each different solid organ tumor for fluorescent image guided surgery.

  15. Towards efficient cancer immunotherapy: advances in developing artificial antigen-presenting cells

    NARCIS (Netherlands)

    Eggermont, L.J.; Paulis, L.E.M.; Tel, J.; Figdor, C.G.

    2014-01-01

    Active anti-cancer immune responses depend on efficient presentation of tumor antigens and co-stimulatory signals by antigen-presenting cells (APCs). Therapy with autologous natural APCs is costly and time-consuming and results in variable outcomes in clinical trials. Therefore, development of artif

  16. Hepatic perivascular epithelioid cell tumor (PEComa): a case report with a review of literatures

    Science.gov (United States)

    Son, Hyun-Jin; Kang, Dong Wook; Kim, Joo Heon; Han, Hyun Young; Lee, Min Koo

    2017-01-01

    Hepatic perivascular epithelioid cell tumors (PEComas) are very rare. We report a primary hepatic PEComa with a review of the literature. A 56-year-old women presented with a nodular mass detected during the management of chronic renal failure and chronic hepatitis C. Diagnostic imaging studies suggested a nodular hepatocellular carcinoma in segment 5 of the liver. The patient underwent partial hepatectomy. A brown-colored expansile mass measuring 3.2×3.0 cm was relatively demarcated from the surrounding liver parenchyma. The tumor was mainly composed of epithelioid cells that were arranged in a trabecular growth pattern. Adipose tissue and thick-walled blood vessels were minimally identified. A small amount of extramedullary hematopoiesis was observed in the sinusoidal spaces between tumor cells. Tumor cells were diffusely immunoreactive for human melanoma black 45 (HMB45) and Melan A, focally immunoreactive for smooth muscle actin, but not for hepatocyte specific antigen (HSA). PMID:28288506

  17. Distribution and differentiation of mesenchymal stem cells in tumor tissue

    Institute of Scientific and Technical Information of China (English)

    ZHAO Hai-feng; CHEN Jun; XU Zhi-shun; ZHANG Ke-qin

    2009-01-01

    Background Tumor has an ability to become enriched in mesenchymal stem cells (MSCs) and of guiding MSCs to migrate to tumor tissue. But there are lack of relevant reports on the distribution and differentiation of MSCs in tumor tissue and the effect on tumor growth after MSCs engrafted in tumor tissue. In this study, we observed the distribution of bone marrow MSCs in tumor tissue and the possibility of MSCs differentiating into myofibroblast under the induction of local tumor microenvironment.Methods Twenty-four New Zealand rabbits were randomly classified into the control group and the test group. MSCs were isolated and cultured for each animal, vx-2 tumor tissue was transplanted under the bladder mucosa of each animal. One week after the transplantation, the self F2 passage MSCs marked by 4',6-diamidino-2-phenylindole were transplanted into tumor tissue in the test group while only Dulbecco's modified Eagle's medium-low glucose was infused into the control group. Ultrasonography was performed for each animal 1,2, 3 and 4 week(s) after the vx-2 tumor mass was transplanted. The maximum bladder tumor diameter of each animal was recorded and the mean value of each group was calculated. One animal from each group was sacrificed in the third week and the remaining animals in the fourth week to observe the tumor development. Another animal treated the same as the test group was sacrificed to observe the distribution of MSCs in tumor tissue one week after self MSCs transplantation. Immunofluorescence was used to trace MSCs in tumor tissue. The double labeling immunofluorescence for α-smooth muscle actin (α-SMA) and vimentin was performed to identify whether the MSCs can differentiate into myofibroblast.Results The ultrasonography showed no tumor mass one week after the vx-2 tumor mass transplantation. The mean maximum tumor diameter of the control group and test group was (0.70±0.14) cm and (0.78±0.14) cm, respectively, and there was no significant difference (t=1

  18. Pineal germ cell tumors: Two cases with review of histopathologies and biomarkers.

    Science.gov (United States)

    Nagasawa, Daniel T; Lagman, Carlito; Sun, Michael; Yew, Andrew; Chung, Lawrance K; Lee, Seung J; Bui, Timothy T; Ooi, Yinn Cher; Robison, R Aaron; Zada, Gabriel; Yang, Isaac

    2017-04-01

    Pineal germ cell tumors (GCTs) are primarily seen in pediatric and Asian populations. These tumors are divided into germinomatous and non-germinomatous GCTs (NGGCTs). GCTs are thought to arise by misplacement of totipotent stem cells en route to gonads during embryogenesis. Intracranial GCTs display an affinity to develop along the pineal-suprasellar axis and have variable manifestations dependent upon the location of the tumor. Management and outcomes are driven by histopathologies. In this study, we highlight two cases of pineal GCTs and present a review of the literature with an emphasis on histopathologies and biomarkers.

  19. Glycan Sulfation Modulates Dendritic Cell Biology and Tumor Growth.

    Science.gov (United States)

    El Ghazal, Roland; Yin, Xin; Johns, Scott C; Swanson, Lee; Macal, Monica; Ghosh, Pradipta; Zuniga, Elina I; Fuster, Mark M

    2016-05-01

    In cancer, proteoglycans have been found to play roles in facilitating the actions of growth factors, and effecting matrix invasion and remodeling. However, little is known regarding the genetic and functional importance of glycan chains displayed by proteoglycans on dendritic cells (DCs) in cancer immunity. In lung carcinoma, among other solid tumors, tumor-associated DCs play largely subversive/suppressive roles, promoting tumor growth and progression. Herein, we show that targeting of DC glycan sulfation through mutation in the heparan sulfate biosynthetic enzyme N-deacetylase/N-sulfotransferase-1 (Ndst1) in mice increased DC maturation and inhibited trafficking of DCs to draining lymph nodes. Lymphatic-driven DC migration and chemokine (CCL21)-dependent activation of a major signaling pathway required for DC migration (as measured by phospho-Akt) were sensitive to Ndst1 mutation in DCs. Lewis lung carcinoma tumors in mice deficient in Ndst1 were reduced in size. Purified CD11c+ cells from the tumors, which contain the tumor-infiltrating DC population, showed a similar phenotype in mutant cells. These features were replicated in mice deficient in syndecan-4, the major heparan sulfate proteoglycan expressed on the DC surface: Tumors were growth-impaired in syndecan-4-deficient mice and were characterized by increased infiltration by mature DCs. Tumors on the mutant background also showed greater infiltration by NK cells and NKT cells. These findings indicate the genetic importance of DC heparan sulfate proteoglycans in tumor growth and may guide therapeutic development of novel strategies to target syndecan-4 and heparan sulfate in cancer.

  20. Glycan Sulfation Modulates Dendritic Cell Biology and Tumor Growth

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    Roland El Ghazal

    2016-05-01

    Full Text Available In cancer, proteoglycans have been found to play roles in facilitating the actions of growth factors, and effecting matrix invasion and remodeling. However, little is known regarding the genetic and functional importance of glycan chains displayed by proteoglycans on dendritic cells (DCs in cancer immunity. In lung carcinoma, among other solid tumors, tumor-associated DCs play largely subversive/suppressive roles, promoting tumor growth and progression. Herein, we show that targeting of DC glycan sulfation through mutation in the heparan sulfate biosynthetic enzyme N-deacetylase/N-sulfotransferase-1 (Ndst1 in mice increased DC maturation and inhibited trafficking of DCs to draining lymph nodes. Lymphatic-driven DC migration and chemokine (CCL21-dependent activation of a major signaling pathway required for DC migration (as measured by phospho-Akt were sensitive to Ndst1 mutation in DCs. Lewis lung carcinoma tumors in mice deficient in Ndst1 were reduced in size. Purified CD11c+ cells from the tumors, which contain the tumor-infiltrating DC population, showed a similar phenotype in mutant cells. These features were replicated in mice deficient in syndecan-4, the major heparan sulfate proteoglycan expressed on the DC surface: Tumors were growth-impaired in syndecan-4–deficient mice and were characterized by increased infiltration by mature DCs. Tumors on the mutant background also showed greater infiltration by NK cells and NKT cells. These findings indicate the genetic importance of DC heparan sulfate proteoglycans in tumor growth and may guide therapeutic development of novel strategies to target syndecan-4 and heparan sulfate in cancer.

