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Sample records for affecting primary tumor

  1. Genes affected by mouse mammary tumor virus (MMTV) proviral insertions in mouse mammary tumors are deregulated or mutated in primary human mammary tumors

    PubMed Central

    Callahan, Robert; Mudunuri, Uma; Bargo, Sharon; Raafat, Ahmed; McCurdy, David; Boulanger, Corinne; Lowther, William; Stephens, Robert; Luke, Brian T.; Stewart, Claudia; Wu, Xiaolin; Munroe, David; Smith, Gilbert H.

    2012-01-01

    The accumulation of mutations is a contributing factor in the initiation of premalignant mammary lesions and their progression to malignancy and metastasis. We have used a mouse model in which the carcinogen is the mouse mammary tumor virus (MMTV) which induces clonal premalignant mammary lesions and malignant mammary tumors by insertional mutagenesis. Identification of the genes and signaling pathways affected in MMTV-induced mouse mammary lesions provides a rationale for determining whether genetic alteration of the human orthologues of these genes/pathways may contribute to human breast carcinogenesis. A high-throughput platform for inverse PCR to identify MMTV-host junction fragments and their nucleotide sequences in a large panel of MMTV-induced lesions was developed. Validation of the genes affected by MMTV-insertion was carried out by microarray analysis. Common integration site (CIS) means that the gene was altered by an MMTV proviral insertion in at least two independent lesions arising in different hosts. Three of the new genes identified as CIS for MMTV were assayed for their capability to confer on HC11 mouse mammary epithelial cells the ability for invasion, anchorage independent growth and tumor development in nude mice. Analysis of MMTV induced mammary premalignant hyperplastic outgrowth (HOG) lines and mammary tumors led to the identification of CIS restricted to 35 loci. Within these loci members of the Wnt, Fgf and Rspo gene families plus two linked genes (Npm3 and Ddn) were frequently activated in tumors induced by MMTV. A second group of 15 CIS occur at a low frequency (2-5 observations) in mammary HOGs or tumors. In this latter group the expression of either Phf19 or Sdc2 was shown to increase HC11 cells invasion capability. Foxl1 expression conferred on HC11 cells the capability for anchorage-independent colony formation in soft agar and tumor development in nude mice. The published transcriptome and nucleotide sequence analysis of gene

  2. Are preoperative sex-related differences of affective symptoms in primary brain tumor patients associated with postoperative histopathological grading?

    PubMed

    Richter, Andre; Jenewein, J; Krayenbühl, N; Woernle, C; Bellut, D

    2016-01-01

    Our objective was to explore the impact of the histopathological tumor type on affective symptoms before surgery among male and female patients with supratentorial primary brain tumors. A total of 44 adult patients were included in the study. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory. Additionally, clinical interviews, including the Hamilton Depression Rating Scale (HDRS), were conducted. The general function of patients was measured with the Karnofsky Performance Status scale (KPS). All measures were obtained before surgery and therefore before the final histopathological diagnosis. All self-rating questionnaires but not the HDRS, showed significantly higher scores in female patients. The functional status assessed with the KPS was lower in female patients and correlated to the somatic part of the BDI. We further found a tendency for higher HDRS scores in male patients with a WHO grade 4 tumor stage compared to female patients. This finding was supported by positive correlations between HDRS scores and WHO grade in male and negative correlations between HDRS scores and WHO grade in female patients. In conclusion the preoperative evaluation of affective symptoms with self-rating questionnaires in patients with brain tumors may be invalidated by the patient’s functional status. Depression should be explored with clinical interviews in these patients. Sex differences of affective symptoms in this patient group may also be related to the malignancy of the tumor, but further studies are needed to disentangle this relationship. PMID:26468140

  3. Are preoperative sex-related differences of affective symptoms in primary brain tumor patients associated with postoperative histopathological grading?

    PubMed

    Richter, Andre; Jenewein, J; Krayenbühl, N; Woernle, C; Bellut, D

    2016-01-01

    Our objective was to explore the impact of the histopathological tumor type on affective symptoms before surgery among male and female patients with supratentorial primary brain tumors. A total of 44 adult patients were included in the study. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory. Additionally, clinical interviews, including the Hamilton Depression Rating Scale (HDRS), were conducted. The general function of patients was measured with the Karnofsky Performance Status scale (KPS). All measures were obtained before surgery and therefore before the final histopathological diagnosis. All self-rating questionnaires but not the HDRS, showed significantly higher scores in female patients. The functional status assessed with the KPS was lower in female patients and correlated to the somatic part of the BDI. We further found a tendency for higher HDRS scores in male patients with a WHO grade 4 tumor stage compared to female patients. This finding was supported by positive correlations between HDRS scores and WHO grade in male and negative correlations between HDRS scores and WHO grade in female patients. In conclusion the preoperative evaluation of affective symptoms with self-rating questionnaires in patients with brain tumors may be invalidated by the patient’s functional status. Depression should be explored with clinical interviews in these patients. Sex differences of affective symptoms in this patient group may also be related to the malignancy of the tumor, but further studies are needed to disentangle this relationship.

  4. Brain tumor - primary - adults

    MedlinePlus

    ... tumor, relieve symptoms, and improve brain function or comfort. Surgery is often needed for most primary brain ... and pressure Anticonvulsants to reduce seizures Pain medicines Comfort measures, safety measures, physical therapy, and occupational therapy ...

  5. Primary tumors of the patella.

    PubMed

    Song, Mingzhi; Zhang, Zhen; Wu, Yuxuan; Ma, Kai; Lu, Ming

    2015-01-01

    The patella is an uncommon location for cancerous occurrence and development. The majority of tumors of the patella are benign, with a significant incidence of giant cell tumors and chondroblastoma. With the development of modern diagnostic technologies, there appear however many other histological types which raise challenges of diagnosis and treatment. In this article, we review the reported histological types of primary patellar tumors. Specifically, epidemiology, symptomatology, imageology, histopathology, and treatment options for these histological lesions will be discussed, respectively. As there is an increasing focus on the diagnosis and the treatment of these lesions, the availability of the integrated information about primary patellar tumors becomes more significant. PMID:25906772

  6. Primary Cardiac Solitary Fibrous Tumors

    PubMed Central

    2015-01-01

    Primary cardiac solitary fibrous tumors were reviewed. They are classified as pericardial tumors. Their incidences are very rare. Only 16 cases were reported in the literature. Basically, surgical treatments are performed. Their prognoses are generally good, although malignant cases are also reported. PMID:26156195

  7. Primary tracheobronchial tumors in children.

    PubMed

    Varela, Patricio; Pio, Luca; Torre, Michele

    2016-06-01

    Primary tracheobronchial tumors are rare lesions that can be benign or malignant, with different location along the airway tree. Symptoms may include wheezing, chronic pneumonia, asthma, chest pain, recurrent cough, atelectasis, haemoptysis, and weight loss. Due to the heterogeneity of symptoms, diagnosis can be difficult and the airway involvement can lead progressively to a bronchial or tracheal obstruction. Due to the rarity of primary tracheobronchial tumors in children, there are not any oncological guidelines on pre-operative work-up, treatment, and follow-up. Only few reports and multicentric studies are reported. In most cases, surgical resection seems to be the treatment of choice. Brachytherapy, endoscopic treatment, and chemotherapy are rarely described. In this article we present an overview on these rare tumors, including pathological aspects, clinical presentation, imaging assessment, and endoscopic or open surgical treatments. We discuss different surgical approaches, according with tumor location. PMID:27301601

  8. How does cancer cell metabolism affect tumor migration and invasion?

    PubMed

    Han, Tianyu; Kang, De; Ji, Daokun; Wang, Xiaoyu; Zhan, Weihua; Fu, Minggui; Xin, Hong-Bo; Wang, Jian-Bin

    2013-01-01

    Cancer metastasis is the major cause of cancer-associated death. Accordingly, identification of the regulatory mechanisms that control whether or not tumor cells become "directed walkers" is a crucial issue of cancer research. The deregulation of cell migration during cancer progression determines the capacity of tumor cells to escape from the primary tumors and invade adjacent tissues to finally form metastases. The ability to switch from a predominantly oxidative metabolism to glycolysis and the production of lactate even when oxygen is plentiful is a key characteristic of cancer cells. This metabolic switch, known as the Warburg effect, was first described in 1920s, and affected not only tumor cell growth but also tumor cell migration. In this review, we will focus on the recent studies on how cancer cell metabolism affects tumor cell migration and invasion. Understanding the new aspects on molecular mechanisms and signaling pathways controlling tumor cell migration is critical for development of therapeutic strategies for cancer patients.

  9. Primary bone tumors of the spine.

    PubMed

    Cañete, A Navas; Bloem, H L; Kroon, H M

    2016-04-01

    Primary bone tumors of the spine are less common than metastases or multiple myeloma. Based on the patient's age and the radiologic pattern and topography of the tumor, a very approximate differential diagnosis can be established for an osseous vertebral lesion. This article shows the radiologic manifestations of the principal primary bone tumors of the spine from a practical point of view, based on our personal experience and a review of the literature. If bone metastases, multiple myeloma, lymphomas, hemangiomas, and enostoses are excluded, only eight types of tumors account for 80% of all vertebral tumors. These are chordomas, osteoblastomas, chondrosarcomas, giant-cell tumors, osteoid osteomas, Ewing's sarcomas, osteosarcomas, and aneurysmal bone cysts. PMID:26917429

  10. Primary bone tumors of the spine.

    PubMed

    Cañete, A Navas; Bloem, H L; Kroon, H M

    2016-04-01

    Primary bone tumors of the spine are less common than metastases or multiple myeloma. Based on the patient's age and the radiologic pattern and topography of the tumor, a very approximate differential diagnosis can be established for an osseous vertebral lesion. This article shows the radiologic manifestations of the principal primary bone tumors of the spine from a practical point of view, based on our personal experience and a review of the literature. If bone metastases, multiple myeloma, lymphomas, hemangiomas, and enostoses are excluded, only eight types of tumors account for 80% of all vertebral tumors. These are chordomas, osteoblastomas, chondrosarcomas, giant-cell tumors, osteoid osteomas, Ewing's sarcomas, osteosarcomas, and aneurysmal bone cysts.

  11. Primary solitary fibrous tumor of the retroperitoneum.

    PubMed

    Charhi, Hind; Bernoussi, Zakiya; Haddan, Azzouz; Mesmoudi, Siham; Elktaibi, Abderrahim; Mansouri, Fatima; Elktaibi, Rachid; Lahlou, Khalid; Jahid, Ahmed; Mahassini, Najat

    2011-09-28

    Solitary fibrous tumor is an uncommon neoplasm affecting adults and typically located in the pleura and can also occur in a large number of other extra thoracic sites. We present the case of a solitary fibrous tumor (SFT) of the retroperitoneum and describe their histopathological and immunohistochemical features. The identification of SFT in the retroperitoneum is of importance because its clinico-pathological behaviour is still unclear. The pathologist plays a fundamental role in establishing both the positive and differential diagnosis.

  12. Primary hepatic neuroendocrine tumor: A case report

    PubMed Central

    MORISHITA, ASAHIRO; YONEYAMA, HIROHITO; NOMURA, TAKAKO; SAKAMOTO, TEPPEI; FUJITA, KOJI; TANI, JOJI; MIYOSHI, HISAAKI; HABA, REIJI; MASAKI, TSUTOMU

    2016-01-01

    We herein present a case of an 87-year-old patient with multiple liver tumors identified on abdominal ultrasound. The assessment performed on admission included physical examination, computed tomography (CT) during hepatic angiography and CT during arterial portography. The examination revealed contrast enhancement of a proportion of the liver tumors (20 mm maximum diameter) during the arterial phase and mild contrast washout of those tumors during the delayed phase. On contrast-enhanced magnetic resonance imaging using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid, certain liver tumors exhibited contrast enhancement during the early phase and contrast washout during the hepatocyte phase in both lobes. By contrast, no lesions were identified during positron emission tomography imaging of the liver. A liver biopsy was performed and immunohistochemical staining revealed enhanced expression of cytokeratin AE1/AE3, synaptophysin, chromogranin A and CD56 and no expression of hepatocyte antigen or CΚ7. The mindbomb E3 ubiquitin protein ligase-1 index was ~2% in most of the tumor. The liver tumors were finally diagnosed as multiple intrahepatic metastases from a primary hepatic neuroendocrine tumor (PHNET). The patient underwent transarterial chemoembolisation with a combination of miriplatin (84 mg) mixed with gelatin sponge particles and lipiodol. To the best of our knowledge, this is the first report of PHNET in an patient aged >85 years. PMID:27284429

  13. Primary renal carcinoid tumor: A radiologic review

    PubMed Central

    Lamb, Leslie; Shaban, Wael

    2015-01-01

    Carcinoid tumor is the classic famous anonym of neuroendocrine neoplasms. Primary renal carcinoid tumors are extremely rare, first described by Resnick and colleagues in 1966, with fewer than a total of 100 cases reported in the literature. Thus, given the paucity of cases, the clinical and histological behavior is not well understood, impairing the ability to predict prognosis. Computed tomography and (occasionally) octreotide studies are used in the diagnosis and followup of these rare entites. A review of 85 cases in the literature shows that no distinctive imaging features differentiate them from other primary renal masses. The lesions tend to demonstrate a hypodense appearance and do not usually enhance in the arterial phases, but can occasionally calcify. Octreotide scans do not seem to help in the diagnosis; however, they are more commonly used in the postoperative followup. In addition, we report a new case of primary renal carcinoid in a horseshoe kidney. PMID:27186242

  14. Primary Hepatic Carcinoid Tumor with Poor Outcome.

    PubMed

    Parkash, Om; Ayub, Adil; Naeem, Buria; Najam, Sehrish; Ahmed, Zubair; Jafri, Wasim; Hamid, Saeed

    2016-03-01

    Primary Hepatic Carcinoid Tumor (PHCT) represents an extremely rare clinical entity with only a few cases reported to date. These tumors are rarely associated with metastasis and surgical resection is usually curative. Herein, we report two cases of PHCT associated with poor outcomes due to late diagnosis. Both cases presented late with non-specific symptoms. One patient presented after a 2-week history of symptoms and the second case had a longstanding two years symptomatic interval during which he remained undiagnosed and not properly worked up. Both these cases were diagnosed with hepatic carcinoid tumor, which originates from neuroendocrine cells. Case 1 opted for palliative care and expired in one month’s time. Surgical resection was advised to the second case, but he left against medical advice. PMID:26975959

  15. Primary Hepatic Carcinoid Tumor with Poor Outcome.

    PubMed

    Parkash, Om; Ayub, Adil; Naeem, Buria; Najam, Sehrish; Ahmed, Zubair; Jafri, Wasim; Hamid, Saeed

    2016-03-01

    Primary Hepatic Carcinoid Tumor (PHCT) represents an extremely rare clinical entity with only a few cases reported to date. These tumors are rarely associated with metastasis and surgical resection is usually curative. Herein, we report two cases of PHCT associated with poor outcomes due to late diagnosis. Both cases presented late with non-specific symptoms. One patient presented after a 2-week history of symptoms and the second case had a longstanding two years symptomatic interval during which he remained undiagnosed and not properly worked up. Both these cases were diagnosed with hepatic carcinoid tumor, which originates from neuroendocrine cells. Case 1 opted for palliative care and expired in one month’s time. Surgical resection was advised to the second case, but he left against medical advice.

  16. CT evaluation of primary benign retroperitoneal tumor.

    PubMed

    Hayasaka, K; Yamada, T; Saitoh, Y; Yoshikawa, D; Aburano, T; Hashimoto, H; Yachiku, S

    1994-01-01

    We studied CT patterns in 21 cases of primary benign retroperitoneal tumor including teratoma in nine cases, schwannoma in six, leiomyoma in three, lipoma in one, lymphangioma in one, and neurofibroma in one. The tumors were analyzed for size, internal homogeneity, CT density, calcification, border with neighboring organs, and contrast enhancement (CE). The mean diameter of the tumors was 10.2 (+/- 4.8) cm. Internal homogeneous distribution was observed in 33%, calcification in 43%, and well-defined border in 86%. The CT density and calcification were compared according to histology, and the results were as follows: teratoma showed fat density in 78%, water density in 100%, and calcification in 89%; schwannoma showed water density in 100% and septal CE in 33%; leiomyoma showed soft tissue density in 100%, CE in 100%, and water density in 33%; lipoma showed fat density and calcification; and lymphangioma and neurofibroma showed water density. Internal homogeneity, fat density, cyst formation, and calcification are considered to be important predictors of primary benign retroperitoneal tumor on CT.

  17. Primary malignant chest wall tumors: analysis of 40 patients

    PubMed Central

    2014-01-01

    Background Primary chest wall tumors originate from different constructions of thoracic wall. We report our multidisciplinary experience on primary thoracic tumor resection and thoracic reconstruction, the need to additional therapy and evaluating prognostic factors affecting survival. Methods We performed a retrospective review of our prospectively maintained database of 40 patients treated for malignant primary chest wall tumor from 1989 to 2009. Patients were evaluated in terms of age, sex, clinical presentation, type of imaging, tissue diagnosis methods, pathology, surgical technique, early complications, hospital mortality, prevalence of recurrence and distant metastases, additional treatment, 3 years survival and factors affecting survival. Results Male/Female (F/M) = 1, with median age of 43.72 years. Mass was the most common symptoms and the soft tissue sarcoma was the most common pathology. Resection without reconstruction was performed in 5 patients and Thirty-five patients (87.5%) had extensive resection and reconstruction with rotatory muscular flap, prosthetic mesh and/or cement. Overall, 12.5% (5/40) of patients received neoadjuvant therapy and 75% (30/40) of patients were treated with adjuvant therapy. The 3-year survival rate was 65%. Recurrences occurred in 24 patients (60%), 14 developed local recurrences, and 10 developed distant metastases. The primary treatment modality for both local and distant recurrences was surgical resection; among them, 10 underwent repeated resection, 9 adjuvant therapy and 5 were treated with lung metastasectomy. The most common site of distant metastasis was lung (n = 7). Factors that affected survival were type of pathology and evidence of distant metastasis. Conclusion Surgery with wide margin is the safe and good technique for treatment of primary chest wall tumors with acceptable morbidity and mortality. PMID:24947314

  18. Clinical epidemiology for childhood primary central nervous system tumors.

    PubMed

    Bauchet, Luc; Rigau, Valérie; Mathieu-Daudé, Hélène; Fabbro-Peray, Pascale; Palenzuela, Gilles; Figarella-Branger, Dominique; Moritz, Jorge; Puget, Stéphanie; Bauchet, Fabienne; Pallusseau, Lorelei; Duffau, Hugues; Coubes, Philippe; Trétarre, Brigitte; Labrousse, François; Dhellemmes, Patrick

    2009-03-01

    This work was conducted by the French Brain Tumor Data Bank (FBTDB) and aims to prospectively record all primary central nervous system tumors (PCNST), in France, for which histological diagnosis is available. Results concerning children are presented. This study analyzes the childhood cases (0-19 years) of newly diagnosed and histologically confirmed PCNST (during the years 2004-2006) which have been recorded by the FBTDB. All French neuropathology and neurosurgery departments participated in this program. Neurosurgeons and neuropathologists completed a data file containing socio-demographic, clinical, radiologic and anatomopathologic information. The Tumor Registry from Herault was authorized to compile the data files with personal identifiers. About 1,017 cases (533 boys and 484 girls) of newly diagnosed childhood PCNST have been recorded (gliomas: 52%, all other neuroepithelial tumors: 31%, craniopharyngioma: 5%, germ cell tumors, meningioma and neurinoma: approximately 3% each, all histological subtypes have been detailed). Tumor resections were performed in 83.3%, and biopsies in 16.7%. The distributions by histology, cryopreservation of the samples, age, sex, tumor site and surgery have been detailed. To our knowledge, this work is the first databank in Europe dedicated to PCNST that includes the collection of clinical, radiological and histological data (including cryopreservation of the specimen). The long term goals of the FBTDB are to create a national registry and a network to perform epidemiological studies, to implement clinical and basic research protocols, and to evaluate and harmonize the healthcare of children and adult patients affected by PCNST. PMID:19020806

  19. Drug response in organoids generated from frozen primary tumor tissues

    PubMed Central

    Walsh, Alex J.; Cook, Rebecca S.; Sanders, Melinda E.; Arteaga, Carlos L.; Skala, Melissa C.

    2016-01-01

    Primary tumor organoids grown in three-dimensional culture provide an excellent platform for studying tumor progression, invasion, and drug response. However, organoid generation protocols require fresh tumor tissue, which limits organoid research and clinical use. This study investigates cellular morphology, viability, and drug response of organoids derived from frozen tissues. The results demonstrate that viable organoids can be grown from flash-frozen and thawed tissue and from bulk tissues slowly frozen in DMSO supplemented media. While the freezing process affects the basal metabolic rate of the cells, the optical metabolic imaging index correlates between organoids derived from fresh and frozen tissue and can be used to detect drug response of organoids grown from frozen tissues. The slow, DMSO frozen tissue yielded organoids with more accurate drug response than the flash frozen tissues, and thus bulk tissue should be preserved for subsequent organoid generation by slow freezing in DMSO supplemented media. PMID:26738962

  20. Early and multiple origins of metastatic lineages within primary tumors

    PubMed Central

    Zhao, Zi-Ming; Zhao, Bixiao; Bai, Yalai; Iamarino, Atila; Gaffney, Stephen G.; Schlessinger, Joseph; Lifton, Richard P.; Rimm, David L.; Townsend, Jeffrey P.

    2016-01-01

    Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary models, reconstructed ancestral states of somatic mutations, and inferred cancer chronograms to yield three conclusions. First, in contrast to a linear model of cancer progression, metastases can originate from divergent lineages within primary tumors. Evolved genetic changes in cancer lineages likely affect only the proclivity toward metastasis. Single genetic changes are unlikely to be necessary or sufficient for metastasis. Second, metastatic lineages can arise early in tumor development, sometimes long before diagnosis. The early genetic divergence of some metastatic lineages directs attention toward research on driver genes that are mutated early in cancer evolution. Last, the temporal order of occurrence of driver mutations can be inferred from phylogenetic analysis of cancer chronograms, guiding development of targeted therapeutics effective against primary tumors and metastases. PMID:26858460

  1. Early and multiple origins of metastatic lineages within primary tumors.

    PubMed

    Zhao, Zi-Ming; Zhao, Bixiao; Bai, Yalai; Iamarino, Atila; Gaffney, Stephen G; Schlessinger, Joseph; Lifton, Richard P; Rimm, David L; Townsend, Jeffrey P

    2016-02-23

    Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary models, reconstructed ancestral states of somatic mutations, and inferred cancer chronograms to yield three conclusions. First, in contrast to a linear model of cancer progression, metastases can originate from divergent lineages within primary tumors. Evolved genetic changes in cancer lineages likely affect only the proclivity toward metastasis. Single genetic changes are unlikely to be necessary or sufficient for metastasis. Second, metastatic lineages can arise early in tumor development, sometimes long before diagnosis. The early genetic divergence of some metastatic lineages directs attention toward research on driver genes that are mutated early in cancer evolution. Last, the temporal order of occurrence of driver mutations can be inferred from phylogenetic analysis of cancer chronograms, guiding development of targeted therapeutics effective against primary tumors and metastases. PMID:26858460

  2. Primary Hyperparathyroidism with Extensive Brown Tumors and Multiple Fractures in a 20-Year-Old Woman

    PubMed Central

    Choi, Ju Hee; Kim, Kyoung Jin; Lee, Ye Jin; Kim, Sun Hwa; Kim, Sin Gon; Jung, Kwang Yoon; Choi, Dong Seop

    2015-01-01

    A brown tumor is a benign fibrotic, erosive bony lesion caused by localized, rapid osteoclastic turnover, resulting from hyperparathyroidism. Although brown tumors are one of the most pathognomonic signs of primary hyperparathyroidism, they are rarely seen in clinical practice. In this report, we present a case of 20-year-old woman with recurrent fractures and bone pain. Plain digital radiographs of the affected bones revealed multiple erosive bone tumors, which were finally diagnosed as brown tumors associated with primary hyperparathyroidism due to a parathyroid adenoma. This case shows that multiple, and clinically severe form of brown tumors can even occur in young patients. PMID:26354493

  3. Cervical lymph node metastases from remote primary tumor sites

    PubMed Central

    López, Fernando; Rodrigo, Juan P.; Silver, Carl E.; Haigentz, Missak; Bishop, Justin A.; Strojan, Primož; Hartl, Dana M.; Bradley, Patrick J.; Mendenhall, William M.; Suárez, Carlos; Takes, Robert P.; Hamoir, Marc; Robbins, K. Thomas; Shaha, Ashok R.; Werner, Jochen A.; Rinaldo, Alessandra; Ferlito, Alfio

    2016-01-01

    Although most malignant lymphadenopathy in the neck represent lymphomas or metastases from head and neck primary tumors, occasionally, metastatic disease from remote, usually infraclavicular, sites presents as cervical lymphadenopathy with or without an obvious primary tumor. In general, these tumors metastasize to supraclavicular lymph nodes, but occasionally may present at an isolated higher neck level. A search for the primary tumor includes information gained by histology, immunohistochemistry, and evaluation of molecular markers that may be unique to the primary tumor site. In addition, 18F-fluoro-2-deoxyglocose positron emission tomography combined with CT (FDG-PET/CT) has greatly improved the ability to detect the location of an unknown primary tumor, particularly when in a remote location. Although cervical metastatic disease from a remote primary site is often incurable, there are situations in which meaningful survival can be achieved with appropriate local treatment. Management is quite complex and requires a truly multidisciplinary approach. PMID:26713674

  4. Primary 4T1 tumor resection provides critical "window of opportunity" for immunotherapy.

    PubMed

    Ghochikyan, Anahit; Davtyan, Arpine; Hovakimyan, Armine; Davtyan, Hayk; Poghosyan, Anna; Bagaev, Alexander; Ataullakhanov, Ravshan I; Nelson, Edward L; Agadjanyan, Michael G

    2014-02-01

    It is believed that primary tumor resection modulates host-tumor immune interaction, but this has not been characterized in a stringent breast cancer tumor model. This report, using the 4T1 murine mammary tumor model, characterizes for the first time the dynamic longitudinal changes in immunosuppressive and effector components of the immune system after resection of an established orthotopic primary tumor with a defined natural history of developing lung metastases. More specifically, we analyzed changes of absolute numbers and frequencies of MDSC, regulatory T cells (Treg), as well as activated CD4 and CD8 positive T cells in spleens and, in some studies, lungs of 4T1 tumor-bearing mice and mice after primary tumor resection. Importantly, using mathematical analyses we established that primary resection of an orthotopic tumor had created a "window of opportunity" with decreased tumor-associated immune suppression that existed for approximately 10 days. Although tumor resection did slightly prolong survival, it did not affect the ultimate development of metastatic disease since animals with resected tumors or intact primary tumors eventually died by day 47 and 43, respectively. This window of opportunity likely occurs in humans providing a rationale and parameters for integration and testing of immunotherapeutic strategies in this critical "window of opportunity" to combat the development of metastatic disease. PMID:24096737

  5. Primary 4T1 tumor resection provides critical "window of opportunity" for immunotherapy.

    PubMed

    Ghochikyan, Anahit; Davtyan, Arpine; Hovakimyan, Armine; Davtyan, Hayk; Poghosyan, Anna; Bagaev, Alexander; Ataullakhanov, Ravshan I; Nelson, Edward L; Agadjanyan, Michael G

    2014-02-01

    It is believed that primary tumor resection modulates host-tumor immune interaction, but this has not been characterized in a stringent breast cancer tumor model. This report, using the 4T1 murine mammary tumor model, characterizes for the first time the dynamic longitudinal changes in immunosuppressive and effector components of the immune system after resection of an established orthotopic primary tumor with a defined natural history of developing lung metastases. More specifically, we analyzed changes of absolute numbers and frequencies of MDSC, regulatory T cells (Treg), as well as activated CD4 and CD8 positive T cells in spleens and, in some studies, lungs of 4T1 tumor-bearing mice and mice after primary tumor resection. Importantly, using mathematical analyses we established that primary resection of an orthotopic tumor had created a "window of opportunity" with decreased tumor-associated immune suppression that existed for approximately 10 days. Although tumor resection did slightly prolong survival, it did not affect the ultimate development of metastatic disease since animals with resected tumors or intact primary tumors eventually died by day 47 and 43, respectively. This window of opportunity likely occurs in humans providing a rationale and parameters for integration and testing of immunotherapeutic strategies in this critical "window of opportunity" to combat the development of metastatic disease.

  6. TUMOR CONTAMINATION IN THE BIOPSY PATH OF PRIMARY MALIGNANT BONE TUMORS

    PubMed Central

    Oliveira, Marcelo Parente; Lima, Pablo Moura de Andrade; de Mello, Roberto José Vieira

    2015-01-01

    Objective: To study factors possibly associated with tumor contamination in the biopsy path of primary malignant bone tumors. Method: Thirty-five patients who underwent surgical treatment with diagnoses of osteosarcoma, Ewing's tumor and chondrosarcoma were studied retrospectively. The sample was analyzed to characterize the biopsy technique used, histological type of the tumor, neoadjuvant chemotherapy used, local recurrences and tumor contamination in the biopsy path. Results: Among the 35 patients studied, four cases of contamination occurred (11.43%): one from osteosarcoma, two from Ewing's tumor and one from chondrosarcoma. There was no association between the type of tumor and presence of tumor contamination in the biopsy path (p = 0.65). There was also no association between the presence of tumor contamination and the biopsy technique (p = 0.06). On the other hand, there were associations between the presence of tumor contamination and local recurrence (p = 0.01) and between tumor contamination and absence of neoadjuvant chemotherapy (p = 0.02). Conclusion: Tumor contamination in the biopsy path of primary malignant bone tumors was associated with local recurrence. On the other hand, the histological type of the tumor and the type of biopsy did not have an influence on tumor contamination. Neoadjuvant chemotherapy had a protective effect against this complication. Despite these findings, tumor contamination is a complication that should always be taken into consideration, and removal of the biopsy path is recommended in tumor resection surgery. PMID:27047877

  7. Cross-talk between tumors can affect responses to therapy

    PubMed Central

    Devaud, Christel; John, Liza B; Westwood, Jennifer A; Yong, Carmen SM; Beavis, Paul A; Schwendener, Reto A; Darcy, Phillip K; Kershaw, Michael H

    2015-01-01

    Advanced stages of cancer often involve multiple tumors in different locations in the body. These tumors are associated with a microenvironment that can influence tumor responses to immunotherapy. Whether tumors and their disparate microenvironment can interact together at distance in a multiple tumor setting, through a form of cross-talk, and affect their responses to immunotherapy has never been described. Our study investigated the cross-talk between two tumors with disparate microenvironments in a mouse model. We demonstrated that immunosuppressive visceral tumors could influence distant subcutaneous (SC) tumors to render them resistant to immunotherapy. We observed distinct modifications in the SC tumor microenvironment following cross-talk with kidney tumors that exhibit a type-2 macrophage-related immunosuppressive microenvironment. Indeed, when a concomitant kidney tumor was present in the mouse, the SC tumors were highly infiltrated with M2 macrophages and had a reduced T cell and NK cell effector immune profile. Finally, blocking the M2-associated chemokine CCL2 or depleting macrophages, significantly improved the effect of immunotherapy on growth of SC tumors in the presence of concomitant kidney tumors. This work emphasizes the potential negative influence that a tumor, with a strong immunosuppressive microenvironment, can exert on distant tumors that would normally be treatment-responsive. This report may lead to a new vision of the prioritization in the treatment of advanced metastatic cancer. PMID:26140251

  8. Enucleation and the appearance of second primary tumors in cats bearing virally induced intraocular tumors.

    PubMed

    Niederkorn, J Y; Shadduck, J A; Albert, D

    1982-12-01

    The effect of enucleation of an eye containing a malignant intraocular neoplasm on the occurrence of secondary tumors was studied in cats with tumors, mainly melanomas, induced by Gardner feline fibrosarcoma virus. Enucleation of eyes containing progressively growing tumors was followed by a sharp increase in the frequency of secondary tumors. Secondary tumors were detected in 13 of 14 (92.8%) cats subjected to enucleation but in only seven of 21 (33.3%) untreated cats. The data suggest that the secondary tumors were not metastases but rather second primary tumors induced by local transformation of fibrosarcoma virus shed from the intraocular neoplasms. The increased incidence of these second primary tumors in cats subjected to enucleation was associated with depressed antibody titers to a tumor-specific transplantation antigen, the feline oncornavirus-associated cell membrane antigen.

  9. Pancreatic metastasis from mycosis fungoides mimicking primary pancreatic tumor.

    PubMed

    Ceriolo, Paola; Fausti, Valentina; Cinotti, Elisa; Bonadio, Silvia; Raffaghello, Lizzia; Bianchi, Giovanna; Orcioni, Giulio Fraternali; Fiocca, Roberto; Rongioletti, Franco; Pistoia, Vito; Borgonovo, Giacomo

    2016-03-28

    Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that can undergo local progression with possible systemic dissemination. We report a case of a patient affected by MF with a pancreatic mass that was a diagnostic challenge between primitive tumor and pancreatic metastasis from MF. Clinical setting findings and imaging studies raised the suspicion of a pancreatic primary neoplasm. A diagnostic clue was provided by the combined histomorphologic/immunohistochemical study of pancreatic and cutaneous biopsies, which revealed a pancreatic localization of MF. Considering the rarity of metastatic localization of MF to the pancreas, we next investigated whether chemokine-chemokine receptor interactions could be involved in the phenomenon to provide new insight into the possible mechanisms underlying metastatic localization of MF to the pancreas. Histological analyses of archival pancreatic tissue demonstrated that glucagon-secreting cells of the pancreatic islets expressed the CCL27 chemokine, which may have attracted in our case metastatic MF cells expressing the complementary receptor CCR10.

  10. Brown tumor of the mandible as first manifestation of primary hyperparathyroidism: diagnosis and treatment.

    PubMed

    Fernández-Sanromán, Jacinto; Antón-Badiola, Iosu María; Costas-López, Alberto

    2005-01-01

    Brown tumor is one of the lesions that develop in patients with hyperparathyroidism. Any of the skeletal bones can be affected including the cranio-maxillofacial ones. Most of the times the brown tumor appears after a final diagnosis of hyperparathyroidism is made. However brown tumor can be the first clinical sign of the disease. A clinical case in which a brown tumor located in the anterior part of the mandible appears as the first sign of primary hyperparathyroidism is presented. The possible differential clinical diagnosis and the recommended treatments are revised.

  11. Primary spinal primitive neuroectodermal tumor on MR imaging.

    PubMed

    Thoriya, Prashant J; Watal, Pankaj; Bahri, Nandini U; Rathod, Ketan

    2015-01-01

    Neoplasms in the region of filum terminale are not uncommon. Myxopapillary ependymoma is the commonest tumor at this location. The differentials reported for this entity are nerve sheath tumor, meningioma, paraganglioma, intradural metastases, lymphoma, other varieties of ependymoma, subependymoma, astrocytoma, ganglioglioma, hemangioblastoma, and primitive neuroectodermal tumor (PNET). PNET may very rarely present as an intradural thoracolumbar mass. We present pre- and post-therapy magnetic resonance imaging (MRI) features of a patient with proven primary spinal primitive neuroectodermal tumor (PSPNET) of peripheral subtype. PMID:26752826

  12. Primary spinal primitive neuroectodermal tumor on MR imaging

    PubMed Central

    Thoriya, Prashant J; Watal, Pankaj; Bahri, Nandini U; Rathod, Ketan

    2015-01-01

    Neoplasms in the region of filum terminale are not uncommon. Myxopapillary ependymoma is the commonest tumor at this location. The differentials reported for this entity are nerve sheath tumor, meningioma, paraganglioma, intradural metastases, lymphoma, other varieties of ependymoma, subependymoma, astrocytoma, ganglioglioma, hemangioblastoma, and primitive neuroectodermal tumor (PNET). PNET may very rarely present as an intradural thoracolumbar mass. We present pre- and post-therapy magnetic resonance imaging (MRI) features of a patient with proven primary spinal primitive neuroectodermal tumor (PSPNET) of peripheral subtype. PMID:26752826

  13. Primary hepatic neuroendocrine tumor: A case report and literature review

    PubMed Central

    Song, Jeong Eun; Kim, Byung Seok; Lee, Chang Hyeong

    2016-01-01

    Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare and difficult to distinguish from other liver tumors, such as hepatocellular carcinoma (HCC) and cholangiocarcinoma, based on medical imaging findings. A 70-year-old man was referred for evaluation of liver mass incidentally discovered on abdominal computed tomography. The characteristic finding from dynamic liver magnetic resonance imaging led to a diagnosis of HCC. The patient underwent right hepatectomy. Histopathological and immunohistochemical examination revealed grade 2 neuroendocrine tumor. The postoperative 24-h urinary excretion of 5-hydroxy-indolacetic acid was within the normal range. Further imaging investigations were performed. No other lesions were found making probable the diagnosis of PHNET. This case shows that the diagnosis of PHNET is a medical challenge, requiring differentiation of PHNETs other hepatic masses and exclusion of occult primary neuroendocrine tumors. The diagnosis of PHNET can be ascertained after long term follow-up to exclude another primary origin. PMID:27574614

  14. Primary pediatric cardiac tumors: a 17 year experience.

    PubMed

    Sallee, D; Spector, M L; van Heeckeren, D W; Patel, C R

    1999-03-01

    We reviewed 22 cases of primary pediatric cardiac tumors followed at our institution from January 1981 through November 1997, analyzing them by subtype, age and manner of presentation, location, associated findings, interventions, and clinical course. Rhabdomyomas were the most common (11), followed by intrapericardial teratomas (2), myxomas (1), fibromas (1), hemangiomas (1), mesotheliomas (1), and rhabdomyosarcomas (1), with 4 undetermined tumors. The majority (77%) of tumors were diagnosed before the age of one year, including six prenatally. The most common presentations were murmurs (5), arrhythmias (5), and abnormal screening fetal ultrasound examinations (4). Tumors were located most frequently in the right ventricle (13) and left ventricle (7), with multiple tumors being present in 10 cases. Eight patients (36%) had associated arrhythmias or conduction abnormalities, and of the 11 patients with rhabdomyomas, tuberous sclerosis was diagnosed in 8. Eight patients underwent cardiac catheterization, including two for electrophysiologic study with radiofrequency ablation, and seven patients had complete or partial tumor resection. The follow-up period ranged from 2 months to 15 years, and there were 3 tumor-related deaths. Therefore, despite the benign histology of most primary pediatric cardiac tumors, there may be significant associated morbidity and occasional mortality. As echocardiographic techniques such as fetal ultrasonography have continued to improve, however, these cardiac tumors have increasingly been detected early before significant symptoms develop.

  15. Rho GTPases in primary brain tumor malignancy and invasion.

    PubMed

    Khalil, Bassem D; El-Sibai, Mirvat

    2012-07-01

    Gliomas are the most common type of malignant primary brain tumor in humans, accounting for 80 % of malignant cases. Expression and activity of Rho GTPases, which coordinate several cellular processes including cell-cycle progression and cell migration, are commonly altered in many types of primary brain tumor. Here we review the suggested effects of deregulated Rho GTPase signaling on brain tumor malignancy, highlighting the controversy in the field. For instance, whereas expression of RhoA and RhoB has been found to be significantly reduced in astrocytic tumors, other studies have reported Rho-dependent LPA-induced migration in glioma cells. Moreover, whereas the Rac1 expression level has been found to be reduced in astrocytic tumor, it was overexpressed and induced invasion in medulloblastoma tumors. In addition to the Rho GTPases themselves, several of their downstream effectors (including ROCK, mDia, and N-WASP) and upstream regulators (including GEFs, GAPs, PI3K, and PTEN) have also been implicated in primary brain tumors.

  16. Primary hepatic carcinoid tumor: case report and literature review

    PubMed Central

    Camargo, Éden Sartor; Viveiros, Marcelo de Melo; Corrêa, Isaac José Felippe; Robles, Laercio; Rezende, Marcelo Bruno

    2014-01-01

    Primary hepatic carcinoid tumors are extremely rare neoplasms derived from hormone-producing neuroendocrine cells. It is difficult to make their diagnosis before biopsy, surgical resection or necropsy. A recent publication described only 94 cases of these tumors. There is no sex predilection and apparently it has no association with cirrhosis or preexisting hepatic disease. The most effective treatment is hepatectomy, and resection is determined by size and location of the lesions. PMID:25628206

  17. The role of integrins in primary and secondary brain tumors.

    PubMed

    Schittenhelm, Jens; Tabatabai, Ghazaleh; Sipos, Bence

    2016-10-01

    The tumor environment plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Integrins, a family of cell surface receptors, bridge the extracellular matrix to the intracellular cytoskeleton. Since their first characterization 25 years ago, a vast amount of work has been performed to understand the essential role of integrins in cell development, tissue organization, tumor growth, vessel development and their signaling mechanisms. Their potential as therapeutic targets in various types of cancer is intensively studied. In this review, we discuss the expression patterns and functional role of integrin in primary brain tumors and brain metastases, provide an overview of clinical data on integrin inhibition and their potential application in imaging and therapy of these tumors. PMID:27097828

  18. Neuromorphometry of primary brain tumors by magnetic resonance imaging.

    PubMed

    Hevia-Montiel, Nidiyare; Rodriguez-Perez, Pedro I; Lamothe-Molina, Paul J; Arellano-Reynoso, Alfonso; Bribiesca, Ernesto; Alegria-Loyola, Marco A

    2015-04-01

    Magnetic resonance imaging is a technique for the diagnosis and classification of brain tumors. Discrete compactness is a morphological feature of two-dimensional and three-dimensional objects. This measure determines the compactness of a discretized object depending on the sum of the areas of the connected voxels and has been used for understanding the morphology of nonbrain tumors. We hypothesized that regarding brain tumors, we may improve the malignancy grade classification. We analyzed the values in 20 patients with different subtypes of primary brain tumors: astrocytoma, oligodendroglioma, and glioblastoma multiforme subdivided into the contrast-enhanced and the necrotic tumor regions. The preliminary results show an inverse relationship between the compactness value and the malignancy grade of gliomas. Astrocytomas exhibit a mean of [Formula: see text], whereas oligodendrogliomas exhibit a mean of [Formula: see text]. In contrast, the contrast-enhanced region of the glioblastoma presented a mean of [Formula: see text], and the necrotic region presented a mean of [Formula: see text]. However, the volume and area of the enclosing surface did not show a relationship with the malignancy grade of the gliomas. Discrete compactness appears to be a stable characteristic between primary brain tumors of different malignancy grades, because similar values were obtained from different patients with the same type of tumor. PMID:26158107

  19. Neuromorphometry of primary brain tumors by magnetic resonance imaging

    PubMed Central

    Hevia-Montiel, Nidiyare; Rodriguez-Perez, Pedro I.; Lamothe-Molina, Paul J.; Arellano-Reynoso, Alfonso; Bribiesca, Ernesto; Alegria-Loyola, Marco A.

    2015-01-01

    Abstract. Magnetic resonance imaging is a technique for the diagnosis and classification of brain tumors. Discrete compactness is a morphological feature of two-dimensional and three-dimensional objects. This measure determines the compactness of a discretized object depending on the sum of the areas of the connected voxels and has been used for understanding the morphology of nonbrain tumors. We hypothesized that regarding brain tumors, we may improve the malignancy grade classification. We analyzed the values in 20 patients with different subtypes of primary brain tumors: astrocytoma, oligodendroglioma, and glioblastoma multiforme subdivided into the contrast-enhanced and the necrotic tumor regions. The preliminary results show an inverse relationship between the compactness value and the malignancy grade of gliomas. Astrocytomas exhibit a mean of 973±14, whereas oligodendrogliomas exhibit a mean of 942±21. In contrast, the contrast-enhanced region of the glioblastoma presented a mean of 919±43, and the necrotic region presented a mean of 869±66. However, the volume and area of the enclosing surface did not show a relationship with the malignancy grade of the gliomas. Discrete compactness appears to be a stable characteristic between primary brain tumors of different malignancy grades, because similar values were obtained from different patients with the same type of tumor. PMID:26158107

  20. Neuromorphometry of primary brain tumors by magnetic resonance imaging.

    PubMed

    Hevia-Montiel, Nidiyare; Rodriguez-Perez, Pedro I; Lamothe-Molina, Paul J; Arellano-Reynoso, Alfonso; Bribiesca, Ernesto; Alegria-Loyola, Marco A

    2015-04-01

    Magnetic resonance imaging is a technique for the diagnosis and classification of brain tumors. Discrete compactness is a morphological feature of two-dimensional and three-dimensional objects. This measure determines the compactness of a discretized object depending on the sum of the areas of the connected voxels and has been used for understanding the morphology of nonbrain tumors. We hypothesized that regarding brain tumors, we may improve the malignancy grade classification. We analyzed the values in 20 patients with different subtypes of primary brain tumors: astrocytoma, oligodendroglioma, and glioblastoma multiforme subdivided into the contrast-enhanced and the necrotic tumor regions. The preliminary results show an inverse relationship between the compactness value and the malignancy grade of gliomas. Astrocytomas exhibit a mean of [Formula: see text], whereas oligodendrogliomas exhibit a mean of [Formula: see text]. In contrast, the contrast-enhanced region of the glioblastoma presented a mean of [Formula: see text], and the necrotic region presented a mean of [Formula: see text]. However, the volume and area of the enclosing surface did not show a relationship with the malignancy grade of the gliomas. Discrete compactness appears to be a stable characteristic between primary brain tumors of different malignancy grades, because similar values were obtained from different patients with the same type of tumor.

  1. [Primary prevention of urologic tumors: prostate cancer].

    PubMed

    Schmitz-Dräger, B J; Lümmen, G; Bismarck, E; Fischer, C

    2011-10-01

    Assessment of the role of vitamins and micronutrients in the primary prevention of prostate cancer has changed dramatically in the past 10 years. Efforts to confirm the efficacy of a single substance have not yet succeeded. Therefore, such recommendations should at present no longer be given. Consideration could even be given to discussing whether additional large-scale interventional studies are expedient in this regard. There is still solid evidence that a well-balanced moderate diet, reduced consumption of milk products, and an Asian or Mediterranean diet are not only beneficial for general good health but can also prevent the development of prostate cancer. This should be the focus of further epidemiological studies. Thus, one can certainly speak of a paradigm shift in the prevention of prostate cancer. In contrast, available data on chemoprevention with 5α-reductase inhibitors is unequivocal: intake of finasteride as well as dutasteride correlates with significantly decreased evidence for prostate cancer. Converting this result into urologic practice remains the topic of extensive controversy. PMID:21927877

  2. Preoperative embolization of primary bone tumors: A case control study

    PubMed Central

    Jha, Roushan; Sharma, Raju; Rastogi, Shishir; Khan, Shah Alam; Jayaswal, Arvind; Gamanagatti, Shivanand

    2016-01-01

    AIM: To study the safety and effectiveness of preoperative embolization of primary bone tumors in relation to intraoperative blood loss, intraoperative blood transfusion volume and surgical time. METHODS: Thirty-three patients underwent preoperative embolization of primary tumors of extremities, hip or vertebrae before resection and stabilization. The primary osseous tumors included giant cell tumors, aneurysmal bone cyst, osteoblastoma, chondroblastoma and chondrosarcoma. Twenty-six patients were included for the statistical analysis (embolization group) as they were operated within 0-48 h within preoperative embolization. A control group (non-embolization group, n = 28) with bone tumor having similar histological diagnosis and operated without embolization was retrieved from hospital record for statistical comparison. RESULTS: The mean intraoperative blood loss was 1300 mL (250-2900 mL), the mean intraoperative blood transfusion was 700 mL (0-1400 mL) and the mean surgical time was 221 ± 76.7 min for embolization group (group I, n = 26). Non-embolization group (group II, n = 28), the mean intraoperative blood loss was 1800 mL (800-6000 mL), the mean intraoperative blood transfusion was 1400 mL (700-8400 mL) and the mean surgical time was 250 ± 69.7 min. On comparison, statistically significant (P < 0.001) difference was found between embolisation group and non-embolisation group for the amount of blood loss and requirement of blood transfusion. There was no statistical difference between the two groups for the surgical time. No patients developed any angiography or embolization related complications. CONCLUSION: Preoperative embolization of bone tumors is a safe and effective adjunct to the surgical management of primary bone tumors that leads to reduction in intraoperative blood loss and blood transfusion volume. PMID:27158424

  3. Investigating Mechanisms of Alkalinization for Reducing Primary Breast Tumor Invasion

    PubMed Central

    Robey, Ian F.; Nesbit, Lance A.

    2013-01-01

    The extracellular pH (pHe) of many solid tumors is acidic as a result of glycolytic metabolism and poor perfusion. Acidity promotes invasion and enhances metastatic potential. Tumor acidity can be buffered by systemic administration of an alkaline agent such as sodium bicarbonate. Tumor-bearing mice maintained on sodium bicarbonate drinking water exhibit fewer metastases and survive longer than untreated controls. We predict this effect is due to inhibition of tumor invasion. Reducing tumor invasion should result in fewer circulating tumor cells (CTCs). We report that bicarbonate-treated MDA-MB-231 tumor-bearing mice exhibited significantly lower numbers of CTCs than untreated mice (P < 0.01). Tumor pHe buffering may reduce optimal conditions for enzymes involved in tumor invasion such as cathepsins and matrix metalloproteases (MMPs). To address this, we tested the effect of transient alkalinization on cathepsin and MMP activity using enzyme activatable fluorescence agents in mice bearing MDA-MB-231 mammary xenografts. Transient alkalinization significantly reduced the fluorescent signal of protease-specific activatable agents in vivo (P ≤ 0.003). Alkalinization, however, did not affect expression of carbonic anhydrase IX (CAIX). The findings suggest a possible mechanism in a live model system for breast cancer where systemic alkalinization slows the rate of invasion. PMID:23936808

  4. Ablation techniques for primary and metastatic liver tumors

    PubMed Central

    Ryan, Michael J; Willatt, Jonathon; Majdalany, Bill S; Kielar, Ania Z; Chong, Suzanne; Ruma, Julie A; Pandya, Amit

    2016-01-01

    Ablative treatment methods have emerged as safe and effective therapies for patients with primary and secondary liver tumors who are not surgical candidates at the time of diagnosis. This article reviews the current literature and describes the techniques, complications and results for radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation. PMID:26839642

  5. Pancreatic metastasis from mycosis fungoides mimicking primary pancreatic tumor

    PubMed Central

    Ceriolo, Paola; Fausti, Valentina; Cinotti, Elisa; Bonadio, Silvia; Raffaghello, Lizzia; Bianchi, Giovanna; Orcioni, Giulio Fraternali; Fiocca, Roberto; Rongioletti, Franco; Pistoia, Vito; Borgonovo, Giacomo

    2016-01-01

    Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that can undergo local progression with possible systemic dissemination. We report a case of a patient affected by MF with a pancreatic mass that was a diagnostic challenge between primitive tumor and pancreatic metastasis from MF. Clinical setting findings and imaging studies raised the suspicion of a pancreatic primary neoplasm. A diagnostic clue was provided by the combined histomorphologic/immunohistochemical study of pancreatic and cutaneous biopsies, which revealed a pancreatic localization of MF. Considering the rarity of metastatic localization of MF to the pancreas, we next investigated whether chemokine-chemokine receptor interactions could be involved in the phenomenon to provide new insight into the possible mechanisms underlying metastatic localization of MF to the pancreas. Histological analyses of archival pancreatic tissue demonstrated that glucagon-secreting cells of the pancreatic islets expressed the CCL27 chemokine, which may have attracted in our case metastatic MF cells expressing the complementary receptor CCR10. PMID:27022231

  6. Primary malignancy, secondary malignancy and semimalignancy of bone tumors.

    PubMed

    Uehlinger, E

    1976-01-01

    1. Bone tumors in contrast to tumors in soft tissue, show a wide variety of clinical behavior qualified by the expressions semimalignancy, low grade of malignancy, sarcomatous degeneration and primarily benign bone tumors and bone lesions. 2. The term semimalignancy is characterized by local invasive and destructive tumor growth with a tendency to recur locally but no hematogeneous spreading. Semimalignancy requires wide en-bloc resection of amputation. 3. The term low grade malignancy is used to describe a tumor of very slow growth and with very late metastasis. Low-grade malignancy requires resection with careful preservation of functional structures. 4. The term secondary malignancy means the sarcomatous degeneration of a primarily benign lesion or bone tumor. This transformation is enhanced by irradiation and probably by acceleration of the normal turnover of bone tissue. In Paget's disease sarcomatous degeneration is to be expected in 2 percent of cases and in fibrous dysplasia in 0.5 percent of cases. 5. Sarcomatous degeneration of bone infarcts is rare, but an increase is to be expected due to an increased frequency of bone infarcts caused by long-term treatment with cortisone. 6. Primary bone tumors and recurrences show the same structure and cytology. In a minority of cases the recurrences are less differentiated; in a very few cases the recurrences are more highly differentiated and have a better prognosis than the initial lesion. PMID:1070716

  7. Massive parallel DNA pyrosequencing analysis of the tumor suppressor BRG1/SMARCA4 in lung primary tumors.

    PubMed

    Rodriguez-Nieto, Salvador; Cañada, Andres; Pros, Eva; Pinto, Ana I; Torres-Lanzas, Juan; Lopez-Rios, Fernando; Sanchez-Verde, Lydia; Pisano, David G; Sanchez-Cespedes, Montse

    2011-02-01

    The tumor suppressor gene, SMARCA4 (or BRG1), which encodes the ATPase component of the chromatin remodeling complex SWI/SNF, is commonly inactivated by mutations and deletions in lung cancer cell lines. However, SMARCA4 alterations appear to be rare in lung primary tumors. Ultra-deep sequencing technologies provide a promising alternative to achieve a sensitivity superior to that of current sequencing strategies. Here we used ultra-deep pyrosequencing to screen for mutations over the entire SMARCA4 coding region in 12 lung tumors without detectable BRG1 protein. While automatic-fluorescence-based sequencing detected one somatic mutation (p.K586X), the pyrosequencing revealed additional variants, thus increasing the sensitivity. One of the variants, which affected a consensus splice site, was confirmed by individual cloning of PCR products, ruling out the possibility of PCR or pyrosequencing artifacts. This mutation, confirmed to be somatic, was present at a frequency of ten percent, suggesting normal cell contamination in the tumor. Our analysis also allowed us to determine the sensitivity and to identify some limitations of the technology. In conclusion, in addition to cell lines, SMARCA4 is biallelically inactivated in a significant proportion of lung primary tumors, thereby constituting one of the most important genes contributing to the development of this type of cancer. PMID:21280140

  8. Rare presentation of four primary pediatric cardiac tumors.

    PubMed

    Schaffer, Lauren R; Caltharp, Shelley A; Milla, Sarah S; Kogon, Brian F; Cundiff, Caitlin A; Dalal, Aarti; Quigley, Phillip C; Shehata, Bahig M

    2016-01-01

    Pediatric cardiac tumors are extremely rare and usually benign. We selected four unique cases of pediatric cardiac tumors from a 15-year period at our institution. The four chosen cases represent unique, rare primary tumors of the heart. Our selection includes a case of Rosai Dorfman disease without systemic involvement, which is, to our knowledge, the second case of isolated cardiac Rosai Dorfman disease in a child. We present a case of subtotal replacement of myocardium by granulocytic sarcoma with minimal bone marrow involvement, representing the first reported case in a child manifested as hypertrophic cardiomyopathy, as well as a case of a primary synovial sarcoma arising from the atrioventricular (AV) node, representing the fourth reported pediatric case of a cardiac synovial sarcoma, and it is the first to arise from the AV node. Finally, we present a primary congenital infantile fibrosarcoma of the heart, which is, to our knowledge, the first confirmed cardiac congenital infantile fibrosarcoma. These four cases represent the need for continued inclusion of rare cardiac conditions in a clinician's differential diagnosis. Furthermore, they present the need for more in-depth molecular and genomic analysis of pediatric cardiac tumors in order to identify their etiopathogenesis.

  9. Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor

    PubMed Central

    Diacovo, Maria Julia

    2016-01-01

    Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT) scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma), with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid), supporting the diagnosis of biphasic malignant mesothelioma. PMID:27660729

  10. Gliosarcoma: A rare primary CNS tumor. Presentation of two cases

    PubMed Central

    Pardo, José; Murcia, Mauricio; García, Felip; Alvarado, Arnaldo

    2010-01-01

    Summary Introduction Gliosarcoma is a very rare primary mixed tumor in the central nervous system, with a biphasic pattern consisting of glial and malignant mesenchymal elements. Its onset is between the fourth and sixth decade of life, and it has a male/female ratio of 1.8/1. Here we present two cases of Gliosarcoma treated in our department. Discussion The monoclonal or biclonal origin of its biphasic nature is still subject to debate; hence the importance of its diagnosis and histogenesis. Results Standard treatment consists in surgical resection of the tumor followed in some cases by external radiotherapy and chemotherapy. PMID:24376932

  11. Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor

    PubMed Central

    Diacovo, Maria Julia

    2016-01-01

    Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT) scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma), with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid), supporting the diagnosis of biphasic malignant mesothelioma.

  12. Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor.

    PubMed

    Gleason, James Benjamin; Tashtoush, Basheer; Diacovo, Maria Julia

    2016-01-01

    Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT) scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma), with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid), supporting the diagnosis of biphasic malignant mesothelioma. PMID:27660729

  13. Factors affecting intellectual outcome in pediatric brain tumor patients

    SciTech Connect

    Ellenberg, L.; McComb, J.G.; Siegel, S.E.; Stowe, S.

    1987-11-01

    A prospective study utilizing repeated intellectual testing was undertaken in 73 children with brain tumors consecutively admitted to Childrens Hospital of Los Angeles over a 3-year period to determine the effect of tumor location, extent of surgical resection, hydrocephalus, age of the child, radiation therapy, and chemotherapy on cognitive outcome. Forty-three patients were followed for at least two sequential intellectual assessments and provide the data for this study. Children with hemispheric tumors had the most general cognitive impairment. The degree of tumor resection, adequately treated hydrocephalus, and chemotherapy had no bearing on intellectual outcome. Age of the child affected outcome mainly as it related to radiation. Whole brain radiation therapy was associated with cognitive decline. This was especially true in children below 7 years of age, who experienced a very significant loss of function after whole brain radiation therapy.

  14. Radionuclide bone scanning in neuroblastoma: skeletal metastases and primary tumor localization of /sup 99m/Tc-MDP

    SciTech Connect

    Podrasky, A.E.; Stark, D.D.; Hattner, R.S.; Gooding, C.A.; Moss, A.A.

    1983-09-01

    Of 42 radionuclide bone scans in 35 children with neuroblastoma, 21 were abnormal for the presence of skeletal metastases. Of the 21 abnormal scans, 16 were corroborated by positive bone-marrow biopsy or clinical data. The false-negative and false-positive rates for bone scanning were 4.8% and 9.5%, respectively. Calcification of the primary tumor was seen on pretreatment computed tomographic (CT) scans in 24 (89%) of 27 cases, while only 13 (48%) of 27 were detectable by plain radiographs. Uptake of /sup 99m/Tc methylene diphosphate /sup 99m/Tc-MDP) by the primary tumor occurred in 20 of 27 cases, but correlation between tumor uptake and calcification was not statistically significant. All children with markedly elevated urinary vanillylmandelic acid exhibited primary tumor uptake. Survival was not affected independently by primary tumor uptake.

  15. Primary gastrointestinal stromal tumor of the liver: A case report

    PubMed Central

    Luo, Xiao-Li; Liu, Dan; Yang, Jian-Jun; Zheng, Min-Wen; Zhang, Jing; Zhou, Xiao-Dong

    2009-01-01

    We report a case of primary gastrointestinal stromal tumor (GIST) of the liver. A 17-year-old man with a solid mass in the anterior segment of the right liver was asymptomatic with negative laboratory examinations with the exception of positive HBV. Contrast-enhanced ultrasound (CEUS) revealed a hypervascular lesion in the arterial phase and hypoechoic features during the portal and late phases. However, enhanced spiral computed tomography (CT) showed hypoattenuation in all three phases. Following biopsy, immunohistochemical evaluation demonstrated positive CD117. Different imaging features of primary GISTs of the liver are due to pathological properties and different working systems between CEUS and enhanced spiral CT. PMID:19653356

  16. Primary extragastrointestinal stromal tumor of the pleura: A case report

    PubMed Central

    ZHANG, CAI-QING; LU, DE-GAN; LIU, QING-FA; XIAO, WEI

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor of the gastrointestinal tract. The stomach and small intestine are the most common sites of occurrence. GISTs are mesenchymal neoplasms originating from the interstitial cells of Cajal (ICCs), and are characterized by positivity for cluster of differentiation (CD) 117, also known as proto-oncogene c-Kit. While the majority of GISTs develop in the alimentary tract, in rare cases they may also be found in extragastrointestinal tissues. This type of GIST is known as an extragastrointestinal stromal tumor (EGIST). Despite the fact that EGISTs have been reported in the mesentery, omentum and retroperitoneum, primary intrathoracic EGISTs, arising from the pleura or lungs, are rare. The patient presented in the current study was a 40-year-old man, who presented with a cough and pyrexia, with pleural effusion on the left side. Multiple nodules throughout the parietal pleura were identified by thoracoscopy and a diagnosis of primary GIST of pleura was established, since they were positive for CD117 and discovered on GIST-1 and there was no evidence of gastrointestinal tumors. Subsequently, the patient was administered with imatinib and had no signs of disease recurrence 2 years later. PMID:27123077

  17. Primary brain tumors, delta 24 and tumor metabolism. Interview by Rona Williamson.

    PubMed

    Gilbert, Mark R

    2013-04-01

    Interview by Rona Williamson, Commissioning Editor Mark R Gilbert studied medicine at the Johns Hopkins School of Medicine in Baltimore (MD, USA). He completed residency training in internal medicine and neurology at the Johns Hopkins Hospital, then was named the first Keck Foundation Fellow in Neuro-Oncology at Johns Hopkins. After 2 years on the faculty at Johns Hopkins, he moved to the University of Pittsburgh to head the Brain Tumor Program. During his tenure at Pittsburgh (PA, USA), he was named Chair of the Brain Tumor Committee of the Eastern Cooperative Oncology Group. In 1996, Dr Gilbert moved to the Emory University in Atlanta (GA, USA) to lead the Medical Neuro-Oncology Program and successfully competed for the program's membership in the New Approaches to Brain Tumor Treatment consortium. Dr Gilbert moved to the MD Anderson Cancer Center in Houston (TX, USA) in 2000 as Deputy Chair of the Department of Neuro-Oncology. During his tenure at MD Anderson, he has created two brain tumor consortia. The Collaborative Ependymoma Research Network is an international effort that is focusing research efforts on patients, both adult and pediatric, with this uncommon central nervous system tumor. The Brain Tumor Trials Collaborative is a 23-institution consortium that focuses on innovative clinical trials for primary glial malignancies. In addition, Dr Gilbert holds a leadership position in the Radiation Therapy Oncology Group and has served as the principal investigator on several large randomized brain tumor clinical trials. His research focus has been in the area of clinical and translational research for primary brain tumors. This includes novel clinical trial designs and the integration of correlative tumor biology with these clinical studies.

  18. Metformin selectively affects human glioblastoma tumor-initiating cell viability

    PubMed Central

    Würth, Roberto; Pattarozzi, Alessandra; Gatti, Monica; Bajetto, Adirana; Corsaro, Alessandro; Parodi, Alessia; Sirito, Rodolfo; Massollo, Michela; Marini, Cecilia; Zona, Gianluigi; Fenoglio, Daniela; Sambuceti, Gianmario; Filaci, Gilberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

    2013-01-01

    Cancer stem cell theory postulates that a small population of tumor-initiating cells is responsible for the development, progression and recurrence of several malignancies, including glioblastoma. In this perspective, tumor-initiating cells represent the most relevant target to obtain effective cancer treatment. Metformin, a first-line drug for type II diabetes, was reported to possess anticancer properties affecting the survival of cancer stem cells in breast cancer models. We report that metformin treatment reduced the proliferation rate of tumor-initiating cell-enriched cultures isolated from four human glioblastomas. Metformin also impairs tumor-initiating cell spherogenesis, indicating a direct effect on self-renewal mechanisms. Interestingly, analyzing by FACS the antiproliferative effects of metformin on CD133-expressing subpopulation, a component of glioblastoma cancer stem cells, a higher reduction of proliferation was observed as compared with CD133-negative cells, suggesting a certain degree of cancer stem cell selectivity in its effects. In fact, glioblastoma cell differentiation strongly reduced sensitivity to metformin treatment. Metformin effects in tumor-initiating cell-enriched cultures were associated with a powerful inhibition of Akt-dependent cell survival pathway, while this pathway was not affected in differentiated cells. The specificity of metformin antiproliferative effects toward glioblastoma tumor-initiating cells was confirmed by the lack of significant inhibition of normal human stem cells (umbilical cord-derived mesenchymal stem cells) in vitro proliferation after metformin exposure. Altogether, these data clearly suggest that metformin exerts antiproliferative activity on glioblastoma cells, showing a higher specificity toward tumor-initiating cells, and that the inhibition of Akt pathway may represent a possible intracellular target of this effect. PMID:23255107

  19. Primary tumors of the trachea. Results of radiation therapy

    SciTech Connect

    Fields, J.N.; Rigaud, G.; Emami, B.N.

    1989-06-15

    From 1959 to 1986, 24 patients with primary malignant tumors of the trachea received radiotherapy as all or part of treatment. Common presentations included respiratory symptoms in 20 patients and hemoptysis in 15. Thirteen patients had squamous carcinomas with undifferentiated and adenoid cystic cancers in five and four patients, respectively. Overall actuarial survival was 45% at 1 year, 25% at 5 years, and 13% at 10 years. Survival was significantly correlated to histologic type (adenoid cystic versus squamous, P less than 0.03), but not to tumor extent or to patient age or sex. Local control was attained in 10 of 24 patients overall and was more frequent for patients with tumors localized to the trachea and for patients who were treated with combined surgery and radiotherapy. For the 18 patients treated with radiotherapy alone, complete response (CR) was seen to be significantly (P less than 0.001) related to dose: six of seven (86%) patients receiving greater than or equal to 6000 cGy attained CR versus one of 11 (9%) receiving less than 6000 cGy. Three patients developed complications related to radiotherapy. Radiotherapy can provide durable local control of localized tracheal tumors and should be considered for medically inoperable patients with localized tumors and for patients with high risk of recurrence after resection.

  20. [One Case about Primary Mediastinal Primary Mediastinal Tumor 
with Mediastinal Sarcoma and Literature Review].

    PubMed

    Du, Jinchen; Li, Qingxin; Chao, Dong; Ban, Yulian; Li, Qunqun

    2016-09-20

    Primary mediastinal seminoma is a kind of germ cell malignancy outside the gonads, and it's rarer with sarcoma component. This disease which has no special clinical manifestations and imaging characteristics is difficult to identify with other mediastinal tumors and mediastinal type lung cancer. This paper reported a case of primary mediastinal seminoma with mediastinal sarcoma. Through the analysis of the diagnosis and treatment process in this patient, we will make a comprehensive review of the disease. PMID:27666557

  1. Jaw tumor in primary hyperparathyroidism is not always a brown tumor

    PubMed Central

    Ennazk, Laila; El Mghari, Ghizlane; El Ansari, Nawal

    2016-01-01

    Summary Primary hyperparthyrodism (PHPT) is a common endocrine disease. It results from an inappropriate parathyroid hormone (PTH) secretion relative to serum ionized calcium level. Clinical manifestation of severe PHPT include bone disease called osteitis fibrosa cystica which reflects an increase osteoclastic resorption and osteoblastic activity. This high bone turnover is responsible of the occurrence of osteoclastomas, also named “brown tumors” (1). Rarely, PHPT may occur in inherited forms with association to fibrous jaw tumor that are unrelated to hyperparathyroidism. In this uncommon disease: hyperparathyroidism-jaw tumor (HPT-JT) syndrome, parathyroid tumor is frequently malignant and usually associated with nonendocrine malignancies (2). We report a case of a HPT-JT syndrome to focus on the differential diagnosis with brown tumors. PMID:27252751

  2. Unusual presentation of pulmonary tumor thrombotic microangiopathy with no detectable primary tumor.

    PubMed

    Seppala, N; Cala, A; Klebe, S

    2009-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare condition characterized by the presence of diffuse thrombotic microthrombi and fibrocellular intimal proliferation in the pulmonary vasculature. Its development is linked to the presence of pulmonary tumor microemboli (PTM) and should be suspected in patients with unexplained dyspnea, especially in the presence of adenocarcinoma. PTTM presents in a similar fashion to respiratory disease such as pulmonary embolism, pulmonary hypertension or pneumonia and is usually only diagnosed post-mortem. We report a case of PTTM identified ante-mortem by bronchial biopsy in an 82-year-old woman presenting with a clinical picture of atypical pneumonia. Autopsy confirmed PTTM, from an unknown primary neoplasm.

  3. Primary brain tumors, neural stem cell, and brain tumor cancer cells: where is the link?

    PubMed Central

    Germano, Isabelle; Swiss, Victoria; Casaccia, Patrizia

    2010-01-01

    The discovery of brain tumor-derived cells (BTSC) with the properties of stem cells has led to the formulation of the hypothesis that neural stem cells could be the cell of origin of primary brain tumors (PBT). In this review we present the most common molecular changes in PBT, define the criteria of identification of BTSC and discuss the similarities between the characteristics of these cells and those of the endogenous population of neural stem cells (NPCs) residing in germinal areas of the adult brain. Finally, we propose possible mechanisms of cancer initiation and progression and suggest a model of tumor initiation that includes intrinsic changes of resident NSC and potential changes in the microenvironment defining the niche where the NSC reside. PMID:20045420

  4. Use of complementary and alternative medical therapy by patients with primary brain tumors.

    PubMed

    Armstrong, Terri S; Gilbert, Mark R

    2008-05-01

    The use of complementary and alternative medicine (CAM) is increasing. CAM includes mind-body interventions, biologically based therapies, energy therapies, and body-based methods. Primary brain tumors arise within the brain and have a poor prognosis when malignant. Even patients with benign tumors suffer neurologic and systemic symptoms as a result of the tumor or its treatment. CAM is used by 30% of brain tumor patients, who often do not report its use to their physician. Herbal medicines may affect the metabolism of prescribed medications or produce adverse effects that may be attributed to other causes. In patients with systemic cancer, mind-body modalities such as meditation and relaxation therapy have been shown to be helpful in reducing anxiety and pain; acupuncture and hypnotherapy may also reduce both pain and nausea. Recent preclinical studies have reported that ginseng, Scutellaria baicalensis, and Angelica sinensis may promote apoptosis of tumor cells or exercise antiangiogenic effects. Further studies are needed to evaluate the impact of CAM on symptom control or tumor growth in this vulnerable patient population.

  5. Primary retroperitoneal mucinous tumors: a clinicopathologic study of 18 cases.

    PubMed

    Roma, Andres Anibal; Malpica, Anais

    2009-04-01

    Primary retroperitoneal mucinous tumors (PRMTs) are uncommon neoplasms occurring almost exclusively in women. PRMTs are divided into mucinous cystadenoma (MC), mucinous borderline tumors or tumors of low malignant potential (MLMP), and mucinous carcinomas (MCas). In this retrospective study, we present the clinicopathologic features of 18 such cases, the largest series to date. All patients were women, ranging in age from 20 to 63 years (mean 38.6 y). All except 2 patients presented with an enlarged mass during a routine examination or by self-palpation. All tumors were located exclusively in the retroperitoneum, with histologic or clinical confirmation of the lack of ovarian involvement. The tumors ranged from 7 to 26 cm (mean 13.2 cm). The gross appearance was variable: unilocular cyst with a thin wall (4 cases), predominantly cystic with papillary areas or nodule(s) (8 cases), multiloculated cyst with or without nodules (1 case each), and predominantly solid with cystic areas (4 cases). Histologically, there were 2 cases of MC, 7 of MLMP (7 cases; 3 of them with intraepithelial carcinoma and 1 with microinvasion), and 9 of MCas (9 cases, 5 of them associated with MLMP and 1 associated with MC). Three of the MCas had areas of anaplastic or sarcomatoid carcinoma whereas 1 had an associated sarcoma. Immunohistochemical studies were performed in 6 cases. Cytokeratin 7 was diffusely positive in all cases studied, whereas cytokeratin 20 and cytokeratin 17 were focally positive in 4 and 2 cases, respectively. All patients underwent surgical resection of the entire tumor. Two patients with MCa and sarcoma or sarcomatoid carcinoma received chemotherapy. Follow-up was available in 16 cases, ranging from 1 to 148 months (mean 40 mo, median 22 mo). Two patients died of disease at 5 and 9 months; both had MCa with anaplastic carcinoma or sarcoma. Three patients with MCa were alive with disease at 14, 26, and 58 months. The remaining patients were alive with no evidence of

  6. Rare Primary Central Nervous System Tumors Encountered in Pediatrics.

    PubMed

    Kramer, Kim

    2016-10-01

    As part of the special issue on Pediatric Neuro-Oncology, this article will focus on 4 of the rarer tumors in this spectrum, including atypical teratoid rhabdoid tumors, embryonal tumors with multilayered rosettes, choroid plexus tumors, and pleomorphic xanthoastrocytoma. Incidence and current understanding of the molecular pathogenesis of these tumors are discussed, and avenues of therapy both current and prospective are explored.

  7. Use of chlorotoxin for targeting of primary brain tumors.

    PubMed

    Soroceanu, L; Gillespie, Y; Khazaeli, M B; Sontheimer, H

    1998-11-01

    Gliomas are primary brain tumors that arise from differentiated glial cells through a poorly understood malignant transformation. Although glioma cells retain some genetic and antigenic features common to glial cells, they show a remarkable degree of antigenic heterogeneity and variable mutations in their genome. Glioma cells have recently been shown to express a glioma-specific chloride ion channel (GCC) that is sensitive to chlorotoxin (CTX), a small peptide purified from Leiurus quinquestriatus scorpion venom [N. Ullrich et al, Neuroreport, 7: 1020-1024, 1996; and N. Ullrich and H. Sontheimer, Am. J. Physiol. (Cell Physiol.), 270: C1511-C1521, 1996]. Using native and recombinant 125I-labeled CTX, we show that toxin binding to glioma cells is specific and involves high affinity [dissociation constant (Kd)=4.2 nM] and low affinity (Kd=660 nml) binding sites. In radioreceptor assays, 125I-labeled CTX binds to a protein with Mr=72,000, presumably GCC or a receptor that modulates GCC activity. In vivo targeting and biodistribution experiments were obtained using 125I- and (131)I-labeled CTX injected into severe combined immunodeficient mice bearing xenografted gliomas. CTX selectively accumulated in the brain of tumor-bearing mice with calculated brain: muscle ratios of 36.4% of injected dose/g (ID/g), as compared to 12.4% ID/g in control animals. In the tumor-bearing severe combined immunodeficient mice, the vast majority of the brain-associated radioactivity was localized within the tumor (tumor:muscle ratio, 39.13% ID/g; contralateral brain:muscle ratio, 6.68%ID/g). Moreover, (131)I-labeled CTX distribution, visualized through in vivo imaging by gamma ray camera scans, demonstrates specific and persistent intratumoral localization of the radioactive ligand. Immunohistochemical studies using biotinylated and fluorescently tagged CTX show highly selective staining of glioma cells in vitro, in situ, and in sections of patient biopsies. Comparison tissues including

  8. P15, MDM2, NF-κB, and Bcl-2 expression in primary bone tumor and correlation with tumor formation and metastasis

    PubMed Central

    Qian, Guibin; Hao, Songnan; Yang, Dawei; Meng, Qinggang

    2015-01-01

    Primary bone tumor is one of the most common malignant tumors in skeletal system. It seriously affected bone movement and development with unclear pathogenesis. In this paper, rabbit VX-2 malignant bone tumor model was applied to explore apoptotic genes P15, MDM2, NF-κB and Bcl-2 correlation with primary bone tumor occurrence and metastasis. 0.3 ml rabbit VX-2 tumor cell suspension (1×106/ml) was injected to the marrow cavity of the right tibia condyle to establish the rabbit malignant bone tumor model, while equal amount of the saline was injected to the left tibia as control. Real-time PCR was applied to determine P15, MDM2, NF-κB and Bcl-2 expression level. Immunohistochemistry was performed to detect the abovementioned genes expression in lung, stomach, kidney and bladder. Compared with control, P15 expression level in the inoculation site surrounding tissues decreased obviously following the inoculate time elongation (P<0.05), while Bcl-2, MDM2 and NF-κB expression significantly increased (P<0.05). Bcl-2 showed significant correlation with MDM2 and NF-κB (P<0.05). At the 2, 4, 6 weeks, Bcl-2, MDM2 and NF-κB in lung, Bcl-2 in kidney, and Bcl-2 and MDM2 in bladder positively expressed (P<0.05), whereas P15 gene exhibited no significant positive expression in these tissues (P>0.05). P15, MDM2, NF-κB, and Bcl-2 genes expression levels can effectively reflect malignant bone tumor growth of rabbit tibia. MDM2, NF-κB and Bcl-2 genes involved in primary bone tumors metastasis directly. It has important clinical significance for early diagnosis and treatment of primary bone tumor. PMID:26823818

  9. CT and angiography of primary extradural juxtasellar tumors

    SciTech Connect

    Moore, T.; Ganti, S.R.; Mawad, M.E.; Hilal, S.K.

