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Sample records for small round-cell tumor

  1. Desmoplastic Small Round Cell Tumor of Stomach

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    Ahmed Abu-Zaid

    2013-01-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT is an extremely uncommon, highly aggressive, and malignant mesenchymal neoplasm of undetermined histogenesis. Less than 200 case reports have been documented in literature so far. Herein, we report a 26-year-old otherwise healthy female patient who presented with a 1-month history of epigastric pain. On physical examination, a palpable, slightly mobile, and tender epigastric mass was detected. All laboratory tests were normal. A chest, abdominal, and pelvic contrast-enhanced computed tomography (CT scans showed a 3.8 × 7.2 × 8.7 cm ill-defined mass, involving gastric fundus and extending into gastric cardia and lower gastroesophageal junction. It was associated with multiple enlarged gastrohepatic lymph nodes; the largest measured 1.2 cm. There was no evidence of ascites or retroperitoneal or mesenteric lymphatic metastases. Patient underwent total gastrectomy with D2 lymphadenectomy, splenectomy, and antecolic Roux-en-Y esophagojejunal anastomosis. Histopathological examination revealed coexpression of mesenchymal, epithelial, and neural markers. The characteristic chromosomal translocation (t(11; 22(p13; q12 was demonstrated on fluorescence in situ hybridization (FISH technique. Diagnosis of DSRCT of stomach was confirmed. Patient received no postoperative radiotherapy or chemotherapy. A postoperative 3-month followup failed to show any recurrence. In addition, a literature review on DSRCT is included.

  2. Primary desmoplastic small round cell tumor of the femur

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

    2008-09-15

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

  3. Primary desmoplastic small round cell tumor of the femur

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    Yoshida, Akihiko; Garcia, Joaquin; Edgar, Mark A.; Meyers, Paul A.; Morris, Carol D.; Panicek, David M.

    2008-01-01

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

  4. Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor.

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    Hayes-Jordan, Andrea A; Ma, Xiao; Menegaz, Brian A; Lamhamedi-Cherradi, Salah-Eddine; Kingsley, Charles V; Benson, Jalen A; Camacho, Pamela E; Ludwig, Joseph A; Lockworth, Cynthia R; Garcia, Gloria E; Craig, Suzanne L

    2018-05-01

    Desmoplastic Small Round Cell Tumor (DSRCT) is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing's sarcoma gene (EWSR1) and the Wilms' tumor suppressor gene (WT1). Patients usually develop multiple abdominal tumors with liver and lymph node metastasis developing later. Survival is poor using a multimodal therapy that includes chemotherapy, radiation and surgical resection, new therapies are needed for better management of DSRCT. Triggering cell apoptosis is the scientific rationale of many cancer therapies. Here, we characterized for the first time the expression of pro-apoptotic receptors, tumor necrosis-related apoptosis-inducing ligand receptors (TRAILR1-4) within an established human DSRCT cell line and clinical samples. The molecular induction of TRAIL-mediated apoptosis using agonistic small molecule, ONC201 in vitro cell-based proliferation assay and in vivo novel orthotopic xenograft animal models of DSRCT, was able to inhibit cell proliferation that was associated with caspase activation, and tumor growth, indicating that a cell-based delivery of an apoptosis-inducing factor could be relevant therapeutic agent to control DSRCT. Copyright © 2018. Published by Elsevier Inc.

  5. Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor

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    Andrea A. Hayes-Jordan

    2018-05-01

    Full Text Available Desmoplastic Small Round Cell Tumor (DSRCT is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing’s sarcoma gene (EWSR1 and the Wilms’ tumor suppressor gene (WT1. Patients usually develop multiple abdominal tumors with liver and lymph node metastasis developing later. Survival is poor using a multimodal therapy that includes chemotherapy, radiation and surgical resection, new therapies are needed for better management of DSRCT. Triggering cell apoptosis is the scientific rationale of many cancer therapies. Here, we characterized for the first time the expression of pro-apoptotic receptors, tumor necrosis-related apoptosis-inducing ligand receptors (TRAILR1-4 within an established human DSRCT cell line and clinical samples. The molecular induction of TRAIL-mediated apoptosis using agonistic small molecule, ONC201 in vitro cell-based proliferation assay and in vivo novel orthotopic xenograft animal models of DSRCT, was able to inhibit cell proliferation that was associated with caspase activation, and tumor growth, indicating that a cell-based delivery of an apoptosis-inducing factor could be relevant therapeutic agent to control DSRCT.

  6. Ultrastructure and pathology of desmoplastic small round cell tumor

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    Xu Bin; Wang Bo; Gu Junlian; Li Xin; Li Yang

    2010-01-01

    Objective: To observe the change of ultrastructure and pathology of desmoplastic small round cell tumor (DSRCT) and recognize the characteristics of DSRCT and improve the standard of diagnosis. Methods: One case of primary DSRCT in right leg was observed by light microscope, immunohistochemical method and electron microscope and analyzed with review of the literatures. Results: The size of tumor was 3.2 cm x 2.4 cm x 1.3 cm with gray-yellow on cross-section. Foci of hemorrhage and necrosis were noted. Under light microscope, the tumor was composed of sharply demarcated nests of small rounded or oval cells. The cellular aggregates were surrounded and separated by abundant fibrous connective tissue. The tumor cells were uniform in size and shape, and showed small to moderate amounts of pale cytoplasm with indistinct cell borders. The nuclei were round to oval, with clumped chromatin and marked hyperchromasia. Some cells had one or two indistinct nucleoli. Numerous mitotic figures and areas of necrosis were dentified. The immunohistochemical results showed that the tumor cells were strongly positive for CK, EMA and NSE. There was focal positive staining for desmin with a perinuclear dot-like pattern. However, the tumor cells were negative for CgA, Myogenin, Syn, LCA, SMA, S-100, NF, GFAP, HMB45, HHF-35, CD3, CD10, Actin, CD99, and CD20. Under electron microscope, the tumor cells showed paranuclear cytoplasmic intermediate filaments arranging in globular or whorl array. Conclusion: DSRCT occurs both in the abdomen and at other sites. The patients with DSRCT range widely in age. DSRCT has distinctive histopathologic and ultrastructural features. This tumor shows immunohistochemical feature of epithelial, mesenchymal as well as neural multidirectional differentiation. RT-PCR may be served as an important diagnostic adjunct for DSRAT. The prognosis of the patients with DSRCT is very poor. (authors)

  7. Whole abdominopelvic radiotherapy for desmoplastic small round-cell tumor

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    Goodman, Karyn A.; Wolden, Suzanne L.; La Quaglia, Michael P.; Kushner, Brian H.

    2002-01-01

    Purpose: Desmoplastic small round-cell tumor (DSRCT) is a rare, recently described intraperitoneal malignancy occurring predominantly in adolescent boys. Our objective was to evaluate the feasibility and outcome of whole abdominopelvic irradiation (WAPI) as part of a combined modality protocol for patients with DSRCT. Methods and Materials: The records of all 21 patients treated with WAPI for DSRCT at our institution from 1992 to 2001 were retrospectively reviewed. Patients were treated on an institutional protocol with 7 cycles of an alkylator-based chemotherapy. After maximal surgical debulking, patients were treated with external beam radiotherapy to the whole abdomen and pelvis to a dose of 30 Gy. Results: All 21 patients completed the prescribed treatment. The median follow-up was 28 months. The overall survival and relapse-free survival rate at 3 years was 48% and 19%, respectively. The median survival was 32 months, and the median time to relapse was 19 months. Most relapses were intraperitoneal and/or hepatic. Acute toxicities included Radiation Therapy Oncology Group Grade 2 upper and lower gastrointestinal toxicity in 81% and 71% of patients, respectively. All patients experienced acute hematologic toxicity, with Grade 4 thrombocytopenia, leukopenia, and anemia in 76%, 29%, and 33%, respectively. The major long-term toxicity was small bowel obstruction, which occurred in 7 patients (33%) after surgery and WAPI. Conclusion: DSRCT is a rare and highly lethal disease, requiring aggressive multimodality therapy. WAPI is feasible in conjunction with intensive chemotherapy and surgery. Hematologic and gastrointestinal toxicities are expected but manageable with diligent supportive care. The long-term efficacy of this therapy remains disappointing, thus novel approaches are being investigated

  8. Intraabdominal desmoplastic small round cell tumor: Report of a case and literature review.

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    Koniari, Katerina; Mahera, Helen; Nikolaou, Marinos; Chatzis, Odysseas; Glezakou, Ourania; Magiasis, Vasilios; Kiratzis, Georgios

    2011-01-01

    Desmoplastic small round cell tumor is a rare malignancy with poor prognosis that predominantly affects young males. Its etiopathogenesis is still unknown and diagnosis can be achieved only by immunohistochemistry and cytogenetic studies. Due to our limited knowledge of the pathologic and clinical nature of this disease, there is no clear consensus regarding the optimal therapeutic procedures for treating this neoplasm. A high degree of care and improvements in diagnostic capabilities are required in order to identify this entity and avoid misdiagnosis. We report a new case of a 29-year-old male who proceeded to our Emergency Department complaining about non-specific abdominal pain. Physical examination revealed no abnormalities except for a palpable mass in the lower abdomen and a diffuse abdominal pain. Computed Tomography scan showed enlarged paraortic and mesenteric lymphadenopathy, thickness of the small bowel wall and dispersed masses intraperitoneally. He underwent an exploratory laparotomy and the resultant biopsy revealed desmoplastic small round cell tumor. Diagnosis of desmoplastic small round cell tumor can easily be missed because it presents with few early warning symptoms and signs, while the routine blood tests are within normal limits. A high degree of suspicion, a thorough physical examination, a full imaging check and an aggressive therapeutic approach are required in order to identify this disease and fight for a better quality of life for these patients. In addition we make a review of the literature in an effort to clarify the epidemiological, clinical and pathological aspects of this entity.

  9. Desmoplastic small round cell tumor: a case report and review of the literature

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    Pinto, Luiz Gustavo Teixeira; Isberner, Rony Klaus; Scolaro, Bruno Lorenzo; Sezerino, Daniel Oseias; Almeida, Daniel da Silva

    2006-01-01

    Desmoplastic small round cell tumor is a rare and highly aggressive neoplasm that predominantly occurs in young adult males. Pain and abdominal distention are frequent, ascites could be observed. His histogenesis is uncertain and the most common location is the peritoneal cavity. This tumor is characterized by presenting a distinct morphology and polyphenotypic differentiation. We present in this report the case of an adolescent admitted in the service of Internal Medicine and Radiology of the Hospital and Maternity Marieta Konder Bornhausen, Itajai, SC, Brazil, in year 2005. (author)

  10. [A Case of an Abdominal Desmoplastic Small Round Cell Tumor with Metastasis in the Medulla Oblongata].

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    Azami, Ayaka; Takano, Yoshinao; Honda, Michitaka; Todate, Yukitoshi; Tada, Takeshi; Waragai, Mitsuru; Fukushima, Daizo; Suzuki, Nobuyasu; Sato, Atai; Abe, Tsuyoshi; Teranishi, Yasushi; Sakuma, Hideo

    2016-11-01

    A desmoplastic small round cell tumor(DSRCT)is a very rare malignant tumor that mainly occurs in the intra-abdominal cavity in young adults.This neoplasm has an extremely poor prognosis, with a clinical course characterized by rapid progression and metastasis.We present a 31-year-old man who presented with chief complaints of dysphagia, ataxic gait, and hoarseness.He first underwent surgical resection of a tumor in the medulla oblongata; however, the lesion was suspected to be a metastatic neoplasm.Following a thorough medical examination, the patient was diagnosed with retroperitoneal DSRCT with multiple metastatic lesions.He received multidisciplinary treatment including debulking surgery for the primary lesion; radiotherapy for metastatic lesions in the brain, abdomen, and cervical lymph nodes; hepatic artery embolization for liver metastasis; and systemic chemotherapy.The patient died of progressive disease 17 months after the initial diagnosis.

  11. Intra-Abdominal Desmoplastic Small Round Cell Tumor with Elevated Serum CA 125: A Case Report

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    Sheau-Fang Yang

    2003-10-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT is a rare and highly aggressive tumor usually involving the peritoneum. It occurs more commonly in young males and is characterized by distinctive clinical, histologic, and immunophenotypic features. The histogenesis of DSRCT remains unknown. Coexpression of epithelial, mesenchymal, and neural antigens in the same cell provides evidence that DSRCT may arise from a primitive pluripotent stem cell with divergent differentiation. Recently, according to cytogenetic studies, some authors have proposed that the divergent differentiation of DSRCT may be the result of the fusion of Ewing's sarcoma gene and Wilms' tumor suppressor gene. Clinically, an elevated serum CA 125 concentration is found in some patients with DSRCT. We present the case of a 29-year-old man with diffuse intra-abdominal DSRCT and elevated serum CA 125 concentration and briefly review the relevant literature.

  12. [Analysis of the diagnosis and treatment of desmoplastic small round cell tumor].

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    Lu, Baojian; Zhang, Wei; Shang, Zhiqun; Sun, Erlin; Nian, Xuewu; Gao, Jingda; Ma, Chengquan; Han, Ruifa

    2015-09-01

    To explore the clinical diagnostic features and treatment of desmoplastic small round cell tumor (DSRCT), and to improve the understanding and management of this tumor. The clinicopathological data of nine patients treated in our hospital from October 2004 to June 2014 were retrospectively analyzed and a review of the literature was made. The clinical manifestations, pathological characteristics, diagnosis and differential diagnosis, treatment and prognosis of this tumor were summarized and analyzed. Nine patients with DSRCT, 5 males and 4 females, with an average age of 21 years (range 8-56 years) were included in this study. Ultrasound examination revealed irregular low-density mass shadow in the abdominal cavity. CT examination found that 6 cases had abdominal and retroperitoneal multiple solid tumor nodules, uneven density, and visible low density fluid area. Postoperative pathological examination revealed that the tumor cells were small, mostly elliptic, gathered to form clear structure of nests with clear irregular boundaries. The central portion of large tumor nests often showed necrosis. Scattered fibroblasts and large amount of hyalinization of collagen fibers were seen in the interstitial tissue around the nests. Six patients received laparotomy surgery, however, all failed to resect the tumor completely. Three patients received postoperative chemotherapy, i. e. two cases had carboplatin and paclitaxel chemotherapy, and one case of chemotherapy regimen not specified. Two patients had radiation and chemotherapy (no concrete plan was available). Another case was lost to follow-up. Two of the three patients without surgery received chemotherapy with CAP (cyclophosphamide+adriamycin+carboplatin) and total rectal lesions, pelvic and inguinal lymph nodes, ilium metastases radiation therapy. Another one patient received EP regimen (DDP+VP16) which was then changed into a TP chemotherapy alone. Eight of the nine cases died shortly after surgery, and only one

  13. Intra-abdominal desmoplastic small round cell tumors: CT findings and clinicopathological correlations in 13 cases

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    Chouli, Malik [Department of Radiology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Viala, Juliette [Department of Radiology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Dromain, Clarisse [Department of Radiology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Fizazi, Karim [Department of Medicine, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Duvillard, Pierre [Department of Histopathology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France); Vanel, Daniel [Department of Radiology, Institute Gustave Roussy, 39 Rue Camille Desmoulines, 94805 Villejuif Cedex (France)]. E-mail: vanel@igr.fr

    2005-06-01

    Purpose: We report computed tomography (CT) findings in 13 patients with a primary abdominal desmoplastic small round cell tumor. Materials and methods: 13 cases (12 men, 1 woman, mean age = 24.8 years) were found in our hospital database between 1991 and 2003. Clinical, CT and histopathological features were studied retrospectively. Results: Peritoneal involvement was the most common feature. In 10 cases, several lobulated peritoneal soft tissue masses (with a mean of four masses per patient) were seen. Two patients had diffused irregular peritoneal carcinomatosis without any distinct peritoneal masses. One patient had a solitary mass in the pelvic space. The main sites of peritoneal involvement were the pelvic space (n 7), omentum (n = 5), retroperitoneal space (n = 4), small bowel mesentery (n = 3), paracolic gutter (n = 2 on the right and n = 1 on the left), transverse colon mesentery (n = 1), peri-splenic space (n = 1), peri-hepatic space (n 1). The soft tissue masses were often bulky (mean 6 cm, range 1-28 cm), lobulated and heterogeneous with hypodense areas (in 73% of cases). In six cases, moderate ascites was seen. In one case of pelvic involvement, unilateral hydronephrosis was seen. Adenopathies were present in seven cases at the time of the diagnosis (at intraperitoneal, retroperitoneal and pelvic sites in six patients and in the groin in one patient). Five patients had liver metastases (four lesions per case excepted one patient with 30 metastases). Associated thoracic metastases were seen in three patients. The diagnosis was confirmed with four CT-guided percutaneous biopsies. Conclusion: Although CT features are nonspecific, the diagnosis of desmoplastic small round cell tumor may be suspected in young men with multiple bulky heterogeneous peritoneal soft tissue masses. Imaging is useful for staging and also to guide biopsies.

  14. Novel Secondary Somatic Mutations in Ewing's Sarcoma and Desmoplastic Small Round Cell Tumors

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    Janku, Filip; Ludwig, Joseph A.; Naing, Aung; Benjamin, Robert S.; Brown, Robert E.; Anderson, Pete; Kurzrock, Razelle

    2014-01-01

    Background Ewing's sarcoma (ES) and desmoplastic small round cell tumors (DSRCT) are small round blue cell tumors driven by an N-terminal containing EWS translocation. Very few somatic mutations have been reported in ES, and none have been identified in DSRCT. The aim of this study is to explore potential actionable mutations in ES and DSRCT. Methodology Twenty eight patients with ES or DSRCT had tumor tissue available that could be analyzed by one of the following methods: 1) Next-generation exome sequencing platform; 2) Multiplex PCR/Mass Spectroscopy; 3) Polymerase chain reaction (PCR)-based single- gene mutation screening; 4) Sanger sequencing; 5) Morphoproteomics. Principal Findings Novel somatic mutations were identified in four out of 18 patients with advanced ES and two of 10 patients with advanced DSRCT (six out of 28 (21.4%));KRAS (n = 1), PTPRD (n = 1), GRB10 (n = 2), MET (n = 2) and PIK3CA (n = 1). One patient with both PTPRD and GRB10 mutations and one with a GRB10 mutation achieved a complete remission (CR) on an Insulin like growth factor 1 receptor (IGF1R) inhibitor based treatment. One patient, who achieved a partial remission (PR) with IGF1R inhibitor treatment, but later developed resistance, demonstrated a KRAS mutation in the post-treatment resistant tumor, but not in the pre-treatment tumor suggesting that the RAF/RAS/MEK pathway was activated with progression. Conclusions We have reported several different mutations in advanced ES and DSRCT that have direct implications for molecularly-directed targeted therapy. Our technology agnostic approach provides an initial mutational roadmap used in the path towards individualized combination therapy. PMID:25119929

  15. A t (11; 22 (p13; q12 EWS-WT 1 positive desmoplastic small round cell tumor of the maxilla: An unusual case indicating the role of molecular diagnosis in round cell sarcomas

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    Rekhi B

    2010-01-01

    Full Text Available A desmoplastic small round cell tumor (DSRCT is an uncommon tumor characterized by polyphenotypic expression and a specific reciprocal translocation t (11; 22 (p13; q12. It has been rarely identified in the head and neck region. Herein, we describe a DSRCT in the maxilla of a young man, who was initially diagnosed with a primitive neuroectodermal tumor (PNET, based on histopathological appearance of a round cell tumor, with MIC2 and -FLI-1 positivity, on immunohistochemistry (IHC. Diagnosis of a DSRCT was confirmed on molecular analysis with positive -RT-PCR and sequencing results for EWS-WT1 transcript and negativity for EWS-FL1. The case is presented to highlight the value of molecular diagnosis in round cell sarcomas at uncommon sites, especially when similar IHC markers can be expressed in a PNET and a DSRCT. An exact diagnosis of a round cell sarcoma has a therapeutic relevance.

  16. Role of Adjuvant Radiation Therapy After Surgery for Abdominal Desmoplastic Small Round Cell Tumors

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    Atallah, Vincent [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Honore, Charles [Department of Digestive Surgery, Gustave-Roussy Institute, Paris (France); Orbach, Daniel; Helfre, Sylvie [Department of Pediatric Oncology, Curie Institute, Paris (France); Ducassou, Anne [Department of Radiation Oncology, Universitary Cancer Institute, Toulouse (France); Thomas, Laurence [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Levitchi, Mihai-Barbu [Department of Radiation Oncology, Alexis-Vautrin Center, Nancy (France); Mervoyer, Augustin [Department of Radiation Oncology, Cancerologie de l' ouest Institute, Nantes (France); Naji, Salem [Department of Radiation Oncology, Paoli-Calmette Institute, Marseille (France); Dupin, Charles [Department of Radiation Oncology, Universitary Hospital, Bordeaux (France); Bosco-Levy, Pauline J. [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Philippe-Chomette, Pascale [Department of Pediatric Surgery, University Paris 7 Denis Diderot, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Paris (France); Kantor, Guy; Henriques de Figueiredo, Benedicte [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Sunyach, Marie-Pierre [Department of Radiation Oncology, Leon-Berard Center, Lyon (France); Sargos, Paul, E-mail: p.sargos@bordeaux.unicancer.fr [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France)

    2016-07-15

    Purpose: To identify the prognostic role of adjuvant abdominal radiation therapy (RT) on oncologic outcomes as a part of multimodal treatment in the management of desmoplastic small round cell tumor (DSRCT) and to determine its impact according to the quality of surgical resection. Methods and Materials: All patients treated for primary abdominal DSRCT in 8 French centers from 1991 to 2014 were included. Patients were retrospectively staged into 3 groups: group A treated with adjuvant RT after cytoreductive surgery, group B without RT after cytoreductive surgery, and group C by exclusive chemotherapy. Peritoneal progression-free survival (PPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. We also performed a direct comparison between groups A and B to evaluate RT after cytoreductive surgery. Radiation therapy was also evaluated according to completeness of surgery: complete cytoreductive surgery (CCS) or incomplete cytoreductive surgery (ICS). Results: Thirty-seven (35.9%), thirty-six (34.9%), and thirty (28.0%) patients were included in groups A, B, and C, respectively. Three-year OS was 61.2% (range, 41.0%-76.0%), 37.6% (22.0%-53.1%), and 17.3% (6.3%-32.8%) for groups A, B, and C, respectively. Overall survival, PPFS, and PFS differed significantly among the 3 groups (P<.001, P<.001, and P<.001, respectively). Overall survival and PPFS were higher in group A (RT group) compared with group B (no RT group) (P=.045 and P=.006, respectively). Three-year PPFS was 23.8% (10.3%-40.4%) for group A and 12.51% (4.0%-26.2%) for group B. After CCS, RT improved PPFS (P=.024), but differences in OS and PFS were not significant (P=.40 and P=.30, respectively). After ICS, RT improved OS (P=.044). A trend of PPFS and PFS increase was observed, but the difference was not statistically significant (P=.073 and P=.076). Conclusions: Adjuvant RT as part of multimodal treatment seems to confer oncologic benefits for patients treated for abdominal DSRCT

  17. Primary intraosseous desmoplastic small round cell tumor of the calvarium: Case report and review of the literature

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    Vadim Khachaturov, MD

    2015-03-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT is a rare, aggressive malignancy typically occurring intra-abdominally in young adolescent males. Rare extra-abdominal primaries have been reported in the mediastinum, head and neck area, central nervous system, paratesticular region, visceral organs, and soft tissue. We report a primary intraosseous DSRCT of the calvarium in a 6-year-old male who presented with right ear pain and swelling. Imaging showed an aggressive-appearing permeative mixed lytic and sclerotic lesion of the right sphenoid and temporal bones with extensive periosteal reaction, clinically concerning for osteosarcoma. An open biopsy was performed, and the tumor was composed of primitive round cells with perinuclear cytoplasmic clearing, arranged in diffuse sheets and ill-defined nests and surrounded by a prominent desmoplastic stroma. Immunohistochemically the tumor cells were reactive for desmin (dot-like, CD99 (membranous and cytokeratin AE1/3 (focal. EWSR1-WT1 chimeric fusion transcript was detected by reverse transcriptase-polymerase chain reaction. Sequencing of the fusion transcript revealed a rare in-frame junction of EWSR1 exon 10 to WT1 exon 8. This is the third documented case of an intraosseous DSRCT with molecular confirmation, but it is the first reported case to arise in the calvarium. While the diagnosis of DSRCT is usually straightforward in the classic clinical setting of an intra-abdominal mass, awareness that this entity may present as a bone primary is necessary to prevent misclassification as osteosarcoma or other malignancy.

  18. Symptomatic Hypoglycemia Related to Inappropriately High IGF-II Serum Levels in a Patient with Desmoplastic Small Round Cell Tumor

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    Williams Fernandes Barra

    2010-01-01

    Full Text Available A 45-year old man was diagnosed with desmoplastic small round cell tumor (DSRCT with involvement of the peritoneum and pelvis. Disease progression was observed despite systemic chemotherapy. Six months after diagnosis, he developed severe hypoglycemia presented with seizures. He received intravenous glucose infusion and hydrocortisone with poor glycemic control, but with seizures resolution. The investigation excluded insulinoma, adrenal, liver and GH deficiencies. Laboratory showed slight rise of IGF-II and significant increase of the ratio IGF-II : IGF-I, which is pathognomonic of non-islet cell tumor hypoglycemia (NICTH. He received the diagnoses of NICTH related to IGF-II inappropriate production by DSRCT. Despite the attempt to control tumor mass and hypoglycemia, the patient died 9 months after diagnosis. NICTH related to inappropriate IGF-II secretion should be investigated in all cancer patients with refractory hypoglycemia whom insulinoma and other metabolic abnormalities were excluded from.

  19. Desmoplastic small round cell tumor: a case report and review of the literature; Tumor desmoplastico de pequenas celulas: relato de caso e revisao da literatura

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    Pinto, Luiz Gustavo Teixeira [Hospital e Maternidade Marieta Konder Bornhausen, Itajai, SC (Brazil). Servico de Medicina Interna; Isberner, Rony Klaus [Hospital e Maternidade Marieta Konder Bornhausen, Itajai, SC (Brazil). Servico de Radiologia]. E-mail: ronyklaus@terra.com.br; Scolaro, Bruno Lorenzo [Universidade do Vale do Itajai, SC (Brazil). Curso de Medicina]. E-mail: brunoscolaro@yahoo.com.br; Sezerino, Daniel Oseias [Universidade do Vale do Itajai, SC (Brazil). Curso de Medicina. Disciplina de Anatomia Patologica; Almeida, Daniel da Silva [Hospital e Maternidade Marieta Konder Bornhausen, Itajai, SC (Brazil). Servico de Radiologia e Diagnostico por Imagem

    2006-10-15

    Desmoplastic small round cell tumor is a rare and highly aggressive neoplasm that predominantly occurs in young adult males. Pain and abdominal distention are frequent, ascites could be observed. His histogenesis is uncertain and the most common location is the peritoneal cavity. This tumor is characterized by presenting a distinct morphology and polyphenotypic differentiation. We present in this report the case of an adolescent admitted in the service of Internal Medicine and Radiology of the Hospital and Maternity Marieta Konder Bornhausen, Itajai, SC, Brazil, in year 2005. (author)

  20. Removal of an intra-abdominal desmoplastic small round cell tumor by repetitive debulking surgery: A case report and literature review

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    SHIMAZAKI, JIRO; MOTOHASHI, GYO; NISHIDA, KIYOTAKA; TABUCHI, TAKANOBU; UBUKATA, HIDEYUKI; TABUCHI, TAKAFUMI

    2014-01-01

    In the current study, a case of recurrent desmoplastic small round cell tumor (DSRCT) is presented, which was successfully treated by repetitive debulking surgery. In May 2010, a 39-year-old male, with a history of surgical resection of intra-abdominal DSRCT, visited the Ibaraki Medical Center, Tokyo Medical University Hospital (Ami, Japan) with severe lower abdominal discomfort. Abdominal computed tomography revealed a large tumor in the pouch of Douglas with a small number of nodules in the...

  1. CT, MRI, and FDG-PET/CT imaging findings of abdominopelvic desmoplastic small round cell tumors: Correlation with histopathologic findings

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    Zhang Weidong; Li Chuanxing; Liu Qingyu; Hu Yingying; Cao Yun; Huang Jinhua

    2011-01-01

    Objective: To analyze computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT imaging features of abdominopelvic desmoplastic small round cell tumor (DSRCT) and to improve the diagnostic efficacy of these techniques for the detection of such tumor. Methods: We retrospectively analyzed 7 cases of abdominopelvic DSRCT confirmed by histopathologic analysis. Among the 7 patients, 5 patients had undergone CT scanning, 2 of which were also examined with FDG-PET/CT imaging, and 2 had undergone MRI. Unenhanced and contrast-enhanced examinations were performed in all patients, and 2 patients had also undergone dynamic CT contrast-enhanced examinations. Image characteristics, such as shape, size, number, edge, attenuation, and intensity of each lesion before and after contrast enhancement were analyzed and compared with the pathomorphology of the tumors. Results: Multiple large masses in the abdominopelvis were detected in 6 cases, and a large mass in the pelvis was detected in 1 case. Six cases showed largest mass in pelvis, and 1 case in mesentery. None of the masses had a definite organ origin. CT showed soft tissue masses with patchy foci of hypodense areas. MR T1-weighted images revealed lesions with mild hypointense areas and patchy hypointense areas in 2 cases and lesions with patchy hyperintense areas in 1 case. T2-weighted images showed lesions with mixed isointense and hyperintense areas in 1 case and lesions with mixed hypointense, isointense, and hyperintense areas in another. Contrast-enhanced CT and T1-weighted images showed mildly heterogeneous enhancement of the lesions. Other associated findings included peritoneal seeding (n = 3), peritoneal effusions (n = 3), hepatic metastasis (n = 2), bone metastasis (n = 1), and mesenteric and retroperitoneal lymphadenopathy (n = 4). FDG-PET/CT showed multiple nodular foci of increased metabolic activity in the abdominopelvic masses, in the hepatic and

  2. Abdominal desmoplastic small round cell tumor without extraperitoneal metastases: Is there a benefit for HIPEC after macroscopically complete cytoreductive surgery?

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    C Honoré

    Full Text Available Desmoplastic Small Round Cell Tumor (DSRCT is a rare disease affecting predominantly children and young adults and for which the benefit of hyperthermic intraperitoneal chemotherapy (HIPEC after complete cytoreductive surgery (CCRS remains unknown.To identify patients with DSRCT without extraperitoneal metastases (EPM who underwent CCRS between 1991 and 2015, a retrospective nation-wide survey was conducted by crossing the prospective and retrospective databases of the French Network for Rare Peritoneal Malignancies, French Reference Network in Sarcoma Pathology, French Sarcoma Clinical Network and French Pediatric Cancer Society.Among the 107 patients with DSRCT, 48 had no EPM and underwent CCRS. The median peritoneal cancer index (PCI was 9 (range: 2-27. Among these 48 patients, 38 (79% had pre- and/or postoperative chemotherapy and 23 (48% postoperative whole abdominopelvic radiotherapy (WAP-RT. Intraperitoneal chemotherapy was administered to 11 patients (23%: two received early postoperative intraperitoneal chemotherapy (EPIC and nine HIPEC. After a median follow-up of 30 months, the median overall survival (OS of the entire cohort was 42 months. The 2-y and 5-y OS were 72% and 19%. The 2-y and 5-y disease-free survival (DFS were 30% and 12%. WAP-RT was the only variable associated with longer peritoneal recurrence-free survival and DFS after CCRS. The influence of HIPEC/EPIC on OS and DFS was not statistically conclusive.The benefit of HIPEC is still unknown and should be evaluated in a prospective trial. The value of postoperative WAP-RT seems to be confirmed.

  3. FDG PET/CT imaging of desmoplastic small round cell tumor: findings at staging, during treatment and at follow-up

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    Ostermeier, Austin; Snyder, Scott E.; Shulkin, Barry L. [St. Jude Children' s Research Hospital, Department of Radiological Sciences, MS 220, Memphis, TN (United States); McCarville, M.B. [St. Jude Children' s Research Hospital, Department of Radiological Sciences, MS 220, Memphis, TN (United States); College of Medicine, University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Navid, Fariba [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); University of Tennessee Health Science Center, Department of Pediatrics, College of Medicine, Memphis, TN (United States)

    2015-08-15

    Desmoplastic small round cell tumor (DSRCT) is a very uncommon soft-tissue tumor of children and young adults. It has an aggressive course with generally poor survival. In general the assessment of tumor burden and response has relied upon CT or MRI. However these tumors are often metabolically active and can be evaluated using FDG PET/CT imaging. The purpose of this study was to determine the metabolic activity of desmoplastic small round cell tumors using FDG PET/CT imaging and the potential utility of FDG PET/CT in this disease. Eight patients (seven male, one female; ages 2-20 years, median 11 years) with confirmed DSRCT underwent 82 positron emission tomography/computed tomography (PET/CT) scans. PET/CT was used for initial staging (seven patients, eight scans), monitoring response to therapy (eight patients, 37 scans) and for surveillance of DSRCT recurrence (six patients, 37 scans). Each scan performed at diagnosis showed abnormally elevated uptake in the primary tumor. Five patients had abdominal pelvic involvement, and two of those also had thoracic disease. Six patients whose scans showed no abnormal sites of uptake at the end of therapy have had progression-free survivals of 2-10 years. One patient whose scan continued to show uptake during treatment died of disease 1.3 years from diagnosis. Another patient with persistent uptake remained in treatment 3 years after initial diagnosis. One surveillance scan identified recurrent disease. FDG PET/CT identified elevated metabolic activity in each patient studied. Despite our small sample size, FDG PET/CT scans appear useful for the management of patients with DSCRT. Patients whose studies become negative during or following treatment may have a prolonged remission. (orig.)

  4. Removal of an intra-abdominal desmoplastic small round cell tumor by repetitive debulking surgery: A case report and literature review.

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    Shimazaki, Jiro; Motohashi, Gyo; Nishida, Kiyotaka; Tabuchi, Takanobu; Ubukata, Hideyuki; Tabuchi, Takafumi

    2014-05-01

    In the current study, a case of recurrent desmoplastic small round cell tumor (DSRCT) is presented, which was successfully treated by repetitive debulking surgery. In May 2010, a 39-year-old male, with a history of surgical resection of intra-abdominal DSRCT, visited the Ibaraki Medical Center, Tokyo Medical University Hospital (Ami, Japan) with severe lower abdominal discomfort. Abdominal computed tomography revealed a large tumor in the pouch of Douglas with a small number of nodules in the abdominal cavity. The recurrent DSRCT was diagnosed and removed via lower anterior resection; however, complete resection was impossible due to multiple peritoneal metastases. One year later, the patient developed pain in the right groin due to the growth of metastasized tumor cells in the groin lymph nodes. The affected lymph nodes were removed utilizing an extra-peritoneal approach. At the time of writing, the patient continues to survive without any symptoms 60 months since the initial surgery. In conclusion, surgical debulking is a significant procedure for relieving patient symptoms as well as improving the survival time of patients with metastatic and recurrent DSRCT.

  5. Superficial EWSR1-negative undifferentiated small round cell sarcoma with CIC/DUX4 gene fusion: a new variant of Ewing-like tumors with locoregional lymph node metastasis.

    Science.gov (United States)

    Machado, Isidro; Cruz, Julia; Lavernia, Javier; Rubio, Luis; Campos, Jorge; Barrios, María; Grison, Camille; Chene, Virginie; Pierron, Gaelle; Delattre, Olivier; Llombart-Bosch, Antonio

    2013-12-01

    The present study describes a new case of EWSR1-negative undifferentiated sarcoma with CIC/DUX4 gene fusion. This case is similar to tumors described as primitive undifferentiated round cell sarcomas that occur mainly in the trunk and display an aggressive behavior. To our knowledge, this is the first report of such a tumor presenting locoregional lymph node metastasis. In view of previous studies that prove the existence of a particular variant of undifferentiated sarcoma with Ewing-like morphology and CIC/DUX-4 gene fusion, a search for this gene fusion in all undifferentiated round cell sarcomas should be considered if a conclusive diagnosis cannot be reached following other conventional studies. Although additional cases with more extensive follow-up studies are needed, we believe that EWSR1-negative undifferentiated small round cell sarcoma with CIC/DUX4 gene fusion should be added to the list of new sarcoma variants with the possibility of lymph node metastasis.

  6. A rare case of primary clear cell sarcoma of the pubic bone resembling small round cell tumor: an unusual morphological variant

    International Nuclear Information System (INIS)

    Nakayama, Shoko; Tsuji, Motomu; Hanafusa, Toshiaki; Yokote, Taiji; Iwaki, Kazuki; Akioka, Toshikazu; Miyoshi, Takuji; Hirata, Yuji; Takayama, Ayami; Nishiwaki, Uta; Masuda, Yuki

    2012-01-01

    Clear cell sarcoma (CCS) and malignant melanoma share overlapping immunohistochemistry with regard to the melanocytic markers HMB45, S100, and Melan-A. However, the translocation t(12; 22)(q13; q12) is specific to CCS. Therefore, although these neoplasms are closely related, they are now considered to be distinct entities. However, the translocation is apparently detectable only in 50%–70% of CCS cases. Therefore, the absence of a detectable EWS/AFT1 rearrangement may occasionally lead to erroneous exclusion of a translocation-negative CCS. Therefore, histological assessment is essential for the correct diagnosis of CCS. Primary CCS of the bone is exceedingly rare. Only a few cases of primary CCS arising in the ulna, metatarsals, ribs, radius, sacrum, and humerus have been reported, and primary CCS arising in the pubic bone has not been reported till date. We present the case of an 81-year-old man with primary CCS of the pubic bone. Histological examination of the pubic bone revealed monomorphic small-sized cells arranged predominantly as a diffuse sheet with round, hyperchromatic nuclei and inconspicuous nucleoli. The cells had scant cytoplasm, and the biopsy findings indicated small round cell tumor (SRCT). Immunohistochemical staining revealed the tumor cells to be positive for HMB45, S100, and Melan-A but negative for cytokeratin (AE1/AE3) and epithelial membrane antigen. To the best of our knowledge, this is the first case report of primary CCS of the pubic bone resembling SRCT. This ambiguous appearance underscores the difficulties encountered during the histological diagnosis of this rare variant of CCS. Awareness of primary CCS of the bone is clinically important for accurate diagnosis and management when the tumor is located in unusual locations such as the pubic bone and when the translocation t(12; 22)(q13; q12) is absent

  7. Desmoplastic small round cell tumour: Cytological and immunocytochemical features

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    Filho Adhemar

    2005-01-01

    Full Text Available Abstract Background Desmoplastic small round cell tumor (DSRCT is a rare and highly aggressive neoplasm. The cytological diagnosis of these tumors can be difficult because they show morphological features quite similar to other small round blue cells tumors. We described four cases of DSRCT with cytological sampling: one obtained by fine needle aspiration biopsy (FNAB and three from serous effusions. The corresponding immunocytochemical panel was also reviewed. Methods Papanicolaou stained samples from FNAB and effusions were morphologically described. Immunoreaction with WT1 antibody was performed in all cytological samples. An immunohistochemical panel including the following antibodies was performed in the corresponding biopsies: 34BE12, AE1/AE3, Chromogranin A, CK20, CK7, CK8, Desmin, EMA, NSE, Vimentin and WT1. Results The smears showed high cellularity with minor size alteration. Nuclei were round to oval, some of them with inconspicuous nucleoli. Tumor cells are clustered, showing rosette-like feature. Tumor cells in effusions and FNA were positive to WT1 in 3 of 4 cytology specimens (2 out 3 effusions and one FNA. Immunohistochemical reactions for vimentin, NSE, AE1/AE3 and WT1 were positive in all cases in tissue sections. Conclusion The use of an adjunct immunocytochemical panel coupled with the cytomorphological characteristics allows the diagnosis of DSRCT in cytological specimens.

  8. Dedifferentiated giant-cell tumor of bone with an undifferentiated round cell mesenchymal component

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    Eréndira G. Estrada-Villaseñor

    2014-08-01

    Full Text Available The dedifferentiated giant-cell tumor of the bone is a very rare variant of the giant-cell tumor (GCT. We report the clinical, radiographic and histological findings of a dedifferentiated GCT in which the dedifferentiated component consisted of small round cells. We also comment on previously reported cases of dedifferentiated GCT, discuss the clinical implications of this dual histology, and analyze the information published about the coexistence of similar genetic abnormalities in GCT and small round cell tumors of the bone.

  9. Reduced Toxicity With Intensity Modulated Radiation Therapy (IMRT) for Desmoplastic Small Round Cell Tumor (DSRCT): An Update on the Whole Abdominopelvic Radiation Therapy (WAP-RT) Experience

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    Desai, Neil B. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Stein, Nicholas F. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); LaQuaglia, Michael P. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Alektiar, Kaled M. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kushner, Brian H.; Modak, Shakeel; Magnan, Heather M. [Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goodman, Karyn [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wolden, Suzanne L., E-mail: woldens@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-01-01

    Purpose: Desmoplastic small round cell tumor (DSRCT) is a rare malignancy typically involving the peritoneum in young men. Whole abdominopelvic radiation therapy (WAP-RT) using conventional 2-dimensional (2D) radiation therapy (RT) is used to address local recurrence but has been limited by toxicity. Our objectives were to assess the benefit of intensity modulated radiation therapy (IMRT) on toxicity and to update the largest series on radiation for DSRCT. Methods and Materials: The records of 31 patients with DSRCT treated with WAP-RT (22 with 2D-RT and 9 with IMRT) between 1992 and 2011 were retrospectively reviewed. All received multi-agent chemotherapy and maximal surgical debulking followed by 30 Gy of WAP-RT. A further focal boost of 12 to 24 Gy was used in 12 cases. Boost RT and autologous stem cell transplantation were nearly exclusive to patients treated with 2D-RT. Toxicities were assessed with the Common Terminology Criteria for Adverse Events. Dosimetric analysis compared IMRT and simulated 2D-RT dose distributions. Results: Of 31 patients, 30 completed WAP-RT, with a median follow-up after RT of 19 months. Acute toxicity was reduced with IMRT versus 2D-RT: P=.04 for gastrointestinal toxicity of grade 2 or higher (33% vs 77%); P=.02 for grade 4 hematologic toxicity (33% vs 86%); P=.01 for rates of granulocyte colony-stimulating factor; and P=.04 for rates of platelet transfusion. Post treatment red blood cell and platelet transfusion rates were also reduced (P=.01). IMRT improved target homogeneity ([D05-D95]/D05 of 21% vs 46%) and resulted in a 21% mean bone dose reduction. Small bowel obstruction was the most common late toxicity (23% overall). Updated 3-year overall survival and progression-free survival rates were 50% and 24%, respectively. Overall survival was associated with distant metastasis at diagnosis on multivariate analysis. Most failures remained intraperitoneal (88%). Conclusions: IMRT for consolidative WAP-RT in DSRCT improves

  10. The oncogenic properties of EWS/WT1 of desmoplastic small round cell tumors are unmasked by loss of p53 in murine embryonic fibroblasts

    International Nuclear Information System (INIS)

    Bandopadhayay, Pratiti; Thomas, David M; Algar, Elizabeth; Ekert, Paul G; Jabbour, Anissa M; Riffkin, Christopher; Salmanidis, Marika; Gordon, Lavinia; Popovski, Dean; Rigby, Lin; Ashley, David M; Watkins, David N

    2013-01-01

    Desmoplastic small round cell tumor (DSRCT) is characterized by the presence of a fusion protein EWS/WT1, arising from the t (11;22) (p13;q12) translocation. Here we examine the oncogenic properties of two splice variants of EWS/WT1, EWS/WT1-KTS and EWS/WT1 + KTS. We over-expressed both EWS/WT1 variants in murine embryonic fibroblasts (MEFs) of wild-type, p53 +/- and p53 -/- backgrounds and measured effects on cell-proliferation, anchorage-independent growth, clonogenicity after serum withdrawal, and sensitivity to cytotoxic drugs and gamma irradiation in comparison to control cells. We examined gene expression profiles in cells expressing EWS/WT1. Finally we validated our key findings in a small series of DSRCT. Neither isoform of EWS/WT1 was sufficient to transform wild-type MEFs however the oncogenic potential of both was unmasked by p53 loss. Expression of EWS/WT1 in MEFs lacking at least one allele of p53 enhanced cell-proliferation, clonogenic survival and anchorage-independent growth. EWS/WT1 expression in wild-type MEFs conferred resistance to cell-cycle arrest after irradiation and daunorubicin induced apoptosis. We show DSRCT commonly have nuclear localization of p53, and copy-number amplification of MDM2/MDMX. Expression of either isoform of EWS/WT1 induced characteristic mRNA expression profiles. Gene-set enrichment analysis demonstrated enrichment of WNT pathway signatures in MEFs expressing EWS/WT1 + KTS. Wnt-activation was validated in cell lines with over-expression of EWS/WT1 and in DSRCT. In conclusion, we show both isoforms of EWS/WT1 have oncogenic potential in MEFs with loss of p53. In addition we provide the first link between EWS/WT1 and Wnt-pathway signaling. These data provide novel insights into the function of the EWS/WT1 fusion protein which characterize DSRCT

  11. Tumor desmoplásico de pequenas células redondas abdominal da infância: relato de caso Abdominal desmoplastic small round cell tumor of childhood: case report

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    Ulysses dos Santos Torres

    2010-02-01

    Full Text Available O tumor desmoplásico de pequenas células redondas (TDPCR é uma neoplasia rara e altamente agressiva, que afeta predominantemente jovens do sexo masculino. Relata-se um caso de TDPCR em um paciente do sexo masculino, de 11 anos, com acometimento intra-abdominal marcado por volumosa massa retroperitoneal em hipocôndrio esquerdo. O estudo histológico da massa revelou presença de blocos de pequenas células tumorais redondas e azuis, envoltas por estroma desmoplásico; a análise imuno-histoquímica evidenciou positividade para desmina, WT-1 e citoceratinas. Após o diagnóstico, o paciente foi submetido a tratamento quimiorradioterápico, tendo evoluído a óbito durante o 24º mês de acompanhamento.Desmoplastic small round cell tumor (DSRCT is a rare and highly aggressive neoplasm, which predominantly affects young males. We report a case of DSRCT affecting an 11-year-old male patient, with intra-abdominal involvement characterized by a large retroperitoneal mass in left hypochondrium. Histological examination of the mass showed the presence of clusters of small blue round tumor cells surrounded by a dense desmoplastic stroma. Immunohistochemical analysis disclosed a positive reaction to desmin, WT-1 and cytokeratins. After diagnosis, the patient underwent chemo radiotherapy treatment, but died at the 24th month of follow-up.

  12. Morphoproteomic profiling of the mammalian target of rapamycin (mTOR) signaling pathway in desmoplastic small round cell tumor (EWS/WT1), Ewing's sarcoma (EWS/FLI1) and Wilms' tumor(WT1).

    Science.gov (United States)

    Subbiah, Vivek; Brown, Robert E; Jiang, Yunyun; Buryanek, Jamie; Hayes-Jordan, Andrea; Kurzrock, Razelle; Anderson, Pete M

    2013-01-01

    Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma in adolescents and young adults. The hallmark of this disease is a EWS-WT1 translocation resulting from apposition of the Ewing's sarcoma (EWS) gene with the Wilms' tumor (WT1) gene. We performed morphoproteomic profiling of DSRCT (EWS-WT1), Ewing's sarcoma (EWS-FLI1) and Wilms' tumor (WT1) to better understand the signaling pathways for selecting future targeted therapies. This pilot study assessed patients with DSRCT, Wilms' tumor and Ewing's sarcoma. Morphoproteomics and immunohistochemical probes were applied to detect: p-mTOR (Ser2448); p-Akt (Ser473); p-ERK1/2 (Thr202/Tyr204); p-STAT3 (Tyr 705); and cell cycle-related analytes along with their negative controls. In DSRCT the PI3K/Akt/mTOR pathway is constitutively activated by p-Akt (Ser 473) expression in the nuclear compartment of the tumor cells and p-mTOR phosphorylated on Ser 2448, suggesting mTORC2 (rictor+mTOR) as the dominant form. Ewing's sarcoma had upregulated p-Akt and p-mTOR, predominantly mTORC2. In Wilm's tumor, the mTOR pathway is also activated with most tumor cells moderately expressing p-mTOR (Ser 2448) in plasmalemmal and cytoplasmic compartments. This coincides with the constitutive activation of one of the downstream effectors of the mTORC1 signaling pathway, namely p-p70S6K (Thr 389). There was constitutive activation of the Ras/Raf/ERK pathway p-ERK 1/2 (Thr202/Tyr204) expression in the Wilms tumor and metastatic Ewing's sarcoma, but not in the DSRCT. MORPHOPROTEOMIC TUMOR ANALYSES REVEALED CONSTITUTIVE ACTIVATION OF THE MTOR PATHWAY AS EVIDENCED BY: (a) expression of phosphorylated (p)-mTOR, p-p70S6K; (b) mTORC 2 in EWS and DSRCT; (c) ERK signaling was seen in the advanced setting indicating these as resistance pathways to IGF1R related therapies. This is the first morphoproteomic study of such pathways in these rare malignancies and may have potential therapeutic implications. Further study using morphoproteomic

  13. Epidemiological Aspects and Differential Diagnosis of the Cutaneous Round Cell Tumors in Dogs

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    Roxana CORA

    2017-05-01

    Full Text Available Round cell neoplasms (RCNs are frequent cutaneous lesions in dogs, with high percentages among skin tumors. In this category are included histiocytoma, mast cell tumor, plasmacytoma, lymphoma and transmissible venereal tumor. The aim of the study was to perform an epidemiological study with reference to the cutaneous round cell tumors in a period of 10 years in the Department of Pathology (Faculty of Veterinary Medicine, Cluj-Napoca, Romania. Additionally, in the recorded cases with round cell tumors (mast cell tumor, histiocytoma and lymphoma we described the main histological and cytological features. The epidemiological data were collected from the records of Pathology Department between 2005-2014. The investigation included dogs diagnosed with cutaneous round cell neoplasms, following necropsy analysis or assessment of biopsies or cytological samples. All collected specimens were analyzed by histopathological and/or cytological techniques. The staining used for histological investigation were Hematoxylin-eosin, Masson’s trichrome and Toluidine blue, whereas Diff Quik and Wright methods were utilized in cytological specimens. The distribution of the cutaneous round cell tumors in relation to age, breed and sex was also assessed. The most frequent round cell tumor type was the mast cell tumor (19.54% followed by histiocytoma (11.33% and lymphoma (1.98%. The round cell tumors recorded were equally distributed in both males and females. Concerning the distribution of cutaneous RCNs by age (average age, histiocytoma occurred in 5 years old subjects, mast cell tumor in 11.9 years old subjects, and lymphoma in 6 years old subjects. Mast cell tumor was more frequent in stray dogs and Boxer breed, while histiocytoma occurred more commonly in stray dogs. Histological and cytological analysis was mandatory to perform the differential diagnosis between RCNs. Microscopic details concerning cytoplasm and nucleus of tumoral cells, together with the

  14. Intensive combined modality therapy of small round cell and undifferentiated sarcomas in children and young adults

    International Nuclear Information System (INIS)

    Bader, J.L.; Dewan, R.; Watkins, E.; Kinsella, T.J.; Glatstein, E.; STeinberg, S.M.

    1989-01-01

    Seventy-five patients (ages 4-35 years) with the following small round cell tumors and undifferentiated sarcoma were treated at the National Cancer Institute: Ewing's sarcome (n=32), peripheral neuroepithelioma (n=14), rhabdomyosarcoma (n=24), undifferentiated sarcoma (n=5). Most patients had poor prognostic features including 36 (48%) with metastatic disease, and 42 (56%) with central (truncal) tumors (22 in the pelvis). Treatment included 5 cycles of intensive induction chemotherapy with vincristine, cyclophosphamide and adriamycin, plus aggressive local radiation therapy using simulation and computerized treatment planning for all patients. Thereafter, complete clinical responses were consolidated with intensive chemotherapy, total body irradiation and autologous bone marrow transplantation. There were three local only failures, 10 local plus distant failures, 36 distant only failures, 3 treatment-related deaths, and one intercurrent death. Overall actuarial survival and event-free survival at 4 years are 49 and 29%, respectively. Actuarial freedom from local progression was seen in 74% of patients at 4 years, quite remarkable considering the bulk and location of most of these tumors. Without aggressive surgery, many of these high risk patients had satisfactory outcomes, but better systemic treatments are still needed.(author). 44 refs.; 8 figs.; 6 tabs

  15. Clinical, ultrasonographic, and laboratory findings in 12 llamas and 12 alpacas with malignant round cell tumors

    Science.gov (United States)

    Martin, Jeanne M.; Valentine, Beth A.; Cebra, Christopher K.

    2010-01-01

    Clinical signs, duration of illness, clinicopathologic findings, and ultrasonographic findings were evaluated in 12 llamas and 12 alpacas with malignant round cell tumors (MRCT). All but 1 animal died or was euthanized. Common clinical findings were anorexia, recumbency or weakness, and weight loss or poor growth. Peripheral lymphadenomegaly occurred in only 7 animals and was detected more often at necropsy than during physical examination. Common clinicopathologic abnormalities were hypoalbuminemia, acidosis, azotemia, anemia, hyperglycemia, and neutrophilia. Ultrasonography detected tumors in 4/6 animals. Cytologic evaluation of fluid or tissue aspirates or histopathology of biopsy tissue was diagnostic in 5/6 cases. A clinical course of 2 wk or less prior to death or euthanasia was more common in animals ≤ 2 y of age (9/11) than in older animals (6/13). Regular examination of camelids to include clinical pathology and evaluation of peripheral lymph nodes may result in early detection of MCRT. PMID:21358931

  16. NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma.

    Science.gov (United States)

    Sugita, Shintaro; Arai, Yasuhito; Aoyama, Tomoyuki; Asanuma, Hiroko; Mukai, Wakako; Hama, Natsuko; Emori, Makoto; Shibata, Tatsuhiro; Hasegawa, Tadashi

    2017-07-01

    CIC-rearranged sarcoma is a new entity of undifferentiated small round cell sarcoma characterized by chimeric fusions with CIC rearrangement. We report a NUTM2A-CIC fusion sarcoma in a 43-year-old woman who died of rapidly progressive disease. Histologic analysis revealed multinodular proliferation of small round tumor cells with mild nuclear pleomorphism. The sclerotic fibrous septa separated the tumor into multiple nodules. Immunohistochemistry showed that the tumor cells were diffusely positive for vimentin, focally positive for cytokeratin, and negative for CD99 and NKX2.2. Tumor cells were also negative for ETV4, which was recently identified as a specific marker for CIC-rearranged sarcoma. High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded clinical sample unveiled a novel NUTM2A-CIC fusion between NUTM2A exon 7 and CIC exon 12, and fluorescence in situ hybridization identified CIC and NUTM2A split signals. This case shared several clinicopathological findings with previously reported CIC-rearranged cases. We recognized the tumor as a genetically distinct variant of CIC-rearranged sarcomas with a novel NUTM2A-CIC fusion. Copyright © 2017. Published by Elsevier Inc.

  17. A Rare Case of Metastatic Desmoplastic Small Round Cell Tumour: Diagnosis and Management

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    Shahzaib Nabi

    2015-01-01

    Full Text Available A 26-year-old male without any significant past medical history presented to the hospital with shortness of breath, cough, pleuritic chest pain, and weight loss for the past 3 months. On chest CT, he was found to have extensive mediastinal and hilar lymphadenopathy and multiple pulmonary nodules. On physical examination, a right groin mass was noted which had been slowly growing for the past 2 years. Ultrasound of the groin showed complex solid mass with internal vascular channels. CT guided biopsy of the mass showed desmoplastic small round cell tumour. His hospital course was complicated by hypoxic respiratory failure requiring emergent intubation and ICU admission where he completed one cycle of vincristine, cyclophosphamide, and doxorubicin with subsequent improvement, followed by extubation. His condition continued to improve after second cycle of chemotherapy and he was ultimately discharged in a stable condition to continue outpatient chemotherapy after a 2-month inpatient stay.

  18. An Unusual Presentation of Desmoplastic Small Round Cell Tumour of the Abdomen: Morphological, Immunohistochemical, Ultrastructural, and Molecular Studies

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    Preethika Angunawela

    2011-01-01

    Full Text Available Desmoplastic small round cell tumour (DSRCT is an aggressive and a rare neoplasm. We report on a 34-year-old male who had abdominal discomfort with a large intraperitoneal mass. Histological examination of the tumour biopsy revealed sheets of small round cells. The cells were positive with vimentin and desmin (with occasional dot positivity and negative for WT1 and CD 99 with immunohistochemistry. Cytogenetics showed a translocation disrupting the EWSR 1 gene on 22 q 12 consistent with DSRCT. Electron microscopic examination showed sparse cytoplasmic organelles. The patient succumbed 34 months from disease presentation after multiple chemotherapies and thereafter radiotherapy. In summary, our case exemplifies that it is crucial to combine clinical, histological, and molecular aspects in diagnosing DSRCT especially when characteristic dot positivity with desmin is weak along with deficient marking of WT1 and CD99 by immunohistochemistry. Histology was also less clear than published examples of this entity with a poor desmoplastic response. A multidisciplinary approach including early referral to specialised centres is recommended in these cases as tertiary referral centres will be required to substantiate the diagnosis.

  19. Primitive neuroectodermal tumor of the orbit in a 5-year-old girl with microphthalmia

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Heegaard, Steffen; Fledelius, Hans C.

    2000-01-01

    ophthalmology, primitive neuroectodermal tumor (PNET), Ewing's sarcoma, small round-cell tumors, retinoblastoma, medulloepithelioma, microphthalmia, orbitotomy......ophthalmology, primitive neuroectodermal tumor (PNET), Ewing's sarcoma, small round-cell tumors, retinoblastoma, medulloepithelioma, microphthalmia, orbitotomy...

  20. Role of immunohistochemistry and fluorescence in-situ hybridization (FISH in the diagnosis of spindle and round cell tumors of the kidney

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    M. Abbas

    2015-09-01

    Conclusion: In summary we advise an immunohistochemical panel for round/spindle cell tumors of the kidney and for unclear cases we advise to add (FISH to get the correct diagnosis, as they are completely different regarding surgical approach and post-operative adjuvant therapy.

  1. Tumor of small bowel

    International Nuclear Information System (INIS)

    Ruiz Lobo, Elmer Jair; Rubio Vargas, Romulo; Cecilia Hani, Albis

    2009-01-01

    Young woman who is having episodes of overt obscure gastrointestinal bleeding that requires transfusions. The endoscopic study consists of 2 endoscopies of the upper digestive system and two colonoscopies. The tests do not find the cause of the digestive hemorrhage. A double-balloon enteroscopy is performed and it is found that the Ileum has an ulcerate subepithelial lesion with neoplasia appearance which is marked with Chinese ink and biopsies are taken from the tissue which are not diagnosed. Studies of staging are performed ant the result is negative. A laparotomy is performed for diagnosis and treatment which includes the intestinal resection of ileum where the tumor is placed. The result of the test shows to be a neuroendocrine carcinoma of high degree of large cells undifferentiated. One appears in addition a revision to overt obscure gastrointestinal bleeding and neuroendocrine tumor of small

  2. Primary malignant small bowel tumor

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Kyung Seung; Suh, Ho Jong; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk [Kosin College, Pusan (Korea, Republic of)

    1990-07-15

    Small bowel tumors are rarely detected unless there is intestinal obstruction or bleeding. In the seven years 1982-1988, at Kosin Medical Center, 25 primary malignant small bowel tumors were studied radiographically with barium and / or computed tomography (CT). CT revealed gastrointestinal abnormalities in 20 patients. In ten, lesion were identified by upper G-I series, in 15 by small bowel series, and in addition, in 3 by colon enema. The most common malignant small bowel tumor was adenocarcinoma (N=15) and was next common lymphoma (N=7). On barium study, primary adenocarcinoma appeared as an irregular stricture (66.7%) and polypoid mass with intussusception was most prominent finding in lymphoma. Leiomyosarcoma appeared as an exophytic mass with excavation or ulceration. CT was found to be accurate in detecting wall thickening, complications and other associated findings. In conclusion, barium study was useful in the diagnosis of primary malignant small bowel tumor and CT was more accurate in detecting secondary findings.

  3. Primary malignant small bowel tumor

    International Nuclear Information System (INIS)

    Oh, Kyung Seung; Suh, Ho Jong; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk

    1990-01-01

    Small bowel tumors are rarely detected unless there is intestinal obstruction or bleeding. In the seven years 1982-1988, at Kosin Medical Center, 25 primary malignant small bowel tumors were studied radiographically with barium and / or computed tomography (CT). CT revealed gastrointestinal abnormalities in 20 patients. In ten, lesion were identified by upper G-I series, in 15 by small bowel series, and in addition, in 3 by colon enema. The most common malignant small bowel tumor was adenocarcinoma (N=15) and was next common lymphoma (N=7). On barium study, primary adenocarcinoma appeared as an irregular stricture (66.7%) and polypoid mass with intussusception was most prominent finding in lymphoma. Leiomyosarcoma appeared as an exophytic mass with excavation or ulceration. CT was found to be accurate in detecting wall thickening, complications and other associated findings. In conclusion, barium study was useful in the diagnosis of primary malignant small bowel tumor and CT was more accurate in detecting secondary findings

  4. Radiation Treatment for Malignant Small Cell Tumor of the Thoracopulmonary Region Primitive Pluripotent Histogenesis and Differential Diagnosis-A Case Report and Review of Literatures-

    International Nuclear Information System (INIS)

    Oh, Won Young; Yang, Jin Yeong; Whang, In Soon

    1991-01-01

    Malignant small round cell tumor (SRCT) of the thoracopulmonary region appears to originate in the soft tissues of the chest wall or the peripheral lung. A differential diagnosis of poorly differentiated small round cell tumors which include Ewing's sarcoma of bone and soft tissue, embryonal rhabdomyosarcoma, Askin tumor, neuroblastoma, peripheral neuroectodermal tumor, small cell osteogenic sarcoma and lymphoma are after difficult by light microscopy alone. In recent, by the extensive studies electron microscopic examination, histochemical study, immunochemical study, cytogenetics and gene analysis, these tumors may be derived from the primitive and pluripotential cells, differentiating into mesenchymal, epithelial and neural features in variable proportions. Treatment for SRCT of thoracopulmonary regin is not determined because of massive involvement of the lung, pleura or soft tissues of the chest wall resulted in a dismal outcome despite aggressive surgery, irradiation and chemotherapy

  5. Tumors of the small intestine

    International Nuclear Information System (INIS)

    Alonso Gamboa, Tatiana

    2013-01-01

    Differential diagnoses are performed to establish the cause of chronic abdominal pain in patients. Histological types are considered in patients with primary tumors of unknown origin. Benign and malignant neoplasms are described, including methods of diagnosis and treatment. Clinical manifestations are cited. Early and accurate diagnoses are important for an acceptable outcome in patients with malignant small bowel tumors. Recurrence is provoked many deaths, suggesting the importance of adjuvant chemotherapy [es

  6. Primary primitive neuroectodermal tumor of the orbit

    Directory of Open Access Journals (Sweden)

    Das Dipankar

    2009-01-01

    Full Text Available Primitive neuroectodermal tumor (PNET is a small round cell malignant tumor of neuroectodermal origin. Most of the PNETs occur in the central nervous system (CNS. PNETs recognized outside of CNS are diagnosed as peripheral PNET (pPNET. This tumor which expresses MIC-2 gene (CD99 seems to be least aggressive after complete tumor resection. We describe a rare case of PNET in a young girl.

  7. Conservative management of small renal tumors

    International Nuclear Information System (INIS)

    Matsuzaki, Masato; Kawano, Yoshiyuki; Morikawa, Hirofumi; Shiga, Yoshiyuki; Murata, Hirokatsu; Komatsu, Hideki

    2007-01-01

    With the widespread use of imaging modalities, incidentally discovered small renal cell carcinomas have increased. Some patients, however, are too old or weak due to various diseases to undergo surgery and other patients occasionally refuse surgery. To investigate the natural history of small renal cell carcinoma, we retrospectively reviewed patients with small renal tumors suggestive of carcinoma. We retrospectively reviewed 15 patients with contrast-enhancing renal masses less than 4.0 cm in diameter who were observed without treatment. The mean follow-up period was 38 months (range, 8-91). The average patient age was 67 years (range, 44-87). The initial average tumor diameter was 2.2 cm (range, 1.0-3.9). The average growth rate was 0.06 cm per year (range, -0.09-0.28). Only 4 tumors grew obviously during the follow-up period. Three tumors were removed surgically by radical nephrectomy, and all tumors were pathologically diagnosed as renal cell carcinoma. None of the patients developed metastases during the follow-up period or after surgery. Two patients died of other causes. Nonsurgical watchful waiting may be an acceptable treatment option for elderly or severely comorbid patients; however, it is not known whether this conservative management can he applied to young or otherwise healthy patients. (author)

  8. A Biphasic Pleural Tumor with Features of an Epithelioid and Small Cell Mesothelioma: Morphologic and Molecular Findings

    Directory of Open Access Journals (Sweden)

    Sarah Hackman

    2016-01-01

    Full Text Available Malignant mesotheliomas are generally classified into epithelioid, sarcomatoid, desmoplastic, and biphasic types with rare reports of a small cell form. These small cell variants display some morphologic overlap with desmoplastic small round cell tumors (DSRCTs which generally occur within the abdominal cavity of young males and are defined by a characteristic t(11;22(p13;q12 translocation. However, there are rare reports of DSRCTs lacking this translocation. We present a 78-year-old man with a pleura-based biphasic neoplasm with features of both epithelioid mesothelioma and a small cell blastema-like neoplasm. The epithelioid portion showed IHC reactivity for pan cytokeratin, CK5/6, D2-40, and calretinin and the small cell portion marked with CD99, pan cytokeratin, WT1, FLI1, S100, CD200, MyoD1, and CD15. Fluorescence in situ hybridization testing for the t(11;22(p13;q12 translocation disclosed loss of the EWSR1 gene in 94% of tumor cell nuclei, but there was no evidence of the classic translocation. Array based-comparative genomic hybridization (a-CGH confirmed the tumor had numerous chromosome copy number losses, including 11p15.5-p11.12 and 22q12.1-q13.33, with loss of the EWSR1 and WT1 gene regions. Herein, we report novel complex CGH findings in a biphasic tumor and review the molecular genetic alterations in both mesothelioma and DSRCTs.

  9. Desmoplastic round small cell tumor: a case report of a neoplasm of difficult diagnosis

    International Nuclear Information System (INIS)

    Ogata, Daniel Cury; Totsugui, Joel Takashi; Ditzel Filho, Leo Fernando da Silva; Ioshii, Sergio Ossamu; Machuca, Tiago Noguchi; Ogata, Alessandro Cury

    2005-01-01

    Desmoplastic Small Round Cell Tumor (DSRCT) is a rare neoplasm of difficult diagnosis, recently described by Gerald et al. There are reports of nearly 101 cases in the literature, being the intra-abdominal region its most common location and children and young adults its preferred age group. This paper reports a case of DSRCT in a young adult of 24 years of age. This patient presented unspecific symptoms of nausea, vomiting and a single episode of haematemesis. Upon physical examination a solid mass on the epigastrium and left hypochondrium was found. Image diagnostic procedures confirmed the existence of the expansive process and also revealed enlarged retroperitoneal lymphonodes. Diagnosis was achieved through videolaparoscopic biopsy. Histologic sections stained with hematoxylin/eosin were inconclusive and immunohistochemical analysis was required to establish the diagnosis. This analysis revealed positivity to epithelial and mesenchymal markers and weak positivity to chromogranin A, characteristic results of DSRCT. Due to the fact that the disease was locally advanced, the patient was treated with chemotherapy (cyclophosphamide and paclytaxel). However, since there was only partial response to the treatment, the patient refused to undergo any second line option of therapy. Presently, the patient is being submitted only to supportive care, within an 18-month follow-up program. (author)

  10. The role of CT in diagnosing small hepatic tumors

    International Nuclear Information System (INIS)

    Usuki, Noriaki; Daikokuya, Hideo; Fukuda, Haruyuki; Saiwai, Shigeo; Nakajima, Hideyuki; Miyamoto, Takeshi; Kudo, Masatoshi

    1992-01-01

    Twenty-seven cases of small hepatic tumors were examined by MRI and CT (ICT). MRI was more sensitive than plain and contrast CT. But ICT could detect more small lesions than MRI. CT is not more superior modality than MRI untill ICT is performed. It is concluded ICT should be done when diagnosing small hepatic tumors by CT. (author)

  11. Metastatic Patterns of Myxoid/Round Cell Liposarcoma: A Review of a 25-Year Experience

    Directory of Open Access Journals (Sweden)

    Naofumi Asano

    2012-01-01

    Full Text Available Myxoid/round cell liposarcoma (MRCL, unlike other soft tissue sarcomas, has been associated with unusual pattern of metastasis to extrapulmonary sites. In an attempt to elucidate the clinical features of MRCL with metastatic lesions, 58 cases, from the medical database of Keio University Hospital were used for the evaluation. 47 patients (81% had no metastases, whereas 11 patients (11% had metastases during their clinical course. Among the 11 patients with metastatic lesions, 8 patients (73% had extrapulmonary metastases and 3 patients (27% had pulmonary metastases. Patients were further divided into three groups; without metastasis, with extrapulmonary metastasis, and with pulmonary metastasis. When the metastatic patterns were stratified according to tumor size, there was statistical significance between the three groups (P=0.028. The 8 cases with extrapulmonary metastases were all larger than 10 cm. Similarly, histological grading had a significant impact on metastatic patterns (P=0.027. 3 cases with pulmonary metastatic lesions were all diagnosed as high grade. In conclusion, large size and low histological grade were significantly associated with extrapulmonary metastasis.

  12. Contrast-enhanced ultrasonography depicts small tumor vessels for the evaluation of pancreatic tumors

    International Nuclear Information System (INIS)

    Okamoto, Yuko; Kawamoto, Hirofumi; Takaki, Akinobu; Ishida, Etsuji; Ogawa, Tsuneyoshi; Kuwaki, Kenji; Kobayashi, Yoshiyuki; Sakaguchi, Kohsaku; Shiratori, Yasushi

    2007-01-01

    Objective: The aim of this study is to evaluate the efficacy of contrast-enhanced ultrasonography for the diagnosis of pancreatic tumors. Materials and methods: Contrast-enhanced ultrasonography with Levovist was performed on 62 consecutive patients (53 with pancreatic cancer, 4 with islet cell tumor, 3 with inflammatory pancreatic tumor, and 2 with metastatic tumor). The vascular and perfusion image phases of the tumors were evaluated and compared with the findings of contrast-enhanced computed tomography. Results: Contrast-enhanced ultrasonography showed tumor vessels around and/or in the tumor at the vascular image phase in 79% of pancreatic cancer patients (42/53). At the perfusion image phase, 96% of pancreatic cancers (51/53) were classified as hypo-enhancement type. However, tiny spotty or irregular heterogeneous enhanced lesions were found in 84% of hypo-enhanced pancreatic cancer patients (43/51). The presence of small vessels at the vascular image phase was closely correlated with the presence of these intratumor regional enhanced lesions at the perfusion image phase (κ coefficient = 0.42). The sensitivity of contrast-enhanced ultrasonography (100%) for pancreatic cancer was superior to that of contrast-enhanced computed tomography (91%), but no significant difference was observed between the two (McNemar test: p = 0.063). Conclusion: Contrast-enhanced ultrasonography with Levovist successfully visualizes fine vessels and enhancement in pancreatic tumors, and is useful for evaluating pancreatic tumors

  13. Radio frequency ablation of small renal tumors:: intermediate results.

    Science.gov (United States)

    Hwang, J J; Walther, M M; Pautler, S E; Coleman, J A; Hvizda, J; Peterson, James; Linehan, W M; Wood, B J

    2004-05-01

    With evolving radio frequency technology, the clinical application of radio frequency ablation (RFA) has been actively investigated in the treatment for small renal tumors. We present our intermediate patient outcomes after RFA. Since January 2001, 17 patients with a total of 24 hereditary renal tumors ranging from 1.2 to 2.85 cm were treated with RFA using the 200 W Cool-tip RF System (Radionics, Burlington, Massachusetts) under laparoscopic (9) or percutaneous (8) guidance and had a minimum 1-year followup. A percutaneous approach was considered unsuitable if kidney tumors were contiguous to bowel, ureter or large vessels. Treatment eligibility criteria included an average tumor diameter of less than 3.0 cm, tumor growth during 1 year and solid appearance with contrast enhancement (HU change greater than 20) on computerized tomography (CT). Postoperative followup consisted of CT with and without intravenous contrast, and renal function assessment at regular intervals. Median patient age was 38 years (range 20 to 51). At a median followup of 385 days (range 342 to 691), median tumor or thermal lesion diameter decreased from 2.26 to 1.62 cm (p = 0.0013), and only 1 lesion (4%), which was located centrally near the hilum, exhibited contrast enhancement (HU change greater than 10) on CT at 12 months. Of the 15 renal tumors ablated laparoscopically, 13 were in direct contact with the bowel and 2 were abutting the ureter, necessitating mobilization before RFA. Laparoscopic ultrasound was used to guide radio frequency electrode placement and monitor the ablation process in these cases. Operative time and intraoperative blood loss (mean +/- standard mean of error) were 243 +/- 29 minutes and 67 +/- 9 cc, respectively. In 1 patient whose ureter was adherent to the tumor a ureteropelvic junction obstruction developed after laparoscopic RFA, requiring open repair. At the minimum 1-year followup 23 of 24 ablated tumors lacked contrast uptake on CT, meeting our radiographic

  14. Histomorphological and immunohistochemical characterization of 172 cutaneous round cell tumours in dogs

    Directory of Open Access Journals (Sweden)

    Marina Rios Araújo

    2012-08-01

    Full Text Available This paper describes the use of a panel of antibodies (CD117, CD3, CD79a, CD45, cytokeratin, vimentin and E-cadherin on formalin-fixed, paraffin-embedded sections of canine cutaneous round cell tumours. Neoplastic tumours were diagnosed by histology and histochemical stains and included 107 mast cell tumours, 31 cutaneous histiocytomas, two localized histiocytic sarcomas, 21 cutaneous lymphomas, three plasma cell tumours, one transmissible venereal tumour and seven unclassified round cell tumours. The histologic diagnosis was modified in 39.5% of the total 172 neoplasms. The staining for CD45 and Ecadherin were variable, and therefore, the final diagnoses of cutaneous histiocytoma and localized histiocytic sarcoma were made based on histology in association with negative results for CD3, CD79a, CD117 and cytokeratin. The cellular origin of unclassified round cell tumours was defined in all cases. Cutaneous B-cell lymphoma and plasma cell tumours were CD79a-positive and could be distinguished from each other by the morphological characteristics. Mast cell tumours and T cell lymphoma were CD117 and CD3 positive, respectively. The positive staining for vimentin and the negative staining for CD3, CD79a, CD117 and cytokeratin favoured the diagnosis of transmissible venereal tumours. Thus, the final diagnosis of cutaneous round cell tumours should be based on the interpretation of immunohistochemical results together with the cellular morphology observed by histology. Therefore, more studies to optimize the specific markers in formalin-fixed, paraffinembedded tissues (especially for histiocytes are required for definitive diagnosis of round cell tumours in dogs.