  1. Functional EpoR pathway utilization is not detected in primary tumor cells isolated from human breast, non-small cell lung, colorectal, and ovarian tumor tissues.

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    Scott D Patterson

    Full Text Available Several clinical trials in oncology have reported increased mortality or disease progression associated with erythropoiesis-stimulating agents. One hypothesis proposes that erythropoiesis-stimulating agents directly stimulate tumor proliferation and/or survival through cell-surface receptors. To test this hypothesis and examine if human tumors utilize the erythropoietin receptor pathway, the response of tumor cells to human recombinant erythropoietin was investigated in disaggregated tumor cells obtained from 186 patients with colorectal, breast, lung, ovarian, head and neck, and other tumors. A cocktail of well characterized tumor growth factors (EGF, HGF, and IGF-1 were analyzed in parallel as a positive control to determine whether freshly-isolated tumor cells were able to respond to growth factor activation ex vivo. Exposing tumor cells to the growth factor cocktail resulted in stimulation of survival and proliferation pathways as measured by an increase in phosphorylation of the downstream signaling proteins AKT and ERK. In contrast, no activation by human recombinant erythropoietin was observed in isolated tumor cells. Though tumor samples exhibited a broad range of cell-surface expression of EGFR, c-Met, and IGF-1R, no cell-surface erythropoietin receptor was detected in tumor cells from the 186 tumors examined (by flow cytometry or Western blot. Erythropoiesis-stimulating agents did not act directly upon isolated tumor cells to stimulate pathways known to promote proliferation or survival of human tumor cells isolated from primary and metastatic tumor tissues.

  2. Atypical presentation of primary renal squamous cell cancer: a case report

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    Mrinal Pahwa

    2014-02-01

    Full Text Available Renal squamous cell cancer is one of the rare primary urothelial tumors with only a handful of cases reported in literature. Because of high grade, advanced and late presentation, they herald a grave prognosis. They are frequently associated with calculus disease, smoking, phenacetin consumption and foci of squamous metaplasia due to chronic irritation. Nephroureterectomy is the treatment of choice for such tumors. We hereby present a case of 59 year old female who presented with squamous cell cancer of renal pelvis. The case presented here is different from what has already been reported in literature, as the patient had no antecedent risk factors for renal squamous cell carcinoma.-------------------------------------------------Cite this article as: Pahwa M, Pahwa AR, Girotra M, Chawla A. Atypical presentation of primary renal squamous cell cancer: a case report. Int J Cancer Ther Oncol 2014; 2(1:02015.DOI: http://dx.doi.org/10.14319/ijcto.0201.5

  3. Tumor Budding Cells, Cancer Stem Cells and Epithelial-Mesenchymal Transition-type Cells in Pancreatic Cancer

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    Eva eKaramitopoulou

    2013-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4 and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with WNT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT. Emerging evidence has demonstrated that cancer stem cells (CSCs, small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5 of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric and ampullary carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs and EMT-type cells in PDAC.

  4. Translational research in ovarian carcinoma : cell biological aspects of drug resistance and tumor aggressiveness

    NARCIS (Netherlands)

    Zee, Ate Gerard Jan van der

    1994-01-01

    In this thesis diverse cell biological features that in cultured (ovarian) tumor cells have been linked to drug resistance and/or tumor aggressiveness are studied in tumor specimens of epithelial ovarian carcinomas.

  5. Intraoral presentation of multiple malignant peripheral nerve sheath tumors associated with neurofibromatosis-1

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    Mahija Janardhanan

    2011-01-01

    Full Text Available Neurofibromatosis-1 (NF-1 is a relatively common autosomal dominant disease characterized by multiple cutaneous fibromatoses and café au lait spots. It is associated with the mutation of NF-1 gene, a tumor suppressor gene located on chromosome 17q11.2. Hence, it can be considered as a familial cancer predisposition syndrome in which the affected individuals are at increased risk of developing malignancies. Intraoral neurofibromas associated with NF-1 are quite common, but the occurrence of malignant peripheral nerve sheath tumor (MPNST in the oral cavity is very rare. Oral MPNST can occur either de novo or by malignant transformation of neurofibromas or very rarely can represent a metastatic lesion. Here, we present a case of MPNST involving the maxillary region, in a patient with NF-1. Since MPNST often creates a diagnostic dilemma, histopathologic criteria for the diagnosis of MPNST are also discussed.

  6. Steroid Cell Tumor of the Ovary in an Adolescent: A Rare Case Report

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    Gokhan Boyraz

    2013-01-01

    Full Text Available Steroid cell tumors (SCTs of the ovary are a rare subgroup of sex cord tumors, account for less than 0.1% of all ovarian tumors, and also will present at any age. These tumors can produce steroids, especially testosterone, and may give symptoms like hirsutism, hair loss, amenorrhea, or oligomenorrhea. For the evaluation of androgen excess, testosterone and dehydroepiandrosterone sulfate (DHEA-S are the first laboratory tests to be measured. A pelvic ultrasound and a magnetic resonance imaging are useful radiologic imaging techniques. Although steroid cell tumors are generally benign, there is a risk of malignant transformation and clinical malignant formation. Surgery is the most important and hallmark treatment.

  7. Aire-dependent thymic development of tumor-associated regulatory T cells*

    Science.gov (United States)

    Malchow, Sven; Leventhal, Daniel S.; Nishi, Saki; Fischer, Benjamin I.; Shen, Lynn; Paner, Gladell P.; Amit, Ayelet S.; Kang, Chulho; Geddes, Jenna E.; Allison, James P.; Socci, Nicholas D.; Savage, Peter A.

    2013-01-01

    Despite considerable interest in the modulation of tumor-associated Foxp3+ regulatory T cells (Tregs) for therapeutic benefit, little is known about the developmental origins of these cells and the nature of the antigens that they recognize. Here, we identified an endogenous population of antigen-specific Tregs (termed “MJ23” Tregs) found recurrently enriched in the tumors of mice with oncogene-driven prostate cancer. MJ23 Tregs were not reactive to a tumor-specific antigen, but instead recognized a prostate-associated antigen that was present in tumor-free mice. MJ23 Tregs underwent Aire-dependent thymic development in both male and female mice. Thus Aire-mediated expression of peripheral tissue antigens drives the thymic development of a subset of organ-specific Tregs, which are likely co-opted by tumors developing within the associated organ. PMID:23471412

  8. Microfluidic cell isolation technology for drug testing of single tumor cells and their clusters

    Science.gov (United States)

    Bithi, Swastika S.; Vanapalli, Siva A.

    2017-01-01

    Drug assays with patient-derived cells such as circulating tumor cells requires manipulating small sample volumes without loss of rare disease-causing cells. Here, we report an effective technology for isolating and analyzing individual tumor cells and their clusters from minute sample volumes using an optimized microfluidic device integrated with pipettes. The method involves using hand pipetting to create an array of cell-laden nanoliter-sized droplets immobilized in a microfluidic device without loss of tumor cells during the pipetting process. Using this technology, we demonstrate single-cell analysis of tumor cell response to the chemotherapy drug doxorubicin. We find that even though individual tumor cells display diverse uptake profiles of the drug, the onset of apoptosis is determined by accumulation of a critical intracellular concentration of doxorubicin. Experiments with clusters of tumor cells compartmentalized in microfluidic drops reveal that cells within a cluster have higher viability than their single-cell counterparts when exposed to doxorubicin. This result suggests that circulating tumor cell clusters might be able to better survive chemotherapy drug treatment. Our technology is a promising tool for understanding tumor cell-drug interactions in patient-derived samples including rare cells. PMID:28150812

  9. Leiomyosarcoma presenting as a spontaneously ruptured renal tumor-case report

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    Ather M

    2002-11-01

    Full Text Available Abstract Background Ruptured renal neoplasms can be a catastrophic clinical presentation. Angiomyolipoma is the commonest renal tumor which presents in this fashion. Renal sarcomas are rare renal neoplasms. Renal leiomyosarcomas are the most common histological subtype of renal sarcomas, accounting for approximately 50–60% of the reported cases. These tumors are usually peripherally located and appear to arise from either the renal capsule or smooth muscle tissue in the renal pelvic wall. Case presentation A 70 years old male, with hypertension and ischemic disease, developed acute left flank pain. The general physician evaluated this using ultrasound, which showed a solid left renal mass. Two weeks later, he presented in the emergency room in a state of shock with a palpable flank mass. CT scan of the abdomen showed a large heterogeneous mass lesion in the left perinephric space with minimal post contrast enhancement. Per-operatively, large retroperitoneal hematoma was found within Gerota's fascia along with spleen plastered to the upper limit of hematoma. Nephrectomy and splenectomy were performed. Postoperative course was uneventful and patient was discharged on the 10th post-operative day. Histopathological evaluation of the specimen showed high-grade leiomyosarcoma Conclusions Spontaneous rupture of renal neoplasm is a rare clinical presentation. Angiomyolipoma is the commonest cause of spontaneous rupture of the kidney. Presentation of a leimyosarcoma as a ruptured renal neoplasm has not been previously reported in the English literature.