    1985-09-01

    The computed tomographic and angiographic features of 15 histologically proven primary extradural juxtasellar tumors were retrospectively reviewed. Five chordomas were characterized by prominent bone erosion and a significant posterior fossa component. Four trigeminal nerve neuromas each demonstrated bone erosion centered about Meckel's cave and moderate to marked contrast enhancement. Two cavernous sinus meningiomas revealed moderate contrast enhancement, expansion of the cavernous sinus, and moderate angiographic stain. Two cavernous hemangiomas of the cavernous sinus were intensely enhancing and demonstrated angiographic stain. Opacification of the sphenoid sinus with prominent bone destruction and lack of contrast enhancement was characteristic of a sphenoid sinus mucocele. The dural reflection could be directly visualized or indirectly inferred in each case.

  10. Pattern of primary tumors and tumor-like lesions of bone in children: retrospective survey of biopsy results

    PubMed Central

    Özkan, Esra Akyüz; Göret, Ceren Canbey; Özdemir, Zeynep Tuğba; Yanık, Serdar; Doğan, Meryem; Gönültaş, Aylin; Akkoca, Ayşe Neslin

    2015-01-01

    Background: Although primary bone tumors are relatively uncommon, they constitute the most important tumors in patients less than 20 years. We aimed to determine the frequencies of primary bone tumors and tumor-like lesions of bone and the anatomical sites of their occurrence. Methods: A retrospective review of histopathology reports of all bone specimens received in a private pathology laboratory in Istanbul between 2009 and 2015. Results: A total of 57 patients (aged 5 to 18 years) with a mean of 13.12 years were studied. Thirty five patients (61.4%) were males and 22 (38.6%) were females. Fifty five (94.4%) of the tumors were benign. Osteochondroma was the commonest tumor accounting for 31 cases (54.3%) followed by osteoid osteoma, 9 cases (15.7%). Chondrosarcoma observed in two patients and Ewing sarcoma in one patient as malignant tumors. Of the 57 bone tumors 13 (22.8%) occurred in the upper extremities, while 44 (77.2%) were in the lower extremities. Proximal humerus was the most commonly involved site in upper extremity tumors, with osteochondromas representing the most frequent type of tumor (4 patients; 7%). In the lower extremities again osteochondromas were the most common type of tumor (8 cases, 14%), with the femur being the most common site of involvement (18 patients, 31.5%). Of the patients with tumor-like lesions; four patients had fibrous dysplasia, 4 patients had non-ossified fibromas, 4 patients had simple bone cysts and 3 had aneurismal bone cyst. Conclusion: This study showed that primary bone tumors were mainly benign, settled predominantly in the lower extremities mostly in the femur with a male preponderance. Osteochondroma was the most common benign bone tumor. We didn’t observed osteosarcoma, which is the most frequent malignant bone tumor. PMID:26617888

  11. Significant predictors of patients' uncertainty in primary brain tumors.

    PubMed

    Lin, Lin; Chien, Lung-Chang; Acquaye, Alvina A; Vera-Bolanos, Elizabeth; Gilbert, Mark R; Armstrong, Terri S

    2015-05-01

    Patients with primary brain tumors (PBT) face uncertainty related to prognosis, symptoms and treatment response and toxicity. Uncertainty is correlated to negative mood states and symptom severity and interference. This study identified predictors of uncertainty during different treatment stages (newly-diagnosed, on treatment, followed-up without active treatment). One hundred eighty six patients with PBT were accrued at various points in the illness trajectory. Data collection tools included: a clinical checklist/a demographic data sheet/the Mishel Uncertainty in Illness Scale-Brain Tumor Form. The structured additive regression model was used to identify significant demographic and clinical predictors of illness-related uncertainty. Participants were primarily white (80 %) males (53 %). They ranged in age from 19-80 (mean = 44.2 ± 12.6). Thirty-two of the 186 patients were newly-diagnosed, 64 were on treatment at the time of clinical visit with MRI evaluation, 21 were without MRI, and 69 were not on active treatment. Three subscales (ambiguity/inconsistency; unpredictability-disease prognoses; unpredictability-symptoms and other triggers) were different amongst the treatment groups (P < .01). However, patients' uncertainty during active treatment was as high as in newly-diagnosed period. Other than treatment stages, change of employment status due to the illness was the most significant predictor of illness-related uncertainty. The illness trajectory of PBT remains ambiguous, complex, and unpredictable, leading to a high incidence of uncertainty. There was variation in the subscales of uncertainty depending on treatment status. Although patients who are newly diagnosed reported the highest scores on most of the subscales, patients on treatment felt more uncertain about unpredictability of symptoms than other groups. Due to the complexity and impact of the disease, associated symptoms, and interference with functional status, comprehensive assessment of patients

  12. Imaging features of primary tumors of the spine: A pictorial essay

    PubMed Central

    Patnaik, Sujata; Jyotsnarani, Y; Uppin, Shantiveer G; Susarla, Rammurti

    2016-01-01

    Primary tumors of spine are rare accounting for less than 5% of new bone tumors diagnosed every year. These tumors may exhibit characteristic imaging features that can help in early diagnosis and improved prognosis. Plasmacytoma/multiple myeloma and lymphoproliferative tumors are the most common malignant primary spinal tumors. Hemangioma is the most common benign tumor of the spine. Computed tomography is useful to assess tumor matrix and osseous change. Magnetic resonance is useful to study associated soft tissue extension, marrow infiltration, and intraspinal extension. Confusing one tumor with the other based on only imaging findings is not uncommon. However, radiologic manifestations of these tumors need to be correlated with the age, sex, location, and presentation to arrive at a close clinical diagnosis. PMID:27413280

  13. Modulation of Tumor Tolerance in Primary Central Nervous System Malignancies

    PubMed Central

    Johnson, Theodore S.; Munn, David H.; Maria, Bernard L.

    2012-01-01

    Central nervous system tumors take advantage of the unique immunology of the CNS and develop exquisitely complex stromal networks that promote growth despite the presence of antigen-presenting cells and tumor-infiltrating lymphocytes. It is precisely this immunological paradox that is essential to the survival of the tumor. We review the evidence for functional CNS immune privilege and the impact it has on tumor tolerance. In this paper, we place an emphasis on the role of tumor-infiltrating myeloid cells in maintaining stromal and vascular quiescence, and we underscore the importance of indoleamine 2,3-dioxygenase activity as a myeloid-driven tumor tolerance mechanism. Much remains to be discovered regarding the tolerogenic mechanisms by which CNS tumors avoid immune clearance. Thus, it is an open question whether tumor tolerance in the brain is fundamentally different from that of peripheral sites of tumorigenesis or whether it simply stands as a particularly strong example of such tolerance. PMID:22312408

  14. Second primary tumors following radiotherapy for childhood cancer

    SciTech Connect

    Hawkins, M.M. )

    1990-11-01

    Among a cohort of 9,279 survivors of childhood neoplasms other than retinoblastoma treated in Britain before 1980, the cumulative risk of a second primary tumor (SPT) by 25 years from 3-year survival was 3.7%. This corresponds to about five times the number expected from rates of cancer occurring in the general population. In the absence of both radiotherapy and chemotherapy, there was four times the expected number of subsequent cancers. The risk of an SPT associated with radiotherapy but not chemotherapy and both radiotherapy and chemotherapy were 6 and 9 times that expected, respectively. There is evidence that radiotherapy was involved in the development of many of the SPT's observed. However, case-control investigations are required to examine the relationship between relative risk of an SPT and therapy in detail. Secondary leukemia appears to occur more frequently among more recently diagnosed children with cancer. It is important to continue to monitor the occurrence of SPT's with a view to identifying the least carcinogenic therapies that are consistent with not compromising survival prospects.

  15. Comparative Membranome expression analysis in primary tumors and derived cell lines.

    PubMed

    Uva, Paolo; Lahm, Armin; Sbardellati, Andrea; Grigoriadis, Anita; Tutt, Andrew; de Rinaldis, Emanuele

    2010-01-01

    Despite the wide use of cell lines in cancer research, the extent to which their surface properties correspond to those of primary tumors is poorly characterized. The present study addresses this problem from a transcriptional standpoint, analyzing the expression of membrane protein genes--the Membranome--in primary tumors and immortalized in-vitro cultured tumor cells. 409 human samples, deriving from ten independent studies, were analyzed. These comprise normal tissues, primary tumors and tumor derived cell lines deriving from eight different tissues: brain, breast, colon, kidney, leukemia, lung, melanoma, and ovary. We demonstrated that the Membranome has greater power than the remainder of the transcriptome when used as input for the automatic classification of tumor samples. This feature is maintained in tumor derived cell lines. In most cases primary tumors show maximal similarity in Membranome expression with cell lines of same tissue origin. Differences in Membranome expression between tumors and cell lines were analyzed also at the pathway level and biological themes were identified that were differentially regulated in the two settings. Moreover, by including normal samples in the analysis, we quantified the degree to which cell lines retain the Membranome up- and down-regulations observed in primary tumors with respect to their normal counterparts. We showed that most of the Membranome up-regulations observed in primary tumors are lost in the in-vitro cultured cells. Conversely, the majority of Membranome genes down-regulated upon tumor transformation maintain lower expression levels also in the cell lines. This study points towards a central role of Membranome genes in the definition of the tumor phenotype. The comparative analysis of primary tumors and cell lines identifies the limits of cell lines as a model for the study of cancer-related processes mediated by the cell surface. Results presented allow for a more rational use of the cell lines as a

  16. Primary osseous tumors of the pediatric spinal column: review of pathology and surgical decision making.

    PubMed

    Ravindra, Vijay M; Eli, Ilyas M; Schmidt, Meic H; Brockmeyer, Douglas L

    2016-08-01

    Spinal column tumors are rare in children and young adults, accounting for only 1% of all spine and spinal cord tumors combined. They often present diagnostic and therapeutic challenges. In this article, the authors review the current management of primary osseous tumors of the pediatric spinal column and highlight diagnosis, management, and surgical decision making. PMID:27476845

  17. Primary osseous tumors of the pediatric spinal column: review of pathology and surgical decision making.

    PubMed

    Ravindra, Vijay M; Eli, Ilyas M; Schmidt, Meic H; Brockmeyer, Douglas L

    2016-08-01

    Spinal column tumors are rare in children and young adults, accounting for only 1% of all spine and spinal cord tumors combined. They often present diagnostic and therapeutic challenges. In this article, the authors review the current management of primary osseous tumors of the pediatric spinal column and highlight diagnosis, management, and surgical decision making.

  18. Epigenetic regulation of human hedgehog interacting protein in glioma cell lines and primary tumor samples

    PubMed Central

    Shahi, Mehdi H.; Zazpe, Idoya; Afzal, Mohammad; Sinha, Subrata; Rebhun, Robert B.; Meléndez, Bárbara; Rey, Juan A.

    2016-01-01

    Glioma constitutes one of the most common groups of brain tumors, and its prognosis is influenced by different genetic and epigenetic modulations. In this study, we demonstrated low or no expression of hedgehog interacting protein (HHIP) in most of the cell lines and primary glioma tumor samples. We further proceeded to promoter methylation study of this gene in the same cell lines and primary tumor samples and found 87 % (7/8) HHIP methylation in glioblastoma cell lines and 75 % (33/44) in primary tumor samples. These methylation pattern correlates with low or unexpressed HHIP in both cell lines and primary tumor samples. Our results suggest the possibility of epigenetic regulation of this gene in glioma, similarly to medulloblastoma, gastric, hepatic, and pancreatic cancers. Also, HHIP might be a diagnostic or prognostic marker in glioma and help to the detection of these tumors in early stages of disease. PMID:25416442

  19. Primary tumor inflammation in gross tumor volume as a prognostic factor for nasopharyngeal carcinoma patients

    PubMed Central

    Peng, Hao; Chen, Lei; Tang, Ling-Long; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    Purpose The objective of this study is to investigate the prognostic value of primary tumor inflammation (PTI) in nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT). Results PTI was observed in 376/1708 (22.0%) patients, and was present in the sphenoid sinus in 289/376 (76.9%), in the nasal cavity in 27 (7.2%), and in both places in 60 (15.9%). The estimated 4-year local relapse-free survival (LRFS), disease-free survival (DFS), overall survival (OS) and distant metastasis-free survival (DMFS) rates for PTI vs. non-PTI group were 89.2% vs. 96.1% (P < 0.001), 73.4% vs. 85.1% (P < 0.001), 85.0% vs. 92.1% (P < 0.001) and 83.6% vs. 91.4% (P < 0.001), respectively. After adjustment for these known prognostic factors, PTI was confirmed as an independent prognostic factor for LRFS (HR 2.152, 95% CI 1.318–3.516, P = 0.002), DFS (HR 1.581, 95% CI 1.204–2.077, P = 0.001) and DMFS (HR 1.682, 95% CI 1.177–2.402, P = 0.004). Conclusions Primary tumor inflammation was identified as a strong prognostic factor for patients with NPC in the era of IMRT and should be considered when devising future treatment strategies aimed at improving survival in NPC patients. Materials and Methods Data on 1708 patients with nonmetastatic, histologically-confirmed NPC treated with IMRT between November 2009 and February 2012 at Sun Yat-Sen University Cancer Center were retrospectively reviewed. Patient survival between PTI and non-PTI groups were compared. PMID:26934649

  20. Gene modification of primary tumor cells for active immunotherapy of human breast and ovarian cancer.

    PubMed

    Philip, R; Clary, B; Brunette, E; Kilinski, L; Murugesh, D; Sorich, M; Yau, J; Lebkowski, J; Lyerly, H K; Philip, M

    1996-01-01

    We have previously shown that cationic liposomes facilitate adeno-associated virus (AAV) plasmid transfections of primary and cultured cell types. To test the clinical feasibility of using genetically modified tumor vaccines for the treatment of breast and ovarian cancers, we have constructed an expression plasmid pMP6IL2 and investigated the use of liposome-mediated gene delivery into primary, uncultured human breast and ovarian tumor cells to produce interleukin 2 (IL-2)-secreting tumor cells. We have demonstrated significant levels of IL-2 expression in tumor cell lines and primary breast and ovarian tumor cells using this AAV-based expression plasmid complexed to cationic liposomes. Transfections with the non-AAV plasmid containing the identical expression cassette as the AAV plasmid induced IL-2 expression in the tumor cell line but failed to produce IL-2 in primary tumor cells. Significant levels of IL-2 were induced with the AAV plasmid regardless of liposome compositions used for transfection. The transfected breast cell line and primary tumor cells were able to express the transgene product for up to 28 days after lethal radiation. The transfection efficiency was comparable for both the tumor cell line and primary tumor cells and ranged from 20 to 50% for both cell types as assessed by intracellular IL-2 staining. Although the primary tumor cell preparations consist of mixed population of cells, at least 40% of the tumor cells expressed the transgene as assessed by immunostaining for IL-2. The ability to efficiently express transgenes in freshly isolated, nondividing tumor cells may potentiate active immunotherapy strategies for gene-based cancer treatment.

  1. Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

    PubMed Central

    Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

    2014-01-01

    The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

  2. Total En Bloc Spondylectomy for Primary and Metastatic Spine Tumors.

    PubMed

    Mesfin, Addisu; El Dafrawy, Mostafa H; Jain, Amit; Hassanzadeh, Hamid; Kebaish, Khaled M

    2015-11-01

    This study reports the surgical and clinical outcomes of spinal tumors managed with total en bloc spondylectomy. The authors searched their prospectively maintained database for patients undergoing total en bloc spondylectomy between 2001 and 2013. Ten patients (9 men, 1 woman; average age, 50.7 years; range, 42-68 years) were identified. The authors obtained demographic information, surgical outcomes (estimated blood loss, complications), and clinical outcomes (recurrence, survival). All patients had pain and were classified as American Spinal Injury Association grade E. The lesions were located in the thoracic (8 patients) and lumbar (2 patients) spine. Anterior column reconstruction was performed with strut allograft (7 patients), mesh cage (2 patients), and polymethyl methacrylate (1 patient). An average of 2.3 (range, 2-4) of 6 portions of the vertebrae were involved, according to the Kostuik classification. Mean estimated blood loss, operative time, and hospital stay were 3.5 L, 500 minutes, and 7.8 days, respectively. Perioperative complications included pleural tear (2 patients) and aortic tear, vena cava tear, retained sponge, pulmonary embolism, urinary tract infection, pneumothorax, anterior column support failure, and prominent instrumentation requiring removal (1 patient each). Postoperatively, all patients remained classified as American Spinal Injury Association grade E. Two patients had recurrence at distant spinal segments, and 1 had a new lesion in the thigh. Five patients had died (mean, 34.5 months after surgery), and 5 were alive a mean of 19.6 months after surgery (range, 6-48 months). Total en bloc spondylectomy is challenging, but in appropriately selected patients, it can be used to treat primary and metastatic spinal lesions.

  3. Cilengitide in Treating Children With Refractory Primary Brain Tumors

    ClinicalTrials.gov

    2013-09-27

    Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  4. Factors affecting the estimate of primary production from space

    NASA Technical Reports Server (NTRS)

    Balch, W. M.; Byrne, C. F.

    1994-01-01

    Remote sensing of primary production in the euphotic zone has been based mostly on visible-band and water-leaving radiance measured with the coastal zone color scanner. There are some robust, simple relationships for calculating integral production based on surface measurements, but they also require knowledge for photoadaptive parameters such as maximum photosynthesis which currently cannot be obtained from spave. A 17,000-station data set is used to show that space-based estimates of maximum photosynthesis could improve predictions of psi, the water column light utiliztion index, which is an important term in many primary productivity models. Temperature is also examined as a factor for predicting hydrographic structure and primary production. A simple model is used to relate temperature and maximum photosynthesis; the model incorporates (1) the positive relationship between maximum photosynthesis and temperature and (2) the strongly negative relationship between temperature and nitrate in the ocean (which directly affects maximum growth rates via nitrogen limitation). Since these two factors relate to carbon and nitrogen, 'balanced carbon/nitrogen assimilation' was calculated using the Redfield ratio, It is expected that the relationship between maximum balanced carbon assimilation versus temperature is concave-down, with the peak dependent on nitrate uptake kinetics, temperature-nitrate relationships,a nd the carbon chlorophyll ration. These predictions were compared with the sea truth data. The minimum turnover time for nitrate was also calculated using this approach. Lastly, sea surface temperature gradients were used to predict the slope of isotherms (a proxy for the slope of isopycnals in many waters). Sea truth data show that at size scales of several hundred kilometers, surface temperature gradients can provide information on the slope of isotherms in the top 200 m of the water column. This is directly relevant to the supply of nutrients into the surface

  5. Factors affecting the estimate of primary production from space

    NASA Astrophysics Data System (ADS)

    Balch, W. M.; Byrne, C. F.

    1994-04-01

    Remote sensing of primary production in the euphotic zone has been based mostly on visible-band water-leaving radiance measured with the coastal zone color scanner. There are some robust, simple relationships for calculating integral production based on surface measurements, but they also require knowledge of photoadaptive parameters such as maximum photosynthesis which currently cannot be obtained from space. A 17,000-station data set is used to show that space-based estimates of maximum photosynthesis could improve predictions of ψ, the water column light utilization index, which is an important term in many primary productivity models. Temperature is also examined as a factor for predicting hydrographic structure and primary production. A simple model is used to relate temperature and maximum photosynthesis; the model incorporates (1) the positive relationship between maximum photosynthesis and temperature and (2) the strongly negative relationship between temperature and nitrate in the ocean (which directly affects maximum growth rates via nitrogen limitation). Since these two factors relate to carbon and nitrogen, "balanced carbon/nitrogen assimilation" was calculated assuming the Redfield ratio. It is expected that the relationship between maximum balanced carbon assimilation versus temperature is concave-down, with the peak dependent on nitrate uptake kinetics, temperature-nitrate relationships, and the carbon/chlorophyll ratio. These predictions were compared with sea truth data. The minimum turnover time for nitrate was also calculated using this approach. Lastly, sea surface temperature gradients were used to predict the slope of isotherms (a proxy for the slope of isopycnals in many waters). Sea truth data show that at size scales of several hundred kilometers, surface temperature gradients can provide information on the slope of isotherms in the top 200 m of the water column. This is directly relevant to the supply of nutrients into the surface mixed

  6. Mutational analysis of multiple tumor suppressor 1 (MTS1) gene in human primary breast tumors and established breast tumor cell lines

    SciTech Connect

    Xu, L.; Sgroi, D.; Sterner, C.

    1994-09-01

    A putative tumor suppressor gene on the short arm of human chromosome 9 has been identified recently and named as multiple tumor suppressor 1 (MTS1). MTS1 is identical to the previously identified cyclin-dependent kinase-4 inhibitor gene p16, a cell cycle regulatory protein. Frequent homozygous deletions of MTS1 gene has been documented recently in cell lines derived from different types of tumors including breast tumors, suggesting that MTS1 is a tumor suppressor gene that is probably involved in a variety of human tumors. To determine the frequency of MTS1 mutations in primary breast tumors, we screened 39 primary breast tumors (16 lobular carcinoma and 23 ductal carcinoma) and 5 established breast tumor cell lines by utilizing single stranded conformational polymorphism (SSCP) analysis. SSCP analysis was carried out for all 3 exons of the MTS1 gene utilizing primers in the flanking intronic sequences. Two of the five breast cancer tumor cell lines analyzed exhibited deletion of the entire MTS1 gene. However, only one of the thirty-nine primary breast tumors revealed a potential SSCP variation in exon 2 of the MTS1 gene which is currently characterized by sequencing. SSCP analysis also revealed two intragenic polymorphisms, one in exon 2 and one in the 3{prime} untranslated region, that could be used to assay allelic loss directly at the MTS1 locus. These results suggest that the mutation of the MTS1 gene may not be a critical genetic change in the formation of primary breast cancer, and the deletions observed in breast tumor cell lines may be due to product of cell growth in vitro.

  7. A multicenter study of primary brain tumor incidence in Australia (2000–2008)

    PubMed Central

    Dobes, Martin; Shadbolt, Bruce; Khurana, Vini G.; Jain, Sanjiv; Smith, Sarah F.; Smee, Robert; Dexter, Mark; Cook, Raymond

    2011-01-01

    There are conflicting reports from Europe and North America regarding trends in the incidence of primary brain tumor, whereas the incidence of primary brain tumors in Australia is currently unknown. We aimed to determine the incidence in Australia with age-, sex-, and benign-versus-malignant histology-specific analyses. A multicenter study was performed in the state of New South Wales (NSW) and the Australian Capital Territory (ACT), which has a combined population of >7 million with >97% rate of population retention for medical care. We retrospectively mined pathology databases servicing neurosurgical centers in NSW and ACT for histologically confirmed primary brain tumors diagnosed from January 2000 through December 2008. Data were weighted for patient outflow and data completeness. Incidence rates were age standardized and trends analyzed using joinpoint analysis. A weighted total of 7651 primary brain tumors were analyzed. The overall US-standardized incidence of primary brain tumors was 11.3 cases 100 000 person-years (±0.13; 95% confidence interval, 9.8–12.3) during the study period with no significant linear increase. A significant increase in primary malignant brain tumors from 2000 to 2008 was observed; this appears to be largely due to an increase in malignant tumor incidence in the ≥65-year age group. This collection represents the most contemporary data on primary brain tumor incidence in Australia. Whether the observed increase in malignant primary brain tumors, particularly in persons aged ≥65 years, is due to improved detection, diagnosis, and care delivery or a true change in incidence remains undetermined. We recommend a direct, uniform, and centralized approach to monitoring primary brain tumor incidence that can be independent of multiple interstate cancer registries. PMID:21727214

  8. Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumor of breast

    PubMed Central

    Srivastava, Smita; Arora, Jyoti; Parakh, Anushri; Goel, Ruchika Kumar

    2016-01-01

    Extraskeletal Ewing's sarcoma (EES) is a rare soft tissue tumor that is morphologically indistinguishable from skeletal ES. We report a case of a 25-year-old female with recurrent EES/primitive neuroectodermal tumor of right breast with imaging findings on mammogram, ultrasound, magnetic resonance imaging breast, and positron emission tomography–computed tomography. PMID:27413270

  9. Primary renal carcinoid tumor: case report and review of the literature

    PubMed Central

    Li, Bin; Cui, Tongyue; Ban, Ziqin; Luo, Lei; Sun, Lijiang

    2016-01-01

    Objective The aim of this case report is to discuss the clinicopathological features of a patient with a primary renal carcinoid tumor. Methods We report on the clinical and pathological information of one case of a patient with a primary renal carcinoid tumor as well as review relative literature. Results The patient was diagnosed with a renal tumor when she received physical examination, and exhibited no positive symptoms. The diameter of tumor was 5 cm, the cross surface of the tumor was light yellow and firm, and the central part was soft with hemorrhage and necrosis. Immunohistochemical staining revealed strong and diffuse staining with synaptophysin, chromogranin A, and neuron-specific enolase. Conclusion A primary renal carcinoid tumor is extremely rare. Surgical resection is a preferred therapeutic method. PMID:26966374

  10. The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors

    PubMed Central

    de Lacerda Almeida, Bernardo Gomes; Bacchi, Carlos E; Carvalho, Jesus P; Ferreira, Cristiane R; Carvalho, Filomena M

    2014-01-01

    OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2. PMID:25518016

  11. Increased risk of concurrent primary malignancies in patients diagnosed with a primary malignant epithelial ovarian tumor.

    PubMed

    van Niekerk, Catharina C; Vooijs, G Peter; Bulten, Johan; van Dijck, Jos A A M; Verbeek, Andre L M

    2007-03-01

    Ovarian cancer and second malignant neoplasms are found to occur rather frequently in the same patient. From a clinical perspective, it is important to have quantitative information on concurrent malignancies in the same year of diagnosis of the epithelial ovarian cancer. In this population-based study, we used data from the Netherlands Nationwide Network for Registry of histo- and cytopathology (PALGA) and the Netherlands Cancer Registry (NCR). Data of the ovarian cancer as well as data on previous or later cancers were obtained. Age-specific cancer rates from the NCR were used to calculate expected numbers of cancer. Between 1987 and 1993, histopathology reports were identified of 4577 patients with primary epithelial malignant or primary borderline malignant ovarian cancers and its longitudinal data. As the database may lack detailed information on histopathology, a recent sample of 789 patients diagnosed with ovarian cancer in 1996-2003 was comprehensively studied as well. In the eventual data analysis of 5366 patients, 244 cases (4.5%) of concurrent primary malignancy were reported in the same year that the malignant epithelial ovarian tumor had been diagnosed against 51 expected. The observed vs expected ratio was 4.8 and the 95% confidence interval (CI) (4.3-5.5). For cancer of the uterus/endometrium the observed vs expected ratio was 62.3 (95% CI 52.5-73.5). For skin, breast, colorectal, urinary bladder, renal and cervical cancer the ratio was also larger than unity. The elevated risk of concurrent cancer may lead to clinical screening protocols. The findings on endometrial cancer may prompt research on common etiologies and biomarkers.

  12. Primary pulmonary carcinoid tumor with metastasis to endometrial polyp

    PubMed Central

    Momeni, Mazdak; Kolev, Valentin; Costin, Dan; Mizrachi, Howard H.; Chuang, Linus; Warner, Richard R.P.; Gretz, Herbert F.

    2012-01-01

    INTRODUCTION A carcinoid tumor occurring in the endometrium has been documented in the literature, but there is no report in regard to carcinoid tumor metastasis to endometrium. PRESENTATION OF CASE We report a case of a malignant carcinoid metastasis to an endometrial polyp. Patient underwent hysteroscopy, and polypectomy. The pathology demonstrated an endometrial polyp containing a 4 mm x 5 mm nodule of metastatic carcinoid tumor, consistent with metastasis from patient's known pulmonary carcinoid. The tumor was morphologically similar to the tumors of the right lung, with similar immune-profile. DISCUSSION This patient presented with a suspicious pelvic ultrasound. Due to her age, the first priority was to exclude uterine cancer. The endometrial polyp, which was found, had a small focus of metastatic carcinoid tumor. To the best of our knowledge, this finding has not been previously recorded in the literature. Our patient also had a history of metastatic carcinoid tumor to breast. This finding is also very uncommon. CONCLUSION This is the first case in the literature described a malignant carcinoid metastasis to an endometrial polyp. PMID:23127865

  13. Genetic background affects susceptibility to tumoral stem cell reprogramming

    PubMed Central

    García-Ramírez, Idoia; Ruiz-Roca, Lucía; Martín-Lorenzo, Alberto; Blanco, Óscar; García-Cenador, María Begoña; García-Criado, Francisco Javier; Vicente-Dueñas, Carolina; Sánchez-García, Isidro

    2013-01-01

    The latest studies of the interactions between oncogenes and its target cell have shown that certain oncogenes may act as passengers to reprogram tissue-specific stem/progenitor cell into a malignant cancer stem cell state. In this study, we show that the genetic background influences this tumoral stem cell reprogramming capacity of the oncogenes using as a model the Sca1-BCRABLp210 mice, where the type of tumor they develop, chronic myeloid leukemia (CML), is a function of tumoral stem cell reprogramming. Sca1-BCRABLp210 mice containing FVB genetic components were significantly more resistant to CML. However, pure Sca1-BCRABLp210 FVB mice developed thymomas that were not seen in the Sca1-BCRABLp210 mice into the B6 background. Collectively, our results demonstrate for the first time that tumoral stem cell reprogramming fate is subject to polymorphic genetic control. PMID:23839033

  14. Molecular biology and genetics affecting pediatric solid tumors.

    PubMed

    Lugo-Vicente, H

    2000-01-01

    Since the discovery of oncogenes more than 20 years ago, it has been proven that cancer is a genetically determined disease. Multiple genetic alteration occurs during the course of an illness for neoplasia to develop. Transformation of positive cell growth regulators (oncogenes) and inactivations of negative cell growth regulators (tumor suppressor genes) merge to express a malignant phenotype. These genetic alterations occur as chromosomal translocations, deletions, inversion, amplification or point mutation. The objective of this review is to introduce basic concepts of molecular biology and describe the molecular genetics and biologic clinical findings of the most important solid malignant tumors in children, namely Neuroblastoma, Wilms and Rhabdomyosarcoma. It is the oncology surgeons responsibility to learn basic molecular genetics and tumor biology to provide rational and appropriate care in the setting of multidisciplinary management. Identifications of new oncogenes will continue to be important milestones in diagnosis, early detection of tumor recurrence, and as potential targets for gene therapy. Fusion proteins generated by mutated translocations are true tumor specific antigens and potential targets for therapy. The predicament is that they are proteins needing therapeutic manipulation within the tumor cell nuclei. Technological advances in molecular and genetics will develop tools necessary to manipulate the cell nuclear DNA and target cancer cell.

  15. Stromal Integrin α11β1 Affects RM11 Prostate and 4T1 Breast Xenograft Tumors Differently

    PubMed Central

    Skogstrand, Trude; Sortland, Kristina; Schmid, Marei Caroline; Reed, Rolf K.; Stuhr, Linda

    2016-01-01

    Purpose It has been implied that the collagen binding integrin α11β1 plays a role in carcinogenesis. As still relatively little is known about how the stromal integrin α11β1 affects different aspects of tumor development, we wanted to examine the direct effects on primary tumor growth, fibrosis, tumor interstitial fluid pressure (PIF) and metastasis in murine 4T1 mammary and RM11 prostate tumors, using an in vivo SCID integrin α11-deficient mouse model. Methods Tumor growth was measured using a caliper, PIF by the wick-in-needle technique, activated fibroblasts by α-SMA immunofluorescence staining and fibrosis by transmission electron microscopy and picrosirius-red staining. Metastases were evaluated using hematoxylin and eosin stained sections. Results RM11 tumor growth was significantly reduced in the SCID integrin α11-deficient (α11-KO) compared to in SCID integrin α11 wild type (WT) mice, whereas there was no similar effect in the 4T1 tumor model. The 4T1 model demonstrated an alteration in collagen fibril diameter in the integrin α11-KO mice compared to WT, which was not found in the RM11 model. There were no significant differences in the amount of activated fibroblasts, total collagen content, collagen organization or PIF in the tumors in integrin α11-deficient mice compared to WT mice. There was also no difference in lung metastases between the two groups. Conclusion Deficiency of stromal integrin α11β1 showed different effects on tumor growth and collagen fibril diameter depending on tumor type, but no effect on tumor PIF or development of lung metastasis. PMID:26990302

  16. HFE polymorphisms affect survival of brain tumor patients.

    PubMed

    Lee, Sang Y; Slagle-Webb, Becky; Sheehan, Jonas M; Zhu, Junjia; Muscat, Joshua E; Glantz, Michael; Connor, James R

    2015-03-01

    The HFE (high iron) protein plays a key role in the regulation of body iron. HFE polymorphisms (H63D and C282Y) are the common genetic variants in Caucasians. Based on frequency data, both HFE polymorphisms have been associated with increased risk in a number of cancers. The prevalence of the two major HFE polymorphisms in a human brain tumor patient populations and the impact of HFE polymorphisms on survival have not been studied. In the present study, there is no overall difference in survival by HFE genotype. However, male GBM patients with H63D HFE (H63D) have poorer overall survival than wild type HFE (WT) male GBM (p = 0.03). In GBM patients with the C282Y HFE polymorphism (C282Y), female patients have poorer survival than male patients (p = 0.05). In addition, female metastatic brain tumor patients with C282Y have shorter survival times post diagnosis than WT patients (p = 0.02) or male metastatic brain tumor patients with C282Y (p = 0.02). There is a tendency toward a lower proportion of H63D genotype in GBM patients than a non-tumor control group (p = 0.09) or other subtypes of brain tumors. In conclusion, our study suggests that HFE genotype impacts survival of brain tumor patients in a gender specific manner. We previously reported that glioma and neuroblastoma cell lines with HFE polymorphisms show greater resistance to chemo and radiotherapy. Taken together, these data suggest HFE genotype is an important consideration for evaluating and planning therapeutic strategies in brain tumor patients.

  17. Peptide-based method for detection of metastatic transformation in primary tumors of breast cancer.

    PubMed

    Li, Hao; Huang, Yue; Yu, Yue; Li, Weiwei; Yin, Yongmei; Li, Genxi

    2015-09-15

    Detection of metastatic activity before the onset of the actual metastasis can be a promising method to combat metastasis, the foremost cause of death in cancer. Therefore, in this work, we have developed an assay method for the detection of metastatic tumor cells in primary tumor, by using a protein of the metastatic cell signaling as the biomarker. In this assay, a peptide-based probe targeting the marker protein and a sensitive nanoparticle doped graphene nanolabel are combined to enable the detection of metastatic cells. Consequently, the metastatic cells can be specifically detected and discriminated from primary tumor cells. By applying this assay method to clinical samples of primary tumor, a low amount of metastatic activity can be detected in the tumor sites, which may suggest the activity of local metastatic transformation. So, these results may point to the prospect of using the proposed method for controlling metastatic cancer.

  18. Factors affecting nutritional status of Malaysian primary school children.

    PubMed

    Zaini, M Z Anuar; Lim, C T; Low, W Y; Harun, F

    2005-01-01

    This paper investigates the nutritional status of a randomly selected cohort of school children and the factors affecting it. This random survey was conducted in the state of Selangor, involving 1,405 primary students (aged 9-10 years from 54 national primary schools). Physical examination was carried out on all the students. Information on the students was also obtained from the parents. Blood samples were taken by using the finger pricking technique. Body mass index (BMI) was used as a measure of physical growth. The students were mainly from urban areas (82.9%). The mean age was 9.71 years and a higher proportion was females (51%). Malays constituted 83.6%, Indians 11.6% and Chinese 4.2% of the study population. The mean weight and height were 32.30 kg and 135.18 cm respectively. The mean BMI was 17.42 kg/m2, with 1.2% of the students underweight, 76.3% normal BMI, 16.3% overweight and 6.3% were obese. Nutritional status was significantly related to blood pressure, history of breast feeding, eating fast food, taking canned/bottled drinks, income and educational level of parents. Significant differences in nutritional status between sexes and locations (rural/urban) were also found. The prevalence of overweight and obese children was of concern. There is thus an urgent need for the School Health Program to periodically monitor the school children's eating habits and physical growth. Appropriate counselling on nutritional intake and physical activities should be given not only to schoolchildren but also to their teachers and parents or caregivers.

  19. Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

    NASA Astrophysics Data System (ADS)

    Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

    2016-08-01

    The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

  20. Primary Pulmonary Salivary Gland-type Tumors: A Review and Update.

    PubMed

    Falk, Nadja; Weissferdt, Annikka; Kalhor, Neda; Moran, Cesar A

    2016-01-01

    Pulmonary salivary gland-type tumors (SGT) comprise a very small proportion of primary lung neoplasms. The most common tumors among this group are mucoepidermoid carcinoma and adenoid cystic carcinoma. Contrary to the head and neck region, benign SGT such as pleomorphic adenomas are exceedingly rare in the pulmonary system. More recently, 2 additional SGT, namely hyalinizing clear cell carcinoma and salivary duct-like carcinoma were recognized as primary lung tumors expanding the spectrum of SGT that have been described to originate in the tracheobronchial system. Primary pulmonary SGT must be clinically excluded from metastatic salivary gland neoplasms as their morphology is indistinguishable from that of their salivary gland counterparts. Little is known about the clinical behavior and best treatment approach for these unusual tumors. In this review, we provide a comprehensive summary of primary pulmonary SGT with particular emphasis on morphologic characteristics and latest developments in terms of immunohistochemical and molecular techniques.

  1. Novel glycosaminoglycan biosynthetic inhibitors affect tumor-associated angiogenesis

    PubMed Central

    Raman, Karthik; Ninomiya, Masayuki; Nguyen, Thao Kim Nu; Tsuzuki, Yasuhiro; Koketsu, Mamoru; Kuberan, Balagurunathan

    2011-01-01

    Heparan sulfate proteoglycans (HSPGs) are essential players in several steps of tumor-associated angiogenesis. As co-receptors for several pro-angiogenic factors such as VEGF and FGF, HSPGs regulate receptor-ligand interactions and play a vital role in signal transduction. Previously, we have employed an enzymatic strategy to show the importance of cell surface HSPGs in endothelial tube formation in vitro. We have recently found several fluoro-xylosides that can selectively inhibit proteoglycan synthesis in endothelial cells. The current study demonstrates that these fluoro-xylosides are effective inhibitors of endothelial tube formation in vitro using a matrigel based assay to simulate tumor-associated angiogenesis. These first generation scaffolds offer a promising stepping-stone to the discovery of more potent fluoro-xylosides that can effectively neutralize tumor growth. PMID:21094131

  2. Brown Tumor of the Patella Caused by Primary Hyperparathyroidism: A Case Report

    PubMed Central

    Irie, Tomoko; Ikemura, Satoshi; Matsui, Gen; Iguchi, Takahiro; Mitsuyasu, Hiroaki

    2015-01-01

    It has been reported that the common sites of brown tumors are the jaw, pelvis, ribs, femurs and clavicles. We report our experience in a case of brown tumor of the patella caused by primary hyperparathyroidism. An initial radiograph and CT showed an osteolytic lesion and MR images showed a mixed solid and multiloculated cystic tumor in the right patella. One month after the parathyroidectomy, rapid bone formation was observed on both radiographs and CT images. PMID:25995691

  3. Primary carcinosarcoma of the spleen: case report of a rare tumor and review of the literature.

    PubMed

    Kochar, Kunal; Vijayasekar, Chandrasekar; Pandey, Urmila; Bhogal, Ricky; Brown, Louise; Mathew, George

    2009-02-01

    Carcinosarcoma of extragenital organs is rare. In this article, a case of primary carcinosarcoma of the spleen, which presented as painful splenomegaly is reported. To the best of our knowledge, this is the second reported case of primary splenic carcinosarcoma in English literature. The pathogenesis of these tumors is incompletely understood. No specific treatment guidelines exist for these aggressive tumors, surgery being the mainstay of treatment. The prognosis remains poor regardless of the adjuvant therapy used.

  4. Chromosomes and causation of human cancer and leukemia. XXX. Banding studies of primary intestinal tumors.

    PubMed

    Sonta, S; Sandberg, A A

    1978-01-01

    The chromosomes of 15 primary intestinal tumors were analyzed with a banding technique. Of the 15 tumors, 12 had some chromosomal abnormalities (8 with numerical changes and 4 with both numerical and structural abnormalities) and in the remaining three no karyotypic abnormalities were found. No common marker chromosomes were seen among the various tumors and no two tumors with chromosomal changes and identical karyotypes, though some chromosomes were involved more often than others. Excessive chromosomes in the primary tumors were usually due to extra chromosomes in the following groups (numbers of tumors involved are shown in parenthesis): No. 8 (7), No. 13 (4), No. 15 (4), No. 17 (6) and No. 21 (6). On the other hand, chromosomes losses, though much less frequent, involved chromosomes No. 5, No. 6, No. 7, No. 10 and No. 16. Most of the tumor cells with chromosomal changes were hyperdiploid and usually contained less than 60 chromosomes. Only one tumor contained hypodiploid cells. The cytogenetic data presented on primary intestinal tumors indicate that they consist primarily of numerical changes, relative infrequency (when compared to metastases) and small number (1-4) of markers. PMID:626926

  5. Development and validation of a microRNA based diagnostic assay for primary tumor site classification of liver core biopsies.

    PubMed

    Perell, Katharina; Vincent, Martin; Vainer, Ben; Petersen, Bodil Laub; Federspiel, Birgitte; Møller, Anne Kirstine; Madsen, Mette; Hansen, Niels Richard; Friis-Hansen, Lennart; Nielsen, Finn Cilius; Daugaard, Gedske

    2015-01-01

    Identification of the primary tumor site in patients with metastatic cancer is clinically important, but remains a challenge. Hence, efforts have been made towards establishing new diagnostic tools. Molecular profiling is a promising diagnostic approach, but tissue heterogeneity and inadequacy may negatively affect the accuracy and usability of molecular classifiers. We have developed and validated a microRNA-based classifier, which predicts the primary tumor site of liver biopsies, containing a limited number of tumor cells. Concurrently we explored the influence of surrounding normal tissue on classification. MicroRNA profiling was performed using quantitative Real-Time PCR on formalin-fixed paraffin-embedded samples. 278 primary tumors and liver metastases, representing nine primary tumor classes, as well as normal liver samples were used as a training set. A statistical model was applied to adjust for normal liver tissue contamination. Performance was estimated by cross-validation, followed by independent validation on 55 liver core biopsies with a tumor content as low as 10%. A microRNA classifier developed, using the statistical contamination model, showed an overall classification accuracy of 74.5% upon independent validation. Two-thirds of the samples were classified with high-confidence, with an accuracy of 92% on high-confidence predictions. A classifier trained without adjusting for liver tissue contamination, showed a classification accuracy of 38.2%. Our results indicate that surrounding normal tissue from the biopsy site may critically influence molecular classification. A significant improvement in classification accuracy was obtained when the influence of normal tissue was limited by application of a statistical contamination model. PMID:25131495

  6. Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord

    PubMed Central

    Wang, Yuxuan; Springer, Simeon; Zhang, Ming; McMahon, K. Wyatt; Kinde, Isaac; Dobbyn, Lisa; Ptak, Janine; Brem, Henry; Chaichana, Kaisorn; Gallia, Gary L.; Gokaslan, Ziya L.; Groves, Mari L.; Jallo, George I.; Lim, Michael; Olivi, Alessandro; Quinones-Hinojosa, Alfredo; Rigamonti, Daniele; Riggins, Greg J.; Sciubba, Daniel M.; Weingart, Jon D.; Wolinsky, Jean-Paul; Ye, Xiaobu; Oba-Shinjo, Sueli Mieko; Marie, Suely K. N.; Holdhoff, Matthias; Agrawal, Nishant; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Bettegowda, Chetan

    2015-01-01

    Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% [95% confidence interval (95% CI) = 57–88%] of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88–100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P < 0.0001, Fisher’s exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord. PMID:26195750

  7. Laxative Related Primary Hyperphosphatemic Tumoral Calcinosis Identified by Bone Scintigraphy.

    PubMed

    Asokendaran, Marcus; Lenzo, Nat Patrick

    2016-09-01

    We describe a case of a 40-year-old female patient presenting with tumor calcinosis where hypertrophic pulmonary osteoarthropathy (HPOA) was suspected given her extensive history of malignancy. Plain X-rays did not show reveal the typical periarticular calcification but did show appearances consistent with HPOA. Bone scintigraphy with (99m)Tc-methylene diphosphonate (MDP) is a sensitive investigation in the detection of hypertrophic osteoarthopathy but did not show findings characteristics of HPOA like bilateral symmetrical increased uptake of the radiopharmaceutical along the cortical margins of the long bones. The final diagnosis of tumor calcinosis was only made after low dose computerized tomography chest showed a moderated sized amorphous calcified cluster in the apical segment of the right upper lobe consistent. In conclusion, bone scintigraphy continues to be a useful investigation for both common and rare conditions like tumor calcinosis. The unusual three phase bone scan finding of diffuse activity throughout both lung fields, which turned to out to be tumoral calcinosis is highlighted in this case. PMID:27651742

  8. Laxative Related Primary Hyperphosphatemic Tumoral Calcinosis Identified by Bone Scintigraphy

    PubMed Central

    Asokendaran, Marcus; Lenzo, Nat Patrick

    2016-01-01

    We describe a case of a 40-year-old female patient presenting with tumor calcinosis where hypertrophic pulmonary osteoarthropathy (HPOA) was suspected given her extensive history of malignancy. Plain X-rays did not show reveal the typical periarticular calcification but did show appearances consistent with HPOA. Bone scintigraphy with 99mTc-methylene diphosphonate (MDP) is a sensitive investigation in the detection of hypertrophic osteoarthopathy but did not show findings characteristics of HPOA like bilateral symmetrical increased uptake of the radiopharmaceutical along the cortical margins of the long bones. The final diagnosis of tumor calcinosis was only made after low dose computerized tomography chest showed a moderated sized amorphous calcified cluster in the apical segment of the right upper lobe consistent. In conclusion, bone scintigraphy continues to be a useful investigation for both common and rare conditions like tumor calcinosis. The unusual three phase bone scan finding of diffuse activity throughout both lung fields, which turned to out to be tumoral calcinosis is highlighted in this case. PMID:27651742

  9. Laxative Related Primary Hyperphosphatemic Tumoral Calcinosis Identified by Bone Scintigraphy

    PubMed Central

    Asokendaran, Marcus; Lenzo, Nat Patrick

    2016-01-01

    We describe a case of a 40-year-old female patient presenting with tumor calcinosis where hypertrophic pulmonary osteoarthropathy (HPOA) was suspected given her extensive history of malignancy. Plain X-rays did not show reveal the typical periarticular calcification but did show appearances consistent with HPOA. Bone scintigraphy with 99mTc-methylene diphosphonate (MDP) is a sensitive investigation in the detection of hypertrophic osteoarthopathy but did not show findings characteristics of HPOA like bilateral symmetrical increased uptake of the radiopharmaceutical along the cortical margins of the long bones. The final diagnosis of tumor calcinosis was only made after low dose computerized tomography chest showed a moderated sized amorphous calcified cluster in the apical segment of the right upper lobe consistent. In conclusion, bone scintigraphy continues to be a useful investigation for both common and rare conditions like tumor calcinosis. The unusual three phase bone scan finding of diffuse activity throughout both lung fields, which turned to out to be tumoral calcinosis is highlighted in this case.

  10. Radiographically determined growth kinetics of primary lung tumors in the dog

    SciTech Connect

    Perry, R.E. . Coll. of Veterinary Medicine Pacific Northwest Lab., Richland, WA ); Weller, R.E.; Buschbom, R.L.; Dagle, G.E.; Park, J.F. )

    1989-10-01

    Tumor growth rate patterns especially tumor doubling time (TDT), have been extensively evaluated in man. Studies involving the determination of TDT in humans are limited, however, by the number of cases, time consistent radiographic tumor measurements, and inability to perform experimental procedures. In animals similar constraints do not exist. Lifespan animal models lend themselves well to tumor growth pattern analysis. Experimental studies have been designed to evaluate both the biological effects and growth patterns of induced and spontaneous tumors. The purpose of this study was to calculate the tumor volume doubling times (TCDT) for radiation-induced and spontaneous primary pulmonary neoplasms in dogs to see if differences existed due to etiology, sex or histologic cell type, and to determine if the time of tumor onset could be extrapolated from the TVDT. 3 refs.

  11. Extratumoral Heme Oxygenase-1 (HO-1) Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth

    PubMed Central

    Adamo, Hanibal; Thysell, Elin; Jernberg, Emma; Stattin, Pär; Widmark, Anders; Wikström, Pernilla; Bergh, Anders

    2016-01-01

    Aggressive tumors induce tumor-supporting changes in the benign parts of the prostate. One factor that has increased expression outside prostate tumors is hemoxygenase-1 (HO-1). To investigate HO-1 expression in more detail, we analyzed samples of tumor tissue and peritumoral normal prostate tissue from rats carrying cancers with different metastatic capacity, and human prostate cancer tissue samples from primary tumors and bone metastases. In rat prostate tumor samples, immunohistochemistry and quantitative RT-PCR showed that the main site of HO-1 synthesis was HO-1+ macrophages that accumulated in the tumor-bearing organ, and at the tumor-invasive front. Small metastatic tumors were considerably more effective in attracting HO-1+ macrophages than larger non-metastatic ones. In clinical samples, accumulation of HO-1+ macrophages was seen at the tumor invasive front, almost exclusively in high-grade tumors, and it correlated with the presence of bone metastases. HO-1+ macrophages, located at the tumor invasive front, were more abundant in bone metastases than in primary tumors. HO-1 expression in bone metastases was variable, and positively correlated with the expression of macrophage markers but negatively correlated with androgen receptor expression, suggesting that elevated HO-1 could be a marker for a subgroup of bone metastases. Together with another recent observation showing that selective knockout of HO-1 in macrophages reduced prostate tumor growth and metastatic capacity in animals, the results of this study suggest that extratumoral HO-1+ macrophages may have an important role in prostate cancer. PMID:27280718

  12. Primary yolk sac tumor of the gluteus: a case report and literature review

    PubMed Central

    Li, Bo; Jiang, Qianqian; Zhang, Shitai; Zhou, Yang; Zhang, Qing-Fu; OuYang, Ling

    2016-01-01

    Yolk sac tumor (YST) is a common malignant primitive germ cell tumor that often exhibits differentiation into endodermal structures. They most commonly occur in childhood and adolescence and are rare after the age of 40 years. Derived from the yolk sac during the embryonic period, YSTs can occur in the gonads and germ cells because the tumor cells migrate from the yolk sac toward the gonads. Here, we present a rare case of primary gluteus YST in a 3-year-old girl. She received BEP chemotherapy (bleomycin + etoposide + cisplatin) after surgical resection. There was no evidence of recurrence 7 months after primary treatment. PMID:27536133

  13. Primary yolk sac tumor of the gluteus: a case report and literature review.

    PubMed

    Li, Bo; Jiang, Qianqian; Zhang, Shitai; Zhou, Yang; Zhang, Qing-Fu; OuYang, Ling

    2016-01-01

    Yolk sac tumor (YST) is a common malignant primitive germ cell tumor that often exhibits differentiation into endodermal structures. They most commonly occur in childhood and adolescence and are rare after the age of 40 years. Derived from the yolk sac during the embryonic period, YSTs can occur in the gonads and germ cells because the tumor cells migrate from the yolk sac toward the gonads. Here, we present a rare case of primary gluteus YST in a 3-year-old girl. She received BEP chemotherapy (bleomycin + etoposide + cisplatin) after surgical resection. There was no evidence of recurrence 7 months after primary treatment. PMID:27536133

  14. Primary malignant peripheral nerve sheath tumor at unusual location

    PubMed Central

    Panigrahi, Souvagya; Mishra, Sudhansu Sekhar; Das, Srikant; Dhir, Manmath Kumar

    2013-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma. Most arise in association with major nerve trunks. Their most common anatomical sites are the proximal portions of the upper and lower extremities and the trunk. MPNSTs have rarely been reported in literature to occur in other unusual body parts. We review all such cases reported till now in terms of site of origin, surgical treatment, adjuvant therapy and outcome and shortly describe our experience with two of these cases. Both of our case presented with lump at unusual sites resembling neurofibroma, one at orbitotemporal area and other in the paraspinal region with characteristic feature of neurofibroma with the exception that both had very short history of progression. They underwent gross total removal of the tumor with adjuvant radiotherapy postoperatively. At 6-month follow-up both are doing well with no evidence of recurrence. PMID:24174807

  15. Advanced Imaging for Biopsy Guidance in Primary Brain Tumors

    PubMed Central

    Tsiouris, Apostolos J; Ramakrishna, Rohan

    2016-01-01

    Accurate glioma sampling is required for diagnosis and establishing eligibility for relevant clinical trials. MR-based perfusion and spectroscopy sequences supplement conventional MR in noninvasively predicting the areas of highest tumor grade for biopsy. We report the case of a patient with gliomatosis cerebri and multifocal patchy enhancement in whom the combination of advanced and conventional imaging attributes successfully guided a diagnostic biopsy. PMID:27014538

  16. Primary solitary fibrous tumor of the thyroid - report of a case and review of the literature.

    PubMed

    Song, Zhigang; Yu, Chunkai; Song, Xin; Wei, Lixin; Liu, Aijun

    2011-01-01

    Solitary fibrous tumor (SFT) is a rare spindle-cell neoplasm, especially in the thyroid. We report a case of primary solitary fibrous tumor of the thyroid gland in a 37 year-old Chinese man. The tumor was characterized by bland-looking spindle cells admixed with thin and thick collagen fibers. On immunohistochemistry study indicated that tumor cells were diffusely positive for CD34, Bcl-2 and CD99, and negative for Desmin, NSE, SMA, S-100, and CD68. The patient remains well 16 months after excision. The morphologic and immunohistochemical features of the thyroid SFTs are similar to their reported counterparts in other anatomic sites.

  17. Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors

    SciTech Connect

    Pasquinelli, C.; Garreau, F.; Bougueleret, L.; Cariani, E.; Thiers, V.; Croissant, O.; Hadchouel, M.; Tiollais, P.; Brechot, C. ); Grzeschik, K.H. )

    1988-02-01

    Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different tumors at one step of liver cell transformation, possible related to HBV integration.

  18. Factors Affecting Outcomes in Patients Treated Surgically for Upper Extremity Tumors and Tumor-Like Lesions

    PubMed Central

    Otero, Jesse E; Graves, Christopher M; TeKippe, Ashley; Buckwalter, Joseph A; Miller, Benjamin J

    2013-01-01

    There is little data available regarding outcomes of patients who have undergone surgery for tumors of the upper extremity. Functional data after surgery for upper extremity tumors would aid in guiding patient expectations in the peri-operative period. The purpose of this study was to identify patient, tumor, and surgery-related characteristics associated with patient-reported physical and emo-tional function before and after surgery for tumors of the upper extremity. Pre- and post-operative mental and physical Medical Outcomes Study Short Form 36 (SF-36) scores were collected from 79 patients with benign and malignant neoplasms of the upper extremity. A retrospective chart review was performed to ascertain whether tumor behavior, type, location, patient sex, age, surgical specimen size, or type of surgery were correlated with differing outcomes. Our outcome measure was patient-reported physi-cal and mental score (SF-36) at less than one year, one to two years, and greater than two years post-operatively. We found that patients with tumors proximal to the elbow and patients with right-sided tumors had statistically significantly lower post-operative physical scores at minimum two-year follow-up (p=0.02). Additionally, lower physical scores were associated with age greater than 50 (p=0.03) and tumor resection rather than curettage (p=0.01). The subset of patients with hereditary multiple exostoses had significantly lower post-operative physical scores than other patient sub-populations. There was no difference in physical function after surgery between patients with benign and malig-nant tumors, patients with tumors larger than 5 cm and less than 5 cm in greatest dimension, and patients with bone versus soft tissue tumors. Inter-estingly, we found that there was no difference in mental function scores between any comparisons. Our results suggest that patient age, tumor location, and type of surgery are correlated with patient-reported physical function following sur

  19. Primary hepatic signet ring cell neuroendocrine tumor: a case report with literature review.

    PubMed

    Zhu, Hongfa; Sun, Katherine; Ward, Stephen C; Schwartz, Myron; Thung, Swan N; Qin, Lihui

    2010-11-01

    Primary hepatic signet ring cell neuroendocrine tumor is extremely rare and is characterized by distinct intracytoplasmic hyaline vacuoles that are mucin negative and cytokeratin positive. The unique histological features may cause difficulty in diagnosis and delay patient care. Here the authors report a 49-year-old man with an incidental finding of a 2.7 cm liver mass in the absence of chronic liver disease. The resected tumor was grossly unencapsulated but well demarcated with friable tissue texture. Microscopically, the entire tumor consisted of sheets of monotonous cells separated by delicate microvasculature. The tumor cells had granular chromatin, inconspicuous nucleoli, and eosinophilic cytoplasm. Many of the tumor cells had eccentric, pale intracytoplasmic vacuoles resembling signet ring cells in adenocarcinoma. Immunohistochemical studies showed that the tumor cells were positive for neuroendocrine markers and that the intracytoplasmic vacuoles were negative for mucin but strongly positive for cytokeratins. Careful systemic search including OctreoScan scintigraphy (Mallinckrodt Medical, Inc., St. Louis, MO) and capsule endoscopy failed to reveal any other tumors. A diagnosis of primary hepatic signet ring cell neuroendocrine tumor was established. Ten months after surgery, the patient is well without any other detectable tumor on radiology. Serological neuroendocrine markers are also within normal limits.

  20. CXCL12-γ in primary tumors drives breast cancer metastasis.

    PubMed

    Ray, P; Stacer, A C; Fenner, J; Cavnar, S P; Meguiar, K; Brown, M; Luker, K E; Luker, G D

    2015-04-16

    Compelling evidence shows that chemokine C-X-C motif chemokine ligand 12 (CXCL12) drives metastasis in multiple malignancies. Similar to other key cytokines in cancer, CXCL12 exists as several isoforms with distinct biophysical properties that may alter signaling and functional outputs. However, effects of CXCL12 isoforms in cancer remain unknown. CXCL12-α, -β and -γ showed cell-type-specific differences in activating signaling through G protein-dependent pathways in cell-based assays, while CXCL12-γ had greatest effects on recruitment of the adapter protein β-arrestin 2. CXCL12-β and -γ also stimulated endothelial tube formation to a greater extent than CXCL12-α. To investigate the effects of CXCL12 isoforms on tumor growth and metastasis, we used a mouse xenograft model of metastatic human breast cancer combining CXCR4+ breast cancer cells and mammary fibroblasts secreting an isoform of CXCL12. Altough all CXCL12 isoforms produced comparable growth of mammary tumors, CXCL12-γ significantly increased metastasis to bone marrow and other sites. Breast cancer cells originating from tumors with CXCL12-γ fibroblasts upregulated RANKL (receptor activator of nuclear factor-κB ligand), contributing to bone marrow tropism of metastatic cancer cells. CXCL12-γ was expressed in metastatic tissues in mice, and we also detected CXCL12-γ in malignant pleural effusions from patients with breast cancer. In our mouse model, mammary fibroblasts disseminated to sites of breast cancer metastases, providing another mechanism to increase levels of CXCL12 in metastatic environments. These studies identify CXCL12-γ as a potent pro-metastatic molecule with important implications for cancer biology and effective therapeutic targeting of CXCL12 pathways.

  1. CXCL12-γ in Primary Tumors Drives Breast Cancer Metastasis

    PubMed Central

    Ray, Paramita; Stacer, Amanda C.; Fenner, Joseph; Cavnar, Stephen P.; Meguiar, Kaille; Brown, Martha; Luker, Kathryn E.; Luker, Gary D.

    2014-01-01

    Compelling evidence shows that chemokine CXCL12 drives metastasis in multiple malignancies. Similar to other key cytokines in cancer, CXCL12 exists as several isoforms with distinct biophysical properties that may alter signaling and functional outputs. However, effects of CXCL12 isoforms in cancer remain unknown. CXCL12-α, β, and γ showed cell-type specific differences in activating signaling through G protein-dependent pathways in cell-based assays, while CXCL12-γ had greatest effects on recruitment of the adapter protein β-arrestin 2. CXCL12-β and γ also stimulated endothelial tube formation to a greater extent than CXCL12-α. To investigate effects of CXCL12 isoforms on tumor growth and metastasis, we used a mouse xenograft model of metastatic human breast cancer combining CXCR4+ breast cancer cells and mammary fibroblasts secreting an isoform of CXCL12. While all CXCL12 isoforms produced comparable growth of mammary tumors, CXCL12-γ significantly increased metastasis to bone marrow and other sites. Breast cancer cells originating from tumors with CXCL12-γ fibroblasts upregulated RANKL, contributing to bone marrow tropism of metastatic cancer cells. CXCL12-γ was expressed in metastatic tissues in mice, and we also detected CXCL12-γ in malignant pleural effusions from patients with breast cancer. In our mouse model, mammary fibroblasts disseminated to sites of breast cancer metastases, providing another mechanism to increase levels of CXCL12 in metastatic environments. These studies identify CXCL12-γ as a potent pro-metastatic molecule with important implications for cancer biology and effective therapeutic targeting of CXCL12 pathways. PMID:24909174

  2. Primary myxoid solitary fibrous tumor involving the seminal vesicle.

    PubMed

    Wei, Yu-Ching; Li, Chien-Feng; Sung, Ming-Tse; Chen, Yen-Ta; Ko, Sheung-Fat; Eng, Hock-Liew; Huang, Hsuan-Ying

    2006-10-01

    Although focal myxoid change is a well-recognized feature of solitary fibrous tumor (SFT), predominantly myxoid SFT are exceedingly rare. Reported herein is the case of a 65-year-old man with SFT containing abundant myxoid matrix, arising from the capsule of the right seminal vesicle. To the authors' knowledge this is the first myxoid SFT involving the male genito-urinary system. Recognition of the myxoid variant of SFT is crucial, given possible confusion with a variety of myxoid spindle cell neoplasms with different biological potential in the pelvic cavity.

  3. [Primary epithelial lacrimal gland tumors: the pathologic classification of 272 cases].

    PubMed

    Ni, C

    1994-12-01

    This paper reports the pathologic classification of 272 cases with primary epithelial lacrimal gland tumors in comparison with that of the salivary glands. The extensive series of lacrimal gland tumors accounts for 70% of the 390 lacrimal fossa lesions and 18% of the 1,530 orbital tumors in one single hospital. Benign mixed tumors ranked the first (52%), adenocystic carcinomas the second (25%) and malignant mixed tumors (9%) the third. Among the other less common tumors the authors identified, for the first time, 3 polymorphous low-grade adenocarcinomas, 2 spindle celled myoepitheliomas and 1 carcinosarcoma of the lacrimal gland. The diagnosis and differential diagnosis of polymorphous low-grade adenocarcinoma and spindle cell myoepithelioma were discussed.

  4. Primary polyoma virus-induced murine thymic epithelial tumors. A tumor model of thymus physiology.

    PubMed Central

    Hoot, G. P.; Kettman, J. R.

    1989-01-01

    Thymic tumors were induced in C3'/Bittner mice by neonatal inoculation with polyoma virus. The objective of this study was to identify the phenotypes of the cells within the tumors and to attempt to determine the origin of the neoplastic cell population(s). At the ultrastructural level, the neoplastic cells resembled normal thymic epithelium with tonofilaments and desmosomes. Immunoperoxidase staining demonstrated the presence of cytokeratin, Iak, -beta 2-microglobulin, -asialo-GM1, the thymic cortical epithelial marker ER-TR4, and the medullary epithelial marker ER-TR5. Islands of normal cortical thymocytes supported by residual normal cortical epithelium and acid phosphatase-positive cortical macrophages were interspersed in the tumors. Residual islands of normal medullary architecture with nonspecific esterase-positive IDCs were rarely identified in tumors. Most lymphocytes in the tumors were normal immature cortical thymocytes with the phenotype Tdt+, PNA+, Thy 1.2bright, Ly-1dull, H-2Kkdull, ThB+, J11d+, and Lyt-2+L3T4+. Lymphocytes in the tumors were steroid-sensitive like normal thymocytes. The proportions of Lyt-2+L3T4- and Lyt-2-L3T4+ cells were generally larger in the tumors than in normal thymus and reflected the higher frequency of lymphocytes in the tumors capable of proliferating in vitro in response to Con A plus IL-2. The data were consistent with the hypothesis that the neoplasia originates from thymic epithelium that is interspersed with normal, developing thymic lymphocytes. Images Figure 4 p[688]-a Figure 1 Figure 2 Figure 3 p687-a Figure 7 PMID:2552813

  5. Huge primary mucinous cystadenoma of the retroperitoneum mimicking a left ovarian tumor.

    PubMed

    Balat, O; Aydin, A; Sirikci, A; Kutlar, I; Aksoy, F

    2001-01-01

    Primary mucinous cystic tumors of the retroperitoneum are rarely encountered and have been reported in approximately 25 cases in the literature. The histogenesis of primary mucinous cystadenomas is not clear. Most authors suggest that it develops through mucinous metaplasia in a pre-existing mesothelium-lined cyst. Surgery is the only treatment. In this report we present an additional case of primary retroperitoneal mucinous cystadenoma in a 44-year-old female.

  6. Analgesic use and the risk of primary adult brain tumor.

    PubMed

    Egan, Kathleen M; Nabors, Louis B; Thompson, Zachary J; Rozmeski, Carrie M; Anic, Gabriella A; Olson, Jeffrey J; LaRocca, Renato V; Chowdhary, Sajeel A; Forsyth, Peter A; Thompson, Reid C

    2016-09-01

    Glioma and meningioma are uncommon tumors of the brain with few known risk factors. Regular use of aspirin has been linked to a lower risk of gastrointestinal and other cancers, though evidence for an association with brain tumors is mixed. We examined the association of aspirin and other analgesics with the risk of glioma and meningioma in a large US case-control study. Cases were persons recently diagnosed with glioma or meningioma and treated at medical centers in the southeastern US. Controls were persons sampled from the same communities as the cases combined with friends and other associates of the cases. Information on past use of analgesics (aspirin, other anti-inflammatory agents, and acetaminophen) was collected in structured interviews. Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for analgesic use adjusted for potential confounders. All associations were considered according to indication for use. A total of 1123 glioma cases, 310 meningioma cases and 1296 controls were included in the analysis. For indications other than headache, glioma cases were less likely than controls to report regular use of aspirin (OR 0.69; CI 0.56, 0.87), in a dose-dependent manner (P trend < 0.001). No significant associations were observed with other analgesics for glioma, or any class of pain reliever for meningioma. Results suggest that regular aspirin use may reduce incidence of glioma. PMID:26894804

  7. Primary spinal tumors in childhood: A single institution 15 year experience

    PubMed Central

    Hung, Po-Cheng; Wu, Chieh-Tsai; Jaing, Tang-Her; Sheen, Jiunn-Ming; Chou, Ming-Liang; Lin, Kuang-Lin

    2016-01-01

    Background: Pediatric primary spinal tumors (PST) are fairly uncommon, with little available data regarding incidence and outcomes. Materials and Methods: We conducted a retrospective review of the 22 consecutive patients less than 18 years old diagnosed with PST between March 1997 and May 2011 and treated at Chang Gung Children Hospital. All patients had undergone magnetic resonance imaging (MRI) for pre-operative evaluation and operations for PST. The extent of tumor removal was assessed by surgical report by the neurosurgeon or by post-operative MRI if available. Results: Ten of them had intramedullary tumors and 12 had intradural extramedullary tumors. All patients were treated with surgery to the primary site. A total of 15 patients underwent gross total tumor resection and seven patients received post-operative radiotherapy. Five patients received adjuvant chemotherapy for their primary tumor. Fourteen patients (64%) survived from study entry without tumor progression. Conclusions: PST encompassed a diverse group of pathologic entities that differ markedly based on the location and age of the children. Total resection of pediatric PST in children could be performed with acceptable risk and satisfactory long-term results.

  8. Primary spinal tumors in childhood: A single institution 15 year experience

    PubMed Central

    Hung, Po-Cheng; Wu, Chieh-Tsai; Jaing, Tang-Her; Sheen, Jiunn-Ming; Chou, Ming-Liang; Lin, Kuang-Lin

    2016-01-01

    Background: Pediatric primary spinal tumors (PST) are fairly uncommon, with little available data regarding incidence and outcomes. Materials and Methods: We conducted a retrospective review of the 22 consecutive patients less than 18 years old diagnosed with PST between March 1997 and May 2011 and treated at Chang Gung Children Hospital. All patients had undergone magnetic resonance imaging (MRI) for pre-operative evaluation and operations for PST. The extent of tumor removal was assessed by surgical report by the neurosurgeon or by post-operative MRI if available. Results: Ten of them had intramedullary tumors and 12 had intradural extramedullary tumors. All patients were treated with surgery to the primary site. A total of 15 patients underwent gross total tumor resection and seven patients received post-operative radiotherapy. Five patients received adjuvant chemotherapy for their primary tumor. Fourteen patients (64%) survived from study entry without tumor progression. Conclusions: PST encompassed a diverse group of pathologic entities that differ markedly based on the location and age of the children. Total resection of pediatric PST in children could be performed with acceptable risk and satisfactory long-term results. PMID:27695552

  9. Primary liver tumors in beagle dogs exposed by inhalation to aerosols of plutonium-238 dioxide

    SciTech Connect

    Gillett, N.A.; Muggenburg, B.A.; Mewhinney, J.A.; Hahn, F.F.; Seiler, F.A.; Boecker, B.B.; McClellan, R.O.

    1988-11-01

    Primary liver tumors developed in Beagle dogs exposed by inhalation to aerosols of /sup 238/PuO/sub 2/. Initial deposition of /sup 238/PuO/sub 2/ in the respiratory tract was followed by translocation of a portion of the /sup 238/Pu to the liver and skeleton, which resulted in a large dose commitment and tumor risk to all three tissues. In a population of 144 dogs exposed to /sup 238/PuO/sub 2/, 112 dogs died or were killed 4000 days after /sup 238/Pu exposure, 100 dogs had osteosarcoma, and 28 dogs had lung cancers. At increasing times after exposure, however, liver lesions have become more pronounced. Ten primary liver tumors in nine animals were diagnosed in the dogs dying before 4000 days after exposure. An additional five primary liver tumors in three dogs occurred in 9 animals killed after 4000 days after exposure. The majority of these tumors have been fibrosarcomas. The liver tumors were usually not the cause of death, and rarely metastasized. The occurrence of liver tumors in this study indicates that /sup 238/Pu is an effective hepatic carcinogen. Liver carcinogenesis is assuming an increasing importance in this study at late times after inhalation exposure. These results suggest that the liver may be an important organ at risk for the development of neoplasia in humans at time periods long after inhalation of /sup 238/Pu.

  10. Primary chemically induced tumors induce profound immunosuppression concomitant with apoptosis and alterations in signal transduction in T cells and NK cells.

    PubMed

    Horiguchi, S; Petersson, M; Nakazawa, T; Kanda, M; Zea, A H; Ochoa, A C; Kiessling, R

    1999-06-15

    Whereas transplantable tumors can be readily cured with immunotherapeutic approaches, similar therapies in cancer patients have been less effective. This difference may be explained by an immunosuppression resulting from the presence of a slowly growing primary tumor in the patient, whereas the immune system in a mouse with a rapidly proliferating transplantable tumor would be less affected. As a more appropriate model to the immune dysfunction in patients, slowly progressing primary tumors were induced by the carcinogen methylcholanthrene (MC) in mice. Their ability to induce immunosuppression in T cells and natural killer (NK) cells was compared to that of rapidly growing transplanted MC-induced tumors. The results demonstrate that mice bearing primary MC tumors had significantly diminished T-cell and NK-cell functions, impaired capacity to produce Th1 cytokines, and markedly reduced levels of the signal-transducing zeta chain in T cells and NK cells, similar to that described in cancer patients. Moreover, a substantial number of CD8+ T cells in mice with large primary MC tumors were undergoing apoptosis, correlating with alterations in CD4/CD8 ratios. In contrast, T cells and NK cells from mice bearing rapidly growing transplanted tumors were only marginally affected. These findings could explain the apparent discrepancy between the consistent findings of a diminished immune response and alterations in signal transduction in cancer patients as compared to the less reproducible observations in murine transplantable tumors. In addition, they could explain the differences in the high efficacy of immunotherapy in mice with transplantable tumors and the low therapeutic results in cancer patients. PMID:10383160

  11. [The importance of angiography in primary retroperitoneal tumors (author's transl)].

    PubMed

    Bardach, G; Grabenwöger, F

    1982-08-01

    During the past ten years, 18 patients with primary retroperitoneal tumours were operated on in the Second Surgical Department of Vienna University. Angiography was performed preoperatively in seven patients. In five out of seven patients, the origin of the tumour and its histological grade could be determined angiographically. Hence, angiography is indicated if surgery is contemplated in addition to the more recent tomographic imaging techniques (ultrasound, computed tomography).

  12. DEPRESSED CELL-MEDIATED IMMUNITY IN PATIENTS WITH PRIMARY INTRACRANIAL TUMORS

    PubMed Central

    Brooks, William H.; Netsky, Martin G.; Normansell, David E.; Horwitz, David A.

    1972-01-01

    Tumor immunity in patients with primary intracranial tumors was assessed in relation to the general status of host immunocompetence. Lymphocyte sensitization to tumor-specific membrane antigens was demonstrated by the proliferative response of lymphocytes in the presence of autochthonous tumor cells. Paradoxically, one-half of the patients could not be sensitized to a primary antigen, dinitrochlorobenzene; existing delayed hypersensitivity was also depressed, as measured by skin tests and lymphocyte transformation in response to common antigens. A heat-stable factor in patients' sera blocked cell-mediated tumor immunity. In addition, these "enhancing" sera consistently suppressed the blastogenic response of autologous and homologous lymphocytes to phytohemagglutinin and to membrane antigens on allogeneic cells in the one-way mixed lymphocyte culture. When patients' leukocytes were washed and autologous plasma replaced with normal plasma, reactivity in the mixed lymphocyte culture increased to normal values. In vitro immunosuppressive activity in patients' plasma or sera correlated with depressed delayed hypersensitivity. After removal of the tumor, suppressor activity disappeared. IgG fractions of patient sera contained strong immunosuppressive activity. These data suggest that the suppressor factor may be an isoantibody elicited by the tumor that also binds to receptors on the lymphocyte membrane. In addition to specifically blocking cell-mediated tumor immunity, enhancing sera may broadly depress host immunocompetence. PMID:4345108

  13. Tumor evolution and intratumor heterogeneity in colorectal carcinoma: insights from comparative genomic profiling of primary tumors and matched metastases

    PubMed Central

    Sylvester, Brooke E.

    2015-01-01

    Metastatic colorectal cancer (CRC) is one of the leading causes of cancer-related mortality among men and women worldwide. Over the past few decades, advances in our understanding of the genetic and epigenetic underpinnings of CRC have led to important insights into the pathogenesis of invasive tumors and have identified different molecular subgroups. Nonetheless, the events that might facilitate dissemination of tumor cells to distant sites giving rise to metastatic disease are not well characterized. Furthermore, in contrast to intertumor heterogeneity the extent of intratumor heterogeneity in different types of CRC has not been fully defined. In this paper, we review studies that have compared the genetic profile of primary invasive carcinomas to that of matched metastases and discuss the implications of their findings for our understanding of tumor evolution and for the clinical management of patients with advanced CRC. PMID:26697200

  14. Magnetic Fluorescent Nanoformulation for Intracellular Drug Delivery to Human Breast Cancer, Primary Tumors, and Tumor Biopsies: Beyond Targeting Expectations.