  15. Small Submucosal Tumors of the Stomach: Differentiation of Gastric Schwannoma from Gastrointestinal Stromal Tumor with CT

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jin Wook; Choi, Dong Gil; Kim, Kyoung Mee; Sohn, Tae Sung; Lee, Jun Haeng; Kim, Hee Jung; Lee, Soon Jin [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-07-15

    To identify the CT features that help differentiate gastric schwannomas (GS) from small (5 cm or smaller) gastrointestinal stromal tumors (GIST) and to assess the growth rates of both tumors. We included 16 small GSs and 56 GISTs located in the stomach. We evaluated the CT features including size, contour, surface pattern, margins, growth pattern, pattern and degree of contrast enhancement, and the presence of intralesional low attenuation area, hemorrhage, calcification, surface dimpling, fistula, perilesional lymph nodes (LNs), invasion to other organs, metastasis, ascites, and peritoneal seeding. We also estimated the tumor volume doubling time. Compared with GISTs, GSs more frequently demonstrated a homogeneous enhancement pattern, exophytic or mixed growth pattern, and the presence of perilesional LNs (each p < 0.05). The intralesional low attenuation area was more common in GISTs than GSs (p < 0.05). Multivariate analyses indicated that a homogeneous enhancement pattern, exophytic or mixed growth pattern, and the presence of perilesional LNs were statistically significant (p < 0.05). Tumor volume doubling times for GSs (mean, 1685.4 days) were significantly longer than that of GISTs (mean, 377.6 days) (p = 0.004). Although small GSs and GISTs show similar imaging findings, GSs more frequently show an exophytic or mixed growth pattern, homogeneous enhancement pattern, perilesional LNs and grow slower than GISTs.

  16. Small Submucosal Tumors of the Stomach: Differentiation of Gastric Schwannoma from Gastrointestinal Stromal Tumor with CT

    International Nuclear Information System (INIS)

    Choi, Jin Wook; Choi, Dong Gil; Kim, Kyoung Mee; Sohn, Tae Sung; Lee, Jun Haeng; Kim, Hee Jung; Lee, Soon Jin

    2012-01-01

    To identify the CT features that help differentiate gastric schwannomas (GS) from small (5 cm or smaller) gastrointestinal stromal tumors (GIST) and to assess the growth rates of both tumors. We included 16 small GSs and 56 GISTs located in the stomach. We evaluated the CT features including size, contour, surface pattern, margins, growth pattern, pattern and degree of contrast enhancement, and the presence of intralesional low attenuation area, hemorrhage, calcification, surface dimpling, fistula, perilesional lymph nodes (LNs), invasion to other organs, metastasis, ascites, and peritoneal seeding. We also estimated the tumor volume doubling time. Compared with GISTs, GSs more frequently demonstrated a homogeneous enhancement pattern, exophytic or mixed growth pattern, and the presence of perilesional LNs (each p < 0.05). The intralesional low attenuation area was more common in GISTs than GSs (p < 0.05). Multivariate analyses indicated that a homogeneous enhancement pattern, exophytic or mixed growth pattern, and the presence of perilesional LNs were statistically significant (p < 0.05). Tumor volume doubling times for GSs (mean, 1685.4 days) were significantly longer than that of GISTs (mean, 377.6 days) (p = 0.004). Although small GSs and GISTs show similar imaging findings, GSs more frequently show an exophytic or mixed growth pattern, homogeneous enhancement pattern, perilesional LNs and grow slower than GISTs.

  17. Small-cell osteosarcoma

    International Nuclear Information System (INIS)

    Edeiken, J.; Raymond, A.K.; Ayala, A.G.; Benjamin, R.S.; Murray, J.A.; Carrasco, H.C.

    1987-01-01

    Small-cell osteosarcoma, a subtype of osteogenic sarcoma, consists of sheets of round cells that produce an osteoid matrix. It may be confused with Ewing sarcoma if the osteoid matrix is not included in the biopsy. The distinctive radiographic features of an osteoblastic tumor and a pattern of permeative destruction will confirm the histologic diagnosis or indicate the true nature if tumor osteoid is not included in the histological sections. We add 13 patients to the 32 previously reported in the literature. Fourteen (31%) of the 45 are living and well, though three have been followed for only 2 months. The treatments have been so varied that a statistically significant evaluation cannot be developed. The radiographic features are not distinctive, but the diagnosis may be suggested when a tumor has osteoblastic features in the metaphysis and extends well down into the shaft with a pattern of permeative destruction. The radiographic features are especially important when limited biopsies reveal only sheets of round cells, thus suggesting Ewing sarcoma. The presence of an osteoid-producing tumor as evident by osteoblastic new bone formation will lead to the correct diagnosis. (orig.)

  18. Alternative polyadenylation of tumor suppressor genes in small intestinal neuroendocrine tumors

    DEFF Research Database (Denmark)

    Rehfeld, Anders Aagaard; Plass, Mireya; Døssing, Kristina

    2014-01-01

    The tumorigenesis of small intestinal neuroendocrine tumors (SI-NETs) is poorly understood. Recent studies have associated alternative polyadenylation (APA) with proliferation, cell transformation, and cancer. Polyadenylation is the process in which the pre-messenger RNA is cleaved at a polyA site...... and a polyA tail is added. Genes with two or more polyA sites can undergo APA. This produces two or more distinct mRNA isoforms with different 3' untranslated regions. Additionally, APA can also produce mRNAs containing different 3'-terminal coding regions. Therefore, APA alters both the repertoire...... and the expression level of proteins. Here, we used high-throughput sequencing data to map polyA sites and characterize polyadenylation genome-wide in three SI-NETs and a reference sample. In the tumors, 16 genes showed significant changes of APA pattern, which lead to either the 3' truncation of mRNA coding regions...

  19. Alternative Polyadenylation of Tumor Suppressor Genes in Small Intestinal Neuroendocrine Tumors

    OpenAIRE

    Rehfeld, Anders; Plass, Mireya; Døssing, Kristina; Knigge, Ulrich; Kjær, Andreas; Krogh, Anders; Friis-Hansen, Lennart

    2014-01-01

    The tumorigenesis of small intestinal neuroendocrine tumors (SI-NETs) is poorly understood. Recent studies have associated alternative polyadenylation (APA) with proliferation, cell transformation, and cancer. Polyadenylation is the process in which the pre-messenger RNA is cleaved at a polyA site and a polyA tail is added. Genes with two or more polyA sites can undergo APA. This produces two or more distinct mRNA isoforms with different 3′ untranslated regions. Additionally, APA can also pro...

  20. BCOR-CCNB3 Fusion Positive Sarcomas: A Clinicopathologic and Molecular Analysis of 36 Cases With Comparison to Morphologic Spectrum and Clinical Behavior of Other Round Cell Sarcomas.

    Science.gov (United States)

    Kao, Yu-Chien; Owosho, Adepitan A; Sung, Yun-Shao; Zhang, Lei; Fujisawa, Yumi; Lee, Jen-Chieh; Wexler, Leonard; Argani, Pedram; Swanson, David; Dickson, Brendan C; Fletcher, Christopher D M; Antonescu, Cristina R

    2018-05-01

    BCOR-CCNB3 sarcoma (BCS) is a recently defined genetic entity among undifferentiated round cell sarcomas, which was initially classified as and treated similarly to the Ewing sarcoma (ES) family of tumors. In contrast to ES, BCS shows consistent BCOR overexpression, and preliminary evidence suggests that these tumors share morphologic features with other tumors harboring BCOR genetic alterations, including BCOR internal tandem duplication (ITD) and BCOR-MAML3. To further investigate the pathologic features, clinical behavior, and their relationship to other round cell sarcomas, we collected 36 molecularly confirmed BCSs for a detailed histologic and immunohistochemical analysis. Four of the cases were also analyzed by RNA sequencing (RNAseq). An additional case with BCOR overexpression but negative CCNB3 abnormality showed a novel KMT2D-BCOR fusion by targeted RNAseq. The patients ranged in age from 2 to 44 years old (mean and median, 15), with striking male predominance (M:F=31:5). The tumor locations were slightly more common in bone (n=20) than soft tissue (n=14), with rare visceral (kidney, n=2) involvement. Histologically, BCS showed a spectrum of round to spindle cells with variable cellularity, monomorphic nuclei and fine chromatin pattern, delicate capillary network, and varying amounts of myxoid or collagenous stroma. The morphologic features and immunoprofile showed considerable overlap with other round cell sarcomas with BCOR oncogenic upregulation, that is, BCOR-MAML3 and BCOR ITD. Follow-up available in 22 patients showed a 5-year overall survival of 72%, which was relatively similar to ES (79%, P=0.738) and significantly better than CIC-DUX4 sarcomas (43%, P=0.005) control groups. Local recurrences occurred in 6 patients and distant metastases (lung, soft tissue/bone, pancreas) in 4. Seven of 9 cases treated with an ES chemotherapy regimen with evaluable histologic response showed >60% necrosis in posttherapy resections. Unsupervised clustering by

  1. The role of CT in diagnosing small hepatic tumors; Usefulness of table incremental dynamic CT (ICT)

    Energy Technology Data Exchange (ETDEWEB)

    Usuki, Noriaki; Daikokuya, Hideo; Fukuda, Haruyuki; Saiwai, Shigeo; Nakajima, Hideyuki; Miyamoto, Takeshi; Kudo, Masatoshi (Kobe General Hospital, Hyogo (Japan))

    1992-11-01

    Twenty-seven cases of small hepatic tumors were examined by MRI and CT (ICT). MRI was more sensitive than plain and contrast CT. But ICT could detect more small lesions than MRI. CT is not more superior modality than MRI untill ICT is performed. It is concluded ICT should be done when diagnosing small hepatic tumors by CT. (author).

  2. Alternative polyadenylation of tumor suppressor genes in small intestinal neuroendocrine tumors.

    Science.gov (United States)

    Rehfeld, Anders; Plass, Mireya; Døssing, Kristina; Knigge, Ulrich; Kjær, Andreas; Krogh, Anders; Friis-Hansen, Lennart

    2014-01-01

    The tumorigenesis of small intestinal neuroendocrine tumors (SI-NETs) is poorly understood. Recent studies have associated alternative polyadenylation (APA) with proliferation, cell transformation, and cancer. Polyadenylation is the process in which the pre-messenger RNA is cleaved at a polyA site and a polyA tail is added. Genes with two or more polyA sites can undergo APA. This produces two or more distinct mRNA isoforms with different 3' untranslated regions. Additionally, APA can also produce mRNAs containing different 3'-terminal coding regions. Therefore, APA alters both the repertoire and the expression level of proteins. Here, we used high-throughput sequencing data to map polyA sites and characterize polyadenylation genome-wide in three SI-NETs and a reference sample. In the tumors, 16 genes showed significant changes of APA pattern, which lead to either the 3' truncation of mRNA coding regions or 3' untranslated regions. Among these, 11 genes had been previously associated with cancer, with 4 genes being known tumor suppressors: DCC, PDZD2, MAGI1, and DACT2. We validated the APA in three out of three cases with quantitative real-time-PCR. Our findings suggest that changes of APA pattern in these 16 genes could be involved in the tumorigenesis of SI-NETs. Furthermore, they also point to APA as a new target for both diagnostic and treatment of SI-NETs. The identified genes with APA specific to the SI-NETs could be further tested as diagnostic markers and drug targets for disease prevention and treatment.

  3. Crioterapia en pequeños tumores malignos palpebrales Cryotherapy in small malignant eyelids tumors

    Directory of Open Access Journals (Sweden)

    Clara Gómez Cabrera

    2003-06-01

    Full Text Available Para determinar la efectividad de la crioterapia como tratamiento del cáncer de los párpados, se realizó un análisis descriptivo de tipo retrospectivo de 10 pacientes con diagnóstico clínico de carcinoma palpebral cuyo máximo tamaño de la lesión fue de 5 mm y que no fuese pigmentado. El 60 % de los pacientes se encontraba entre los 31 y los 60 años de edad y el 80 % pertenece al sexo femenino. El párpado superior estuvo afectado en un 80 % y el 90 % de las lesiones fueron por clínica diagnosticadas como carcinoma basocelular.y respondieron al tratamiento. La crioterapia es un tratamiento efectivo y curativo en pequeños tumores palpebrales.To determine the effectiveness of cryotherapy to treat eyelids cancer, a descriptive retrospective analysis was made in 10 patients with clinical diagnosis of non-pigmented eyelids carcinoma with a maximun size of 5 mm. 60 % of the patients were between 31 and 60 years old, whereas 80 % were females. The upper eyelid was affected in 80 % and 90 % of the lesions were clinically diagnosed as basal cell carcinoma and responded to treatment. Cryotherapy is an effective and curative treatment in small eyelids tumors.

  4. Intra-abdominal desmoplastic small cell tumor in a girl : a case report

    International Nuclear Information System (INIS)

    Lee, Young Seok

    1998-01-01

    Desmoplastic small cell tumor is a rare primary intra-abdominal disease with a predilection for the adolescent boy. This aggressive tumor involved multiple intraperitoneal organs, peritoneal, mesentery and omental seedings, and sometimes retroperitoneal extension. The author reports a case of this rare tumor, demonstrated by CT, MRI and US, in a 14-year-old girl. (author). 9 refs., 2 figs

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-09-15

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

  6. Small Animal [18F]FDG PET Imaging for Tumor Model Study

    International Nuclear Information System (INIS)

    Woo, Sang Keun; Kim, Kyeong Min; Cheon, Gi Jeong

    2008-01-01

    PET allows non-invasive, quantitative and repetitive imaging of biological function in living animals. Small animal PET imaging with [ 18 F]FDG has been successfully applied to investigation of metabolism, receptor, ligand interactions, gene expression, adoptive cell therapy and somatic gene therapy. Experimental condition of animal handling impacts on the biodistribution of [ 18 F]FDG in small animal study. The small animal PET and CT images were registered using the hardware fiducial markers and small animal contour point. Tumor imaging in small animal with small animal [ 18 F]FDG PET should be considered fasting, warming, and isoflurane anesthesia level. Registered imaging with small animal PET and CT image could be useful for the detection of tumor. Small animal experimental condition of animal handling and registration method will be of most importance for small lesion detection of metastases tumor model

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

    Directory of Open Access Journals (Sweden)

    Vinod Shinde

    2015-01-01

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

  8. Primitive neuroectodermal tumor presenting as a presacral mass: A rare case report with review of literature

    Directory of Open Access Journals (Sweden)

    Pradnya S Bhadarge

    2017-01-01

    Full Text Available Primitive neuroectodermal tumors (PNETs are a group of highly malignant small round cell tumor (SRCT of neuroectodermal origin. They exhibit a great diversity in their clinical manifestations and pathologic similarities with other SRCTs. PNET commonly occurs in the central nervous system, head and neck region, paravertebral region, pelvis, and lower extremities. PNET presenting as a presacral mass is very rare. We present a case of 65-year-old female patient presented with a mass in the abdomen. Exploratory laparotomy with excision of mass was carried out. Histopathology revealed the diagnosis of PNET. The rarity of PNET at presacral region prompted the description of this case.

  9. Congenital Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumor: A Case Report and Review of the Literature.

    Science.gov (United States)

    Jin, Shu-Guang; Jiang, Xiao-Ping; Zhong, Lin

    2016-10-01

    Ewing's sarcoma (EWS) and peripheral primitive neuroectodermal tumor (pPNET) are small round cell malignancies that develop in soft tissue and bone. They very rarely affect newborns. A diagnosis of EWS/pPNET depends mainly on immunohistochemistry and molecular/genetic assays. Since these tumors are highly aggressive, patient prognosis is typically very poor, and treatment remains a challenge. Here, we report a 13-day-old newborn diagnosed with congenital EWS/pPNET and describe its treatment. Copyright © 2014. Published by Elsevier B.V.

  10. Congenital Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumor: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Shu-Guang Jin

    2016-10-01

    Full Text Available Ewing's sarcoma (EWS and peripheral primitive neuroectodermal tumor (pPNET are small round cell malignancies that develop in soft tissue and bone. They very rarely affect newborns. A diagnosis of EWS/pPNET depends mainly on immunohistochemistry and molecular/genetic assays. Since these tumors are highly aggressive, patient prognosis is typically very poor, and treatment remains a challenge. Here, we report a 13-day-old newborn diagnosed with congenital EWS/pPNET and describe its treatment.

  11. Laparoscopic Cryoablation Of Small Renal Tumors – Does Anatomical Tumor Complexity Affect Treatment Outcome?

    DEFF Research Database (Denmark)

    Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Andersen, Gratien

    risk in relation to nephron sparing surgery, but they may also be useful when planning cryoablation. Aim: The aim of the present study was to investigate whether patients with an anatomical complex tumor, represented by a high PADUA-score (≥10), carried a higher risk of residual unablated tumor...... compared to patients with a less anatomical complex tumor when treated with laparoscopic cryoablation. Material and methods: A retrospective review of Aarhus Cryoablation Register identified 120 patients with a single biopsy-verified pT1a renal tumor, treated with primary laparoscopic cryoablation between....... This relative risk of 2.9 (95%CI 1.1;7.6) was statistically significant (p=0.03). The mean follow-up time from treatment to diagnosis of treatment failure was 13 months (95%CI 8;18), which was not significantly different between the two groups. Conclusion: Patients with an anatomical complex tumor, represented...

  12. Laparoscopic Cryoablation Of Small Renal Tumors – Does Anatomical Tumor Complexity Effect Treatment Outcome?

    DEFF Research Database (Denmark)

    Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Andersen, Gratien

    risk in relation to nephron sparing surgery, but they may also be useful when planning cryoablation. Aim: The aim of the present study was to investigate whether patients with an anatomical complex tumor, represented by a high PADUA-score (≥10), carried a higher risk of residual unablated tumor...... compared to patients with a less anatomical complex tumor when treated with laparoscopic cryoablation. Material and methods: A retrospective review of Aarhus Cryoablation Register identified 120 patients with a single biopsy-verified pT1a renal tumor, treated with primary laparoscopic cryoablation between....... This relative risk of 2.9 (95%CI 1.1;7.6) was statistically significant (p=0.03). The mean follow-up time from treatment to diagnosis of treatment failure was 13 months (95%CI 8;18), which was not significantly different between the two groups. Conclusion: Patients with an anatomical complex tumor, represented...

  13. Prognostic factors of tumor recurrence in completely resected non-small cell lung cancer

    International Nuclear Information System (INIS)

    Tantraworasin, Apichat; Saeteng, Somcharoen; Lertprasertsuke, Nirush; Arreyakajohn, Nuttapon; Kasemsarn, Choosak; Patumanond, Jayanton

    2013-01-01

    Patients with completely resected non-small cell lung cancer (NSCLC) have an excellent outcome; however tumor recurs in 30%–77% of patients. This study retrospectively analyzed the clinicopathologic features of patients with any operable stage of NSCLC to identify the prognostic factors that influence tumor recurrence, including intratumoral blood vessel invasion (IVI), tumor size, tumor necrosis, and intratumoral lymphatic invasion. From January 2002 to December 2011, 227 consecutive patients were enrolled in this study. They were divided into two groups: the “no recurrence” group and the “recurrence” group. Recurrence-free survival was analyzed by multivariable Cox regression analysis, stratified by tumor staging, chemotherapy, and nodal involvement. IVI, tumor necrosis, tumor diameter more than 5 cm, and nodal involvement were identified as independent prognostic factors of tumor recurrence. The hazard ratio (HR) of patients with IVI was 2.1 times higher than that of patients without IVI (95% confident interval [CI]: 1.4–3.2) (P = 0.001).The HR of patients with tumor necrosis was 2.1 times higher than that of patients without tumor necrosis (95% CI: 1.3–3.4) (P = 0.001). Patients who had a maximum tumor diameter greater than 5 cm had significantly higher risk of recurrence than patients who had a maximum tumor diameter of less than 5 cm (HR 1.9, 95% CI: 1.0–3.5) (P = 0.033). IVI, tumor diameter more than 5 cm, and tumor necrosis are prognostic factors of tumor recurrence in completely resected NSCLC. Therefore, NSCLC patients, with or without nodal involvement, who have one or more prognostic factors of tumor recurrence may benefit from adjuvant chemotherapy for prevention of tumor recurrence

  14. Validity of bioluminescence measurements for noninvasive in vivo imaging of tumor load in small animals

    NARCIS (Netherlands)

    Klerk, Clara P. W.; Overmeer, Renée M.; Niers, Tatjana M. H.; Versteeg, Henri H.; Richel, Dick J.; Buckle, Tessa; van Noorden, Cornelis J. F.; van Tellingen, Olaf

    2007-01-01

    A relatively new strategy to longitudinally monitor tumor load in intact animals and the effects of therapy is noninvasive bioluminescence imaging (BLI). The validity of BLI for quantitative assessment of tumor load in small animals is critically evaluated in the present review. Cancer cells are

  15. Radical stereotactic radiosurgery with real-time tumor motion tracking in the treatment of small peripheral lung tumors

    Directory of Open Access Journals (Sweden)

    Chang Thomas

    2007-10-01

    Full Text Available Abstract Background Recent developments in radiotherapeutic technology have resulted in a new approach to treating patients with localized lung cancer. We report preliminary clinical outcomes using stereotactic radiosurgery with real-time tumor motion tracking to treat small peripheral lung tumors. Methods Eligible patients were treated over a 24-month period and followed for a minimum of 6 months. Fiducials (3–5 were placed in or near tumors under CT-guidance. Non-isocentric treatment plans with 5-mm margins were generated. Patients received 45–60 Gy in 3 equal fractions delivered in less than 2 weeks. CT imaging and routine pulmonary function tests were completed at 3, 6, 12, 18, 24 and 30 months. Results Twenty-four consecutive patients were treated, 15 with stage I lung cancer and 9 with single lung metastases. Pneumothorax was a complication of fiducial placement in 7 patients, requiring tube thoracostomy in 4. All patients completed radiation treatment with minimal discomfort, few acute side effects and no procedure-related mortalities. Following treatment transient chest wall discomfort, typically lasting several weeks, developed in 7 of 11 patients with lesions within 5 mm of the pleura. Grade III pneumonitis was seen in 2 patients, one with prior conventional thoracic irradiation and the other treated with concurrent Gefitinib. A small statistically significant decline in the mean % predicted DLCO was observed at 6 and 12 months. All tumors responded to treatment at 3 months and local failure was seen in only 2 single metastases. There have been no regional lymph node recurrences. At a median follow-up of 12 months, the crude survival rate is 83%, with 3 deaths due to co-morbidities and 1 secondary to metastatic disease. Conclusion Radical stereotactic radiosurgery with real-time tumor motion tracking is a promising well-tolerated treatment option for small peripheral lung tumors.

  16. Clinical Efficacy of Various Diagnostic Tests for Small Bowel Tumors and Clinical Features of Tumors Missed by Capsule Endoscopy

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    Jung Wan Han

    2015-01-01

    Full Text Available Background. We aimed to evaluate the efficacy of various diagnostic tools such as computerized tomography (CT, small bowel follow-through (SBFT, and capsule endoscopy (CE in diagnosing small bowel tumors (SBTs. Additionally, we aimed to evaluate the clinical features of SBTs missed by CE. Methods. We retrospectively studied 79 patients with histologically proven SBT. Clinical data were analyzed with particular attention to the efficacy of CT, SBFT, and CE in detecting SBT preoperatively. We also analyzed the clinical features of SBTs missed by CE. Results. The most common symptoms of SBT were bleeding (43% and abdominal pain (13.9%. Diagnostic yields were as follows: CT detected 55.8% of proven SBTs; SBFT, 46.1%; and CE, 83.3%. The sensitivity for detecting SBTs was 40.4% for CT, 43.9% for SBFT, and 79.6% for CE. Two patients with nondiagnostic but suspicious findings on CE and seven patients with negative findings on CE were eventually found to have SBT. These nine patients were eventually diagnosed with gastrointestinal stromal tumor (4, small polyps (3, inflammatory fibroid polyp (1, and adenocarcinoma (1. These tumors were located in the proximal jejunum (5, middle jejunum (1, distal jejunum (1, and proximal ileum (1. Conclusion. CE is more efficacious than CT or SBFT for detecting SBTs. However, significant tumors may go undetected with CE, particularly when located in the proximal jejunum.

  17. Intrarenal neuroblastoma mimics Wilms' tumor

    International Nuclear Information System (INIS)

    Muniz, Maria T. Cartaxo; Soares, Andrezza B.; Freitas, Elizabete M.; Araujo, Marcela; Pureza, Leda M.M.; Morais, Adriana; Antunes, Consuelo; Salles, Terezinha de J. Marques; Borges, Josenilda C.; Morais, Vera L.L. de; Romualdo Filho, Jose; Magalhaes, Mario H.

    2005-01-01

    This work reports the case history of a child with intrarenal neuroblastoma, initially diagnosed as Wilms' tumor. The patient, a one year and three months old girl, presented a hard abdominal mass on the left flank that extended to the meso gastric region, plus fever and paleness. The ultrasound of the entire abdomen revealed an intrarenal mass. Biopsy with fine needle in many points of the tumor revealed Wilms' tumor. The scarcely of the material, however, made immunohistoquemistry impossible at that moment. Because of the child's severe condition the SIOP protocol was started. As no clinical response was observed, an exploratory laparotomy was indicated with partial resection of the tumor and bone marrow aspiration (MO). The histopathologic study revealed a malignant neoplasia of small cells, poorly differentiated. IHQ was negative for WT-1 and positive for NB-84, synaptofisin, cromogranine. N-myc amplification was observed by molecular biology. The bone marrow aspiration identified metastatic small round cells infiltration. Intrarenal neuroblastoma is a rare entity that clinically and radiographically resembles Wilms' tumor. The objective of this case report is to show the importance of immunohistochemical and molecular analysis in the diagnosis of intrarenal neuroblastoma. (author)

  18. A rare case of retroperitoneal malignant triton tumor invading renal vein and small intestine

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    Mijović Žaklina

    2013-01-01

    Full Text Available Introduction. Malignant Triton tumor is a very rare malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation. Most of those tumors occur in patients with von Recklinghausen’s disease or as a late complication of irradiation and commonly seen in the head, neck, extremities and trunk. Case report. We reported retroperitoneal malignant Triton tumor in a 57-year-old female patient. Skin lesions were not present, and there was no family history of neurofibromatosis or previous irradiation. The presented case is one of a few recorded in the specialized literature that occurs in the retroperitoneal space in sporadic form. In this case, tumor consisted of a multilobular mass was in close relation with the abdominal aorta and inferior vena cava and involved the renal vein with gross invasion of the small intestine. The patient underwent total resection of the tumor and left nefrectomy was performed. The small intestine 10 cm in length was also resected and end-to-end anastomosis was conducted. The postoperative course was uneventful and the patient was discharged from the hospital ten days after the surgery. Conclusion. Diagnostically, it is crucial to recognize this uncommon histological variant because malignant Triton tumor has a worse prognosis than classic malignant peripheral nerve sheath tumor does. The use of the immunohistochemistry is essential in making the correct diagnosis. Only appropriate pathological evaluation supported by immunostaining with S-100 protein and desmin confirmed the diagnosis. Aggressive surgical management treatment improves the prognosis of such cases with adjuvant radiotherapy.

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

    Science.gov (United States)

    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

  20. Endoscopic excavation for the treatment of small esophageal subepithelial tumors originating from the muscularis propria.

    Science.gov (United States)

    Ye, Li-ping; Zhu, Lin-hong; Zhou, Xian-bin; Mao, Xin-li; Zhang, Yu

    2015-01-01

    This study was designed to evaluate the safety and efficacy of endoscopic excavation for esophageal subepithelial tumors originating from the muscularis propria. Forty-five patients with esophageal subepithelial tumors originating from the muscularis propria were treated with endoscopic excavation between January 2010 and June 2012. The key steps were: (1) making several dots around the tumor; (2) incising the mucosa along with the marker dots, and then seperating the tumor from the muscularis propria by using a hook knife or an insulated-tip knife; (3) closing the artificial ulcer with clips after the tumor was removed. The mean tumor diameter was 1.1 ± 0.6 cm. Endoscopic excavation was successfully performed in 43 out of 45 cases (95.6%), the other 2 cases were ligated with nylon rope. During the procedure perforation occurred in 4 (8.9%) patients, who recovered after conservative treatment. No massive bleeding or delayed bleeding occurred. Histologic diagnosis was obtained from 43 (95.6%) patients. Pathological diagnoses of these tumors were leiomyomas (38/43) and gastrointestinal stromal tumors (5/43). Endoscopic excavation is a safe and effective method for the treatment of small esophageal subepithelial tumors originating from the muscularis propria.

  1. Prognostic factors of tumor recurrence in completely resected non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Tantraworasin A

    2013-06-01

    Full Text Available Apichat Tantraworasin,1 Somcharean Seateang,1 Nirush Lertprasertsuke,2 Nuttapon Arreyakajohn,3 Choosak Kasemsarn,4 Jayanton Patumanond5 1General Thoracic Unit, Department of Surgery, Faculty of Medicine, Chiang Mai University Hospital, Chiang Mai, Thailand; 2Department of Pathology, Faculty of Medicine, Chiang Mai University Hospital, Chiang Mai, Thailand; 3Cardiovascular Thoracic Unit, Department of Surgery, Lampang Hospital, Lampang, Thailand; 4Cardiovascular Thoracic Unit, Department of Surgery, Chest Institute, Nonthaburi, Thailand; 5Department of Community Medicine, Faculty of Medicine, Chiang Mai University Hospital, Chiang Mai, Thailand Background: Patients with completely resected non-small cell lung cancer (NSCLC have an excellent outcome; however tumor recurs in 30%-77% of patients. This study retrospectively analyzed the clinicopathologic features of patients with any operable stage of NSCLC to identify the prognostic factors that influence tumor recurrence, including intratumoral blood vessel invasion (IVI, tumor size, tumor necrosis, and nodal involvement. Methods: From January 2002 to December 2011, 227 consecutive patients were enrolled in this study. They were divided into two groups: the “no recurrence” group and the “recurrence” group. Recurrence-free survival was analyzed by multivariable Cox regression analysis, stratified by tumor staging, chemotherapy, and lymphatic invasion. Results: IVI, tumor necrosis, tumor diameter more than 5 cm, and nodal involvement were identified as independent prognostic factors of tumor recurrence. The hazard ratio (HR of patients with IVI was 2.1 times higher than that of patients without IVI (95% confident interval [CI]: 1.4–3.2 (P = 0.001.The HR of patients with tumor necrosis was 2.1 times higher than that of patients without tumor necrosis (95% CI: 1.3–3.4 (P = 0.001. Patients who had a maximum tumor diameter greater than 5 cm had significantly higher risk of recurrence than

  2. Small bowel Gastrointestinal Stromal Tumors can physiologically alter gut motility before causing mechanical obstruction

    OpenAIRE

    Kothari, Manish S; Kosmoliaptsis, Vasilis; Meyrick-Thomas, John

    2005-01-01

    Background Gastro Intestinal Stromal Tumors (GISTs) are rare stromal neoplasms that represent the most common mesenchymal tumor of the G.I. tract, accounting for 5% of all sarcomas [1,2]. Originating from interstitial cells of Cajal, which are regulators of gut peristalsis, they are preferentially located in the stomach and the small intestine [3] and clinical presentation is variable, ranging from vague complaints to major G.I. bleeding. Surgical resection is the mainstay of treatment for pa...

  3. Value of percutaneous needle biopsy of small renal tumors in patients referred for cryoablation.

    Science.gov (United States)

    Iguchi, Toshihiro; Hiraki, Takao; Gobara, Hideo; Fujiwara, Hiroyasu; Sakurai, Jun; Matsui, Yusuke; Araki, Motoo; Nasu, Yasutomo; Kanazawa, Susumu

    2017-04-01

    To retrospectively evaluate the safety and diagnostic yield of needle biopsy of small renal tumors, and the clinical consequences of performing needle biopsy in patients referred for percutaneous cryoablation before their treatment. Biopsy was performed for 120 tumors (mean diameter, 2.2 cm) in 119 patients. All procedures were divided into diagnostic and non-diagnostic biopsies. Various variables were compared between the two groups. All cryoablation procedures were divided into two groups: procedures with or without simultaneous biopsy. The rates of benign or non-diagnostic tumors in each group were compared. After performing 120 initial and eight repeat biopsies, Grade 1 bleedings occurred in 44 cases. Six tumors were non-diagnostic and 114 were pathologically diagnosed. There were no significant variables between the diagnostic and non-diagnostic biopsies. Unnecessary cryoablation was avoided in nine benign lesions by performing biopsy in advance. Cryoablation performed simultaneously with biopsy included significantly more benign or non-diagnostic tumors than cryoablation performed after biopsy (15.2% vs. 1.4%; p = .01). Percutaneous biopsy of small renal tumors referred for cryoablation was a safe procedure with high diagnostic yield. The confirmation of pathological diagnosis prior to cryoablation is necessary because patients with benign tumors can avoid unnecessary treatment.

  4. Collision tumor of Small Cell Carcinoma and Squamous Cell Carcinoma of maxillary sinus

    Directory of Open Access Journals (Sweden)

    Irfan Sugianto

    2016-06-01

    Full Text Available Two kinds of different malignant tumors occurring within the same organ is defined as collision tumor. Small Cell Carcinoma (SmCC is high-grade derived from neuroendocrine cell tumors, occurance in the head and neck is rare. Squamous Cell Carcinoma (SCC is the most common malignancies encountered in head and neck area, but the occuranceof collision tumor is very rare. This report describe a 82 year-old woman patient with a SmCC and SCC that occurred in the maxillary sinus. CT was performed including with enhancement, MRI examination was T1WI, STIR and contrast enhancement. We also conducted analysis of Dynamic Contrast Enhancement (DCE. Histopathologic examination revealed small cell carcinoma. A distant metastasis was not detected. After patient received chemoradiotherapy (CCRT, most of  tumorwas reduced although a part of the tumor was remained. Pathological examination of surgery tumor specimen revealed that specimen consisted of SCC and SmCC was disappeared, and six months after surgery, the patient suffered tumor recurrence and multiple metastasis to the organs in the abdomen. This time we have to report that the experience one cases that are considered collision cancer of SmCC and SCC that occurred in the maxillary sinus.

  5. New percutaneous ablative modalities in nephron-sparing surgery of small renal tumors

    Science.gov (United States)

    de Riese, Werner T. W.; Nelius, Thomas; Aronoff, David R.; Mittemeyer, Bernhard T.

    2004-07-01

    Renal tumors are increasingly detected on abdominal imaging studies. Standard treatment of small renal tumors includes partial or radical nephrectomy, done either open or laparoscopically. Several in situ ablative techniques to treat small renal lesions are currently in various phases of evolution. All involve imparting destructive energy to the tumor while minimizing injury to adjacent normal tissue. Cryotherapy (CryoT), radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFUS) and high-intensity radiation (HIR) are all being evaluated as tools to ablate renal tumors. The goal with these modalities is to minimize the blood loss, tissue manipulation, and morbidity associated with excisional approaches. Animal studies have shown that large, reproducible lesions can be ablated in normal kidney tissue by these new techniques. Studies of human renal tissue response to RFA are just beginning. Ex vivo studies reveal large, reproducible controlled lesions in normal renal tissue, similar to animal studies. In vivo studies have shown no significant toxicity, while efficacy is currently under evaluation. Preliminary clinical studies in humans have revealed that renal tumors are slow to regress after treatment, but about 75% of these small renal tumors appeared well treated. Mixed responses have been observed in the remaining cases. This paper presents a concise review of efficacy, advantages and disadvantages of these new minimal invasive techniques and their possible clinical implication in the future.

  6. Primitive neuroectodermal tumor or small cell carcinoma of the kidney, arare neoplasm: Case Report

    International Nuclear Information System (INIS)

    Radhi, A.; Ratnakar, K.S.; Al-Durazi, M.; Khalifa, F.

    2002-01-01

    Small cell carcinoma is a malignancy primarily recognized in thebronchopulmonary region. Extrapulmonary locations are extremely uncommon. Wereport here a case of renal tumor encountered in a 34-year-old female, withextensive metastases in liver, lung and bone. Histological examination wasmost compatible with primitive neuroectodermal tumor (PNET) small cellcarcinoma. There were negative immunohistochemical markers for cytokeratin,any hormonal peptides and epithelial membrane antigens, which is consistentwith the designation of neoplasm as PNET. Previously reported cases have allbeen in the elderly and, to the best of our knowledge, this is the first caseof proven PNET of the kidney described in a young female. (author)

  7. [Specific features of mammographic visualization of "small" breast tumors developing on the background of fibrocystic disease].

    Science.gov (United States)

    Bukharin, D G; Velichko, S A; Slonimskaia, E M; Frolova, I G; Luneva, S V; Garbukov, E Iu; Doroshenko, A V

    2011-01-01

    All complications diagnosed at early stages of breast cancer were associated with small tumors, especially with those arising in the aftermath of fibrocystic disease. Hence, our task was to study the XR-semiotics of lesions of less than 15 mm in diameter and of the same origin. 100 mammograms of breast cancer patients with benign disease of the breast were studied. The presence of moderate-to-severe fibrocystic disease significantly affected the visualization of lesions of less than 10 mm in diameter. Since the XR-semiotics of small tumors failed to reveal malignancy features, all lesions visualized by mammography required additional diagnostic procedures using ultrasound and invasive radiology.

  8. Anesthesia condition for 18F-FDG imaging of lung metastasis tumors using small animal PET

    International Nuclear Information System (INIS)

    Woo, Sang-Keun; Lee, Tae Sup; Kim, Kyeong Min; Kim, June-Youp; Jung, Jae Ho; Kang, Joo Hyun; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo

    2008-01-01

    Small animal positron emission tomography (PET) with 18 F-FDG has been increasingly used for tumor imaging in the murine model. The aim of this study was to establish the anesthesia condition for imaging of lung metastasis tumor using small animal 18 F-FDG PET. Methods: To determine the impact of anesthesia on 18 F-FDG distribution in normal mice, five groups were studied under the following conditions: no anesthesia, ketamine and xylazine (Ke/Xy), 0.5% isoflurane (Iso 0.5), 1% isoflurane (Iso 1) and 2% isoflurane (Iso 2). The ex vivo counting, standard uptake value (SUV) image and glucose SUV of 18 F-FDG in various tissues were evaluated. The 18 F-FDG images in the lung metastasis tumor model were obtained under no anesthesia, Ke/Xy and Iso 0.5, and registered with CT image to clarify the tumor region. Results: Blood glucose concentration and muscle uptake of 18 F-FDG in the Ke/Xy group markedly increased more than in the other groups. The Iso 2 group increased 18 F-FDG uptake in heart compared with the other groups. The Iso 0.5 anesthesized group showed the lowest 18 F-FDG uptake in heart and chest wall. The small size of lung metastasis tumor (2 mm) was clearly visualized by 18 F-FDG image with the Iso 0.5 anesthesia. Conclusion: Small animal 18 F-FDG PET imaging with Iso 0.5 anesthesia was appropriate for the detection of lung metastasis tumor. To acquire 18 F-FDG PET images with small animal PET, the type and level of anesthetic should be carefully considered to be suitable for the visualization of target tissue in the experimental model

  9. [Construction of 2-dimensional tumor microvascular architecture phenotype in non-small cell lung cancer].

    Science.gov (United States)

    Liu, Jin-kang; Wang, Xiao-yi; Xiong, Zeng; Zhou, Hui; Zhou, Jian-hua; Fu, Chun-yan; Li, Bo

    2008-08-01

    To construct a technological platform of 2-dimensional tumor microvascular architecture phenotype (2D-TAMP) expression. Thirty samples of non-small cell lung cancer (NSCLC) were collected after surgery. The corresponding sections of tumor tissue specimens to the slice of CT perfusion imaging were selected. Immunohistochemical staining,Gomori methenamine silver stain, and electron microscope observation were performed to build a technological platform of 2D-TMAP expression by detecting the morphology and the integrity of basement membrane of microvasculature, microvascular density, various microvascular subtype, the degree of the maturity and lumenization of microvasculature, and the characteristics of immunogenetics of microvasculature. The technological platform of 2D-TMAP expression was constructed successfully. There was heterogeneity in 2D-TMAP expression of non-small cell lung cancer. The microvascular of NSCLC had certain characteristics. 2D-TMAP is a key technology that can be used to observe the overall state of micro-environment in tumor growth.

  10. Prognostic impact of cytological fluid tumor markers in non-small cell lung cancer.

    Science.gov (United States)

    Cho, Arthur; Hur, Jin; Hong, Yoo Jin; Lee, Hye-Jeong; Kim, Young Jin; Hong, Sae Rom; Suh, Young Joo; Im, Dong Jin; Kim, Yun Jung; Lee, Jae Seok; Shim, Hyo Sup; Choi, Byoung Wook

    2016-03-01

    The serum tumor markers CYFRA 21-1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCCA) are useful in diagnosis and prognosis of non-small cell lung cancer (NSCLC). Cytologic tumor markers obtained during needle aspiration biopsies (NAB) of lung lesions are useful for NSCLC diagnosis. This study investigated the incremental prognostic value of cytologic tumor markers compared to serum tumor markers. This prospective study included 253 patients diagnosed with NSCLC by NAB with cytologic tumor marker analysis. Levels of cytologic CYFRA 21-1, CEA, SCCA, and their serum counterparts were followed up for survival analysis. Optimal cutoff values for each tumor marker were obtained for overall survival (OS) and progression-free survival (PFS) analyses. All patients were followed up for a median of 22.8 months. Using cutoff values of 0.44 ng/ml for C-SCCA, 2.0 ng/ml for S-SCCA, and 3.3 ng/ml for S-CYFRA, a multivariate analysis revealed that high S-SCCA (hazard ratio, HR, 1.84) and high C-SCCA (HR, 1.63) were independent predictive factors of OS. The 3-year overall survival rate was 55 vs. 80 % for high and low C-SCCA, respectively. Cytologic tumor marker level detection is easily obtainable and provides prognostic information for NSCLC. Cytologic tumor markers provide comparable prognostic information relative to serum tumor markers, with C-SCCA acting as a strong prognostic factor of overall survival and PFS.

  11. Multimodality Treatment in Ewing's Sarcoma Family Tumors of the Maxilla and Maxillary Sinus: Review of the Literature

    Science.gov (United States)

    Mamot, Christoph; Krasniqi, Fatime; Metternich, Frank

    2016-01-01

    The Ewing sarcoma family of tumors (ESFT) encompasses a group of highly aggressive, morphologically similar, malignant neoplasms sharing a common spontaneous genetic translocation that affect mostly children and young adults. These predominantly characteristic, small round-cell tumors include Ewing's sarcoma of the bone and soft tissue, as well as primitive neuroectodermal tumors (PNETs) involving the bone, soft tissue, and thoracopulmonary region (Askin's tumor). Extraosseous ESFTs are extremely rare, especially in the head and neck region, where literature to date consists of sporadic case reports and very small series. We hereby present a review of the literature published on ESFTs reported in the maxilla and maxillary sinus region from 1968 to 2016. PMID:27413360

  12. Diagnosis of Retrobulbar Round Cell Neoplasia in a Macaroni Penguin ( Eudyptes chrysolophus ) Through Use of Computed Tomography.

    Science.gov (United States)

    Woodhouse, Sarah J; Rose, Michelle; Desjardins, Danielle R; Agnew, Dalen W

    2015-03-01

    A 25-year-old female macaroni penguin (Eudyptes chrysolophus) was diagnosed with exophthalmos secondary to retrobulbar neoplasia through use of computed tomography (CT). Histopathologic examination of the mass supported a diagnosis of malignant round cell neoplasia. Immunohistochemical (IHC) labeling was applied to determine cell origin; the neoplastic cells did not label with T-cell marker CD3 or B-cell marker BLA.36 and could not be further characterized. The scleral ossicles precluded evaluation of the retrobulbar space by ultrasonography; therefore, CT scanning is recommended for examination of intraorbital structures in penguin and other avian species.

  13. [Hydrocephalus Associated with Small Clinoidal Meningioma that Resolved after Tumor Removal:A Case Report].

    Science.gov (United States)

    Fujiwara, Hidemoto; Aiba, Toyotaka; Watanabe, Toru; Hiraishi, Tetsuya; Fujii, Yukihiko

    2016-12-01

    Small meningiomas causing hydrocephalus without obstruction of the ventricular system are rare. Herein, we report a case of small clinoidal meningioma with communicating hydrocephalus, which resolved after tumor removal. A 70-year-old woman presented with a 1-month history of memory disturbance followed by gait disturbance. MR images revealed a right clinoidal meningioma, 2 cm in diameter, and dilatation of the ventricles suggesting communicating hydrocephalus. The cerebrospinal fluid(CSF)pressure was 130 mmH2O, as determined via a lumbar puncture. High concentrations of protein(65mg/dL)were detected in the lumbar CSF. The tumor was completely removed via a frontotemporal craniotomy. Higher protein concentrations(94mg/dL)were detected in the CSF obtained intraoperatively from the sylvian cistern. The histopathological diagnosis was meningothelial meningioma. The patient's symptoms improved markedly after surgery. Postoperative MR images revealed resolution of the hydrocephalus. The lumbar CSF protein concentration returned to normal(43mg/dL). Neither tumor recurrence nor progression of hydrocephalus has been observed for 4 years. Communicating hydrocephalus, associated with a small meningioma at the supratentorial region, has not been described. Previous studies have shown that patients with meningioma may develop communicating hydrocephalus after tumor removal or stereotactic radiosurgery. Thus, it is interesting that the small supratentorial meningioma in our case developed communicating hydrocephalus without any therapeutic intervention. Considering the CSF protein concentration, we speculate that the hydrocephalus was the result of CSF malabsorption associated with high CSF protein concentration and CSF pathway obstruction at the suprasellar cistern caused by the tumor.

  14. Survived case of tardive small bowel injury resulting from radiotherapy for ovarial tumor

    Energy Technology Data Exchange (ETDEWEB)

    Haruyama, H; Hattori, K; Okubo, H; Ishizaki, Y; Kanemoto, T [National Hospital of Sapporo (Japan)

    1981-07-01

    In a patient who underwent surgical excision of recurrent tumor of ovarian disgerminoma, small bowel injury following radiotherapy was treated by extensive excision of the small intestine followed by intravenous hyperalimentation (I.V.H.) and hyperbaric oxygen therapy. From its clinical course and treatment, we concluded that 1) In small bowel complication due to radiation injury, especially perforation of the small bowel, radical excision of the diseased segment is most promising, if the general and local conditions permit. 2) I.V.H. is effective for protecting and improving postoperative malnutrition after extensive excision of the small bowel. 3) Hyperbaric oxygen therapy is very effective for postoperative paralytic ileus in the case in which surgical operation cannot be performed. 4) Zinc deficiency as a complication of prolonged I.V.H. therapy must be protected. 5) It is necessary to study pathophysiology of short bowel syndrome following the extensive excision and to continue treatment and careful long-term follow-up.

  15. Lymphovascular invasion in more than one-quarter of small rectal neuroendocrine tumors

    Science.gov (United States)

    Kwon, Mi Jung; Kang, Ho Suk; Soh, Jae Seung; Lim, Hyun; Kim, Jong Hyeok; Park, Choong Kee; Park, Hye-Rim; Nam, Eun Sook

    2016-01-01

    AIM To identify the frequency, clinicopathological risk factors, and prognostic significance of lymphovascular invasion (LVI) in endoscopically resected small rectal neuroendocrine tumors (NETs). METHODS Between June 2005 and December 2015, 104 cases of endoscopically resected small (≤ 1 cm) rectal NET specimens at Hallym University Sacred Heart Hospital in Korea were retrospectively evaluated. We compared the detected rate of LVI in small rectal NET specimens by two methods: hematoxylin and eosin (H&E) and ancillary immunohistochemical staining (D2-40 and Elastica van Gieson); in addition, LVI detection rate difference between endoscopic procedures were also evaluated. Patient characteristics, prognosis and endoscopic resection results were reviewed by medical charts. RESULTS We observed LVI rates of 25.0% and 27.9% through H&E and ancillary immunohistochemical staining. The concordance rate between H&E and ancillary studies was 81.7% for detection of LVI, which showed statistically strong agreement between two methods (κ = 0.531, P 5 mm, P = 0.007), tumor grade 2 (P = 0.006). Among those factors, tumor grade 2 was the only independent predictive factor for the presence of LVI (HR = 4.195, 95%CI: 1.321-12.692, P = 0.015). No recurrence was observed over 28.8 mo regardless of the presence of LVI. CONCLUSION LVI may be present in a high percentage of small rectal NETs, which may not be associated with short-term prognosis. PMID:27895428

  16. Multi-small molecule conjugations as new targeted delivery carriers for tumor therapy

    Directory of Open Access Journals (Sweden)

    Shan L

    2015-09-01

    Full Text Available Lingling Shan,1 Ming Liu,2 Chao Wu,1 Liang Zhao,1 Siwen Li,3 Lisheng Xu,1 Wengen Cao,1 Guizhen Gao,1 Yueqing Gu3 1Institute of Pharmaceutical Biotechnology, School of Biology and Food Engineering, Suzhou University, Suzhou, People’s Republic of China; 2Department of Biology, University of South Dakota, Vermillion, SD, USA; 3Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: In response to the challenges of cancer chemotherapeutics, including poor physicochemical properties, low tumor targeting ability, and harmful side effects, we developed a new tumor-targeted multi-small molecule drug delivery platform. Using paclitaxel (PTX as a model therapeutic, we prepared two prodrugs, ie, folic acid-fluorescein-5(6-isothiocyanate-arginine-paclitaxel (FA-FITC-Arg-PTX and folic acid-5-aminofluorescein-glutamic-paclitaxel (FA-5AF-Glu-PTX, composed of folic acid (FA, target, amino acids (Arg or Glu, linker, and fluorescent dye (fluorescein in vitro or near-infrared fluorescent dye in vivo in order to better understand the mechanism of PTX prodrug targeting. In vitro and acute toxicity studies demonstrated the low toxicity of the prodrug formulations compared with the free drug. In vitro and in vivo studies indicated that folate receptor-mediated uptake of PTX-conjugated multi-small molecule carriers induced high antitumor activity. Notably, compared with free PTX and with PTX-loaded macromolecular carriers from our previous study, this multi-small molecule-conjugated strategy improved the water solubility, loading rate, targeting ability, antitumor activity, and toxicity profile of PTX. These results support the use of multi-small molecules as tumor-targeting drug delivery systems. Keywords: multi-small molecules, paclitaxel, prodrugs, targeting, tumor therapy

  17. The potential diagnostic power of circulating tumor cell analysis for non-small-cell lung cancer.

    Science.gov (United States)

    Ross, Kirsty; Pailler, Emma; Faugeroux, Vincent; Taylor, Melissa; Oulhen, Marianne; Auger, Nathalie; Planchard, David; Soria, Jean-Charles; Lindsay, Colin R; Besse, Benjamin; Vielh, Philippe; Farace, Françoise

    2015-01-01

    In non-small-cell lung cancer (NSCLC), genotyping tumor biopsies for targetable somatic alterations has become routine practice. However, serial biopsies have limitations: they may be technically difficult or impossible and could incur serious risks to patients. Circulating tumor cells (CTCs) offer an alternative source for tumor analysis that is easily accessible and presents the potential to identify predictive biomarkers to tailor therapies on a personalized basis. Examined here is our current knowledge of CTC detection and characterization in NSCLC and their potential role in EGFR-mutant, ALK-rearranged and ROS1-rearranged patients. This is followed by discussion of the ongoing issues such as the question of CTC partnership as diagnostic tools in NSCLC.

  18. PTPRZ1 regulates calmodulin phosphorylation and tumor progression in small-cell lung carcinoma

    International Nuclear Information System (INIS)

    Makinoshima, Hideki; Ishii, Genichiro; Kojima, Motohiro; Fujii, Satoshi; Higuchi, Youichi; Kuwata, Takeshi; Ochiai, Atsushi

    2012-01-01

    Small-cell lung carcinoma (SCLC) is a neuroendocrine tumor subtype and comprises approximately 15% of lung cancers. Because SCLC is still a disease with a poor prognosis and limited treatment options, there is an urgent need to develop targeted molecular agents for this disease. We screened 20 cell lines from a variety of pathological phenotypes established from different organs by RT-PCR. Paraffin-embedded tissue from 252 primary tumors was examined for PTPRZ1 expression using immunohistochemistry. shRNA mediated PTPRZ1 down-regulation was used to study impact on tyrosine phosphorylation and in vivo tumor progression in SCLC cell lines. Here we show that PTPRZ1, a member of the protein tyrosine- phosphatase receptor (PTPR) family, is highly expressed in SCLC cell lines and specifically exists in human neuroendocrine tumor (NET) tissues. We also demonstrate that binding of the ligand of PTPRZ1, pleiotrophin (PTN), activates the PTN/PTPRZ1 signaling pathway to induce tyrosine phosphorylation of calmodulin (CaM) in SCLC cells, suggesting that PTPRZ1 is a regulator of tyrosine phosphorylation in SCLC cells. Furthermore, we found that PTPRZ1 actually has an important oncogenic role in tumor progression in the murine xenograft model. PTPRZ1 was highly expressed in human NET tissues and PTPRZ1 is an oncogenic tyrosine phosphatase in SCLCs. These results imply that a new signaling pathway involving PTPRZ1 could be a feasible target for treatment of NETs

  19. Multi-slice spiral CT detects spread of small laryngeal tumors

    International Nuclear Information System (INIS)

    Bruening, R.; Schoepf, U.; Becker, C.; Reiser, M.; Hong, C.; Sturm, C.; Wollenberg, B.

    1999-01-01

    The purpose of the study was to preoperatively investigate small laryngeal carcinomas using multi-slice spiral CT (MSCT) and subsequent multiplanar reconstructions (MPR) and to compare the results to the detailed spread found a surgery and histology. Nine patients with small (T1, T2) laryngeal cancer were investigated on a MSCT scanner (Siemens plus 4 Volume Zoom, Siemens). A 4x1 mm collimation, 120 kV, 200 mAs and a 0.5 seconds rotation time were used, allowing a coverage of the entire larynx in approximately 10 seconds within a single breathhold. Multiplanar reconstruction's (MPR) in sagittal and coronal plane were reconstructed in all patients and rated in consensus reading. In 8 of nine patients, the glottic spread was detected by MSCT, in one case of a supraglottic tumor a glottic invasion was excluded. The infiltration of the anterior commissure, the infiltration into the subglottic space and the extension into the hypo-pharynx was correctly assessed in all patients. MSCT was not able to predict infiltration of the arythnoids in two patients. The use of multi-slice CT for the preoperative assessment of small laryngeal tumors shows great promise. The detection or exclusion of subtle spread of these tumors into the supra- or subglottic space and along the glottic level was possible with high accuracy. As the examination time is short, artifacts are rare and multiplanar reconstructions gain in clinical importance. (orig.) [de

  20. Comparison of Endoscopic and Open Resection for Small Gastric Gastrointestinal Stromal Tumor

    Directory of Open Access Journals (Sweden)

    Fan Feng

    2015-12-01

    Full Text Available The National Comprehensive Cancer Network recommends conservative follow-up for gastric gastrointestinal stromal tumors (GISTs less than 2 cm. We have previously reported that the mitotic index of 22.22% of small gastric GISTs exceeded 5 per 50 high-power fields and recommended that all small gastric GISTs should be resected once diagnosed. The aim of the present study is to compare the safety and outcomes of endoscopic and open resection of small gastric GISTs. From May 2010 to March 2014, a total of 90 small gastric GIST patients were enrolled in the present study, including 40 patients who underwent surgical resection and 50 patients who underwent endoscopic resection. The clinicopathological characteristics, resection-related factors, and clinical outcomes were recorded and analyzed. The clinicopathological characteristics were comparable between the two groups except for tumor location and DOG-1 expression. Compared with the surgical resection group, the operation time was shorter (P = .000, blood loss was less (P = .000, pain intensity was lower (P < .05, duration of first flatus and defecation was shorter (P < .05, and medical cost of hospitalization was lower (P = .027 in the endoscopic resection group. The complications and postoperative hospital stay were comparable between the two groups. No in situ recurrence or liver metastasis was observed during follow-up. Endoscopic resection of small gastric GISTs is safe and feasible compared with surgical resection, although perforation could not be totally avoided during and after resection. The clinical outcome of endoscopic resection is also favorable.

  1. Endoscopic Cerenkov luminescence imaging: in vivo small animal tumor model validation

    Science.gov (United States)

    Song, Tianming; Bao, Chengpeng; Hu, Zhenhua; Wang, Kun; Liu, Xia; Tian, Jie

    2015-03-01

    Background: Cerenkov luminescence imaging (CLI) provides a great potential for clinical translation of optical molecular imaging techniques through using clinical approved radiotracers. However, it is difficult to obtain the Cerenkov luminescence signal of deeper biological tissues due to the small magnitude of the signal. To efficiently acquire the weak Cerenkov luminescence, we developed an endoscopic Cerenkov luminescence imaging (ECLI) system to reduce the in vivo imaging depth with minimum invasion, and validated the system on small animal tumor models. Methods: For the ECLI system, the laparoscope was connected to a high sensitive charge-couple device (CCD) camera (DU888+, Andor, UK) by a custom made adapter. We conducted a series of in vitro and in vivo experiments by use of the system. In the in vitro experiment, the endoscopic luminescence images of the 18F-FDG with various activities in EP tubes were acquired using ECLI system, and the sensitivity was compared with conventional CLI system. In the in vivo tumor experiment, 18F-FDG with the activity of 200μCi were intravenously injected into 3 tumor mice. Then the ECLI system was used to acquire the optical images for both non-invasive and invasive conditions. Conclusion: Experimental data showed the ECLI system could detect the 18F-FDG with the activity as low as 1μCi. Furthermore, our preliminary results indicated the possibility of ECLI technique for detecting Cerenkov signals inside the tumor tissue with deeper depth and guiding the surgical operation of tumor excision. We believe that this technique can help to accelerate the clinical translation of CLI.

  2. Copy number alterations in small intestinal neuroendocrine tumors determined by array comparative genomic hybridization

    International Nuclear Information System (INIS)

    Hashemi, Jamileh; Fotouhi, Omid; Sulaiman, Luqman; Kjellman, Magnus; Höög, Anders; Zedenius, Jan; Larsson, Catharina

    2013-01-01

    Small intestinal neuroendocrine tumors (SI-NETs) are typically slow-growing tumors that have metastasized already at the time of diagnosis. The purpose of the present study was to further refine and define regions of recurrent copy number (CN) alterations (CNA) in SI-NETs. Genome-wide CNAs was determined by applying array CGH (a-CGH) on SI-NETs including 18 primary tumors and 12 metastases. Quantitative PCR analysis (qPCR) was used to confirm CNAs detected by a-CGH as well as to detect CNAs in an extended panel of SI-NETs. Unsupervised hierarchical clustering was used to detect tumor groups with similar patterns of chromosomal alterations based on recurrent regions of CN loss or gain. The log rank test was used to calculate overall survival. Mann–Whitney U test or Fisher’s exact test were used to evaluate associations between tumor groups and recurrent CNAs or clinical parameters. The most frequent abnormality was loss of chromosome 18 observed in 70% of the cases. CN losses were also frequently found of chromosomes 11 (23%), 16 (20%), and 9 (20%), with regions of recurrent CN loss identified in 11q23.1-qter, 16q12.2-qter, 9pter-p13.2 and 9p13.1-11.2. Gains were most frequently detected in chromosomes 14 (43%), 20 (37%), 4 (27%), and 5 (23%) with recurrent regions of CN gain located to 14q11.2, 14q32.2-32.31, 20pter-p11.21, 20q11.1-11.21, 20q12-qter, 4 and 5. qPCR analysis confirmed most CNAs detected by a-CGH as well as revealed CNAs in an extended panel of SI-NETs. Unsupervised hierarchical clustering of recurrent regions of CNAs revealed two separate tumor groups and 5 chromosomal clusters. Loss of chromosomes 18, 16 and 11 and again of chromosome 20 were found in both tumor groups. Tumor group II was enriched for alterations in chromosome cluster-d, including gain of chromosomes 4, 5, 7, 14 and gain of 20 in chromosome cluster-b. Gain in 20pter-p11.21 was associated with short survival. Statistically significant differences were observed between primary

  3. Small cell lung cancer: Recruitment of macrophages by circulating tumor cells.

    Science.gov (United States)

    Hamilton, Gerhard; Rath, Barbara; Klameth, Lukas; Hochmair, Maximilan J

    2016-03-01

    Tumor-associated macrophages (TAMs) play an important role in tumor progression, suppression of antitumor immunity and dissemination. Blood monocytes infiltrate the tumor region and are primed by local microenvironmental conditions to promote tumor growth and invasion. Although many of the interacting cytokines and factors are known for the tumor-macrophage interactions, the putative contribution of circulating tumor cells (CTCs) is not known so far. These specialized cells are characterized by increased mobility, ability to degrade the extracellular matrix (ECM) and to enter the blood stream and generate secondary lesions which is a leading cause of death for the majority of tumor patients. The first establishment of two permanent CTC lines, namely BHGc7 and 10, from blood samples of advanced stage small cell lung cancer (SCLC) patients allowed us to investigate the CTC-immune cell interaction. Cocultures of peripheral blood mononuclear cells (PBMNCs) with CTCs or addition of CTC-conditioned medium (CTC-CM) in vitro resulted in monocyte-macrophage differentiation and appearance of CD14 + , CD163 weak and CD68 + macrophages expressing markers of TAMs. Furthermore, we screened the supernatants of CTC-primed macrophages for presence of approximately 100 cytokines and compared the expression with those induced by the local metastatic SCLC26A cell line. Macrophages recruited by SCLC26A-CM showed expression of osteopontin (OPN), monocyte chemoattractant protein-1 (MCP-1), IL-8, chitinase3-like 1 (CHI3L1), platelet factor (Pf4), IL-1ra and matrix metalloproteinase-9 (MMP-9) among other minor cytokines/chemokines. In contrast, BHGc7-CM induced marked overexpression of complement factor D (CFD)/adipsin and vitamin D-BP (VDBP), as well as increased secretion of OPN, lipocalin-2 (LCN2), CHI3L1, uPAR, MIP-1 and GDF-15/MIC-1. BHGc10, derived independently from relapsed SCLC, revealed an almost identical pattern with added expression of ENA-78/CXCL5. CMs of the non-tumor HEK293

  4. Estimation of organ motion for gated PET imaging in small animal using artificial tumor

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    Woo, Sang Keun; Yu, Jung Woo; Lee, Yong Jin [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2011-10-15

    The image quality is lowered by reducing of contrast and signal due to breathing and heart motion when acquire Positron Emission Tomography (PET) image of small animal tumor. Therefore motion correction is required for betterment of quantitative estimation of tumor. The gated PET using external monitoring device is commonly used for motion correction. But that method has limitation by reason of detection from the outside. Therefore, we had devised the in-vivo motion assessment. In-vivo motion has been demonstrated in lung, liver and abdomen region of rats by coated molecular sieve. In PET image analysis, count and SNR were drawn in the target region. The motion compensation PET image for optimal gate number was confirmed by FWHM. Artificial motion evaluation of tumor using molecular sieve suggests possibility of motion correction modeling without external monitoring devices because it estimates real internal motion of lung, liver, and abdomen. The purpose of this study was to assess the optimal gates number for each region and to improve quantitative estimation of tumor

  5. Prognostic value of tumor burden measurement using the number of tumors in non-surgical patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    Zhang, Hao; Wroblewski, Kristen; Pu, Yonglin

    2012-01-01

    Background: No study to test the feasibility and prognostic value of the number of primary tumors, the number of positive lymph nodes, and the total number of tumors in the whole body as tumor burden measurements on FDG PET/CT imaging has been reported. Purpose: To determine whether the number of tumors seen in 18F-FDG PET scans can be a prognostic factor in non-surgical patients with non-small cell lung cancer (NSCLC). Material and Methods: One hundred and forty patients with histologically proven NSCLC and baseline 18F-FDG PET scan before therapy were identified in this retrospective analysis. The total number of tumors (TTn) in the whole body, the number of primary tumors (Tn), positive lymph nodes (Nn), and distant metastases (Mn), along with the maximum standardized uptake values (SUVmax) of the tumors were measured. Inter-observer variability of the total number of tumors, counted by two radiologists, was assessed. Survival analyses were performed to determine the prognostic value of the number of tumors. Results: Concordance correlation coefficients for the TTn, Tn, Nn, and Mn were all greater than 0.85. TTn and Nn were strong prognostic factors of NSCLC patients' overall survival (OS). In univariate Cox regression models, gender, stage, TTn, Nn, and Mn were statistically significant factors (P = 0.016, 0.032, 4. Conclusion: Measuring the number of tumors on FDG PET imaging is easy to perform with minimal inter-observer variability. The total number of tumors and number of nodal metastases, as metabolic tumor burden measurements in 18F-FDG PET/CT, are prognostic markers independent of clinical stage, age, gender, and SUV measurement in non-surgical patients with NSCLC

  6. Performance of next-generation sequencing on small tumor specimens and/or low tumor content samples using a commercially available platform.

    Directory of Open Access Journals (Sweden)

    Scott Morris

    Full Text Available Next generation sequencing tests (NGS are usually performed on relatively small core biopsy or fine needle aspiration (FNA samples. Data is limited on what amount of tumor by volume or minimum number of FNA passes are needed to yield sufficient material for running NGS. We sought to identify the amount of tumor for running the PCDx NGS platform.2,723 consecutive tumor tissues of all cancer types were queried and reviewed for inclusion. Information on tumor volume, success of performing NGS, and results of NGS were compiled. Assessment of sequence analysis, mutation calling and sensitivity, quality control, drug associations, and data aggregation and analysis were performed.6.4% of samples were rejected from all testing due to insufficient tumor quantity. The number of genes with insufficient sensitivity make definitive mutation calls increased as the percentage of tumor decreased, reaching statistical significance below 5% tumor content. The number of drug associations also decreased with a lower percentage of tumor, but this difference only became significant between 1-3%. The number of drug associations did decrease with smaller tissue size as expected. Neither specimen size or percentage of tumor affected the ability to pass mRNA quality control. A tumor area of 10 mm2 provides a good margin of error for specimens to yield adequate drug association results.Specimen suitability remains a major obstacle to clinical NGS testing. We determined that PCR-based library creation methods allow the use of smaller specimens, and those with a lower percentage of tumor cells to be run on the PCDx NGS platform.

  7. FOXD3 suppresses tumor growth and angiogenesis in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Yan, Jun-Hai; Zhao, Chun-Liu; Ding, Lan-Bao; Zhou, Xi

    2015-01-01

    The transcription factor forkhead box D3 (FOXD3), widely studied as a transcriptional repressor in embryogenesis, participates in the carcinogenesis of many cancers. However, the expression pattern and role of FOXD3 in non-small cell lung cancer (NSCLC) have not been well characterized. We report that FOXD3 is significantly downregulated in NSCLC cell lines and clinical tissues. FOXD3 overexpression significantly inhibits cell growth and results in G1 cell cycle arrest in NSCLC A549 and H1299 cells. In a xenograft tumor model, FOXD3 overexpression inhibits tumor growth and angiogenesis. Remarkably, expression of vascular endothelial growth factor (VEGF) was reduced in FOXD3 overexpression models both in vitro and in vivo. These findings suggest that FOXD3 plays a potential tumor suppressor role in NSCLC progression and represents a promising clinical prognostic marker and therapeutic target for this disease. - Highlights: • FOXD3 is downregulated in NSCLC cell lines and tissues. • FOXD3 overexpression inhibited cell proliferation in NSCLC cells. • FOXD3 overexpression led to decreased angiogenesis in NSCLC cells in vitro and in vivo.

  8. Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

    Directory of Open Access Journals (Sweden)

    Laura Sarah Sasportas

    Full Text Available Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

  9. Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

    Science.gov (United States)

    Sasportas, Laura Sarah; Gambhir, Sanjiv Sam

    2014-01-01

    Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs) into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM) strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

  10. FOXD3 suppresses tumor growth and angiogenesis in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Jun-Hai; Zhao, Chun-Liu [Department of Respiratory Medicine, Luwan Branch of Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 20020 (China); Ding, Lan-Bao [Department of Nuclear Medicine, Shanghai 10th People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Zhou, Xi, E-mail: modelmap@139.com [Department of Respiratory Medicine, Luwan Branch of Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 20020 (China)

    2015-10-09

    The transcription factor forkhead box D3 (FOXD3), widely studied as a transcriptional repressor in embryogenesis, participates in the carcinogenesis of many cancers. However, the expression pattern and role of FOXD3 in non-small cell lung cancer (NSCLC) have not been well characterized. We report that FOXD3 is significantly downregulated in NSCLC cell lines and clinical tissues. FOXD3 overexpression significantly inhibits cell growth and results in G1 cell cycle arrest in NSCLC A549 and H1299 cells. In a xenograft tumor model, FOXD3 overexpression inhibits tumor growth and angiogenesis. Remarkably, expression of vascular endothelial growth factor (VEGF) was reduced in FOXD3 overexpression models both in vitro and in vivo. These findings suggest that FOXD3 plays a potential tumor suppressor role in NSCLC progression and represents a promising clinical prognostic marker and therapeutic target for this disease. - Highlights: • FOXD3 is downregulated in NSCLC cell lines and tissues. • FOXD3 overexpression inhibited cell proliferation in NSCLC cells. • FOXD3 overexpression led to decreased angiogenesis in NSCLC cells in vitro and in vivo.

  11. SU-G-IeP4-11: Monitoring Tumor Growth in Subcutaneous Murine Tumor Model in Vivo: A Comparison Between MRI and Small Animal CT

    Energy Technology Data Exchange (ETDEWEB)

    Wang, B; He, W; Cvetkovic, D; Chen, L; Fan, J; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2016-06-15

    Purpose: The purpose of the study is to compare the volume measurement of subcutaneous tumors in mice with different imaging platforms, namely a GE MRI and a Sofie-Biosciences small animal CT scanner. Methods: A549 human lung carcinoma cells and FaDu human head and neck squamous cell carcinoma cells were implanted subcutaneously into flanks of nude mice. Three FaDu tumors and three A549 tumors were included in this study. The MRI scans were done with a GE Signa 1.5 Tesla MR scanner using a fast T2-weighted sequence (70mm FOV and 1.2mm slice thickness), while the CT scans were done with the CT scanner on a Sofie-Biosciences G8 PET/CT platform dedicated for small animal studies (48mm FOV and 0.2mm slice thickness). Imaging contrast agent was not used in this study. Based on the DICOM images from MRI and CT scans, the tumors were contoured with Philips DICOM Viewer and the tumor volumes were obtained by summing up the contoured area and multiplied by the slice thickness. Results: The volume measurements based on the CT scans agree reasonably with that obtained with MR images for the subcutaneous tumors. The mean difference in the absolute tumor volumes between MRI- and CT-based measurements was found to be −6.2% ± 1.0%, with the difference defined as (VMR – VCT)*100%/VMR. Furthermore, we evaluated the normalized tumor volumes, which were defined for each tumor as V/V{sub 0} where V{sub 0} stands for the volume from the first MR or CT scan. The mean difference in the normalized tumor volumes was found to be 0.10% ± 0.96%. Conclusion: Despite the fact that the difference between normal and abnormal tissues is often less clear on small animal CT images than on MR images, one can still obtain reasonable tumor volume information with the small animal CT scans for subcutaneous murine xenograft models.

  12. Communicating Hydrocephalus Associated with Small- to Medium-Sized Vestibular Schwannomas: Clinical Significance of the Tumor Apparent Diffusion Coefficient Map.

    Science.gov (United States)

    Taniguchi, Masaaki; Nakai, Tomoaki; Kohta, Masaaki; Kimura, Hidehito; Kohmura, Eiji

    2016-10-01

    The etiology of hydrocephalus associated with the small- to medium-sized vestibular schwannomas is still controversial. We investigated tumor-specific factors related to the association of hydrocephalus with small- to medium-sized vestibular schwannomas. Among the 77 patients with vestibular schwannoma smaller than 30 mm, 9 patients demonstrated associated communicating hydrocephalus. Patient medical records, radiologic data, and histopathologic specimens were reviewed retrospectively. The age of the patients, and size, mean apparent diffusion coefficient (ADC) value, and histologic features of the tumors were compared with those of patients without hydrocephalus. The symptoms related to hydrocephalus improved in all patients after tumor removal. Both the mean size and ADC values exhibited a statistically significant difference between the tumors with and without hydrocephalus (P hydrocephalus. The increased tumor ADC value was considered to be the result of degenerative change and suggested the involvement of protein sloughing in the etiology of the associated hydrocephalus. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice

    International Nuclear Information System (INIS)

    Li, Guodong; Kong, Bo; Zhu, Yan; Zhan, Le; Williams, Jessica A.; Tawfik, Ossama; Kassel, Karen M.; Luyendyk, James P.; Wang, Li; Guo, Grace L.

    2013-01-01

    Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis. Induction of SHP serves as a major mechanism of FXR in suppressing gene expression. Both FXR −/− and SHP −/− mice develop spontaneous hepatocellular carcinoma (HCC). SHP is one of the most strongly induced genes by FXR in the liver and is a tumor suppressor, therefore, we hypothesized that deficiency of SHP contributes to HCC development in the livers of FXR −/− mice and therefore, increased SHP expression in FXR −/− mice reduces liver tumorigenesis. To test this hypothesis, we generated FXR −/− mice with overexpression of SHP in hepatocytes (FXR −/− /SHP Tg ) and determined the contribution of SHP in HCC development in FXR −/− mice. Hepatocyte-specific SHP overexpression did not affect liver tumor incidence or size in FXR −/− mice. However, SHP overexpression led to a lower grade of dysplasia, reduced indicator cell proliferation and increased apoptosis. All tumor-bearing mice had increased serum bile acid levels and IL-6 levels, which was associated with activation of hepatic STAT3. In conclusion, SHP partially protects FXR −/− mice from HCC formation by reducing tumor malignancy. However, disrupted bile acid homeostasis by FXR deficiency leads to inflammation and injury, which ultimately results in uncontrolled cell proliferation and tumorigenesis in the liver. - Highlights: • SHP does not prevent HCC incidence nor size in FXR KO mice but reduces malignancy. • Increased SHP promotes apoptosis. • Bile acids and inflammation maybe critical for HCC formation with FXR deficiency

  14. Loss of Chromosome 18 in Neuroendocrine Tumors of the Small Intestine: The Enigma Remains.

    Science.gov (United States)

    Nieser, Maike; Henopp, Tobias; Brix, Joachim; Stoß, Laura; Sitek, Barbara; Naboulsi, Wael; Anlauf, Martin; Schlitter, Anna M; Klöppel, Günter; Gress, Thomas; Moll, Roland; Bartsch, Detlef K; Heverhagen, Anna E; Knoefel, Wolfram T; Kaemmerer, Daniel; Haybaeck, Johannes; Fend, Falko; Sperveslage, Jan; Sipos, Bence

    2017-01-01

    Neuroendocrine tumors of the small intestine (SI-NETs) exhibit an increasing incidence and high mortality rate. Until now, no fundamental molecular event has been linked to the tumorigenesis and progression of these tumors. Only the loss of chromosome 18 (Chr18) has been shown in up to two thirds of SI-NETs, whereby the significance of this alteration is still not understood. We therefore performed the first comprehensive study to identify Chr18-related events at the genetic, epigenetic and gene/protein expression levels. We did expression analysis of all seven putative Chr18-related tumor suppressors by quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry. Next-generation exome sequencing and SNP array analysis were performed with five SI-NETs with (partial) loss of Chr18. Finally, we analyzed all microRNAs (miRNAs) located on Chr18 by qRT-PCR, comparing Chr18+/- and Chr18+/+ SI-NETs. Only DCC (deleted in colorectal cancer) revealed loss of/greatly reduced expression in 6/21 cases (29%). No relevant loss of SMAD2, SMAD4, elongin A3 and CABLES was detected. PMAIP1 and maspin were absent at the protein level. Next-generation sequencing did not reveal relevant recurrent somatic mutations on Chr18 either in an exploratory cohort of five SI-NETs, or in a validation cohort (n = 30). SNP array analysis showed no additional losses. The quantitative analysis of all 27 Chr18-related miRNAs revealed no difference in expression between Chr18+/- and Chr18+/+ SI-NETs. DCC seems to be the only Chr18-related tumor suppressor affected by the monoallelic loss of Chr18 resulting in a loss of DCC protein expression in one third of SI-NETs. No additional genetic or epigenetic alterations were present on Chr18. © 2016 S. Karger AG, Basel.