  10. Combination of Id2 Knockdown Whole Tumor Cells and Checkpoint Blockade: A Potent Vaccine Strategy in a Mouse Neuroblastoma Model.

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    Lina Chakrabarti

    Full Text Available Tumor vaccines have held much promise, but to date have demonstrated little clinical success. This lack of success is conceivably due to poor tumor antigen presentation combined with immuno-suppressive mechanisms exploited by the tumor itself. Knock down of Inhibitor of differentiation protein 2 (Id2-kd in mouse neuroblastoma whole tumor cells rendered these cells immunogenic. Id2-kd neuroblastoma (Neuro2a cells (Id2-kd N2a failed to grow in most immune competent mice and these mice subsequently developed immunity against further wild-type Neuro2a tumor cell challenge. Id2-kd N2a cells grew aggressively in immune-compromised hosts, thereby establishing the immunogenicity of these cells. Therapeutic vaccination with Id2-kd N2a cells alone suppressed tumor growth even in established neuroblastoma tumors and when used in combination with immune checkpoint blockade eradicated large established tumors. Mechanistically, immune cell depletion studies demonstrated that while CD8+ T cells are critical for antitumor immunity, CD4+ T cells are also required to induce a sustained long-lasting helper effect. An increase in number of CD8+ T-cells and enhanced production of interferon gamma (IFNγ was observed in tumor antigen stimulated splenocytes of vaccinated mice. More importantly, a massive influx of cytotoxic CD8+ T-cells infiltrated the shrinking tumor following combined immunotherapy. These findings show that down regulation of Id2 induced tumor cell immunity and in combination with checkpoint blockade produced a novel, potent, T-cell mediated tumor vaccine strategy.

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

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    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. Involvement of ERK-Nrf-2 signaling in ionizing radiation induced cell death in normal and tumor cells.

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    Raghavendra S Patwardhan

    Full Text Available Prolonged oxidative stress favors tumorigenic environment and inflammation. Oxidative stress may trigger redox adaptation mechanism(s in tumor cells but not normal cells. This may increase levels of intracellular antioxidants and establish a new redox homeostasis. Nrf-2, a master regulator of battery of antioxidant genes is constitutively activated in many tumor cells. Here we show that, murine T cell lymphoma EL-4 cells show constitutive and inducible radioresistance via activation of Nrf-2/ERK pathway. EL-4 cells contained lower levels of ROS than their normal counterpart murine splenic lymphocytes. In response to radiation, the thiol redox circuits, GSH and thioredoxin were modified in EL-4 cells. Pharmacological inhibitors of ERK and Nrf-2 significantly enhanced radiosensitivity and reduced clonogenic potential of EL-4 cells. Unirradiated lymphoma cells showed nuclear accumulation of Nrf-2, upregulation of its dependent genes and protein levels. Interestingly, MEK inhibitor abrogated its nuclear translocation suggesting role of ERK in basal and radiation induced Nrf-2 activation in tumor cells. Double knockdown of ERK and Nrf-2 resulted in higher sensitivity to radiation induced cell death as compared to individual knockdown cells. Importantly, NF-kB which is reported to be constitutively active in many tumors was not present at basal levels in EL-4 cells and its inhibition did not influence radiosensitivity of EL-4 cells. Thus our results reveal that, tumor cells which are subjected to heightened oxidative stress employ master regulator cellular redox homeostasis Nrf-2 for prevention of radiation induced cell death. Our study reveals the molecular basis of tumor radioresistance and highlights role of Nrf-2 and ERK.

  13. Cell fusion in tumor progression: the isolation of cell fusion products by physical methods

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    Vincitorio Massimo

    2011-09-01

    Full Text Available Abstract Background Cell fusion induced by polyethylene glycol (PEG is an efficient but poorly controlled procedure for obtaining somatic cell hybrids used in gene mapping, monoclonal antibody production, and tumour immunotherapy. Genetic selection techniques and fluorescent cell sorting are usually employed to isolate cell fusion products, but both procedures have several drawbacks. Results Here we describe a simple improvement in PEG-mediated cell fusion that was obtained by modifying the standard single-step procedure. We found that the use of two PEG undertreatments obtains a better yield of cell fusion products than the standard method, and most of these products are bi- or trinucleated polykaryocytes. Fusion rate was quantified using fluorescent cell staining microscopy. We used this improved cell fusion and cell isolation method to compare giant cells obtained in vitro and giant cells obtained in vivo from patients with Hodgkin's disease and erythroleukemia. Conclusions In the present study we show how to improve PEG-mediated cell fusion and that cell separation by velocity sedimentation offers a simple alternative for the efficient purification of cell fusion products and to investigate giant cell formation in tumor development.

  14. HAMLET interacts with histones and chromatin in tumor cell nuclei.

    Science.gov (United States)

    Düringer, Caroline; Hamiche, Ali; Gustafsson, Lotta; Kimura, Hiroshi; Svanborg, Catharina

    2003-10-24

    HAMLET is a folding variant of human alpha-lactalbumin in an active complex with oleic acid. HAMLET selectively enters tumor cells, accumulates in their nuclei and induces apoptosis-like cell death. This study examined the interactions of HAMLET with nuclear constituents and identified histones as targets. HAMLET was found to bind histone H3 strongly and to lesser extent histones H4 and H2B. The specificity of these interactions was confirmed using BIAcore technology and chromatin assembly assays. In vivo in tumor cells, HAMLET co-localized with histones and perturbed the chromatin structure; HAMLET was found associated with chromatin in an insoluble nuclear fraction resistant to salt extraction. In vitro, HAMLET bound strongly to histones and impaired their deposition on DNA. We conclude that HAMLET interacts with histones and chromatin in tumor cell nuclei and propose that this interaction locks the cells into the death pathway by irreversibly disrupting chromatin organization.

  15. Dendritic Cell as Therapeutic Vaccines against Tumors and Its Role in Therapy for Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Kang Sun; Liang Wang; Yanyun Zhang

    2006-01-01

    Dendritic cells (DCs) are the most potent professional antigen-presenting cells, and capable of stimulating naive T cells and driving primary immune responses. DCs are poised to capture antigen, migrate to draining lymphoid organs, and after a process of maturation, select antigen-specific !ymphocytes to which they present the processed antigen, thereby inducing immune responses. The development of protocols for the ex vivo generation of DCs may provide a rationale for designing and developing DC-based vaccination for the treatment of tumors. There are now several strategies being applied to upload antigens to DCs and manipulate DC vaccines. DC vaccines are able to induce therapeutic and protective antitumor immunity. Numerous studies indicated that hepatocellular carcinoma (HCC) immunotherapies utilizing DC-presenting tumor-associated antigens could stimulate an antitumour T cell response leading to clinical benefit without any significant toxicity. DC-based tumor vaccines have become a novel immunoadjuvant therapy for HCC.

  16. In vitro model for study the interaction between tumor and stromal cells

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    Shkarina K. A.

