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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. 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)

  3. 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

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

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

    2012-04-01

    A 12-year-old boy presented acutely after an episode of syncope with perioral cyanosis. He died 19 hours after admission due to cor pulmonale as a complication of metastatic desmoplastic small round cell tumor in the lungs with associated tumor thrombotic microangiopathy. Copyright © 2012 Mosby, Inc. All rights reserved.

  5. Desmoplastic small round cell tumor: a report of two cases and a review of the literature

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    Ruiz, E.; Lopez, G.; Touma, C.; Concha, A.

    2001-01-01

    The desmoplastic small round cell tumor is a malignant neoplasm that typically presents as an abdominopelvic mass in young men in their second or third decade of life. We report two cases of this rare lesion, describing the computed tomography and pathological findings. We also provide a brief review of the literature, stressing the radiological features of the tumor. (Author) 17 refs

  6. Desmoplastic small round cell tumor: a clinicopathologic, immunohistochemical, and molecular study of 32 tumors.

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    Lae, Marick E; Roche, Patrick C; Jin, Long; Lloyd, Ricardo V; Nascimento, Antonio G

    2002-07-01

    Desmoplastic small round cell tumor is a rare, aggressive neoplasm that mainly affects young male patients and is characterized by a reciprocal translocation t(11;22)(p13;q12) associated with the EWS-WT1 gene fusion transcript. Clinical, histopathologic, immunohistochemical, and molecular genetics features were reviewed for 32 tumors. There were 29 male and three female patients, with ages from 6 to 54 years (mean, 25 years). The main clinical signs and symptoms included abdominal pain (eight patients), weight loss (five patients), and presence of umbilical hernia (four patients). Two tumors primarily involved the ethmoid sinus and the soft tissues of the scalp; the other tumors (mean size, 10 cm) involved the abdominal cavity (88%). One patient presented initially with an axillary lymph node metastasis. Generally, all tumors showed the typical histologic findings of variably sized clusters of small, round, or spindled cells lying in a desmoplastic stroma. The neoplastic cells in formalin-fixed, paraffin-embedded tissue sections were positive for desmin (dot pattern) (81% of the cases), WT1 (91%), keratin (87%), neuron-specific enolase (84%), CD99 (23%), and actin (3%). The EWS-WT1 gene fusion transcript was detected in 29 of 30 tumors. One tumor with typical clinicopathologic and immunohistochemical features did not show the gene fusion. Follow-up for 27 patients showed that 19 patients (70%) died of uncontrolled, local, or widespread metastatic disease 3-46 months (mean, 20 months) after diagnosis, and eight patients were alive with known evidence of disease. Occasionally, desmoplastic small round cell tumor lacks the classic clinical, histologic, and immunohistochemical features. This study emphasizes the utility of analysis of the EWS-WT1 gene fusion transcript, which was performed on paraffin-embedded tissues, to confirm the diagnosis.

  7. 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)

  8. [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

  9. 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.

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

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    Atallah, Vincent; Honore, Charles; Orbach, Daniel; Helfre, Sylvie; Ducassou, Anne; Thomas, Laurence; Levitchi, Mihai-Barbu; Mervoyer, Augustin; Naji, Salem; Dupin, Charles; Bosco-Levy, Pauline J.; Philippe-Chomette, Pascale; Kantor, Guy; Henriques de Figueiredo, Benedicte; Sunyach, Marie-Pierre; Sargos, Paul

    2016-01-01

    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

  11. 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

  12. Amelanotic melanoma masquerading as a superficial small round cell tumor: A diagnostic challenge

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    Archana Shetty

    2014-01-01

    Full Text Available Malignant melanoma poses a remarkable capacity for morphological diversity and often presents as a diagnostic challenge due to its wide clinical presentation. We present a case of a 73-year-old lady, with a large superficial ulcerative nodular mass on the flexor aspect of the right upper arm. On fine needle aspiration poorly differentiated round cell tumor was suggested, with histopathology also supporting the same diagnosis. A final diagnosis of amelanotic melanoma was given following immunohistochemical work-up using a panel of relevant markers. We are presenting this case, not only for its rare clinical presentation, but also for the diagnostic difficulties encountered by us in cytology and histopathology to reach the final diagnosis.

  13. Atypical presentation of a desmoplastic small round cell tumor in the orbit: Case report and review of the literature

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    Sojitra P

    2016-08-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT is a rare malignant neoplasm. Typically it occurs in young adult males and involves the abdomen or pelvis. Other primary sites are uncommon. Only one other case of orbital DSRCT has been reported in the literature. The diagnosis of DSRCTs can be extremely challenging since they often have overlapping histologic and immunohistochemical profile with other small round blue cell tumors. This is particularly true when the tumor occurs in an unusual location, and especially when it lacks the classic histologic pattern. Molecular confirmation is critical when the biopsy sample is limited. Herein, we report a case of DSRCT involving the right orbit of a 3-year-old male with immunohistological and molecular confirmation for DSRCT.

  14. 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.

  15. 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.

  16. Superficial small round-cell tumors with special reference to the Ewing's sarcoma family of tumors and the spectrum of differential diagnosis.

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    Machado, Isidro; Traves, Victor; Cruz, Julia; Llombart, Beatriz; Navarro, Samuel; Llombart-Bosch, Antonio

    2013-02-01

    Superficial/cutaneous small round-cell tumors comprise a heterogeneous group of neoplasms including sarcoma, carcinoma, melanoma, and lymphomas. Among superficial sarcomas, the Ewing's sarcoma family of tumors (ESFT) represents a poorly understood rare variant, having a behavioral difference characterized by a relative favorable prognosis. Several problems are still to be resolved in superficial ESFT, including the differential diagnosis between ESFT of bone (intraosseous or periosteal) with superficial infiltration and superficial ESFT with bone infiltration, especially in the fingers. Our aim is to review the most common types of small round-cell tumors included in the differential diagnosis of superficial ESFT, analyzing the histopathology, phenotype, and molecular alterations of each entity. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. 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

  18. 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.)

  19. Fine-needle aspiration in desmoplastic small round cell tumor: a report of 10 new tumors in 8 patients with clinicopathological and molecular correlations with review of the literature.

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    Klijanienko, Jerzy; Colin, Pierre; Couturier, Jérôme; Lagacé, Réal; Fréneaux, Paul; Pierron, Gaëlle; Laé, Marick; Klijanienko, Alice; Brisse, Hervé; Orbach, Daniel; Theocharis, Stamatios

    2014-05-01

    Desmoplastic small round cell tumor (DSRCT) is a rare round cell sarcoma entity characterized by a specific t(11;22)(p13;q12) translocation, usually intra-abdominal localization and an aggressive clinical outcome. To date, only 35 DSRCT cases diagnosed by fine-needle aspiration have been described. This study reports the cytological diagnosis of DSRCT. Ten tumors from 8 patients were sampled for diagnosis and analyzed to search the characteristic translocation using fluorescence in situ hybridization or reverse transcription polymerase chain reaction methods. Smears were always hypercellular and consisted of nonspecific round cell sarcoma. Nuclei were polymorphic round, kidney-, or heart-shaped. Nuclear molding was usually present. Paranuclear cytoplasmic densities were obvious and noted in 7 cases. Cytonuclear atypia, mitotic figures, numerous crushed nuclei, and apoptosis were frequently seen. Purple-stained stroma was present in 8 cases (ranging from few connective tissue fragments to large hyalinized deposits). Molecular studies based on cytological aspirates were performed in 8 patients. The presence of the fusion gene EWSR1-WT 1 transcript was identified in all, which confirmed the diagnosis of DSRCT. Smears showing poorly differentiated round cells associated with cytoplasmic densities and connective stoma, in a specific clinical context, young adult age, intra-abdominal localization, suggestive immunocytochemical profile, and a unique cytogenetic abnormality are highly specific and allow an accurate diagnosis of DSRCT. © 2014 American Cancer Society.

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

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    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

  1. 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

    International Nuclear Information System (INIS)

    Desai, Neil B.; Stein, Nicholas F.; LaQuaglia, Michael P.; Alektiar, Kaled M.; Kushner, Brian H.; Modak, Shakeel; Magnan, Heather M.; Goodman, Karyn; Wolden, Suzanne L.

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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

  5. 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

  6. Histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with CIC-DUX4 and BCOR-CCNB3 fusion genes.

    Science.gov (United States)

    Yamada, Yuichi; Kuda, Masaaki; Kohashi, Kenichi; Yamamoto, Hidetaka; Takemoto, Junkichi; Ishii, Takeaki; Iura, Kunio; Maekawa, Akira; Bekki, Hirofumi; Ito, Takamichi; Otsuka, Hiroshi; Kuroda, Makoto; Honda, Yumi; Sumiyoshi, Shinji; Inoue, Takeshi; Kinoshita, Naoe; Nishida, Atsushi; Yamashita, Kyoko; Ito, Ichiro; Komune, Shizuo; Taguchi, Tomoaki; Iwamoto, Yukihide; Oda, Yoshinao

    2017-04-01

    CIC-DUX4 and BCOR-CCNB3 fusion-gene-associated small round cell sarcomas account for a proportion of pediatric small round cell sarcomas, but their pathological features have not been sufficiently clarified. We reviewed a large number of soft tissue tumors registered at our institution, retrieved the cases of unclassified tumors with a small round cell component, and subjected them to histopathological, immunohistochemical, and gene profile analysis. We reviewed 164 cases of unclassified tumors with a small round cell component and analyzed them by RT-PCR and FISH. Tumors positive for a specific fusion-gene were also subjected to histopathological and immunohistochemical examinations. We identified 16 cases of BCOR-CCNB3/CIC-associated (CIC-DUX4 or CIC gene rearrangement-positive) sarcomas. These included seven BCOR-CCNB3 sarcomas and nine CIC-associated sarcomas. Heterogeneous elements included a myxoid spindle cell component in three BCOR-CCNB3 sarcomas and an epithelioid cell component in two CIC-associated sarcomas (one CIC-DUX4-positive and one CIC-DUX4-negative sarcomas). Mitotic activity was low in both heterogeneous components. By immunohistochemistry, in seven BCOR-CCNB3 sarcomas expression of EMA was positive in two cases, of p63 in three, of CD56 in six, of TLE1 in seven, of NKX2.2 in two, of CCNB3 in seven, and of BCOR in six cases (one case could not be tested for BCOR). In nine cases of CIC-associated sarcoma, CD56 was expressed in five, alpha-smooth muscle actin in one, ERG in three, and CD99, WT1 and TLE1 each in eight cases. Both sarcoma types showed not only a small round cell component, but also a myxoid/epithelioid component with low mitotic activity.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Round cell anaplastic carcinoma of the pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jae Hoon; Lee, Dong Ho; Ko, Young Tae; Yang, Moon Ho [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1989-02-15

    Ultrasonography of the upper abdomen disclosed an oval well defined mass in the pancreas. Round cell anaplastic carcinoma is one of sarcomatoid pancreatic carcinoma, microscopically characterized by monotonous sheaths of small round plump cells with rare giant cells and thus more or less reminiscent of malignant lymphoma. Whether this tumor is of ductal or acinar cell origin remains to be determined. Clinically, this tumor does not differ significantly from ordinary adenocarcinoma of the pancreas. We report a cases of round cell anaplastic carcinoma and describe the CT and sonographic findings, and discuss the differential points from other solid pancreatic tumors.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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...

  12. 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

  13. Malignant small Cell Tumor of the Thoracopulmonary Region-Report of One Case and a Review of the Literature

    International Nuclear Information System (INIS)

    Choi, Myung Sun; Chung, Kyoo Byung

    1986-01-01

    The malignant small round cell tumor of the thoracopulmonary region was described by Askin in 1979 and called as Askin Tumor. The Askin tumor is a rare, arises from the soft tissues of the chest wall or peripheral lung which is predominantly in younger generation. Clinical and pathologic appearance were very similar to Ewing's sarcoma and rhabdomyosarcoma but when examined it by electron microscopy, there was some different in morphology. The tumor tended to recur locally and did not seem to disseminated widely but the median survival was only 8 months

  14. 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

  15. Cell Senescence in Myxoid/Round Cell Liposarcoma

    Directory of Open Access Journals (Sweden)

    Christina Kåbjörn Gustafsson

    2014-01-01

    Full Text Available Myxoid/round cell liposarcoma (MLS/RCLS is the second most common liposarcoma type and characterized by the fusion oncogenes FUS-DDIT3 or EWSR1-DDIT3. Previous analysis of cell cycle regulatory proteins revealed a prominent expression of G1-cyclins, cyclin dependent kinases, and their inhibitors but very few cells progressing through the G1/S boundary. Here, we extend the investigation to proteins involved in cell senescence in an immunohistochemistry based study of 17 MLS/RCLS cases. Large subpopulations of tumor cells expressed the RBL2 pocket protein and senescence associated heterochromatin 1γ and IL8 receptor β. We conclude that MLS/RCLS tissues contain major populations of senescent tumor cells and this may explain the slow growth rate of this tumor type.

  16. Primary cutaneous Ewing's sarcoma/primitive neuroectodermal tumor manifesting numerous small and huge ulcerated masses: its complete remission by chemotherapy and magnetic resonance imaging findings

    International Nuclear Information System (INIS)

    Bahk, Won-Jong; Chang, Eun-Deok; Lee, An-Hee; Bae, Jung Min; Kim, Jin Woo; Chun, Kyung-Ah; Rho, Sang-Young

    2010-01-01

    Extraskeletal Ewing's sarcoma (ES) and primitive neuroectodermal tumor (PNET) are widely regarded as clinically and histologically identical tumors which consist of small blue round cells. Extraskeletal ESs/PNETs usually occur in the deep soft tissues of the paraspinal region, chest wall, or lower extremities. However, superficially located cases, so-called cutaneous ESs/PNETs, are exceedingly rare, and the vast majority of the reported cases present as a single small mass. We present magnetic resonance imaging (MRI) findings and clinical course of a unique case of primary cutaneous ES/PNET presenting as numerous huge masses with severe ulceration on them. (orig.)

  17. Primary cutaneous Ewing's sarcoma/primitive neuroectodermal tumor manifesting numerous small and huge ulcerated masses: its complete remission by chemotherapy and magnetic resonance imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Bahk, Won-Jong [The Catholic University of Korea, Department of Orthopedic Surgery, Uijeongbu St. Mary' s Hospital, Uijeongbu (Korea); Chang, Eun-Deok; Lee, An-Hee [The Catholic University of Korea, Department of Pathology, Uijeongbu St. Mary' s Hospital, Uijeongbu (Korea); Bae, Jung Min; Kim, Jin Woo [The Catholic University of Korea, Department of Dermatology, Uijeongbu St. Mary' s Hospital, Uijeongbu (Korea); Chun, Kyung-Ah [The Catholic University of Korea, Department of Radiology, Uijeongbu St. Mary' s Hospital, Uijeongbu (Korea); Rho, Sang-Young [The Catholic University of Korea, Department of Hemato-oncology, Uijeongbu St. Mary' s Hospital, Uijeongbu (Korea)

    2010-06-15

    Extraskeletal Ewing's sarcoma (ES) and primitive neuroectodermal tumor (PNET) are widely regarded as clinically and histologically identical tumors which consist of small blue round cells. Extraskeletal ESs/PNETs usually occur in the deep soft tissues of the paraspinal region, chest wall, or lower extremities. However, superficially located cases, so-called cutaneous ESs/PNETs, are exceedingly rare, and the vast majority of the reported cases present as a single small mass. We present magnetic resonance imaging (MRI) findings and clinical course of a unique case of primary cutaneous ES/PNET presenting as numerous huge masses with severe ulceration on them. (orig.)

  18. SMARCA4 (BRG1) loss of expression is a useful marker for the diagnosis of ovarian small cell carcinoma of the hypercalcemic type (ovarian rhabdoid tumor): a comprehensive analysis of 116 rare gynecologic tumors, 9 soft tissue tumors, and 9 melanomas.

    Science.gov (United States)

    Karanian-Philippe, Marie; Velasco, Valérie; Longy, Michel; Floquet, Anne; Arnould, Laurent; Coindre, Jean-Michel; Le Naoures-Méar, Cécile; Averous, Gerlinde; Guyon, Frédéric; MacGrogan, Gaëtan; Croce, Sabrina

    2015-09-01

    Ovarian small cell carcinoma of the hypercalcemic type (SCCOHT)/ovarian rhabdoid tumor is a rare and highly malignant tumor that typically occurs in young women. Up until now the diagnosis has been made on the basis of morphology without any specific immunohistochemical (IHC) markers. However, several authors have shown recently that SCCOHTs are characterized by inactivation of the SMARCA4 gene (encoding the BRG1 protein) resulting in a loss of BRG1 protein expression in IHC. We evaluated BRG1 and INI1 expression in 12 SCCOHTs and in a series of 122 tumors that could mimic SCCOHT morphologically: 9 juvenile granulosa cell tumors, 47 adult granulosa cell tumors, 33 high-grade ovarian serous carcinomas, 9 desmoplastic round cell tumors, 13 Ewing sarcomas (5 from the pelvis and 8 from soft tissues), 1 round cell sarcoma associated with CIC-DUX4 translocation from soft tissue (thigh), 1 case of high-grade endometrial stromal sarcoma of the ovary, and 9 melanomas. Forty-four adult granulosa cell tumors were interpretable by IHC. All 12 SCCOHTs were devoid of BRG1 expression and expressed INI1. All other interpretable 119 tumors showed BRG1 nuclear positivity, with variable staining proportions, ranging from 10% to 100% of positive cells (mean: 77%, median: 80%), variable intensities (weak: 5%, moderate: 37%, strong: 58%), and distributions: diffuse in 82 cases (70%) and heterogenous in 36 cases (30%). BRG1 positivity was heterogenous in desmoplastic round cell tumors and adult granulosa cell tumors. Overall, BRG1 is a useful diagnostic marker in SCCOHT, showing the absence of expression in SCCOHT. Nevertheless, the possible heterogeneity and the variable intensity of this staining warrant caution in the interpretation of BRG1 staining in biopsy specimens.

  19. Immunohistochemical Profile of MYC Protein in Pediatric Small Round Blue Cell Tumors.

    Science.gov (United States)

    Chisholm, Karen M; Krishnan, Chandra; Heerema-McKenney, Amy; Natkunam, Yasodha

    2017-06-01

    Deregulation of MYC oncoprotein in cancers can result from multiple oncogenic mechanisms. Although MYC translocations define Burkitt lymphoma and MYC protein expression is a poor prognostic factor in undifferentiated neuroblastomas, the distribution of MYC protein (c-MYC) across other pediatric small round blue cell tumors (SRBCT) has not been well characterized. We undertook this study to assess MYC protein expression in a large cohort of pediatric lymphomas, sarcomas, and other SRBCT. Tissue microarrays containing 302 SRBCT were successfully evaluated by immunohistochemistry using anti-MYC clone Y69, with nuclear positivity scored as 0%, 1%-25%, 26%-50%, 51%-75%, or 76%-100%. MYC protein staining of >50% of lesional cells was identified in 60% of Burkitt lymphomas, 50% of B lymphoblastic lymphomas, 33% of T lymphoblastic lymphomas, 31% of rhabdomyosarcomas, 33% of Ewing sarcomas, and 25% of soft tissue sarcomas, not otherwise specified. Only 14% of neuroblastomas showed >50% staining, and of these, if known, MYCN was not amplified. No cases of Wilms tumor, synovial sarcoma, or desmoplastic small round cell tumor had >50% staining. Recurrences and metastases often had the same percentage of MYC staining (15/30). In conclusion, MYC protein exhibited variable expression across and within pediatric SRBCT subtypes. Overall, these findings provide a baseline for MYC expression in pediatric SRBCT and suggest that there may be multiple mechanisms of MYC upregulation in these different neoplasms.

  20. 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.

  1. 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)

  2. 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.