  15. Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Duncker-Rohr, V.; Nestle, U. [Universitaetsklinikum Freiburg (Germany); Momm, F. [Ortenau Klinikum Offenburg (Germany)] [and others

    2013-01-15

    Background: Stereotactic ablative body radiotherapy (SBRT, SABR) is being increasingly applied because of its high local efficacy, e.g., for small lung tumors. However, the optimum dosage is still under discussion. Here, we report data on 45 lung lesions [non-small cell lung cancer (NSCLC) or metastases] in 39 patients treated between 2009 and 2010 by SABR. Patients and methods: SABR was performed with total doses of 35 Gy (5 fractions) or 37.5 Gy (3 fractions) prescribed to the 60% isodose line encompassing the planning target volume. Three-monthly follow-up CT scans were supplemented by FDG-PET/CT if clinically indicated. Results: The median follow-up was 17 months. Local progression-free survival rates were 90.5% (all patients), 95.0% (NSCLC), and 81.8% (metastases) at 1 year. At 2 years, the respective local progression-free survival rates were 80.5%, 95.0%, and 59.7%. Overall survival rates were 71.1% (all patients), 65.4% (NSCLC), and 83.3% (metastases) at 1 year. Overall survival rates at 2 years were 52.7%, 45.9%, and 66.7%, respectively. Acute side effects were mild. Conclusion: With the moderate dose schedule used, well-tolerated SABR led to favorable local tumor control as in other published series. Standardization in reporting the dose prescription for SABR is needed to allow comparison of different series in order to determine optimum dosage. (orig.)

  16. Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

    2014-01-01

    The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors.

  17. Single-balloon enteroscopy following videocapsule endoscopy for diagnosis of small bowel tumors: preliminary experiences.

    Science.gov (United States)

    Trifan, A; Singeap, A M; Cojocariu, C; Sfarti, C; Tarcoveanu, E; Georgescu, S

    2010-01-01

    Small bowel tumors (SBTs), either benign or malignant, are rare, accounting for 3-6% of all digestive neoplasms. Videocapsule endoscopy (VCE) and double-balloon enteroscopy (DBE) have revolutionized the diagnosis and management of patients with small bowel diseases, including SBTs. A novel method using the single-balloon enteroscopy (SBE) has recently been developed. The aim of present study was to present our preliminary experience with SBE in patients with suspected SBTs on VCE examination. Patients in whom VCE showed one or more lesions suggesting SBTs underwent SBE. Three patients (2 males, 1 female; mean age 52 +/- 11 years) underwent SBE, and then surgery. There were two gastrointestinal stromal tumors and one adenocarcinoma. Clinically, all patients had iron-deficiency anemia and abdominal pain, and one patient had episodes of nausea/ vomiting. SBE was well tolerated without adverse events. SBE is a safe procedure and overcomes the limitations of VCE. Both procedures are complimentary in patients with suspected SBTs. VCE should be used first for initial diagnosis, followed by SBE for histopathological confrmation of the diagnosis and, if necessary, endoscopic therapy.

  18. Quantification of Tumor Volume Changes During Radiotherapy for Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Fox, Jana; Ford, Eric; Redmond, Kristin; Zhou, Jessica; Wong, John; Song, Danny Y.

    2009-01-01

    Purpose: Dose escalation for lung cancer is limited by normal tissue toxicity. We evaluated sequential computed tomography (CT) scans to assess the possibility of adaptively reducing treatment volumes by quantifying the tumor volume reduction occurring during a course of radiotherapy (RT). Methods and Materials: A total of 22 patients underwent RT for Stage I-III non-small-cell lung cancer with conventional fractionation; 15 received concurrent chemotherapy. Two repeat CT scans were performed at a nominal dose of 30 Gy and 50 Gy. Respiration-correlated four-dimensional CT scans were used for evaluation of respiratory effects in 17 patients. The gross tumor volume (GTV) was delineated on simulation and all individual phases of the repeat CT scans. Parenchymal tumor was evaluated unless the nodal volume was larger or was the primary. Subsequent image sets were spatially co-registered with the simulation data for evaluation. Results: The median GTV reduction was 24.7% (range, -0.3% to 61.7%; p 100 cm 3 vs. 3 , and hilar and/or mediastinal involvement vs. purely parenchymal or pleural lesions. A tendency toward a greater volume reduction with increasing dose was seen, although this did not reach statistical significance. Conclusion: The results of this study have demonstrated significant alterations in the GTV seen on repeat CT scans during RT. These observations raise the possibility of using an adaptive approach toward RT of non-small-cell lung cancer to minimize the dose to normal structures and more safely increase the dose directed at the target tissues.

  19. Impact of respiratory movement on the computed tomographic images of small lung tumors in three-dimensional (3D) radiotherapy

    International Nuclear Information System (INIS)

    Shimizu, Shinichi; Shirato, Hiroki; Kagei, Kenji; Nishioka, Takeshi; Bo Xo; Dosaka-Akita, Hirotoshi; Hashimoto, Seiko; Aoyama, Hidefumi; Tsuchiya, Kazuhiko; Miyasaka, Kazuo

    2000-01-01

    Purpose: Three-dimensional (3D) treatment planning has often been performed while patients breathe freely, under the assumption that the computed tomography (CT) images represent the average position of the tumor. We investigated the impact of respiratory movement on the free-breathing CT images of small lung tumors using sequential CT scanning at the same table position. Methods: Using a preparatory free-breathing CT scan, the patient's couch was fixed at the position where each tumor showed its maximum diameter on image. For 16 tumors, over 20 sequential CT images were taken every 2 s, with a 1-s acquisition time occurring during free breathing. For each tumor, the distance between the surface of the CT table and the posterior border of the tumor was measured to determine whether the edge of the tumor was sufficiently included in the planning target volume (PTV) during normal breathing. Results: In the sequential CT scanning, the tumor itself was not visible in the examination slice in 21% (75/357) of cases. There were statistically significant differences between lower lobe tumors (39.4%, 71/180) and upper lobe tumors (0%, 0/89) (p < 0.01) and between lower lobe tumors and middle lobe tumor (8.9%, 4/45) (p < 0.01) in the incidence of the disappearance of the tumor from the image. The mean difference between the maximum and minimum distances between the surface of the CT table and the posterior border of the tumor was 6.4 mm (range 2.1-24.4). Conclusion: Three-dimensional treatment planning for lung carcinoma would significantly underdose many lesions, especially those in the lower lobe. The excess 'safety margin' might call into question any additional benefit of 3D treatment. More work is required to determine how to control respiratory movement

  20. Malignant round cell tumours of bone: atypical clinical and imaging features

    International Nuclear Information System (INIS)

    Saifuddin, A.; Whelan, J.; Pringle, J.A.S.; Cannon, S.R.

    2000-01-01

    Objective. To describe the clinical, radiological and MRI features of six atypical cases of histologically proven appendicular Ewing sarcoma/ primitive neuroectodermal tumour (PNET). Design. Retrospective review of case notes and available imaging was carried out. Patients. Six patients (4 male, 2 female; mean age 27 years, range 19-44 years), presenting over a 77-month period, were identified from the Bone Tumour Register. All had unusual clinical and imaging features for Ewing sarcoma/PNET.Results and conclusions. Four tumours were centred on the distal femoral metaphysis, one in the proximal tibial metaphysis and one in the distal tibial metaphysis. Plain radiographs were available in four cases and showed minor cortical changes. MRI demonstrated a relatively small, eccentrically located intraosseous component with a large, eccentric extraosseous component. Extension into the epiphysis was seen in three cases and into the adjacent joint in two cases. Intraosseous ''skip'' metastases were present in three cases. The clinical and imaging features were atypical for conventional intraosseous Ewing sarcoma/PNET and the exact site of origin (intraosseous, periosteal or soft-tissue) was unclear. (orig.)

  1. [Primitive neuroectodermal tumor/Ewing's sarcoma of the penis in children: a case report and review of the literature].

    Science.gov (United States)

    Zhang, Da-Wei; Jin, Mei; Zhou, Chun-Ju; Song, Hong-Cheng; Ma, Xiao-Li

    2012-12-01

    To investigate the clinical manifestations, pathological characteristics and treatment of primitive neuroectodermal tumor/Ewing's sarcoma (PNET/EWS) of the penis in children. We analyzed the clinical data of a case of PNET/EWS and reviewed relevant literature. The patient was a 5-year-old boy, admitted for penis swelling with pain for 11 months. Biopsy showed a small round cell tumor, CD99 positive by immunohistochemical staining, with EWS translocation by fluorescence in situ hybridization on molecular biological examination. The tumor was confirmed to be PNET/EWS of the penis, and disappeared after 45 weeks of chemotherapy and local radiotherapy. PNET/EWS of the penis is an extremely rare disease, with no specific clinical symptoms except penis enlargement with pain. Immunohistochemistry and molecular biological examination contribute to its diagnosis.

  2. Portal imaging to assess set-up errors, tumor motion and tumor shrinkage during conformal radiotherapy of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Erridge, Sara C.; Seppenwoolde, Yvette; Muller, Sara H.; Herk, Marcel van; Jaeger, Katrien de; Belderbos, Jose S.A.; Boersma, Liesbeth J.; Lebesque, Joos V.

    2003-01-01

    Purpose: To investigate patient set-up, tumor movement and shrinkage during 3D conformal radiotherapy for non-small cell lung cancer. Materials and methods: In 97 patients, electronic portal images (EPIs) were acquired and corrected for set-up using an off-line correction protocol based on a shrinking action level. For 25 selected patients, the orthogonal EPIs (taken at random points in the breathing cycle) throughout the 6-7 week course of treatment were assessed to establish the tumor position in each image using both an overlay and a delineation technique. The range of movement in each direction was calculated. The position of the tumor in the digitally reconstructed radiograph (DRR) was compared to the average position of the lesion in the EPIs. In addition, tumor shrinkage was assessed. Results: The mean overall set-up errors after correction were 0, 0.6 and 0.2 mm in the x (left-right), y (cranial-caudal) and z (anterior-posterior) directions, respectively. After correction, the standard deviations (SDs) of systematic errors were 1.4, 1.5 and 1.3 mm and the SDs of random errors were 2.9, 3.1 and 2.0 mm in the x-, y- and z-directions, respectively. Without correction, 41% of patients had a set-up error of more than 5 mm vector length, but with the set-up correction protocol this percentage was reduced to 1%. The mean amplitude of tumor motion was 7.3 (SD 2.7), 12.5 (SD 7.3) and 9.4 mm (SD 5.2) in the x-, y- and z-directions, respectively. Tumor motion was greatest in the y-direction and in particular for lower lobe tumors. In 40% of the patients, the projected area of the tumor regressed by more than 20% during treatment in at least one projection. In 16 patients it was possible to define the position of the center of the tumor in the DRR. There was a mean difference of 6 mm vector length between the tumor position in the DRR and the average position in the portal images. Conclusions: The application of the correction protocol resulted in a significant

  3. RPL41, a Small Ribosomal Peptide Deregulated in Tumors, Is Essential for Mitosis and Centrosome Integrity

    Directory of Open Access Journals (Sweden)

    Shan Wang

    2010-03-01

    Full Text Available Ribosomal large subunit protein RPL41 is a basic (positively charged peptide consisting of only 25 amino acids. An antisense-based functional screening revealed that the down-regulation of RPL41 led to an anchorage-independent growth of NIH3T3 cells in soft agar plates. RPL41 depletion with gene-specific small interfering RNA also resulted in malignant transformation of NIH3T3 cells including increased tumor growth in mice. RPL41 deletion was detected in 59% of tumor cell lines by fluorescence in situ hybridization analyses and RPL41 down-regulation in 75% of primary breast cancers by real-time quantitative reverse transcription-polymerase chain reaction. These studies suggest a tumor suppression role for RPL41. By mass spectrometry, RPL41 was associated with several cytoskeleton components including tubulin β, γ, and myosin IIA, which was confirmed by Western blot analysis on both cellular lysis and individually in vitro-expressed proteins. RPL41 also bound directly to polymerized tubulins. Cells overexpressing a GFP-RPL41 were resistant to nocodazole-induced microtubule depolymerization. A synthetic RPL41 induced cellular α-tubulin acetylation and G2/M cell cycle arrest. These results indicate a stabilizing role of RPL41 on microtubule. Microtubule spindles are essential for chromosome segregation during mitosis. Cells with RPL41 knock-down showed abnormal spindles, frequent failure of cytokinesis, and formation of polynuclear cells. In interphase cells, RPL41-depleted cells had premature splitting of centrosome. Our results provide evidence that RPL41 is a microtubule-associated protein essential for functional spindles and for the integrity of centrosome and that the abnormal mitosis and disrupted centrosome associated with the RPL41 down-regulation may be related to malignant transformation.

  4. Lung cancer-associated tumor antigens and the present status of immunotherapy against non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Yasumoto, Kosei; Hanagiri, Takeshi; Takenoyama, Mitsuhiro

    2009-01-01

    Despite recent advances in surgery, irradiation, and chemotherapy, the prognosis of patients with lung cancer is still poor. Therefore, the development and application of new therapeutic strategies are essential for improving the prognosis of this disease. Significant progress in our understanding of tumor immunology and molecular biology has allowed us to identify the tumor-associated antigens recognized by cytotoxic T lymphocytes. Immune responses and tumor-associated antigens against not only malignant melanoma but also lung cancer have been elucidated at the molecular level. In a theoretical sense, tumor eradication is considered possible through antigen-based immunotherapy against such diseases. However, many clinical trials of cancer vaccination with defined tumor antigens have resulted in objective clinical responses in only a small number of patients. Tumor escape mechanisms from host immune surveillance remain a major obstacle for cancer immunotherapy. A better understanding of the immune escape mechanisms employed by tumor cells is necessary before we can develop a more effective immunotherapeutic approach to lung cancer. We review recent studies regarding the identification of tumor antigens in lung cancer, tumor immune escape mechanisms, and clinical vaccine trials in lung cancer. (author)

  5. Tumor cavitation in patients with stage III non-small-cell lung cancer undergoing concurrent chemoradiotherapy: incidence and outcomes.

    Science.gov (United States)

    Phernambucq, Erik C J; Hartemink, Koen J; Smit, Egbert F; Paul, Marinus A; Postmus, Pieter E; Comans, Emile F I; Senan, Suresh

    2012-08-01

    Commonly reported complications after concurrent chemoradiotherapy (CCRT) in patients with stage III non-small-cell lung cancer (NSCLC) include febrile neutropenia, radiation esophagitis, and pneumonitis. We studied the incidence of tumor cavitation and/or "tumor abscess" after CCRT in a single-institutional cohort. Between 2003 and 2010, 87 patients with stage III NSCLC underwent cisplatin-based CCRT and all subsequent follow-up at the VU University Medical Center. Diagnostic and radiotherapy planning computed tomography scans were reviewed for tumor cavitation, which was defined as a nonbronchial air-containing cavity located within the primary tumor. Pulmonary toxicities scored as Common Toxicity Criteria v3.0 of grade III or more, occurring within 90 days after end of radiotherapy, were analyzed. In the entire cohort, tumor cavitation was observed on computed tomography scans of 16 patients (18%). The histology in cavitated tumors was squamous cell (n = 14), large cell (n = 1), or adenocarcinoma (n = 1). Twenty patients (23%) experienced pulmonary toxicity of grade III or more, other than radiation pneumonitis. Eight patients with a tumor cavitation (seven squamous cell carcinoma) developed severe pulmonary complications; tumor abscess (n = 5), fatal hemorrhage (n = 2), and fatal embolism (n = 1). Two patients with a tumor abscess required open-window thoracostomy post-CCRT. The median overall survival for patients with or without tumor cavitation were 9.9 and 16.3 months, respectively (p = 0.09). With CCRT, acute pulmonary toxicity of grade III or more developed in 50% of patients with stage III NSCLC, who also had radiological features of tumor cavitation. The optimal treatment of patients with this presentation is unclear given the high risk of a tumor abscess.

  6. Prognostic value of tumor-to-blood standardized uptake ratio in patients with resectable non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Seung Hyeon; Pak, Kyoung June; Kim, In Joo [Dept. of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan(Korea, Republic of); Kim, Bum Soo; Kim, Seong Jang [Dept. of Nuclear Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2017-09-15

    Previously published studies showed that the standard tumor-to-blood standardized uptake value (SUV) ratio (SUR) was a more accurate prognostic method than tumor maximum standardized uptake value (SUVmax). This study evaluated and compared prognostic value of positron emission tomography (PET) parameters and normalized value of PET parameters by blood pool SUV in non-small-cell lung cancer (NSCLC) patients who received curative surgery.

  7. Prognostic value of tumor-to-blood standardized uptake ratio in patients with resectable non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Shin, Seung Hyeon; Pak, Kyoung June; Kim, In Joo; Kim, Bum Soo; Kim, Seong Jang

    2017-01-01

    Previously published studies showed that the standard tumor-to-blood standardized uptake value (SUV) ratio (SUR) was a more accurate prognostic method than tumor maximum standardized uptake value (SUVmax). This study evaluated and compared prognostic value of positron emission tomography (PET) parameters and normalized value of PET parameters by blood pool SUV in non-small-cell lung cancer (NSCLC) patients who received curative surgery

  8. Gamma-aminobutyric acid, a potential tumor suppressor for small airway-derived lung adenocarcinoma.

    Science.gov (United States)

    Schuller, Hildegard M; Al-Wadei, Hussein A N; Majidi, Mourad

    2008-10-01

    Pulmonary adenocarcinoma (PAC) is the leading type of lung cancer in smokers and non-smokers that arises in most cases from small airway epithelial cells. PAC has a high mortality due to its aggressive behavior and resistance to cancer therapeutics. We have shown previously that the proliferation of human PAC cells NCI-H322 and immortalized human small airway epithelial cells HPL1D is stimulated by cyclic adenosine monophosphate (cAMP)/protein kinase A-dependent phosphorylation of cyclic adenosine monophosphate response element-binding (CREB) protein and transactivation of the epidermal growth factor receptor and that this pathway is activated by beta-1-adrenoreceptors (beta(1)-ARs) and the non-genomic estrogen receptor beta. Our current in vitro studies with HPL1D and NCI-H322 cells showed that signaling via the gamma-amino butyric acid receptor (GABA(B)R) strongly inhibited base level and isoproterenol-induced cAMP, p-CREB, cyclic adenosine monophosphate response element-luciferase activity and p-extracellular regulated kinase-1 (ERK1)/2 and effectively blocked DNA synthesis and cell migration. The inhibitory effects of gamma-amino butyric acid (GABA) were disinhibited by the GABA(B)R antagonist CGP-35348 or GABA(B)R knockdown. Immunohistochemical investigation of hamster lungs showed significant underexpression of GABA in animals with small airway-derived PACs induced by the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These findings suggest that GABA may have tumor suppressor function in small airway epithelia and the PACs derived from them and that downregulation of GABA by NNK may contribute to the development of this cancer in smokers. Our findings suggest that marker-guided treatment with GABA or a GABA(B)R agonist of individuals with downregulated pulmonary GABA may provide a novel targeted approach for the prevention of PAC in smokers.

  9. Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine

    Directory of Open Access Journals (Sweden)

    Kathryn S. Brown

    2014-01-01

    Full Text Available Background. Premature infants are commonly subject to intestinal inflammation. Since the human small intestine does not reach maturity until term gestation, premature infants have a unique challenge, as either acute or chronic inflammation may alter the normal development of the intestinal tract. Tumor necrosis factor (TNF has been shown to acutely alter goblet cell numbers and villus length in adult mice. In this study we tested the effects of TNF on villus architecture and epithelial cells at different stages of development of the immature small intestine. Methods. To examine the effects of TNF-induced inflammation, we injected acute, brief, or chronic exposures of TNF in neonatal and juvenile mice. Results. TNF induced significant villus blunting through a TNF receptor-1 (TNFR1 mediated mechanism, leading to loss of villus area. This response to TNFR1 signaling was altered during intestinal development, despite constant TNFR1 protein expression. Acute TNF-mediated signaling also significantly decreased Paneth cells. Conclusions. Taken together, the morphologic changes caused by TNF provide insight as to the effects of inflammation on the developing intestinal tract. Additionally, they suggest a mechanism which, coupled with an immature immune system, may help to explain the unique susceptibility of the immature intestine to inflammatory diseases such as NEC.

  10. Splenectomy inhibits non-small cell lung cancer growth by modulating anti-tumor adaptive and innate immune response

    Science.gov (United States)

    Levy, Liran; Mishalian, Inbal; Bayuch, Rachel; Zolotarov, Lida; Michaeli, Janna; Fridlender, Zvi G

    2015-01-01

    It has been shown that inhibitors of the immune system reside in the spleen and inhibit the endogenous antitumor effects of the immune system. We hypothesized that splenectomy would inhibit the growth of relatively large non-small lung cancer (NSCLC) tumors by modulating the systemic inhibition of the immune system, and in particular Myeloid Derived Suppressor Cells (MDSC). The effect of splenectomy was evaluated in several murine lung cancer models. We found that splenectomy reduces tumor growth and the development of lung metastases, but only in advanced tumors. In immune-deficient NOD-SCID mice the effect of splenectomy on tumor growth and metastatic spread disappeared. Splenectomy significantly reduced the presence of MDSC, and especially monocytic-MDSC in the circulation and inside the tumor. Specific reduction of the CCR2+ subset of monocytic MDSC was demonstrated, and the importance of the CCL2-CCR2 axis was further shown by a marked reduction in CCL2 following splenectomy. These changes were followed by changes in the macrophages contents of the tumors to become more antitumorigenic, and by increased activation of CD8+ Cytotoxic T-cells (CTL). By MDSC depletion, and adoptive transfer of MDSCs, we demonstrated that the effect of splenectomy on tumor growth was substantially mediated by MDSC cells. We conclude that the spleen is an important contributor to tumor growth and metastases, and that splenectomy can blunt this effect by depletion of MDSC, changing the amount and characteristics of myeloid cells and enhancing activation of CTL. PMID:26137413

  11. Radiotherapy and chemotherapy change vessel tree geometry and metastatic spread in a small cell lung cancer xenograft mouse tumor model.

    Directory of Open Access Journals (Sweden)

    Thorsten Frenzel

    Full Text Available Tumor vasculature is critical for tumor growth, formation of distant metastases and efficiency of radio- and chemotherapy treatments. However, how the vasculature itself is affected during cancer treatment regarding to the metastatic behavior has not been thoroughly investigated. Therefore, the aim of this study was to analyze the influence of hypofractionated radiotherapy and cisplatin chemotherapy on vessel tree geometry and metastasis formation in a small cell lung cancer xenograft mouse tumor model to investigate the spread of malignant cells during different treatments modalities.The biological data gained during these experiments were fed into our previously developed computer model "Cancer and Treatment Simulation Tool" (CaTSiT to model the growth of the primary tumor, its metastatic deposit and also the influence on different therapies. Furthermore, we performed quantitative histology analyses to verify our predictions in xenograft mouse tumor model.According to the computer simulation the number of cells engrafting must vary considerably to explain the different weights of the primary tumor at the end of the experiment. Once a primary tumor is established, the fractal dimension of its vasculature correlates with the tumor size. Furthermore, the fractal dimension of the tumor vasculature changes during treatment, indicating that the therapy affects the blood vessels' geometry. We corroborated these findings with a quantitative histological analysis showing that the blood vessel density is depleted during radiotherapy and cisplatin chemotherapy. The CaTSiT computer model reveals that chemotherapy influences the tumor's therapeutic susceptibility and its metastatic spreading behavior.Using a system biological approach in combination with xenograft models and computer simulations revealed that the usage of chemotherapy and radiation therapy determines the spreading behavior by changing the blood vessel geometry of the primary tumor.

  12. Malignant tumors of head and neck region - a retrospective analysis

    International Nuclear Information System (INIS)

    Aziz, F.; Ahmed, S.; Malik, A.; Afsar, A.; Yousaf, N.W.

    2001-01-01

    To evaluate the spectrum of malignant tumors of head and neck region. The data of total 375 neoplastic lesions of both the sexes between 8-70 years of age was collected and compared with the findings reported from centers in other parts of the country. Among the total 375 cases of neoplastic lesions, 148 were benign whereas 227 proved to be malignant histologically in 155 male and 72 female patients. Squamous cell carcinoma (SCC) was the most frequently encountered histological category (45.8%) followed by lymphoma (14.5%), basal cell carcinoma (10.5%), carcinoma thyroid (10.5%) and salivary gland tumors (8.80%). These were followed by infrequently encountered tumors including nasopharyngeal carcinoma (n=5), small blue round cell tumors (n=3), undifferentiated carcinoma (n=3), retinoblastoma (n=2) and transitional carcinoma nose (n=1). The anatomical regions involved with this tumor were larynx (53.5% of all SCC) followed by pharynx (18.7%) tongue (10.71%) oral cavity (4.4%) metastasis (5.3%) and skin (2.60%). (author)

  13. Dose enhancement in radiotherapy of small lung tumors using inline magnetic fields: A Monte Carlo based planning study

    Energy Technology Data Exchange (ETDEWEB)

    Oborn, B. M., E-mail: brad.oborn@gmail.com [Illawarra Cancer Care Centre (ICCC), Wollongong, NSW 2500, Australia and Centre for Medical Radiation Physics (CMRP), University of Wollongong, Wollongong, NSW 2500 (Australia); Ge, Y. [Sydney Medical School, University of Sydney, NSW 2006 (Australia); Hardcastle, N. [Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, NSW 2065 (Australia); Metcalfe, P. E. [Centre for Medical Radiation Physics (CMRP), University of Wollongong, Wollongong NSW 2500, Australia and Ingham Institute for Applied Medical Research, Liverpool, NSW 2170 (Australia); Keall, P. J. [Sydney Medical School, University of Sydney, NSW 2006, Australia and Ingham Institute for Applied Medical Research, Liverpool, NSW 2170 (Australia)

    2016-01-15

    Purpose: To report on significant dose enhancement effects caused by magnetic fields aligned parallel to 6 MV photon beam radiotherapy of small lung tumors. Findings are applicable to future inline MRI-guided radiotherapy systems. Methods: A total of eight clinical lung tumor cases were recalculated using Monte Carlo methods, and external magnetic fields of 0.5, 1.0, and 3 T were included to observe the impact on dose to the planning target volume (PTV) and gross tumor volume (GTV). Three plans were 6 MV 3D-CRT plans while 6 were 6 MV IMRT. The GTV’s ranged from 0.8 to 16 cm{sup 3}, while the PTV’s ranged from 1 to 59 cm{sup 3}. In addition, the dose changes in a 30 cm diameter cylindrical water phantom were investigated for small beams. The central 20 cm of this phantom contained either water or lung density insert. Results: For single beams, an inline magnetic field of 1 T has a small impact in lung dose distributions by reducing the lateral scatter of secondary electrons, resulting in a small dose increase along the beam. Superposition of multiple small beams leads to significant dose enhancements. Clinically, this process occurs in the lung tissue typically surrounding the GTV, resulting in increases to the D{sub 98%} (PTV). Two isolated tumors with very small PTVs (3 and 6 cm{sup 3}) showed increases in D{sub 98%} of 23% and 22%. Larger PTVs of 13, 26, and 59 cm{sup 3} had increases of 9%, 6%, and 4%, describing a natural fall-off in enhancement with increasing PTV size. However, three PTVs bounded to the lung wall showed no significant increase, due to lack of dose enhancement in the denser PTV volume. In general, at 0.5 T, the GTV mean dose enhancement is around 60% lower than that at 1 T, while at 3 T, it is 5%–60% higher than 1 T. Conclusions: Monte Carlo methods have described significant and predictable dose enhancement effects in small lung tumor plans for 6 MV radiotherapy when an external inline magnetic field is included. Results of this study

  14. Assessing tumor treatment response and prognosis in non-small cell lung cancer with perfusion CT

    International Nuclear Information System (INIS)

    Wang Jianwei; Wu Ning; Song Ying

    2010-01-01

    Objective: To prospectively investigate whether any of the perfusion parameters would predict early tumor response to chemotherapy and/or radiotherapy and prognosis in non-small cell lung cancer (NSCLC). Methods: In a prospective series, Perfusion CT were performed in 152 patients suspected lung cancer with 16-slice or 8-slice multislice CT. Contrast medium (50 ml) was injected at a rate of 4 ml/s with a power injector. The scanning delay was 10 seconds and the scanning time was 50 seconds. Among 152 patients, 123 patients were proved lung cancer by pathology. With the perfusion 3.0 software, the parameters including blood flow (BF), blood volume (BV), mean transit time (MTT) and capillary permeability surface area product (PS) were calculated. The perfusion image quality was evaluated on a 4-1eveal scale. The treatment response after chemotherapy and (or) radiotherapy was assessed with Response Evaluation Criteria in Solid Tumors (RECIST), and then the relationship between perfusion parameters with early tumor response to chemotherapy and (or) radiotherapy was evaluated. Student t test and Kaplan-Meier estimates were used for data analysis. Results: In 84 patients (68.3%), the perfusion image quality was staged level 2 (moderate) and level 3 (good). Among them, 35 patients with NSCLC were assessed with RECIST after chemotherapy and (or) radiotherapy. In these 35 patients, The BF of responders and nonresponders was (81.0 ± 33.6)and (56.3 ± 23.1) ml · min -1 ·100 g -1 , respectively, which was significantly different(t=2.393, P=0.023). The median PFS of low-BF group (BF ≤ 80 ml · min -1 · 100 g -1 ) and high-BF group (BF>80 ml · min -1 · 100 g -1 ) was 11.8 and 8.0 months respectively (P>0.05), and the median PFS of low-BV group (BF ≤ 6 ml/100 g -1 ) and high-BV group (BF>6 ml/100 g -1 ) was 9.2 and 8.0 months respectively(P>0.05), both of them were not significantly different. Conclusion: NSCLC in high perfusion are relatively sensitive to chemotherapy

  15. Anesthesia condition for {sup 18}F-FDG imaging of lung metastasis tumors using small animal PET

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sang-Keun; Lee, Tae Sup; Kim, Kyeong Min; Kim, June-Youp; Jung, Jae Ho; Kang, Joo Hyun [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Cheon, Gi Jeong [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of)], E-mail: larry@kcch.re.kr; Choi, Chang Woon; Lim, Sang Moo [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of)

    2008-01-15

    Small animal positron emission tomography (PET) with {sup 18}F-FDG has been increasingly used for tumor imaging in the murine model. The aim of this study was to establish the anesthesia condition for imaging of lung metastasis tumor using small animal {sup 18}F-FDG PET. Methods: To determine the impact of anesthesia on {sup 18}F-FDG distribution in normal mice, five groups were studied under the following conditions: no anesthesia, ketamine and xylazine (Ke/Xy), 0.5% isoflurane (Iso 0.5), 1% isoflurane (Iso 1) and 2% isoflurane (Iso 2). The ex vivo counting, standard uptake value (SUV) image and glucose SUV of {sup 18}F-FDG in various tissues were evaluated. The {sup 18}F-FDG images in the lung metastasis tumor model were obtained under no anesthesia, Ke/Xy and Iso 0.5, and registered with CT image to clarify the tumor region. Results: Blood glucose concentration and muscle uptake of {sup 18}F-FDG in the Ke/Xy group markedly increased more than in the other groups. The Iso 2 group increased {sup 18}F-FDG uptake in heart compared with the other groups. The Iso 0.5 anesthesized group showed the lowest {sup 18}F-FDG uptake in heart and chest wall. The small size of lung metastasis tumor (2 mm) was clearly visualized by {sup 18}F-FDG image with the Iso 0.5 anesthesia. Conclusion: Small animal {sup 18}F-FDG PET imaging with Iso 0.5 anesthesia was appropriate for the detection of lung metastasis tumor. To acquire {sup 18}F-FDG PET images with small animal PET, the type and level of anesthetic should be carefully considered to be suitable for the visualization of target tissue in the experimental model.

  16. A small interfering RNA screen of genes involved in DNA repair identifies tumor-specific radiosensitization by POLQ knockdown

    DEFF Research Database (Denmark)

    Higgins, Geoff S; Prevo, Remko; Lee, Yin-Fai

    2010-01-01

    The effectiveness of radiotherapy treatment could be significantly improved if tumor cells could be rendered more sensitive to ionizing radiation (IR) without altering the sensitivity of normal tissues. However, many of the key therapeutically exploitable mechanisms that determine intrinsic tumor...... radiosensitivity are largely unknown. We have conducted a small interfering RNA (siRNA) screen of 200 genes involved in DNA damage repair aimed at identifying genes whose knockdown increased tumor radiosensitivity. Parallel siRNA screens were conducted in irradiated and unirradiated tumor cells (SQ20B......) and irradiated normal tissue cells (MRC5). Using gammaH2AX foci at 24 hours after IR, we identified several genes, such as BRCA2, Lig IV, and XRCC5, whose knockdown is known to cause increased cell radiosensitivity, thereby validating the primary screening end point. In addition, we identified POLQ (DNA...

  17. Gain-of-function mutant p53 activates small GTPase Rac1 through SUMOylation to promote tumor progression.

    Science.gov (United States)

    Yue, Xuetian; Zhang, Cen; Zhao, Yuhan; Liu, Juan; Lin, Alan W; Tan, Victor M; Drake, Justin M; Liu, Lianxin; Boateng, Michael N; Li, Jun; Feng, Zhaohui; Hu, Wenwei

    2017-08-15

    Tumor suppressor p53 is frequently mutated in human cancer. Mutant p53 often promotes tumor progression through gain-of-function (GOF) mechanisms. However, the mechanisms underlying mutant p53 GOF are not well understood. In this study, we found that mutant p53 activates small GTPase Rac1 as a critical mechanism for mutant p53 GOF to promote tumor progression. Mechanistically, mutant p53 interacts with Rac1 and inhibits its interaction with SUMO-specific protease 1 (SENP1), which in turn inhibits SENP1-mediated de-SUMOylation of Rac1 to activate Rac1. Targeting Rac1 signaling by RNAi, expression of the dominant-negative Rac1 (Rac1 DN), or the specific Rac1 inhibitor NSC23766 greatly inhibits mutant p53 GOF in promoting tumor growth and metastasis. Furthermore, mutant p53 expression is associated with enhanced Rac1 activity in clinical tumor samples. These results uncover a new mechanism for Rac1 activation in tumors and, most importantly, reveal that activation of Rac1 is an unidentified and critical mechanism for mutant p53 GOF in tumorigenesis, which could be targeted for therapy in tumors containing mutant p53. © 2017 Yue et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Characterization of tumor heterogeneity using dynamic contrast enhanced CT and FDG-PET in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Elmpt, Wouter van; Das, Marco; Hüllner, Martin; Sharifi, Hoda; Zegers, Catharina M.L.; Reymen, Bart; Lambin, Philippe; Wildberger, Joachim E.; Troost, Esther G.C.; Veit-Haibach, Patrick; De Ruysscher, Dirk

    2013-01-01

    Purpose: Dynamic contrast-enhanced CT (DCE-CT) quantifies vasculature properties of tumors, whereas static FDG-PET/CT defines metabolic activity. Both imaging modalities are capable of showing intra-tumor heterogeneity. We investigated differences in vasculature properties within primary non-small cell lung cancer (NSCLC) tumors measured by DCE-CT and metabolic activity from FDG-PET/CT. Methods: Thirty three NSCLC patients were analyzed prior to treatment. FDG-PET/CT and DCE-CT were co-registered. The tumor was delineated and metabolic activity was segmented on the FDG-PET/CT in two regions: low (<50% maximum SUV) and high (⩾50% maximum SUV) metabolic uptake. Blood flow, blood volume and permeability were calculated using a maximum slope, deconvolution algorithm and a Patlak model. Correlations were assessed between perfusion parameters for the regions of interest. Results: DCE-CT provided additional information on vasculature and tumor heterogeneity that was not correlated to metabolic tumor activity. There was no significant difference between low and high metabolic active regions for any of the DCE-CT parameters. Furthermore, only moderate correlations between maximum SUV and DCE-CT parameters were observed. Conclusions: No direct correlation was observed between FDG-uptake and parameters extracted from DCE-CT. DCE-CT may provide complementary information to the characterization of primary NSCLC tumors over FDG-PET/CT imaging

  19. Angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular tumors in the liver: A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Il; Shin, Min Woo; Shin, Won Seon [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); and others

    2016-09-15

    To evaluate the feasibility of angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular liver tumors abutting abdominal wall, in order to traverse normal liver parenchyma, and thereby, obtain favorable configuration of ablation margin. In this study, we retrospectively analyzed 15 small superficial subcapsular liver tumors abutting abdominal wall in 15 patients, treated with radiofrequency ablation from March 2013 to June 2015 using a cool-tip electrode manually modified to create 25–35° angle at the junction between exposed and insulated segments. The tumors were hepatocellular carcinoma (n = 13) and metastases (n = 2: cholangiocellular carcinoma and rectosigmoid cancer), with maximum diameter of 10–26 mm (mean, 15.68 ± 5.29 mm). Under ultrasonographic guidance, the electrode tip was advanced to the depth of the tumors' epicenter about 1 cm from the margin. The tip was re-directed to penetrate the tumor for radiofrequency ablation. Minimal ablation margin was measured at immediate post-treatment CT. Radiological images and medical records were evaluated for success rate, length of minimal ablation margin and complications. Technical success rate of obtaining complete necrosis of the tumors was 100%, with no procedure-related complication. Minimal ablation margin ranged from 3–12 mm (mean, 7.07 ± 2.23 mm). CT/MRI follow-up at 21–1022 days (mean, 519.47 ± 304.51 days) revealed no local recurrence, but distant recurrence in 9 patients. Using an angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular tumors abutting abdominal wall may be a feasible technique for obtaining adequate ablation margin and lower complication rate.

  20. Angled Cool-Tip Electrode for Radiofrequency Ablation of Small Superficial Subcapsular Tumors in the Liver: A Feasibility Study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Il [Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul 03722 (Korea, Republic of); Kim, Il Jung [Department of Radiology, Bucheon St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Bucheon 14647 (Korea, Republic of); Lee, Shin Jae [Department of Radiology, CHA Bundang Medical Center, CHA University, Seongnam 13496 (Korea, Republic of); Shin, Min Woo; Shin, Won Sun; Chung, Yong Eun; Kim, Gyoung Min; Kim, Man Deuk; Won, Jong Yun; Lee, Do Yun [Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul 03722 (Korea, Republic of); Choi, Jin Sub [Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul 03722 (Korea, Republic of); Han, Kwang-Hyub [Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722 (Korea, Republic of)

    2016-11-01

    To evaluate the feasibility of angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular liver tumors abutting abdominal wall, in order to traverse normal liver parenchyma, and thereby, obtain favorable configuration of ablation margin. In this study, we retrospectively analyzed 15 small superficial subcapsular liver tumors abutting abdominal wall in 15 patients, treated with radiofrequency ablation from March 2013 to June 2015 using a cool-tip electrode manually modified to create 25–35° angle at the junction between exposed and insulated segments. The tumors were hepatocellular carcinoma (n = 13) and metastases (n = 2: cholangiocellular carcinoma and rectosigmoid cancer), with maximum diameter of 10–26 mm (mean, 15.68 ± 5.29 mm). Under ultrasonographic guidance, the electrode tip was advanced to the depth of the tumors' epicenter about 1 cm from the margin. The tip was re-directed to penetrate the tumor for radiofrequency ablation. Minimal ablation margin was measured at immediate post-treatment CT. Radiological images and medical records were evaluated for success rate, length of minimal ablation margin and complications. Technical success rate of obtaining complete necrosis of the tumors was 100%, with no procedure-related complication. Minimal ablation margin ranged from 3–12 mm (mean, 7.07 ± 2.23 mm). CT/MRI follow-up at 21–1022 days (mean, 519.47 ± 304.51 days) revealed no local recurrence, but distant recurrence in 9 patients. Using an angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular tumors abutting abdominal wall may be a feasible technique for obtaining adequate ablation margin and lower complication rate.

  1. Angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular tumors in the liver: A feasibility study

    International Nuclear Information System (INIS)

    Park, Sung Il; Shin, Min Woo; Shin, Won Seon

    2016-01-01

    To evaluate the feasibility of angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular liver tumors abutting abdominal wall, in order to traverse normal liver parenchyma, and thereby, obtain favorable configuration of ablation margin. In this study, we retrospectively analyzed 15 small superficial subcapsular liver tumors abutting abdominal wall in 15 patients, treated with radiofrequency ablation from March 2013 to June 2015 using a cool-tip electrode manually modified to create 25–35° angle at the junction between exposed and insulated segments. The tumors were hepatocellular carcinoma (n = 13) and metastases (n = 2: cholangiocellular carcinoma and rectosigmoid cancer), with maximum diameter of 10–26 mm (mean, 15.68 ± 5.29 mm). Under ultrasonographic guidance, the electrode tip was advanced to the depth of the tumors' epicenter about 1 cm from the margin. The tip was re-directed to penetrate the tumor for radiofrequency ablation. Minimal ablation margin was measured at immediate post-treatment CT. Radiological images and medical records were evaluated for success rate, length of minimal ablation margin and complications. Technical success rate of obtaining complete necrosis of the tumors was 100%, with no procedure-related complication. Minimal ablation margin ranged from 3–12 mm (mean, 7.07 ± 2.23 mm). CT/MRI follow-up at 21–1022 days (mean, 519.47 ± 304.51 days) revealed no local recurrence, but distant recurrence in 9 patients. Using an angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular tumors abutting abdominal wall may be a feasible technique for obtaining adequate ablation margin and lower complication rate

  2. Angled Cool-Tip Electrode for Radiofrequency Ablation of Small Superficial Subcapsular Tumors in the Liver: A Feasibility Study

    International Nuclear Information System (INIS)

    Park, Sung Il; Kim, Il Jung; Lee, Shin Jae; Shin, Min Woo; Shin, Won Sun; Chung, Yong Eun; Kim, Gyoung Min; Kim, Man Deuk; Won, Jong Yun; Lee, Do Yun; Choi, Jin Sub; Han, Kwang-Hyub

    2016-01-01

    To evaluate the feasibility of angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular liver tumors abutting abdominal wall, in order to traverse normal liver parenchyma, and thereby, obtain favorable configuration of ablation margin. In this study, we retrospectively analyzed 15 small superficial subcapsular liver tumors abutting abdominal wall in 15 patients, treated with radiofrequency ablation from March 2013 to June 2015 using a cool-tip electrode manually modified to create 25–35° angle at the junction between exposed and insulated segments. The tumors were hepatocellular carcinoma (n = 13) and metastases (n = 2: cholangiocellular carcinoma and rectosigmoid cancer), with maximum diameter of 10–26 mm (mean, 15.68 ± 5.29 mm). Under ultrasonographic guidance, the electrode tip was advanced to the depth of the tumors' epicenter about 1 cm from the margin. The tip was re-directed to penetrate the tumor for radiofrequency ablation. Minimal ablation margin was measured at immediate post-treatment CT. Radiological images and medical records were evaluated for success rate, length of minimal ablation margin and complications. Technical success rate of obtaining complete necrosis of the tumors was 100%, with no procedure-related complication. Minimal ablation margin ranged from 3–12 mm (mean, 7.07 ± 2.23 mm). CT/MRI follow-up at 21–1022 days (mean, 519.47 ± 304.51 days) revealed no local recurrence, but distant recurrence in 9 patients. Using an angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular tumors abutting abdominal wall may be a feasible technique for obtaining adequate ablation margin and lower complication rate

  3. Overexpression of Pokemon in non-small cell lung cancer and foreshowing tumor biological behavior as well as clinical results.

    Science.gov (United States)

    Zhao, Zhi-Hong; Wang, Sheng-Fa; Yu, Liang; Wang, Ju; Chang, Hao; Yan, Wei-Li; Zhang, Jian; Fu, Kai

    2008-10-01

    Transcription factor Pokemon, a central regulation gene of the important tumor suppressor alternative reading frame (ARF), exerted its activity by acting upstream of many tumor-suppressing genes and proto-oncogenes. Its expression in non-small cell lung cancer (NSCLC) and its clinical significance remains unclear. The aim of this study was to investigate the expression of Pokemon in non-small cell lung cancer and to explore its correlation with the clinical pathological characteristics and its influence on patients' prognosis. Observe the expression of Pokemon in NSCLC and investigate its mechanism and clinical significance. Determine the expression of Pokemon in human NSCLC cell lines as well as 55 cases of NSCLC tumor tissues, tumor adjacent tissues and surrounding tissues by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, and analyze the relationship between Pokemon expression in NSCLC tumor tissues and clinicopathological features. Determine 62 NSCLC tumor tissues (5 years ago) and p14(ARF) expression with immunohistochemical technique, discuss the correlation between them and assess the effect of Pokemon on prognosis of patients with lung cancer. Pokemon mRNA and protein took on high expression in lung cancer cell lines, and the expression difference between cancer tissues, tumor adjacent tissues and surrounding tissues had statistical significance (PPokemon expression and p14(ARF) expression were negatively correlated (r=-0.287). The expression of Pokemon was determined not to be associated with the patient's sex, age, smoking condition, tumor differentiation degree, histology and lymph node metastasis condition. However, its relationship with TNM staging was established (PPokemon expression was significantly higher than that of those with positive Pokemon expression (P=0.004), therefore, the expression of Pokemon is believed to be an independent factor affecting prognosis (P=0.034). There was high expression of Pokemon in NSCLC

  4. A Case of Renal Primitive Neuroectodermal Tumor Confirmed by Fluorescence in situ Hybridization

    Directory of Open Access Journals (Sweden)

    Toshiki Etani

    2015-04-01

    Full Text Available Primitive neuroectodermal tumor (PNET is a member of the Ewing's sarcoma family of tumors (ESFT. We report a case of PNET in a 66-year-old male who presented with a large solid tumor within the parenchyma of the middle pole of the left kidney with metastases to the left adrenal gland and right ischium. A fine-needle biopsy was performed and showed a small round cell tumor. Results of immunohistochemical staining suggested this tumor belonged to ESFT. Preoperative VDC-IE (combined vincristine, doxorubicin and cyclophosphamide followed by another combination of ifosfamide and etoposide chemotherapy and left radical nephrectomy and adrenalectomy were performed. The histopathological findings of the resected tumor were similar to those in the biopsy specimen, but the results of AE1/AE3 were different. For the diagnosis, fluorescence in situ hybridization was performed. Split signals of the EWSR1 gene were detected, and transmission electron microscopy showed neuroendocrine granules and microtubules. The final diagnosis of this tumor was PNET of the kidney.

  5. Imaging of lung metastasis tumor mouse model using [{sup 18}F]FDG small animal PET and CT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, June Youp; Woo, Sang Keun; Lee, Tae Sup [Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul (Korea, Republic of)] (and others)

    2007-02-15

    The purpose of this study is to image metastaic lung melanoma model with optimal pre-conditions for animal handling by using [{sup 18}F]FDG small animal PET and clinical CT. The pre-conditions for lung region tumor imaging were 16-22 h fasting and warming temperature at 30 .deg. C. Small animal PET image was obtained at 60 min postinjection of 7.4 MBq [{sup 18}F]FDG and compared pattern of [{sup 18}F]FDG uptake and glucose standard uptake value (SUVG) of lung region between Ketamine/Xylazine (Ke/Xy) and Isoflurane (Iso) anesthetized group in normal mice. Metastasis tumor mouse model to lung was established by intravenous injection of B16-F10 cells in C57BL/6 mice. In lung metastasis tumor model, [{sup 18}F]FDG image was obtained and fused with anatomical clinical CT image. Average blood glucose concentration in normal mice were 128.0 {+-} 22.87 and 86.0 {+-} 21.65 mg/dL in Ke/Xy group and Iso group, respectively. Ke/Xy group showed 1.5 fold higher blood glucose concentration than Iso group. Lung to Background ratio (L/B) in SUVG image was 8.6 {+-} 0.48 and 12.1 {+-}0.63 in Ke/Xy group and Iso group, respectively. In tumor detection in lung region, [{sup 18}F]FDG image of Iso group was better than that of Ke/Xy group, because of high L/B ratio. Metastatic tumor location in [{sup 18}F]FDG small animal PET image was confirmed by fusion image using clinical CT. Tumor imaging in small animal lung region with [{sup 18}F]FDG small animal PET should be considered pre-conditions which fasting, warming and an anesthesia during [{sup 18}F]FDG uptake. Fused imaging with small animal PET and CT image could be useful for the detection of metastatic tumor in lung region.

  6. Small round blue cell tumor of seminal vesicle in a young patient

    Directory of Open Access Journals (Sweden)

    Adriano A. De Paula

    2006-10-01

    Full Text Available Seminal vesicle tumor is a rare disease with unclear origin. Generally, it is presented as a pelvic mass that can be detected by sonography and digital rectal exam. The authors report a 25-year-old patient with a pelvic mass which the magnetic resonance and surgical specimen reveal a seminal vesicle tumor. Immunohistochemical findings favored a primitive neuroectodermal tumor of the seminal vesicle. Herein, the treatment, histological and histochemical findings of this entity are discussed.

  7. Imprint cytology of clear cell sarcoma-like tumor of the gastrointestinal tract in the small intestine: A case report.

    Science.gov (United States)

    Kato, Takashi; Ichihara, Shin; Gotoda, Hiroko; Muraoka, Shunji; Kubo, Terufumi; Sugita, Shintaro; Hasegawa, Tadashi

    2017-12-01

    Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT) is an extremely rare malignant neoplasm in the digestive tract. Its cytomorphologic features have never previously been reported. Here, we describe a case of CCSLGT, including its cytologic examination findings. A 47-year-old woman presented with a mass in the small intestine, which was resected and sent for imprint cytology. Imprint smears revealed tumor cells with light eosinophilic or clear cytoplasm in a necrotic background. Many of the tumor cells were arranged in a perivascular growth with a pseudopapillary formation, and there were some non-neoplastic osteoclast-like giant cells. Histological examination revealed solid nests and a pseudopapillary pattern of the tumor cells with clear or pale eosinophilic cytoplasm and large nuclei with small nucleoli. Immunohistochemistry showed positive for vimentin, S-100, and SOX-10, and negative for SMA, c-KIT, cytokeratin, HMB-45, and MelanA. The EWSR1 gene split signal was detected by reverse transcriptase fluorescence in situ hybridization, and EWSR1-CREB1 gene fusion was indicated by reverse transcriptase polymerase chain reaction analysis. From these findings, we diagnosed the tumor as CCSLGT. To best of our knowledge, this is the first description of the imprint cytology features of CCSLGT. © 2017 Wiley Periodicals, Inc.

  8. Chemo-radioresistance of small cell lung cancer cell lines derived from untreated primary tumors obtained by diagnostic bronchofiberscopy

    International Nuclear Information System (INIS)

    Tanio, Yoshiro; Watanabe, Masatoshi; Inoue, Tamotsu

    1990-01-01

    New cell lines of small cell lung cancer (SCLC) were established from specimens of untreated primary tumors biopsied by diagnostic bronchofiberscopy. The advantage of this method was ease of obtaining specimens from lung tumors. Establishment of cell lines was successful with 4 of 13 specimens (30%). Clinical responses of the tumors showed considerable variation, but were well correlated with the in vitro sensitivity of the respective cell lines to chemotherapeutic drugs and irradiation. One of the cell lines was resistant to all drugs tested and irradiation, while another was sensitive to all of them. Although the acquired resistance of SCLC is the biggest problem in treatment, the natural resistance to therapy is another significant problem. Either acquired or natural, resistance mechanisms of SCLC may be elucidated by the use of such cell lines derived from untreated tumors. This method and these SCLC cell lines are expected to be useful for the serial study of biologic and genetic changes of untreated and pre-treated tumors, or primary and secondary tumors. (author)

  9. Primary Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Stomach

    Directory of Open Access Journals (Sweden)

    Safi Khuri

    2016-11-01

    Full Text Available Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET is a tumor of small round cells arising in skeletal tissues. These tumors rarely arise in the stomach. We present a 31-year-old healthy female patient who was admitted to our surgical ward due to upper gastrointestinal hemorrhage. Upper endoscopy revealed a large ulcerated bleeding mass originating from the lesser curvature. Biopsy revealed tumor cell immunoreactivity positive for CD99, vimentin, and Ki67 (an index of proliferation. These findings were compatible with gastric ES/PNET. The fluorescence in situ hybridization analysis result for the EWSR1 gene rearrangement (11: 22 translocation was positive. The patient refused neoadjuvant treatment and thus underwent an operation during which a mass at the lesser curvature of the stomach was found. The mass was adhering to the pancreatic tail and to the mesentery of the transverse and descending colon. Total gastrectomy, distal pancreatectomy, splenectomy, and left adrenalectomy were done. The patient refused adjuvant treatment. She is free of disease 3 years after surgery.

  10. Time-dependent transcriptional response of GOT1 human small intestine neuroendocrine tumor after 177Lu[Lu]-octreotate therapy.

    Science.gov (United States)

    Spetz, Johan; Rudqvist, Nils; Langen, Britta; Parris, Toshima Z; Dalmo, Johanna; Schüler, Emil; Wängberg, Bo; Nilsson, Ola; Helou, Khalil; Forssell-Aronsson, Eva

    2018-05-01

    Patients with neuroendocrine tumors expressing somatostatin receptors are often treated with 177 Lu[Lu]-octreotate. Despite being highly effective in animal models, 177 Lu[Lu]-octreotate-based therapies in the clinical setting can be optimized further. The aims of the study were to identify and elucidate possible optimization venues for 177 Lu[Lu]-octreotate tumor therapy by characterizing transcriptional responses in the GOT1 small intestine neuroendocrine tumor model in nude mice. GOT1-bearing female BALB/c nude mice were intravenously injected with 15 MBq 177 Lu[Lu]-octreotate (non-curative amount) or mock-treated with saline solution. Animals were killed 1, 3, 7 or 41 d after injection. Total RNA was extracted from the tumor samples and profiled using Illumina microarray expression analysis. Differentially expressed genes were identified (treated vs. control) and pathway analysis was performed. Distribution of differentially expressed transcripts indicated a time-dependent treatment response in GOT1 tumors after 177 Lu[Lu]-octreotate administration. Regulation of CDKN1A, BCAT1 and PAM at 1 d after injection was compatible with growth arrest as the initial response to treatment. Upregulation of APOE and BAX at 3 d, and ADORA2A, BNIP3, BNIP3L and HSPB1 at 41 d after injection suggests first activation and then inhibition of the intrinsic apoptotic pathway during tumor regression and regrowth, respectively. Transcriptional analysis showed radiation-induced apoptosis as an early response after 177 Lu[Lu]-octreotate administration, followed by pro-survival transcriptional changes in the tumor during the regrowth phase. Time-dependent changes in cell cycle and apoptosis-related processes suggest different time points after radionuclide therapy when tumor cells may be more susceptible to additional treatment, highlighting the importance of timing when administering multiple therapeutic agents. Copyright © 2018 The Authors. Published by Elsevier Inc. All

  11. Application of small-angle X-ray scattering for differentiation among breast tumors

    International Nuclear Information System (INIS)

    Changizi, V.; Kheradmand, A. Arab; Oghabian, M.A.

    2008-01-01

    Small-angle X-ray scattering (SAXS) is an X-ray diffraction-based technique where a narrow collimated beam of X-rays is focused onto a sample and the scattered X-rays recorded by a detector. The pattern of the scattered X-rays carries information on the molecular structure of the material. As breast cancer is the most widespread cancer in women and differentiation among its tumors is important, this project compared the results of coherent X-ray scattering measurements obtained from benign and malignant breast tissues. The energy-dispersive method with a setup including X-ray tube, primary collimator, sample holder, secondary collimator and high-purity germanium (HpGe) detector was used. One hundred thirty-one breast-tissue samples, including normal, fibrocystic changes and carcinoma, were studied at the 6 deg scattering angle. Diffraction profiles (corrected scattered intensity versus momentum transfer) of normal, fibrocystic changes and carcinoma were obtained. These profiles showed a few peak positions for adipose (1.15 ± 0.06 nm -1 ), mixed normal (1.15 ± 0.06 nm -1 and 1.4 ± 0.04 nm -1 ), fibrocystic changes (1.46 ± 0.05 nm -1 and 1.74 ± 0.04 nm -1 ) and carcinoma (1.55 ± 0.04 nm -1 , 1.73 ± 0.06 nm -1 , 1.85 ± 0.05 nm -1 ). We were able to differentiate between normal, fibrocystic changes (benign) and carcinoma (malignant) breast tissues by SAXS. However, we were unable to differentiate between different types of carcinoma. (author)

  12. Application of small-angle X-ray scattering for differentiation among breast tumors

    Directory of Open Access Journals (Sweden)

    Changizi V

    2008-01-01

    Full Text Available Small-angle X-ray scattering (SAXS is an X-ray diffraction-based technique where a narrow collimated beam of X-rays is focused onto a sample and the scattered X-rays recorded by a detector. The pattern of the scattered X-rays carries information on the molecular structure of the material. As breast cancer is the most widespread cancer in women and differentiation among its tumors is important, this project compared the results of coherent X-ray scattering measurements obtained from benign and malignant breast tissues. The energy-dispersive method with a setup including X-ray tube, primary collimator, sample holder, secondary collimator and high-purity germanium (HpGe detector was used. One hundred thirty-one breast-tissue samples, including normal, fibrocystic changes and carcinoma, were studied at the 6° scattering angle. Diffraction profiles (corrected scattered intensity versus momentum transfer of normal, fibrocystic changes and carcinoma were obtained. These profiles showed a few peak positions for adipose (1.15 ± 0.06 nm -1 , mixed normal (1.15 ± 0.06 nm -1 and 1.4 ± 0.04 nm -1 , fibrocystic changes (1.46 ± 0.05 nm -1 and 1.74 ± 0.04 nm -1 and carcinoma (1.55 ± 0.04 nm -1 , 1.73 ± 0.06 nm -1 , 1.85 ± 0.05 nm -1 . We were able to differentiate between normal, fibrocystic changes (benign and carcinoma (malignant breast tissues by SAXS. However, we were unable to differentiate between different types of carcinoma.

  13. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer.

    Science.gov (United States)

    Pailler, E; Auger, N; Lindsay, C R; Vielh, P; Islas-Morris-Hernandez, A; Borget, I; Ngo-Camus, M; Planchard, D; Soria, J-C; Besse, B; Farace, F

    2015-07-01

    Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration. ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24-55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7-11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN. We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged patients show considerable heterogeneity of ROS1-gene

  14. Inhibition of endothelial cell proliferation by targeting Rac1 GTPase with small interference RNA in tumor cells

    International Nuclear Information System (INIS)

    Xue Yan; Bi Feng; Zhang Xueyong; Pan Yanglin; Liu Na; Zheng Yi; Fan Daiming

    2004-01-01

    Hypoxia-induced angiogenesis plays an important role in the malignancy of solid tumors. A number of recent studies including our own have suggested that Rho family small GTPases are involved in this process, and Rac1, a prominent member of the Rho family, may be critical in regulating hypoxia-induced gene activation of several angiogenesis factors and tumor suppressors. To further define Rac1 function in angiogenesis and to explore novel approaches to modulate angiogenesis, we employed the small interference RNA technique to knock down gene expression of Rac1 in gastric cancer cell line AGS that expresses a high level of Rac1. Both the mRNA and protein levels of Rac1 in the AGS cells were decreased dramatically after transfection with a Rac1-specific siRNA vector. When the conditioned medium derived from the Rac1 downregulated AGS cells was applied to the human endothelial cells, it could significantly inhibit the cell proliferation. Further study proved that, VEGF and HIF-1α, two angiogenesis promoting factors, were found to be downregulated whereas p53 and VHL, which are tumor suppressors and angiogenesis inhibitors, were upregulated in the Rac1 siRNA transfected cells. Our results suggest that Rac1 may be involved in angiogenesis by controlling the expression of angiogenesis-related factors and provide a possible strategy for the treatment of tumor angiogenesis by targeting the Rac1 GTPase

  15. Small neuroendocrine tumor of the duodenal bulb: Endoscopic submucosal dissection, laparoscopic and endoscopic cooperative surgery or surgery?

    Directory of Open Access Journals (Sweden)

    Nikolaos V Chrysanthos

    2016-01-01

    Full Text Available Neuroendocrine neoplasms of the gastric tube are less common than adenocarcinomas. Topography includes stomach, small intestine, Vater ampulla, and gross intestine. They are graded as neuroendocrine tumors grade I and II (NETs GI and GII and neuroendocrine carcinomas GIII based on Ki-67 index and mitotic count. [1] Endoscopic treatment for GI NETs ≤1 cm that does not extend beyond the submucosal layer and does not demonstrate lymph node metastasis is recommended. Tumors ≥2 cm, with lymph node metastasis, are indicated for surgical treatment. The treatment strategy for tumors between 10 and 20 mm in size remains controversial. [2] We present a rare case of a 60-year-old male patient with end-stage renal failure who underwent a screening pretransplantation endoscopic control. Colonoscopy had no pathological findings. Gastroscopy reveals an abnormal mucosa in the anterior upper part of the duodenal bulb that was described as a micronodular mucosa and a central nodule of 6 mm with erythematous mucosa. Histology of the micronodular mucosa reveals a heterotopic gastric mucosa and a small hyperplastic polyp. Biopsies from the nodule reveal a carcinoid tumor (NET GI. Immunohistochemistry: Positive chromogranin levels, low mitotic index (1/10 HPF, and Ki-67 index 2 cm and those of the duodenal bulb with histological extensions and the lack of assessing depth invasion.

  16. Testis sparing surgery for treatment of small testicular lesions: Is it feasible even in germ cell tumors?

    Science.gov (United States)

    Bojanic, Nebojsa; Bumbasirevic, Uros; Bojanic, Gordana; Vukovic, Ivan; Milojevic, Bogomir; Pekmezovic, Tatjana

    2017-03-01

    To evaluate the results of testis-sparing surgery (TSS) in patients, with small testicular lesions and a normal contralateral testicle. In all, 28 patients were treated with TSS for small testicular lesions and a normal contralateral testicle. TSS was considered in patients with testicular lesions smaller than 2 cm and no evidence of metastatic disease. The mean age of patients was 35.3 ± 7.3 years, while the mean diameter of the testicular lesions was 11.4 ± 3.7 mm. After pathological examination, 18 patients (64.3%) were diagnosed with stromal tumors and miscellaneous lesions, while 10 (35.7%) had a germ cell tumor. The median follow-up time for the former group was 33 months and no recurrences were observed. In one patient with germ cell tumor, immediate orchiectomy was performed, while the remaining nine were followed-up (median time, 45 months). One patient developed local recurrence after 39 months. Excellent outcomes for benign lesions could be achieved using TSS. TSS could be offered safely in highly selected patients with germ cell tumors, specifically within a clinical trial but there is more data needed regarding the potential risks and benefits. J. Surg. Oncol. 2017;115:287-290. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model.

    Science.gov (United States)

    Koskimaki, Jacob E; Karagiannis, Emmanouil D; Tang, Benjamin C; Hammers, Hans; Watkins, D Neil; Pili, Roberto; Popel, Aleksander S

    2010-02-01

    Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. We previously introduced a bioinformatics-based methodology to identify endogenous anti-angiogenic peptide sequences, and validated these predictions in vitro in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays. One family of peptides with high activity is derived from the alpha-fibrils of type IV collagen. Based on the results from the in vitro screening, we have evaluated the ability of a 20 amino acid peptide derived from the alpha5 fibril of type IV collagen, pentastatin-1, to suppress vessel growth in an angioreactor-based directed in vivo angiogenesis assay (DIVAA). In addition, pentastatin-1 suppressed tumor growth with intraperitoneal peptide administration in a small cell lung cancer (SCLC) xenograft model in nude mice using the NCI-H82 human cancer cell line. Pentastatin-1 decreased the invasion of vessels into angioreactors in vivo in a dose dependent manner. The peptide also decreased the rate of tumor growth and microvascular density in vivo in a small cell lung cancer xenograft model. The peptide treatment significantly decreased the invasion of microvessels in angioreactors and the rate of tumor growth in the xenograft model, indicating potential treatment for angiogenesis-dependent disease, and for translational development as a therapeutic agent for lung cancer.

  18. Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model

    International Nuclear Information System (INIS)

    Koskimaki, Jacob E; Karagiannis, Emmanouil D; Tang, Benjamin C; Hammers, Hans; Watkins, D Neil; Pili, Roberto; Popel, Aleksander S

    2010-01-01

    Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. We previously introduced a bioinformatics-based methodology to identify endogenous anti-angiogenic peptide sequences, and validated these predictions in vitro in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays. One family of peptides with high activity is derived from the α-fibrils of type IV collagen. Based on the results from the in vitro screening, we have evaluated the ability of a 20 amino acid peptide derived from the α5 fibril of type IV collagen, pentastatin-1, to suppress vessel growth in an angioreactor-based directed in vivo angiogenesis assay (DIVAA). In addition, pentastatin-1 suppressed tumor growth with intraperitoneal peptide administration in a small cell lung cancer (SCLC) xenograft model in nude mice using the NCI-H82 human cancer cell line. Pentastatin-1 decreased the invasion of vessels into angioreactors in vivo in a dose dependent manner. The peptide also decreased the rate of tumor growth and microvascular density in vivo in a small cell lung cancer xenograft model. The peptide treatment significantly decreased the invasion of microvessels in angioreactors and the rate of tumor growth in the xenograft model, indicating potential treatment for angiogenesis-dependent disease, and for translational development as a therapeutic agent for lung cancer

  19. Pyruvate Dehydrogenase and Pyruvate Dehydrogenase Kinase Expression in Non Small Cell Lung Cancer and Tumor-Associated Stroma

    Directory of Open Access Journals (Sweden)

    Michael I. Koukourakis

    2005-01-01

    Full Text Available Pyruvate dehydrogenase (PDH catalyzes the conversion of pyruvate to acetyl-coenzyme A, which enters into the Krebs cycle, providing adenosine triphosphate (ATP to the cell. PDH activity is under the control of pyruvate dehydrogenase kinases (PDKs. Under hypoxic conditions, conversion of pyruvate to lactate occurs, a reaction catalyzed by lactate dehydrogenase 5 (LDH5. In cancer cells, however, pyruvate is transformed to lactate occurs, regardless of the presence of oxygen (aerobic glycolysis/Warburg effect. Although hypoxic intratumoral conditions account for HIFia stabilization and induction of anaerobic metabolism, recent data suggest that high pyruvate concentrations also result in HIFia stabilization independently of hypoxia. In the present immunohistochemical study, we provide evidence that the PDH/PDK pathway is repressed in 73% of non small cell lung carcinomas, which may be a key reason for HIFia stabilization and “aerobic glycolysis.” However, about half of PDHdeficient carcinomas are not able to switch on the HIF pathway, and patients harboring these tumors have an excellent postoperative outcome. A small subgroup of clinically aggressive tumors maintains a coherent PDH and HIF/LDH5 expression. In contrast to cancer cells, fibroblasts in the tumor-supporting stroma exhibit an intense PDH but reduced PDK1 expression favoring maximum PDH activity. This means that stroma may use lactic acid produced by tumor cells, preventing the creation of an intolerable intratumoral acidic environment at the same time.

  20. Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non-small-cell lung cancer.

    Science.gov (United States)

    Pailler, Emma; Adam, Julien; Barthélémy, Amélie; Oulhen, Marianne; Auger, Nathalie; Valent, Alexander; Borget, Isabelle; Planchard, David; Taylor, Melissa; André, Fabrice; Soria, Jean Charles; Vielh, Philippe; Besse, Benjamin; Farace, Françoise

    2013-06-20

    The diagnostic test for ALK rearrangement in non-small-cell lung cancer (NSCLC) for crizotinib treatment is currently done on tumor biopsies or fine-needle aspirations. We evaluated whether ALK rearrangement diagnosis could be performed by using circulating tumor cells (CTCs). The presence of an ALK rearrangement was examined in CTCs of 18 ALK-positive and 14 ALK-negative patients by using a filtration enrichment technique and filter-adapted fluorescent in situ hybridization (FA-FISH), a FISH method optimized for filters. ALK-rearrangement patterns were determined in CTCs and compared with those present in tumor biopsies. ALK-rearranged CTCs and tumor specimens were characterized for epithelial (cytokeratins, E-cadherin) and mesenchymal (vimentin, N-cadherin) marker expression. ALK-rearranged CTCs were monitored in five patients treated with crizotinib. All ALK-positive patients had four or more ALK-rearranged CTCs per 1 mL of blood (median, nine CTCs per 1 mL; range, four to 34 CTCs per 1 mL). No or only one ALK-rearranged CTC (median, one per 1 mL; range, zero to one per 1 mL) was detected in ALK-negative patients. ALK-rearranged CTCs harbored a unique (3'5') split pattern, and heterogeneous patterns (3'5', only 3') of splits were present in tumors. ALK-rearranged CTCs expressed a mesenchymal phenotype contrasting with heterogeneous epithelial and mesenchymal marker expressions in tumors. Variations in ALK-rearranged CTC levels were detected in patients being treated with crizotinib. ALK rearrangement can be detected in CTCs of patients with ALK-positive NSCLC by using a filtration technique and FA-FISH, enabling both diagnostic testing and monitoring of crizotinib treatment. Our results suggest that CTCs harboring a unique ALK rearrangement and mesenchymal phenotype may arise from clonal selection of tumor cells that have acquired the potential to drive metastatic progression of ALK-positive NSCLC.

  1. v-Ha-ras oncogene insertion: A model for tumor progression of human small cell lung cancer

    International Nuclear Information System (INIS)

    Mabry, M.; Nakagawa, Toshitaro; Nelkin, B.D.; McDowell, E.; Gesell, M.; Eggleston, J.C.; Casero, R.A. Jr.; Baylin, S.B.

    1988-01-01

    Small cell lung cancer (SCLC) manifests a range of phenotypes in culture that may be important in understanding its relationship to non-SCLCs and to tumor progression events in patients. Most SCLC-derived cell lines, termed classic SCLC lines, have properties similar to SCLC tumors in patients. To delineate further the relationships between these phenotypes and the molecular events involved, the authors inserted the v-Ha-ras gene in SCLC cell lines with (biochemical variant) and without (classic) an amplified c-myc gene. These two SCLC subtypes had markedly different phenotypic responses to similar levels of expression of v-Ha-ras RNA. No biochemical or morphologic changes were observed in classic SCLC cells. In contrast, in biochemical variant SCLC cells, v-Ha-ras expression induced features typical of large cell undifferentiated lung carcinoma. Expression of v-Ha-ras in biochemical variant SCLC cells directly demonstrates that important transitions can occur between phenotypes of human lung cancer cells and that these may play a critical role in tumor progression events in patients. The finding provide a model system to study molecular events involved in tumor progression steps within a series of related tumor types

  2. Stereotactic radiotherapy with real-time tumor tracking for non-small cell lung cancer: Clinical outcome

    International Nuclear Information System (INIS)

    Voort van Zyp, Noelle C. van der; Prevost, Jean-Briac; Hoogeman, Mischa S.; Praag, John; Holt, Bronno van der; Levendag, Peter C.; Klaveren, Robertus J. van; Pattynama, Peter; Nuyttens, Joost J.

    2009-01-01

    Purpose: To report the clinical outcome of treatment using real-time tumor tracking for 70 patients with inoperable stage I non-small cell lung cancer (NSCLC). Materials and methods: Seventy inoperable patients with peripherally located early-stage NSCLC were treated with 45 or 60 Gy in three fractions using CyberKnife. Pathology was available in 51% of patients. Thirty-nine patients had a T1-tumor and 31 had a T2-tumor. Markers were placed using the vascular, percutaneous intra-, or extra-pulmonary approach, depending on the risk of pneumothorax. Results: The actuarial 2-year local control rate for patients treated with 60 Gy was 96%, compared to 78% for patients treated with a total dose of 45 Gy (p = 0.197). All local recurrences (n = 4) occurred in patients with T2-tumors. Overall survival for the whole group at two years was 62% and the cause specific survival was 85%. The median follow-up was 15 months. Grade 3 toxicity occurred in two patients (3%) after marker placement. Treatment-related late grade 3 toxicity occurred in 7 patients (10%). No grade ≥4 toxicity occurred. Conclusion: Excellent local control of 96% at 1- and 2-years was achieved using 60 Gy in three fractions for NSCLC patients treated with the real-time tumor tracking. Toxicity was low.

  3. Development of a New Positron Emission Tomography Tracer for Targeting Tumor Angiogenesis: Synthesis, Small Animal Imaging, and Radiation Dosimetry

    Directory of Open Access Journals (Sweden)

    David S. Lalush

    2013-05-01

    Full Text Available Angiogenesis plays a key role in cancer progression and correlates with disease aggressiveness and poor clinical outcomes. Affinity ligands discovered by screening phage display random peptide libraries can be engineered to molecularly target tumor blood vessels for noninvasive imaging and early detection of tumor aggressiveness. In this study, we tested the ability of a phage-display-selected peptide sequence recognizing specifically bone marrow- derived pro-angiogenic tumor-homing cells, the QFP-peptide, radiolabeled with 64Cu radioisotope to selectively image tumor vasculature in vivo by positron emission tomography (PET. To prepare the targeted PET tracer we modified QFP-phage with the DOTA chelator and radiolabeled the purified QFP-phage-DOTA intermediate with 64Cu to obtain QFP-targeted radioconjugate with high radiopharmaceutical yield and specific activity. We evaluated the new PET tracer in vivo in a subcutaneous (s.c. Lewis lung carcinoma (LLC mouse model and conducted tissue distribution, small animal PET/CT imaging study, autoradiography, histology, fluorescence imaging, and dosimetry assessments. The results from this study show that, in the context of the s.c. LLC immunocompetent mouse model, the QFP-tracer can target tumor blood vessels selectively. However, further optimization of the biodistribution and dosimetry profile of the tracer is necessary to ensure efficient radiopharmaceutical applications enabled by the biological specificity of the QFP-peptide.