    2013-01-01

    Full Text Available Aim. To develop a model to study the interaction between tumor and stromal cells in three-dimensional culture. Methods. Cultivation of HeLa cell lines and human dermal fibroblasts in monolayer and three-dimensional culture, immunofluorescent and immunohistochemical analysis. Results. In this work we present an approach based on a direct interaction between the cells of multicellular tumor spheroids and spheroids of fibroblasts. Subsequent immunofluorescence analysis allows to determine an origin of cells in the area of their contact. Conclusions. This model will be useful to study the basic mechanisms of carcinogenesis, and to find targets for anticancer therapy.

  17. Unusual morphology of desmoplastic small round cell tumor from an ascitic fluid in the postchemotherapy setting

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    Ricardo González-Arango

    2015-01-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT is a malignant neoplasm that most often presents in male adolescents as an abdominal mass. Cytological features have been previously described, but only two reports noted post chemotherapy changes on effusions. We report a case of a 15-year-old male with DSRCT status postchemotherapy that presented with ascitis. Unusual morphology was seen: Numerous malignant large and single cells with prominent nucleoli and abundant cytoplasm in a background without the stroma, occasional mitosis, and the abundant apoptosis. Cell block immunocytochemistry was confirmatory. Awareness of the postchemotherapy changes in this tumor will allow us to diagnose recurrence.

  18. Genetic alteration andmutation proifling ofcirculating cell-free tumor DNA (cfDNA) fordiagnosis andtargeted therapy ofgastrointestinal stromal tumors

    Institute of Scientific and Technical Information of China (English)

    WeixinYan; AiguoZhang; MichaelJPowell

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive type of tumor, different from smooth muscle and neural tumors of the gastrointestinal tract. The identiifcation of genetic aberrations in proto-oncogenes that drive the growth of GISTs is critical for improving the effcacy of cancer therapy by match-ing targeted drugs to speciifc mutations. Research into the oncogenic mechanisms of GISTs has found that these tumors frequently contain activating gene mutations in either platelet-derived growth factor receptor A (PDGFRA) or a receptor tyrosine protein associated with a mast cell growth factor receptor encoded by theKIT gene. Mutant cancer subpopulations have the potential to disrupt durable patient responses to molecularly targeted therapy for GISTs, yet the prevalence and size of subpopulations remain largely unexplored. Detection of the cancer subpopulations that harbor low-frequency mutant alleles of target proto-oncogenes through the use of molecular genetic methods, such as polymerase chain reaction (PCR) target ampliifcation technology, is hampered by the high abundance of wild-type alleles, which limit the sensitivity of detection of these minor mutant alleles. This is especially true in the case of mutant tumor DNA derived “driver” and “drug-resistant” alleles that are present in the circulating cell-free tumor DNA (cfDNA) in the peripheral blood circulation of GIST patients. So-called “liquid biopsy” allows for the dynamic monitor-ing of the patients’ tumor status during treatment using minimally invasive sampling. New methodologies, such as a technology that employs a xenonucleic acid (XNA) clamping probe to block the PCR ampliifcation of wild-type templates, have allowed improved molecular detection of these low-frequency alleles both in tissue biopsy samples and in cfDNA. These new methodologies could be widely applied for minimally invasive molecular testing in the therapeutic management of GISTs.

  19. Myoepithelial cells: Current perspectives in salivary gland tumors

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    C Pramod Redder

    2013-01-01

    Full Text Available Myoepithelial cells are normal constituent of the salivary acini and smaller ducts, and are found between the epithelial cells and the basement membrane. Microscopic examination shows that myoepithelial cells are thin and spindle-shaped and situated between the basement membrane and epithelial cells. Ultrastructurally they possess a number of cytoplasmic processes that extend between and over the acinar and ductal-lining cells. They display features of both smooth muscle and epithelium, such as numerous microfilaments with focal densities in the cytoplasmic processes, and desmosomes which attach the myoepithelial to the epithelial cells. Neoplastic myoepithelial cells in both benign and malignant tumors can take several forms, including epithelioid, spindle, plasmacytoid, and clear, and this variability largely accounts for difficulties in histopathological diagnosis. This review article highlights the role of myoepithelial cells in salivary gland tumors.

  20. Induction of abscopal anti-tumor immunity and immunogenic tumor cell death by ionizing irradiation - implications for cancer therapies.

    Science.gov (United States)

    Frey, B; Rubner, Y; Wunderlich, R; Weiss, E-M; Pockley, A G; Fietkau, R; Gaipl, U S

    2012-01-01

    Although cancer progression is primarily driven by the expansion of tumor cells, the tumor microenvironment and anti-tumor immunity also play important roles. Herein, we consider how tumors can become established by escaping immune surveillance and also how cancer cells can be rendered visible to the immune system by standard therapies such as radiotherapy or chemotherapy, either alone or in combination with additional immune stimulators. Although local radiotherapy results in DNA damage (targeted effects), it is also capable of inducing immunogenic forms of tumor cell death which are associated with a release of immune activating danger signals (non-targeted effects), such as necrosis. Necrotic tumor cells may result from continued exposure to death stimuli and/or an impaired phosphatidylserine (PS) dependent clearance of the dying tumor cells. In such circumstances, mature dendritic cells take up tumor antigen and mediate the induction of adaptive and innate anti-tumor immunity. Locally-triggered, systemic immune activation can also lead to a spontaneous regression of tumors or metastases that are outside the radiation field - an effect which is termed abscopal. Preclinical studies have demonstrated that combining radiotherapy with immune stimulation can induce anti-tumor immunity. Given that it takes time for immunity to develop following exposure to immunogenic tumor cells, we propose practical combination therapies that should be considered as a basis for future research and clinical practice. It is essential that radiation oncologists become more aware of the importance of the immune system to the success of cancer therapy.

  1. Targeted therapy of animal eyes with tumors by laser-generated focused ultrasound (Conference Presentation)

    Science.gov (United States)

    Lee, Taehwa; Luo, Wei; Demirci, Hakan; Guo, L. Jay

    2016-03-01

    Cavitation therapy based on high-amplitude focused ultrasound (e.g., Histotripsy) has shown great promise in clinical trials. The technique realizes localized treatments of tissues and diseased cells by controlling cavitation zones, which can be even smaller than its acoustic spot sizes. Also, the short pressure pulse used in the technique can minimize the unwanted heat accumulation, which the conventional piezoelectric transducers suffer from due to low operating frequencies and relatively long acoustic pulses. However, this modality requires bulky system composed of array of piezoelectric elements and electric amplifiers in order to obtain high pressure amplitude. Moreover, especially when treating an area much smaller than the acoustic spot size, this approach may be vulnerable to nucleation sites within the focal volume, which can potentially induce cavitation and thus enlarge the total treatment area. Here, we show targeted cell-level therapy by using laser generated ultrasound. By employing a concave lens coated by a carbon nanotube (CNT)-polymer composite, high-amplitude acoustic pressure can be obtained at a tight focal spot (<100 um). The small focal spot, comparable to cavitation zone, lead to controlled cavitation treatment. Such feature can be exploited for treating intraocular tumors but without harming other parts of the eye (e.g. healthy retina and choroid) and therefore preserve the vision of the patients. We demonstrate that the localized disruption effects can be used for cell-level surgery to remove cells and to kill cells. Some experimental examples are shown using animal eyeballs.

  2. Hsp60 is actively secreted by human tumor cells.

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    Anna M Merendino

    Full Text Available BACKGROUND: Hsp60, a Group I mitochondrial chaperonin, is classically considered an intracellular chaperone with residence in the mitochondria; nonetheless, in the last few years it has been found extracellularly as well as in the cell membrane. Important questions remain pertaining to extracellular Hsp60 such as how generalized is its occurrence outside cells, what are its extracellular functions and the translocation mechanisms that transport the chaperone outside of the cell. These questions are particularly relevant for cancer biology since it is believed that extracellular chaperones, like Hsp70, may play an active role in tumor growth and dissemination. METHODOLOGY/PRINCIPAL FINDINGS: Since cancer cells may undergo necrosis and apoptosis, it could be possible that extracellular Hsps are chiefly the result of cell destruction but not the product of an active, physiological process. In this work, we studied three tumor cells lines and found that they all release Hsp60 into the culture media by an active mechanism independently of cell death. Biochemical analyses of one of the cell lines revealed that Hsp60 secretion was significantly reduced, by inhibitors of exosomes and lipid rafts. CONCLUSIONS/SIGNIFICANCE: Our data suggest that Hsp60 release is the result of an active secretion mechanism and, since extracellular release of the chaperone was demonstrated in all tumor cell lines investigated, our observations most likely reflect a general physiological phenomenon, occurring in many tumors.