  3. Improved classification, diagnosis and prognosis of canine round cell tumours

    NARCIS (Netherlands)

    Cangul, Taci

    2001-01-01

    As the name suggests, canine round cell tumour (RCTs) are composed of cells with a round morphology. There is some discrepancy amongst authors as to which tumours belong to this category, but most designate lymphomas, melanomas, plasmacytomas, transmissible venereal tumours (TVTs), histiocytomas,

  4. 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)

  5. 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)

  6. The cancer-testis antigen NY-ESO-1 is highly expressed in myxoid and round cell subset of liposarcomas.

    Science.gov (United States)

    Hemminger, Jessica A; Ewart Toland, Amanda; Scharschmidt, Thomas J; Mayerson, Joel L; Kraybill, William G; Guttridge, Denis C; Iwenofu, O Hans

    2013-02-01

    Liposarcomas are a heterogenous group of fat-derived sarcomas, and surgery with or without chemoradiation therapy remains the main stay of treatment. NY-ESO-1 is a cancer-testis antigen expressed in various cancers where it can induce both cellular and humoral immunity. Immunotherapy has shown promise in clinical trials involving NY-ESO-1-expressing tumors. Gene expression studies have shown upregulation of the gene for NY-ESO-1, CTAG1B, in myxoid and round cell liposarcomas. Herein, we evaluated the expression of NY-ESO-1 among liposarcoma subtypes by quantitative real-time PCR, western blot analysis, and immunohistochemistry. Frozen tissue for quantitative real-time PCR and western blot analysis was obtained for the following liposarcoma subtypes (n=15): myxoid and round cell (n=8); well-differentiated (n=4), and dedifferentiated (n=3). Formalin-fixed paraffin-embedded blocks were obtained for the following liposarcoma subtypes (n=44): myxoid and round cell (n=18); well-differentiated (n=10); dedifferentiated (n=10); and pleomorphic (n=6). Full sections were stained with monoclonal antibody NY-ESO-1, and staining was assessed for intensity (1-3+), percentage of tumor positivity, and location. In all, 7/8 (88%) and 16/18 (89%) myxoid and round cell expressed CTAG1B and NY-ESO-1 by quantitative real-time PCR and immunohistochemistry, respectively. Western blot correlated with mRNA expression levels. By immunohistochemistry, 94% (15/16) of positive cases stained homogenously with 2-3+ intensity. Also, 3/6 (50%) pleomorphic liposarcomas demonstrated a range of staining: 1+ intensity in 50% of cells; 2+ intensity in 5% of cells; and 3+ intensity in 90% of cells. One case of dedifferentiated liposarcoma showed strong, diffuse staining (3+ intensity in 75% of cells). Our study shows that both CTAG1B mRNA and protein are overexpressed with high frequency in myxoid and round cell liposarcoma, enabling the potential use of targeted immunotherapy in the treatment of this

  7. The morphological profile of small bowel tumors - our experience.

    Science.gov (United States)

    Mărgăritescu, Nicolae Dragoş; Ciobanu, Mircea Ovidiu; Nemeş, Răducu Nicolae; Ghelase, Ştefan Mugurel; Pleşea, Răzvan Mihail; Georgescu, Ion; Voinea, Bogdan; Pleşea, Iancu Emil; ChiuŢu, LuminiŢa Cristina

    2016-01-01

    The authors assessed the morphological profile of tumor masses belonging to the small bowel discovered in their daily practice. 31 tumor masses located in different segments of small intestine operated between 2002 and 2013 in the 1st Surgical Department, Emergency County Hospital of Craiova, Romania, were analyzed. The investigated parameters were: tumor location and number, tumor dimensions, gross assessment, tumor extension and histological assessment. Tumor masses belonging to small intestine were rare. They usually expressed by their complications. In many cases, they were placed at the extremities of the small intestine. They were usually small but sometimes large and developing outwards intestinal wall. Commonly they had a fungating and ulcerated appearance. They were rather of mesenchymal origin than epithelial. However, some of them were inflammatory pseudotumors. Almost all neoplastic proliferations had a malignant phenotype, most often with regional extension. Our series of tumors had a morphological profile somehow similar with the profile described in the literature but with some particularities: the polarization to the extremities of the intestinal segment, a significant number of large tumors, clinical expression through different complications, the balance inclined in favor of mesenchymal origin of tumors and the clear predominance of malignant aggressive phenotype.

  8. NY-ESO-1 is a sensitive and specific immunohistochemical marker for myxoid and round cell liposarcomas among related mesenchymal myxoid neoplasms.

    Science.gov (United States)

    Hemminger, Jessica A; Iwenofu, O Hans

    2013-09-01

    Myxoid and round cell liposarcomas constitute approximately one-third of all liposarcomas, a relatively common group of fat-derived soft tissue sarcomas. The histomorphology is a continuum between highly differentiated myxoid and poorly differentiated round cell components. The gold standard of diagnosis is dependent on histomorphology and/or identification of t(12;16)(q13;p11) translocation by cytogenetics or demonstration of DDIT3 rearrangements by fluorescence in situ hybridization. There are currently no diagnostic immunohistochemical stains available. The broad range of myxoid neoplasms in the differential diagnosis includes a variety of sarcomas. Given the notable differences in disease biology among myxoid neoplasms, which range from benign to aggressive, an accurate diagnosis is imperative for proper treatment and prognostication. Prompted by our recent study showing frequent expression of the cancer testis antigen NY-ESO-1 in myxoid and round cell liposarcomas, we sought to evaluate the utility of NY-ESO-1 as an immunohistochemical marker for myxoid and round cell liposarcoma among mesenchymal myxoid neoplasms within the differential diagnosis. Formalin-fixed, paraffin-embedded blocks were obtained for the following mesenchymal myxoid neoplasms (n=138): myxoid and round cell liposarcoma (n=38); well-differentiated liposarcoma (n=12); lipoma (n=20; 4 with myxoid change); extra-cardiac soft tissue myxoma (n=39); extraskeletal myxoid chondrosarcoma (n=12); myxofibrosarcoma (n=10: 5 low grade, 2 intermediate grade, 3 high grade); and low-grade fibromyxoid sarcoma (n=7). Utilizing standard immunohistochemistry protocols, full sections were stained with NY-ESO-1 (clone E978), and staining was assessed for intensity (1-2+), percentage of tumor positivity, and location. In all, 36/38 (95%) of the myxoid and round cell liposarcomas demonstrated NY-ESO-1 immunoreactivity. The majority of the positive cases (34/36; 94%) showed strong, homogenous staining (>50% tumor

  9. Thoracic Primitive Neuroectodermal Tumor: An Unusual Case and Literature Review

    Directory of Open Access Journals (Sweden)

    Kubra Erol Kalkan

    2013-01-01

    Full Text Available We describe herein a rare case of a primary primitive neuroectodermal tumor (PNET in the mediastinum of a 75-year-old man. Grossly, the tumor was located in the left upper anterior mediastinum. Transcutaneous fine-needle biopsy (TCNB revealed small round-cell proliferation. The expression immunohistochemical analysis was confirmed the diagnosis of PNET. He was successfully treated with chemotherapy and is alive with no sign of recurrence for 17 months after the diagnosis.

  10. Malignant small cell tumor of the thoracopulmonary region(Askin tumor)

    International Nuclear Information System (INIS)

    Choi, Young Chil; Oh, Yu Whan; Park, Cheol Min; Chung, Kyoo Byung; Choi, Myung Sun; Choi, Young Ho

    1989-01-01

    A series of malignant small cell tumors primarily involve the soft tissue of the chest wall and lung was described by Askin in 1970. This rate tumor has a neuroepithelial origin and affects children and young adult, characteristically. Histologic overlap between other small cell neoplasms usually makes differentiation difficult, and immunochemical and electron microscopic features play a role in differentiation. Radiologic appearance was chest wall or pleural based mass with or without rib destruction and/or pleural change. Authors experienced two cases of malignant small cell tumor of the thoracopulmonary region, and report with review of literatures

  11. 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

  12. Colonofluorography in diagnosis of small-size colon tumors

    International Nuclear Information System (INIS)

    Dvojris, M.S.; Popovich, V.V.

    1988-01-01

    The authors investigated the potentialities of colonofluorography (CFG) in the recognition of small-size colon tumors (not exceeding 3 cm). Among 1029 examinees were persons followedup for colitis, nonspecific ulcerative colitis, diverticulosis and colon polyps, patients after radical colon operations, patients with complaints of colon discomfort, blood and mucus in the stools, and cancer patients. 98 timors not exceeding 3 cm were detected. Comparison of the results of CFG whith those of endoscopy, surgery, and histology demonstrated high resolution of the method in the detection of primary and secondary small-size colon tumors. The simplicity, low cost, short duration, and low radiation exposure in combination with effectiveness make CFG appropriate in prophylactic medical examination of patients identified as high risk groups

  13. Small submucosal tumors of the stomach: differentiation of gastric schwannoma from gastrointestinal stromal tumor with CT.

    Science.gov (United States)

    Choi, Jin Wook; Choi, Dongil; 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.

  14. 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.

  15. NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma.

    Science.gov (United States)

    Pollack, Seth M; Jungbluth, Achim A; Hoch, Benjamin L; Farrar, Erik A; Bleakley, Marie; Schneider, David J; Loggers, Elizabeth T; Rodler, Eve; Eary, Janet F; Conrad, Ernest U; Jones, Robin L; Yee, Cassian

    2012-09-15

    Myxoid/round cell liposarcoma (MRCL) is the second most common liposarcoma subtype, accounting for >33% of liposarcomas and approximately 10% of all soft tissue sarcomas. Although MRCL is a chemosensitive subtype, patients with metastatic disease have a poor outcome. NY-ESO-1 is a cancer-testis antigen (also known as cancer germ cell antigen) that has been successfully targeted in vaccine trials and in adoptive T-cell therapy trials for the treatment of several solid tumors. The authors investigated the feasibility of targeting NY-ESO-1 in patients with MRCL by evaluating the prevalence of NY-ESO-1 expression in tumors using immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction analysis. NY-ESO-1-specific tumor recognition by NY-ESO-1-specific T-cells also was analyzed using a chromium release assay. A search of the University of Washington Sarcoma Tissue Bank identified paraffin-embedded tumor samples from 25 patients with MRCL. NY-ESO-1 expression was observed in every MRCL tumor assessed (100%); in 18 tumors (72%), staining was homogenous. In all but 2 tumors, staining was sufficiently robust (2+) that such patients would be eligible for clinical trials of NY-ESO-1-directed therapy. By using NY-ESO-1 specific, CD8-positive T-cells, the in vitro sensitivity of myxoid liposarcoma cell lines to antigen-specific lysis was demonstrated. The current results establish NY-ESO-1 as an important target antigen for the treatment of patients with MRCL. Copyright © 2012 American Cancer Society.

  16. 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.

  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. Desmoplastic round small cell tumor: a case report of a neoplasm of difficult diagnosis; Tumor desmoplasico de pequenas celulas redondas: relato de um caso de uma neoplasia de dificil diagnostico

    Energy Technology Data Exchange (ETDEWEB)

    Ogata, Daniel Cury; Totsugui, Joel Takashi; Ditzel Filho, Leo Fernando da Silva; Ioshii, Sergio Ossamu [Pontificia Universidade Catolica do Parana, Curitiba, PR (Brazil); Machuca, Tiago Noguchi [Universidade Federal do Parana, Curitiba, PR (Brazil); Ogata, Alessandro Cury [Hospital Nossa Senhora das Gracas, Curitiba, PR (Brazil)]. E-mail: daniel_ogata@medcenter.com

    2005-07-01

    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)

  19. 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...

  20. Tumor del estroma gastrointestinal del intestino delgado Gastrointestinal stromal tumor of small intestine

    Directory of Open Access Journals (Sweden)

    Magaly Marión Luna Gozá

    2011-12-01

    the low belly accompanied by vomiting, fatigue and weakness. She was operated on and is diagnosed with a stump acute appendicitis and of occlusive type en elderly without to rule out an adhesion occlusion. Carrying out the laparotomy it was found that this not-coagulating cavity was blood-free and also a stalked hemorrhagic tumor with movements towards the terminal ileum. Authors carried out its exeresis resecting approximately 5 cm of small intestine with a termino-terminal suture later. A significant cleaning of peritoneal cavity was carried out with the habitual closure achieving a satisfactory evolution with her discharge at 7 days. Patient remains asymptomatic at one a half year postoperative and biopsy yielded a 5 cm-small intestine tumor with a low grade of malignancy.

  1. Primitive Neuro Ectodermal Tumor (PNET in infant diagnosed by histopathology and immunohistochemistry techniques

    Directory of Open Access Journals (Sweden)

    G. A. Artha

    2007-06-01

    Full Text Available Primitive Neuro Ectodermal Tumor (PNET is rare and difficult to diagnose. A case of PNET was diagnosed based on histopathological and immunohistochemical findings. A 4-month-old infant was admitted to the hospital with a tumor on the midline of his chest wall since he was 3 days old. The tumor was fixed on the chest wall and had ill-defined margin, enlarged over time and reached more than 10 cm in diameter when he was brought to a clinician. Two small ulcers were seen on the skin overlying the tumor. It was diagnosed as soft tissue tumor suggestive of a hemangioma. The tumor was 17 x 13 x 5.5 cm in size, white colored and firm to the touch. Microscopic examination revealed malignant small round cells with round to ovoid nuclei, coarse chromatin and scanty cytoplasm. Most cells were arranged in a solid pattern with scattered Homer-Wright rosettes. The mitotic count was 7/10 HPF, and necrosis was minimal (less than 25%. On immunohistochemical examination, the cells showed weak to moderate immunoreactivity to Vimentin and CD99, but showed negative to weak positive reactivity to NSE and Chromogranin. Based on the clinical features, gross findings, histopathologic and immunohistochemical examinations, the case was diagnosed as a malignant small round cell tumor consistent with PNET / ES (Ewing’s Sarcoma. To confirm the diagnosis, cytogenetic examination is suggested. (Med J Indones 2007; 16:108-12 Keywords: PNET, histopathology, immunohistochemistry

  2. Obscure Gastrointestinal Bleeding Due to a Small Intestinal Gastrointestinal Stromal Tumor in a Young Adult

    Directory of Open Access Journals (Sweden)

    Mami Yamamoto

    2016-11-01

    Full Text Available The source of most cases of gastrointestinal bleeding is the upper gastrointestinal tract. Since bleeding from the small intestine is very rare and difficult to diagnose, time is required to identify the source. Among small intestine bleeds, vascular abnormalities account for 70–80%, followed by small intestine tumors that account for 5–10%. The reported peak age of the onset of small intestinal tumors is about 50 years. Furthermore, rare small bowel tumors account for only 1–2% of all gastrointestinal tumors. We describe a 29-year-old man who presented with obscure anemia due to gastrointestinal bleeding and underwent laparotomy. Surgical findings revealed a well-circumscribed lesion measuring 45 × 40 mm in the jejunum that initially appeared similar to diverticulosis with an abscess. However, the postoperative pathological diagnosis was a gastrointestinal stromal tumor with extramural growth.

  3. 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

  4. 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.

  5. MR-based volumetric analysis of small tumor volumes: accuracy of phantom examinations of simulated eye tumors

    International Nuclear Information System (INIS)

    Lemke, A.-J.; Kazi, I.; Felix, R.; Hosten, N.; Bechrakis, N.E.; Foerster, M.H.

    2003-01-01

    Purpose: The determination of tumor volume in ocular tumors is very important for the planning and success of radiation therapy. This study uses an animal model to evaluate the accuracy of MR-based volumetry of ocular tumors. Materials and methods: In a total of 25 porcine eyes obtained from the slaughterhouse, ocular tumors were produced by injecting a mixture of hand creme and Gd-DTPA under ophthalmoscopic guidance. The injected volume varied between 0.05 ml and 2.7 ml. The eyes were examined with a 1.5 Tesla scanner and a 4 cm circular surface coil especially developed for ocular MRI. After data transfer to a separate workstation, volumetric analysis was carried out by three independent radiologists using semiautomated software. The determined volume was compared with the injected volume. Results: Of the 25 prepared porcine eyes, 23 were suitable for volumetric analysis. The injection of the mixture of hand creme and GD-DTPA produced two different types of tumors. Ophthalmoscopically, 14 ellipsoid and 9 lobulated to mushroom-shaped tumors were found and confirmed by MRI. Minor deviation was found between injected volume and volume calculated by MRI, with a correlation coefficient of 0.96. Conclusion: Using appropriate technique, MRI is capable of determining small tumor volumes with high accuracy in an animal model. Minor differences can be expected when transferring the results to clinical studies. (orig.) [de

  6. The common mechanisms of transformation by the small DNA tumor viruses: The inactivation of tumor suppressor gene products: p53.

    Science.gov (United States)

    Levine, Arnold J

    2009-02-20

    The small DNA tumor viruses, Polyoma virus, Simian Vacuolating Virus 40, the Papilloma viruses and the human Adenoviruses, were first described during a period of intense virus discovery (1930-1960s) and shown to produce tumors in animals. In each of these cases the viral DNA was shown to persist (commonly integrated into a host chromosome) and only a selected portion of this DNA was expressed as m-RNA and proteins in these cancers. The viral encoded tumor antigens were identified and shown to be required to both establish the tumor and maintain the transformed cell phenotype. The functions of these viral tumor antigens were explored and shown to have common features and mechanisms even though they appear to have evolved from diverse genes. The SV40 large tumor antigen, the human Papilloma virus E7 protein and the Adenovirus E1A protein were shown to bind to and inactivate the functions of the Retinoblastoma proteins in transformed cells. This resulted in the activation of the E2F and DP transcription factors and the entry of cells into the S-phase of DNA synthesis which was required for viral DNA replication. These events triggered the activation of p53 which promotes apoptosis of these virus infected cells limiting virus replication and tumor formation. These viruses responded by evolving and producing the SV40 large tumor antigen, the human Papilloma virus E6 protein and the Adenovirus E1b-55Kd protein which binds to and inactivates the p53 functions in both the infected cells and transformed cells. Some of the human Papilloma viruses and one of the Polyoma viruses have been shown to cause selected cancers in humans. Both the p53 tumor suppressor gene, which was uncovered in the studies with these viruses, and the retinoblastoma protein, have been shown to play a central role in the origins of human cancers via both somatic and germ line mutations in those genes.

  7. 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.

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

    International Nuclear Information System (INIS)

    Collins, Brian T; Levy, Elliot; Chang, Thomas; Jamis-Dow, Carlos; Banovac, Filip; Anderson, Eric D; Erickson, Kelly; Reichner, Cristina A; Collins, Sean P; Gagnon, Gregory J; Dieterich, Sonja; McRae, Don A; Zhang, Ying; Yousefi, Shadi

    2007-01-01

    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. 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. 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. Radical stereotactic radiosurgery with real-time tumor motion tracking is a promising well-tolerated treatment option for small peripheral lung tumors

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

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

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

    Background: Renal cryoablation is a valid treatment option for localized pT1a renal tumors and has been the modality of choice at Aarhus University Hospital since 2005. Anatomical tumor classification systems such as PADUA and RENAL scores were initially introduced as tools to evaluate complication...... August 2005 and December 2013. Patients were followed-up postoperatively with contrast-CT for up to 5 years or until a residual unablated tumor was diagnosed. Results: Mean patient age: 63 years (95%CI 61;65). Mean BMI: 27 kg/m2 (95%CI 26;28). Mean ASA-score: 2.1 (95%CI 2;2.2). Mean ECOC performance...

  11. 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)

  12. [Effect of resection margin and tumor number on survival of patients with small liver cancer].