    PubMed

    El-Boubbou, Kheireddine; Ali, Rizwan; Bahhari, Hassan M; AlSaad, Khaled O; Nehdi, Atef; Boudjelal, Mohamed; AlKushi, Abdulmohsen

    2016-06-15

    We report the development of a chemotherapeutic nanoformulation made of polyvinylpyrrolidone-stabilized magnetofluorescent nanoparticles (Fl-PMNPs) loaded with anticancer drugs as a promising drug carrier homing to human breast cancer cells, primary tumors, and solid tumors. First, nanoparticle uptake and cell death were evaluated in three types of human breast cells: two metastatic cancerous MCF-7 and MDA-MB-231 cells and nontumorigenic MCF-10A cells. While Fl-PMNPs were not toxic to cells even at the highest concentrations used, Dox-loaded Fl-PMNPs showed significant potency, effectively killing the different breast cancer cells, albeit at different affinities. Interestingly and superior to free Dox, Dox-loaded Fl-PMNPs were found to be more effective in killing the metastatic cells (2- to 3-fold enhanced cytotoxicities for MDA-MB-231 compared to MCF-7), compared to the normal noncancerous MCF-10A cells (up to 8-fold), suggesting huge potentials as selective anticancer agents. Electron and live confocal microscopy imaging mechanistically confirmed that the nanoparticles were successfully endocytosed and packaged into vesicles inside the cytoplasm, where Dox is released and then translocated to the nucleus exerting its cytotoxic action and causing apoptotic cell death. Furthermore, commendable and enhanced penetration in 3D multilayered primary tumor cells derived from primary lesions as well as in patient breast tumor biopsies was observed, killing the tumor cells inside. The designed nanocarriers described here can potentially open new opportunities for breast cancer patients, especially in theranostic imaging and hyperthermia. While many prior studies have focused on targeting ligands to specific receptors to improve efficacies, we discovered that even with passive-targeted tailored delivery system enhanced toxic responses can be attained. PMID:27269304

  15. Magnetic Fluorescent Nanoformulation for Intracellular Drug Delivery to Human Breast Cancer, Primary Tumors, and Tumor Biopsies: Beyond Targeting Expectations.

    PubMed

    El-Boubbou, Kheireddine; Ali, Rizwan; Bahhari, Hassan M; AlSaad, Khaled O; Nehdi, Atef; Boudjelal, Mohamed; AlKushi, Abdulmohsen

    2016-06-15

    We report the development of a chemotherapeutic nanoformulation made of polyvinylpyrrolidone-stabilized magnetofluorescent nanoparticles (Fl-PMNPs) loaded with anticancer drugs as a promising drug carrier homing to human breast cancer cells, primary tumors, and solid tumors. First, nanoparticle uptake and cell death were evaluated in three types of human breast cells: two metastatic cancerous MCF-7 and MDA-MB-231 cells and nontumorigenic MCF-10A cells. While Fl-PMNPs were not toxic to cells even at the highest concentrations used, Dox-loaded Fl-PMNPs showed significant potency, effectively killing the different breast cancer cells, albeit at different affinities. Interestingly and superior to free Dox, Dox-loaded Fl-PMNPs were found to be more effective in killing the metastatic cells (2- to 3-fold enhanced cytotoxicities for MDA-MB-231 compared to MCF-7), compared to the normal noncancerous MCF-10A cells (up to 8-fold), suggesting huge potentials as selective anticancer agents. Electron and live confocal microscopy imaging mechanistically confirmed that the nanoparticles were successfully endocytosed and packaged into vesicles inside the cytoplasm, where Dox is released and then translocated to the nucleus exerting its cytotoxic action and causing apoptotic cell death. Furthermore, commendable and enhanced penetration in 3D multilayered primary tumor cells derived from primary lesions as well as in patient breast tumor biopsies was observed, killing the tumor cells inside. The designed nanocarriers described here can potentially open new opportunities for breast cancer patients, especially in theranostic imaging and hyperthermia. While many prior studies have focused on targeting ligands to specific receptors to improve efficacies, we discovered that even with passive-targeted tailored delivery system enhanced toxic responses can be attained.

  16. Selective expression of constitutively active pro-apoptotic protein BikDD gene in primary mammary tumors inhibits tumor growth and reduces tumor initiating cells.

    PubMed

    Rahal, Omar M; Nie, Lei; Chan, Li-Chuan; Li, Chia-Wei; Hsu, Yi-Hsin; Hsu, Jennifer; Yu, Dihua; Hung, Mien-Chie

    2015-01-01

    Our previous study showed that specifically delivering BikDD, a constitutive active mutant of pro-apoptotic protein Bik, to breast cancer cell xenografts in immunocompromised mice has a potent activity against tumor initiating cells (TICs), and that the combination between tyrosine kinase inhibitors (TKI) and BikDD gene therapy yielded synergistic effect on EGFR and HER2 positive breast cancer cells in immunodeficient nude mice. Those encouraging results have allowed us to propose a clinical trial using the liposome-complexing plasmid DNA expressing BikDD gene which has been approved by the NIH RAC Advisory committee. However, it is imperative to test whether systemic delivery of BikDD-expressing plasmid DNAs with liposomes into immunocompetent mice has therapeutic efficacy and tolerable side effects as what we observed in the nude mice model. In this study, we investigated the effects of BikDD gene-therapy on the primary mammary tumors, especially on tumor initiating cells (TICs), of a genetically engineered immunocompetent mouse harboring normal microenvironment and immune response. The effects on TIC population in tumors were determined by FACS analysis with different sets of murine specific TIC markers, CD49f(high)CD61(high) and CD24(+)Jagged1(-). First we showed in vitro that ectopic expression of BikDD in murine N202 cells derived from MMTV-HER2/Neu transgenic mouse tumors induced apoptosis and decreased the number of TICs. Consistently, systemic delivery of VISA-Claudin4-BikDD by liposome complexes significantly inhibited mammary tumor growth and slowed down residual tumor growth post cessation of therapy in MMTV-HER2/Neu transgenic mice compared to the controls. In addition, the anti-tumor effects of BikDD in vivo were consistent with decreased TIC population assessed by FACS analysis and in vitro tumorsphere formation assay of freshly isolated tumor cells. Importantly, systemic administration of BikDD did not cause significant cytotoxic response in

  17. The degree of intratumor mutational heterogeneity varies by primary tumor sub-site

    PubMed Central

    Eterovic, Agda Karina; Wick, Jo; Chen, Ken; Zhao, Hao; Tazi, Loubna; Manna, Pradip; Kerley, Spencer; Joshi, Radhika; Wang, Lin; Chiosea, Simion I.; Garnett, James David; Tsue, Terance Ted; Chien, Jeremy; Mills, Gordon B.; Grandis, Jennifer Rubin; Thomas, Sufi Mary

    2016-01-01

    In an era where mutational profiles inform treatment options, it is critical to know the extent to which tumor biopsies represent the molecular profile of the primary and metastatic tumor. Head and neck squamous cell carcinoma (HNSCC) arise primarily in the mucosal lining of oral cavity and oropharynx. Despite aggressive therapy the 5-year survival rate is at 50%. The primary objective of this study is to characterize the degree of intratumor mutational heterogeneity in HNSCC. We used multi-region sequencing of paired primary and metastatic tumor DNA of 24 spatially distinct samples from seven patients with HNSCC of larynx, floor of the mouth (FOM) or oral tongue. Full length, in-depth sequencing of 202 genes implicated in cancer was carried out. Larynx and FOM tumors had more than 69.2% unique SNVs between the paired primary and metastatic lesions. In contrast, the oral tongue HNSCC had only 33.3% unique SNVs across multiple sites. In addition, HNSCC of the oral tongue had fewer mutations than larynx and FOM tumors. These findings were validated on the Affymetrix whole genome 6.0 array platform and were consistent with data from The Cancer Genome Atlas (TCGA). This is the first report demonstrating differences in mutational heterogeneity varying by subsite in HNSCC. The heterogeneity within laryngeal tumor specimens may lead to an underestimation of the genetic abnormalities within tumors and may foster resistance to standard treatment protocols. These findings are relevant to investigators and clinicians developing personalized cancer treatments based on identification of specific mutations in tumor biopsies. PMID:27034009

  18. Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach

    PubMed Central

    Jiang, Meng-jie; Weng, Shan-Shan; Cao, Ying; Li, Xiao-Fen; Wang, Liu-Hong; Xu, Jing-Hong; Yuan, Ying

    2015-01-01

    Abstract Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common. Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes. Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients. PMID:26356712

  19. Primary tumor- and metastasis-derived colon cancer cells differently modulate connexin expression and function in human capillary endothelial cells

    PubMed Central

    Thuringer, Dominique; Berthenet, Kevin; Cronier, Laurent; Solary, Eric; Garrido, Carmen

    2015-01-01

    A gradual loss of functional gap junction between tumor cells has been reported with colorectal cancer (CRC) progression. Here, we explored if colon cancer cells could also affect gap junctions in blood capillary cells. Human microvascular endothelial cells (HMEC) were cultured with two CRC cell lines established from a unique patient. SW480 cells, derived from the primary tumor, migrate much faster across HMEC monolayer than SW620 cells derived from a metastatic site. The motile SW480 cells highly express and release HSP27 that increases gap junction formation with HMEC. Soluble HSP27 phosphorylates the connexin Cx43 on serine residues and induces its interaction with the oncoprotein 14-3-3, which promotes Cx43 delivery at the plasma membrane. The factors secreted by less motile SW620 cells do not affect Cx43 expression but up-regulate the expression of the connexin Cx32 through an activation of the chemokine receptor CXCR2. In turn, SW620 secreted factors induce tubulogenesis and ATP release. Altogether, cell lines derived from CRC primary tumor and metastasis differentially adapt endothelial cell functions by modulating connexin expression through released mediators. PMID:26320187

  20. Loss of stromal JUNB does not affect tumor growth and angiogenesis.

    PubMed

    Braun, Jennifer; Strittmatter, Karin; Nübel, Tobias; Komljenovic, Dorde; Sator-Schmitt, Melanie; Bäuerle, Tobias; Angel, Peter; Schorpp-Kistner, Marina

    2014-03-15

    The transcription factor AP-1 subunit JUNB has been shown to play a pivotal role in angiogenesis. It positively controls angiogenesis by regulating Vegfa as well as the transcriptional regulator Cbfb and its target Mmp13. In line with these findings, it has been demonstrated that tumor cell-derived JUNB promotes tumor growth and angiogenesis. In contrast to JUNB's function in tumor cells, the role of host-derived stromal JUNB has not been elucidated so far. Here, we show that ablation of Junb in stromal cells including endothelial cells (ECs), vascular smooth muscle cells (SMCs) and fibroblasts does not affect tumor growth in two different syngeneic mouse models, the B16-F1 melanoma and the Lewis lung carcinoma model. In-depth analyses of the tumors revealed that tumor angiogenesis remains unaffected as assessed by measurements of the microvascular density and relative blood volume in the tumor. Furthermore, we could show that the maturation status of the tumor vasculature, analyzed by the SMC marker expression, α-smooth muscle actin and Desmin, as well as the attachment of pericytes to the endothelium, is not changed upon ablation of Junb. Taken together, these results indicate that the pro-angiogenic functions of stromal JUNB are well compensated with regard to tumor angiogenesis and tumor growth. PMID:24027048

  1. Primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma: A case report.

    PubMed

    Orsi, Nicolas M; Menon, Mini

    2016-08-01

    Primary ovarian carcinoid tumors are exceptionally rare entities accounting for approximately 0.1% of all ovarian neoplasms. This report describes a primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma in a 65 year-old woman. Macroscopically, the unilateral adnexal tumor was composed of cystic, solid and mucinous elements which resolved into a dual component lesion histologically. The majority of the tumor displayed an organoid architecture with mild to moderate pleomorphism and no discernible mitotic activity, while approximately 10% consisted of sheets and groups of cells with highly pleomorphic nuclei, necrosis and occasional mitoses. Features of a mature cystic teratoma were seen very focally. Immunohistochemistry revealed strong, diffuse positivity for CD56 and synaptophysin. Chromogranin immunonegativity was noted and there was an absence of nuclear β-catenin accumulation. Ki-67 index was 10-12%. Although there is no established diagnostic framework for primary ovarian carcinoid tumors, this case was diagnosed as a well-differentiated neuroendocrine tumor, Grade 2 (intermediate grade), arising in association with a mature cystic teratoma/dermoid cyst. This case highlights the need to develop ovarian diagnostic criteria in this area. PMID:27508272

  2. Frequent aberrant methylation of p16{sup INK4a} in primary rat lung tumors

    SciTech Connect

    Swafford, D.S.; Middleton, S.K.; Palmisano, W.A.

    1997-03-01

    The p16{sup INK4a} (p16) tumor suppressor gene is frequently inactivated by homozygous deletion or methylation of the 5{prime} CpG island in cell lines derived from human non-small-cell lung cancers. However, the frequency of dysfunction in primary tumors appears to be significantly lower than that in cell lines. This discordance could result from the occurrence or selection of p16 dysfunction during cell culture. Alternatively, techniques commonly used to examine tumors for genetic and epigenetic alterations may not be sensitive enough to detect all dysfunctions within the heterogeneous cell population present in primary tumors. If p16 inactivation plays a central role in development of non-small-cell lung cancer, then the frequency of gene inactivation in primary tumors should parallel that observed in cell lines. A further goal was to determine whether the aberrant p16 gene methylation seen in human tumors is a conserved event in this animal model. The rat p16 gene was cloned and sequenced, and the predicted amino acid sequence of its product found to be 62% homologous to the amino acid sequence of the human analog. Homozygous deletion accounted for loss of p16 expression in 8 of 20 cell lines, while methylation of the CpG island extending throughout exon 1 was observed in 9 of 20 cell lines. The methylated phenotype seen in cell lines showed an absolute correlation with detection of methylation in primary tumors. Aberrant methylation was also detected in four of eight primary tumors in which the derived cell line contained a deletion in p16. These results substantiate the primary tumor as the origin for dysfunction of the p16 gene and implicate CpG island methylation as the major mechanism for inactivating this gene in the rat lung tumors examined. Furthermore, rat lung cancer appears to be an excellent model in which to investigate the mechanisms of gene methylation and the role of p16 dysfunction in the progression of neoplasia. 48 refs., 8 figs. 2 tabs.

  3. Primary Tumor Resection and Survival in Patients with Stage IV Gastric Cancer

    PubMed Central

    Mutlu, Hasan; Karaağaç, Mustafa; Eryilmaz, Melek Karakurt; Gündüz, Şeyda; Artaç, Mehmet

    2016-01-01

    Purpose The aim of this study was to determine whether surgical resection of the primary tumor contributes to survival in patients with metastatic gastric cancer. Materials and Methods A total of 288 patients with metastatic gastric cancer from the Akdeniz University, Antalya Training and Research Hospital, and the Meram University of Konya database were retrospectively analyzed. The effect of primary tumor resection on survival of patients with metastatic gastric cancer was investigated using the log-rank test. Kaplan-Meier survival estimates were calculated. Multivariate analysis was performed using Cox proportional hazards regression modeling. Results The median overall survival was 12.0 months (95% confidence intewrval [CI], 10.4~13.6 months) and 7.8 months (95% CI, 5.5~10.0 months) for patients with and without primary tumor resection, respectively (P<0.001). The median progression-free survival was 8.3 months (95% CI, 7.1~9.5 months) and 6.2 months (95% CI, 5.8~6.7 months) for patients with and without primary tumor resection, respectively (P=0.002). Conclusions Non-curative gastrectomy in patients with metastatic gastric cancer might increase their survival rate regardless of the occurrence of life-threatening tumor-related complications. PMID:27433392

  4. The clinical pathological features, diagnosis, treatment and prognosis of small intestine primary malignant tumors.

    PubMed

    Guo, Xiaochuan; Mao, Zhiyuan; Su, Dan; Jiang, Zhaocai; Bai, Li

    2014-04-01

    The aim of the study was to describe and analyze the clinicopathological features and diagnosis of Chinese patients with small intestine primary malignant tumors and to explore the best therapy to small bowel adenocarcinoma (SBA). More than 26,000 patients with digestive tract malignant tumors received treatment in PLA hospital from 2000 to 2011, and among them, there were 887 patients who had small intestine primary malignant tumors, and 666 of 887 patients had the completed basic clinical documents. We retrospectively analyzed the correlation between clinical and pathological features of the 666 patients and analyzed the survival and prognosis of 173 SBA patients with follow-up data. Both the number of patients with primary malignant tumors of the small intestine and the number of patients who received chemotherapy showed an increasing trend. The ratio of male to female was 1.58:1. The male patients significantly exceed the female patients with tumors of non-ampullary duodenum, jejunum and duodenal ampulla; and most of the patients are over 60 years of age. For patients burdened with either of the pathological types of tumors, the males exceeded the females, but there was no significant difference. Abdominal pain was the main clinical manifestation for patients with tumors of non-ampullary duodenum, jejunum and ileum, and the most common clinical manifestations were jaundice and abdominal pain for patients with ampullary duodenal tumors, adenocarcinoma, neuroendocrine tumors and sarcoma. In addition, patients with stromal tumors were prone to gastrointestinal bleeding. Gastrointestinal endoscopy was the most common examinational procedure. Patients under 60 years of age were prone to surgery and chemotherapy after surgery, and patients over 60 years of age were prone to supportive treatment and chemotherapy without surgery. The medium overall survival of patients who received surgery without chemotherapy, chemotherapy after surgery, chemotherapy without surgery

  5. Differentiating histologic malignancy of primary brain tumors: Pentavalent Technetium-99m-DMSA

    SciTech Connect

    Hirano, Tsuneo; Otake, Hidenori; Shibasaki, Takashi

    1997-01-01

    This study assessed pentavalent {sup 99m}Tc-DMSA uptake in primary brain tumors and evaluated the relationship between retention and histologic malignancy. SPECT images of the brain were obtained at 30 min and 3 hr after intravenous administration of approximately 555 MBq {sup 99m}Tc(V)-DMSA in patients with brain tumors. Sixty studies were performed in 57 patients and 63 lesions were demonstrated: 11 glioblastomas, 13 anaplastic astrocytomas (Grade 3), 11 astrocytomas (Grade 2), 18 meningiomas and 10 schwannomas. Uptake ratios, retention ratio and retention index were calculated and compared with tumor histology and malignancy grade. Approximately 95% of both benign and malignant primary brain tumors were demonstrated by {sup 99m}Tc(V)-DMSA SPECT images. False negative was noted in three cases. The early uptake ratios were closely related to the tumor vascularity but had no statistically significant difference in the tumor vascularity but had no statistically significant difference in the tumor histology or histologic malignancy. 16 refs., 6 figs., 2 tabs.

  6. MiRNA-21 Expression Decreases from Primary Tumors to Liver Metastases in Colorectal Carcinoma

    PubMed Central

    Feiersinger, Fabian; Nolte, Elke; Wach, Sven; Rau, Tilman T.; Vassos, Nikolaos; Geppert, Carol; Konrad, Andreas; Merkel, Susanne; Taubert, Helge; Stürzl, Michael; Croner, Roland S.

    2016-01-01

    Objective Metastasis is the major cause of death in colorectal cancer patients. Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of colorectal cancer and the initiation of metastasis. In this study, we compared miRNA expression in primary colorectal cancer and corresponding liver metastases in order to get an idea of the oncogenic importance of the miRNAs in established metastases. Methods We analyzed the expression of miRNA-21, miRNA-31 and miRNA-373 in corresponding formalin-fixed paraffin-embedded (FFPE) tissue samples of primary colorectal cancer, liver metastasis and healthy tissues of 29 patients by quantitative real-time PCR. Results All three miRNAs were significantly up-regulated in the primary tumor tissues as compared to healthy colon mucosa of the respective patients (p < 0.01). MiRNA-21 and miRNA-31 were also higher expressed in liver metastases as compared to healthy liver tissues (p < 0.01). No significant difference of expression of miRNA-31 and miRNA-373 was observed between primary tumors and metastases. Of note, miRNA-21 expression was significantly reduced in liver metastases as compared to the primary colorectal tumors (p < 0.01). Conclusion In the context of previous studies demonstrating increased miRNA-21 expression in metastatic primary tumors, our findings raise the question whether miRNA-21 might be involved in the initiation but not in the perpetuation and growth of metastases. PMID:26845148

  7. Reassessing the need for primary tumor surgery in unresectable metastatic colorectal cancer: overview and perspective.

    PubMed

    Poultsides, George A; Paty, Phillip B

    2011-01-01

    In the absence of symptoms, primary tumor resection in patients who present with unresectable metastatic colorectal cancer is of uncertain benefit. Prophylactic surgery has been traditionally considered in this setting in order to prevent subsequent complications of perforation, obstruction, or bleeding later during the treatment course, which may require urgent surgery associated with higher mortality. However, recent data have called into question the efficacy of this upfront surgical strategy. We provide a brief overview of how current combinations of systemic chemotherapy including fluorouracil, oxaliplatin, irinotecan, and targeted biologic agents have allowed improved local (in addition to distant) tumor control, significantly decreasing the incidence of late primary-related complications requiring surgery from roughly 20% in the era of single-agent fluoropyrimidine chemotherapy to almost 7% in the era of modern triple-drug chemotherapy. In addition, we attempt to highlight those factors most associated with subsequent primary tumor-related complications in an effort to identify the subset of patients with synchronous metastatic colorectal cancer who might benefit from a surgery-first approach. Finally, we discuss modern nonsurgical options available for palliation of the primary colorectal tumor and review the outcome of patients for which emergent surgery is eventually required to address primary-related symptoms. PMID:21789154

  8. Cdk4 deficiency inhibits skin tumor development but does not affect normal keratinocyte proliferation.

    PubMed

    Rodriguez-Puebla, Marcelo L; Miliani de Marval, Paula L; LaCava, Margaret; Moons, David S; Kiyokawa, Hiroaki; Conti, Claudio J

    2002-08-01

    Most human tumors have mutations that result in deregulation of the cdk4/cyclin-Ink4-Rb pathway. Overexpression of D-type cyclins or cdk4 and inactivation of Ink4 inhibitors are common in human tumors. Conversely, lack of cyclin D1 expression results in significant reduction in mouse skin and mammary tumor development. However, complete elimination of tumor development was not observed in these models, suggesting that other cyclin/cdk complexes play an important role in tumorigenesis. Here we described the effects of cdk4 deficiency on mouse skin proliferation and tumor development. Cdk4 deficiency resulted in a 98% reduction in the number of tumors generated through the two-stage carcinogenesis model. The absence of cdk4 did not affect normal keratinocyte proliferation and both wild-type and cdk4 knockout epidermis are equally affected after topical treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), resulting in epidermal hyperplasia. In similar fashion, cdk4 knockout keratinocytes proliferated well in an in vivo model of wound-induced proliferation. Biochemical studies in mouse epidermis showed that cdk6 activity increased twofold in cdk4-deficient mice compared to wild-type siblings. These results suggest that therapeutic approaches to inhibit cdk4 activity could provide a target to inhibit tumor development with minimal or no effect in normal tissue.

  9. cdk4 Deficiency Inhibits Skin Tumor Development but Does Not Affect Normal Keratinocyte Proliferation

    PubMed Central

    Rodriguez-Puebla, Marcelo L.; Miliani de Marval, Paula L.; LaCava, Margaret; Moons, David S.; Kiyokawa, Hiroaki; Conti, Claudio J.

    2002-01-01

    Most human tumors have mutations that result in deregulation of the cdk4/cyclin-Ink4-Rb pathway. Overexpression of D-type cyclins or cdk4 and inactivation of Ink4 inhibitors are common in human tumors. Conversely, lack of cyclin D1 expression results in significant reduction in mouse skin and mammary tumor development. However, complete elimination of tumor development was not observed in these models, suggesting that other cyclin/cdk complexes play an important role in tumorigenesis. Here we described the effects of cdk4 deficiency on mouse skin proliferation and tumor development. Cdk4 deficiency resulted in a 98% reduction in the number of tumors generated through the two-stage carcinogenesis model. The absence of cdk4 did not affect normal keratinocyte proliferation and both wild-type and cdk4 knockout epidermis are equally affected after topical treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), resulting in epidermal hyperplasia. In similar fashion, cdk4 knockout keratinocytes proliferated well in an in vivo model of wound-induced proliferation. Biochemical studies in mouse epidermis showed that cdk6 activity increased twofold in cdk4-deficient mice compared to wild-type siblings. These results suggest that therapeutic approaches to inhibit cdk4 activity could provide a target to inhibit tumor development with minimal or no effect in normal tissue. PMID:12163365

  10. Bone Windows for Distinguishing Malignant from Benign Primary Bone Tumors on FDG PET/CT

    PubMed Central

    Costelloe, Colleen M.; Chuang, Hubert H.; Chasen, Beth A.; Pan, Tinsu; Fox, Patricia S.; Bassett, Roland L.; Madewell, John E.

    2013-01-01

    Objective. The default window setting on PET/CT workstations is soft tissue. This study investigates whether bone windowing and hybrid FDG PET/CT can help differentiate between malignant and benign primary bone tumors. Materials and methods. A database review included 98 patients with malignant (n=64) or benign primary bone (n=34) tumors. The reference standard was biopsy for malignancies and biopsy or >1 year imaging follow-up of benign tumors. Three radiologists and/or nuclear medicine physicians blinded to diagnosis and other imaging viewed the lesions on CT with bone windows (CT-BW) without and then with PET (PET/CT-BW), and separate PET-only images for malignancy or benignity. Three weeks later the tumors were viewed on CT with soft tissue windows (CT-STW) without and then with PET (PET/CT-STW). Results. Mean sensitivity and specificity for identifying malignancies included: CT-BW: 96%, 90%; CT-STW: 90%, 90%; PET/CT-BW: 95%, 85%, PET/CT-STW: 95%, 86% and PET-only: 96%, 75%, respectively. CT-BW demonstrated higher specificity than PET-only and PET/CT-BW (p=0.0005 and p=0.0103, respectively) and trended toward higher sensitivity than CT-STW (p=0.0759). Malignant primary bone tumors were more avid than benign lesions overall (p<0.0001) but the avidity of benign aggressive lesions (giant cell tumors and Langerhans Cell Histiocytosis) trended higher than the malignancies (p=0.08). Conclusion. Bone windows provided high specificity for distinguishing between malignant and benign primary bone tumors and are recommended when viewing FDG PET/CT. PMID:23983816

  11. Metastasizing mixed tumor of the parotid: initial presentation as a solitary kidney tumor and ultimate carcinomatous transformation at the primary site.

    PubMed

    Czader, M; Eberhart, C G; Bhatti, N; Cummings, C; Westra, W H

    2000-08-01

    Benign mixed tumors of the salivary glands are generally regarded as indolent and harmless neoplasms. A subset of benign mixed tumors, however, can undergo carcinomatous transformation (that is, carcinoma ex-mixed tumor). Even more rarely, a mixed tumor that is seemingly benign at the microscopic level will metastasize like a true carcinoma (that is, metastasizing mixed tumor [MZMT]). Despite the benign appearance of the metastatic implants, there is usually little doubt regarding their true nature and origin. Patients invariably have had a mixed tumor removed from the parotid or some other salivary gland, and metastatic spread is usually preceded by multiple episodes of local tumor recurrence. We report a case of MZMT that presented as a solitary kidney mass. In the absence of a previous or concurrent salivary gland tumor, its metastatic nature was not appreciated and it was regarded as an unusual but benign kidney adenoma. One year after removal of the kidney mass, the patient presented with signs and symptoms of an aggressive parotid tumor. Pathologic examination of the tumor in the parotid demonstrated a high-grade carcinoma arising from a mixed tumor. This case underscores the importance of considering MZMT when a seemingly benign mixed tumor is encountered at a nonsalivary site, even in patients without a supportive history. Failure to do so may cause an unnecessary delay in primary tumor diagnosis and management, allow the primary tumor to progress toward a more malignant phenotype, and deny the patient a high expectation for a complete cure.

  12. Primary Tumor Location as a Prognostic Factor in Metastatic Colorectal Cancer

    PubMed Central

    Loupakis, Fotios; Yang, Dongyun; Yau, Linda; Feng, Shibao; Cremolini, Chiara; Zhang, Wu; Maus, Martin K. H.; Antoniotti, Carlotta; Langer, Christiane; Scherer, Stefan J.; Müller, Thomas; Hurwitz, Herbert I.; Saltz, Leonard; Falcone, Alfredo

    2015-01-01

    Background: We sought to clarify the prognostic impact of primary tumor location in metastatic colorectal cancer (mCRC). Methods: We evaluated the association between tumor location and survival parameters in patients with previously untreated mCRC receiving first-line chemotherapy ± bevacizumab in three independent cohorts: a prospective pharmacogenetic study (PROVETTA) and two randomized phase III trials, AVF2107g and NO16966. Cancers proximal or distal of the splenic flexure were classified as right-sided or left-sided, respectively. The primary end point was overall survival (OS). Data were analyzed with Cox proportional hazards and logistic regression models. All statistical tests were two-sided. Results: Among evaluable patients in the PROVETTA (n = 200), AVF2107g (n = 559), and NO16966 (n = 1268) studies, 72.0%, 63.1%, and 73.7% had left-sided tumors, respectively. In PROVETTA, patients with left-sided tumors had superior OS (left-sided vs right-sided: hazard ratio [HR] = .44, 95% confidence interval [CI] = .28 to .70, P < .001) and progression-free survival (HR = .52, 95% CI = .36 to .75, P < .001) outcomes. Multivariable analyses confirmed right-sided location as a negative prognostic variable, independent of mucinous histology and BRAF mutational status. Data from the AVF2107g (HR for OS = .55, 95% CI = .43 to .70) and NO16966 trials (HR for OS = .71, 95% CI = .62 to .82 both P < .001) also showed favorable outcomes in patients with left-sided tumors. In both randomized studies, the efficacy of bevacizumab was independent of tumor location. Conclusions: These data demonstrate that primary tumor location is an important prognostic factor in previously untreated mCRC. Given the consistency across an exploratory set and two confirmatory phase III studies, side of tumor origin should be considered for stratification in randomized trials. PMID:25713148

  13. Ipsilateral Breast Tumor Relapse: Local Recurrence Versus New Primary Tumor and the Effect of Whole-Breast Radiotherapy on the Rate of New Primaries

    SciTech Connect

    Gujral, Dorothy M.; Sumo, Georges; Owen, John R.; Ashton, Anita; Bliss, Judith M.; Haviland, Joanne; Yarnold, John R.

    2011-01-01

    Purpose: The justification for partial breast radiotherapy after breast conservation surgery assumes that ipsilateral breast tumor relapses (IBTR) outside the index quadrant are mostly new primary (NP) tumors that develop despite radiotherapy. We tested the hypothesis that whole-breast radiotherapy (WBRT) is ineffective in preventing NP by comparing development rates in irradiated and contralateral breasts after tumor excision and WBRT. Methods and Materials: We retrospectively reviewed 1,410 women with breast cancer who were entered into a prospective randomized trial of radiotherapy fractionation and monitored annually for ipsilateral breast tumor relapses (IBTR) and contralateral breast cancer (CLBC). Cases of IBTR were classified into local recurrence (LR) or NP tumors based on location and histology and were subdivided as definite or likely depending on clinical data. Rates of ipsilateral NP and CLBC were compared over a 15-year period of follow-up. Results: At a median follow-up of 10.1 years, there were 150 documented cases of IBTR: 118 (79%) cases were definite or likely LR; 27 (18%) cases were definite or likely NP; and 5 (3%) cases could not be classified. There were 71 cases of CLBC. The crude proportion of definite-plus-likely NP was 1.9% (27/1,410) patients compared with 5% (71/1,410) CLBC patients. Cumulative incidence rates at 5, 10, and 15 years were 0.8%, 2.0%, and 3.5%, respectively, for definite-plus-likely NP and 2.4%, 5.8%, and 7.9%, respectively for CLBC, suggesting a difference in the rates of NP and CLBC. Conclusions: This analysis suggests that WBRT reduces the rate of ipsilateral NP tumors. The late presentation of NP has implications for the reporting of trials that are testing partial breast radiotherapy.

  14. Respiratory Syncytial Virus Infections in Infants Affected by Primary Immunodeficiency

    PubMed Central

    Capretti, Maria Grazia; Lazzarotto, Tiziana; Faldella, Giacomo

    2014-01-01

    Primary immunodeficiencies are rare inherited disorders that may lead to frequent and often severe acute respiratory infections. Respiratory syncytial virus (RSV) is one of the most frequent pathogens during early infancy and the infection is more severe in immunocompromised infants than in healthy infants, as a result of impaired T- and B-cell immune response unable to efficaciously neutralize viral replication, with subsequent increased viral shedding and potentially lethal lower respiratory tract infection. Several authors have reported a severe clinical course after RSV infections in infants and children with primary and acquired immunodeficiencies. Environmental prophylaxis is essential in order to reduce the infection during the epidemic season in hospitalized immunocompromised infants. Prophylaxis with palivizumab, a humanized monoclonal antibody against the RSV F protein, is currently recommended in high-risk infants born prematurely, with chronic lung disease or congenital heart disease. Currently however the prophylaxis is not routinely recommended in infants with primary immunodeficiency, although some authors propose the extension of prophylaxis to this high risk population. PMID:25089282

  15. Inhibition of polyamine oxidase activity affects tumor development during the maize-Ustilago maydis interaction.

    PubMed

    Jasso-Robles, Francisco Ignacio; Jiménez-Bremont, Juan Francisco; Becerra-Flora, Alicia; Juárez-Montiel, Margarita; Gonzalez, María Elisa; Pieckenstain, Fernando Luis; García de la Cruz, Ramón Fernando; Rodríguez-Kessler, Margarita

    2016-05-01

    Ustilago maydis is a biotrophic plant pathogenic fungus that leads to tumor development in the aerial tissues of its host, Zea mays. These tumors are the result of cell hypertrophy and hyperplasia, and are accompanied by the reprograming of primary and secondary metabolism of infected plants. Up to now, little is known regarding key plant actors and their role in tumor development during the interaction with U. maydis. Polyamines are small aliphatic amines that regulate plant growth, development and stress responses. In a previous study, we found substantial increases of polyamine levels in tumors. In the present work, we describe the maize polyamine oxidase (PAO) gene family, its contribution to hydrogen peroxide (H2O2) production and its possible role in tumor development induced by U. maydis. Histochemical analysis revealed that chlorotic lesions and maize tumors induced by U. maydis accumulate H2O2 to significant levels. Maize plants inoculated with U. maydis and treated with the PAO inhibitor 1,8-diaminooctane exhibit a notable reduction of H2O2 accumulation in infected tissues and a significant drop in PAO activity. This treatment also reduced disease symptoms in infected plants. Finally, among six maize PAO genes only the ZmPAO1, which encodes an extracellular enzyme, is up-regulated in tumors. Our data suggest that H2O2 produced through PA catabolism by ZmPAO1 plays an important role in tumor development during the maize-U. maydis interaction.

  16. A case of primary spinal atypical teratoid/rhabdoid tumor in a 5-year-old child

    PubMed Central

    Mankotia, Dipanker Singh; Tandon, Vivek; Sharma, Bhawani Shankar; Rajeshwari, Madhu; Sharma, Mehar Chand

    2016-01-01

    Atypical teratoid/rhabdoid tumor (AT/RT) is a rare central nervous system neoplasm affecting children, and isolated primary spinal involvement is extremely rare. Authors describe a case of spinal AT/RT in a 5-year-old male child presenting with rapidly progressing quadriparesis diagnosed and managed surgically and medically. Biopsy revealed large, rhabdoid cells with prominent nucleoli in nest and immunohistochemistry further showed loss of integrase integrator 1 expression considered to be gold standard for diagnosis. AT/RT has extremely poor prognosis with median survival being 6 months. PMID:27606020

  17. A case of primary spinal atypical teratoid/rhabdoid tumor in a 5-year-old child.

    PubMed

    Mankotia, Dipanker Singh; Tandon, Vivek; Sharma, Bhawani Shankar; Rajeshwari, Madhu; Sharma, Mehar Chand

    2016-01-01

    Atypical teratoid/rhabdoid tumor (AT/RT) is a rare central nervous system neoplasm affecting children, and isolated primary spinal involvement is extremely rare. Authors describe a case of spinal AT/RT in a 5-year-old male child presenting with rapidly progressing quadriparesis diagnosed and managed surgically and medically. Biopsy revealed large, rhabdoid cells with prominent nucleoli in nest and immunohistochemistry further showed loss of integrase integrator 1 expression considered to be gold standard for diagnosis. AT/RT has extremely poor prognosis with median survival being 6 months. PMID:27606020

  18. Radiotherapy and death from cerebrovascular disease in patients with primary brain tumors.

    PubMed

    Aizer, Ayal A; Du, Rose; Wen, Patrick Y; Arvold, Nils D

    2015-09-01

    Radiotherapy is often used in the management of primary brain tumors, but late cerebrovascular risks remain incompletely characterized. We examined the relationship between radiotherapy and the risk of death from cerebrovascular disease (CVD) in this population. We used the Surveillance, Epidemiology, and End Results Program to identify 19,565 patients of any age diagnosed with a primary brain tumor between 1983-2002. Multivariable competing risks analysis and an interaction model were used to determine whether receipt of radiotherapy was associated with an increased risk of CVD-specific death, adjusting for tumor proximity to central arterial circulations of the brain. The median follow up in surviving patients was 12.75 years. Baseline characteristics were similar in patients who did and did not receive radiotherapy. Ten-year CVD-specific mortality in patients with tumors near central arterial circulations who did and did not receive radiotherapy were 0.64 % (95 % CI 0.42-0.93 %) versus 0.16 % (95 % CI 0.055-0.40 %), p = 0.01. After adjustment for demographic, tumor-related, and treatment-related covariates, patients with tumors near central arterial circulations were significantly more likely to experience CVD-specific mortality after radiotherapy (HR 2.81; 95 % CI 1.25-6.31; p = 0.01); no association was observed among patients with more distant tumors (HR 0.77; 95 % CI 0.50-1.16; p = 0.21). The interaction model showed that tumor location was a key predictor of the risk of radiotherapy-associated, CVD-specific mortality (p-interaction = 0.004). Patients receiving radiotherapy for tumors near but not distant from the central vasculature of the brain are at increased risk for death secondary to CVD, which should be considered when counseling patients.

  19. Characterization of the activities of actin-affecting drugs on tumor cell migration

    SciTech Connect

    Hayot, Caroline; Debeir, Olivier; Ham, Philippe van; Damme, Marc van; Kiss, Robert; Decaestecker, Christine . E-mail: cdecaes@ulb.ac.be

    2006-02-15

    Metastases kill 90% of cancer patients. It is thus a major challenge in cancer therapy to inhibit the spreading of tumor cells from primary tumor sites to those particular organs where metastases are likely to occur. Whereas the actin cytoskeleton is a key component involved in cell migration, agents targeting actin dynamics have been relatively poorly investigated. Consequently, valuable in vitro pharmacological tools are needed to selectively identify this type of agent. In response to the absence of any standardized process, the present work aims to develop a multi-assay strategy for screening actin-affecting drugs with anti-migratory potentials. To validate our approach, we used two cancer cell lines (MCF7 and A549) and three actin-affecting drugs (cytochalasin D, latrunculin A, and jasplakinolide). We quantified the effects of these drugs on the kinetics of actin polymerization in tubes (by means of spectrofluorimetry) and on the dynamics of actin cytoskeletons within whole cells (by means of fluorescence microscopy). Using quantitative videomicroscopy, we investigated the actual effects of the drugs on cell motility. Finally, the combined drug effects on cell motility and cell growth were evaluated by means of a scratch-wound assay. While our results showed concordant drug-induced effects on actin polymerization occurring in vitro in test tubes and within whole cells, the whole cell assay appeared more sensitive than the tube assay. The inhibition of actin polymerization induced by cytochalasin D was paralleled by a decrease in cell motility for both cell types. In the case of jasplakinolide, which induces actin polymerization, while it significantly enhanced the locomotion of the A549 cells, it significantly inhibited that of the MCF-7 ones. All these effects were confirmed by means of the scratch-wound assay except of the jasplakinolide-induced effects on MCF-7 cell motility. These later seemed compensated by an additional effect occurring during wound

  20. Transoral Robotic Surgery and the Unknown Primary: A Cost-Effective Technique to Identify the Tumor

    PubMed Central

    Byrd, J. Kenneth; Smith, Kenneth J.; de Almeida, John R.; Albergotti, W. Greer; Davis, Kara S.; Kim, Seungwon W.; Johnson, Jonas T.; Ferris, Robert L.; Duvvuri, Umamaheswar

    2014-01-01

    Objective To evaluate the cost-effectiveness of transoral robotic surgery (TORS) for diagnosis and treatment of cervical unknown primary squamous cell carcinoma (CUP). Study Design Retrospective Review Subjects and Methods A retrospective chart review was performed on patients with new occult primary squamous cell carcinoma of the head and neck with non-diagnostic imaging and/or endoscopy who were treated with TORS at a tertiary hospital between 2009 and 2012. Direct costs ($) were obtained from the hospital’s billing system, and national data were used for inpatient hospital costs and physician fees. The proportion of tumors found in three strategies was used as effectiveness to calculate the incremental cost-effectiveness ratio. Results 206 head and neck robotic cases were performed at our institution between December 2009 and December 2012. Three surgeons performed TORS on 22 patients for occult primary squamous cell carcinoma. The primary tumor was located in 19/22 (86.4%) patients. The incremental cost-effectiveness ratio for sequential and simultaneous EUA and TORS base of tongue resection was $8619 and $5774 per additional primary identified, respectively. Conclusion TORS is a cost-effective procedure to locate the primary tumor in patients with cervical lymph node metastases and no obvious source. Bilateral base of tongue resection should be considered as part of the exam under anesthesia for these patients, particularly if the palatine tonsils have already been removed. PMID:24618502

  1. Multi-course PDT of malignant tumors: the influence on primary tumor, metastatic spreading and homeostasis of cancer patients

    NASA Astrophysics Data System (ADS)

    Sokolov, Victor V.; Chissov, Valery I.; Yakubovskaya, Raisa I.; Filonenko, E. V.; Sukhin, Garry M.; Nemtsova, E. R.; Belous, T. A.; Zharkova, Natalia N.

    1996-12-01

    The first clinical trials of photodynamic therapy (PDT) of cancer with two photosensitizers, PHOTOHEME and PHOTOSENS, were started in P.A. Hertzen Research Oncological Institute (Moscow, Russia) in 1992 and 1994. Up to now, 208 patients with primary, recurrent and metastatic malignant tumors (469) of skin (34 patients/185 tumors), breast cancer (24/101), head and neck (30/31), trachea and bronchus (31/42), esophagus (35/35), stomach (31/32), rectum (4/4), vagina and uterine cervix (7/8) and bladder (12/31) have been treated by PDT. One-hundred-thirty patients were injected with PHOTOHEME, 64 patients were injected with PHOTOSENS, 14 patients were injected with PHOTOHEME and PHOTOSENS. Totally, 302 courses of treatment were performed: 155 patients had one course and 53 patients were subjected to two to nine PDT sources with intervals from 1 to 18 months. A therapeutic effect of a one-course and multi- course PDT of malignant tumors (respiratory, digestive and urogenital systems) was evaluated clinically, histologically, roentgenologically, sonographically and endoscopically. The biochemical, hematological and immunological investigations were performed for all the patients in dynamics. Results of our study showed that a multi-course PDT method seems to be perspective in treatment of malignant tumors of basic localizations.

  2. Adult Antisocial Behavior and Affect Regulation among Primary Crack/Cocaine-Using Women

    ERIC Educational Resources Information Center

    Litt, Lisa Caren; Hien, Denise A.; Levin, Deborah

    2003-01-01

    The relationship between deficits in affect regulation and Adult Antisocial Behavior (ASB) in primary crack/cocaine-using women was explored in a sample of 80 inner-city women. Narrative early memories were coded for two components of affect regulation, Affect Tolerance and Affect Expression, using the Epigenetic Assessment Rating Scale (EARS;…

  3. Primary brain tumors associated with cerebral aneurysm: report of three cases.

    PubMed

    Suslu, Hikmet Turan; Bozbuga, Mustafa

    2011-01-01

    The primary brain tumors associated with cerebral aneurysms are rare in neurosurgical practice. The present article constitutes an evaluation of the management of coexistent primary brain tumor and cerebral aneurysm. A retrospective study of three cases of primary brain tumor with cerebral aneurysm was performed. We evaluated the complications and clinic outcomes by assessing the clinical and imaging findings. Case 1 presented with a subarachnoid hemorrhage from an aneurysm of the anterior communicating artery, with an incidental left frontal oligodendroglioma. Case 2 presented with chronic headache due to left frontal convexity meningioma, with proximal internal carotid artery aneurysm which was found incidentally during preoperative magnetic resonance angiography. Case 3 was admitted to our hospital complaining of headache, memory disturbance, and weakness in her left lower extremity. Magnetic resonance imaging revealed right frontal lymphoma and an unruptured aneurysm at the left middle cerebral artery. Preoperative magnetic resonance imaging revealed right frontal lymphoma and unruptured left middle cerebral artery. The frequency of primary brain tumor and cerebral aneurysm coexistence is increasing due to improvements in high-resolution imaging. In these complicated cases, the management will differ according to each pathology present, and this is an important problem for a neurosurgeon.

  4. Acute lymphoblastic leukemia as second primary tumor in a patient with retinoblastoma

    PubMed Central

    Ganguly, Anasua; Kaliki, Swathi; Mohammad, Faraz Ali; Mishra, Dilip K.; Vanajakshi, S.; Reddy, Vijay Anand

    2016-01-01

    Second primary tumor (SPT) is defined as a second tumor that presents either simultaneously or after the diagnosis of an index tumor. Second primary malignancies are the leading cause of death in patients with heritable retinoblastoma (RB). Acute lymphoblastic leukemia (ALL), as SPT in RB patients, is extremely rare. To the best of our knowledge, only five cases of ALL as SPT in patients with RB has been documented in the literature. Herein, we report a case of a 6-year-old girl with bilateral RB, who developed ALL during the course of treatment of RB. This case highlights the importance of reviewing blood investigations regularly to diagnose leukemia as SPT in RB and also the necessity for proper counseling and lifelong follow-up in these patients. PMID:27433042

  5. Acute lymphoblastic leukemia as second primary tumor in a patient with retinoblastoma.

    PubMed

    Ganguly, Anasua; Kaliki, Swathi; Mohammad, Faraz Ali; Mishra, Dilip K; Vanajakshi, S; Reddy, Vijay Anand

    2016-01-01

    Second primary tumor (SPT) is defined as a second tumor that presents either simultaneously or after the diagnosis of an index tumor. Second primary malignancies are the leading cause of death in patients with heritable retinoblastoma (RB). Acute lymphoblastic leukemia (ALL), as SPT in RB patients, is extremely rare. To the best of our knowledge, only five cases of ALL as SPT in patients with RB has been documented in the literature. Herein, we report a case of a 6-year-old girl with bilateral RB, who developed ALL during the course of treatment of RB. This case highlights the importance of reviewing blood investigations regularly to diagnose leukemia as SPT in RB and also the necessity for proper counseling and lifelong follow-up in these patients. PMID:27433042

  6. Gene mutations in primary tumors and corresponding patient-derived xenografts derived from non-small cell lung cancer

    PubMed Central

    Peng, Shaohua; Cao, Mengru; Li, Hongyu; Hu, Jing; Huang, Xiao; Liu, Wei; Zhang, Hui; Wu, Shuhong; Pataer, Apar; Heymach, John V.; Eterovic, Agda Karina; Zhang, Qingxiu; Shaw, Kenna R.; Chen, Ken; Futreal, Andrew; Wang, Michael; Hofstetter, Wayne; Mehran, Reza; Rice, David; Roth, Jack A.; Sepesi, Boris; Swisher, Stephen G.; Vaporciyan, Ara; Walsh, Garrett L.; Johnson, Faye M.; Fang, Bingliang

    2014-01-01

    Molecular annotated patient-derived xenograft (PDX) models are useful for the preclinical investigation of anticancer drugs and individualized anticancer therapy. We established 23 PDXs from 88 surgical specimens of lung cancer patients and determined gene mutations in these PDXs and their paired primary tumors by ultradeep exome sequencing on 202 cancer-related genes. The numbers of primary tumors with deleterious mutations in TP53, KRAS, PI3KCA, ALK, STK11, and EGFR were 43.5%, 21.7%, 17.4%, 17.4%, 13.0%, and 8.7%, respectively. Other genes with deleterious mutations in ≥3 (13.0%) primary tumors were MLL3, SETD2, ATM, ARID1A, CRIPAK, HGF, BAI3, EP300, KDR, PDGRRA and RUNX1. Of 315 mutations detected in the primary tumors, 293 (93%) were also detected in their corresponding PDXs, indicating that PDXs have the capacity to recapitulate the mutations in primary tumors. Nevertheless, a substantial number of mutations had higher allele frequencies in the PDXs than in the primary tumors, or were not detectable in the primary tumor, suggesting the possibility of tumor cell enrichment in PDXs or heterogeneity in the primary tumors. The molecularly annotated PDXs generated from this study could be useful for future translational studies. PMID:25444907

  7. Gene mutations in primary tumors and corresponding patient-derived xenografts derived from non-small cell lung cancer.

    PubMed

    Hao, Chuncheng; Wang, Li; Peng, Shaohua; Cao, Mengru; Li, Hongyu; Hu, Jing; Huang, Xiao; Liu, Wei; Zhang, Hui; Wu, Shuhong; Pataer, Apar; Heymach, John V; Eterovic, Agda Karina; Zhang, Qingxiu; Shaw, Kenna R; Chen, Ken; Futreal, Andrew; Wang, Michael; Hofstetter, Wayne; Mehran, Reza; Rice, David; Roth, Jack A; Sepesi, Boris; Swisher, Stephen G; Vaporciyan, Ara; Walsh, Garrett L; Johnson, Faye M; Fang, Bingliang

    2015-02-01

    Molecular annotated patient-derived xenograft (PDX) models are useful for the preclinical investigation of anticancer drugs and individualized anticancer therapy. We established 23 PDXs from 88 surgical specimens of lung cancer patients and determined gene mutations in these PDXs and their paired primary tumors by ultradeep exome sequencing on 202 cancer-related genes. The numbers of primary tumors with deleterious mutations in TP53, KRAS, PI3KCA, ALK, STK11, and EGFR were 43.5%, 21.7%, 17.4%, 17.4%, 13.0%, and 8.7%, respectively. Other genes with deleterious mutations in ≥3 (13.0%) primary tumors were MLL3, SETD2, ATM, ARID1A, CRIPAK, HGF, BAI3, EP300, KDR, PDGRRA and RUNX1. Of 315 mutations detected in the primary tumors, 293 (93%) were also detected in their corresponding PDXs, indicating that PDXs have the capacity to recapitulate the mutations in primary tumors. Nevertheless, a substantial number of mutations had higher allele frequencies in the PDXs than in the primary tumors, or were not detectable in the primary tumor, suggesting the possibility of tumor cell enrichment in PDXs or heterogeneity in the primary tumors. The molecularly annotated PDXs generated from this study could be useful for future translational studies.

  8. Scoparone affects lipid metabolism in primary hepatocytes using lipidomics

    PubMed Central

    Zhang, Aihua; Qiu, Shi; Sun, Hui; Zhang, Tianlei; Guan, Yu; Han, Ying; Yan, Guangli; Wang, Xijun

    2016-01-01

    Lipidomics, which focuses on the global study of molecular lipids in biological systems, could provide valuable insights about disease mechanisms. In this study, we present a nontargeted lipidomics strategy to determine cellular lipid alterations after scoparone exposure in primary hepatocytes. Lipid metabolic profiles were analyzed by high-performance liquid chromatography coupled with time-of-flight mass spectrometry, and a novel imaging TransOmics tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. Chemometric and statistical analyses of the obtained lipid fingerprints revealed the global lipidomic alterations and tested the therapeutic effects of scoparone. Identification of ten proposed lipids contributed to the better understanding of the effects of scoparone on lipid metabolism in hepatocytes. The most striking finding was that scoparone caused comprehensive lipid changes, as represented by significant changes of the identificated lipids. The levels of identified PG(19:1(9Z)/14:0), PE(17:1(9Z)/0:0), PE(19:1(9Z)/0:0) were found to be upregulated in ethanol-induced group, whereas the levels in scoparone group were downregulated. Lipid metabolism in primary hepatocytes was changed significantly by scoparone treatment. We believe that this novel approach could substantially broaden the applications of high mass resolution mass spectrometry for cellular lipidomics. PMID:27306123

  9. Factors affecting patient outcome in primary cutaneous aspergillosis

    PubMed Central

    Tatara, Alexander M.; Mikos, Antonios G.; Kontoyiannis, Dimitrios P.

    2016-01-01

    Abstract Primary cutaneous aspergillosis (PCA) is an uncommon infection of the skin. There is a paucity of organized literature regarding this entity in regard to patient characteristics, associated Aspergillus species, and treatment modalities on outcome (disease recurrence, disease dissemination, and mortality). We reviewed all published reports of PCA from 1967 to 2015. Cases were deemed eligible if they included the following: patient baseline characteristics (age, sex, underlying condition), evidence of proven or probable PCA, primary treatment strategy, and outcome. We identified 130 eligible cases reported from 1967 to 2015. The patients were predominantly male (63.8%) with a mean age of 30.4 ± 22.1 years. Rates of PCA recurrence, dissemination, and mortality were 10.8%, 18.5%, and 31.5%, respectively. In half of the cases, there was an association with a foreign body. Seven different Aspergillus species were reported to cause PCA. Systemic antifungal therapy without surgery was the most common form of therapy (60% of cases). Disease dissemination was more common in patients with underlying systemic conditions and occurred on average 41.4 days after PCA diagnosis (range of 3–120 days). In a multivariate linear regression model of mortality including only patients with immunosuppressive conditions, dissemination and human immunodeficiency virus/acquired immune deficiency syndrome were statistically significantly associated with increased mortality. Nearly one-third of patients with PCA die with the disease. Dissemination and host status are critical in patient outcome. PMID:27367980

  10. Primary cilia mechanics affects cell mechanosensation: A computational study.

    PubMed

    Khayyeri, Hanifeh; Barreto, Sara; Lacroix, Damien

    2015-08-21

    Primary cilia (PC) are mechanical cell structures linked to the cytoskeleton and are central to how cells sense biomechanical signals from their environment. However, it is unclear exactly how PC mechanics influences cell mechanosensation. In this study we investigate how the PC mechanical characteristics are involved in the mechanotransduction process whereby cilium deflection under fluid flow induces strains on the internal cell components that regulate the cell׳s mechanosensitive response. Our investigation employs a computational approach in which a finite element model of a cell consisting of a nucleus, cytoplasm, cortex, microtubules, actin bundles and a primary cilium was used together with a finite element representation of a flow chamber. Fluid-structure interaction analysis was performed by simulating perfusion flow of 1mm/s on the cell model. Simulations of cells with different PC mechanical characteristics, showed that the length and the stiffness of PC are responsible for the transmission of mechanical stimuli to the cytoskeleton. Fluid flow deflects the cilium, with the highest strains found at the base of the PC and in the cytoplasm. The PC deflection created further strains on the cell nucleus but did not influence microtubules and actin bundles significantly. Our results indicate that PC deflection under fluid flow stimulation transmits mechanical strain primarily to other essential organelles in the cytoplasm, such as the Golgi complex, that regulate cells' mechanoresponse. The simulations further suggest that cell mechanosensitivity can be altered by targeting PC length and rigidity.

  11. Assessing Achievement of Primary Grader Students and Factors Affecting Achievement in Pakistan

    ERIC Educational Resources Information Center

    Saeed, Muhammad; Gondal, Muhammad Bashir; Bushra

    2005-01-01

    Purpose: This paper aims to focus on achievement level of primary grade students in different subjects taught at primary level and the factors affecting the student achievement in this regard. Design/methodology/approach: The study was carried out on a sample of 1,080 students of grade 3 and 5 drawn from randomly selected 36 primary/elementary…

  12. Surgical treatment of potentially primary malignant adrenal tumors: an unresolved issue.

    PubMed

    Zografos, George N; Perysinakis, Iraklis; Kyrodimou, Eustathia; Kassi, Eva; Kaltsas, Gregory

    2015-01-01

    Although the great majority of incidentalomas are adrenocortical adenomas, a number of them, depending on the size and radiological characteristics of the lesions, will turn out to be carcinomas. These tumors may present as suspicious on initial evaluation and potentially malignant or malignant on histology. Adrenocortical carcinoma is a rare and aggressive malignancy with evolving diagnostic and therapeutic approaches. Laparoscopic surgery has become the gold standard for surgery of benign adrenal tumors. Despite the extensive experience gained in laparoscopic adrenalectomy, controversy still remains in the management of adrenal tumors with high suspicion or evidence of malignancy. The aim of this review is to update the existing information regarding the diagnostic approach and surgical management of suspicious and potentially malignant primary adrenal tumors.The interpretation of radiologic characteristics is a cornerstone in pre-operative assessment of large adrenal masses, since open surgery remains the preferred procedure when malignancy is suspected in large tumors with possible local invasion. Despite the improvement of imaging techniques, they lack sufficient accuracy to exclude primary malignancy in tumors from 4 cm to 10 cm in size. An initial laparoscopic approach can be used in this group of patients, but early conversion to open technique is mandatory if curative resection cannot be performed. Adrenal tumors >10 cm of malignant potential should be treated by the open approach from the start. Solitary adrenal metastasis from another primary malignancy is usually amenable to laparoscopic surgery. Patients with suspected adrenal cancer should be referred to tertiary centers that perform laparoscopic and open adrenal surgery with minimal morbidity and mortality.

  13. Comparative genomic analysis of primary tumors and metastases in breast cancer

    PubMed Central

    Bertucci, François; Carbuccia, Nadine; Monneur, Audrey; Charafe-Jauffret, Emmanuelle; Goncalves, Anthony; Viens, Patrice; Birnbaum, Daniel; Chaffanet, Max

    2016-01-01

    Personalized medicine uses genomic information for selecting therapy in patients with metastatic cancer. An issue is the optimal tissue source (primary tumor or metastasis) for testing. We compared the DNA copy number and mutational profiles of primary breast cancers and paired metastases from 23 patients using whole-genome array-comparative genomic hybridization and next-generation sequencing of 365 “cancer-associated” genes. Primary tumors and metastases harbored copy number alterations (CNAs) and mutations common in breast cancer and showed concordant profiles. The global concordance regarding CNAs was shown by clustering and correlation matrix, which showed that each metastasis correlated more strongly with its paired tumor than with other samples. Genes with recurrent amplifications in breast cancer showed 100% (ERBB2, FGFR1), 96% (CCND1), and 88% (MYC) concordance for the amplified/non-amplified status. Among all samples, 499 mutations were identified, including 39 recurrent (AKT1, ERBB2, PIK3CA, TP53) and 460 non-recurrent variants. The tumors/metastases concordance of variants was 75%, higher for recurrent (92%) than for non-recurrent (73%) variants. Further mutational discordance came from very different variant allele frequencies for some variants. We showed that the chosen targeted therapy in two clinical trials of personalized medicine would be concordant in all but one patient (96%) when based on the molecular profiling of tumor and paired metastasis. Our results suggest that the genotyping of primary tumor may be acceptable to guide systemic treatment if the metastatic sample is not obtainable. However, given the rare but potentially relevant divergences for some actionable driver genes, the profiling of metastatic sample is recommended. PMID:27028851

  14. Effect of anti-tumor necrosis factor alpha antibodies on histopathology of primary Salmonella infections.

    PubMed

    Mastroeni, P; Skepper, J N; Hormaeche, C E

    1995-09-01

    We reported that administration of anti-tumor necrosis factor alpha (anti-TNF-alpha) antibodies exacerbates the course of a Salmonella infection in both susceptible and resistant mice by preventing the suppression of bacterial growth in the reticuloendothelial system. In the present study, we evaluated the effect of in vivo neutralization of TNF-alpha on the histopathology of primary Salmonella infections. We show that in primary infections, the suppression of bacterial growth in the reticuloendothelial system coincides with granuloma formation in the spleen and liver. Administration of anti-TNF-alpha globulins on day -1 of salmonellosis affected neither the histological picture nor the course of the infection in the early stages of the disease (days 1 to 3), with splenic and hepatic lesions consisting mainly of polymorphonuclear leukocytes (PMNs); conversely, later in infection (days 3 to 7), the treatment inhibited the formation of granulomas. When the anti-TNF-alpha treatment was started well after the suppression of bacterial growth in the reticuloendothelial system and the formation of granulomatous lesions in the spleen and liver, a prompt relapse of the infection and regression of already established granulomas were seen. In anti-TNF-alpha-treated mice, salmonellae were found inside macrophages and PMNs and extracellularly in the necrotic tissue of the spleen, while in the liver the organisms were seen mainly in inflammatory mononuclear cells, resident Kupffer cells, and hepatocytes and occasionally in the extracellular compartment within necrotic lesions. The bacteria appeared most often in clusters, being morphologically intact when in the extracellular space or within hepatocytes, while undergoing various degrees of degeneration when inside phagocytes. The results suggest that TNF-alpha is required for granuloma formation in salmonellosis and that its neutralization does not completely abrogate the bactericidal activity of macrophages and PMNs

  15. Primary bronchial tumors in childhood. A clinicopathologic study of six cases.

    PubMed

    Lack, E E; Harris, G B; Eraklis, A J; Vawter, G F

    1983-02-01

    A primary bronchial tumor was diagnosed in six children younger than age 12 years. These cases include four bronchial carcinoids, a low-grade mucoepidermoid carcinoma, and a granular cell tumor ("myoblastoma"). Lobar or segmental resection was performed in each case and remains the treatment of choice. The most common bronchial tumors in childhood are carcinoids with 17 other evaluable cases in the English Literature. This series includes the youngest child to be reported with bilateral choroidal metastases leading to blindness; in addition, there were clinical manifestations of gigantism and acromegaly possibly related to ectopic hormone production. Low-grade mucoepidermoid carcinomas rank second in frequency to carcinoids and have an excellent prognosis. Judging from the childhood bronchial tumors reported to date, proved examples of bronchogenic carcinoma are vanishingly rare. PMID:6295603

  16. Malignant mixed müllerian tumor of primary peritoneal origin☆

    PubMed Central

    Kanis, Margaux; Kesterson, Joshua P.; Shroff, Stuti; Lele, Shashikant; Mhawech-Fauceglia, Paulette

    2016-01-01

    The aim of this study was to describe 2 cases of primary peritoneal malignant mixed müllerian tumor (MMMT). Two patients with primary peritoneal MMMT were examined for their clinical and pathologic features. We describe 2 cases of primary peritoneal MMMT in which the carcinomatous and mesenchymal components were readily identifiable, predominantly involving the peritoneum, with no ovarian involvement. The peritoneum and ovaries, with their common embryologic origin, likely account for the peritoneum’s ability to undergo a similar malignant transformation, with the resultant genesis of an MMMT of peritoneal origin. PMID:20952288

  17. Age–incidence patterns of primary CNS tumors in children, adolescents, and adults in England

    PubMed Central

    Arora, Ramandeep S.; Alston, Robert D.; Eden, Tim O.B.; Estlin, Edward J.; Moran, Anthony; Birch, Jillian M.

    2009-01-01

    Around 25% of all tumors in those 0–14 years of age and 9% in those 15–24 years of age involve the CNS. They are the most common cause of cancer-related deaths in both age groups. In adults 25–84 years of age, the proportion of CNS tumors is 2%; 5-year overall survival is 10%–15%; and survivors have considerable morbidity. Comprehensive up-to-date population-based incidence data on these tumors are lacking. We present incidence rates for primary CNS tumors based on data derived from the high-quality national cancer registration system in England. A total of 54,336 CNS tumors of malignant, benign, and uncertain behavior were registered across the whole of England from 1995 through 2003. The age-standardized rates for all ages (0–84 years) was 9.21 per 100,000 person-years. This is higher than previously reported for England because it includes nonmalignant CNS tumors and hence gives a more accurate picture of burden of disease. The age-standardized rates for those 0–14 years of age, 15–24 years of age, and 25–84 years of age were 3.56, 3.26, and 14.57 per 100,000 person-years, respectively. In this article, we describe the changing patterns in the epidemiology of primary CNS tumors in these three age groups with respect to sex, tumor behavior, and histology using the current WHO classification. This information will provide a reference for future studies nationally and internationally and make comparisons relevant and meaningful. PMID:19033157

  18. Primary Glial and Neuronal Tumors of the Ovary or Peritoneum: A Clinicopathologic Study of 11 Cases.

    PubMed

    Liang, Li; Olar, Adriana; Niu, Na; Jiang, Yi; Cheng, Wenjun; Bian, Xiu-Wu; Yang, Wentao; Zhang, Jing; Yemelyanova, Anna; Malpica, Anais; Zhang, Zhihong; Fuller, Gregory N; Liu, Jinsong

    2016-06-01

    Primary glial and neuronal tumors of the ovary or peritoneum are rare neuroectodermal-type tumors similar to their counterparts in the central nervous system. We retrospectively reviewed 11 cases. These cases included 4 ependymomas, 6 astrocytic tumors, and 1 neurocytoma. Patients' age ranged from 9 to 50 years (mean, 26 y; median, 24 y). All ependymal tumors with detailed clinical history (n=3) were not associated with any other ovarian neoplasm. In contrast, all astrocytic tumors were associated with immature teratoma (n=4), mature cystic teratoma (n=1), or mixed germ cell tumor (n=1). The neurocytoma arose in association with mature teratomatous components in a patient with a history of treated mixed germ cell tumor. Immunohistochemical staining showed that 7 of 7 ependymal and astrocytic tumors (100%) were positive for glial fibrillary acidic protein, and 2 of 2 ependymomas (100%) were positive for both estrogen and progesterone receptors. The neurocytoma was positive for synaptophysin and negative for S100 protein, glial fibrillary acidic protein, and SALL4. No IDH1-R132H mutation was detected in 2 of 2 (0%) astrocytomas by immunohistochemistry. Next-generation sequencing was performed on additional 2 ependymomas and 2 astrocytomas but detected no mutations in a panel of 50 genes that included IDH1, IDH2, TP53, PIK3CA, EGFR, BRAF, and PTEN. Follow-up information was available for 8 patients, with the follow-up period ranging from 4 to 59 months (mean, 15 mo; median, 8.5 mo), of which 3 had no evidence of disease and 5 were alive with disease. In conclusion, primary glial and neuronal tumors of the ovary can arise independently or in association with other ovarian germ cell tumor components. Pathologists should be aware of these rare tumors and differentiate them from other ovarian neoplasms. Even though an IDH1 or IDH2 mutation is found in the majority of WHO grade II and III astrocytomas, and in secondary glioblastomas arising from them, such mutations were

  19. Brain tumors.

    PubMed Central

    Black, K. L.; Mazziotta, J. C.; Becker, D. P.

    1991-01-01

    Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors. Images PMID:1848735

  20. Presentation and Management of Bipolar Affective Disorders in Primary Care

    PubMed Central

    Latimer, Elizabeth

    1982-01-01

    The author reviews four case summaries of patients presenting to her family practice within a 12 month period. Each patient presented unique features, which on careful history review, fit the pattern of bipolar affective disorder, the features of which are described. Management of these patients includes mandatory psychiatric consultation and lithium for treatment of acute mania, and prophylaxis of mania and depression. Guidelines for lithium therapy are presented. The family physician is in an ideal position to detect bipolar illness and to manage patients once stabilized on longterm lithium therapy. PMID:21289854

  1. Primary carcinoid tumors of the testis: a clinicopathologic study of 29 cases.

    PubMed

    Wang, Wenle P; Guo, Charles; Berney, Daniel M; Ulbright, Thomas M; Ubright, Thomas M; Hansel, Donna E; Shen, Rulong; Ali, Tehmina; Epstein, Jonathan I

    2010-04-01

    Testicular carcinoid tumors are rare with only limited studies. We identified 29 primary testicular carcinoid cases from 7 academic institutions. Patients ranged in age from 12 to 65 years old (mean 36). The most common presenting symptom was the sole finding of either a testicular mass or swelling seen in 15/24 cases with available information. The next most common mode of presentation was as an incidental finding seen in 6 cases. Two patients had carcinoid syndrome including diarrhea, hot flashes, and palpitations. Nineteen were pure carcinoid tumors, 3 were associated with cystic teratoma, 2 with cysts lacking epithelial lining, 4 with epidermoid cyst, and 1 with dermoid cyst. The mean size was 2.5 cm. All 29 primary carcinoids lacked associated intratubular germ cell neoplasia, unclassified type. Mitotic figures were rare in primary carcinoid tumors with only 3 cases showing more than 2 per 10 HPF; necrosis was found in only 1 case. Random scattered mild to moderate nuclear atypia was seen in 12/29 cases. Of the 28 cases found premortem, treatment included focal excision in 3 patients and radical orchiectomy in 25 patients. Follow-up, available in 24 cases, ranged from 1 to 228 months (mean 52.7 mo); of the 20 patients with testicular typical carcinoid tumors found premortem, all were alive at last follow-up without recurrences or metastases. Of the 4 patients with a primary atypical carcinoid tumor, 1 at the time of diagnosis had retroperitoneal and lung metastases who after chemotherapy underwent resection of the retroperitoneal tumor showing metastatic yolk sac tumor and embryonal carcinoma. After resection, serum AFP levels remained elevated and the patient is scheduled for salvage chemotherapy and bone marrow transplant. The other 2 patients with atypical carcinoid and follow-up had no evidence of disease at 68 and 114 months. Most primary carcinoid tumors of the testis have a benign clinical course even if associated with epidermoid/dermoid cysts, or

  2. Primary gastrointestinal stromal tumor of the liver: A case report and review of the literature

    PubMed Central

    Cheng, Xiaobin; Chen, Dong; Chen, Wenbin; Sheng, Qinsong

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors located in the alimentary tract. A small portion of GISTs are observed in extra-gastrointestinal regions, primarily in the omentum, mesentery and retroperioneum, and these types of GISTs are referred to as extra-gastrointestinal stromal tumors. The present study reports of a patient with unique primary liver GIST. The patient underwent en bloc resection and post-operative administration of imatinib, and subsequently experienced a good prognosis. The present case is followed by a brief review of reported cases of liver GISTs identified in the literature. The literature revealed that primary liver GISTs are usually large in size and possess a high mitotic index, which contributes to malignant characterization, thus classifying these tumors as high-risk. En bloc resection remains the mainstay of treatment for resectable primary liver GISTs. However, the prognosis of these patients is not favorable. Perioperative administration of imatinib may be useful to a certain extent, and interventional therapy, including radiofrequency ablation, should be considered.

  3. Cardiovascular magnetic resonance of primary tumors of the heart: A review.

    PubMed

    Fieno, David S; Saouaf, Rola; Thomson, Louise E J; Abidov, Aiden; Friedman, John D; Berman, Daniel S

    2006-01-01

    Overall, the prevalence of primary cardiac neoplasms is approximately 0.3% and these masses should be distinguished from the myriad of other primary and secondary processes that can occur in the heart. Tumors within, attached to, or near the heart can cause direct cardiac damage, can result in thrombus formation, can compromise blood flow and can embolize distally. Hence, proper diagnosis is clinically important. It has been suggested that cardiovascular magnetic resonance (CMR) imaging is a useful tool for diagnosing and characterizing cardiac tumors. In this report, we present a case example of a patient with a large, mobile right atrial myxoma imaged by CMR with results of histopathologic analysis after excision. We also demonstrate the utilization of CMR for characterization of cardiac lesions, review the basic characteristics of primary cardiac neoplasms, provide an overview of published cases describing use of CMR, and give suggested guidelines for imaging of cardiac masses with emphasis on diagnosis of cardiac tumors. CMR is an important technique for diagnosing and characterizing cardiac tumors. PMID:17060107

  4. Primary gastrointestinal stromal tumor of the liver: A case report and review of the literature

    PubMed Central

    Cheng, Xiaobin; Chen, Dong; Chen, Wenbin; Sheng, Qinsong

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors located in the alimentary tract. A small portion of GISTs are observed in extra-gastrointestinal regions, primarily in the omentum, mesentery and retroperioneum, and these types of GISTs are referred to as extra-gastrointestinal stromal tumors. The present study reports of a patient with unique primary liver GIST. The patient underwent en bloc resection and post-operative administration of imatinib, and subsequently experienced a good prognosis. The present case is followed by a brief review of reported cases of liver GISTs identified in the literature. The literature revealed that primary liver GISTs are usually large in size and possess a high mitotic index, which contributes to malignant characterization, thus classifying these tumors as high-risk. En bloc resection remains the mainstay of treatment for resectable primary liver GISTs. However, the prognosis of these patients is not favorable. Perioperative administration of imatinib may be useful to a certain extent, and interventional therapy, including radiofrequency ablation, should be considered. PMID:27698856

  5. Proliferative potential in benign mixed salivary gland tumors and its value in primary and recurrent neoplasms.

    PubMed

    Kazanceva, Anna; Groma, Valerie; Smane, Liene; Kornevs, Egils; Teibe, Uldis

    2011-01-01

    OBJECTIVE. Mixed salivary gland tumors are characterized by a marked diversity in the cell proliferation. It course in the stromal component, and, especially in recurrent neoplasms, is not completely understood. This study evaluated cell proliferative potential, its value and the clinical course of primary and recurrent salivary gland pleomorphic adenomas (PA). MATERIALS AND METHODS. 322 benign salivary gland tumors were used in this study. The cell proliferation was estimated by Ki-67 expression levels. RESULTS. Ki-67 immunoreactivity showed a wide range of spectra; in the epithelial and stromal type of PA the cell proliferation had the value from 0.07±0.03 (95% CI 0.01-0.14) to 4.81±0.60 (95% CI 3.61-6.02) and from 0 to 0.79±0.11 (95% CI 0.57-1.00), respectively. The Ki-67 value was higher in recurrent tumors compared with primary, and the mean number of Ki-67-positive cells per visual microscopic field constituted 2.14±1.60 (95% CI 1.47-2.47) comparing with 1.43 (95% CI 0.97-1.55) revealed in primary tumors. CONCLUSION. Cell proliferation values correlate with a recurrence of neoplasm, and elevation of proliferation potential in the stromal component of recurrent PA is indicative of clinical course change for the worse.

  6. Evaluation and management of the pregnant patient with suspected primary musculoskeletal tumor or metastatic carcinoma to bone.

    PubMed

    Puvanesarajah, Varun; Spiker, Andrea M; Shannon, Brett A; Grundy, Maureen; Levin, Adam S; Morris, Carol D

    2016-09-01

    Primary musculoskeletal cancer and metastatic disease to bone in pregnant patients presents major treatment challenges. Although uncommon, musculoskeletal malignancies in pregnant women have been reported. When diagnosing and treating these patients, the mother's health must be managed appropriately while ensuring that fetal development is not deleteriously affected. Extensive radiographic imaging and more advanced techniques are often necessary to fully characterize the extent of disease. When possible, magnetic resonance imaging should be used instead of computed tomography to limit exposure of the conceptus to radiation. If treatment is needed, therapeutic radiation, chemotherapy, and surgery should be considered. Surgical resection is the foundation of treatment of early-stage primary bone tumors and soft-tissue sarcomas during pregnancy. With surgery, anesthesia and thromboprophylaxis are important considerations. If chemotherapy is required, administration should be avoided in the first trimester to limit harm to the fetus. Therapeutic radiation should similarly be avoided during the first trimester and often can be postponed until after delivery. PMID:27566025

  7. Modulation of primary antibody response by protein A in tumor bearing mice.

    PubMed

    Zaidi, S I; Singh, K P; Raisuddin, S; Jafri, A; Saxena, A K; Choudhary, S; Ray, P K

    1995-11-01

    Protein A (PA) is a cell wall glycoprotein of Staphylococcus aureus Cowan I, which possess a number of immunomodulatory and antitumor properties. We have previously shown that PA suppresses the anti-sheep erythrocyte primary antibody response in normal mice. The present investigation evaluates the effect of protein A on the anti-sheep erythrocyte primary antibody response in tumor-bearing mice. The primary antibody response in tumor-bearing mice immunized with sheep red blood cells (SRBC) was suppressed by the intraperitoneal administration of PA in a dose-dependent fashion. The plaque forming cell (PFC) assay was used to assess this response. Maximum suppression of the PFC response was observed at 12 micrograms PA/animal (p < 0.001) and could be observed at doses as low as 1 microgram PA/animal (p < 0.01). The amount of suppression was proportional to the number of PA doses administered. In addition this effect was critically dependent on the timing of PA administration. PA showed no significant effect on PFC when injected after immunization, but it produced pronounced suppression when injected prior to the immunization with SRBC. Maximum suppression of the PFC response was observed when PA was administered one day before the antigen challenge. PA also reduced splenic localization of 51Cr labeled SRBC to 42% (p < 0.01). The altered localization of antigen in spleen may be responsible for reduced PFC response in tumor-bearing mice. Depletion of B-lymphocyte is reported to exhibit tumor inhibition. Therefore, we propose that the suppression of the primary antibody response by PA helps in tumor regression by reducing the soluble immunosuppressive immune complexes. PMID:8537611

  8. Primary Ewing Family of Tumors of the Jaw has a better Prognosis compared to Tumors of Extragnathic sites

    PubMed Central

    Owosho, Adepitan A.; Ko, Eugene; Rosenberg, Haley I.; Yom, SaeHee K.; Antonescu, Cristina R.; Huryn, Joseph M.; Estilo, Cherry L.