  4. Biodistribution of ultra small gadolinium-based nanoparticles as theranostic agent: application to brain tumors.

    Science.gov (United States)

    Miladi, Imen; Duc, Géraldine Le; Kryza, David; Berniard, Aurélie; Mowat, Pierre; Roux, Stéphane; Taleb, Jacqueline; Bonazza, Pauline; Perriat, Pascal; Lux, François; Tillement, Olivier; Billotey, Claire; Janier, Marc

    2013-09-01

    Gadolinium-based nanoparticles are novel objects with interesting physical properties, allowing their use for diagnostic and therapeutic applications. Gadolinium-based nanoparticles were imaged following intravenous injection in healthy rats and rats grafted with 9L gliosarcoma tumors using magnetic resonance imaging and scintigraphic imaging. Quantitative biodistribution using gamma-counting of each sampled organ confirmed that these nanoparticles were rapidly cleared essentially by renal excretion. Accumulation of these nanoparticles in 9L gliosarcoma tumors implanted in the rat brain was quantitated. This passive and long-duration accumulation of gadolinium-based nanoparticles in tumor, which is related to disruption of the blood-brain barrier, is in good agreement with the use of these nanoparticles as radiosensitizers for brain tumors.

  5. Effects of experimental radiotherapy and hyperthermia on tumors and normal tissues in small animals

    International Nuclear Information System (INIS)

    Wondergem, J.

    1985-01-01

    Experiments on responses of tumors, implanted subcutaneously in the leg, to irradiation alone or combined with heat are reported. The influence of factors modifying the fraction of hypoxic cells (e.g. anesthesia of the animal and tumor volume) is also discussed. The radiosensitivity of developing lung tumors was examined for spontaneous as well as for artificial lung metastases. Both experimental tumor models were compared with regard to their value in experimental radiotherapy. Data obtained on the response of artificial metastases and lung tissue to combined treatment with irradiation and several drugs are presented. Data on damage of the mouse foot, as a result of heat and/or irradiation treatments are presented. In particular the influence of thermotolerance on thermal enhancement of the radiation induced skin reaction was studied. Tolerance of the skin of previously irradiated mice to retreatment with irradiation, to hyperthermia alone and combined with X-rays was assessed. (Auth.)

  6. Hidradenocarcinoma: A Rare Sweat Gland Neoplasm Presenting as Small Turban Tumor of the Scalp.

    Science.gov (United States)

    Asati, Dinesh P; Brahmachari, Swagata; Kudligi, Chandramohan; Gupta, Chandramohan

    2015-01-01

    Hidradenocarcinomas are very rare malignant sweat gland tumors that possess an infiltrative and/or low metastatic potential. Here we describe an interesting case of hidradenoma on the fronto-parietal region of the scalp of an elderly female, part of which had developed carcinomatous changes, infiltrating up to the pericranium. She developed intense itching, pain, spontaneous ulceration and rapid increase in the size of the tumor correlating with the expression of malignant behavior of the neoplasm. An initial incision biopsy suggested features of benign poroid hidradenoma, while the histology from the excised tumor exhibited a fairly well circumscribed epithelial neoplasm in dermis consisting of interconnected nodules as well as differentiated ducts, the neoplastic cells showing mild pleomorphism of nuclei, mitotic figures and abundant pale cytoplasm. Clefts, sclerotic stroma and foci of necrosis en mass were also seen. The final diagnosis was a well differentiated and slow growing hidradenocarcinoma. The tumor recurred locally despite total excision.

  7. Hidradenocarcinoma: A rare sweat gland neoplasm presenting as small turban tumor of the scalp

    Directory of Open Access Journals (Sweden)

    Dinesh P Asati

    2015-01-01

    Full Text Available Hidradenocarcinomas are very rare malignant sweat gland tumors that possess an infiltrative and/or low metastatic potential. Here we describe an interesting case of hidradenoma on the fronto-parietal region of the scalp of an elderly female, part of which had developed carcinomatous changes, infiltrating up to the pericranium. She developed intense itching, pain, spontaneous ulceration and rapid increase in the size of the tumor correlating with the expression of malignant behavior of the neoplasm. An initial incision biopsy suggested features of benign poroid hidradenoma, while the histology from the excised tumor exhibited a fairly well circumscribed epithelial neoplasm in dermis consisting of interconnected nodules as well as differentiated ducts, the neoplastic cells showing mild pleomorphism of nuclei, mitotic figures and abundant pale cytoplasm. Clefts, sclerotic stroma and foci of necrosis en mass were also seen. The final diagnosis was a well differentiated and slow growing hidradenocarcinoma. The tumor recurred locally despite total excision.

  8. BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors

    International Nuclear Information System (INIS)

    Samuelson, Emma; Karlsson, Sara; Partheen, Karolina; Nilsson, Staffan; Szpirer, Claude; Behboudi, Afrouz

    2012-01-01

    Development of breast cancer is a multistage process influenced by hormonal and environmental factors as well as by genetic background. The search for genes underlying this malignancy has recently been highly productive, but the etiology behind this complex disease is still not understood. In studies using animal cancer models, heterogeneity of the genetic background and environmental factors is reduced and thus analysis and identification of genetic aberrations in tumors may become easier. To identify chromosomal regions potentially involved in the initiation and progression of mammary cancer, in the present work we subjected a subset of experimental mammary tumors to cytogenetic and molecular genetic analysis. Mammary tumors were induced with DMBA (7,12-dimethylbenz[a]anthrazene) in female rats from the susceptible SPRD-Cu3 strain and from crosses and backcrosses between this strain and the resistant WKY strain. We first produced a general overview of chromosomal aberrations in the tumors using conventional kartyotyping (G-banding) and Comparative Genome Hybridization (CGH) analyses. Particular chromosomal changes were then analyzed in more details using an in-house developed BAC (bacterial artificial chromosome) CGH-array platform. Tumors appeared to be diploid by conventional karyotyping, however several sub-microscopic chromosome gains or losses in the tumor material were identified by BAC CGH-array analysis. An oncogenetic tree analysis based on the BAC CGH-array data suggested gain of rat chromosome (RNO) band 12q11, loss of RNO5q32 or RNO6q21 as the earliest events in the development of these mammary tumors. Some of the identified changes appear to be more specific for DMBA-induced mammary tumors and some are similar to those previously reported in ACI rat model for estradiol-induced mammary tumors. The later group of changes is more interesting, since they may represent anomalies that involve genes with a critical role in mammary tumor development. Genetic

  9. Studies on colon cancer prone rats. Spontaneous small intestinal carcinomas and tumor induction of small intestine by x-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Maeura, Y [Osaka Univ. (Japan). Faculty of Medicine

    1979-12-01

    Histological investigation was carried out for Wister-Furth (WF) rats, prone to cancers of the colon and small intestine. Gastric cancer was observed in about 1/4 of the rats with the cancers of the colon and the small intestine, indicating that these rats could be the model animals of the cancer family syndrome with multi-cancers in the gastrointestinal tracts. The small intestine of WF and SD (Sprague-Dowley) rats as exposed to 1000, 2 x 1000, 1500, and 2000 R of x-rays at a dose rate of 157 R/min. In each group the stomach, small intestine, cecum, and colon were histologically investigated, immediately and 15, 25, and 35 weeks after irradiation. The rates of cancer occurrence in 15, 25, and 35 weeks were 5/17, 9/19, and 9/14 for WF strain and 1/8, 2/7, and 2/8 for SD strain, respectively. The rate increased with the increment of the days after irradiation. It was suggested that the atypical epithelium of the gastrointestinal tracts induced the cancer in high rates when some trigger was added.

  10. Pancreatic islet cell tumor

    Science.gov (United States)

    ... cell tumors; Islet of Langerhans tumor; Neuroendocrine tumors; Peptic ulcer - islet cell tumor; Hypoglycemia - islet cell tumor ... stomach acid. Symptoms may include: Abdominal pain Diarrhea ... and small bowel Vomiting blood (occasionally) Glucagonomas make ...

  11. Effect of small dose of radiation on induction of apoptosis in murine tumors

    International Nuclear Information System (INIS)

    Seong, Jin Sil; Pyo, Hong Ryull; Chung, Eun Ji; Kim, Sung Hee; Suh, Chang Ok

    1999-01-01

    To investigate the presence of adaptive response by low dose radiation in murine tumors in relation to radiation induced apoptosis as well as related mechanism. Syngeneic murine tumors, OCa-1 and HCa-l, were given 0.05 Gy pretreatment followed by therapeutic dose of 25 Gy radiation. Induction of apoptosis was analyzed for each treatment group. Regulating molecules of apoptosis. p53, Bcl-2, Sax, Bel-X, were also analyzed by Western blotting. In 0.05 Gy pretreatment group of OCa-l, 25 Gy-induced apoptosis per 1000 cells was 229, which was estimated at 30% lower level than the expected (p<0.05). In contrast, this reduction in radiation induced apoptosis was not seen in HCa-1. In the expression of apoptosis regulating molecules, p53 increased in both tumors in response to radiation. Bcl-2 and Bax did not show significant change in both tumors however, the expression of Bcl-2 surpassed that of Bax in 0.05 Gy pretreatment group of OCa-1. Bcl-X was not expressed in OCa-1. In HCa-l, ScI-X showed increased expression even with 0.05 Gy. Adaptive response by low dose radiation is shown in one murine tumor, OCa-I, in relation to radiation induced apoptosis. Apoptosis regulating molecules including Bcl-2/Bax and Bcl-X, appear to related. This study shows an evidence that adaptive response is present, but not a generalized phenomenon in vivo

  12. Inconspicuous insertion 22;12 in myxoid/round cell liposarcoma accompanied by the secondary structural abnormality der(16)t(1;16).

    Science.gov (United States)

    Birch, Nathan C; Antonescu, Cristina R; Nelson, Marilu; Sarran, Lisa; Neff, James R; Seemayer, Thomas; Bridge, Julia A

    2003-08-01

    In myxoid/round cell liposarcoma, the t(12;16)(q13;p11) and its associated fusion transcript, FUS-CHOP, characterize greater than 95% of cases. The variant translocation t(12;22)(q13;q12) and associated EWS-CHOP fusion transcript are rare. A second non-random aberration observed in roughly 20% of Ewing's sarcomas, and to a lesser extent other select sarcomas, is the unbalanced 1;16 translocation. Recognition of this secondary aberration in the absence of an obvious primary karyotypic abnormality strongly suggests that the use of other genetic approaches will be informative in uncovering a clinically suspected primary anomaly. The following case illustrates the utility of molecular cytogenetic and reverse transcriptase-polymerase chain reaction techniques in diagnosing an ins(22;12)(q12;q13q14) and associated EWS-CHOP fusion transcript in a myxoid/round cell liposarcoma exhibiting a der(16)t(1;16)(q11;q11).

  13. Systemic inflammation, nutritional status and tumor immune microenvironment determine outcome of resected non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Marco Alifano

    Full Text Available BACKGROUND: Hypothesizing that nutritional status, systemic inflammation and tumoral immune microenvironment play a role as determinants of lung cancer evolution, the purpose of this study was to assess their respective impact on long-term survival in resected non-small cell lung cancers (NSCLC. METHODS AND FINDINGS: Clinical, pathological and laboratory data of 303 patients surgically treated for NSCLC were retrospectively analyzed. C-reactive protein (CRP and prealbumin levels were recorded, and tumoral infiltration by CD8+ lymphocytes and mature dendritic cells was assessed. We observed that factors related to nutritional status, systemic inflammation and tumoral immune microenvironment were correlated; significant correlations were also found between these factors and other relevant clinical-pathological parameters. With respect to outcome, at univariate analysis we found statistically significant associations between survival and the following variables: Karnofsky index, American Society of Anesthesiologists (ASA class, CRP levels, prealbumin concentrations, extent of resection, pathologic stage, pT and pN parameters, presence of vascular emboli, and tumoral infiltration by either CD8+ lymphocytes or mature dendritic cells and, among adenocarcinoma type, tumor grade (all p285 mg/L prealbumin levels and high (>96/mm2 CD8+ cell count had a 5-year survival rate of 80% [60.9-91.1] as compared to 18% [7.9-35.6] in patients with an opposite pattern of values. When stages I-II were considered alone, the prognostic significance of these factors was even more pronounced. CONCLUSIONS: Our data show that nutrition, systemic inflammation and tumoral immune contexture are prognostic determinants that, taken together, may predict outcome.

  14. Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer.

    Science.gov (United States)

    Vanderlaan, Paul A; Yamaguchi, Norihiro; Folch, Erik; Boucher, David H; Kent, Michael S; Gangadharan, Sidharta P; Majid, Adnan; Goldstein, Michael A; Huberman, Mark S; Kocher, Olivier N; Costa, Daniel B

    2014-04-01

    Identification of some somatic molecular alterations in non-small-cell lung cancer (NSCLC) has become evidence-based practice. The success and failure rate of using commercially available tumor genotyping techniques in routine day-to-day NSCLC pathology samples is not well described. We sought to evaluate the success and failure rate of EGFR mutation, KRAS mutation, and ALK FISH in a cohort of lung cancers subjected to routine clinical tumor genotype. Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 381 patient-tumor samples. From these 381 patients with lung cancer, the mean age was 65 years, 61.2% were women, 75.9% were white, 27.8% were never smokers, 73.8% had advanced NSCLC and 86.1% had adenocarcinoma histology. The tumor tissue was obtained from surgical specimens in 48.8%, core needle biopsies in 17.9%, and as cell blocks from aspirates or fluid in 33.3% of cases. Anatomic sites for tissue collection included lung (49.3%), lymph nodes (22.3%), pleura (11.8%), bone (6.0%), brain (6.0%), among others. The overall success rate for EGFR mutation analysis was 94.2%, for KRAS mutation 91.6% and for ALK FISH 91.6%. The highest failure rates were observed when the tissue was obtained from image-guided percutaneous transthoracic core-needle biopsies (31.8%, 27.3%, and 35.3% for EGFR, KRAS, and ALK tests, respectively) and bone specimens (23.1%, 15.4%, and 23.1%, respectively). In specimens obtained from bone, the failure rates were significantly higher for biopsies than resection specimens (40% vs. 0%, p=0.024 for EGFR) and for decalcified compared to non-decalcified samples (60% vs. 5.5%, p=0.021 for EGFR). Tumor genotype techniques are feasible in most samples, outside small image-guided percutaneous transthoracic core-needle biopsies and bone samples from core biopsies with decalcification, and therefore expansion of routine tumor genotype into the care of patients with NSCLC may not require special

  15. Small renal masses: The molecular markers associated with outcome of patients with kidney tumors 7 cm or less

    Science.gov (United States)

    Spirina, L. V.; Usynin, Y. A.; Kondakova, I. V.; Yurmazov, Z. A.; Slonimskaya, E. M.; Pikalova, L. V.

    2016-08-01

    The investigation of molecular mechanisms of tumor cell behavior in small renal masses is required to achieve the better cancer survival. The aim of the study is to find molecular markers associated with outcome of patients with kidney tumors 7 cm or less. A homogenous group of 20 patients T1N0M0-1 (mean age 57.6 ± 2.2 years) with kidney cancer was selected for the present analysis. The content of transcription and growth factors was determined by ELISA. The levels of AKT-mTOR signaling pathway components were measured by Western blotting analysis. The molecular markers associated with unfavorable outcome of patients with kidney tumors 7 cm or less were high levels of NF-kB p50, NF-kB p65, HIF-1, HIF-2, VEGF and CAIX. AKT activation with PTEN loss also correlated with the unfavorable outcome of kidney cancer patients with tumor size 7 cm or less. It is observed that the biological features of kidney cancer could predict the outcome of patients.

  16. Additional diagnostic value of tumor markers in cytological fluid for diagnosis of non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Hur Jin

    2012-09-01

    Full Text Available Abstract Background Cytological fluid from a needle aspiration biopsy (NAB is obtained directly from tumor tissue, therefore many biomarker candidates will be present in high concentrations. The aim of this study was to prospectively assess and validate the tumor markers CYFRA 21–1, CEA, and SCC in cytological fluid obtained from NAB samples to determine if they improved the performance of NAB for diagnosing non-small cell lung cancer (NSCLC. Methods A total of 194 patients (M:F = 128:66, mean age 63.7 years with suspected malignant pulmonary lesions were prospectively enrolled and underwent percutaneous NAB. Levels of CYFRA 21–1, CEA, and SCC were measured by immunoassay in serum and cytological fluid obtained during aspiration biopsy. Cut-off values to determined malignancy were 3.3 ng/mL in serum and 15.7 ng/mL in cytological fluid for CYFRA 21–1, 5 ng/mL and 0.6 ng/mL for CEA, and 2 ng/mL and 0.86 ng/mL for SCC. Results Of 194 patients, 139 patients (71.6% had NSCLC and 55 (28.4% had benign lesions. Sensitivity increased significantly for NAB combined with cytological tumor markers compared with NAB alone (CYFRA 21–1: 95% versus 83.5%, p Conclusion Of the tested tumor markers, cytological fluid measurements of CYFRA 21–1 improved the diagnostic performance of NAB for NSCLC.

  17. Novel small molecule drugs inhibit tumor cell metabolism and show potent anti-tumorigenic potential

    DEFF Research Database (Denmark)

    Trojel-Hansen, Christina; Erichsen, Kamille Dumong; Christensen, Mette Knak

    2011-01-01

    oxyphenisatine analogs TOP001 and TOP216 exert their anti-cancer effect by affecting tumor cell metabolism and inducing intracellular amino acid deprivation, leading to a block of cell proliferation. GCN2-mediated phosphorylation of eIF2a as well as mTOR pathway inhibition supports the above notion. In addition...

  18. Novel small molecule drugs inhibit tumor cell metabolism and show potent anti-tumorigenic potential

    DEFF Research Database (Denmark)

    Trojel-Hansen, Christina; Erichsen, Kamille Dumong; Christensen, Mette Knak

    2011-01-01

    oxyphenisatine analogs TOP001 and TOP216 exert their anti-cancer effect by affecting tumor cell metabolism and inducing intracellular amino acid deprivation, leading to a block of cell proliferation. GCN2-mediated phosphorylation of eIF2α as well as mTOR pathway inhibition supports the above notion. In addition...

  19. Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice.

    Science.gov (United States)

    Verhaegen, Monique E; Mangelberger, Doris; Harms, Paul W; Eberl, Markus; Wilbert, Dawn M; Meireles, Julia; Bichakjian, Christopher K; Saunders, Thomas L; Wong, Sunny Y; Dlugosz, Andrzej A

    2017-06-15

    Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a nonproliferative population of neuroendocrine cells that arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of preterm transgenic mice, we show that epidermis-targeted coexpression of sT and the cell fate-determinant atonal bHLH transcription factor 1 (ATOH1) leads to development of widespread cellular aggregates, with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. Cancer Res; 77(12); 3151-7. ©2017 AACR . ©2017 American Association for Cancer Research.

  20. [Mesh structure of two-dimensional tumor microvascular architecture phenotype heterogeneity in non-small cell lung cancer].

    Science.gov (United States)

    Xiong, Zeng; Zhou, Hui; Liu, Jin-Kang; Hu, Cheng-Ping; Zhou, Mo-Ling; Xia, Yu; Zhou, Jian-Hua

    2009-11-01

    To investigate the structural characteristics and clinical significance of two-dimensional tumor microvascular architecture phenotype (2D-TMAP) in non-small cell lung cancer (NSCLC). Thirty surgical specimens of NSCLC were collected. The sections of the tumor tissues corresponding to the slice of CT perfusion imaging were selected to construct the 2D-TMAP expression. Spearman correlation analysis was used to examine the relation between the 2D-TMAP expression and the clinicopathological features of NSCLC. A heterogeneity was noted in the 2D-TMAP expression of NSCLC. The microvascular density (MVD) in the area surrounding the tumor was higher than that in the central area, but the difference was not statistically significant. The density of the microvessels without intact lumen was significantly greater in the surrounding area than in the central area (P=0.030). The total MVD was not correlated to tumor differentiation (r=0.042, P=0.831). The density of the microvessels without intact lumen in the surrounding area was positively correlated to degree of tumor differentiation and lymph node metastasis (r=0.528 and 0.533, P=0.041 and 0.028, respectively), and also to the expressions of vascular endothelial growth factor (VEGF), ephrinB2, EphB4, and proliferating cell nuclear antigen (PCNA) (r=0.504, 0.549, 0.549, and 0.370; P=0.005, 0.002, 0.002, and 0.048, respectively). The degree of tumor differentiation was positively correlated to PCNA and VEGF expression (r=0.604 and 0.370, P=0.001 and 0.048, respectively), but inversely to the integrity of microvascular basement membrane (r=-0.531, P=0.033). The 2D-TMAP suggests the overall state of the micro-environment for tumor growth. The 2D-TMAP of NSCLC regulates angiogenesis and tumor cell proliferation through a mesh-like structure, and better understanding of the characteristics and possible mechanism of 2D-TMAP expression can be of great clinical importance.

  1. Radiological image interpretation for hematoma and small tumors simulated in a head and neck phantom

    International Nuclear Information System (INIS)

    Thompson, Larissa; Campos, Tarcisio Passos Ribeiro

    2009-01-01

    Subarachnoidal hemorrhages (HSA) are caused by aneurysms and their symptom usually becomes evident after a rupture. Nevertheless, there are situations in which the aneurysms compress a nerve or produce a bleed before the rupture happens, as consequence one alert signal like headache occurs. It, often occurs after minutes or weeks previous the major rupture. The main goal is to prevent a massive hemorrhage. Thus the Computer Tomography (CT) scan of skull provides a basic and specific function: to reveal the position where the hemorrhage was produced, guiding to a additional medical procedures. On the other hand, CT does not prevent the cerebral tumor development, but precise diagnostic for some symptoms such as vomits, nauseas, epileptic attacks, weakness in arms or legs, require this image protocol. CT has its fundamental importance to tumor detection. Indeed CT reveals its importance in the tumor early diagnosis. Specialized training in CT analysis shall be done. Ahead of a precise diagnosis to manager an early intervention, a CT diagnostic training is suitable for a favorable prognostic. In this context, focusing on propose of radiological inquires; a head and neck phantom will be used to simulate hematomas and cerebral tumors. Images of CT of skull will be used to identify these lesions physically implanted in phantom. The radiological response will be analyzed with the purpose of validation of the skull's CT diagnosis, for a double blind test. The diagnostic with non contrast CT shows only higher 5mm diameter subjects (tumors) identified by the double blind test. Hemorrhage is identified by only the administrator (single-blind test). As conclusion, the author's launches the hypothesis that this object simulator shall provide assistance for specialized training on pathology interpretation on radiological images. (author)

  2. Anti-tumor activity of a novel HS-mimetic-vascular endothelial growth factor binding small molecule.

    Directory of Open Access Journals (Sweden)

    Kazuyuki Sugahara

    Full Text Available The angiogenic process is controlled by variety of factors of which the vascular endothelial growth factor (VEGF pathway plays a major role. A series of heparan sulfate mimetic small molecules targeting VEGF/VEGFR pathway has been synthesized. Among them, compound 8 (2-butyl-5-chloro-3-(4-nitro-benzyl-3H-imidazole-4-carbaldehyde was identified as a significant binding molecule for the heparin-binding domain of VEGF, determined by high-throughput-surface plasmon resonance assay. The data predicted strong binding of compound 8 with VEGF which may prevent the binding of VEGF to its receptor. We compared the structure of compound 8 with heparan sulfate (HS, which have in common the functional ionic groups such as sulfate, nitro and carbaldehyde that can be located in similar positions of the disaccharide structure of HS. Molecular docking studies predicted that compound 8 binds at the heparin binding domain of VEGF through strong hydrogen bonding with Lys-30 and Gln-20 amino acid residues, and consistent with the prediction, compound 8 inhibited binding of VEGF to immobilized heparin. In vitro studies showed that compound 8 inhibits the VEGF-induced proliferation migration and tube formation of mouse vascular endothelial cells, and finally the invasion of a murine osteosarcoma cell line (LM8G7 which secrets high levels of VEGF. In vivo, these effects produce significant decrease of tumor burden in an experimental model of liver metastasis. Collectively, these data indicate that compound 8 may prevent tumor growth through a direct effect on tumor cell proliferation and by inhibition of endothelial cell migration and angiogenesis mediated by VEGF. In conclusion, compound 8 may normalize the tumor vasculature and microenvironment in tumors probably by inhibiting the binding of VEGF to its receptor.

  3. Detecting small lung tumors in mouse models by refractive-index microradiology

    Energy Technology Data Exchange (ETDEWEB)

    Chien, Chia-Chi; Hwu, Y. [Academia Sinica, Institute of Physics, Taipei (China); National Tsing Hua University, Department of Engineering and System Science, Hsinchu (China); Zhang, Guilin; Yue, Weisheng; Li, Yan; Xue, Hongjie [Chinese Academy of Sciences, Shanghai Institute of Applied Physics, Shanghai (China); Liu, Ping; Sun, Jianqi; Xu, Lisa X. [Shanghai Jiao Tong University, Shanghai (China); Wang, Chang Hai; Chen, Nanyow; Lu, Chien Hung; Lee, Ting-Kuo [Academia Sinica, Institute of Physics, Taipei (China); Yang, Yuh-Cheng; Lu, Yen-Ta [Mackay Memorial Hospital, Taipei City (China); Ching, Yu-Tai [National Chiao Tung University, Department of Computer Science, Hsinchu (China); Shih, T.F.; Yang, P.C. [National Taiwan University, College of Medicine, Taipei (China); Je, J.H. [Pohang University of Science and Technology Pohang, X-ray Imaging Center, Pohang CT, Kyungbuk (Korea, Republic of); Margaritondo, G. [Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne (Switzerland)

    2011-08-15

    Refractive-index (phase-contrast) radiology was able to detect lung tumors less than 1 mm in live mice. Significant micromorphology differences were observed in the microradiographs between normal, inflamed, and lung cancer tissues. This was made possible by the high phase contrast and by the fast image taking that reduces the motion blur. The detection of cancer and inflammation areas by phase contrast microradiology and microtomography was validated by bioluminescence and histopathological analysis. The smallest tumor detected is less than 1 mm{sup 3} with accuracy better than 1 x 10{sup -3} mm{sup 3}. This level of performance is currently suitable for animal studies, while further developments are required for clinical application. (orig.)

  4. Detecting small lung tumors in mouse models by refractive-index microradiology

    International Nuclear Information System (INIS)

    Chien, Chia-Chi; Hwu, Y.; Zhang, Guilin; Yue, Weisheng; Li, Yan; Xue, Hongjie; Liu, Ping; Sun, Jianqi; Xu, Lisa X.; Wang, Chang Hai; Chen, Nanyow; Lu, Chien Hung; Lee, Ting-Kuo; Yang, Yuh-Cheng; Lu, Yen-Ta; Ching, Yu-Tai; Shih, T.F.; Yang, P.C.; Je, J.H.; Margaritondo, G.

    2011-01-01

    Refractive-index (phase-contrast) radiology was able to detect lung tumors less than 1 mm in live mice. Significant micromorphology differences were observed in the microradiographs between normal, inflamed, and lung cancer tissues. This was made possible by the high phase contrast and by the fast image taking that reduces the motion blur. The detection of cancer and inflammation areas by phase contrast microradiology and microtomography was validated by bioluminescence and histopathological analysis. The smallest tumor detected is less than 1 mm 3 with accuracy better than 1 x 10 -3 mm 3 . This level of performance is currently suitable for animal studies, while further developments are required for clinical application. (orig.)

  5. Frequency domain fluorescent diffuse tomography of small animals with DsRed2-expressed tumors

    Science.gov (United States)

    Turchin, Ilya V.; Savitsky, Alexander P.; Kamensky, Vladislav A.; Plehanov, Vladimir I.; Orlova, Anna G.; Sergeeva, Ekaterina A.; Kleshnin, Mikhail S.; Shirmanova, Marina V.

    2006-02-01

    The main applications of fluorescent proteins (FPs) are monitoring tumor growth, angiogenesis, metastases formation and effects of new classes of drugs. Different types of tomography allow fluorescence imaging of tumors located deep in human or animal tissue. These techniques were used for investigation of the distribution of near-infrared fluorescent probes, but only a few works are devoted to fluorescence tomography in visible light. In this work, preliminary results of the frequency domain fluorescent diffuse tomography (FD FDT) method in application to DsRed2 protein as a fluorescent agent are presented. For the first step of our experiments we utilized second harmonic generation of Nd:YAG laser (532 nm) modulated by low frequency (1 kHz) in the experimental setup. The transilluminative planar configuration was used in the setup. A series of model experiments has been conducted and show good agreement between theoretical and experimental fluorescence intensity. Post mortem experiments with capsules containing DsRed2 and scattering solution introduced into esophagus of rats to simulate tumor formation have been conducted. The results of these experiments show that sensitivity of the setup is sufficient to detect DsRed2 in concentrations similar to those in FP-expressed tumor, but the contrast is not enough high to separate fluorescence of DsRed2 and surrounding tissues. The setup can be significantly improved by utilizing high-frequency modulation (110 MHz using acousto-optical modulator) of the excitation light and precise phase measurements due to difference in fluorescence life-time of FPs and surrounding tissues. An algorithm of processing a fluorescent image based on calculating zero of maximum curvature was employed for detection of fluorescent inclusions boundaries in the image.

  6. Rare solitary focal tuberculous involvement of liver masquerading as hepatic metastasis on FDG PET/CT in a case of fibular round cell tumor

    International Nuclear Information System (INIS)

    Puranik, Ameya D; Purandare, Nilendu C; Sridhar, Epari; Agrawal, Archi; Shah, Sneha; Rangarajan, Venkatesh

    2015-01-01

    Finding of focal 18F-fluoro-deoxyglucose (FDG) uptake in liver on FDG positron emission tomography/computed tomography (FDG PET/CT) in a known case of malignancy is often considered to be metastases. We report a similar finding on FDG PET/CT in a case of Ewing's sarcoma of thigh, which turned out to be of tuberculous etiology, an unusual cause of false positive FDG uptake in the liver

  7. Tumor markers as prognostic factors in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Nieder, C.; Nestle, U.; Ukena, D.; Niewald, M.; Sybrecht, G.W.; Schnabel, K.

    1995-01-01

    The data of 300 patients who had been irradiated for their primary tumor were analysed retrospectively. The serum concentrations of CEA, SCCA, NSE, and LDH were available before treatment and 3 months thereafter in a sufficient number of cases. The prognostic factors for survival and progression-free survival resulting from univariate tests were further evaluated by a Cox-proportional-hazards model. The serum levels of the particular tumor markers were pathologically elevated in 25 to 36.5% of the cases. Their values correlated with the stage of the disease and separately the N-stage too. A normalization of increased marker levels after irradiation occurred in 37.5 to 67% of the cases. Survival of patients with increased pretherapeutic values of CEA, SCCA, and LDH was significantly worse compared to those with normal values. In the case of a posttherapeutic return to normal levels, prognosis was significantly better than for those where the elevation persistet. However, after inclusion of all other parameters in multivariate analysis the tumor markers were meaningless. Karnofsky-performance status, total dose of radiotherapy, stage of the disease, and weight-loss evolved as independent prognostic factors for survival. For progression-free survival only stage of the disease was important. All subgroup analyses (restriction on patients with favorable prognosis) showed the same results. A prognostic importance of NSE could not be demonstrated. CEA, SCCA, and LDH were univariate predictors for survival and progression-free survival. But they proved to be dependent on the stage of the disease and were not confirmed as independent variables in the Cox-model. Their importance during the follow-up is diminished by the frequent lack of therapeutic approaches in the case of disease progression. Certainly a more favorable prognosis in case of a posttherapeutic normalization of previously elevated values was found. (orig./MG) [de

  8. [What future for circulating tumor DNA? Current data and prospects in colorectal, non-small cell lung and pancreatic cancers].

    Science.gov (United States)

    Pietrasz, Daniel; Pécuchet, Nicolas; Fabre, Elizabeth; Blons, Hélène; Chevalier, Line; Taly, Valérie; Laurent-Puig, Pierre; Bachet, Jean-Baptiste

    2016-01-01

    Ten years after the discovery of the predictive value of KRAS status for anti-EGFR antibodies, other genes involved in oncogenesis and therapeutic responses were identified and are now systematically sought. Molecular diagnosis often requires invasive procedures, sometimes iatrogenic, and is limited by feasibility problems, quantity and quality of samples. Identifying these mutations from blood biomarkers would reduce costs and diagnostic delay. The circulating tumor DNA (ctDNA) is one of the most promising blood biomarkers. In this review, we report and discuss the latest results obtained with ctDNA in colorectal cancer, non-small cell lung cancer, and adenocarcinoma of the pancreas. If the methods highlighting appear very heterogeneous, the correlation between mutations found in tumor and those identified in the blood exceeds 95 % specificity in numerous studies. The detection sensitivity is in turn strongly related to tumor stage patients. The presence of ctDNA appears as a prognostic factor for progression-free survival and overall survival. Finally, recent studies have shown that the changing rate ctDNA during systemic treatments had a predictive value for therapeutic efficacy. These results allow to consider the use of ctDNA in monitoring patients to identify early recurrence or progression. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  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.

    Science.gov (United States)

    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.

  10. Tumor-Selective Targeting of Androgen Receptor Expression by Novel Small-Molecule Agents

    Science.gov (United States)

    2013-05-01

    Cancer Res 2003;9(17):6395–6400. 24. Vanaja DK, Grossmann ME, Cheville JC, Gazi MH, Gong A, Zhang JS, Ajtai K, Burghardt TP, Young CY. PDLIM4, an...2627−2633. (22) Young , C. D.; Anderson, S. M. Sugar and fat - that’s where it’s at: metabolic changes in tumors. Breast Cancer Res. 2008, 10, 202... anabolic pathways to synthesize the nucleic acids, proteins, and fatty acids needed for extensive cell proliferation (3–7). Although this metabolic

  11. Mutational status of synchronous and metachronous tumor samples in patients with metastatic non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Quéré, Gilles; Descourt, Renaud; Robinet, Gilles; Autret, Sandrine; Raguenes, Odile; Fercot, Brigitte; Alemany, Pierre; Uguen, Arnaud; Férec, Claude; Quintin-Roué, Isabelle; Le Gac, Gérald

    2016-01-01

    Despite reported discordance between the mutational status of primary lung cancers and their metastases, metastatic sites are rarely biopsied and targeted therapy is guided by genetic biomarkers detected in the primary tumor. This situation is mostly explained by the apparent stability of EGFR-activating mutations. Given the dramatic increase in the range of candidate drugs and high rates of drug resistance, rebiopsy or liquid biopsy may become widespread. The purpose of this study was to test genetic biomarkers used in clinical practice (EGFR, ALK) and candidate biomarkers identified by the French National Cancer Institute (KRAS, BRAF, PIK3CA, HER2) in patients with metastatic non-small-cell lung cancer for whom two tumor samples were available. A retrospective study identified 88 tumor samples collected synchronously or metachronously, from the same or two different sites, in 44 patients. Mutation analysis used SNaPshot (EGFR, KRAS, BRAF missense mutations), pyrosequencing (EGFR and PIK3CA missense mutations), sizing assays (EGFR and HER2 indels) and IHC and/or FISH (ALK rearrangements). About half the patients (52 %) harbored at least one mutation. Five patients had an activating mutation of EGFR in both the primary tumor and the metastasis. The T790M resistance mutation was detected in metastases in 3 patients with acquired resistance to EGFR tyrosine kinase inhibitors. FISH showed discordance in ALK status between a small biopsy sample and the surgical specimen. KRAS mutations were observed in 36 % of samples, six patients (14 %) having discordant genotypes; all discordances concerned sampling from different sites. Two patients (5 %) showed PI3KCA mutations. One metastasis harbored both PI3KCA and KRAS mutations, while the synchronously sampled primary tumor was mutation free. No mutations were detected in BRAF and HER2. This study highlighted noteworthy intra-individual discordance in KRAS mutational status, whereas EGFR status was stable. Intratumoral

  12. Predictors of Individual Tumor Local Control After Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases

    International Nuclear Information System (INIS)

    Garsa, Adam A.; Badiyan, Shahed N.; DeWees, Todd; Simpson, Joseph R.; Huang, Jiayi; Drzymala, Robert E.; Barani, Igor J.; Dowling, Joshua L.; Rich, Keith M.; Chicoine, Michael R.; Kim, Albert H.; Leuthardt, Eric C.; Robinson, Clifford G.

    2014-01-01

    Purpose: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). Methods and Materials: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. Results: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. Conclusions: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective

  13. Additional diagnostic value of tumor markers in cytological fluid for diagnosis of non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Hur, Jin; Chung, Kyung Young; Lee, Hye Sun; Choi, Byoung Wook; Lee, Hye-Jeong; Nam, Ji Eun; Kim, Young Jin; Hong, Yoo Jin; Kim, Hee Yeong; Kim, Se Kyu; Chang, Joon; Kim, Joo-Hang

    2012-01-01

    Cytological fluid from a needle aspiration biopsy (NAB) is obtained directly from tumor tissue, therefore many biomarker candidates will be present in high concentrations. The aim of this study was to prospectively assess and validate the tumor markers CYFRA 21–1, CEA, and SCC in cytological fluid obtained from NAB samples to determine if they improved the performance of NAB for diagnosing non-small cell lung cancer (NSCLC). A total of 194 patients (M:F = 128:66, mean age 63.7 years) with suspected malignant pulmonary lesions were prospectively enrolled and underwent percutaneous NAB. Levels of CYFRA 21–1, CEA, and SCC were measured by immunoassay in serum and cytological fluid obtained during aspiration biopsy. Cut-off values to determined malignancy were 3.3 ng/mL in serum and 15.7 ng/mL in cytological fluid for CYFRA 21–1, 5 ng/mL and 0.6 ng/mL for CEA, and 2 ng/mL and 0.86 ng/mL for SCC. Of 194 patients, 139 patients (71.6%) had NSCLC and 55 (28.4%) had benign lesions. Sensitivity increased significantly for NAB combined with cytological tumor markers compared with NAB alone (CYFRA 21–1: 95% versus 83.5%, p < 0.001, CEA: 92.1% versus 83.5%, p = 0.002, SCC: 91.4% versus 83.5%, p = 0.003). Accuracy improved significantly for NAB combined with cytological CYFRA 21–1 compared with NAB alone (95.9% versus 88.1%, p < 0.001). The area under curve (AUC) of NAB with cytological CYFRA 21–1 was significantly larger than for NAB alone (0.966 versus 0.917, p = 0.009). Of the tested tumor markers, cytological fluid measurements of CYFRA 21–1 improved the diagnostic performance of NAB for NSCLC

  14. Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with advance non-small cell lung cancer.

    Science.gov (United States)

    Liu, Hui; Zhang, Tiantuo; Ye, Jin; Li, Hongtao; Huang, Jing; Li, Xiaodong; Wu, Benquan; Huang, Xubing; Hou, Jinghui

    2012-10-01

    Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. The predictive significance of tumor-infiltrating lymphocytes (TILs) for response to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to investigate the prognostic and predictive value of TIL subtypes in patients with advanced NSCLC treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. The prevalence of CD3(+), CD4(+), CD8(+) and Foxp3(+) TILs was assessed by immunohistochemistry in tumor tissue obtained before chemotherapy. The density of TILs subgroups was treated as dichotomous variables using the median values as cutoff. Survival curves were estimated by the Kaplan-Meier method, and differences in overall survival between groups were determined using the Log-rank test. Prognostic effects of TIL subsets density were evaluated by Cox regression analysis. The presence of CD3(+), CD4(+), CD8(+), and FOXP3(+) TILs was not correlated with any clinicopathological features. Neither the prevalence of TILs nor combined analysis displayed obvious prognostic performances for overall survival in Cox regression model. Instead, higher FOXP3(+)/CD8(+) ratio in tumor sites was an independent factor for poor response to platinum-based chemotherapy in overall cohort. These findings suggest that immunological CD8(+) and FOXP3(+)Tregs cell infiltrate within tumor environment is predictive of response to platinum-based neoadjuvant chemotherapy in advanced NSCLC patients. The understanding of the clinical relevance of the microenvironmental immunological milieu might provide an important clue for the design of novel strategies in cancer immunotherapy.

  15. Investigating the benefits of molecular profiling of advanced non-small cell lung cancer tumors to guide treatments.

    Science.gov (United States)

    Alifrangis, Costi; Carter, Philip; Cereser, Biancastella; Chandrasinghe, Pramodh; Belluz, Lisa Del Bel; Lim, Eric; Moderau, Nina; Poyia, Fotini; Tabassum, Neha; Zhang, Hua; Krell, Jonathan; Stebbing, Justin

    2018-02-27

    In this study we utilized data on patient responses to guided treatments, and we evaluated their benefit for a non-small cell lung cancer cohort. The recommended therapies used were predicted using tumor molecular profiles that involved a range of biomarkers but primarily used immunohistochemistry markers. A dataset describing 91 lung non-small cell lung cancer patients was retrospectively split into two. The first group's drugs were consistent with a treatment plan whereby all drugs received agreed with their tumor's molecular profile. The second group each received one or more drug that was expected to lack benefit. We found that there was no significant difference in overall survival or mortality between the two groups. Patients whose treatments were predicted to be of benefit survived for an average of 402 days, compared to 382 days for those that did not ( P = 0.7934). In the matched treatment group, 48% of patients were deceased by the time monitoring had finished compared to 53% in the unmatched group ( P = 0.6094). The immunohistochemistry biomarker for the ERCC1 receptor was found to be a marker that could be used to predict future survival; ERCC1 loss was found to be predictive of poor survival.

  16. Inhibition of Androgen Receptor Nuclear Localization and Castration-Resistant Prostate Tumor Growth by Pyrroloimidazole-based Small Molecules.

    Science.gov (United States)

    Masoodi, Khalid Z; Xu, Yadong; Dar, Javid A; Eisermann, Kurtis; Pascal, Laura E; Parrinello, Erica; Ai, Junkui; Johnston, Paul A; Nelson, Joel B; Wipf, Peter; Wang, Zhou

    2017-10-01

    The androgen receptor (AR) is a ligand-dependent transcription factor that controls the expression of androgen-responsive genes. A key step in androgen action, which is amplified in castration-resistant prostate cancer (CRPC), is AR nuclear translocation. Small molecules capable of inhibiting AR nuclear localization could be developed as novel therapeutics for CRPC. We developed a high-throughput screen and identified two structurally-related pyrroloimidazoles that could block AR nuclear localization in CRPC cells. We show that these two small molecules, 3-(4-ethoxyphenyl)-6,7-dihydro-5 H -pyrrolo[1,2- a ]imidazole (EPPI) and 3-(4-chlorophenyl)-6,7-dihydro-5 H -pyrrolo[1,2- a ]imidazole (CPPI) can inhibit the nuclear localization and transcriptional activity of AR and reduce the proliferation of AR-positive but not AR-negative prostate cancer cell lines. EPPI and CPPI did not inhibit nuclear localization of the glucocorticoid receptor or the estrogen receptor, suggesting they selectively target AR. In LNCaP tumor xenografts, CPPI inhibited the proliferation of relapsed LNCaP tumors. These findings suggest that EPPI and CPPI could serve as lead structures for the development of therapeutic agents for CRPC. Mol Cancer Ther; 16(10); 2120-9. ©2017 AACR . ©2017 American Association for Cancer Research.

  17. Small bowel perforation without tumor recurrence after radiotherapy for cervical carcinoma: report of seven cases.

    Science.gov (United States)

    Yamashita, Hideomi; Nakagawa, Keiichi; Tago, Masao; Igaki, Hiroshi; Shiraishi, Kenshirou; Nakamura, Naoki; Sasano, Nakashi; Yamakawa, Sen; Ohtomo, Kuni

    2006-04-01

    We describe the clinical presentation, evaluation, management and outcome of patients experiencing small bowel perforation following radiation therapy for cervical cancer. A database consisting of 95 Japanese women with stage 0-4 A cervix cancer treated between 1991 and 2004 contained seven patients (7.4%) with small bowel perforation. The median age at the time of perforation was 72.5 years (range 62-78). The median time from completion of radiotherapy to perforation was 6 months (range 2-58). Surgery (one small bowel resection and anastomosis with diversion; six small bowel resection and anastomosis) was performed immediately in all seven patients. One of seven patients died of small bowel perforation (i.e. mortality rate was 14%). Bowel adhesion was detected during the operation in only three cases (43%). Signs of peritonitis were absent in six cases (86%). Severe abdominal pain was seen in all seven patients. The perforation site was ileum in all seven cases. In all patients, pathological changes were compatible with postirradiation injury of the gastrointestinal tract. The presenting complaints of patients with bowel perforation following radiotherapy vary, and signs of peritonitis may be absent. Emergency physicians must be alert for these complications in patients who have been treated with radiotherapy.

  18. Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

    Science.gov (United States)

    Cui, Tao; Hurtig, Monica; Elgue, Graciela; Li, Su-Chen; Veronesi, Giulia; Essaghir, Ahmed; Demoulin, Jean-Baptiste; Pelosi, Giuseppe; Alimohammadi, Mohammad; Öberg, Kjell; Giandomenico, Valeria

    2010-12-30

    Small intestine neuroendocrine tumors (SI-NETs) belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2) as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC), to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA) for the risk of recurrence after radical operation of these tumors.

  19. Fluorodeoxyglucose positron emission tomography and chemotherapy-related tumor marker expression in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Duan, Xiao-Yi; Wang, Wen; Wang, Jian-Sheng; Shang, Jin; Gao, Jun-Gang; Guo, You-Min

    2013-01-01

    The chemotherapy resistance of non-small cell lung cancer (NSCLC) remains a clinic challenge and is closely associated with several biomarkers including epidermal growth factor receptor (EGFR) (Drugs 72(Suppl 1):28–36, 012.), p53 (Med Sci Monit 11(6):HY11–HY20, 2005.) and excision repair cross complementing gene 1 (ERCC1) (J Thorac Oncol 8(5):582–586, 2013.). Fluorodeoxyglucose positron emission tomography (FDG–PET) is the best non-invasive surrogate for tumor biology with the maximal standardized uptake values (SUV max ) being the most important paradigm. However, there are limited data correlating FDG-PET with the chemotherapy resistant tumor markers. The purpose of this study was to determine the correlation of chemotherapy related tumor marker expression with FDG–PET SUV max in NSCLC. FDG–PET SUV max was calculated in chemotherapy naïve patients with NSCLC (n = 62) and immunohistochemical analysis was performed for EGFR, p53 or ERCC1 on the intraoperative NSCLC tissues. Each tumor marker was assessed independently by two pathologists using common grading criteria. The SUV max difference based on the histologic characteristics, gender, differentiation, grading and age as well as correlation analysis among these parameters were performed. Multiple stepwise regression analysis was further performed to determine the primary predictor for SUV max and the receiver operating characteristics (ROC) curve analysis was performed to detect the optimized sensitivity and specificity for SUV max in suggesting chemotherapy resistant tumor markers. The significant tumor type (P = 0.045), differentiation (P = 0.021), p53 (P = 0.000) or ERCC1 (P = 0.033) positivity dependent differences of SUV max values were observed. The tumor differentiation is significantly correlated with SUV max (R = -0.327), tumor size (R = -0.286), grading (R = -0.499), gender (R = 0.286) as well as the expression levels for p53 (R = -0.605) and ERCC1 (R = -0.644). The expression level of p53

  20. The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Dai, Fuqiang; Liu, Lunxu; Che, Guowei; Yu, Nanbin; Pu, Qiang; Zhang, Shangfu; Ma, Junliang; Ma, Lin; You, Zongbing

    2010-01-01

    Tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells, and infiltrating immune cells. Tumor-associated immune cells may inhibit or promote tumor growth and progression. This study was conducted to determine whether the number and microlocalization of macrophages, mature dendritic cells and cytotoxic T cells in non-small cell lung cancer are associated with patient's survival time. Ninety-nine patients with non-small cell lung cancer (NSCLC) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical staining for CD68 (marker for macrophages), CD83 (marker for mature dendritic cells), and CD8 (marker for cytotoxic T cells) was performed and evaluated in a blinded fashion. The numbers of immune cells in tumor islets and stroma, tumor islets, or tumor stroma were counted under a microscope. Correlation of the cell numbers and patient's survival time was analyzed using the Statistical Package for the Social Sciences (version 13.0). The numbers of macrophages, mature dendritic cells and cytotoxic T cells were significantly more in the tumor stroma than in the tumor islets. The number of macrophages in the tumor islets was positively associated with patient's survival time, whereas the number of macrophages in the tumor stroma was negatively associated with patient's survival time in both univariate and multivariate analyses. The number of mature dendritic cells in the tumor islets and stroma, tumor islets only, or tumor stroma only was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets and stroma was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets only or stroma

  1. SU-F-R-54: CT-Texture Based Early Tumor Treatment Response Assessment During Radiation Therapy Delivery: Small Cell Versus Non-Small Cell Lung Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Paul, J; Gore, E; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

    2016-06-15

    Purpose: Tumor treatment response may potentially be assessed during radiation therapy (RT) by analyzing changes in CT-textures. We investigated the different early RT-responses between small cell (SCLC) and non-small cell lung cancer (NSCLC) as assessed by CT-texture. Methods: Daily diagnostic-quality CT acquired during routine CT-guided RT using a CT-on-Rails for 13-NSCLC and 5-SCLC patients were analyzed. These patient had ages ranging from 45–78 and 38–63 years, respectively, for NSCLC and SCLC groups, and tumor-stages ranging from T2-T4, and were treated with either RT or chemotherapy and RT with 45–66Gy/ 20–34 fractions. Gross-tumor volume (GTV) contour was generated on each daily CT by populating GTV contour from simulation to daily CTs with manual editing if necessary. CT-texture parameters, such as Hounsfield Unit (HU) histogram, mean HU, skewness, kurtosis, entropy, and short-run high-gray level emphasis (SRHGLE), were calculated in GTV from each daily CT-set using an in house software tool. Difference in changes of these texture parameters during RT between NSCLC and SCLC was analyzed and compared with GTV volume changes. Results: Radiation-induced changes in CT-texture were different between SCLC and NSCLC. Average changes from first to the last fractions for NSCLC and SCLC in GTV were 28±10(12–44) and 30±15(11–47) HU (mean HU reduction), 12.7% and 18.3% (entropy), 50% and 55% (SRHGLE), 19% and 22% (kurtosis), and 5.2% and 22% (skewness), respectively. Good correlation in kurtosis changes and GTV was seen (R{sup 2}=0.8923) for SCLC, but not for NSCLC (R{sup 2}=0.4748). SCLC had better correlations between GTV volume reduction and entropy (SCLC R{sup 2}=0.847; NSCLC R{sup 2}=0.6485), skewness (SCLC R{sup 2}=0.935; NSCLC R{sup 2}=0.7666), or SRHGLE (SCLC R{sup 2}=0.9619; NSCLC R{sup 2}=0.787). Conclusion: NSCLC and SCLC exhibited different early RT-responses as assessed by CT-texture changes during RT-delivery. The observed larger changes in

  2. A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors

    DEFF Research Database (Denmark)

    Dumanski, Jan P; Rasi, Chiara; Björklund, Peyman

    2017-01-01

    . The inactivation of this gene leads to specific increase of G:C- > T:A transversions in DNA sequence and has been shown to cause various cancers in humans and experimental animals. Our results suggest that p.(Gly396Asp) in MUTYH, and potentially other mutations in additional members of the same DNA excision......-generation sequencing of exome- and/or whole-genome of blood DNA, and in selected cases, tumor DNA, from 24 patients from 15 families with the history of SI-NETs. We identified seven candidate mutations in six genes that were further studied using 215 sporadic SI-NET patients. The result was compared with the frequency...

  3. Application of detecting cerebrospinal fluid circulating tumor cells in the diagnosis of meningeal metastasis of non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Rong JIANG

    2014-08-01

    Full Text Available Objective To observe a new technology for the detection and enumeration of cerebrospinal fluid (CSF circulating tumor cells (CTCs in the diagnosis of non-small cell lung cancer (NSCLC with meningeal metastasis (MM.  Methods Five cases of NSCLC with MM that were diagnosed by CSF cytology were selected, and 20 ml CSF samples were obtained by lumbar puncture for every patient. The tumor marker immunostaining-fluorescence in situ hybridization (TM-iFISH technology was adapted to detect enrichment and enumeration of circulating tumor cells in 7.50 ml CSF samples; CSF cytology was checked in 10 ml CSF samples; CSF tumor markers were detected in 2.50 ml CSF samples. All of 5 cases were examined by MRI enhancement scan.  Results TM-iFISH detection found circulating tumor cells numbers ranging 18-1823/7.50 ml. Only 2 cases of patients with CSF cytology examination showed the tumor cells. The results of CSF tumor markers in all samples were higher than normal serum tumor markers detection results. The enhanced MRI scan of 5 cases revealed typical signs of MM.  Conclusions The TM-iFISH test showed certain advantages in the detection of malignant tumor cells in CSF. This technology may be a new method of detection and enumeration of tumor cells in CSF, but more studies are needed to prove its sensitivity and specificity. doi: 10.3969/j.issn.1672-6731.2014.08.011

  4. Complex microcirculation patterns detected by confocal indocyanine green angiography predict time to growth of small choroidal melanocytic tumors: MuSIC Report II.

    Science.gov (United States)

    Mueller, Arthur J; Freeman, William R; Schaller, Ulrich C; Kampik, Anselm; Folberg, Robert

    2002-12-01

    Multiple independent laboratories have confirmed the histologic observation that some tumor microcirculation patterns (MCPs) in uveal melanomas are associated strongly with death resulting from metastatic disease. Because these patterns are imageable with confocal indocyanine green angiography (ICG), we designed a prospective study to evaluate whether these angiographically detectable MCPs predict time to tumor growth. Observational case series, prospective, non-randomized. Ninety-eight patients with unilateral, small, choroidal melanocytic tumors. The following information and tumor characteristics were recorded for each patient: demographic parameters, best-corrected visual acuity, intraocular pressure, related visual symptoms, location and dimension of tumor, pigmentation, orange pigment, drusen, tumor-associated hemorrhage, subretinal fluid, and confocal ICG angiographically determined microcirculation patterns-silent (avascularity), normal (preexisting normal choroidal vessels within the tumor), straight vessels, parallel without and with cross-linking, arcs without and with branching, loops, and networks. Time to growth of the tumor, with growth defined as an increase in the maximal apical tumor height of 0.5 mm measured by standardized A-scan ultrasonography, photographic documentation of an increase of the largest basal diameter of at least 1.5 mm, advancement of one tumor border of at least 0.75 mm, or a combination thereof. Twenty-eight of the 98 tumors in this study (29%) met the predetermined criteria for tumor growth. The median time to growth was 127 days (range, 51-625 days). The following tumor characteristics were significantly associated with time to tumor growth: flashes (P = 0.0224), orange pigment (P = 0.012), subretinal fluid (P < 0.001), maximum basal tumor diameter at initial examination (P = 0.015), maximum apical tumor height (P < 0.001), parallel with cross-linking MCP (P < 0.001), arcs with branching MCP (P = 0.006), loops (P < 0

  5. Anti-tumor effect of bisphosphonate (YM529 on non-small cell lung cancer cell lines

    Directory of Open Access Journals (Sweden)

    Date Hiroshi

    2007-01-01

    Full Text Available Abstract Background YM529 is a newly developed nitrogen-containing bisphosphonate (BP classified as a third-generation BP that shows a 100-fold greater potency against bone resorption than pamidronate, a second-generation BP. This agent is, therefore expected to be extremely useful clinically for the treatment of osteoporosis and hypercalcemia. Recently, YM529 as well as other third-generation BPs have also been shown to exert anti-tumor effects against various types of cancer cells both in vitro or/and in vivo. In this study, we investigate the anti-tumor effect of YM529 on non-small cell lung cancer (NSCLC. Methods Direct anti-tumor effect of YM529 against 8 NSCLC cell lines (adenocarcinoma: H23, H1299, NCI-H1819, NCI-H2009, H44, A549, adenosquamous cell carcinoma: NCI-H125, squamous cell carcinoma: NCI-H157 were measured by MTS assay and calculated inhibition concentration 50 % (IC50 values. YM529 induced apoptosis of NCI-H1819 was examined by DNA fragmentation of 2 % agarose gel electrophoresis and flowcytometric analysis (sub-G1 method. We examined where YM529 given effect to apoptosis of NSCLC cells in signaling pathway of the mevalonate pathway by western blotting analysis. Results We found that there was direct anti-tumor effect of YM529 on 8 NSCLC cell lines in a dose-dependent manner and their IC50 values were 2.1 to 7.9 μM and YM529 induced apoptosis and G1 arrest cell cycle with dose-dependent manner and YM529 caused down regulation of phospholyration of ERK1/2 in signaling pathways of NSCLC cell line (NCI-H1819. Conclusion Our study demonstrate that YM529 showed direct anti-tumor effect on NSCLC cell lines in vitro, which supports the possibility that third-generation BPs including YM529 can be one of therapeutic options for NSCLC.

  6. Small cell neuroendocrine carcinoma of the endometrium, a rare aggressive tumor

    International Nuclear Information System (INIS)

    Rajab, Khalil E.; Sandhu, Amarjit K.; Rajeswari, Mangla S.; Malik, A.

    2005-01-01

    This is a report of a young infertile woman with a history of 8 years amenorrhea, who presented with history of vaginal bleeding of 2 months duration. Investigations revealed a small cell neuroendocrine carcinoma of the endometrium, which penetrated half of the thickness of uterine wall. We have described the clinical progress and management of this rare and highly malignant cancer. A review of the pathological types and behavior of clear cell neuroendocrine carcinoma is presented. (author)

  7. [Small bowel tumors: experience at the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"].

    Science.gov (United States)

    Sánchez-Ramón, A; Cerino-Palomino, V; Medina-Franco, H

    2012-01-01

    Malignant tumors of the small bowel are uncommon and include multiple histologic strains, which helps explain the existing limited understanding of them. The aim of this study was to evaluate surgically treated small bowel tumors and to determine the clinical and pathological characteristics that can have an impact on patient outcome. A retrospective, observational, and descriptive study was carried out. The case records of patients with small bowel tumor that were surgically treated at the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" from 1990 to August 2011 were analyzed using the SPSS version 17.0 statistical package. Thirty-eight small bowel tumor patients were found that had been operated on within the time frame studied. Fifteen of them were women (39.50%) and 23 were men (60.50%), and the mean age was 55.6 years. The histologic distribution was 13 adenocarcinomas (34.20%), 10 neuroendocrine tumors (26.30%), 8 sarcomas (21.10%) and 4 lymphomas (10.50%). There was an increase in the incidence of sarcomas and adenocarcinomas, whereas lymphomas and neuroendocrine tumors were evenly distributed. An increase in small bowel tumor incidence in the last few years was observed and adenocarcinoma was the most frequent tumor in the study population. It is important to have a high degree of suspicion for this disease when patients present with symptoms such as gastrointestinal bleeding, bowel obstruction, anemia, and weight loss, because early diagnosis is essential for guaranteeing favorable outcome. Copyright © 2012 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  8. Clinical Evaluation of Tumor Markers for Diagnosis in Patients with Non-small Cell Lung Cancer in China.

    Science.gov (United States)

    Ma, Li; Xie, Xiao-Wei; Wang, Hai-Yan; Ma, Ling-Yun; Wen, Zhong-Guang

    2015-01-01

    To evaluate the value of combined detection of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and carbohydrateantigen 125 (CA125) for the clinical diagnosis of non- small cell lung cancer (NSCLC). Serum CEA, CYFRA21-1 and CA125 were assessed in 140 patients with NSCLC, 90 patients with benign lung disease and 90 normal control subjects, and differences of expression were compared in each group, and joint effects of these tumor markers in the diagnosis of NSCLC were analyzed. Serum CEA, CYFRA21-1 and CA125 in patients with NSCLC were significantly higher than those with benign lung disease and normal controls (PCEA, CYFRA21-1 and CA125 were 49.45%, 59.67%, and 44.87% respectively. As expected, combinations of these tumor markers improved their sensitivity for NSCLC. The combined detection of CEA+CYFRA21-1 was the most cost-effective combination which had higher sensitivity and specificity in NSCLC. Elevation of serum CEA and CYFRA21-1 was significantly associated with pathological types (PCEA, CYFRA21-1 and CA125 was significantly associated with TNM staging (PCEA, CYFRA21-1 and CA125 is of diagnostic value in the diagnosis of lung cancer, and a joint detection of these three tumor markers, could greatly improve the sensitivity of diagnosis on NSCLC. Combined detection of CEA+CYFRA21-1 proved to be the most economic and practical strategy in diagnosis of NSCLC, which can be used to screen the high-risk group.

  9. [Evaluation of three-dimensional tumor microvascular architecture phenotype heterogeneity in non-small cell carcinoma and its significance].

    Science.gov (United States)

    Zhou, Hui; Liu, Jinkang; Chen, Shengxi; Xiong, Zeng; Zhou, Jianhua; Tong, Shiyu; Chen, Hao; Zhou, Moling

    2012-06-01

    To explore the degree, mechanism and clinical significance of three-dimensional tumor microvascular architecture phenotype heterogeneity (3D-TMAPH) in non-small cell carcinoma (NSCLC). Twenty-one samples of solitary pulmonary nodules were collected integrally. To establish two-dimensional tumor microvascular architecture phenotype (2D-TMAP) and three-dimensional tumor microvascular architecture phenotype (3D-TMAP), five layers of each nodule were selected and embedded in paraffin. Test indices included the expressions of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), EphB4, ephfinB2 and microvascular density marked by anti-CD34 (CD34-MVD). The degrees of 3D-TMAPH were evaluated by the coefficient of variation and extend of heterogeneity. Spearman rank correlation analysis was used to investigate the relationships between 2D-TMAP, 3D-TMAP and clinicopathological features. 3D-TMAPH showed that 2D-TMAP heterogeneity was expressed in the tissues of NSCLC. The heterogeneities in the malignant nodules were significantly higher than those in the active inflammatory nodules and tubercular nodules. In addition, different degrees of heterogeneity of CD34-MVD and PCNA were found in NSCLC tissues. The coefficients of variation of CD34- MVD and PCNA were positively related to the degree of differentiation (all P0.05). The level of heterogeneity of various expression indexes (ephrinB2, EphB4, VEGF) in NSCLC tissues were inconsistent, but there were no significant differences in heterogeneity in NSCLC tissues with different histological types (P>0.05). 3D-TMAPH exists widely in the microenvironment during the genesis and development of NSCLC and has a significant impact on its biological complexity.

  10. Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets.

    Science.gov (United States)

    Best, Myron G; Sol, Nik; In 't Veld, Sjors G J G; Vancura, Adrienne; Muller, Mirte; Niemeijer, Anna-Larissa N; Fejes, Aniko V; Tjon Kon Fat, Lee-Ann; Huis In 't Veld, Anna E; Leurs, Cyra; Le Large, Tessa Y; Meijer, Laura L; Kooi, Irsan E; Rustenburg, François; Schellen, Pepijn; Verschueren, Heleen; Post, Edward; Wedekind, Laurine E; Bracht, Jillian; Esenkbrink, Michelle; Wils, Leon; Favaro, Francesca; Schoonhoven, Jilian D; Tannous, Jihane; Meijers-Heijboer, Hanne; Kazemier, Geert; Giovannetti, Elisa; Reijneveld, Jaap C; Idema, Sander; Killestein, Joep; Heger, Michal; de Jager, Saskia C; Urbanus, Rolf T; Hoefer, Imo E; Pasterkamp, Gerard; Mannhalter, Christine; Gomez-Arroyo, Jose; Bogaard, Harm-Jan; Noske, David P; Vandertop, W Peter; van den Broek, Daan; Ylstra, Bauke; Nilsson, R Jonas A; Wesseling, Pieter; Karachaliou, Niki; Rosell, Rafael; Lee-Lewandrowski, Elizabeth; Lewandrowski, Kent B; Tannous, Bakhos A; de Langen, Adrianus J; Smit, Egbert F; van den Heuvel, Michel M; Wurdinger, Thomas

    2017-08-14

    Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA-sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Differences in pulmonary function before vs. 1 year after hypofractionated stereotactic radiotherapy for small peripheral lung tumors

    International Nuclear Information System (INIS)

    Ohashi, Toshio; Takeda, Atsuya; Shigematsu, Naoyuki; Kunieda, Etsuo; Ishizaka, Akitoshi; Fukada, Junichi; Deloar, Hossain M.; Kawaguchi, Osamu; Takeda, Toshiaki; Takemasa, Kazuhiko; Isobe, Kouichi; Kubo, Atsushi

    2005-01-01

    Purpose: To evaluate long-term pulmonary toxicity of stereotactic radiotherapy (SRT) by pulmonary function tests (PFTs) performed before and after SRT for small peripheral lung tumors. Methods and Materials: A total of 17 lesions in 15 patients with small peripheral lung tumors, who underwent SRT between February 2000 and April 2003, were included in this study. Twelve patients had primary lung cancer, and 3 patients had metastatic lung cancer. Primary lung cancer was T1-2N0M0 in all cases. Smoking history was assessed by the Brinkman index (number of cigarettes smoked per day multiplied by number of years of smoking). Prescribed radiation doses at the 80% isodose line were 40-60 Gy in 5-8 fractions. PFTs were performed immediately before SRT and 1 year after SRT. Test parameters included total lung capacity (TLC), vital capacity (VC), forced expiratory volume in 1 s (FEV1.0), and diffusing capacity of lung for carbon monoxide (DLCO). PFT changes were evaluated in relation to patient- and treatment-related factors, including age, the Brinkman index, internal target volume, the percentages of lung volume irradiated with >15, 20, 25, and 30 Gy (V15, V20, V25, and V30, respectively), and mean lung dose. Results: There were no significant changes in TLC, VC, or FEV1.0 before vs. after SRT. The mean percent change from baseline in DLCO was significantly increased by 128.2%. Univariate and multivariate analyses revealed a correlation between DLCO and the Brinkman index. Conclusions: One year after SRT as compared with before SRT, there were no declines in TLC, VC, and FEV1.0. DLCO improved in patients who had been heavy smokers before SRT, suggesting a correlation between DLCO and smoking cessation. SRT seems to be tolerable in view of long-term lung function

  12. Performance characteristics of a reverse transcriptase-polymerase chain reaction assay for the detection of tumor-specific fusion transcripts from archival tissue.

    Science.gov (United States)

    Fritsch, Michael K; Bridge, Julia A; Schuster, Amy E; Perlman, Elizabeth J; Argani, Pedram

    2003-01-01

    Pediatric small round cell tumors still pose tremendous diagnostic problems. In difficult cases, the ability to detect tumor-specific gene fusion transcripts for several of these neoplasms, including Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/PNET), synovial sarcoma (SS), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round cell tumor (DSRCT) using reverse transcriptase-polymerase chain reaction (RT-PCR), can be extremely helpful. Few studies to date, however, have systematically examined several different tumor types for the presence of multiple different fusion transcripts in order to determine the specificity and sensitivity of the RT-PCR method, and no study has addressed this issue for formalin-fixed material. The objectives of this study were to address the specificity, sensitivity, and practicality of such an assay applied strictly to formalin-fixed tissue blocks. Our results demonstrate that, for these tumors, the overall sensitivity for detecting each fusion transcript is similar to that reported in the literature for RT-PCR on fresh or formalin-fixed tissues. The specificity of the assay is very high, being essentially 100% for each primer pair when interpreting the results from visual inspection of agarose gels. However, when these same agarose gels were examined using Southern blotting, a small number of tumors also yielded reproducibly detectable weak signals for unexpected fusion products, in addition to a strong signal for the expected fusion product. Fluorescence in situ hybridization (FISH) studies in one such case indicated that a rearrangement that would account for the unexpected fusion was not present, while another case was equivocal. The overall specificity for each primer pair used in this assay ranged from 94 to 100%. Therefore, RT-PCR using formalin-fixed paraffin-embedded tissue sections can be used to detect chimeric transcripts as a reliable, highly sensitive, and highly specific diagnostic assay. However, we

  13. Small Cell Anaplastic Carcinoma of Primary Lung Tumor in a Miniature Schnauzer Dog

    Directory of Open Access Journals (Sweden)

    J. M. Kim, H. J. Han, B. Ku, G. Kim, K. M. Shim1, S. S. Kang2 and S. H. Choi*

    2011-04-01

    Full Text Available A seven-year-old male, an intact miniature Schnauzer dog with history of vomiting, abdominal distention, anorexia, and dyspnea was referred for further evaluation and treatment. Thoracic radiographs showed the well marginated solitary mass with soft density in the right caudal lung field, and abdominal radiographs showed signs of ascites, such as abdominal distention and moderate serosal detail loss. On ultrasonograph and computed tomograph, it was observed that the mass compressed the caudal vena cava (CVC and adhered to the heart. Exploratory thoracotomy was performed, and then it was showed that mass adhered heart, CVC, and diaphragm. The mass was fully resected although adhered part of CVC could not be completely resected. On histopathological findings, the mass was diagnosed as small-cell anaplastic carcinoma.

  14. The contemporary role of renal mass biopsy in the management of small renal tumors

    International Nuclear Information System (INIS)

    Lim, Amy; O'Neil, Brock; Heilbrun, Marta E.; Dechet, Christopher; Lowrance, William T.

    2012-01-01

    The selective use of percutaneous biopsy for diagnosis in renal masses is a relatively uncommon approach when compared to the management of other solid neoplasms. With recent advancements in imaging techniques and their widespread use, the incidental discovery of asymptomatic, small renal masses (SRM) is on the rise and a substantial percentage of these SRM are benign. Recent advances in diagnostics have significantly improved accuracy rates of renal mass biopsy (RMB), making it a potentially powerful tool in the management of SRM. In this review, we will discuss the current management of SRM, problems with the traditional view of RMB, improvements in the diagnostic power of RMB, cost-effectiveness of RMB, and risks associated with RMB. RMB may offer important information enabling treating clinicians to better risk-stratify patients and ultimately provide a more personalized treatment approach for SRM.

  15. Small cell anaplastic carcinoma of primary lung tumor in a miniature schnauzer dog

    International Nuclear Information System (INIS)

    Kim, J.M.; Han, H.J.; Ku, B.; Kim, G.; Shim, K.M.; Kang, S.S.; Choi, S.H.

    2011-01-01

    A seven-year-old male, an intact miniature Schnauzer dog with history of vomiting, abdominal distention, anorexia, and dyspnea was referred for further evaluation and treatment. Thoracic radiographs showed the well marginated solitary mass with soft density in the right caudal lung field, and abdominal radiographs showed signs of ascites, such as abdominal distention and moderate serosal detail loss. On ultrasonograph and computed tomograph, it was observed that the mass compressed the caudal vena cava (CVC) and adhered to the heart. Exploratory thoracotomy was performed, and then it was showed that mass adhered heart, CVC, and diaphragm. The mass was fully rejected although adhered part of CVC could not be completely rejected. On histopathological findings, the mass was diagnosed as small-cell anaplastic carcinoma

  16. The Impact of Tumor Size on Outcomes After Stereotactic Body Radiation Therapy for Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Allibhai, Zishan [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto (Canada); Taremi, Mojgan [Department of Radiation Oncology, Stronach Regional Cancer Centre, Newmarket (Canada); Bezjak, Andrea; Brade, Anthony; Hope, Andrew J.; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto (Canada); Cho, B.C. John, E-mail: john.cho@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto (Canada)

    2013-12-01

    Purpose: Stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC) offers excellent control rates. Most published series deal mainly with small (usually <4 cm), peripheral, solitary tumors. Larger tumors are associated with poorer outcomes (ie, lower control rates, higher toxicity) when treated with conventional RT. It is unclear whether SBRT is sufficiently potent to control these larger tumors. We therefore evaluated and examined the influence of tumor size on treatment outcomes after SBRT. Methods and Materials: Between October 2004 and October 2010, 185 medically inoperable patients with early (T1-T2N0M0) NSCLC were treated on a prospective research ethics board-approved single-institution protocol. Prescription doses were risk-adapted based on tumor size and location. Follow-up included prospective assessment of toxicity (as per Common Terminology Criteria for Adverse Events, version 3.0) and serial computed tomography scans. Patterns of failure, toxicity, and survival outcomes were calculated using Kaplan-Meier method, and the significance of tumor size (diameter, volume) with respect to patient, treatment, and tumor factors was tested. Results: Median follow-up was 15.2 months. Tumor size was not associated with local failure but was associated with regional failure (P=.011) and distant failure (P=.021). Poorer overall survival (P=.001), disease-free survival (P=.001), and cause-specific survival (P=.005) were also significantly associated with tumor size (with tumor volume more significant than diameter). Gross tumor volume and planning target volume were significantly associated with grade 2 or worse radiation pneumonitis. However, overall rates of grade ≥3 pneumonitis were low and not significantly affected by tumor or target size. Conclusions: Currently employed stereotactic body radiation therapy dose regimens can provide safe effective local therapy even for larger solitary NSCLC tumors (up to 5.7 cm

  17. The relationship between Glasgow Prognostic Score and serum tumor markers in patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

    2015-05-10

    Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. Median levels of CYFRA21-1 were 1.5 ng/ml (0.1-3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7-35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4-89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9-134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (PGPS, CEA and GPS, TPS and GPS. The Spearman's rank correlation coefficient were 0.67 (P GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. Our results showed GPS were positive correlated with CYFRA21-1, CEA and TPS in patients with advanced NSCLC. However, GPS was more efficient in predicting prognosis of advanced NSCLC than these three single prognosis related tumor markers.

  18. The relationship between glasgow prognostic score and serum tumor markers in patients with advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

    2015-01-01

    Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non–small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21–1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. Median levels of CYFRA21–1 were 1.5 ng/ml (0.1–3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7–35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4–89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9–134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (P < 0.05). Similar results were found for median levels of CEA and TPS in healthy controls and NSCLC patients (P < 0.05). In NSCLC patients, positive correlations were found between CYFRA21-1 and GPS, CEA and GPS, TPS and GPS. The Spearman’s rank correlation coefficient were 0.67 (P < 0.05), 0.61 (P < 0.05) and 0.55 (P < 0.05), respectively. Survival analyses showed GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. Our results showed GPS were positive correlated

  19. Application of detecting cerebrospinal fluid circulating tumor cells in the diagnosis of meningeal metastasis of non-small cell lung cancer

    OpenAIRE

    Rong JIANG; Chun-hua MA; Zi-long ZHU; Jin-duo LI; Bin WANG; Li-wei SUN; Yuan LÜ

    2014-01-01

    Objective To observe a new technology for the detection and enumeration of cerebrospinal fluid (CSF) circulating tumor cells (CTCs) in the diagnosis of non-small cell lung cancer (NSCLC) with meningeal metastasis (MM).  Methods Five cases of NSCLC with MM that were diagnosed by CSF cytology were selected, and 20 ml CSF samples were obtained by lumbar puncture for every patient. The tumor marker immunostaining-fluorescence in situ hybridization (TM-iFISH) technology was adapted to detect...