    Science.gov (United States)

    Rong, Weiqi; Yu, Weibo; Wu, Fan; Wu, Jianxiong; Wang, Liming; Tian, Fei; An, Songlin; Feng, Li; Liu, Faqiang

    2015-12-01

    To explore the significance of resection margin and tumor number on survival of patients with small liver cancer after hepatectomy. We collected 219 cases with small liver cancer undergoing hepatectomy in Cancer Hospital, Chinese Academy of Medical Sciences between December 2003 to July 2013. The survival rates were compared by log-rank test between two resection margin groups (≥ 1 cm vs. number groups (single tumor vs. multiple tumors). We also performed a multifactor analysis by Cox model. The 1-, 3-, 5- and 10- year overall survival rates were 95.9%, 85.3%, 67.8% and 53.3%, respectively, in all patients. The median survival time was 28 months in the group of number on the patients' survival. For small liver cancer, the resection margin of 1 cm might be advised. Increasing resection margin in further could probably not improve therapeutic effect. Standardized operation and combined treatment will decrease the negative influence of multiple tumors on overall survival.

  13. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

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

  14. Obstructive mobile small intestinal tumor without radiographic stigmata of bezoar

    Directory of Open Access Journals (Sweden)

    Elif Onursal

    2017-01-01

    Conclusion: In the absence of clear clinical or radiographic etiology for obstruction, developing a heightened degree of suspicion for native tissue “bezoar” may allow quick and appropriate management of similar cases and limit complications associated with prolonged obstruction. To our knowledge, this is the first reported case of mobile intraluminal leiomyoma causing small bowel obstruction.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Small bud of probable gastrointestinal stromal tumor within a laparoscopically-resected gastric schwannoma.

    Science.gov (United States)

    Cho, Haruhiko; Watanabe, Takafumi; Aoyama, Toru; Hayashi, Tsutomu; Yamada, Takanobu; Ogata, Takashi; Yoshikawa, Takaki; Tsuburaya, Akira; Sekiguchi, Hironobu; Nakamura, Yoshiyasu; Sakuma, Yuji; Kameda, Yoichi; Miyagi, Yohei

    2012-06-01

    Submucosal tumors (SMTs) of the gastrointestinal (GI) tract can be potentially difficulty to diagnose pathologically. We report a case of a gastric SMT that was resected by laparoscopic partial gastrectomy. Although the initial histological and immunohistochemical examinations considered the tumor as a schwannoma, mRNA-based KIT genotyping indicated that the tumor included cells with KIT gene expression, and that a small number of cells carried a deletion mutation in exon 11. Additional histopathological investigations revealed small aggregates of enlarged spindle to epithelioid cells, which were positive for KIT, CD34 and DOG1, and negative for S-100, scattered among the S-100-positive schwannoma cells. We consider that the cells carrying the KIT gene mutation are microscopic buds of a gastrointestinal stroma tumor (GIST), and to the best of our knowledge, this is the first report of probable GIST tissues identified in a schwannoma. Our observations raised the significance of genotyping for diagnosis of GI tract SMTs.

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

    Directory of Open Access Journals (Sweden)

    Annkathrin eHanssen

    2015-09-01

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

  18. 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...

  19. Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread.

    Science.gov (United States)

    Bachmayr-Heyda, Anna; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Deycmar, Simon; Reiner, Agnes T; Polterauer, Stephan; Dekan, Sabine; Pils, Dietmar

    2016-06-28

    High grade serous ovarian cancer (HGSOC) is among the most deadly malignancies in women, frequently involving peritoneal tumor spread. Understanding molecular mechanisms of peritoneal metastasis is essential to develop urgently needed targeted therapies. We described two peritoneal tumor spread types in HGSOC apparent during surgery: miliary (numerous millet-sized implants) and non-miliary (few big, bulky implants). The former one is defined by a more epithelial-like tumor cell characteristic with less immune cell reactivity and with significant worse prognosis, even if corrected for typical clinicopathologic factors.23 HGSOC patients were enrolled in this study. Isolated tumor cells from fresh tumor tissues of ovarian and peritoneal origin and from ascites were used for ribosomal RNA depleted RNA and small RNA sequencing. RT-qPCR was used to validate results and an independent cohort of 32 patients to validate the impact on survival. Large and small RNA sequencing data were integrated and a new gene-miRNA set analysis method was developed.Thousands of new small RNAs (miRNAs and piwi-interacting RNAs) were predicted and a 13 small RNA signature was developed to predict spread type from formalin-fixed paraffin-embedded tissues. Furthermore, integrative analyses of RNA sequencing and small RNA sequencing data revealed a global upregulation of the competing endogenous RNA network in tumor tissues of non-miliary compared to miliary spread, i.e. higher expression of circular RNAs and long non-coding RNAs compared to coding RNAs but unchanged abundance of small RNAs. This global deregulated expression pattern could be co-responsible for the spread characteristic, miliary or non-miliary, in ovarian cancer.

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

    OpenAIRE

    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.

    2015-01-01

    Background 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. Patients and methods Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluoresce...

  1. 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

  2. Small-size betatron for electron therapy of superficial tumors and its clinical testing

    International Nuclear Information System (INIS)

    Musabaeva, L.I.; Lisin, V.A.; Polishchuk, P.F.; Chakhlov, V.L.; Tomskij Politekhnicheskij Inst.

    1987-01-01

    The paper is concerned with the physicotechnical characteristics of a small-size betatron (with the energy of 7 MeV) designed in the Tomsk Polytechnical Institute for therapy of patients with superficial malignant tumors. An electron beam with the energy of 7 MeV was produced on the small-size betatron irradiation fields were formed, and absorbed dose distribution was studied. The efficacy of the use of the beam in 110 patients with superficial malignant tumors was analyzed. The use of electron beam radiation was found promising for therapy of patients with locally spread types of skin and lower lip cancers and breast cancer local recurrences. Complete tumor regression was noted in 75-90% of the patients. Intraoral cone electron therapy combined with 60 Co-therapy of surgery was employed for early cancer of the oral cavity

  3. Cancer Stem Cells, Epithelial to Mesenchymal Markers, and Circulating Tumor Cells in Small Cell Lung Cancer

    NARCIS (Netherlands)

    Pore, M.M.; Meijer, C.; de Bock, G.H.; Boersma-van Ek, W.; Terstappen, Leonardus Wendelinus Mathias Marie; Groen, H.J.M.; Timens, W.; Kruyt, F.A.E.; Hiltermann, T.N.J.

    2016-01-01

    Background Small cell lung cancer (SCLC) has a poor prognosis, and even with localized (limited) disease, the 5-year survival has only been around 20%. Elevated levels of circulating tumor cells (CTCs) have been associated with a worse prognosis, and markers of cancer stem cells (CSCs) and

  4. Circulating tumor cells in small-cell lung cancer : a predictive and prognostic factor

    NARCIS (Netherlands)

    Hiltermann, T J N; Pore, M M; van den Berg, Anke; Timens, W; Boezen, H M; Liesker, J J W; Schouwink, J H; Wijnands, W J A; Kerner, G S M A; Kruyt, F A E; Tissing, H; Tibbe, A G J; Terstappen, L W M M; Groen, H J M

    2012-01-01

    BACKGROUND: Initial response of small-cell lung cancer (SCLC) to chemotherapy is high, and recurrences occur frequently, leading to early death. This study investigated the prognostic value of circulating tumor cells (CTCs) in patients with SCLC and whether changes in CTCs can predict response to

  5. 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.

  6. The Surgical Management of Small Bowel Neuroendocrine Tumors: Consensus Guidelines of the North American Neuroendocrine Tumor Society.

    Science.gov (United States)

    Howe, James R; Cardona, Kenneth; Fraker, Douglas L; Kebebew, Electron; Untch, Brian R; Wang, Yi-Zarn; Law, Calvin H; Liu, Eric H; Kim, Michelle K; Menda, Yusuf; Morse, Brian G; Bergsland, Emily K; Strosberg, Jonathan R; Nakakura, Eric K; Pommier, Rodney F

    2017-07-01

    Small bowel neuroendocrine tumors (SBNETs) have been increasing in frequency over the past decades, and are now the most common type of small bowel tumor. Consequently, general surgeons and surgical oncologists are seeing more patients with SBNETs in their practices than ever before. The management of these patients is often complex, owing to their secretion of hormones, frequent presentation with advanced disease, and difficulties with making the diagnosis of SBNETs. Despite these issues, even patients with advanced disease can have long-term survival. There are a number of scenarios which commonly arise in SBNET patients where it is difficult to determine the optimal management from the published data. To address these challenges for clinicians, a consensus conference was held assembling experts in the field to review and discuss the available literature and patterns of practice pertaining to specific management issues. This paper summarizes the important elements from these studies and the recommendations of the group for these questions regarding the management of SBNET patients.

  7. Small median tumor diameter at cure threshold (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.

  8. [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.

  9. Osteopontin induces growth of metastatic tumors in a preclinical model of non-small lung cancer

    Directory of Open Access Journals (Sweden)

    Shojaei Farbod

    2012-03-01

    Full Text Available Abstract Osteopontin (OPN, also known as SPP1 (secreted phosphoprotein, is an integrin binding glyco-phosphoprotein produced by a variety of tissues. In cancer patients expression of OPN has been associated with poor prognosis in several tumor types including breast, lung, and colorectal cancers. Despite wide expression in tumor cells and stroma, there is limited evidence supporting role of OPN in tumor progression and metastasis. Using phage display technology we identified a high affinity anti-OPN monoclonal antibody (hereafter AOM1. The binding site for AOM1 was identified as SVVYGLRSKS sequence which is immediately adjacent to the RGD motif and also spans the thrombin cleavage site of the human OPN. AOM1 efficiently inhibited OPNa binding to recombinant integrin αvβ3 with an IC50 of 65 nM. Due to its unique binding site, AOM1 is capable of inhibiting OPN cleavage by thrombin which has been shown to produce an OPN fragment that is biologically more active than the full length OPN. Screening of human cell lines identified tumor cells with increased expression of OPN receptors (αvβ3 and CD44v6 such as mesothelioma, hepatocellular carcinoma, breast, and non-small cell lung adenocarcinoma (NSCLC. CD44v6 and αvβ3 were also found to be highly enriched in the monocyte, but not lymphocyte, subset of human peripheral blood mononuclear cells (hPBMCs. In vitro, OPNa induced migration of both tumor and hPBMCs in a transwell migration assay. AOM1 significantly blocked cell migration further validating its specificity for the ligand. OPN was found to be enriched in mouse plasma in a number of pre-clinical tumor model of non-small cell lung cancers. To assess the role of OPN in tumor growth and metastasis and to evaluate a potential therapeutic indication for AOM1, we employed a KrasG12D-LSLp53fl/fl subcutaneously implanted in vivo model of NSCLC which possesses a high capacity to metastasize into the lung. Our data indicated that treatment of tumor

  10. 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.

  11. A rare neuronal tumor of the cerebellum with myoid features ...

    African Journals Online (AJOL)

    We report an extremely rare tumor presenting with myoid features in the left cerebellar hemisphere in a 62-year-old man. This tumor consisted of medium to large round cells with focal lipomatous and myoid differentiation. Immunohistochemically, the tumor cells expressed synaptophysin, GFAP (glial fibrillary acidic protein) ...

  12. A rare neuronal tumor of the cerebellum with myloid features ...

    African Journals Online (AJOL)

    We report an extremely rare tumor presenting with myoid features in the left cerebellar hemisphere in a 62- year-old man. This tumor consisted of medium to large round cells with focal lipomatous and myoid differentiation. Immunohistochemically, the tumor cells expressed synaptophysin, GFAP (glial fibrillary acidic protein) ...

  13. 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

  14. Profiling of metastatic small intestine neuroendocrine tumors reveals characteristic miRNAs detectable in plasma.

    Science.gov (United States)

    Bowden, Michaela; Zhou, Chensheng W; Zhang, Sui; Brais, Lauren; Rossi, Ashley; Naudin, Laurent; Thiagalingam, Arunthi; Sicinska, Ewa; Kulke, Matthew H

    2017-08-15

    Current diagnostic and prognostic blood-based biomarkers for neuroendocrine tumors are limited. MiRNAs have tumor-specific expression patterns, are relatively stable, and can be measured in patient blood specimens. We performed a multi-stage study to identify and validate characteristic circulating miRNAs in patients with metastatic small intestine neuroendocrine tumors, and to assess associations between miRNA levels and survival. Using a 742-miRNA panel, we identified candidate miRNAs similarly expressed in 19 small intestine neuroendocrine tumors and matched plasma samples. We refined our panel in an independent cohort of plasma samples from 40 patients with metastatic small intestine NET and 40 controls, and then validated this panel in a second, large cohort of 120 patients with metastatic small intestine NET and 120 independent controls. miRNA profiling of 19 matched small intestine neuroendocrine tumors and matched plasma samples revealed 31 candidate miRNAs similarly expressed in both tissue and plasma. We evaluated expression of these 31 candidate miRNAs in 40 independent cases and 40 normal controls, and identified 4 miRNAs (miR-21-5p, miR-22-3p, miR-29b-3p, and miR-150-5p) that were differently expressed in cases and controls (p<0.05). We validated these 4 miRNAs in a separate, larger panel of 120 cases and 120 controls. We confirmed that high circulating levels of miR-22-3p (p<0.0001), high levels of miR 21-5p, and low levels of miR-150-5p (p=0.027) were associated with the presence of metastatic small intestine NET. While levels of 29b-3p were lower in cases than in controls in both the initial cohort and the validation cohort, the difference in the validation cohort did not reach statistical significance. We further found that high levels of circulating miR-21-5p, high levels of circulating miR-22-3p and low levels of circulating miR-150-5p were each independently associated with shorter overall survival. A combined analysis using all three markers

  15. Tumoral tissue specific promoter hypermethylation of distinct tumor suppressor genes in a case with non--small cell lung carcinoma: A case report

    Directory of Open Access Journals (Sweden)

    Arslan Sulhattin

    2008-01-01

    Full Text Available Objective: Non-small cell lung carcinoma is an aggressive phenomenon and the epigenetical alterations of some tumor supressor genes have been reported for the different tumor types. Case Presentation: It is presented a case report concerning a 43 years old male with NSCLC on the lower segment of the right lung. The patient underwent a diag-nostic excisional thin-needle biopsy and after the histological confirmation. We examined the promoter methylation status of some distinct tumor supressor genes in tumoral and blood tissues of the case after sodium bisulfite conversion and DNA amplification with methylation specific multiplex PCR technique. Both tissues were also searched for G to A transitions in codons 12 and 13 of the K-ras proto-oncogene. Results: Tumor specimen showed fully methyl pattern profiles for the SFRP2, p16, DAPK1 and partially hyper-methylated profile for the p53 and MGMT genes in this case with non-small lung carci-noma. Blood speicemen showed normal hypomethylated profiles for all studied TS genes. The K-ras proto-oncogene was in normal structure both in blood and tumoral spiecemens that examined. Conclusion: Results indicate that genes exhibit tumor suppressor activi-ties in blood, but exhibit epigenetic inactivation in carcinoma cell. These findings strongly support the hypothesis that epigenetic mechanisms may play an important role in the non-small cell lung carcinogenesis in human.

  16. [Genetic Aberration and Pathological Diagnosis in Bone and Soft-Tissue Tumors].

    Science.gov (United States)

    Iura, Kunio; Oda, Yoshinao

    2016-03-01

    Bone and soft-tissue sarcomas comprise a rare, complex, and heterogeneous group of tumors for which it is difficult for even experienced pathologists to provide a conclusive diagnosis. The number of diagnoses made using genetic analysis has increased since the detection of fusion genes in several soft-tissue tumors in the 1990s. Moreover, other specific genetic aberrations have been reported in various bone and soft-tissue tumors. In addition, molecular therapeutic targets have been sought in advanced cases of soft-tissue and bone tumors similar to other organ malignancies. To enable the pathological diagnosis of bone and soft-tissue tumors, it is necessary to combine histological diagnosis with immunohistochemistry and gene analysis findings including fusion gene or other genetic aberrations. In this review, we describe the fusion genes recently reported in bone and soft-tissue tumors such as solitary fibrous tumor, aneurysmal bone cyst, nodular fasciitis, CIC-DUX4 fusion gene-positive small round cell tumors, or BCOR-CCNB3-positive sarcoma as well as other genetic aberrations in dedifferentiated liposarcoma, malignant rhabdoid tumor, cartilaginous tumor, Langerhans cell histiocytosis chondroblastoma, or giant cell tumor of the bone. We also demonstrate their association with pathological diagnosis.

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

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    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.

  18. Small molecule inhibitor regorafenib inhibits RET signaling in neuroblastoma cells and effectively suppresses tumor growthin vivo.

    Science.gov (United States)

    Chen, Zhenghu; Zhao, Yanling; Yu, Yang; Pang, Jonathan C; Woodfield, Sarah E; Tao, Ling; Guan, Shan; Zhang, Huiyuan; Bieerkehazhi, Shayahati; Shi, Yan; Patel, Roma; Vasudevan, Sanjeev A; Yi, Joanna S; Muscal, Jodi A; Xu, Guo-Tong; Yang, Jianhua

    2017-11-28

    Neuroblastoma (NB), the most common extracranial pediatric solid tumor, continues to cause significant cancer-related morbidity and mortality in children. Dysregulation of oncogenic receptor tyrosine kinases (RTKs) has been shown to contribute to tumorigenesis in various human cancers and targeting these RTKs has had therapeutic benefit. RET is an RTK which is commonly expressed in NB, and high expression of RET correlates with poor outcomes in patients with NB. Herein we report that RET is required for NB cell proliferation and that the small molecule inhibitor regorafenib (BAY 73-4506) blocks glial cell derived neurotrophic factor (GDNF)-induced RET signaling in NB cells and inhibits NB growth both in vitro and in vivo . We found that regorafenib significantly inhibited cell proliferation and colony formation ability of NB cells. Moreover, regorafenib suppressed tumor growth in both an orthotopic xenograft NB mouse model and a TH-MYCN transgenic NB mouse model. Finally, regorafenib markedly improved the overall survival of TH-MYCN transgenic tumor-bearing mice. In summary, our study suggests that RET is a potential therapeutic target in NB, and that using a novel RET inhibitor, like regorafenib, should be investigated as a therapeutic treatment option for children with NB.

  19. 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.

  20. Prognosis in patients with non-small cell lung cancer and satellite tumors.

    Science.gov (United States)

    Kocaturk, C I; Gunluoglu, M Z; Cansever, L; Dincer, I S; Bedirhan, M A

    2011-09-01

    Aim of the study was to identify factors affecting survival in patients with lung cancer and satellite tumors (ST). Between 2001 and 2008, there were 102 patients with synchronous multiple lung cancers among the 1355 lung resections performed in lung cancer patients. Satellite tumors were found to be near the primary lung cancer (PLC) in 29 patients. Complete resection was achieved in all patients, and the 5-year survival rate was 52 %. The independent "T" stages of the PLCs and STs did not affect survival ( P = 0.98 and P = 0.54, respectively). A distance between the PLC and ST longer or shorter than 2, 3, or 4 cm also did not affect survival ( P = 0.78, P = 0.57, and P = 0.62, respectively). The survival of patients treated with adjuvant therapy was significantly higher than that of patients who did not receive adjuvant therapy ( P = 0.0043). Satisfactory survival was achieved after surgical therapy for non-small cell lung cancer associated with ST. While the PLC and ST characteristics and the distance between tumors did not affect survival rates, the introduction of adjuvant chemotherapy with/without radiotherapy positively affected survival. © Georg Thieme Verlag KG Stuttgart · New York.

  1. 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.