    2016-01-01

    Purpose Primary Ewing sarcoma of the jaw is rare. The aim of this study was to describe new cases of primary Ewing sarcoma of the jaw and investigate reported prognostic factors of Ewing sarcoma in this series and treatment outcome. Materials and Methods Six patients with primary Ewing sarcoma of the jaw were treated at the Memorial Sloan Kettering Cancer Center (MSKCC) from 1992 through 2013. Clinical data, pathology reports, treatment prescribed, treatment regimens, outcome, and follow-up information were reviewed. Results Five of 6 patients were female and 5 cases were in the mandible. No patient presented with metastatic disease at diagnosis. All cases were positive for CD99, and 3 patients with genetic confirmation were positive for EWS-FLI1 fusion or EWSR1 gene rearrangement. All patients received induction multiagent chemotherapy and surgical resection and 2 patients received adjuvant radiotherapy. Total (grade IV) or nearly total (grade III) tumor necrosis in 3 of 5 patients (60%) assessed for histologic response to chemotherapy indicated intense sensitivity. All patients were alive and free of disease, with no history of local recurrence, at a median follow-up period of 6.5 years. Conclusion Patients with primary Ewing sarcoma of the jaw have a good prognosis and metastasis is an uncommon occurrence at initial presentation. PMID:26679553

  9. Happiness as a motivator: positive affect predicts primary control striving for career and educational goals.

    PubMed

    Haase, Claudia M; Poulin, Michael J; Heckhausen, Jutta

    2012-08-01

    What motivates individuals to invest time and effort and overcome obstacles (i.e., strive for primary control) when pursuing important goals? We propose that positive affect predicts primary control striving for career and educational goals, and we explore the mediating role of control beliefs. In Study 1, positive affect predicted primary control striving for career goals in a two-wave longitudinal study of a U.S. sample. In Study 2, positive affect predicted primary control striving for career and educational goals and objective career outcomes in a six-wave longitudinal study of a German sample. Control beliefs partially mediated the longitudinal associations with primary control striving. Thus, when individuals experience positive affect, they become more motivated to invest time and effort, and overcome obstacles when pursuing their goals, in part because they believe they have more control over attaining their goals. PMID:22569224

  10. Epidemiology of primary brain tumors: current concepts and review of the literature.

    PubMed Central

    Wrensch, Margaret; Minn, Yuriko; Chew, Terri; Bondy, Melissa; Berger, Mitchel S.

    2002-01-01

    The purpose of this review is to provide a sufficiently detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Regarding risk factors, studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines. PMID:12356358

  11. Epidemiology of Primary Brain Tumors in the Middle Eastern Population in California, 2001–2005

    PubMed Central

    Nasseri, Kiumarss; Mills, John R.

    2009-01-01

    Background The fast growing Middle Eastern (ME) population has rarely been studied in the US. The purpose of this study was to compare the epidemiology of primary brain tumors in this ethnic population with the non-Hispanic, non-Middle Eastern White (NHNMW) in California. Methods ME cases were identified by surname in the California cancer registry and ME population estimates were based on ancestry. Data for 683 cases of primary brain tumors (429 benign, 238 malignant, 16 uncertain) in the ME and 15,589 cases (8,352 benign, 6,812 malignant, 425 uncertain) in the NHNMW were available for this study. Results ME patients were significantly (p<0.05) younger and their age-adjusted incidence rates per 100,000 for benign tumors of 10.0 in men and 17.6 in women were higher than similar rates of 7.3 and 10.6 in the NHNMW group (p<0.05). Rates for malignant tumors were similar. Meningioma was the main histology responsible for the observed increase in patients over 40 years of age. Also increased were benign tumors of the pituitary and pineal glands. The overall mortality in patients with benign tumors was significantly lower than malignant tumors. Conclusions This study presents a significantly high incidence of benign meningioma in the ME population in California. This may be due to higher susceptibility or exposure of this ethnic group to the risk factor(s) for this neoplasm. Considering the reported causal association of benign meningioma with childhood radiation exposure from Israel, exposure to this risk factor in this ethnic group needs to be evaluated in future studies. PMID:19588542

  12. Controlled release microspheres loaded with BMP7 suppress primary tumors from human glioblastoma.

    PubMed

    González-Gómez, Pilar; Crecente-Campo, Jose; Zahonero, Cristina; de la Fuente, Maria; Hernández-Laín, Aurelio; Mira, Helena; Sánchez-Gómez, Pilar; Garcia-Fuentes, Marcos

    2015-05-10

    Glioblastoma tumor initiating cells are believed to be the main drivers behind tumor recurrence, and therefore therapies that specifically manage this population are of great medical interest. In a previous work, we synthesized controlled release microspheres optimized for intracranial delivery of BMP7, and showed that these devices are able to stop the in vitro growth of a glioma cell line. Towards the translational development of this technology, we now explore these microspheres in further detail and characterize the mechanism of action and the in vivo therapeutic potential using tumor models relevant for the clinical setting: human primary glioblastoma cell lines. Our results show that BMP7 can stop the proliferation and block the self-renewal capacity of those primary cell lines that express the receptor BMPR1B. BMP7 was encapsulated in poly (lactic-co-glycolic acid) microspheres in the form of a complex with heparin and Tetronic, and the formulation provided effective release for several weeks, a process controlled by carrier degradation. Data from xenografts confirmed reduced and delayed tumor formation for animals treated with BMP7-loaded microspheres. This effect was coincident with the activation of the canonical BMP signaling pathway. Importantly, tumors treated with BMP7-loaded microspheres also showed downregulation of several markers that may be related to a malignant stem cell-like phenotype: CD133(+), Olig2, and GFAPδ. We also observed that tumors treated with BMP7-loaded microspheres showed enhanced expression of cell cycle inhibitors and reduced expression of the proliferation marker PCNA. In summary, BMP7-loaded controlled release microspheres are able to inhibit GBM growth and reduce malignancy markers. We envisage that this kind of selective therapy for tumor initiating cells could have a synergistic effect in combination with conventional cytoreductive therapy (chemo-, radiotherapy) or with immunotherapy.

  13. Controlled release microspheres loaded with BMP7 suppress primary tumors from human glioblastoma.

    PubMed

    González-Gómez, Pilar; Crecente-Campo, Jose; Zahonero, Cristina; de la Fuente, Maria; Hernández-Laín, Aurelio; Mira, Helena; Sánchez-Gómez, Pilar; Garcia-Fuentes, Marcos

    2015-05-10

    Glioblastoma tumor initiating cells are believed to be the main drivers behind tumor recurrence, and therefore therapies that specifically manage this population are of great medical interest. In a previous work, we synthesized controlled release microspheres optimized for intracranial delivery of BMP7, and showed that these devices are able to stop the in vitro growth of a glioma cell line. Towards the translational development of this technology, we now explore these microspheres in further detail and characterize the mechanism of action and the in vivo therapeutic potential using tumor models relevant for the clinical setting: human primary glioblastoma cell lines. Our results show that BMP7 can stop the proliferation and block the self-renewal capacity of those primary cell lines that express the receptor BMPR1B. BMP7 was encapsulated in poly (lactic-co-glycolic acid) microspheres in the form of a complex with heparin and Tetronic, and the formulation provided effective release for several weeks, a process controlled by carrier degradation. Data from xenografts confirmed reduced and delayed tumor formation for animals treated with BMP7-loaded microspheres. This effect was coincident with the activation of the canonical BMP signaling pathway. Importantly, tumors treated with BMP7-loaded microspheres also showed downregulation of several markers that may be related to a malignant stem cell-like phenotype: CD133(+), Olig2, and GFAPδ. We also observed that tumors treated with BMP7-loaded microspheres showed enhanced expression of cell cycle inhibitors and reduced expression of the proliferation marker PCNA. In summary, BMP7-loaded controlled release microspheres are able to inhibit GBM growth and reduce malignancy markers. We envisage that this kind of selective therapy for tumor initiating cells could have a synergistic effect in combination with conventional cytoreductive therapy (chemo-, radiotherapy) or with immunotherapy. PMID:25860932

  14. Roentgenologic diagnosis of primary corticotropin-producing carcinoid tumors of the mediastinum

    SciTech Connect

    Brown, L.R.; Aughenbaugh, G.L.; Wick, M.R.; Baker, B.A.; Salassa, R.M.

    1982-01-01

    A study was undertaken of five patients with Cushing syndrome due to adrenocorticotropin (ACTH) production by thymic carcinoid tumor (primary mediastinal Apudomas), including two recent patients examined by computed tomography (CT) of the chest. Plain roentgenography of the chest initially failed to detect tumor in four of the five patients, while CT of the chest yielded definitive diagnostic information in both patients in whom it was employed. For one of these patients, a mediastinal tumor could be seen retrospectively on plain roentgenograms of the chest, although it had been missed on the first examination. One of the tumors appeared to be partially calcified on CT scan, a finding not previously reported. Blastic osseous metastasis, which is common when malignant carcinoid tumors spread to bone, was seen in one patient. Our data suggest that in patients with suspected ectopic ACTH production, CT scanning of the mediastinum should be performed early in order to avoid delay in diagnosis of an ACTH-secreting carcinoid tumor of the mediastinum.

  15. Identification of Molecular Determinants of Primary and Metastatic Tumor Re-Initiation in Breast Cancer

    PubMed Central

    Ross, Jason B.; Huh, Doowon; Noble, Lisa B.; Tavazoie, Sohail F.

    2015-01-01

    Through in vivo selection of multiple ER-negative human breast cancer populations for enhanced tumor-forming capacity, we have derived sub-populations that generate tumors more efficiently than their parental populations at low cell numbers. Tumorigenic-enriched (TE) sub-populations displayed increased expression of LAMA4, FOXQ1 and NAP1L3—genes that are also expressed at greater levels by independently derived metastatic sub-populations. These genes promote metastatic efficiency. FOXQ1 promotes LAMA4 expression, while LAMA4 enhances clonal expansion upon substratum-detachment in vitro, tumor re-initiation in multiple organs, and disseminated metastatic cell proliferation and colonization. LAMA4’s promotion of cancer cell proliferation and tumor re-initiation requires β1-integrin. Increased LAMA4 expression marks the transition of human pre-malignant breast lesions to malignant carcinomas, while tumoral LAMA4 over-expression predicts reduced relapse-free survival in ER-negative patients. Our findings reveal common features that govern primary and metastatic tumor re-initiation and identify a key molecular determinant of these processes. PMID:25866923

  16. Near-infrared pH-activatable fluorescent probes for imaging primary and metastatic breast tumors.

    PubMed

    Lee, Hyeran; Akers, Walter; Bhushan, Kumar; Bloch, Sharon; Sudlow, Gail; Tang, Rui; Achilefu, Samuel

    2011-04-20

    Highly tumor selective near-infrared (NIR) pH-activatable probe was developed by conjugating pH-sensitive cyanine dye to a cyclic arginine-glycine-aspartic acid (cRGD) peptide targeting α(v)β(3) integrin (ABIR), a protein that is highly overexpressed in endothelial cells during tumor angiogenesis. The NIR pH-sensitive dye used to construct the probe exhibits high spectral sensitivity with pH changes. It has negligible fluorescence above pH 6 but becomes highly fluorescent below pH 5, with a pK(a) of 4.7. This probe is ideal for imaging acidic cell organelles such as tumor lysosomes or late endosomes. Cell microscopy data demonstrate that binding of the cRGD probe to ABIR facilitated the endocytosis-mediated lysosomal accumulation and subsequent fluorescence enhancement of the NIR pH-activatable dye in tumor cells (MDA-MB-435 and 4T1/luc). A similar fluorescence enhancement mechanism was observed in vivo, where the tumors were evident within 4 h post injection. Moreover, lung metastases were also visualized in an orthotopic tumor mouse model using this probe, which was further confirmed by histologic analysis. These results demonstrate the potential of using the new integrin-targeted pH-sensitive probe for the detection of primary and metastatic cancer.

  17. Trends in incidence of primary brain tumors in the United States, 1985-1994.

    PubMed Central

    Jukich, P. J.; McCarthy, B. J.; Surawicz, T. S.; Freels, S.; Davis, F. G.

    2001-01-01

    Brain tumor incidence has increased over the last 20 years in all age groups, both overall and for specific histologies. Reasons attributed to these increases include increase in lymphoma due to HIV/AIDS, introduction of computed tomography/magnetic resonance imaging, and changes in coding/classification. The purpose of this study was to describe overall and histologic-specific incidence trends in a population-based series of primary benign and malignant brain tumors. Data from the Central Brain Tumor Registry of the United States from 1985 through 1994 were used to determine incidence trends in the broad age groups 0-19, 20-64, and > or = 65 years, both overall and for selected histologies. Poisson regression was used to express trends as average annual percentage change. Overall, incidence increased modestly (annual percentage change 0.9%, 95% confidence interval, 0.4, 1.4). When lymphomas were excluded, this result was not statistically significant (annual percentage change 0.5%, 95% confidence interval, -0.1, 1.1). Specific histologies that were increasing were lymphomas in individuals aged 20 to 64 years and in males aged 65 years or older, ependymomas in the population aged 20 to 64 years, nerve sheath tumors in males, and pituitary tumors in females. Increases that were not specific to any population subgroup were seen for glioblastoma, oligodendrogliomas, and astrocytomas, excluding not otherwise specified (NOS) tumors. Corresponding decreases were noted for NOS, astrocytoma NOS, and glioma NOS. Increasing incidence trends for lymphomas were consistent with previous literature. Improvements in diagnostic technology in addition to changes in classification and coding were likely to be responsible for decreases seen in incidence of NOS subgroups and corresponding increases in glioma subgroups. In contrast, the increases identified for ependymomas, nerve sheath tumors, and pituitary tumors were less likely to be artifacts of improvements in diagnosis, and they

  18. Clinically aggressive primary solid pseudopapillary tumor of the ovary in a 45-year-old woman

    PubMed Central

    Syriac, Susanna; Kesterson, Joshua; Izevbaye, Iyare; de Mesy Bentley, Karen L.; Lele, Shashikant; Mhawech-Fauceglia, Paulette

    2016-01-01

    We report the first case of primary solid pseudopapillary tumor of the ovary with aggressive behavior and fatal outcome in a 45-year-old woman. The patient presented with weight loss, decrease of appetite, and abdominal bloating for the last several weeks. Computed tomography scan revealed an ovarian mass, omental caking, complex ascites, and 2 hepatic lesions. The pancreas was unremarkable. Grossly, the ovarian mass showed severe capsular adhesion, and the cut surface was cystic and solid. On histologic examination, the tumor was composed of diffuse solid pseudopapillary and pseudocystic patterns. The neoplastic cells were uniform and round with very dispersed chromatin. The cytoplasm was faintly pink. There was mild atypia, but the mitotic rate was as high as 62 per 50 high-power field, and the Ki-67 was elevated at 20%. The tumor exhibited severe necrosis. Numerous foci of lymphovascular invasion were also seen. The tumor cells were positive for cytokeratin (focal) and for β-catenin (cytoplasmic and nuclear patterns). They were negative for chromogranin, synaptophysin, thyroglobulin, calcitonin, hepatocyte-paraffin 1, epithelial membrane antigen, calretinin, and α-inhibin. Electron microscopic study revealed nests of tumor cells with oval nuclei. The cytoplasm contained numerous pleomorphic mitochondria interspersed among short strands of rough endoplasmic reticulum. The tumor involved the fallopian tube, omentum, cul-de-sac, and abdominal wall. The pelvic washing was also positive for tumor cells. Despite chemotherapy, the patient's condition had worsened, and she died of her disease 8 months after the initial diagnosis. We discuss the differential diagnosis of this tumor and the hypothesis of its origin. PMID:21778097

  19. Giant primary ossified cavernous hemangioma of the skull in an adult: A rare calvarial tumor

    PubMed Central

    Tyagi, Devendra K; Balasubramaniam, Srikant; Sawant, Hemant V

    2011-01-01

    Primary intraosseous cavernous hemangiomas (PICHs) of the cranium are rare benign vascular tumors that account for about 0.2 % of all bone tumors and 10 % of benign skull tumors. They generally present as osteolytic lesions with honeycomb pattern of calcification. Completely ossified cavernous hemangioma of the calvarium in an adult has not been reported previously. A 28-year-old female presented to us with a large right parietal skull mass that had been present since the last 15 years. Total resection of the lesion was performed. Pathological examination was suggestive of cavernous hemangioma of the skull bone. Cavernous hemangioma should be considered as one of the differential diagnosis in any case of bony swelling of the calvarium so that adequate preoperative planning can be made to minimize blood loss and subsequent morbidity. PMID:21897684

  20. Primary tumors of the external and middle ear. Benign and malignant glandular neoplasms.

    PubMed

    Dehner, L P; Chen, K T

    1980-01-01

    Glandular neoplasms represented 14% of primary tumors of the external and middle ear at the University of Minnesota. Although the collective term "ceruminoma" has been used in the past, four distinctive histopathologic patterns were recognized among our 12 cases: adenoma (four cases), pleomorphic adenoma (one case), adenoid cystic carcinoma (two cases) and adenocarcinoma (five cases). The prognosis correlated with these subgroups. A thorough review of the English literature also tended to support the rationale for the subclassification of so-called ceruminomas. The prevailing histogenetic view is that these tumors are derived from the modified apocrine glands of the auditory canal, the ceruminous glands. In some instances, these tumors may originate from ectopic salivary gland tissue.

  1. [Primary malignant solitary fibrous tumor/hemangiopericytoma of the parotid gland].

    PubMed

    Messa-Botero, Oscar Alberto; Romero-Rojas, Alfredo Ernesto; Chinchilla Olaya, Sandra Isabel; Díaz-Pérez, Julio Alexander; Tapias-Vargas, Luis Felipe

    2011-01-01

    Solitary fibrous tumor (SFT) was first described in the pleura by Lietaud in 1767; later in 1870, Wagner described the localized nature of this type of tumor and Klemperer and Rabin classified pleural tumors into two types: diffuse mesotheliomas and localized mesotheliomas. Recent years have seen the redefinition of this neoplasm, due to better technology; it is now proven that this neoplasm may have multiple different extrapleural origins including the head and neck regions. This diversity of locations is related to the particular mesenchymal histogenesis of SFT which allows its development from very unusual sites such as the salivary glands (SGs). In this particular site, this neoplasm is very infrequent and most of reported cases refer to benign disease, with just one case informed so far of primary malignant SFT.

  2. Tubulin glycylases are required for primary cilia, control of cell proliferation and tumor development in colon

    PubMed Central

    Rocha, Cecilia; Papon, Laura; Cacheux, Wulfran; Marques Sousa, Patricia; Lascano, Valeria; Tort, Olivia; Giordano, Tiziana; Vacher, Sophie; Lemmers, Benedicte; Mariani, Pascale; Meseure, Didier; Medema, Jan Paul; Bièche, Ivan; Hahne, Michael; Janke, Carsten

    2014-01-01

    TTLL3 and TTLL8 are tubulin glycine ligases catalyzing posttranslational glycylation of microtubules. We show here for the first time that these enzymes are required for robust formation of primary cilia. We further discover the existence of primary cilia in colon and demonstrate that TTLL3 is the only glycylase in this organ. As a consequence, colon epithelium shows a reduced number of primary cilia accompanied by an increased rate of cell division in TTLL3-knockout mice. Strikingly, higher proliferation is compensated by faster tissue turnover in normal colon. In a mouse model for tumorigenesis, lack of TTLL3 strongly promotes tumor development. We further demonstrate that decreased levels of TTLL3 expression are linked to the development of human colorectal carcinomas. Thus, we have uncovered a novel role for tubulin glycylation in primary cilia maintenance, which controls cell proliferation of colon epithelial cells and plays an essential role in colon cancer development. PMID:25180231

  3. KRAS Mutations in Primary Colorectal Cancer Tumors and Related Metastases: A Potential Role in Prediction of Lung Metastasis

    PubMed Central

    Cejas, Paloma; López-Gómez, Miriam; Aguayo, Cristina; Madero, Rosario; de Castro Carpeño, Javier; Belda-Iniesta, Cristóbal; Barriuso, Jorge; Moreno García, Víctor; Larrauri, Javier; López, Rocío; Casado, Enrique; Gonzalez-Barón, Manuel; Feliu, Jaime

    2009-01-01

    Background KRAS mutations in colorectal cancer primary tumors predict resistance to anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody therapy in patients with metastatic colorectal cancer, and thus represent a true indicator of EGFR pathway activation status. Methodology/Principal Findings KRAS mutations were retrospectively studied using polymerase chain reactions and subsequent sequencing of codons 12 and 13 (exon 2) in 110 patients with metastatic colorectal tumors. These studies were performed using tissue samples from both the primary tumor and their related metastases (93 liver, 84%; 17 lung, 16%). All patients received adjuvant 5-Fluorouracil-based polychemotherapy after resection of metastases. None received anti-EGFR therapy. Mutations in KRAS were observed in 37 (34%) of primary tumors and in 40 (36%) of related metastases, yielding a 94% level of concordance (kappa index 0.86). Patients with primary tumors possessing KRAS mutations had a shorter disease-free survival period after metastasis resection (12.0 vs 18.0 months; P = 0.035) than those who did not. A higher percentage of KRAS mutations was detected in primary tumors of patiens with lung metastases than in patients with liver metastases (59% vs 32%; p = 0.054). To further evaluate this finding we analyzed 120 additional patients with unresectable metastatic colorectal cancer who previously had their primary tumors evaluated for KRAS mutational status for clinical purposes. Separately, the analysis of these 120 patients showed a tendency towards a higher degree of KRAS mutations in primary tumors of patients with lung metastases, although it did not reach statistical significance. Taken together the group of 230 patients showed that KRAS was mutated significantly more often in the primary tumors of patients with lung metastases (57% vs 35%; P = 0.006). Conclusions/Significance Our results suggest a role for KRAS mutations in the propensity of primary colorectal tumors to

  4. Primary Tumor Site as a Predictor of Treatment Outcome for Definitive Radiotherapy of Advanced-Stage Oral Cavity Cancers

    SciTech Connect

    Lin, Chien-Yu; Wang, Hung-Ming; Kang, Chung-Jan; Lee, Li-Yu; Huang, Shiang-Fu; Fan, Kang-Hsing; Chen, Eric Yen-Chao

    2010-11-15

    Purpose: To evaluate the outcome of definitive radiotherapy (RT) for oral cavity cancers and to assess prognostic factors. Methods and Materials: Definitive RT was performed on 115 patients with oral cavity cancers at Stages III, IVA, and IVB, with a distribution of 6%, 47%, and 47%, respectively. The median dose of RT was 72Gy (range, 62-76Gy). Cisplatin-based chemotherapy was administered to 95% of the patients. Eleven patients underwent salvage surgery after RT failure. Results: Eight-eight (76.5%) patients responded partially and 23 (20%) completely; of the patients who responded, 18% and 57%, respectively, experienced a durable effect of treatment. The 3-year overall survival, disease-specific survival, and progression-free survival were 22%, 27%, and 25%, respectively. The 3-year PFS rates based on the primary tumor sites were as follows: Group I (buccal, mouth floor, and gum) 51%, Group II (retromolar and hard palate) 18%, and Group III (tongue and lip) 6% (p < 0.0001). The 3-year progression-free survival was 41% for N0 patients and 19% for patients with N+ disease (p = 0.012). The T stage and RT technique did not affect survival. The patients who underwent salvage surgery demonstrated better 3-year overall survival and disease-specific survival (53% vs. 19%, p = 0.015 and 53% vs. 24%, p = 0.029, respectively). Subsite group, N+, and salvage surgery were the only significant prognostic factors for survival after multivariate analysis. Conclusion: The primary tumor site and neck stage are prognostic predictors in advanced-stage oral cancer patients who received radical RT. The primary tumor extension and RT technique did not influence survival.

  5. Management of the Primary Tumor and Limited Metastases in Patients With Metastatic Pancreatic Cancer.

    PubMed

    Herman, Joseph M; Hoffman, John P; Thayer, Sarah P; Wolff, Robert A

    2015-05-01

    New combinations of cytotoxic chemotherapy have been proven to increase response rates and survival times compared with single-agent gemcitabine for patients with metastatic pancreatic cancer. These responses have been dramatic for a subset of patients, therefore raising questions about the management of limited metastatic disease with surgery or other ablative methods. Similarly, for patients having a complete radiographic response to chemotherapy in the metastatic compartment, whether to consider local therapy in the form of radiation or surgery for the primary tumor is now an appropriate question. Therefore, collaboration among experts in surgery, medical oncology, and radiation oncology has led to the development of guiding principles for local therapies to the primary intact pancreatic tumor for patients with limited metastatic disease and those who have had a significant response after systemic therapy.

  6. Primary pericardial extragastrointestinal stromal tumor: A case report and literature review

    PubMed Central

    ARPACI, TANER; TOKAT, FATMA; ARPACI, RABIA BOZDOGAN; AKBAS, TUGANA; UGURLUER, GAMZE; YAVUZ, SINAN

    2015-01-01

    Gastrointestinal stromal tumors (GISTs) are the most prevalent mesenchymal tumors of the gastrointestinal tract. GISTs are considered to originate from the interstitial cells of Cajal, the pacemakers of the peristaltic activity of the gastrointestinal tract. More than 95% of GISTs express KIT protein and discovered on GIST-1. GISTs may also be encountered in locations outside the gastrointestinal tract, in which case they are referred to as extra-GISTs (EGISTs) and often behave more aggressively. This is the case report of a primary pericardial EGIST in a 53-year-old male patient, confirmed by immunohistochemistry. To the best of our knowledge, this is the third case of EGIST diagnosed above the diaphragm, without being associated with the esophageal wall. Two cases of primary EGIST arising from the pleura were reported previously. In addition, this is the first reported case of an EGIST originating from the pericardium. PMID:26137136

  7. Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors.

    PubMed

    Blumenthal, Deborah T; Yalon, Michal; Vainer, Gilad W; Lossos, Alexander; Yust, Shlomit; Tzach, Lior; Cagnano, Emanuela; Limon, Dror; Bokstein, Felix

    2016-09-01

    Patients with progressive primary brain tumors (PBT) are attracted to promising new treatments, even prior to convincing data. Anti-PD1 immunotherapies have been in the spotlight since publication of groundbreaking results for metastatic melanoma with pembrolizumab (PBL). Our objective was to report on the response and toxicity of PBL in patients with advanced PBT. We retrospectively reviewed the charts of 22 patients (17 adults and 5 children) with recurrent central nervous system tumors treated with PBL. We analyzed prior antineoplastic therapies, steroid usage, and outcomes. Patients received a median of two neoplastic therapies prior to PBL, and a median of three infusions of PBL in adults and four in children. Twelve patients (9 adults and 3 children) started PBL on steroids (median dose in adults 4 mg; range 2-8, and in children 1.5 mg, range 0.5-4) and five patients received steroids later during PBL treatment. Twelve patients (10 adults and 2 children) received concomitant bevacizumab with PBL. Side effects were minimal. All patients showed progressive tumor growth during therapy. Median OS from the start of PBL was 2.6 months in adults and 3.2 months in children. Two GB patients underwent tumor resection following treatment with PBL. Tumor-lymphocytic response in these cases was unremarkable, and PD-L1 immuno-staining was negative. In this series of 22 patients with recurrent primary brain tumors, PBL showed no clinical or histologic efficacy. We do not recommend further use of PBL for recurrent PBT unless convincing prospective clinical trial data are published.

  8. Stereotactic body radiotherapy (SBRT) with or without surgery for primary and metastatic liver tumors

    PubMed Central

    Kirichenko, Alexander; Gayou, Olivier; Parda, David; Kudithipudi, Vijay; Tom, Kusum; Khan, Akhtar; Abrams, Peter; Szramowski, Molly; Oliva, Jose; Monga, Dulabh; Raj, Moses; Thai, Ngoc

    2015-01-01

    Objectives We report single center experience on the outcome and toxicity of SBRT alone or in combination with surgery for inoperable primary and metastatic liver tumors between 2007 and 2014. Patients and methods Patients with 1–4 hepatic lesions and tumor diameter ≤9 cm received SBRT at 46.8Gy ± 3.7 in 4–6 fractions. The primary end point was local control with at least 6 months of radiographic followup, and secondary end points were toxicity and survival. Results Eighty-seven assessable patients (114 lesions) completed liver SBRT for hepatoma (39) or isolated metastases (48) with a median followup of 20.3 months (range 1.9–64.1). Fourteen patients underwent liver transplant with SBRT as a bridging treatment or for tumor downsizing. Eight patients completed hepatic resections in combination with planned SBRT for unresectable tumors. Two-year local control was 96% for hepatoma and 93.8% for metastases; it was 100% for lesions ≤4 cm. Two-year overall survival was 82.3% (hepatoma) and 64.3% (metastases). No incidence of grade >2 treatment toxicity was observed. Conclusion In this retrospective analysis we demonstrate that liver SBRT alone or in combination with surgery is safe and effective for the treatment of isolated inoperable hepatic malignancies and provides excellent local control rates. PMID:26776856

  9. The role and clinical significance of DNA damage response and repair pathways in primary brain tumors

    PubMed Central

    2013-01-01

    Primary brain tumors, in particular, glioblastoma multiforme (GBM), continue to have dismal survivability despite advances in treating other neoplasms. The goal of new anti-glioma therapy development is to increase their therapeutic ratios by enhancing tumor control and/or decreasing the severity and incidence of side effects. Because radiotherapy and most chemotherapy agents rely on DNA damage, the cell’s DNA damage repair and response (DRR) pathways may hold the key to new therapeutic strategies. DNA double-strand breaks (DSBs) generated by ionizing radiation and chemotherapeutic agents are the most lethal form of damage, and are repaired via either homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways. Understanding and exploitation of the differences in the use of these repair pathways between tumor and normal brain cells will allow for an increase in tumor cell killing and decreased normal tissue damage. A literature review and discussion on new strategies which can improve the anti-glioma therapeutic ratio by differentially targeting HR and NHEJ function in tumor and normal neuronal tissues is the focus of this article. PMID:23388100

  10. Bone and Gallium scintigraphy in primary malignant and benign bone tumors of the extremities

    SciTech Connect

    Sepahdari, S.; Martin, W.B.; Ryan, J.; Simon, M.; Kirchner, P.

    1985-05-01

    A six yer prospective evaluation of 129 patients suspected of having a primary bone tumor included Tc-99m MDP bone scintigraphy followed by Ga-67 imaging at 48-72 hours. Blood pool images were part of bone scintigraphy in nearly half of the patients. Extent and intensity of tracer uptake in tumor and adjacent bone and joints were recorded for each tracer by two observers blind to the diagnosis. Tissue samples obtained in every patient by biopsy or tumor excision after scintigraphy, revealed 72 malignant and 57 benign bone tumors. The bone scan was positive in 95% (69/72) of malignancies. The scintigraphic intensity of benign and malignant lesions was comparable with both Tc-99m MDP and Ga-67. On the other hand, bone scintigraphy showed 72% (52/72) of bone malignancies to have abnormal proximal and distal bone/joint uptake whereas the Ga-67 images revealed this in only 6% (4/65) of malignancies. Benign lesions manifested this enhanced contiguous bone/joint uptake on only 8% (5/55) of bone and 0% of Ga-67 scans. This study concludes positive bone, blood pool, or Ga-67 images have less specificity for malignancy than the presence of increased Tc-99m MDP deposition in a contiguous bone/joint, but negative scintigraphic results strongly favor a benign lesion. Ga-67 was more accurate than Tc-99m MDP in portraying intraosseous extent of malignant tumors; however, this is now preferably done with C.T.

  11. Factors Affecting the Motivation of Turkish Primary Students for Science Learning

    ERIC Educational Resources Information Center

    Cavas, Pinar

    2011-01-01

    In this study, Turkish primary students' (sixth to eighth grade) motivation toward science learning was investigated and factors affecting this determined. The sample for the study consisted of 376 students from 5 different primary schools in Izmir. The data were collected through a Students' Motivation toward Science Learning (SMTSL)…

  12. Comparison of KRAS/BRAF mutations between primary tumors and serum in colorectal cancer: Biological and clinical implications.

    PubMed

    Pu, Xingxiang; Pan, Zhizhong; Huang, Ying; Tian, Ying; Guo, Hongqiang; Wu, Lin; He, Xuexing; Chen, Xinggui; Zhang, Shaodan; Lin, Tongyu

    2013-01-01

    In colorectal cancer (CRC), KRAS and BRAF mutations in primary tumors are associated with resistance to anti-epidermal growth factor receptor (anti-EGFR)-based therapies. However, the correlation between KRAS/BRAF mutation in primary tumors and serum has not been well studied. To evaluate the degree of concordance of KRAS/BRAF mutations between the primary tumors and the matched serum samples in CRC, serum and tumor tissues were collected from 115 patients with CRC and KRAS/BRAF mutations were examined by nested polymerase chain reaction (PCR) and direct sequencing. BRAF mutations were present in 3.5% (4/115) of the primary tumor tissue samples and 0.87% (1/115) of the serum samples. In the 4 primary tumors with BRAF mutations, identical mutations were not observed in the corresponding serum samples (κ=-0.016). KRAS mutations were observed in 32.2% (37/115) of the primary tumors and 11.3% (13/115) of the serum samples. Of the 37 tumor cases with KRAS mutations, 9 had identical mutations in the corresponding serum sample, with a concordance rate of 24.3% (9/37). Discordance was observed in 32 (27.8%) patients. The concordance between KRAS mutations in the primary tumors and KRAS mutations in the matched serums was low (κ=0.231). The results of the present study suggest that the possibility of differences in the mutational status of KRAS/BRAF between primary tumors and matched serum samples should be considered when patients are selected for anti-EGFR-based therapies.

  13. Imaging features of primary anorectal gastrointestinal stromal tumors with clinical and pathologic correlation

    PubMed Central

    Koch, M.R.; Jagannathan, J.P.; Krajewski, K.M.; Raut, C.P.; Hornick, J.L.; Ramaiya, N.H.

    2012-01-01

    Abstract Purpose: To evaluate the imaging features of anorectal gastrointestinal stromal tumors (GISTs) with clinical and histopathologic correlation. Materials and methods: In this Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, 16 patients (12 men; mean age 66 years (30–89 years)) with pathologically proven anorectal GISTs seen at our institution from January 2001 to July 2011 were identified. Electronic medical records were reviewed to obtain clinical data. Pretreatment imaging studies (computed tomography (CT) in 16 patients, magnetic resonance imaging (MRI) in 9 patients and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT in 8 patients) were evaluated by 2 radiologists until consensus. The location, size and imaging features of the primary tumor and metastases at presentation, if any, were recorded, and correlated with clinical data and pathologic features (histologic type, presence of necrosis, mitotic activity, risk category, immunohistochemical profile). Results: The mean tumor size was 6.9 × 6.0 cm. Of the 16 tumors, 11 (68.7%) were infralevator, 4 (25%) supra and infralevator and 1 (6.3%) supralevator; 9 (56.2%) were exophytic, 6 (37.5%) both exophytic and intraluminal, and 1 (6.3%) was intraluminal. The tumors were iso- to minimally hypoattenuating to muscle on CT, iso- to minimally hypointense on T1-weighted images, hyperintense on T2-weighted images and showed variable enhancement. Necrosis was seen in 4 (25%), and hemorrhage and calcification in 2 (12.5%) patients each. The tumors were FDG avid with a mean maximum standardized uptake value of 11 (8.4–16.8). All tumors were positive for KIT and CD34. Distant metastasis to liver was seen in 1 patient (6.3%) at presentation. Conclusion: Anorectal GISTs are well-circumscribed, non-circumferential, predominantly infralevator, intramural or exophytic, FDG-avid, hypoattenuating masses, and present without

  14. Clinicopathologic features of incident and subsequent tumors in patients with multiple primary cutaneous melanomas

    PubMed Central

    Murali, Rajmohan; Goumas, Chris; Kricker, Anne; From, Lynn; Busam, Klaus J.; Begg, Colin B.; Dwyer, Terence; Gruber, Stephen B.; Kanetsky, Peter A.; Orlow, Irene; Rosso, Stefano; Thomas, Nancy E.; Berwick, Marianne; Scolyer, Richard A.; Armstrong, Bruce K.

    2011-01-01

    Background 0.6–12.7% of patients with primary cutaneous melanoma will develop additional melanomas. Pathologic features of tumors in patients with multiple primary cutaneous melanomas have not been well described. In this large international multi-center case-control study, we compared the clinicopathologic features of a subsequent melanoma with the preceding (usually the first) melanoma in patients with multiple primary cutaneous melanomas, and with those of melanomas in patients with single primary cutaneous melanomas. Methods Multiple primary melanoma (cases) and single primary invasive melanoma (controls) patients from the Genes, Environment and Melanoma (GEM) study were included if their tumors were available for pathologic review and confirmed as melanoma. Clinicopathologic characteristics of invasive subsequent and first melanomas in cases and invasive single melanomas in controls were compared. Results 473 pairs comprising a subsequent and a first melanoma and 1989 single melanomas were reviewed. Forward stepwise regression modeling in 395 pairs with complete data showed that, compared to first melanomas, subsequent melanomas were: more commonly contiguous with a dysplastic nevus; more prevalent on the head/neck and legs than other sites; and thinner. Compared with single primary melanomas, subsequent melanomas were also more likely to be: associated with a contiguous dysplastic nevus; more prevalent on the head/neck and legs; and thinner. The same differences were observed when subsequent melanomas were compared with single melanomas. First melanomas were more likely than single melanomas to have associated solar elastosis and no observed mitoses. Conclusions Thinner subsequent than first melanomas suggest earlier diagnosis, perhaps due to closer clinical scrutiny. The association of subsequent melanomas with dysplastic nevi is consistent with the latter being risk factors or risk markers for melanoma. PMID:21913010

  15. Outcome of Primary Tumor in Patients With Synchronous Stage IV Colorectal Cancer Receiving Combination Chemotherapy Without Surgery As Initial Treatment

    PubMed Central

    Poultsides, George A.; Servais, Elliot L.; Saltz, Leonard B.; Patil, Sujata; Kemeny, Nancy E.; Guillem, Jose G.; Weiser, Martin; Temple, Larissa K.F.; Wong, W. Douglas; Paty, Phillip B.

    2009-01-01

    Purpose The purpose of this study was to describe the frequency of interventions necessary to palliate the intact primary tumor in patients who present with synchronous, stage IV colorectal cancer (CRC) and who receive up-front modern combination chemotherapy without prophylactic surgery. Patients and Methods By using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin; bolus fluorouracil, leucovorin, and irinotecan; or fluorouracil, leucovorin, and irinotecan) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded. Results Of 233 patients, 217 (93%) never required surgical palliation of their primary tumor. Sixteen patients (7%) required emergent surgery for primary tumor obstruction or perforation, 10 patients (4%) required nonoperative intervention (ie, stent or radiotherapy), and 213 (89%) never required any direct symptomatic management for their intact primary tumor. Of those 213 patients, 47 patients (20%) ultimately underwent elective colon resection at the time of metastasectomy, and eight patients (3%) underwent this resection during laparotomy for hepatic artery infusion pump placement. Use of bevacizumab, location of the primary tumor in the rectum, and metastatic disease burden were not associated with increased intervention rate. Conclusion Most patients with synchronous, stage IV CRC who receive up-front modern combination chemotherapy never require palliative surgery for their intact primary tumor. These data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary

  16. Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries.

    PubMed

    McCarthy, Bridget J; Shibui, Soichiro; Kayama, Takamasa; Miyaoka, Etsuo; Narita, Yoshitaka; Murakami, Michiko; Matsuda, Ayako; Matsuda, Tomohiro; Sobue, Tomotaka; Palis, Bryan E; Dolecek, Therese A; Kruchko, Carol; Engelhard, Herbert H; Villano, J Lee

    2012-09-01

    Intracranial germ cell tumors (GCTs) are relatively rare. Their incidence has been considered to be higher in East Asia than in the United States. This study estimates the incidence of CNS GCTs in Japan and the United States, investigates gender discrepancies in each country, and describes treatment outcomes. Data on primary CNS GCTs from 4 databases were utilized: population-based malignant incidence data from (1) the Japan Cancer Surveillance Research Group (2004-2006; 14 registries), malignant and nonmalignant incidence data from (2) the Surveillance, Epidemiology, and End Results Program (2004-2008; 17 registries), and hospital-based observed survival data from (3) the Brain Tumor Registry of Japan (1984-2000) and (4) the US National Cancer Data Base (1990-2003). Incidence rates per 100 000 for malignant GCTs were not statistically significantly different between Japan (males = 0.143, females = 0.046) and the United States (males = 0.118, females = 0.030). The malignant incidence-rate ratio was higher for pineal GCTs versus nonpineal (ie, the rest of the brain) GCTs in Japan (11.5:1 vs 1.9:1, respectively) and the United States (16.0:1 vs 1.7:1, respectively). In general, 5-year survival estimates were high: over 75% for all GCTs, and over 81% for germinomas, regardless of the type of treatment in either Japan or the United States. The incidence of primary GCTs is similar between Japan and the United States and has the same gender-based patterns by location. High rates of survival were observed in both countries.

  17. [Magnetic resonance imaging of non-organic bulky masses of the retroperitoneal space. Part 2. Primary and metastatic tumors].

    PubMed

    Dombrovskiĭ, V I

    2003-01-01

    Based on MRI findings in 15 patients with primary non-organic tumors and 9 patients with metastatic neoplasms of the retroperitoneal space, the paper describes the MRI-semiotics of these diseases and proposes methodological approaches to their identification in its second part. By comparing the data of MRI and autopsies, the author defines the values of the sensitivity, specificity, and accuracy of the technique in detecting primary and metastatic non-organic tumors of the retroperitoneal space. The author emphasizes the advantages and disadvantages of MRI, shows how difficult to make a differential diagnosis of benign and malignant types of primary non-organic tumors by means of this method.

  18. Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens

    PubMed Central

    Baine, Marina K.; Turcu, Gabriela; Zito, Christopher R.; Adeniran, Adebowale J.; Camp, Robert L.; Chen, Lieping

    2015-01-01

    Renal cell carcinoma (RCC) is one of the most chemo- and radio-resistant malignancies, with poor associated patient survival if the disease metastasizes. With recent advances in immunotherapy, particularly with PD-1/PD-L1 blockade, outcomes are improving, but a substantial subset of patients does not respond to the new agents. Identifying such patients and improving the therapeutic ratio has been a challenge, although much effort has been made to study PD-1/PD-L1 status in pre-treatment tumor. However, tumor infiltrating lymphocyte (TIL) content might also be predictive of response, and our goal was to characterize TIL content and PD-L1 expression in RCC tumors from various anatomic sites. Utilizing a quantitative immunofluorescence technique, TIL subsets were examined in matched primary and metastatic specimens. In metastatic specimens, we found an association between low CD8+ to Foxp3+ T-cell ratios and high levels of PD-L1. High PD-L1-expressing metastases were also found to be associated with tumors that were high in both CD4+ and Foxp3+ T-cell content. Taken together these results provide the basis for combining agents that target the PD-1/PD-L1 pathway with agonist of immune activation, particularly in treating RCC metastases with unfavorable tumor characteristics and microenvironment. In addition, CD8+ TIL density and CD8:Foxp3 T-cell ratio were higher in primary than metastatic specimens, supporting the need to assess distant sites for predictive biomarkers when treating disseminated disease. PMID:26317902

  19. Study of factors determining caregiver burden among primary caregivers of patients with intracranial tumors

    PubMed Central

    Dhandapani, Manju; Gupta, Sandhya; Dhandapani, Sivashanmugam; Kaur, Prabhjot; Samra, Kanwaljit; Sharma, Kirti; Dolma, Kunchok; Mohanty, Manju; Singla, Navneet; Gupta, Sunil K.

    2015-01-01

    Background: Caregivers of patients with intracranial tumors handle physical, cognitive, and behavioral impairments of patients. The purpose of this study was to assess the magnitude of burden experienced by primary caregivers of patients operated for intracranial tumors and evaluate factors influencing it. Methods: Descriptive cross-sectional design was used to assess home-care burden experienced by primary caregivers of patients operated for intracranial tumors. Using purposive sampling, 70 patient-caregiver pairs were enrolled. Modified caregiver strain index (MCSI) was used to assess the caregiver burden. Mini mental status examination (MMSE), Katz index of independence in activities of daily living (ADL), and neuropsychiatric inventory questionnaire (NPI-Q) were used to assess the status of patients. Results: Of 70 caregivers, 45 had mild, and 22 had moderate MCSI burden. A number of behavioral changes in NPI-Q had a significant correlation with MCSI burden (P < 0.001), whereas MMSE and Katz-ADL of patients did not show significant relation with caregiver burden. In NPI-Q, irritability, agitation, anxiety, depression, and sleep disturbances had a significant impact on MCSI. Among caregiver factors, unemployment, low per capita income, time spent, inability to meet household needs, quitting the job, and health problems had a significant impact on MCSI. In separate multivariate analyses, irritability component (P = 0.004) among behavioral changes of patients and caregivers’ inability to meet household needs (P < 0.001) had a significant association with caregiver burden independent of other factors. Conclusions: Behavioral changes in patients (especially irritability) and financial constraints had a significant independent impact on the burden experienced by primary caregivers of patients operated for intracranial tumors. Identifying and managing, these are essential for reducing caregiver burden. PMID:26543669

  20. Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution

    PubMed Central

    Kim, Hoon; Zheng, Siyuan; Amini, Seyed S.; Virk, Selene M.; Mikkelsen, Tom; Brat, Daniel J.; Grimsby, Jonna; Sougnez, Carrie; Muller, Florian; Hu, Jian; Sloan, Andrew E.; Cohen, Mark L.; Van Meir, Erwin G.; Scarpace, Lisa; Laird, Peter W.; Weinstein, John N.; Lander, Eric S.; Gabriel, Stacey; Getz, Gad; Meyerson, Matthew; Chin, Lynda; Barnholtz-Sloan, Jill S.

    2015-01-01

    Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity. PMID:25650244

  1. Complement-dependent cytotoxicity in rats bearing human adenovirus type 12-induced primary retinoblastoma-like tumor in the eye.

    PubMed

    Nishida, T; Mukai, N; Solish, S P

    1981-01-01

    Using an animal model of retinoblastoma in inbred rats and cultured human adenovirus type 12-induced retinoblastoma-like tumor cells (RAO 188), complement-dependent cytotoxicity was determined by measuring release of 3H-uridine labelled RNA. Sera from rats in which tumors did not grow after adenovirus type 12 inoculation had higher cytotoxicity against RAO 188 cells than sera from rats bearing primary adenovirus type 12-induced retinoblastoma-like tumor. These results showed that the rat which could raise antibodies against adenovirus type 12-induced retinoblastoma-like tumor cells did not allow the tumor growth in the eye after virus inoculation.

  2. Distinguishing primary from secondary mucinous ovarian tumors: an algorithm using the novel marker DPEP1.

    PubMed

    Okamoto, Takako; Matsumura, Noriomi; Mandai, Masaki; Oura, Tomonori; Yamanishi, Yukio; Horiuchi, Akiko; Hamanishi, Junzo; Baba, Tsukasa; Koshiyama, Masafumi; Shiozawa, Tanri; Konishi, Ikuo

    2011-02-01

    Distinguishing primary mucinous ovarian cancers from ovarian metastases of digestive organ cancers is often challenging. Dipeptidase 1 was selected as the candidate novel marker of colorectal cancer based on an analysis of a gene expression microarray. Immunohistochemical analysis indicated that 13/16 ovarian metastases of colorectal cancers, but only 1/58 primary mucinous ovarian cancers, were dipeptidase 1-positive (threshold; ≧25% expression, P<0.0001). Next, five immunohistochemical markers (dipeptidase 1, estrogen receptor-α, cytokeratin 7, cytokeratin 20, and caudal type homeobox 2) were analyzed in combination. In a hierarchical clustering analysis, the mutually exclusive expression of cytokeratin 7 and dipeptidase 1 specifically identified the ovarian metastases of colorectal cancers (P<0.0001). In a decision tree analysis, cytokeratin 7, caudal type homeobox 2, and dipeptidase 1 classified primary mucinous ovarian cancers and ovarian metastases of digestive organ cancers with 90% accuracy. Finally, the five immunohistochemical markers were combined with six preoperative factors (patient's age, tumor size, laterality, serum CEA, CA19-9, and CA125) and combinations were analyzed. Of the 11 factors, 4 (dipeptidase 1, cytokeratin 7, caudal type homeobox 2, and tumor size) were used to generate a decision tree to classify primary mucinous ovarian cancers and metastases of digestive organ cancers with 93% accuracy. In conclusion, we identified a novel immunohistochemical marker, dipeptidase 1, to distinguish primary mucinous ovarian cancers from ovarian metastasis of colorectal cancers. The algorithm using immunohistochemical and clinical factors to distinguish metastases of digestive organ cancers from primary mucinous ovarian cancers will be useful to establish a protocol for the diagnosis of ovarian metastasis.

  3. Non-seminomatous germ cell tumors of the testis. Analysis of CEA production in primary tumors and in retroperitoneal lymph node metastases after PVB chemotherapy.

    PubMed

    Suurmeijer, A J; Oosterhuis, J W; Marrink, J; Ockhuizen, T; Sleijfer, D T; Schraffordt Koops, H; Fleuren, G J

    1984-05-01

    In the present investigation we compared CEA immunoperoxidase staining in testicular tumors (before PVB chemotherapy) and retroperitoneal tumors (after PVB chemotherapy) with CEA levels in the cyst fluid of retroperitoneal mature teratoma and in the patients' serum. CEA had no value as a serum tumor marker since serum CEA elevations were not associated with tumor activity. Only one elevated CEA level after chemotherapy was associated with bleomycin pneumonitis. Despite normal serum levels, CEA was localized immunohistochemically in yolk sac tumor and mature teratoma in the primary tumors and in retroperitoneal mature teratoma following PVB chemotherapy. The presence of CEA in cells lining cystic mature teratoma was associated with high CEA levels in the cyst fluid.

  4. Affect on survival per increase in each millimeter of tumor depth in tongue cancer.

    PubMed

    Gokavarapu, Sandhya; Ahmed, Murtaza; Parvataneni, Nagendra; Raju, K V V N; Chander, Ravi; Chandrasekhara Rao S, L M

    2015-03-01

    The critical tumor depth at which the risk of occult metastasis increases in tongue cancer has been demonstrated as ≥4-5 mm. Conventional T staging might not be an accurate predictor for survival in situations wherein infiltrative growth pattern is easily overlooked. Thus risk of death associated with increase in tumor depth per millimeter might be useful to understand patient's disease status during follow up. Historical cohorts of patients with pT1N0 and pT2N0 primary squamous cell carcinoma of tongue treated between January 2010 and December 2011 were selected and analyzed in univariate and multivariate cox-regression model to indicate the risk of death associated with an increase in each millimeter of tumor depth. The median period of follow up was 34 months. Total 67 patients fulfilled the above mentioned criteria, among them 11 patients died by the end of study period. The mean (SD) age of the patients studied was 49.7 (12.7) years and their age ranged from 21 to 74 years. Among these 66 % (n = 44) were males. In the univariate log-rank test, margin status (p = 0.016), t-stage (p = 0.018) and increased tumor depth (p < 0.0001) were risk factors for occurrence of death. When adjusted for other risk factors in the multivariate cox-regression model, per one unit increase of tumor depth (mm) there was 1.07 (95 % CI 0.95, 1.21) units increased risk of death. Depth of tumor with increase in each millimeter in tongue cancer appears to be associated with risk of death irrespective of regional lymphatic spread.

  5. Occult Primary Neuroendocrine Tumor Metastasis to the Breast Detected on Screening Mammogram

    PubMed Central

    Policeni, Fabiana; Pakalniskis, Brittany; Yang, Limin

    2016-01-01

    Metastatic tumors are rare in the breast. Well-differentiated neuroendocrine tumors (WDNETs) are slow-growing neoplasms that arise from neuroendocrine cells, particularly in the gastrointestinal tract and bronchial tree. Metastatic WDNET to the breast is a rare entity. We present a case report of ileal WDNET metastatic to the breast which was initially identified as a small mass in the patient's left breast on screening mammography. Targeted ultrasound identified a suspicious mass, and ultrasound-guided percutaneous core biopsy was performed. Pathology revealed metastatic WDNET. Breast magnetic resonance imaging (MRI) was then performed and demonstrated left axillary Level 2 lymphadenopathy, and liver lesions were suspicious for metastasis. The patient underwent abdominal computed tomography (CT) to evaluate for distant metastatic disease. A spiculated mass was found near the ileocecal valve, suggestive of primary ileal WDNET. In addition, CT identified multiple liver lesions, most compatible with metastasis. Indium 111 OctreoScan confirmed radiotracer uptake in the ileum consistent with primary neuroendocrine tumor. In this report, we review the imaging characteristics of metastatic WDNET to the breast by different imaging modalities including mammogram, ultrasound, and breast MRI. PMID:27761301

  6. Malignant characteristics of circulating tumor cells and corresponding primary tumor in a patient with esophageal squamous cell carcinoma before and after surgery.

    PubMed

    Ren, Chuanli; He, Ping; Zhang, Jinqiang; Zheng, Zhaoxu; Qiao, Yuanyuan; Zhao, Xiaohang

    2011-04-01

    We report the malignant characteristics of circulating tumor cells (CTCs) and the corresponding molecular features of the primary tumor in a patient with esophageal squamous cell carcinoma (ESCC). A 70-year-old male patient was diagnosed with TNM stage T3N0M0 ESCC. Before surgery, seven intact CTCs and 12 CTCs with a fragmented membrane were detected in 7.5 mL of peripheral blood by immunofluorescence staining. One week after radical resection of the primary tumor, four CTCs were identified in 7.5ml peripheral blood. All CTCs were confirmed as having a malignant phenotype by chromosomal analysis and routine cell staining. Ninety percent of the CTCs were found to have polysomic chromosomes 8 and 20 by fluorescence in situ hybridization (FISH). Immunofluorescence analysis showed that all of the primary tumor cells detected were cytokeratin8/18/19 (CK8/18/19)-positive, but only 1% were CD133-positive. The serum CA19-9 and CEA level were normal in the process of diseases. The patient died 6 months after surgery as a result of lung metastases and other complications. The results of this study suggest that the dynamics and malignant characteristics of both CTCs and the corresponding primary tumor during the disease process may predict tumor burden and the risk of relapse and metastasis.

  7. Imaging Features of Primary Tumors and Metastatic Patterns of the Extraskeletal Ewing Sarcoma Family of Tumors in Adults: A 17-Year Experience at a Single Institution

    PubMed Central

    Huh, Jimi; Park, Seong Joon; Kim, Hyoung Jung; Lee, Jong Seok; Ha, Hyun Kwon; Tirumani, Sree Harsha; Ramaiya, Nikhil H.

    2015-01-01

    Objective To comprehensively analyze the spectrum of imaging features of the primary tumors and metastatic patterns of the Extraskeletal Ewing sarcoma family of tumors (EES) in adults. Materials and Methods We performed a computerized search of our hospital's data-warehouse from 1996 to 2013 using codes for Ewing sarcoma and primitive neuroectodermal tumors as well as the demographic code for ≥ 18 years of age. We selected subjects who were histologically confirmed to have Ewing sarcoma of extraskeletal origin. Imaging features of the primary tumor and metastatic disease were evaluated for lesion location, size, enhancement pattern, necrosis, margin, and invasion of adjacent organs. Results Among the 70 patients (mean age, 35.8 ± 15.6 years; range, 18-67 years) included in our study, primary tumors of EES occurred in the soft tissue and extremities (n = 20), abdomen and pelvis (n = 18), thorax (n = 14), paravertebral space (n = 8), head and neck (n = 6), and an unknown primary site (n = 4). Most primary tumors manifested as large and bulky soft-tissue masses (mean size, 9.0 cm; range, 1.3-23.0 cm), frequently invading adjacent organs (45.6%) and showed heterogeneous enhancement (73.7%), a well-defined (66.7%) margin, and partial necrosis/cystic degeneration (81.9%). Notably, 29 patients had metastatic disease detected at their initial diagnosis. The most frequent site of metastasis was lymph nodes (75.9%), followed by bone (31.0%), lung (20.7%), abdominal solid organs (13.8%), peritoneum (13.8%), pleura (6.9%), and brain (3.4%). Conclusion Primary tumors of EES can occur anywhere and mostly manifest as large and bulky, soft-tissue masses. Lymph nodes are the most frequent metastasis sites. PMID:26175577

  8. Palliative resection of a primary tumor in patients with unresectable colorectal cancer: could resection type improve survival?

    PubMed Central

    Jang, Hyun Seok; Kim, Chang Hyun; Lee, Soo Young; Kim, Hyeong Rok; Kim, Young Jin

    2016-01-01

    Purpose The aim of this study was to evaluate the impact of extended resection of primary tumor on survival outcome in unresectable colorectal cancer (UCRC). Methods A retrospective analysis was conducted for 190 patients undergoing palliative surgery for UCRC between 1998 and 2007 at a single institution. Variables including demographics, histopathological characteristics of tumors, surgical procedures, and course of the disease were examined. Results Kaplan-Meier survival curve indicated a significant increase in survival times in patients undergoing extended resection of the primary tumor (P < 0.001). Multivariate analysis showed that extra-abdominal metastasis (P = 0.03), minimal resection of the primary tumor (P = 0.034), and the absence of multimodality adjuvant therapy (P < 0.001) were significantly associated poor survival outcome. The histological characteristics were significantly associated with survival times. Patients with well to moderate differentiation tumors that were extensively resected had significantly increased survival time (P < 0.001), while those with poor differentiation tumors that were extensively resected did not have increase survival time (P = 0.786). Conclusion Extended resection of primary tumors significantly improved overall survival compared to minimal resection, especially in well to moderately differentiated tumors (survival time: extended resection, 27.8 ± 2.80 months; minimal resection, 16.5 ± 2.19 months; P = 0.002). PMID:27757394

  9. Differential Motion Between Mediastinal Lymph Nodes and Primary Tumor in Radically Irradiated Lung Cancer Patients

    SciTech Connect

    Schaake, Eva E.; Rossi, Maddalena M.G.; Buikhuisen, Wieneke A.; Burgers, Jacobus A.; Smit, Adrianus A.J.; Belderbos, José S.A.; Sonke, Jan-Jakob

    2014-11-15

    Purpose/Objective: In patients with locally advanced lung cancer, planning target volume margins for mediastinal lymph nodes and tumor after a correction protocol based on bony anatomy registration typically range from 1 to 1.5 cm. Detailed information about lymph node motion variability and differential motion with the primary tumor, however, is lacking from large series. In this study, lymph node and tumor position variability were analyzed in detail and correlated to the main carina to evaluate possible margin reduction. Methods and Materials: Small gold fiducial markers (0.35 × 5 mm) were placed in the mediastinal lymph nodes of 51 patients with non-small cell lung cancer during routine diagnostic esophageal or bronchial endoscopic ultrasonography. Four-dimensional (4D) planning computed tomographic (CT) and daily 4D cone beam (CB) CT scans were acquired before and during radical radiation therapy (66 Gy in 24 fractions). Each CBCT was registered in 3-dimensions (bony anatomy) and 4D (tumor, marker, and carina) to the planning CT scan. Subsequently, systematic and random residual misalignments of the time-averaged lymph node and tumor position relative to the bony anatomy and carina were determined. Additionally, tumor and lymph node respiratory amplitude variability was quantified. Finally, required margins were quantified by use of a recipe for dual targets. Results: Relative to the bony anatomy, systematic and random errors ranged from 0.16 to 0.32 cm for the markers and from 0.15 to 0.33 cm for the tumor, but despite similar ranges there was limited correlation (0.17-0.71) owing to differential motion. A large variability in lymph node amplitude between patients was observed, with an average motion of 0.56 cm in the cranial-caudal direction. Margins could be reduced by 10% (left-right), 27% (cranial-caudal), and 10% (anteroposterior) for the lymph nodes and −2%, 15%, and 7% for the tumor if an online carina registration protocol replaced a

  10. Primary atypical teratoid/rhabdoid tumor of the spine in an adult patient

    PubMed Central

    Li, Luyuan; Patel, Mohit; Nguyen, Ha Son; Doan, Ninh; Sharma, Abhishiek; Maiman, Dennis

    2016-01-01

    Background: Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive neoplasm of the central nervous system that generally arises intracranially in patients under 2 years of age. Primary spinal AT/RT in an adult is rare. Case Description: A 23-year-old female presented with left lower extremity sciatica attributed to a magnetic resonance imaging (MRI)-documented intradural mass between L2 and L4. The lesion was biopsied (was unresectable) and treated with high-dose chemotherapy (methotrexate, vincristine, cyclophosphamide, etoposide, and cisplatin) with autologous hematopoietic stem cells rescue, followed by 2 months of radiation therapy (36 Gy to craniospinal axis, 20 Gy to lumbar region) with concurrent temozolomide; the latter was discontinued after 3 weeks due to myelosuppression. Tumor relapsed 1 year later at C7–T1 level. She was started on oral metronomic therapy, and bevacizumab was added 2 months later. Three months later, a cervical MRI showed progression of the tumor, along with new lesions in the thoracic/lumbar spine plus intracranial punctate nodular tumors. Following resection of the C7/T1 lesion, she was started on palliative alisertib; a month later, a cranial computed tomography showed progression of her disease with hydrocephalus. Treatment was discontinued, and she expired 12 months after initial diagnosis. Conclusion: Primary spinal AT/RT in the adult patient is rare. The pathology is associated with early recurrence and a poor prognosis. Although potential benefits of metronomic chemotherapy and alisertib have been reported, the patient in this study did not favorably respond to these modalities. PMID:27069744

  11. Clinicopathological and immunohistochemical features of primary central nervous system germ cell tumors: a 24-years experience.

    PubMed

    Gao, Yuping; Jiang, Jiyao; Liu, Qiang

    2014-01-01

    Primary central nervous system (CNS) germ cell tumors (GCTs) are a rare heterogeneous group of lesions, which the clinicopathological features have a marked degree of heterogeneity comparing with that of gonadal GCTs. Accurately diagnosing CNS GCTs might be extremely difficult and requires immunohistochemical verification. This study was to investigate the biological feature of CNS GCTs and diagnostic value of immunohistochemical markers OCT3/4, C-kit, PLAP, and CD30 in CNS GCTs. A retrospective study was performed on 34 patients with CNS germ cell tumors between 1990 and 2014. 34 CNS GCTs account for 9.2% of all primary CNS neoplasms. The sellar region (35.3%) and pineal gland (17.6%) were the most common sites of intracranial GCTs. Hydrocephalus (82.4%) and diplopia (46.9%) were the two most common clinical presentations. The most common histological subtypes were germinoma (67.6%). PLAP, c-kit, OCT3/4 were highly expressed in gernimomas. CD30 and CK AE1/3 stainings were positive in embryonal carcinoma. Yolk sac tumor component showed positive staining for AFP and CK AE1/3. β-HCG staining was positive in choriocarcinoma and STGC. Patients with mature teratomas and germinomas had a better prognosis (a 5-year survival rate) than those with embryonal carcinoma and choriocarcinoma (a 5-year survival rates were 0). Our finding suggest that the incidences of primary CNS GCTs are higher in South China than in the West, but mixed GCTs are uncommon in our study. The judicious use of a panel of selected markers is helpful in diagnosing and predicting the prognosis for CNS GCTs.

  12. Tumor-specific Anti-Nucleosome Antibody Improves Therapeutic Efficacy of Doxorubicin-Loaded Long-Circulating Liposomes against Primary and Metastatic Tumor in Mice

    PubMed Central

    ElBayoumi, Tamer A.; Torchilin, Vladimir P.

    2009-01-01

    The efficacy of drug delivery systems can be significantly enhanced by making them target-specific via the attachment of various ligands to their surface. We attempted to enhance tumor accumulation and therapeutic effect of doxorubicin-loaded long-circulating liposomes (Doxil®, ALZA Corp.) by coupling to their surface the anti-cancer monoclonal antibody 2C5 (mAb 2C5) with nuclesome (NS)-restricted activity, that can recognize the surface of various tumor but not normal cells via the surface-bound nucleosomes released from the apoptotically dying neighboring tumor cells and specifically targets pharmaceutical carriers to tumor cells in vitro and in vivo. Antibody coupling to PEGylated doxorubicin-liposomes was performed by the “post-insertion” technique. The pharmacokinetics of plain and immuno-targeted Doxil®-mimicking liposomes, as well as their accumulation in primary Lewis Lung Carcinoma (LLC) tumors in mice was followed by real-time gamma-scintigraphy upon liposomal membrane labeling with 111In. Therapeutic action of various liposomal formulations was followed by registering primary tumor growth, determining tumor weigh upon mice sacrifice, and by counting the number of metastases in the liver and lungs. 2C5 antibody-targeted liposomes demonstrate significantly enhanced accumulation in LLC tumors. Targeted doxorubicin-loaded PEG-liposomes were significantly more effective in inhibiting tumor growth and metastatic process in the LLC tumor models in mice. Our results clearly show the remarkable capability of 2C5-targeted Doxil® to specifically deliver its cargo into various tumor manifestations (solid and metastatic) significantly increasing the efficacy of therapy. PMID:19049322

  13. Solid Tumor Second Primary Neoplasms: Who is at Risk, What Can We Do?

    PubMed Central

    Oeffinger, Kevin C.; Baxi, Shrujal S.; Friedman, Danielle Novetsky; Moskowitz, Chaya S.

    2014-01-01

    Eighteen percent of incident malignancies in the U.S. are a second (or subsequent) cancer. Second primary neoplasms (SPN), particularly solid tumors, are a major cause of mortality and serious morbidity among cancer survivors successfully cured of their first cancer. Multiple etiologies may lead to a cancer survivor subsequently being diagnosed with an SPN, including radiotherapy for the first cancer, unhealthy lifestyle behaviors, germline and somatic mutations, aging, or an interaction between any of these factors. In this article, we discuss these factors and synthesize this information for use in clinical practice, including preventive strategies and screening recommendations for SPNs. PMID:24331190

  14. Isolation of the Ubiquitin-Proteome from Tumor Cell Lines and Primary Cells Using TUBEs.

    PubMed

    Xolalpa, Wendy; Mata-Cantero, Lydia; Aillet, Fabienne; Rodriguez, Manuel S

    2016-01-01

    Tandem ubiquitin-binding entities (TUBEs) act as molecular traps to isolate polyubiquitylated proteins facilitating the study of this highly reversible posttranslational modification. We provide here sample preparation and adaptations required for TUBE-based enrichment of the ubiquitin proteome from tumor cell lines or primary cells. Our protocol is suitable to identify ubiquitin substrates, enzymes involved in the ubiquitin proteasome pathway, as well as proteasome subunits by mass spectrometry. This protocol was adapted to prepare affinity columns, reduce background, and improve the protein recovery depending on the sample source and necessities. PMID:27613034

  15. [The first experience in interstitial brachytherapy for primary and metastatic tumors of the brain].

    PubMed

    Bentsion, D L; Gvozdev, P B; Sakovich, V P; Fialko, N V; Kolotvinov, V S; Baiankina, S N

    2006-01-01

    In 2001-2002, the authors performed a course of brachytherapy in 15 patients with inoperable primary, recurrent, and metastatic brain tumors. The histostructural distribution was as follows: low-grade astrocytoma (grade II according to the WHO classification) in 2 patients, anaplastic astrocytoma (AA) in 3, glioblastoma multiforme (GBM) in 5. Five patients had solid tumor deposits in the brain. Computer tomographic (CT) and magnetic resonance imaging (MRI) data were used to define a path for forthcoming biopsy and implantation at a "Stryker" navigation station, by taking into account the anatomy of the brain, vessels, and functionally significant areas. After having histological findings, plastic intrastats whose number had been determined by the volume of a target were implanted into a tumor by the predetermined path. Dosimetric planning was accomplished by using CT and MRI images on an "Abacus" system. The final stage involved irradiation on a "GammaMed plus" with a source of 192Ir. Irradiation was given, by hyperfractionating its dose (3-4 Gy twice daily at an interval of 4-5 hours) to the total focal dose (TFD) of 36-44 Gy. Patients with gliomas untreated with radiation also underwent external radiation in a TFD of 54-56 Gy and patients with brain metastases received total external irradiation of the brain in a TFD of 36-40 Gy. The tolerance of a course of irradiation was fair. In patients with AA and GBM, one-year survival was observed in 66 and 60%, respectively; in those having metastasis, it was in 20%. Six patients died from progressive disease. All patients with low-grade astrocytoma and one patient with anaplastic astrocytoma were alive at month 24 after treatment termination. The mean lifespan of patients with malignant gliomas and solid tumor metastasis was 11.5 and 5.8 months, respectively. Brachytherapy is a noninvasive and tolerable mode of radiotherapy that increases survival in some groups of patients with inoperable brain tumors.

  16. Cell differentiation within a yeast colony: metabolic and regulatory parallels with a tumor-affected organism.

    PubMed

    Cáp, Michal; Stěpánek, Luděk; Harant, Karel; Váchová, Libuše; Palková, Zdena

    2012-05-25

    Nutrient sensing and metabolic reprogramming are crucial for metazoan cell aging and tumor growth. Here, we identify metabolic and regulatory parallels between a layered, multicellular yeast colony and a tumor-affected organism. During development, a yeast colony stratifies into U and L cells occupying the upper and lower colony regions, respectively. U cells activate a unique metabolism controlled by the glutamine-induced TOR pathway, amino acid-sensing systems (SPS and Gcn4p) and signaling from mitochondria with lowered respiration. These systems jointly modulate U cell physiology, which adapts to nutrient limitations and utilize the nutrients released from L cells. Stress-resistant U cells share metabolic pathways and other similar characteristics with tumor cells, including the ability to proliferate. L cells behave similarly to stressed and starving cells, which activate degradative mechanisms to provide nutrients to U cells. Our data suggest a nutrient flow between both cell types, resembling the Cori cycle and glutamine-NH(4)(+) shuttle between tumor and healthy metazoan cells.

  17. The renal tumor morphological characteristics that affect surgical planning for laparoscopic or open partial nephrectomy.

    PubMed

    Funahashi, Yasuhito; Murotani, Kenta; Yoshino, Yasushi; Sassa, Naoto; Ishida, Shohei; Gotoh, Momokazu

    2015-02-01

    The purpose of this study is to investigate the morphological characteristics of renal tumors which affect the surgeons' decision-making for the selection of open or laparoscopic partial nephrectomy. We included 147 patients who underwent partial nephrectomy for renal masses with elective indications in this study. Laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN) were performed in 72 and 75 patients, respectively. Preoperative trans-sectional images were used to assess tumor characteristics such as tumor size, endophyticity, distance from the sinus, distance from the kidney equator, hilar designation, inside designation, and R.E.N.A.L. nephrometry score. Univariate logistic regression analyses demonstrated that tumor size, endophyticity, distance from the sinus, hilar designation, inside designation, and R.E.N.A.L. nephrometry score were associated with decision of laparoscopic partial nephrectomy. Among these factors, multiple regression analyses showed that endophyticity (odds ratio = 0.92, p = 0.007) and distance from the sinus (odds ratio = 1.201, p < 0.001) had statistically significant associations with the type of operation performed. ROC analyses demonstrated cut-off values of 16 mm for endophyticity (sensitivity 69%, specificity 77%) and of 4 mm for distance from the sinus (sensitivity 79%, specificity 65%) for predicting the selection of laparoscopic surgery. In conclusion, this study revealed that endophyticity and distance from the sinus were important for the surgical planning of partial nephrectomy.

  18. How sequestration cuts affect primary care physicians and graduate medical education.

    PubMed

    Chauhan, Bindiya; Coffin, Janis

    2013-01-01

    On April 1, 2013, sequestration cuts went into effect impacting Medicare physician payments, graduate medical education, and many other healthcare agencies. The cuts range from 2% to 5%, affecting various departments and organizations. There is already a shortage of primary care physicians in general, not including rural or underserved areas, with limited grants for advanced training. The sequestration cuts negatively impact the future of many primary care physicians and hinder the care many Americans will receive over time. PMID:24044191

  19. Cranial nerve root entry zone primary cerebellopontine angle gliomas: a rare and poorly recognized subset of extraparenchymal tumors.

    PubMed

    Arnautovic, K I; Husain, M M; Linskey, M E

    2000-09-01

    With the exception of patients with neurofibromatosis type II, pediatric extraparenchymal cerebellopontine angle (CPA) tumors of any sort are extremely rare. Most gliomas encountered in the CPA in either children or adults involve the CPA as exophytic extensions of primary brain stem and/or cerebellar tumors. We encountered an unusual case of a giant CPA pilocytic astrocytoma arising from the proximal trigeminal nerve, completely separate from the brain stem. A nine-year-old girl with no evidence for any neurocutaneous syndrome, presented with headaches, mild obstructive hydrocephalus, trigeminal hypesthesia and a subtle peripheral facial paresis. Pre-operative neuroimaging suggested a petroclival meningioma. The tumor was completely resected via a right pre-sigmoid, retro-labyrinthine, subtemporal, transtentorial ('petrosal') approach, using intraoperative neurophysiological monitoring, with minimal morbidity. This appears to be the first reported case of a pediatric primary CPA glioma and the seventh reported case of primary CPA glioma, overall. It represents the second reported case of a primary CPA pilocytic astrocytoma. Given the findings in this case and the six other cases of primary CPA gliomas reported in the literature, as well as the results of histological studies of normal cranial nerves, we hypothesize that the point of origin of these rare and unusual tumors is the root entry zone of the involved cranial nerves. The differential diagnosis of primary CPA tumors should be expanded to include cranial nerve root entry zone primary CPA gliomas.

  20. DNA methylation profiling of primary neuroblastoma tumors using methyl-CpG-binding domain sequencing

    PubMed Central

    Decock, Anneleen; Ongenaert, Maté; Van Criekinge, Wim; Speleman, Frank; Vandesompele, Jo

    2016-01-01

    Comprehensive genome-wide DNA methylation studies in neuroblastoma (NB), a childhood tumor that originates from precursor cells of the sympathetic nervous system, are scarce. Recently, we profiled the DNA methylome of 102 well-annotated primary NB tumors by methyl-CpG-binding domain (MBD) sequencing, in order to identify prognostic biomarker candidates. In this data descriptor, we give details on how this data set was generated and which bioinformatics analyses were applied during data processing. Through a series of technical validations, we illustrate that the data are of high quality and that the sequenced fragments represent methylated genomic regions. Furthermore, genes previously described to be methylated in NB are confirmed. As such, these MBD sequencing data are a valuable resource to further study the association of NB risk factors with the NB methylome, and offer the opportunity to integrate methylome data with other -omic data sets on the same tumor samples such as gene copy number and gene expression, also publically available. PMID:26836295

  1. DNA methylation profiling of primary neuroblastoma tumors using methyl-CpG-binding domain sequencing.

    PubMed

    Decock, Anneleen; Ongenaert, Maté; Van Criekinge, Wim; Speleman, Frank; Vandesompele, Jo

    2016-01-01

    Comprehensive genome-wide DNA methylation studies in neuroblastoma (NB), a childhood tumor that originates from precursor cells of the sympathetic nervous system, are scarce. Recently, we profiled the DNA methylome of 102 well-annotated primary NB tumors by methyl-CpG-binding domain (MBD) sequencing, in order to identify prognostic biomarker candidates. In this data descriptor, we give details on how this data set was generated and which bioinformatics analyses were applied during data processing. Through a series of technical validations, we illustrate that the data are of high quality and that the sequenced fragments represent methylated genomic regions. Furthermore, genes previously described to be methylated in NB are confirmed. As such, these MBD sequencing data are a valuable resource to further study the association of NB risk factors with the NB methylome, and offer the opportunity to integrate methylome data with other -omic data sets on the same tumor samples such as gene copy number and gene expression, also publically available. PMID:26836295

  2. A novel somatic MAPK1 mutation in primary ovarian mixed germ cell tumors.

    PubMed

    Zou, Yang; Deng, Wei; Wang, Feng; Yu, Xiao-Hong; Liu, Fa-Ying; Yang, Bi-Cheng; Huang, Mei-Zhen; Guo, Jiu-Bai; Xie, Qiu-Hua; He, Ming; Huang, Ou-Ping

    2016-02-01

    A recent exome-sequencing study revealed prevalent mitogen-activated protein kinase 1 (MAPK1) p.E322K mutation in cervical carcinoma. It remains largely unknown whether ovarian carcinomas also harbor MAPK1 mutations. As paralogous gene mutations co‑occur frequently in human malignancies, we analyzed here a total of 263 ovarian carcinomas for the presence of MAPK1 and paralogous MAPK3 mutations by DNA sequencing. A previously unreported MAPK1 p.D321N somatic mutation was identified in 2 out of 18 (11.1%) ovarian mixed germ cell tumors, while no other MAPK1 or MAPK3 mutation was detected in our samples. Of note, OCC‑115, the MAPK1‑mutated sample with bilateral cancerous ovaries affected, harbored MAPK1 mutation in the right ovary while retained the left ovary intact, implicating that the genetic alterations underlying ovarian mixed germ cell tumor may be different, even in patients with similar genetic backgrounds and tumor microenvironments. The results of evolutionary conservation and protein structure modeling analysis implicated that MAPK1 p.D321N mutation may be pathogenic. Additionally, mutations in protein phosphatase 2 regulatory subunit α (PPP2R1A), ring finger protein 43 (RNF43), DNA directed polymerase ε (POLE1), ribonuclease type III (DICER1), CCCTC‑binding factor (CTCF), ribosomal protein L22 (RPL22), DNA methyltransferase 3α (DNMT3A), transformation/transcription domain‑associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 were not detected in ovarian mixed germ cell tumors, implicating these genetic alterations may be not associated with MAPK1 mutation in the development of this malignancy. The present study identified a previously unreported MAPK1 mutation in ovarian mixed germ cell tumors for the first time, and this mutation may be actively involved in the tumorigenesis of this disease.