  3. Acute scrotum due to arterial bleeding mimicking non-seminomatous germ cell tumor

    Institute of Scientific and Technical Information of China (English)

    F.Christoph; M.Schradert; A.Amirmaki; K.Miller

    2004-01-01

    Men with testicular tumors usually present with painless increase in testis size incidentally noticed by the patient. We report a case of a young patient presenting as an emergency with acute onset of massive right-sided testicular pain without previous injury. After physical examination testicular torsion could not be excluded. Ultrasound examination of the tesds was suspicious for tesdcular tumor. Surgical exploration of the right testis by inguinal approach was performed revealing subcapsular arterial bleeding due to a small nonseminomatous germ cell tumor non-palpable on clinical examination. (Asian J Andro12004 Dec;6:379-381)

  4. Contrast-enhanced ultrasound in ovarian tumors – diagnostic parameters: method presentation and initial experience

    Science.gov (United States)

    MAXIM, ANITA-ROXANA; BADEA, RADU; TAMAS, ATILLA; TRAILA, ALEXANDRU

    2013-01-01

    The aim of this paper is to discuss and illustrate the use of contrast-enhanced ultrasound in evaluating ovarian tumors compared to conventional ultrasound, Doppler ultrasound and the histopathological analysis and suggest how this technique may best be used to distinguish benign from malignant ovarian masses. We present the method and initial experience of our center by analyzing the parameters used in contrast-enhanced ultrasound in 6 patients with ovarian tumors of uncertain etiology. For examination we used a Siemens ultrasound machine with dedicated contrast software and the contrast agent SonoVue, Bracco. The patients underwent conventional ultrasound, Doppler ultrasound and i.v. administration of the contrast agent. The parameters studied were: inflow of contrast (rise time), time to peak enhancement, mean transit time. The series of patients is part of an extensive prospective PhD study aimed at elaborating a differential diagnosis protocol for benign versus malignant ovarian tumors, by validating specific parameters for contrast-enhanced ultrasound. Although the method is currently used with great success in gastroenterology, urology and senology, its validation in gynecology is still in the early phases. Taking into consideration that the method is minimally invasive and much less costly that CT/MRI imaging, demonstrating its utility in oncologic gynecology would be a big step in preoperative evaluation of these cases. PMID:26527912

  5. Advanced Research on Circulating Tumor Cells in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hui LI

    2012-11-01

    Full Text Available Lung cancer is the malignant disease with the highest rate in terms of incidence and mortality in China. Early diagnosis and timely monitoring tumor recurrence and metastasis are extremely important for improving 5-year survival rate of lung cancer patients. Circulating tumor cells (CTCs, as a "liquid biopsy specimens” for the primary tumor, provide the possibility to perform real-time, non-invasive histological identification for lung cancer patients. The detection of CTCs contributes to early diagnosis, surveillance of tumor recurrence and metastasis, and prediction of therapeutic efficacy and prognosis. Furthermore, CTCs-dependent detection emerges as a new approach for molecularly pathologic examination, study of molecular mechanisms involved in drug resistance, and resolution for tumor heterogeneity. This study reviewed the recent progress of CTCs in lung cancer research field.

  6. Good syndrome presenting with CD8+ T-Cell large granular lymphocyte leukemia

    OpenAIRE

    Caperton, Caroline; Agrawal, Sudhanshu; Gupta, Sudhir

    2015-01-01

    Good Syndrome is an adult-onset combined immunodeficiency defined by hypogammaglobulinemia, low or absent number of B cells, T cell deficiency and thymic tumor. We have characterized CD8+ T cells from a patient with Good syndrome that presented with CD8+T-cell large granular lymphocytic leukemia (LGL). Characterization of peripheral blood CD8+ T cells revealed that majority of CD8+ T cells were terminally differentiated effector memory phenotype (TEMRA; CD8+CCR7-CD45RA+), and were PD-1high (C...

  7. Effects of charged particles on human tumor cells

    Directory of Open Access Journals (Sweden)

    Kathryn D Held

    2016-02-01

    Full Text Available The use of charged particle therapy in cancer treatment is growing rapidly, in large part because the exquisite dose localization of charged particles allows for higher radiation doses to be given to tumor tissue while normal tissues are exposed to lower doses and decreased volumes of normal tissues are irradiated. In addition, charged particles heavier than protons have substantial potential clinical advantages because of their additional biological effects including greater cell killing effectiveness, decreased radiation resistance of hypoxic cells in tumors and reduced cell cycle dependence of radiation response. These biological advantages depend on many factors such as endpoint, cell or tissue type, dose, dose rate or fractionation, charged particle type and energy, and oxygen concentration. This review summarizes the unique biological advantages of charged particle therapy and highlights recent research and areas of particular research needs, such as quantification of Relative Biological Effectiveness (RBE for various tumor types and radiation qualities, role of genetic background of tumor cells in determining response to charged particles, sensitivity of cancer stem-like cells to charged particles, role of charged particles in tumors with hypoxic fractions and importance of fractionation, including use of hypofractionation, with charged particles.

  8. Cyclophilin A enhances cell proliferation and tumor growth of liver fluke-associated cholangiocarcinoma

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    Sawanyawisuth Kanlayanee

    2011-08-01

    Full Text Available Abstract Background Cyclophilin A (CypA expression is associated with malignant phenotypes in many cancers. However, the role and mechanisms of CypA in liver fluke-associated cholangiocarcinoma (CCA are not presently known. In this study, we investigated the expression of CypA in CCA tumor tissues and CCA cell lines as well as regulation mechanisms of CypA in tumor growth using CCA cell lines. Methods CypA expression was determined by real time RT-PCR, Western blot or immunohistochemistry. CypA silence or overexpression in CCA cells was achieved using gene delivery techniques. Cell proliferation was assessed using MTS assay or Ki-67 staining. The effect of silencing CypA on CCA tumor growth was determined in nude mice. The effect of CypA knockdown on ERK1/2 activation was assessed by Western blot. Results CypA was upregulated in 68% of CCA tumor tissues. Silencing CypA significantly suppressed cell proliferation in several CCA cell lines. Likewise, inhibition of CypA peptidyl-prolyl cis-trans isomerase (PPIase activity using cyclosporin A (CsA decreased cell proliferation. In contrast, overexpression of CypA resulted in 30% to 35% increases in proliferation of CCA cell lines. Interestingly, neither silence nor overexpression of CypA affected cell proliferation of a non-tumor human cholangiocyte cell line, MMNK1. Suppression of CypA expression attenuated ERK1/2 activity in CCA M139 cells by using both transient and stable knockdown methods. In the in vivo study, there was a 43% reduction in weight of tumors derived from CypA-silenced CCA cell lines compared with control vector CCA tumors in mice; these tumors with stable CypA silencing showed a reduced cell proliferation. Conclusions CypA is upregulated in majority of CCA patients' tissues and confers a significant growth advantage in CCA cells. Suppression of CypA expression decreases proliferation of CCA cell lines in vitro and reduces tumor growth in the nude mouse model. Inhibition of Cyp

  9. Human leukocyte antigen E contributes to protect tumor cells from lysis by natural killer cells.

    Science.gov (United States)

    Lo Monaco, Elisa; Tremante, Elisa; Cerboni, Cristina; Melucci, Elisa; Sibilio, Leonardo; Zingoni, Alessandra; Nicotra, Maria Rita; Natali, Pier Giorgio; Giacomini, Patrizio