  2. The clinical significance of the tumor cell D2-40 immunoreactivity in non-small cell lung cancer.

    Science.gov (United States)

    Kadota, Kyuichi; Huang, Cheng-Long; Liu, Dage; Nakashima, Nariyasu; Yokomise, Hiroyasu; Ueno, Masaki; Haba, Reiji

    2010-10-01

    A monoclonal antibody D2-40 has been widely used for tumor lymphangiogenesis and lymphatic vessel invasion (LVI) in human cancers. However, the clinical significance of the tumor cell D2-40 immunoreactivity has not been clearly understood. We evaluated the tumor cell D2-40 immunoreactivity in non-small cell lung cancer (NSCLC). One hundred and forty-seven NSCLC patients were investigated. Immunohistochemistry using D2-40 was performed to evaluate the tumor cell D2-40 immunoreactivity, micro-lymphatic vessel density (Micro-LVD) and LVI. The intratumoral microvessels density (MVD) was evaluated by the CD34-immunostaining, and tumor proliferation was evaluated by the Ki-67-immunostaining. The percentage of D2-40-positive tumor cells was significantly higher in squamous cell carcinomas than in adenocarcinomas (P<0.0001), and all D2-40-strong tumors were squamous cell carcinomas. The percentage of D2-40-strong tumors was significantly higher in moderately to poorly differentiated tumors than in well-differentiated tumors (P=0.0332). Furthermore, the Ki-67 proliferation index in D2-40-strong tumors was significantly the highest. However, the tumor cell D2-40 immunoreactivity was not associated with Micro-LVD, LVI, or MVD. Regarding the patient survival, the overall survival was significantly lower in patients with D2-40-strong tumors than in patients with D2-40-negative or D2-40-weak tumors (P=0.0005). Multivariate analyses also revealed the tumor cell D2-40 immunoreactivity to be a significant prognostic factor of poor prognosis for NSCLC patients (P=0.0007). The D2-40 immunostaining is useful to identify aggressive squamous cell carcinomas of the lung. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

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

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    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.

  4. Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome.

    Science.gov (United States)

    Kuroda, Naoto; Furuya, Mitsuko; Nagashima, Yoji; Gotohda, Hiroko; Moritani, Suzuko; Kawakami, Fumi; Imamura, Yoshiaki; Bando, Yoshimi; Takahashi, Masayuki; Kanayama, Hiro-omi; Ota, Satoshi; Michal, Michal; Hes, Ondrej; Nakatani, Yukio

    2014-06-01

    In this article, we searched for the common histologic characteristic of renal tumors in patients with Birt-Hogg-Dubé syndrome (BHDS). We selected 6 patients with histologically confirmed renal tumor in BHDS. Germline FLCN gene mutation has been identified in 5 patients. Multifocality and bilaterality of the renal tumors were pathologically or radiologically confirmed in 5 and 2 cases, respectively. Histologic subtypes of the dominant tumor included 3 previously described hybrid oncocytic tumors, one composite chromophobe/papillary/clear cell renal cell carcinoma (RCC) and one unclassified RCC resembling hybrid chromophobe/clear cell RCC. In one case, chromophobe RCC and clear cell RCC were separately observed. Small papillary lesions located in the peripheral area of the tumor, which we designated as intratumoral peripheral small papillary tufts, were identified in all patients. In conclusion, multifocality/bilaterality of renal tumors, discordance of histologic subtypes, and the presence of intratumoral peripheral small papillary tufts may be important clues to identify BHDS-associated renal tumors. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. 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.

  6. 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

  7. 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

  8. Small intestinal gastrointestinal stromal tumor in a young adult woman: a case report and review of the literature.

    Science.gov (United States)

    Manxhuka-Kerliu, Suzana; Sahatciu-Meka, Vjollca; Kerliu, Irma; Juniku-Shkololli, Argjira; Kerliu, Lloreta; Kastrati, Mevlyde; Kotorri, Vesa

    2014-09-28

    Gastrointestinal stromal tumor is the most common sarcoma of the gastrointestinal tract. We report a case of gastrointestinal stromal tumor in a small intestine, initially suspected for leiomyosarcoma given that gastrointestinal stromal tumors in young adult patients are limited due to their rarity. A 30-year-old Caucasian ethnic Albanian woman from Kosovo presented with abdominal pain, nausea and vomiting. Subsequently, the tumor was detected in her small intestine, as an infiltrating mass approximately 10 cm in diameter. The tumor was resected en bloc and duodenojejunal terminal-terminal anastomosis was performed. The tumor was a large, bulky, intramural mass, with fish-flesh to tan-brown appearance, as well as with foci of hemorrhage and necrosis. On histological examination the tumor showed transmural growth, deep infiltrative pattern and malignant feature, with mitotic count >5 per 50 high-power field, dense cellularity with plump spindle cells, and with eosinophilic cytoplasm within variably hyalinized and edematous stroma, skeinoid fibers (extracellular collagen globules) and foci of hemorrhage. In addition, the tumor was composed of areas with epithelioid morphology. The immunohistochemistry results showed high expression of proto-oncogene c-kit, CD117, CD34 and vimentin, whereas α-smooth muscle actin was focally positive. Desmin and S-100 protein were negative. Gastrointestinal stromal tumor should be included in the differential diagnoses of intestinal mesenchymal tumors presenting as a single mass in young female adults. Given that gastrointestinal stromal tumors in young adults represent a more heterogeneous group than gastrointestinal stromal tumor in pediatric cases, more effort should be made to investigate its pathogenesis and potentially more specific treatment.

  9. WE-G-BRD-05: Inline Magnetic Fields Enhance Tumor Dose for Small Lung Cancers

    International Nuclear Information System (INIS)

    Oborn, B; Ge, Y; Hardcastle, N; Metcalfe, P; Keall, P

    2015-01-01

    Purpose: To report on significant dose enhancement effects caused by magnetic fields aligned parallel to 6MV photon beam radiotherapy of small lung tumors. Findings are applicable to future inline MRI-guided radiotherapy systems. Methods: 9 clinical lung plans were recalculated using Monte Carlo methods and external inline (parallel to the beam direction) magnetic fields of 0.5 T, 1.0 T and 3 T were included. Three plans were 6MV 3D-CRT and six were 6MV IMRT. The GTV’s ranged from 0.8 cc to 73 cc, while the PTV ranged from 1 cc to 180 cc. Results: The inline magnetic field has a moderate impact in lung dose distributions by reducing the lateral scatter of secondary electrons and causing a small local dose increase. Superposition of multiple small beams acts to superimpose the small dose increases and can lead to significant dose enhancements, especially when the GTV is low density. Two plans with very small, low mean density GTV’s (<1 cc, ρ(mean)<0.35g/cc) showed uniform increases of 16% and 23% at 1 T throughout the PTV. Three plans with moderate mean density PTV’s (3–13 cc, ρ(mean)=0.58–0.67 g/cc) showed 6% mean dose enhancement at 1 T in the PTV, however not uniform throughout the GTV/PTV. Replanning would benefit these cases. The remaining 5 plans had large dense GTV’s (∼ 1 g/cc) and so only a minimal (<2%) enhancement was seen. In general the mean dose enhancement at 0.5 T was 60% less than 1 T, while 5–50% higher at 3 T. Conclusions: A paradigm shift in the efficacy of small lung tumor radiotherapy is predicted with future inline MRI-linac systems. This will be achieved by carefully taking advantage of the reduction of lateral electronic disequilibrium withing lung tissue that is induced naturally inside strong inline magnetic fields

  10. 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

  11. Porcine small intestine submucosal grafts for post-tumor resection orbital reconstruction.

    Science.gov (United States)

    Phillips, James; Riley, Kristen O; Woodworth, Bradford A

    2014-06-01

    Removal of the medial orbital wall for sinonasal tumor involvement is required to obtain complete oncologic resection. However, orbital fat herniation can produce significant morbidity, including enophthalmos and diplopia. The purpose of the current study was to evaluate outcomes following use of porcine small intestine submucosa (SIS) grafts for orbital reconstruction following extirpation of sinonasal malignancies. Case series in a tertiary hospital setting. Review of prospectively collected data regarding orbital reconstruction using SIS was performed. Demographics, tumor histology, size of orbital defect, adjuvant treatment, clinical status, and complications were recorded. Seventeen patients (average age, 58 years; range, 27-82 years) had SIS grafting of the medial orbital wall over a 5-year period at our tertiary academic institution. The average orbital wall defect size was 4.6 cm(2) (range, 1 cm(2)-24 cm(2)). Tumor histopathology included esthesioneuroblastoma (n = 5), squamous cell carcinoma (n = 4), adenocarcinoma (n = 2), sinonasal undifferentiated carcinoma (n = 2), melanoma (n = 3), and neuroendocrine carcinoma (n = 1). Surgical goals were curative intent in all patients. Ten patients had postoperative radiation therapy, whereas five individuals had surgical extirpation following neoadjuvant chemotherapy and radiation. All patients had complete locoregional control at last clinical follow-up (average, 16 months; range, 2-54 months), although three patients developed distant metastases. The only orbital complications noted were enophthalmos (n = 1), periorbital cellulitis (n = 1), and orbital wall crusting (n = 1). SIS reconstruction of orbital wall defects was effective in the current series of patients, with only one patient developing noticeable enophthalmos and a low incidence of surgical complications. 4. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  12. 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.

  13. Charcoal Suspension Tattoo: A New Technique for Intraoperative Detection of Small Tumors of the Parotid Gland.

    Science.gov (United States)

    Tirelli, Giancarlo; Cova, Maria Assunta; Boscolo-Rizzo, Paolo; Da Mosto, Maria Cristina; Makuc, Elisa; Gardenal, Nicoletta

    2016-07-01

    The current surgical trend in the treatment of pleomorphic adenomas of the parotid gland is to limit the extent of resection. This raises the need to correctly identify the mass within the normal parenchyma so as to avoid dissecting the entire superficial lobe of the gland. We describe ultrasound-guided tattooing as a technique to facilitate identification and excision of parotid pleomorphic adenomas. We reviewed 23 consecutive patients with pleomorphic adenoma of the parotid gland. All patients underwent ultrasound-guided tattooing of the lesions with a charcoal suspension. Baseline tumor and patients' characteristics, major and minor complications, and subjective tolerance to the procedure were recorded. We assessed the number of intralesionally marked masses and the percentage of intraoperatively detected marked lesions. The injection was well tolerated. No major complications were recorded. In 2 cases (9%), a transient increase in lesion size was observed. No other minor complications were encountered. Charcoal was found inside the tumor in 19 cases (83%). In 4 cases (17%), it was found in the tissues above the lesion. Twenty-three lesions were intraoperatively detected (100%) and dissected. Charcoal suspension tattooing is safe and well tolerated for the detection of small pleomorphic adenomas during parotid surgery. © The Author(s) 2016.

  14. Intracranial pressure following complete removal of a small demarcated brain tumor

    DEFF Research Database (Denmark)

    Andresen, Morten; Juhler, Marianne

    2014-01-01

    and therapeutic purposes. This study documents normal ICP in humans. METHODS: In this study the authors included adult patients scheduled for complete removal of a solitary, clearly demarcated, small brain tumor. The mean age of these patients was 67 years old (range 58-85 years old). Exclusion criteria were...... intended to create a study population with as normal brains as possible. A new telemetric ICP monitoring device was implanted at the end of surgery and monitoring was conducted 2 and 4 weeks postoperatively. RESULTS: In the supine position, mean ICP was 0.5 ± 4.0 mm Hg at 4 weeks postoperatively. Postural...... human brain decreases to negative values when assuming the upright position. If these results are later confirmed in a larger series, they might provide reference values for diagnosis and treatment in patients with CSF-related disorders. New normal values also have implications for future shunt design...

  15. Tumor biomarker testing in non-small-cell lung cancer: A decade of change.

    Science.gov (United States)

    VanderLaan, Paul A; Rangachari, Deepa; Majid, Adnan; Parikh, Mihir S; Gangadharan, Sidharta P; Kent, Michael S; McDonald, Danielle C; Huberman, Mark S; Kobayashi, Susumu S; Costa, Daniel B

    2018-02-01

    Although a growing list of essential genomic/immune-based biomarkers are linked to approved non-small-cell lung cancer (NSCLC) therapies worldwide, few reports have detailed the evolution of NSCLC predictive biomarker assessment in routine clinical practice. We retrospectively reviewed the first one thousand plus NSCLC patient specimens from our institution analyzed for predictive biomarkers from 2004 to 2017 and evaluated patterns of testing as well as correlation with clinical-pathologic characteristics. The majority of 1009 NSCLC patients had advanced stages of adenocarcinoma with most tissues obtained from the lung, mediastinal/hilar nodes, or pleura. The majority of testing was performed on cytology or small biopsy specimens. All were tested for EGFR mutations, 895 for ALK rearrangement, 841 for KRAS mutation, 537 for ROS1 rearrangement, and 179 using comprehensive genomic profiling. Implementation of near-universal genomic biomarker testing at our institution for EGFR, ALK, ROS1 and PD-L1 all occurred within the first year following evidence of clinical activity or regulatory body approval of an associated inhibitor. The overall testing failure rate after use of the best specimen for the most common tests was ≤5.5%. A quarter of tumors had a driver oncogene identified (EGFR/ALK/ROS1/BRAF V600E) with an approved oral targeted therapy, with the highest prevalence in those patients with no or light (≤15 pack-years) history of tobacco use. Tumor biomarker testing using clinical NSCLC specimens in routine oncologic care evolves rapidly following approval of targeted therapies linked to diagnostic assays. Our practice's decade plus experience highlights the rapid evolution of biomarker testing and confirms the therapeutic relevance of such testing in all patients-particularly those patients with light/no history of tobacco use. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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)

  1. 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.

  2. 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

  3. The cell-cell interaction between tumor-associated macrophages and small cell lung cancer cells is involved in tumor progression via STAT3 activation.

    Science.gov (United States)

    Iriki, Toyohisa; Ohnishi, Koji; Fujiwara, Yukio; Horlad, Hasita; Saito, Yoichi; Pan, Cheng; Ikeda, Koei; Mori, Takeshi; Suzuki, Makoto; Ichiyasu, Hidenori; Kohrogi, Hirotsugu; Takeya, Motohiro; Komohara, Yoshihiro

    2017-04-01

    Small cell lung cancer (SCLC) is an aggressive tumor with a poor prognosis. It is well known that various stromal cells, including macrophages, play a role in tumor progression in several types of malignant tumors; however, the significance of tumor-associated macrophages (TAMs) in SCLC has not been fully elucidated. Signal transducer and activator of transcription 3 (STAT3) is a molecule well-known to be related to tumor progression. In the present study, we investigated the relationship of TAMs and SCLC cells to test the hypothesis that TAMs induce tumor progression in SCLC via STAT3 activation. We performed immunohistochemical analysis using surgically resected tumor specimens and in vitro co-culture experiments using human SCLC cell lines and human monocyte-derived macrophages. We first demonstrated via immunostaining that STAT3 activation in tumor cells was predominantly observed in the peripheral areas of tumor nests existing near TAMs in stroma. The indirect co-culture of SCLC cells and macrophages induced STAT3 activation in both cell types, and macrophage-derived culture supernatant (CS) significantly activated STAT3 in SCLC cells. Macrophage-derived CS induced tumor cell proliferation and invasion via STAT3 activation. In addition, chemo-resistance and sphere formation were also increased by macrophage-derived CS. Macrophage-derived interleukin-6 and CC chemokine ligand 4 (CCL4/MIP-1β) were suggested to be associated with STAT3 activation in SCLC cells. CS-induced STAT3 activation in SCLC cells was suppressed by anti-IL-6 receptor antibody, but not by anti-CCL4/MIP-1β antibody. These results suggest that TAMs are likely involved in SCLC progression via STAT3 activation and TAM-derived IL-6 is indicated to be one of molecules related to STAT3 activation in SCLC cells. Thus, the cell-cell interaction between TAMs and SCLC cells might be a target for therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Prognostic Effect of Tumor Lymphocytic Infiltration in Resectable Non–Small-Cell Lung Cancer

    Science.gov (United States)

    Le Teuff, Gwénaël; Marguet, Sophie; Lantuejoul, Sylvie; Dunant, Ariane; Graziano, Stephen; Pirker, Robert; Douillard, Jean-Yves; Le Chevalier, Thierry; Filipits, Martin; Rosell, Rafael; Kratzke, Robert; Popper, Helmut; Soria, Jean-Charles; Shepherd, Frances A.; Seymour, Lesley; Tsao, Ming Sound

    2016-01-01

    Purpose Tumor lymphocytic infiltration (TLI) has differing prognostic value among various cancers. The objective of this study was to assess the effect of TLI in lung cancer. Patients and Methods A discovery set (one trial, n = 824) and a validation set (three trials, n = 984) that evaluated the benefit of platinum-based adjuvant chemotherapy in non–small-cell lung cancer were used as part of the LACE-Bio (Lung Adjuvant Cisplatin Evaluation Biomarker) study. TLI was defined as intense versus nonintense. The main end point was overall survival (OS); secondary end points were disease-free survival (DFS) and specific DFS (SDFS). Hazard ratios (HRs) and 95% CIs associated with TLI were estimated through a multivariable Cox model in both sets. TLI-histology and TLI-treatment interactions were explored in the combined set. Results Discovery and validation sets with complete data included 783 (409 deaths) and 763 (344 deaths) patients, respectively. Median follow-up was 4.8 and 6 years, respectively. TLI was intense in 11% of patients in the discovery set compared with 6% in the validation set (P < .001). The prognostic value of TLI in the discovery set (OS: HR, 0.56; 95% CI, 0.38 to 0.81; P = .002; DFS: HR, 0.59; 95% CI, 0.42 to 0.83; P = .002; SDFS: HR, 0.56; 95% CI, 0.38 to 0.82; P = .003) was confirmed in the validation set (OS: HR, 0.45; 95% CI, 0.23 to 0.85; P = .01; DFS: HR, 0.44; 95% CI, 0.24 to 0.78; P = .005; SDFS: HR, 0.42; 95% CI, 0.22 to 0.80; P = .008) with no heterogeneity across trials (P ≥ .38 for all end points). No significant predictive effect was observed for TLI (P ≥ .78 for all end points). Conclusion Intense lymphocytic infiltration, found in a minority of tumors, was validated as a favorable prognostic marker for survival in resected non–small-cell lung cancer. PMID:26834066

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. Surgical treatment and prognostic analysis for gastrointestinal stromal tumors (GISTs of the small intestine: before the era of imatinib mesylate

    Directory of Open Access Journals (Sweden)

    Jan Yi-Yin

    2006-10-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GISTs, the most common type of mesenchymal tumors of the gastrointestinal (GI tract, demonstrate positive kit staining. We report our surgical experience with 100 small intestine GIST patients and identify predictors for long-term disease-free survival (DFS and overall survival (OS to clarify the difference between high- and low-risk patients. Methods The clinicopathologic and follow-up records of 100 small intestine GIST patients who were treated at Chung Gung Memorial Hospital between 1983 and 2002 were retrospectively reviewed. Clinical and pathological factors were assessed for long-term DFS and OS by using a univariate log-rank test and a multivariate Cox proportional hazard model. Results The patients included 52 men and 48 women. Their ages ranged from 27 to 82 years. Among the 85 patients who underwent curative resection, 44 (51.8% developed disease recurrence (liver metastasis was the most common form of recurrence. The follow-up period ranged from 5 to 202 months (median: 33.2 months. The 1-, 3-, and 5-year DFS and OS rates were 85.2%, 53.8%, and 43.7%, and 91.5%, 66.6%, and 50.5%, respectively. Using multivariate analysis, it was found that high tumor cellularity, mitotic count >5/50 high-power field, and a Ki-67 index ≧10% were three independent factors that were inversely associated with DFS. However, absence of tumor perforation, mitotic count Conclusion Tumors with low cellularity, low mitotic count, and low Ki-67 index, which indicate low risk, predict a more favorable DFS for small intestine GIST patients undergoing curative resection. Absence of tumor perforation with low mitotic count and low cellularity, which indicates low risk, can predict long-term OS for small intestine GIST patients who have undergone curative resection.

  10. Tumor Immunology and Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Jung, Chi Young; Antonia, Scott J

    2018-01-01

    Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths worldwide. Although progress in the treatment of advanced non-small cell lung cancer (NSCLC) has been made over the past decade, the 5-year survival rate in patients with lung cancer remains only 10%-20%. Obviously, new therapeutic options are required for patients with advanced NSCLC and unmet medical needs. Cancer immunotherapy is an evolving treatment modality that uses a patient's own immune systems to fight cancer. Theoretically, cancer immunotherapy can result in long-term cancer remission and may not cause the same side effects as chemotherapy and radiation. Immuno-oncology has become an important focus of basic research as well as clinical trials for the treatment of NSCLC. Immune checkpoint inhibitors are the most promising approach for cancer immunotherapy and they have become the standard of care for patients with advanced NSCLC. This review summarizes basic tumor immunology and the relevant clinical data on immunotherapeutic approaches, especially immune checkpoint inhibitors in NSCLC. Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.