  3. Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors.

    PubMed

    Li, Fang; Liu, Xinjian; Sampson, John H; Bigner, Darell D; Li, Chuan-Yuan

    2016-09-01

    Cancer stem-like cells (CSC) are thought to drive brain cancer, but their cellular and molecular origins remain uncertain. Here, we report the successful generation of induced CSC (iCSC) from primary human astrocytes through the expression of defined genetic factors. Combined transduction of four factors, Myc, Oct-4, p53DD, and Ras, induced efficient transformation of primary human astrocytes into malignant cells with powerful tumor-initiating capabilities. Notably, transplantation of 100 transduced cells into nude mice was sufficient for tumor formation. The cells showed unlimited self-renewal ability with robust telomerase activities. In addition, they expressed typical glioma stem-like cell markers, such as CD133, CD15, and CD90. Moreover, these cells could form spheres in culture and differentiate into neuron-like, astrocyte-like, and oligodendrocyte-like cells. Finally, they also displayed resistance to the widely used brain cancer drug temozolomide. These iCSCs could provide important tools for studies of glioma biology and therapeutics development. Cancer Res; 76(17); 5143-50. ©2016 AACR. PMID:27364552

  4. Case Report of Contrast-Enhanced Ultrasound Features of Primary Hepatic Neuroendocrine Tumor

    PubMed Central

    Li, Wei; Zhuang, Bo-wen; Wang, Zhu; Liao, Bing; Hong, Ling-yao; Xu, Ming; Lin, Xiao-na; Xie, Xiao-yan; Lu, Ming-de; Chen, Li-da; Wang, Wei

    2016-01-01

    Abstract Primary hepatic neuroendocrine tumors (PHNETs) are very rare and their clinical features and treatment outcomes are not well understood. It is difficult to reach a proper diagnosis before biopsy or resection. The aim of this study was to analyze the imaging features of PHNETs on contrast-enhanced ultrasound (CEUS). The clinical characteristics, CEUS findings, pathological features, treatment and prognosis of 6 patients with PHNET treated in our hospital were retrospectively analyzed. Most PHNETs occurred in middle-aged patients, and the most common clinical manifestation was right upper quadrant palpable mass and abdominal pain. Multiple small anechoic intralesional cavities occurred frequently in PHNET. Multilocular cystic with internal septation or monolocular with wall nodule could also be detected. On contrast-enhanced ultrasonography (CEUS), heterogeneous hyperenhancement in the arterial phase and wash-out hypoenhancement were observed in most patients, while computed tomography scanning yielded similar results. Diagnosis of PHNET was confirmed by immunohistochemical result and follow-up with the absence of extrahepatic primary sites. Five patients received surgical resection and 2 cases exhibited recurrence. Transcatheter arterial chemoembolization was performed in 1 patient with recurrence. Only 1 patient received conservative care. The median overall survival in 5 patients who underwent surgical treatment was 27 months (18–36 months). PHNET is a rare tumor, and its diagnosis is difficult. The CEUS features reported in this series may enrich the knowledge base for characterization of PHNET. PMID:27227910

  5. Hotspot mutation panel testing reveals clonal evolution in a study of 265 paired primary and metastatic tumors

    PubMed Central

    Goswami, Rashmi S.; Patel, Keyur P.; Singh, Rajesh R.; Meric-Bernstam, Funda; Kopetz, E. Scott; Subbiah, Vivek; Alvarez, Ricardo H.; Davies, Michael A.; Jabbar, Kausar J.; Roy-Chowdhuri, Sinchita; Lazar, Alexander J.; Medeiros, L. Jeffrey; Broaddus, Russell R.; Luthra, Rajyalakshmi; Routbort, Mark J.

    2016-01-01

    Purpose We used a clinical next-generation sequencing hotspot mutation panel to investigate clonal evolution in paired primary and metastatic tumors. Experimental Design A total of 265 primary and metastatic tumor pairs were sequenced using a 46-gene cancer mutation panel capable of detecting one or more single nucleotide variants as well as small insertions/deletions. Mutations were tabulated together with tumor type and percentage, mutational variant frequency, time interval between onset of primary tumor and metastasis, and neoadjuvant therapy status. Results 227 of 265 (85.7%) tumor-metastasis pairs showed identical mutation calls. Of the tumor pairs with identical mutation calls, 160 (60.4%) possessed defining somatic mutation signatures and 67 (25.3%) did not exhibit any somatic mutations. There were 38 (14.3%) cases that showed at least one novel mutation call between the primary and metastasis. Metastases were almost two times more likely to show novel mutations (n=20, 7.5%) than primary tumors (n=12, 4.5%). TP53 was the most common additionally mutated gene in metastatic lesions, followed by PIK3CA and SMAD4. PIK3CA mutations were more often associated with metastasis in colon carcinoma samples. Conclusions Clinical next-generation sequencing hotspot panels can be useful in analyzing clonal evolution within tumors as well as in determining subclonal mutations that can expand in future metastases. PIK3CA, SMAD4 and TP53 are most often involved in clonal divergence, providing potential targets that may help guide the clinical management of tumor progression or metastases. PMID:25695693

  6. Phenotypic differentiation does not affect tumorigenicity of primary human colon cancer initiating cells.

    PubMed

    Dubash, Taronish D; Hoffmann, Christopher M; Oppel, Felix; Giessler, Klara M; Weber, Sarah; Dieter, Sebastian M; Hüllein, Jennifer; Zenz, Thorsten; Herbst, Friederike; Scholl, Claudia; Weichert, Wilko; Werft, Wiebke; Benner, Axel; Schmidt, Manfred; Schneider, Martin; Glimm, Hanno; Ball, Claudia R

    2016-02-28

    Within primary colorectal cancer (CRC) a subfraction of all tumor-initiating cells (TIC) drives long-term progression in serial xenotransplantation. It has been postulated that efficient maintenance of TIC activity in vitro requires serum-free spheroid culture conditions that support a stem-like state of CRC cells. To address whether tumorigenicity is indeed tightly linked to such a stem-like state in spheroids, we transferred TIC-enriched spheroid cultures to serum-containing adherent conditions that should favor their differentiation. Under these conditions, primary CRC cells did no longer grow as spheroids but formed an adherent cell layer, up-regulated colon epithelial differentiation markers, and down-regulated TIC-associated markers. Strikingly, upon xenotransplantation cells cultured under either condition equally efficient formed serially transplantable tumors. Clonal analyses of individual lentivirally marked TIC clones cultured under either culture condition revealed no systematic differences in contributing clone numbers, indicating that phenotypic differentiation does not select for few individual clones adapted to unfavorable culture conditions. Our results reveal that CRC TIC can be propagated under conditions previously thought to induce their elimination. This phenotypic plasticity allows addressing primary human CRC TIC properties in experimental settings based on adherent cell growth.

  7. Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

    ClinicalTrials.gov

    2013-05-01

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Extra-adrenal Paraganglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  8. Relation between primary tumor FDG avidity and site of first distant metastasis in patients with breast cancer

    PubMed Central

    Lim, Chae Hong; Moon, Seung Hwan; Cho, Young Seok; Im, Young-Hyuck; Choe, Yearn Seong; Kim, Byung-Tae; Lee, Kyung-Han

    2016-01-01

    Abstract Identification of tumor imaging features associated with metastatic pattern may allow better understanding of cancer dissemination. Here, we investigated how primary tumor 18F-fluorodeoxyglucose (FDG) avidity influences the first site of breast cancer metastasis. Subjects were 264 patients with advanced breast cancer who underwent positron emission tomography/computed tomography at diagnosis and had metastasis at presentation (n = 193) or metastatic relapse after surgery (n = 71). Primary tumor FDG avidity (maximum SUV [SUVmax] ≥10.1) was compared with histology and first metastatic sites. The most common site of first metastasis was the bone, occurring in 62.7% of patients with metastasis at presentation and 38.0% of those with metastatic relapse. First metastasis to lung occurred in 30.1% and 35.2%, and to liver in 25.4% and 15.2% of respective groups. In patients with metastasis at presentation, primary tumors were FDG avid in 98/193 cases, and this was associated with more frequent first metastasis to lung (37.8% vs 22.1%; P = 0.018). In patients with metastasis relapse, primary tumors were FDG avid in 31/71 cases, and this was associated with more frequent first metastasis to lung (48.4% vs 25.0%; P = 0.041) and liver (29.0% vs 5.0%; P = 0.008). In patients with metastasis relapse, primary tumors that were FDG avid but hormone receptor negative had more first metastasis to lung (57.9% vs 26.9%; P = 0.016). FDG-avid primary breast tumors have favored first spread to the lung and liver, which suggests that tumor cells with heightened glycolytic activity better colonize these organs. PMID:27512840

  9. Relation between primary tumor FDG avidity and site of first distant metastasis in patients with breast cancer.

    PubMed

    Lim, Chae Hong; Moon, Seung Hwan; Cho, Young Seok; Im, Young-Hyuck; Choe, Yearn Seong; Kim, Byung-Tae; Lee, Kyung-Han

    2016-08-01

    Identification of tumor imaging features associated with metastatic pattern may allow better understanding of cancer dissemination. Here, we investigated how primary tumor F-fluorodeoxyglucose (FDG) avidity influences the first site of breast cancer metastasis.Subjects were 264 patients with advanced breast cancer who underwent positron emission tomography/computed tomography at diagnosis and had metastasis at presentation (n = 193) or metastatic relapse after surgery (n = 71). Primary tumor FDG avidity (maximum SUV [SUVmax] ≥10.1) was compared with histology and first metastatic sites.The most common site of first metastasis was the bone, occurring in 62.7% of patients with metastasis at presentation and 38.0% of those with metastatic relapse. First metastasis to lung occurred in 30.1% and 35.2%, and to liver in 25.4% and 15.2% of respective groups. In patients with metastasis at presentation, primary tumors were FDG avid in 98/193 cases, and this was associated with more frequent first metastasis to lung (37.8% vs 22.1%; P = 0.018). In patients with metastasis relapse, primary tumors were FDG avid in 31/71 cases, and this was associated with more frequent first metastasis to lung (48.4% vs 25.0%; P = 0.041) and liver (29.0% vs 5.0%; P = 0.008). In patients with metastasis relapse, primary tumors that were FDG avid but hormone receptor negative had more first metastasis to lung (57.9% vs 26.9%; P = 0.016).FDG-avid primary breast tumors have favored first spread to the lung and liver, which suggests that tumor cells with heightened glycolytic activity better colonize these organs.

  10. Senescence Process in Primary Wilms' Tumor Cell Culture Induced by p53 Independent p21 Expression

    PubMed Central

    Theerakitthanakul, Korkiat; Saetang, Jirakrit; Kruatong, Jirasak; Graidist, Potchanapond; Raungrut, Pritsana; Kayasut, Kanita; Sangkhathat, Surasak

    2016-01-01

    Wilms tumor (WT) is an embryonal tumor occurring in developing kidney tissue. WT cells showing invasive cancer characteristics, also retain renal stem cell behaviours. In-vitro culture of WT is hampered by limited replicative potential. This study aimed to establish a longterm culture of WT cells to enable the study of molecular events to attempt to explain its cellular senescence. Methods: Primary cell cultures from fresh WT tumor specimen were established. Of 5 cultures tried, only 1 could be propagated for more than 7 passages. One culture, identified as PSU-SK-1, could be maintained > 35 passages and was then subjected to molecular characterization and evaluation for cancer characteristics. The cells consistently harbored concomitant mutations of CTNNB1 (Ser45Pro) and WT1 (Arg413Stop) thorough the cultivation. On Transwell invasion assays, the cells exhibited migration and invasion at 55% and 27% capability of the lung cancer cells, A549. On gelatin zymography, PSU-SK-1 showed high expression of the matrix metaloproteinase. The cells exhibited continuous proliferation with 24-hour doubling time until passages 28-30 when the growth slowed, showing increased cell size, retention of cells in G1/S proportion and positive β-galactosidase staining. As with those evidence of senescence in advanced cell passages, expression of p21 and cyclin D1 increased when the expression of β-catenin and its downstream protein, TCF, declined. There was also loss-of-expression of p53 in this cell line. In conclusion, cellular senescence was responsible for limited proliferation in the primary culture of WT, which was also associated with increased expression of p21 and was independent of p53 expression. Decreased activation of the Wnt signalling might explain the induction of p21 expression. PMID:27698927

  11. Senescence Process in Primary Wilms' Tumor Cell Culture Induced by p53 Independent p21 Expression

    PubMed Central

    Theerakitthanakul, Korkiat; Khrueathong, Jeerasak; Kruatong, Jirasak; Graidist, Potchanapond; Raungrut, Pritsana; Kayasut, Kanita; Sangkhathat, Surasak

    2016-01-01

    Wilms tumor (WT) is an embryonal tumor occurring in developing kidney tissue. WT cells showing invasive cancer characteristics, also retain renal stem cell behaviours. In-vitro culture of WT is hampered by limited replicative potential. This study aimed to establish a longterm culture of WT cells to enable the study of molecular events to attempt to explain its cellular senescence. Methods: Primary cell cultures from fresh WT tumor specimen were established. Of 5 cultures tried, only 1 could be propagated for more than 7 passages. One culture, identified as PSU-SK-1, could be maintained > 35 passages and was then subjected to molecular characterization and evaluation for cancer characteristics. The cells consistently harbored concomitant mutations of CTNNB1 (Ser45Pro) and WT1 (Arg413Stop) thorough the cultivation. On Transwell invasion assays, the cells exhibited migration and invasion at 55% and 27% capability of the lung cancer cells, A549. On gelatin zymography, PSU-SK-1 showed high expression of the matrix metaloproteinase. The cells exhibited continuous proliferation with 24-hour doubling time until passages 28-30 when the growth slowed, showing increased cell size, retention of cells in G1/S proportion and positive β-galactosidase staining. As with those evidence of senescence in advanced cell passages, expression of p21 and cyclin D1 increased when the expression of β-catenin and its downstream protein, TCF, declined. There was also loss-of-expression of p53 in this cell line. In conclusion, cellular senescence was responsible for limited proliferation in the primary culture of WT, which was also associated with increased expression of p21 and was independent of p53 expression. Decreased activation of the Wnt signalling might explain the induction of p21 expression.

  12. Concordance of folate receptor-α expression between biopsy, primary tumor and metastasis in breast cancer and lung cancer patients

    PubMed Central

    Beck, Ann-Jean; Charehbili, Ayoub; Hoogstins, Charlotte E.S.; Prevoo, Hendrica A. J. M.; Singhal, Sunil; Low, Philip S.; van de Velde, Cornelis J. H.; Vahrmeijer, Alexander L.

    2016-01-01

    Folate receptor alpha (FRα) is known to be upregulated in a variety of cancers, including non-small cell lung cancer (NSCLC) and breast cancer. To ensure reliable implementation of diagnostic- and therapeutic agents, concordance of FRα expression between biopsy, primary tumor and metastases is important. Using immunohistochemistry (Mab 26B3.F2) these concordances were investigated in 60 NSCLC and 40 breast cancer patients. False positivity of FRα expression on breast and lung cancer biopsies was limited to less than 5%. In NSCLC, FRα expression was shown in 21/34 adenocarcinomas and 4/26 squamous cell carcinomas (SCC). Concordance of FRα expression between biopsy and primary tumor was achieved in respectively 83% and 91% of adenocarcinomas and SCCs. Approximately 80% of all local and distant metastases of NSCLC patients showed concordant FRα expression as their corresponding primary tumor. In breast cancer, FRα positivity was shown in 12/40 biopsies, 20/40 lumpectomies and 6/20 LN metastases, with concordance of 68% between biopsy and primary tumor and 60% between primary tumor and LN metastases. In conclusion, this study shows high concordance rates of FRα expression between biopsies and metastases compared to primary NSCLC and breast cancers, underscoring the applicability of FRα-targeted agents in these patients. PMID:26943581

  13. Primary primitive neuroectodermal tumor of the conus medullaris in an elderly patient: a case report and review of the literature.

    PubMed

    Shimosawa, H; Matsumoto, M; Yabe, H; Mukai, M; Toyama, Y; Morioka, H

    2011-05-01

    Primary spinal primitive neuroectodermal tumors (PNETs) are very rare conditions. Most of these tumors occur in children and young adults. A 63-year-old man with a primary spinal PNET in the conus medullaris from the L1 to L2 level is presented in this report. The optimal treatment of primary spinal PNETs is yet unknown. Surgical resection, radiation therapy, and chemotherapy have been advocated for the treatment of spinal PNET based on PNETs at other sites. However, the outcome is very poor. There are a few reports of cases with long-term survival and no recurrence. In these patients, en bloc resections were performed.

  14. Conditional Survival of All Primary Brain Tumor Patients by Age, Behavior, and Histology

    PubMed Central

    Porter, Kimberly R.; McCarthy, Bridget J.; Berbaum, Michael L.; Davis, Faith G.

    2011-01-01

    Background Survival statistics commonly reflect survival from the time of diagnosis but do not take into account survival already achieved after a diagnosis. The objective of this study was to provide conditional survival estimates for brain tumor patients as a more accurate measure of survival for those who have already survived for a specified amount of time after diagnosis. Methods Data on primary malignant and nonmalignant brain tumor cases diagnosed from 1985–2005 from selected SEER state cancer registries were obtained. Relative survival up to 15 years postdiagnosis and varying relative conditional survival rates were computed using the life-table method. Results The overall 1-year relative survival estimate derived from time of diagnosis was 67.8% compared to the 6-month relative conditional survival rate of 85.7% for 6-month survivors (the probability of surviving to 1 year given survival to 6 months). The 10-year overall relative survival rate was 49.5% from time of diagnosis compared to the 8-year relative conditional survival rate of 79.2% for 2-year survivors. Conditional survival estimates and standard survival estimates varied by histology, behavior, and age at diagnosis. The 5-year relative survival estimate derived from time of diagnosis for glioblastoma was 3.6% compared to the 3-year relative conditional survival rate of 36.4% for 2-year survivors. For most nonmalignant tumors, the difference between relative survival and the corresponding conditional survival estimates were minimal. Older age groups had greater numeric gains in survival but lower conditional survival estimates than other age groups. Similar findings were seen for other conditional survival intervals. Conclusions Conditional survival is a useful disease surveillance measure for clinicians and brain tumor survivors to provide them with better ‘real-time’ estimates and hope. PMID:21677447

  15. Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells.

    PubMed

    Oliveira-Costa, Joao Paulo; de Carvalho, Alex Fiorini; da Silveira, da Giorgia Gobbi; Amaya, Peter; Wu, Yongqi; Park, Kyoung-Joo Jenny; Gigliola, Mabel Pinilla; Lustberg, Maryam; Buim, Marcilei Eliza Cavicchioli; Ferreira, Elisa Napolitano; Kowalski, Luiz Paulo; Chalmers, Jeffrey J; Soares, Fernando Augusto; Carraro, Dirce Maria; Ribeiro-Silva, Alfredo

    2015-08-28

    Oral squamous cell carcinoma (OSCC) is the most common tumor of the oral cavity and has been associated with poor prognosis. Scarce prognostic markers are available for guiding treatment and/or sub-classifying patients. This study aims to identify biomarkers by searching for genes whose expression is increased or decreased during tumor progression (through T1 to T4 stages). Thirty-six samples from all tumor size stages (from T1 to T4) were analyzed using cDNA microarrays. Selected targets were analyzed by immunohistochemistry and in circulating tumor cells by immunofluorescence and Nanostring. Correlation was shown between PD-L1 and tumor size and lymph node metastasis, HOXB9 and tumor size, BLNK and perineural invasion, and between ZNF813 and perineural invasion. PD-L1 positivity was an independent prognostic factor in this cohort (p = 0.044, HH = 0.426). In CTCs from patients with locally advanced OSCC, we found a strong cytoplasmatic expression of PD-L1. PD-L1 is a ligand of PD-1 and is believed to limit T cell activity in inflammatory responses and limit autoimmune diseases. We demonstrated an important role for PD-L1 in primary tumors according to tumor size, and in disease specific survival. Therefore, we could further determine individuals with PD-L1+ CTCs, and possibly follow treatment using CTCs. PMID:26041877

  16. Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells

    PubMed Central

    Oliveira-Costa, Joao Paulo; de Carvalho, Alex Fiorini; da Silveira, Giorgia Gobbi; Amaya, Peter; Wu, Yongqi; Park, Kyoung-Joo Jenny; Gigliola, Mabel Pinilla; Lustberg, Maryam; Buim, Marcilei Eliza Cavicchioli; Ferreira, Elisa Napolitano; Kowalski, Luiz Paulo; Chalmers, Jeffrey J.; Soares, Fernando Augusto; Carraro, Dirce Maria; Ribeiro-Silva, Alfredo

    2015-01-01

    Oral squamous cell carcinoma (OSCC) is the most common tumor of the oral cavity and has been associated with poor prognosis. Scarce prognostic markers are available for guiding treatment and/or sub-classifying patients. This study aims to identify biomarkers by searching for genes whose expression is increased or decreased during tumor progression (through T1 to T4 stages). Thirty-six samples from all tumor size stages (from T1 to T4) were analyzed using cDNA microarrays. Selected targets were analyzed by immunohistochemistry and in circulating tumor cells by immunofluorescence and Nanostring. Correlation was shown between PD-L1 and tumor size and lymph node metastasis, HOXB9 and tumor size, BLNK and perineural invasion, and between ZNF813 and perineural invasion. PD-L1 positivity was an independent prognostic factor in this cohort (p = 0.044, HH = 0.426). In CTCs from patients with locally advanced OSCC, we found a strong cytoplasmatic expression of PD-L1. PD-L1 is a ligand of PD-1 and is believed to limit T cell activity in inflammatory responses and limit autoimmune diseases. We demonstrated an important role for PD-L1 in primary tumors according to tumor size, and in disease specific survival. Therefore, we could further determine individuals with PD-L1+ CTCs, and possibly follow treatment using CTCs. PMID:26041877

  17. The Socio-Affective Approach in Education for International Understanding at the Primary Level

    ERIC Educational Resources Information Center

    Cohen, Rachel

    1978-01-01

    Considers whether a socio-affective approach can be effective in promoting international understanding among pupils in primary grades and suggests learning activities which reinforce personal fulfillment, experience sharing, and empathy. Activities involve students in investigation of group social life, alternative ways of comprehending,…

  18. Factors Affecting Teachers' Participation in Continuing Professional Development (CPD): From Hong Kong Primary School Teachers' Perspectives

    ERIC Educational Resources Information Center

    Wan, Sally Wai-Yan.; Lam, Patrick Hak-Chung

    2010-01-01

    This paper presents the findings from a small-scale case study of Hong Kong primary teachers' perceptions of the factors affecting teachers' participation in continuing professional development (CPD). The study applies a multiple approach with mixed research methods, including using a self-developed survey questionnaire on the basis of the CPD…

  19. Activation of Inaccurate Prior Knowledge Affects Primary-School Students' Metacognitive Judgments and Calibration

    ERIC Educational Resources Information Center

    van Loon, Mariette H.; de Bruin, Anique B. H.; van Gog, Tamara; van Merrienboer, Jeroen J. G.

    2013-01-01

    The study investigated whether activation of inaccurate prior knowledge before study contributes to primary-school children's commission errors and overconfidence in these errors when learning new concepts. Findings indicate that inaccurate prior knowledge affects children's learning and calibration. The level of children's judgments of learning…

  20. An Investigation of Factors Affecting the Use of Educational Technology in Turkish Primary Schools

    ERIC Educational Resources Information Center

    Kazu, Ibrahim Yasar

    2011-01-01

    The main purpose of this study is to investigate the related factors that affect the usage of educational technology in primary schools. This study depends on literature analysis and the questionnaire to collect data. Specifically, the items employed in this study were derived from the teachers' and school administrators' perceptions of using…

  1. FOXL2 molecular status in adult granulosa cell tumors of the ovary: A study of primary and metastatic cases

    PubMed Central

    Zannoni, Gian Franco; Improta, Giuseppina; Petrillo, Marco; Pettinato, Angela; Scambia, Giovanni; Fraggetta, Filippo

    2016-01-01

    Granulosa cell tumors (GCTs) of the ovary are uncommon neoplasms, accounting for ~5% of all malignant ovarian tumors. GCTs are a relatively homogeneous group of tumors, categorized into two distinct subtypes, juvenile GCT and adult GCT (AGCT), likely arising from a limited set of molecular events usually involving the disruption of pathways that regulate granulosa cell proliferation. In the present study, the presence of forkheadbox L2 (FOXL2) c.402C>G mutation was investigated in a series of 42 samples of primary and metastatic AGCT of the ovary. The samples consisted of 37 primary and 5 metastatic ovarian AGCTs from 37 patients. FOXL2 mutational status was evaluated using a pyrosequencing approach on 2.5-µm sections of formalin-fixed paraffin-embedded tissue. FOXL2 c.402C>G mutation was found in 33/37 (89.2%) primary AGCTs and in 4/5 (80.0%) metastases, with the molecular status of the metastases recapitulating that of the primary tumors (4 mutated cases and 1 wild-type case). Overall, FOXL2 mutation is present in the majority of primary and metastatic AGCTs, and could be used as a valid tool in the diagnosis of the disease and in cases of metastatic lesions from an unknown primary origin. Moreover the concordance of FOXL2 molecular status in primary and associated metastases suggests its early appearance and genomic stability in AGCT tumorigenesis. PMID:27446412

  2. Primary hyperparathyroidism diagnosed after surgical ablation of a costal mass mistaken for giant-cell bone tumor: a case report

    PubMed Central

    2011-01-01

    Introduction Primary hyperparathyroidism is a common endocrine disorder characterized by elevated parathyroid hormone levels, which cause continuous osteoclastic bone resorption. Giant cell tumor of bone is an expansile osteolytic tumor that contains numerous osteoclast-like giant cells. There are many similarities in the radiological and histological features of giant cell tumor of bone and brown tumor. This is a rare benign focal osteolytic process most commonly caused by hyperparathyroidism. Case presentation We report the unusual case of a 40-year-old Caucasian woman in which primary hyperparathyroidism was diagnosed after surgical ablation of a costal mass. The mass was suspected of being neoplastic and histopathology was compatible with a giant cell tumor of bone. On the basis of the biochemical results (including serum calcium, phosphorous and intact parathyroid hormone levels) primary hyperparathyroidism was suspected and a brown tumor secondary to refractory hyperparathyroidism was diagnosed. Conclusions Since giant cell tumor is a bone neoplasm that has major implications for the patient, the standard laboratory tests in patients with bone lesions are important for a correct diagnosis. PMID:22204520

  3. Comparative study of primary and secondary tumors from patients with laryngeal and oropharyngeal cancer, using transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Ghetea, Ligia Gabriela; Niculescu, Ana-Maria; Motoc, Rozalia Magda; Mihaescu, Grigore; Duma, Virgil-Florin; Manu, Dorel Augustin; Gavrila, Lucian

    2008-04-01

    In modern laboratories, the study of cancer is performed using a series of cellular and molecular methods based on optical instruments measurements. Optical and electron microscopy are valuable tools for revealing morphological features of cancer cells. Our study was focused on laryngeal and oropharyngeal cancers, which have nowadays an increased incidence, especially for women, due to unhealthy habits like tobacco and alcohol consumption. We used transmission electron microscopy (TEM) for highlighting the ultrastructural features of cancer cells, both in primary and secondary tumors. The primary tumor is considered that which appears for the first time, at a certain organ; the secondary tumor is that which reappears at the same region or neighbouring regions, at a certain interval of time after the primary one has been surgically removed. The differences between the inner architecture of the cells from primary and secondary tumors where correlated with the expression of some genes (oncogenes and tumor suppressor factors), in order to establish the aggressiveness of the tumor, in different disease stages. The main stress in the study is placed upon electron microscopy, in order to achieve a more precise characterization of both these type of cancer cells. These ultrastructural data complete the image of laryngeal and pharyngeal cancer cells, along with molecular data obtained by Real-Time PCR.

  4. Second primary tumors and field cancerization in oral and oropharyngeal cancer: molecular techniques provide new insights and definitions.

    PubMed

    Braakhuis, Boudewijn J M; Tabor, Maarten P; Leemans, C René; van der Waal, Isaac; Snow, Gordon B; Brakenhoff, Ruud H

    2002-02-01

    Second primary tumors (SPTs) are a significant problem in treating oral and oropharyngeal squamous cell carcinoma and have a negative impact on survival. In most studies the definition of SPT is based on the criteria of Warren and Gates, published in 1932. These criteria, however, are ill-defined and lead to confusion. Recent molecular studies have shown that a tumor can be surrounded by a mucosal field consisting of genetically altered cells. Furthermore, evidence has been provided that SPTs (defined by classical criteria) can share some or even all genetic markers with the index tumor, indicating that both tumors have arisen from a common cell clone. We propose that these secondary neoplastic lesions should not be considered SPTs, implying that the present concept of SPT needs revision. This review describes a novel classification of the secondary tumors that develop after treatment of a carcinoma in the oral cavity or oropharynx. On the basis of the molecular analysis of the tumors and the genetically altered mucosal field in between, we propose definitions for a "true SPT," a local recurrence, a "SFT" (second field tumor derived from the same genetically altered mucosal field as the primary tumor), and a metastasis. Considering the etiologic differences of these lesions, we believe that an accurate molecular definition is essential to make headway with the clinical management of oral and oropharyngeal cancer.

  5. Efficient and sustained gene expression in primary T lymphocytes and primary and cultured tumor cells mediated by adeno-associated virus plasmid DNA complexed to cationic liposomes.

    PubMed

    Philip, R; Brunette, E; Kilinski, L; Murugesh, D; McNally, M A; Ucar, K; Rosenblatt, J; Okarma, T B; Lebkowski, J S

    1994-04-01

    We have used cationic liposomes to facilitate adeno-associated virus (AAV) plasmid transfections of primary and cultured cell types. AAV plasmid DNA complexed with liposomes showed levels of expression several fold higher than those of complexes with standard plasmids. In addition, long-term expression (> 30 days) of the gene, unlike the transient expression demonstrated by typical liposome-mediated transfection with standard plasmids, was observed. Southern analysis of chromosomal DNA further substantiated the hypothesis that the long-term expression was due to the presence of the transgene in the AAV plasmid-transfected group and not in the standard plasmid-transfected group. AAV plasmid-liposome complexes induced levels of transgene expression comparable to those obtained by recombinant AAV transduction. Primary breast, ovarian, and lung tumor cells were transfectable with the AAV plasmid DNA-liposome complexes. Transfected primary and cultured tumor cells were able to express transgene product even after lethal irradiation. High-level gene expression was also observed in freshly isolated CD3+, CD4+, and CD8+ T cells from normal human peripheral blood. Transfection efficiency ranged from 10 to 50% as assessed by intracellular interleukin-2 levels in interleukin-2-transfected cells. The ability to express transgenes in primary tumor and lymphoid cells may be applied toward tumor vaccine studies and protocols which may eventually permit highly specific modulation of the cellular immune response in cancer and AIDS.

  6. Efficient and sustained gene expression in primary T lymphocytes and primary and cultured tumor cells mediated by adeno-associated virus plasmid DNA complexed to cationic liposomes.

    PubMed Central

    Philip, R; Brunette, E; Kilinski, L; Murugesh, D; McNally, M A; Ucar, K; Rosenblatt, J; Okarma, T B; Lebkowski, J S

    1994-01-01

    We have used cationic liposomes to facilitate adeno-associated virus (AAV) plasmid transfections of primary and cultured cell types. AAV plasmid DNA complexed with liposomes showed levels of expression several fold higher than those of complexes with standard plasmids. In addition, long-term expression (> 30 days) of the gene, unlike the transient expression demonstrated by typical liposome-mediated transfection with standard plasmids, was observed. Southern analysis of chromosomal DNA further substantiated the hypothesis that the long-term expression was due to the presence of the transgene in the AAV plasmid-transfected group and not in the standard plasmid-transfected group. AAV plasmid-liposome complexes induced levels of transgene expression comparable to those obtained by recombinant AAV transduction. Primary breast, ovarian, and lung tumor cells were transfectable with the AAV plasmid DNA-liposome complexes. Transfected primary and cultured tumor cells were able to express transgene product even after lethal irradiation. High-level gene expression was also observed in freshly isolated CD3+, CD4+, and CD8+ T cells from normal human peripheral blood. Transfection efficiency ranged from 10 to 50% as assessed by intracellular interleukin-2 levels in interleukin-2-transfected cells. The ability to express transgenes in primary tumor and lymphoid cells may be applied toward tumor vaccine studies and protocols which may eventually permit highly specific modulation of the cellular immune response in cancer and AIDS. Images PMID:8139545

  7. The Effect of Mushroom Beta-Glucans from Solid Culture of Ganoderma lucidum on Inhibition of the Primary Tumor Metastasis

    PubMed Central

    Hung, Ming-Hsin; Chen, Sherwin; Wang, William; Lu, Chung-Lun

    2014-01-01

    This study evaluates the effect of mushroom beta-glucans (MBGS) derived from solid culture of Ganoderma lucidum on tumor inhibition by examining size of the primary tumor and rate of metastasis in Lewis lung carcinoma (LLC) bearing mice (C57BL/6), given oral administration of MBGS with radiation therapy. A previous result showed that MBGS enhances NK cell-mediated cytotoxicity in mice without LLC bearing in advance. Furthermore, applications of MBGS in conjunction with radiation therapy were effective in controlling tumor growth, and rate of metastasis, life threatening, and can potentially serve as a protective factor for wounds and hair loss that resulted from the overgrowth of primary tumor in LLC bearing mice. PMID:24799937

  8. Genome-wide copy number analysis of cerebrospinal fluid tumor cells and their corresponding archival primary tumors.

    PubMed

    Magbanua, Mark Jesus M; Roy, Ritu; Sosa, Eduardo V; Hauranieh, Louai; Kablanian, Andrea; Eisenbud, Lauren E; Ryazantsev, Artem; Au, Alfred; Scott, Janet H; Melisko, Michelle; Park, John W

    2014-12-01

    A debilitating complication of breast cancer is the metastatic spread of tumor cells to the leptomeninges or cerebrospinal fluid (CSF). Patients diagnosed with this aggressive clinical syndrome, known as leptomeningeal carcinomatosis, have very poor prognosis. Despite improvements in detecting cerebrospinal fluid tumor cells (CSFTCs), information regarding their molecular biology is extremely limited. In our recent work, we utilized a protocol previously used for circulating tumor cell isolation to purify tumor cells from the CSF. We then performed genomic characterization of CSFTCs as well as archival tumors from the same patient. Here, we describe the microarray data and quality controls associated with our study published in the Cancer Research journal in 2013 [1]. We also provide an R script containing code for quality control of microarray data and assessment of copy number calls. The microarray data has been deposited into Gene Expression Omnibus under accession # GSE46068.

  9. Ascorbate availability affects tumor implantation-take rate and increases tumor rejection in Gulo−/− mice

    PubMed Central

    Campbell, Elizabeth J; Vissers, Margreet CM; Dachs, Gabi U

    2016-01-01

    In solid tumors, HIF1 upregulates the expression of hundreds of genes involved in cell survival, tumor growth, and adaptation to the hypoxic microenvironment. HIF1 stabilization and activity are suppressed by prolyl and asparagine hydroxylases, which require oxygen as a substrate and ascorbate as a cofactor. This has led us to hypothesize that intracellular ascorbate availability could modify the hypoxic HIF1 response and influence tumor growth. In this study, we investigated the effect of variable intracellular ascorbate levels on HIF1 induction in cancer cells in vitro, and on tumor-take rate and growth in the Gulo−/− mouse. These mice depend on dietary ascorbate, and were supplemented with 3,300 mg/L, 330 mg/L, or 33 mg/L ascorbate in their drinking water, resulting in saturating, medium, or low plasma and tissue ascorbate levels, respectively. In Lewis lung carcinoma cells (LL/2) in culture, optimal ascorbate supplementation reduced HIF1 accumulation under physiological but not pathological hypoxia. LL/2, B16-F10 melanoma, or CMT-93 colorectal cancer cells were implanted subcutaneously into Gulo−/− mice at a range of cell inocula. Establishment of B16-F10 tumors in mice supplemented with 3,300 mg/L ascorbate required an increased number of cancer cells to initiate tumor growth compared with the number of cells required in mice on suboptimal ascorbate intake. Elevated ascorbate intake was also associated with decreased tumor ascorbate levels and a reduction in HIF1α expression and transcriptional activity. Following initial growth, all CMT-93 tumors regressed spontaneously, but mice supplemented with 33 mg/L ascorbate had lower plasma ascorbate levels and grew larger tumors than optimally supplemented mice. The data from this study indicate that improved ascorbate intake is consistent with increased intracellular ascorbate levels, reduced HIF1 activity and reduced tumor initiation and growth, and this may be advantageous in the management of cancer

  10. Surgical treatment of primary hyperparathyroidism due to parathyroid tumor: A 15-year experience

    PubMed Central

    Feng, Lu; Zhang, Xu; Liu, Shan-Ting

    2016-01-01

    The aim of this study was to highlight our experience over a 15-year period in dealing with primary hyperparathyroidism (PHPT) due to a parathyroid tumor. Parathyroidectomy is the standard therapy for patients with PHPT. Our study included all patients with PHPT treated by parathyroidectomy at the Affiliated Cancer Hospital of Zhengzhou University, China. Between 1998 and 2013, a total of 107 patients were recruited. Their clinical data, presentation, laboratory examinations, imageological diagnoses and surgical approaches were analyzed retrospectively. Eighty-four cases (78.5%) were followed up. During a median follow-up period of 5.7 years, a total of 80 patients were without recurrence and metastasis. The main symptoms of PHPT patients were palpable neck mass, joint pains and pathological fracture. The high levels of preoperative parathyroid hormone (PTH) and serum calcium in PHPT patients decreased to below the normal upper limit within 3 days of surgery. The sensitivity of neck ultrasonography, sestamibi scanning, CT, MRI and the combination of three or four types of test were 86.0%, 90.4%, 80.8%, 79.6% and 96.1%, respectively. A 50% or greater drop in PTH levels within 20 min compared with the highest PTH levels before surgery occurred in 95/107 cases (88.8%). Transient hypocalcemia was the most common surgical complication. The ultrasonography and sestamibi scan is the most effective examination for parathyroid tumor. The 20 min PTH measurement appears to be extremely useful, and avoids unnecessary bilateral exploration.

  11. Primary Indeterminate Dendritic Cell Tumor of Skin Correlated to Mosquito Bite

    PubMed Central

    Mo, Xianglan; Guo, Wenwen; Ye, Hongtao

    2015-01-01

    Abstract Primary indeterminate dendritic cell tumor (IDCT) is an extremely neoplastic dendritic cell disorder. Little is known about its pathogenesis, etiology, and prognostic factors because of its rarity. Herein, we present a case report of a skin IDCT that arose in mosquito bite and discuss the correlation between hypersensitivity to mosquito bites and leukemia/lymphoma. A 28-year old man presented with multiple widespread cutaneous plaques and nodules 8 months after being bitten by a mosquito on his back. Dermatological examination revealed multiple skin-colored, well-demarcated plaques and nodules measuring approximately 0.5 to 1.8 cm in diameter all over the body. A biopsy of the skin lesion was taken. Morphologically, the dermis was effaced by round or polygonal cells with oval nuclei and abundant eosinophilic cytoplasm, arranged in nests and in some areas in a sheet-like pattern. The tumor cells were positive for CD68, CD1a, and S-100, whereas negative for Langerin and lack Birbeck granules ultrastructurally. A diagnosis of IDCT was made. No treatment was given. The patient was alive with spontaneous disease regression after 17 months of follow-up. IDCT is an extremely rare disease and may be associated with mosquito bite. PMID:26313805

  12. Surgical treatment of primary hyperparathyroidism due to parathyroid tumor: A 15-year experience

    PubMed Central

    Feng, Lu; Zhang, Xu; Liu, Shan-Ting

    2016-01-01

    The aim of this study was to highlight our experience over a 15-year period in dealing with primary hyperparathyroidism (PHPT) due to a parathyroid tumor. Parathyroidectomy is the standard therapy for patients with PHPT. Our study included all patients with PHPT treated by parathyroidectomy at the Affiliated Cancer Hospital of Zhengzhou University, China. Between 1998 and 2013, a total of 107 patients were recruited. Their clinical data, presentation, laboratory examinations, imageological diagnoses and surgical approaches were analyzed retrospectively. Eighty-four cases (78.5%) were followed up. During a median follow-up period of 5.7 years, a total of 80 patients were without recurrence and metastasis. The main symptoms of PHPT patients were palpable neck mass, joint pains and pathological fracture. The high levels of preoperative parathyroid hormone (PTH) and serum calcium in PHPT patients decreased to below the normal upper limit within 3 days of surgery. The sensitivity of neck ultrasonography, sestamibi scanning, CT, MRI and the combination of three or four types of test were 86.0%, 90.4%, 80.8%, 79.6% and 96.1%, respectively. A 50% or greater drop in PTH levels within 20 min compared with the highest PTH levels before surgery occurred in 95/107 cases (88.8%). Transient hypocalcemia was the most common surgical complication. The ultrasonography and sestamibi scan is the most effective examination for parathyroid tumor. The 20 min PTH measurement appears to be extremely useful, and avoids unnecessary bilateral exploration. PMID:27602126

  13. Primary Indeterminate Dendritic Cell Tumor of Skin Correlated to Mosquito Bite.

    PubMed

    Mo, Xianglan; Guo, Wenwen; Ye, Hongtao

    2015-08-01

    Primary indeterminate dendritic cell tumor (IDCT) is an extremely neoplastic dendritic cell disorder. Little is known about its pathogenesis, etiology, and prognostic factors because of its rarity. Herein, we present a case report of a skin IDCT that arose in mosquito bite and discuss the correlation between hypersensitivity to mosquito bites and leukemia/lymphoma.A 28-year old man presented with multiple widespread cutaneous plaques and nodules 8 months after being bitten by a mosquito on his back. Dermatological examination revealed multiple skin-colored, well-demarcated plaques and nodules measuring approximately 0.5 to 1.8 cm in diameter all over the body. A biopsy of the skin lesion was taken. Morphologically, the dermis was effaced by round or polygonal cells with oval nuclei and abundant eosinophilic cytoplasm, arranged in nests and in some areas in a sheet-like pattern. The tumor cells were positive for CD68, CD1a, and S-100, whereas negative for Langerin and lack Birbeck granules ultrastructurally. A diagnosis of IDCT was made. No treatment was given. The patient was alive with spontaneous disease regression after 17 months of follow-up.IDCT is an extremely rare disease and may be associated with mosquito bite.

  14. Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach: A Case Report.

    PubMed

    Jiang, Meng-Jie; Weng, Shan-Shan; Cao, Ying; Li, Xiao-Fen; Wang, Liu-Hong; Xu, Jing-Hong; Yuan, Ying

    2015-09-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common.Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes.Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients.

  15. Primary Esophageal Intramural Squamous Cell Carcinoma Masquerading as a Submucosal Tumor: A Rare Presentation of a Common Disease

    PubMed Central

    Sonthalia, Nikhil; Jain, Samit S.; Surude, Ravindra G.; Pawar, Vinay B.; Udgirkar, Suhas; Rathi, Pravin M.

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is the commonest primary malignant esophageal tumor, which typically presents as endoscopically visible surface mucosal ulcerations, irregularities, or polyploidal masses. We here report a rare case of primary ESCC with completely intramural growth under a normal looking intact nondysplastic surface squamous epithelium disguising as a submucosal tumor. Upper gastrointestinal endoscopy-guided mucosal biopsy was negative for malignancy. Endoscopic ultrasound (EUS) revealed a heteroechoic solid mass originating from the muscularis propria of the distal esophagus. Cytological study of EUS-guided fine needle aspiration from the mass was suggestive of squamous cell carcinoma, which was confirmed on immunohistochemistry. There was no evidence of metastatic origin of this tumor or continuous cancer involvement from the surrounding structures, including the head, neck, and lungs on bronchoscopy, computed tomography scan, and positron emission tomography scan. Exclusive intramural squamous cell carcinoma with normal overlying mucosa is an exceedingly rare presentation of primary ESCC with only four cases reported in the literature so far. A high index of suspicion is required by the gastroenterologists and pathologists in diagnosing these cases as these tumors closely mimic the mesenchymal submucosal tumors such as lipoma, leiomyoma, and gastrointestinal stromal tumors. EUS is an indispensable tool in making a preoperative diagnosis and therapeutic decision making. PMID:27721663

  16. Prognostic relevance of Ki-67 in the primary tumor for survival after a diagnosis of distant metastasis.

    PubMed

    Loehberg, Christian R; Almstedt, Katrin; Jud, Sebastian M; Haeberle, Lothar; Fasching, Peter A; Hack, Carolin C; Lux, Michael P; Thiel, Falk C; Schrauder, Michael G; Brunner, Michaela; Bayer, Christian M; Hein, Alexander; Heusinger, Katharina; Heimrich, Jutta; Bani, Mayada R; Renner, Stefan P; Hartmann, Arndt; Beckmann, Matthias W; Wachter, David L

    2013-04-01

    Prediction of the prognosis for metastatic breast cancer patients depends on molecular subtypes similar to those found in patients with primary breast cancer. Several studies have shown that estrogen receptor (ER) and progesterone receptor (PR) status determine the course of the disease and the prognosis. As Ki-67 helps to differentiate molecular subtypes in patients with primary breast cancer, the aim of this study was to assess the prognostic relevance of Ki-67 in the primary tumor in relation to its prognostic relevance for patients with metastatic breast cancer. A total of 467 patients with invasive breast cancer were identified in the database of a single breast cancer center, in whom Ki-67 had been assessed in tumor material from the breast at the time of the primary diagnosis and who had developed a metastasis at any time during the subsequent course. For these patients, tumor and patient characteristics were used to determine prognostic factors relative to overall survival after the diagnosis of distant metastases. Ki-67 was added to this model to investigate whether this might improve the prediction of overall survival. In the multivariate Cox model, age at diagnosis, body mass index, nodal status, tumor size, ER and PR status, and time from diagnosis to metastasis were identified as relevant prognostic factors. Adding Ki-67 to the model improved the prediction of overall survival. There was also a significant and relevant interaction with the PR status. In patients with a low-proliferation primary tumor, a high level of PR expression would indicate an extraordinarily good prognosis (HR 0.39; 95 % CI, 0.23-0.66). In patients with higher-proliferation primary tumors, PR status was not capable of differentiating prognostic groups. Ki-67 is useful in addition to known prognostic factors for breast cancer. It is able to indicate a group of women with a poorer prognosis, specifically in the group of patients with PR-positive breast cancer.

  17. Feasibility of Primary Tumor Culture Models and Preclinical Prediction Assays for Head and Neck Cancer: A Narrative Review

    PubMed Central

    Dohmen, Amy J. C.; Swartz, Justin E.; Van Den Brekel, Michiel W. M.; Willems, Stefan M.; Spijker, René; Neefjes, Jacques; Zuur, Charlotte L.

    2015-01-01

    Primary human tumor culture models allow for individualized drug sensitivity testing and are therefore a promising technique to achieve personalized treatment for cancer patients. This would especially be of interest for patients with advanced stage head and neck cancer. They are extensively treated with surgery, usually in combination with high-dose cisplatin chemoradiation. However, adding cisplatin to radiotherapy is associated with an increase in severe acute toxicity, while conferring only a minor overall survival benefit. Hence, there is a strong need for a preclinical model to identify patients that will respond to the intended treatment regimen and to test novel drugs. One of such models is the technique of culturing primary human tumor tissue. This review discusses the feasibility and success rate of existing primary head and neck tumor culturing techniques and their corresponding chemo- and radiosensitivity assays. A comprehensive literature search was performed and success factors for culturing in vitro are debated, together with the actual value of these models as preclinical prediction assay for individual patients. With this review, we aim to fill a gap in the understanding of primary culture models from head and neck tumors, with potential importance for other tumor types as well. PMID:26343729

  18. Computed tomography and magnetic resonance imaging features of a rare case of a primary epidermoid tumor of the jugular foramen

    PubMed Central

    Mahajan, Parag Suresh; Mahajan, Anuradha Parag; Al Moosawi, Nawal M.

    2015-01-01

    We present computed tomography (CT) and magnetic resonance imaging (MRI) features of a very rare case of a primary epidermoid tumor of the jugular foramen (JF). A 45-year-old male patient presented with gradually progressive vertigo and tinnitus. CT and MRI scans revealed a 3.5 cm right-sided JF tumor with characteristic bright signal (restricted diffusion) on diffusion-weighted MRI (DWI). DWI may be useful in accurately differentiating the lesion from other cystic neoplasms of the JF. We describe the imaging features of intracranial epidermoid and JF tumors and discuss its differential diagnosis. PMID:25810672

  19. Primary vaginal Ewing's sarcoma or primitive neuroectodermal tumor in a 17-year-old woman: a case report

    PubMed Central

    2010-01-01

    Introduction Primary Ewing's sarcoma or primitive neuroectodermal tumor of the genital tract of women is uncommon. Rarer still is its occurrence in the vagina, with only five cases described so far. Out of these, only one case was confirmed using molecular analysis. Case presentation We present an extremely rare case of Ewing's sarcoma or primitive neuroectodermal tumor in a 17-year-old Indian girl. She presented with a vaginal mass that was initially diagnosed as a malignant round cell tumor. Immunohistochemistry showed diffuse positivity for vimentin, membranous positivity for MIC2, and positivity for BCL2 and FLI-1. On the other hand, she was negative for cytokeratin, epithelial membrane antigen, desmin, Myo D-1, myogenin and smooth muscle actin. A diagnosis of primitive neuroectodermal tumor was thus offered. Furthermore, a molecular analysis of our patient using reverse transcription-polymerase chain reaction technique showed positivity for t(11; 22) (q24; q12) (EWSR1-FLI1), thus confirming the diagnosis of a Ewing's sarcoma/primitive neuroectodermal tumor. Our patient was offered chemotherapy on Institutional protocol EFT 2001. Conclusion This is a rare case of primary vaginal Ewing's sarcoma or primitive neuroectodermal tumor, which was confirmed with molecular analysis, in the youngest patient known so far. This study reinforces the value of integrating morphological features with membranous MIC2 positivity, along with application of molecular techniques in objective identification of an Ewing's sarcoma or primitive neuroectodermal tumor at uncommon sites. PMID:20233457

  20. Tumor microcirculation during a course of combined chemoradiation in patients with primary rectal carcinoma measured with dynamic T1 mapping

    NASA Astrophysics Data System (ADS)

    Kremser, Christian; Judmaier, Werner; De Vries, Alexander

    2003-05-01

    A recently introduced dynamic T1 mapping technique was used to investigate changes of tumor microcirculatory parameters in 16 patients with clinically staged T3) primary rectal carcinoma during a course of preoperative combined chemoradiation. For dynamic T1 mapping an ultra-fast snapshot FLASH T1 mapping sequence was implemented on a 1.5T whole body MR scanner. Acquiring a series of T1 maps contrast media (CM) uptake and washout over an examination time of 40 min was monitored. From the obtained series of T1-maps perfusion-indices (PI) were calculated as the ratio of maximum slope of the tumor CM curve and the maximum of the arterial CM curve. Using pathologic classification of the resected tumors after therapy the patient group could be divided into patients with and without response to therapy. It was found that mean pre-therapy PI values of tumors showing therapy-response were significantly lower than for tumors without no therapy-response. In addition a different behavior of PI distributions within tumors for both groups was observed. The presented study indicates that PI values and their distributions within a tumor seem to be of predictive value for therapy outcome of preoperative therapy in patients with primary rectal carcinoma.

  1. Making a Difference: Distinguishing Two Primaries From Metastasis in Synchronous Tumors of the Ovary and Uterus.

    PubMed

    Dizon, Don S; Birrer, Michael J

    2016-06-01

    For women with early-stage ovarian or endometrial cancers, prognosis is very good, with overall survival for both sites between 80% and 90%. This stands in stark contrast to metastatic disease (advanced stage), where the overall survival is less than 15%. We have long recognized that subtypes of disease also inform these statistics, with high-grade serous carcinomas conferring a far worse prognosis compared with others, including low-grade serous or endometrioid tumors. Yet even with our present understanding, a not uncommon finding is the diagnosis of women with carcinoma at both the ovary and the uterus (a situation that occurs in up to 10% of patients), raising the question of synchronous primaries or of metastatic disease. The implications of these clinical scenarios are very relevant: If a conclusion of synchronous primaries is made, then prognosis should be excellent and hence no further treatment beyond surgery is required for cure. However, the finding of metastatic disease (from the ovary to the uterus or vice versa) will substantially change the prognostic implications, with these patients having a higher risk of recurrence and death from metastatic disease. In addition, this differential diagnosis can change therapeutic recommendations, with metastatic disease requiring more aggressive adjuvant therapy. Thus, the issue is both a biologic and clinical one. PMID:26832772

  2. Can PPH3 be helpful to assess the discordant grade in primary and metastatic enteropancreatic neuroendocrine tumors?

    PubMed

    Dumars, Clotilde; Foubert, Fanny; Touchefeu, Yann; Regenet, Nicolas; Senellart, Hélène; Matysiak-Budnik, Tamara; Heymann, Marie-Françoise

    2016-08-01

    Therapeutic strategy in neuroendocrine tumors (NETs) is based on histological characteristics of the primary tumor (PT), even in case of metastatic disease. Our aim was to compare the tumor grade between PT and their liver metastases (LM) in patients with enteropancreatic NETs. Forty-one patients treated for sporadic NETs (10 pancreatic, 31 intestinal) were included. All presented synchronous (35) or metachronous (6) LM. Tumor grade was evaluated for PT and LM according to the WHO classification, using Ki-67 labeling and mitotic count (MC) evaluated with or without phospho-histone H3 (PPH3). Tumor grade differed between primary and metastatic tumor in 16/41 patients (39 %), with an increase of grade in 13 of them (32 %). The median Ki-67, MC, and PPH3 in metastases were statistically higher than in PT (p = 0.0002, 0.02, and 0.01). In 17 of 65 cases tested with PPH3 (26 %), this antibody was more efficient in assessing the grade compared to the usual MC, and in 2/65 cases compared to the Ki-67. A better correlation was observed between Ki-67 and PPH3 (p = 0.0001) than between Ki-67 and MC without immunohistochemistry. There is a significant difference in tumor grade between primary and metastatic NETs, underlining the necessity of a systematic biopsy on LM for patient management. Moreover, PPH3 appears to be a powerful antibody to assess the MC and the tumor grade much more accurately when associated with Ki-67. PMID:27048356

  3. Receptor-Activator of Nuclear KappaB Ligand Expression as a New Therapeutic Target in Primary Bone Tumors

    PubMed Central

    Yamagishi, Tetsuro; Kawashima, Hiroyuki; Ogose, Akira; Ariizumi, Takashi; Sasaki, Taro; Hatano, Hiroshi; Hotta, Tetsuo; Endo, Naoto

    2016-01-01

    The receptor-activator of nuclear kappaB ligand (RANKL) signaling pathway plays an important role in the regulation of bone growth and mediates the formation and activation of osteoclasts. Osteoclasts are involved in significant bone resorption and destruction. Denosumab is a fully human monoclonal antibody against RANKL that specifically inhibits osteoclast differentiation and bone resorption. It has been approved for use for multiple myeloma and bone metastases, as well as for giant cell tumor of bone. However, there is no previous report quantitatively, comparing RANKL expression in histologically varied bone tumors. Therefore, we analyzed the mRNA level of various bone tumors and investigated the possibility of these tumors as a new therapeutic target for denosumab. We examined RANKL mRNA expression in 135 clinical specimens of primary and metastatic bone tumors using real-time PCR. The relative quantification of mRNA expression levels was performed via normalization with RPMI8226, a human multiple myeloma cell line that is recognized to express RANKL. Of 135 cases, 64 were also evaluated for RANKL expression by using immunohistochemistry. Among all of the tumors investigated, RANKL expression and the RANKL/osteoprotegerin ratio were highest in giant cell tumor of bone. High RANKL mRNA expression was observed in cases of aneurysmal bone cyst, fibrous dysplasia, osteosarcoma, chondrosarcoma, and enchondroma, as compared to cases of multiple myeloma and bone lesions from metastatic carcinoma. RANKL-positive stromal cells were detected in six cases: five cases of GCTB and one case of fibrous dysplasia. The current study findings indicate that some primary bone tumors present new therapeutic targets for denosumab, particularly those tumors expressing RANKL and those involving bone resorption by osteoclasts. PMID:27163152

  4. Receptor-Activator of Nuclear KappaB Ligand Expression as a New Therapeutic Target in Primary Bone Tumors.

    PubMed

    Yamagishi, Tetsuro; Kawashima, Hiroyuki; Ogose, Akira; Ariizumi, Takashi; Sasaki, Taro; Hatano, Hiroshi; Hotta, Tetsuo; Endo, Naoto

    2016-01-01

    The receptor-activator of nuclear kappaB ligand (RANKL) signaling pathway plays an important role in the regulation of bone growth and mediates the formation and activation of osteoclasts. Osteoclasts are involved in significant bone resorption and destruction. Denosumab is a fully human monoclonal antibody against RANKL that specifically inhibits osteoclast differentiation and bone resorption. It has been approved for use for multiple myeloma and bone metastases, as well as for giant cell tumor of bone. However, there is no previous report quantitatively, comparing RANKL expression in histologically varied bone tumors. Therefore, we analyzed the mRNA level of various bone tumors and investigated the possibility of these tumors as a new therapeutic target for denosumab. We examined RANKL mRNA expression in 135 clinical specimens of primary and metastatic bone tumors using real-time PCR. The relative quantification of mRNA expression levels was performed via normalization with RPMI8226, a human multiple myeloma cell line that is recognized to express RANKL. Of 135 cases, 64 were also evaluated for RANKL expression by using immunohistochemistry. Among all of the tumors investigated, RANKL expression and the RANKL/osteoprotegerin ratio were highest in giant cell tumor of bone. High RANKL mRNA expression was observed in cases of aneurysmal bone cyst, fibrous dysplasia, osteosarcoma, chondrosarcoma, and enchondroma, as compared to cases of multiple myeloma and bone lesions from metastatic carcinoma. RANKL-positive stromal cells were detected in six cases: five cases of GCTB and one case of fibrous dysplasia. The current study findings indicate that some primary bone tumors present new therapeutic targets for denosumab, particularly those tumors expressing RANKL and those involving bone resorption by osteoclasts. PMID:27163152

  5. Incidence and Outcomes of Patients With Oral Cavity Squamous Cell Carcinoma and Fourth Primary Tumors

    PubMed Central

    Adel, Mohamad; Liao, Chun-Ta; Lee, Li-Yu; Hsueh, Chuen; Lin, Chien-Yu; Fan, Kang-Hsing; Wang, Hung-Ming; Ng, Shu-Hang; Lin, Chih-Hung; Tsao, Chung-Kan; Huang, Shiang-Fu; Kang, Chung-Jan; Fang, Ku-Hao; Wang, Yu-Chien; Chang, Kai-Ping; Fang, Tuan-Jen; Yang, Lan Yan; Yen, Tzu-Chen

    2016-01-01

    Abstract The aim of this study was to explore the incidence and outcomes of patients with oral cavity squamous cell carcinoma (OSCC) and fourth primary tumors (PTs) in a betel-chewing endemic area. We retrospectively examined the records of 1836 OSCC patients who underwent radical tumor resection between 1996 and 2014. The outcome measures included the incidence and number of multiple PTs, the main risk factors, and their associations with overall survival (OS). Of the 1836 patients, 1400 (76.3%) had a single PT, 344 (18.7%) a second PT, 67 (3.6%) a third PT, and 25 (1.4%) a fourth PT. Univariate analyses (log-rank test) identified the following factors as significantly associated with a fourth PT: simultaneous first and second PTs, betel quid chewing, buccal subsite, and pT3–4 status. After allowance for the potential confounding effect of other risk factors, all of these factors retained their independent prognostic significance in stepwise multivariate analyses, the only exception being betel chewing. The incidences of second, third, and fourth PTs at 5 and 10 years were 20.2%/34.6%, 4.0%/8.6%, and 1.0%/2.3%, respectively. The 5 and 10-year OS rates (calculated from the diagnosis of each PTs) for patients with a single, second, third, and fourth PTs were 68%/61%, 43%/37%, 45%/39%%, and 30%/30%, respectively (P < 0.0001). Among patients with a fourth PT, those who underwent radical surgery showed a significantly higher 3-year OS than those who did not (57% vs 13%; P = 0.0442). Fourth PTs are rarely observed in OSCC patients in a betel quid-chewing endemic area. Long-term survival rates of patients treated with radical surgery seems acceptable, being 4-fold higher than their counterparts. PMID:27015170

  6. Quality of Life After Stereotactic Body Radiation Therapy for Primary and Metastatic Liver Tumors

    SciTech Connect

    Mendez Romero, Alejandra Wunderink, Wouter; Os, Rob M. van; Nowak, Peter J.C.M.; Heijmen, Ben J.M.; Nuyttens, Joost J.; Brandwijk, Rene P.; Verhoef, Cornelis; IJzermans, Jan N.M.; Levendag, Peter C.

    2008-04-01

    Purpose: Stereotactic body radiation therapy (SBRT) provides a high local control rate for primary and metastatic liver tumors. The aim of this study is to assess the impact of this treatment on the patient's quality of life. This is the first report of quality of life associated with liver SBRT. Methods and Materials: From October 2002 to March 2007, a total of 28 patients not suitable for other local treatments and with Karnofsky performance status of at least 80% were entered in a Phase I-II study of SBRT for liver tumors. Quality of life was a secondary end point. Two generic quality of life instruments were investigated, EuroQol-5D (EQ-5D) and EuroQoL-Visual Analogue Scale (EQ-5D VAS), in addition to a disease-specific questionnaire, the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ C-30). Points of measurement were directly before and 1, 3, and 6 months after treatment. Mean scores and SDs were calculated. Statistical analysis was performed using paired-samples t-test and Student t-test. Results: The calculated EQ-5D index, EQ-5D VAS and QLQ C-30 global health status showed that mean quality of life of the patient group was not significantly influenced by treatment with SBRT; if anything, a tendency toward improvement was found. Conclusions: Stereotactic body radiation therapy combines a high local control rate, by delivering a high dose per fraction, with no significant change in quality of life. Multicenter studies including larger numbers of patients are recommended and under development.

  7. Simultaneous Detection of Disseminated and Circulating Tumor Cells in Primary Breast Cancer Patients

    PubMed Central

    Hartkopf, Andreas D.; Wallwiener, Markus; Hahn, Markus; Fehm, Tanja N.; Brucker, Sara Y.; Taran, Florin-Andrei

    2016-01-01

    Purpose Disseminated tumor cells (DTCs) from bone marrow (BM) are a surrogate of minimal residual disease (MRD) in primary breast cancer (PBC) patients and associated with an adverse prognosis. However, BM sampling is an invasive procedure. Although there is growing evidence that circulating tumor cells (CTCs) from the blood are also suitable for monitoring MRD, data on the simultaneous detection of DTCs and CTCs are limited. Materials and Methods We determined the presence of DTCs using immunocytochemistry and the pan-cytokeratin antibody A45-B/B3. CTCs were determined simultaneously using a reverse transcription-polymerase chain reaction–based assay (AdnaTest Breast Cancer) and CellSearch (at least one CTC per 7.5 mL blood). We compared the detection of DTCs and CTCs and evaluated their impact on disease-free and overall survival. Results Of 585 patients, 131 (22%) were positive for DTCs; 19 of 202 (9%) and 18 of 383 (5%) patients were positive for CTCs, as shown by AdnaTest and CellSearch, respectively. No significant association was observed between DTCs and CTCs (p=0.248 and p=0.146 as shown by AdnaTest and CellSearch, respectively). The presence of DTCs (p=0.046) and the presence of CTCs as shown by CellSearch (p=0.007) were predictive of disease-free survival. Conclusion Our data confirm the prognostic relevance of DTCs and CTCs in patients with PBC. As we found no significant relationship between DTCs and CTCs, prospective trials should include their simultaneous detection. Within those trials, the question of whether or not DTCs and CTCs are independent subpopulations of malignant cell clones should be determined by molecular characterization. PMID:25687853

  8. Prognostic Value of the Sum of Metabolic Tumor Volume of Primary Tumor and Lymph Nodes Using 18F-FDG PET/CT in Patients With Cervical Cancer

    PubMed Central

    Hong, Jin Hwa; Min, Kyung Jin; Lee, Jae Kwan; So, Kyeong A; Jung, Un Suk; Kim, Sungeun; Eo, Jae Seon

    2016-01-01

    Abstract This is an observational study to determine the most relevant parameter of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for predicting recurrence in cervical cancer. Fifty-six patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IVA cervical cancer who underwent pretreatment 18F-FDG PET/CT were enrolled. PET parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of both primary tumor and pelvic and/or para-aortic lymph nodes were analyzed. SUVmax-S was defined as the sum of the SUVmax of primary tumor and the higher SUVmax of either pelvic or para-aortic lymph nodes. MTV-S was defined as the sum of the MTV of primary tumor and pelvic and para-aortic lymph nodes. TLG-S was calculated in the same way as MTV-S. We evaluated the relationship between these PET parameters and recurrence-free survival (RFS). Univariate analysis revealed that higher FIGO stage (hazard ratio [HR] = 5.61, 95% confidence interval [CI]: 1.68–18.68, P = 0.005), lymph node metastasis (HR = 3.42, 95% CI: 1.08–10.84, P = 0.037), MTV of primary tumor >47.81 cm3 (HR = 6.20, 95% CI: 1.35–28.48, P = 0.019), TLG of primary tumor >215.02 (HR = 11.82, 95% CI: 1.52–91.96, P = 0.018), MTV-S > 59.01 cm3 (HR = 8.24, 95% CI: 1.80–37.77, P = 0.007), and TLG-S > 224.15 (HR =  13.09, 95% CI: 1.68–101.89, P = 0.014) were associated with RFS. In multivariate analysis, FIGO stage (HR = 4.87, 95% CI: 1.38–17.18, P = 0.014) and MTV-S > 59.01 cm3 (HR = 7.37, 95% CI: 1.54–35.16, P = 0.012) were determined to be independent predictive factors for RFS. Our preliminary results reveal that MTV-S is an independent prognostic factor for RFS in patients with cervical cancer treated by definitive chemoradiotherapy. PMID:26945420

  9. High CD49f expression is associated with osteosarcoma tumor progression: a study using patient-derived primary cell cultures

    PubMed Central

    Penfornis, Patrice; Cai, David Z; Harris, Michael R; Walker, Ryan; Licini, David; Fernandes, Joseph D A; Orr, Griffin; Koganti, Tejaswi; Hicks, Chindo; Induru, Spandana; Meyer, Mark S; Khokha, Rama; Barr, Jennifer; Pochampally, Radhika R

    2014-01-01

    Overall prognosis for osteosarcoma (OS) is poor despite aggressive treatment options. Limited access to primary tumors, technical challenges in processing OS tissues, and the lack of well-characterized primary cell cultures has hindered our ability to fully understand the properties of OS tumor initiation and progression. In this study, we have isolated and characterized cell cultures derived from four central high-grade human OS samples. Furthermore, we used the cell cultures to study the role of CD49f in OS progression. Recent studies have implicated CD49f in stemness and multipotency of both cancer stem cells and mesenchymal stem cells. Therefore, we investigated the role of CD49f in osteosarcomagenesis. First, single cell suspensions of tumor biopsies were subcultured and characterized for cell surface marker expression. Next, we characterized the growth and differentiation properties, sensitivity to chemotherapy drugs, and anchorage-independent growth. Xenograft assays showed that cell populations expressing CD49fhi/CD90lo cell phenotype produced an aggressive tumor. Multiple lines of evidence demonstrated that inhibiting CD49f decreased the tumor-forming ability. Furthermore, the CD49fhi/CD90lo cell population is generating more aggressive OS tumor growth and indicating this cell surface marker could be a potential candidate for the isolation of an aggressive cell type in OSs. PMID:24802970

  10. Coexisting and possible primary extra-gastrointestinal stromal tumors of the pancreas and liver: A single case report

    PubMed Central

    LIU, LEI; ZHU, YINGQIAO; WANG, DONGXUAN; YANG, CHANGBIN; ZHANG, QI; LI, XIUKUN; BAI, YANG

    2016-01-01

    Gastrointestinal stromal tumors (GIST) are mesenchymal neoplasms of the gastrointestinal tract (GI) that are defined, in part, by the expression of CD117, a c-Kit proto-oncogene protein. GISTs emerge outside of the GI at a very low frequency, typically in a single organ or location. GISTs that occasionally emerge outside of the GI are classified as extra-gastrointestinal stromal tumors (EGIST). The present study reports an extremely rare case of EGIST detected in the pancreas and the liver. The pancreatic and liver tumors were 4.5×2.5 cm and 2.0×1.5 cm in size, respectively. Both tumors consisted of CD117-positive spindle cells with a similar mitotic rate of 1–2 per 50 high power fields. The pancreatic and the hepatic EGISTs were at a low risk of malignancy, and both tumors were proposed to be primary stromal tumors. To the best of our knowledge, this is the first report of likely primary EGIST identified in the pancreas and liver of the same patient. PMID:27123107

  11. High CD49f expression is associated with osteosarcoma tumor progression: a study using patient-derived primary cell cultures.

    PubMed

    Penfornis, Patrice; Cai, David Z; Harris, Michael R; Walker, Ryan; Licini, David; Fernandes, Joseph D A; Orr, Griffin; Koganti, Tejaswi; Hicks, Chindo; Induru, Spandana; Meyer, Mark S; Khokha, Rama; Barr, Jennifer; Pochampally, Radhika R

    2014-08-01

    Overall prognosis for osteosarcoma (OS) is poor despite aggressive treatment options. Limited access to primary tumors, technical challenges in processing OS tissues, and the lack of well-characterized primary cell cultures has hindered our ability to fully understand the properties of OS tumor initiation and progression. In this study, we have isolated and characterized cell cultures derived from four central high-grade human OS samples. Furthermore, we used the cell cultures to study the role of CD49f in OS progression. Recent studies have implicated CD49f in stemness and multipotency of both cancer stem cells and mesenchymal stem cells. Therefore, we investigated the role of CD49f in osteosarcomagenesis. First, single cell suspensions of tumor biopsies were subcultured and characterized for cell surface marker expression. Next, we characterized the growth and differentiation properties, sensitivity to chemotherapy drugs, and anchorage-independent growth. Xenograft assays showed that cell populations expressing CD49f(hi) /CD90(lo) cell phenotype produced an aggressive tumor. Multiple lines of evidence demonstrated that inhibiting CD49f decreased the tumor-forming ability. Furthermore, the CD49f(hi) /CD90(lo) cell population is generating more aggressive OS tumor growth and indicating this cell surface marker could be a potential candidate for the isolation of an aggressive cell type in OSs. PMID:24802970

  12. Activated neu oncogene sequences in primary tumors of the peripheral nervous system induced in rats by transplacental exposure to ethylnitrosourea

    SciTech Connect

    Perantoni, A.O.; Rice, J.M.; Reed, C.D.; Watatani, M.; Wenk, M.L.

    1987-09-01

    Neurogenic tumors were selectively induced in high incidence in F344 rats by a single transplacental exposure to the direct-acting alkylating agent N-ethyl-N-nitrosourea (EtNU). The authors prepared DNA for transfection of NIH 3T3 cells from primary glial tumors of the brain and form schwannomas of the cranial and spinal nerves that developed in the transplacentally exposed offspring between 20 and 40 weeks after birth. DNA preparations from 6 of 13 schwannomas, but not from normal liver, kidney, or intestine of tumor-bearing rats, transformed NIH 3T3 cells. NIH 3T3 clones transformed by schwannoma DNA contained rat repetitive DNA sequences, and all isolates contained rat neu oncogene sequences. A point mutation in the transmembrane region of the putative protein product of neu was identified in all six transformants and in the primary tumors from which they were derived as well as in 5 of 6 schwannomas tested that did not transform NIH 3T3 cells. Of 59 gliomas, only one yielded transforming DNA, and an activated N-ras oncogen was identified. The normal cellular neu sequence for the transmembrane region, but not the mutated sequence, was identified in DNA from all 11 gliomas surveyed by oligonucleotide hybridization. Activation of the neu oncogene, originally identified in cultured cell lines derived from EtNU-induced neurogenic tumors appears specifically associated with tumors of the peripheral nervous system in the F344 inbred strain.

  13. Comprehensive models of human primary and metastatic colorectal tumors in immunodeficient and immunocompetent mice by chemokine targeting.

    PubMed

    Chen, Huanhuan Joyce; Sun, Jian; Huang, Zhiliang; Hou, Harry; Arcilla, Myra; Rakhilin, Nikolai; Joe, Daniel J; Choi, Jiahn; Gadamsetty, Poornima; Milsom, Jeff; Nandakumar, Govind; Longman, Randy; Zhou, Xi Kathy; Edwards, Robert; Chen, Jonlin; Chen, Kai Yuan; Bu, Pengcheng; Wang, Lihua; Xu, Yitian; Munroe, Robert; Abratte, Christian; Miller, Andrew D; Gümüş, Zeynep H; Shuler, Michael; Nishimura, Nozomi; Edelmann, Winfried; Shen, Xiling; Lipkin, Steven M

    2015-06-01

    Current orthotopic xenograft models of human colorectal cancer (CRC) require surgery and do not robustly form metastases in the liver, the most common site clinically. CCR9 traffics lymphocytes to intestine and colorectum. We engineered use of the chemokine receptor CCR9 in CRC cell lines and patient-derived cells to create primary gastrointestinal (GI) tumors in immunodeficient mice by tail-vein injection rather than surgery. The tumors metastasize inducibly and robustly to the liver. Metastases have higher DKK4 and NOTCH signaling levels and are more chemoresistant than paired subcutaneous xenografts. Using this approach, we generated 17 chemokine-targeted mouse models (CTMMs) that recapitulate the majority of common human somatic CRC mutations. We also show that primary tumors can be modeled in immunocompetent mice by microinjecting CCR9-expressing cancer cell lines into early-stage mouse blastocysts, which induces central immune tolerance. We expect that CTMMs will facilitate investigation of the biology of CRC metastasis and drug screening.

  14. Differential Effects of Drugs Targeting Cancer Stem Cell (CSC) and Non-CSC Populations on Lung Primary Tumors and Metastasis

    PubMed Central

    Larzabal, Leyre; El-Nikhely, Nefertiti; Redrado, Miriam; Seeger, Werner; Savai, Rajkumar; Calvo, Alfonso

    2013-01-01

    Cancer stem cells (CSCs) are thought to be responsible for tumor initiation and recurrence after chemotherapy. Targeting CSCs and non-CSCs with specific compounds may be an effective approach to reduce lung cancer growth and metastasis. The aim of this study was to investigate the effect of salinomycin, a selective inhibitor of CSCs, with or without combination with paclitaxel, in a metastatic model. To evaluate the effect of these drugs in metastasis and tumor microenvironment we took advantage of the immunocompetent and highly metastatic LLC mouse model. Aldefluor assays were used to analyze the ALDH+/− populations in murine LLC and human H460 and H1299 lung cancer cells. Salinomycin reduced the proportion of ALDH+ CSCs in LLC cells, whereas paclitaxel increased such population. The same effect was observed for the H460 and H1299 cell lines. Salinomycin reduced the tumorsphere formation capacity of LLC by more than 7-fold, but paclitaxel showed no effect. In in vivo experiments, paclitaxel reduced primary tumor volume but increased the number of metastatic nodules (p<0.05), whereas salinomycin had no effect on primary tumors but reduced lung metastasis (p<0.05). Combination of both drugs did not improve the effect of single therapies. ALDH1A1, SOX2, CXCR4 and SDF-1 mRNA levels were higher in metastatic lesions than in primary tumors, and were significantly elevated in both locations by paclitaxel treatment. On the contrary, such levels were reduced (or in some cases did not change) when mice were administered with salinomycin. The number of F4/80+ and CD11b+ cells was also reduced upon administration of both drugs, but particularly in metastasis. These results show that salinomycin targets ALDH+ lung CSCs, which has important therapeutic effects in vivo by reducing metastatic lesions. In contrast, paclitaxel (although reducing primary tumor growth) promotes the selection of ALDH+ cells that likely modify the lung microenvironment to foster metastasis. PMID

  15. Differential effects of drugs targeting cancer stem cell (CSC) and non-CSC populations on lung primary tumors and metastasis.