  20. Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

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    Tao Cui

    Full Text Available BACKGROUND: Small intestine neuroendocrine tumors (SI-NETs belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2 as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. METHODOLOGY/PRINCIPAL FINDINGS: A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC, to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. CONCLUSION: Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA for the risk of recurrence after radical operation of these tumors.

  1. Correlation between the progressive cytoplasmic expression of a novel small heat shock protein (Hsp16.2) and malignancy in brain tumors

    International Nuclear Information System (INIS)

    Pozsgai, Eva; Gomori, Eva; Szigeti, Andras; Boronkai, Arpad; Gallyas, Ferenc Jr; Sumegi, Balazs; Bellyei, Szabolcs

    2007-01-01

    Small heat shock proteins are molecular chaperones that protect proteins against stress-induced aggregation. They have also been found to have anti-apoptotic activity and to play a part in the development of tumors. Recently, we identified a new small heat shock protein, Hsp16.2 which displayed increased expression in neuroectodermal tumors. Our aim was to investigate the expression of Hsp16.2 in different types of brain tumors and to correlate its expression with the histological grade of the tumor. Immunohistochemistry with a polyclonal antibody to Hsp16.2 was carried out on formalin-fixed, paraffin-wax-embedded sections using the streptavidin-biotin method. 91 samples were examined and their histological grade was defined. According to the intensity of Hsp16.2 immunoreactivity, low (+), moderate (++), high (+++) or none (-) scores were given. Immunoblotting was carried out on 30 samples of brain tumors using SDS-polyacrylamide gel electrophoresis and Western-blotting. Low grade (grades 1–2) brain tumors displayed low cytoplasmic Hsp16.2 immunoreactivity, grade 3 tumors showed moderate cytoplasmic staining, while high grade (grade 4) tumors exhibited intensive cytoplasmic Hsp16.2 staining. Immunoblotting supported the above mentioned results. Normal brain tissue acted as a negative control for the experiment, since the cytoplasm did not stain for Hsp16.2. There was a positive correlation between the level of Hsp16.2 expression and the level of anaplasia in different malignant tissue samples. Hsp16.2 expression was directly correlated with the histological grade of brain tumors, therefore Hsp16.2 may have relevance as becoming a possible tumor marker

  2. Correlation between the progressive cytoplasmic expression of a novel small heat shock protein (Hsp16.2 and malignancy in brain tumors

    Directory of Open Access Journals (Sweden)

    Gallyas Ferenc

    2007-12-01

    Full Text Available Abstract Background Small heat shock proteins are molecular chaperones that protect proteins against stress-induced aggregation. They have also been found to have anti-apoptotic activity and to play a part in the development of tumors. Recently, we identified a new small heat shock protein, Hsp16.2 which displayed increased expression in neuroectodermal tumors. Our aim was to investigate the expression of Hsp16.2 in different types of brain tumors and to correlate its expression with the histological grade of the tumor. Methods Immunohistochemistry with a polyclonal antibody to Hsp16.2 was carried out on formalin-fixed, paraffin-wax-embedded sections using the streptavidin-biotin method. 91 samples were examined and their histological grade was defined. According to the intensity of Hsp16.2 immunoreactivity, low (+, moderate (++, high (+++ or none (- scores were given. Immunoblotting was carried out on 30 samples of brain tumors using SDS-polyacrylamide gel electrophoresis and Western-blotting. Results Low grade (grades 1–2 brain tumors displayed low cytoplasmic Hsp16.2 immunoreactivity, grade 3 tumors showed moderate cytoplasmic staining, while high grade (grade 4 tumors exhibited intensive cytoplasmic Hsp16.2 staining. Immunoblotting supported the above mentioned results. Normal brain tissue acted as a negative control for the experiment, since the cytoplasm did not stain for Hsp16.2. There was a positive correlation between the level of Hsp16.2 expression and the level of anaplasia in different malignant tissue samples. Conclusion Hsp16.2 expression was directly correlated with the histological grade of brain tumors, therefore Hsp16.2 may have relevance as becoming a possible tumor marker.

  3. EPID-based in vivo dosimetry for stereotactic body radiotherapy of non-small cell lung tumors: Initial clinical experience.

    Science.gov (United States)

    Consorti, R; Fidanzio, A; Brainovich, V; Mangiacotti, F; De Spirito, M; Mirri, M A; Petrucci, A

    2017-10-01

    EPID-based in vivo dosimetry (IVD) has been implemented for stereotactic body radiotherapy treatments of non-small cell lung cancer to check both isocenter dose and the treatment reproducibility comparing EPID portal images. 15 patients with lung tumors of small dimensions and treated with volumetric modulated arc therapy were enrolled for this initial experience. IVD tests supplied ratios R between in vivo reconstructed and planned isocenter doses. Moreover a γ-like analysis between daily EPID portal images and a reference one, in terms of percentage of points with γ-value smaller than 1, P γlevels of 5% for R ratio, P γlevel, and an average P γ90%. Paradigmatic discrepancies were observed in three patients: a set-up error and a patient morphological change were identified thanks to CBCT image analysis whereas the third discrepancy was not fully justified. This procedure can provide improved patient safety as well as a first step to integrate IVD and CBCT dose recalculation. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  4. Clinical introduction of Monte Carlo treatment planning: A different prescription dose for non-small cell lung cancer according to tumor location and size

    International Nuclear Information System (INIS)

    Voort van Zyp, Noelle C. van der; Hoogeman, Mischa S.; Water, Steven van de; Levendag, Peter C.; Holt, Bronno van der; Heijmen, Ben J.M.; Nuyttens, Joost J.

    2010-01-01

    Purpose: To provide a prescription dose for Monte Carlo (MC) treatment planning in patients with non-small-cell lung cancer according to tumor size and location. Methods: Fifty-three stereotactic radiotherapy plans designed using the equivalent path-length (EPL) algorithm were re-calculated using MC. Plans were compared by the minimum dose to 95% of the PTV (D95), the heterogeneity index (HI) and the mean dose to organs at risk (OARs). Based on changes in D95, the prescription dose was converted from EPL to MC. Based on changes in HI, we examined the feasibility of MC prescription to plans re-calculated but not re-optimized with MC. Results: The MC fraction dose for peripheral tumors is 16-18 Gy depending on tumor size. For central tumors the MC dose was reduced less than for peripheral tumors. The HI decreased on average by 4-9% in peripheral tumors and 3-5% in central tumors. The mean dose to OARs was lower for MC than EPL, and correlated strongly (R 2 = 0.98-0.99). Conclusion: For the conversion from EPL to MC we recommend a separate prescription dose according to tumor size. MC optimization is not required if a HI ≥ 70% is accepted. Dose constraints to OARs can be easily converted due to the high EPL-MC correlation.

  5. Strategy to find molecular signatures in a small series of rare cancers: validation for radiation-induced breast and thyroid tumors.

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    Nicolas Ugolin

    Full Text Available Methods of classification using transcriptome analysis for case-by-case tumor diagnosis could be limited by tumor heterogeneity and masked information in the gene expression profiles, especially as the number of tumors is small. We propose a new strategy, EMts_2PCA, based on: 1 The identification of a gene expression signature with a great potential for discriminating subgroups of tumors (EMts stage, which includes: a a learning step, based on an expectation-maximization (EM algorithm, to select sets of candidate genes whose expressions discriminate two subgroups, b a training step to select from the sets of candidate genes those with the highest potential to classify training tumors, c the compilation of genes selected during the training step, and standardization of their levels of expression to finalize the signature. 2 The predictive classification of independent prospective tumors, according to the two subgroups of interest, by the definition of a validation space based on a two-step principal component analysis (2PCA. The present method was evaluated by classifying three series of tumors and its robustness, in terms of tumor clustering and prediction, was further compared with that of three classification methods (Gene expression bar code, Top-scoring pair(s and a PCA-based method. Results showed that EMts_2PCA was very efficient in tumor classification and prediction, with scores always better that those obtained by the most common methods of tumor clustering. Specifically, EMts_2PCA permitted identification of highly discriminating molecular signatures to differentiate post-Chernobyl thyroid or post-radiotherapy breast tumors from their sporadic counterparts that were previously unsuccessfully classified or classified with errors.

  6. PRIMA-1Met/APR-246 induces apoptosis and tumor growth delay in small cell lung cancer expressing mutant p53

    DEFF Research Database (Denmark)

    Zandi, Roza; Selivanova, Galina; Christensen, Camilla Laulund

    2011-01-01

    Small cell lung cancer (SCLC) is a highly malignant disease with poor prognosis, necessitating the need to develop new and efficient treatment modalities. PRIMA-1(Met) (p53-dependent reactivation of massive apoptosis), also known as APR-246, is a small molecule, which restores tumor suppressor...... function to mutant p53 and induces cancer cell death in various cancer types. Since p53 is mutated in more than 90% of SCLC, we investigated the ability of PRIMA-1(Met) to induce apoptosis and inhibit tumor growth in SCLC with different p53 mutations....

  7. SU-E-T-427: Cell Surviving Fractions Derived From Tumor-Volume Variation During Radiotherapy for Non-Small Cell Lung Cancer: Comparison with Predictive Assays

    International Nuclear Information System (INIS)

    Chvetsov, A; Schwartz, J; Mayr, N; Yartsev, S

    2014-01-01

    Purpose: To show that a distribution of cell surviving fractions S 2 in a heterogeneous group of patients can be derived from tumor-volume variation curves during radiotherapy for non-small cell lung cancer. Methods: Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancer with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage (MV) computed tomography (CT). Statistical distributions of cell surviving fractions S 2 and cell clearance half-lives of lethally damaged cells T1/2 have been reconstructed in each patient group by using a version of the two-level cell population tumor response model and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Results: Non-small cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractions S 2 for non-small cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S 2 reconstructed from tumor volume variation agree with the PDF measured in vitro. Comparison of the reconstructed cell surviving fractions with patient survival data shows that the patient survival time decreases as the cell surviving fraction increases. Conclusion: The data obtained in this work suggests that the cell surviving fractions S 2 can be reconstructed from the tumor volume variation curves measured

  8. Antitumor activity of erlotinib (OSI-774, Tarceva) alone or in combination in human non-small cell lung cancer tumor xenograft models.

    Science.gov (United States)

    Higgins, Brian; Kolinsky, Kenneth; Smith, Melissa; Beck, Gordon; Rashed, Mohammad; Adames, Violeta; Linn, Michael; Wheeldon, Eric; Gand, Laurent; Birnboeck, Herbert; Hoffmann, Gerhard

    2004-06-01

    Our objective was the preclinical assessment of the pharmacokinetics, monotherapy and combined antitumor activity of the epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor erlotinib in athymic nude mice bearing non-small cell lung cancer (NSCLC) xenograft models. Immunohistochemistry determined the HER1/EGFR status of the NSCLC tumor models. Pharmacokinetic studies assessed plasma drug concentrations of erlotinib in tumor- and non-tumor-bearing athymic nude mice. These were followed by maximum tolerated dose (MTD) studies for erlotinib and each chemotherapy. Erlotinib was then assessed alone and in combination with these chemotherapies in the NSCLC xenograft models. Complete necropsies were performed on most of the animals in each study to further assess antitumor or toxic effects. Erlotinib monotherapy dose-dependently inhibited tumor growth in the H460a tumor model, correlating with circulating levels of drug. There was antitumor activity at the MTD with each agent tested in both the H460a and A549 tumor models (erlotinib 100 mg/kg: 71 and 93% tumor growth inhibition; gemcitabine 120 mg/kg: 93 and 75% tumor growth inhibition; cisplatin 6 mg/kg: 81 and 88% tumor growth inhibition). When each compound was given at a fraction of the MTD, tumor growth inhibition was suboptimal. Combinations of gemcitabine or cisplatin with erlotinib were assessed at 25% of the MTD to determine efficacy. In both NSCLC models, doses of gemcitabine (30 mg/kg) or cisplatin (1.5 mg/kg) with erlotinib (25 mg/kg) at 25% of the MTD were well tolerated. For the slow growing A549 tumor, there was significant tumor growth inhibition in the gemcitabine/erlotinib and cisplatin/erlotinib combinations (above 100 and 98%, respectively), with partial regressions. For the faster growing H460a tumor, there was significant but less remarkable tumor growth inhibition in these same combinations (86 and 53% respectively). These results show that in NSCLC xenograft tumors with similar

  9. The impact of microscopic disease on the tumor control probability in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Siedschlag, Christian; Boersma, Liesbeth; Loon, Judith van; Rossi, Maddalena; Baardwijk, Angela van; Gilhuijs, Kenneth; Stroom, Joep

    2011-01-01

    Purpose: To indicate which clinical target volume (CTV) margin (if any) is needed for an adequate treatment of non-small-cell lung cancer (NSCLC) using either 3D conformal or stereotactic radiotherapy, taking the distribution of the microscopic disease extension (MDE) into account. Methods and materials: On the basis of the linear-quadratic biological model, a Monte-Carlo simulation was used to study the impact of MDE and setup deviations on the tumor control probability (TCP) after typical 3D conformal and stereotactic irradiation techniques. Setup deviations were properly accounted for in the planning target volume (PTV) margin. Previously measured distributions of MDE outside the macroscopic tumor in NSCLC patients were used. The dependence of the TCP on the CTV margins was quantified. Results: The presence of MDE had a demonstratable influence on the TCP in both the 3D conformal and the stereotactic technique when no CTV margins were employed. The impact of MDE on the TCP values was greater in the 3D conformal scenario (67% TCP with MDE; 84% TCP without MDE) than for stereotactic radiotherapy (91% TCP with MDE; 100% TCP without MDE). Accordingly, an increase of the CTV margin had the greatest impact for the 3D conformal technique. Larger setup errors, with appropriate PTV margins, lead to an increase in TCP for both techniques, showing the interdependence of CTV and PTV margins. Conclusions: MDE may not always be eradicated by the beam penumbra or existing PTV margins using either 3D conformal or stereotactic radiotherapy. Nonetheless, TCP modeling indicates an overall local control rate above 90% for the stereotactic technique, while a non-zero CTV margin is recommended for better local control of MDE when using the 3D conformal technique.

  10. Anti-tumor effect of 131I labeled 17-allylamino-17-demethoxygeldanamycin on human non-small cell lung cancer in xenograft-bearing nude mice

    International Nuclear Information System (INIS)

    Sun Jin; Liu Lu; Zhu Xiaoli; Chen Daozhen; Gao Wen; Jiang Xinyu; Huang Ying

    2008-01-01

    Objective: 17-allylamino-17-demethoxygeldanamycin (17-AAG) has been developed as a novel heat shock protein 90 (HSP90) inhibitor being used in clinical trials. HSP90 is known as a molecular target for tumor therapy. The goal of this study was to investigate the inhibitive effects of 131 I labeled 17-AAG on human non-small cell lung cancer in xenograft-bearing nude mice. Methods: 17-AAG was labeled with 131 I. Twenty-eight BALB/c nude mice bearing H460 human non-small cell lung carcinoma tumor xenograft were randomly divided into seven groups, one control group and six treatment groups according to the route of administration (via tail vein injection or intratumoral injection) and the doses of injected radio-activity (5.5 MBq x 2 with 8 d interval, 11.0 MBq and 5.5 MBq). Two additional mice were treated with intratumoral injection of Na 131 I solution that was served as seintigraphic imaging controls. In each group two mice underwent scintigraphy at 2 h, 6 h, 24 h, 2 d, 3 d, 7 d, 10 d and 16 d. After 16 d the tumor inhibition rate was calculated. Then all of the mice were sacrificed and the tumor tissues were obtained for histological examination and immunohistochemical assay. Results: Persistent accumulation of 131 I-17-AAG in the tumors was seen on seintigraphic images. Tumor inhibiting effect was demonstrated in all treatment groups with varying degrees. The highest tumor inhibition rate (86.77 ± 4.57)% was shown in the group with interval intratumoral injection (5.5 MBq x 2). There was no significant difference of tumor inhibition rates between 5.5 MBq x 2 group (via tail vein injection) and 11.0 MBq group( via tail vein injection, q=1.67, P>0.05). While among the other treatment groups, there was significant difference in tumor inhibition rates( q=3.16-24.34, all P 131 I-17-AAG may effectively inhibit the tumor growth and expression of HSP90α antigen expression in non-small cell lung cancer bearing nude mice. The more prominent anti-tumor effect may be

  11. KRAS Genotype Correlates with Proteasome Inhibitor Ixazomib Activity in Preclinical In Vivo Models of Colon and Non-Small Cell Lung Cancer: Potential Role of Tumor Metabolism.

    Directory of Open Access Journals (Sweden)

    Nibedita Chattopadhyay

    Full Text Available In non-clinical studies, the proteasome inhibitor ixazomib inhibits cell growth in a broad panel of solid tumor cell lines in vitro. In contrast, antitumor activity in xenograft tumors is model-dependent, with some solid tumors showing no response to ixazomib. In this study we examined factors responsible for ixazomib sensitivity or resistance using mouse xenograft models. A survey of 14 non-small cell lung cancer (NSCLC and 6 colon xenografts showed a striking relationship between ixazomib activity and KRAS genotype; tumors with wild-type (WT KRAS were more sensitive to ixazomib than tumors harboring KRAS activating mutations. To confirm the association between KRAS genotype and ixazomib sensitivity, we used SW48 isogenic colon cancer cell lines. Either KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cells to generate cells that stably express activated KRAS. SW48 KRAS WT tumors, but neither SW48-KRAS-G13D tumors nor SW48-KRAS-G12V tumors, were sensitive to ixazomib in vivo. Since activated KRAS is known to be associated with metabolic reprogramming, we compared metabolite profiling of SW48-WT and SW48-KRAS-G13D tumors treated with or without ixazomib. Prior to treatment there were significant metabolic differences between SW48 WT and SW48-KRAS-G13D tumors, reflecting higher oxidative stress and glucose utilization in the KRAS-G13D tumors. Ixazomib treatment resulted in significant metabolic regulation, and some of these changes were specific to KRAS WT tumors. Depletion of free amino acid pools and activation of GCN2-eIF2α-pathways were observed both in tumor types. However, changes in lipid beta oxidation were observed in only the KRAS WT tumors. The non-clinical data presented here show a correlation between KRAS genotype and ixazomib sensitivity in NSCLC and colon xenografts and provide new evidence of regulation of key metabolic pathways by proteasome inhibition.

  12. KRAS Genotype Correlates with Proteasome Inhibitor Ixazomib Activity in Preclinical In Vivo Models of Colon and Non-Small Cell Lung Cancer: Potential Role of Tumor Metabolism.

    Science.gov (United States)

    Chattopadhyay, Nibedita; Berger, Allison J; Koenig, Erik; Bannerman, Bret; Garnsey, James; Bernard, Hugues; Hales, Paul; Maldonado Lopez, Angel; Yang, Yu; Donelan, Jill; Jordan, Kristen; Tirrell, Stephen; Stringer, Bradley; Xia, Cindy; Hather, Greg; Galvin, Katherine; Manfredi, Mark; Rhodes, Nelson; Amidon, Ben

    2015-01-01

    In non-clinical studies, the proteasome inhibitor ixazomib inhibits cell growth in a broad panel of solid tumor cell lines in vitro. In contrast, antitumor activity in xenograft tumors is model-dependent, with some solid tumors showing no response to ixazomib. In this study we examined factors responsible for ixazomib sensitivity or resistance using mouse xenograft models. A survey of 14 non-small cell lung cancer (NSCLC) and 6 colon xenografts showed a striking relationship between ixazomib activity and KRAS genotype; tumors with wild-type (WT) KRAS were more sensitive to ixazomib than tumors harboring KRAS activating mutations. To confirm the association between KRAS genotype and ixazomib sensitivity, we used SW48 isogenic colon cancer cell lines. Either KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cells to generate cells that stably express activated KRAS. SW48 KRAS WT tumors, but neither SW48-KRAS-G13D tumors nor SW48-KRAS-G12V tumors, were sensitive to ixazomib in vivo. Since activated KRAS is known to be associated with metabolic reprogramming, we compared metabolite profiling of SW48-WT and SW48-KRAS-G13D tumors treated with or without ixazomib. Prior to treatment there were significant metabolic differences between SW48 WT and SW48-KRAS-G13D tumors, reflecting higher oxidative stress and glucose utilization in the KRAS-G13D tumors. Ixazomib treatment resulted in significant metabolic regulation, and some of these changes were specific to KRAS WT tumors. Depletion of free amino acid pools and activation of GCN2-eIF2α-pathways were observed both in tumor types. However, changes in lipid beta oxidation were observed in only the KRAS WT tumors. The non-clinical data presented here show a correlation between KRAS genotype and ixazomib sensitivity in NSCLC and colon xenografts and provide new evidence of regulation of key metabolic pathways by proteasome inhibition.

  13. Prognostic Impact of Radiation Therapy to the Primary Tumor in Patients With Non-small Cell Lung Cancer and Oligometastasis at Diagnosis

    International Nuclear Information System (INIS)

    Lopez Guerra, Jose Luis; Gomez, Daniel; Zhuang, Yan; Hong, David S.; Heymach, John V.; Swisher, Stephen G.; Lin, Steven H.; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing

    2012-01-01

    Purpose: We investigated prognostic factors associated with survival in patients with non-small cell lung cancer (NSCLC) and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis. Methods and Materials: From January 2000 through June 2011, 78 consecutive patients with oligometastatic NSCLC ( 80 (P=.007), had a gross tumor volume ≤124 cm 3 (P=.002), had adenocarcinoma histology (P=.002), or had no history of respiratory disease (P=.016). On multivariate analysis, radiation dose, performance status, and tumor volume retained significance (P=.004, P=.006, and P<.001, respectively). The radiation dose also maintained significance when patients with and without brain metastases were analyzed separately. Conclusions: Tumor volume, KPS, and receipt of at least 63 Gy to the primary tumor are associated with improved OS in patients with oligometastatic NSCLC at diagnosis. Our results suggest that a subset of such patients may benefit from definitive local therapy.

  14. Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

    International Nuclear Information System (INIS)

    Roman, Nicholas O.; Shepherd, Wes; Mukhopadhyay, Nitai; Hugo, Geoffrey D.; Weiss, Elisabeth

    2012-01-01

    Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior–posterior), and z (superior–inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy–based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

  15. Impact of tumor extent and location on treatment outcome in patients with stage III non-small cell lung cancer treated with radiation therapy

    International Nuclear Information System (INIS)

    Hayakawa, Kazushige; Mitsuhashi, Norio; Saito, Yoshihiro

    1996-01-01

    The results of treatment of 141 patients with stage III non-small cell lung cancer (NSCLC) who received definitive radiation therapy at Gunma University Hospital between 1976 and 1989 were retrospectively analyzed. Radiation was given with standard fractionation for a planned prophylactic dose of 40 Gy over 4 weeks and a definitive dose of 60 Gy over 6 weeks or more. The two- and five-year survival rates were 27% and 12% for stage IIIA, and 18% and 8% for stage IIIB, respectively (P=0.052). By univariate analysis, a primary tumor less than 5 cm in diameter was also an important predictor of survival (P=0.008). As for tumor location, the patients with primary tumors in the upper lobes or the superior segment of the lower lobes of the lung lived longer than those with primary tumors at any other site (P=0.032). Patients with epidermoid carcinoma had a higher survival rate at 5 years than those with other histologic types (14% vs 3%, P=0.074). Multivariate analysis showed that among tumor characteristics, the site of the primary tumor, the pattern of tumor spread and N stage were significantly associated with overall survival. Among the patients with stage III NSCLC, those with stage IIIA epidermoid carcinoma in the upper lobe or the superior segment of the lower lobe of the lung were considered to be the most favorable candidates for definitive radiation therapy. (author)

  16. Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Roman, Nicholas O., E-mail: nroman@mcvh-vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Shepherd, Wes [Department of Pulmonology, Virginia Commonwealth University, Richmond, VA (United States); Mukhopadhyay, Nitai [Department of Biostatistics, Virginia Commonwealth University, Richmond, VA (United States); Hugo, Geoffrey D.; Weiss, Elisabeth [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States)

    2012-08-01

    Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior-posterior), and z (superior-inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy-based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

  17. Endometrioid like yolk sac tumor of the testis with small teratomatous foci: A case report and review of the literature.

    Science.gov (United States)

    Hazarika, Prabir

    2015-01-01

    I have reported a case of endometrioid like yolk sac tumor of the testis in a 20-year-old boy. Endometrioid like yolk sac tumor is a rare tumor. A few cases have been reported in ovary. In case of male, a case of pure glandular endometrioid like yolk sac tumor is reported in a 43 years male in right undescended testis and another case of abdominal metastasis showing endometrioid pattern from mixed testicular germ cell tumor comprising of teratoma and embryonal carcinoma. My patient was a 20-year-old male presented with painless enlargement of right testis. Grossly the tumor was glistening creamish white with a multicystic appearance. Histopathological examination showed the tumor to be composed of glandular elements resembling early secretory endometrium, foci of keratinized thin squamous epithelium and a single focus of benign cartilage. The glandular elements show immunohistochemical positivity for AFP, cytokeratin 7 (CK7) and epithelial membrane antigen (EMA).

  18. Endometrioid like yolk sac tumor of the testis with small teratomatous foci: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Prabir Hazarika

    2015-01-01

    Full Text Available I have reported a case of endometrioid like yolk sac tumor of the testis in a 20-year-old boy. Endometrioid like yolk sac tumor is a rare tumor. A few cases have been reported in ovary. In case of male, a case of pure glandular endometrioid like yolk sac tumor is reported in a 43 years male in right undescended testis and another case of abdominal metastasis showing endometrioid pattern from mixed testicular germ cell tumor comprising of teratoma and embryonal carcinoma. My patient was a 20-year-old male presented with painless enlargement of right testis. Grossly the tumor was glistening creamish white with a multicystic appearance. Histopathological examination showed the tumor to be composed of glandular elements resembling early secretory endometrium, foci of keratinized thin squamous epithelium and a single focus of benign cartilage. The glandular elements show immunohistochemical positivity for AFP, cytokeratin 7 (CK7 and epithelial membrane antigen (EMA.

  19. Dynamic {sup 11}C-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas: an experimental study using small animal PET

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Songji; Zhao, Yan [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo (Japan); Hokkaido University, Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Sapporo (Japan); Kuge, Yuji; Hatano, Toshiyuki [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Yi, Min; Kohanawa, Masashi [Hokkaido University, Department of Advanced Medicine, Graduate School of Medicine, Sapporo (Japan); Magota, Keiichi; Tamaki, Nagara [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo (Japan); Nishijima, Ken-ichi [Hokkaido University, Department of Molecular Imaging, Graduate School of Medicine, Sapporo (Japan)

    2011-10-15

    We evaluated whether the dynamic profile of L-{sup 11}C-methionine ({sup 11}C-MET) may have an additional value in differentiating malignant tumors from granulomas in experimental rat models by small animal positron emission tomography (PET). Rhodococcus aurantiacus and allogenic rat C6 glioma cells were inoculated, respectively, into the right and left calf muscles to generate a rat model bearing both granulomas and tumors (n = 6). Ten days after the inoculations, dynamic {sup 11}C-MET PET was performed by small animal PET up to 120 min after injection of {sup 11}C-MET. The next day, after overnight fasting, the rats were injected with {sup 18}F-2-deoxy-2-fluoro-D-glucose ({sup 18}F-FDG), and dynamic {sup 18}F-FDG PET was performed up to 180 min. The time-activity curves, static images, and mean standardized uptake value (SUV) in the lesions were calculated. {sup 11}C-MET uptake in the granuloma showed a slow exponential clearance after an initial distribution, while the uptake in the tumor gradually increased with time. The dynamic pattern of {sup 11}C-MET uptake in the granuloma was significantly different from that in the tumor (p < 0.001). In the static analysis of {sup 11}C-MET, visual assessment and SUV analysis could not differentiate the tumor from the granuloma in all cases, although the mean SUV in the granuloma (1.48 {+-} 0.09) was significantly lower than that in the tumor (1.72 {+-} 0.18, p < 0.01). The dynamic patterns, static images, and mean SUVs of {sup 18}F-FDG in the granuloma were similar to those in the tumor (p = NS). Dynamic {sup 11}C-MET PET has an additional value for differentiating malignant tumors from granulomatous lesions, which deserves further elucidation in clinical settings. (orig.)

  20. Dynamic 11C-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas: an experimental study using small animal PET

    International Nuclear Information System (INIS)

    Zhao, Songji; Zhao, Yan; Kuge, Yuji; Hatano, Toshiyuki; Yi, Min; Kohanawa, Masashi; Magota, Keiichi; Tamaki, Nagara; Nishijima, Ken-ichi

    2011-01-01

    We evaluated whether the dynamic profile of L- 11 C-methionine ( 11 C-MET) may have an additional value in differentiating malignant tumors from granulomas in experimental rat models by small animal positron emission tomography (PET). Rhodococcus aurantiacus and allogenic rat C6 glioma cells were inoculated, respectively, into the right and left calf muscles to generate a rat model bearing both granulomas and tumors (n = 6). Ten days after the inoculations, dynamic 11 C-MET PET was performed by small animal PET up to 120 min after injection of 11 C-MET. The next day, after overnight fasting, the rats were injected with 18 F-2-deoxy-2-fluoro-D-glucose ( 18 F-FDG), and dynamic 18 F-FDG PET was performed up to 180 min. The time-activity curves, static images, and mean standardized uptake value (SUV) in the lesions were calculated. 11 C-MET uptake in the granuloma showed a slow exponential clearance after an initial distribution, while the uptake in the tumor gradually increased with time. The dynamic pattern of 11 C-MET uptake in the granuloma was significantly different from that in the tumor (p 11 C-MET, visual assessment and SUV analysis could not differentiate the tumor from the granuloma in all cases, although the mean SUV in the granuloma (1.48 ± 0.09) was significantly lower than that in the tumor (1.72 ± 0.18, p 18 F-FDG in the granuloma were similar to those in the tumor (p = NS). Dynamic 11 C-MET PET has an additional value for differentiating malignant tumors from granulomatous lesions, which deserves further elucidation in clinical settings. (orig.)

  1. The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time

    International Nuclear Information System (INIS)

    Ma, Junliang; Liu, Lunxu; Che, Guowei; Yu, Nanbin; Dai, Fuqiang; You, Zongbing

    2010-01-01

    Tumor-associated macrophages (TAMs) play an important role in growth, progression and metastasis of tumors. In non-small cell lung cancer (NSCLC), TAMs' anti-tumor or pro-tumor role is not determined. Macrophages are polarized into M1 (with anti-tumor function) and M2 (with pro-tumor function) forms. This study was conducted to determine whether the M1 and M2 macrophage densities in NSCLC are associated with patient's survival time. Fifty patients with an average of 1-year survival (short survival group) and 50 patients with an average of 5-year survival (long survival group) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical double-staining of CD68/HLA-DR (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded fashion. The M1 and M2 macrophage densities in the tumor islets, stroma, or islets and stroma were determined using computer-aided microscopy. Correlation of the macrophage densities and patient's survival time was analyzed using the Statistical Package for the Social Sciences. Approximately 70% of TAMs were M2 macrophages and the remaining 30% were M1 macrophages in NSCLC. The M2 macrophage densities (approximately 78 to 113 per mm 2 ) in the tumor islets, stroma, or islets and stroma were not significantly different between the long survival and short survival groups. The M1 macrophage densities in the tumor islets (approximately 70/mm 2 ) and stroma (approximately 34/mm 2 ) of the long survival group were significantly higher than the M1 macrophage densities in the tumor islets (approximately 7/mm 2 ) and stroma (13/mm 2 ) of the short survival group (P < 0.001 and P < 0.05, respectively). The M2 macrophage densities were not associated with patient's survival time. The M1 macrophage densities in the tumor islets, stroma, or islets and stroma

  2. A prospective examination of circulating tumor cell profiles in non-small-cell lung cancer molecular subgroups.

    Science.gov (United States)

    Lindsay, C R; Faugeroux, V; Michiels, S; Pailler, E; Facchinetti, F; Ou, D; Bluthgen, M V; Pannet, C; Ngo-Camus, M; Bescher, G; Caramella, C; Billiot, F; Remon, J; Planchard, D; Soria, J-C; Besse, B; Farace, F

    2017-07-01

    We report the first study examining the clinical, numerical and biological properties of circulating tumor cells according to molecular subtypes of non-small-cell lung cancer. 125 patients with treatment-naïve stage IIIb-IV NSCLC were prospectively recruited for CellSearch analysis. Anti-vimentin antibody was included for examination of CTCs to assess their mesenchymal character. Associations of total CTCs and vimentin-positive (vim +) CTCs with clinical characteristics, tumor genotype, and survival were assessed. 51/125 patients (40.8%) were total CTC+ and 26/125 (20.8%) were vim CTC+ at baseline. Multivariate analysis showed patients with ≥5 total CTCs had significantly reduced OS (HR 0.55, 95% CI 0.33-0.92, P = 0.022) but not PFS (HR 0.68, 95% CI 0.42-1.1, P = 0.118) compared to patients with <5 total CTCs. No OS difference was evident between vim+ CTC and vim-negative CTC patients overall (HR 1.24, 95% CI 0.67-2.28, P = 0.494), but after subdivision according to NSCLC driver mutation, we found an increase of vim+ CTCs in the EGFR-mutated subgroup (N = 21/94 patients; mean 1.24 vs 1.22 vim+ CTCs, P = 0.013), a reduction of total CTCs in the ALK-rearranged subgroup (N = 13/90 patients; mean 1.69 vs 5.82 total CTCs, P = 0.029), and a total absence of vim+ CTCs in KRAS-mutated adenocarcinomas (N = 19/78 patients; mean 0 vs 1.4 vim+ CTCs, P = 0.006). We validate that the baseline presence of ≥5 total CTCs in advanced NSCLC confers a poor prognosis. CTCs from EGFR-mutant NSCLC express epithelial-mesenchymal transition characteristics, not seen in CTCs from patients with KRAS-mutant adenocarcinoma. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Gastrointestinal Stromal Tumor of the Stomach with Narrow Stalk-Like Based, Uneven Protruding Appearance Presenting with Severe Acute Anemia despite Small Size

    Directory of Open Access Journals (Sweden)

    Tomomitsu Tahara

    2010-03-01

    Full Text Available We report the case of a 56-year-old woman who had a gastrointestinal stromal tumor (GIST of the stomach. She was admitted to our hospital for epigastric pain, nausea, and severe acute anemia (hemoglobin level 4.3 g/dl. Esophagogastroduodenoscopy revealed a narrow stalk-like based, hemorrhagic and uneven protruding lesion in the lesser curvature of the gastric upper corpus. Although the tumor was less than 2 cm in diameter and was probably a benign GIST according to histology, laparoscopy-assisted local resection was needed because the patient had continuous severe anemia and epigastric pain. Histological assessment showed that the elongated spindle-like tumor cells originated from the intrinsic muscle layer, and was shown with growth to the mucosal side, cropping out to the surface in most areas of the protruding lesion. Only a small part of the tumor was within nontumoral gastric mucosa. Most of the tumor cells demonstrated immunoreactivity for KIT and CD34 in the cytoplasm but not for αSMA, S100, and desmin. Mitotic activity (0/50 high power field and the labeling index for MIB-1 (about 1% were low. The GIST of the stomach described in this report was a rare case with a narrow stalk-like based, uneven protruding mass presenting with severe acute anemia despite small size.

  4. INTRAOCULAR TRANSMISSIBLE VENEREAL TUMOR IN A DOG TUMOR VENÉREO TRANSMISSÍVEL INTRA-OCULAR EM CÃO

    Directory of Open Access Journals (Sweden)

    Geórgia Nadalini Rodrigues

    2001-02-01

    Full Text Available Canine transmissible venereal tumor (TVT is a round cell neoplasm occurring on the external genital mucosa of male and female dogs. Transmission is by cell implantation during coitus, licking, or other interaction between an affected dog and a susceptible host. Metastasis of the tumor rarely occurs. This report describes an unusual presentation of TVT with intraocular involvement and inguinal lymph nodes metastasis. The subject was a six-year-old, intact, male, Brazilian Terrier dog with a history of abnormal masses in the right eye, penis and several subcutaneous nodules in the inguinal area. Histopathological examination of the eye specimens as well as cytologic examination of penile mass and subcutaneous nodules revealed similar findings. The examination revealed round cells containing a large nuclei with prominent, central located nucleoli and a pale cytoplasm containing few small, clear round vacuoles. Histologically, the subcutaneous nodules in the inguinal area were lymph nodes. The diagnosis of TVT with intraocular involvement and lymph nodes metastasis was based on clinical, cytologic and histopathologic findings.Tumor venéreo transmissível (TVT é uma neoplasia de células redondas que acomete a mucosa genital externa de cães, machos e fêmeas. A transmissão decorre da implantação de células tumorais durante o coito, brigas ou interações entre animais portadores e susceptíveis. Existem relatos referindo-se a localizações atípicas do TVT, mas metástases raramente ocorrem. O presente relato descreve um caso incomum de TVT, com acometimento intra-ocular e metástases nos linfonodos ingüinais, num cão Terrier Brasileiro, com seis anos de idade. O animal apresentava massas anormais de tecido no olho direito, extremidade do pênis e aumento de volume de linfonodos da região ingüinal. A histopatologia do globo ocular e as citologias da massa peniana e dos nódulos subcutâneos evidenciaram aspectos citológicos semelhantes

  5. Small median tumor diameter at cure threshold (lung cancers in male smokers predicts both chest X-ray and CT screening outcomes in a novel simulation framework.

    Science.gov (United States)

    Goldwasser, Deborah L; Kimmel, Marek

    2013-01-01

    The effectiveness of population-wide lung cancer screening strategies depends on the underlying natural course of lung cancer. We evaluate the expected stage distribution in the Mayo CT screening study under an existing simulation model of non-small cell lung cancer (NSCLC) progression calibrated to the Mayo lung project (MLP). Within a likelihood framework, we evaluate whether the probability of 5-year NSCLC survival conditional on tumor diameter at detection depends significantly on screening detection modality, namely chest X-ray and computed tomography. We describe a novel simulation framework in which tumor progression depends on cellular proliferation and mutation within a stem cell compartment of the tumor. We fit this model to randomized trial data from the MLP and produce estimates of the median radiologic size at the cure threshold. We examine the goodness of model fit with respect to radiologic tumor size and 5-year NSCLC survival among incident cancers in both the MLP and Mayo CT studies. An existing model of NSCLC progression under-predicts the number of advanced-stage incident NSCLCs among males in the Mayo CT study (p-value = 0.004). The probability of 5-year NSCLC survival conditional on tumor diameter depends significantly on detection modality (p-value = 0.0312). In our new model, selected solution sets having a median tumor diameter of 16.2-22.1 mm at cure threshold among aggressive NSCLCs predict both MLP and Mayo CT outcomes. We conclude that the median lung tumor diameter at cure threshold among aggressive NSCLCs in male smokers may be small (<20 mm). Copyright © 2012 UICC.

  6. RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor

    Directory of Open Access Journals (Sweden)

    Christina Brzezniak

    2017-03-01

    Full Text Available Small cell carcinoma of the vagina is rare, so rare in fact that the total number reported in English-language journals is less than 30. Due to this extremely low incidence, no specific treatment guidelines have been established, and most of what is clinically known is derived from a handful of single case reports. However, as befitting its highly aggressive histologic features, which are reminiscent of small cell lung cancer (SCLC, first-line treatment is modeled after SCLC. Herein is reported the case of a 51-year-old African-American patient with metastatic biopsy-proven small cell carcinoma of the vagina that progressed through multiple therapies: first-line cisplatin and etoposide (making it platinum-resistant and radiotherapy, followed by the tumor macrophage-stimulating agent RRx-001 in a clinical trial called QUADRUPLE THREAT, which per protocol preceded a mandated rechallenge with cisplatin and etoposide. RECIST v.1.1 tumor progression on both RRx-001 and cisplatin/etoposide was accompanied by central necrosis in several of the enlarged lymph nodes and hepatic metastases, which may have been evidence of pseudoprogression, accounting for her ongoing longer-than-expected survival, since the necrotic tissue may have primed the activity of the PD-1 inhibitor. The lack of response to RRx-001 is hypothesized to have correlated with sparse tumor macrophage infiltration, seen on pre- and post-treatment biopsies, since the mechanism of action of RRx-001 relates to stimulation of tumor-associated macrophages.

  7. Serial megavoltage CT imaging during external beam radiotherapy for non-small-cell lung cancer: Observations on tumor regression during treatment

    International Nuclear Information System (INIS)

    Kupelian, Patrick A.; Ramsey, Chester; Meeks, Sanford L.; Willoughby, Twyla R.; Forbes, Alan; Wagner, Thomas H.; Langen, Katja M.

    2005-01-01

    Purpose: The ability to obtain soft-tissue imaging in the treatment room, such as with megavoltage CT imaging, enables the observation of tumor regression during a course of external beam radiation therapy. In this current study, we report on the most extensive study looking at the rate of regression of non-small-cell lung cancers during a course of external beam radiotherapy by analyzing serial megavoltage CT images obtained on 10 patients. Methods and Materials: The analysis is performed on 10 patients treated with the Helical Tomotherapy Hi*Art device. All 10 patients had non-small-cell lung cancer. A total of 274 megavoltage CT sets were obtained on the 10 patients (average, 27 scans per patient; range, 9-35). All patients had at least a scan at beginning and at the end of treatment. The frequency of scanning was determined by the treating physician. The treatment was subsequently delivered with the Tomotherapy Hi*Art system. The gross tumor volumes (GTVs) were later contoured on each megavoltage CT scan, and tumor volumes were calculated. Although some patients were treated to draining nodal areas in addition to the primary tumor, only the primary GTVs were tracked. Response to treatment was quantified by the relative decrease in tumor volume over time, i.e., elapsed days from the first day of therapy. The individual GTVs ranged from 5.9 to 737.2 cc in volume at the start of treatment. In 6 of the 10 patients, dose recalculations were also performed to document potential variations in delivered doses within the tumors. The megavoltage CT scans were used, and the planned treatment was recalculated on the daily images. The hypothesis was that dose deposited in the target would increase throughout the course of radiotherapy because of tumor shrinkage and subsequent decreasing attenuation. Specifically, the dose received by 95% of the GTV (D 95 ) was monitored over time for each of the 6 patients treated at M.D. Anderson Cancer Center Orlando. Results: Regression

  8. Production and dosimetric aspects of the potent Auger emitter 58mCo for targeted radionuclide therapy of small tumors

    International Nuclear Information System (INIS)

    Thisgaard, H.; Elema, D.R.; Jensen, M.

    2011-01-01

    Purpose: Based on theoretical calculations, the Auger emitter 58m Co has been identified as a potent nuclide for targeted radionuclide therapy of small tumors. During the production of this isotope, the coproduction of the long-lived ground state 58g Co is unfortunately unavoidable, as is ingrowth of the ground state following the isomeric decay of 58m Co. The impact of 58g Co as a β + - and γ-emitting impurity should be included in the dosimetric analysis. The purpose of this study was to investigate this critical part of dosimetry based on experimentally determined production yields of 58m Co and 58g Co using a low-energy cyclotron. Also, the cellular S-values for 58m Co have been calculated and are presented here for the first time. Methods: 58m Co was produced via the 58 Fe(p,n) 58m Co nuclear reaction on highly enriched 58 Fe metal. In addition, radiochemical separations of produced radio-cobalt from nat Fe target material were performed. The theoretical subcellular dosimetry calculations for 58m Co and 58g Co were performed using the MIRD formalism, and the impact of the increasing ground state impurity on the tumor-to-normal-tissue dose ratios (TND) per disintegration as a function of time after end of bombardment (EOB) was calculated. Results: 192 ± 8 MBq of 58m Co was produced in the irradiation corresponding to a production yield of 10.7 MBq/μAh. The activity of 58g Co was measured to be 0.85% ± 0.04% of the produced 58m Co activity at EOB. The radio-cobalt yields in the rapid separations were measured to be >97% with no detectable iron contaminations in the cobalt fractions. Due to the unavoidable coproduction and ingrowth of the long-lived ground state 58g Co, the TND and the potency of the 58m Co decrease with time after EOB. If a future treatment with a 58m Co labeled compound is not initiated before, e.g., 21 h after EOB, the resulting TND will be approximately 50% of the TND of 'pure' 58m Co as a result of the increased normal tissue dose from

  9. An observational study of circulating tumor cells and (18F-FDG PET uptake in patients with treatment-naive non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Viswam S Nair

    Full Text Available We investigated the relationship of circulating tumor cells (CTCs in non-small cell lung cancer (NSCLC with tumor glucose metabolism as defined by (18F-fluorodeoxyglucose (FDG uptake since both have been associated with patient prognosis.We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or "HD-CTCs". We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis.We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0-3.6 and median maximum standardized uptake value (SUVmax was 7.2 (IQR 3.7-15.5. More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71 or in stage I disease (27 of 43. HD-CTCs were weakly correlated with partial volume corrected tumor SUVmax (r = 0.27, p-value = 0.03 and not correlated with tumor diameter (r = 0.07; p-value = 0.60. For a given partial volume corrected SUVmax or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease.CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.

  10. Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results

    Directory of Open Access Journals (Sweden)

    Ayakawa Shiho

    2009-05-01

    Full Text Available Abstract Background In stereotactic body radiotherapy (SBRT for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO2 levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system. Methods Between 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC, 10 were metastatic lung cancers, and 3 were local recurrences of NSCLC. Tumor movement was measured with fluoroscopy under breath holding, free breathing on a couch, and free breathing in the BodyFIX system. SpO2 levels were measured with a finger pulseoximeter under each condition. The delivered dose was 44, 48 or 52 Gy, depending on tumor diameter, in 4 fractions over 10 or 11 days. Results By using the BodyFIX system, respiratory tumor movements were significantly reduced compared with the free-breathing condition in both craniocaudal and lateral directions, although the amplitude of reduction in the craniocaudal direction was 3 mm or more in only 27% of the patients. The average SpO2 did not decrease by using the system. At 3 years, the local control rate was 80% for all lesions. Overall survival was 76%, cause-specific survival was 92%, and local progression-free survival was 76% at 3 years in primary NSCLC patients. Grade 2 radiation pneumonitis developed in 7 patients. Conclusion Respiratory tumor movement was modestly suppressed by the BodyFIX system, while the SpO2 level did not decrease. It was considered a simple and effective method for SBRT of lung tumors. Preliminary results were encouraging.

  11. Non-small cell lung cancer: Whole-lesion histogram analysis of the apparent diffusion coefficient for assessment of tumor grade, lymphovascular invasion and pleural invasion.

    Science.gov (United States)

    Tsuchiya, Naoko; Doai, Mariko; Usuda, Katsuo; Uramoto, Hidetaka; Tonami, Hisao

    2017-01-01

    Investigating the diagnostic accuracy of histogram analyses of apparent diffusion coefficient (ADC) values for determining non-small cell lung cancer (NSCLC) tumor grades, lymphovascular invasion, and pleural invasion. We studied 60 surgically diagnosed NSCLC patients. Diffusion-weighted imaging (DWI) was performed in the axial plane using a navigator-triggered single-shot, echo-planar imaging sequence with prospective acquisition correction. The ADC maps were generated, and we placed a volume-of-interest on the tumor to construct the whole-lesion histogram. Using the histogram, we calculated the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC, skewness, and kurtosis. Histogram parameters were correlated with tumor grade, lymphovascular invasion, and pleural invasion. We performed a receiver operating characteristics (ROC) analysis to assess the diagnostic performance of histogram parameters for distinguishing different pathologic features. The ADC mean, 10th, 25th, 50th, 75th, 90th, and 95th percentiles showed significant differences among the tumor grades. The ADC mean, 25th, 50th, 75th, 90th, and 95th percentiles were significant histogram parameters between high- and low-grade tumors. The ROC analysis between high- and low-grade tumors showed that the 95th percentile ADC achieved the highest area under curve (AUC) at 0.74. Lymphovascular invasion was associated with the ADC mean, 50th, 75th, 90th, and 95th percentiles, skewness, and kurtosis. Kurtosis achieved the highest AUC at 0.809. Pleural invasion was only associated with skewness, with the AUC of 0.648. ADC histogram analyses on the basis of the entire tumor volume are able to stratify NSCLCs' tumor grade, lymphovascular invasion and pleural invasion.

  12. Celecoxib enhances radiation response of secondary bone tumors of a human non-small cell lung cancer via antiangiogenesis in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Klenke, Frank Michael [Bern Univ. (Switzerland). Dept. of Orthopedic Surgery; Abdollahi, Amir [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Tufts Univ. School of Medicine, Boston, MA (United States). Center of Cancer Systems Biology; Bischof, Marc; Huber, Peter E. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Gebhard, Martha-Maria [Heidelberg Univ. (Germany). Dept. of Experimental Surgery; Ewerbeck, Volker [Heidelberg Univ. (Germany). Dept. of Orthopedic Surgery; Sckell, Axel [Charite Univ. Medical Center, Berlin (Germany). Dept. of Orthopedic, Trauma and Reconstructive Surgery

    2011-01-15

    Purpose: Cyclooxygenase-2 (COX-2) inhibitors mediate a systemic antitumor activity via antiangiogenesis and seem to enhance the response of primary tumors to radiation. Radiosensitizing effects of COX-2 inhibition have not been reported for bone metastases. Therefore, the aim of this study was the investigation of the radiosensitizing effects of the selective COX-2 inhibitor celecoxib in secondary bone tumors of a non-small cell lung carcinoma in vivo. Materials and Methods: Human A549 lung carcinomas were implanted into a cranial window preparation in male SCID mice (n = 24). Animals were treated with either celecoxib or radiation (7 Gy single photon dose) alone or a combination of celecoxib and radiation, respectively. Untreated animals served as controls. The impact of radiation and COX-2 inhibition on angiogenesis, microcirculation, and tumor growth was analyzed over 28 days by means of intravital microscopy and histological methods. Results: Monotherapies with radiation as well as celecoxib had significant antitumor effects compared to untreated controls. Both therapies reduced tumor growth and vascularization to a similar extent. The simultaneous administration of celecoxib and radiation further enhanced the antitumor and antiangiogenic effects of single-beam radiation. With the combined treatment approach, tumor vascularization and tumor size were decreased by 57% and 51%, respectively, as compared to monotherapy with radiation. Conclusion: The combined application of radiation therapy and COX-2 inhibition showed synergistic effects concerning the inhibition of tumor growth and tumor angiogenesis. Therefore, the combination of radiation with COX-2 inhibitor therapy represents a promising approach to improve the therapeutic efficacy of radiotherapy of bone metastases. (orig.)

  13. Improvement of internal tumor volumes of non-small cell lung cancer patients for radiation treatment planning using interpolated average CT in PET/CT.

    Directory of Open Access Journals (Sweden)

    Yao-Ching Wang

    Full Text Available Respiratory motion causes uncertainties in tumor edges on either computed tomography (CT or positron emission tomography (PET images and causes misalignment when registering PET and CT images. This phenomenon may cause radiation oncologists to delineate tumor volume inaccurately in radiotherapy treatment planning. The purpose of this study was to analyze radiology applications using interpolated average CT (IACT as attenuation correction (AC to diminish the occurrence of this scenario. Thirteen non-small cell lung cancer patients were recruited for the present comparison study. Each patient had full-inspiration, full-expiration CT images and free breathing PET images by an integrated PET/CT scan. IACT for AC in PET(IACT was used to reduce the PET/CT misalignment. The standardized uptake value (SUV correction with a low radiation dose was applied, and its tumor volume delineation was compared to those from HCT/PET(HCT. The misalignment between the PET(IACT and IACT was reduced when compared to the difference between PET(HCT and HCT. The range of tumor motion was from 4 to 17 mm in the patient cohort. For HCT and PET(HCT, correction was from 72% to 91%, while for IACT and PET(IACT, correction was from 73% to 93% (*p<0.0001. The maximum and minimum differences in SUVmax were 0.18% and 27.27% for PET(HCT and PET(IACT, respectively. The largest percentage differences in the tumor volumes between HCT/PET and IACT/PET were observed in tumors located in the lowest lobe of the lung. Internal tumor volume defined by functional information using IACT/PET(IACT fusion images for lung cancer would reduce the inaccuracy of tumor delineation in radiation therapy planning.

  14. The Added Diagnostic Value of 18F-Fluorodihydroxyphenylalanine PET/CT in the Preoperative Work-Up of Small Bowel Neuroendocrine Tumors.

    Science.gov (United States)

    Addeo, Pietro; Poncet, Gilles; Goichot, Bernard; Leclerc, Loic; Brigand, Cécile; Mutter, Didier; Romain, Benoit; Namer, Izzie-Jacques; Bachellier, Philippe; Imperiale, Alessio

    2018-04-01

    The precise localization of the primary tumor and/or the identification of multiple primary tumors improves the preoperative work-up in patients with small bowel (SB) neuroendocrine tumor (NET). The present study assesses the diagnostic value of 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) positron emission tomography/computed tomography (PET/CT) during the preoperative wok-up of SB NETs. Between January 2010 and June 2017, all consecutive patients with SB NETs undergoing preoperative 18 F-FDOPA PET/CT and successive resection were analyzed. Preoperative work-up included computed tomography (CT), somatostatin receptor scintigraphy (SRS), and 18 F-FDOPA PET/CT. Sensitivity and accuracy ratio for primary and multiple tumor detection were compared with data from surgery and pathology. There were 17 consecutive patients with SB NETs undergoing surgery. Nine patients (53%) had multiple tumors, 15 (88%) metastatic lymph nodes, 3 (18%) peritoneal carcinomatosis, and 9 patients (53%) liver metastases. A total of 70 SB NETs were found by pathology. Surgery identified the primary in 17/17 (100%) patients and recognized seven of 9 patients (78%) with multiple synchronous SB. Preoperatively, 18 F-FDOPA PET/CT displayed a statistically significant higher sensitivity for primary tumor localization (100 vs. 23.5 vs. 29.5%) and multiple tumor detection (78 vs. 22 vs. 11%) over SRS and CT. Compared with pathology, 18 F-FDOPA PET/CT displayed the highest accuracy ratio for number of tumor detected over CT and SRS (2.0 ± 2.2 vs. 0.4 ± 0.7 vs. 0.6 ± 1.5, p = 0.0003). 18 F-FDOPA PET/CT significantly increased the sensitivity and accuracy for primary and multiple SB NET identification. 18 F-FDOPA PET/CT should be included systematically in the preoperative work-up of SB NET.

  15. SU-E-T-427: Cell Surviving Fractions Derived From Tumor-Volume Variation During Radiotherapy for Non-Small Cell Lung Cancer: Comparison with Predictive Assays

    Energy Technology Data Exchange (ETDEWEB)

    Chvetsov, A; Schwartz, J; Mayr, N [University of Washington, Seattle, WA (United States); Yartsev, S [London Health Sciences Centre, London, Ontario (Canada)

    2014-06-01

    Purpose: To show that a distribution of cell surviving fractions S{sub 2} in a heterogeneous group of patients can be derived from tumor-volume variation curves during radiotherapy for non-small cell lung cancer. Methods: Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancer with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage (MV) computed tomography (CT). Statistical distributions of cell surviving fractions S{sup 2} and cell clearance half-lives of lethally damaged cells T1/2 have been reconstructed in each patient group by using a version of the two-level cell population tumor response model and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Results: Non-small cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractions S{sub 2} for non-small cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S{sup 2} reconstructed from tumor volume variation agree with the PDF measured in vitro. Comparison of the reconstructed cell surviving fractions with patient survival data shows that the patient survival time decreases as the cell surviving fraction increases. Conclusion: The data obtained in this work suggests that the cell surviving fractions S{sub 2} can be reconstructed from the tumor volume

  16. Pituitary Tumors

    Science.gov (United States)

    ... Association (ABTA) International RadioSurgery Association National Brain Tumor Society National Institute of Child Health and Human Development ... Definition The pituitary is a small, bean-sized gland ...

  17. Investigations of (99m)Tc-labeled glucarate as a SPECT radiotracer for non-small cell lung cancer (NSCLC) and potential tumor uptake mechanism.

    Science.gov (United States)

    Meng, Lanfang; Xiu, Yan; Li, Yanli; Xu, Xiaobo; Li, Shanqun; Li, Xiao; Pak, Koon Y; Shi, Hongcheng; Cheng, Dengfeng

    2015-07-01

    This study attempted to evaluate the feasibility of (99m)Tc-labeled glucarate ((99m)Tc-GLA) imaging in non-small cell lung cancer (NSCLC) and the potential tumor uptake mechanism. Cell lysates from two NSCLC cell lines, H292 and H1975, were immunoblotted with anti-glucose transporter 5 (GLUT5) antibody for Western blotting. Thereafter, the two cell lines were used to examine cellular uptake of (99m)Tc-GLA with or without fructose. SPECT/CT imaging studies were performed on small animals bearing H292 and H1975 tumors. Biodistribution studies were also conducted to achieve accurate tissue uptake of this tracer in two tumor models. Hematoxylin & eosin (H&E) staining and GLUT5, Ki67 and cytokeratin-7 (CK-7) immunohistochemistry (IHC) analysis were further investigated on tumor tissues. In Western blotting, H292 cells showed higher levels of GLUT5 compared to the H1975 cells. Meanwhile, the in vitro cell assays indicated GLUT5-dependent uptake of (99m)Tc-GLA in H292 and H1975 cells. The fructose competition assays showed a significant decrease in (99m)Tc-GLA uptake by H292 and H1975 cells when fructose was added. The (99m)Tc-GLA accumulation was as much as two-fold higher in H292 implanted tumors than in H1975 implanted tumors. (99m)Tc-GLA exhibited rapid clearance pharmacokinetics and reasonable uptake in human NSCLC H292 (1.69±0.37 ID%/g) and H1975 (0.89±0.06 ID%/g) implanted tumors at 30min post injection. Finally, the expression of GLUT5, Ki67 and CK-7 on tumor tissues also exhibited positive correlation with the in vitro cell test results and in vivo SPECT/CT imaging results in xenograft tumors. Both in vitro and ex vivo studies demonstrated that the uptake of (99m)Tc-GLA in NSCLC is highly related to GLUT5 expression. Imaging and further IHC results support that (99m)Tc-GLA could be a promising SPECT imaging agent for NSCLC diagnosis and prognosis evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. First application of liquid-metal-jet sources for small-animal imaging: High-resolution CT and phase-contrast tumor demarcation

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, Daniel H.; Lundstroem, Ulf; Burvall, Anna; Hertz, Hans M. [Department of Applied Physics, KTH Royal Institute of Technology/Albanova, 10691 Stockholm (Sweden); Westermark, Ulrica K.; Arsenian Henriksson, Marie [Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, 17177 Stockholm (Sweden)

    2013-02-15

    Purpose: Small-animal studies require images with high spatial resolution and high contrast due to the small scale of the structures. X-ray imaging systems for small animals are often limited by the microfocus source. Here, the authors investigate the applicability of liquid-metal-jet x-ray sources for such high-resolution small-animal imaging, both in tomography based on absorption and in soft-tissue tumor imaging based on in-line phase contrast. Methods: The experimental arrangement consists of a liquid-metal-jet x-ray source, the small-animal object on a rotating stage, and an imaging detector. The source-to-object and object-to-detector distances are adjusted for the preferred contrast mechanism. Two different liquid-metal-jet sources are used, one circulating a Ga/In/Sn alloy and the other an In/Ga alloy for higher penetration through thick tissue. Both sources are operated at 40-50 W electron-beam power with {approx}7 {mu}m x-ray spots, providing high spatial resolution in absorption imaging and high spatial coherence for the phase-contrast imaging. Results: High-resolution absorption imaging is demonstrated on mice with CT, showing 50 {mu}m bone details in the reconstructed slices. High-resolution phase-contrast soft-tissue imaging shows clear demarcation of mm-sized tumors at much lower dose than is required in absorption. Conclusions: This is the first application of liquid-metal-jet x-ray sources for whole-body small-animal x-ray imaging. In absorption, the method allows high-resolution tomographic skeletal imaging with potential for significantly shorter exposure times due to the power scalability of liquid-metal-jet sources. In phase contrast, the authors use a simple in-line arrangement to show distinct tumor demarcation of few-mm-sized tumors. This is, to their knowledge, the first small-animal tumor visualization with a laboratory phase-contrast system.

  19. Early prediction of therapy response and disease free survival after induction chemotherapy in stage III non-small cell lung cancer by FDG-PET: Correlation between tumor FDG-metabolism and morphometric tumor response

    International Nuclear Information System (INIS)

    Baum, R.P.; Schmuecking, M.; Niesen, A.; Przetak, C.; Griesinger, F.

    2002-01-01

    Aim: Chemotherapy with Docetaxel and Carboplatin (DC) has shown high response rates in advanced non-small cell lung cancer (NSCLC). Histologic tumor response after chemotherapy or combined chemoradiotherapy is strongly associated with systemic tumor control and potentially cure. Metabolic tumor response assessed by FDG-PET after induction VIP-chemotherapy has been shown to be predictive of outcome in NSCLC. The aim of the present study was to correlate the tumor FDG metabolism as measured by F-18 FDG-PET with morphometric findings after DC induction chemotherapy plus Erythropoietin (10,000 IU Epo s.c. three times a week). Material and Methods: In this prospective multicenter study, 54 patients with NSCLC stage IIIA (9 patients) or IIIB (45 patients) were enrolled and received neoadjuvant treatment with D 100 mg/m 2 d1 and C AUC 7.5 d2 q21 days for 4 cycles prior to surgery. Postoperatively, all patients received adjuvant radiotherapy. WB-PET-studies (ECAT Exact 47) were obtained p.i. of 400 MBq F-18 FDG. Standardized uptake values (SUV), metabolic tumor diameter (MTD) and metabolic tumor index (MTI SUV x MTD) were assessed. Image fusion of PET and CT data was applied on a HERMES computer. Results: Of 54 enrolled patients, 46 were evaluable for response by CT. 30/46 patients (65%) achieved complete remission (CR, 1 patient) or partial remission (PR 29 patients.). Of the 46 patients, 37 patients completed neoadjuvant chemotherapy (Chx) and were studied before and after Chx by FDG-PET. 14 (30% of the 46 evaluable patients) had SUV < 2.5, corresponding to metabolic complete remission (mCR), 23 had PR or stable disease (non-mCR); in 9 patients, PET was not performed because of progressive disease demonstrated by CT. The R0-resection rate was 56% (27/48 evaluable patients). Of the 14 patients with metabolic CR, 9 were evaluated by morphometry. All had regression grades III (no vital tumor cells) or grade IIB (< 10% vital tumor cells and induced apoptosis). With a median

  20. Risk-stratifying capacity of PET/CT metabolic tumor volume in stage IIIA non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Finkle, Joshua H.; Jo, Stephanie Y.; Yuan, Cindy; Pu, Yonglin [University of Chicago, Department of Radiology, Chicago, IL (United States); Ferguson, Mark K. [University of Chicago, Department of Surgery, Chicago, IL (United States); Liu, Hai-Yan [First Hospital of Shanxi Medical University, Department of Nuclear Medicine, Taiyuan, Shanxi (China); Zhang, Chenpeng [Shanghai Jiao Tong University, Department of Nuclear Medicine, RenJi Hospital, School of Medicine, Shanghai (China); Zhu, Xuee [Nanjing Medical University, Department of Radiology, BenQ Medical Center, Nanjing, Jiangsu Province (China)

    2017-08-15

    Stage IIIA non-small cell lung cancer (NSCLC) is heterogeneous in tumor burden, and its treatment is variable. Whole-body metabolic tumor volume (MTV{sub WB}) has been shown to be an independent prognostic index for overall survival (OS). However, the potential of MTV{sub WB} to risk-stratify stage IIIA NSCLC has previously been unknown. If we can identify subgroups within the stage exhibiting significant OS differences using MTV{sub WB}, MTV{sub WB} may lead to adjustments in patients' risk profile evaluations and may, therefore, influence clinical decision making regarding treatment. We estimated the risk-stratifying capacity of MTV{sub WB} in stage IIIA by comparing OS of stratified stage IIIA with stage IIB and IIIB NSCLC. We performed a retrospective review of 330 patients with clinical stage IIB, IIIA, and IIIB NSCLC diagnosed between 2004 and 2014. The patients' clinical TNM stage, initial MTV{sub WB}, and long-term survival data were collected. Patients with TNM stage IIIA disease were stratified by MTV{sub WB}. The optimal MTV{sub WB} cutoff value for stage IIIA patients was calculated using sequential log-rank tests. Univariate and multivariate cox regression analyses and Kaplan-Meier OS analysis with log-rank tests were performed. The optimal MTV{sub WB} cut-point was 29.2 mL for the risk-stratification of stage IIIA. We identified statistically significant differences in OS between stage IIB and IIIA patients (p < 0.01), between IIIA and IIIB patients (p < 0.01), and between the stage IIIA patients with low MTV{sub WB} (below 29.2 mL) and the stage IIIA patients with high MTV{sub WB} (above 29.2 mL) (p < 0.01). There was no OS difference between the low MTV{sub WB} stage IIIA and the cohort of stage IIB patients (p = 0.485), or between the high MTV{sub WB} stage IIIA patients and the cohort of stage IIIB patients (p = 0.459). Similar risk-stratification capacity of MTV{sub WB} was observed in a large range of cutoff values from 15 to 55 mL in

  1. The anti-apoptotic BAG3 protein is expressed in lung carcinomas and regulates small cell lung carcinoma (SCLC) tumor growth.

    Science.gov (United States)

    Chiappetta, Gennaro; Basile, Anna; Barbieri, Antonio; Falco, Antonia; Rosati, Alessandra; Festa, Michelina; Pasquinelli, Rosa; Califano, Daniela; Palma, Giuseppe; Costanzo, Raffaele; Barcaroli, Daniela; Capunzo, Mario; Franco, Renato; Rocco, Gaetano; Pascale, Maria; Turco, Maria Caterina; De Laurenzi, Vincenzo; Arra, Claudio

    2014-08-30

    BAG3, member the HSP70 co-chaperones family, has been shown to play a relevant role in the survival, growth and invasiveness of different tumor types. In this study, we investigate the expression of BAG3 in 66 specimens from different lung tumors and the role of this protein in small cell lung cancer (SCLC) tumor growth. Normal lung tissue did not express BAG3 while we detected the expression of BAG3 by immunohistochemistry in all the 13 squamous cell carcinomas, 13 adenocarcinomas and 4 large cell carcinomas. Furthermore, we detected BAG3 expression in 22 of the 36 SCLCs analyzed. The role on SCLC cell survival was determined by down-regulating BAG3 levels in two human SCLC cell lines, i.e. H69 and H446, in vitro and measuring cisplatin induced apoptosis. Indeed down-regulation of BAG3 determines increased cell death and sensitizes cells to cisplatin treatment. The effect of BAG3 down-regulation on tumor growth was also investigated in an in vivo xenograft model by treating mice with an adenovirus expressing a specific bag3 siRNA. Treatment with bag3 siRNA-Ad significantly reduced tumor growth and improved animal survival. In conclusion we show that a subset of SCLCs over express BAG3 that exerts an anti-apoptotic effect resulting in resistance to chemotherapy.

  2. Adenosarcoma of the uterine body initially presenting as an interstitial small tumor of the uterus: a case report.

    Science.gov (United States)

    Miyata, H; Tsuji, N; Jimi, T; Butsuhara, Y; Terakawa, K; Nagano, T

    2014-01-01

    Adenosarcoma of the uterine body is a rare mixed tumor in which a benign epithelial component is mixed with a malignant stromal element. It has been considered that this tumor originates from the endometrium and its most common finding of imaging is a polypoid tumor occupying the uterine cavity. The authors herein present a case of 37-year-old female with a complaint of abnormal vaginal bleeding. At the first visit, transvaginal ultrasound and magnetic resonance imaging (MRI) showed a round mass with a diameter of one cm in the uterine wall. No malignant pathological finding was detected. The patient visited the authors again one year later, because of continuous bleeding. At that time, they found a polypoid tumor in the uterine cavity, which turned out to be adenosarcoma with sarcomatous overgrowth. The round mass in the uterus detected at first time seems to have been incipience of adenosarcoma. Prodromal sign of adenosarcoma has not been reported previously.

  3. Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

    Science.gov (United States)

    2016-12-01

    ABT-263 (Fig. 2I and SI Appendix, Fig. S6A). We therefore sought to identify pharmacological strategies that could suppress MCL-1 levels and increase...resonance imaging ( MRI ) of the thorax was performed 1 day before starting treatment and on day 21 of treatment, and lung tumor volumes pre- and...spread on MRI were included in the analysis. Tumors progressed in all untreated animals (n = 7), although we observed significant variability in the

  4. Tumor implantation model for rapid testing of lymphatic dye uptake from paw to node in small animals

    Science.gov (United States)

    DSouza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; Barth, Richard J.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

    2015-03-01

    Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully deploy and test an intra-nodal cancer-cell injection model to enable planar fluorescence imaging of a clinically relevant blue dye, specifically methylene blue - used in the sentinel lymph node procedure - in normal and tumor-bearing animals, and subsequently segregate tumor-bearing from normal lymph nodes. This direct-injection based tumor model was employed in athymic rats (6 normal, 4 controls, 6 cancer-bearing), where luciferase-expressing breast cancer cells were injected into axillary lymph nodes. Tumor presence in nodes was confirmed by bioluminescence imaging before and after fluorescence imaging. Lymphatic uptake from the injection site (intradermal on forepaw) to lymph node was imaged at approximately 2 frames/minute. Large variability was observed within each cohort.

  5. Restoration of tumor suppressor gene function by gene replacement or small molecule strategies for the treatment of small cell lung cancer

    DEFF Research Database (Denmark)

    Zandi, Roza

    2011-01-01

    markedly. PRIMA-1 Met also induced significant tumor growth delay in human SCLC mouse models without any signs of toxicity. These results suggest that PRIMA-1 Met can reactivate mutant p53 in SCLC cells, leading to the induction of apoptosis and tumor growth delay. To study the growth inhibitory effect......-mediated gene transfer in SCLC cells expressing various levels of endogenous FHIT protein. FHIT overexpression led to growth inhibition in all of the SCLC cell lines studied; although more effectively in cell lines with high levels of endogenous FHIT protein and transduction efficiency. FHIT-induced inhibition...... as potential therapeutic strategies for SCLC. However, as mutant p53 proteins tend to accumulate in SCLC cells, reintroduction of wild-type p53 may not be effective due to dominant-negative effects of the mutant protein. Therefore, a more effective approach would be to reactivate the endogenous mutant p53...

  6. Primary carcinoid tumor arising within mature teratoma of the kidney: report of a rare entity and review of the literature

    Directory of Open Access Journals (Sweden)

    Parwani Anil V

    2007-05-01

    Full Text Available Abstract Background Primary carcinoid tumor arising within mature teratoma of the kidney is extremely rare, and their clinicopathologic features are not well described. Our objective was to further define the clinical features and pathologic spectra of primary carcinoid tumor arising within mature teratoma of the kidney. Methods Six previously reported case reports were identified using MEDLINE and a subsequent bibliographic search of all pertinent reports and reviews was performed. We also searched the electronic medical archival records of our institution and identified one additional unreported case. Data were extracted on the demographics, predisposing factors, clinical presentation, radiographic features, gross pathology, microscopic pathology, immunophenotype, therapy, and outcome of each of these seven cases. Results Primary carcinoid tumor arising within mature teratoma of the kidney was found at a mean age of 41.4 years. Of the 7 cases, 3 were female and 4 were male. Two of the 7 cases (28.6% were associated with horseshoe kidney. It typically presented with abdominal pain without carcinoid syndrome. It typical radiologic appearance was well circumscribed partly calcified Bosniak II-III lesion. Histologically, the carcinoid tumor showed monotonous small round cells arranged in classic anastomosing cords/ribbons intermixed with solid nests. Surgery was curative, no additional treatment was required, no local recurrences occurred, and no metastases occurred in all 7 cases. The 3 cases with available outcome data were alive at the time of publication of their respective cases (mean, 5 months. Conclusion Primary carcinoid tumor arising within mature teratoma of the kidney is a rare tumor that typically presents with abdominal pain without carcinoid syndrome. It is not associated with local recurrence and metastasis, is surgically curable, and has excellent prognosis.

  7. Are pretreatment 18F-FDG PET tumor textural features in non-small cell lung cancer associated with response and survival after chemoradiotherapy?