  11. FEN1 promotes tumor progression and confers cisplatin resistance in non-small-cell lung cancer.

    Science.gov (United States)

    He, Lingfeng; Luo, Libo; Zhu, Hong; Yang, Huan; Zhang, Yilan; Wu, Huan; Sun, Hongfang; Jiang, Feng; Kathera, Chandra S; Liu, Lingjie; Zhuang, Ziheng; Chen, Haoyan; Pan, Feiyan; Hu, Zhigang; Zhang, Jing; Guo, Zhigang

    2017-06-01

    Lung cancer is one of the leading causes of cancer mortality worldwide. The therapeutic effect of chemotherapy is limited due to the resistance of cancer cells, which remains a challenge in cancer therapeutics. In this work, we found that flap endonuclease 1 (FEN1) is overexpressed in lung cancer cells. FEN1 is a major component of the base excision repair pathway for DNA repair systems and plays important roles in maintaining genomic stability through DNA replication and repair. We showed that FEN1 is critical for the rapid proliferation of lung cancer cells. Suppression of FEN1 resulted in decreased DNA replication and accumulation of DNA damage, which subsequently induced apoptosis. Manipulating the amount of FEN1 altered the response of lung cancer cells to chemotherapeutic drugs. A small-molecule inhibitor (C20) was used to target FEN1 and this enhanced the therapeutic effect of cisplatin. The FEN1 inhibitor significantly suppressed cell proliferation and induced DNA damage in lung cancer cells. In mouse models, the FEN1 inhibitor sensitized lung cancer cells to a DNA damage-inducing agent and efficiently suppressed cancer progression in combination with cisplatin treatment. Our study suggests that targeting FEN1 may be a novel and efficient strategy for a tumor-targeting therapy for lung cancer. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  12. SALL4 expression in germ cell and non-germ cell tumors: a systematic immunohistochemical study of 3215 cases.

    Science.gov (United States)

    Miettinen, Markku; Wang, Zengfeng; McCue, Peter A; Sarlomo-Rikala, Maarit; Rys, Janusz; Biernat, Wojciech; Lasota, Jerzy; Lee, Yi-Shan

    2014-03-01

    The SALL4 transcription factor is associated with embryonic cell pluripotency and has been shown as a useful immunohistochemical marker for germ cell tumors. However, information of SALL4 distribution in normal human tissues and non-germ cell tumors is limited. In this study we examined normal human tissues and 3215 tumors for SALL4 expression using a monoclonal antibody 6E3 and automated immunohistochemistry. In a 10-week embryo, SALL4 was expressed in ovocytes, intestine, kidney, and some hepatocytes. In adult tissues, it was only detected in germ cells. SALL4 was consistently expressed in all germ cell tumors except some trophoblastic tumors and mature components of teratomas, in which it was selectively expressed in intestinal-like and some squamous epithelia. In non-germ cell carcinomas, SALL4 was detected in 20% of cases or more of serous carcinoma of the ovary, urothelial high-grade carcinoma, and gastric adenocarcinoma (especially the intestinal type). SALL4 was only rarely (≤ 5%) expressed in mammary, colorectal, prostatic, and squamous cell carcinomas. Many SALL4-positive carcinomas showed poorly differentiated patterns, and some showed positivity in most tumor cells mimicking the expression in germ cell tumors. SALL4 was commonly expressed in rhabdoid tumors of the kidney and extrarenal sites and in the Wilms tumor. Expression of SALL4 was rare in other mesenchymal and neuroendocrine tumors but was occasionally detected in melanoma, desmoplastic small round cell tumor, epithelioid sarcoma, and rhabdomyosarcoma. All hematopoietic tumors were negative. SALL4 is an excellent marker of nonteratomatous germ cell tumors, but it is also expressed in other tumors, sometimes extensively. Such expression may reflect stem cell-like differentiation and must be considered when using SALL4 as a marker for germ cell tumors. Observed lack of other pluripotency factors, OCT4 and NANOG, in SALL4-positive non-germ cell tumors can also be diagnostically helpful.

  13. SALL4 EXPRESSION IN GERM CELL AND NON GERM-CELL TUMORS – A SYSTEMATIC IMMUNOHISTOCHEMICAL STUDY OF 3215 CASES

    Science.gov (United States)

    Miettinen, Markku; Wang, Zengfeng; Mc. Cue, Peter A.; Sarlomo-Rikala, Maarit; Rys, Janusz; Biernat, Wojciech; Lasota, Jerzy; Lee, Yi-Shan

    2014-01-01

    SALL4 transcription factor is associated with embryonic cell pluripotency and has been shown as a useful immunohistochemical marker for germ cell tumors. However, information of SALL4 distribution in normal human tissues and non germ-cell tumors is limited. In this study we examined normal human tissues and 3215 tumors for SALL4 expression using a monoclonal antibody 6E3 and automated immunohistochemistry. In a 10th week embryo, SALL4 was expressed in ovocytes, intestine, kidney, and some hepatocytes. In adult tissues, it was only detected in germ cells. SALL4 was consistently expressed in all germ cell tumors except some trophoblastic tumors and mature components of teratomas, where it was selectively expressed in intestinal-like and some squamous epithelia. In non germ-cell carcinomas, SALL4 was detected in 20% of cases or more of serous carcinoma of ovary, urothelial high-grade carcinoma, and gastric adenocarcinoma (especially the intestinal type). SALL4 was only rarely (≤5%) expressed in mammary, colorectal, prostatic, and squamous cell carcinomas. Many SALL4 positive carcinomas showed poorly differentiated patterns and some showed positivity in most tumor cells mimicking the expression in germ cell tumors. SALL4 was commonly expressed in rhabdoid tumors of kidney and extrarenal sites, and in Wilms tumor. Expression of SALL4 was rare in other mesenchymal and neuroendocrine tumors but was occasionally detected in melanoma, desmoplastic small round cell tumor, epithelioid sarcoma, and rhabdomyosarcoma. All hematopoietic tumors were negative. SALL4 is an excellent marker of non-teratomatous germ cell tumors, but it is also expressed in other tumors, sometimes extensively. Such expression may reflect stem-cell like differentiation and must be considered when using SALL4 as a marker for germ cell tumors. Observed lack of other pluripotency factors, OCT4 and NANOG, in SALL4-positive non-germ cell tumors can also be diagnostically helpful. PMID:24525512

  14. 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.

  15. Diagnosis and treatment of small intestinal stromal tumor: an analysis of 45 cases

    Directory of Open Access Journals (Sweden)

    Yan ZENG

    2014-08-01

    Full Text Available Objective To study the clinical features, diagnosis and treatment of small intestinal stromal tumor (SIST. Methods Clinical data of 45 SIST patients admitted to our hospital from July 2007 to December 2013 were analyzed retrospectively. The diagnosis was confirmed pathologically in all the patients. Results The clinical manifestations of SIST were non-specific, and the most common manifestations were as follows: gastrointestinal bleeding in 29 patients (64.4 %, abdominal pain in 15 (33.3% and abdominal mass in 4 (8.9%. The most common predilection sites of SIST were jejunum (n=21, 46.7%, duodenum (n=13, 28.9% and ileum (n=9, 20.0%. The tumor was located at the jejunoileal junction in 2 patients (4.4%. The diagnostic rate of SIST by spiral CT was 73.7% (28/38, and it was the most accurate among all the examinations. Surgical operation was the most effective therapeutic method for SIST. All the 45 patients received surgical treatment, and according to Fletcher's criteria, there were 6 patients (13.3% at very low-risk, 16 (35.6% at low-risk, 8 (17.8% at moderate-risk and 15 (33.3% at highrisk of SIST. The postoperative immunohistochemistry showed that the positive rate of CD117 was 100%, while the positive rate of CD34 was 67.0% (30/45. Imatinib mesylate was helpful for patients who had palliative operation and for preventing postoperative recurrence. Reoperation could prolong the survival of patients who had a local recurrence or distant metastasis. Conclusions  Clinical manifestations of SIST are non-specific, and its early diagnosis is difficult. However, spiral CT has a high diagnostic value for SIST. The surgical operation is the main method for treatment of SIST, and long-time oral imatinib mesylate medication after surgery can attain a better result for a long duration. DOI: 10.11855/j.issn.0577-7402.2014.07.11

  16. 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)

  17. Identification of I1171N resistance mutation in ALK-positive non-small-cell lung cancer tumor sample and circulating tumor DNA.

    Science.gov (United States)

    Johnson, Alison C; Dô, Pascal; Richard, Nicolas; Dubos, Catherine; Michels, Jean Jacques; Bonneau, Jessica; Gervais, Radj

    2016-09-01

    Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) is sensitive to ALK inhibitor therapy, but resistance invariably develops and can be mediated by certain secondary mutations. The detection of these mutations is useful to guide treatment decisions, but tumors are not always easily accessible to re-biopsy. We report the case of a patient with ALK-rearranged NSCLC who presented acquired resistance to crizotinib and then alectinib. Sequencing analyses of DNA from a liver metastasis biopsy sample and circulating tumor DNA both found the same I1171N ALK kinase domain mutation, known to confer resistance to certain ALK inhibitors. However, the patient then received ceritinib, a 2nd generation ALK inhibitor, and achieved another partial response. This case underlines how ALK resistance mutation detection in peripheral blood could be a reliable, safer, and less invasive alternative to tissue-based samples in NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. 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

    ) 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...... 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...

  19. The influence of the pituitary tumor transforming gene-1 (PTTG-1 on survival of patients with small cell lung cancer and non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Geddert Helene

    2006-01-01

    Full Text Available Abstract Background PTTG-1 (pituitary tumor transforming gene is a novel oncogene that is overexpressed in tumors, such as pituitary adenoma, breast and gastrointestinal cancers as well as in leukemia. In this study, we examined the role of PTTG-1 expression in lung cancer with regard to histological subtype, the correlation of PTTG-1 to clinical parameters and relation on patients' survival. Methods Expression of PTTG-1 was examined immunohistochemically on formalin-fixed, paraffin-embedded tissue sections of 136 patients with small cell lung cancer (SCLC and 91 patients with non-small cell lung cancer (NSCLC, retrospectively. The intensity of PTTG-1 expression as well as the proportion of PTTG-1 positive cells within a tumor was used for univariate and multivariate analysis. Results PTTG-1 expression was observed in 64% of SCLC tumors and in 97.8% of NSCLC tumors. In patients with SCLC, negative or low PTTG-1 expression was associated with a shorter mean survival time compared with patients with strong PTTG-1 expression (265 ± 18 days vs. 379 ± 66 days; p = 0.0291. Using the Cox regression model for multivariate analysis, PTTG-1 expression was a significant predictor for survival next to performance status, tumor stage, LDH and hemoglobin. In contrast, in patients with NSCLC an inverse correlation between survival and PTTG-1 expression was seen. Strong PTTG-1 expression was associated with a shorter mean survival of 306 ± 58 days compared with 463 ± 55 days for those patients with no or low PTTG-1 intensities (p = 0.0386. Further, PTTG-1 expression was associated with a more aggressive NSCLC phenotype with an advanced pathological stage, extensive lymph node metastases, distant metastases and increased LDH level. Multivariate analysis using Cox regression confirmed the prognostic relevance of PTTG-1 expression next to performance status and tumor stage in patients with NSCLC. Conclusion Lung cancers belong to the group of tumors expressing

  20. The influence of the pituitary tumor transforming gene-1 (PTTG-1) on survival of patients with small cell lung cancer and non-small cell lung cancer.

    Science.gov (United States)

    Rehfeld, Nina; Geddert, Helene; Atamna, Abedelsalam; Rohrbeck, Astrid; Garcia, Guillermo; Kliszewski, Slawek; Neukirchen, Judith; Bruns, Ingmar; Steidl, Ulrich; Fenk, Roland; Gabbert, Helmut E; Kronenwett, Ralf; Haas, Rainer; Rohr, Ulrich-Peter

    2006-01-20

    PTTG-1 (pituitary tumor transforming gene) is a novel oncogene that is overexpressed in tumors, such as pituitary adenoma, breast and gastrointestinal cancers as well as in leukemia. In this study, we examined the role of PTTG-1 expression in lung cancer with regard to histological subtype, the correlation of PTTG-1 to clinical parameters and relation on patients' survival. Expression of PTTG-1 was examined immunohistochemically on formalin-fixed, paraffin-embedded tissue sections of 136 patients with small cell lung cancer (SCLC) and 91 patients with non-small cell lung cancer (NSCLC), retrospectively. The intensity of PTTG-1 expression as well as the proportion of PTTG-1 positive cells within a tumor was used for univariate and multivariate analysis. PTTG-1 expression was observed in 64% of SCLC tumors and in 97.8% of NSCLC tumors. In patients with SCLC, negative or low PTTG-1 expression was associated with a shorter mean survival time compared with patients with strong PTTG-1 expression (265 +/- 18 days vs. 379 +/- 66 days; p = 0.0291). Using the Cox regression model for multivariate analysis, PTTG-1 expression was a significant predictor for survival next to performance status, tumor stage, LDH and hemoglobin. In contrast, in patients with NSCLC an inverse correlation between survival and PTTG-1 expression was seen. Strong PTTG-1 expression was associated with a shorter mean survival of 306 +/- 58 days compared with 463 +/- 55 days for those patients with no or low PTTG-1 intensities (p = 0.0386). Further, PTTG-1 expression was associated with a more aggressive NSCLC phenotype with an advanced pathological stage, extensive lymph node metastases, distant metastases and increased LDH level. Multivariate analysis using Cox regression confirmed the prognostic relevance of PTTG-1 expression next to performance status and tumor stage in patients with NSCLC. Lung cancers belong to the group of tumors expressing PTTG-1. Dependent on the histological subtype of lung

  1. 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.

  2. Small activating RNA restores the activity of the tumor suppressor HIC-1 on breast cancer.

    Directory of Open Access Journals (Sweden)

    Feng Zhao

    Full Text Available HIC-1 is a gene that is hypermethylated in cancer, and commonly downregulated in human breast cancer. However, the precise mechanisms and molecular pathways regulated by HIC-1 remain unclear. We assessed HIC-1 expression on a tissue microarray containing 80 cases of breast cancer. We also analyzed its biological function by restoring HIC-1 expression using 5-aza-2' deoxycytidine (5-CdR and small-activating RNAs for the reversal of HIC-1 tumor suppressive effects on MCF-7 and MDA-MB-231 cell lines. An Agilent Q44h global expressing microarray was probed after restoring the expression of HIC-1. Data demonstrated that HIC-1 expression was reduced significantly in breast cancer tissues. HIC-1 immunohistochemistry resulted in mean staining scores in cancer tissue and normal ductal epithelia of 3.54 and 8.2, respectively (p<0.01. 5-CdR partially reversed HIC-1 expression, and modulated cell growth and apoptosis. dsHIC1-2998, an saRNA, showed activating efficacy in breast cancer cells. A group of differentially expressed genes were characterized by cDNA microarray. Upon saRNA treatment, genes upregulated included those involved in immune activation, cell cycle interference, the induction of apoptosis, anti-metastasis, and cell differentiation. Downregulated genes included oncogenes and those that play roles in cell invasion, cell growth, and cell division. Our findings may provide valuable resources not only for gene functional studies, but also for potential clinical applications to develop novel drug targets.

  3. Intraabdominal desmoplastic small cell tumor: radiological aspects - a case report; Tumor de pequenas celulas desmoplasico intra-abdominal - relato de um caso

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Leonardo Velloso; Siciliano, Antonio Alexandre O.; D' Annunciacao, Gisele Esteves; Nunes, Vania Cristina S.R. [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil). Dept. de Radiologia; Marchiori, Edson [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia

    1999-06-01

    The authors describe a case of a 21-year-old white female admitted with abdominal pain and distension, as well as bowel movement alteration. A hard, lobulated and painful abdominal mass was found at physical exam and signs of ascitis were also presented. Abdominal and pelvic ultrasound and computed tomography demonstrated and heterogeneous mass, adhering to the anterior abdominal wall, extending from the umbilicus to the pelvis and displacing the urinary bladder inferiorly and bowel loops posteriorly. Cul-the-sac implants were also noted. The major omentum was diffusely infiltrated by nodules as laparotomy. A desmoplastic small cell tumor was found after histopathological analysis of the surgical specimen. (author)

  4. 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.

  5. 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

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

    Science.gov (United States)

    Alifano, Marco; Mansuet-Lupo, Audrey; Lococo, Filippo; Roche, Nicolas; Bobbio, Antonio; Canny, Emelyne; Schussler, Olivier; Dermine, Hervé; Régnard, Jean-François; Burroni, Barbara; Goc, Jérémy; Biton, Jérôme; Ouakrim, Hanane; Cremer, Isabelle; Dieu-Nosjean, Marie-Caroline; Damotte, Diane

    2014-01-01

    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). 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 pnutrition and tumoral immune microenvironment allowed robust prognostic discrimination; indeed patients with undetectable CRP, high (>285 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. Our data show that nutrition, systemic inflammation and tumoral immune contexture are prognostic determinants that, taken together, may predict outcome.

  7. 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.

  8. 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.

  9. 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

  10. 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.)

  11. 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.

  12. 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.

  13. 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.

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

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    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.

  15. 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

  16. 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.

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

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    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.

  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 eIF2a as well as mTOR pathway inhibition supports the above notion. In addition...

  19. 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...

  20. 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

    , these novel anti-cancer compounds inhibit DNA and protein synthesis and induce apoptosis in a broad spectrum of cancer cell lines. In vivo, the compounds induce tumor stasis and regression in mouse xenograft models of human breast, prostate, ovarian and pancreatic cancer, both when administered intravenously...

  1. Adrenal Incidentalomas: Should We Operate on Small Tumors in the Era of Laparoscopy?

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    Michał Pędziwiatr

    2014-01-01

    Full Text Available Tumor size smaller than 4 cm as an indication for surgical treatment of incidentaloma is still a subject of discussion. Our aim was the estimation of the incidence of malignancy and analysis of treatment outcomes in patients with incidentaloma smaller than 4 cm in comparison to bigger lesions. 132 patients who underwent laparoscopic adrenalectomy for nonsecreting tumors were divided into two groups: group 1 (55 pts., size  40 mm. Operation parameters and histopathological results were analyzed. No differences in group characteristics, mean operation time, and estimated blood loss were noted. Complications in groups 1 and 2 occurred in 3.6% and 5.2% of patients, respectively (P=0.67. Malignancy in groups 1 and 2 was present in 1 and 6 patients, respectively (P=0.13. Potentially malignant lesions were identified in 4 patients in group 1 and 4 patients in group 2 (P=0.39. The results do not allow for straightforward recommendations for surgical treatment of smaller adrenal tumors. The safety of laparoscopy and minimal, but impossible to omit, risk of malignancy support decisions for surgery. On the other hand, the risk of malignancy in smaller adrenal tumors is lower than surgical complications, which provides an important argument against surgery.

  2. [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.

  3. 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)

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

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    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.

  5. 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

    PURPOSE: Large interindividual variations in volume regression of non-small cell lung cancer (NSCLC) are observable on standard cone beam computed tomography (CBCT) during fractionated radiation therapy. Here, a method for automated assessment of tumor volume regression is presented and its...... therapy provides biological information on the specific tumor. This could potentially form the basis for personalized response adaptive therapy....

  6. 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.)