    PubMed

    Larzabal, Leyre; El-Nikhely, Nefertiti; Redrado, Miriam; Seeger, Werner; Savai, Rajkumar; Calvo, Alfonso

    2013-01-01

    Cancer stem cells (CSCs) are thought to be responsible for tumor initiation and recurrence after chemotherapy. Targeting CSCs and non-CSCs with specific compounds may be an effective approach to reduce lung cancer growth and metastasis. The aim of this study was to investigate the effect of salinomycin, a selective inhibitor of CSCs, with or without combination with paclitaxel, in a metastatic model. To evaluate the effect of these drugs in metastasis and tumor microenvironment we took advantage of the immunocompetent and highly metastatic LLC mouse model. Aldefluor assays were used to analyze the ALDH+/- populations in murine LLC and human H460 and H1299 lung cancer cells. Salinomycin reduced the proportion of ALDH+ CSCs in LLC cells, whereas paclitaxel increased such population. The same effect was observed for the H460 and H1299 cell lines. Salinomycin reduced the tumorsphere formation capacity of LLC by more than 7-fold, but paclitaxel showed no effect. In in vivo experiments, paclitaxel reduced primary tumor volume but increased the number of metastatic nodules (p<0.05), whereas salinomycin had no effect on primary tumors but reduced lung metastasis (p<0.05). Combination of both drugs did not improve the effect of single therapies. ALDH1A1, SOX2, CXCR4 and SDF-1 mRNA levels were higher in metastatic lesions than in primary tumors, and were significantly elevated in both locations by paclitaxel treatment. On the contrary, such levels were reduced (or in some cases did not change) when mice were administered with salinomycin. The number of F4/80+ and CD11b+ cells was also reduced upon administration of both drugs, but particularly in metastasis. These results show that salinomycin targets ALDH+ lung CSCs, which has important therapeutic effects in vivo by reducing metastatic lesions. In contrast, paclitaxel (although reducing primary tumor growth) promotes the selection of ALDH+ cells that likely modify the lung microenvironment to foster metastasis. PMID

  16. [Clinical perspectives of the study of RANK/RANKL/OPG system components in primary and metastatic bone tumor].

    PubMed

    Kushlinskiĭ, N E; Timofeev, Iu S; Gershteĭn, E S; Solov'ev, Iu N

    2014-01-01

    Disbalance of bone homeostasis, associated with malfunctioning of RANK/RANKL/OPG system underlies the oncological processes such as the destruction of bone, metastasis development, tumor progression. Pathological activity of system was described in such conditions, as breast cancer, prostate cancer, multiple myeloma, squamous cell carcinoma, Hodgkin's disease, and also metastasis in bones from lung cancer and other malignant diseases. In the literature, there is evidence of involvement of RANK/RANKL/OPG system in the pathogenesis of bone tumors (osteosarcoma, giant cell tumor of bone, chondroblastoma). Experimental data show that RANKL inhibitors can play a role in reducing tumor-induced lesions of bone in multiple myeloma, breast cancer, prostate cancer and lung cancer. Also this review presents data from clinical studies of the drug efficacy targeted on RANK/RANKL/OPG system and results of authors' study of the levels of this system's components and proinflammatory cytokines in blood serum of primary bone sarcoma patients. PMID:25552059

  17. Primary Cerebellar Neuroendocrine Tumors: Chimeras or Real Entities? A Case Report with a 6-Year Follow-Up

    PubMed Central

    Vernieri, Claudio; Femia, Daniela; Pusceddu, Sara; Capella, Carlo; Rosai, Juan; Calareso, Giuseppina; Concas, Laura; Prinzi, Natalie; Russo, Giuseppe Lo; de Braud, Filippo; Buzzoni, Roberto

    2016-01-01

    We report the case of a 38-year-old patient who was diagnosed with a cerebellar well-differentiated neuroendocrine tumor (WDNET) in 2009. At first glance, we believed that it was a metastasis from an unrecognized WDNET arising outside the cerebellum. However, despite a prolonged follow-up of 6 years, an extracranial WDNET has never been found. During this time, the tumor recurred locally twice, and the patient was treated with surgery and radiotherapy. At the moment, he enjoys good general conditions and his tumor is under control. Due to the histopathological characteristics and clinical behavior of the tumor, we believe that this is the first report to date of a primary cerebellar WDNET. PMID:27721764

  18. Primary and Central Hypothyroidism After Radiotherapy for Head-and-Neck Tumors

    SciTech Connect

    Bhandare, Niranjan; Kennedy, Laurence; Malyapa, Robert S.; Morris, Christopher G.; Mendenhall, William M. . E-mail: mendewil@shands.ufl.edu

    2007-07-15

    Purpose: To investigate the incidence of radiotherapy (RT)-induced central and primary hypothyroidism regarding total dose, fractionation, and adjuvant chemotherapy. Methods and Materials: We retrospectively reviewed the data from 312 patients treated with RT for extracranial head-and-neck tumors between 1964 and 2000. The cervical lymph nodes were irradiated in 197 patients. The radiation doses to the thyroid gland and hypothalamic-pituitary axis were estimated by reconstructing the treatment plans. Results: Clinical central hypothyroidism (CH) was observed in 17 patients (5.4%); the median clinical latency was 4.8 years. Clinical primary hypothyroidism (PH) was observed in 40 patients (20.3%); the median clinical latency was 3.1 years. Multivariate analysis of clinical CH revealed that fractionation, adjuvant chemotherapy, and total dose to the pituitary were not significant. Multivariate analysis of clinical PH revealed that the total dose to the thyroid (p = 0.043) was significant, but adjuvant chemotherapy, age, and gender were not. Of the patients tested for hypopituitarism, 14 (20.3%) of 69 demonstrated subclinical CH and 17 (27.4%) of 62 demonstrated subclinical PH. The 5-year and 10-year rates of freedom from clinical CH and PH were 97% and 87% and 68% and 67%, respectively. Of the patients tested, the 5-year and 10-year rates of freedom from subclinical CH and PH were 91% and 78% and 71% and 71%, respectively. Conclusion: Clinical and subclinical manifestations of late radiation toxicity were observed in the thyroid and hypothalamic-pituitary axis. Although CH did not indicate a dependence on fractionation, adjuvant chemotherapy, or total dose to the pituitary, PH showed a dependence on the total dose to the thyroid gland.

  19. Atypical Teratoid/Rhabdoid Tumor (AT/RT) Arising From Ependymoma: A Type of AT/RT Secondarily Developing From Other Primary Central Nervous System Tumors.

    PubMed

    Nobusawa, Sumihito; Hirato, Junko; Sugai, Tsutomu; Okura, Naoki; Yamazaki, Tatsuya; Yamada, Seiji; Ikota, Hayato; Nakazato, Yoichi; Yokoo, Hideaki

    2016-02-01

    Atypical teratoid/rhabdoid tumors (AT/RT) are rare, aggressive, embryonal brain tumors that occur most frequently in very young children; they are characterized by rhabdoid cells and loss of INI1 protein nuclear expression. Here, we report the case of a 24-year-old man with a left frontal lobe tumor that was composed mainly of rhabdoid cells showing loss of INI1 nuclear reactivity and polyphenotypic immunohistochemical expression, with a small INI1-positive component of ependymoma. Array comparative genomic hybridization separately conducted for each histologically distinct component revealed 22 shared identical copy number alterations, including loss of heterozygosity of chromosome 22q containing the INI1 locus. Furthermore, we found the C11orf95-RELA fusion gene, the genetic hallmark of supratentorial ependymomas, not only in the ependymoma component but also in the AT/RT component by fluorescence in situ hybridization analysis, suggesting that the AT/RT cells secondarily progressed from the preexisting ependymoma cells. A second genetic inactivating event in the INI1 gene was not detected in the AT/RT component. There are several reported cases of AT/RT (or INI1-negative rhabdoid tumors) arising in the setting of other primary brain tumors (gangliogliomas, pleomorphic xanthoastrocytomas, and high-grade gliomas), but the present case PMID:26769252

  20. [The expression of MKP-1 and p-ERK(1/2) in primary ovarian epithelial tumor tissues].

    PubMed

    Zhou, Jian Wei; Gan, Ning Yue; Zhang, Wei Jiang

    2009-06-01

    To investigate the expression of mitogen activated protein kinase phosphatase-1 (MKP-1) and phosphorylation extracellular signal-regulated kinases (p-ERK(1/2)) in primary ovarian epithelial tumor tissues, and provide experiment's foundation on the new treatment in ovarian cancer. Expression of MKP-1 and p-ERK(1/2) in tissues from 64 patients with primary ovarian epithelial tumor, 35 patients with ovarian epithelial bordline tumor, 32 patients with ovarian epithelial benign tumor and 26 normal ovarian tissues was detected by immunohistochemistry. Western-blot was also used for detecting the expression of MKP-1 and p-ERK(1/2) protein in these tissues. Immunohistochemistry and Western-blot assay showed that the expression of MKP-1 was gradually decreased in normal ovarian tissues, benign tumor, bordline tumor and carcinoma respectively, and there were significant differences among them (P < 0.01). The MKP-1 expression level in the carcinoma tissues of stage III/IV patients was significantly lower than that of stage I/II patients. However, the expression of p-ERK(1/2) was gradually increased in normal ovarian tissues, benign tumor, bordline tumor and carcinoma respectively, and there were also significant differences among them (P < 0.01), the p-ERK(1/2) expression level in the carcinoma tissues of stage III/IV patients was significantly higher than that of stage I/II patients. Expression of MKP-1 and p-ERK(1/2) in same ovarian carcinoma tissues detected by immunohistochemistry and Western-blot assay showed significant negative correlation (r = -0.90, P < 0.01 and r = -0.78, P < 0.01 respectively). The expression changes of MKP-1 and ERKs may play a role in the development of ovarian carcinoma. The abnormal expression of MKP-1 and p-ERK(1/2) probably assists in promoting the development and progression of ovarian carcinoma.

  1. Primary hepatic solitary fibrous tumor with histologically benign and malignant areas.

    PubMed

    Silvanto, Anna; Karanjia, Nariman D; Bagwan, Izhar N

    2015-12-01

    Extrapleural solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm, presenting most commonly in the intrathoracic sites but which has been reported at numerous extrathoracic locations. The majority of intra-thoracic SFTs are benign, but 10%-15% behave aggressively. We report a case of primary hepatic SFT with histologically benign and malignant areas. A 65-year-old man underwent an abdominal CT scan following a cerebrovascular accident, which demonstrated a sharply demarcated large liver mass with a heterogenous enhancing area and occupying most of the left lobe of the liver. Histological examination following a hemihepatectomy showed an SFT with morphological patterns ranging from benign to malignant areas, including pleomorphism, increased cellularity, herringbone pattern, necrosis and a raised mitotic count. On review of the literature, only an occasional case report with malignant areas in a hepatic SFT was identified. This case highlights that SFT should be included in the differential diagnosis of a hepatic spindle cell lesion, and that on rare occasions, malignant areas can occur in this already uncommon neoplasm. PMID:26663016

  2. Exploring Spirituality in Family Caregivers of Patients With Primary Malignant Brain Tumors Across the Disease Trajectory

    PubMed Central

    Newberry, Alyssa G.; Jean Choi, Chien-Wen; Donovan, Heidi S.; Schulz, Richard; Bender, Catherine; Given, Barbara; Sherwood, Paula

    2013-01-01

    Purpose/Objectives To determine whether the perceived level of spirituality in family caregivers of patients with primary malignant brain tumors (PMBTs) changes across the disease trajectory. Design Ongoing descriptive, longitudinal study. Setting Southwestern Pennsylvania. Sample 50 family caregivers of patients with PMBT. Methods Caregivers and care recipients were recruited at time of diagnosis. Participants were interviewed at two subse-quent time points, four and eight months following diagnosis. Main Research Variables Care recipients’ symptoms, neuro-psychologic status, and physical function, as well as caregiver social support. Findings Results showed no significant difference in spirituality scores reported at baseline and eight months (p = 0.8), suggesting that spirituality may be a stable trait across the disease trajectory. Conclusions Spirituality remains relatively stable along the course of the disease trajectory. Reports of caregiver depressive symptoms and anxiety were lower when paired with higher reports of spirituality. Implications for Nursing Clinicians can better identify caregivers at risk for negative outcomes by identifying those who report lower levels of spirituality. Future interventions should focus on the development and implementation of interventions that provide protective buffers such as increased social support. Knowledge Translation Spirituality is a relatively stable trait. High levels of spirituality can serve as a protective buffer from negative mental health outcomes. Caregivers with low levels of spirituality may be at risk for greater levels of burden, anxiety, and stress. PMID:23615145

  3. Primary hepatic solitary fibrous tumor with histologically benign and malignant areas.

    PubMed

    Silvanto, Anna; Karanjia, Nariman D; Bagwan, Izhar N

    2015-12-01

    Extrapleural solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm, presenting most commonly in the intrathoracic sites but which has been reported at numerous extrathoracic locations. The majority of intra-thoracic SFTs are benign, but 10%-15% behave aggressively. We report a case of primary hepatic SFT with histologically benign and malignant areas. A 65-year-old man underwent an abdominal CT scan following a cerebrovascular accident, which demonstrated a sharply demarcated large liver mass with a heterogenous enhancing area and occupying most of the left lobe of the liver. Histological examination following a hemihepatectomy showed an SFT with morphological patterns ranging from benign to malignant areas, including pleomorphism, increased cellularity, herringbone pattern, necrosis and a raised mitotic count. On review of the literature, only an occasional case report with malignant areas in a hepatic SFT was identified. This case highlights that SFT should be included in the differential diagnosis of a hepatic spindle cell lesion, and that on rare occasions, malignant areas can occur in this already uncommon neoplasm.

  4. Clinical Outcomes of Surgical Treatments for Primary Malignant Bone Tumors Arising in the Acetabulum

    PubMed Central

    Fujiwara, Tomohiro; Ogura, Koichi; Kobayashi, Eisuke; Tanzawa, Yoshikazu; Nakatani, Fumihiko; Chuman, Hirokazu; Kawai, Akira

    2015-01-01

    The functional and oncologic results of eighteen patients with primary malignant periacetabular tumors were reviewed to determine the impact of surgical treatment. The reconstruction procedures were endoprosthesis (11), hip transposition (4), iliofemoral arthrodesis (2), and frozen bone autograft (1). After a mean follow-up of 62 months, 13 patients were alive and 5 had died of their disease; the 5-year overall survival rate was 67.2%. The corresponding mean MSTS scores of patients with endoprosthesis (11) and other reconstructions (7) were 42% and 55% (49%, 68%, and 50%), respectively. Overall, postoperative complications including deep infection or dislocation markedly worsened the functional outcome. Iliofemoral arthrodesis provided better function than the other procedures, whereas endoprosthetic reconstruction demonstrated poor functional outcome except for patients who were reconstructed with the adequate soft tissue coverage. Avoiding postoperative complications is highly important for achieving better function, suggesting that surgical procedures with adequate soft tissue coverage or without the massive use of nonbiological materials are preferable. Appropriate selection of the reconstructive procedures for individual patients, considering the amount of remaining bone and soft tissues, would lead to better clinical outcomes. PMID:26451129

  5. Biomodulation of capecitabine by paclitaxel and carboplatin in advanced solid tumors and adenocarcinoma of unknown primary.

    PubMed

    Mikhail, Sameh; Lustberg, Maryam B; Ruppert, Amy S; Mortazavi, Amir; Monk, Paul; Kleiber, Barbara; Villalona-Calero, Miguel; Bekaii-Saab, Tanios

    2015-11-01

    Paclitaxel and carboplatin upregulate thymidine phosphorylase and thus may provide synergistic antitumor activity in combination with capecitabine (CTX). We, therefore, performed a phase I/II study of CTX. In the phase I study, patients with advanced solid tumors received carboplatin on day 1, paclitaxel on days 1, 8, 15 and capecitabine orally twice a day on days 8-21, every 4 weeks. Phase II patients with advanced adenocarcinoma of unknown primary (ACUP) were treated at the maximal tolerable dose. The phase I study enrolled 29 patients evaluable for dose limiting toxicity. The recommended phase II dose was capecitabine 750 mg/m(2) bid, paclitaxel 60 mg/m(2)/week and carboplatin AUC of 6. There were 9 confirmed responses, 5 partial responses and disease stabilization >3 months in 14 patients. The phase II study was prematurely terminated at 25 patients due to cessation of funding. The objective response rate was 32 % (95 % CI 0.15-0.54), the median progression-free survival 5.5 months (95 % CI 2.8-10.8 months) and the median overall survival 10.8 months (95 % CI 6.0-32.0 months). CTX demonstrated acceptable tolerability and antitumor activity. At the recommended dose level in patients with ACUP, this regimen showed encouraging preliminary activity.

  6. [Intraoperative extracorporeal irradiation and replantation in local treatment of primary malignant bone tumors].

    PubMed

    Sabo, D; Bernd, L; Buchner, M; Treiber, M; Wannenmacher, M; Ewerbeck, V; Parsch, D

    2003-11-01

    In 13 patients with primary malignant bone tumors (10 Ewing's sarcoma, 1 parosteal osteosarcoma, 1 adamantinoma recurrence, and 1 MFH) local therapy was performed as intraoperative extracorporeal irradiation and replantation (IEIR) of the involved bone segment (5 tibia, 2 femur, and 6 pelvis). Of the 13 patients (69%), 9 are alive at the time of the follow-up (5 CDF, 4 AWM(treated)) and 4 patients died of disease (DOD). Up to now during the follow-up of 32 months (6-57), no local recurrence was observed in the replanted bone segments. The complication rate was very high (18 complications in 11 of the 13 patients, including 6 cases with complication V degrees according to Ruggieri with loss of the reconstruction). The typical complication is severe local infection necessitating removal of the replant. In cases of mechanical failure, the replanted segment could mostly be preserved by surgical revision and autologous bone grafting. If serious complications can be managed or avoided, functional results can be achieved. IEIR must be seen as an extraordinary reconstruction procedure in cases where established procedures such as endoprosthesis, biological reconstructions, or rotationplasties cannot be used or are refused by the patient. PMID:14615850

  7. Tumor suppressor genes FHIT and WWOX are deleted in primary effusion lymphoma (PEL) cell lines

    PubMed Central

    Roy, Debasmita; Sin, Sang-Hoon; Damania, Blossom

    2011-01-01

    Primary effusion lymphoma (PEL) is a diffuse-large B-cell lymphoma with poor prognosis. One hundred percent of PELs carry the genome of Kaposi sarcoma–associated herpesvirus and a majority are coinfected with Epstein-Barr virus (EBV). We profiled genomic aberrations in PEL cells using the Affymetrix 6.0 SNP array. This identified for the first time individual genes that are altered in PEL cells. Eleven of 13 samples (85%) were deleted for the fragile site tumor suppressors WWOX and FHIT. Alterations were also observed in the DERL1, ETV1, RASA4, TPK1, TRIM56, and VPS41 genes, which are yet to be characterized for their roles in cancer. Coinfection with EBV was associated with significantly fewer gross genomic aberrations, and PEL could be segregated into EBV-positive and EBV-negative clusters on the basis of host chromosome alterations. This suggests a model in which both host genetic aberrations and the 2 viruses contribute to the PEL phenotype. PMID:21685375

  8. The 5p12 breast cancer susceptibility locus affects MRPS30 expression in estrogen-receptor positive tumors

    PubMed Central

    Quigley, David A.; Fiorito, Elisa; Nord, Silje; Van Loo, Peter; Alnæs, Grethe Grenaker; Fleischer, Thomas; Tost, Jorg; Vollan, Hans Kristian Moen; Tramm, Trine; Overgaard, Jens; Bukholm, Ida R; Hurtado, Antoni; Balmain, Allan; Børresen-Dale, Anne-Lise; Kristensen, Vessela

    2014-01-01

    Genome-wide association studies have identified numerous loci linked to breast cancer susceptibility, but the mechanism by which variations at these loci influence susceptibility is usually unknown. Some variants are only associated with particular clinical subtypes of breast cancer. Understanding how and why these variants influence subtype-specific cancer risk contributes to our understanding of cancer etiology. We conducted a genome-wide expression Quantitative Trait Locus (eQTL) study in a discovery set of 287 breast tumors and 97 normal mammary tissue samples and a replication set of 235 breast tumors. We found that the risk-associated allele of rs7716600 in the 5p12 estrogen receptor-positive (ER-positive) susceptibility locus was associated with elevated expression of the nearby gene MRPS30 exclusively in ER-positive tumors. We replicated this finding in 235 independent tumors. Further, we showed the rs7716600 risk genotype was associated with decreased MRPS30 promoter methylation exclusively in ER-positive breast tumors. In vitro studies in MCF-7 cells carrying the protective genotype showed that estrogen stimulation decreased MRPS30 promoter chromatin availability and mRNA levels. In contrast, in 600MPE cells carrying the risk genotype, estrogen increased MRPS30 expression and did not affect promoter availability. Our data suggest the 5p12 risk allele affects MRPS30 expression in estrogen-responsive tumor cells after tumor initiation by a mechanism affecting chromatin availability. These studies emphasize that the genetic architecture of breast cancer is context-specific, and integrated analysis of gene expression and chromatin remodeling in normal and tumor tissues will be required to explain the mechanisms of risk alleles. PMID:24388359

  9. Existential Well-Being and Meaning Making in the Context of Primary Brain Tumor: Conceptualization and Implications for Intervention

    PubMed Central

    Ownsworth, Tamara; Nash, Kimberley

    2015-01-01

    When faced with a significant threat to life, people tend to reflect more intensely upon existential issues, such as the meaning and purpose of one’s life. Brain tumor poses a serious threat to a person’s life, functioning, and personhood. Although recognized as an important dimension of quality of life, existential well-being is not well understood and reflects an overlooked area of support for people with brain tumor. This perspective article reviews the historical underpinnings of the concept of existential well-being and integrates this discussion with theoretical perspectives and research on meaning making and psychological adjustment to primary brain tumor. We then provide an overview of psychosocial support interventions for people with brain tumor and describe the findings of a recently published psychotherapy trial targeting existential well-being. Overall, this article highlights the importance of assessing the existential support needs of people with primary brain tumor and their family members, and providing different avenues of support to facilitate the meaning-making process across the illness trajectory. PMID:25964883

  10. The inhibition of Akt-Pdpk1 interaction efficiently suppresses the growth of murine primary liver tumor cells.

    PubMed

    Mäemets-Allas, Kristina; Belitškin, Denis; Jaks, Viljar

    2016-05-20

    The lack of primary liver tumor cells has hampered testing of potential chemotherapeutic agents in vitro. To overcome this issue we developed a primary mouse liver tumor cell line K07074. The K07074 cells were immortal, exhibited a biliary phenotype, formed colonies in soft agar and displayed an increase in Hedgehog, Notch and Akt signaling. To study the effect of single and combined inhibition of the liver tumor-related pathways on the growth of K07074 cells we treated these with small-molecule antitumor agents. While the inhibition of Akt and Notch pathways strongly inhibited the growth of K07074 cells the inhibition of Wnt and Hedgehog pathways was less efficient in cell growth suppression. Interestingly, the inhibition of Akt pathway at the level of Akt-Pdpk1 interaction was sufficient to suppress the growth of tumor cells and no significant additive effect could be detected when co-treated with the inhibitors of Wnt, Hedgehog or Notch pathways. Only when suboptimal doses of Akt-Pdpk1 interaction inhibitor NSC156529 were used an additive effect with Notch inhibition was seen. We conclude that the Akt pathway inhibitor NSC156529 is potentially useful as single treatment for liver tumors with hyperactivated Akt signaling. PMID:27103434

  11. Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

    SciTech Connect

    Gu Yongpeng; Li Hongzhen; Miki, Jun; Kim, Kee-Hong; Furusato, Bungo; Sesterhenn, Isabell A.; Chu, Wei-Sing; McLeod, David G.; Srivastava, Shiv; Ewing, Charles M.; Isaacs, William B.; Rhim, Johng S. . E-mail: jrhim@cpdr.org

    2006-04-01

    In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferative capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents.

  12. Association between vascular-poor area of primary tumors and epidermal growth factor receptor gene status in advanced lung adenocarcinoma.

    PubMed

    Togashi, Yosuke; Masago, Katsuhiro; Kubo, Takeshi; Fujimoto, Daichi; Sakamori, Yuichi; Nagai, Hiroki; Kim, Young Hak; Togashi, Kaori; Mishima, Michiaki

    2012-12-01

    Mutation of the epidermal growth factor receptor gene (EGFR mutation) is a very important marker in the treatment for non-small cell lung cancer. Since signaling from this receptor induces tumor-associated angiogenesis, we hypothesized that lung cancers with EGFR mutations tend to develop locally with increased angiogenesis. Thus, the association between vascular-poor area of primary tumors and EGFR status was retrospectively investigated in advanced lung adenocarcinomas. To assess vascular-poor area, contrast-enhanced computed tomography scans taken before initial treatment for lung cancer were analyzed, together with primary tumor location (peripheral or central) and size. We analyzed 178 patients with advanced lung adenocarcinoma. EGFR mutations were detected in 95 of the 178 patients (53.4 %). EGFR mutation was found to be significantly related to women (P = 0.0070), never-smokers (P < 0.0001), and tumors without vascular-poor area (P < 0.0001). Based on a multivariate analysis, presence of EGFR mutations was independently associated with never-smokers (P = 0.0046), lack of vascular-poor area (P = 0.0001), and tumor size >30 mm (P = 0.0080). EGFR mutations were found in 41 of 51 never-smokers without vascular-poor area (80.4 %), 19 of 36 never-smokers with vascular-poor area (52.8 %), 19 of 37 current or former-smokers without vascular-poor area (51.4 %), and 16 of 54 current or former-smokers with vascular-poor area (29.6 %). This study showed an association between vascular-poor area of primary tumors and EGFR status. As a consequence, evaluation using a combination of smoking status and vascular-poor area allows us to predict presence of EGFR mutations at a high frequency.

  13. Addition of Anti-Angiogenetic Therapy with Bevacizumab to Chemo- and Radiotherapy for Leptomeningeal Metastases in Primary Brain Tumors

    PubMed Central

    Burger, Michael C.; Zeiner, Pia S.; Jahnke, Kolja; Wagner, Marlies; Mittelbronn, Michel; Steinbach, Joachim P.

    2016-01-01

    Leptomeningeal dissemination of a primary brain tumor is a condition which is challenging to treat, as it often occurs in rather late disease stages in highly pretreated patients. Its prognosis is dismal and there is still no accepted standard of care. We report here a good clinical effect with a partial response in three out of nine patients and a stable disease with improvement on symptoms in two more patients following systemic anti-angiogenic treatment with bevacizumab (BEV) alone or in combination with chemo- and/or radiotherapy in a series of patients with leptomeningeal dissemination from primary brain tumors (diffuse astrocytoma WHO°II, anaplastic astrocytoma WHO°III, anaplastic oligodendroglioma WHO°III, primitive neuroectodermal tumor and glioblastoma, both WHO°IV). This translated into effective symptom control in five out of nine patients, but only moderate progression-free and overall survival times were reached. Partial responses as assessed by RANO criteria were observed in three patients (each one with anaplastic oligodendroglioma, primitive neuroectodermal tumor and glioblastoma). In these patients progression-free survival (PFS) intervals of 17, 10 and 20 weeks were achieved. In three patients (each one with diffuse astrocytoma, anaplastic astrocytoma and primitive neuroectodermal tumor) stable disease was observed with PFS of 13, 30 and 8 weeks. Another three patients (all with glioblastoma) were primary non-responders and deteriorated rapidly with PFS of 3 to 4 weeks. No severe adverse events were seen. These experiences suggest that the combination of BEV with more conventional therapy schemes with chemo- and/or radiotherapy may be a palliative treatment option for patients with leptomeningeal dissemination of brain tumors. PMID:27253224

  14. Differential Peripheral Blood Gene Expression Profile Based on Her2 Expression on Primary Tumors of Breast Cancer Patients

    PubMed Central

    Tudoran, Oana; Virtic, Oana; Balacescu, Loredana; Pop, Laura; Dragla, Flaviu; Eniu, Alexandru; Fetica, Bogdan; Balacescu, Ovidiu; Berindan-Neagoe, Ioana

    2014-01-01

    Breast cancer prognosis and treatment is highly dependent on the molecular features of the primary tumors. These tumors release specific molecules into the environment that trigger characteristic responses into the circulatory cells. In this study we investigated the expression pattern of 84 genes known to be involved in breast cancer signaling in the peripheral blood of breast cancer patients with ER-, PR- primary tumors. The patients were grouped according to Her2 expression on the primary tumors in Her2+ and Her2- cohorts. Transcriptional analysis revealed 15 genes to be differentially expressed between the two groups highlighting that Her2 signaling in primary tumors could be associated with specific blood gene expression. We found CCNA1 to be up-regulated, while ERBB2, RASSF1, CDH1, MKI67, GATA3, GLI1, SFN, PTGS2, JUN, NOTCH1, CTNNB1, KRT8, SRC, and HIC1 genes were down-regulated in the blood of triple negative breast cancer patients compared to Her2+ cohort. IPA network analysis predicts that the identified genes are interconnected and regulate each other. These genes code for cell cycle regulators, cell adhesion molecules, transcription factors or signal transducers that modulate immune signaling, several genes being also associated with cancer progression and treatment response. These results indicate an altered immune signaling in the peripheral blood of triple negative breast cancer patients. The involvement of the immune system is necessary in favorable treatment response, therefore these results could explain the low response rates observed for triple negative breast cancer patients. PMID:25068292

  15. Primary tumor regression speed after radiotherapy and its prognostic significance in nasopharyngeal carcinoma: a retrospective study

    PubMed Central

    2014-01-01

    Background To observe the primary tumor (PT) regression speed after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) and evaluate its prognostic significance. Methods One hundred and eighty-eight consecutive newly diagnosed NPC patients were reviewed retrospectively. All patients underwent magnetic resonance imaging and fiberscope examination of the nasopharynx before RT, during RT when the accumulated dose was 46–50 Gy, at the end of RT, and 3–4 months after RT. Results Of 188 patients, 40.4% had complete response of PT (CRPT), 44.7% had partial response of PT (PRPT), and 14.9% had stable disease of PT (SDPT) at the end of RT. The 5-year overall survival (OS) rates for patients with CRPT, PRPT, and SDPT at the end of RT were 84.0%, 70.7%, and 44.3%, respectively (P < 0.001, hazard ratio [HR] = 2.177, 95% confidence interval [CI] = 1.480-3.202). The 5-year failure-free survival (FFS) and distant metastasis-free survival (DMFS) rates also differed significantly (87.8% vs. 74.3% vs. 52.7%, P = 0.001, HR = 2.148, 95% CI, 1.384-3.333; 91.7% vs. 84.7% vs. 66.1%, P = 0.004, HR = 2.252, 95% CI = 1.296-3.912). The 5-year local relapse–free survival (LRFS) rates were not significantly different (95.8% vs. 86.0% vs. 81.8%, P = 0.137, HR = 1.975, 95% CI, 0.976-3.995). By multivariate analyses, the PT regression speed at the end of RT was the only independent prognostic factor of OS, FFS, and DMFS (P < 0.001, P = 0.001, and P = 0.004, respectively). The 5-year FFS rates for patients with CRPT during RT and CRPT only at the end of RT were 80.2% and 97.1%, respectively (P = 0.033). For patients with persistent PT at the end of RT, the 5-year LRFS rates of patients without and with boost irradiation were 87.1% and 84.6%, respectively (P = 0.812). Conclusions PT regression speed at the end of RT was an independent prognostic factor of OS, FFS, and DMFS in NPC patients. Immediate strengthening treatment may be provided to patients with poor

  16. Surgical treatment of double primary liver cancer: An observational study for a rare type of tumor.

    PubMed

    Li, Aijun; Ma, Senlin; Pawlik, Timothy; Wu, Bin; Yang, Xiaoyu; Cui, Longjiu; Wu, Mengchao

    2016-08-01

    Double primary liver cancer (DPLC) is a special type of clinical situation. As such, a detailed analysis of the surgical management and prognosis of patients with DPLC is lacking. The objective of the current study was to define the management and outcome of patients undergoing surgery for DPLC at a major hepatobiliary center.A total of 87 patients treated by surgical resection at the Eastern Hepatobiliary Surgery Hospital from January 1st, 2007 to October 31st, 2013 who had DPLC demonstrated by final pathological diagnosis were identified. Among these, 50 patients had complete clinical and prognostic data. Demographic and tumor characteristics as well as the prognosis were analyzed.The proportion of hepatitis B surface antigen (HBsAg) (+) and hepatitis B virus e antigen (HBeAg) (+), HBsAg (+), and HBeAg (-) hepatocirrhosis in all patients was 21.84%, 67.82%, and 63.22%, respectively. Incidental findings accounted for 58.62% of patients; among those who had symptoms, the main symptom was abdominal pain (31.03%). Nonanatomic wedge resection was the main operative approach (62.07%). Postoperatively, the main complications included seroperitoneum (11.49%), hypoproteinemia (10.34%), and pleural effusion (8.05%). Factors associated with disease-free survival (DFS) included intrahepatic cholangiocarcinoma (ICC) tumor size (P = 0.002) and use of postoperative prophylactic transcatheter arterial chemoembolization (TACE) treatment (P = 0.015). Meanwhile, hepatocellular carcinoma (HCC) size (P = 0.045), ICC size (P < 0.001), and liver function (including aspartate aminotransferase [P = 0.001] and r-glutamyl transferase [P < 0.001]) were associated with overall survival (OS).Hepatitis B virus (HBV)-related hepatitis or cirrhosis is also an important factor in the pathogenesis of DPLC and surgical treatment is safe for it with low complication rates. In addition, it is effective to prolong DFS that DPLC patients undergo postoperative prophylactic TACE

  17. Cell surface fucosylation does not affect development of colon tumors in mice with germline Smad3 mutation

    PubMed Central

    Domino, Steven E.; Karnak, David M.; Hurd, Elizabeth A.

    2006-01-01

    Background/Aims: Neoplasia-related alterations in cell surface α(1,2)fucosylated glycans have been reported in multiple tumors including colon, pancreas, endometrium, cervix, bladder, lung, and choriocarcinoma. Spontaneous colorectal tumors from mice with a germline null mutation of transforming growth factor-β signaling gene Smad3 (Madh3) were tested for α(1,2)fucosylated glycan expression. Methods: Ulex Europaeus Agglutinin-I lectin staining, fucosyltransferase gene northern blot analysis, and a cross of mutant mice with Fut2 and Smad3 germline mutations were performed. Results: Spontaneous colorectal tumors from Smad3 (-/-) homozygous null mice were found to express α(1,2)fucosylated glycans in an abnormal pattern compared to adjacent nonneoplastic colon. Northern blot analysis of α(1,2)fucosyltransferase genes Fut1 and Fut2 revealed that Fut2, but not Fut1, steady-state mRNA levels were significantly increased in tumors relative to adjacent normal colonic mucosa. Mutant mice with a Fut2-inactivating germline mutation were crossed with Smad3 targeted mice. In Smad3 (-/-)/Fut2 (-/-) double knock-out mice, UEA-I lectin staining was eliminated from colon and colon tumors, however, the number and size of tumors present by 24 weeks of age did not vary regardless of the Fut2 genotype. Conclusions: In this model of colorectal cancer, cell surface α(1,2)fucosylation does not affect development of colon tumors. PMID:17264540

  18. Hardness, elasticity, and ultrastructure of bonded sound and caries-affected primary tooth dentin.

    PubMed

    Hosoya, Y; Tay, F R

    2007-04-01

    Biomechanical properties of bonded dentin are important factors for resin restoration. We evaluated the hardness and elastic modulus of bonded sound and caries-affected primary tooth dentin using a one-step adhesive system, and observed the microstructure of the bonded interface. Six sound and six carious primary teeth were used. For sound teeth, flat occlusal dentin surfaces were prepared with a water-cooled high-speed diamond bur. For carious teeth, infected dentin was stained with a caries detector and removed with a water-cooled low-speed round steel bur and hand instruments. The prepared dentin was bonded with One-Up Bond F Plus (Tokuyama Dental Co., Tokyo, Japan). The resin-dentin interface and dentin beneath the interface were measured with a nano-indentation tester and observed with SEM and TEM. For both the carious and sound teeth, there was no significant difference between the hardness of the interfacial dentin and dentin 10-80 microm beneath the interface. However, the Young's modulus of the interfacial dentin was significantly lower than the dentin 40-80 microm (carious teeth) or 50-80 microm (sound teeth) beneath the interface. Both the hardness and Young's modulus of the interfacial dentin were not significantly different between the carious and sound teeth. Compared to the sound dentin, the hybrid layer on the caries-affected dentin was thicker and exhibited more complicated morphologic features. The thickness of the hybrid layers was generally less than 1 microm.

  19. The efficacy of nuclease-resistant Chol-siRNA in primary breast tumors following complexation with PLL-PEG(5K).

    PubMed

    Ambardekar, Vishakha V; Wakaskar, Rajesh R; Sharma, Bhawna; Bowman, Joy; Vayaboury, Willy; Singh, Rakesh K; Vetro, Joseph A

    2013-07-01

    Modifying the sense strand of nuclease-resistant siRNA with 3'-cholesterol (Chol-*siRNA) increases mRNA suppression after i.v. administration but with relatively low efficacy. We previously found evidence in vitro that suggests complexation of Chol-siRNA with PLL-PEG(5K), a block copolymer of poly-l-lysine and 5 kDa polyethylene glycol, may increase the efficacy of Chol-siRNA in vivo in a PLL block length-dependent manner. In this study, the extent that polyplexes of PLL10-PEG(5K), PLL30-PEG(5K), and PLL50-PEG(5K) protect complexed Chol-siRNA in high concentrations of murine serum and affect the activity of Chol-*siRNA in murine 4T1 breast tumor epithelial cells in vitro and in primary orthotopic tumors of 4T1 was compared. PLL-PEG(5K) required 3'-Chol to protect full-length siRNA from nuclease degradation in 90% (v/v) murine serum and protection was increased by increasing PLL block length and nuclease resistance of Chol-siRNA. Polyplexes of Chol-*siLuc suppressed stably expressed luciferase in 4T1-Luc cells to different levels in vitro where PLL30 > PLL50 > PLL10. In contrast, only polyplexes of Chol-*siLuc and PLL30-PEG(5K) or PLL50-PEG(5K) suppressed high levels of luciferase in primary orthotopic tumors of 4T1-Luc after i.v. administration, whereas polyplexes of Chol-*siLuc and PLL10-PEG(5K), inactive Chol-*siCtrl polyplexes of PLL-PEG(5K), or Chol-*siLuc alone had no detectable activity. As a whole, these results indicate that polyplexes of PLL-PEG(5K) increase the efficacy of nuclease-resistant Chol-siRNA in primary breast tumors after i.v. administration in a PLL block length-dependent manner. Thus, complexation of Chol-siRNA with PLL-PEG(5K) may be a promising approach to increase the efficacy of Chol-siRNA in a wide range of primary tumors, metastases, and other tissues but likely requires a PLL block length that balances polymer-related adverse effects, Chol-siRNA bioavailability, and subsequent activity in the target cell.

  20. Fine-needle aspiration cytology of primary granulosa cell tumor of the adrenal gland: a case report.

    PubMed

    Hameed, A; Coleman, R L

    2000-02-01

    Extraovarian granulosa cell tumors are extremely rare. We report on a primary granulosa cell tumor of the adrenal gland. A 69-yr-old African-American female presented with a 1-yr history of irregular uterine bleeding and a palpable right abdominal mass. CT scan showed a 9.0-cm suprarenal mass as well as an enlarged uterus. CT-guided fine-needle aspiration (FNA) cytology of the adrenal mass was interpreted as a malignant neoplasm. She underwent exploratory laparotomy, right nephrectomy, and hysterectomy with bilateral salpingo-oophorectomy. The gross, histologic, and immunohistochemical findings of the adrenal mass were characteristic of a granulosa cell tumor. The uterus contained multiple leiomyomas. The endometrium showed simple hyperplasia. Both fallopian tubes and ovaries showed no pathologic abnormality. There was no evidence of tumor elsewhere. Although rare, extraovarian granulosa cell tumor should be considered in the differential diagnosis of adrenal tumors in women showing the FNA features described herein, especially when there is evidence of excessive estrogen production. Diagn. Cytopathol. 2000;22:107-109.

  1. Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma.

    PubMed

    Hung, Noelyn A; Eiholzer, Ramona A; Kirs, Stenar; Zhou, Jean; Ward-Hartstonge, Kirsten; Wiles, Anna K; Frampton, Chris M; Taha, Ahmad; Royds, Janice A; Slatter, Tania L

    2016-03-01

    Telomere maintenance is a hallmark of cancer and likely to be targeted in future treatments. In glioblastoma established methods of identifying telomerase and alternative lengthening of telomeres leave a significant proportion of tumors with no defined telomere maintenance mechanism. This study investigated the composition of these tumors using RNA-Seq. Glioblastomas with an indeterminate telomere maintenance mechanism had an increased immune signature compared with alternative lengthening of telomeres and telomerase-positive tumors. Immunohistochemistry for CD163 confirmed that the majority (80%) of tumors with an indeterminate telomere maintenance mechanism had a high presence of tumor-associated macrophages. The RNA-Seq and immunostaining data separated tumors with no defined telomere maintenance mechanism into three subgroups: alternative lengthening of telomeres like tumors with a high presence of tumor-associated macrophages and telomerase like tumors with a high presence of tumor-associated macrophages. The third subgroup had no increase in tumor-associated macrophages and may represent a distinct category. The presence of tumor-associated macrophages conferred a worse prognosis with reduced patient survival times (alternative lengthening of telomeres with and without macrophages P=0.0004, and telomerase with and without macrophages P=0.013). The immune signatures obtained from RNA-Seq were significantly different between telomere maintenance mechanisms. Alternative lengthening of telomeres like tumors with macrophages had increased expression of interferon-induced proteins with tetratricopeptide repeats (IFIT1-3). Telomerase-positive tumors with macrophages had increased expression of macrophage receptor with collagenous structure (MARCO), CXCL12 and sushi-repeat containing protein x-linked 2 (SRPX2). Telomerase-positive tumors with macrophages were also associated with a reduced frequency of total/near total resections (44% vs >76% for all other subtypes

  2. Nucleolin antagonist triggers autophagic cell death in human glioblastoma primary cells and decreased in vivo tumor growth in orthotopic brain tumor model.

    PubMed

    Benedetti, Elisabetta; Antonosante, Andrea; d'Angelo, Michele; Cristiano, Loredana; Galzio, Renato; Destouches, Damien; Florio, Tiziana Marilena; Dhez, Anne Chloé; Astarita, Carlo; Cinque, Benedetta; Fidoamore, Alessia; Rosati, Floriana; Cifone, Maria Grazia; Ippoliti, Rodolfo; Giordano, Antonio; Courty, José; Cimini, Annamaria

    2015-12-01

    Nucleolin (NCL) is highly expressed in several types of cancer and represents an interesting therapeutic target. It is expressed at the plasma membrane of tumor cells, a property which is being used as a marker for several human cancer including glioblastoma. In this study we investigated targeting NCL as a new therapeutic strategy for the treatment of this pathology. To explore this possibility, we studied the effect of an antagonist of NCL, the multivalent pseudopeptide N6L using primary culture of human glioblastoma cells. In this system, N6L inhibits cell growth with different sensitivity depending to NCL localization. Cell cycle analysis indicated that N6L-induced growth reduction was due to a block of the G1/S transition with down-regulation of the expression of cyclin D1 and B2. By monitoring autophagy markers such as p62 and LC3II, we demonstrate that autophagy is enhanced after N6L treatment. In addition, N6L-treatment of mice bearing tumor decreased in vivo tumor growth in orthotopic brain tumor model and increase mice survival. The results obtained indicated an anti-proliferative and pro-autophagic effect of N6L and point towards its possible use as adjuvant agent to the standard therapeutic protocols presently utilized for glioblastoma.

  3. Primary brain tumors treated with steroids and radiotherapy: Low CD4 counts and risk of infection

    SciTech Connect

    Hughes, Michael A.; Parisi, Michele; Grossman, Stuart; Kleinberg, Lawrence . E-mail: kleinla@jhmi.edu

    2005-08-01

    Purpose: Patients with primary brain tumors are often treated with high doses of corticosteroids for prolonged periods to reduce intracranial swelling and alleviate symptoms such as headaches. This treatment may lead to immunosuppression, placing the patient at risk of life-threatening opportunistic infections, such as Pneumocystis carinii pneumonia. The risk of contracting some types of infection may be reduced with prophylactic antibiotics. The purpose of this study was to determine the occurrence of low CD4 counts and whether monitoring CD4 counts during and after radiotherapy (RT) is warranted. Methods and Materials: CD4 counts were measured during RT in 70 of 76 consecutive patients with newly diagnosed Grade III and IV astrocytoma and anaplastic oligodendroglioma treated with corticosteroids and seen at the Johns Hopkins Hospital. Weekly CD4 measurements were taken in the most recent 25 patients. Prophylactic trimethoprim-sulfamethoxazole (160 mg/800 mg p.o. every Monday, Wednesday, and Friday) or dapsone (100 mg p.o. daily) in those with sulfa allergy was prescribed only if patients developed a low CD4 count. Carmustine chemotherapy wafers were placed at surgery in 23% of patients, evenly distributed between the groups. No patient received any other chemotherapy concurrent with RT. Results: CD4 counts decreased to <200/mm{sup 3} in 17 (24%) of 70 patients. For the 25 patients with weekly CD4 counts, all CD4 counts were >450/mm{sup 3} before RT, but 6 (24%) of 25 fell to <200/mm{sup 3} during RT. Patients with counts <200/mm{sup 3} were significantly more likely to be hospitalized (41% vs. 9%, p <0.01) and be hospitalized for infection (23% vs. 4%, p <0.05) during RT. Overall survival was not significantly different between the groups. All patients with low CD4 counts were treated with prophylactic antibiotics, and no patient developed Pneumocystis carinii pneumonia. No patients developed a serious adverse reaction to antibiotic therapy. The mean dose of

  4. Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture.

    PubMed

    Guo, H Y; Herrera, H; Groce, A; Hoffman, R M

    1993-06-01

    Methionine dependence is a metabolic defect that occurs in many human tumor cell lines but not normal in unestablished cell strains. Methionine-dependent tumor cell lines are unable to proliferate and arrest in the late S/G2 phase of the cell cycle when methionine is replaced by its immediate precursor homocysteine in the culture medium (MET-HCY+ medium). However, it is not known whether methionine dependence occurs in fresh patient tumors as it does in cell lines. In order to determine whether methionine dependence occurs in fresh patient tumors as well as whether methionine dependence occurs in fresh patient tumors as well as in cell lines we took advantage of the technique of sponge-gel-supported histoculture to grow tumors directly from surgery. We then measured nuclear DNA content by image analysis to determine the cell cycle position in MET-HCY+ compared to MET+HCY- medium in 21 human patient tumors. Human tumor cell lines found to be methionine dependent by cell count were used as positive controls and were found to have marked reduction of cells in G1 compared to total cells in the cell cycle in MET-HCY+ medium with respect to the G1: total cell ratio in MET+HCY- medium. Therefore late cell cycle arrest was used as a marker of methionine dependence for histocultured patient tumors. We found that 5 human tumors of 21, including tumors of the colon, breast, ovary, prostate, and a melanoma, were methionine dependent based on cell cycle analysis. These data on fresh human tumors indicate that methionine dependence may frequently occur in the cancer patient population. Implications for potential therapy based on methionine dependence are discussed. PMID:8495409

  5. Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma

    PubMed Central

    Meves, Alexander; Nikolova, Ekaterina; Heim, Joel B.; Squirewell, Edwin J.; Cappel, Mark A.; Pittelkow, Mark R.; Otley, Clark C.; Behrendt, Nille; Saunte, Ditte M.; Lock-Andersen, Jorgen; Schenck, Louis A.; Weaver, Amy L.; Suman, Vera J.

    2015-01-01

    Purpose Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma. Patients and Methods Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. Results ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk). Conclusion The addition of cell adhesion–linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis. PMID:26150443

  6. How Are Assistant Heads Affecting Primary School Management and How Do Their Opinions, Attitudes and Beliefs Affect Their Work?

    ERIC Educational Resources Information Center

    Watson, Keith

    2005-01-01

    This article examines the emergence of assistant heads onto the landscape of primary school leadership. Through the use of job descriptions, questionnaires, interviews and a case study, the functions that assistant heads are performing in primary schools is examined and their opinions, attitudes and beliefs about their work are considered. The…

  7. Cross-sectional Imaging Features of Primary Retroperitoneal Tumors and Their Subsequent Treatment.

    PubMed

    Acar, Turker; Harman, Mustafa; Guneyli, Serkan; Gemici, Kazim; Efe, Duran; Guler, Ibrahim; Yildiz, Melda

    2015-01-01

    Basically malignant tumors in the retroperitoneal region arise from a heterogeneous group of tissues: mesodermal, neurogenic, germ cell, and lymphoid. Although rare, benign tumors and cystic masses can be also encountered in retroperitoneal space. Developments in computed tomography (CT) and magnetic resonance imaging (MRI) have contributed to both diagnosis and staging of the retroperitoneal tumors. High spatial resolution and superiority in calcification make CT indispensable; on the other hand, MRI has a better soft-tissue contrast resolution which is essential for the assessment of vascular invasion and tissue characterization. The aim of this article is to review the CT and MRI features of retroperitoneal tumors and their subsequent management. PMID:25973288

  8. Tumor

    MedlinePlus

    ... plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by viruses are: Cervical cancer (human papillomavirus) Hepatocellular carcinoma (hepatitis B and hepatitis C ...

  9. A primary screen of the bovine genome for quantitative trait loci affecting carcass and growth traits.

    PubMed

    Stone, R T; Keele, J W; Shackelford, S D; Kappes, S M; Koohmaraie, M

    1999-06-01

    A primary genomic screen for quantitative trait loci (QTL) affecting carcass and growth traits was performed by genotyping 238 microsatellite markers on 185 out of 300 total progeny from a Bos indicus x Bos taurus sire mated to Bos taurus cows. The following traits were analyzed for QTL effects: birth weight (BWT), weaning weight (WW), yearling weight (YW), hot carcass weight (HCW), dressing percentage (DP), fat thickness (FT), marbling score (MAR), longissimus muscle area (LMA), rib bone (RibB), rib fat (RibF), and rib muscle (RibM), and the predicted whole carcass traits, retail product yield (RPYD), fat trim yield (FATYD), bone yield (BOYD), retail product weight (RPWT), fat weight (FATWT), and bone weight (BOWT). Data were analyzed by generating an F-statistic profile computed at 1-cM intervals for each chromosome by the regression of phenotype on the conditional probability of receiving the Brahman allele from the sire. There was compelling evidence for a QTL allele of Brahman origin affecting an increase in RibB and a decrease in DP on chromosome 5 (BTA5). Putative QTL at or just below the threshold for genome-wide significance were as follows: an increase in RPYD and component traits on BTA2 and BTA13, an increase in LMA on BTA14, and an increase in BWT on BTA1. Results provided represent a portion of our efforts to identify and characterize QTL affecting carcass and growth traits. PMID:10375215

  10. A primary screen of the bovine genome for quantitative trait loci affecting carcass and growth traits.

    PubMed

    Stone, R T; Keele, J W; Shackelford, S D; Kappes, S M; Koohmaraie, M

    1999-06-01

    A primary genomic screen for quantitative trait loci (QTL) affecting carcass and growth traits was performed by genotyping 238 microsatellite markers on 185 out of 300 total progeny from a Bos indicus x Bos taurus sire mated to Bos taurus cows. The following traits were analyzed for QTL effects: birth weight (BWT), weaning weight (WW), yearling weight (YW), hot carcass weight (HCW), dressing percentage (DP), fat thickness (FT), marbling score (MAR), longissimus muscle area (LMA), rib bone (RibB), rib fat (RibF), and rib muscle (RibM), and the predicted whole carcass traits, retail product yield (RPYD), fat trim yield (FATYD), bone yield (BOYD), retail product weight (RPWT), fat weight (FATWT), and bone weight (BOWT). Data were analyzed by generating an F-statistic profile computed at 1-cM intervals for each chromosome by the regression of phenotype on the conditional probability of receiving the Brahman allele from the sire. There was compelling evidence for a QTL allele of Brahman origin affecting an increase in RibB and a decrease in DP on chromosome 5 (BTA5). Putative QTL at or just below the threshold for genome-wide significance were as follows: an increase in RPYD and component traits on BTA2 and BTA13, an increase in LMA on BTA14, and an increase in BWT on BTA1. Results provided represent a portion of our efforts to identify and characterize QTL affecting carcass and growth traits.

  11. Primary spinal intradural extraskeletal Ewing sarcoma mimicking a giant nerve sheath tumor: case report and review of the literature

    PubMed Central

    Zhao, Mingfei; Zhang, Buyi; Liang, Feng; Zhang, Jianmin

    2014-01-01

    Primary intradural extraskeletal Ewing sarcoma is a very rare form of malignant neoplasm. Only few cases have been reported on the literature. Here, we report a case of a 14-year-old boy who had a chief complaint of pain and tingling in the right lower limb. The patient initially seemed to have a giant nerve sheath tumor but was eventually diagnosed with intradural extraskeletal Ewing sarcoma arising from the nerve roots of the cauda equine. The literature with regard to primary spinal intradural extraskeletal Ewing sarcoma is reviewed. PMID:25674292

  12. Primary osteoclast-like giant cell tumor of parotid gland: A rare extraskeletal presentation with diagnostic challenges

    PubMed Central

    Singh, Ritika; Zaheer, Sufian; Mandal, Ashish K

    2016-01-01

    Primary osteoclast-like giant cell tumor (OC-GCT) has been rarely described in extraskeletal sites. The diagnosis primarily hinges on the detection of giant cells. However, these giant cells are also seen in many giant cell lesions, thus creating diagnostic confusion and dilemma. Here, we describe a rare case of a 24-year-old male with primary extraskeletal, OC-GCT presenting as a swelling in the right parotid region and highlight its cytological, histological and immunohistochemical characteristics with diagnostic challenges. PMID:27601838

  13. Primary osteoclast-like giant cell tumor of parotid gland: A rare extraskeletal presentation with diagnostic challenges.

    PubMed

    Singh, Ritika; Zaheer, Sufian; Mandal, Ashish K

    2016-01-01

    Primary osteoclast-like giant cell tumor (OC-GCT) has been rarely described in extraskeletal sites. The diagnosis primarily hinges on the detection of giant cells. However, these giant cells are also seen in many giant cell lesions, thus creating diagnostic confusion and dilemma. Here, we describe a rare case of a 24-year-old male with primary extraskeletal, OC-GCT presenting as a swelling in the right parotid region and highlight its cytological, histological and immunohistochemical characteristics with diagnostic challenges. PMID:27601838

  14. Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease

    PubMed Central

    Olsson, Eleonor; Winter, Christof; George, Anthony; Chen, Yilun; Howlin, Jillian; Tang, Man-Hung Eric; Dahlgren, Malin; Schulz, Ralph; Grabau, Dorthe; van Westen, Danielle; Fernö, Mårten; Ingvar, Christian; Rose, Carsten; Bendahl, Pär-Ola; Rydén, Lisa; Borg, Åke; Gruvberger-Saal, Sofia K; Jernström, Helena; Saal, Lao H

    2015-01-01

    Metastatic breast cancer is usually diagnosed after becoming symptomatic, at which point it is rarely curable. Cell-free circulating tumor DNA (ctDNA) contains tumor-specific chromosomal rearrangements that may be interrogated in blood plasma. We evaluated serial monitoring of ctDNA for earlier detection of metastasis in a retrospective study of 20 patients diagnosed with primary breast cancer and long follow-up. Using an approach combining low-coverage whole-genome sequencing of primary tumors and quantification of tumor-specific rearrangements in plasma by droplet digital PCR, we identify for the first time that ctDNA monitoring is highly accurate for postsurgical discrimination between patients with (93%) and without (100%) eventual clinically detected recurrence. ctDNA-based detection preceded clinical detection of metastasis in 86% of patients with an average lead time of 11 months (range 0–37 months), whereas patients with long-term disease-free survival had undetectable ctDNA postoperatively. ctDNA quantity was predictive of poor survival. These findings establish the rationale for larger validation studies in early breast cancer to evaluate ctDNA as a monitoring tool for early metastasis detection, therapy modification, and to aid in avoidance of overtreatment. PMID:25987569

  15. Novel Genes Implicated in Embryonal, Alveolar, and Pleomorphic Rhabdomyosarcoma: A Cytogenetic and Molecular Analysis of Primary Tumors1

    PubMed Central

    Goldstein, Myriam; Meller, Isaac; Issakov, Josephine; Orr-Urtreger, Avi

    2006-01-01

    Abstract Rhabdomyosarcoma, the most common pediatric soft tissue sarcoma, likely results from deregulation of the skeletal myogenesis program. Although associations between PAX3, PAX7, FOXO1A, and RMS tumorigenesis are well recognized, the entire spectrum of genetic factors underlying RMS development and progression is unclear. Using a combined approach of spectral karyotyping, array-based comparative genomic hybridization (CGH), and expression analysis, we examined 10 primary RMS tumors, including embryonal, alveolar, and the rare adult pleomorphic variant, to explore the involvement of different genes and genetic pathways in RMS tumorigenesis. A complete karyotype established for each tumor revealed a high aneuploidy level, mostly tetraploidy, with double minutes and additional structural aberrations. Quantitative expression analysis detected the overexpression of the AURKA gene in all tumors tested, suggesting a role for this mitotic regulator in the aneuploidy and chromosomal instability observed in RMS. Array-based CGH analysis in primary RMS tumors detected copy number changes of genes involved in multiple genetic pathways, including transcription factors such as MYC-related gene from lung cancer and the cytoskeleton and cell adhesion-encoding genes laminin γ-2 and p21-activated kinase-1. Our data suggest the involvement of genes encoding cell adhesion, cytoskeletal signaling, and transcriptional and cell cycle components in RMS tumorigenesis. PMID:16790082

  16. Primary tumor prevalence has an impact on the constituent ratio of metastases to the jaw but not on metastatic sites

    PubMed Central

    Zhang, Fu-gui; Hua, Cheng-ge; Shen, Mo-lun; Tang, Xiu-fa

    2011-01-01

    This article provides an overview of metastases to jaws (MJ), mainly concerning the differences between American and Chinese patients, and exploring the relationship between the primary tumors' prevalence (PTP) and constituent ratio of MJ. Information concerning of 399 MJ cases in 215 papers, including one new case in our hospital, was subjected to statistic analysis. The main clinical features of MJ, such as constituent ratio of PTP and that of MJ, metastatic sites, treatments, and prognosis were summarized. Breast, lung, kidney, prostate and thyroid (in descending order) were the leading primary sites of MJ. Furthermore, the constituent ratio of MJ was found to be correlated with that of PTP in all subjects including American and Chinese subjects in our study. As to metastatic sites in the mandible, a specific “M” shaped pattern appeared regardless of the tumor type or constituent ratios of MJ were in all subjects. Almost all subjects received traditionally palliative treatments, and the prognosis was quite poor. The PTP had a significant impact on the constituent ratio of MJ. However, it was the properties of the microenvironment rather than characteristics or constituent ratios of tumor cells, that decided the metastatic sites in various tumor subjects. PMID:21789963

  17. Prognostic significance of tissue DF3 antigen and CA15-3 tumor marker in primary breast cancer.

    PubMed

    Dimas, C; Fragos-Plemenos, M; Gennatas, C; Kouskouni, E; Kondi-Paphitis, A

    2000-01-01

    The specific monoclonal antibody, DF3, for breast cancer and the corresponding tumor marker CA15-3 were evaluated in 108 patients with primary cancer of the breast. These antigens correlated poorly with the known prognostic parameters. Elevated CA15-3 serum values were associated with the cytoplasmic distribution of the DF3 antigen in the cell. The DF3 distribution pattern and the CA15-3 serum values had prognostic significance for disease-free interval.

  18. Metformin selectively affects human glioblastoma tumor-initiating cell viability: A role for metformin-induced inhibition of Akt.

    PubMed

    Würth, Roberto; Pattarozzi, Alessandra; Gatti, Monica; Bajetto, Adirano; Corsaro, Alessandro; Parodi, Alessia; Sirito, Rodolfo; Massollo, Michela; Marini, Cecilia; Zona, Gianluigi; Fenoglio, Daniela; Sambuceti, Gianmario; Filaci, Gilberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

    2013-01-01

    Cancer stem cell theory postulates that a small population of tumor-initiating cells is responsible for the development, progression and recurrence of several malignancies, including glioblastoma. In this perspective, tumor-initiating cells represent the most relevant target to obtain effective cancer treatment. Metformin, a first-line drug for type II diabetes, was reported to possess anticancer properties affecting the survival of cancer stem cells in breast cancer models. We report that metformin treatment reduced the proliferation rate of tumor-initiating cell-enriched cultures isolated from four human glioblastomas. Metformin also impairs tumor-initiating cell spherogenesis, indicating a direct effect on self-renewal mechanisms. Interestingly, analyzing by FACS the antiproliferative effects of metformin on CD133-expressing subpopulation, a component of glioblastoma cancer stem cells, a higher reduction of proliferation was observed as compared with CD133-negative cells, suggesting a certain degree of cancer stem cell selectivity in its effects. In fact, glioblastoma cell differentiation strongly reduced sensitivity to metformin treatment. Metformin effects in tumor-initiating cell-enriched cultures were associated with a powerful inhibition of Akt-dependent cell survival pathway, while this pathway was not affected in differentiated cells. The specificity of metformin antiproliferative effects toward glioblastoma tumor-initiating cells was confirmed by the lack of significant inhibition of normal human stem cells (umbilical cord-derived mesenchymal stem cells) in vitro proliferation after metformin exposure. Altogether, these data clearly suggest that metformin exerts antiproliferative activity on glioblastoma cells, showing a higher specificity toward tumor-initiating cells, and that the inhibition of Akt pathway may represent a possible intracellular target of this effect.

  19. Apoptin T108 phosphorylation is not required for its tumor-specific nuclear localization but partially affects its apoptotic activity

    SciTech Connect

    Lee, Y.-H.; Cheng, C.-M.; Chang, Y.-F.; Wang, T.-Y.; Yuo, C.-Y.; E-mail: m815006@kmu.edu.tw

    2007-03-09

    Apoptin, a chicken anemia virus-encoded protein, induces apoptosis in human tumor cells but not in normal cells. In addition, Apoptin also exhibits tumor-specific nuclear localization and tumor-specific phosphorylation on threonine 108 (T108). Here, we studied the effects of T108 phosphorylation on the tumor-specific nuclear localization and apoptotic activity of Apoptin. We first showed that a hemagglutinin (HA)-tagged Apoptin, but not the green fluorescent protein-fused Apoptin used in many previous studies, exhibited the same intracellular distribution pattern as native Apoptin. We then made and analyzed an HA-Apoptin mutant with its T108 phosphorylation site abolished. We found that Apoptin T108 phosphorylation is not required for its tumor-specific nuclear localization and abolishing the T108 phosphorylation of Apoptin does affect its apoptotic activity in tumor cells but only partially. Our results support the previous finding that Apoptin contains two distinct apoptosis domains located separately at the N- and C-terminal regions and suggest that the T108 phosphorylation may only be required for the apoptotic activity mediated through the C-terminal apoptosis domain.

  20. [Primary research on anti-tumor activity of panaxadiol fatty acid esters].

    PubMed

    Zhang, Chun-Hong; Zhang, Lian-Xue; Li, Xiang-Gao; Gao, Yu-Gang; Liu, Ya-Jing

    2006-11-01

    For making use of Ginseng resources and finding new anti-tumor drugs, the anti-tumor activity of three kinds of new panaxadiol fatty acid ester derivates: 3beta-acetoxy panaxadiol (I), 3beta-palmitic acid aceloxy panaxadiol (II), 3beta-octadecanoic acid aceloxy panaxadiol (Ill) and panaxaiol were compared through the method of cell stain and counting. Tumor cell was Vero cell line. Positive control was 5-FU. Blank was RPM11640 culture medium. Negative control was RPM11640 culture medium and the solvent for subjected drugs. The result showed that compound I had the strongest anti-tumor activity, second was panaxadiol, II and III had the same and the weakest antitumor activity. Furthermore, the anti-tumor activities of panaxadiol fatty acid ester derivates showed positive correlation with subjects' concentrations, but no relationship with molecular weight of fatty acid. PMID:17228662

  1. A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells.

    PubMed

    Matthew, Elizabeth M; Zhou, Lanlan; Yang, Zhaohai; Dicker, David T; Holder, Sheldon L; Lim, Bora; Harouaka, Ramdane; Zheng, Si-Yang; Drabick, Joseph J; Lamparella, Nicholas E; Truica, Cristina I; El-Deiry, Wafik S

    2016-01-26

    Real-time, single-cell multiplex immunophenotyping of circulating tumor cells (CTCs) is hypothesized to inform diagnosis of tissue of origin in patients with carcinoma of unknown primary (CUP). In 20 to 50% of CUP patients, the primary site remains unidentified, presenting a challenge for clinicians in diagnosis and treatment. We developed a post-CellSearch CTC assay using multiplexed Q-dot or DyLight conjugated antibodies with the goal of detecting multiple markers in single cells within a CTC population. We adapted our approach to size-based CTC enrichment protocols for capturing CTCs and subsequent immunofluorescence (IF) using a minimal set of markers to predict the primary sites for common metastatic tumors. The carcinomas are characterized with cytokeratin 7 (CK7), cytokeratin 20 (CK20), thyroid transcription factor 1 (TTF-1), estrogen receptor (ER) or prostate-specific antigen (PSA. IF has been optimized in cultured tumor cells with individual antibodies, then with conjugated antibodies to form a multiplex antibody set. With IF, we evaluated antibodies specific to these 5 markers in lung, breast, colorectal, and prostate cancer cell lines and blood from metastatic prostate and breast cancer patients. This advanced technology provides a noninvasive, diagnostic blood test as an adjunct to routine tissue biopsy. Its further implementation requires prospective clinical testing.

  2. A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells

    PubMed Central

    Yang, Zhaohai; Dicker, David T.; Holder, Sheldon L.; Lim, Bora; Harouaka, Ramdane; Zheng, Si-Yang; Drabick, Joseph J.; Lamparella, Nicholas E.; Truica, Cristina I.; El-Deiry, Wafik S.

    2016-01-01

    Real-time, single-cell multiplex immunophenotyping of circulating tumor cells (CTCs) is hypothesized to inform diagnosis of tissue of origin in patients with carcinoma of unknown primary (CUP). In 20 to 50% of CUP patients, the primary site remains unidentified, presenting a challenge for clinicians in diagnosis and treatment. We developed a post-CellSearch CTC assay using multiplexed Q-dot or DyLight conjugated antibodies with the goal of detecting multiple markers in single cells within a CTC population. We adapted our approach to size-based CTC enrichment protocols for capturing CTCs and subsequent immunofluorescence (IF) using a minimal set of markers to predict the primary sites for common metastatic tumors. The carcinomas are characterized with cytokeratin 7 (CK7), cytokeratin 20 (CK20), thyroid transcription factor 1 (TTF-1), estrogen receptor (ER) or prostate-specific antigen (PSA. IF has been optimized in cultured tumor cells with individual antibodies, then with conjugated antibodies to form a multiplex antibody set. With IF, we evaluated antibodies specific to these 5 markers in lung, breast, colorectal, and prostate cancer cell lines and blood from metastatic prostate and breast cancer patients. This advanced technology provides a noninvasive, diagnostic blood test as an adjunct to routine tissue biopsy. Its further implementation requires prospective clinical testing. PMID:26695546

  3. Systematic Review of Interventions to Improve the Provision of Information for Adults with Primary Brain Tumors and Their Caregivers

    PubMed Central

    Langbecker, Danette; Janda, Monika

    2014-01-01

    Background: Adults with primary brain tumors and their caregivers have significant information needs. This review assessed the effect of interventions to improve information provision for adult primary brain tumor patients and/or their caregivers. Methods: We included randomized or non-randomized trials testing educational interventions that had outcomes of information provision, knowledge, understanding, recall, or satisfaction with the intervention, for adults diagnosed with primary brain tumors and/or their family or caregivers. PubMed, MEDLINE, EMBASE, and Cochrane Reviews databases were searched for studies published between 1980 and June 2014. Results: Two randomized controlled, 1 non-randomized controlled, and 10 single group pre–post trials enrolled more than 411 participants. Five group, four practice/process change, and four individual interventions assessed satisfaction (12 studies), knowledge (4 studies), and information provision (2 studies). Nine studies reported high rates of satisfaction. Three studies showed statistically significant improvements over time in knowledge and two showed greater information was provided to intervention than control group participants, although statistical testing was not performed. Discussion: The trials assessed intermediate outcomes such as satisfaction, and only 4/13 reported on knowledge improvements. Few trials had a randomized controlled design and risk of bias was either evident or could not be assessed in most domains. PMID:25667919

  4. Mindfulness Training in Primary Schools Decreases Negative Affect and Increases Meta-Cognition in Children

    PubMed Central

    Vickery, Charlotte E.; Dorjee, Dusana

    2016-01-01

    Studies investigating the feasibility and impact of mindfulness programs on emotional well-being when delivered by school teachers in pre-adolescence are scarce. This study reports the findings of a controlled feasibility pilot which assessed acceptability and emotional well-being outcomes of an 8-week mindfulness program (Paws b) for children aged 7–9 years. The program was delivered by school teachers within a regular school curriculum. Emotional well-being was measured using self-report questionnaires at baseline, post-training and 3 months follow-up, and informant reports were collected at baseline and follow-up. Seventy one participants aged 7–9 years were recruited from three primary schools in the UK (training group n = 33; control group n = 38). Acceptability of the program was high with 76% of children in the training group reporting ‘liking’ practicing mindfulness at school, with a strong link to wanting to continue practicing mindfulness at school (p < 0.001). Self-report comparisons revealed that relative to controls, the training group showed significant decreases in negative affect at follow-up, with a large effect size (p = 0.010, d = 0.84). Teacher reports (but not parental ratings) of meta-cognition also showed significant improvements at follow-up with a large effect size (p = 0.002, d = 1.08). Additionally, significant negative correlations were found between changes in mindfulness and emotion regulation scores from baseline to post-training (p = 0.038) and baseline to follow-up (p = 0.033). Findings from this study provide initial evidence that the Paws b program in children aged 7–9 years (a) can be feasibly delivered by primary school teachers as part of the regular curriculum, (b) is acceptable to the majority of children, and (c) may significantly decrease negative affect and improve meta-cognition. PMID:26793145

  5. Aesthetic and Functional Rehabilitation of the Primary Dentition Affected by Amelogenesis Imperfecta

    PubMed Central

    Marquezin, Maria Carolina Salomé; Zancopé, Bruna Raquel; Pacheco, Larissa Ferreira; Gavião, Maria Beatriz Duarte; Pascon, Fernanda Miori

    2015-01-01

    The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI) in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child's psychosocial development. PMID:25705526

  6. Aesthetic and functional rehabilitation of the primary dentition affected by amelogenesis imperfecta.

    PubMed

    Marquezin, Maria Carolina Salomé; Zancopé, Bruna Raquel; Pacheco, Larissa Ferreira; Gavião, Maria Beatriz Duarte; Pascon, Fernanda Miori

    2015-01-01

    The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI) in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child's psychosocial development. PMID:25705526

  7. Sexual dimorphism of liver metastasis by murine pancreatic neuroendocrine tumors is affected by expression of complement C5

    PubMed Central

    Contractor, Tanupriya; Kobayashi, Shinta; da Silva, Edaise; Clausen, Richard; Chan, Chang; Vosburgh, Evan; Tang, Laura H.; Levine, Arnold J.; Harris, Chris R.

    2016-01-01

    In a mouse model for neuroendocrine tumors of the pancreas (PanNETs), liver metastasis occurred at a higher frequency in males. Male mice also had higher serum and intratumoral levels of the innate immunity protein complement C5. In mice that lost the ability to express complement C5, there was a lower frequency of metastasis, and males no longer had a higher frequency of metastasis than females. Treatment with PMX53, a small molecule antagonist of C5aR1/CD88, the receptor for complement C5a, also reduced metastasis. Mice lacking a functional gene for complement C5 had smaller primary tumors, which were less invasive and lacked the CD68+ macrophages that have previously been associated with metastasis in this type of tumor. This is the first report of a gene that causes sexual dimorphism of metastasis in a mouse model. In the human disease, which also shows sexual dimorphism for metastasis, clinically advanced tumors expressed more complement C5 than less advanced tumors. PMID:27105526

  8. Reconstruction of the natural history of metastatic cancer and assessment of the effects of surgery: Gompertzian growth of the primary tumor.

    PubMed

    Hanin, Leonid; Bunimovich-Mendrazitsky, Svetlana

    2014-01-01

    This work deals with retrospective reconstruction of the individual natural history of solid cancer and assessment of the effects of treatment on metastatic progression. This is achieved through a mathematical model of cancer progression accounting for the growth of the primary tumor, shedding of metastases, their dormancy and growth at secondary sites. To describe dynamics of the primary tumor, we used the Gompertz law, a parsimonious model of tumor growth accounting for its saturation. Parameters of the model were estimated from the age and volume of the primary tumor at surgery and volumes of detectable bone metastases collected from one breast cancer patient and one prostate cancer patient. This allowed us to estimate, for each patient, the ages at cancer onset and inception of all detected metastases, the expected metastasis latency time, parameters of the Gompertzian growth of the primary tumor, and the rates of growth of metastases before and after surgery. We found that for both patients: (1) onset of metastasis occurred when primary tumor was undetectable; (2) inception of all surveyed metastases except one occurred before surgery; and most importantly, (3) resection of the primary tumor led to a dramatic increase in the rate of growth of metastases. The model provides an excellent fit to the observed volumes of bone metastases in both patients. Our results agree well with those obtained previously based on exponential growth of the primary tumor, which serves as model validation. Our findings support the notion of metastatic dormancy and indirectly confirm the existence of stem-like cancer cells in breast and prostate tumors. We also explored the logistic law of primary tumor growth; however, it degenerated into the exponential law for both patients analyzed. The conclusions of this work are supported by a vast body of experimental, clinical and epidemiological knowledge accumulated over the last century. PMID:24211826

  9. Receptor affinity and extracellular domain modifications affect tumor recognition by ROR1-specific chimeric antigen receptor T-cells

    PubMed Central

    Hudecek, Michael; Lupo-Stanghellini, Maria-Teresa; Kosasih, Paula L.; Sommermeyer, Daniel; Jensen, Michael C.; Rader, Christoph; Riddell, Stanley R.