    2011-09-01

    The nonclassic class I human leukocyte antigen E (HLA-E) molecule engages the inhibitory NKG2A receptor on several cytotoxic effectors, including natural killer (NK) cells. Its tissue distribution was claimed to be wider in normal than in neoplastic tissues, and surface HLA-E was undetectable in most tumor cell lines. Herein, these issues were reinvestigated taking advantage of HLA-E-specific antibodies, immunohistochemistry, and biochemical methods detecting intracellular and surface HLA-E regardless of conformation. Contrary to published evidence, HLA-E was detected in a few normal epithelia and in a large fraction (approximately 1/3) of solid tumors, including those derived from HLA-E-negative/low-normal counterparts. Remarkably, HLA-E was detected in 30 of 30 tumor cell lines representative of major lymphoid and nonlymphoid lineages, and in 11 of 11, it was surface-expressed, although in a conformation poorly reactive with commonly used antibodies. Coexpression of HLA-E and HLA class I ligand donors was not required for surface expression but was associated with NKG2A-mediated protection from lysis by the cytotoxic cell line NKL and polyclonal NK cells from healthy donors, as demonstrated by antibody-mediated relief of protection in 10% to 20% of the tested target-effector combinations. NKG2A-mediated protection of additional targets became evident on NK effector blocking with antibodies to activating receptors (DNAM-1, natural cytotoxicity receptors, and NKG2D). Thus, initial evidence that the long-elusive HLA-E molecule is enhanced by malignant transformation and is functional in tumor cells is presented here, although its importance and precise functional role remain to be addressed in the context of a general understanding of the NK ligand-receptor network.

  10. Human Leukocyte Antigen E Contributes to Protect Tumor Cells from Lysis by Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Elisa Lo Monaco

    2011-09-01

    Full Text Available The nonclassic class I human leukocyte antigen E (HLA-E molecule engages the inhibitory NKG2A receptor on several cytotoxic effectors, including natural killer (NK cells. Its tissue distribution was claimed to be wider in normal than in neoplastic tissues, and surface HLA-E was undetectable in most tumor cell lines. Herein, these issues were reinvestigated taking advantage of HLA-E-specific antibodies, immunohistochemistry, and biochemical methods detecting intracellular and surface HLA-E regardless of conformation. Contrary to published evidence, HLA-E was detected in a few normal epithelia and in a large fraction (approximately 1/3 of solid tumors, including those derived from HLA-E-negative/low-normal counterparts. Remarkably, HLA-E was detected in 30 of 30 tumor cell lines representative of major lymphoid and nonlymphoid lineages, and in 11 of 11, it was surface-expressed, although in a conformation poorly reactive with commonly used antibodies. Coexpression of HLA-E and HLA class I ligand donors was not required for surface expression but was associated with NKG2A-mediated protection from lysis by the cytotoxic cell line NKL and polyclonal NK cells from healthy donors, as demonstrated by antibody-mediated relief of protection in 10% to 20% of the tested target-effector combinations. NKG2A-mediated protection of additional targets became evident on NK effector blocking with antibodies to activating receptors (DNAM-1, natural cytotoxicity receptors, and NKG2D. Thus, initial evidence that the long-elusive HLA-E molecule is enhanced by malignant transformation and is functional in tumor cells is presented here, although its importance and precise functional role remain to be addressed in the context of a general understanding of the NK ligand-receptor network.

  11. Human Leukocyte Antigen E Contributes to Protect Tumor Cells from Lysis by Natural Killer Cells12

    Science.gov (United States)

    Monaco, Elisa Lo; Tremante, Elisa; Cerboni, Cristina; Melucci, Elisa; Sibilio, Leonardo; Zingoni, Alessandra; Nicotra, Maria Rita; Natali, Pier Giorgio; Giacomini, Patrizio

    2011-01-01

    The nonclassic class I human leukocyte antigen E (HLA-E) molecule engages the inhibitory NKG2A receptor on several cytotoxic effectors, including natural killer (NK) cells. Its tissue distribution was claimed to be wider in normal than in neoplastic tissues, and surface HLA-E was undetectable in most tumor cell lines. Herein, these issues were reinvestigated taking advantage of HLA-E-specific antibodies, immunohistochemistry, and biochemical methods detecting intracellular and surface HLA-E regardless of conformation. Contrary to published evidence, HLA-E was detected in a few normal epithelia and in a large fraction (approximately 1/3) of solid tumors, including those derived from HLA-E-negative/low-normal counterparts. Remarkably, HLA-E was detected in 30 of 30 tumor cell lines representative of major lymphoid and nonlymphoid lineages, and in 11 of 11, it was surface-expressed, although in a conformation poorly reactive with commonly used antibodies. Coexpression of HLA-E and HLA class I ligand donors was not required for surface expression but was associated with NKG2A-mediated protection from lysis by the cytotoxic cell line NKL and polyclonal NK cells from healthy donors, as demonstrated by antibody-mediated relief of protection in 10% to 20% of the tested target-effector combinations. NKG2A-mediated protection of additional targets became evident on NK effector blocking with antibodies to activating receptors (DNAM-1, natural cytotoxicity receptors, and NKG2D). Thus, initial evidence that the long-elusive HLA-E molecule is enhanced by malignant transformation and is functional in tumor cells is presented here, although its importance and precise functional role remain to be addressed in the context of a general understanding of the NK ligand-receptor network. PMID:21969815

  12. HAMLET binding to α-actinin facilitates tumor cell detachment.

    Science.gov (United States)

    Trulsson, Maria; Yu, Hao; Gisselsson, Lennart; Chao, Yinxia; Urbano, Alexander; Aits, Sonja; Mossberg, Ann-Kristin; Svanborg, Catharina

    2011-03-08

    Cell adhesion is tightly regulated by specific molecular interactions and detachment from the extracellular matrix modifies proliferation and survival. HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a protein-lipid complex with tumoricidal activity that also triggers tumor cell detachment in vitro and in vivo, suggesting that molecular interactions defining detachment are perturbed in cancer cells. To identify such interactions, cell membrane extracts were used in Far-western blots and HAMLET was shown to bind α-actinins; major F-actin cross-linking proteins and focal adhesion constituents. Synthetic peptide mapping revealed that HAMLET binds to the N-terminal actin-binding domain as well as the integrin-binding domain of α-actinin-4. By co-immunoprecipitation of extracts from HAMLET-treated cancer cells, an interaction with α-actinin-1 and -4 was observed. Inhibition of α-actinin-1 and α-actinin-4 expression by siRNA transfection increased detachment, while α-actinin-4-GFP over-expression significantly delayed rounding up and detachment of tumor cells in response to HAMLET. In response to HAMLET, adherent tumor cells rounded up and detached, suggesting a loss of the actin cytoskeletal organization. These changes were accompanied by a reduction in β1 integrin staining and a decrease in FAK and ERK1/2 phosphorylation, consistent with a disruption of integrin-dependent cell adhesion signaling. Detachment per se did not increase cell death during the 22 hour experimental period, regardless of α-actinin-4 and α-actinin-1 expression levels but adherent cells with low α-actinin levels showed increased death in response to HAMLET. The results suggest that the interaction between HAMLET and α-actinins promotes tumor cell detachment. As α-actinins also associate with signaling molecules, cytoplasmic domains of transmembrane receptors and ion channels, additional α-actinin-dependent mechanisms are discussed.

  13. Fine-needle aspiration cytology of ovarian steroid cell tumor: A rare case report

    Directory of Open Access Journals (Sweden)

    Nidhi Agrawal

    2015-01-01

    Full Text Available Steroid cell tumors (SCTs of the ovary are a rare subgroup of sex cord tumors that account for less than 0.1% of all ovarian tumors. These tumors can produce steroids, especially testosterone, which produces symptoms such as hirsutism, amenorrhea/oligomenorrhea, and male patterned voice. For evaluation of the androgen excess, testosterone and dehydroepiandrosterone sulfate (DHEA-S are the first laboratory tests to be measured. Abdominal ultrasound and magnetic resonance imaging (MRI are useful radiologic imaging techniques. Although SCTs are generally benign, the risk of malignant transformation is always present. Surgical excision of tumor is the most important and hallmark treatment. The present case signifies the early preoperative diagnosis of a virilizing SCT, based on cytological features and its careful correlation with clinicopathological and radiological findings.