    Science.gov (United States)

    Cook, Gary J R; Yip, Connie; Siddique, Muhammad; Goh, Vicky; Chicklore, Sugama; Roy, Arunabha; Marsden, Paul; Ahmad, Shahreen; Landau, David

    2013-01-01

    There is evidence in some solid tumors that textural features of tumoral uptake in (18)F-FDG PET images are associated with response to chemoradiotherapy and survival. We have investigated whether a similar relationship exists in non-small cell lung cancer (NSCLC). Fifty-three patients (mean age, 65.8 y; 31 men, 22 women) with NSCLC treated with chemoradiotherapy underwent pretreatment (18)F-FDG PET/CT scans. Response was assessed by CT Response Evaluation Criteria in Solid Tumors (RECIST) at 12 wk. Overall survival (OS), progression-free survival (PFS), and local PFS (LPFS) were recorded. Primary tumor texture was measured by the parameters coarseness, contrast, busyness, and complexity. The following parameters were also derived from the PET data: primary tumor standardized uptake values (SUVs) (mean SUV, maximum SUV, and peak SUV), metabolic tumor volume, and total lesion glycolysis. Compared with nonresponders, RECIST responders showed lower coarseness (mean, 0.012 vs. 0.027; P = 0.004) and higher contrast (mean, 0.11 vs. 0.044; P = 0.002) and busyness (mean, 0.76 vs. 0.37; P = 0.027). Neither complexity nor any of the SUV parameters predicted RECIST response. By Kaplan-Meier analysis, OS, PFS, and LPFS were lower in patients with high primary tumor coarseness (median, 21.1 mo vs. not reached, P = 0.003; 12.6 vs. 25.8 mo, P = 0.002; and 12.9 vs. 20.5 mo, P = 0.016, respectively). Tumor coarseness was an independent predictor of OS on multivariable analysis. Contrast and busyness did not show significant associations with OS (P = 0.075 and 0.059, respectively), but PFS and LPFS were longer in patients with high levels of each (for contrast: median of 20.5 vs. 12.6 mo, P = 0.015, and median not reached vs. 24 mo, P = 0.02; and for busyness: median of 20.5 vs. 12.6 mo, P = 0.01, and median not reached vs. 24 mo, P = 0.006). Neither complexity nor any of the SUV parameters showed significant associations with the survival parameters. In NSCLC, baseline (18)F

  8. Comparison of three approaches to delineate internal gross tumor volume based on four-dimensional CT simulation images of non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Li Fengxiang; Li Jianbin; Zhang Yingjie; Shang Dongping; Liu Tonghai; Tian Shiyu; Xu Min; Ma Changsheng

    2011-01-01

    Objective: To compare positional and volumetric differences of internal gross tumor volume (IGTV) delineated separately by three approaches based on four-dimensional CT (4DCT) for the primary tumor of non-small cell lung cancer (NLCLC). Methods: Twenty-one patients with NLCLC underwent big bore 4DCT simulation scan of the thorax. IGTVs of the primary tumor of NSCLC were delineated using three approaches as followed: (1) the gross tumor volume (GTV) on each of the ten the respiratory phases of the 4DCT image set were delineated and the ten GTV were fused to produce IGTV 10 ; (2) the GTV delineated separately based on 0% and 50% phase were fused to produce IGTV EI+EE ; (3) the visible tumor on the MIP images were delineated to produce IGTV MIP . The position of the target center, the volume of target, the degree of inclusion (DI) and the matching index (MI) were compared reciprocally between IGTV 10 , IGTV EI+EE and IGTV MIP . Results: Average differences between the position of the center of IGTVs on direction of x, y and z axes were less than 1 mm, with no statistically significant difference. The volume of IGTV 10 was larger than that of IGTV EI+EE , the difference was statistically significant (t=2.37, P=0.028); the volume of IGTV 10 was larger than that of IGTV MIP , but the difference was not statistically significant (t=1.95, P=0.065). The ratio of IGTV EI+EE with IGTV 10 , IGTV MIP with IGTV 10 were 0.85±0.08 and 0.92±0.11, respectively. DI of IGTV EI+EE in IGTV 10 , IGTV MIP in IGTV 10 were 84.78% ± 8. 95% and 88.47% ±9.04%. MI between IGTV 10 and IGTV EI+EE , IGTV 10 and IGTV MIP were 0.85 ±0.09, 0.86±0.09, respectively. Conclusions: The center displacement of the IGTVs delineated separately by the three different techniques based on 4DCT images are not obvious; IGTV EI+EE and IGTV MIP can not replace IGTV 10 , however, IGTV MIP is more close to IGTV 10 comparing to IGTV EI+EE . The ratio of GTV EI+EE with IGTV 10 is correlated to the tumor motion

  9. Simultaneous down-regulation of tumor suppressor genes RBSP3/CTDSPL, NPRL2/G21 and RASSF1A in primary non-small cell lung cancer

    International Nuclear Information System (INIS)

    Senchenko, Vera N; Zabarovsky, Eugene R; Anedchenko, Ekaterina A; Kondratieva, Tatiana T; Krasnov, George S; Dmitriev, Alexei A; Zabarovska, Veronika I; Pavlova, Tatiana V; Kashuba, Vladimir I; Lerman, Michael I

    2010-01-01

    The short arm of human chromosome 3 is involved in the development of many cancers including lung cancer. Three bona fide lung cancer tumor suppressor genes namely RBSP3 (AP20 region),NPRL2 and RASSF1A (LUCA region) were identified in the 3p21.3 region. We have shown previously that homozygous deletions in AP20 and LUCA sub-regions often occurred in the same tumor (P < 10 -6 ). We estimated the quantity of RBSP3, NPRL2, RASSF1A, GAPDH, RPN1 mRNA and RBSP3 DNA copy number in 59 primary non-small cell lung cancers, including 41 squamous cell and 18 adenocarcinomas by real-time reverse transcription-polymerase chain reaction based on TaqMan technology and relative quantification. We evaluated the relationship between mRNA level and clinicopathologic characteristics in non-small cell lung cancer. A significant expression decrease (≥2) was found for all three genes early in tumor development: in 85% of cases for RBSP3; 73% for NPRL2 and 67% for RASSF1A (P < 0.001), more strongly pronounced in squamous cell than in adenocarcinomas. Strong suppression of both, NPRL2 and RBSP3 was seen in 100% of cases already at Stage I of squamous cell carcinomas. Deregulation of RASSF1A correlated with tumor progression of squamous cell (P = 0.196) and adenocarcinomas (P < 0.05). Most likely, genetic and epigenetic mechanisms might be responsible for transcriptional inactivation of RBSP3 in non-small cell lung cancers as promoter methylation of RBSP3 according to NotI microarrays data was detected in 80% of squamous cell and in 38% of adenocarcinomas. With NotI microarrays we tested how often LUCA (NPRL2, RASSF1A) and AP20 (RBSP3) regions were deleted or methylated in the same tumor sample and found that this occured in 39% of all studied samples (P < 0.05). Our data support the hypothesis that these TSG are involved in tumorigenesis of NSCLC. Both genetic and epigenetic mechanisms contribute to down-regulation of these three genes representing two tumor suppressor clusters in 3p21

  10. Prognostic impact of radiation therapy to the primary tumor in patients with non-small cell lung cancer and oligometastasis at diagnosis.

    Science.gov (United States)

    Lopez Guerra, Jose Luis; Gomez, Daniel; Zhuang, Yan; Hong, David S; Heymach, John V; Swisher, Stephen G; Lin, Steven H; Komaki, Ritsuko; Cox, James D; Liao, Zhongxing

    2012-09-01

    We investigated prognostic factors associated with survival in patients with non-small cell lung cancer (NSCLC) and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis. From January 2000 through June 2011, 78 consecutive patients with oligometastatic NSCLC (oligometastasis (P=.041), had a Karnofsky performance status (KPS) score >80 (P=.007), had a gross tumor volume ≤124 cm³ (P=.002), had adenocarcinoma histology (P=.002), or had no history of respiratory disease (P=.016). On multivariate analysis, radiation dose, performance status, and tumor volume retained significance (P=.004, P=.006, and P<.001, respectively). The radiation dose also maintained significance when patients with and without brain metastases were analyzed separately. Tumor volume, KPS, and receipt of at least 63 Gy to the primary tumor are associated with improved OS in patients with oligometastatic NSCLC at diagnosis. Our results suggest that a subset of such patients may benefit from definitive local therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Integrin-Targeted Hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography for Imaging Tumor Progression and Early Response in Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaopeng Ma

    2017-01-01

    Full Text Available Integrins play an important role in tumor progression, invasion and metastasis. Therefore we aimed to evaluate a preclinical imaging approach applying ανβ3 integrin targeted hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT for monitoring tumor progression as well as early therapy response in a syngeneic murine Non-Small Cell Lung Cancer (NSCLC model. Lewis Lung Carcinomas were grown orthotopically in C57BL/6 J mice and imaged in-vivo using a ανβ3 targeted near-infrared fluorescence (NIRF probe. ανβ3-targeted FMT-XCT was able to track tumor progression. Cilengitide was able to substantially block the binding of the NIRF probe and suppress the imaging signal. Additionally mice were treated with an established chemotherapy regimen of Cisplatin and Bevacizumab or with a novel MEK inhibitor (Refametinib for 2 weeks. While μCT revealed only a moderate slowdown of tumor growth, ανβ3 dependent signal decreased significantly compared to non-treated mice already at one week post treatment. ανβ3 targeted imaging might therefore become a promising tool for assessment of early therapy response in the future.

  12. Genetic and Epigenetic Tumor Suppressor Gene Silencing are Distinct Molecular Phenotypes Driven by Growth Promoting Mutations in Non small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Marsit, C. J.; Kelsey, K. T.; Houseman, E. A.; Kelsey, K. T.; Houseman, E. A.; Nelson, H. H.

    2008-01-01

    Both genetic and epigenetic alterations characterize human non small cell lung cancer (NSCLC), but the biological processes that create or select these alterations remain incompletely investigated. Our hypothesis posits that a roughly reciprocal relationship between the propensity for promoter hyper methylation and a propensity for genetic deletion leads to distinct molecular phenotypes of lung cancer. To test this hypothesis, we examined promoter hyper methylation of 17 tumor suppressor genes, as a marker of epigenetic alteration propensity, and deletion events at the 3p21 region, as a marker of genetic alteration. To model the complex biology between these somatic alterations, we utilized an item response theory model. We demonstrated that tumors exhibiting LOH at greater than 30% of informative alleles in the 3p21 region have a significantly reduced propensity for hyper methylation. At the same time, tumors with activating KRAS mutations showed a significantly increased propensity for hyper methylation of the loci examined, a result similar to what has been observed in colon cancer. These data suggest that NSCLCs have distinct epigenetic or genetic alteration phenotypes acting upon tumor suppressor genes and that mutation of oncogenic growth promoting genes, such as KRAS, is associated with the epigenetic phenotype.

  13. Prognostic Impact of Radiation Therapy to the Primary Tumor in Patients With Non-small Cell Lung Cancer and Oligometastasis at Diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Guerra, Jose Luis [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Instituto Madrileno de Oncologia/Grupo IMO, Madrid (Spain); Gomez, Daniel, E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang, Yan; Hong, David S. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Heymach, John V. [Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Swisher, Stephen G. [Department of Thoracic Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H.; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-09-01

    Purpose: We investigated prognostic factors associated with survival in patients with non-small cell lung cancer (NSCLC) and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis. Methods and Materials: From January 2000 through June 2011, 78 consecutive patients with oligometastatic NSCLC (<5 metastases) at diagnosis underwent definitive chemoradiation therapy ({>=}45 Gy) to the primary site. Forty-four of these patients also received definitive local treatment for the oligometastases. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results: Univariate Cox proportional hazard analysis revealed better overall survival (OS) for those patients who received at least 63 Gy of radiation to the primary site (P=.002), received definitive local treatment for oligometastasis (P=.041), had a Karnofsky performance status (KPS) score >80 (P=.007), had a gross tumor volume {<=}124 cm{sup 3} (P=.002), had adenocarcinoma histology (P=.002), or had no history of respiratory disease (P=.016). On multivariate analysis, radiation dose, performance status, and tumor volume retained significance (P=.004, P=.006, and P<.001, respectively). The radiation dose also maintained significance when patients with and without brain metastases were analyzed separately. Conclusions: Tumor volume, KPS, and receipt of at least 63 Gy to the primary tumor are associated with improved OS in patients with oligometastatic NSCLC at diagnosis. Our results suggest that a subset of such patients may benefit from definitive local therapy.

  14. Analysis of primary tumor metabolic volume during chemoradiotherapy in locally advanced non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Roengvoraphoj, Olarn; Eze, Chukwuka; Li, Minglun; Dantes, Maurice; Taugner, Julian [LMU Munich, Department of Radiation Oncology, University Hospital, Munich (Germany); Wijaya, Cherylina [Asklepios Fachkliniken Muenchen-Gauting, Department of Pulmonology, Munich (Germany); Tufman, Amanda; Huber, Rudolf Maria [Ludwig-Maximilians-University of Munich and Thoracic Oncology Centre Munich, Respiratory Medicine and Thoracic Oncology, Internal Medicine V, Munich (Germany); German Centre for Lung Research (DZL CPC-M) (Germany); Belka, Claus; Manapov, Farkhad [LMU Munich, Department of Radiation Oncology, University Hospital, Munich (Germany); German Centre for Lung Research (DZL CPC-M) (Germany)

    2018-02-15

    Positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-d-glucose integrated with computed tomography (18F-FDG-PET/CT) has an established role in the initial diagnosis and staging of lung cancer. However, a prognostic value of PET/CT during multimodality treatment has not yet been fully clarified. This study evaluated the role of primary tumor metabolic volume (PT-MV) changes on PET/CT before, during, and after chemoradiotherapy (CRT). A total of 65 patients with non-small-cell lung cancer (NSCLC) UICC stage IIIA/B (TNM 7th Edition) were treated with definitive chemoradiotherapy (sequential or concurrent setting). PET/CT was acquired before the start, at the end of the third week, and 6 weeks following CRT. Median overall survival (OS) for the entire cohort was 16 months (95% confidence interval [CI]: 12-20). In all, 60 (92.3%) patients were eligible for pre-treatment (pre-PT-MV), 28 (43%) for mid-treatment (mid-PT-MV), and 53 (81.5%) for post-treatment (post-PT-MV) volume analysis. Patients with pre-PT-MV >63 cm{sup 3} had worse OS (p < 0.0001). A reduction from mid-PT-MV to post-PT-MV of >15% improved OS (p = 0.001). In addition, patients with post-PT-MV > 25 cm{sup 3} had significantly worse outcome (p = 0.001). On multivariate analysis, performance status (p = 0.002, hazard ratio [HR] 0.007; 95% CI 0.00-0.158), pre-PT-MV1 < 63 cm{sup 3} (p = 0.027, HR 3.98; 95% CI 1.17-13.49), post-PT-MV < 25 cm{sup 3} (p = 0.013, HR 11.90; 95% CI 1.70-83.27), and a reduction from mid-PT-MV to post-PT-MV > 15% (p = 0.004, HR 0.25; 95% CI 0.02-0.31) correlated with improved OS. Our results demonstrated that pre- and post-treatment PT-MV, as well as an at least 15% reduction in mid- to post-PT-MV, significantly correlates with OS in patients with inoperable locally advanced NSCLC. (orig.) [German] Die kombinierte Positronenemissionstomographie (PET) mit {sup 18}F-2-Fluor-2-desoxy-D-Glukose und Computertomographie ({sup 18}F-FDG-PET/CT) hat sich in der initialen

  15. Routine clinical use of circulating tumor cells for diagnosis of mutations and chromosomal rearrangements in non-small cell lung cancer-ready for prime-time?

    Science.gov (United States)

    Pailler, Emma; Faugeroux, Vincent; Oulhen, Marianne; Catelain, Cyril; Farace, Françoise

    2017-08-01

    In non-small cell lung cancer (NSCLC), diagnosis of predictive biomarkers for targeted therapies is currently done in small tumor biopsies. However, tumor biopsies can be invasive, in some cases associated with risk, and tissue adequacy, both in terms of quantity and quality is often insufficient. The development of efficient and non-invasive methods to identify genetic alterations is a key challenge which circulating tumor cells (CTCs) have the potential to be exploited for. CTCs are extremely rare and phenotypically diverse, two characteristics that impose technical challenges and impact the success of robust molecular analysis. Here we introduce the clinical needs in this disease that mainly consist of the diagnosis of epidermal growth factor receptor ( EGFR ) activating alterations and anaplastic lymphoma kinase ( ALK ) rearrangement. We present the proof-of-concept studies that explore the detection of these genetic alterations in CTCs from NSCLC patients. Finally, we discuss steps that are still required before CTCs are routinely used for diagnosis of EGFR -mutations and ALK -rearrangements in this disease.

  16. Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets

    NARCIS (Netherlands)

    Best, Myron G.; Sol, Nik; In ‘t Veld, Sjors G.J.G.; Vancura, Adrienne; Muller, Mirte; Niemeijer, Anna Larissa N.; Fejes, Aniko V.; Tjon Kon Fat, Lee Ann; Huis in 't Veld, Anna E; Leurs, Cyra; Le Large, Tessa Y.; Meijer, Laura L.; Kooi, Irsan E.; Rustenburg, François; Schellen, Pepijn; Verschueren, Heleen; Post, Edward; Wedekind, Laurine E.; Bracht, Jillian; Esenkbrink, Michelle; Wils, Leon; Favaro, Francesca; Schoonhoven, Jilian D.; Tannous, Jihane; Meijers-Heijboer, Hanne; Kazemier, Geert; Giovannetti, Elisa; Reijneveld, Jaap C.; Idema, Sander; Killestein, Joep; Heger, Michal; de Jager, Saskia C.; Urbanus, Rolf T.; Hoefer, Imo E.; Pasterkamp, Gerard; Mannhalter, Christine; Gomez-Arroyo, Jose; Bogaard, Harm-Jan; Noske, David P.; Vandertop, W. Peter; van den Broek, Daan; Ylstra, Bauke; Nilsson, R. Jonas A; Wesseling, Pieter; Karachaliou, Niki; Rosell, Rafael; Lee-Lewandrowski, Elizabeth; Lewandrowski, Kent B.; Tannous, Bakhos A.; de Langen, Adrianus J.; Smit, Egbert F.; van den Heuvel, Michel M; Wurdinger, Thomas

    2017-01-01

    Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from

  17. [Indication for limited surgery on small lung cancer tumors measuring 1cm or less in diameter on preoperative computed tomography and long-term results].

    Science.gov (United States)

    Togashi, K; Koike, T; Emura, I; Usuda, H

    2008-07-01

    Non-invasive lung cancers showed a good prognosis after limited surgery. But it is still uncertain about invasive lung cancers. We investigated the indications for limited surgery for small lung cancer tumors measuring 1 cm or less in diameter on preoperative computed tomography (CT). This study retrospectively analyzed of 1,245 patients who underwent complete resection of lung cancer between 1989 and 2004 in our hospital. Sixty-two patients (5%) had tumors measuring 1 cm or less in diameter. The probability of survival was calculated using the Kaplan-Meier method. All diseases were detected by medical checkup, 52 % of the patients were not definitively diagnosed with lung cancer before surgery. Adenocarcinoma was histologically diagnosed in 49 patients (79%). Other histologic types included squamous cell carcinoma (8), large cell carcinoma (1), small cell carcinoma (1), carcinoid (2), and adenosquamous cell carcinoma (1). Fifty-seven patients (92%) showed pathologic stage IA. The other stages were IB (2), IIA (1), and IIIB (2). There were 14 bronchioloalveolar carcinomas (25% of IA diseases). The 5-year survival rates of IA patients were 90%. The 5-year survival rate of patients with tumors measuring 1cm or less diameter was 91% after lobectomy or pneumonectomy, and 90% after wedge resection or segmentectomy. There were 3 deaths from cancer recurrence, while there were no deaths in 14 patients with bronchioloalveolar carcinoma After limited surgery, non-invasive cancer showed good long-term results, while invasive cancer showed a recurrence rate of 2.3% to 79% even though the tumor measured 1 cm or less in diameter on preoperative CT.

  18. SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Lindsay, WD; Berlind, CG; Gee, JC; Simone, CB

    2015-01-01

    Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

  19. SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, WD [University of Pennsylvania, Philadelphia, PA (United States); Oncora Medical, LLC, Philadelphia, PA (United States); Berlind, CG [Georgia Institute of Technology, Atlanta, GA (Georgia); Oncora Medical, LLC, Philadelphia, PA (United States); Gee, JC; Simone, CB [University of Pennsylvania, Philadelphia, PA (United States)

    2015-06-15

    Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

  20. CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical Patients with Stage I Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Viola J.; Oermann, Eric [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States); Vahdat, Saloomeh [Department of Pathology, Georgetown University Hospital, Washington, DC (United States); Rabin, Jennifer; Suy, Simeng; Yu, Xia; Collins, Sean P. [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States); Subramaniam, Deepa [Division of Hematology and Oncology, Georgetown University Hospital, Washington, DC (United States); Banovac, Filip [Department of Radiology, Georgetown University Hospital, Washington, DC (United States); Anderson, Eric [Division of Pulmonary, Critical Care and Sleep Medicine, Georgetown University Hospital, Washington, DC (United States); Collins, Brian T., E-mail: collinsb@gunet.georgetown.edu [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States)

    2012-02-01

    Published data suggests that wedge resection for stage I non-small cell lung cancer (NSCLC) is associated with improved overall survival compared to stereotactic body radiation therapy. We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed for staging. Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references. Gross tumor volumes (GTVs) were contoured using lung windows; the margins were expanded by 5 mm to establish the planning treatment volume (PTV). Treatment plans were designed using a mean of 156 pencil beams. Doses delivered to the PTV ranged from 42 to 60 Gy in three fractions. The 30 Gy isodose contour extended at least 1 cm from the GTV to eradicate microscopic disease. Treatments were delivered using the CyberKnife system with tumor tracking. Examination and PET/CT imaging occurred at 3 month follow-up intervals. Forty patients (median age 76) with a median maximum tumor diameter of 2.6 cm (range, 1.4–5.0 cm) and a mean post-bronchodilator percent predicted forced expiratory volume in 1 s (FEV1) of 57% (range, 21–111%) were treated. A median dose of 48 Gy was delivered to the PTV over 3–13 days (median, 7 days). The 30 Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44 months (range, 12–72 months) follow-up, the 3 year Kaplan–Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91 and 75%, respectively. CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection, eradicating tumors with 1–2 cm margins in order to preserve lung function. Prospective randomized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence.

  1. Downregulation of miR-497 promotes tumor growth and angiogenesis by targeting HDGF in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Zhao, Wen-yan; Wang, Yan; An, Zhong-jun; Shi, Chang-guo; Zhu, Guang-ai; Wang, Bin; Lu, Ming-yan; Pan, Chang-kun; Chen, Peng

    2013-01-01

    Highlights: •MiR-497 is down-regulated in NSCLC cells and tissues. •MiR-497 inhibits NSCLC cell growth in vitro. •HDGF is a target gene of miR-497. •MiR-497 inhibits NSCLC cell growth by downregulating HDGF. •miR-497 inhibits tumor growth and angiogenesis in vivo. -- Abstract: MicroRNAs (miRNAs) play important roles in the development of various cancers. MiRNA-497 functions as a tumor-suppressor that is downregulated in several malignancies; however, its role in non-small cell lung cancer (NSCLC) has not been examined in detail. Here, we showed that miR-497 is downregulated in NSCLC tumors and cell lines and its ectopic expression significantly inhibits cell proliferation and colony formation. Integrated analysis identified HDGF as a downstream target of miR-497, and the downregulation of HDGF by miR-497 overexpression confirmed their association. Rescue experiments showed that the inhibitory effect of miR-497 on cell proliferation and colony formation is predominantly mediated by the modulation of HDGF levels. Furthermore, tumor samples from NSCLC patients showed an inverse relationship between miR-497 and HDGF levels, and ectopic expression of miR-497 significantly inhibited tumor growth and angiogenesis in a SCID mouse xenograft model. Our results suggest that miR-497 may serve as a biomarker in NSCLC, and the modulation of its activity may represent a novel therapeutic strategy for the treatment of NSCLC patients

  2. Comparison of Tumor Volumes as Determined by Pathologic Examination and FDG-PET/CT Images of Non-Small-Cell Lung Cancer: A Pilot Study

    International Nuclear Information System (INIS)

    Yu Jinming; Li Xinke; Xing Ligang; Mu Dianbin; Fu Zheng; Sun Xiaorong; Sun Xiangyu; Yang Guoren; Zhang Baijiang; Sun Xindong; Ling, C. Clifton

    2009-01-01

    Purpose: To determine the cut-off standardized uptake value (SUV) on 18 F fluoro-2-deoxy-glucose (FDG) positron emission tomography/computed tomography (FDG-PET/CT) images that generates the best volumetric match to pathologic gross tumor volume (GTV path ) for non-small-cell lung cancer (NSCLC). Methods and Materials: Fifteen patients with NSCLC who underwent FDG-PET/CT scans followed by lobectomy were enrolled. The surgical specimen was dissected into 5-7-μm sections at approximately 4-mm intervals and stained with hematoxylin and eosin. The tumor-containing area was outlined slice by slice and the GTV path determined by summing over all the slices, taking into account the interslice thickness and fixation-induced volume reduction. The gross tumor volume from the PET images, GTV PET , was determined as a function of cut-off SUV. The optimal threshold or optimal absolute SUV was defined as the value at which the GTV PET was the same as the GTV path . Results: The fixation process induced a volumetric reduction to 82% ± 10% (range, 62-100%) of the original. The maximal SUV was 10.1 ± 3.6 (range, 4.2-18.7). The optimal threshold and absolute SUV were 31% ± 11% and 3.0 ± 1.6, respectively. The optimal threshold was inversely correlated with GTV path and tumor diameter (p path or tumor diameter (p > 0.05). Conclusion: This study evaluated the use of GTV path as a criterion for determining the optimal cut-off SUV for NSCLC target volume delineation. Confirmatory studies including more cases are being performed.

  3. Predicting tumor hypoxia in non-small cell lung cancer by combining CT, FDG PET and dynamic contrast-enhanced CT.

    Science.gov (United States)

    Even, Aniek J G; Reymen, Bart; La Fontaine, Matthew D; Das, Marco; Jochems, Arthur; Mottaghy, Felix M; Belderbos, José S A; De Ruysscher, Dirk; Lambin, Philippe; van Elmpt, Wouter

    2017-11-01

    Most solid tumors contain inadequately oxygenated (i.e., hypoxic) regions, which tend to be more aggressive and treatment resistant. Hypoxia PET allows visualization of hypoxia and may enable treatment adaptation. However, hypoxia PET imaging is expensive, time-consuming and not widely available. We aimed to predict hypoxia levels in non-small cell lung cancer (NSCLC) using more easily available imaging modalities: FDG-PET/CT and dynamic contrast-enhanced CT (DCE-CT). For 34 NSCLC patients, included in two clinical trials, hypoxia HX4-PET/CT, planning FDG-PET/CT and DCE-CT scans were acquired before radiotherapy. Scans were non-rigidly registered to the planning CT. Tumor blood flow (BF) and blood volume (BV) were calculated by kinetic analysis of DCE-CT images. Within the gross tumor volume, independent clusters, i.e., supervoxels, were created based on FDG-PET/CT. For each supervoxel, tumor-to-background ratios (TBR) were calculated (median SUV/aorta SUV mean ) for HX4-PET/CT and supervoxel features (median, SD, entropy) for the other modalities. Two random forest models (cross-validated: 10 folds, five repeats) were trained to predict the hypoxia TBR; one based on CT, FDG, BF and BV, and one with only CT and FDG features. Patients were split in a training (trial NCT01024829) and independent test set (trial NCT01210378). For each patient, predicted, and observed hypoxic volumes (HV) (TBR > 1.2) were compared. Fifteen patients (3291 supervoxels) were used for training and 19 patients (1502 supervoxels) for testing. The model with all features (RMSE training: 0.19 ± 0.01, test: 0.27) outperformed the model with only CT and FDG-PET features (RMSE training: 0.20 ± 0.01, test: 0.29). All tumors of the test set were correctly classified as normoxic or hypoxic (HV > 1 cm 3 ) by the best performing model. We created a data-driven methodology to predict hypoxia levels and hypoxia spatial patterns using CT, FDG-PET and DCE-CT features in NSCLC. The

  4. Reproducibility of 'Intelligent' Contouring of Gross Tumor Volume in Non-Small-Cell Lung Cancer on PET/CT Images Using a Standardized Visual Method

    International Nuclear Information System (INIS)

    Bayne, Michael; Hicks, Rodney J.; Everitt, Sarah; Fimmell, Natalie

    2010-01-01

    Purpose: Positron emission tomography/computed tomography (PET/CT) is increasingly used for delineating gross tumor volume (GTV) in non-small-cell lung cancer (NSCLC). The methodology for contouring tumor margins remains controversial. We developed a rigorous visual protocol for contouring GTV that uses all available clinical information and studied its reproducibility in patients from a prospective PET/CT planning trial. Methods and Materials: Planning PET/CT scans from 6 consecutive patients were selected. Six 'observers' (two radiation oncologists, two nuclear medicine physicians, and two radiologists) contoured GTVs for each patient using a predefined protocol and subsequently recontoured 2 patients. For the estimated GTVs and axial distances, least-squares means for each observer and for each case were calculated and compared, using the F test and pairwise t-tests. In five cases, tumor margins were also autocontoured using standardized uptake value (SUV) cutoffs of 2.5 and 3.5 and 40% SUV max . Results: The magnitude of variation between observers was small relative to the mean (coefficient of variation [CV] = 3%), and the total variation (intraclass correlation coefficient [ICC] = 3%). For estimation of superior/inferior (SI), left/right (LR), and anterior/posterior (AP) borders of the GTV, differences between observers were also small (AP, CV = 2%, ICC = 0.4%; LR, CV = 6%, ICC = 2%; SI, CV 4%, ICC = 2%). GTVs autocontoured generated using SUV 2.5, 3.5, and 40% SUV max differed widely in each case. An SUV contour of 2.5 was most closely correlated with the mean GTV defined by the human observers. Conclusions: Observer variation contributed little to total variation in the GTV and axial distances. A visual contouring protocol gave reproducible results for contouring GTV in NSCLC.

  5. A case of limbic encephalitis with small cell lung carcinoma in which the cognitive function improved and redeteriorated during tumor therapy

    International Nuclear Information System (INIS)

    Fujimoto, So; Yamaguchi, Yasuhiro; Gotanda, Hiroshi

    2010-01-01

    We report the findings regarding a 70-year-old man with paraneoplastic limbic encephalitis. He presented with a chief complaint of inability to recall any events. He had been well until one month before admission, and then he abruptly began to show progressive amnesia. At admission, the patient's score on the Revised Hasegawa Dementia Scale (HDS-R) showed a decline to 13/30, thus indicating the existence of severe disorientation and an impaired memory. The brain CT and electroencephalogram (EEG) showed no specific abnormalities and an analysis of cerebrospinal fluid showed only a mild increase in the total protein level. A chest X-ray film revealed a mass in the right hilum, while a histological analysis of the biopsied specimen finally established a diagnosis of small cell lung carcinoma. The fluorodeoxyglucose (FDG)-positron emission tomography (PET) and the enhanced brain MRI showed a single small metastatic lesion in the cerebellum. After the 1st course of chemotherapy and whole brain radiation, cognitive function, especially the short-term memory, remarkably improved and the HDS-R score increased to 21/30. However, the tumor again increased in size during the 3rd and 4th courses of chemotherapy. Interestingly, cognitive function also worsened again and the score of HDS-R declined to 15/30, 20 weeks after the start of chemotherapy. Limbic encephalitis can be associated with malignant tumors, such as small cell lung carcinoma, and some reported cases have shown a cognitive improvement after tumor therapy. In our case, we also observed a reworsening of the cognitive function in association with the acquired chemoresistence. (author)

  6. Radioimmunotherapy of small cell lung cancer xenograft mice with a 90Y anti-ROBO1 monoclonal antibody: Pathological study of effects on tumor and normal organs

    International Nuclear Information System (INIS)

    Fujiwara, K.; Koyama, K.; Kitada, T.; Takahashi, M.; Momose, T.; Suga, K.

    2015-01-01

    Full text of publication follows. ROBO1 is a membrane protein that is concerned about axon guidance. It is reported that ROBO1 contributes to tumor metastasis and angio genesis. ROBO1 is specifically expressed at high levels in small cell lung cancer (SCLC). In this study, we performed radioimmunotherapy (RIT) to SCLC models, and analyzed pathological alteration of tumor and organs. Methods: For the biodistribution study, 111 In-DOTA anti-ROBO1 IgG (about 370 kBq, 111 In anti-ROBO1) was injected into NCI-H69 xenograft mice via tail vein. To evaluate antitumor effect, RIT study was performed. 90 Y-DOTA anti-ROBO1 IgG (about 7.4 MBq, 90 Y anti-ROBO1) was injected. The experiments measured tumor volume, mouse weights and blood cell counts periodically. The tumors and organs (liver, kidney, intestine, spleen, femoral and sternum) of mice were obtained, and histopathologic analysis were carried out. Results: as a result of biodistribution study, the specific accumulation in the tumor of 111 In anti-ROBO1 was observed. Liver, kidney, spleen and lung showed comparatively high accumulation of 111 In anti-ROBO1. In the RIT study, 90 Y anti-ROBO1 significantly reduced tumor volume compared with original volume and increased median survival time to 58 days (p<0.01, versus saline, 28 days), while 90 Y anti-ROBO1 induced transient pancytopenia. Histopathologic analysis of tumors and organs further validated the therapeutic efficacy and the systemic toxicity of 90 Y anti-ROBO1. In day 7 when tumor volume reduced to 60% compared with original volume, irreversible nuclear denaturation and fibrosis were observed. The percentage of TUNEL-positive cells increased to 11.4%±5.1 in the day 7 (p<0.01, versus control, 4.14%±1.4), which showed increase of DNA fragmentation and apoptosis in the tumor tissues. Normal organs excluding spleen and sternum showed no significant injury. In day 7 post injection, spleen showed transient reduction of hematopoietic cells. Hematopoietic cells in

  7. Cytomorphology and immunohistochemistry of extrarenal rhabdoid tumor: A case report with review of literature

    Directory of Open Access Journals (Sweden)

    Manjula Jain

    2011-01-01

    Full Text Available Extrarenal rhabdoid tumor (ERRT is a rare, aggressive tumor with extremely poor prognosis. We report a case of ERRT with intraspinal extension in a 1.5-year-old child diagnosed by fine needle aspiration cytology (FNAC and immunohistochemistry. The child presented with a right lumbar region lump of two months duration. Ultrasound guided FNAC was performed and cell block was prepared. Smears were highly cellular and showed a dispersed population of large round cells having abundant pale eosinophillic cytoplasm, centrally to eccentrically placed nucleus with large prominent nucleoli. Immunohistochemistry was carried out on cell block which was positive for epithelial membrane antigen EMA and Vimentin. It was negative for leucocyte common antigen [LCA], wilms tumor 1, WT1, desmin and neuron specific enolaseNSE, thus ruling out other tumors like lymphoma, Wilms tumor, rhabdomyosarcoma, and neuroblastoma. A final diagnosis of ERRT was given. ERRT is an extremely rare tumor of retroperitoneal area; it should be included in the differential diagnosis of malignant round cell tumor in children. Cell block in this case is mandatory for putting up the panel of immunohistochemistry which can clinch the diagnosis of rhabdoid tumor and treatment can be started as early as possible.

  8. Validation of Digital Microscopy Compared With Light Microscopy for the Diagnosis of Canine Cutaneous Tumors.

    Science.gov (United States)

    Bertram, Christof A; Gurtner, Corinne; Dettwiler, Martina; Kershaw, Olivia; Dietert, Kristina; Pieper, Laura; Pischon, Hannah; Gruber, Achim D; Klopfleisch, Robert

    2018-07-01

    Integration of new technologies, such as digital microscopy, into a highly standardized laboratory routine requires the validation of its performance in terms of reliability, specificity, and sensitivity. However, a validation study of digital microscopy is currently lacking in veterinary pathology. The aim of the current study was to validate the usability of digital microscopy in terms of diagnostic accuracy, speed, and confidence for diagnosing and differentiating common canine cutaneous tumor types and to compare it to classical light microscopy. Therefore, 80 histologic sections including 17 different skin tumor types were examined twice as glass slides and twice as digital whole-slide images by 6 pathologists with different levels of experience at 4 time points. Comparison of both methods found digital microscopy to be noninferior for differentiating individual tumor types within the category epithelial and mesenchymal tumors, but diagnostic concordance was slightly lower for differentiating individual round cell tumor types by digital microscopy. In addition, digital microscopy was associated with significantly shorter diagnostic time, but diagnostic confidence was lower and technical quality was considered inferior for whole-slide images compared with glass slides. Of note, diagnostic performance for whole-slide images scanned at 200× magnification was noninferior in diagnostic performance for slides scanned at 400×. In conclusion, digital microscopy differs only minimally from light microscopy in few aspects of diagnostic performance and overall appears adequate for the diagnosis of individual canine cutaneous tumors with minor limitations for differentiating individual round cell tumor types and grading of mast cell tumors.

  9. Prognostic Significance of Tumor Size of Small Lung Adenocarcinomas Evaluated with Mediastinal Window Settings on Computed Tomography

    OpenAIRE

    Sakao, Yukinori; Kuroda, Hiroaki; Mun, Mingyon; Uehara, Hirofumi; Motoi, Noriko; Ishikawa, Yuichi; Nakagawa, Ken; Okumura, Sakae

    2014-01-01

    BACKGROUND: We aimed to clarify that the size of the lung adenocarcinoma evaluated using mediastinal window on computed tomography is an important and useful modality for predicting invasiveness, lymph node metastasis and prognosis in small adenocarcinoma. METHODS: We evaluated 176 patients with small lung adenocarcinomas (diameter, 1-3 cm) who underwent standard surgical resection. Tumours were examined using computed tomography with thin section conditions (1.25 mm thick on high-resolution ...

  10. G-protein inwardly rectifying potassium channel 1 (GIRK 1) gene expression correlates with tumor progression in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Takanami, Iwao; Inoue, Yoshimasa; Gika, Masatoshi

    2004-01-01

    G-protein inwardly rectifying potassium channel 1 (GIRK1) is thought to play a role in cell proliferation in cancer, and GIRK1 gene expression level may define a more aggressive phenotype. We detected GIRK1 expression in tissue specimens from patients with non-small cell lung cancers (NSCLCs) and assessed their clinical characteristics. Using reverse transcription-polymerase chain reaction (RT-PCR) analyses, we quantified the expression of GIRK1 in 72 patients with NSCLCs to investigate the relationship between GIRK1 expression and clinicopathologic factors and prognosis. In 72 NSCLC patients, 50 (69%) samples were evaluated as having high GIRK1 gene expression, and 22 (31%) were evaluated as having low GIRK1 gene expression. GIRK1 gene expression was significantly associated with lymph node metastasis, stage (p = 0.0194 for lymph node metastasis; p = 0.0207 for stage). The overall and stage I survival rates for patients with high GIRK1 gene expressed tumors was significantly worse than for those individuals whose tumors had low GIRK1 expression (p = 0.0004 for the overall group; p = 0.0376 for stage I). These data indicate that GIRK1 may contribute to tumor progression and GIRK1 gene expression can serve as a useful prognostic marker in the overall and stage I NSCLCs

  11. Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma.

    Science.gov (United States)

    Patwardhan, Parag P; Ivy, Kathryn S; Musi, Elgilda; de Stanchina, Elisa; Schwartz, Gary K

    2016-01-26

    Sarcomas are rare but highly aggressive mesenchymal tumors with a median survival of 10-18 months for metastatic disease. Mutation and/or overexpression of many receptor tyrosine kinases (RTKs) including c-Met, PDGFR, c-Kit and IGF1-R drive defective signaling pathways in sarcomas. MGCD516 (Sitravatinib) is a novel small molecule inhibitor targeting multiple RTKs involved in driving sarcoma cell growth. In the present study, we evaluated the efficacy of MGCD516 both in vitro and in mouse xenograft models in vivo. MGCD516 treatment resulted in significant blockade of phosphorylation of potential driver RTKs and induced potent anti-proliferative effects in vitro. Furthermore, MGCD516 treatment of tumor xenografts in vivo resulted in significant suppression of tumor growth. Efficacy of MGCD516 was superior to imatinib and crizotinib, two other well-studied multi-kinase inhibitors with overlapping target specificities, both in vitro and in vivo. This is the first report describing MGCD516 as a potent multi-kinase inhibitor in different models of sarcoma, superior to imatinib and crizotinib. Results from this study showing blockade of multiple driver signaling pathways provides a rationale for further clinical development of MGCD516 for the treatment of patients with soft-tissue sarcoma.

  12. Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Hisao Imai

    2015-01-01

    Full Text Available Objectives: The effects of first-line chemotherapy on overall survival (OS might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC. We examined whether progression-free survival (PFS, post-progression survival (PPS, and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Methods: Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Results: Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R 2 = 0.94, PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.24, and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R 2 = 0.13. The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05. Conclusion: PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.

  13. Molecular-Targeted Immunotherapeutic Strategy for Melanoma via Dual-Targeting Nanoparticles Delivering Small Interfering RNA to Tumor-Associated Macrophages.

    Science.gov (United States)

    Qian, Yuan; Qiao, Sha; Dai, Yanfeng; Xu, Guoqiang; Dai, Bolei; Lu, Lisen; Yu, Xiang; Luo, Qingming; Zhang, Zhihong

    2017-09-26

    Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancer immunotherapy. Targeted delivery of therapeutic drugs to the tumor-promoting M2-like TAMs is challenging. Here, we developed M2-like TAM dual-targeting nanoparticles (M2NPs), whose structure and function were controlled by α-peptide (a scavenger receptor B type 1 (SR-B1) targeting peptide) linked with M2pep (an M2 macrophage binding peptide). By loading anti-colony stimulating factor-1 receptor (anti-CSF-1R) small interfering RNA (siRNA) on the M2NPs, we developed a molecular-targeted immunotherapeutic approach to specifically block the survival signal of M2-like TAMs and deplete them from melanoma tumors. We confirmed the validity of SR-B1 for M2-like TAM targeting and demonstrated the synergistic effect of the two targeting units (α-peptide and M2pep) in the fusion peptide (α-M2pep). After being administered to tumor-bearing mice, M2NPs had higher affinity to M2-like TAMs than to tissue-resident macrophages in liver, spleen, and lung. Compared with control treatment groups, M2NP-based siRNA delivery resulted in a dramatic elimination of M2-like TAMs (52%), decreased tumor size (87%), and prolonged survival. Additionally, this molecular-targeted strategy inhibited immunosuppressive IL-10 and TGF-β production and increased immunostimulatory cytokines (IL-12 and IFN-γ) expression and CD8 + T cell infiltration (2.9-fold) in the tumor microenvironment. Moreover, the siRNA-carrying M2NPs down-regulated expression of the exhaustion markers (PD-1 and Tim-3) on the infiltrating CD8 + T cells and stimulated their IFN-γ secretion (6.2-fold), indicating the restoration of T cell immune function. Thus, the dual-targeting property of M2NPs combined with RNA interference provides a potential strategy of molecular-targeted cancer immunotherapy for clinical application.

  14. Early Change in Metabolic Tumor Heterogeneity during Chemoradiotherapy and Its Prognostic Value for Patients with Locally Advanced Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Xinzhe Dong

    Full Text Available To observe the early change of metabolic tumor heterogeneity during chemoradiotherapy and to determine its prognostic value for patients with locally advanced non-small cell lung cancer (NSCLC.From January 2007 to March 2010, 58 patients with NSCLC were included who were received 18F-fluorodeoxyglucose (18F-FDG PET/CT before and following 40 Gy radiotherapy with the concurrent cisplatin-based chemotherapy (CCRT. Primary tumor FDG uptake heterogeneity was determined using global and local scale textural features extracted from standardized uptake value (SUV histogram analysis (coefficient of variation [COV], skewness, kurtosis, area under the curve of the cumulative SUV histogram [AUC-CSH] and normalized gray-level co-occurrence matrix (contrast, dissimilarity, entropy, homogeneity. SUVmax and metabolic tumor volume (MTV were also evaluated. Correlations were analyzed between parameters on baseline or during treatments with tumor response, progression-free survival (PFS, and overall survival (OS.Compared with non-responders, responders showed significantly greater pre-treatment COV, contrast and MTV (AUC = 0.781, 0.804, 0.686, respectively. Receiver-operating-characteristic curve analysis showed that early change of tumor textural analysis serves as a response predictor with higher sensitivity (73.2%~92.1% and specificity (80.0%~83.6% than baseline parameters. Change in AUC-CSH and dissimilarity during CCRT could also predict response with optimal cut-off values (33.0% and 28.7%, respectively. The patients with greater changes in contrast and AUC-CSH had significantly higher 5-year OS (P = 0.008, P = 0.034 and PFS (P = 0.007, P = 0.039. In multivariate analysis, only change in contrast was found as the independent prognostic factor of PFS (HR 0.476, P = 0.021 and OS (HR 0.519, P = 0.015.The metabolic tumor heterogeneity change during CCRT characterized by global and local scale textural features may be valuable for predicting treatment response

  15. Favorable prognosis of operable non-small cell lung cancer (NSCLC) patients harboring an increased expression of tumor endothelial markers (TEMs).

    Science.gov (United States)

    Pircher, Andreas; Fiegl, Michael; Untergasser, Gerold; Heidegger, Isabel; Medinger, Michael; Kern, Johann; Hilbe, Wolfgang

    2013-08-01

    Genome analyses of endothelial cells identified genes specifically expressed by tumor endothelial cells, called tumor endothelial markers (TEMs). Currently there are no data available concerning the role of TEMs in non-small cell lung cancer (NSCLC). Therefore, the aim of this study was to investigate the role of TEMs in NSCLC in vitro and in vivo. First we evaluated the expression of various TEMs (Robo4, Clec14 and ECSCR) by qRT-PCR and Western blot analyses in three NSCLC cell lines (A549, Calu1, Colo699) and compared them to human umbilical vein endothelial cells (HUVECs), endothelial colony forming cells (ECFCs) and human bronchial epithelial cells (HBEpCs). Next the expression of TEMs was measured in resected tumor tissue of NSCLC patients (n = 63) by qRT-PCR and compared to adjacent non-cancerous lung tissue (n = 52). Further, immunohistochemical analysis of Robo4 expression in tumor tissue (n = 33) and adjacent non-cancerous tissue (n = 27) was performed. We found that NSCLC cell lines and HBEpC did not express TEMs on the mRNA level compared to HUVECs (p = 0.001). In the contrary, a significant up-regulation of Robo4 and Clec14 was found in tumor samples (Robo4 p = 0.03, Clec14 p = 0.002). Both facts clearly indicate that these proteins are allocated to the tumor stromal department. Correlation with clinical data showed that increased TEM expression correlated with prolonged overall survival of operated NSCLC patients (Robo4 high 120.5 vs. Robo4 low 47.6 months, Clec14 high 108.1 vs. Clec14 low 54.5 months and ECSCR high 120.5 vs. ECSCR low 42.2 months). In summary, we found that TEMs are overexpressed in NSCLC stromal tissue and that an increased TEM expression correlated with an increased overall survival in early stage NSCLC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Phase I Study of SU5416, a Small Molecule Inhibitor of the Vascular Endothelial Growth Factor Receptor (VEGFR) in Refractory Pediatric Central Nervous System Tumors

    Science.gov (United States)

    Kieran, Mark W.; Supko, Jeffrey G.; Wallace, Dana; Fruscio, Robert; Poussaint, Tina Young; Phillips, Peter; Pollack, Ian; Packer, Roger; Boyett, James M.; Blaney, Susan; Prados, Michael; Geyer, Russ; Friedman, Henry; Goldman, Stewart; Kun, Larry E.; MacDonald, Tobey

    2009-01-01

    SU5416 is a novel small molecule tyrosine kinase inhibitor of the VEGF receptors 1 and 2. A phase I dose escalation study stratified by concurrent use (stratum II) or absence (Stratum I) of enzyme-inducing anticonvulsant drugs was undertaken to estimate the maximum-tolerated dose (MTD) and to describe the toxicity profile of SU5416 in pediatric patients with refractory brain tumors. Dose escalations were conducted independently for stratum I starting at 110mg/m2 while stratum II started at 48mg/m2. Thirty-three eligible patients were treated on stratum I (n=23) and stratum II (n=10). Tumor types included 23 glial tumors, 4 neural tumors, 4 ependymomas and 2 choroid plexus carcinomas. The MTD in Stratum I was initially estimated to be 110mg/m2. The protocol was amended to determine the MTD after excluding transient AST elevation. Re-estimation of the MTD began at the 145mg/m2 dose level but due to development of SU5416 being stopped by the sponsor, the trial was closed before completion. The most serious drug-related toxicities were grade 3 liver enzyme abnormalities, arthralgia and hallucinations. The plasma pharmacokinetics of SU5416 was not significantly affected by the concurrent administration of enzyme-inducing anticonvulsant drugs. Mean values of the total body clearance, apparent volume of distribution, and terminal phase half-life of SU5416 for the 19 patients in Stratum I were 26.1 ± 12.5 liter/h/m2, 41.9 ± 21.4 liter/m2, and 1.11 ± 0.41 h, respectively. The plasma pharmacokinetics of SU5416 in children was similar to previously reported findings in adult cancer patients. Prolonged disease stabilization was observed in 4 of 16 stratum 1 patients. PMID:19065567

  17. Comparison of different threshold 18FDG PET with computer tomography for defining gross tumor volume in non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Chen Shaoqing; Yu Jinming; Xing Ligang; Gong Heyi; Fu Zheng; Yang Guoren

    2006-01-01

    Objective: Under different standard uptake value(SUV), to assess gross tumor volume (GTV) definition for non-small cell lung cancer (NSCLC) with 18-fluoro-deoxy-glueose positron emission tomography( 18 FDG PET) both under definite threshold (42 percent threshold) and various relative threshold (threshold SUV/maximum SUV) derived from the linear regressive function, threshold SUV=0.307 x (mean target SUV) + 0.588, with computer tomography(CT). Methods: Of 20 patients with non-small cell lung cancer, the CT GTV (GTV CT ), PET GTV with 42 percents threshold (GTV 42% ) and PET GTV with relative threshold (GTV relate ) were obtained and compared. Results: The mean GTV 42% , mean GTV relate and mean GTV CT was (13 812.5±13 841.4), (24 325.3±22 454.7) and (28350.9± 26 079.8) mm 3 , respectively, with the difference in mean GTV among these three methods significant (F =. 10, P 42% was smaller than the GTV relate and the GTV CT (P relate and GTV CT (P = 0.125 ). Conclusion: The relative threshold is more suitable to define the gross tumor volume than the definite threshold. (authors)

  18. Tumor endothelial marker 5 expression in endothelial cells during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Vallon, Mario, E-mail: m.vallon@arcor.de [Nuklearmedizinische Klinik und Poliklinik, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich (Germany); Rohde, Franziska; Janssen, Klaus-Peter [Chirurgische Klinik und Poliklinik, Technische Universitaet Muenchen, Munich (Germany); Essler, Markus [Nuklearmedizinische Klinik und Poliklinik, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich (Germany)

    2010-02-01

    Tumor endothelial marker (TEM) 5 is an adhesion G-protein-coupled receptor upregulated in endothelial cells during tumor and physiologic angiogenesis. So far, the mechanisms leading to upregulation of TEM5 and its function during angiogenesis have not been identified. Here, we report that TEM5 expression in endothelial cells is induced during capillary-like network formation on Matrigel, during capillary morphogenesis in a three-dimensional collagen I matrix, and upon confluence on a two-dimensional matrix. TEM5 expression was not induced by a variety of soluble angiogenic factors, including VEGF and bFGF, in subconfluent endothelial cells. TEM5 upregulation was blocked by toxin B from Clostridium difficile, an inhibitor of the small GTPases Rho, Rac, and Cdc42. The Rho inhibitor C3 transferase from Clostridium botulinum did not affect TEM5 expression, whereas the Rac inhibitor NSC23766 suppressed TEM5 upregulation. An excess of the soluble TEM5 extracellular domain or an inhibitory monoclonal TEM5 antibody blocked contact inhibition of endothelial cell proliferation resulting in multilayered islands within the endothelial monolayer and increased vessel density during capillary formation. Based on our results we conclude that TEM5 expression during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of proliferation in endothelial cells.

  19. Imaging Tumor Response and Tumoral Heterogeneity in Non-Small Cell Lung Cancer Treated With Antiangiogenic Therapy: Comparison of the Prognostic Ability of RECIST 1.1, an Alternate Method (Crabb), and Image Heterogeneity Analysis.

    Science.gov (United States)

    Yip, Connie; Tacelli, Nunzia; Remy-Jardin, Martine; Scherpereel, Arnaud; Cortot, Alexis; Lafitte, Jean-Jacques; Wallyn, Frederic; Remy, Jacques; Bassett, Paul; Siddique, Musib; Cook, Gary J R; Landau, David B; Goh, Vicky

    2015-09-01

    We aimed to assess computed tomography (CT) intratumoral heterogeneity changes, and compared the prognostic ability of the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an alternate response method (Crabb), and CT heterogeneity in non-small cell lung cancer treated with chemotherapy with and without bevacizumab. Forty patients treated with chemotherapy (group C) or chemotherapy and bevacizumab (group BC) underwent contrast-enhanced CT at baseline and after 1, 3, and 6 cycles of chemotherapy. Radiologic response was assessed using RECIST 1.1 and an alternate method. CT heterogeneity analysis generating global and locoregional parameters depicting tumor image spatial intensity characteristics was performed. Heterogeneity parameters between the 2 groups were compared using the Mann-Whitney U test. Associations between heterogeneity parameters and radiologic response with overall survival were assessed using Cox regression. Global and locoregional heterogeneity parameters changed with treatment, with increased tumor heterogeneity in group BC. Entropy [group C: median -0.2% (interquartile range -2.2, 1.7) vs. group BC: 0.7% (-0.7, 3.5), P=0.10] and busyness [-27.7% (-62.2, -5.0) vs. -11.5% (-29.1, 92.4), P=0.10] showed a greater reduction in group C, whereas uniformity [1.9% (-8.0, 9.8) vs. -5.0% (-13.9, 5.6), P=0.10] showed a relative increase after 1 cycle but did not reach statistical significance. Two (9%) and 1 (6%) additional responders were identified using the alternate method compared with RECIST in group C and group BC, respectively. Heterogeneity parameters were not significant prognostic factors. The alternate response method described by Crabb identified more responders compared with RECIST. However, both criteria and baseline imaging heterogeneity parameters were not prognostic of survival.

  20. Steep Dose-Response Relationship for Stage I Non-Small-Cell Lung Cancer Using Hypofractionated High-Dose Irradiation by Real-Time Tumor-Tracking Radiotherapy

    International Nuclear Information System (INIS)

    Onimaru, Rikiya; Fujino, Masaharu; Yamazaki, Koichi; Onodera, Yuya; Taguchi, Hiroshi; Katoh, Norio; Hommura, Fumihiro; Oizumi, Satoshi; Nishimura, Masaharu; Shirato, Hiroki

    2008-01-01

    Purpose: To investigate the clinical outcomes of patients with pathologically proven, peripherally located, Stage I non-small-cell lung cancer who had undergone stereotactic body radiotherapy using real-time tumor tracking radiotherapy during the developmental period. Methods and Materials: A total of 41 patients (25 with Stage T1 and 16 with Stage T2) were admitted to the study between February 2000 and June 2005. A 5-mm planning target volume margin was added to the clinical target volume determined with computed tomography at the end of the expiratory phase. The gating window ranged from ±2 to 3 mm. The dose fractionation schedule was 40 or 48 Gy in four fractions within 1 week. The dose was prescribed at the center of the planning target volume, giving more than an 80% dose at the planning target volume periphery. Results: For 28 patients treated with 48 Gy in four fractions, the overall actuarial survival rate at 3 years was 82% for those with Stage IA and 32% for those with Stage IB. For patients treated with 40 Gy in four fractions within 1 week, the overall actuarial survival rate at 3 years was 50% for those with Stage IA and 0% for those with Stage IB. A significant difference was found in local control between those with Stage IB who received 40 Gy vs. 48 Gy (p = 0.0015) but not in those with Stage IA (p = 0.5811). No serious radiation morbidity was observed with either dose schedule. Conclusion: The results of our study have shown that 48 Gy in four fractions within 1 week is a safe and effective treatment for peripherally located, Stage IA non-small-cell lung cancer. A steep dose-response curve between 40 and 48 Gy using a daily dose of 12 Gy delivered within 1 week was identified for Stage IB non-small-cell lung cancer in stereotactic body radiotherapy using real-time tumor tracking radiotherapy

  1. The prognostic value of ERCC1 and RRM1 gene expression in completely resected non-small cell lung cancer: tumor recurrence and overall survival

    International Nuclear Information System (INIS)

    Tantraworasin, Apichat; Saeteng, Somcharoen; Lertprasertsuke, Nirush; Arayawudhikul, Nuttapon; Kasemsarn, Choosak; Patumanond, Jayanton

    2013-01-01

    The roles of excision repair cross-complementing group 1 gene (ERCC1) expression and ribonucleotide reductase subunit M1 gene (RRM1) expression in completely resected non-small cell lung cancer (NSCLC) are still debatable. Previous studies have shown that both genes affected the overall survival and outcomes of patients who received platinum-based chemotherapy; however, some studies did not show this correlation. The aim of this study was to evaluate the prognostic values of ERCC1 and RRM1 gene expression in predicting tumor recurrence and overall survival in patients with completely resected NSCLC who received adjuvant chemotherapy and in those who did not. A retrospective cohort study was conducted in 247 patients with completely resected NSCLC. All patients had been treated with anatomic resection (lobectomy or pneumonectomy) with systematic mediastinal lymphadenectomy between January 2002 and December 2011 at Chiang Mai University Hospital, Chiang Mai, Thailand. They were divided into two groups: recurrence and no recurrence. Protein expression of ERCC1 and RRM1 was determined by immunohistochemistry. Correlations between clinicopathologic variables, including ERCC1 and RRM1 expression and tumor recurrence, were analyzed. Univariate and multivariate Cox proportional hazards regression analysis stratified by nodal involvement, tumor staging, intratumoral blood vessel invasion, intratumoral lymphatic invasion, and tumor necrosis was used to identify the prognostic roles of ERCC1 and RRM1. ERCC1 and RRM1 expression did not demonstrate prognostic value for tumor recurrence and overall survival in patients with completely resected NSCLC. In patients who did not receive adjuvant chemotherapy treatment, those with high ERCC1 and high RRM1 expression seemed to have greater potential for tumor recurrence and shorter overall survival than did those who had low ERCC1 and low RRM1 (hazard ratio [HR] =1.7, 95% confidence interval [CI] =0.6–4.3, P=0.292 and HR =1.6, 95% CI

  2. Xenograft tumors derived from malignant pleural effusion of the patients with non-small-cell lung cancer as models to explore drug resistance.

    Science.gov (United States)

    Xu, Yunhua; Zhang, Feifei; Pan, Xiaoqing; Wang, Guan; Zhu, Lei; Zhang, Jie; Wen, Danyi; Lu, Shun

    2018-05-09

    Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions show dramatic responses to specific tyrosine kinase inhibitors (TKIs); however, after 10-12 months, secondary mutations arise that confer resistance. We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively. Genotypes of patient biopsies and xenograft tumors were determined by whole exome sequencing (WES), and patients and xenograft-bearing mice received targeted treatment (crizotinib or osimertinib) accordingly. Xenograft mice were also treated for prolonged periods to identify whether the development of drug resistance and/or treatment responses were associated with tumor size. Finally, the pathology of patients biopsies and xenograft tumors were compared histologically. The histological characteristics and chemotherapy responses of xenograft tumors were similar to the actual patients. WES showed that the genotypes of the xenograft and patient tumors were similar (an echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) gene fusion (patient/xenograft: CTC15035 EML4-ALK ) and EGFR L858R and T790M mutations (patient/xenograft: CTC15063 EGFR L858R, T790M )). After continuous crizotinib or osimertinib treatment, WES data suggested that acquired ALK E1210K mutation conferred crizotinib resistance in the CTC15035 EML4-ALK xenograft, while decreased frequencies of EGFR L858R and T790M mutations plus the appearance of v-RAF murine sarcoma viral oncogene homolog B (BRAF) G7V mutations and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha (PIK3C2A) A86fs frame shift mutations led to osimertinib resistance in the CTC15063 EGFR L858R, T790M xenografts. We successfully developed a new method of generating

  3. Identification and Characterization of a Small Inhibitory Peptide That Can Target DNA-PKcs Autophosphorylation and Increase Tumor Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Sun Xiaonan [Department of Radiation Oncology, Sir Run Run Shaw Hospital, Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou (China); Yang Chunying [Department of Radiation Oncology, Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX (United States); Liu Hai; Wang Qi [Department of Radiation Oncology, Sir Run Run Shaw Hospital, Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou (China); Wu Shixiu [Department of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou (China); Li Xia; Xie Tian [Research Center of Biomedicine and Health, Hangzhou Normal University, Hangzhou (China); Brinkman, Kathryn L.; Teh, Bin S.; Butler, E. Brian [Department of Radiation Oncology, Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX (United States); Xu Bo, E-mail: bxu@tmhs.org [Department of Radiation Oncology, Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX (United States); Zheng, Shu, E-mail: zhengshu@zju.edu.cn [Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China)

    2012-12-01

    Purpose: The DNA protein kinase catalytic subunit (DNA-PKcs) is one of the critical elements involved in the DNA damage repair process. Inhibition of DNA-PKcs results in hypersensitivity to ionizing radiation (IR); therefore, this approach has been explored to develop molecular targeted radiosensitizers. Here, we aimed to develop small inhibitory peptides that could specifically target DNA-PKcs autophosphorylation, a critical step for the enzymatic activation of the kinase in response to IR. Methods and Materials: We generated several small fusion peptides consisting of 2 functional domains, 1 an internalization domain and the other a DNA-PKcs autophosphorylation inhibitory domain. We characterized the internalization, toxicity, and radiosensitization activities of the fusion peptides. Furthermore, we studied the mechanisms of the inhibitory peptides on DNA-PKcs autophosphorylation and DNA repair. Results: We found that among several peptides, the biotin-labeled peptide 3 (BTW3) peptide, which targets DNA-PKcs threonine 2647 autophosphorylation, can abrogate IR-induced DNA-PKcs activation and cause prolonged {gamma}-H2AX focus formation. We demonstrated that BTW3 exposure led to hypersensitivity to IR in DNA-PKcs-proficient cells but not in DNA-PKcs-deficient cells. Conclusions: The small inhibitory peptide BTW3 can specifically target DNA-PKcs autophosphorylation and enhance radiosensitivity; therefore, it can be further developed as a novel class of radiosensitizer.

  4. Identification and Characterization of a Small Inhibitory Peptide That Can Target DNA-PKcs Autophosphorylation and Increase Tumor Radiosensitivity

    International Nuclear Information System (INIS)

    Sun Xiaonan; Yang Chunying; Liu Hai; Wang Qi; Wu Shixiu; Li Xia; Xie Tian; Brinkman, Kathryn L.; Teh, Bin S.; Butler, E. Brian; Xu Bo; Zheng, Shu

    2012-01-01

    Purpose: The DNA protein kinase catalytic subunit (DNA-PKcs) is one of the critical elements involved in the DNA damage repair process. Inhibition of DNA-PKcs results in hypersensitivity to ionizing radiation (IR); therefore, this approach has been explored to develop molecular targeted radiosensitizers. Here, we aimed to develop small inhibitory peptides that could specifically target DNA-PKcs autophosphorylation, a critical step for the enzymatic activation of the kinase in response to IR. Methods and Materials: We generated several small fusion peptides consisting of 2 functional domains, 1 an internalization domain and the other a DNA-PKcs autophosphorylation inhibitory domain. We characterized the internalization, toxicity, and radiosensitization activities of the fusion peptides. Furthermore, we studied the mechanisms of the inhibitory peptides on DNA-PKcs autophosphorylation and DNA repair. Results: We found that among several peptides, the biotin-labeled peptide 3 (BTW3) peptide, which targets DNA-PKcs threonine 2647 autophosphorylation, can abrogate IR-induced DNA-PKcs activation and cause prolonged γ-H2AX focus formation. We demonstrated that BTW3 exposure led to hypersensitivity to IR in DNA-PKcs-proficient cells but not in DNA-PKcs-deficient cells. Conclusions: The small inhibitory peptide BTW3 can specifically target DNA-PKcs autophosphorylation and enhance radiosensitivity; therefore, it can be further developed as a novel class of radiosensitizer.

  5. Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Yachida, Shinichi; Vakiani, Efsevia; White, Catherine M; Zhong, Yi; Saunders, Tyler; Morgan, Richard; de Wilde, Roeland F; Maitra, Anirban; Hicks, Jessica; Demarzo, Angelo M; Shi, Chanjuan; Sharma, Rajni; Laheru, Daniel; Edil, Barish H; Wolfgang, Christopher L; Schulick, Richard D; Hruban, Ralph H; Tang, Laura H; Klimstra, David S; Iacobuzio-Donahue, Christine A

    2012-02-01

    Poorly differentiated neuroendocrine carcinomas (NECs) of the pancreas are rare malignant neoplasms with a poor prognosis. The aim of this study was to determine the clinicopathologic and genetic features of poorly differentiated NECs and compare them with other types of pancreatic neoplasms. We investigated alterations of KRAS, CDKN2A/p16, TP53, SMAD4/DPC4, DAXX, ATRX, PTEN, Bcl2, and RB1 by immunohistochemistry and/or targeted exomic sequencing in surgically resected specimens of 9 small cell NECs, 10 large cell NECs, and 11 well-differentiated neuroendocrine tumors (PanNETs) of the pancreas. Abnormal immunolabeling patterns of p53 and Rb were frequent (p53, 18 of 19, 95%; Rb, 14 of 19, 74%) in both small cell and large cell NECs, whereas Smad4/Dpc4, DAXX, and ATRX labeling was intact in virtually all of these same carcinomas. Abnormal immunolabeling of p53 and Rb proteins correlated with intragenic mutations in the TP53 and RB1 genes. In contrast, DAXX and ATRX labeling was lost in 45% of PanNETs, whereas p53 and Rb immunolabeling was intact in these same cases. Overexpression of Bcl-2 protein was observed in all 9 small cell NECs (100%) and in 5 of 10 (50%) large cell NECs compared with only 2 of 11 (18%) PanNETs. Bcl-2 overexpression was significantly correlated with higher mitotic rate and Ki67 labeling index in neoplasms in which it was present. Small cell NECs are genetically similar to large cell NECs, and these genetic changes are distinct from those reported in PanNETs. The finding of Bcl-2 overexpression in poorly differentiated NECs, particularly small cell NEC, suggests that Bcl-2 antagonists/inhibitors may be a viable treatment option for these patients.

  6. SU-F-J-207: Non-Small Cell Lung Cancer Patient Survival Prediction with Quantitative Tumor Textures Analysis in Baseline CT

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Y; Zou, J; Murillo, P; Nosher, J; Amorosa, J; Bramwit, M; Yue, N; Jabbour, S; Foran, D [Rutgers University, New Brunswick, NJ (United States)

    2016-06-15

    Purpose: Chemo-radiation therapy (CRT) is widely used in treating patients with locally advanced non-small cell lung cancer (NSCLC). Determination of the likelihood of patient response to treatment and optimization of treatment regime is of clinical significance. Up to date, no imaging biomarker has reliably correlated to NSCLC patient survival rate. This pilot study is to extract CT texture information from tumor regions for patient survival prediction. Methods: Thirteen patients with stage II-III NSCLC were treated using CRT with a median dose of 6210 cGy. Non-contrast-enhanced CT images were acquired for treatment planning and retrospectively collected for this study. Texture analysis was applied in segmented tumor regions using the Local Binary Pattern method (LBP). By comparing its HU with neighboring voxels, the LBPs of a voxel were measured in multiple scales with different group radiuses and numbers of neighbors. The LBP histograms formed a multi-dimensional texture vector for each patient, which was then used to establish and test a Support Vector Machine (SVM) model to predict patients’ one year survival. The leave-one-out cross validation strategy was used recursively to enlarge the training set and derive a reliable predictor. The predictions were compared with the true clinical outcomes. Results: A 10-dimensional LBP histogram was extracted from 3D segmented tumor region for each of the 13 patients. Using the SVM model with the leave-one-out strategy, only 1 out of 13 patients was misclassified. The experiments showed an accuracy of 93%, sensitivity of 100%, and specificity of 86%. Conclusion: Within the framework of a Support Vector Machine based model, the Local Binary Pattern method is able to extract a quantitative imaging biomarker in the prediction of NSCLC patient survival. More patients are to be included in the study.

  7. SU-F-J-207: Non-Small Cell Lung Cancer Patient Survival Prediction with Quantitative Tumor Textures Analysis in Baseline CT

    International Nuclear Information System (INIS)

    Wu, Y; Zou, J; Murillo, P; Nosher, J; Amorosa, J; Bramwit, M; Yue, N; Jabbour, S; Foran, D

    2016-01-01

    Purpose: Chemo-radiation therapy (CRT) is widely used in treating patients with locally advanced non-small cell lung cancer (NSCLC). Determination of the likelihood of patient response to treatment and optimization of treatment regime is of clinical significance. Up to date, no imaging biomarker has reliably correlated to NSCLC patient survival rate. This pilot study is to extract CT texture information from tumor regions for patient survival prediction. Methods: Thirteen patients with stage II-III NSCLC were treated using CRT with a median dose of 6210 cGy. Non-contrast-enhanced CT images were acquired for treatment planning and retrospectively collected for this study. Texture analysis was applied in segmented tumor regions using the Local Binary Pattern method (LBP). By comparing its HU with neighboring voxels, the LBPs of a voxel were measured in multiple scales with different group radiuses and numbers of neighbors. The LBP histograms formed a multi-dimensional texture vector for each patient, which was then used to establish and test a Support Vector Machine (SVM) model to predict patients’ one year survival. The leave-one-out cross validation strategy was used recursively to enlarge the training set and derive a reliable predictor. The predictions were compared with the true clinical outcomes. Results: A 10-dimensional LBP histogram was extracted from 3D segmented tumor region for each of the 13 patients. Using the SVM model with the leave-one-out strategy, only 1 out of 13 patients was misclassified. The experiments showed an accuracy of 93%, sensitivity of 100%, and specificity of 86%. Conclusion: Within the framework of a Support Vector Machine based model, the Local Binary Pattern method is able to extract a quantitative imaging biomarker in the prediction of NSCLC patient survival. More patients are to be included in the study.

  8. Investigation of the Relationship Between Gross Tumor Volume Location and Pneumonitis Rates Using a Large Clinical Database of Non-Small-Cell Lung Cancer Patients

    International Nuclear Information System (INIS)

    Vinogradskiy, Yevgeniy; Tucker, Susan L.; Liao Zhongxing; Martel, Mary K.

    2012-01-01

    Purpose: Studies have suggested that function may vary throughout the lung, and that patients who have tumors located in the base of the lung are more susceptible to radiation pneumonitis. The purpose of our study was to investigate the relationship between gross tumor volume (GTV) location and pneumonitis rates using a large clinical database of 547 patients with non–small-cell lung cancer. Methods and Materials: The GTV centroids of all patients were mapped onto one common coordinate system, in which the boundaries of the coordinate system were defined by the extreme points of each individual patient lung. The data were qualitatively analyzed by graphing all centroids and displaying the data according to the presence of severe pneumonitis, tumor stage, and smoking status. The centroids were grouped according to superior–inferior segments, and the pneumonitis rates were analyzed. In addition, we incorporated the GTV centroid information into a Lyman–Kutcher–Burman normal tissue complication probability model and tested whether adding spatial information significantly improved the fit of the model. Results: Of the 547 patients analyzed, 111 (20.3%) experienced severe radiation pneumonitis. The pneumonitis incidence rates were 16%, 23%, and 21% for the superior, middle, and inferior thirds of the lung, respectively. Qualitatively, the GTV centroids of nonsmokers were notably absent from the superior portion of the lung. In addition, the GTV centroids of patients who had Stage III and IV clinical staging were concentrated toward the medial edge of the lung. The comparison between the GTV centroid model and the conventional dose–volume model did not yield a statistically significant difference in model fit. Conclusions: Lower pneumonitis rates were noted for the superior portion of the lung; however the differences were not statistically significant. For our patient cohort, incorporating GTV centroid information did not lead to a statistically significant

  9. Development of a Novel SPECT Tracer to Image c-Met Expression in Non-Small Cell Lung Cancer in a Human Tumor Xenograft.

    Science.gov (United States)

    Han, Zhaoguo; Xiao, Yadi; Wang, Kai; Yan, Ji; Xiao, Zunyu; Fang, Fang; Jin, Zhongnan; Liu, Yang; Sun, Xilin; Shen, Baozhong

    2018-05-18

    Rationale: Elevated expression of the c-Met receptor plays a crucial role in cancers. In non-small cell lung cancer (NSCLC), aberrant activation of c-Met signaling pathway contributes to tumorigenesis and cancer progression, and may mediate acquired resistance to epidermal growth factor receptor-targeted therapy. c-Met is therefore emerging as a promising therapeutic target for treating NSCLC, and the methods for noninvasive in vivo assessment of c-Met expression will improve NSCLC treatment and diagnosis. Methods: A new peptide-based (cMBP) radiotracer targeting c-Met, 99m Tc-hydrazine nicotinamide (HYNIC)-cMBP, was developed for single photon emission computed tomography (SPECT) imaging. Cell uptake assays were performed on two NSCLC cell lines with different c-Met expression: H1993 (high expression) and H1299 (no expression). In vivo tumor specificity was assessed by SPECT imaging in tumor-bearing mice at 0.5, 1, 2 and 4 h after injection of the probe. Blocking assays, biodistribution and autoradiography were also conducted to determine probe specificity. Results: 99m Tc-HYNIC-cMBP was prepared with high efficiency and showed higher uptake in H1993 cells than H1299 cells. Biodistribution and autoradiography also showed significantly higher accumulation of 99m Tc-HYNIC-cMBP in H1993 tumors than H1299 (H1993: 4.74±1.43 %ID/g and H1299: 1.00±0.37 %ID/g at 0.5h, pc-Met was demonstrated by competitive block with excess un-radiolabeled peptide. Conclusion: We developed a novel SPECT tracer, 99m Tc-HYNIC-cMBP, for c-Met-targeted imaging in NSCLC that specifically bound to c-Met with favorable pharmacokinetics in vitro and in vivo. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  10. Antihelminthic drug niclosamide inhibits CIP2A and reactivates tumor suppressor protein phosphatase 2A in non-small cell lung cancer cells.

    Science.gov (United States)

    Kim, Myeong-Ok; Choe, Min Ho; Yoon, Yi Na; Ahn, Jiyeon; Yoo, Minjin; Jung, Kwan-Young; An, Sungkwan; Hwang, Sang-Gu; Oh, Jeong Su; Kim, Jae-Sung

    2017-11-15

    Protein phosphatase 2A (PP2A) is a critical tumor suppressor complex responsible for the inactivation of various oncogenes. Recently, PP2A reactivation has emerged asan anticancer strategy. Cancerous inhibitor of protein phosphatase 2A (CIP2A), an endogenous inhibitor of PP2A, is upregulated in many cancer cells, including non-small cell lung cancer (NSCLC) cells. We demonstrated that the antihelminthic drug niclosamide inhibited the expression of CIP2A and reactivated the tumor suppressor PP2A in NSCLC cells. We performed a drug-repurposing screen and identified niclosamide asa CIP2A suppressor in NSCLC cells. Niclosamide inhibited cell proliferation, colony formation, and tumor sphere formation, and induced mitochondrial dysfunction through increased mitochondrial ROS production in NSCLC cells; however, these effects were rescued by CIP2A overexpression, which indicated that the antitumor activity of niclosamide was dependent on CIP2A. We found that niclosamide increased PP2A activity through CIP2A inhibition, which reduced the phosphorylation of several oncogenic proteins. Moreover, we found that a niclosamide analog inhibited CIP2A expression and increased PP2A activity in several types of NSCLC cells. Finally, we showed that other well-known PP2A activators, including forskolin and FTY720, did not inhibit CIP2A and that their activities were not dependent on CIP2A. Collectively, our data suggested that niclosamide effectively suppressed CIP2A expression and subsequently activated PP2A in NSCLC cells. This provided strong evidence for the potential use of niclosamide asa PP2A-activating drug in the clinical treatment of NSCLC. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Utilization of Cell-Transfer Technique for Molecular Testing on Hematoxylin-Eosin-Stained Sections: A Viable Option for Small Biopsies That Lack Tumor Tissues in Paraffin Block.

    Science.gov (United States)

    Wu, Howard H; Jovonovich, Stephen M; Randolph, Melissa; Post, Kristin M; Sen, Joyashree D; Curless, Kendra; Cheng, Liang

    2016-12-01

    - In some instances the standard method of doing molecular testing from formalin-fixed, paraffin-embedded block is not possible because of limited tissue. Tumor cell-enriched cell-transfer technique has been proven useful for performing immunocytochemistry and molecular testing on cytologic smears. - To establish the cell-transfer technique as a viable option for isolating tumor cells from hematoxylin-eosin (H&E)-stained slides. - Molecular testing was performed by using the cell-transfer technique on 97 archived H&E-stained slides from a variety of different tumors. Results were compared to the conventional method of molecular testing. - Polymerase chain reaction-based molecular testing via the cell-transfer technique was successfully performed on 82 of 97 samples (85%). This included 39 of 47 cases for EGFR, 10 of 11 cases for BRAF, and 33 of 39 cases for KRAS mutations. Eighty-one of 82 cell-transfer technique samples (99%) showed agreement with previous standard method results, including 4 mutations and 35 wild-type alleles for EGFR, 4 mutations and 6 wild-type alleles for BRAF, and 11 mutations and 21 wild-type alleles for KRAS. There was only 1 discrepancy: a cell-transfer technique with a false-negative >KRAS result (wild type versus G12C). - Molecular testing performed on H&E-stained sections via cell-transfer technique is useful when tissue from cell blocks and small surgical biopsy samples is exhausted and the only available material for testing is on H&E-stained slides.