  7. Metastatic Small Bowel Tumor from Descending Colon Cancer with Extensive Hematogenous or Lymphogenous Spread: Survey of the Japanese Literature

    Directory of Open Access Journals (Sweden)

    Yutaka Kojima

    2010-09-01

    Full Text Available We present the case of a 68-year-old female patient who was diagnosed with cancer of the descending colon in July 1994 and underwent partial resection of the colon (type 2, moderately to well differentiated adenocarcinoma, se, ly1, v1, n(–. In April 1996, she was admitted to a nearby hospital for symptoms of ileus, which improved at the hospital. However, she was referred to our hospital for melena. In blood test, Hb was 8.7 g/dl, showing anemia, and carcinoembryonic antigen level was elevated to 50.7 ng/ml. Abdominal CT and small bowel series showed only mild expansion of the small bowel, suggesting no obvious occlusion. Abdominal surgery was performed in May 1995 for repeated development of ileus symptoms and suspicion of bleeding from the small bowel. Since the findings of the abdominal surgery showed a circular tumor in the lower ileum, partial resection of the small bowel was performed. Histopathological examination showed type 3, moderately to well differentiated adnocarcinoma, se, ly2, v0, n = 1/13. The principal tumor was located within the subserosa and grew up exclusively through the muscularis propria and the submucosa, into the mucous layer. The mucosa remained slightly on the surface layer. Based on these findings, the patient was diagnosed with metastasis of descending colon cancer to the small bowel. Her prognosis was good, and neither metastasis nor redevelopment of the cancer have been confirmed to date, 11 years and 7 months since the surgery.

  8. Radical cyberknife radiosurgery with tumor tracking: an effective treatment for inoperable small peripheral stage I non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Esposito Giuseppe

    2009-01-01

    Full Text Available Abstract Objective Curative surgery is not an option for many patients with clinical stage I non-small-cell lung carcinoma (NSCLC, but radical radiosurgery may be effective. Methods Inoperable patients with small peripheral clinical stage I NSCLC were enrolled in this study. Three-to-five fiducial markers were implanted in or near tumors under CT guidance. Gross tumor volumes (GTVs were contoured using lung windows. The GTV margin was expanded by 5 mm to establish the planning treatment volume (PTV. A dose of 42–60 Gy was delivered to the PTV in 3 equal fractions in less than 2 weeks using the CyberKnife radiosurgery system. The 30-Gy isodose contour extended at least 1 cm from the GTV. Physical examination, CT imaging and pulmonary function testing were completed at 6 months intervals for three years following treatment. Results Twenty patients with an average maximum tumor diameter of 2.2 cm (range, 1.1 – 3.5 cm and a mean FEV1 of 1.08 liters (range, 0.53 – 1.71 L were treated. Pneumothorax requiring tube thoracostomy occurred following CT-guided fiducial placement in 25% of the patients. All patients completed treatment with few acute side effects and no procedure-related mortality. Transient chest wall discomfort developed in 8 of the 12 patients with lesions within 5 mm of the pleura. The mean percentage of the total lung volume receiving a minimum of 15 Gy was 7.3% (range, 2.4% to 11.3%. One patient who received concurrent gefitinib developed short-lived, grade III radiation pneumonitis. The mean percent predicted DLCO decreased by 9% and 11% at 6 and 12 months, respectively. There were no local failures, regional lymph node recurrences or distant metastases. With a median follow-up of 25 months for the surviving patients, Kaplan-Meier overall survival estimate at 2 years was 87%, with deaths due to COPD progression. Conclusion Radical CyberKnife radiosurgery is a well-tolerated treatment option for inoperable patients with small

  9. [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.

  10. 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

  11. Optimized time-resolved imaging of contrast kinetics (TRICKS) in dynamic contrast-enhanced MRI after peptide receptor radionuclide therapy in small animal tumor models.

    Science.gov (United States)

    Haeck, Joost; Bol, Karin; Bison, Sander; van Tiel, Sandra; Koelewijn, Stuart; de Jong, Marion; Veenland, Jifke; Bernsen, Monique

    2015-01-01

    Anti-tumor efficacy of targeted peptide-receptor radionuclide therapy (PRRT) relies on several factors, including functional tumor vasculature. Little is known about the effect of PRRT on tumor vasculature. With dynamic contrast-enhanced (DCE-) MRI, functional vasculature is imaged and quantified using contrast agents. In small animals DCE-MRI is a challenging application. We optimized a clinical sequence for fast hemodynamic acquisitions, time-resolved imaging of contrast kinetics (TRICKS), to obtain DCE-MRI images at both high spatial and high temporal resolution in mice and rats. Using TRICKS, functional vasculature was measured prior to PRRT and longitudinally to investigate the effect of treatment on tumor vascular characteristics. Nude mice bearing H69 tumor xenografts and rats bearing syngeneic CA20948 tumors were used to study perfusion following PRRT administration with (177) lutetium octreotate. Both semi-quantitative and quantitative parameters were calculated. Treatment efficacy was measured by tumor-size reduction. Optimized TRICKS enabled MRI at 0.032 mm(3) voxel size with a temporal resolution of less than 5 s and large volume coverage, a substantial improvement over routine pre-clinical DCE-MRI studies. Tumor response to therapy was reflected in changes in tumor perfusion/permeability parameters. The H69 tumor model showed pronounced changes in DCE-derived parameters following PRRT. The rat CA20948 tumor model showed more heterogeneity in both treatment outcome and perfusion parameters. TRICKS enabled the acquisition of DCE-MRI at both high temporal resolution (Tres ) and spatial resolutions relevant for small animal tumor models. With the high Tres enabled by TRICKS, accurate pharmacokinetic data modeling was feasible. DCE-MRI parameters revealed changes over time and showed a clear relationship between tumor size and Ktrans . Copyright © 2015 John Wiley & Sons, Ltd.

  12. 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

  13. Temozolomide Therapy for Aggressive Pituitary Tumors: Results in a Small Series of Patients from Argentina

    Directory of Open Access Journals (Sweden)

    Oscar D. Bruno

    2015-01-01

    Full Text Available We evaluated results of temozolomide (TMZ therapy in six patients, aged 34–78 years, presenting aggressive pituitary tumors. In all the patients tested O6-methylguanine-DNA methyltransferase (MGMT immunoexpression in surgical specimens was absent. Patients received temozolomide 140–320 mg/day for 5 days monthly for at least 3 months. In two patients minimum time for evaluation could not be reached because of death in a 76-year-old man with a malignant prolactinoma and of severe neutro-thrombopenia in a 47-year-old woman with nonfunctioning pituitary adenoma. In two patients (a 34-year-old acromegalic woman and a 39-year-old woman with Nelson’s syndrome no response was observed after 4 and 6 months, respectively, and the treatment was stopped. Conversely, two 52- and 42-year-old women with Cushing’s disease had long-term total clinical and radiological remissions which persisted after stopping temozolomide. We conclude that TMZ therapy may be of variable efficacy depending on—until now—incompletely understood factors. Cooperative work on a greater number of cases of aggressive pituitary tumors should be crucial to establish the indications, doses, and duration of temozolomide administration.

  14. 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

  15. MiR-138 Inhibits Tumor Growth Through Repression of EZH2 in Non-Small Cell Lung Cancer

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    Huijun Zhang

    2013-01-01

    Full Text Available Background/Aims: MicroRNAs (miRNAs play important roles in tumorigenesis. We investigated the roles and mechanisms of miR-138 in human non-small cell lung cancer (NSCLC. Methods: The expression of miR-138 was first examined in NSCLC cell lines and tumourtissues by real-time PCR The in vitro and in vivo functional effect of miR-138 was examined further. A luciferase reporter assay was conducted to confirm target association between miR-138 and the enhancer of zeste homolog 2 (EZH2. Results: miR-138 was frequently downregulated in NSCLC cells and tissues. Overexpression of miR-138 inhibited proliferation of NSCLC cells in vitro and tumor growth in vivo. The EZH2 oncogene, which is often overexpressed in various human cancers and acts as an important regulator of cell growth and tumor invasion, was identified as a novel target of miR-138. miR-138 can bind to the 3′ untranslated region (3′ UTR of EZH2 and suppress the expression of EZH2 at both mRNA and protein levels. Furthermore, knockdown of EZH2 phenocopied the tumor suppressive effects of miR-138 in cell models, whereas ectopic expression of EZH2 rescued the suppressive effects of miR-138. Conclusion: These findings define a tumor suppressor function for miR-138 in NSCLC and further suggest that miR-138 may represent a potential therapeutic target for NSCLC patients.

  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. 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

  18. 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

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

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    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

  20. Inhibition of TGF-β Signaling in Tumor Cells by Small Molecule Src Family Kinase Inhibitors.

    Science.gov (United States)

    Bartscht, Tobias; Rosien, Benjamin; Rades, Dirk; Kaufmann, Roland; Biersack, Harald; Lehnerta, Hendrik; Ungefroren, Hendrik

    2017-01-01

    In a series of studies carried out over the last couple of years in various cell types, it was observed that the experimentally used Src family kinase inhibitors PP1 and PP2 and the clinically used Src/Abl inhibitors AZM475271 and dasatinib are potent inhibitors of TGF-β mediated cellular responses such as Smad and p38 mitogen-activated protein kinase phosphorylation, Smad-dependent transcriptional activation, growth inhibition, epithelial-mesenchymal transition (EMT), and cell motility. While for PP1/PP2 it was demonstrated that these agents directly inhibit the kinase activity of the TGF-β type I receptor activin receptor-like kinase 5, the mechanism of the anti-TGF-β effect of AZM475271 and dasatinib is less clear. In contrast, the anti-TGF-β effect of yet another Src/Abl inhibitor, bosutinib, is more variable with respect to the type of the TGF-β response and the cell type affected, and lacks a clear dose-dependency. In the light of their strong anti-activin receptor-like kinase 5 kinase effect, PP1 and PP2 should not be used when studying the role of c-Src as downstream mediators in TGF-β/activin receptor-like kinase 5 signaling. On the other hand, based upon in vitro findings, it is conceivable that part of the therapeutic effects of AZM475271 and dasatinib seen in preclinical and clinical studies with solid tumors was caused by inhibition of prometastatic TGF-β rather than Src signaling. If AZM475271 and dasatinib can indeed act as dual Src / TGF-β inhibitors in vivo, this may be beneficial for prevention of metastatic disease in more advanced tumor stages. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Promoter Methylation Primarily Occurs in Tumor Cells of Patients with Non-small Cell Lung Cancer

    NARCIS (Netherlands)

    De Jong, Wouter K.; Verpooten, Gonda F.; Kramer, Henk; Louwagie, Joost; Groen, Harry J. M.

    Background: The distribution of promoter methylation throughout the lungs of patients with non-small cell lung cancer (NSCLC) is unknown. In this explorative study, we assessed the methylation status of the promoter region of 11 genes in brush samples of 3 well-defined endobronchial locations in

  2. CEUS Helps to Rerate Small Breast Tumors of BI-RADS Category 3 and Category 4

    Directory of Open Access Journals (Sweden)

    Jian-xing Zhang

    2014-01-01

    Full Text Available Purpose. The primary aim of this study was to explore if classification, whether using the BI-RADS categories based on CEUS or conventional ultrasound, was conducive to the identification of benign and malignant category 3 or 4 small breast lesions. Material and Methods. We evaluated 30 malignant and 77 benign small breast lesions using CEUS. The range of enhancement, type of enhancement strength, intensity of enhancement, and enhancement patterns were independent factors included to assess the BI-RADS categories. Results. Of the nonenhanced breast lesions, 97.8% (44/45 were malignant, while, of the hyperplasic nodules, 96.8% (30/31 showed no enhancement in our study. Category changes of the lesions were made according to the features determined using CEUS. The results showed that these features could improve diagnostic sensitivity (from 70.0 to 80.0, 80.0, 90.0, and 90.0%, reduce the negative likelihood ratio (from 0.33 to 0.22, 0.25, 0.11, and 0.12, and improve the NPV (from 88.8 to 92.2, 91.2, 96.2, and 95.5%. However, this was not conducive to improve diagnostic specificity or the PPV. Conclusion. The vast majority of nonenhanced small breast lesions were malignant and most of the hyperplasic nodules showed no contrast enhancement. As a reference, CEUS was helpful in identifying BI-RADS category 3 or 4 small breast lesions.

  3. 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

  4. 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.

  5. Tumor glucose metabolism imaged in vivo in small animals with whole-body photoacoustic computed tomography

    Science.gov (United States)

    Chatni, Muhammad Rameez; Xia, Jun; Sohn, Rebecca; Maslov, Konstantin; Guo, Zijian; Zhang, Yu; Wang, Kun; Xia, Younan; Anastasio, Mark; Arbeit, Jeffrey; Wang, Lihong V.

    2012-07-01

    With the increasing use of small animals for human disease studies, small-animal whole-body molecular imaging plays an important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose molecular information, leading to higher costs of building dual-modality systems. Even with image co-registration, the spatial resolution of the molecular imaging modality is not improved. Utilizing a ring-shaped confocal photoacoustic computed tomography system, we demonstrate, for the first time, that both anatomy and glucose uptake can be imaged in a single modality. Anatomy was imaged with the endogenous hemoglobin contrast, and glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose.

  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. Highly Stable Organic Small Molecular Nanoparticles as an Advanced and Biocompatible Phototheranostic Agent of Tumor in Living Mice.

    Science.gov (United States)

    Qi, Ji; Fang, Yuan; Kwok, Ryan T K; Zhang, Xiaoyan; Hu, Xianglong; Lam, Jacky W Y; Ding, Dan; Tang, Ben Zhong

    2017-07-25

    Near-infrared (NIR)-absorbing organic small molecules hold great promise as the phototheranostic agents for clinical translation by virtue of their intrinsic advantages such as well-defined chemical structure, high purity, and good reproducibility. However, most of the currently available ones face the challenges in varying degrees in terms of photothermal instability, and photobleaching/reactive oxygen nitrogen species (RONS) inresistance, which indeed impair their practical applications in precise diagnosis and treatment of diseases. Herein, we developed highly stable and biocompatible organic nanoparticles (ONPs) for effective phototheranostic application by design and synthesis of an organic small molecule (namely TPA-T-TQ) with intensive absorption in the NIR window. The TPA-T-TQ ONPs with no noticeable in vivo toxicity possess better capacities in photothermal conversion and photoacoustic imaging (PAI), as well as show far higher stabilities including thermal/photothermal stabilities, and photobleaching/RONS resistances, when compared with the clinically popularly used indocyanine green. Thanks to the combined merits, the ONPs can serve as an efficient probe for in vivo PAI in a high-contrast manner, which also significantly causes the stoppage of tumor growth in living mice through PAI-guided photothermal therapy. This study thus provides an insight into the development of advanced NIR-absorbing small molecules for practical phototheranostic applications.

  9. 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.

  10. Cisplatin and photodynamic therapy exert synergistic inhibitory effects on small-cell lung cancer cell viability and xenograft tumor growth.

    Science.gov (United States)

    Cheng, You-Shuang; Peng, Yin-Bo; Yao, Min; Teng, Ji-Ping; Ni, Da; Zhu, Zhi-Jun; Zhuang, Bu-Feng; Yang, Zhi-Yin

    2017-06-03

    Lung cancer is the leading cause of cancer death worldwide. Small-cell lung cancer (SCLC) is an aggressive type of lung cancer that shows an overall 5-year survival rate below 10%. Although chemotherapy using cisplatin has been proven effective in SCLC treatment, conventional dose of cisplatin causes adverse side effects. Photodynamic therapy, a form of non-ionizing radiation therapy, is increasingly used alone or in combination with other therapeutics in cancer treatment. Herein, we aimed to address whether low dose cisplatin combination with PDT can effectively induce SCLC cell death by using in vitro cultured human SCLC NCI-H446 cells and in vivo tumor xenograft model. We found that both cisplatin and PDT showed dose-dependent cytotoxic effects in NCI-H446 cells. Importantly, co-treatment with low dose cisplatin (1 μM) and PDT (1.25 J/cm 2 ) synergistically inhibited cell viability and cell migration. We further showed that the combined therapy induced a higher level of intracellular ROS in cultured NCI-H446 cells. Moreover, the synergistic effect by cisplatin and PDT was recapitulated in tumor xenograft as revealed by a more robust increase in the staining of TUNEL (a marker of cell death) and decrease in tumor volume. Taken together, our findings suggest that low dose cisplatin combination with PDT can be an effective therapeutic modality in the treatment of SCLC patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 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.

  12. 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

  13. Ascaris lumbricoides-induced acute pancreatitis: diagnosis during EUS for a suspected small pancreatic tumor.

    Science.gov (United States)

    Mangiavillano, Benedetto; Carrara, Silvia; Petrone, Maria Chiara; Arcidiacono, Paolo Giorgio; Testoni, Pier Alberto

    2009-09-04

    Ascaris lumbricoides is the second most common intestinal parasite world-wide and, although the infection can be asymptomatic, in some cases it can present with complications, such as acute pancreatitis. We describe the case of a 37-year-old man, with a history of travelling in Eastern countries who presented with Ascaris lumbricoides-induced acute pancreatitis mimicking a small pancreatic cancer, diagnosed during an upper EUS. The endoscopy revealeda roundworm floating in the duodenum; its endoultrasonographic appearance showed a diffuse inhomogeneous pattern, with hypoechoic echotexture, such as in acute pancreatitis. Microbiological examination of the worm revealed a 20 cm long Ascaris lumbricoides. In non endemic countries, acute pancreatitis induced by Ascaris lumbricoides is an unusual diagnosis, and should be suspected especially in patients with history of traveling in endemic areas.

  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 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

  17. Assessment of arterial tumor vascularity in small hepatocellular carcinoma. Comparison between color Doppler ultrasonography and radiographic imagings with contrast medium: dynamic CT, angiography, and CT hepatic arteriography

    International Nuclear Information System (INIS)

    Furuse, Junji; Maru, Yasushi; Yoshino, Masahiro; Mera, Kiyomi; Sumi, Hajime; Sekiguchi, Ryuzo; Satake, Mitsuo; Hasebe, Takahiro; Ochiai, Atsushi

    2000-01-01

    Hepatocellular carcinoma (HCC) is characterized by tumor vascularization from the hepatic artery. The objective of our work was to compare color Doppler ultrasonography (CDU), including power Doppler ultrasonography (PDU) with radiographic imagings with contrast medium in regard to the detection of the arterial tumor vascularity of small hepatocellular carcinomas (HCC). We examined 42 small HCC lesions 2 cm or less in diameter in 37 patients for arterial tumor vascularity by conventional CDU, PDU, dynamic computed tomography (dCT), digital subtraction angiography (DSA), and CT hepatic arteriography (CTA). Color images were detected in 25 (59.5%) and 28 (66.7%) of the 42 lesions with conventional CDU and PDU, respectively, and tumor vascularity was detected in 26 (61.9%) by dCT, 23 (54.8%) by DSA, and 29 (69.0%) by CTA. Tumor vascularity could be detected in 51.9% by PDU and CTA, more than by conventional CDU, dCT, and DSA (44.4, 44.4, and 33.3%, respectively) in well-differentiated HCC, whereas the detection rates by these techniques were almost equal (86.7% by CDU, 93.3% by PDU, dCT, and DSA, 100% by CTA, respectively) in moderately and poorly differentiated HCC. PDU is superior to CDU, dCT and DSA and equal to CTA for the detection of tumor vascularity in small HCC, particularly in well-differentiated HCC

  18. Molecular conformation of the full-length tumor suppressor NF2/Merlin--a small-angle neutron scattering study.

    Science.gov (United States)

    Ali Khajeh, Jahan; Ju, Jeong Ho; Atchiba, Moussoubaou; Allaire, Marc; Stanley, Christopher; Heller, William T; Callaway, David J E; Bu, Zimei

    2014-07-29

    The tumor suppressor protein Merlin inhibits cell proliferation upon establishing cell-cell contacts. Because Merlin has high level of sequence similarity to the Ezrin-Radixin-Moesin family of proteins, the structural model of Ezrin-Radixin-Moesin protein autoinhibition and cycling between closed/resting and open/active conformational states is often employed to explain Merlin function. However, recent biochemical studies suggest alternative molecular models of Merlin function. Here, we have determined the low-resolution molecular structure and binding activity of Merlin and a Merlin(S518D) mutant that mimics the inactivating phosphorylation at S518 using small-angle neutron scattering and binding experiments. Small-angle neutron scattering shows that, in solution, both Merlin and Merlin(S518D) adopt a closed conformation, but binding experiments indicate that a significant fraction of either Merlin or Merlin(S518D) is capable of binding to the target protein NHERF1. Upon binding to the phosphatidylinositol 4,5-bisphosphate lipid, the wild-type Merlin adopts a more open conformation than in solution, but Merlin(S518D) remains in a closed conformation. This study supports a rheostat model of Merlin in NHERF1 binding and contributes to resolving a controversy about the molecular conformation and binding activity of Merlin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. 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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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....