    2013-01-01

    Purpose The adoptive transfer of T-cells modified to express a chimeric antigen receptor (CAR) comprised of an extracellular single chain antibody (scFV) fragment specific for a tumor cell surface molecule, and linked to an intracellular signaling module has activity in advanced malignancies. ROR1 is a tumor-associated molecule expressed on prevalent B-lymphoid and epithelial cancers, and is absent on normal mature B-cells and vital tissues, making it a candidate for CAR T-cell therapy. Experimental Design We constructed ROR1-CARs from scFVs with different affinities and containing extracellular IgG4-Fc spacer domains of different lengths, and evaluated the ability of T-cells expressing each CAR to recognize ROR1+ hematopoietic and epithelial tumors in vitro, and to eliminate human mantle cell lymphoma engrafted into immunodeficient mice. Results ROR1-CARs containing a short ‘Hinge-only’ extracellular spacer conferred superior lysis of ROR1+ tumor cells and induction of T-cell effector functions compared to CARs with long ‘Hinge-CH2-CH3’ spacers. CARs derived from a higher affinity scFV conferred maximum T-cell effector function against primary CLL and ROR1+ epithelial cancer lines in vitro without inducing activation induced T-cell death. T-cells modified with an optimal ROR1-CAR were equivalently effective as CD19-CAR modified T-cells in mediating regression of JeKo-1 mantle cell lymphoma in immunodeficient mice. Conclusions Our results demonstrate that customizing spacer design and increasing affinity of ROR1-CARs enhances T-cell effector function and recognition of ROR1+ tumors. T-cells modified with an optimized ROR1-CAR have significant anti-tumor efficacy in a preclinical model in vivo, suggesting they may be useful to treat ROR1+ tumors in clinical applications. PMID:23620405

  10. Tumor Shrinkage With Lanreotide Autogel 120 mg as Primary Therapy in Acromegaly: Results of a Prospective Multicenter Clinical Trial

    PubMed Central

    Bevan, John S.; Petersenn, Stephan; Flanagan, Daniel; Tabarin, Antoine; Prévost, Gaëtan; Maisonobe, Pascal; Clermont, Antoine

    2014-01-01

    Context: Methodological shortcomings often compromise investigations into the effects of primary somatostatin-analog treatment on tumor size in acromegaly. There are also limited data for the long-acting lanreotide formulation. Objective: The aim of the study was to better characterize the effects of primary lanreotide Autogel treatment on tumor size in patients with GH-secreting macroadenomas. Design: PRIMARYS was a 48-week, multicenter, open-label, single-arm study. Setting: The study was conducted at specialist endocrine centers. Patients: Treatment-naïve acromegalic patients with GH-secreting macroadenomas participated in the study. Intervention: Lanreotide Autogel 120 mg was administered sc every 28 days (without dose titration). Outcome Measures: The primary endpoint was the proportion of patients with clinically significant (≥20%) tumor volume reduction (TVR) at week 48/last post-baseline value available using central assessments from three readers. The null hypothesis (H0) for the primary endpoint was that the proportion with TVR was ≤55%. Secondary endpoints included: TVR at other time points, GH and IGF-1, acromegalic symptoms, quality of life (QoL), and safety. Results: Sixty-four of 90 (71.1%) patients completed the study. Clinically significant TVR at 48 weeks/last post-baseline value available was achieved by 62.9% (95% confidence interval, 52.0, 72.9) of 89 patients in the primary analysis (intention-to-treat population; H0 not rejected) and 71.9–75.3% in sensitivity (n = 89) and secondary analyses (n = 63) (H0 rejected). At 12 weeks, 54.1% had clinically significant TVR. Early and sustained improvements also occurred in GH and IGF-1, acromegalic symptoms, and QoL. No patients withdrew due to gastrointestinal intolerance. Conclusions: Primary treatment with lanreotide Autogel, administered at 120 mg (highest available dose) without dose titration, in patients with GH-secreting macroadenomas provides early and sustained reductions in tumor

  11. Prospective assessment of quality of life in adult patients with primary brain tumors in routine neurooncology practice.

    PubMed

    Budrukkar, Ashwini; Jalali, Rakesh; Dutta, Debnarayan; Sarin, Rajiv; Devlekar, Rashmi; Parab, Sachin; Kakde, Anagha

    2009-12-01

    The aim of this article is to evaluate and assess the impact of various factors on quality of life (QOL) in adult patients with primary brain tumors seen consecutively in routine neurooncology practice. Two hundred and fifty-seven adult patients, after undergoing surgical intervention and histologically proven primary brain neoplasms were registered in the NeuroOncology Clinic at our centre during 1 full calendar year. The study included detailed neurological assessment, evaluation of QOL using EORTC questionnaire (QLQ-30) and specific Brain Cancer module (BN 20). In the present analysis, QOL scores before starting adjuvant treatment were measured and impact of patient and tumor related factors were analyzed. Baseline global QOL data of all patients (available in 243) was relatively low including in all histological tumor types. Physical function, role function, emotion function, cognitive and social function scores were 80, 78, 65.7, 70 and 70.5 (higher values better), respectively. Domains of future uncertainty, visual disorder, motor deficit, communication deficit, headache, seizures and drowsiness scores were 19.6, 18.2, 28.5, 30.7, 21, 31.8 and 16 (lower values better), respectively. Elderly patients had poorer global score (21 points difference; p = 0.161). Patients with lower performance status (KPS < 70) had a lower global QOL (KPS >or= 80 vs. tumors (p = <0.001). Illiterate patients had lower QOL score (p = 0.005). Tumor type is an important patient related factor that influences baseline global scores (LGG vs. HGG 62 and 52; p = 0.015). Economic status significantly influence QOL scores in HGG (p = 0.052). Type of surgery (biopsy/complete excision) (p = 0.284) and site of tumor (p = 0.309) did not show any impact on QOL score. Patients with primary brain tumours before starting adjuvant therapy have

  12. AZD2171 in Treating Young Patients With Recurrent, Progressive, or Refractory Primary CNS Tumors

    ClinicalTrials.gov

    2016-03-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma

  13. Primary mixed malignant tumor of bone in an 18-year-old male: Report of a case with radiologic-pathologic correlation

    PubMed Central

    Courtier, Jesse; Robbins, Elizabeth; Soares, Bruno; Horvai, Andrew; Mackenzie, John D.

    2012-01-01

    We report a case of primary malignant mixed tumor (MMT) of bone in an 18-year-old boy with X-ray, CT, MR, scintigraphic, FDG PET, and pathologic correlation. Primary MMT of bone is a highly aggressive tumor and presents both a diagnostic and clinical treatment challenge. This tumor is extremely rare and to the best of our knowledge, this is the first report of the diagnostic imaging findings for primary MMT arising from bone in a patient of this age group. PMID:26909264

  14. Cultivar and Year Rather than Agricultural Practices Affect Primary and Secondary Metabolites in Apple Fruit

    PubMed Central

    Renard, Catherine M. G. C.; Plenet, Daniel; Gautier, Hélène; Touloumet, Line; Girard, Thierry; Simon, Sylvaine

    2015-01-01

    Many biotic and abiotic parameters affect the metabolites involved in the organoleptic and health value of fruits. It is therefore important to understand how the growers' decisions for cultivar and orchard management can affect the fruit composition. Practices, cultivars and/or year all might participate to determine fruit composition. To hierarchize these factors, fruit weight, dry matter, soluble solids contents, titratable acidity, individual sugars and organics acids, and phenolics were measured in three apple cultivars (‘Ariane’, ‘Melrose’ and ‘Smoothee’) managed under organic, low-input and conventional management. Apples were harvested at commercial maturity in the orchards of the cropping system experiment BioREco at INRA Gotheron (Drôme, 26) over the course of three years (2011, 2012 and 2013). The main factors affecting primary and secondary metabolites, in both apple skin and flesh, were by far the cultivar and the yearly conditions, while the management system had a very limited effect. When considering the three cultivars and the year 2011 to investigate the effect of the management system per se, only few compounds differed significantly between the three systems and in particular the total phenolic content did not differ significantly between systems. Finally, when considering orchards grown in the same pedoclimatic conditions and of the same age, instead of the usual organic vs. conventional comparison, the effect of the management system on the apple fruit quality (Fruit weight, dry matter, soluble solids content, titratable acidity, individual sugars, organic acids, and phenolics) was very limited to non-significant. The main factors of variation were the cultivar and the year of cropping rather than the cropping system. More generally, as each management system (e.g. conventional, organic…) encompasses a great variability of practices, this highlights the importance of accurately documenting orchard practices and design beside the

  15. Cultivar and Year Rather than Agricultural Practices Affect Primary and Secondary Metabolites in Apple Fruit.

    PubMed

    Le Bourvellec, Carine; Bureau, Sylvie; Renard, Catherine M G C; Plenet, Daniel; Gautier, Hélène; Touloumet, Line; Girard, Thierry; Simon, Sylvaine

    2015-01-01

    Many biotic and abiotic parameters affect the metabolites involved in the organoleptic and health value of fruits. It is therefore important to understand how the growers' decisions for cultivar and orchard management can affect the fruit composition. Practices, cultivars and/or year all might participate to determine fruit composition. To hierarchize these factors, fruit weight, dry matter, soluble solids contents, titratable acidity, individual sugars and organics acids, and phenolics were measured in three apple cultivars ('Ariane', 'Melrose' and 'Smoothee') managed under organic, low-input and conventional management. Apples were harvested at commercial maturity in the orchards of the cropping system experiment BioREco at INRA Gotheron (Drôme, 26) over the course of three years (2011, 2012 and 2013). The main factors affecting primary and secondary metabolites, in both apple skin and flesh, were by far the cultivar and the yearly conditions, while the management system had a very limited effect. When considering the three cultivars and the year 2011 to investigate the effect of the management system per se, only few compounds differed significantly between the three systems and in particular the total phenolic content did not differ significantly between systems. Finally, when considering orchards grown in the same pedoclimatic conditions and of the same age, instead of the usual organic vs. conventional comparison, the effect of the management system on the apple fruit quality (Fruit weight, dry matter, soluble solids content, titratable acidity, individual sugars, organic acids, and phenolics) was very limited to non-significant. The main factors of variation were the cultivar and the year of cropping rather than the cropping system. More generally, as each management system (e.g. conventional, organic…) encompasses a great variability of practices, this highlights the importance of accurately documenting orchard practices and design beside the generic

  16. Cultivar and Year Rather than Agricultural Practices Affect Primary and Secondary Metabolites in Apple Fruit.

    PubMed

    Le Bourvellec, Carine; Bureau, Sylvie; Renard, Catherine M G C; Plenet, Daniel; Gautier, Hélène; Touloumet, Line; Girard, Thierry; Simon, Sylvaine

    2015-01-01

    Many biotic and abiotic parameters affect the metabolites involved in the organoleptic and health value of fruits. It is therefore important to understand how the growers' decisions for cultivar and orchard management can affect the fruit composition. Practices, cultivars and/or year all might participate to determine fruit composition. To hierarchize these factors, fruit weight, dry matter, soluble solids contents, titratable acidity, individual sugars and organics acids, and phenolics were measured in three apple cultivars ('Ariane', 'Melrose' and 'Smoothee') managed under organic, low-input and conventional management. Apples were harvested at commercial maturity in the orchards of the cropping system experiment BioREco at INRA Gotheron (Drôme, 26) over the course of three years (2011, 2012 and 2013). The main factors affecting primary and secondary metabolites, in both apple skin and flesh, were by far the cultivar and the yearly conditions, while the management system had a very limited effect. When considering the three cultivars and the year 2011 to investigate the effect of the management system per se, only few compounds differed significantly between the three systems and in particular the total phenolic content did not differ significantly between systems. Finally, when considering orchards grown in the same pedoclimatic conditions and of the same age, instead of the usual organic vs. conventional comparison, the effect of the management system on the apple fruit quality (Fruit weight, dry matter, soluble solids content, titratable acidity, individual sugars, organic acids, and phenolics) was very limited to non-significant. The main factors of variation were the cultivar and the year of cropping rather than the cropping system. More generally, as each management system (e.g. conventional, organic…) encompasses a great variability of practices, this highlights the importance of accurately documenting orchard practices and design beside the generic

  17. Myocardial Infarction Secondary to Inflammatory Myofibroblastic Tumor Obstruction of the Left Main: Treated With Primary PCI

    PubMed Central

    Nguyen, James; Sethi, Salil; Ahmed, Hinan; Prasad, Anand

    2016-01-01

    Introduction Cardiac inflammatory myofibroblastic tumor is a rare tumor that can cause potentially fatal outcomes. Case Presentation We describe a case where the tumor originated on the mitral valve and extended through the left ventricular outflow tract and aortic valve and into the left main artery obstructing it. Due to the hemodynamic instability of the patient, we proceeded for cardiac catheterization with the intention to aspirate the mass but were forced to do percutaneous intervention to stabilize the patient and bridge him to surgery. Conclusions The patient underwent surgery several days later with complete resection of the tumor and coronary stent retrieval but his left ventricular ejection fraction remained poor after several months and he was referred for cardiac transplantation. PMID:27800457

  18. Inhibition of primary and metastatic tumors in mice by E-selectin-targeted polymer-drug conjugates.

    PubMed

    Shamay, Yosi; Raviv, Lior; Golan, Moran; Voronov, Elena; Apte, Ron N; David, Ayelet

    2015-11-10

    There is currently no effective means to prevent or control metastatic dissemination of cancer cells. E-selectin, an adhesion molecule expressed exclusively on inflamed and angiogenic blood vessels, plays an important role in several rate-limiting steps of cancer metastasis. In this study, we assessed the in vivo antitumor efficacy of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers conjugated to an E-selectin binding peptide (Esbp, DITWDQLWDLMK) and equipped with the chemotherapeutic drug doxorubicin (P-(Esbp)-DOX) or with the proapoptotic peptide D(KLAKLAK)2 (P-(Esbp)-KLAK). Following a single intravenous injection, P-(Esbp)-DOX reduced tumor growth rate and prolonged the survival of mice bearing primary Lewis lung carcinoma (3LL) tumors significantly more than treatment with a non-targeted copolymer (P-DOX) or with free DOX. In an experimental B16-F10 lung metastasis model, a single intravenous dose of P-(Esbp)-DOX or P-(Esbp)-KLAK prolonged mice survival time significantly more than the non-targeted copolymers or the free drugs, and the percentage of complete tumor regression increased with increasing doses and with dosing frequency. In addition, mice pretreated with an E-selectin-targeted "drug-free" copolymer (P-(Esbp)-FITC) exhibited significantly fewer B16-F10 tumor foci in the lungs as compared with non-treated mice, demonstrating the anti-metastatic properties of the copolymer and its ability to control cancer spread through E-selectin-mediated interactions. Biodistribution analysis further confirmed the preferential accumulation of the E-selectin-targeted near-infrared fluorescently-labeled copolymer P-(Esbp)-IR783 in B16-F10 lung metastases. Taken together, this study demonstrates, for the first time, that the E-selectin targeted copolymer-drug conjugates can inhibit primary tumor growth and prevent metastases in vivo. PMID:26297207

  19. Inhibition of primary and metastatic tumors in mice by E-selectin-targeted polymer-drug conjugates.

    PubMed

    Shamay, Yosi; Raviv, Lior; Golan, Moran; Voronov, Elena; Apte, Ron N; David, Ayelet

    2015-11-10

    There is currently no effective means to prevent or control metastatic dissemination of cancer cells. E-selectin, an adhesion molecule expressed exclusively on inflamed and angiogenic blood vessels, plays an important role in several rate-limiting steps of cancer metastasis. In this study, we assessed the in vivo antitumor efficacy of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers conjugated to an E-selectin binding peptide (Esbp, DITWDQLWDLMK) and equipped with the chemotherapeutic drug doxorubicin (P-(Esbp)-DOX) or with the proapoptotic peptide D(KLAKLAK)2 (P-(Esbp)-KLAK). Following a single intravenous injection, P-(Esbp)-DOX reduced tumor growth rate and prolonged the survival of mice bearing primary Lewis lung carcinoma (3LL) tumors significantly more than treatment with a non-targeted copolymer (P-DOX) or with free DOX. In an experimental B16-F10 lung metastasis model, a single intravenous dose of P-(Esbp)-DOX or P-(Esbp)-KLAK prolonged mice survival time significantly more than the non-targeted copolymers or the free drugs, and the percentage of complete tumor regression increased with increasing doses and with dosing frequency. In addition, mice pretreated with an E-selectin-targeted "drug-free" copolymer (P-(Esbp)-FITC) exhibited significantly fewer B16-F10 tumor foci in the lungs as compared with non-treated mice, demonstrating the anti-metastatic properties of the copolymer and its ability to control cancer spread through E-selectin-mediated interactions. Biodistribution analysis further confirmed the preferential accumulation of the E-selectin-targeted near-infrared fluorescently-labeled copolymer P-(Esbp)-IR783 in B16-F10 lung metastases. Taken together, this study demonstrates, for the first time, that the E-selectin targeted copolymer-drug conjugates can inhibit primary tumor growth and prevent metastases in vivo.

  20. Primary intracranial neuroendocrine tumor with ectopic adrenocorticotropic hormone syndrome: A rare and complicated case report and literature review

    PubMed Central

    LIU, HAILONG; ZHANG, MINGSHAN; WANG, XUAN; QU, YANMING; ZHANG, HONGWEI; YU, CHUNJIANG

    2016-01-01

    Neuroendocrine tumors (NETs) and ectopic adrenocorticotropic hormone (ACTH) syndrome are frequent in adult patients. However, primary intracranial NETs, exhibiting immunonegativity for ACTH, high serum ACTH level and treated with anterior skull base reconstruction, are rare and complicated. We herein present a case of a primary intracranial NET immunonegative for ACTH, resulting in ectopic ACTH syndrome. A 40-year-old woman presented with intermittent rhinorrhea, rapid weight gain, polydipsia, polyuria, hypertension, dimness, bilateral exophthalmus, diminution of vision in the left eye and pigmentation of the skin of the face and trunk. Computed tomography (CT) and magnetic resonance imaging scans revealed a sizeable enhancing tumor in the anterior cranial fossa, which infiltrated the sphenoid and ethmoid sinuses bilaterally, the left maxillary sinus and the nasal cavity. Abdominal CT scans revealed bilateral adrenal hyperplasia. The biochemical findings included hypokalemia and high glucose, cortisol, plasma ACTH, 24-h urinary free cortisol and testosterone levels. The neoplasm was exposed through a right frontal craniotomy, while anterior skull base reconstruction was performed during surgery. The intracranial surgery achieved gross removal of the tumor; however, part of the tumor remained in the nasal cavity. Histopathological examination of the surgical specimen confirmed the diagnosis of a low-grade small-cell NET, exhibiting immunonegativity for ACTH. A postoperative abdominal CT scan demonstrated bilateral regression of the adrenal gland hyperplasia and the serum ACTH level returned to normal after 16 days. To the best of our knowledge, there are no previous reports of primary intracranial NETs, immunohistochemically negative for ACTH, resulting in ectopic ACTH syndrome. PMID:27330775

  1. Interactive effect of negative affectivity and anxiety sensitivity in terms of mental health among Latinos in primary care.

    PubMed

    Zvolensky, Michael J; Paulus, Daniel J; Bakhshaie, Jafar; Garza, Monica; Ochoa-Perez, Melissa; Medvedeva, Angela; Bogiaizian, Daniel; Robles, Zuzuky; Manning, Kara; Schmidt, Norman B

    2016-09-30

    From a public health perspective, primary care medical settings represent a strategic location to address mental health disapirty among Latinos. Yet, there is little empirical work that addresses affective vulnerability processes for mental health problems in such settings. To help address this gap in knowledge, the present investigation examined an interactive model of negative affectivity (tendency to experience negative mood states) and anxiety sensitivity (fear of the negative consequences of aversive sensations) among a Latino sample in primary care in terms of a relatively wide range of anxiety/depression indices. Participants included 390 Latino adults (Mage=38.7, SD=11.3; 86.9% female; 95.6% reported Spanish as first language) from a primary care health clinic. Primary dependent measures included depressive, suicidal, social anxiety, and anxious arousal symptoms, number of mood and anxiety disorders, and disability. Consistent with prediction, the interaction between negative affectivity and anxiety sensitivity was significantly related to suicidal, social anxiety, and anxious arousal symptoms, as well as number of mood/anxiety diagnoses and disability among the primary care Latino sample. The form of the interactions indicated a synergistic effect, such that the greatest levels of each outcome were found among those with high negative affectivity and high anxiety sensitivity. There was a trending interaction for depressive symptoms. Overall, these data provide novel empirical evidence suggesting that there is a clinically-relevant interplay between anxiety sensitivity and negative affectivity in regard to the expression of anxiety and depressive symptoms among a Latino primary care sample.

  2. Descriptive epidemiology and risk factors of primary central nervous system tumors: Current knowledge.

    PubMed

    Pouchieu, C; Baldi, I; Gruber, A; Berteaud, E; Carles, C; Loiseau, H

    2016-01-01

    Although comparisons are difficult due to differences in methodologies, the annual incidence rates of central nervous system (CNS) tumors range from 8.5 to 21.4/100,000 population according to cancer registries, with a predominance of neuroepithelial tumors in men and meningiomas in women. An increase in the incidence of CNS tumors has been observed during the past decades in several countries. It has been suggested that this trend could be due to aging of the population, and improvements in diagnostic imaging and healthcare access, but these factors do not explain differences in incidence by gender and histological subtypes. Several etiological hypotheses related to intrinsic (sociodemographic, anthropometric, hormonal, immunological, genetic) and exogenous (ionizing radiation, electromagnetic fields, diet, infections, pesticides, drugs) risk factors have led to analytical epidemiological studies to establish relationships with CNS tumors. The only established environmental risk factor for CNS tumors is ionizing radiation exposure. However, for other risk factors, studies have been inconsistent and inconclusive due to systematic differences in study design and difficulties in accurately measuring exposures. Thus, the etiology of CNS tumors is complex and may involve several genetic and/or environmental factors that may act differently according to histological subtype. PMID:26708326

  3. AMACR amplification and overexpression in primary imatinib-naïve gastrointestinal stromal tumors: a driver of cell proliferation indicating adverse prognosis

    PubMed Central

    Li, Chien-Feng; Chen, Li-Tzong; Lan, Jui; Chou, Fong-Fu; Lin, Ching-Yih; Chen, Yen-Yang; Chen, Tzu-Ju; Li, Shau-Hsuan; Yu, Shih-Chen; Fang, Fu-Ming; Tai, Hui-Chun; Huang, Hsuan-Ying

    2014-01-01

    Non-random gains of chromosome 5p have been observed in clinically aggressive gastrointestinal stromal tumors, whereas the driving oncogenes on 5p remain to be characterized. We used an integrative genomic and functional approach to identify amplified oncogenes on 5p and to evaluate the relevance of AMACR amplification at 5p13.3 and its overexpression in gastrointestinal stromal tumors. Thirty-seven tumor samples, imatinib-sensitive GIST882 cell line, and imatinib-resistant GIST48 cell line were analyzed for DNA imbalances using array-based genomic profiling. Forty-one fresh tumor samples of various risk categories were enriched for pure tumor cells by laser capture microdissection and quantified for AMACR mRNA expression. AMACR-specific fluorescence in situ hybridization and immunohistochemistry were both informative in tissue microarray sections of 350 independent primary gastrointestinal stromal tumors, including 213 cases with confirmed KIT /PDGFRA genotypes. To assess the oncogenic functions of AMACR, GIST882 and GIST48 cell lines were stably silenced against their endogenous AMACR expression. In 59% of cases featuring 5p gains, two major amplicons encompassed discontinuous chromosomal regions that were differentially overrepresented in high-risk cases, including the one harboring the mRNA-upregulated AMACR gene. Gene amplification was detected in 19.7% of cases (69/350) and strongly related to protein overexpression (p<0.001), although 52% of AMACR-overexpressing cases exhibited no amplification. Both gene amplification and protein overexpression were significantly associated with epithelioid histology, larger size, increased mitoses, higher risk levels, and unfavorable genotypes (all p≤0.03). They were also independently predictive of decreased disease-free survival (overexpression, p<0.001; amplification, p=0.020) in the multivariate analysis. Concomitant with downregulated cyclin D1, cyclin E, and CDK4, AMACR knockdown suppressed cell proliferation and

  4. SU-E-J-175: Comparison of the Treatment Reproducibility of Tumors Affected by Breathing Motion

    SciTech Connect

    Adamczyk, M; Piotrowski, T; Adamczyk, S

    2015-06-15

    Purpose: The aim of the dose distribution simulations was to form a global idea of intensity-modulated radiation therapy (IMRT) realization, by its comparison to three-dimensional conformal radiation therapy (3DCRT) delivery for tumors affected by respiratory motion. Methods: In the group of 10patients both 3DCRT and IMRT plans were prepared.For each field the motion kernel was generated with the largest movement amplitude of 4;6 and 8mm.Additionally,the sets of reference measurements were made in no motion conditions(0 mm).The evaluation of plan delivery,using a diode array placed on moving platform,was based on the Gamma Index analysis with distance to agreement of 3mm and dose difference of 3%. Results: IMRT plans tended to spare doses delivered to lungs compared to 3DCRT.Nonetheless,analyzed volumes showed no significant difference between the static and dynamic techniques,except for the volumes of both lungs receiving 10 and 15Gy.After adding the components associated with the respiratory movement,all IMRT lung parameters evaluated for the ipsilateral,contralateral and both lungs together,revealed considerable differences between the 0vs.6, 0vs.8 and 4vs.8-mm amplitudes.Similar results were obtained for the 3DCRT lung measurements,but without significance between the 0vs.6-mm amplitude.Taking into account the CTV score parameter in 3DCRT and IMRT plans,there was no statistically significant difference between the motion patterns with the smallest amplitudes.The differences were found for the 8-mm amplitude when it was compared both with static conditions and 4-mm amplitude (for 3DCRT) and between 0vs.6, 0vs.8 and 4vs.8-mm amplitudes (for IMRT).All accepted and measured 3DCRT and IMRT doses to spinal cord,esophagus and heart were always below the QUANTEC limits. Conclusion: The application of IMRT technique in lung radiotherapy affords possibilities for reducing the lung doses.For maximal amplitudes of breathing trajectory below 4mm,the disagreement between CTV

  5. An important role of the hepcidin-ferroportin signaling in affecting tumor growth and metastasis.

    PubMed

    Guo, Wenli; Zhang, Shuping; Chen, Yue; Zhang, Daoqiang; Yuan, Lin; Cong, Haibo; Liu, Sijin

    2015-09-01

    Epidemiological and experimental studies have suggested that deregulated hepcidin-ferroportin (FPN) signaling is associated with the increased risk of cancers. However, the effects of deregulated hepcidin-FPN signaling on tumor behaviors such as metastasis and epithelial to mesenchymal transition (EMT) have not been closely investigated. In this study, LL/2 cancer cells were found to exhibit an impaired propensity to home into lungs, and a reduced ability to develop tumors was also demonstrated in lungs of Hamp1(-/-) mice. Moreover, hepatic hepcidin deficiency was found to considerably favor tumor-free survival in Hamp1(-/-) mice, compared with wild-type mice. These data thus underscored a contributive role of hepatic hepcidin in promoting lung cancer cell homing and fostering tumor progression. To explore the role of FPN in regulating tumor progression, we genetically engineered 4T1 cells with FPN over-expression upon induction by doxycycline. With this cell line, it was discovered that increased FPN expression reduced cell division and colony formation in vitro, without eliciting significant cell death. Analogously, FPN over-expression impeded tumor growth and metastasis to lung and liver in mice. At the molecular level, FPN over-expression was identified to undermine DNA synthesis and cell cycle progression. Importantly, FPN over-expression inhibited EMT, as reflected by the significant decrease of representative EMT markers, such as Snail1, Twist1, ZEB2, and vimentin. Additionally, there was also a reduction of lactate production in cells upon induction of FPN over-expression. Together, our results highlighted a crucial role of the hepcidin-FPN signaling in modulating tumor growth and metastasis, providing new evidence to understand the contribution of this signaling in cancers.

  6. Potato Snakin-1 Gene Silencing Affects Cell Division, Primary Metabolism, and Cell Wall Composition1[W

    PubMed Central

    Nahirñak, Vanesa; Almasia, Natalia Inés; Fernandez, Paula Virginia; Hopp, Horacio Esteban; Estevez, José Manuel; Carrari, Fernando; Vazquez-Rovere, Cecilia

    2012-01-01

    Snakin-1 (SN1) is an antimicrobial cysteine-rich peptide isolated from potato (Solanum tuberosum) that was classified as a member of the Snakin/Gibberellic Acid Stimulated in Arabidopsis protein family. In this work, a transgenic approach was used to study the role of SN1 in planta. Even when overexpressing SN1, potato lines did not show remarkable morphological differences from the wild type; SN1 silencing resulted in reduced height, which was accompanied by an overall reduction in leaf size and severe alterations of leaf shape. Analysis of the adaxial epidermis of mature leaves revealed that silenced lines had 70% to 90% increases in mean cell size with respect to wild-type leaves. Consequently, the number of epidermal cells was significantly reduced in these lines. Confocal microscopy analysis after agroinfiltration of Nicotiana benthamiana leaves showed that SN1-green fluorescent protein fusion protein was localized in plasma membrane, and bimolecular fluorescence complementation assays revealed that SN1 self-interacted in vivo. We further focused our study on leaf metabolism by applying a combination of gas chromatography coupled to mass spectrometry, Fourier transform infrared spectroscopy, and spectrophotometric techniques. These targeted analyses allowed a detailed examination of the changes occurring in 46 intermediate compounds from primary metabolic pathways and in seven cell wall constituents. We demonstrated that SN1 silencing affects cell division, leaf primary metabolism, and cell wall composition in potato plants, suggesting that SN1 has additional roles in growth and development beyond its previously assigned role in plant defense. PMID:22080603

  7. Identification of CD146 as a marker enriched for tumor-propagating capacity reveals targetable pathways in primary human sarcoma

    PubMed Central

    Voisin, Veronique; Sato, Shingo; Hirata, Makoto; Whetstone, Heather; Han, Ilkyu; Ailles, Laurie; Bader, Gary D.; Wunder, Jay; Alman, Benjamin A.

    2015-01-01

    Tumor-propagating cells (TPCs) are believed to drive cancer initiation, progression and recurrence. These cells are characterized by enhanced tumorigenicity and self-renewal. The ability to identify such cells in primary human sarcomas relies on the dye exclusion ability of tumor side population (SP) cells. Here, we performed a high-throughput cell surface antigen screen and found that CD146 is enriched in the SP population. In vivo serial transplantation assays showed that CD146+ cells are highly tumorigenic, capable of self-renewal and thus enriches for the TPC population. In addition, depletion of SP cells from the CD146+ population show that CD146+ cells and SP cells are a distinct and overlapping TPC populations. Gene expression profiling of CD146+ and SP cells revealed multiple pathways commonly upregulated in both of these populations. Inhibition of one of these upregulated pathways, Notch signaling, significantly reduced tumor growth and self-renewal. Our data demonstrate that CD146 is an effective cell surface marker for enriching TPCs in primary human sarcomas. Targeting differentially activated pathways in TPCs may provide new therapeutic strategies for treating sarcoma. PMID:26517673

  8. Luciferase expression and bioluminescence does not affect tumor cell growth in vitro or in vivo.

    PubMed

    Tiffen, Jessamy C; Bailey, Charles G; Ng, Cynthia; Rasko, John E J; Holst, Jeff

    2010-01-01

    Live animal imaging is becoming an increasingly common technique for accurate and quantitative assessment of tumor burden over time. Bioluminescence imaging systems rely on a bioluminescent signal from tumor cells, typically generated from expression of the firefly luciferase gene. However, previous reports have suggested that either a high level of luciferase or the resultant light reaction produced upon addition of D-luciferin substrate can have a negative influence on tumor cell growth. To address this issue, we designed an expression vector that allows simultaneous fluorescence and luminescence imaging. Using fluorescence activated cell sorting (FACS), we generated clonal cell populations from a human breast cancer (MCF-7) and a mouse melanoma (B16-F10) cell line that stably expressed different levels of luciferase. We then compared the growth capabilities of these clones in vitro by MTT proliferation assay and in vivo by bioluminescence imaging of tumor growth in live mice. Surprisingly, we found that neither the amount of luciferase nor biophotonic activity was sufficient to inhibit tumor cell growth, in vitro or in vivo. These results suggest that luciferase toxicity is not a necessary consideration when designing bioluminescence experiments, and therefore our approach can be used to rapidly generate high levels of luciferase expression for sensitive imaging experiments. PMID:21092230

  9. Gene silencing in primary and metastatic tumors by small interfering RNA delivery in mice: quantitative analysis using melanoma cells expressing firefly and sea pansy luciferases.

    PubMed

    Takahashi, Yuki; Nishikawa, Makiya; Kobayashi, Naoki; Takakura, Yoshinobu

    2005-07-20

    Silencing of oncogenes or other genes contributing to tumor malignancy or progression by RNA interference (RNAi) offers a promising approach to treating tumor patients. To achieve RNAi-based tumor therapy, a small interfering RNA (siRNA) or siRNA-expressing vector needs to be delivered to tumor cells, but little information about its in vivo delivery has been reported. In this study, we examined whether the expression of the target gene in tumor cells can be suppressed by the delivery of RNAi effectors to primary and metastatic tumor cells. To quantitatively evaluate the RNAi effects in tumor cells, mouse melanoma B16-BL6 cells were stably transfected with both firefly (a model target gene) and sea pansy (an internal standard gene) luciferase genes to obtain B16-BL6/dual Luc cells. The target gene expression in subcutaneous primary tumors of B16-BL6/dual Luc cells was significantly suppressed by direct injection of the RNAi effectors followed by electroporation. The expression in metastatic hepatic tumors was also significantly reduced by an intravenous injection of either RNAi effector by the hydrodynamics-based procedure. These results indicate that the both RNAi effectors have a potential to silence target gene in tumor cells in vivo when successfully delivered to tumor cells. PMID:15936841

  10. Second primary tumors (SPT) of head and neck: distinguishing of "true" SPT from micrometastasis by LOH analysis of selected chromosome regions.

    PubMed

    Giefing, M; Rydzanicz, M; Szukala, K; Wozniak, A; Wierzbicka, M; Szyfter, K; Kujawski, M

    2005-01-01

    The reason of treatment failures in head and neck tumors is often connected with the appearance of second primary tumors (SPT). Three mechanisms of SPT development of clonal or non clonal secondary tumors were described: 1. via micrometastases (clonal); 2. from a common carcinogenic field - Second Field Tumors (SFT - partially clonal); 3. via independent events (from different carcinogenic fields - "true" SPT - not clonal). Assessing the clonality of diagnosed tumors carries important clinical implications including chemoprevention, radiotherapy and general patient management. In this study a set of 12 microsatellite markers was used to find similarities and/or differences in allelic imbalance patterns between 22 pairs of tumors (the first tumor designate as index and SPT). The aim of the study was to identify a potential clonal origin and progression within given pairs of tumors. The results indicate that within the tumors diagnosed by clinical examination as SPT at least two mechanisms mentioned above should be taken into account as 6/23 (26%) were clonally unrelated ("true" SPT) and 3/23 (13%) carried clonal genetic changes (formation by micrometastasis or SFT). In 14/23 (61%) cases the results were insufficient or ambiguous to determine the clonality status. The final results indicate the complexity of carcinogenesis in these tumors and thus stress that clinical diagnosis of second primary tumors should be considered carefully.

  11. Primary Neuroendocrine Tumor of the Parotid Gland: A Case Report and a Comprehensive Review of a Rare Entity.

    PubMed

    Martínez-Sáez, Olga; Molina-Cerrillo, Javier; Moreno García Del Real, Carmen; Barberá Durban, Rafael; Díez, Juan J; Alonso-Gordoa, Teresa; Pulido, Enrique Grande

    2016-01-01

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies from cells derived from the neural crest with neuroendocrine differentiation. Despite the differences in the site of origin, nomenclature, biological behavior, and functional status, NETs share certain ultrastructural and immunohistochemical features. NETs are relative rare tumors with an annual incidence of 5.76 new cases per 100.000 inhabitants and they usually appear in the gastrointestinal tract or in the pulmonary system. Head and neck NETs are uncommon with limited information regarding frequency, most of them showing small cell carcinoma features. NETs that arise from the salivary glands are exceedingly rare. Regardless of their low frequency, it is imperative to accurately differentiate these tumors from the much more common squamous cell carcinomas and from metastasis from another primary tumor due to the completely different therapeutic approaches and prognosis. The diagnosis is based on the recognition of the typical neuroendocrine architecture and immunohistochemical staining and on an exhaustive work-up. Hereby, we report a case of a moderately differentiated NET of the parotid gland that was treated with a complete parotidectomy. We summarize the clues that led to the final diagnosis and major strategies that were employed to manage the patient. We also perform a comprehensive review of the scarce available literature on this topic.

  12. Primary Neuroendocrine Tumor of the Parotid Gland: A Case Report and a Comprehensive Review of a Rare Entity.

    PubMed

    Martínez-Sáez, Olga; Molina-Cerrillo, Javier; Moreno García Del Real, Carmen; Barberá Durban, Rafael; Díez, Juan J; Alonso-Gordoa, Teresa; Pulido, Enrique Grande

    2016-01-01

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies from cells derived from the neural crest with neuroendocrine differentiation. Despite the differences in the site of origin, nomenclature, biological behavior, and functional status, NETs share certain ultrastructural and immunohistochemical features. NETs are relative rare tumors with an annual incidence of 5.76 new cases per 100.000 inhabitants and they usually appear in the gastrointestinal tract or in the pulmonary system. Head and neck NETs are uncommon with limited information regarding frequency, most of them showing small cell carcinoma features. NETs that arise from the salivary glands are exceedingly rare. Regardless of their low frequency, it is imperative to accurately differentiate these tumors from the much more common squamous cell carcinomas and from metastasis from another primary tumor due to the completely different therapeutic approaches and prognosis. The diagnosis is based on the recognition of the typical neuroendocrine architecture and immunohistochemical staining and on an exhaustive work-up. Hereby, we report a case of a moderately differentiated NET of the parotid gland that was treated with a complete parotidectomy. We summarize the clues that led to the final diagnosis and major strategies that were employed to manage the patient. We also perform a comprehensive review of the scarce available literature on this topic. PMID:27610258

  13. Primary Neuroendocrine Tumor of the Parotid Gland: A Case Report and a Comprehensive Review of a Rare Entity

    PubMed Central

    Molina-Cerrillo, Javier; Moreno García del Real, Carmen; Díez, Juan J.; Alonso-Gordoa, Teresa; Pulido, Enrique Grande

    2016-01-01

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies from cells derived from the neural crest with neuroendocrine differentiation. Despite the differences in the site of origin, nomenclature, biological behavior, and functional status, NETs share certain ultrastructural and immunohistochemical features. NETs are relative rare tumors with an annual incidence of 5.76 new cases per 100.000 inhabitants and they usually appear in the gastrointestinal tract or in the pulmonary system. Head and neck NETs are uncommon with limited information regarding frequency, most of them showing small cell carcinoma features. NETs that arise from the salivary glands are exceedingly rare. Regardless of their low frequency, it is imperative to accurately differentiate these tumors from the much more common squamous cell carcinomas and from metastasis from another primary tumor due to the completely different therapeutic approaches and prognosis. The diagnosis is based on the recognition of the typical neuroendocrine architecture and immunohistochemical staining and on an exhaustive work-up. Hereby, we report a case of a moderately differentiated NET of the parotid gland that was treated with a complete parotidectomy. We summarize the clues that led to the final diagnosis and major strategies that were employed to manage the patient. We also perform a comprehensive review of the scarce available literature on this topic.

  14. Primary Neuroendocrine Tumor of the Parotid Gland: A Case Report and a Comprehensive Review of a Rare Entity

    PubMed Central

    Molina-Cerrillo, Javier; Moreno García del Real, Carmen; Díez, Juan J.; Alonso-Gordoa, Teresa; Pulido, Enrique Grande

    2016-01-01

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies from cells derived from the neural crest with neuroendocrine differentiation. Despite the differences in the site of origin, nomenclature, biological behavior, and functional status, NETs share certain ultrastructural and immunohistochemical features. NETs are relative rare tumors with an annual incidence of 5.76 new cases per 100.000 inhabitants and they usually appear in the gastrointestinal tract or in the pulmonary system. Head and neck NETs are uncommon with limited information regarding frequency, most of them showing small cell carcinoma features. NETs that arise from the salivary glands are exceedingly rare. Regardless of their low frequency, it is imperative to accurately differentiate these tumors from the much more common squamous cell carcinomas and from metastasis from another primary tumor due to the completely different therapeutic approaches and prognosis. The diagnosis is based on the recognition of the typical neuroendocrine architecture and immunohistochemical staining and on an exhaustive work-up. Hereby, we report a case of a moderately differentiated NET of the parotid gland that was treated with a complete parotidectomy. We summarize the clues that led to the final diagnosis and major strategies that were employed to manage the patient. We also perform a comprehensive review of the scarce available literature on this topic. PMID:27610258

  15. Clinical, Biologic, and Prognostic Differences on the Basis of Primary Tumor Site in Neuroblastoma: A Report From the International Neuroblastoma Risk Group Project

    PubMed Central

    Vo, Kieuhoa T.; Matthay, Katherine K.; Neuhaus, John; London, Wendy B.; Hero, Barbara; Ambros, Peter F.; Nakagawara, Akira; Miniati, Doug; Wheeler, Kate; Pearson, Andrew D.J.; Cohn, Susan L.; DuBois, Steven G.

    2014-01-01

    Purpose Neuroblastoma (NB) is a heterogeneous tumor arising from sympathetic tissues. The impact of primary tumor site in influencing the heterogeneity of NB remains unclear. Patients and Methods Children younger than age 21 years diagnosed with NB or ganglioneuroblastoma between 1990 and 2002 and with known primary site were identified from the International Neuroblastoma Risk Group database. Data were compared between sites with respect to clinical and biologic features, as well as event-free survival (EFS) and overall survival (OS). Results Among 8,369 children, 47% had adrenal tumors. All evaluated clinical and biologic variables differed statistically between primary sites. The features that were > 10% discrepant between sites were stage 4 disease, MYCN amplification, elevated ferritin, elevated lactate dehydrogenase, and segmental chromosomal aberrations, all of which were more frequent in adrenal versus nonadrenal tumors (P < .001). Adrenal tumors were more likely than nonadrenal tumors (adjusted odds ratio, 2.09; 95% CI, 1.67 to 2.63; P < .001) and thoracic tumors were less likely than nonthoracic tumors (adjusted odds ratio, 0.20; 95% CI, 0.11 to 0.39; P < .001) to have MYCN amplification after controlling for age, stage, and histologic grade. EFS and OS differed significantly according to the primary site (P < .001 for both comparisons). After controlling for age, MYCN status, and stage, patients with adrenal tumors had higher risk for events (hazard ratio, 1.13 compared with nonadrenal tumors; 95% CI, 1.03 to 1.23; P = .008), and patients with thoracic tumors had lower risk for events (HR, 0.79 compared with nonthoracic; 95% CI, 0.67 to 0.92; P = .003). Conclusion Clinical and biologic features show important differences by NB primary site, with adrenal and thoracic sites associated with inferior and superior survival, respectively. Future studies will need to investigate the biologic origin of these differences. PMID:25154816

  16. SU-E-I-100: Heterogeneity Studying for Primary and Lymphoma Tumors by Using Multi-Scale Image Texture Analysis with PET-CT Images

    SciTech Connect

    Li, Dengwang; Wang, Qinfen; Li, H; Chen, J

    2014-06-01

    Purpose: The purpose of this research is studying tumor heterogeneity of the primary and lymphoma by using multi-scale texture analysis with PET-CT images, where the tumor heterogeneity is expressed by texture features. Methods: Datasets were collected from 12 lung cancer patients, and both of primary and lymphoma tumors were detected with all these patients. All patients underwent whole-body 18F-FDG PET/CT scan before treatment.The regions of interest (ROI) of primary and lymphoma tumor were contoured by experienced clinical doctors. Then the ROI of primary and lymphoma tumor is extracted automatically by using Matlab software. According to the geometry size of contour structure, the images of tumor are decomposed by multi-scale method.Wavelet transform was performed on ROI structures within images by L layers sampling, and then wavelet sub-bands which have the same size of the original image are obtained. The number of sub-bands is 3L+1.The gray level co-occurrence matrix (GLCM) is calculated within different sub-bands, thenenergy, inertia, correlation and gray in-homogeneity were extracted from GLCM.Finally, heterogeneity statistical analysis was studied for primary and lymphoma tumor using the texture features. Results: Energy, inertia, correlation and gray in-homogeneity are calculated with our experiments for heterogeneity statistical analysis.Energy for primary and lymphomatumor is equal with the same patient, while gray in-homogeneity and inertia of primaryare 2.59595±0.00855, 0.6439±0.0007 respectively. Gray in-homogeneity and inertia of lymphoma are 2.60115±0.00635, 0.64435±0.00055 respectively. The experiments showed that the volume of lymphoma is smaller than primary tumor, but thegray in-homogeneity and inertia were higher than primary tumor with the same patient, and the correlation with lymphoma tumors is zero, while the correlation with primary tumor isslightly strong. Conclusion: This studying showed that there were effective heterogeneity

  17. CAF-like state in primary skin fibroblasts with constitutional BRCA1 epimutation sheds new light on tumor suppressor deficiency-related changes in healthy tissue.

    PubMed

    Etzold, Anna; Galetzka, Danuta; Weis, Eva; Bartsch, Oliver; Haaf, Thomas; Spix, Claudia; Itzel, Timo; Schweiger, Susann; Strand, Dennis; Strand, Susanne; Zechner, Ulrich

    2016-01-01

    Constitutive epimutations of tumor suppressor genes are increasingly considered as cancer predisposing factors equally to sequence mutations. In light of the emerging role of the microenvironment for cancer predisposition, initiation, and progression, we aimed to characterize the consequences of a BRCA1 epimutation in cells of mesenchymal origin. We performed a comprehensive molecular and cellular comparison of primary dermal fibroblasts taken from a monozygous twin pair discordant for recurrent cancers and BRCA1 epimutation, whose exceptional clinical case we previously reported in this journal. Comparative transcriptome analysis identified differential expression of extracellular matrix-related genes and pro-tumorigenic growth factors, such as collagens and CXC chemokines. Moreover, genes known to be key markers of so called cancer-associated fibroblasts (CAFs), such as ACTA2, FAP, PDPN, and TNC, were upregulated in fibroblasts of the affected twin (BRCA1(mosMe)) in comparison to those of the healthy twin (BRCA1(wt)). Further analyses detected CAF-typical cellular features, including an elevated growth rate, enhanced migration, altered actin architecture and increased production of ketone bodies in BRCA1(mosMe) fibroblasts compared to BRCA1(wt) fibroblasts. In addition, conditioned medium of BRCA1(mosMe) fibroblasts was more potent than conditioned medium of BRCA1(wt) fibroblasts to promote cell proliferation in an epithelial and a cancer cell line. Our data demonstrate, that a CAF-like state is not an exclusive feature of tumor-associated tissue but also exists in healthy tissue with tumor suppressor deficiency. The naturally occurring phenomenon of twin fibroblasts differing in their BRCA1 methylation status revealed to be a unique powerful tool for exploring tumor suppressor deficiency-related changes in healthy tissue, reinforcing their significance for cancer predisposition.

  18. CAF-like state in primary skin fibroblasts with constitutional BRCA1 epimutation sheds new light on tumor suppressor deficiency-related changes in healthy tissue.

    PubMed

    Etzold, Anna; Galetzka, Danuta; Weis, Eva; Bartsch, Oliver; Haaf, Thomas; Spix, Claudia; Itzel, Timo; Schweiger, Susann; Strand, Dennis; Strand, Susanne; Zechner, Ulrich

    2016-01-01

    Constitutive epimutations of tumor suppressor genes are increasingly considered as cancer predisposing factors equally to sequence mutations. In light of the emerging role of the microenvironment for cancer predisposition, initiation, and progression, we aimed to characterize the consequences of a BRCA1 epimutation in cells of mesenchymal origin. We performed a comprehensive molecular and cellular comparison of primary dermal fibroblasts taken from a monozygous twin pair discordant for recurrent cancers and BRCA1 epimutation, whose exceptional clinical case we previously reported in this journal. Comparative transcriptome analysis identified differential expression of extracellular matrix-related genes and pro-tumorigenic growth factors, such as collagens and CXC chemokines. Moreover, genes known to be key markers of so called cancer-associated fibroblasts (CAFs), such as ACTA2, FAP, PDPN, and TNC, were upregulated in fibroblasts of the affected twin (BRCA1(mosMe)) in comparison to those of the healthy twin (BRCA1(wt)). Further analyses detected CAF-typical cellular features, including an elevated growth rate, enhanced migration, altered actin architecture and increased production of ketone bodies in BRCA1(mosMe) fibroblasts compared to BRCA1(wt) fibroblasts. In addition, conditioned medium of BRCA1(mosMe) fibroblasts was more potent than conditioned medium of BRCA1(wt) fibroblasts to promote cell proliferation in an epithelial and a cancer cell line. Our data demonstrate, that a CAF-like state is not an exclusive feature of tumor-associated tissue but also exists in healthy tissue with tumor suppressor deficiency. The naturally occurring phenomenon of twin fibroblasts differing in their BRCA1 methylation status revealed to be a unique powerful tool for exploring tumor suppressor deficiency-related changes in healthy tissue, reinforcing their significance for cancer predisposition. PMID:26949839

  19. Stress and morphine affect survival of rats challenged with a mammary ascites tumor (MAT 13762B).

    PubMed

    Lewis, J W; Shavit, Y; Terman, G W; Gale, R P; Liebeskind, J C

    We have previously shown that exposure to inescapable footshock stress decreases survival of rats injected with a mammary ascites tumor (MAT 13762B). This increased vulnerability to the tumor challenge was prevented by an opiate antagonist, naltrexone, suggesting mediation by opioid peptides. Supporting this hypothesis, we now report that a high dose of an opiate agonist, morphine, also reduces survival of rats given the same tumor. This effect shows tolerance after 14 daily injections. The adverse effect of stress, however, did not show other signs of opioid involvement: it manifested neither tolerance with repeated stress exposures nor cross-tolerance in morphine-tolerant rats. Our recent findings that stress and morphine reduce natural killer cell cytotoxicity in a similar fashion suggest an immune mechanism that may explain the present results.

  20. Γ-aminobutyric acid receptors affect the progression and migration of tumor cells.

    PubMed

    Zhang, Xiaoxue; Du, Zuoyi; Liu, Jun; He, Jianxing

    2014-12-01

    Γ-aminobutyric acid (GABA) is a multifunctional molecule found in the nervous system and non-neuronal tissues. GABA receptors combine with GABA molecules and transmit signal stimuli into cells. In addition to traditional neurotransmission and regulation of secretion, GABA and GABA receptors are involved in cell differentiation and proliferation throughout peripheral organs, as well as in tumorigenesis. The exact mechanism of the GABAergic system in regulating tumor development is unclear, but many studies have revealed that GABA receptors exert critical regulative effects on tumor cell proliferation and migration. In this review, the molecular structure, distribution and biological function of GABA receptors associated with tumorigenesis are described. Recent advances in the elucidation of mechanisms underlying GABAergic signaling control over tumor growth are also discussed.

  1. Rheumatic manifestations of primary and metastatic bone tumors and paraneoplastic bone disease.

    PubMed

    Waimann, Christian A; Lu, Huifang; Suarez Almazor, Maria E

    2011-11-01

    Bone tumors can show a wide range of nonspecific rheumatic manifestations. The presence of unexplained or atypical chronic bone pain, an enlarging bone mass, neurovascular compression syndromes, or pathologic fractures should alert us to the possibility of a bone tumor causing these symptoms. These patients must undergo a complete physical examination; adequate imaging; and, if needed, a biopsy to confirm their diagnosis and offer them an opportune treatment. In addition, bone tumors and other malignancies can present remote clinical manifestations and unusual laboratory findings (eg, HOA, hypophosphatemia, hyperphosphaturia, and hypercalcemia) that may be the first and early manifestation of an occult cancer. These findings should motivate a cancer screening according to age, sex, and personal history. Cancer therapies also have a big impact on bone health, increasing the risk of osteoporosis, osteomalacia, and/or osteonecrosis. Rheumatologists should be aware of possible long-term adverse events of cancer treatment to avoid future complications.

  2. Subgingival bacteria in a case of prepubertal periodontitis, before and one year after extractions of the affected primary teeth.

    PubMed

    Ram, D; Bimstein, E

    1994-01-01

    The treatment of children with prepubertal periodontitis (PP), may be complicated by the extent of the lesions and the possibility of tetracycline stain of the developing permanent dentition. Therefore, with the purpose of preventing the infection of permanent teeth during the mixed dentition, it has been recommended that the treatment of children with PP, should include the early extraction of the primary teeth affected with alveolar bone loss (ABL). Still, there is little evidence which confirms that extraction of the affected primary teeth do in fact reduce the periodonto-pathogens load of the subgingival plaque. The present study reports values of colony forming units (CFU) of total anaerobic bacteria, Actinobacillus actynomicetemcomitans (Aa) and Porphyromonas gingivalis (Pg) from the subgingival plaque from a child with PP, collected immediately before and 1 year after extractions of the primary teeth affected with ABL. CFU of Aa and Pg developed only from the subgingival plaque collected before the extraction of the primary teeth affected with ABL. These findings suggest that in cases of PP, extraction of the affected primary teeth may reduce the possibility of infection of the periodontum of the permanent teeth during the mixed dentition period.

  3. Should Patient Setup in Lung Cancer Be Based on the Primary Tumor? An Analysis of Tumor Coverage and Normal Tissue Dose Using Repeated Positron Emission Tomography/Computed Tomography Imaging

    SciTech Connect

    Elmpt, Wouter van; Oellers, Michel; Lambin, Philippe; De Ruysscher, Dirk

    2012-01-01

    Purpose: Evaluation of the dose distribution for lung cancer patients using a patient setup procedure based on the bony anatomy or the primary tumor. Methods and materials: For 39 patients with non-small-cell lung cancer, the planning fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scan was registered to a repeated FDG-PET/CT scan made in the second week of treatment. Two patient setup methods were analyzed based on the bony anatomy or the primary tumor. The original treatment plan was copied to the repeated scan, and target and normal tissue structures were delineated. Dose distributions were analyzed using dose-volume histograms for the primary tumor, lymph nodes, lungs, and spinal cord. Results: One patient showed decreased dose coverage of the primary tumor caused by progressive disease and required replanning to achieve adequate coverage. For the other patients, the minimum dose to the primary tumor did not significantly deviate from the planned dose: -0.2 {+-} 1.7% (p = 0.71) and -0.1 {+-} 1.7% (p = 0.85) for the bony anatomy setup and the primary tumor setup, respectively. For patients (n = 31) with nodal involvement, 10% showed a decrease in minimum dose larger than 5% for the bony anatomy setup and 13% for the primary tumor setup. The mean lung dose exceeded the maximum allowed 20 Gy in 21% of the patients for the bony anatomy setup and in 13% for the primary tumor setup, whereas for the spinal cord this occurred in 10% and 13% of the patients, respectively. Conclusions: In 10% and 13% of patients with nodal involvement, setup based on bony anatomy or primary tumor, respectively, led to important dose deviations in nodal target volumes. Overdosage of critical structures occurred in 10-20% of the patients. In cases of progressive disease, repeated imaging revealed underdosage of the primary tumor. Development of practical ways for setup procedures based on repeated high-quality imaging of all tumor sites during radiotherapy

  4. [Surgical treatment of primary multiple tumoral lesions of the large intestine].

    PubMed

    Todurov, I M; Belianskiĭ, L S; Perekhrestenko, A V

    2008-03-01

    Experience of treatment of 37 patients, suffering primarily-multiple cancer of large intestine, including 17--with synchronous and 20--metachronous tumors, and an acute obturational ileus of large intestine, is presented. There was conducted the analysis and peculiarities of surgical tactics suggested as well as various methods of such patients treatment were determined. The investigation results trust the necessity of application of individual perioperative tactics in patients, suffering primarily-multiple tumors of large intestine leading to achieve better outcomes of their surgical treatment.

  5. Histopathological, immunohistochemical, and image analytic parameters characterizing the stromal component in primary and recurrent giant cell tumor of bone.

    PubMed

    Saxena, Charu Chandra; Safaya, Rajni; Kawatra Madan, Neha; Khan, Shah Alam; Iyer, Venkateswaran K

    2016-01-01

    Giant cell tumor (GCT) of bone is a benign locally aggressive tumor whose biological behavior is unpredictable. Currently, there are no definitive clinical, histological, biochemical, or immunological parameters that can predict its behavior. This study was undertaken to examine whether delineation of reactive and neoplastic stromal component of GCT can help in this regard. 55 cases of GCT (30 primary, 25 recurrent) were subjected to histopathological grading, immunohistochemistry, and image analysis. Spindling of stroma was more frequent in recurrent GCT with 64% cases having more than 50% spindled stroma (p < 0.001). Number of mitosis/10 HPF and higher grade were more in recurrent GCT. Mean percentage positivity for CD68 (38.36%) and α1-ACT (70.86%) was higher in primary than recurrent GCT. PCNA and MiB-1 labeling indices were higher in recurrent (42.62% and 9.18%, respectively) than in primary group (24.75% and 7.7%, respectively). A single numerical parameter encompassing stromal cell population and its proliferation was derived as ratio of PCNA/CD68 and PCNA/α1-ACT. Both ratios were higher in recurrent (0.81 ± 0.38; 1.58 ± 1.50) than in primary GCT (0.58 ± 0.62; 0.34 ± 0.29) (p = 0.002; 0.01). On image analysis, parameters significantly different between the two groups were nuclear area and nuclear integrated optical density. It was thus concluded that recurrent GCT shows higher grade, increased mitosis, more spindling, fewer reactive components, and higher proliferation than primary GCT. Delineation of reactive component (α1-ACT positive) and proliferating component (PCNA positive cells) using immunohistochemistry with calculation of the PCNA/ACT ratio delivers more information than image analysis.

  6. Does Cost of Schooling Affect Enrollment by the Poor? Universal Primary Education in Uganda.

    ERIC Educational Resources Information Center

    Deininger, Klaus

    2003-01-01

    Evaluates the impact of Uganda's program of "Universal Primary Education," which, starting from 1997, dispensed with fees for primary enrollment. Finds, for example, that while the program was associated with a dramatic increase in primary school attendance and that inequalities in attendance related to gender, income, and region were…

  7. Primary Tumor Volume Is an Important Predictor of Clinical Outcomes Among Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Treated With Definitive Chemoradiotherapy

    SciTech Connect

    Strongin, Anna; Yovino, Susannah; Taylor, Rodney; Wolf, Jeffrey; Cullen, Kevin; Zimrin, Ann; Strome, Scott; Regine, William; Suntharalingam, Mohan

    2012-04-01

    Purpose: The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy. Methods and Materials: A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis. Results: The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm{sup 3}, and patients with a tumor volume <35 cm{sup 3} had a significantly better prognosis than those with a tumor volume >35 cm{sup 3} at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume <35 cm{sup 3} had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p = < .001). On multivariate analysis, the primary tumor volume was the best predictor of recurrence (hazard ratio 4.7, 95% confidence interval 1.9-11.6; p = .001) and survival (hazard ratio 10.0, 95% confidence interval 2.9-35.1; p = < .001). In contrast, the T stage and N stage were not significant factors. Analysis of variance revealed that tumors with locoregional failure were on average 21.6 cm{sup 3} larger than tumors without locoregional failure (p = .028) and 27.1-cm{sup 3} larger than tumors that recurred as distant metastases (p = .020). Conclusion: The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer

  8. Compartmentalized Epidermal Activation of β-Catenin Differentially Affects Lineage Reprogramming and Underlies Tumor Heterogeneity.

    PubMed

    Kretzschmar, Kai; Weber, Christine; Driskell, Ryan R; Calonje, Eduardo; Watt, Fiona M

    2016-01-12

    Wnt/β-catenin activation in adult epidermis can induce new hair follicle formation and tumor development. We used lineage tracing to uncover the relative contribution of different stem cell populations. LGR6(+) and LRIG1(+) stem cells contributed to ectopic hair follicles formed in the sebaceous gland upon β-catenin activation, whereas LGR5(+) cells did not. Lgr6, but not Lrig1 or Lgr5, was expressed in a subpopulation of interfollicular epidermal cells that were competent to form new hair follicles. Oncogenic β-catenin expression in LGR5(+) cells led to formation of pilomatricomas, while LRIG1(+) cells formed trichoadenomas and LGR6(+) cells formed dermatofibromas. Tumor formation was always accompanied by a local increase in dermal fibroblast density and transient extracellular matrix remodeling. However, each tumor had a distinct stromal signature in terms of immune cell infiltrate and expression of CD26 and CD44. We conclude that compartmentalization of epidermal stem cells underlies different responses to β-catenin and skin tumor heterogeneity. PMID:26771241

  9. Retroperitoneal primary mucinous adenocarcinoma with a mural nodule of anaplastic tumor: a case report and literature review.

    PubMed

    Mikami, Mikio; Tei, Chisei; Takehara, Kyoko; Komiyama, Shinichi; Suzuki, Atsushi; Hirose, Takanori

    2003-04-01

    A 38-year-old female presented with a lower abdominal mass. During the operation the mass was found to be retroperitoneal and was excised. Gross examination revealed a mucin-containing cystic lesion with a mural nodule. On microscopic examination, the cystic areas were lined by an invasive mucinous adenocarcinoma and the nodule was composed of an anaplastic sarcomatoid tumor that was immunoreactive for cytokeratin. This present case is the 21st example of a retroperitoneal primary mucinous cystadenocarcinoma and the fourth with a mural nodule. Three of four cases with a mural nodule, including our case, had a rapidly fatal outcome.

  10. Fine-needle aspiration for the diagnosis of primary epithelial tumors of the lacrimal gland and ocular adnexa.

    PubMed

    Sturgis, C D; Silverman, J F; Kennerdell, J S; Raab, S S

    2001-02-01

    Results of fine-needle aspiration (FNA) of solid-tissue neoplasms arising in the periocular glands are infrequently reported in the literature. To our knowledge, no previous series relating to this topic exist. Neoplastic processes that arise in the semiconfined area of the orbit behave as space-occupying lesions. Such lesions can exert significant pressure on the globe, be responsible for altered vision, and result in proptosis. When noninvasive techniques fail to confirm or rule out the suspicion of a neoplastic lacrimal or adnexal lesion, FNA may be of use in establishing a diagnosis in an efficient, reliable, timely, cost-effective, and safe manner. During the 14-yr interval from 1986-1999, 77 orbital/ocular needle aspiration biopsies were conducted by staff ophthalmologists at Allegheny General Hospital (Pittsburgh, PA). Review of the diagnoses for these specimens revealed seven primary solid-tissue lesions of the lacrimal gland and other adnexal glands, all arising in adult patients (age range, 45-92 yr; mean age, 74 yr). Primary lacrimal and adnexal gland neoplasms were found to represent approximately 9% of orbital fine-needle aspirations (7/79). The 7 cases included 3 lacrimal gland lesions diagnosed as benign mixed tumors, 3 lesions diagnosed as adenoid cystic carcinoma of the lacrimal gland, and 1 tumor diagnosed as sebaceous carcinoma of the meibomian holocrine glands. Cytologic diagnoses were rendered using standard criteria for salivary gland-type tumors. Tissue confirmation was available from surgical follow-up in 4 of the 7 cases, with 100% correlation. Although primary neoplasms of the lacrimal gland and glands of the eyelids are rare, accurate diagnoses of such lesions may be established with minimally invasive aspiration techniques. Preoperative aspiration biopsy diagnoses provide a great advantage to ophthalmic surgeons who routinely operate in a conservative fashion in an area of the body requiring great attention to cosmesis. Our experience

  11. Xenogenization by tetanus toxoid loading into lymphoblastoid cell lines and primary human tumor cells mediated by polycations and liposomes.

    PubMed

    Felzmann, T; Buchberger, M; Jechlinger, M; Kircheis, R; Wagner, E; Gadner, H

    2000-12-20

    We explored the potential of the xenogenization concept as an adjuvant procedure in anti-tumor immunity. To mediate effective loading we used polyarginine (pArg) molecules of various degrees of polymerization, cationic liposomes, or chimeric molecules of transferrin (Tf) and the polycation polyethyleneimine (PEI). Tetanus toxoid (TT) was loaded onto primary human leukemia cells, culture adapted primary human neuroblastoma cells, and human lymphoblastoid cell lines (LCLs) with high efficiency by all procedures. Trypsin treatment of loaded cells provided evidence that only liposomes and Tf-PEI mediated internalization of TT. Lymphocytes primed with xenogenized LCLs and challenged with unmodified LCLs showed increased IFNgamma secretion compared with lymphocytes primed with non-xenogenized LCLs.

  12. Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study.

    PubMed

    van Hoesel, Anneke Q; van de Velde, Cornelis J H; Kuppen, Peter J K; Liefers, Gerrit Jan; Putter, Hein; Sato, Yusuke; Elashoff, David A; Turner, Roderick R; Shamonki, Jaime M; de Kruijf, Esther M; van Nes, Johanna G H; Giuliano, Armando E; Hoon, Dave S B

    2012-08-01

    Long interspersed element 1 (LINE-1), a non-coding genomic repeat sequence, methylation status can influence tumor progression. In this study, the clinical significance of LINE-1 methylation status was assessed in primary breast cancer in young versus old breast cancer patients. LINE-1 methylation index (MI) was assessed by absolute quantitative assessment of methylated alleles (AQAMA) PCR assay. Initially, LINE-1 MI was assessed in a preliminary study of 235 tissues representing different stages of ductal breast cancer development. Next, an independent cohort of 379 primary ductal breast cancer patients (median follow-up 18.9 years) was studied. LINE-1 hypomethylation was shown to occur in DCIS and invasive breast cancer. In primary breast cancer it was associated with pathological tumor stage (p = 0.026), lymph node metastasis (p = 0.022), and higher age at diagnosis (>55, p < 0.001). In multivariate analysis, LINE-1 hypomethylation was associated with decreased OS (HR 2.19, 95 % CI 1.17-4.09, log-rank p = 0.014), DFS (HR 2.05, 95 % CI 1.14-3.67, log-rank p = 0.016) and increased DR (HR 2.83, 95 % CI 1.53-5.21, log-rank p = 0.001) in younger (≤55 years), but not older patients (>55 years). LINE-1 analysis of primary breast cancer demonstrated cancer-related age-dependent hypomethylation. In patients ≤55 years, LINE-1 hypomethylation portends a high-risk of DR.

  13. Steroid replacement in primary adrenal failure does not appear to affect circulating adipokines.

    PubMed

    Fichna, Marta; Fichna, Piotr; Gryczyńska, Maria; Czarnywojtek, Agata; Żurawek, Magdalena; Ruchała, Marek

    2015-03-01

    Despite continuous efforts for an optimal steroid replacement, recent observations suggest increased cardiometabolic risk and related mortality in primary adrenal insufficiency (PAI). Adipokines are peptides from the adipose tissue, markers of cardiometabolic dysfunction. This study was aimed to evaluate serum levels of adipokines: leptin, adiponectin, and resistin in PAI during conventional steroid substitution. The analysis comprised 63 patients (mean age 42.7 ± 14.1 years) and 63 healthy controls. Serum adipokines, lipid profile, and plasma glucose were assessed in both cohorts. ACTH, serum insulin, HOMA-IR, DHEA-S, cortisol and 24 h urinary free cortisol were determined in PAI. Body mass composition was analyzed by Dual-Energy X-ray Absorptiometry. Mean BMI in the control group was 24.1 ± 3.9 kg/m(2) and 23.7 ± 3.9 kg/m(2) in the PAI cohort. Serum leptin and adiponectin levels were similar in both groups, whereas resistin appeared significantly lower among affected subjects (p = 0.0002). Its levels were weakly correlated with HOMA-IR (p = 0.048). Leptin was independently correlated with fasting insulin, HOMA-IR, BMI, and body fat (p < 0.001). At the multiple regression analysis only weight (p = 0.017), total and HDL cholesterol (p < 0.001) appeared significant predictors of adiponectin level. No adipokine correlations with serum cortisol or daily hydrocortisone dose were found. Patients receiving DHEA substitution displayed lower leptin and adiponectin levels (p < 0.05). In conclusion, our study did not provide evidence of an adverse adipokine profile in patients with PAI under conventional glucocorticoid replacement. Serum adipokines in treated PAI follow similar correlations to those reported in healthy subjects. Further prospective studies are warranted to verify and explain plausible excess of cardiovascular mortality in PAI. PMID:25129652

  14. Variation in NGFB is Associated with Primary Affective Disorders in Women

    PubMed Central

    Cui, Donghong; Zhang, Huiping; Yang, Bao-Zhu; Listman, Jennifer B.; Li, Dawei; Price, Lawrence H.; Carpenter, Linda L.; Tyrka, Audrey R.; Anton, Raymond F.; Kranzler, Henry R.; Gelernter, Joel

    2011-01-01

    Affective disorders (AFDs) are highly comorbid with substance dependence (SD) and both are genetically influenced. However, the specific etiology of the comorbidity is not well understood. We genotyped an array of 1,350 single nucleotide polymorphisms (SNPs) in or near 130 genes in 868 European-Americans (EAs), including 182 individuals with primary AFDs (PAFDs), 214 with SD comorbid with AFD (CAFD), and 472 screened controls. NGFB, which encodes nerve growth factor β and was represented in the array by 15 SNPs, showed the strongest evidence of association, but only among women with PAFDs. Six of the SNPs showed a nominally significant association with PAFDs in women (Ps = 0.0007–0.01); three (rs2856813, rs4332358, and rs10776799) were empirically significant based on 1,000,000 permutations (Ps = 0.008–0.015). Seven haplotypes were significantly associated with PAFDs in women (Ps = 0.0014–0.01), of which six were significant based on empirical permutation analysis (minimal P = 0.0045). Four diplotypes were significantly associated with PAFDs in women (global Ps = 0.001–0.01). The specific diplotype GG-TC, reconstructed from rs2856813 and rs6678788, showed the strongest evidence of association with PAFDs in women (OR = 4.07, P = 4.2E-05). No SNPs or haplotypes were associated with PAFDs in men or with CAFDs in either sex. We conclude that variation in NGFB is a risk factor for PAFDs in women, but not for CAFD. PMID:21294249

  15. [Amelioration of secondary hypertrophic osteoarthropathy following tumor resection in a patient with primary lung cancer].

    PubMed

    Akizuki, M; Homma, M

    1991-06-01

    A 41 year-old female presented with swelling of lower extremities and polyarthralgia involving both knee joints. Physical examination revealed presence of finger clubbing, tenderness and pain-on-motion in knee and foot joints. A chest X-ray film showed a solitary tumor in the right mid-lung field. There were subperiosteal new bone formation and radioisotope accumulation in the legs bilaterally. The clubbing, periostitis and arthritis confirmed a diagnosis of hypertrophic osteoarthropathy. Adenocarcinoma was the biopsy diagnosis of the lung tumor. The characteristic features of hypertrophic osteoarthropathy resolved after surgical resection of the pulmonary lesion followed by chemotherapy. This case demonstrates a typical example of identification of a treatable malignant condition by rheumatic symptoms.

  16. Primary solitary fibrous tumors of liver: a case report and literature review

    PubMed Central

    2013-01-01

    A 42-year-old male presented right upper abdomen pain for more than 6 days, which misdiagnose calculus of intrahepatic duct and acute cholecystitis. An approximately 1.5 cm x 1.0 cm x 1.0 cm nodule was found and resected in left lateral lobe of hepatic. Pathological examination showed spindle cell and fibroblast -like cells within the collagenous stroma. Immunohistochemically, these spindle tumor cells showed diffuse Vim and Bcl-2 positive reactivity, but S-100 protein and HMB45 were negative. The post-operative course was uneventful. Solitary fibrous tumors of the liver, although rare, should be differentiated from mesenchymal lesions of the liver. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4214341041091088. PMID:24294990

  17. Advances in the biology of bone metastasis: how the skeleton affects tumor behavior.

    PubMed

    Sterling, Julie A; Edwards, James R; Martin, T John; Mundy, Gregory R

    2011-01-01

    It is increasingly evident that the microenvironment of bone can influence the cancer phenotype in many ways that favor growth in bone. The ability of cancer cells to adhere to bone matrix and to promote osteoclast formation are key requirements for the establishment and growth of bone metastases. Several cytokine products of breast cancers (e.g. PTHrP, IL-11, IL-8) have been shown to act upon host cells of the bone microenvironment to promote osteoclast formation, allowing for excessive bone resorption. The increased release of matrix-derived growth factors, especially TGF-β, acts back upon the tumor to facilitate further tumor expansion and enhance cytokine production, and also upon osteoblasts to suppress bone formation. This provides a self-perpetuating cycle of bone loss and tumor growth within the skeleton. Other contributing factors favoring tumor metastasis and colonization in bone include the unique structure and stiffness of skeletal tissue, along with the diverse cellular composition of the marrow environment (e.g. bone cells, stromal fibroblasts, immune cells), any of which can contribute to the phenotypic changes that can take place in metastatic deposits that favor their survival. Additionally, it is also apparent that breast cancer cells begin to express different bone specific proteins as well as proteins important for normal breast development and lactation that allow them to grow in bone and stimulate bone destruction. Taken together, these continually emerging areas of study suggest new potential pathways important in the pathogenesis of bone metastasis and potential areas for targeting therapeutics.

  18. Mining metastasis related genes by primary-secondary tumor comparisons from large-scale databases

    PubMed Central

    Kim, Sangwoo; Lee, Doheon

    2009-01-01

    Background Metastasis is the most dangerous step in cancer progression and causes more than 90% of cancer death. Although many researchers have been working on biological features and characteristics of metastasis, most of its genetic level processes remain uncertain. Some studies succeeded in elucidating metastasis related genes and pathways, followed by predicting prognosis of cancer patients, but there still is a question whether the result genes or pathways contain enough information and noise features have been controlled appropriately. Methods We set four tumor type classes composed of various tumor characteristics such as tissue origin, cellular environment, and metastatic ability. We conducted a set of comparisons among the four tumor classes followed by searching for genes that are consistently up or down regulated through the whole comparisons. Results We identified four sets of genes that are consistently differently expressed in the comparisons, each of which denotes one of four cellular characteristics respectively – liver tissue, colon tissue, liver viability and metastasis characteristics. We found that our candidate genes for tissue specificity are consistent with the TiGER database. And we also found that the metastasis candidate genes from our method were more consistent with the known biological background and independent from other noise features. Conclusion We suggested a new method for identifying metastasis related genes from a large-scale database. The proposed method attempts to minimize the influences from other factors except metastatic ability including tissue originality and tissue viability by confining the result of metastasis unrelated test combinations. PMID:19344478

  19. Interactive effect of negative affectivity and anxiety sensitivity in terms of mental health among Latinos in primary care.

    PubMed

    Zvolensky, Michael J; Paulus, Daniel J; Bakhshaie, Jafar; Garza, Monica; Ochoa-Perez, Melissa; Medvedeva, Angela; Bogiaizian, Daniel; Robles, Zuzuky; Manning, Kara; Schmidt, Norman B

    2016-09-30

    From a public health perspective, primary care medical settings represent a strategic location to address mental health disapirty among Latinos. Yet, there is little empirical work that addresses affective vulnerability processes for mental health problems in such settings. To help address this gap in knowledge, the present investigation examined an interactive model of negative affectivity (tendency to experience negative mood states) and anxiety sensitivity (fear of the negative consequences of aversive sensations) among a Latino sample in primary care in terms of a relatively wide range of anxiety/depression indices. Participants included 390 Latino adults (Mage=38.7, SD=11.3; 86.9% female; 95.6% reported Spanish as first language) from a primary care health clinic. Primary dependent measures included depressive, suicidal, social anxiety, and anxious arousal symptoms, number of mood and anxiety disorders, and disability. Consistent with prediction, the interaction between negative affectivity and anxiety sensitivity was significantly related to suicidal, social anxiety, and anxious arousal symptoms, as well as number of mood/anxiety diagnoses and disability among the primary care Latino sample. The form of the interactions indicated a synergistic effect, such that the greatest levels of each outcome were found among those with high negative affectivity and high anxiety sensitivity. There was a trending interaction for depressive symptoms. Overall, these data provide novel empirical evidence suggesting that there is a clinically-relevant interplay between anxiety sensitivity and negative affectivity in regard to the expression of anxiety and depressive symptoms among a Latino primary care sample. PMID:27359301

  20. Electrotransfer of gene encoding endostatin into normal and neoplastic mouse tissues: inhibition of primary tumor growth and metastatic spread.

    PubMed

    Cichoń, Tomasz; Jamrozy, Laura; Glogowska, Joanna; Missol-Kolka, Ewa; Szala, Stanisław

    2002-09-01

    Electroporation-mediated gene transfer relies upon direct delivery of plasmids into cells permeabilized by electric fields, a method more efficient than transfer using nonviral vectors, although neither approaches the transfer efficiency of viral vectors. Here we studied electrotransfer of a gene encoding an angiogenesis inhibitor (endostatin) into primary tumors and muscle tissues, which would serve as a site of synthesis and secretion into the bloodstream of a therapeutic antimetastatic protein with systemic effects. Optimum electroporation conditions (voltage, number and duration of impulses, separation of caliper electrodes) were first established to maximize expression of a reporter gene transferred into murine Renca kidney carcinoma, B16(F10) melanoma, or skeletal muscle tissues. In neoplastic tissues, electrotransfer of plasmid DNA was far more efficient than electroporation with lipoplexes, but no differences between naked DNA and lipoplexes were found in case of electroporated muscles. We then studied the electrotransfer of plasmid DNA carrying the endostatin gene into pre-established experimental Renca tumors. A significant inhibition of tumor growth was observed in animals electroporated with this construct. Electrotransfer of the endostatin gene into muscle tissues resulted in reduced numbers of experimental B16(F10) metastases in the lungs. This study clearly shows that electroporation may be used to efficiently transfer antiangiogenic genes into both normal and neoplastic tissues. PMID:12189527

  1. Therapeutic Touch Has Significant Effects on Mouse Breast Cancer Metastasis and Immune Responses but Not Primary Tumor Size.