  14. SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma.

    Science.gov (United States)

    Son, Myung Jin; Woolard, Kevin; Nam, Do-Hyun; Lee, Jeongwu; Fine, Howard A

    2009-05-08

    CD133+ populations of human glioblastoma multiforme (GBM) cells are reportedly enriched for tumor stem cells (TSCs) or tumor-initiating cells (TICs). Approximately 40% of freshly isolated GBM specimens, however, do not contain CD133+ tumor cells, raising the possibility that CD133 may not be a universal enrichment marker for GBM TSCs/TICs. Here we demonstrate that stage-specific embryonic antigen 1(SSEA-1/LeX)+ GBM cells fulfill the functional criteria for TSC/TIC, since (1) SSEA-1+ cells are highly tumorigenic in vivo, unlike SSEA-1- cells; (2) SSEA-1+ cells can give rise to both SSEA-1+ and SSEA-1- cells, thereby establishing a cellular hierarchy; and (3) SSEA-1+ cells have self-renewal and multilineage differentiation potentials. A distinct subpopulation of SSEA-1+ cells was present in all but one of the primary GBMs examined (n = 24), and most CD133+ tumor cells were also SSEA-1+, suggesting that SSEA-1 may be a general TSC/TIC enrichment marker in human GBMs.

  15. T cells activate the tumor necrosis factor-alpha system during hemodialysis, resulting in tachyphylaxis

    NARCIS (Netherlands)

    van Riemsdijk, I C; Baan, C C; Loonen, E H; Knoop, C J; Navarro Betonico, G; Niesters, H G; Zietse, R; Weimar, W

    2001-01-01

    BACKGROUND: The immunosuppressive state of hemodialysis (HD) patients is accompanied by activation of antigen-presenting cell-derived cytokines, for example, tumor necrosis factor-alpha (TNF-alpha), which are required for T-cell activation. To test whether an activated TNF-alpha system results in im

  16. UNIPARENTAL ORIGIN OF I(12P) IN HUMAN GERM-CELL TUMORS

    NARCIS (Netherlands)

    SINKE, RJ; SUIJKERBUIJK, RF; DEJONG, B; OOSTERHUIS, JW; VANKESSEL, AG

    1993-01-01

    We present molecular data to demonstrate that the isochromosome 12p, specific for human germ cell tumors (GCTs), is of uniparental origin. Eight GCT-derived cell lines, containing one or more copies of i(12p) and/or other 12p anomalies, were analyzed with different 12p-derived polymorphic markers. T

  17. Wilms’ Tumor Blastemal Stem Cells Dedifferentiate to Propagate the Tumor Bulk

    Directory of Open Access Journals (Sweden)

    Rachel Shukrun

    2014-07-01

    Full Text Available An open question remains in cancer stem cell (CSC biology whether CSCs are by definition at the top of the differentiation hierarchy of the tumor. Wilms’ tumor (WT, composed of blastema and differentiated renal elements resembling the nephrogenic zone of the developing kidney, is a valuable model for studying this question because early kidney differentiation is well characterized. WT neural cell adhesion molecule 1-positive (NCAM1+ aldehyde dehydrogenase 1-positive (ALDH1+ CSCs have been recently isolated and shown to harbor early renal progenitor traits. Herein, by generating pure blastema WT xenografts, composed solely of cells expressing the renal developmental markers SIX2 and NCAM1, we surprisingly show that sorted ALDH1+ WT CSCs do not correspond to earliest renal stem cells. Rather, gene expression and proteomic comparative analyses disclose a cell type skewed more toward epithelial differentiation than the bulk of the blastema. Thus, WT CSCs are likely to dedifferentiate to propagate WT blastema.

  18. Characterization of tumor cells and stem cells by differential nuclear methylation imaging

    Science.gov (United States)

    Tajbakhsh, Jian; Wawrowsky, Kolja A.; Gertych, Arkadiusz; Bar-Nur, Ori; Vishnevsky, Eugene; Lindsley, Erik H.; Farkas, Daniel L.

    2008-02-01

    DNA methylation plays a key role in cellular differentiation. Aberrant global methylation patterns are associated with several cancer types, as a result of changes in long-term activation status of up to 50% of genes, including oncogenes and tumor-suppressor genes, which are regulated by methylation and demethylation of promoter region CpG dinucleotides (CpG islands). Furthermore, DNA methylation also occurs in nonisland CpG sites (> 95% of the genome), present once per 80 dinucleotides on average. Nuclear DNA methylation increases during the course of cellular differentiation while cancer cells usually show a net loss in methylation. Given the large dynamic range in DNA methylation load, the methylation pattern of a cell can provide a valuable distinction as to its status during differentiation versus the disease state. By applying immunofluorescence, confocal microscopy and 3D image analysis we assessed the potential of differential nuclear distribution of methylated DNA to be utilized as a biomarker to characterize cells during development and when diseased. There are two major fields that may immediately benefit from this development: (1) the search for factors that contribute to pluripotency and cell fate in human embryonic stem cell expansion and differentiation, and (2) the characterization of tumor cells with regard to their heterogeneity in molecular composition and behavior. We performed topological analysis of the distribution of methylated CpG-sites (MeC) versus heterochromatin. This innovative approach revealed significant differences in colocalization patterns of MeC and heterochromatin-derived signals between undifferentiated and differentiated human embryonic stem cells, as well as untreated AtT20 mouse pituitary tumor cells compared to a subpopulation of these cells treated with 5-azacytidine for 48 hours.

  19. Malignant chondroblastoma presenting as a recurrent pelvic tumor with DNA aneuploidy and p53 mutation as supportive evidence of malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Ostrowski, M.L. [Department of Pathology and Laboratory Medicine, Baylor College of Medicine, The Methodist Hospital and Texas Children' s Hospital, Houston, Texas (United States); Department of Pathology and Laboratory Medicine, Houston, TX (United States). Methodist Hospital; Johnson, M.E. [Department of Orthopedic Surgery, Baylor College of Medicine, The Methodist Hospital and Texas Children' s Hospital, Houston, Texas (United States); Truong, L.D.; Hicks, M.J.; Spjut, H.J. [Department of Pathology and Laboratory Medicine, Baylor College of Medicine, The Methodist Hospital and Texas Children' s Hospital, Houston, Texas (United States); Smith, F.E. [Department of Oncology, Baylor College of Medicine, The Methodist Hospital and Texas Children' s Hospital, Houston, Texas (United States)

    1999-11-01

    We report a rare case of malignant chondroblastoma, which presented in a 47-year-old man as a recurrent tumor, 18 years following wide excision of a typical pelvic chondroblastoma. Radiologic studies of the recurrent tumor showed a large, lytic, destructive lesion of the right pelvic bones and femur, with a pathologic fracture of the latter, a large pelvic soft tissue mass, and multiple pulmonary metastases. Biopsy tissue showed typical features of chondroblastoma, but also increased nuclear atypia, hyperchromasia, and pleomorphism, compared to the original tumor, and, most significantly, abnormal mitotic figures. Immunohistochemical studies of the recurrent tumor revealed p53 mutation and extensive proliferative activity, and flow cytometric studies showed DNA aneuploidy, none of which was present in the original tumor. The patient received chemotherapy and radiation, but died of disease eight months after presentation. We also review chondroblastoma in general, to assign this unusual lesion to a tumor subtype. (orig.)