  3. 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

  4. The potential of the CMB305 vaccine regimen to target NY-ESO-1 and improve outcomes for synovial sarcoma and myxoid/round cell liposarcoma patients.

    Science.gov (United States)

    Pollack, Seth M

    2018-02-01

    Synovial Sarcoma (SS) and Myxoid Round Cell Liposarcoma (MRCL) are devastating sarcoma subtypes with few treatment options and poor outcomes in the advanced setting. However, both these diseases may be ideal for novel immunotherapies targeting the cancer-testis antigen, NY-ESO-1. Areas covered: In this review, we discuss the novel NY-ESO-1 targeted vaccine regimen, CMB305. This regimen uses a unique integration-deficient, dendritic-cell targeting lentiviral vector from the ZVex® platform, LV305, in order to prime NY-ESO-1 specific T cells. LV305 has single agent activity, and, in one case, caused a durable partial response in a refractory SS patient. CMB305 also includes a boost from a NY-ESO-1 protein vaccine given along with a potent toll-like-4 receptor agonist, glycopyranosyl lipid A. CMB305 induces NY-ESO-1 specific T cell responses in both SS and MRC patients and these patients had excellent overall survival (OS) outcomes in the initial phase I study. Expert commentary: CMB305 is a therapeutic vaccine regimen targeting NY-ESO-1 based on the lentiviral vaccine vector, LV305. Phase I studies have proven this vaccine is active immunologically. Data suggesting this vaccine may improve OS for SS and MRCL patients is exciting but early, and on-going work is testing the impact of CMB305 on patient outcomes.

  5. Correlation of transcription of MALAT-1, a novel noncoding RNA, with deregulated expression of tumor suppressor p53 in small DNA tumor virus models

    OpenAIRE

    Jeffers, Liesl K.; Duan, Kaiwen; Ellies, Lesley G.; Seaman, William T.; Burger-Calderon, Raquel A.; Diatchenko, Luda B.; Webster-Cyriaque, Jennifer

    2013-01-01

    Although metastasis-associated lung adenocarcinoma transcript (MALAT)-1 is known to be consistently upregulated in several epithelial malignancies, little is known about its function or regulation. We therefore examined the relationship between MALAT-1 expression and candidate modulators such as DNA tumor virus oncoproteins human papillomavirus (HPV)-16 E6 and E7, BK virus T antigen (BKVTAg), mouse polyoma virus middle T antigen (MPVmTAg) and tumor suppressor genes p53 and pRb. Using suppress...

  6. 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

  7. Tumor vaccines

    International Nuclear Information System (INIS)

    Frank, M.; Ihan, A.

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regiments. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tumor vaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which immune tolerance exists. That is why the population of tumor-specific lymphocytes is represented by a small number of low-affinity T-lymphocytes that induce weak antitumor immune response. Simultaneously, tumors evolve many mechanisms to actively evade immune system, what makes them poorly immunogenic or even tolerogenic. Novel immunotherapeutic strategies are directed toward breaking immune tolerance to tumor antigens, enhancing immunogenicity of tumor vaccines and overcoming mechanisms of tumor escape. There are several approaches, unfortunately, all of them still far away from an ideal tumor vaccine that would reject a tumor. Difficulties in the activation of antitumor immune response by tumor vaccines have led to the development of alternative immunotherapeutic strategies that directly focus on effector mechanisms of immune system (adoptive tumor- specific T-lymphocyte transfer and tumor specific monoclonal antibodies). (author)

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Dual-Energy CT in Patients Treated with Anti-Angiogenic Agents for Non-Small Cell Lung Cancer: New Method of Monitoring Tumor Response?

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Na; Lee, Ho Yun; Lee, Kyung Soo; Chung, Myung Jin; Ahn, Myung Ju; Park, Keun Chil; Kim, Tae Sung; Yi, Chin A [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Seo, Joon Beom [Dept. of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2012-11-15

    To evaluate tumor responses in patients treated with anti-angiogenic agents for non-small cell lung cancer (NSCLC) by assessing intratumoral changes using a dual-energy CT (DECT) (based on Choi's criteria) and to compare it to traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Ten NSCLC patients treated with bevacizumab underwent DECT. Tumor responses to anti-angiogenic therapy were assessed and compared with the baseline CT results using both RECIST (size changes only) and Choi's criteria (reflecting net tumor enhancement). Kappa statistics was used to evaluate agreements between tumor responses assessed by RECIST and Choi's criteria. The weighted {kappa} value for the comparison of tumor responses between the RECIST and Choi's criteria was 0.72. Of 31 target lesions (21 solid nodules, 8 lymph nodes, and two ground-glass opacity nodules [GGNs]), five lesions (16%) showed discordant responses between RECIST and Choi's criteria. Iodine-enhanced images allowed for a distinction between tumor enhancement and hemorrhagic response (detected in 14% [4 of 29, excluding GGNs] of target lesions on virtual nonenhanced images). DECT may serve as a useful tool for response evaluation after anti-angiogenic treatment in NSCLC patients by providing information on the net enhancement of target lesions without obtaining non-enhanced images.

  13. 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).

  14. 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.

  15. 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.)

  16. Tumor Delineation and Quantitative Assessment of Glucose Metabolic Rate within Histologic Subtypes of Non-Small Cell Lung Cancer by Using Dynamic 18F Fluorodeoxyglucose PET

    NARCIS (Netherlands)

    Meijer, T.W.H.; Geus-Oei, L.F. de; Visser, E.P.; Oyen, W.J.G.; Looijen-Salamon, M.G.; Visvikis, D.; Verhagen, A.F.T.M.; Bussink, J.; Vriens, D.

    2017-01-01

    Purpose To assess whether dynamic fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static 18F-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

  17. Clinical Dutch-English Lambert-Eaton Myasthenic Syndrome (LEMS) Tumor Association Prediction Score Accurately Predicts Small-Cell Lung Cancer in the LEMS

    NARCIS (Netherlands)

    Titulaer, Maarten J.; Maddison, Paul; Sont, Jacob K.; Wirtz, Paul W.; Hilton-Jones, David; Klooster, Rinse; Willcox, Nick; Potman, Marko; Smitt, Peter A. E. Sillevis; Kuks, Jan B. M.; Roep, Bart O.; Vincent, Angela; van der Maarel, Silvere M.; van Dijk, J. Gert; Lang, Bethan; Verschuuren, Jan J. G. M.

    2011-01-01

    Purpose Approximately one half of patients with Lambert-Eaton myasthenic syndrome (LEMS) have small-cell lung carcinomas (SCLC), aggressive tumors with poor prognosis. In view of its profound impact on therapy and survival, we developed and validated a score to identify the presence of SCLC early in

  18. MAGEA4 expression in bone and soft tissue tumors: its utility as a target for immunotherapy and diagnostic marker combined with NY-ESO-1.

    Science.gov (United States)

    Iura, Kunio; Kohashi, Kenichi; Ishii, Takeaki; Maekawa, Akira; Bekki, Hirofumi; Otsuka, Hiroshi; Yamada, Yuichi; Yamamoto, Hidetaka; Matsumoto, Yoshihiro; Iwamoto, Yukihide; Oda, Yoshinao

    2017-07-26

    Cancer-testis (CT) antigens have promise as targets for immunotherapy, because of their restricted expression in tumor or testis tissue. MAGEA4 is both a MAGE family member and a CT antigen, and has attracted attention as a potential immunotherapeutic target. We investigated MAGEA4 expression by immunohistochemistry in bone and soft tissue tumor specimens that consisted of 35 malignant or intermediate and 24 benign histological subtypes, in order to evaluate its possible utility as an immunotherapy target and its potential use as a diagnostic marker when combined with another CT antigen, NY-ESO-1. Among these tumors, MAGEA4 was detected in 82.2% of synovial sarcomas, 67.7% of myxoid liposarcomas, 43.8% of osteosarcomas, 41.4% of angiosarcomas, 24.6% of malignant peripheral nerve sheath tumors (MPNSTs), and 21.4% of chondrosarcomas. NY-ESO-1 expression was found in 88.2% of myxoid liposarcomas, 61.1% of synovial sarcomas, 31.3% of osteosarcomas, 21.4% of pleomorphic liposarcomas, 16.7% of desmoplastic small round cell tumors, and 14.3% of chondrosarcomas. Benign tumors and non-tumorous tissue, except for testis tissue, did not express MAGEA4 or NY-ESO-1. Combined use of MAGEA4 and NY-ESO-1 increased the sensitivity, specificity, positive predictive values, and negative predictive values for distinguishing synovial sarcoma from spindle cell tumors and other mimicking tumors, compared to individual use of MAGEA4 or NY-ESO-1. Our results support the immunotherapy targeting MAGEA4 or NY-ESO-1 can be an ancillary therapy in the above-mentioned tumors, and the potential utility of MAGEA4 as an ancillary diagnostic marker for synovial sarcoma combined with NY-ESO-1.

  19. Respiratory motion variability of primary tumors and lymph nodes during radiotherapy of locally advanced non-small-cell lung cancers

    International Nuclear Information System (INIS)

    Jan, Nuzhat; Hugo, Geoffrey D.; Mukhopadhyay, Nitai; Weiss, Elisabeth

    2015-01-01

    The need for target adjustment due to respiratory motion variation and the value of carina as a motion surrogate is evaluated for locally advanced non-small-cell lung cancer. Using weekly 4D CTs (with audio-visual biofeedback) of 12 patients, respiratory motion variation of primary tumors (PT), lymph nodes (LN) and carina (C) were determined. Mean (SD) 3D respiratory motion ranges of PT, LN and C were 4 (3), 5 (3) and 5 (3) mm. PT and LN (p = 0.003), and LN and C motion range were correlated (p = 0.03). Only 20 %/5 % of all scans had variations >3 mm/5 mm. Large respiratory motion range on the initial scan was associated with larger during-treatment variations for PT (p = 0.03) and LN (p = 0.001). Mean (SD) 3D relative displacements of PT-C, LN-C and PT-LN were each 6 (2) mm. Variations of displacements >3 mm/5 mm were observed in 28 %/6 % of scans for PT-LN, 20 %/9 % for PT-C, and 20 %/8 % for LN-C. Motion reassessment is recommended in patients with large initial motion range. Relative motion-related displacements between PT and LN were larger than PT and LN motion alone. Both PT and C appear to be comparable surrogates for LN respiratory motion

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.)

  6. 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.

  7. 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.

  8. Choline molecular imaging with small-animal PET for monitoring tumor cellular response to photodynamic therapy of cancer

    Science.gov (United States)

    Fei, Baowei; Wang, Hesheng; Wu, Chunying; Meyers, Joseph; Xue, Liang-Yan; MacLennan, Gregory; Schluchter, Mark

    2009-02-01

    We are developing and evaluating choline molecular imaging with positron emission tomography (PET) for monitoring tumor response to photodynamic therapy (PDT) in animal models. Human prostate cancer (PC-3) was studied in athymic nude mice. A second-generation photosensitizer Pc 4 was used for PDT in tumor-bearing mice. MicroPET images with 11C-choline were acquired before PDT and 48 h after PDT. Time-activity curves of 11C-choline uptake were analyzed before and after PDT. For treated tumors, normalized choline uptake decreased significantly 48 h after PDT, compared to the same tumors pre-PDT (p PET imaging with 11C-choline is sensitive to detect early tumor response to PDT in the animal model of human prostate cancer.

  9. Tumor Markers

    Science.gov (United States)

    ... only a small number of people will test positive for the disease who do not have it—in other words, it will result in very few false-positive results. Although tumor markers are extremely useful in ...

  10. ARQ-197, an oral small-molecule inhibitor of c-Met for the treatment of solid tumors.

    Science.gov (United States)

    Bagai, Rakesh; Fan, Weiwen; Ma, Patrick C

    2010-06-01

    ARQ-197 is an oral, selective c-Met inhibitor under development by ArQule Inc, in partnership with Daiichi Sankyo Co Ltd and Asian licensee Kyowa Hakko Kirin Co Ltd, for the potential treatment of solid tumors, including NSCLC, hepatocellular carcinoma and pancreatic cancer, as well as microphthalmia transcription factor-driven tumors. c-Met, a key cell surface receptor tyrosine kinase involved in diverse regulatory functions, is often aberrantly activated in human cancers. While the precise mechanism of action of ARQ-197 remains undefined, data from preclinical studies have demonstrated that ARQ-197 inhibits c-Met activation in numerous human tumor cell lines and specifically targets c-Met in various cancer types; uniquely, ARQ-197 inhibits c-Met in a non-ATP-competitive manner. Phase I/II clinical trials demonstrated promise in terms of both tolerability and tumor response. Intriguingly, dose-limiting adverse effects were hematological in nature. Combinational trials are also ongoing to take advantage of the signaling crosstalk between c-Met and other oncogenic signaling systems. Prioritization of the clinical development of c-Met inhibitors, such as ARQ-197, among different tumor disease types is a key challenge at present; an improved understanding of the prediction of molecular determinants in tumors with respect to c-Met kinase as the driver oncogenic receptor, and of the prediction of tumor response, is still urgently needed.

  11. [Expression of RRM1 and ERCC1 genes in tumor tissues and peripheral blood lymphocytes of advanced non-small cell lung cancer].

    Science.gov (United States)

    Zhang, Guo-bin; Chen, Jian; Wang, Lin-run; Li, Jun; Li, Min-wei; Xu, Nong; Shen-Tu, Jian-zhong

    2012-09-01

    To investigate the expression of RRM1 and ERCC1 genes in tumor tissues and peripheral blood lymphocytes of advanced non-small cell lung cancer (NSCLC). Tissue and peripheral blood samples were collected from 49 advanced NSCLC patients treated with gemcitabine plus carboplatin. The expressions of RRM1 and ERCC1 mRNA in tumor tissue and peripheral lymphocytes were detected by real-time fluorescent quantitative PCR. The relationship of gene expression with clinical characteristics,chemotherapy response and prognosis was analyzed. The RRM1 expression in tumor tissues was positively correlated with that in peripheral blood lymphocytes,while no significant correlation was observed between ERCC1 expression in tumor tissues and that in peripheral blood (rs=0.332 and 0.258; P=0.020 and 0.073, respectively). The expression of RRM1 and ERCC1 in tumor tissues peripheral lymphocytes was synchronous (rs=0.634 and 0.351; P0.05). Significant difference was found in response rate to chemotherapy (Ptissues or low RRM1 expression levels in peripheral blood and those with high RRM1 and ERCC1 expression levels. The patients with low ERCC1 expression levels in tumor tissues gained higher 2-year survival rate (Pblood with the response to chemotherapy and prognosis (P>0.05). The expression of RRMI and ERCC1 genes in tumor tissues and RRM1 in peripheral blood lymphocytes is closely correlated with the response to chemotherapy and prognosis of patients with advanced NSCLC treated with gemcitabine plus carboplatin.

  12. The metastatic potential of renal tumors: Influence of histologic subtypes on definition of small renal masses, risk stratification, and future active surveillance protocols.

    Science.gov (United States)

    Daugherty, Michael; Sedaghatpour, Dillon; Shapiro, Oleg; Vourganti, Srinivas; Kutikov, Alexander; Bratslavsky, Gennady

    2017-04-01

    The influence of histology in metastatic potential is often overlooked when discussing the management options of small renal masses (SRM), with size or growth rate often serving as the triggers for the intervention. We aim to re-examine the definition of a SRM by evaluating the metastatic potential of renal masses incorporating tumor size and histology to create metastatic risk tables. Surveillance Epidemiology and End Results (SEER)-18 registries database was queried for all cases of clear cell, papillary, and chromophobe renal cell carcinoma (RCC) diagnosed between 2004 and 2012. There were 55,478 cases identified that included 43,783, 8,587, and 3,208 cases of clear cell, papillary, and chromophobe, respectively. Tumors were stratified using 1-cm increments to determine the metastatic potential by calculating the metastatic rate at presentation for different size intervals in histologic categories. For all 3 histologies, tumors measuring 5cm or less had a rate of metastatic RCC at presentation of less than 4%. The metastatic potential was highest for clear cell, followed by papillary and then chromophobe tumors. Setting a cutoff of no more than 3% for metastatic potential to be called a SRM, makes clear cell carcinoma and papillary carcinoma a SRM up to 4cm, whereas the chromophobe RCC would be considered a SRM up to 7cm. Although clinical staging and tumor size have been the key determinants in decision-making of patients with solid renal tumors, the histology-specific risks of metastatic potential are different for each mass. The definition of a SRM should be based on the metastatic potential and not on tumor size alone. This information could be helpful for counseling and managing patients with SRMs as well as for modifying active surveillance protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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    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

  14. 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.

  15. Tumor volume determines the feasibility of cell-free DNA sequencing for mutation detection in non-small cell lung cancer.

    Science.gov (United States)

    Ohira, Tatsuo; Sakai, Kazuko; Matsubayashi, Jun; Kajiwara, Naohiro; Kakihana, Masatoshi; Hagiwara, Masaru; Hibi, Masaaki; Yoshida, Koichi; Maeda, Junichi; Ohtani, Keishi; Nagao, Toshitaka; Nishio, Kazuto; Ikeda, Norihiko

    2016-11-01

    Next-generation sequencing (NGS) and digital PCR technologies allow analysis of the mutational profile of circulating cell-free DNA (cfDNA) in individuals with advanced lung cancer. We have now evaluated the feasibility of cfDNA sequencing for mutation detection in patients with non-small cell lung cancer at earlier stages. A total of 150 matched tumor and serum samples were collected from non-small cell lung cancer patients at stages IA-IIIA. Amplicon sequencing with DNA extracted from tumor tissue detected frequent mutations in EGFR (37% of patients), TP53 (39%), and KRAS (10%), consistent with previous findings. In contrast, NGS of cfDNA identified only EGFR, TP53, and PIK3CA mutations in three, five, and one patient, respectively, even though adequate amounts of cfDNA were extracted (median of 4936 copies/mL serum). Next-generation sequencing showed a high accuracy (98.8%) compared with droplet digital PCR for cfDNA mutation detection, suggesting that the low frequency of mutations in cfDNA was not due to a low assay sensitivity. Whereas the yield of cfDNA did not differ among tumor stages, the cfDNA mutations were detected in seven patients at stages IIA-IIIA and at T2b or T3. Tumor volume was significantly higher in the cfDNA mutation-positive patients than in the negative patients at stages T2b-T4 (159.1 ± 58.0 vs. 52.5 ± 9.9 cm 3 , P = 0.014). Our results thus suggest that tumor volume is a determinant of the feasibility of mutation detection with cfDNA as the analyte. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  16. In Vivo Measurements of Tumor Metabolism and Growth after Administration of Enzastaurin Using Small Animal FDG Positron Emission Tomography

    Directory of Open Access Journals (Sweden)

    Karen E. Pollok

    2009-01-01

    Full Text Available Background. The use of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG may help to establish the antitumor activity of enzastaurin, a novel protein kinase C-beta II (PKC-II inhibitor, in mouse xenografts. Methods. The hematologic cell line RAJI and the solid tumor cell line U87MG were each implanted in NOD/SCID mice. Standard tumor growth measurements and [18F]FDG PET imaging were performed weekly for up to three weeks after tumor implantation and growth. Results. Concomitant with caliper measurements, [18F]FDG PET imaging was performed to monitor glucose metabolism. Heterogeneity of glucose uptake in various areas of the tumors was observed after vehicle or enzastaurin treatment. This heterogeneity may limit the use of [18F]FDG PET imaging to measure enzastaurin-associated changes in xenograft tumors. Conclusion. [18F]FDG PET imaging technique does not correlate with standard caliper assessments in xenografts to assess the antitumor activity of enzastaurin. Future studies are needed to determine the use of [18F]FDG PET imaging in preclinical models.