    PubMed

    Gronowicz, Gloria; Secor, Eric R; Flynn, John R; Jellison, Evan R; Kuhn, Liisa T

    2015-01-01

    Evidence-based integrative medicine therapies have been introduced to promote wellness and offset side-effects from cancer treatment. Energy medicine is an integrative medicine technique using the human biofield to promote well-being. The biofield therapy chosen for study was Therapeutic Touch (TT). Breast cancer tumors were initiated in mice by injection of metastatic 66cl4 mammary carcinoma cells. The control group received only vehicle. TT or mock treatments were performed twice a week for 10 minutes. Two experienced TT practitioners alternated treatments. At 26 days, metastasis to popliteal lymph nodes was determined by clonogenic assay. Changes in immune function were measured by analysis of serum cytokines and by fluorescent activated cells sorting (FACS) of immune cells from the spleen and lymph nodes. No significant differences were found in body weight gain or tumor size. Metastasis was significantly reduced in the TT-treated mice compared to mock-treated mice. Cancer significantly elevated eleven cytokines. TT significantly reduced IL-1-a, MIG, IL-1b, and MIP-2 to control/vehicle levels. FACS demonstrated that TT significantly reduced specific splenic lymphocyte subsets and macrophages were significantly elevated with cancer. Human biofield therapy had no significant effect on primary tumor but produced significant effects on metastasis and immune responses in a mouse breast cancer model.

  2. Therapeutic Touch Has Significant Effects on Mouse Breast Cancer Metastasis and Immune Responses but Not Primary Tumor Size

    PubMed Central

    Gronowicz, Gloria; Secor, Eric R.; Flynn, John R.; Jellison, Evan R.; Kuhn, Liisa T.

    2015-01-01

    Evidence-based integrative medicine therapies have been introduced to promote wellness and offset side-effects from cancer treatment. Energy medicine is an integrative medicine technique using the human biofield to promote well-being. The biofield therapy chosen for study was Therapeutic Touch (TT). Breast cancer tumors were initiated in mice by injection of metastatic 66cl4 mammary carcinoma cells. The control group received only vehicle. TT or mock treatments were performed twice a week for 10 minutes. Two experienced TT practitioners alternated treatments. At 26 days, metastasis to popliteal lymph nodes was determined by clonogenic assay. Changes in immune function were measured by analysis of serum cytokines and by fluorescent activated cells sorting (FACS) of immune cells from the spleen and lymph nodes. No significant differences were found in body weight gain or tumor size. Metastasis was significantly reduced in the TT-treated mice compared to mock-treated mice. Cancer significantly elevated eleven cytokines. TT significantly reduced IL-1-a, MIG, IL-1b, and MIP-2 to control/vehicle levels. FACS demonstrated that TT significantly reduced specific splenic lymphocyte subsets and macrophages were significantly elevated with cancer. Human biofield therapy had no significant effect on primary tumor but produced significant effects on metastasis and immune responses in a mouse breast cancer model. PMID:26113869

  3. Expanding the Spectrum of Renal Tumors in Children: Primary Renal Myoepithelial Carcinomas With a Novel EWSR1-KLF15 Fusion.

    PubMed

    Cajaiba, Mariana M; Jennings, Lawrence J; Rohan, Stephen M; Leuer, Katrin M; Anagnost, Miran R; Fahner, James B; Fulton, Barbara K; Geller, James I; Perlman, Elizabeth J

    2016-03-01

    We report the first 2 examples of primary renal myoepithelial carcinoma (MEC), both occurring in children. Both tumors had the unique morphologic features, immunophenotype, and EWSR1 gene rearrangements supporting the diagnosis. In keeping with the previous observations of an aggressive behavior in pediatric MEC, both cases presented with advanced local stage and distant metastases at the time of diagnosis. The EWSR1 translocation partner was identified as the Kruppel-like factor 15 (KLF15) gene in both tumors, and the novel EWSR1-KLF15 gene fusion transcripts were verified using reverse transcription polymerase chain reaction and Sanger dideoxy sequencing. So far, a role for KLF15 in carcinogenesis has not been established, in contrast to other members of the Kruppel-like family of transcription factors, and no rearrangements involving this gene have been documented to our knowledge. These findings expand the spectrum of pediatric renal tumors to include MEC. The characterization of novel EWSR1-KLF15 fusion transcripts carries important diagnostic implications, as well as clues to understand the pathogenesis of these neoplasms. PMID:26523541

  4. Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer

    ClinicalTrials.gov

    2016-07-22

    Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

  5. Multiple myeloma cell lines and primary tumors proteoma: protein biosynthesis and immune system as potential therapeutic targets

    PubMed Central

    Mazzotti, Diego Robles; Evangelista, Adriane Feijó; Braga, Walter Moisés Tobias; de Lourdes Chauffaille, Maria; Leme, Adriana Franco Paes; Colleoni, Gisele Wally Braga

    2015-01-01

    Despite great advance in multiple myeloma (MM) treatment since 2000s, it is still an incurable disease and novel therapies are welcome. Therefore, the purpose of this study was to explore MM plasma cells' (MM-PC) proteome, in comparison with their normal counterparts (derived from palatine tonsils of normal donors, ND-PC), in order to find potential therapeutic targets expressed on the surface of these cells. We also aimed to evaluate the proteome of MM cell lines with different genetic alterations, to confirm findings obtained with primary tumor cells. Bone marrow (BM) samples from eight new cases of MM and palatine tonsils from seven unmatched controls were submitted to PC separation and, in addition to two MM cell lines (U266, RPMI-8226), were submitted to protein extraction for mass spectrometry analyses. A total of 81 proteins were differentially expressed between MM-PC and ND-PC - 72 upregulated and nine downregulated; U266 vs. RPMI 8226 cell lines presented 61 differentially expressed proteins - 51 upregulated and 10 downregulated. On primary tumors, bioinformatics analyses highlighted upregulation of protein biosynthesis machinery, as well as downregulation of immune response components, such as MHC class I and II, and complement receptors. We also provided comprehensive information about U266 and RPMI-8226 cell lines' proteome and could confirm some patients' findings. PMID:26807199

  6. Primary Tumor Resection Is Associated with Improved Survival in Stage IV Colorectal Cancer: An Instrumental Variable Analysis

    PubMed Central

    Xu, Hong; Xia, Zuguang; Jia, Xiaoyan; Chen, Kai; Li, Dapeng; Dai, Yun; Tao, Min; Mao, Yixiang

    2015-01-01

    Primary tumor resection (PTR) is recommended for patients with unresectable stage IV colorectal cancer (CRC) who present with symptoms related to their primary tumor. However, the survival benefit of PTR for asymptomatic patients is controversial. We investigated the change in PTR rates and the contribution of PTR to survival in patients with unresectable stage IV CRC over the past two decades in the United States. Clinicopathological factors and long-term survival were compared for 44 514 patients diagnosed with unresectable stage IV CRC from January 1, 1988, through December 31, 2010, who had or had not undergone PTR. Multivariable Cox regression and the instrumental variable method were used to identify independent factors for survival. Of the 44 514 patients with unresectable stage IV CRC, 27 931 (62.7%) had undergone PTR. The annual rate of PTR decreased from 74.4% to 50.2% diagnosed in 1988 and 2010, and the median overall survival increased for both PTR and non-PTR patients. Instrumental variable analyses revealed that PTR was associated with better overall, cancer-specific, and other-cause survival of patients with unresectable stage IV CRC. PMID:26563729

  7. Multiple myeloma cell lines and primary tumors proteoma: protein biosynthesis and immune system as potential therapeutic targets.

    PubMed

    Fernando, Rodrigo Carlini; de Carvalho, Fabricio; Mazzotti, Diego Robles; Evangelista, Adriane Feijó; Braga, Walter Moisés Tobias; de Lourdes Chauffaille, Maria; Paes Leme, Adriana Franco; Colleoni, Gisele Wally Braga

    2015-11-01

    Despite great advance in multiple myeloma (MM) treatment since 2000s, it is still an incurable disease and novel therapies are welcome. Therefore, the purpose of this study was to explore MM plasma cells' (MM-PC) proteome, in comparison with their normal counterparts (derived from palatine tonsils of normal donors, ND-PC), in order to find potential therapeutic targets expressed on the surface of these cells. We also aimed to evaluate the proteome of MM cell lines with different genetic alterations, to confirm findings obtained with primary tumor cells. Bone marrow (BM) samples from eight new cases of MM and palatine tonsils from seven unmatched controls were submitted to PC separation and, in addition to two MM cell lines (U266, RPMI-8226), were submitted to protein extraction for mass spectrometry analyses. A total of 81 proteins were differentially expressed between MM-PC and ND-PC - 72 upregulated and nine downregulated; U266 vs. RPMI 8226 cell lines presented 61 differentially expressed proteins - 51 upregulated and 10 downregulated. On primary tumors, bioinformatics analyses highlighted upregulation of protein biosynthesis machinery, as well as downregulation of immune response components, such as MHC class I and II, and complement receptors. We also provided comprehensive information about U266 and RPMI-8226 cell lines' proteome and could confirm some patients' findings. PMID:26807199

  8. Gastrointestinal stromal tumor and other primary metachronous or synchronous neoplasms as a suspicion criterion for syndromic setting.

    PubMed

    Ponti, Giovanni; Luppi, Gabriele; Martorana, Davide; Rossi, Giulio; Losi, Lorena; Bertolini, Federica; Sartori, Giuliana; Pellacani, Giovanni; Seidenari, Stefania; Boni, Elisa; Neri, Tauro Maria; Silini, Enrico; Tamburini, Elisa; Maiorana, Antonio; Conte, Pier Franco

    2010-02-01

    Gastrointestinal stromal tumors (GISTs) may be sporadic or inherited. Although KIT and PDGFRA activating mutations are the oncogenic mechanisms in most sporadic and inherited GISTs, a small subset of GISTs are negative for both. Besides the classical Familial GIST Syndrome, GIST can occur as part of multi-neoplastic disease. The present study was designed to analyze the synchronous and metachronous tumors developed among GIST patients assessed by our institution for GIST Syndrome setting recognition. Patients (n=141) with primary GIST (77 men and 64 women) were recruited between 1988 and 2007 and their clinical and pathological records were reviewed. Mutation analysis of KIT, PDGFRA, NF1 and MMR genes was performed on somatic and peripheral blood DNA. GISTs occurred associated with other primary malignancies in 46 of 141 (32.6%) patients. The most common neoplasms were gastrointestinal and genitourinary. A novel exon 6 germline large deletion of NF1 was identified in the NF1/GIST kindred. The development of GIST associated with other neoplasms is common and diagnosis of peculiar benign associated-neoplasms warrants the search for familial cancer susceptibility. In particular, syndromic or familial settings have to be suspected in the presence of neurofibroma or lung chordoma in C-KIT and PDGFRA negative GIST patients.

  9. Supporting mental health in South African HIV-affected communities: primary health care professionals’ understandings and responses

    PubMed Central

    Burgess, Rochelle Ann

    2015-01-01

    How do practitioners respond to the mental distress of HIV-affected women and communities? And do their understandings of patients’ distress matter? The World Health Organization (WHO) along with advocates from the Movement for Global Mental Health (MGMH) champion a primary mental health care model to address burgeoning mental health needs in resource-poor HIV-affected settings. Whilst a minority of studies have begun to explore interventions to target this group of women, there is a dearth of studies that explore the broader contexts that will likely shape service outcomes, such as health sector dynamics and competing definitions of mental ill-health. This study reports on an in-depth case study of primary mental health services in a rural HIV-affected community in Northern KwaZulu-Natal. Health professionals identified as the frontline staff working within the primary mental health care model (n = 14) were interviewed. Grounded thematic analysis of interview data highlighted that practitioners employed a critical and socially anchored framework for understanding their patients’ needs. Poverty, gender and family relationships were identified as intersecting factors driving HIV-affected patients’ mental distress. In a divergence from existing evidence, practitioner efforts to act on their understandings of patient needs prioritized social responses over biomedical ones. To achieve this whilst working within a primary mental health care model, practitioners employed a series of modifications to services to increase their ability to target the sociostructural realities facing HIV-affected women with mental health issues. This article suggests that beyond attention to the crucial issues of funding and human resources that face primary mental health care, attention must also be paid to promoting the development of policies that provide practitioners with increased and more consistent opportunities to address the complex social realities that frame the mental

  10. Expression of epithelial cell adhesion molecule in carcinoma cells present in blood and primary and metastatic tumors.

    PubMed

    Rao, Chandra G; Chianese, David; Doyle, Gerald V; Miller, M Craig; Russell, Thomas; Sanders, Renouard A; Terstappen, Leon W M M

    2005-07-01

    The epithelial cell adhesion molecule (EpCAM) is involved in homophilic cell-cell adhesion in normal epithelia and is frequently overexpressed in primary and metastatic adenocarcinomas. It has been postulated that during detachment and dissemination of tumor cells, EpCAM may be down-regulated. Circulating tumor cells (CTC) may demonstrate this phenomenon as they have successfully escaped their local microenvironment and entered the circulation. EpCAM expression of CTC was compared to tumor cells in paraffin-embedded tissue arrays containing various benign diseases and carcinomas. EpCAM expression on CTC was determined by flow cytometry (FCM) and by immunohistochemistry (IHC) in paraffin-embedded tissue. To permit comparison of FCM results to those derived by IHC, EpCAM was quantified on cancer cell lines by FCM and then paraffin-embedded cell-blocks of these lines were used as staining guides for IHC analysis of tissue arrays. By IHC, 97% (384/397) of solid tissues analyzed had detectable EpCAM, with 72% of tissues showing antigen expression levels of > or =400,000 EpCAM molecules per cell. FCM analysis of CTC from 100 metastatic carcinoma patients with > or =2 CTC/90 microl blood showed EpCAM expression ranging from 9,900 to 246,000 (mean 49,700) antigens per cell. EpCAM expression was approximately 10-fold lower on CTC as compared to primary and metastatic tissues, suggesting that EpCAM expression is transient and dependent upon the local micro-environment. This supports the hypothesis that this adhesion molecule is down-regulated on carcinoma cells in the circulation.

  11. BDNF is associated with SFRP1 expression in luminal and basal-like breast cancer cell lines and primary breast cancer tissues: a novel role in tumor suppression?

    PubMed

    Huth, Laura; Rose, Michael; Kloubert, Veronika; Winkens, Wiebke; Schlensog, Martin; Hartmann, Arndt; Knüchel, Ruth; Dahl, Edgar

    2014-01-01

    Secreted frizzled related protein 1 (SFRP1) functions as an important inhibitor of the Wnt pathway and is a known tumor suppressor gene, which is epigenetically silenced in a variety of tumors e.g. in breast cancer. However, it is still unclear how SFRP1 exactly affects the Wnt pathway. Our aim was to decipher SFRP1 involvement in biochemical signaling in dependency of different breast cancer subtypes and to identify novel SFRP1-regulated genes. We generated SFRP1 over-expressing in vitro breast cancer models, reflecting the two major subtypes by using basal-like BT20 and luminal-like HER2-positive SKBR3 cells. DNA microarray expression profiling of these models revealed that SFRP1 expression potentially modulates Bone morphogenetic protein- and Smoothened signaling (p<0.01), in addition to the known impact on Wnt signaling. Importantly, further statistical analysis revealed that in dependency of the cancer subtype model SFRP1 may affect the canonical and non-canonical Wnt pathway (p<0.01), respectively. While SFRP1 re-expression generally mediated distinct patterns of transcriptionally induced or repressed genes in BT20 and SKBR3 cells, brain derived neurotrophic factor (BDNF) was identified as a SFRP1 induced gene in both cell lines. Although BDNF has been postulated as a putative oncogene, the co-regulation with SFRP1 indicates a potential suppressive function in breast cancer. Indeed, a positive correlation between SFRP1 and BDNF protein expression could be shown (p<0.001) in primary breast cancer samples. Moreover, TCGA dataset based analysis clearly underscores that BDNF mRNA is down-regulated in primary breast cancer samples predicting a poor prognosis of these patients. In line, we functionally provide evidence that stable BDNF re-expression in basal-like BT20 breast cancer cells blocks tumor cell proliferation. Hence, our results suggest that BDNF might rather mediate suppressive than promoting function in human breast cancer whose mode of action should be

  12. FDG-PET/CT for detection of the unknown primary head and neck tumor.

    PubMed

    Johansen, J; Petersen, H; Godballe, C; Loft, A; Grau, C

    2011-10-01

    The benefit of FDG-PET in addition to standard work-up for carcinoma of unknown primary (CUP) and metastatic neck lesions has been widely described. However, most studies have been of retrospective nature with large heterogeneities in terms of workup standards and patient selection leaving several questions to be answered regarding the real value of PET in CUP. We here present an overview of the literature with focus on the current evidence of FDG-PET in detecting a primary in CUP and discuss the rationale of PET/CT in the diagnostic armamentarium of CUP. PMID:22019707

  13. Evaluation of the Safety and Benefit of Phase I Oncology Trials for Patients With Primary CNS Tumors

    PubMed Central

    Gounder, Mrinal M.; Nayak, Lakshmi; Sahebjam, Solmaz; Muzikansky, Alona; Sanchez, Armando J.; Desideri, Serena; Ye, Xiaobu; Ivy, S. Percy; Nabors, L. Burt; Prados, Michael; Grossman, Stuart; DeAngelis, Lisa M.; Wen, Patrick Y.

    2016-01-01

    Purpose Patients with high-grade gliomas (HGG) are frequently excluded from first-in-human solid tumor trials because of perceived poor prognosis, excessive toxicities, concomitant drug interactions, and poor efficacy. We conducted an analysis of outcomes from select, single-agent phase I studies in patients with HGG. We compared outcomes to pooled analysis of published studies in solid tumors with various molecular and cytotoxic drugs evaluated as single agents or as combinations. Patient and Methods Individual records of patients with recurrent HGG enrolled onto Adult Brain Tumor Consortium trials of single-agent, cytotoxic or molecular agents from 2000 to 2008 were analyzed for baseline characteristics, toxicities, responses, and survival. Results Our analysis included 327 patients with advanced, refractory HGG who were enrolled onto eight trials involving targeted molecular (n = 5) and cytotoxic (n = 3) therapies. At enrollment, patients had a median Karnofsky performance score of 90 and median age of 52 years; 62% were men, 63% had glioblastoma, and the median number of prior systemic chemotherapies was one. Baseline laboratory values were in an acceptable range to meet eligibility criteria. Patients were on the study for a median of two cycles (range, < one to 56 cycles), and 96% were evaluable for primary end points. During cycle 1, grade ≥ 3 nonhematologic and grade ≥ 4 hematologic toxicities were 5% (28 of 565 adverse events) and 0.9% (five of 565 adverse events), respectively, and 66% of these occurred at the highest dose level. There was one death attributed to drug. Overall response rate (complete and partial response) was 5.5%. Median progression-free and overall survival times were 1.8 and 6 months, respectively. Conclusion Patients with HGG who meet standard eligibility criteria may be good candidates for solid tumor phase I studies with single-agent molecular or cytotoxic drugs with favorable preclinical rationale and pharmacokinetic properties

  14. Temporary treatment during primary HIV infection does not affect virologic response to subsequent long-term treatment.

    PubMed

    Grijsen, Marlous L; Wit, Ferdinand W N M; Jurriaans, Suzanne; Kroon, Frank P; Schippers, Emile F; Koopmans, Peter; Gras, Luuk; Lange, Joep M A; Prins, Jan M

    2014-01-01

    Temporary cART during primary HIV-infection (PHI) did not select for drug resistance mutations after treatment interruption and did not affect the subsequent virological response to long-term cART. Our data demonstrate that fear of drug resistance development is not a valid argument to refrain from temporary early treatment during PHI.

  15. Pretreatment Primary Tumor SUVmax Measured by FDG-PET and Pathologic Tumor Depth Predict for Poor Outcomes in Patients With Oral Cavity Squamous Cell Carcinoma and Pathologically Positive Lymph Nodes

    SciTech Connect

    Liao, C.-T.; Chang, Joseph T.-C.; Wang, H.-M.; Ng, S.-H.; Hsueh, C.; Lee, L.-Y.; Lin, C.-H.; Chen, I.-H.; Huang, S.-F.

    2009-03-01

    Purpose: The pathologic tumor depth is an independent prognosticator for local control (LC) and survival in patients with oral cavity squamous cell carcinoma (OSCC). We sought to investigate the prognostic value of the preoperative maximal standardized uptake value (SUVmax) at the primary tumor in OSCC patients with pathologically positive lymph nodes. Methods and Materials: A total of 109 OSCC patients with pathologically positive lymph nodes were investigated. All patients underwent 2-deoxy-2[(18)F]fluoro-D-glucose-positron emission tomography within 2 weeks before surgery and neck dissection. All patients were followed for {>=}24 months after surgery or until death. The optimal cutoff value for the primary tumor SUVmax was selected according to the 5-year LC rate. Independent prognosticators were identified by Cox regression analysis. Results: The median follow-up for all patients was 26 months (39 months for surviving patients). A cutoff SUVmax of 19.3 provided the greatest prognostic information for the 5-year LC rate (55% vs. 88%, p = 0.0135). A tumor depth {>=}12 mm appeared to be the most appropriate cutoff for predicting the 5-year LC rate (76% vs. 95%, p = 0.0075). A scoring system using the primary tumor SUVmax and tumor depth was formulated to define distinct prognostic groups. Patients with both a SUVmax of {>=}19.3 and tumor depth of {>=}12 mm (n = 8) had significantly poorer 5-year LC, 5-year disease-free, 5-year disease-specific, and 5-year overall survival rates compared with the other patient groups. Conclusion: The combination of the primary tumor SUVmax ({>=}19.3) and pathologic tumor depth ({>=}12 mm) identified a subgroup of OSCC patients at greatest risk of poor LC and death.

  16. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers.

    PubMed

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-06-01

    A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers

  17. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers

    PubMed Central

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-01-01

    Abstract A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414–13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674–18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292–13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097–14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects. GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new

  18. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers.

    PubMed

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-06-01

    A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers

  19. Ewing’s Sarcoma: An Analysis of miRNA Expression Profiles and Target Genes in Paraffin-Embedded Primary Tumor Tissue

    PubMed Central

    Parafioriti, Antonina; Bason, Caterina; Armiraglio, Elisabetta; Calciano, Lucia; Daolio, Primo Andrea; Berardocco, Martina; Di Bernardo, Andrea; Colosimo, Alessia; Luksch, Roberto; Berardi, Anna C.

    2016-01-01

    The molecular mechanism responsible for Ewing’s Sarcoma (ES) remains largely unknown. MicroRNAs (miRNAs), a class of small non-coding RNAs able to regulate gene expression, are deregulated in tumors and may serve as a tool for diagnosis and prediction. However, the status of miRNAs in ES has not yet been thoroughly investigated. This study compared global miRNAs expression in paraffin-embedded tumor tissue samples from 20 ES patients, affected by primary untreated tumors, with miRNAs expressed in normal human mesenchymal stromal cells (MSCs) by microarray analysis. A miRTarBase database was used to identify the predicted target genes for differentially expressed miRNAs. The miRNAs microarray analysis revealed distinct patterns of miRNAs expression between ES samples and normal MSCs. 58 of the 954 analyzed miRNAs were significantly differentially expressed in ES samples compared to MSCs. Moreover, the qRT-PCR analysis carried out on three selected miRNAs showed that miR-181b, miR-1915 and miR-1275 were significantly aberrantly regulated, confirming the microarray results. Bio-database analysis identified BCL-2 as a bona fide target gene of the miR-21, miR-181a, miR-181b, miR-29a, miR-29b, miR-497, miR-195, miR-let-7a, miR-34a and miR-1915. Using paraffin-embedded tissues from ES patients, this study has identified several potential target miRNAs and one gene that might be considered a novel critical biomarker for ES pathogenesis. PMID:27144561

  20. Factors affecting motivation and retention of primary health care workers in three disparate regions in Kenya

    PubMed Central

    2014-01-01

    Background The World Health Organization (WHO) and the Government of Kenya alike identify a well-performing health workforce as key to attaining better health. Nevertheless, the motivation and retention of health care workers (HCWs) persist as challenges. This study investigated factors influencing motivation and retention of HCWs at primary health care facilities in three different settings in Kenya - the remote area of Turkana, the relatively accessible region of Machakos, and the disadvantaged informal urban settlement of Kibera in Nairobi. Methods A cross-sectional cluster sample design was used to select 59 health facilities that yielded interviews with 404 health care workers, grouped into 10 different types of service providers. Data were collected in November 2011 using structured questionnaires and a Focus Group Discussion guide. Findings were analyzed using bivariate and multivariate methods of the associations and determinants of health worker motivation and retention. Results The levels of education and gender factors were lowest in Turkana with female HCWs representing only 30% of the workers against a national average of 53%. A smaller proportion of HCWs in Turkana feel that they have adequate training for their jobs. Overall, 13% of the HCWs indicated that they had changed their job in the last 12 months and 20% indicated that they could leave their current job within the next two years. In terms of work environment, inadequate access to electricity, equipment, transport, housing, and the physical state of the health facility were cited as most critical, particularly in Turkana. The working environment is rated as better in private facilities. Adequate training, job security, salary, supervisor support, and manageable workload were identified as critical satisfaction factors. Family health care, salary, and terminal benefits were rated as important compensatory factors. Conclusions There are distinct motivational and retention factors that affect

  1. Does Local Recurrence of Prostate Cancer After Radiation Therapy Occur at the Site of Primary Tumor? Results of a Longitudinal MRI and MRSI Study

    SciTech Connect

    Arrayeh, Elnasif; Westphalen, Antonio C.; Kurhanewicz, John; Roach, Mack; Jung, Adam J.; Carroll, Peter R.; Coakley, Fergus V.

    2012-04-01

    Purpose: To determine if local recurrence of prostate cancer after radiation therapy occurs at the same site as the primary tumor before treatment, using longitudinal magnetic resonance (MR) imaging and MR spectroscopic imaging to assess dominant tumor location. Methods and Materials: This retrospective study was HIPAA compliant and approved by our Committee on Human Research. We identified all patients in our institutional prostate cancer database (1996 onward) who underwent endorectal MR imaging and MR spectroscopic imaging before radiotherapy for biopsy-proven prostate cancer and again at least 2 years after radiotherapy (n = 124). Two radiologists recorded the presence, location, and size of unequivocal dominant tumor on pre- and postradiotherapy scans. Recurrent tumor was considered to be at the same location as the baseline tumor if at least 50% of the tumor location overlapped. Clinical and biopsy data were collected from all patients. Results: Nine patients had unequivocal dominant tumor on both pre- and postradiotherapy imaging, with mean pre- and postradiotherapy dominant tumor diameters of 1.8 cm (range, 1-2.2) and 1.9 cm (range, 1.4-2.6), respectively. The median follow-up interval was 7.3 years (range, 2.7-10.8). Dominant recurrent tumor was at the same location as dominant baseline tumor in 8 of 9 patients (89%). Conclusions: Local recurrence of prostate cancer after radiation usually occurs at the same site as the dominant primary tumor at baseline, suggesting supplementary focal therapy aimed at enhancing local tumor control would be a rational addition to management.

  2. Gallotannin-rich Caesalpinia spinosa fraction decreases the primary tumor and factors associated with poor prognosis in a murine breast cancer model

    PubMed Central

    2013-01-01

    Background Several treatment alternatives are available for primary breast cancer, although those for metastatic disease or inflammation associated with tumor progression are ineffective. Therefore, there is a great need for new therapeutic alternatives capable of generating an immune response against residual tumor cells, thus contributing to eradication of micrometastases and cancer stem cells. The use of complex natural products is an excellent therapeutic alternative widely used by Chinese, Hindu, Egyptian, and ancestral Latin-American Indian populations. Methods The present study evaluated cytotoxic, antitumor, and tumor progression activities of a gallotannin-rich fraction derived from Caesalpinia spinosa (P2Et). The parameters evaluated in vitro were mitochondrial membrane depolarization, phosphatidylserine externalization, caspase 3 activation, DNA fragmentation, and clonogenic activity. The parameters evaluated in vivo were tumor growth, leukocyte number, metastatic cell number, and cytokine production by flow cytometry. Results The in vitro results showed that the P2Et fraction induced apoptosis with mitochondrial membrane potential loss, phosphatidylserine externalization, caspase 3 activation, DNA fragmentation, and decreased clonogenic capacity of 4T1 cells. In vivo, the P2Et fraction induced primary tumor reduction in terms of diameter and weight in BALB/c mice transplanted with 4T1 cells and decreased numbers of metastatic cells, mainly in the spleen. Furthermore, decreases in the number of peripheral blood leukocytes (leukemoid reaction) and interleukin 6 (IL-6) serum levels were found, which are events associated with a poor prognosis. The P2Et fraction exerts its activity on the primary tumor, reduces cell migration to distant organs, and decreases IL-6 serum levels, implying tumor microenvironment mechanisms. Conclusions Overall, the P2Et fraction lessens risk factors associated with tumor progression and diminishes primary tumor size, showing

  3. True Recurrence Versus New Primary: An Analysis of Ipsilateral Breast Tumor Recurrences After Breast-Conserving Therapy

    SciTech Connect

    Panet-Raymond, Valerie; Truong, Pauline T.; McDonald, Rachel E.; Alexander, Cheryl; Ross, Louetta; Ryhorchuk, Aleata; Watson, Peter H.

    2011-10-01

    Purpose: Ipsilateral breast tumor recurrence (IBTR) can occur in 5-20% of women with early-stage breast cancer treated with breast-conserving therapy. Two entities of IBTR have been described: true recurrence (TR), suggested to be regrowth of disease at the tumor bed, and new primary (NP), distinct from the index lesion in histology and location. This study compared survival outcomes between two patient cohorts classified clinically as having either TR or NP. Methods and Materials: Between 1989 and 1999, 6,020 women were referred to the BC Cancer Agency with newly diagnosed pT1-2, N0-1, M0 invasive breast cancer, treated with breast-conserving surgery. Of these, 289 patients had pathologically confirmed IBTR. Retrospective analysis was performed, and a set of decision rules was applied to classify cases as TR or NP based on change in histology, grade, hormone receptor status, and tumor location. Of 289 patients, 129 (45%) were classified as having TR and 139 (48%) as having NP; 21 (7%) were unclassified. Results: The distributions of age at diagnosis, age at recurrence, and histopathologic factors were similar in the TR and NP cohorts (all p > 0.05). The mean time to recurrence was shorter in TR patients than in NP patients (4.8 years vs. 6.3 years, p = 0.001). Treatment of the IBTR did not differ between the two groups. In the TR and NP cohorts, breast cancer-specific survival was 55.7% vs. 61.3% (p = 0.93), and overall survival was 43.7% vs. 54.8% (p = 0.53). Conclusions: Time to recurrence is significantly shorter in patients with IBTR classified as true recurrence compared to new primary. Non-statistically significant trends for less favorable survival were observed for patients with TR. Further investigation of the hypothesis that TR and NP tumors are distinct entities with different survival prognoses will require standardized pathology review and molecular analyses.

  4. Extrauterine epithelioid trophoblastic tumors presenting as primary lung carcinomas: morphologic and immunohistochemical features to resolve a diagnostic dilemma.

    PubMed

    Lewin, Sharyn N; Aghajanian, Carol; Moreira, Andre L; Soslow, Robert A

    2009-12-01

    Our objective was to describe the clinicopathologic features of epithelioid trophoblastic tumors (ETTs) in a series of patients who presented with elevated beta-human chorionic gonadotrophin (hCG) levels and extrauterine lesions resembling primary lung carcinomas. Clinical and pathologic materials were reviewed and Shih and Kurman's diagnostic criteria were applied. Three parous women (38, 49, and 34 y of age) with elevated beta-hCG levels had nondiagnostic gynecologic evaluations, including negative dilation and curettage specimens. Imaging revealed isolated pulmonary lesions, 2 to 8.5 cm in size, resembling primary lung carcinomas. Two patients received multiagent chemotherapy consisting of etoposide, methotrexate, dactinomycin, alternating with cisplatin and etoposide, and all underwent pulmonary resection. Histologically, the cytologic features, epithelioid growth pattern, and hyaline-like material simulated the appearance of nonsmall cell lung carcinoma, but overall, the histologic features along with the immunophenotype supported classification as ETT. Follow-up hysterectomy specimens were histologically normal. All 3 patients are alive and well. The rarity of ETT and its resemblance to squamous and pleomorphic carcinomas of lung have led to diagnostic difficulties. When reproductive-age women present with elevated beta-hCG levels, a pulmonary lesion, and no apparent intrauterine disease, primary pulmonary ETT should be considered. Correlating clinical indices with specific morphologic and immunohistochemical features can ensure diagnostic accuracy and appropriate treatment for favorable outcomes.

  5. Chinese expert consensus workshop report: Guidelines for thermal ablation of primary and metastatic lung tumors.

    PubMed

    Ye, Xin; Fan, Weijun; Chen, Jun-Hui; Feng, Wei-Jian; Gu, Shan-Zhi; Han, Yue; Huang, Guang-Hui; Lei, Guang-Yan; Li, Xiao-Guang; Li, Yu-Liang; Li, Zhen-Jia; Lin, Zheng-Yu; Liu, Bao-Dong; Liu, Ying; Peng, Zhong-Min; Wang, Hui; Yang, Wu-Wei; Yang, Xia; Zhai, Bo; Zhang, Jun

    2015-01-01

    Although surgical resection is the primary means of curing both primary and metastatic lung cancers, about 80% of lung cancers cannot be removed by surgery. As most patients with unresectable lung cancer receive only limited benefits from traditional radiotherapy and chemotherapy, many new local treatment methods have emerged, including local ablation therapy. The Minimally Invasive and Comprehensive Treatment of Lung Cancer Branch, Professional Committee of Minimally Invasive Treatment of Cancer of the Chinese Anti-Cancer Association has organized multidisciplinary experts to develop guidelines for this treatment modality. These guidelines aim at standardizing thermal ablation procedures and criteria for selecting treatment candidates and assessing outcomes; and for preventing and managing post-ablation complications. PMID:26273346

  6. Metastatic Malignant Melanoma of Parotid Gland with a Regressed Primary Tumor

    PubMed Central

    Aynali, Giray; Ceyhan, Ali Murat; Çiriş, Metin

    2016-01-01

    Malignant melanoma of the parotid gland is often metastatic and mainly originates from malignant melanomas in the head and neck. Nevertheless, some malignant melanomas may metastasize and subsequently regress. Therefore, it may not be possible to observe a metastatic malignant melanoma and its primary melanoma simultaneously. The investigation of a patient's old photographs may help in the detection of preexisting and regressed pigmented lesions in the facial and neck regions. PMID:27478668

  7. Can Locoregional Treatment of the Primary Tumor Improve Outcomes for Women With Stage IV Breast Cancer at Diagnosis?

    SciTech Connect

    Nguyen, David H.A.; Truong, Pauline T.; Alexander, Cheryl; Walter, Caroline V.; Hayashi, Emily; Christie, Jennifer; Lesperance, Mary

    2012-09-01

    Purpose: To examine the effect of locoregional treatment (LRT) of the primary tumor on survival in patients with Stage IV breast cancer at diagnosis. Methods and Materials: The study cohort comprised 733 women referred to the British Columbia Cancer Agency between 1996 and 2005 with newly diagnosed clinical or pathologic M1 breast cancer. Tumor and treatment characteristics, overall survival (OS), and locoregional progression-free survival were compared between patients treated with (n = 378) and without (n = 355) LRT of the primary disease. Multivariable analysis was performed with Cox regression modeling. Results: The median follow-up time was 1.9 years. LRT consisted of surgery alone in 67% of patients, radiotherapy alone in 22%, and both in 11%. LRT was used more commonly in women with age <50 years, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, Stage T1-2 tumors, N0-1 disease, limited M1 burden, and asymptomatic M1 disease (all p < 0.05). Systemic therapy was used in 92% of patients who underwent LRT and 85% of patients who did not. In patients treated with LRT compared with those without LRT, the 5-year OS rates were 21% vs. 14% (p < 0.001), and the rates of locoregional progression-free survival were 72% vs. 46% (p < 0.001). Among 378 patients treated with LRT, the rates of 5-year OS were higher in patients with age <50, ECOG performance status 0-1, estrogen receptor-positive disease, clear surgical margins, single subsite, bone-only metastasis, and one to four metastatic lesions (all p < 0.003). On multivariable analysis, LRT was associated with improved OS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.94, p = 0.009). Conclusion: Locoregional treatment of the primary disease is associated with improved survival in some women with Stage IV breast cancer at diagnosis. Among those treated with LRT, the most favorable rates of survival were observed in subsets with young age, good performance status, estrogen receptor-positive disease

  8. IL6/JAK1/STAT3 Signaling Blockade in Endometrial Cancer Affects the ALDHhi/CD126+ Stem-like Component and Reduces Tumor Burden.

    PubMed

    van der Zee, Marten; Sacchetti, Andrea; Cansoy, Medine; Joosten, Rosalie; Teeuwssen, Miriam; Heijmans-Antonissen, Claudia; Ewing-Graham, Patricia C; Burger, Curt W; Blok, Leen J; Fodde, Riccardo

    2015-09-01

    Cancer stem-like cells (CSC) may be critical to maintain the malignant behavior of solid and hematopoietic cancers. Recently, patients with endometrial cancer whose tumors expressed high levels of aldehyde dehydrogenase (ALDH), a detoxifying enzyme characteristic of many progenitor and stem cells, exhibited a relative reduction in survival compared with patients with low levels of ALDH. Given evidence of its role as a CSC marker, we hypothesized that high level of ALDH activity (ALDH(hi)) in a tumor might positively correlate with the presence of stem- and progenitor-like tumor cells in this disease setting. In support of this hypothesis, ALDH could be used to enrich for CSC in endometrial cancer cell lines and primary tumors, as illustrated by the increased tumor-initiating capacity of ALDH(hi) cells in immunodeficient mice. ALDH(hi) cells also exhibited greater clonogenic and organoid-forming capacity compared with ALDH(lo) cells. Notably, the number of ALDH(hi) cells in tumor cell lines and primary tumors inversely correlated with differentiation grade. Expression analysis revealed upregulation of IL6 receptor subunits and signal transducers CD126 and GP130 in ALDH(hi) endometrial cancer cells. Accordingly, targeted inhibition of the IL6 receptor and its downstream effectors JAK1 and STAT3 dramatically reduced tumor cell growth. Overall, our results provide a preclinical rationale to target IL6 or its effector functions as a novel therapeutic option in endometrial cancer.

  9. ACRIN CT Colonography Trial: Does Reader’s Preference for Primary Two-dimensional versus Primary Three-dimensional Interpretation Affect Performance?

    PubMed Central

    Blevins, Meridith; Chen, Mei-Hsiu; Dachman, Abraham H.; Kuo, Mark D.; Menias, Christine O.; Siewert, Bettina; Cheema, Jugesh I.; Obregon, Richard G.; Fidler, Jeff L.; Zimmerman, Peter; Horton, Karen M.; Coakley, Kevin J.; Iyer, Revathy B.; Halvorsen, Robert A.; Casola, Giovanna; Yee, Judy; Herman, Benjamin A.; Johnson, C. Daniel

    2011-01-01

    Purpose: To determine whether the reader’s preference for a primary two-dimensional (2D) or three-dimensional (3D) computed tomographic (CT) colonographic interpretation method affects performance when using each technique. Materials and Methods: In this institutional review board–approved, HIPAA-compliant study, images from 2531 CT colonographic examinations were interpreted by 15 trained radiologists by using colonoscopy as a reference standard. Through a survey at study start, study end, and 6-month intervals, readers were asked whether their interpretive preference in clinical practice was to perform a primary 2D, primary 3D, or both 2D and 3D interpretation. Readers were randomly assigned a primary interpretation method (2D or 3D) for each CT colonographic examination. Sensitivity and specificity of each method (primary 2D or 3D), for detecting polyps of 10 mm or larger and 6 mm or larger, based on interpretive preference were estimated by using resampling methods. Results: Little change was observed in readers’ preferences when comparing them at study start and study end, respectively, as follows: primary 2D (eight and seven readers), primary 3D (one and two readers), and both 2D and 3D (six and six readers). Sensitivity and specificity, respectively, for identifying examinations with polyps of 10 mm or larger for readers with a primary 2D preference (n = 1128 examinations) were 0.84 and 0.86, which was not significantly different from 0.84 and 0.83 for readers who preferred 2D and 3D (n = 1025 examinations) or from 0.76 and 0.82 for readers with a primary 3D preference (n = 378 examinations). When performance by using the assigned 2D or 3D method was evaluated on the basis of 2D or 3D preference, there was no difference among those readers by using their preferred versus not preferred method of interpretation. Similarly, no significant difference among readers or preferences was seen when performance was evaluated for detection of polyps of 6 mm or

  10. Cytogenetic characterization of three cell lines derived from primary cervical tumors of different histologic grade

    SciTech Connect

    Hann, E.; Beauregard, L.; Mikumo, R.

    1994-09-01

    Braum et al.(1993) established three cell lines from keratinizing and nonkeratinizing cervical carcinomas. These cell lines were subsequently analyzed for growth properties and the physical state of the human papillomavirus type 16 genome. TC140, derived from a keratinizing cervical tumor, contains human papillomavirus type 16 in the episomal state. TC-146A and TC-146B, derived from a nonkeratinizing large-cell cervical carcinoma, contain human papillomavirus type 16 in the integrated state. The goal of the present study was to cytogenetically characterize these cell lines, developed from cervical carcinoma with a defined histopathology, in order to shed additional light on the biological basis of the histological and clinical heterogeneity of cervical cancers. Information on solid tumors has been limited because they are often difficult to culture and the karyotypes on the available metaphases are often complex with unidentifiable markers. The chromosomes of these three cell lines were characterized in the present study using GTG-banding. For cell line 140, the most striking chromosomal abnormalities noted were the presence of an i(5p) or i(12p) marker, an isochromosome 8q marker and multiple copies of chromosome 9. For cell line 146A, the most notable chromosomal abnormalities noted were the presence of a marker chromosome 7 with additional materials present on the long arms, an isochomosome of the long arms of chromosome 8 and a question of chromosome 19 markers. For cell line 146B, the most notable chromosomal abnormalities were found to be a deleted X chromosome, a marker chromosome 7 with additional material on the long arm, an isochromosome 8q marker, and isochromosome 16q marker and one or more copies of an isochromosome 17q marker. Fluorescent in situ hybridization experiments performed using select probes further corroborate the results of the above-mentioned conventional cytogenetic studies.

  11. New agents for targeting of IL-13RA2 expressed in primary human and canine brain tumors.

    PubMed

    Debinski, Waldemar; Dickinson, Peter; Rossmeisl, John H; Robertson, John; Gibo, Denise M

    2013-01-01

    appropriate candidates for IL-13RA2-targeted imaging/therapies. Canine spontaneous primary brain tumors represent an excellent translational model for human counterparts. PMID:24147065

  12. New Agents for Targeting of IL-13RA2 Expressed in Primary Human and Canine Brain Tumors

    PubMed Central

    Debinski, Waldemar; Dickinson, Peter; Rossmeisl, John H.; Robertson, John; Gibo, Denise M.

    2013-01-01

    appropriate candidates for IL-13RA2-targeted imaging/therapies. Canine spontaneous primary brain tumors represent an excellent translational model for human counterparts. PMID:24147065

  13. Comparison of IGRT Registration Strategies for Optimal Coverage of Primary Lung Tumors and Involved Nodes Based on Multiple Four-Dimensional CT Scans Obtained Throughout the Radiotherapy Course

    SciTech Connect

    Mohammed, Nasiruddin; Kestin, Larry; Grills, Inga; Shah, Chirag; Glide-Hurst, Carri; Yan, Di; Ionascu, Dan

    2012-03-15

    Purpose: To investigate the impact of primary tumor and involved lymph node (LN) geometry (centroid, shape, volume) on internal target volume (ITV) throughout treatment for locally advanced non-small cell lung cancer using weekly four-dimensional computed tomography (4DCT). Methods and Materials: Eleven patients with advanced non-small cell lung cancer were treated using image-guided radiotherapy with acquisition of weekly 10-Phase 4DCTs (n = 51). Initial ITV was based on planning 4DCT. Master-ITV incorporated target geometry across the entire treatment (all 4DCTs). Geographic miss was defined as the % Master-ITV positioned outside of the initial planning ITV after registration is complete. Registration strategies considered were bony (B), primary tumor soft tissue alone (T), and registration based on primary tumor and involved LNs (T{sub L}N). Results: The % geographic miss for the primary tumor, mediastinal, and hilar lymph nodes based on each registration strategy were (1) B: 30%, 30%, 30%; (2) T: 21%, 40%, 36%; and (3) T{sub L}N: 26%, 26%, 27%. Mean geographic expansions to encompass 100% of the primary tumor and involved LNs were 1.2 {+-} 0.7 cm and 0.8 {+-} 0.3 cm, respectively, for B and T{sub L}N. Primary and involved LN expansions were 0.7 {+-} 0.5 cm and 1.1 {+-} 0.5 cm for T. Conclusion: T is best for solitary targets. When treatments include primary tumor and LNs, B and T{sub L}N provide more comprehensive geographic coverage. We have identified high % geographic miss when considering multiple registration strategies. The dosimetric implications are the subject of future study.

  14. Mindfulness, Resilience, and Burnout Subtypes in Primary Care Physicians: The Possible Mediating Role of Positive and Negative Affect

    PubMed Central

    Montero-Marin, Jesús; Tops, Mattie; Manzanera, Rick; Piva Demarzo, Marcelo M.; Álvarez de Mon, Melchor; García-Campayo, Javier

    2015-01-01

    Purpose: Primary care health professionals suffer from high levels of burnout. The aim of the present study was to evaluate the associations of mindfulness and resilience with the features of the burnout types (overload, lack of development, neglect) in primary care physicians, taking into account the potential mediating role of negative and positive affect. Methods: A cross-sectional design was used. Six hundred and twenty-two Spanish primary care physicians were recruited from an online survey. The Mindful Attention Awareness Scale (MAAS), Connor-Davidson Resilience Scale (CD-RISC), Positive and Negative Affect Schedule (PANAS), and Burnout Clinical Subtype Questionnaire (BCSQ-12) questionnaires were administered. Polychoric correlation matrices were calculated. The unweighted least squares (ULS) method was used for developing structural equation modeling. Results: Mindfulness and resilience presented moderately high associations (φ = 0.46). Links were found between mindfulness and overload (γ = −0.25); resilience and neglect (γ = −0.44); mindfulness and resilience, and negative affect (γ = −0.30 and γ = −0.35, respectively); resilience and positive affect (γ = 0.70); negative affect and overload (β = 0.36); positive affect and lack of development (β = −0.16). The links between the burnout types reached high and positive values between overload and lack of development (β = 0.64), and lack of development and neglect (β = 0.52). The model was a very good fit to the data (GFI = 0.96; AGFI = 0.96; RMSR = 0.06; NFI = 0.95; RFI = 0.95; PRATIO = 0.96). Conclusions: Interventions addressing both mindfulness and resilience can influence burnout subtypes, but their impact may occur in different ways, potentially mediated by positive and negative affect. Both sorts of trainings could constitute possible tools against burnout; however, while mindfulness seems a suitable intervention for preventing its initial stages, resilience may be more effective for

  15. Factors affecting meiotic and developmental competence of primary spermatocyte nuclei injected into mouse oocytes.

    PubMed

    Kimura, Y; Tateno, H; Handel, M A; Yanagimachi, R

    1998-10-01

    Mature mouse oocytes that have received the nuclei of pachytene primary spermatocytes (or metaphase I chromosomes of primary spermatocytes) can develop into fertile offspring. However, success rate in this study was low. No more than 3.8% of transferred 2-cell embryos arising from spermatocyte-injected oocytes developed to full term. Nevertheless, the birth of normal offspring seems to suggest that at least in some primary spermatocytes the functional genomic imprinting is complete before transfer and/or consolidated after the transfer. Although injected spermatocyte nuclei could undergo two successive meiotic divisions within oocytes, abnormalities of both divisions were commonly observed, and sister chromatids often separated prematurely during the second meiotic division. Chromosome breakage/rearrangements were also frequently seen before the first cleavage. Such abnormalities of chromosome behavior are probably the major causes of the poor preimplantation development of zygotes arising from primary spermatocyte-injected oocytes. Thus, clinical use of primary spermatocytes as substitutes for spermatozoa in assisted fertilization is not advisable until the causes of chromosomal abnormalities are better understood through extensive animal studies. PMID:9746737

  16. Centralized databases available for describing primary brain tumor incidence, survival, and treatment: Central Brain Tumor Registry of the United States; Surveillance, Epidemiology, and End Results; and National Cancer Data Base.

    PubMed Central

    Davis, F. G.; McCarthy, B. J.; Berger, M. S.

    1999-01-01

    Characteristics of three databases--the Central Brain Tumor Registry of the United States (CBTRUS) database; the Surveillance, Epidemiology and End Results (SEER) database; and the National Cancer Data Base (NCDB)--containing information on primary brain tumors are discussed. The recently developed population-based CBTRUS database comprises incidence data on all primary brain tumors from 11 collaborating state registries; however, follow-up data are not available. SEER, the population-based gold standard for cancer data, collects incidence and follow-up data on malignant brain tumors only. While not population-based, the NCDB identifies newly diagnosed cases and conducts follow-up on all primary brain tumors from hospitals accredited by the American College of Surgeons. The NCDB is the largest of the three databases and also contains more complete information regarding treatment of these tumors than either the SEER or CBTRUS databases. Additional strengths and limitations of each of these are described, and their judicious use for supporting research, education, and health care planning is encouraged. PMID:11554389

  17. Active and Passive Commuting to School: Influences on Affect in Primary School Children

    ERIC Educational Resources Information Center

    Hulley, Angela; Bentley, Nick; Clough, Catherine; Fishlock, Adelle; Morrell, Frances; O'Brien, James; Radmore, Joseph

    2008-01-01

    Active commuting among school children is being encouraged for physical and environmental reasons, but little is known about its influence on affect. The aim of this study was to test the hypothesis that children who walk further to school experience increased arousal and affective valence compared with children who walk a short distance. This was…

  18. Causal Predominance of Cognitions in Disturbed Affects among Finnish Primary School Teachers.

    ERIC Educational Resources Information Center

    Rajala, Raimo

    1990-01-01

    A putative causal relationship of cognitions to affects in different phases of teachers' stress cycles was studied for 414 elementary school teachers in Finland. Results provide only negligible support for the causal predominance of cognitions in disturbed affects; the opposite seemed to prevail. Implications for teacher satisfaction are…

  19. Radiological contribution to the diagnosis of early postoperative complications after lung resection for primary tumor: a revisional study.

    PubMed

    Cardinale, Luciano; Priola, Adriano Massimiliano; Priola, Sandro Massimo; Boccuzzi, Francesco; Dervishi, Najada; Lisi, Elena; Veltri, Andrea; Ardissone, Francesco

    2016-08-01

    In the post-operative course of the interventions of lung resection for primary tumor, complications of different nature and severity can arise, recognizing different pathogenetic mechanisms and differing according to the type of resection performed and to the time elapsed after surgery. The low diagnostic accuracy of chest radiography requires a thorough knowledge of the radiologist about all radiographic findings, both normal and pathological, which can be found in the immediate post-operative period (within 30 days after surgery). This article aims to describe the incidence, the clinical features and the radiological aspects of immediate complications following pulmonary resections, with specific reference to those in which the diagnostic imaging provides a fundamental contribution. PMID:27621893

  20. Radiological contribution to the diagnosis of early postoperative complications after lung resection for primary tumor: a revisional study

    PubMed Central

    Priola, Adriano Massimiliano; Priola, Sandro Massimo; Boccuzzi, Francesco; Dervishi, Najada; Lisi, Elena; Veltri, Andrea; Ardissone, Francesco

    2016-01-01

    In the post-operative course of the interventions of lung resection for primary tumor, complications of different nature and severity can arise, recognizing different pathogenetic mechanisms and differing according to the type of resection performed and to the time elapsed after surgery. The low diagnostic accuracy of chest radiography requires a thorough knowledge of the radiologist about all radiographic findings, both normal and pathological, which can be found in the immediate post-operative period (within 30 days after surgery). This article aims to describe the incidence, the clinical features and the radiological aspects of immediate complications following pulmonary resections, with specific reference to those in which the diagnostic imaging provides a fundamental contribution. PMID:27621893

  1. Sleep Loss and Its Effects on Health of Family Caregivers of Individuals with Primary Malignant Brain Tumors

    PubMed Central

    Lee, Shih-Yu; Clark, Patricia C.; Sherwood, Paula R.

    2013-01-01

    Sleep loss places caregivers at risk for poor health. Understanding correlates of sleep loss and relationships to health may enable improvement of health of caregivers of individuals with primary malignant brain tumors (PMBT). In this cross-sectional, descriptive study of 133 caregivers, relationships were examined between sleep loss and physical, mental, emotional, and social health at time of patient diagnosis. Sleep loss was not related to physical health. Shorter total sleep time was associated with greater fatigue and social support. Sleep quality was positively associated with quality of life. Further study is needed of the role of sleep loss in the PMBT caregiving trajectory and its long-term relationship with health outcomes. PMID:23633116

  2. Sleep loss and its effects on health of family caregivers of individuals with primary malignant brain tumors.

    PubMed

    Pawl, Jean D; Lee, Shih-Yu; Clark, Patricia C; Sherwood, Paula R

    2013-08-01

    Sleep loss places caregivers at risk for poor health. Understanding correlates of sleep loss and relationships to health may enable improvement of health of caregivers of individuals with primary malignant brain tumors (PMBT). In this cross-sectional, descriptive study of 133 caregivers, relationships were examined between sleep loss and physical, mental, emotional, and social health at time of patient diagnosis. Sleep loss was not related to physical health. Shorter total sleep time was associated with greater fatigue and social support. Sleep quality was positively associated with quality of life. Further study is needed of the role of sleep loss in the PMBT caregiving trajectory and its long-term relationship with health outcomes.

  3. Epithelial-mesenchymal transition markers in lymph node metastases and primary breast tumors - relation to dissemination and proliferation

    PubMed Central

    Markiewicz, Aleksandra; Wełnicka-Jaśkiewicz, Marzena; Seroczyńska, Barbara; Skokowski, Jarosław; Majewska, Hanna; Szade, Jolanta; Żaczek, Anna J

    2014-01-01

    Epithelial-mesenchymal transition (EMT) was shown to enhance metastatic abilities of cancer cells, but it remains elusive in clinical samples. Moreover, EMT is rarely studied in lymph node metastases (LNM), thus limiting our understanding of its role outside of the primary tumors (PT). We collected a set of samples including triplets - PT, circulating tumor cells (CTCs)-enriched blood samples and LNM from 108 early breast cancer patients. With immunohistochemistry we analyzed levels of EMT effectors – E-cadherin, vimentin and N-cadherin in LNM, central areas and margins of PT. Additionally, expression of EMT core regulators TWIST1, SNAI1, SNAI2 was measured with RT-qPCR. Patients with E-cadherin loss had CTCs in 45% of the cases in comparison to 23% with normal E-cadherin level (P = 0.05). Mesenchymal phenotype of CTCs-enriched blood fractions was five-times more frequent in patients with E-cadherin loss in PT compared to PT with normal E-cadherin levels (P = 0.01). Epithelial/mesenchymal status of matched samples at different stages of dissemination was frequently discordant, especially for pairs involving CTCs, indicating high plasticity of tumor cells. LNM showed increased expression of TWIST1, SNAI1, SNAI2 accompanied by decreased Ki67 labeling index, with median Ki67 of 15% in PT and 10% in LNM (P = 0.0002). Our findings demonstrate that E-cadherin loss, not only in PT margin, might lead to seeding of especially malignant CTCs with mesenchymal phenotype. In comparison to PT, cells in LNM re-express E-cadherin, upregulate EMT transcription factors and reduce cell division rate, which could be viewed as their long-term survival strategy. PMID:25628790

  4. Tumor Vascular Permeability Pattern Is Associated With Complete Response in Immunocompetent Patients With Newly Diagnosed Primary Central Nervous System Lymphoma

    PubMed Central

    Chung, Sae Rom; Choi, Young Jun; Kim, Ho Sung; Park, Ji Eun; Shim, Woo Hyun; Kim, Sang Joon

    2016-01-01

    Abstract A dynamic contrast-enhanced MR imaging (DCE-MRI) could provide the information about tumor drug delivery efficacy. We investigated the potential utility of the permeability pattern of DCE-MRI for predicting tumor response to high dose-methotrexate treatment and progression-free survival (PFS) in patients with primary CNS lymphoma (PCNSL). Clinical and conventional imaging parameters were assessed as potential predictors of tumor response in 48 immunocompetent PCNSL patients in a preliminary study. Fifty additional immunocompetent patients (27 men and 23 women; mean age, 60.6 years) with PCNSL underwent DCE-MRI before starting first-line treatment with high dose-methotrexate. The DCE-MRI pattern was categorized as diffuse or nondiffuse. After 4 courses of high dose methotrexate, patients underwent follow-up brain MR imaging to identify their complete response (CR). Predictors of CR and PFS were analyzed using clinical parameters, conventional MRI, and DCE-MRI. CR was noted in 20 (74.1%) of 27 patients with diffuse DCE-MRI pattern and in 4 (17.4%) of 23 patients with nondiffuse DCE-MRI pattern. The diffuse DCE-MRI pattern showed a significantly higher association with CR than the nondiffuse pattern (P < 0.001). Multivariate Cox proportional hazards model revealed that the DCE-MRI pattern (hazard ratio = 0.70; P = 0.045), age (hazard ratio = 1.47; P = 0.041), and adjuvant autologous stem-cell transplantation (hazard ratio = 6.97; P = 0.003) tended to be associated with a PFS. The pretreatment diffuse DCE-MRI pattern can be used as a potential imaging biomarker for predicting CR and a longer PFS in patients with newly diagnosed PCNSLs. PMID:26871782

  5. Health system factors affecting communication with pediatricians: gendered work culture in primary care.

    PubMed

    Lynch, Sean

    2011-01-01

    This qualitative study examined the roles that practice setting, education level, and gender may play in social workers' communication satisfaction with pediatricians. Taking an ethnographic approach, the researcher interviewed social workers and pediatricians who worked together to provide mental health services in primary care. The results suggested that gender at the health system level may be an issue and that gendered work culture in primary care was a factor in communication. In particular, reimbursement, an aspect of the gendered work culture, was a substantial communication barrier, and the implications for Medicaid billing are discussed. PMID:22085327

  6. Single Unpurified Breast Tumor-Initiating Cells from Multiple Mouse Models Efficiently Elicit Tumors in Immune-Competent Hosts

    PubMed Central

    Kurpios, Natasza A.; Girgis-Gabardo, Adele; Hallett, Robin M.; Rogers, Stephen; Gludish, David W.; Kockeritz, Lisa; Woodgett, James; Cardiff, Robert; Hassell, John A.

    2013-01-01

    The tumor-initiating cell (TIC) frequency of bulk tumor cell populations is one of the criteria used to distinguish malignancies that follow the cancer stem cell model from those that do not. However, tumor-initiating cell frequencies may be influenced by experimental conditions and the extent to which tumors have progressed, parameters that are not always addressed in studies of these cells. We employed limiting dilution cell transplantation of minimally manipulated tumor cells from mammary tumors of several transgenic mouse models to determine their tumor-initiating cell frequency. We determined whether the tumors that formed following tumor cell transplantation phenocopied the primary tumors from which they were isolated and whether they could be serially transplanted. Finally we investigated whether propagating primary tumor cells in different tissue culture conditions affected their resident tumor-initiating cell frequency. We found that tumor-initiating cells comprised between 15% and 50% of the bulk tumor cell population in multiple independent mammary tumors from three different transgenic mouse models of breast cancer. Culture of primary mammary tumor cells in chemically-defined, serum-free medium as non-adherent tumorspheres preserved TIC frequency to levels similar to that of the primary tumors from which they were established. By contrast, propagating the primary tumor cells in serum-containing medium as adherent populations resulted in a several thousand-fold reduction in their tumor-initiating cell fraction. Our findings suggest that experimental conditions, including the sensitivity of the transplantation assay, can dramatically affect estimates of tumor initiating cell frequency. Moreover, conditional on cell culture conditions, the tumor-initiating cell fraction of bulk mouse mammary tumor cell preparations can either be maintained at high or low frequency in vitro thus permitting comparative studies of tumorigenic and non-tumorigenic cancer cells

  7. Children's Perceptions of Parental Attitude Affecting Breakfast Skipping in Primary Sixth-Grade Students

    ERIC Educational Resources Information Center

    Cheng, Tereza Sy; Tse, Lap Ah; Yu, Ignatius Tak-Sun; Griffiths, Sian

    2008-01-01

    Background: Breakfast skipping is an international public health concern. This study investigated the prevalence of breakfast skipping among primary sixth-grade students in Hong Kong and the impact of students' perceptions of parental attitudes on breakfast skipping. Methods: A total of 426 students aged 10-14 years in 4 local schools participated…

  8. Brain tumor (image)

    MedlinePlus

    Brain tumors are classified depending on the exact site of the tumor, the type of tissue involved, benign ... tendencies of the tumor, and other factors. Primary brain tumors can arise from the brain cells, the meninges ( ...

  9. Ajoene inhibits both primary tumor growth and metastasis of B16/BL6 melanoma cells in C57BL/6 mice.

    PubMed

    Taylor, Peter; Noriega, Raquel; Farah, Carla; Abad, María-Jesús; Arsenak, Miriam; Apitz, Rafael

    2006-08-01

    Ajoene is an organosulphur compound derived from garlic with important effects on several membrane-associated processes such as platelet aggregation, as well as being cytotoxic for tumor cell lines in vitro. In the present study, we investigated the effect of ajoene on different cell types in vitro, as well as its inhibitory effects on both primary tumors and metastasis in a mouse model. We found ajoene to inhibit tumor cell growth in vitro, but also to inhibit strongly metastasis to lung in the B16/BL6 melanoma tumor model in C57BL/6 mice. As far as we are aware, this is the first report of the anti-metastatic effect of ajoene. Ajoene also inhibited tumor-endothelial cell adhesion, as well as the in vivo TNF-alpha response to lipopolysaccharide. Possible mechanisms of its antitumoral activity are discussed in the light of these results.

  10. Clouds and silver linings: positive experiences associated with primary affective disorders.

    PubMed

    Jamison, K R; Gerner, R H; Hammen, C; Padesky, C

    1980-02-01

    Clinical psychiatry has focused almost entirely on the psychopathology of the affective disorders. The authors studied responses of 61 patients (35 bipolar. 26 unipolar) to questions about perceived short- and long-term benefits (increased sensitivity, sexuality, productivity, creativity, and social outgoingness) they attributed to their affective illness. Bipolar patients strongly indicated positive experiences associated with manic-depressive illness; few unipolar patients perceived their disorder in such a way. Significant sex differences emerged in the attributions made by bipolar patients.

  11. Expression of S-100 protein, epithelial membrane antigen, carcinoembryonic antigen and alpha fetoprotein in normal salivary glands and primary salivary gland tumors.

    PubMed

    Günhan, O; Evren, G; Demiriz, M; Can, C; Celasun, B; Finci, R

    1992-12-01

    The distribution of S-100 protein, epithelial membrane antigen, carcinoembryonic antigen and alpha fetoprotein was studied in 38 primary salivary gland tumors. S-100 protein, a useful marker of myoepithelial cells, was demonstrated in some benign tumors. Carcinoembryonic antigen expression was consistently positive in adenoid cystic carcinoma. Demonstration of epithelial membrane antigen helped to confirm the epithelial nature of some neoplastic cells. Alpha fetoprotein was not expressed in any of the cases examined. No correlation was found between immunopositivity and tumor behavior in the present series.

  12. CDK2 activation in mouse epidermis induces keratinocyte proliferation but does not affect skin tumor development.

    PubMed

    Macias, Everardo; Miliani de Marval, Paula L; De Siervi, Adriana; Conti, Claudio J; Senderowicz, Adrian M; Rodriguez-Puebla, Marcelo L

    2008-08-01

    It has been widely assumed that elevated CDK2 kinase activity plays a contributory role in tumorigenesis. We have previously shown that mice overexpressing CDK4 under control of the keratin 5 promoter (K5CDK4 mice) develop epidermal hyperplasia and increased susceptibility to squamous cell carcinomas. In this model, CDK4 overexpression results in increased CDK2 activity associated with the noncatalytic function of CDK4, sequestration of p21(Cip1) and p27(Kip1). Furthermore, we have shown that ablation of Cdk2 reduces Ras-Cdk4 tumorigenesis, suggesting that increased CDK2 activity plays an important role in Ras-mediated tumorigenesis. To investigate this hypothesis, we generated two transgenic mouse models of elevated CDK2 kinase activity, K5Cdk2 and K5Cdk4(D158N) mice. The D158N mutation blocks CDK4 kinase activity without interfering with its binding capability. CDK2 activation via overexpression of CDK4(D158N), but not of CDK2, resulted in epidermal hyperplasia. We observed elevated levels of p21(Cip1) in K5Cdk2, but not in K5Cdk4(D158N), epidermis, suggesting that CDK2 overexpression elicits a p21(Cip1) response to maintain keratinocyte homeostasis. Surprisingly, we found that neither CDK2 overexpression nor the indirect activation of CDK2 enhanced skin tumor development. Thus, although the indirect activation of CDK2 is sufficient to induce keratinocyte hyperproliferation, activation of CDK2 alone does not induce malignant progression in Ras-mediated tumorigenesis.

  13. CDK2 Activation in Mouse Epidermis Induces Keratinocyte Proliferation but Does Not Affect Skin Tumor Development

    PubMed Central

    Macias, Everardo; Miliani de Marval, Paula L.; De Siervi, Adriana; Conti, Claudio J.; Senderowicz, Adrian M.; Rodriguez-Puebla, Marcelo L.

    2008-01-01

    It has been widely assumed that elevated CDK2 kinase activity plays a contributory role in tumorigenesis. We have previously shown that mice overexpressing CDK4 under control of the keratin 5 promoter (K5CDK4 mice) develop epidermal hyperplasia and increased susceptibility to squamous cell carcinomas. In this model, CDK4 overexpression results in increased CDK2 activity associated with the noncatalytic function of CDK4, sequestration of p21Cip1 and p27Kip1. Furthermore, we have shown that ablation of Cdk2 reduces Ras-Cdk4 tumorigenesis, suggesting that increased CDK2 activity plays an important role in Ras-mediated tumorigenesis. To investigate this hypothesis, we generated two transgenic mouse models of elevated CDK2 kinase activity, K5Cdk2 and K5Cdk4D158N mice. The D158N mutation blocks CDK4 kinase activity without interfering with its binding capability. CDK2 activation via overexpression of CDK4D158N, but not of CDK2, resulted in epidermal hyperplasia. We observed elevated levels of p21Cip1 in K5Cdk2, but not in K5Cdk4D158N, epidermis, suggesting that CDK2 overexpression elicits a p21Cip1 response to maintain keratinocyte homeostasis. Surprisingly, we found that neither CDK2 overexpression nor the indirect activation of CDK2 enhanced skin tumor development. Thus, although the indirect activation of CDK2 is sufficient to induce keratinocyte hyperproliferation, activation of CDK2 alone does not induce malignant progression in Ras-mediated tumorigenesis. PMID:18599613

  14. Tumor homogeneity between primary and metastatic sites for BRAF status in metastatic melanoma determined by immunohistochemical and molecular testing.

    PubMed

    Boursault, Lucile; Haddad, Véronique; Vergier, Béatrice; Cappellen, David; Verdon, Severine; Bellocq, Jean-Pierre; Jouary, Thomas; Merlio, Jean-Philippe

    2013-01-01

    BRAF inhibitors have demonstrated improvement of overall survival in patients with metastatic melanoma and BRAF(V600) mutations. In order to evaluate BRAF tumor heterogeneity between primary and metastatic site, we have evaluated the performance of immunohistochemistry (IHC) with an anti-BRAF(V600E) antibody in both localization by comparison with high resolution melting analysis followed by Sanger sequencing in a parallel blinded study. A total of 230 samples distributed as primary melanoma (n = 88) and different types of metastatic samples (n = 142) were studied in 99 patients with advanced or metastatic melanoma (stage III or IV). The prevalence of each BRAF mutation was c.1799T>A, BRAF(V600E) (45.2%), c.1799_1800TG>AA, BRAF(V600E2) (3.0%), c.1798_1799GT>AA, BRAF(V600K) (3.0%), c.1801 A>G, BRAF(K601E) (1.3%), c.1789_1790CT>TC, BRAF(L597S) (0.4%), c.1780G>A, BRAF(D594N) (0.9%) respectively. IHC was positive in 109/112 samples harboring BRAF(V600E/E2) mutations and negative in other cases. The cytoplasmic staining was either strongly positive in tumor cells of BRAF(V600E) mutated cases. It appeared strong brown, different from the vesicular grey cytoplasmic pigmentation of melanophages. Concordance between the two techniques was 96.4%. Sensitivity of IHC for detecting the BRAF(V600E/E2) mutations was 97.3%, while specificity was 100%. Both our IHC and molecular study demonstrated homogeneity between primary and metastatic sites for BRAF status in melanoma. This study also provides evidence that IHC may be a cost-effective first-line method for BRAF(V600E) detection. Thereafter, molecular techniques should be used in negative, ambiguous or non-contributive cases.

  15. The anti-Fn14 antibody BIIB036 inhibits tumor growth in xenografts and patient derived primary tumor models and enhances efficacy of chemotherapeutic agents in multiple xenograft models.

    PubMed

    Michaelson, Jennifer S; Kelly, Rebecca; Yang, Lu; Zhang, Xiamei; Wortham, Kathleen; Joseph, Ingrid B J K

    2012-07-01

    Agonistic antibodies targeting Fn14, the receptor for TWEAK, have demonstrated anti-tumor activity in xenograft models. Herein, we further explore the therapeutic potential of the humanized anti-Fn14 agonistic antibody, BIIB036, as a single agent and in combination with standard of care cancer therapeutics. Pharmacokinetic studies of BIIB036 in tumor-bearing mice revealed a half-life of approximately three days suggesting twice a week dosing would be necessary to maintain efficacy. However, in multiple xenograft models, BIIB036 treatment resulted in extended tumor growth inhibition up to 40-50 d following cessation of dosing, suggesting that frequent administration of BIIB036 may not be necessary to maintain prolonged anti-tumor activity. Subsequent xenograft studies revealed that maximal efficacy was achieved with BIIB036 dosing once every two weeks, by either intraperitoneal or subcutaneous administration. Xenograft tumors that were initially treated with BIBI036 and then re-grew up to 1000 mm³ following cessation of the first cycle of treatment remained sensitive to a second cycle of treatment. BIIB036 was also evaluated in patient derived primary colon tumor models, where efficacy compared favorably with a standard of care agent. Lastly, BIIB036 enhanced the efficacy of several standard of care chemotherapeutics, including paclitaxel in MDA-MBA-231 breast tumor xenografts, paclitaxel or carboplatin in HOP62 non-small cell lung xenografts, and 5-FU in NCI-N87 gastric xenografts, with no overlapping toxicities. These studies thus establish BIIB036 as a promising therapeutic agent with durable anti-tumor activity in human xenografts as well as patient derived primary tumor models, and enhanced activity and tolerability in combination with standard of care chemotherapeutics. Taken together, the data presented herein suggest that BIIB036 warrants evaluation in the clinic.

  16. Evaluation of some physical hazards which may affect health in primary schools

    PubMed Central

    Bakır, Bilal; Babayiğit, Mustafa Alparslan; Tekbaş, Ömer Faruk; Oğur, Recai; Kılıç, Abdullah; Ulus, Serdar

    2014-01-01

    Aim: This study was performed with the objective to determine the levels of some physical hazards in primary schools. Material and Methods: This study is a cross-sectional field survey. In this study which was conducted in 31 primary schools selected by appropriate sampling from the district of Keçiören of the province of Ankara, measurements related with temperature, light, electromagnetic field (EMF) and noise levels were done at hundreds of points. Approval was obtained from Gülhane Military Medical Faculty Ethics Committee (2007/97). Results: Only 47.1% of the classes had a temperature value within the recommended limits (20–21°C). It was found that the illumination levels in 96.8% of the schools were above the standard values. However, the levels of illumination were found to be statistically significantly decreased towards the door and the back line (p<0.05). It was found that electromagnetic field levels were significantly higher in the schools who had a source of electromagnetic field nearby compared to the schools who did not have such a source nearby (p<0.001). It was found that the electromagnetic field levels in computer classes were statistically significantly higher compared to the other classes (p<0.001). Noise levels were found to be statistically significantly higher in classes which had 35 and more students (p<0.05). No statistically significant difference was found in schools near intensive vehicle traffic in terms of noise levels (62.8±5.0 (n=72), 62.0±6.4 (n=79), respectively, p>0.05). Conclusions: It was found that primary schools in the region of Keçiören had aspects which had to be improved in terms of building age, building location, brightness, electromagnetic field and noise levels. School health programs directed to improve negative enviromental factors should be developed. PMID:26078666

  17. Interorganizational factors affecting the delivery of primary care to older Americans.

    PubMed Central

    Kaluzny, A D; Zuckerman, H S; Rabiner, D J

    1998-01-01

    OBJECTIVE: To discuss different types and forms of interorganizational linkages involved in the provision of primary care to older Americans, along with their distinguishing characteristics. RESEARCH STRATEGY: To take advantage of these linkage characteristics. The strategy requires a partnership with health services organizations and providers actually involved in the provision of services along with a planned sequence of activities involving hypotheses and methods development, intervention trials, and finally, demonstration and implementation. CONCLUSION: Because older Americans are frequent users of health services, their need for continuity and access provides an opportunity to examine changes to the delivery system and to monitor the system's capability for meeting their healthcare needs. PMID:9618676

  18. Axitinib affects cell viability and migration of a primary foetal lung adenocarcinoma culture.

    PubMed

    Menna, Cecilia; De Falco, Elena; Pacini, Luca; Scafetta, Gaia; Ruggieri, Paola; Puca, Rosa; Petrozza, Vincenzo; Ciccone, Anna Maria; Rendina, Erino Angelo; Calogero, Antonella; Ibrahim, Mohsen

    2014-01-01

    Fetal lung adenocarcinoma (FLAC) is a rare variant of lung adenocarcinoma. Studies regarding FLAC have been based only on histopathological observations, thus representative in vitro models of FLAC cultures are unavailable. We have established and characterized a human primary FLAC cell culture, exploring its biology, chemosensitivity, and migration. FLAC cells and specimen showed significant upregulation of VEGF165 and HIF-1α mRNA levels. This observation was confirmed by in vitro chemosensitivity and migration assay, showing that only Axitinib was comparable to Cisplatin treatment. We provide a suitable in vitro model to further investigate the nature of this rare type of cancer. PMID:24380379

  19. Multifunctional T Lymphocytes Generated After Therapy With an Antitumor Gallotanin-Rich Normalized Fraction Are Related to Primary Tumor Size Reduction in a Breast Cancer Model.

    PubMed

    Urueña, Claudia; Gomez, Alejandra; Sandoval, Tito; Hernandez, John; Li, Shaoping; Barreto, Alfonso; Fiorentino, Susana

    2015-09-01

    Natural compounds are promising sources for anticancer therapies because of their multifunctional activity and low toxicity. Although the host immune response (IR) is clearly implicated in tumor control, the relationship between natural therapies and IR has not yet been elucidated. The present work evaluates IR induction after treatment with a gallotannin-rich fraction from Caesalpinia spinosa (P2Et). Breast tumor 4T1 cells were used to evaluate antitumor properties and IR activation. Apoptosis and expression of immunogenic cell death (ICD) markers were assessed in vitro, whereas IR and postvaccination tumor evolution were assessed in vivo. P2Et fraction induced apoptotic cell death, displaying phosphatidylserine externalization and DNA fragmentation. ICD markers such as calreticulin, high-mobility group box 1 translocation from nuclei to cytoplasm, and ATP secretion were observed. Primary tumor control was improved by vaccination with P2Et-pretreated 4T1 cells (t-P2Et), yielding long-lasting ex vivo multifunctional CD4(+) and CD8(+) T lymphocytes (interleukin [IL]-2(+), tumor necrosis factor [TNF]-α(+), interferon [IFN]-γ(+)) that secrete IL-2, TNF-α, IL-4, IL-5, and IFN-γ after specific 4T1 cell stimulation. The present study constitutes the first demonstration of a long-lasting antitumor IR induction and primary tumor reduction induced by a complex natural fraction. These data reveal the potential use of this fraction