  12. Tumor cell heterogeneity in Small Cell Lung Cancer (SCLC: phenotypical and functional differences associated with Epithelial-Mesenchymal Transition (EMT and DNA methylation changes.

    Directory of Open Access Journals (Sweden)

    Alexander Krohn

    Full Text Available Small Cell Lung Cancer (SCLC is a specific subtype of lung cancer presenting as highly metastatic disease with extremely poor prognosis. Despite responding initially well to chemo- or radiotherapy, SCLC almost invariably relapses and develops resistance to chemotherapy. This is suspected to be related to tumor cell subpopulations with different characteristics resembling stem cells. Epithelial-Mesenchymal Transition (EMT is known to play a key role in metastatic processes and in developing drug resistance. This is also true for NSCLC, but there is very little information on EMT processes in SCLC so far. SCLC, in contrast to NSCLC cell lines, grow mainly in floating cell clusters and a minor part as adherent cells. We compared these morphologically different subpopulations of SCLC cell lines for EMT and epigenetic features, detecting significant differences in the adherent subpopulations with high levels of mesenchymal markers such as Vimentin and Fibronectin and very low levels of epithelial markers like E-cadherin and Zona Occludens 1. In addition, expression of EMT-related transcription factors such as Snail/Snai1, Slug/Snai2, and Zeb1, DNA methylation patterns of the EMT hallmark genes, functional responses like migration, invasion, matrix metalloproteases secretion, and resistance to chemotherapeutic drug treatment all differed significantly between the sublines. This phenotypic variability might reflect tumor cell heterogeneity and EMT during metastasis in vivo, accompanied by the development of refractory disease in relapse. We propose that epigenetic regulation plays a key role during phenotypical and functional changes in tumor cells and might therefore provide new treatment options for SCLC patients.

  13. Wide-field lifetime-based FRET imaging for the assessment of early functional distribution of transferrin-based delivery in breast tumor-bearing small animals

    Science.gov (United States)

    Sinsuebphon, Nattawut; Rudkouskaya, Alena; Barroso, Margarida; Intes, Xavier

    2016-02-01

    Targeted drug delivery is a critical aspect of successful cancer therapy. Assessment of dynamic distribution of the drug provides relative concentration and bioavailability at the target tissue. The most common approach of the assessment is intensity-based imaging, which only provides information about anatomical distribution. Observation of biomolecular interactions can be performed using Förster resonance energy transfer (FRET). Thus, FRET-based imaging can assess functional distribution and provide potential therapeutic outcomes. In this study, we used wide-field lifetime-based FRET imaging for the study of early functional distribution of transferrin delivery in breast cancer tumor models in small animals. Transferrin is a carrier for cancer drug delivery. Its interaction with its receptor is within a few nanometers, which is suitable for FRET. Alexa Fluor® 700 and Alexa Fluor® 750 were conjugated to holo-transferrin which were then administered via tail vein injection to the mice implanted with T47D breast cancer xenografts. Images were continuously acquired for 60 minutes post-injection. The results showed that transferrin was primarily distributed to the liver, the urinary bladder, and the tumor. The cellular uptake of transferrin, which was indicated by the level of FRET, was high in the liver but very low in the urinary bladder. The results also suggested that the fluorescence intensity and FRET signals were independent. The liver showed increasing intensity and increasing FRET during the observation period, while the urinary bladder showed increasing intensity but minimal FRET. Tumors gave varied results corresponding to their FRET progression. These results were relevant to the biomolecular events that occurred in the animals.

  14. Investigation of the relationship between gross tumor volume location and pneumonitis rates using a large clinical database of non-small-cell lung cancer patients.

    Science.gov (United States)

    Vinogradskiy, Yevgeniy; Tucker, Susan L; Liao, Zhongxing; Martel, Mary K

    2012-04-01

    Studies have suggested that function may vary throughout the lung, and that patients who have tumors located in the base of the lung are more susceptible to radiation pneumonitis. The purpose of our study was to investigate the relationship between gross tumor volume (GTV) location and pneumonitis rates using a large clinical database of 547 patients with non-small-cell lung cancer. The GTV centroids of all patients were mapped onto one common coordinate system, in which the boundaries of the coordinate system were defined by the extreme points of each individual patient lung. The data were qualitatively analyzed by graphing all centroids and displaying the data according to the presence of severe pneumonitis, tumor stage, and smoking status. The centroids were grouped according to superior-inferior segments, and the pneumonitis rates were analyzed. In addition, we incorporated the GTV centroid information into a Lyman-Kutcher-Burman normal tissue complication probability model and tested whether adding spatial information significantly improved the fit of the model. Of the 547 patients analyzed, 111 (20.3%) experienced severe radiation pneumonitis. The pneumonitis incidence rates were 16%, 23%, and 21% for the superior, middle, and inferior thirds of the lung, respectively. Qualitatively, the GTV centroids of nonsmokers were notably absent from the superior portion of the lung. In addition, the GTV centroids of patients who had Stage III and IV clinical staging were concentrated toward the medial edge of the lung. The comparison between the GTV centroid model and the conventional dose-volume model did not yield a statistically significant difference in model fit. Lower pneumonitis rates were noted for the superior portion of the lung; however the differences were not statistically significant. For our patient cohort, incorporating GTV centroid information did not lead to a statistically significant improvement in the fit of the pneumonitis model. Copyright

  15. Prognostic value of tumor-infiltrating lymphocytes differs depending on histological type and smoking habit in completely resected non-small-cell lung cancer.

    Science.gov (United States)

    Kinoshita, T; Muramatsu, R; Fujita, T; Nagumo, H; Sakurai, T; Noji, S; Takahata, E; Yaguchi, T; Tsukamoto, N; Kudo-Saito, C; Hayashi, Y; Kamiyama, I; Ohtsuka, T; Asamura, H; Kawakami, Y

    2016-11-01

    T-cell infiltration in tumors has been used as a prognostic tool in non-small-cell lung cancer (NSCLC). However, the influence of smoking habit and histological type on tumor-infiltrating lymphocytes (TILs) in NSCLC remains unclear. We evaluated the prognostic significance of TILs (CD4 + , CD8 + , CD20 + , and FOXP3 + ) according to histological type and smoking habit using automatic immunohistochemical staining and cell counting in 218 patients with NSCLC. In multivariate survival analyses of clinical, pathological, and immunological factors, a high ratio of FOXP3 + to CD4 + T cells (FOXP3/CD4) [hazard ratio (HR): 4.46, P smoking habit in AD, a high FOXP3/CD4 ratio was poorly prognostic with a smoking history (HR: 5.21, P smoking habit on the immunological environment may lead to the establishment of immunological diagnosis and appropriate individualized immunotherapy for NSCLC. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. Pharmacokinetic-Pharmacodynamic Modeling of the Anti-Tumor Effect of Sunitinib Combined with Dopamine in the Human Non-Small Cell Lung Cancer Xenograft.

    Science.gov (United States)

    Hao, Fangran; Wang, Siyuan; Zhu, Xiao; Xue, Junsheng; Li, Jingyun; Wang, Lijie; Li, Jian; Lu, Wei; Zhou, Tianyan

    2017-02-01

    To investigate the anti-tumor effect of sunitinib in combination with dopamine in the treatment of nu/nu nude mice bearing non-small cell lung cancer (NSCLC) A549 cells and to develop the combination PK/PD model. Further, simulations were conducted to optimize the administration regimens. A PK/PD model was developed based on our preclinical experiment to explore the relationship between plasma concentration and drug effect quantitatively. Further, the model was evaluated and validated. By fixing the parameters obtained from the PK/PD model, simulations were built to predict the tumor suppression under various regimens. The synergistic effect was observed between sunitinib and dopamine in the study, which was confirmed by the effect constant (GAMA, estimated as 2.49). The enhanced potency of dopamine on sunitinib was exerted by on/off effect in the PK/PD model. The optimal dose regimen was selected as sunitinib (120 mg/kg, q3d) in combination with dopamine (2 mg/kg, q3d) based on the simulation study. The synergistic effect of sunitinib and dopamine was demonstrated by the preclinical experiment and confirmed by the developed PK/PD model. In addition, the regimens were optimized by means of modeling as well as simulation, which may be conducive to clinical study.

  17. Predictive and prognostic value of preoperative serum tumor markers is EGFR mutation-specific in resectable non-small-cell lung cancer

    Science.gov (United States)

    Jiang, Richeng; Wang, Xinyue; Li, Kai

    2016-01-01

    Background The predictive and prognostic value of carcinoembryonic antigen (CEA), cytokeratin-19 fragments (Cyfra21-1), squamous cell carcinoma antigen (SCCA) and neuron-specific enolase (NSE) has been investigated in non-small-cell lung cancer (NSCLC) patients. However, few studies have directly focused on the association between these markers and epidermal growth factor receptor (EGFR) mutation status or mutation subtypes. Patients and methods We retrospectively analyzed 1016 patients with stage I-IIIA NSCLC who underwent complete resection between 2008 and 2012. Correlations between serum tumor marker levels and EGFR mutations and survival parameters were analyzed and prognostic factors were identified. Results Cyfra21-1 levels (P = 0.032 for disease-free survival [DFS]; P CEA levels (P CEA (P = 0.005) and clinical stage were predictive factors of DFS, while elevated CEA (P = 0.005) and Cyfra21-1 (P = 0.027) were independent prognostic factors. Conclusion Cyfra21-1 and CEA exhibit different predictive and prognostic values between EGFR-mutated and wild-type adenocarcinomas, as well as between EGFR mutation subtypes. The prognostic impact of preoperative serum tumor markers should be evaluated together with EGFR mutation status. PMID:27072585

  18. Early tumor shrinkage served as a prognostic factor for patients with stage III non-small cell lung cancer treated with concurrent chemoradiotherapy.

    Science.gov (United States)

    Wei, Min; Ye, Qingqing; Wang, Xuan; Wang, Men; Hu, Yan; Yang, Yonghua; Yang, Jiyuan; Cai, Jun

    2018-05-01

    Lung cancer is the most common cause of cancer death. About 80% of patients are diagnosed at stage III in the non-small cell lung cancer (NSCLC). It is extremely important to understand the progression of this disease which has low survival times despite the advancing treatment modalities. We aimed to investigate the relationship between early tumor shrinkage (ETS) after initial concurrent chemoradiotherapy (C-CRT) and survival outcome in patients with stage III (NSCLC). A retrospective review of 103 patients with stage III NSCLC who had received C-CRT from January 2006 to October 2011 was performed. Patients were treated with systemic chemotherapy regimen of Cisplatin/Vp-16 and concurrent thoracic radiotherapy at a median dose of 66 Gy (range 60-70 Gy). All patients received a computed tomography (CT) examination before treatment. Also subsequently, chest CT scans were performed with the same imaging parameters at approximately 5 weeks after the initiation of treatment. ETS is here stratified by a decrease in tumor size ≥30% and cancer-related death (P < .05) in stage IIINSCLC. ETS may be served as a useful prognostic factor to predict the outcome of stage III NSCLC patients treated with CCRT.

  19. Cholinesterase response in the rhabdomyosarcoma tumor and small intestine of the BALB/c mice and the radioprotective actions of exogenous ATP after lethal dose of neutron radiation

    International Nuclear Information System (INIS)

    Szeinfeld, D.; De Villiers, N.

    1993-01-01

    The rhabdomyosarcoma tumors were subjected to different doses of 2.0, 3.8 and 7.0 Gy from a neutron beam facility p(66 MeV)/Be. Elevated levels of cholinesterase activity are observed in which there is a correlation between the different doses of neutron radiation and the augmentation response of this enzyme. The increase of cholinesterase activity after 7 Gy neutron irradiation as a feature of involvement in the homeostatic mechanism maintaining the proper choline/acetylcholine ratio in the cell is also observed at 1 and 24 h in both tissues, rhabdomyosarcoma and small intestine. The activity of the enzyme after neutron irradiation with prior administration of ATP showed smaller increases when compared with increase observed after neutron irradiation alone. Moreover in the present work the protective mechanism of ATP in the response of cholinesterase activity is marked differential between both, normal and tumoral tissue and correlated inversely with the administered of the following concentrations of exogenous ATP (8, 25, 80, 250, and 700 mg/kg body weight) prior to exposure to 7 Gy neutron radiation. These results reflect the radioprotective ability of exogenous ATP to exert a number of metabolic adaptations as a defense mechanism in which the cell exposed to neutron radiation could remain viable because the injury is potentially repairable. (orig.) [de

  20. Case Report: A Non-small Cell Lung Cancer Patient Treated with GcMAF, Sonodynamic Therapy and Tumor Treating Fields.

    Science.gov (United States)

    Inui, Toshio; Amitani, Haruka; Kubo, Kentaro; Kuchiike, Daisuke; Uto, Yoshihiro; Nishikata, Takahito; Mette, Martin

    2016-07-01

    Macrophage activating factor (MAF)-based immunotherapy has a wide application for use in treating many diseases via macrophage activation. Sonodynamic therapy (SDT) using low-intensity ultrasound and tumor treating field (TTF) therapy are novel therapeutic modalities. SDT is usually combined with ozone therapy to improve local hypoxia within the tumor environment. We treated a 77-year-old male diagnosed with non-small cell lung cancer ((NSCLC) stage 3B) using second-generation serum GcMAF and oral colostrum MAF-based immunotherapy combined with SDT, TTF and ozone therapies. This case report demonstrates that GcMAF, oral colostrum MAF, SDT, TTF and ozone therapy can be used for NSCLC without adverse effects. This case report suggests a new concept of cancer treatment using local destruction of cancer tissue, in this case conducted with SDT and TTF therapy, to be used in combination with serum GcMAF and colostrum MAF immunotherapy as a systemic treatment. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Miniaturizing 3D assay for high-throughput drug and genetic screens for small patient-derived tumor samples (Conference Presentation)

    Science.gov (United States)

    Rotem, Asaf; Garraway, Levi; Su, Mei-Ju; Basu, Anindita; Regev, Aviv; Struhl, Kevin

    2017-02-01

    Three-dimensional growth conditions reflect the natural environment of cancer cells and are crucial to be performed at drug screens. We developed a 3D assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the 50-year old benchmark assay-soft agar. Using GILA, we performed high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. This phenotypic approach is complementary to our genetic approach that utilizes single-cell RNA-sequencing of a patient sample to identify putative oncogenes that confer sensitivity to drugs designed to specifically inhibit the identified oncoprotein. Currently, we are dealing with a big challenge in our field- the limited number of cells that might be extracted from a biopsy. Small patient-derived samples are hard to test in the traditional multiwell plate and it will be helpful to minimize the culture area and the experimental system. We managed to design a suitable microfluidic device for limited number of cells and perform the assay using image analysis. We aim to test drugs on tumor cells, outside of the patient body- and recommend on the ideal treatment that is tailored to the individual. This device will help to minimize biopsy-sampling volumes and minimize interventions in the patient's tumor.

  2. Tumor Delineation and Quantitative Assessment of Glucose Metabolic Rate within Histologic Subtypes of Non-Small Cell Lung Cancer by Using Dynamic 18F Fluorodeoxyglucose PET.

    Science.gov (United States)

    Meijer, Tineke W H; de Geus-Oei, Lioe-Fee; Visser, Eric P; Oyen, Wim J G; Looijen-Salamon, Monika G; Visvikis, Dimitris; Verhagen, Ad F T M; Bussink, Johan; Vriens, Dennis

    2017-05-01

    Purpose To assess whether dynamic fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static 18 F-FDG PET for tumor delineation in non-small cell lung cancer (NSCLC) radiation therapy planning by using pathology volumes as the reference standard and to compare pharmacokinetic rate constants of 18 F-FDG metabolism, including regional variation, between NSCLC histologic subtypes. Materials and Methods The study was approved by the institutional review board. Patients gave written informed consent. In this prospective observational study, 1-hour dynamic 18 F-FDG PET/computed tomographic examinations were performed in 35 patients (36 resectable NSCLCs) between 2009 and 2014. Static and parametric images of glucose metabolic rate were obtained to determine lesion volumes by using three delineation strategies. Pathology volume was calculated from three orthogonal dimensions (n = 32). Whole tumor and regional rate constants and blood volume fraction (V B ) were computed by using compartment modeling. Results Pathology volumes were larger than PET volumes (median difference, 8.7-25.2 cm 3 ; Wilcoxon signed rank test, P PET images is in best agreement with pathology volume and could be useful for NSCLC autocontouring. Differences in glycolytic rate and V B between SCC and AC are relevant for research in targeting agents and radiation therapy dose escalation. © RSNA, 2016 Online supplemental material is available for this article.

  3. Identification and characterization of small molecule inhibitors of the calcium-dependent S100B-p53 tumor suppressor interaction.

    Science.gov (United States)

    Markowitz, Joseph; Chen, Ijen; Gitti, Rossi; Baldisseri, Donna M; Pan, Yongping; Udan, Ryan; Carrier, France; MacKerell, Alexander D; Weber, David J

    2004-10-07

    The binding of S100B to p53 down-regulates wild-type p53 tumor suppressor activity in cancer cells such as malignant melanoma, so a search for small molecules that bind S100B and prevent S100B-p53 complex formation was undertaken. Chemical databases were computationally searched for potential inhibitors of S100B, and 60 compounds were selected for testing on the basis of energy scoring, commercial availability, and chemical similarity clustering. Seven of these compounds bound to S100B as determined by steady state fluorescence spectroscopy (1.0 microM model of one such inhibitor, pentamidine, bound to Ca(2+)-loaded S100B was calculated using intermolecular NOE data between S100B and the drug, and indicates that pentamidine binds into the p53 binding site on S100B defined by helices 3 and 4 and loop 2 (termed the hinge region).

  4. Prognostic significance of tumor size of small lung adenocarcinomas evaluated with mediastinal window settings on computed tomography.

    Directory of Open Access Journals (Sweden)

    Yukinori Sakao

    Full Text Available BACKGROUND: We aimed to clarify that the size of the lung adenocarcinoma evaluated using mediastinal window on computed tomography is an important and useful modality for predicting invasiveness, lymph node metastasis and prognosis in small adenocarcinoma. METHODS: We evaluated 176 patients with small lung adenocarcinomas (diameter, 1-3 cm who underwent standard surgical resection. Tumours were examined using computed tomography with thin section conditions (1.25 mm thick on high-resolution computed tomography with tumour dimensions evaluated under two settings: lung window and mediastinal window. We also determined the patient age, gender, preoperative nodal status, tumour size, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and pathological status (lymphatic vessel, vascular vessel or pleural invasion. Recurrence-free survival was used for prognosis. RESULTS: Lung window, mediastinal window, tumour disappearance ratio and preoperative nodal status were significant predictive factors for recurrence-free survival in univariate analyses. Areas under the receiver operator curves for recurrence were 0.76, 0.73 and 0.65 for mediastinal window, tumour disappearance ratio and lung window, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant predictive factors for lymph node metastasis in univariate analyses; areas under the receiver operator curves were 0.61, 0.76, 0.72 and 0.66, for lung window, mediastinal window, tumour disappearance ratio and preoperative serum carcinoembryonic antigen levels, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant factors for lymphatic vessel, vascular vessel or pleural invasion in univariate analyses; areas under the receiver operator curves were 0

  5. Prognostic Significance of Tumor Size of Small Lung Adenocarcinomas Evaluated with Mediastinal Window Settings on Computed Tomography

    Science.gov (United States)

    Sakao, Yukinori; Kuroda, Hiroaki; Mun, Mingyon; Uehara, Hirofumi; Motoi, Noriko; Ishikawa, Yuichi; Nakagawa, Ken; Okumura, Sakae

    2014-01-01

    Background We aimed to clarify that the size of the lung adenocarcinoma evaluated using mediastinal window on computed tomography is an important and useful modality for predicting invasiveness, lymph node metastasis and prognosis in small adenocarcinoma. Methods We evaluated 176 patients with small lung adenocarcinomas (diameter, 1–3 cm) who underwent standard surgical resection. Tumours were examined using computed tomography with thin section conditions (1.25 mm thick on high-resolution computed tomography) with tumour dimensions evaluated under two settings: lung window and mediastinal window. We also determined the patient age, gender, preoperative nodal status, tumour size, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and pathological status (lymphatic vessel, vascular vessel or pleural invasion). Recurrence-free survival was used for prognosis. Results Lung window, mediastinal window, tumour disappearance ratio and preoperative nodal status were significant predictive factors for recurrence-free survival in univariate analyses. Areas under the receiver operator curves for recurrence were 0.76, 0.73 and 0.65 for mediastinal window, tumour disappearance ratio and lung window, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant predictive factors for lymph node metastasis in univariate analyses; areas under the receiver operator curves were 0.61, 0.76, 0.72 and 0.66, for lung window, mediastinal window, tumour disappearance ratio and preoperative serum carcinoembryonic antigen levels, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant factors for lymphatic vessel, vascular vessel or pleural invasion in univariate analyses; areas under the receiver operator curves were 0.60, 0.81, 0

  6. Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors

    International Nuclear Information System (INIS)

    Bystroem, C.; Larsson, C.; Blomberg, C.; Nordenskjoeld, M.; Sandelin, K.; Falkmer, U.; Werner, S.; Skogseid, B.; Oeberg, K.

    1990-01-01

    The gene for multiple endocrine neoplasia type 1 (MEN1), and inherited predisposition to neuroendocrine neoplasm of the parathyroid glands, the pancreatic islet parenchyma, and the anterior pituitary gland, was recently mapped to chromosome 11q13 based on genetic linkage in families. The authors now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmasking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms. By examination of allele losses in MEN1-associated lesions, they could define deletions of chromosome 11 and map the MEN1 locus to a small region within chromosome band 11q13, telomeric to the PYGM locus. In contrast, a low incidence of deletions involving the MEN1 gene was found in sporadic pituitary adenomas

  7. Quantitative analysis of tumor shrinkage due to chemotherapy and its implication for radiation treatment planning in limited-stage small-cell lung cancer

    International Nuclear Information System (INIS)

    Xia, Bing; Wang, Jia-Zhou; Liu, Qi; Cheng, Jing-Yi; Zhu, Zheng-Fei; Fu, Xiao-Long

    2013-01-01

    The optimal timing of chemoradiotherapy in limited-stage small-cell lung cancer (LS-SCLC) hasn’t been established, although evidence from studies supported that patients can benefit from early radiation therapy. The purpose of this study was to quantify tumor shrinkage in response to induction chemotherapy (IC), evaluate the impact of tumor shrinkage on radiation dosimetric parameters and determine its implication for the timing of radiation therapy for patients with LS-SCLC. Twenty patients with LS-SCLC who were treated with IC followed by concomitant radiation therapy were investigated retrospectively. Ten patients received 1 cycle of IC, and 10 patients received 2 cycles of IC. Pre-IC CT imaging was coregistered with a simulation CT, and virtual radiation plans were created for pre- and post-IC thoracic disease in each case. The changes in the gross target volume (GTV), planning target volume (PTV) and dosimetric factors associated with the lungs, esophagus and heart were analyzed. The mean GTV and PTV for all of the patients decreased by 60.9% and 40.2%, respectively, which resulted in a significant reduction in the radiation exposure to the lungs, esophagus and heart. Changes in the PTV and radiation exposure of normal tissue were not significantly affected by the number of chemotherapy cycles delivered, although patients who received 2 cycles of IC had a greater decrease in GTV than those who received only 1 cycle of IC (69.6% vs. 52.1%, p = 0.273). Our data showed that targeting the tumor post-IC may reduce the radiation dose to normal tissue in patients with LS-SCLC. However, the benefit to the normal tissue was not increased by an additional cycle of IC. These findings suggest that the first cycle of chemotherapy is very important for tumor shrinkage and that initiating thoracic radiation therapy at the second cycle of chemotherapy may be a reasonable strategy for timing of radiation therapy in LS-SCLC treatment

  8. Small structural changes on a hydroquinone scaffold determine the complex I inhibition or uncoupling of tumoral oxidative phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Urra, Félix A., E-mail: felix.urra@qf.uchile.cl [Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia 1027, Casilla 7, Santiago (Chile); Córdova-Delgado, Miguel [Departamento de Química Orgánica y Físico-Química, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 1 (Chile); Lapier, Michel; Orellana-Manzano, Andrea [Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia 1027, Casilla 7, Santiago (Chile); Acevedo-Arévalo, Luis; Pessoa-Mahana, Hernán; González-Vivanco, Jaime M. [Departamento de Química Orgánica y Físico-Química, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 1 (Chile); Martínez-Cifuentes, Maximiliano [Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca (Chile); and others

    2016-01-15

    Mitochondria participate in several distinctiveness of cancer cell, being a promising target for the design of anti-cancer compounds. Previously, we described that ortho-carbonyl hydroquinone scaffold 14 inhibits the complex I-dependent respiration with selective anti-proliferative effect on mouse mammary adenocarcinoma TA3/Ha cancer cells; however, the structural requirements of this hydroquinone scaffold to affect the oxidative phosphorylation (OXPHOS) of cancer cells have not been studied in detail. Here, we characterize the mitochondrial metabolism of TA3/Ha cancer cells, which exhibit a high oxidative metabolism, and evaluate the effect of small structural changes of the hydroquinone scaffold 14 on the respiration of this cell line. Our results indicate that these structural changes modify the effect on OXPHOS, obtaining compounds with three alternative actions: inhibitors of complex I-dependent respiration, uncoupler of OXPHOS and compounds with both actions. To confirm this, the effect of a bicyclic hydroquinone (9) was evaluated in isolated mitochondria. Hydroquinone 9 increased mitochondrial respiration in state 4o without effects on the ADP-stimulated respiration (state 3{sub ADP}), decreasing the complexes I and II-dependent respiratory control ratio. The effect on mitochondrial respiration was reversed by 6-ketocholestanol addition, indicating that this hydroquinone is a protonophoric uncoupling agent. In intact TA3/Ha cells, hydroquinone 9 caused mitochondrial depolarization, decreasing intracellular ATP and NAD(P)H levels and GSH/GSSG ratio, and slightly increasing the ROS levels. Moreover, it exhibited selective NAD(P)H availability-dependent anti-proliferative effect on cancer cells. Therefore, our results indicate that the ortho-carbonyl hydroquinone scaffold offers the possibility to design compounds with specific actions on OXPHOS of cancer cells. - Highlights: • Small changes on a hydroquinone scaffold modify the action on OXPHOS of cancer

  9. PET/CT evaluation of response to chemotherapy in non-small cell lung cancer: PET response criteria in solid tumors (PERCIST) versus response evaluation criteria in solid tumors (RECIST).

    Science.gov (United States)

    Ding, Qiyong; Cheng, Xu; Yang, Lu; Zhang, Qingbo; Chen, Jianwei; Li, Tiannv; Shi, Haibin

    2014-06-01

    (18)F-FDG PET/CT is increasingly used in evaluation of treatment response for patients with non-small cell lung cancer (NSCLC). There is a need for an accurate criterion to evaluate the effect and predict the prognosis. The aim of this study is to evaluate therapeutic response in NSCLC with comparing PET response criteria in solid tumors (PERCIST) to response evaluation criteria in solid tumors (RECIST) criteria on PET/CT. Forty-four NSCLC patients who received chemotherapy but no surgery were studied. Chemotherapeutic responses were evaluated using (18)F-FDG PET and CT according to the RECIST and PERCIST methodologies. PET/CT scans were obtained before chemotherapy and after 2 or 4-6 cycles' chemotherapy. The percentage changes of tumor longest diameters and standardized uptake value (SUV) (corrected for lean body mass, SUL) before and after treatment were compared using paired t-test. The response was categorized into 4 levels according to RECIST and PERCIST: CR (CMR) =1, PR (PMR) =2, SD (SMD) =3, PD (PMD) =4. Pearson chi-square test was used to compare the proportion of four levels in RECIST and PERCIST. Finally the relationship between progression-free survival (PFS) and clinicopathologic parameters (such as TNM staging, percentage changes in diameters and SUL, RECIST and PERCIST results etc.) were evaluated using univariate and multivariate Cox proportional hazards regression method. The difference of percentage changes between diameters and SUL was not significant using paired t-test (t=-1.69, P=0.098). However the difference was statistically significant in the 40 cases without increasing SUL (t=-3.31, P=0.002). The difference of evaluation results between RECIST and PERCIST was not significant by chi-square test (χ(2)=5.008, P=0.171). If RECIST evaluation excluded the new lesions which could not be found or identified on CT images the difference between RECIST and PERCIST was significant (χ(2)=11.759, P=0.007). Reduction rate of SULpeak (%), RECIST and

  10. The In Vitro Anti-Tumor Activity of Phycocyanin against Non-Small Cell Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Shuai Hao

    2018-05-01

    Full Text Available Phycocyanin, a type of functional food colorant, is shown to have a potent anti-cancer property. Non-small cell lung cancer (NSCLC is one of the most aggressive form of cancers with few effective therapeutic options. Previous studies have demonstrated that phycocyanin exerts a growth inhibitory effect on NSCLC A549 cells. However, its biological function and underlying regulatory mechanism on other cells still remain unknown. Here, we investigated the in vitro function of phycocyanin on three typical NSCLC cell lines, NCI-H1299, NCI-H460, and LTEP-A2, for the first time. The results showed that phycocyanin could significantly induce apoptosis, cell cycle arrest, as well as suppress cell migration, proliferation, and the colony formation ability of NSCLC cells through regulating multiple key genes. Strikingly, phycocyanin was discovered to affect the cell phenotype through regulating the NF-κB signaling of NSCLC cells. Our findings demonstrated the anti-neoplastic function of phycocyanin and provided valuable information for the regulation of phycocyanin in NSCLC cells.

  11. A general aspect on soft-tissue sarcoma and c-kit expression in primitive neuroectodermal tumor and Ewings sarcoma

    International Nuclear Information System (INIS)

    Kara, Ismail O.; Sahin, B.; Gonlusen, G.; Ergin, M.; Erdogan, S.

    2005-01-01

    Within soft-tissue sarcoma, primitive neuroectodermal tumors have been shown to cover a wide spectrum of small round cell sarcomas, including Ewings sarcomas (Es) and primitive neuroectodermal tumors (PET). The role of the stem cell factor/kit pathway has been investigated in different human tumors especially in chronic metallically leukemia and gastrointestinal stromal tumor and an autocrine loop has been assumed in small cell lung carcinoma, and recently in Es and PET. Our aim is to investigate the c-kit expression in Es and PET and also to assessed if c-kit has any role in disease process. We thoroughly searched the archives of the Department of Pathology, Faculty of Medicine, Cukurova University Turkey, between 2000 and 2004; and found 14 ES and 14 PNET paraffin embedded tissues. We carried out the detection of the c-kit expression by immunohistochemical staining. The patients median age was 23.7 +/-14.6 (12 male and 16 female). Five were diagnosed as metastatic disease whereas 23 were diagnosed as non-metastatic disease at admission. The mean follow up period was 38.9 +/- 22.3 months. The main localization of the disease was lower extremity (32.1%), and others were as follows: head and neck 25%, thorax and abdomen 14.3%, pelvic and upper extremity 7.1% (11 were localized skeletal and 17 were extraskeletal). According to treatment modalities, 10 were treated with surgery alone, 11 with surgery and chemotherapy, and 7 with surgery, radiation therapy and also with chemotherapy. The primary tumor was lower than 5 cm in its dimension in 21 patients. While in 5 patients, tumor was more than 5 cm but did not exceed 10 cm, it was >10 cm in 2 patients. The c-kit expression was positive in 7 patients both cytoplasmic and membranously, whereas 8 patients were positive cytoplasmically. In 5 PNET patients, c-kit expression were stained immunohistochemically in over 50% and in 3 of ES patients. There was no significant correlation between c-kit expression and gender

  12. Disruption of focal adhesion kinase and p53 interaction with small molecule compound R2 reactivated p53 and blocked tumor growth

    International Nuclear Information System (INIS)

    Golubovskaya, Vita M; Ho, Baotran; Zheng, Min; Magis, Andrew; Ostrov, David; Morrison, Carl; Cance, William G

    2013-01-01

    Focal Adhesion Kinase (FAK) is a 125 kDa non-receptor kinase that plays a major role in cancer cell survival and metastasis. We performed computer modeling of the p53 peptide containing the site of interaction with FAK, predicted the peptide structure and docked it into the three-dimensional structure of the N-terminal domain of FAK involved in the complex with p53. We screened small molecule compounds that targeted the site of the FAK-p53 interaction and identified compounds (called Roslins, or R compounds) docked in silico to this site. By different assays in isogenic HCT116p53 + / + and HCT116 p53 - / - cells we identified a small molecule compound called Roslin 2 (R2) that bound FAK, disrupted the binding of FAK and p53 and decreased cancer cell viability and clonogenicity in a p53-dependent manner. In addition, dual-luciferase assays demonstrated that the R2 compound increased p53 transcriptional activity that was inhibited by FAK using p21, Mdm-2, and Bax-promoter targets. R2 also caused increased expression of p53 targets: p21, Mdm-2 and Bax proteins. Furthermore, R2 significantly decreased tumor growth, disrupted the complex of FAK and p53, and up-regulated p21 in HCT116 p53 + / + but not in HCT116 p53 - / - xenografts in vivo. In addition, R2 sensitized HCT116p53 + / + cells to doxorubicin and 5-fluorouracil. Thus, disruption of the FAK and p53 interaction with a novel small molecule reactivated p53 in cancer cells in vitro and in vivo and can be effectively used for development of FAK-p53 targeted cancer therapy approaches

  13. The complex relationship between lung tumor volume and survival in patients with non-small cell lung cancer treated by definitive radiotherapy: A prospective, observational prognostic factor study of the Trans-Tasman Radiation Oncology Group (TROG 99.05)

    International Nuclear Information System (INIS)

    Ball, David L.; Fisher, Richard J.; Burmeister, Bryan H.; Poulsen, Michael G.; Graham, Peter H.; Penniment, Michael G.; Vinod, Shalini K.; Krawitz, Hedley E.; Joseph, David J.; Wheeler, Greg C.; McClure, Bev E.

    2013-01-01

    Background and purpose: To investigate the hypothesis that primary tumor volume is prognostic independent of T and N stages in patients with non-small cell lung cancer (NSCLC) treated by definitive radiotherapy. Materials and methods: Multicenter prospective observational study. Patient eligibility: pathologically proven stage I–III non-small cell lung cancer planned for definitive radiotherapy (minimum 50 Gy in 20 fractions) using CT-based contouring. Volumes of the primary tumor and enlarged nodes were measured according to a standardized protocol. Survival was adjusted for the effect of T and N stage. Results: There were 509 eligible patients. Five-year survival rates for tumor volume grouped by quartiles were, for increasing tumor volume, 22%, 14%, 15% and 21%. Larger primary tumor volume was associated with shorter survival (HR = 1.060 (per doubling); 95% CI 1.01–1.12; P = 0.029). However, after adjusting for the effects of T and N stage, there was no evidence for an association (HR = 1.029, 95% CI, 0.96–1.10, P = 0.39). There was evidence, however, that larger primary tumor volume was associated with an increased risk of dying, independently of T and N stage, in the first 18 months but not beyond. Conclusions: In patients treated by non-surgical means we were unable to show that lung tumor volume, overall, provides additional prognostic information beyond the T and N stage (TNM, 6th edition). There is evidence, however, that larger primary tumor volume adversely affects outcome only within the first 18 months. Larger tumor size alone should not by itself exclude patients from curative (chemo)radiotherapy

  14. Comprehensive genomic profiling reveals inactivating SMARCA4 mutations and low tumor mutational burden in small cell carcinoma of the ovary, hypercalcemic-type.

    Science.gov (United States)

    Lin, Douglas I; Chudnovsky, Yakov; Duggan, Bridget; Zajchowski, Deborah; Greenbowe, Joel; Ross, Jeffrey S; Gay, Laurie M; Ali, Siraj M; Elvin, Julia A

    2017-12-01

    Small cell carcinoma of the ovary, hypercalcemic-type (SCCOHT) is a rare, extremely aggressive neoplasm that usually occurs in young women and is characterized by deleterious germline or somatic SMARCA4 mutations. We performed comprehensive genomic profiling (CGP) to potentially identify additional clinically and pathophysiologically relevant genomic alterations in SCCOHT. CGP assessment of all classes of coding alterations in up to 406 genes commonly altered in cancer and intronic regions for up to 31 genes commonly rearranged in cancer was performed on 18 SCCOHT cases (16 exhibiting classic morphology and 2 cases exhibiting exclusive a large cell variant morphology). In addition, a retrospective database search for clinically advanced ovarian tumors with genomic profiles similar to SCCOHT yielded 3 additional cases originally diagnosed as non-SCCOHT. CGP revealed inactivating SMARCA4 alterations and low tumor mutational burden (TMB) (<6mutations/Mb) in 94% (15/16) of SCCOHT with classic morphology. In contrast, both (2/2) cases exhibiting only large cell variant morphology were hypermutated (TMB scores of 90 and 360mut/Mb) and were wildtype for SMARCA4. In our retrospective search, an index ovarian cancer patient harboring inactivating SMARCA4 alterations, initially diagnosed as endometrioid carcinoma, was re-classified as SCCOHT and responded to an SCCOHT chemotherapy regimen. The vast majority of SCCOHT demonstrate genomic SMARCA4 loss with only rare co-occurring alterations. Our data support a role for CGP in the diagnosis and management of SCCOHT and of other lesions with overlapping histological and clinical features, since identifying the former by genomic profile suggests benefit from an appropriate regimen and treatment decisions, as illustrated by an index patient. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Circulating Tumor Cells with Aberrant ALK Copy Number Predict Progression-Free Survival during Crizotinib Treatment in ALK-Rearranged Non-Small Cell Lung Cancer Patients.

    Science.gov (United States)

    Pailler, Emma; Oulhen, Marianne; Borget, Isabelle; Remon, Jordi; Ross, Kirsty; Auger, Nathalie; Billiot, Fanny; Ngo Camus, Maud; Commo, Frédéric; Lindsay, Colin R; Planchard, David; Soria, Jean-Charles; Besse, Benjamin; Farace, Françoise

    2017-05-01

    The duration and magnitude of clinical response are unpredictable in ALK -rearranged non-small cell lung cancer (NSCLC) patients treated with crizotinib, although all patients invariably develop resistance. Here, we evaluated whether circulating tumor cells (CTC) with aberrant ALK -FISH patterns [ ALK -rearrangement, ALK -copy number gain ( ALK -CNG)] monitored on crizotinib could predict progression-free survival (PFS) in a cohort of ALK -rearranged patients. Thirty-nine ALK -rearranged NSCLC patients treated with crizotinib as first ALK inhibitor were recruited prospectively. Blood samples were collected at baseline and at an early time-point (2 months) on crizotinib. Aberrant ALK -FISH patterns were examined in CTCs using immunofluorescence staining combined with filter-adapted FISH after filtration enrichment. CTCs were classified into distinct subsets according to the presence of ALK -rearrangement and/or ALK -CNG signals. No significant association between baseline numbers of ALK -rearranged or ALK -CNG CTCs and PFS was observed. However, we observed a significant association between the decrease in CTC number with ALK -CNG on crizotinib and a longer PFS (likelihood ratio test, P = 0.025). In multivariate analysis, the dynamic change of CTC with ALK -CNG was the strongest factor associated with PFS (HR, 4.485; 95% confidence interval, 1.543-13.030, P = 0.006). Although not dominant, ALK -CNG has been reported to be one of the mechanisms of acquired resistance to crizotinib in tumor biopsies. Our results suggest that the dynamic change in the numbers of CTCs with ALK -CNG may be a predictive biomarker for crizotinib efficacy in ALK -rearranged NSCLC patients. Serial molecular analysis of CTC shows promise for real-time patient monitoring and clinical outcome prediction in this population. Cancer Res; 77(9); 2222-30. ©2017 AACR . ©2017 American Association for Cancer Research.

  16. Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer.

    Science.gov (United States)

    Liang, Yan; Tian, Baocheng; Zhang, Jing; Li, Keke; Wang, Lele; Han, Jingtian; Wu, Zimei

    2017-01-01

    Gemcitabine (GEM) and paclitaxel (PTX) are effective combination anticancer agents against non-small-cell lung cancer (NSCLC). At the present time, a main challenge of combination treatment is the precision of control that will maximize the combined effects. Here, we report a novel method to load GEM (hydrophilic) and PTX (hydrophobic) into simplex tumor-targeted nanostructured lipid carriers (NLCs) for accurate control of the ratio of the two drugs. We covalently preconjugated the dual drugs through a hydrolyzable ester linker to form drug conjugates. N -acetyl-d-glucosamine (NAG) is a glucose receptor-targeting ligand. We added NAG to the formation of NAG-NLCs. In general, synthesis of poly(6- O -methacryloyl-d-galactopyranose)-GEM/PTX (PMAGP-GEM/PTX) conjugates was demonstrated, and NAG-NLCs were prepared using emulsification and solvent evaporation. NAG-NLCs displayed sphericity with an average diameter of 120.3±1.3 nm, a low polydispersity index of 0.233±0.04, and accurate ratiometric control over the two drugs. A cytotoxicity assay showed that the NAG-NLCs had better antitumor activity on NSCLC cells than normal cells. There was an optimal ratio of the two drugs, exhibiting the best cytotoxicity and combinatorial effects among all the formulations we tested. In comparison with both the free-drug combinations and separately nanopackaged drug conjugates, PMAGP-GEM/PTX NAG-NLCs (3:1) exhibited superior synergism. Flow cytometry and confocal laser scanning microscopy showed that NAG-NLCs exhibited higher uptake efficiency in A549 cells via glucose receptor-mediated endocytosis. This combinatorial delivery system settles problems with ratiometric coloading of hydrophilic and hydrophobic drugs for tumor-targeted combination therapy to achieve maximal anticancer efficacy in NSCLC.

  17. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

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    Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Kim, Sinae [Division of Biometrics, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Department of Biostatistics, School of Public Health, Rutgers University, New Brunswick, New Jersey (United States); Haider, Syed A. [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Xu, Xiaoting [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Soochow (China); Wu, Alson [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Surakanti, Sujani; Aisner, Joseph [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Langenfeld, John [Division of Surgery, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Yue, Ning J.; Haffty, Bruce G.; Zou, Wei [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States)

    2015-07-01

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes.

  18. Different metastasis promotive potency of small G-proteins RalA and RalB in in vivo hamster tumor model

    Directory of Open Access Journals (Sweden)

    Trukhanova Lyubov S

    2011-06-01

    Full Text Available Abstract Background Previously we have shown that oncogenic Ha-Ras stimulated in vivo metastasis through RalGEF-Ral signaling. RalA and RalB are highly homologous small G proteins belonging to Ras superfamily. They can be activated by Ras-RalGEF signaling pathway and influence cellular growth and survival, motility, vesicular transport and tumor progression in humans and in animal models. Here we first time compared the influence of RalA and RalB on tumorigenic, invasive and metastatic properties of RSV transformed hamster fibroblasts. Methods Retroviral vectors encoding activated forms or effector mutants of RalA or RalB proteins were introduced into the low metastatic HET-SR cell line. Tumor growth and spontaneous metastatic activity (SMA were evaluated on immunocompetent hamsters after subcutaneous injection of cells. The biological properties of cells, including proliferation, clonogenicity, migration and invasion were determined using MTT, wound healing, colony formation and Boyden chamber assays respectively. Protein expression and phosphorylation was detected by Westen blot analysis. Extracellular proteinases activity was assessed by substrate-specific zymography. Results We have showed that although both Ral proteins stimulated SMA, RalB was more effective in metastasis stimulation in vivo as well as in potentiating of directed movement and invasion in vitro. Simultaneous expression of active RalA and RalB didn't give synergetic effect on metastasis formation. RalB activity decreased expression of Caveolin-1, while active RalA stimulated MMP-1 and uPA proteolytic activity, as well as CD24 expression. Both Ral proteins were capable of Cyclin D1 upregulation, JNK1 kinase activation, and stimulation of colony growth and motility. Among three main RalB effectors (RalBP1, exocyst complex and PLD1, PLD1 was essential for RalB-dependent metastasis stimulation. Conclusions Presented results are the first data on direct comparison of RalA and Ral

  19. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Jabbour, Salma K.; Kim, Sinae; Haider, Syed A.; Xu, Xiaoting; Wu, Alson; Surakanti, Sujani; Aisner, Joseph; Langenfeld, John; Yue, Ning J.; Haffty, Bruce G.; Zou, Wei

    2015-01-01

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes

  20. Thin-section multiplanar reformats from multidetector-row CT data: Utility for assessment of regional tumor extent in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Higashino, Takanori; Ohno, Yoshiharu; Takenaka, Daisuke; Watanabe, Hirokazu; Nogami, Munenobu; Ohbayashi, Chiho; Yoshimura, Masahiro; Satouchi, Miyako; Nishimura, Yoshihiro; Fujii, Masahiko; Sugimura, Kazuro

    2005-01-01

    Purpose: To determine the clinical utility of thin-section multiplanar reformats (MPRs) from multidetector-row CT (MDCT) data sets for assessing the extent of regional tumors in non-small cell lung cancer (NSCLC) patients. Materials and methods: Sixty consecutive NSCLC patients, who were considered candidates for surgical treatment, underwent contrast-enhanced MDCT examinations, surgical resection and pathological examinations. All MDCT examinations were performed with a 4-detector row computed tomography (CT). From each raw CT data set, 5 mm section thickness CT images (routine CT), 1.25 mm section thickness CT images (thin-section CT) and 1.25 mm section thickness sagittal (thin-section sagittal MPR) and coronal images (thin-section coronal MPR) were reconstructed. A 4-point visual score was used to assess mediastinal, interlobar and chest wall invasions on each image set. For assessment of utility in routine clinical practice, mean reading times for each image set were compared by means of Fisher's protected least significant difference (PLSD) test. A receiver operator characteristic (ROC) analysis was performed to determine the diagnostic capability of each of the image data sets. Finally, sensitivity, specificity and accuracy of the reconstructed images were compared by McNemar test. Results: Mean reading times for thin-section sagittal and coronal MPRs were significantly shorter than those for routine CT and thin-section CT (p < 0.05). Areas under the curve (Azs) showing interlobar invasion on thin-section sagittal and coronal MPRs were significantly larger than that on routine CT (p = 0.03), and the Az on thin-section sagittal MPR was also significantly larger than that on routine CT (p = 0.02). Accuracy of chest wall invasion by thin-section sagittal MPR was significantly higher than that by routine CT (p = 0.04). Conclusion: Thin-section multiplanar reformats from multidetector-row CT data sets are useful for assessing the extent of regional tumors in non-small

  1. Comparison of six methods of segmentation of tumor volume on the 18F-F.D.G. PET scan with reference histological volume in non small cell bronchopulmonary cancers

    International Nuclear Information System (INIS)

    Venel, Y.; Garhi, H.; Baulieu, J.L.; Prunier-Aesch, C.; Muret, A. de; Barillot, I.

    2008-01-01

    The 18 F-F.D.G. PET has demonstrated its importance in oncology, for initial extension and efficacy of anti tumoral therapeutics. Several studies have attempted to prove its utility to define tumoral volumes for conformational radiotherapy in non small cell lung cancers. Some authors have suggested the use of threshold of tumor intensity uptake with 40 or 50% of maximal intensity. Black et al. have determined contouring with linear regression formula of mean semi-quantitative index of tumor uptake (standard uptake value): SUV threshold = 0.307 Sub average + 0.588. Nestle et al. have taken into account the background noise intensity and mean intensity of the tumor: I threshold = β I average +I noise with β 0.15. Our study was done in collaboration with Inserm U618 team and has compared volumes defined on PET scan defined according to different methods based on intensity or S.U.V. to the tumour volume determined on CT scan by radio physicist. We have compared those volumes with histological volume that we considered for reference. Four patients have been included. They had 18 F-F.D.G. PET scan followed by complete tumoral removal surgery. Specific histological procedure allowed to define complete size of the tumor in re expanded lung. Comparatively to pathology, the volumes obtained using I max 40 and I max 50 are all underestimated. The volumes defined by Black's et al. method are under evaluated for the two largest tumours (15.8% to 22%) and overestimated for the two smallest ones (17.9 to 82.9%). Nestle's et al. method, using β = 0.15, correctly estimates two tumor volumes over 2 cm, but overestimates the two small tumors (79.6 to 124%). Finally, the corrected Nestle's et al. formula (using β = 0.264) overestimates three tumours. Volumes defined on CT scan by radio physicist are correct for one lesion, underestimated for one and overestimated for two other ones (44 and 179.5%). Nestle's et al. method seems to be the most accurate for tumours over 2 cm of

  2. Positive correlation between postoperative tumor recurrence and changes in circulating tumor cell counts in pulmonary venous blood (pvCTC) during surgical manipulation in non-small cell lung cancer.

    Science.gov (United States)

    Hashimoto, Masaki; Tanaka, Fumihiro; Yoneda, Kazue; Takuwa, Teruhisa; Matsumoto, Seiji; Okumura, Yoshitomo; Kondo, Nobuyuki; Tsujimura, Tohru; Nakano, Takashi; Hasegawa, Seiki

    2018-01-01

    In non-small cell lung cancer (NSCLC), circulating tumor cells (CTC) are shed and circulate to the peripheral blood through the pulmonary vein. Previously, CTC count in pulmonary venous blood (pvCTC) was shown to significantly increase after surgical manipulation. Therefore, we assessed the correlation between the changes in the pvCTC count (ΔpvCTC) and clinical outcomes. Consecutive patients with peripheral-type, NSCLC, who underwent lobectomy or bi-lobectomy through open thoracotomy, were enrolled prospectively. Before and after lobectomy, 2.5 mL of blood was drawn from the associated lobar pulmonary vein (PV), and was served for the quantitative evaluation of CTC using the CellSearch ® system. The cut-off point of ΔpvCTC was determined according to clinical outcomes and ΔpvCTC using receiver operation characteristic (ROC) curve. Then the correlation between ΔpvCTC and clinical outcomes was evaluated by Kaplan-Meier analyses and log-rank test. In addition, the correlation between ΔpvCTC and perioperative variables was assessed. A total of 30 patients were enrolled, tumor recurrence occurred in 11 patients over a median follow-up of 64.4 months. Of these, 7 patients had distant metastasis and 4 had local recurrence. The median ΔpvCTC was 49 cells/2.5 mL, and pvCTC-count was increased during surgical manipulation in 24 patients (80%). We divided patients into two groups based on ΔpvCTC with the cut-off value as 119 cells/2.5 mL according to ROC curve. Significant shorter time to distant metastasis (TDM) (P=0.0123) was observed in high ΔpvCTC group (ΔpvCTC ≥119 cells/2.5 mL) than low ΔpvCTC group (ΔpvCTC <119 cells/ 2.5mL). Neither disease-free survival (DFS) nor overall survival (OS) was significantly correlated with ΔpvCTC. Increasing pvCTC count during surgical manipulation was significantly correlated with postoperative distant metastasis in completely resected NSCLC patients. Significant shorter TDM was observed in patient with high ΔpvCTC group.

  3. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  4. Intervention with the hypoxic tumor cell sensitizer etanidazole in the combined modality treatment of limited stage small-cell lung cancer. A one-institution study

    International Nuclear Information System (INIS)

    Urtasun, Raul C.; Palmer, Martin; Kinney, Brenda; Belch, Andrew; Hewitt, Joanne; Hanson, John

    1998-01-01

    Purpose: We report the toxicity, patterns of failure and survival of a cohort of patients with limited disease (LD) small-cell lung cancer (SCLC) treated with combined radiation and chemotherapy. During the course of thoracic irradiation, we added intravenous (i.v.) etanidazole (SR-2508, a third-generation 2-nitroimidazole) as a hypoxic cell sensitizer in an attempt to reduce the primary local failure rate and improve survival. Methods and Materials: Between July 1988 and August 1990, 30 consecutive patients with limited disease SCLC were enrolled and treated on a Phase II protocol receiving a standard combination chemotherapy regimen utilizing i.v. cisplatin 25 mg/m 2 /day x 3 days, i.v. etoposide 100 mg/m 2 /day x 3 days alternating with intravenous cyclophosphamide 1000 mg/m 2 /day, intravenous doxorubicin 15 mg/m 2 , and intravenous vincristine 2 mg (CAV) to a total of six cycles every 3 weeks. Radiotherapy and etanidazole were started after the first cycle of chemotherapy. Etanidazole was administered intravenously at a dose of 2 g/m 2 three times per week for a total of 30 g/m 2 during the course of thoracic radiation that delivered 50.00 Gy tumor dose in 25 fractions in an overall time of 6 weeks. Results: The overall response rate of the primary lesion in the thorax was 96% (CR + PR), with 64% complete responses. The median time to treatment failure was 18 months. Of the patients that have relapsed, only 18% failed in the thorax (alone or concomitant with other sites). This is a marked improvement compared to the 40-50% rate reported in the literature. The 2-year crude survival was 46%. The 3- and 5-year crude survival rate with no evidence of disease was 33 and 30%, respectively. We have observed a 10% increase in the incidence of transient etanidazole related peripheral neuropathies compared to previous etanidazole studies not utilizing systemic chemotherapy. There was no increased incidence of radiation esophagitis, pulmonary toxicity, or nephro- or

  5. The Novel miR-9600 Suppresses Tumor Progression and Promotes Paclitaxel Sensitivity in Non–small-cell Lung Cancer Through Altering STAT3 Expression

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    Cheng-Cao Sun

    2016-01-01

    Full Text Available MicroRNAs have been identified to be involved in center stage of cancer biology. They accommodate cell proliferation and migration by negatively regulate gene expression either by hampering the translation of targeted mRNAs or by promoting their degradation. We characterized and identified the novel miR-9600 and its target in human non–small-cell lung cancer (NSCLC. Our results demonstrated that the miR-9600 were downregulated in NSCLC tissues and cells. It is confirmed that signal transducer and activator of transcription 3 (STAT3, a putative target gene, is directly inhibited by miR-9600. The miR-9600 markedly suppressed the protein expression of STAT3, but with no significant influence in corresponding mRNA levels, and the direct combination of miR-9600 and STAT3 was confirmed by a luciferase reporter assay. miR-9600 inhibited cell growth, hampered expression of cell cycle-related proteins and inhibited cell migration and invasion in human NSCLC cell lines. Further, miR-9600 significantly suppressed tumor growth in nude mice. Similarly, miR-9600 impeded tumorigenesis and metastasis through directly targeting STAT3. Furthermore, we identified that miR-9600 augmented paclitaxel and cisplatin sensitivity by downregulating STAT3 and promoting chemotherapy-induced apoptosis. These data demonstrate that miR-9600 might be a useful and novel therapeutic target for NSCLC.

  6. Adenovirus small E1A employs the lysine acetylases p300/CBP and tumor suppressor Rb to repress select host genes and promote productive virus infection.

    Science.gov (United States)

    Ferrari, Roberto; Gou, Dawei; Jawdekar, Gauri; Johnson, Sarah A; Nava, Miguel; Su, Trent; Yousef, Ahmed F; Zemke, Nathan R; Pellegrini, Matteo; Kurdistani, Siavash K; Berk, Arnold J

    2014-11-12

    Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with the host lysine acetylases p300/CBP and the tumor suppressor RB. How these interactions influence cellular gene expression remains unclear. We find that e1a displaces RBs from E2F transcription factors and promotes p300 acetylation of RB1 K873/K874 to lock it into a repressing conformation that interacts with repressive chromatin-modifying enzymes. These repressing p300-e1a-RB1 complexes specifically interact with host genes that have unusually high p300 association within the gene body. The TGF-β, TNF-, and interleukin-signaling pathway components are enriched among such p300-targeted genes. The p300-e1a-RB1 complex condenses chromatin in a manner dependent on HDAC activity, p300 lysine acetylase activity, the p300 bromodomain, and RB K873/K874 and e1a K239 acetylation to repress host genes that would otherwise inhibit productive virus infection. Thus, adenovirus employs e1a to repress host genes that interfere with viral replication. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Decision tree sensitivity analysis for cost-effectiveness of chest FDG-PET in patients with a pulmonary tumor (non-small cell carcinoma)

    International Nuclear Information System (INIS)

    Kosuda, Shigeru; Watanabe, Masumi; Kobayashi, Hideo; Kusano, Shoichi; Ichihara, Kiyoshi

    1998-01-01

    Decision tree analysis was used to assess cost-effectiveness of chest FDG-PET in patients with a pulmonary tumor (non-small cell carcinoma, ≤Stage IIIB), based on the data of the current decision tree. Decision tree models were constructed with two competing strategies (CT alone and CT plus chest FDG-PET) in 1,000 patient population with 71.4% prevalence. Baselines of FDG-PET sensitivity and specificity on detection of lung cancer and lymph node metastasis, and mortality and life expectancy were available from references. Chest CT plus chest FDG-PET strategy increased a total cost by 10.5% when a chest FDG-PET study costs 0.1 million yen, since it increased the number of mediastinoscopy and curative thoracotomy despite reducing the number of bronchofiberscopy to half. However, the strategy resulted in a remarkable increase by 115 patients with curable thoracotomy and decrease by 51 patients with non-curable thoracotomy. In addition, an average life expectancy increased by 0.607 year/patient, which means increase in medical cost is approximately 218,080 yen/year/patient when a chest FDG-PET study costs 0.1 million yen. In conclusion, chest CT plus chest FDG-PET strategy might not be cost-effective in Japan, but we are convinced that the strategy is useful in cost-benefit analysis. (author)

  8. Inhibition of adipose triglyceride lipase (ATGL) by the putative tumor suppressor G0S2 or a small molecule inhibitor attenuates the growth of cancer cells.

    Science.gov (United States)

    Zagani, Rachid; El-Assaad, Wissal; Gamache, Isabelle; Teodoro, Jose G

    2015-09-29

    The G0/G1 switch gene 2 (G0S2) is methylated and silenced in a wide range of human cancers. The protein encoded by G0S2 is an endogenous inhibitor of lipid catabolism that directly binds adipose triglyceride lipase (ATGL). ATGL is the rate-limiting step in triglyceride metabolism. Although the G0S2 gene is silenced in cancer, the impact of ATGL in the growth and survival of cancer cells has never been addressed. Here we show that ectopic expression of G0S2 in non-small cell lung carcinomas (NSCL) inhibits triglyceride catabolism and results in lower cell growth. Similarly, knockdown of ATGL increased triglyceride levels, attenuated cell growth and promoted apoptosis. Conversely, knockdown of endogenous G0S2 enhanced the growth and invasiveness of cancer cells. G0S2 is strongly induced in acute promyelocytic leukemia (APL) cells in response to all trans retinoic acid (ATRA) and we show that inhibition of ATGL in these cells by G0S2 is required for efficacy of ATRA treatment. Our data uncover a novel tumor suppressor mechanism by which G0S2 directly inhibits activity of a key intracellular lipase. Our results suggest that elevated ATGL activity may be a general property of many cancer types and potentially represents a novel target for chemotherapy.

  9. Adaptive Radiotherapy for Locally Advanced Non–Small-Cell Lung Cancer Does Not Underdose the Microscopic Disease and has the Potential to Increase Tumor Control

    International Nuclear Information System (INIS)

    Guckenberger, Matthias; Richter, Anne; Wilbert, Juergen; Flentje, Michael; Partridge, Mike

    2011-01-01

    Purpose: To evaluate doses to the microscopic disease (MD) in adaptive radiotherapy (ART) for locally advanced non–small-cell lung cancer (NSCLC) and to model tumor control probability (TCP). Methods and Materials: In a retrospective planning study, three-dimensional conformal treatment plans for 13 patients with locally advanced NSCLC were adapted to shape and volume changes of the gross tumor volume (GTV) once or twice during conventionally fractionated radiotherapy with total doses of 66 Gy; doses in the ART plans were escalated using an iso-mean lung dose (MLD) approach compared to non-adapted treatment. Dose distributions to the volumes of suspect MD were simulated for a scenario with synchronous shrinkage of the MD and GTV and for a scenario of a stationary MD despite GTV shrinkage; simulations were performed using deformable image registration. TCP calculations considering doses to the GTV and MD were performed using three different models. Results: Coverage of the MD at 50 Gy was not compromised by ART. Coverage at 60 Gy in the scenario of a stationary MD was significantly reduced from 92% ± 10% to 73% ± 19% using ART; however, the coverage was restored by iso-MLD dose escalation. Dose distributions in the MD were sufficient to achieve a TCP >80% on average in all simulation experiments, with the clonogenic cell density the major factor influencing TCP. The combined TCP for the GTV and MD was 19.9% averaged over all patients and TCP models in non-adaptive treatment with 66 Gy. Iso-MLD dose escalation achieved by ART increased the overall TCP by absolute 6% (adapting plan once) and by 8.7% (adapting plan twice) on average. Absolute TCP values were significantly different between the TCP models; however, all TCP models suggested very similar TCP increase by using ART. Conclusions: Adaptation of radiotherapy to the shrinking GTV did not compromise dose coverage of volumes of suspect microscopic disease and has the potential to increase TCP by >40% compared

  10. Focal Adhesion Kinase Inhibitors in Combination with Erlotinib Demonstrate Enhanced Anti-Tumor Activity in Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Grant A Howe

    Full Text Available Blockade of epidermal growth factor receptor (EGFR activity has been a primary therapeutic target for non-small cell lung cancers (NSCLC. As patients with wild-type EGFR have demonstrated only modest benefit from EGFR tyrosine kinase inhibitors (TKIs, there is a need for additional therapeutic approaches in patients with wild-type EGFR. As a key component of downstream integrin signalling and known receptor cross-talk with EGFR, we hypothesized that targeting focal adhesion kinase (FAK activity, which has also been shown to correlate with aggressive stage in NSCLC, would lead to enhanced activity of EGFR TKIs. As such, EGFR TKI-resistant NSCLC cells (A549, H1299, H1975 were treated with the EGFR TKI erlotinib and FAK inhibitors (PF-573,228 or PF-562,271 both as single agents and in combination. We determined cell viability, apoptosis and 3-dimensional growth in vitro and assessed tumor growth in vivo. Treatment of EGFR TKI-resistant NSCLC cells with FAK inhibitor alone effectively inhibited cell viability in all cell lines tested; however, its use in combination with the EGFR TKI erlotinib was more effective at reducing cell viability than either treatment alone when tested in both 2- and 3-dimensional assays in vitro, with enhanced benefit seen in A549 cells. This increased efficacy may be due in part to the observed inhibition of Akt phosphorylation when the drugs were used in combination, where again A549 cells demonstrated the most inhibition following treatment with the drug combination. Combining erlotinib with FAK inhibitor was also potent in vivo as evidenced by reduced tumor growth in the A549 mouse xenograft model. We further ascertained that the enhanced sensitivity was irrespective of the LKB1 mutational status. In summary, we demonstrate the effectiveness of combining erlotinib and FAK inhibitors for use in known EGFR wild-type, EGFR TKI resistant cells, with the potential that a subset of cell types, which includes A549, could be

  11. Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Liang Y

    2017-03-01

    Full Text Available Yan Liang,1 Baocheng Tian,1 Jing Zhang,1 Keke Li,1 Lele Wang,1 Jingtian Han,1,* Zimei Wu2,* 1School of Pharmacy, Binzhou Medical University, 2School of Pharmacy, Yantai University, Yantai, China *These authors contributed equally to this work Abstract: Gemcitabine (GEM and paclitaxel (PTX are effective combination anticancer agents against non-small-cell lung cancer (NSCLC. At the present time, a main challenge of combination treatment is the precision of control that will maximize the combined effects. Here, we report a novel method to load GEM (hydrophilic and PTX (hydrophobic into simplex tumor-targeted nanostructured lipid carriers (NLCs for accurate control of the ratio of the two drugs. We covalently preconjugated the dual drugs through a hydrolyzable ester linker to form drug conjugates. N-acetyl-D-glucosamine (NAG is a glucose receptor-targeting ligand. We added NAG to the formation of NAG-NLCs. In general, synthesis of poly(6-O-methacryloyl-d-galactopyranose–GEM/PTX (PMAGP-GEM/PTX conjugates was demonstrated, and NAG-NLCs were prepared using emulsification and solvent evaporation. NAG-NLCs displayed sphericity with an average diameter of 120.3±1.3 nm, a low polydispersity index of 0.233±0.04, and accurate ratiometric control over the two drugs. A cytotoxicity assay showed that the NAG-NLCs had better antitumor activity on NSCLC cells than normal cells. There was an optimal ratio of the two drugs, exhibiting the best cytotoxicity and combinatorial effects among all the formulations we tested. In comparison with both the free-drug combinations and separately nanopackaged drug conjugates, PMAGP-GEM/PTX NAG-NLCs (3:1 exhibited superior synergism. Flow cytometry and confocal laser scanning microscopy showed that NAG-NLCs exhibited higher uptake efficiency in A549 cells via glucose receptor-mediated endocytosis. This combinatorial delivery system settles problems with ratiometric coloading of hydrophilic and hydrophobic drugs for tumor

  12. Correlation of F-18 FDG PET with morphometric tumor response after neoadjuvant chemoradiation in locally advanced (stage III) non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Baum, R.P.; Schmuecking, M.; Bonnet, R.; Presselt, N.; Przetak, C.; Junker, K.; Schneider, C.P.; Hoeffken, K.; Wendt, T.G.

    2002-01-01

    Aim: To determine the role of 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) positron emission tomography (PET) in morphometric tumor response after neoadjuvant chemoradiation, findings in 32 patients were analyzed prospectively in an ongoing multicenter trial (LUCAS-MD, Germany). Material and Methods: Inclusion criteria was histologically confirmed NSCLC stage IIIA/IIIB. For staging all patients received a PET scan in addition to a spiral CT and/or MRI before therapy. Neoadjuvant treatment consisted of 2-3 cycles of chemotherapy with paclitaxel (225 mg/m 2 ) and carboplatin (AUC 6), each d1 q22 and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant with paclitaxel (50 mg/m 2 ) and carboplatin (AUC = 2), each d1, d8, d15) followed by surgery. All patients received a second PET after completion of neoadjuvant therapy prior to surgery. Whole-body PET (ECAT Exact 47) studies (attenuation corrected, iteratively reconstructed) were obtained 60 min. after injection of 6 MBq/kg body weight F-18 FDG. For semi-quantitative analysis, the tumor standardized uptake values (SUV), the tumor to background SUV ratio (T/B ratio), the metabolic tumor diameter (MTD) and the metabolic tumor index (MTI = SUV x MTD) were assessed in all primary tumors and in metastatic lymph nodes. Additionally, image fusion of PET with CT data was applied (using a HERMES Computer, Nuclear Diagnostics, Sweden). Results: So far, all patients (7/32) with complete metabolic response in lymph node metastases detected by PET, had no vital tumor cells (morphometric regression grade III). In primary tumors showing complete metabolic response, the regression grade was IIB (less than 10% vital tumor cells) or III. Conclusion: Morphometric tumor response after neoadjuvant therapy correlates strongly with metabolic remission by FDG-PET. PET precedes the tumor response as measured by CT after neoadjuvant treatment and may predict the long term therapeutic outcome in stage III NSCLC

  13. Production and dosimetric aspects of the potent Auger emitter {sup 58m}Co for targeted radionuclide therapy of small tumors

    Energy Technology Data Exchange (ETDEWEB)

    Thisgaard, H.; Elema, D.R.; Jensen, M. [PET and Cyclotron Unit, Nuclear Medicine Department, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense, Denmark and Institute of Clinical Research, University of Southern Denmark, Winsloewparken 19, DK-5000 Odense (Denmark); The Hevesy Laboratory, Risoe National Laboratory for Sustainable Energy, Technical University of Denmark, P.O. Box 49, DK-4000 Roskilde (Denmark)

    2011-08-15

    Purpose: Based on theoretical calculations, the Auger emitter {sup 58m}Co has been identified as a potent nuclide for targeted radionuclide therapy of small tumors. During the production of this isotope, the coproduction of the long-lived ground state {sup 58g}Co is unfortunately unavoidable, as is ingrowth of the ground state following the isomeric decay of {sup 58m}Co. The impact of {sup 58g}Co as a {beta}{sup +}- and {gamma}-emitting impurity should be included in the dosimetric analysis. The purpose of this study was to investigate this critical part of dosimetry based on experimentally determined production yields of {sup 58m}Co and {sup 58g}Co using a low-energy cyclotron. Also, the cellular S-values for {sup 58m}Co have been calculated and are presented here for the first time. Methods: {sup 58m}Co was produced via the {sup 58}Fe(p,n){sup 58m}Co nuclear reaction on highly enriched {sup 58}Fe metal. In addition, radiochemical separations of produced radio-cobalt from {sup nat}Fe target material were performed. The theoretical subcellular dosimetry calculations for {sup 58m}Co and {sup 58g}Co were performed using the MIRD formalism, and the impact of the increasing ground state impurity on the tumor-to-normal-tissue dose ratios (TND) per disintegration as a function of time after end of bombardment (EOB) was calculated. Results: 192 {+-} 8 MBq of {sup 58m}Co was produced in the irradiation corresponding to a production yield of 10.7 MBq/{mu}Ah. The activity of {sup 58g}Co was measured to be 0.85% {+-} 0.04% of the produced {sup 58m}Co activity at EOB. The radio-cobalt yields in the rapid separations were measured to be >97% with no detectable iron contaminations in the cobalt fractions. Due to the unavoidable coproduction and ingrowth of the long-lived ground state {sup 58g}Co, the TND and the potency of the {sup 58m}Co decrease with time after EOB. If a future treatment with a {sup 58m}Co labeled compound is not initiated before, e.g., 21 h after EOB, the

  14. Metabolic tumor volume measured by F 18 FDG PET/CT can further stratify the prognosis of patients with stage IV Non Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Su Woong; Kim, Ja Hae; Chong, Ar I; Kwon, Seong Young; Min, Jung Joon; Song, Ho Chun; Bom, Hee Seung [Chonnam National Univ. Hwasun Hospital, Gwangju (Korea, Republic of)

    2012-12-15

    This study aimed to further stratify prognostic factors in patients with stage IV non small cell lung cancer (NSCLC) by measuring their metabolic tumor volume (MTV) using F 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). The subjects of this retrospective study were 57 patients with stage IV NSCLC. MTV, total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured on F 18 FDG PET/CT in both the primary lung lesion as well as metastatic lesions in torso. Optimal cutoff values of PET parameters were mea measured by receiver operating characteristic (ROC) curve anal analysis. Kaplan Meier survival (PET). The univariate and multivariate cox proportional hazards models were used to select the significant prognostic factors. Univariate analysis showed that both MTV and TLG of primary lung lesion (MTV lung and TLG lung) were significant factors for prediction of PFS ( <0.001 =0.038, respectively). Patients showing lower values of MTV lung and TLG lung than the cutoff values had significantly longer mean PFS than those with higher values. hazard ratios (95% confidence interval) of MTV lung and TLG lung measured by univariate analysis were 6.4 (2.5 16.3) and 2.4 (1.0 5.5), respectively. multivariate analysis revealed that MTV lung was the only significant factor for prediction of prognosis. Hazard ratio was 13,5 (1.6 111.1, =0,016). patients with stage IV NSCLC could be further stratified into subgroups of significantly better and worse prognosis by MTV of primary lung lesion.

  15. Metabolic tumor volume measured by F 18 FDG PET/CT can further stratify the prognosis of patients with stage IV Non Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Yoo, Su Woong; Kim, Ja Hae; Chong, Ar I; Kwon, Seong Young; Min, Jung Joon; Song, Ho Chun; Bom, Hee Seung

    2012-01-01

    This study aimed to further stratify prognostic factors in patients with stage IV non small cell lung cancer (NSCLC) by measuring their metabolic tumor volume (MTV) using F 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). The subjects of this retrospective study were 57 patients with stage IV NSCLC. MTV, total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured on F 18 FDG PET/CT in both the primary lung lesion as well as metastatic lesions in torso. Optimal cutoff values of PET parameters were mea measured by receiver operating characteristic (ROC) curve anal analysis. Kaplan Meier survival (PET). The univariate and multivariate cox proportional hazards models were used to select the significant prognostic factors. Univariate analysis showed that both MTV and TLG of primary lung lesion (MTV lung and TLG lung) were significant factors for prediction of PFS ( <0.001 =0.038, respectively). Patients showing lower values of MTV lung and TLG lung than the cutoff values had significantly longer mean PFS than those with higher values. hazard ratios (95% confidence interval) of MTV lung and TLG lung measured by univariate analysis were 6.4 (2.5 16.3) and 2.4 (1.0 5.5), respectively. multivariate analysis revealed that MTV lung was the only significant factor for prediction of prognosis. Hazard ratio was 13,5 (1.6 111.1, =0,016). patients with stage IV NSCLC could be further stratified into subgroups of significantly better and worse prognosis by MTV of primary lung lesion

  16. Prognostic and predictive role of FOXP3 positive tumor infiltrating lymphocytes (TILs in curatively resected non small cell lung cancer other than stage IA

    Directory of Open Access Journals (Sweden)

    Fatih Kose

    2017-12-01

    Full Text Available Lung cancer is the leading cause of cancer-related mortality and responsible for 1.6 million deaths per year through world-wide. Surgical resection with negative margin combined with the adjuvant therapy [except for stage IA and IB (<4 cm] is the Standard treatment for early-stage Non-small cell lung cancer (NSCLC. Early-stage NSCLC, however, has relapse rate over 40% mostly at distant sites. Therefore, high relapse rate necessitates urgent novel biomarker for these patients. In this study, we aim to evaluate the predictive and prognostic role of FOXP3+ Treg cells along with well defined Clinicohistopathological factors in early-stage non-small cell lung cancer (NSCLC. FOXP3 expression in tumor infiltrating lymphocytes (TIL was examined by immunohistochemical staining from resected early-stage 48 NSCLC patients. Data of patients and FOXP3 expression status along with common clinicohistopathological prognostic factors were evaluated retrospectively. Median age of patients was 62 years-old (range 43–78. Mean follow-up, median overall survival (OS, and disease-free survival (DFS were 49, 49 and 30 months, respectively. FOXP3 expression was positive in 23 (47.9% patients. Adjuvant chemotherapy (4 cycles of cisplatin-vinorelbine was given to 16 patients (33.3% at physician discretion. Patients with a FOXP3 expression of 25% or higher significantly lower OS and DFS when compared with patients with a FOXP3 staining lower than 25% with p-value of 0.016 and 0.032, respectively. In the patients with high FOXP3 expression, platin-based adjuvant chemotherapy had showed a detrimental effect on DFS and OS. These results suggest that FOXP3 expression may be used as useful prognostic biomarker in resected NSCLC. Our findings also suggest that resected NSCLC patients with FOXP3 expression of 25% or higher staining intensity may not get any benefit even disfavor from adjuvant platin chemotherapy.