  20. Cdh11 acts as a tumor suppressor in a murine retinoblastoma model by facilitating tumor cell death.

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    Mellone N Marchong

    2010-04-01

    Full Text Available CDH11 gene copy number and expression are frequently lost in human retinoblastomas and in retinoblastomas arising in TAg-RB mice. To determine the effect of Cdh11 loss in tumorigenesis, we crossed Cdh11 null mice with TAg-RB mice. Loss of Cdh11 had no gross morphological effect on the developing retina of Cdh11 knockout mice, but led to larger retinal volumes in mice crossed with TAg-RB mice (p = 0.01. Mice null for Cdh11 presented with fewer TAg-positive cells at postnatal day 8 (PND8 (p = 0.01 and had fewer multifocal tumors at PND28 (p = 0.016, compared to mice with normal Cdh11 alleles. However, tumor growth was faster in Cdh11-null mice between PND8 and PND84 (p = 0.003. In tumors of Cdh11-null mice, cell death was decreased 5- to 10-fold (p<0.03 for all markers, while proliferation in vivo remained unaffected (p = 0.121. Activated caspase-3 was significantly decreased and beta-catenin expression increased in Cdh11 knockdown experiments in vitro. These data suggest that Cdh11 displays tumor suppressor properties in vivo and in vitro in murine retinoblastoma through promotion of cell death.

  1. Prowling wolves in sheep's clothing: the search for tumor stem cells.

    Science.gov (United States)

    Alkatout, Ibrahim; Kabelitz, Dieter; Kalthoff, Holger; Tiwari, Sanjay

    2008-07-01

    The importance of a subset of cells which have 'stem like' characteristics and are capable of tumor initiation has been reported for a range of tumors. Isolation of these tumor-initiating cells (TICs) has largely been based on differential cell surface protein expression. However, there is still much debate on the functional significance of these markers in initiating tumors, as many properties of tumor initiation are modified by cell-cell interactions. In particular, the relationship between TICs and their microenvironment is poorly understood but has therapeutic implications, as the microenvironment can maintain tumor cells in a prolonged period of quiescence. However, a major limitation in advancing our understanding of the crosstalk between TICs and their microenvironment is the lack of sensitive techniques which allow the in vivo tracking and monitoring of TICs. Application of new in vivo cellular and molecular imaging technologies holds much promise in uncovering the mysteries of TIC behavior at the three-dimensional level. This review will describe recent advances in our understanding of the TIC concept and how the application of in vivo imaging techniques can advance our understanding of the biological fate of TICs. A supplementary resource guide describing TICs from different malignancies is also presented.

  2. Molecular aspects of tumor cell migration and invasion

    Directory of Open Access Journals (Sweden)

    Giuseppina Bozzuto

    2010-03-01

    Full Text Available Cell migration and invasion are crucial steps in many physiological events. However, they are also implicated in the physiopathology of many diseases, such as cancer. To spread through the tissues, tumor cells use mechanisms that involve several molecular actors: adhesion receptor families, receptor tyrosine kinases, cytoskeleton proteins, adapter and signalling proteins interplay in a complex scenario. The balance of cellular signals for proliferation and survival responses also regulates migratory behaviours of tumor cells. To complicate the scene of crime drug resistance players can interfere thus worsening this delicate situation. The complete understanding of this molecular jungle is an impossible mission: some molecular aspects are reviewed in this paper.

  3. Apoptosis induced by norcantharidin in human tumor cells

    Institute of Scientific and Technical Information of China (English)

    Zhen Xiao Sun; Qing Wen Ma; Tian De Zhao; Yu Lin Wei; Guang Sheng Wang; Jia Shi Li

    2000-01-01

    @@INTRODUCTION The antitumor activity of norcantharidin (NCTD),the demethylated analogue of cantharidin, was studied in the early 1980s in China. NCTD has no side effects on urinary organs which cantharidin has shown and is easier to synthesize, and it can inhibit the proliferation of several tumor cell lines as well as transplanted tumors. Clinical trials with NCTD as a monotherapeutic agent indicated that NCTD had beneficial effects in patients with different kinds of digestive tract cancers, such as primary hepatoma,carcinomas of esophagus and gastric cancer, but no depressive effect on bone marrow cells. NCTD can increase the white blood cell count by stimulating the bone marrow and has some antagonistic effect against leukopenia caused by other agents. The exact cellular and molecular mechanisms of NCTD on tumor cells have not yet been elucidated to date[1-3].

  4. Tumor metabolism: cancer cells give and take lactate.

    Science.gov (United States)

    Semenza, Gregg L

    2008-12-01

    Tumors contain well-oxygenated (aerobic) and poorly oxygenated (hypoxic) regions, which were thought to utilize glucose for oxidative and glycolytic metabolism, respectively. In this issue of the JCI, Sonveaux et al. show that human cancer cells cultured under hypoxic conditions convert glucose to lactate and extrude it, whereas aerobic cancer cells take up lactate via monocarboxylate transporter 1 (MCT1) and utilize it for oxidative phosphorylation (see the related article beginning on page 3930). When MCT1 is inhibited, aerobic cancer cells take up glucose rather than lactate, and hypoxic cancer cells die due to glucose deprivation. Treatment of tumor-bearing mice with an inhibitor of MCT1 retarded tumor growth. MCT1 expression was detected exclusively in nonhypoxic regions of human cancer biopsy samples, and in combination, these data suggest that MCT1 inhibition holds potential as a novel cancer therapy.

  5. Adaptive resistance to immunotherapy directed against p53 can be overcome by global expression of tumor antigens in dendritic cells

    Directory of Open Access Journals (Sweden)

    Matjaz eHumar

    2014-10-01

    Full Text Available Immunotherapy of cancer utilizes dendritic cells (DC for antigen presentation and the induction of tumor-specific immune responses. However, the therapeutic induction of anti-tumor immunity is limited by tumor escape mechanisms. In this study immortalized dendritic D2SC/1 cells were transduced with a mutated version of the p53 tumor suppressor gene, p53M234I or p53C132F/E164G, which are overexpressed in MethA fibrosarcoma tumor cells. In addition, D2SC/1 cells were fused with MethA tumor cells to generate a vaccine that potentially expresses a large repertoire of tumor antigens. Cellular vaccines were transplanted onto Balb/c mice and MethA tumor growth and anti-tumor immune responses were examined in vaccinated animals. D2SC/1-p53M234I and D2SC/1-p53C132F/E168G cells induced strong therapeutic and protective MethA tumor immunity upon transplantation in Balb/c mice. However, in a fraction of immunized mice MethA tumor growth resumed after an extended latency period. Analysis of these tumors indicated loss of p53 expression. Mice, pre-treated with fusion hybrids generated from D2SC/1 and MethA tumor cells, suppressed MethA tumor growth and averted adaptive immune escape. Polyclonal B-cell responses directed against various MethA tumor proteins could be detected in the sera of D2SC/1-MethA inoculated mice. Athymic nude mice and Balb/c mice depleted of CD4+ or CD8+ T-cells were not protected against MethA tumor cell growth after immunization with D2SC/1-MethA hybrids. Our results highlight a potential drawback of cancer immunotherapy by demonstrating that the induction of a specific anti-tumor response favours the acquisition of tumor phenotypes promoting immune evasion. In contrast, the application of DC/tumor cell fusion hybrids prevents adaptive immune escape by a T-cell dependent mechanism and provides a simple strategy for personalized anti-cancer treatment without the need of selectively priming the host immune system.

  6. Dendritic cells and their role in tumor immunosurveillance

    NARCIS (Netherlands)

    Strioga, M.M.; Schijns, V.E.J.C.; Powell, D.J.; Pasukoniene, V.; Dobrovolskiene, N.T.; Michalek, J.

    2013-01-01

    Dendritic cells (DCs) comprise a heterogeneous population of cells that play a key role in initiating, directing and regulating adaptive immune responses, including those critically involved in tumor immunosurveillance. As a riposte to the central role of DCs in the generation of antitumor immune re

  7. Dynamic Fluctuation of Circulating Tumor Cells during Cancer Progression

    Directory of Open Access Journals (Sweden)

    Mazen A. Juratli

    2014-01-01

    Full Text Available Circulating tumor cells (CTCs are a promising diagnostic and prognostic biomarker for metastatic tumors. We demonstrate that CTCs’ diagnostic value might be increased through real-time monitoring of CTC dynamics. Using preclinical animal models of breast cancer and melanoma and in vivo flow cytometry with photoacoustic and fluorescence detection schematics, we show that CTC count does not always correlate with the primary tumor size. Individual analysis elucidated many cases where the highest level of CTCs was detected before the primary tumor starts progressing. This phenomenon could be attributed to