  17. FDG uptake and glut-1 expression in primary tumors and loco-regional lymph nodes in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Lee, Won Woo; Nguyen, Xuan Canh; Chung, Jin Haeng; Park, So Yeon; Kim, Sang Eun

    2007-01-01

    FDG uptake level by primary tumors in NSCLC may affect the likelihood of malignant involvement in loco-regional lymph nodes (LNs). FDG uptake in tumors has been reported to be mediated by glucose transporter type 1 (Glut-I). Here, we investigated the correlations between primary tumors and loco-regional LNs in NSCLC regarding FDG uptake and Glut-1 expression. 126 NSCLC patients (M: F=103: 23, age=659.7y) who underwent curative resection and loco-regional LN dissection within 4 week period after FDG-PET study were enrolled. Maximum standardized uptake value (maxSUV) by PET and %Glut-1 expression by immunostaining were compared between primary tumors and FDG uptake positive loco-regional LNs. Significant correlations were found between 52 malignant LNs and 37 primary tumors in terms of maxSUV (r=0.6451, p<0.0001) and %Glut-1 expression (r=0.8341, p<0.0001). Linear regression of the relation between maxSUVs of malignant LNs (Y) and maxSUVs of primary tumors (X) yielded the expression Y = 0.5938 + 0.4808 X with an r2 value of 0.4162. On the other hand, no significant correlation was observed between 144 benign LNs and 75 primary tumors in terms of maxSUVs (r= -0.0125, p 0.8831). Moreover, %Glut-1 expressions of pathologically proven benign LNs and primary tumors were found to be correlated (r=0.3863, p=0.0004), but r2 value was low at 0.1492. High correlations were found between primary tumors and loco-regional metastatic LNs in NSCLC regarding FDG uptake and Glut-1 expression. Mediastinal LN staging of NSCLC by FDG-PET may be improved by considering the linear correlation between FDG uptakes of metastatic LNs and primary tumors

  18. Primary peripheral primitive neuroectodermal tumor/Ewing's tumor of the testis in a 46-year-old man-differential diagnosis and review of the literature.

    Science.gov (United States)

    Heikaus, Sebastian; Schaefer, Karl-Ludwig; Eucker, Jan; Hogrebe, Esther; Danebrock, Raihanatou; Wai, Daniel H; Krenn, Veit; Gabbert, Helmut E; Poremba, Christopher

    2009-06-01

    Peripheral primitive neuroectodermal tumor/Ewing's tumors are rare bone and soft tissue malignancies with a highly aggressive clinical course and early metastases occurring at multiple peripheral sites. Here, we present for the first time a case of a 46-year-old man with a primary peripheral primitive neuroectodermal tumor/Ewing's tumor of the testis. The diagnosis of peripheral primitive neuroectodermal tumor/Ewing's tumor was established by histology, immunohistochemistry, and molecular pathology. The tumor revealed a rapid progress in 2 months' time. Therefore, the patient was included in the EURO-E.W.I.N.G.99 study and was placed on chemotherapy. However, the tumor progressed during ongoing therapy, and the patient died in March 2008. In conclusion, though being reported here for the first time, peripheral primitive neuroectodermal tumor/Ewing's tumors should be considered in the differential diagnosis of blue round cell tumors of the testis. A rapid and correct diagnosis of this entity is crucial for fast and accurate therapy, which is stressed by the fatal case presented here.

  19. Bone tumors

    International Nuclear Information System (INIS)

    Unni, K.K.

    1988-01-01

    This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

  20. NUC041, a Prodrug of the DNA Methytransferase Inhibitor 5-aza-2′,2′-Difluorodeoxycytidine (NUC013, Leads to Tumor Regression in a Model of Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Richard Daifuku

    2018-04-01

    Full Text Available 5-aza-2′,2′-difluorodeoxycytidine (NUC013 has been shown to be significantly safer and more effective than decitabine in xenograft models of human leukemia and colon cancer. However, it suffers from a similar short half-life as other DNA methyltransferase inhibitors with a 5-azacytosine base, which is problematic for nucleosides that primarily target tumor cells in S phase. Because of the relative instability of 5-azanucleosides, a prodrug approach was developed to improve the pharmacology of NUC013. NUC013 was conjugated with trimethylsilanol (TMS at the 3′ and 5′ position of the sugar, rendering the molecule hydrophobic and producing 3′,5′-di-trimethylsilyl-2′,2′-difluoro-5-azadeoxycytidine (NUC041. NUC041 was designed to be formulated in a hydrophobic vehicle, protecting it from deamination and hydrolysis. In contact with blood, the TMS moieties are readily hydrolyzed to release NUC013. The half-life of NUC013 administered intravenously in mice is 20.1 min, while that of NUC013 derived from intramuscular NUC041 formulated in a pegylated-phospholipid depot is 3.4 h. In a NCI-H460 xenograft of non-small cell lung cancer, NUC013 was shown to significantly inhibit tumor growth and improve survival. Treatment with NUC041 also led to significant tumor growth inhibition. However, NUC041-treated mice had significantly more tumors ulcerate than either NUC013 treated mice or saline control mice, and such ulceration occurred at significantly lower tumor volumes. In these nude mice, tumor regression was likely mediated by the derepression of the tumor suppressor gene p53 and resultant activation of natural killer (NK cells.

  1. Predictive Treatment Management: Incorporating a Predictive Tumor Response Model Into Robust Prospective Treatment Planning for Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Pengpeng, E-mail: zhangp@mskcc.org [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yorke, Ellen; Hu, Yu-Chi; Mageras, Gig [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Rimner, Andreas [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Deasy, Joseph O. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-02-01

    Purpose: We hypothesized that a treatment planning technique that incorporates predicted lung tumor regression into optimization, predictive treatment planning (PTP), could allow dose escalation to the residual tumor while maintaining coverage of the initial target without increasing dose to surrounding organs at risk (OARs). Methods and Materials: We created a model to estimate the geometric presence of residual tumors after radiation therapy using planning computed tomography (CT) and weekly cone beam CT scans of 5 lung cancer patients. For planning purposes, we modeled the dynamic process of tumor shrinkage by morphing the original planning target volume (PTV{sub orig}) in 3 equispaced steps to the predicted residue (PTV{sub pred}). Patients were treated with a uniform prescription dose to PTV{sub orig}. By contrast, PTP optimization started with the same prescription dose to PTV{sub orig} but linearly increased the dose at each step, until reaching the highest dose achievable to PTV{sub pred} consistent with OAR limits. This method is compared with midcourse adaptive replanning. Results: Initial parenchymal gross tumor volume (GTV) ranged from 3.6 to 186.5 cm{sup 3}. On average, the primary GTV and PTV decreased by 39% and 27%, respectively, at the end of treatment. The PTP approach gave PTV{sub orig} at least the prescription dose, and it increased the mean dose of the true residual tumor by an average of 6.0 Gy above the adaptive approach. Conclusions: PTP, incorporating a tumor regression model from the start, represents a new approach to increase tumor dose without increasing toxicities, and reduce clinical workload compared with the adaptive approach, although model verification using per-patient midcourse imaging would be prudent.

  2. Anti-tumor activity of high-dose EGFR tyrosine kinase inhibitor and sequential docetaxel in wild type EGFR non-small cell lung cancer cell nude mouse xenografts

    OpenAIRE

    Tang, Ning; Zhang, Qianqian; Fang, Shu; Han, Xiao; Wang, Zhehai

    2016-01-01

    Treatment of non-small-cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) is still a challenge. This study explored antitumor activity of high-dose icotinib (an EGFR tyrosine kinase inhibitor) plus sequential docetaxel against wild-type EGFR NSCLC cells-generated nude mouse xenografts. Nude mice were subcutaneously injected with wild-type EGFR NSCLC A549 cells and divided into different groups for 3-week treatment. Tumor xenograft volumes were monitored and record...

  3. Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

    International Nuclear Information System (INIS)

    Wendel, Marco; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H; Marrinucci, Dena; Kuhn, Peter

    2012-01-01

    Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL −1 (range 0–515.6) and a mean of 44.7 (±95.2) HD-CTCs mL −1 . No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0–178.2), stage III (n = 34, range 0–515.6) and stages I/II (n = 13, range 0–442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and

  4. Evaluating Tumor Response of Non-Small Cell Lung Cancer Patients With {sup 18}F-Fludeoxyglucose Positron Emission Tomography: Potential for Treatment Individualization

    Energy Technology Data Exchange (ETDEWEB)

    Toma-Dasu, Iuliana, E-mail: Iuliana.Livia.Dasu@ki.se [Medical Radiation Physics, Stockholm University and Karolinska Institutet, Stockholm (Sweden); Uhrdin, Johan [RaySearch Laboratories AB, Stockholm (Sweden); Lazzeroni, Marta [Medical Radiation Physics, Karolinska Institutet, Stockholm (Sweden); Carvalho, Sara; Elmpt, Wouter van; Lambin, Philippe [Department of Radiation Oncology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Dasu, Alexandru [Department of Radiation Physics and Department of Medical and Health Sciences, Linköping University, Linköping (Sweden)

    2015-02-01

    Objective: To assess early tumor responsiveness and the corresponding effective radiosensitivity for individual patients with non-small cell lung cancer (NSCLC) based on 2 successive {sup 18}F-fludeoxyglucose positron emission tomography (FDG-PET) scans. Methods and Materials: Twenty-six NSCLC patients treated in Maastricht were included in the study. Fifteen patients underwent sequential chemoradiation therapy, and 11 patients received concomitant chemoradiation therapy. All patients were imaged with FDG before the start and during the second week of radiation therapy. The sequential images were analyzed in relation to the dose delivered until the second image. An operational quantity, effective radiosensitivity, α{sub eff}, was determined at the voxel level. Correlations were sought between the average α{sub eff} or the fraction of negative α{sub eff} values and the overall survival at 2 years. Separate analyses were performed for the primary gross target volume (GTV), the lymph node GTV, and the clinical target volumes (CTVs). Results: Patients receiving sequential treatment could be divided into responders and nonresponders, using a threshold for the average α{sub eff} of 0.003 Gy{sup −1} in the primary GTV, with a sensitivity of 75% and a specificity of 100% (P<.0001). Choosing the fraction of negative α{sub eff} as a criterion, the threshold 0.3 also had a sensitivity of 75% and a specificity of 100% (P<.0001). Good prognostic potential was maintained for patients receiving concurrent chemotherapy. For lymph node GTV, the correlation had low statistical significance. A cross-validation analysis confirmed the potential of the method. Conclusions: Evaluation of the early response in NSCLC patients showed that it is feasible to determine a threshold value for effective radiosensitivity corresponding to good response. It also showed that a threshold value for the fraction of negative α{sub eff} could also be correlated with poor response. The proposed

  5. Support Vector Machine-Based Prediction of Local Tumor Control After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Klement, Rainer J.; Allgäuer, Michael; Appold, Steffen; Dieckmann, Karin; Ernst, Iris; Ganswindt, Ute; Holy, Richard; Nestle, Ursula; Nevinny-Stickel, Meinhard; Semrau, Sabine; Sterzing, Florian; Wittig, Andrea; Andratschke, Nicolaus; Guckenberger, Matthias

    2014-01-01

    Background: Several prognostic factors for local tumor control probability (TCP) after stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) have been described, but no attempts have been undertaken to explore whether a nonlinear combination of potential factors might synergistically improve the prediction of local control. Methods and Materials: We investigated a support vector machine (SVM) for predicting TCP in a cohort of 399 patients treated at 13 German and Austrian institutions. Among 7 potential input features for the SVM we selected those most important on the basis of forward feature selection, thereby evaluating classifier performance by using 10-fold cross-validation and computing the area under the ROC curve (AUC). The final SVM classifier was built by repeating the feature selection 10 times with different splitting of the data for cross-validation and finally choosing only those features that were selected at least 5 out of 10 times. It was compared with a multivariate logistic model that was built by forward feature selection. Results: Local failure occurred in 12% of patients. Biologically effective dose (BED) at the isocenter (BED ISO ) was the strongest predictor of TCP in the logistic model and also the most frequently selected input feature for the SVM. A bivariate logistic function of BED ISO and the pulmonary function indicator forced expiratory volume in 1 second (FEV1) yielded the best description of the data but resulted in a significantly smaller AUC than the final SVM classifier with the input features BED ISO , age, baseline Karnofsky index, and FEV1 (0.696 ± 0.040 vs 0.789 ± 0.001, P<.03). The final SVM resulted in sensitivity and specificity of 67.0% ± 0.5% and 78.7% ± 0.3%, respectively. Conclusions: These results confirm that machine learning techniques like SVMs can be successfully applied to predict treatment outcome after SBRT. Improvements over traditional TCP modeling are

  6. Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen

    International Nuclear Information System (INIS)

    Zhao, Jun; Zheng, Shuang; Zhou, Qiyin; Li, Heming; Liu, Yunpeng; Qu, Xiujuan; Zhao, Mingfang; Jin, Bo; Yu, Ping; Hu, Xuejun; Teng, Yuee; Zhang, Jingdong; Luo, Ying; Zhang, Lingyun

    2012-01-01

    Hyperfibrinogenemia is a common problem associated with various carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to chemotherapeutic response and prognosis. The purposes of this study were to: 1) analyze the association between chemotherapy-induced changes in plasma fibrinogen level and the chemotherapeutic response after the first two courses of standard first-line platinum-based chemotherapy; and 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with advanced NSCLC. In this retrospective study, the data from 160 patients with advanced NSCLC were collected. The association between the changes in fibrinogen and the response to chemotherapy, or between the pre-and post-chemotherapy fibrinogen levels and patient clinical characteristics, were analyzed using SPSS software. In addition, the prognostic value of pre-chemotherapy fibrinogen levels was assessed. The median pre-chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma fibrinogen levels correlated significantly with gender (p = 0.041). Post-chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre-chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a significant link between the decrease in fibrinogen level, and initial partial response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and multivariate analysis revealed that higher levels of fibrinogen (≥4.4 g/L) and ECOG 1 were positively associated with shorter overall survival (OS). CEA and CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after chemotherapy. This study showed that the reduction in plasma fibrinogen levels

  7. Support Vector Machine-Based Prediction of Local Tumor Control After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Klement, Rainer J., E-mail: rainer_klement@gmx.de [Department of Radiation Oncology, University of Würzburg (Germany); Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital, Schweinfurt (Germany); Allgäuer, Michael [Department of Radiotherapy, Barmherzige Brüder Regensburg, Regensburg (Germany); Appold, Steffen [Department of Radiation Oncology, Technische Universität Dresden (Germany); Dieckmann, Karin [Department of Radiotherapy, Medical University of Vienna (Austria); Ernst, Iris [Department of Radiotherapy, University Hospital Münster (Germany); Ganswindt, Ute [Department of Radiation Oncology, Ludwigs-Maximilians-University Munich, München (Germany); Holy, Richard [Department of Radiation Oncology, RWTH Aachen University, Aachen (Germany); Nestle, Ursula [Department of Radiation Oncology, University Hospital Freiburg, Freiburg i Br (Germany); Nevinny-Stickel, Meinhard [Department of Therapeutic Radiology and Oncology, Innsbruck Medical University (Austria); Semrau, Sabine [Department of Radiation Oncology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen (Germany); Sterzing, Florian [Department of Radiation Oncology, University Hospital Heidelberg (Germany); Wittig, Andrea [Department of Radiotherapy and Radiation Oncology, Philipps-University Marburg (Germany); Andratschke, Nicolaus [Department of Radiation Oncology, Technische Universität München (Germany); Guckenberger, Matthias [Department of Radiation Oncology, University of Würzburg (Germany)

    2014-03-01

    Background: Several prognostic factors for local tumor control probability (TCP) after stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) have been described, but no attempts have been undertaken to explore whether a nonlinear combination of potential factors might synergistically improve the prediction of local control. Methods and Materials: We investigated a support vector machine (SVM) for predicting TCP in a cohort of 399 patients treated at 13 German and Austrian institutions. Among 7 potential input features for the SVM we selected those most important on the basis of forward feature selection, thereby evaluating classifier performance by using 10-fold cross-validation and computing the area under the ROC curve (AUC). The final SVM classifier was built by repeating the feature selection 10 times with different splitting of the data for cross-validation and finally choosing only those features that were selected at least 5 out of 10 times. It was compared with a multivariate logistic model that was built by forward feature selection. Results: Local failure occurred in 12% of patients. Biologically effective dose (BED) at the isocenter (BED{sub ISO}) was the strongest predictor of TCP in the logistic model and also the most frequently selected input feature for the SVM. A bivariate logistic function of BED{sub ISO} and the pulmonary function indicator forced expiratory volume in 1 second (FEV1) yielded the best description of the data but resulted in a significantly smaller AUC than the final SVM classifier with the input features BED{sub ISO}, age, baseline Karnofsky index, and FEV1 (0.696 ± 0.040 vs 0.789 ± 0.001, P<.03). The final SVM resulted in sensitivity and specificity of 67.0% ± 0.5% and 78.7% ± 0.3%, respectively. Conclusions: These results confirm that machine learning techniques like SVMs can be successfully applied to predict treatment outcome after SBRT. Improvements over traditional TCP

  8. Correlation of FDG-PET measurements with morphometric tumor response after induction chemotherapy and adjuvant radiotherapy in stage III non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Baum, R.P.; Niesen, A.; Griesinger, F.

    2002-01-01

    Full text: Docetaxel (D) and carboplatin (C) combination chemotherapy (DC) has shown high response rates in advanced NSCLC. Histologic tumor response after chemotherapy or combined modality induction is strongly associated with systemic tumor control and potentially cure. Metabolic tumor response assessed by FDG-PET after induction chemotherapy with etoposide, ifosfamide and cisplatin (VIP) has been shown to be predictive of outcome in NSCLC. Finally, erythropoietin (EPO) may prevent the decrease in hemoglobin levels that was seen in a previous study of DC (median drop 2.7 g/dl) and thus may enhance treatment efficacy. The aim of the present study was to correlate FDG-PET studies with histomorphometric findings after DC induction chemotherapy plus Epo. 33 patients (pts) with NSCLC stage IIIA (7 pts) or IIIB (24 pts) were enrolled and received treatment with D 100 mg/m 2 dl and C AUC 7.5 d2 q21 days for 4 cycles. Epo was given at 10,000 IU s.c. three times a week. All pts received adjuvant radiotherapy. Of 33 enrolled patients, 22 were evaluable for response by CT imaging. 14/22 pts (64 %) achieved PR. Of the 22 responders, 20 were evaluable for repeated FDG-PET studies. 13/20 pts had a decrease of standardized uptake values (SUV) and of the metabolic tumor index (MTI) by >50 %, 9/20 had SUV <2.5 (CR). Seven of these 9 pts underwent tumor resection, and specimens were subjected to morphometric analysis. In 7/7 cases, no vital tumor cells were detected in the specimens. In contrast to our previous study, hemoglobin levels increased by a median of 0.3 g/dl. Morphometric tumor response after induction chemotherapy correlates strongly with metabolic remission by FDG-PET. FDG-PET appears to be a useful non-invasive diagnostic tool to predict pathologic response and potentially long-term outcome in stage III NSCLC. (author)

  9. Small Intestine Cancer—Health Professional Version

    Science.gov (United States)

    Adenocarcinoma is the most common type of small intestine cancer. Other types of small intestine cancer are sarcomas, carcinoid tumors, gastrointestinal stromal tumors, and lymphomas. Find evidence-based information on small intestine cancer treatment, research, and statistics.

  10. PET-CT-Based Auto-Contouring in Non-Small-Cell Lung Cancer Correlates With Pathology and Reduces Interobserver Variability in the Delineation of the Primary Tumor and Involved Nodal Volumes

    International Nuclear Information System (INIS)

    Baardwijk, Angela van; Bosmans, Geert; Boersma, Liesbeth; Buijsen, Jeroen; Wanders, Stofferinus; Hochstenbag, Monique; Suylen, Robert-Jan van; Dekker, Andre; Dehing-Oberije, Cary; Houben, Ruud; Bentzen, Soren M.; Kroonenburgh, Marinus van; Lambin, Philippe; Ruysscher, Dirk de

    2007-01-01

    Purpose: To compare source-to-background ratio (SBR)-based PET-CT auto-delineation with pathology in non-small-cell lung cancer (NSCLC) and to investigate whether auto-delineation reduces the interobserver variability compared with manual PET-CT-based gross tumor volume (GTV) delineation. Methods and Materials: Source-to-background ratio-based auto-delineation was compared with macroscopic tumor dimensions to assess its validity in 23 tumors. Thereafter, GTVs were delineated manually on 33 PET-CT scans by five observers for the primary tumor (GTV-1) and the involved lymph nodes (GTV-2). The delineation was repeated after 6 months with the auto-contour provided. This contour was edited by the observers. For comparison, the concordance index (CI) was calculated, defined as the ratio of intersection and the union of two volumes (A intersection B)/(A union B). Results: The maximal tumor diameter of the SBR-based auto-contour correlated strongly with the macroscopic diameter of primary tumors (correlation coefficient = 0.90) and was shown to be accurate for involved lymph nodes (sensitivity 67%, specificity 95%). The median auto-contour-based target volumes were smaller than those defined by manual delineation for GTV-1 (31.8 and 34.6 cm 3 , respectively; p = 0.001) and GTV-2 (16.3 and 21.8 cm 3 , respectively; p 0.02). The auto-contour-based method showed higher CIs than the manual method for GTV-1 (0.74 and 0.70 cm 3 , respectively; p 3 , respectively; p = 0.11). Conclusion: Source-to-background ratio-based auto-delineation showed a good correlation with pathology, decreased the delineated volumes of the GTVs, and reduced the interobserver variability. Auto-contouring may further improve the quality of target delineation in NSCLC patients

  11. First-In-Class Small Molecule ONC201 Induces DR5 and Cell Death in Tumor but Not Normal Cells to Provide a Wide Therapeutic Index as an Anti-Cancer Agent.

    Science.gov (United States)

    Allen, Joshua E; Crowder, Roslyn N; Crowder, Roslyn; El-Deiry, Wafik S

    2015-01-01

    We previously identified ONC201 (TIC10) as a first-in-class orally active small molecule with robust antitumor activity that is currently in clinical trials in advanced cancers. Here, we further investigate the safety characteristics of ONC201 in preclinical models that reveal an excellent safety profile at doses that exceed efficacious doses by 10-fold. In vitro studies indicated a strikingly different dose-response relationship when comparing tumor and normal cells where maximal effects are much stronger in tumor cells than in normal cells. In further support of a wide therapeutic index, investigation of tumor and normal cell responses under identical conditions demonstrated large apoptotic effects in tumor cells and modest anti-proliferative effects in normal cells that were non-apoptotic and reversible. Probing the underlying mechanism of apoptosis indicated that ONC201 does not induce DR5 in normal cells under conditions that induce DR5 in tumor cells; DR5 is a pro-apoptotic TRAIL receptor previously linked to the anti-tumor mechanism of ONC201. GLP toxicology studies in Sprague-Dawley rats and beagle dogs at therapeutic and exaggerated doses revealed no dose-limiting toxicities. Observations in both species at the highest doses were mild and reversible at doses above 10-fold the expected therapeutic dose. The no observed adverse event level (NOAEL) was ≥42 mg/kg in dogs and ≥125 mg/kg in rats, which both correspond to a human dose of approximately 1.25 g assuming standard allometric scaling. These results provided the rationale for the 125 mg starting dose in dose escalation clinical trials that began in 2015 in patients with advanced cancer.

  12. First-In-Class Small Molecule ONC201 Induces DR5 and Cell Death in Tumor but Not Normal Cells to Provide a Wide Therapeutic Index as an Anti-Cancer Agent.

    Directory of Open Access Journals (Sweden)

    Joshua E Allen

    Full Text Available We previously identified ONC201 (TIC10 as a first-in-class orally active small molecule with robust antitumor activity that is currently in clinical trials in advanced cancers. Here, we further investigate the safety characteristics of ONC201 in preclinical models that reveal an excellent safety profile at doses that exceed efficacious doses by 10-fold. In vitro studies indicated a strikingly different dose-response relationship when comparing tumor and normal cells where maximal effects are much stronger in tumor cells than in normal cells. In further support of a wide therapeutic index, investigation of tumor and normal cell responses under identical conditions demonstrated large apoptotic effects in tumor cells and modest anti-proliferative effects in normal cells that were non-apoptotic and reversible. Probing the underlying mechanism of apoptosis indicated that ONC201 does not induce DR5 in normal cells under conditions that induce DR5 in tumor cells; DR5 is a pro-apoptotic TRAIL receptor previously linked to the anti-tumor mechanism of ONC201. GLP toxicology studies in Sprague-Dawley rats and beagle dogs at therapeutic and exaggerated doses revealed no dose-limiting toxicities. Observations in both species at the highest doses were mild and reversible at doses above 10-fold the expected therapeutic dose. The no observed adverse event level (NOAEL was ≥42 mg/kg in dogs and ≥125 mg/kg in rats, which both correspond to a human dose of approximately 1.25 g assuming standard allometric scaling. These results provided the rationale for the 125 mg starting dose in dose escalation clinical trials that began in 2015 in patients with advanced cancer.

  13. Serum tumor markers CEA, CYFRA21-1, and CA-125 are associated with worse prognosis in advanced non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Cedrés, Susana; Nuñez, Isaac; Longo, Marina; Martinez, Pablo; Checa, Eva; Torrejón, Davis; Felip, Enriqueta

    2011-05-01

    Serum tumor markers are considered a negative prognostic factor in early-stages NSCLC but its role in advanced disease is controversial. The aim of this study is to analyze the prognostic value of tumor markers in advanced NSCLC. Two hundred and seventy seven patients diagnosed in our institution were retrospectively reviewed. Baseline prognostic factors analyzed were gender, histology and brain metastases. Baseline patients characteristics: median age 63 years (30-81 years); males 84.4%, stage IV: 61.7%; adenocarcinoma 38.6%, squamous carcinoma 22.4%. High levels of CEA, CYFRA21-1, and CA125 levels were detected in 179 (55.9%), 119 (65%), and 129 (46.6%) patients respectively. Significant higher levels of CEA and CA125 at baseline were present in adenocarcinoma (P CEA, CYFRA21-1, and CA125 was 5.3 months (m), 3.5 m and 4.6 m versus 7.4 m, 6.2 m and 7.5 m in patients with normal levels (P tumor markers was 10.0 m vs 14.0 m (P = 0.085) for CEA; 5.6 vs 12.1 m for CYFRA21-1 (P = .002), and 8.7 vs 14.0 (P = .03) for CA125. In the multivariate analysis high levels of tumor markers, histology and clinical stage were significant correlated with worse prognostic. Patients with all the tumor markers elevated presented the worst prognosis (3.6 m for PFS and 7.1 m for OS, P tumor markers at baseline are correlated with worse survival in stage III-IV NSCLC patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. SU-F-J-64: Comparison of Dosimetric Robustness Between Proton Therapy and IMRT Plans Following Tumor Regression for Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Teng, C; Ainsley, C; Teo, B; Burgdorf, B; Berman, A; Levin, W; Xiao, Y; Lin, L; Simone, C; Solberg, T [University of Pennsylvania, Philadelphia, PA (United States); Janssens, G [IBA, Louvain-la-Neuve (Belgium)

    2016-06-15

    Purpose: In the light of tumor regression and normal tissue changes, dose distributions can deviate undesirably from what was planned. As a consequence, replanning is sometimes necessary during treatment to ensure continued tumor coverage or to avoid overdosing organs at risk (OARs). Proton plans are generally thought to be less robust than photon plans because of the proton beam’s higher sensitivity to changes in tissue composition, suggesting also a higher likely replanning rate due to tumor regression. The purpose of this study is to compare dosimetric deviations between forward-calculated double scattering (DS) proton plans with IMRT plans upon tumor regression, and assesses their impact on clinical replanning decisions. Methods: Ten consecutive locally advanced NSCLC patients whose tumors shrank > 50% in volume and who received four or more CT scans during radiotherapy were analyzed. All the patients received proton radiotherapy (6660 cGy, 180 cGy/fx). Dosimetric robustness during therapy was characterized by changes in the planning objective metrics as well as by point-by-point root-mean-squared differences for the entire PTV, ITV, and OARs (heart, cord, esophagus, brachial plexus and lungs) DVHs. Results: Sixty-four pairs of DVHs were reviewed by three clinicians, who requested a replanning rate of 16.7% and 18.6% for DS and IMRT plans, respectively, with a high agreement between providers. Robustness of clinical indicators was found to depend on the beam orientation and dose level on the DVH curve. Proton dose increased most in OARs distal to the PTV along the beam path, but these changes were primarily in the mid to low dose levels. In contrast, the variation in IMRT plans occurred primarily in the high dose region. Conclusion: Robustness of clinical indicators depends where on the DVH curves comparisons are made. Similar replanning rates were observed for DS and IMRT plans upon large tumor regression.

  15. Locoregional control of non-small cell lung cancer in relation to automated early assessment of tumor regression on cone beam computed tomography

    DEFF Research Database (Denmark)

    Brink, Carsten; Bernchou, Uffe; Bertelsen, Anders

    2014-01-01

    was estimated on the basis of the first one third and two thirds of the scans. The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearson's correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2...... for other clinical characteristics. RESULTS: Automatic measurement of the tumor regression from standard CBCT images was feasible. Pearson's correlation coefficient between manual and automatic measurement was 0.86 in a sample of 9 patients. Most patients experienced tumor volume regression, and this could...

  16. Reliability of using circulating tumor cells for detecting epidermal growth factor receptor mutation status in advanced non-small-cell lung cancer patients: a meta-analysis and systematic review

    Directory of Open Access Journals (Sweden)

    Hu F

    2018-03-01

    Full Text Available Fang Hu,* Xiaowei Mao,* Yujun Zhang, Xiaoxuan Zheng, Ping Gu, Huimin Wang, Xueyan ZhangDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this workPurpose: To evaluate the clinical value of circulating tumor cells as a surrogate to detect epidermal growth factor receptor mutation in advanced non-small-cell lung cancer (NSCLC patients.Methods: We searched the electronic databases, and all articles meeting predetermined selection criteria were included in this study. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated. The evaluation indexes of the diagnostic performance were the summary receiver operating characteristic curve and area under the summary receiver operating characteristic curve.Results: Eight eligible publications with 255 advanced NSCLC patients were included in this meta-analysis. Taking tumor tissues as reference, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of circulating tumor cells for detecting the epidermal growth factor receptor mutation status were found to be 0.82 (95% confidence interval [CI]: 0.50–0.95, 0.95 (95% CI: 0.24–1.00, 16.81 (95% CI: 0.33–848.62, 0.19 (95% CI: 0.06–0.64, and 86.81 (95% CI: 1.22–6,154.15, respectively. The area under the summary receiver operating characteristic curve was 0.92 (95% CI: 0.89–0.94. The subgroup analysis showed that the factors of blood volume, histological type, EGFR-tyrosine kinase inhibitor therapy, and circulating tumor cell and tissue test methods for EGFR accounted for the significant difference of the pooled specificity. No significant difference was found between the pooled sensitivity of the subgroup.Conclusion: Our meta-analysis confirmed that circulating tumor cells are a good surrogate for

  17. SU-E-J-266: Cone Beam Computed Tomography (CBCT) Inter-Scan and Inter-Observer Tumor Volume Variability Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-Small Cell Lung Cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Y; Aileen, C; Kozono, D; Killoran, J; Wagar, M; Lee, S; Hacker, F; Aerts, H; Lewis, J; Mak, R [Brigham and Women’s Hospital, Boston, MA (United States)

    2015-06-15

    Purpose: Quantification of volume changes on CBCT during SBRT for NSCLC may provide a useful radiological marker for radiation response and adaptive treatment planning, but the reproducibility of CBCT volume delineation is a concern. This study is to quantify inter-scan/inter-observer variability in tumor volume delineation on CBCT. Methods: Twenty earlystage (stage I and II) NSCLC patients were included in this analysis. All patients were treated with SBRT with a median dose of 54 Gy in 3 to 5 fractions. Two physicians independently manually contoured the primary gross tumor volume on CBCTs taken immediately before SBRT treatment (Pre) and after the same SBRT treatment (Post). Absolute volume differences (AVD) were calculated between the Pre and Post CBCTs for a given treatment to quantify inter-scan variability, and then between the two observers for a given CBCT to quantify inter-observer variability. AVD was also normalized with respect to average volume to obtain relative volume differences (RVD). Bland-Altman approach was used to evaluate variability. All statistics were calculated with SAS version 9.4. Results: The 95% limit of agreement (mean ± 2SD) on AVD and RVD measurements between Pre and Post scans were −0.32cc to 0.32cc and −0.5% to 0.5% versus −1.9 cc to 1.8 cc and −15.9% to 15.3% for the two observers respectively. The 95% limit of agreement of AVD and RVD between the two observers were −3.3 cc to 2.3 cc and −42.4% to 28.2% respectively. The greatest variability in inter-scan RVD was observed with very small tumors (< 5 cc). Conclusion: Inter-scan variability in RVD is greatest with small tumors. Inter-observer variability was larger than inter-scan variability. The 95% limit of agreement for inter-observer and inter-scan variability (∼15–30%) helps define a threshold for clinically meaningful change in tumor volume to assess SBRT response, with larger thresholds needed for very small tumors. Part of the work was funded by a Kaye

  18. SU-E-J-266: Cone Beam Computed Tomography (CBCT) Inter-Scan and Inter-Observer Tumor Volume Variability Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-Small Cell Lung Cancer (NSCLC)

    International Nuclear Information System (INIS)

    Hou, Y; Aileen, C; Kozono, D; Killoran, J; Wagar, M; Lee, S; Hacker, F; Aerts, H; Lewis, J; Mak, R

    2015-01-01

    Purpose: Quantification of volume changes on CBCT during SBRT for NSCLC may provide a useful radiological marker for radiation response and adaptive treatment planning, but the reproducibility of CBCT volume delineation is a concern. This study is to quantify inter-scan/inter-observer variability in tumor volume delineation on CBCT. Methods: Twenty earlystage (stage I and II) NSCLC patients were included in this analysis. All patients were treated with SBRT with a median dose of 54 Gy in 3 to 5 fractions. Two physicians independently manually contoured the primary gross tumor volume on CBCTs taken immediately before SBRT treatment (Pre) and after the same SBRT treatment (Post). Absolute volume differences (AVD) were calculated between the Pre and Post CBCTs for a given treatment to quantify inter-scan variability, and then between the two observers for a given CBCT to quantify inter-observer variability. AVD was also normalized with respect to average volume to obtain relative volume differences (RVD). Bland-Altman approach was used to evaluate variability. All statistics were calculated with SAS version 9.4. Results: The 95% limit of agreement (mean ± 2SD) on AVD and RVD measurements between Pre and Post scans were −0.32cc to 0.32cc and −0.5% to 0.5% versus −1.9 cc to 1.8 cc and −15.9% to 15.3% for the two observers respectively. The 95% limit of agreement of AVD and RVD between the two observers were −3.3 cc to 2.3 cc and −42.4% to 28.2% respectively. The greatest variability in inter-scan RVD was observed with very small tumors (< 5 cc). Conclusion: Inter-scan variability in RVD is greatest with small tumors. Inter-observer variability was larger than inter-scan variability. The 95% limit of agreement for inter-observer and inter-scan variability (∼15–30%) helps define a threshold for clinically meaningful change in tumor volume to assess SBRT response, with larger thresholds needed for very small tumors. Part of the work was funded by a Kaye

  19. An exploratory study of volumetric analysis for assessing tumor response with (18)F-FAZA PET/CT in patients with advanced non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Kerner, Gerald S M A; Bollineni, Vikram R; Hiltermann, Thijo J N; Sijtsema, Nanna M; Fischer, Alexander; Bongaerts, Alphons H H; Pruim, Jan; Groen, Harry J M

    2016-12-01

    Hypoxia is associated with resistance to chemotherapy and radiotherapy and is randomly distributed within malignancies. Characterization of changes in intratumoral hypoxic regions is possible with specially developed PET tracers such as (18)F-fluoroazomycin arabinoside ((18)F-FAZA) while tumor metabolism can be measured with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG). The purpose of this study was to study the effects of chemotherapy on (18)F-FAZA and (18)F-FDG uptake simultaneously in non-small-cell lung cancer (NSCLC) patients At baseline and after the second chemotherapy cycle, both PET/CT with (18)F-FDG and (18)F-FAZA was performed in seven patients with metastasized NSCLC. (18)F-FAZA and (18)F-FDG scans were aligned with deformable image registration using Mirada DBx. The primary tumors were contoured, and on the (18)F-FDG scan, volumes of interest (VOI) were drawn using a 41 % adaptive threshold technique. Subsequently, the resulting VOI was transferred to the (18)F-FAZA scan. (18)F-FAZA maximum tumor-to-background (T/Bgmax) ratio and the fractional hypoxic volume (FHV) were assessed. Measurements were corrected for partial volume effects. Finally, a voxel-by-voxel analysis of the primary tumor was performed to assess regional uptake differences. In the primary tumor of all seven patients, median (18)F-FDG standard uptake value (SUVmax) decreased significantly (p = 0.03). There was no significant decrease in (18)F-FAZA uptake as measured with T/Bgmax (p = 0.24) or the FHV (p = 0.35). Additionally, volumetric voxel-by-voxel analysis showed that low hypoxic tumors did not significantly change in hypoxic status between baseline and two cycles of chemotherapy, whereas highly hypoxic tumors did. Individualized volumetric voxel-by-voxel analysis revealed that hypoxia and metabolism were not associated before and after 2 cycles of chemotherapy. Tumor hypoxia and metabolism are independent dynamic events as measured by (18)F-FAZA PET and (18)F

  20. Computed Tomography-Based Anatomic Assessment Overestimates Local Tumor Recurrence in Patients With Mass-like Consolidation After Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dunlap, Neal E. [Department of Radiation Oncology, University of Louisville, Louisville, KY (United States); Yang Wensha [Department of Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA (United States); McIntosh, Alyson [Department of Radiation Oncology, John and Dorothy Morgan Cancer Center, Lehigh Valley Hospital, Allentown, PA (United States); Sheng, Ke [Department of Radiation Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA (United States); Benedict, Stanley H.; Read, Paul W. [Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States); Larner, James M., E-mail: jml2p@virginia.edu [Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States)

    2012-12-01

    Purpose: To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. Methods and Materials: Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET) CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. Results: Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade {>=}2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). Conclusion: Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will

  1. CyberKnife with tumor tracking: An effective alternative to wedge resection for high-risk surgical patients with stage I non-small cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Sean eCollins

    2012-02-01

    Full Text Available Published data suggests that wedge resection for stage I NSCLC results in improved overall survival compared to stereotactic body radiation therapy (SBRT. We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed for staging. Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references. Gross tumor volumes (GTVs were contoured using lung windows; the margins were expanded by 5 mm to establish the planning treatment volume (PTV. Treatment plans were designed using hundreds of pencil beams. Doses delivered to the PTV ranged from 42-60 Gy in 3 fractions. The 30-Gy isodose contour extended at least 1cm from the GTV to eradicate microscopic disease. Treatments were delivered using the CyberKnife system with tumor tracking. Examination and PET/CT imaging occurred at 3-month follow-up intervals. Forty patients (median age 76 with a median maximum tumor diameter of 2.6 cm (range, 1.4-5.0 cm and a mean post-bronchodilator percent predicted forced expiratory volume in 1 second (FEV1 of 57% (range, 21 - 111% were treated. A mean dose of 50 Gy was delivered to the PTV over 3 to 13 days (median, 7 days. The 30-Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44 months (range, 12 -72 months follow-up, the 3-year Kaplan-Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91% and 75% , respectively. CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection, eradicating tumors with 1 to 2 cm margins in order to preserve lung function. Prospective randomized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence.

  2. Targeting cell migration and the endoplasmic reticulum stress response with calmodulin antagonists: a clinically tested small molecule phenocopy of SEC62 gene silencing in human tumor cells

    International Nuclear Information System (INIS)

    Linxweiler, Maximilian; Greiner, Markus; Schorr, Stefan; Schäuble, Nico; Jung, Martin; Linxweiler, Johannes; Langer, Frank; Schäfers, Hans-Joachim; Cavalié, Adolfo; Zimmermann, Richard

    2013-01-01

    Tumor cells benefit from their ability to avoid apoptosis and invade other tissues. The endoplasmic reticulum (ER) membrane protein Sec62 is a key player in these processes. Sec62 is essential for cell migration and protects tumor cells against thapsigargin-induced ER stress, which are both linked to cytosolic Ca 2+ . SEC62 silencing leads to elevated cytosolic Ca 2+ and increased ER Ca 2+ leakage after thapsigargin treatment. Sec62 protein levels are significantly increased in different tumors, including prostate, lung and thyroid cancer. In lung cancer, the influence of Sec62 protein levels on patient survival was analyzed using the Kaplan-Meier method and log-rank test. To elucidate the underlying pathophysiological functions of Sec62, Ca 2+ imaging techniques, real-time cell analysis and cell migration assays were performed. The effects of treatment with the calmodulin antagonists, trifluoperazine (TFP) and ophiobolin A, on cellular Ca 2+ homeostasis, cell growth and cell migration were compared with the effects of siRNA-mediated Sec62 depletion or the expression of a mutated SEC62 variant in vitro. Using Biacore analysis we examined the Ca 2+ -sensitive interaction of Sec62 with the Sec61 complex. Sec62 overproduction significantly correlated with reduced patient survival. Therefore, Sec62 is not only a predictive marker for this type of tumor, but also an interesting therapeutic target. The present study suggests a regulatory function for Sec62 in the major Ca 2+ leakage channel in the ER, Sec61, by a direct and Ca 2+ -sensitive interaction. A Ca 2+ -binding motif in Sec62 is essential for its molecular function. Treatment of cells with calmodulin antagonists mimicked Sec62 depletion by inhibiting cell migration and rendering the cells sensitive to thapsigargin treatment. Targeting tumors that overproduce Sec62 with calmodulin antagonists in combination with targeted thapsigargin analogues may offer novel personalized therapeutic options

  3. A pilot study to image the vascular network of small melanocytic choroidal tumors with speckle noise-free 1050-nm swept source optical coherence tomography (OCT choroidal angiography).

    Science.gov (United States)

    Maloca, Peter; Gyger, Cyrill; Hasler, Pascal W

    2016-06-01

    To visualize and measure the vascular network of melanocytic choroidal tumors with speckle noise-free swept source optical coherence tomography (SS-OCT choroidal angiography). Melanocytic choroidal tumors from 24 eyes were imaged with 1050-nm optical coherence tomography (Topcon DRI OCT-1 Atlantis). A semi-automated algorithm was developed to remove speckle noise and to extract and measure the volume of the choroidal vessels from the obtained OCT data. In all cases, analysis of the choroidal vessels could be performed with SS-OCT without the need for pupillary dilation. The proposed method allows speckle noise-free, structure-guided visualization and measurement of the larger choroidal vessels in three dimensions. The obtained data suggest that speckle noise-free OCT may be more effective at identifying choroidal structures than traditional OCT methods. The measured volume of the extracted choroidal vessels of Haller's layer and Sattler's layer in the examined tumorous eyes was on average 0.982463955 mm(3) /982463956 μm(3) (range of 0.209764406 mm(3) /209764405.9 μm(3)to 1.78105544 mm(3) /1781055440 μm(3)). Full thickness obstruction of the choroidal vasculature by the tumor was found in 18 cases (72 %). In seven cases (18 %), choroidal vessel architecture did not show pronounced morphological abnormalities (18 %). Speckle noise-free OCT may serve as a new illustrative imaging technology and enhance visualization of the choroidal vessels without the need for dye injection. OCT can be used to identify and evaluate the choroidal vessels of melanocytic choroidal tumors, and may represent a potentially useful tool for imaging and monitoring of choroidal nevi and melanoma.

  4. Comparison of six methods of segmentation of tumor volume on the {sup 18}F-F.D.G. PET scan with reference histological volume in non small cell bronchopulmonary cancers; Comparaison de six methodes de segmentation du volume tumoral sur la {sup 18}F-FDG TEP-TDM avec le volume de reference anatomopathologique dans les cancers bronchopulmonaires non a petites cellules

    Energy Technology Data Exchange (ETDEWEB)

    Venel, Y.; Garhi, H.; Baulieu, J.L.; Prunier-Aesch, C. [CHRU de Tours-Bretonneau, Service de Medecine Nucleaire, 37 - Tours (France); Muret, A. de [CHRU de Tours-Bretonneau, Service de Radiotherapie, 37 - Tours (France); Barillot, I. [CHRU de Tours-Bretonneau, Service d' Anatomopathologie, 37 - Tours (France)

    2008-06-15

    The {sup 18}F-F.D.G. PET has demonstrated its importance in oncology, for initial extension and efficacy of anti tumoral therapeutics. Several studies have attempted to prove its utility to define tumoral volumes for conformational radiotherapy in non small cell lung cancers. Some authors have suggested the use of threshold of tumor intensity uptake with 40 or 50% of maximal intensity. Black et al. have determined contouring with linear regression formula of mean semi-quantitative index of tumor uptake (standard uptake value): SUV{sub threshold} = 0.307 Sub{sub average} + 0.588. Nestle et al. have taken into account the background noise intensity and mean intensity of the tumor: I{sub threshold} = {beta} I{sub average} +I{sub noise} with {beta} 0.15. Our study was done in collaboration with Inserm U618 team and has compared volumes defined on PET scan defined according to different methods based on intensity or S.U.V. to the tumour volume determined on CT scan by radio physicist. We have compared those volumes with histological volume that we considered for reference. Four patients have been included. They had {sup 18}F-F.D.G. PET scan followed by complete tumoral removal surgery. Specific histological procedure allowed to define complete size of the tumor in re expanded lung. Comparatively to pathology, the volumes obtained using I{sub max} 40 and I{sub max} 50 are all underestimated. The volumes defined by Black's et al. method are under evaluated for the two largest tumours (15.8% to 22%) and overestimated for the two smallest ones (17.9 to 82.9%). Nestle's et al. method, using {beta} = 0.15, correctly estimates two tumor volumes over 2 cm, but overestimates the two small tumors (79.6 to 124%). Finally, the corrected Nestle's et al. formula (using {beta} = 0.264) overestimates three tumours. Volumes defined on CT scan by radio physicist are correct for one lesion, underestimated for one and overestimated for two other ones (44 and 179.5%). Nestle

  5. EXTRAOSSEOUS EWINGS/PNET-A CASE REPORT BY FNAC

    OpenAIRE

    Bharath; Rakesh

    2013-01-01

    INTRODUCTION: Ewing sarcoma is one of the most common primary tumo r of the bone, but extra-skeletal type is rare. Ewing's sarcoma (ES) and primitive neuroectodermal t umor (PNET) are small round cell tumors showing varying (usuall y minimal) neuroectodermal differentiation [1] .These tumors occur predominately in adolescents and young adults,but rare below four years of age. The cytomorphologic feature s may be confused with other small round cell tu...

  6. Influence of Fractionation Scheme and Tumor Location on Toxicities After Stereotactic Body Radiation Therapy for Large (≥5 cm) Non-Small Cell Lung Cancer: A Multi-institutional Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Verma, Vivek [Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska (United States); Shostrom, Valerie K. [Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska (United States); Zhen, Weining; Zhang, Mutian [Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska (United States); Braunstein, Steve E. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Holland, John [Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon (United States); Hallemeier, Christopher L. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Harkenrider, Matthew M. [Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, Illinois (United States); Iskhanian, Adrian [Department of Radiation Oncology, University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida (United States); Jabbour, Salma K. [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey (United States); Attia, Albert [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Lee, Percy [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); Wang, Kyle [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Decker, Roy H. [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); McGarry, Ronald C. [Department of Radiation Oncology, University of Kentucky, Lexington, Kentucky (United States); Simone, Charles B., E-mail: charlessimone@umm.edu [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States)

    2017-03-15

    Purpose: To describe the impact of fractionation scheme and tumor location on toxicities in stereotactic body radiation therapy (SBRT) for ≥5-cm non-small cell lung cancer (NSCLC), as part of a multi-institutional analysis. Methods: Patients with primary ≥5-cm N0 M0 NSCLC who underwent ≤5-fraction SBRT were examined across multiple high-volume SBRT centers. Collected data included clinical/treatment parameters; toxicities were prospectively assessed at each institution according to the Common Terminology Criteria for Adverse Events. Patients treated daily were compared with those treated every other day (QOD)/other nondaily regimens. Stratification between central and peripheral tumors was also performed. Results: Ninety-two patients from 12 institutions were evaluated (2004-2016), with median follow-up of 12 months. In total there were 23 (25%) and 6 (7%) grade ≥2 and grade ≥3 toxicities, respectively. Grades 2 and 3 pulmonary toxicities occurred in 9% and 4%, respectively; 1 patient treated daily experienced grade 5 radiation pneumonitis. Of the entire cohort, 46 patients underwent daily SBRT, and 46 received QOD (n=40)/other nondaily (n=6) regimens. Clinical/treatment parameters were similar between groups; the QOD/other group was more likely to receive 3-/4-fraction schemas. Patients treated QOD/other experienced significantly fewer grade ≥2 toxicities as compared with daily treatment (7% vs 43%, P<.001). Patients treated daily also had higher rates of grade ≥2 pulmonary toxicities (P=.014). Patients with peripheral tumors (n=66) were more likely to receive 3-/4-fraction regimens than those with central tumors (n=26). No significant differences in grade ≥2 toxicities were identified according to tumor location (P>.05). Conclusions: From this multi-institutional study, toxicity of SBRT for ≥5-cm lesions is acceptable, and daily treatment was associated with a higher rate of toxicities.

  7. Small interfering RNA targeted to IGF-IR delays tumor growth and induces proinflammatory cytokines in a mouse breast cancer model.

    Directory of Open Access Journals (Sweden)

    Tiphanie Durfort

    Full Text Available Insulin-like growth factor I (IGF-I and its type I receptor (IGF-IR play significant roles in tumorigenesis and in immune response. Here, we wanted to know whether an RNA interference approach targeted to IGF-IR could be used for specific antitumor immunostimulation in a breast cancer model. For that, we evaluated short interfering RNA (siRNAs for inhibition of in vivo tumor growth and immunological stimulation in immunocompetent mice. We designed 2'-O-methyl-modified siRNAs to inhibit expression of IGF-IR in two murine breast cancer cell lines (EMT6, C4HD. Cell transfection of IGF-IR siRNAs decreased proliferation, diminished phosphorylation of downstream signaling pathway proteins, AKT and ERK, and caused a G0/G1 cell cycle block. The IGF-IR silencing also induced secretion of two proinflammatory cytokines, TNF- α and IFN-γ. When we transfected C4HD cells with siRNAs targeting IGF-IR, mammary tumor growth was strongly delayed in syngenic mice. Histology of developing tumors in mice grafted with IGF-IR siRNA treated C4HD cells revealed a low mitotic index, and infiltration of lymphocytes and polymorphonuclear neutrophils, suggesting activation of an antitumor immune response. When we used C4HD cells treated with siRNA as an immunogen, we observed an increase in delayed-type hypersensitivity and the presence of cytotoxic splenocytes against wild-type C4HD cells, indicative of evolving immune response. Our findings show that silencing IGF-IR using synthetic siRNA bearing 2'-O-methyl nucleotides may offer a new clinical approach for treatment of mammary tumors expressing IGF-IR. Interestingly, our work also suggests that crosstalk between IGF-I axis and antitumor immune response can mobilize proinflammatory cytokines.

  8. Assessment of the mode of action underlying development of rodent small intestinal tumors following oral exposure to hexavalent chromium and relevance to humans

    Science.gov (United States)

    Proctor, Deborah M.; Suh, Mina; Haws, Laurie C.; Kirman, Christopher R.; Harris, Mark A.

    2013-01-01

    Chronic exposure to high concentrations of hexavalent chromium (Cr(VI)) in drinking water causes intestinal adenomas and carcinomas in mice, but not in rats. Cr(VI) causes damage to intestinal villi and crypt hyperplasia in mice after only one week of exposure. After two years of exposure, intestinal damage and crypt hyperplasia are evident in mice (but not rats), as are intestinal tumors. Although Cr(VI) has genotoxic properties, these findings suggest that intestinal tumors in mice arise as a result of chronic mucosal injury. To better understand the mode of action (MOA) of Cr(VI) in the intestine, a 90-day drinking water study was conducted to collect histological, biochemical, toxicogenomic and pharmacokinetic data in intestinal tissues. Using MOA analyses and human relevance frameworks proposed by national and international regulatory agencies, the weight of evidence supports a cytotoxic MOA with the following key events: (a) absorption of Cr(VI) from the intestinal lumen, (b) toxicity to intestinal villi, (c) crypt regenerative hyperplasia and (d) clonal expansion of mutations within the crypt stem cells, resulting in late onset tumorigenesis. This article summarizes the data supporting each key event in the MOA, as well as data that argue against a mutagenic MOA for Cr(VI)-induced intestinal tumors. PMID:23445218

  9. PD-L1 Expression of Tumor Cells, Macrophages, and Immune Cells in Non-Small Cell Lung Cancer Patients with Malignant Pleural Effusion.

    Science.gov (United States)

    Tseng, Yen-Han; Ho, Hsiang-Ling; Lai, Chiung-Ru; Luo, Yung-Hung; Tseng, Yen-Chiang; Whang-Peng, Jacqueline; Lin, Yi-Hsuan; Chou, Teh-Ying; Chen, Yuh-Min

    2018-03-01

    Whether immunohistochemical staining of programmed death ligand 1 (PD-L1) on cells of pleural effusion could be used to predict response to immunotherapy treatment has not been reported. We retrospectively enrolled patients who had undergone malignant pleural effusion drainage and had effusion cell block specimens from 2014 to 2016. Immunohistochemical staining for PD-L1 was performed with tumor cells, immune cells, and macrophages of all cell block specimens. Immunoactivity was scored as 0 for absence of staining and 1+ for faint, 2+ for moderate, and 3+ for intense membranous staining. Patients' clinicopathological characteristics were also collected. PD-L1 expression of pleural effusion tumor cells was associated with the PD-L1 expression of macrophages (p = 0.003) and immune cells (p pleural effusion tumor cells and macrophages. The low intensity of PD-L1 expression in immune cells is associated with the poor survival of patients with lung cancer with malignant pleural effusion. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  10. Peripheral primitive neuroectodermal tumor of seminal vesicles: Is there a role for relatively aggressive treatment modalities?

    Directory of Open Access Journals (Sweden)

    Alessandro Crestani

    2014-12-01

    Full Text Available A 50 year old white man received an incidental ultrasound diagnosis of hypoechoic mass interesting the right seminal vesicle. A CT scan showed the presence of a 7.8 cm roundish cyst, originating from the right seminal vesicle. He had been followed by the removal of the right seminal vesicle and both the cystic lesion. The histological findings of the specimen documented the presence of small round cells compatible with Ewing’s sarcoma/PPNET. The patient received also adjuvant chemotherapy and radiation treatment. After 10 years, the follow-up is still negative.

  11. ERCC1 and Ki67 in Small Cell Lung Carcinoma and Other Neuroendocrine Tumors of the Lung Distribution and Impact on Survival

    DEFF Research Database (Denmark)

    Skov, Birgit Guldhammer; Holm, B.; Erreboe, A.

    2010-01-01

    .001). The difference between TC and AC was significant (p = 0.02), as was the difference between low grade (TC + AC) and high grade NE (LCNEC + SCLC) (p ... with platinum-based chemotherapy has no impact on survival. High expression of ERCC1 in TC might represent a clue to the failure of platinum-based therapy in these patients. ERCC1 expression has prognostic impact in lung carcinoids. Ki 67 might be considered as a supplementary test to the histopatologic...... classification of NE tumors...

  12. Pituitary tumors containing cholecystokinin

    DEFF Research Database (Denmark)

    Rehfeld, J F; Lindholm, J; Andersen, B N

    1987-01-01

    We found small amounts of cholecystokinin in the normal human adenohypophysis and therefore examined pituitary tumors from 87 patients with acromegaly, Cushing's disease, Nelson's syndrome, prolactinoma, or inactive pituitary adenomas. Five adenomas associated with Nelson's syndrome contained......'s disease and 7 acromegaly with adenomas containing ACTH. The cholecystokinin peptides from the tumors were smaller and less sulfated than cholecystokinin from normal pituitary glands. We conclude that ACTH-producing pituitary cells may also produce an altered form of cholecystokinin....

  13. Rhabdomyosarcoma of the urinary bladder in adults: predilection for alveolar morphology with anaplasia and significant morphologic overlap with small cell carcinoma.

    Science.gov (United States)

    Paner, Gladell P; McKenney, Jesse K; Epstein, Jonathan I; Amin, Mahul B

    2008-07-01

    Rhabdomyosarcoma (RMS) represents the most common malignant soft tissue tumor in children and adolescents with the urinary bladder representing a frequent site. Most of these urinary bladder tumors are embryonal RMS, predominantly the botryoid subtype. RMSs of the urinary bladder in adults are distinctively rare and the subject of only case reports. We report the clinicopathologic features of 5 bladder neoplasms with rhabdomyosarcomatous differentiation in adults and emphasize the differential diagnosis in the adult setting. The patients, 4 men and 1 woman, ranged in age from 23 to 85 years (mean 65.4 y). Gross hematuria was the most common initial symptom, although 2 patients had metastatic disease at presentation. Four cases were pure primary RMSs of the bladder and 1 case was a sarcomatoid urothelial carcinoma with RMS representing the extensive heterologous component. All 5 cases demonstrated a diffuse growth pattern (ie, non-nested), of which 4 cases had nuclear anaplasia (Wilms criteria without the atypical mitotic figure requirement); only 1 case (the sarcomatoid carcinoma) showed obvious rhabdomyoblastic differentiation (ie, strap cells). Three cases were of the alveolar subtype (1 admixed with embryonal histology) and 2 were RMS, not further classified. Microscopically, all tumors had a primitive undifferentiated morphology with cells containing scant cytoplasm, varying round to fusiform nuclei with even chromatin distribution, and frequent mitoses. The degree of morphologic overlap with small cell carcinoma of the bladder, a relatively more common round cell tumor in adults, was striking. The epithelial component of the sarcomatoid carcinoma was high-grade invasive urothelial carcinoma with glandular differentiation. No other case had previous history of bladder cancer or concurrent carcinoma in situ or invasive urothelial carcinoma. All tumors showed immunohistochemical expression for desmin, myogenin, and/or MyoD1. Synaptophysin was performed in 4 cases

  14. Three-Dimensional Radiation Therapy to the Primary Tumor With Concurrent Chemotherapy in Patients With Stage IV Non-Small Cell Lung Cancer: Results of a Multicenter Phase 2 Study From PPRA-RTOG, China

    Energy Technology Data Exchange (ETDEWEB)

    Su, ShengFa [Department of Thoracic Oncology, Affiliated Hospital of Guizhou Medical University, and Guizhou Cancer Hospital, Guiyang (China); Teaching and Research Section of Oncology, Guizhou Medical University, Guiyang (China); Li, Tao [Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu (China); Lu, Bing, E-mail: lbgymaaaa@163.com [Department of Thoracic Oncology, Affiliated Hospital of Guizhou Medical University, and Guizhou Cancer Hospital, Guiyang (China); Teaching and Research Section of Oncology, Guizhou Medical University, Guiyang (China); Wang, XiaoHu, E-mail: xhwanggansu@163.com [Department of Radiation Oncology, Gansu Cancer Hospital, Lanzhou (China); Li, JianCheng [Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fuzhou (China); Chen, Ming [Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou (China); Lu, You [Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu (China); Bai, YuJu [Department of Oncology, Affiliated Hospital of Zunyi Medical College, Zunyi (China); Hu, YinXiang; Ouyang, WeiWei; Ma, Zhu; Li, QingSong; Li, HuiQin; Wang, Yu [Department of Thoracic Oncology, Affiliated Hospital of Guizhou Medical University, and Guizhou Cancer Hospital, Guiyang (China); Teaching and Research Section of Oncology, Guizhou Medical University, Guiyang (China)

    2015-11-15

    Purpose: The aim of this prospective multi-institutional phase 2 study was to investigate disease control, survival outcomes, and toxicity after thoracic three-dimensional radiation therapy (3D-RT) with concurrent chemotherapy for newly diagnosed stage IV non-small cell lung cancer (NSCLC). Methods and Materials: Eligible patients were 18 to 80 years of age, had a Karnofsky performance status (KPS) score ≥70%, and newly diagnosed stage IV NSCLC with limited metastatic disease (defined as involving ≤3 organs). Patients received platinum-doublet chemotherapy with concurrent irradiation to the primary tumor. Primary endpoints were overall survival (OS) and acute toxicity. Results: From May 2008 to May 2012, 198 eligible patients were enrolled from 7 cancer centers. Most patients died with distant metastasis; only 10% died with isolated primary recurrence. Median OS time was 13.0 months (95% confidence interval [CI]: 11.7-14.3); OS rates were 53.5% at 1 year, 15.8% at 2 years, and 9.2% at 3 years. Median progression-free survival (PFS) time was 9.0 months (95% CI: 7.7-10.3); corresponding PFS rates were 30.8%, 8.2%, and 6.1%. The 1-year, 2-year, and 3-year local (primary tumor) control rates were 78.8%, 57.7%, and 55.4%. Multivariate analysis showed that delivery of ≥63 Gy to the primary tumor (P=.014), having a primary tumor volume <134 cm{sup 3} (P=.008), and having a stable or higher KPS score after treatment (P=.01) were independent predictors of better OS. The most common severe (grades 3-4) acute toxicities were hematologic: leukopenia (37.9%), thrombocytopenia (10.1%), and anemia (6.9%). No patients experienced grade 4 or 5 radiation-related toxicity; 2.5% had acute grade 3 pneumonitis, and 6.6% had acute grade 3 radiation esophagitis. Conclusions: Thoracic 3D-RT to the primary tumor with concurrent chemotherapy led to satisfactory survival outcomes with acceptable toxicity. Radiation dose, primary tumor volume, and PFS after treatment all

  15. Evaluation of gross tumor size using CT, 18F-FDG PET, integrated 18F-FDG PET/CT and pathological analysis in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Yu Huiming; Liu Yunfang; Hou Ming; Liu Jie; Li Xiaonan; Yu Jinming

    2009-01-01

    Purpose: The correlation of gross tumor sizes between combined 18 F-FDG PET/CT images and macroscopic surgical samples has not yet been studied in detail. In the present study, we compared CT, 18 F-FDG PET and combined 18 F-FDG PET/CT for the delineation of gross tumor volume (GTV) and validated the results through examination of the macroscopic surgical specimen. Methods: Fifty-two operable non-small cell lung cancer (NSCLC) patients had integrated 18 F-FDG PET/CT scans preoperatively and pathological examination post-operation. Four separate maximal tumor sizes at X (lateral direction), Y (ventro-dorsal direction) and Z (cranio-caudal direction) axis were measured on 18 F-FDG PET, CT, combined 18 F-FDG PET/CT and surgical specimen, respectively. Linear regression was calculated for each of the three imaging measurements versus pathological measurement. Results: No significant differences were observed among the tumor sizes measured by three images and pathological method. Compared with pathological measurement, CT size at X, Y, Z axis was larger, whereas combined 18 F-FDG PET/CT and 18 F-FDG PET size were smaller. Combined 18 F-FDG PET/CT size was more similar to the pathological size than that of 18 F-FDG PET or CT. Results of linear regressions showed that integrated 18 F-FDG PET/CT was the most accurate modality in measuring the size of cancer. Conclusions: 18 F-FDG PET/CT correlates more faithfully with pathological findings than 18 F-FDG PET or CT. Integrated 18 F-FDG PET/CT is an effective tool to define the target of GTV in radiotherapy.

  16. WE-E-17A-05: Complementary Prognostic Value of CT and 18F-FDG PET Non-Small Cell Lung Cancer Tumor Heterogeneity Features Quantified Through Texture Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Desseroit, M; Cheze Le Rest, C; Tixier, F [CHU Poitiers Poitiers (France); INSERM LaTIM UMR 1101, Brest (France); Majdoub, M; Visvikis, D; Hatt, M [INSERM LaTIM UMR 1101, Brest (France); Guillevin, R; Perdrisot, R [CHU Poitiers Poitiers (France)

    2014-06-15

    Purpose: Previous studies have shown that CT or 18F-FDG PET intratumor heterogeneity features computed using texture analysis may have prognostic value in Non-Small Cell Lung Cancer (NSCLC), but have been mostly investigated separately. The purpose of this study was to evaluate the potential added value with respect to prognosis regarding the combination of non-enhanced CT and 18F-FDG PET heterogeneity textural features on primary NSCLC tumors. Methods: One hundred patients with non-metastatic NSCLC (stage I–III), treated with surgery and/or (chemo)radiotherapy, that underwent staging 18F-FDG PET/CT images, were retrospectively included. Morphological tumor volumes were semi-automatically delineated on non-enhanced CT using 3D SlicerTM. Metabolically active tumor volumes (MATV) were automatically delineated on PET using the Fuzzy Locally Adaptive Bayesian (FLAB) method. Intratumoral tissue density and FDG uptake heterogeneities were quantified using texture parameters calculated from co-occurrence, difference, and run-length matrices. In addition to these textural features, first order histogram-derived metrics were computed on the whole morphological CT tumor volume, as well as on sub-volumes corresponding to fine, medium or coarse textures determined through various levels of LoG-filtering. Association with survival regarding all extracted features was assessed using Cox regression for both univariate and multivariate analysis. Results: Several PET and CT heterogeneity features were prognostic factors of overall survival in the univariate analysis. CT histogram-derived kurtosis and uniformity, as well as Low Grey-level High Run Emphasis (LGHRE), and PET local entropy were independent prognostic factors. Combined with stage and MATV, they led to a powerful prognostic model (p<0.0001), with median survival of 49 vs. 12.6 months and a hazard ratio of 3.5. Conclusion: Intratumoral heterogeneity quantified through textural features extracted from both CT and FDG PET

  17. Flat-Panel Cone-Beam Ct-Guided Radiofrequency Ablation of Very Small (≤1.5 cm) Liver Tumors: Technical Note on a Preliminary Experience

    Energy Technology Data Exchange (ETDEWEB)

    Cazzato, Roberto Luigi, E-mail: r.cazzato@unicampus.it; Buy, Xavier, E-mail: x.buy@bordeaux.unicancer.fr; Alberti, Nicolas, E-mail: nicoalbertibdx@gmail.com; Fonck, Mariane, E-mail: m.fonk@bordeaux.unicancer.fr [Institut Bergonié 229 Cours de l’Argonne, Department of Radiology (France); Grasso, Rosario Francesco, E-mail: r.grasso@unicampus.it [Università “Campus Bio-Medico di Roma”, Department of Radiology and Diagnostic Imaging (Italy); Palussière, Jean, E-mail: j.palussiere@bordeaux.unicancer.fr [Institut Bergonié 229 Cours de l’Argonne, Department of Radiology (France)

    2015-02-15

    PurposeThe aim of the present study was to investigate the technical feasibility of flat-panel cone-beam CT (CBCT)-guided radiofrequency ablation (RFA) of very small (<1.5 cm) liver tumors.Materials and MethodsPatients included were candidates for hepatic percutaneous RFA as they had single biopsy-proven hepatic tumors sized ≤1.5 cm and poorly defined on ultrasonography. Following apnea induction, unenhanced CBCT scans were acquired and used to deploy the RF electrode with the aid of a virtual navigation system. If the tumor was not clearly identified on the unenhanced CBCT scan, a right retrograde arterial femoral access was established to carry out hepatic angiography and localize the tumor. Patients’ lesions and procedural variables were recorded and analyzed.ResultsThree patients (2 male and 1 female), aged 68, 76, and 87 years were included; 3 lesions (2 hepato-cellular carcinoma and 1 metastasis from colorectal cancer) were treated. One patient required hepatic angiography. Cycles of apnea used to acquire CBCT images and to deploy the electrode lasted <120 s. Mean fluoroscopic time needed to deploy the electrode was 36.6 ± 5.7 min. Mean overall procedural time was 66.0 ± 22.9 min. No peri- or post-procedural complications were noted. No cases of incomplete ablation were noted at 1-month follow-up.ConclusionPercutaneous CBCT-guided liver RFA with or without arterial hepatic angiography is technically feasible.

  18. Sinus Tumors

    Science.gov (United States)

    ... RESOURCES Medical Societies Patient Education About this Website Font Size + - Home > CONDITIONS > Sinus Tumors Adult Sinusitis Pediatric ... and they vary greatly in location, size and type. Care for these tumors is individualized to each ...

  19. Tumors markers

    International Nuclear Information System (INIS)

    Yamaguchi-Mizumoto, N.H.

    1989-01-01

    In order to study blood and cell components alterations (named tumor markers) that may indicate the presence of a tumor, several methods are presented. Aspects as diagnostic, prognostic, therapeutic value and clinical evaluation are discussed. (M.A.C.)

  20. Wilms tumor

    Science.gov (United States)

    ... suggested. Alternative Names Nephroblastoma; Kidney tumor - Wilms Images Kidney anatomy Wilms tumor References Babaian KN, Delacroix SE, Wood CG, Jonasch E. Kidney cancer. In: Skorecki K, Chertow GM, Marsden PA, ...

  1. Pituitary gland tumors

    International Nuclear Information System (INIS)

    Jesser, J.; Schlamp, K.; Bendszus, M.

    2014-01-01

    This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15 % of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65 % of pituitary gland adenomas secrete hormones whereby approximately 50 % secrete prolactin, 10 % secrete growth hormone (somatotropin) and 6 % secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10 % of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland. (orig.) [de

  2. [Pituitary gland tumors].

    Science.gov (United States)

    Jesser, J; Schlamp, K; Bendszus, M

    2014-10-01

    This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15% of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65% of pituitary gland adenomas secrete hormones whereby approximately 50% secrete prolactin, 10% secrete growth hormone (somatotropin) and 6% secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10% of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland.

  3. Serum GRP78 as a Tumor Marker and Its Prognostic Significance in Non-Small Cell Lung Cancers: A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Xiao Ma

    2015-01-01

    Full Text Available Introduction. Glucose-regulated protein 78 (78 kDa, GRP78, which is also known as immunoglobulin heavy chain binding protein (BIP, is a major chaperone in the endoplasmic reticulum (ER. The expression and clinical significance of GRP78 in the serum of non-small cell lung cancer patients have not yet been clearly described. The aims of the present study were to investigate the expression of GRP78 in the serum of non-small cell lung cancer patients, the relationships with clinicopathological parameters, and the potential implications for survival. Patients and Methods. A total of 163 peripheral blood samples from non-small cell lung cancer patients were prospectively collected at the Department of Thoracic Surgery, Fudan University Shanghai Cancer, China. Clinical characteristics data, including age, gender, stage, overall survival (OS time, and relapse-free survival (RFS time, were also collected. Serum GRP78 levels were measured using a commercially available ELISA kit. The associations between GRP78 levels and clinicopathological characteristics and survival were examined using Student’s t-test, Kaplan-Meier, or Cox regression analyses. Results. The mean ± standard error (SE value of GRP78 was 326.5 ± 49.77 pg/mL. This level was significantly lower compared with the level in late-stage non-small cell lung cancer patients (1227 ± 223.6, p=0.0001. There were no significant correlations with the clinicopathological parameters. No significant difference was found between high GRP78 expression and low GRP78 expression with regard to RFS (p=0.1585. However, the OS of patients with higher GRP78 expression was significantly poorer (p=0.0334. Conclusions. GRP78 was expressed in non-small cell lung cancer patients and was highly enriched in late-stage lung cancer. GRP78 may have an important role in the carcinogenesis of non-small cell lung cancer and may be a prognostic marker for non-small cell lung cancer.

  4. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  5. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  6. Urogenital tumors

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  7. Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2018-01-12

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  8. MicroRNA-429 induces tumorigenesis of human non-small cell lung cancer cells and targets multiple tumor suppressor genes

    Energy Technology Data Exchange (ETDEWEB)

    Lang, Yaoguo; Xu, Shidong; Ma, Jianqun; Wu, Jun [Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China); Jin, Shi; Cao, Shoubo [Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China); Yu, Yan, E-mail: yuyan@hrbmu.edu.cn [Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China)

    2014-07-18

    Highlights: • MiR-429 expression is upregulated in non-small cell lung cancer (NSCLC). • MiR-429 inhibits PTEN, RASSF8 and TIMP2 expression. • MiR-429 promotes metastasis and proliferation. • We report important regulatory mechanisms involved in NSCLC progression. • MiR-429 is a potential therapeutic target and diagnostic marker. - Abstract: Lung cancer is the major cause of cancer death globally. MicroRNAs are evolutionally conserved small noncoding RNAs that are critical for the regulation of gene expression. Aberrant expression of microRNA (miRNA) has been implicated in cancer initiation and progression. In this study, we demonstrated that the expression of miR-429 are often upregulated in non-small cell lung cancer (NSCLC) compared with normal lung tissues, and its expression level is also increased in NSCLC cell lines compared with normal lung cells. Overexpression of miR-429 in A549 NSCLC cells significantly promoted cell proliferation, migration and invasion, whereas inhibition of miR-429 inhibits these effects. Furthermore, we demonstrated that miR-429 down-regulates PTEN, RASSF8 and TIMP2 expression by directly targeting the 3′-untranslated region of these target genes. Taken together, our results suggest that miR-429 plays an important role in promoting the proliferation and metastasis of NSCLC cells and is a potential target for NSCLC therapy.

  9. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

    Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

  10. Anti-tumor activity of high-dose EGFR tyrosine kinase inhibitor and sequential docetaxel in wild type EGFR non-small cell lung cancer cell nude mouse xenografts

    Science.gov (United States)

    Tang, Ning; Zhang, Qianqian; Fang, Shu; Han, Xiao; Wang, Zhehai

    2017-01-01

    Treatment of non-small-cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) is still a challenge. This study explored antitumor activity of high-dose icotinib (an EGFR tyrosine kinase inhibitor) plus sequential docetaxel against wild-type EGFR NSCLC cells-generated nude mouse xenografts. Nude mice were subcutaneously injected with wild-type EGFR NSCLC A549 cells and divided into different groups for 3-week treatment. Tumor xenograft volumes were monitored and recorded, and at the end of experiments, tumor xenografts were removed for Western blot and immunohistochemical analyses. Compared to control groups (negative control, regular-dose icotinib [IcoR], high-dose icotinib [IcoH], and docetaxel [DTX]) and regular icotinib dose (60 mg/kg) with docetaxel, treatment of mice with a high-dose (1200 mg/kg) of icotinib plus sequential docetaxel for 3 weeks (IcoH-DTX) had an additive effect on suppression of tumor xenograft size and volume (P Icotinib-containing treatments markedly reduced phosphorylation of EGFR, mitogen activated protein kinase (MAPK), and protein kinase B (Akt), but only the high-dose icotinib-containing treatments showed an additive effect on CD34 inhibition (P icotinib plus docetaxel had a similar effect on mouse weight loss (a common way to measure adverse reactions in mice), compared to the other treatment combinations. The study indicate that the high dose of icotinib plus sequential docetaxel (IcoH-DTX) have an additive effect on suppressing the growth of wild-type EGFR NSCLC cell nude mouse xenografts, possibly through microvessel density reduction. Future clinical trials are needed to confirm the findings of this study. PMID:27852073

  11. EGFR T790M mutation testing of non-small cell lung cancer tissue and blood samples artificially spik