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

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    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.

  18. 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

  19. 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.

  20. Potent anti-tumor activity of telomerase-dependent and HSV-TK armed oncolytic adenovirus for non-small cell lung cancer in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Ren Peng-Kang

    2010-05-01

    Full Text Available Abstract Background Non-small cell lung cancer (NSCLC is the leading cause of cancer related mortality, any improvements in therapeutic strategies are urgently required. In this study we generated a novel 'suicide gene' armed oncolytic adenoviral vector and investigated its antitumor effect both in vitro and in vivo. Methods Since the up-regulated expression of human telomerase reverse transcriptase (hTERT is a hallmark of alltypes of NSCLC, we chose hTERT promoter to transcriptionally control E1A gene expression to obtain adenoviral replication in NSCLC. In order to further enhance anti-tumor effect of this oncolytic adenoviral vector, we inserted a 'suicide gene' i.e. Herpes Simplex Virus Thymidine Kinase (HSV-TK into oncolytic adenoviral vector to engineer a novel armed oncolytic adenoviral vector 'Ad.hTERT-E1A-TK'. Results Ad.hTERT-E1A-TK efficiently killed different types of tumor cells including two types of NSCLC cells in vitro, causing no damage to normal primary fibroblasts. Furthermore, Ad.hTERT-E1A-TK infection combined with administration of prodrug gancyclovir (GCV resulted in more potent cytotoxicity on NSCLC cells, and synergistically suppressed human NSCLC tumor growth in nude mice. Conclusion The results from this study showed that Ad.hTERT-E1A-TK/GCV could be a potent but safe anti-tumor strategy for NSCLC biotherapy.

  1. Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors.

    Science.gov (United States)

    Patnaik, Amita; Rosen, Lee S; Tolaney, Sara M; Tolcher, Anthony W; Goldman, Jonathan W; Gandhi, Leena; Papadopoulos, Kyriakos P; Beeram, Muralidhar; Rasco, Drew W; Hilton, John F; Nasir, Aejaz; Beckmann, Richard P; Schade, Andrew E; Fulford, Angie D; Nguyen, Tuan S; Martinez, Ricardo; Kulanthaivel, Palaniappan; Li, Lily Q; Frenzel, Martin; Cronier, Damien M; Chan, Edward M; Flaherty, Keith T; Wen, Patrick Y; Shapiro, Geoffrey I

    2016-07-01

    We evaluated the safety, pharmacokinetic profile, pharmacodynamic effects, and antitumor activity of abemaciclib, an orally bioavailable inhibitor of cyclin-dependent kinases (CDK) 4 and 6, in a multicenter study including phase I dose escalation followed by tumor-specific cohorts for breast cancer, non-small cell lung cancer (NSCLC), glioblastoma, melanoma, and colorectal cancer. A total of 225 patients were enrolled: 33 in dose escalation and 192 in tumor-specific cohorts. Dose-limiting toxicity was grade 3 fatigue. The maximum tolerated dose was 200 mg every 12 hours. The most common possibly related treatment-emergent adverse events involved fatigue and the gastrointestinal, renal, or hematopoietic systems. Plasma concentrations increased with dose, and pharmacodynamic effects were observed in proliferating keratinocytes and tumors. Radiographic responses were achieved in previously treated patients with breast cancer, NSCLC, and melanoma. For hormone receptor-positive breast cancer, the overall response rate was 31%; moreover, 61% of patients achieved either response or stable disease lasting ≥6 months. Abemaciclib represents the first selective inhibitor of CDK4 and CDK6 with a safety profile allowing continuous dosing to achieve sustained target inhibition. This first-in-human experience demonstrates single-agent activity for patients with advanced breast cancer, NSCLC, and other solid tumors. Cancer Discov; 6(7); 740-53. ©2016 AACR.See related commentary by Lim et al., p. 697This article is highlighted in the In This Issue feature, p. 681. ©2016 American Association for Cancer Research.

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

    Science.gov (United States)

    Ma, Xiaopeng; Phi Van, Valerie; Kimm, Melanie A; Prakash, Jaya; Kessler, Horst; Kosanke, Katja; Feuchtinger, Annette; Aichler, Michaela; Gupta, Aayush; Rummeny, Ernst J; Eisenblätter, Michel; Siveke, Jens; Walch, Axel K; Braren, Rickmer; Ntziachristos, Vasilis; Wildgruber, Moritz

    2017-01-01

    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. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. 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.

  4. 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.

  5. 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

  6. Co-existence of acute appendicitis and inflammatory myofibroblastic tumor of the small intestine: A case report

    Directory of Open Access Journals (Sweden)

    Nurcan Unver

    2015-09-01

    Conclusion: Coexistence of inflammatory myofibroblastic tumor located in the gastrointestinal system with acute appendicitis is a rare event. Complete surgical excision should be regarded as the mainstay of the treatment. Long-term follow up with serial imaging techniques is recommended.

  7. 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

  8. Enhanced Anti-Tumor Efficacy of Lipid-Modified Platinum Derivatives in Combination with Survivin Silencing siRNA in Resistant Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Mattheolabakis, George; Ling, Dandan; Ahmad, Gulzar; Amiji, Mansoor

    2016-12-01

    Cisplatin, is recognized as a first line therapeutic for the treatment of non-small cell lung cancer (NSCLC). Cisplatin resistance is identified as the most detrimental complication during treatment and has been associated with upregulation of several genes, such as the anti-apoptotic gene survivin. In this study, we have evaluated the cytotoxic activity of lipid (C6 and C8)-modified platinum compounds in combination with a survivin-silencing siRNA against cisplatin resistant tumors. We synthesized and characterized several lipid-modified platinum compounds and evaluated their cytotoxic activity alone or in combination with survivin-silencing siRNA in vitro and in vivo against A549 DDP cells and in vivo in tumor xenograft model. The lipid-modified compounds exhibited significantly stronger cytotoxic activity in vitro compared to cisplatin, with CDDP-C6 and CDDP-C8 producing the most pronounced effect, in both A549 and A549 DDP cells. Pre-treatment of the A549 DDP cells with survivin-silencing siRNA enhanced the cytotoxic activity of these compounds. In vivo, the co-treatment of the survivin-silencing siRNA and CDDP-C8 produced the strongest tumor growth inhibition effect (64.5%, p cancer mouse model of chemoresistant lung cancer. In contrast, cisplatin treatment exhibited no significant tumor growth inhibition (4.5%, no p). Co-treatment of lipid-modified compounds and survivin-silencing siRNA can constitute a reliable alternative to cisplatin treatment for cisplatin-resistant lung tumors that merit further evaluation.

  9. Early intervention with a small molecule inhibitor for tumor nefosis factor-α prevents cognitive deficits in a triple transgenic mouse model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Gabbita S

    2012-05-01

    Full Text Available Abstract Background Chronic neuroinflammation is an important component of Alzheimer’s disease and could contribute to neuronal dysfunction, injury and loss that lead to disease progression. Multiple clinical studies implicate tumor necrosis factor-α as an inflammatory mediator of neurodegeneration in patients with Alzheimer’s because of elevated levels of this cytokine in the cerebrospinal fluid, hippocampus and cortex. Current Alzheimer’s disease interventions are symptomatic treatments with limited efficacy that do not address etiology. Thus, a critical need exists for novel treatments directed towards modifying the pathophysiology and progression. Methods To investigate the effect of early immune modulation on neuroinflammation and cognitive outcome, we treated triple transgenic Alzheimer’s disease mice (harboring PS1M146V, APPSwe, and tauP301L transgenes with the small molecule tumor necrosis factor-α inhibitors, 3,6′-dithiothalidomide and thalidomide, beginning at four months of age. At this young age, mice do not exhibit plaque or tau pathology but do show mild intraneuronal amyloid beta protein staining and a robust increase in tumor necrosis factor-α. After 10 weeks of treatment, cognitive performance was assessed using radial arm maze and neuroinflammation was assessed using biochemical, stereological and flow cytometric endpoints. Results 3,6′-dithiothalidomide reduced tumor necrosis factor-α mRNA and protein levels in the brain and improved working memory performance and the ratio of resting to reactive microglia in the hippocampus of triple transgenic mice. In comparison to non-transgenic controls, triple transgenic Alzheimer’s disease mice had increased total numbers of infiltrating peripheral monomyelocytic/granulocytic leukocytes with enhanced intracytoplasmic tumor necrosis factor-α, which was reduced after treatment with 3,6′-dithiothalidomide. Conclusions These results suggest that modulation of tumor

  10. 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

    drug sen- sitivity in cancer cells. Nature 483(7391):570–575. 14. Adams JM, et al. (2005) Subversion of the Bcl-2 life/death switch in cancer de ...SCLC (N=15) other solid tumors (N=229) P= 0.001 Faber et al. Sup. Figure 3 # Cancer type 1 biliary tract 2 bladder 3 breast 4 cervix 5...lung cancer (SCLC), Genetically engineered mouse model (GEMM), BH3 mimetic, TORC inhibitor, Apoptosis, Preclinical therapeutics 16. SECURITY

  11. 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)

  12. Report of two cases of pseudoprogression in patients with non-small cell lung cancer treated with nivolumab-including histological analysis of one case after tumor regression.

    Science.gov (United States)

    Tanizaki, Junko; Hayashi, Hidetoshi; Kimura, Masatomo; Tanaka, Kaoru; Takeda, Masayuki; Shimizu, Shigeki; Ito, Akihiko; Nakagawa, Kazuhiko

    2016-12-01

    The recent approval of nivolumab and other immune-checkpoint inhibitors for the treatment of certain solid tumors including non-small cell lung cancer (NSCLC) has transformed cancer therapy. However, it will be important to characterize effects of such agents not seen with classical cytotoxic drugs or other targeted therapeutics. We here report two cases of NSCLC showing so-called pseudoprogression during nivolumab treatment. In both cases, imaging assessment revealed that liver metastatic lesions initially progressed but subsequently shrank during continuous nivolumab administration, with treatment also resulting in a decline in serum levels of carcinoembryonic antigen. Histological evaluation of the liver metastatic lesion of one case after regression revealed fibrotic tissue containing infiltrated lymphocytes positive for CD3, CD4, or CD8 but no viable tumor cells, suggestive of a durable immune reaction even after a pathological complete response. Given the increasing use of immune-checkpoint inhibitors in patients with NSCLC or other solid tumors, further clinical evaluation and pathological assessment are warranted to provide a better understanding of such pseudoprogression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. miR-212 increases tumor necrosis factor-related apoptosis-inducing ligand sensitivity in non-small cell lung cancer by targeting the antiapoptotic protein PED.

    Science.gov (United States)

    Incoronato, Mariarosaria; Garofalo, Michela; Urso, Loredana; Romano, Giulia; Quintavalle, Cristina; Zanca, Ciro; Iaboni, Margherita; Nuovo, Gerald; Croce, Carlo Maria; Condorelli, Gerolama

    2010-05-01

    PED/PEA-15 (PED) is a death effector domain family member of 15 kDa with a broad antiapoptotic function found overexpressed in a number of different human tumors, including lung cancer. To date, the mechanisms that regulate PED expression are unknown. Therefore, we address this point by the identification of microRNAs that in non-small cell lung cancer (NSCLC) modulate PED levels. In this work, we identify miR-212 as a negative regulator of PED expression. We also show that ectopic expression of this miR increases tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death in NSCLC cells. In contrast, inhibition of endogenous miR-212 by use of antago-miR results in increase of PED protein expression and resistance to TRAIL treatment. Besides, in NSCLC, we show both in vitro and in vivo that PED and miR-212 expressions are inversely correlated, that is, PED is upregulated and miR-212 is rarely expressed. In conclusion, these findings suggest that miR-212 should be considered as a tumor suppressor because it negatively regulates the antiapoptotic protein PED and regulates TRAIL sensitivity. (c)2010 AACR.

  14. Combined use of EpCAM and FRα enables the high-efficiency capture of circulating tumor cells in non-small cell lung cancer.

    Science.gov (United States)

    Chen, Luojun; Peng, Min; Li, Na; Song, Qibin; Yao, Yi; Xu, Bin; Liu, Huali; Ruan, Peng

    2018-01-19

    Circulating tumor cells (CTCs) provide a new approach for auxiliary diagnosis, therapeutic effect evaluation, and prognosis prediction for cancer patients. The epithelial cell adhesion molecule (EpCAM)-based separation method (CellSearch) showed good clinical use in multiple types of cancer. Nevertheless, some non-small cell lung cancer (NSCLC) tumor cells have a lower expression of EpCAM and are less frequently detected by CellSearch. Here, we present a highly sensitive immunomagnetic separation method to capture CTCs based on two cell surface markers for NSCLC, EpCAM and Folate receptor alpha (FRα). Our method has been demonstrated to be more efficient in capturing NSCLC cells (P capture rate (48.78% vs. 73.17%) was obtained, and by using a cutoff value of 0 CTC per 2 ml of blood, the sensitivities were 53.66% and 75.61% and the specificities were 100% and 90% for anti-EpCAM-MNs or a combination of anti-EpCAM-MNs and anti-FRα-MNs, respectively. Compared with the tumor-specific LT-PCR based on FRα, our method can isolate intact FRα + CTCs, and it is advantageous for additional CTC-related downstream analysis. Our results provide a new method to increase the CTC capture efficiency of NSCLC.

  15. 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.

  16. Comprehensive adipocytic and neurogenic tissue microarray analysis of NY-ESO-1 expression - a promising immunotherapy target in malignant peripheral nerve sheath tumor and liposarcoma.

    Science.gov (United States)

    Shurell, Elizabeth; Vergara-Lluri, Maria E; Li, Yunfeng; Crompton, Joseph G; Singh, Arun; Bernthal, Nicholas; Wu, Hong; Eilber, Fritz C; Dry, Sarah M

    2016-11-08

    Immunotherapy targeting cancer-testis antigen NY-ESO-1 shows promise for tumors with poor response to chemoradiation. Malignant peripheral nerve sheath tumors (MPNSTs) and liposarcomas (LPS) are chemoresistant and have few effective treatment options. Materials Methods: Using a comprehensive tissue microarray (TMA) of both benign and malignant tumors in primary, recurrent, and metastatic samples, we examined NY-ESO-1 expression in peripheral nerve sheath tumor (PNST) and adipocytic tumors. The PNST TMA included 42 MPNSTs (spontaneous n = 26, NF1-associated n = 16), 35 neurofibromas (spontaneous n = 22, NF-1 associated n = 13), 11 schwannomas, and 18 normal nerves. The LPS TMA included 48 well-differentiated/dedifferentiated (WD/DD) LPS, 13 myxoid/round cell LPS, 3 pleomorphic LPS, 8 lipomas, 1 myelolipoma, and 3 normal adipocytic tissue samples. Stained in triplicate, NY-ESO-1 intensity and density were scored. NY-ESO-1 expression was exclusive to malignant tumors. 100% of myxoid/round cell LPS demonstrated NY-ESO-1 expression, while only 6% of WD/DD LPS showed protein expression, one of which was WD LPS. Of MPNST, 4/26 (15%) spontaneous and 2/16 (12%) NF1-associated MPNSTs demonstrated NY-ESO-1 expression. Strong NY-ESO-1 expression was observed in myxoid/round cell and dedifferentiated LPS, and MPNST in primary, neoadjuvant, and metastatic settings. We found higher prevalence of NY-ESO-1 expression in MPNSTs than previously reported, highlighting a subset of MPNST patients who may benefit from immunotherapy. This study expands our understanding of NY-ESO-1 in WD/DD LPS and is the first demonstration of staining in a WD LPS and metastatic/recurrent myxoid/round cell LPS. These results suggest immunotherapy targeting NY-ESO-1 may benefit patients with aggressive tumors resistant to conventional therapy.

  17. Detection of Epidermal Growth Factor Receptor Mutations in Non-small Cell Lung Cancer Tumor Specimens from Various Ways by Denaturing High-performance Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    Siyuan CHEN

    2010-09-01

    Full Text Available Background and objective Epidermal growth factor receptor (EGFR is the most important therapeutic target in non-small cell lung cancer (NSCLC. EGFR mutations may predict responsiveness to tyrosine kinase inhibitors (TKIs. These mutations are commonly identified using direct sequencing, which is considered the gold standard. But direct sequencing is time-consuming and hyposensitive. In addition, this method requires a lot of tumor specimens. Denaturing highperformance liquid chromatography (DHPLC is a rapid automated sensitive and specific method in mutant gene detection. The aim of this study is to evaluate DHPLC as a rapid detection method for EGFR mutations in NSCLC tumor specimens. Methods DHPLC was used to evaluate the accuracy and sensitivity of detection the serial dilutions of mutant and wild type EGFR plasma DNA. Frozen tumor specimens of 83 NSCLC patients from various ways had been included, after DNA extraction and polymerase chain reaction (PCR on EGFR exon 19 and 21, the results from the direct sequencing and DHPLC were compared. Results Mutant plasma DNA can be detected in the serial dilution of 1:100 by DHPLC and 1:10 by direct sequencing respectively. The results from DHPLC showed 22 EGFR mutations were detected in 83 NSCLC patients, and only 19 mutation samples had been conformed by direct sequencing. Moreover, the other 61 samples were deemed as wild type by DHPLC and direct sequencing. The sensitivity and specificity of DHPLC was 100% and 95.13% respectively. The detection of the tumor specimens from CT-guided transthoracic needle lung biopsy, lymph node biopsy and surgical resection all showed high sensitivity and specificity. EGFR mutation has strong correlation with gender and pathologic type, but irrelevant to age and smoking status. Conclusion DHPLC was a precise rapid preliminary screening method for detection of NSCLC EGFR genotype.

  18. Antitumor effects of a novel chromosome region maintenance 1 (CRM1 inhibitor on non-small cell lung cancer cells in vitro and in mouse tumor xenografts.

    Directory of Open Access Journals (Sweden)

    Shuai Wang

    Full Text Available BACKGROUND: Chromosome Region Maintenance 1 (CRM1 is a nuclear exporter and its inhibitor has anti-tumor activity in various cancers. This study assessed the therapeutic efficiency of the novel CRM1 inhibitor KPT-185 on non-small cell lung cancer (NSCLC. METHODS: NSCLC cell lines were treated with KPT-185 to assess changes in cell viability, cell cycle, apoptosis, and protein expression. NOD-SCID mice carrying NSCLC cell xenografts were orally treated with KPT-276, a clinical analog of KPT-185, to examine the efficacy and side effects of KPT-276 in vivo. RESULTS: KPT-185 significantly reduced the viability of six NSCLC cell lines in a time- and dose-dependent manner, including epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI-resistant H1975 and H1650GR cell lines. In addition, KPT-185 induced these NSCLC cells to arrest at G1 phase of the cell cycle and caused apoptosis in a dose-dependent manner. KPT-185 treatment also reduced CRM1 protein levels in six NSCLC cell lines, and the reduction could be completely abolished by the proteasome inhibitor bortezomib. KPT-185 activated caspase 3, 8, and 9, but inhibited survivin expression in NSCLC cells. In a mouse H1975 cell xenograft model, tumor growth was significantly inhibited by oral KPT-276 administration, and there was no significant mouse body weight loss or other side effects. CONCLUSIONS: The current study demonstrated the anti-tumor effects of KPT-185 in NSCLC cells, including EGFR-TKI-resistant NSCLC cell lines. Further studies will assess anti-tumor activity of KPT-185 in a clinical trial for NSCLC patients.

  19. 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.

  20. Detection of small bowel tumor in wireless capsule endoscopy images using an adaptive neuro-fuzzy inference system

    Science.gov (United States)

    Alizadeh, Mahdi; Maghsoudi, Omid Haji; Sharzehi, Kaveh; Hemati, Hamid Reza; Asl, Alireza Kamali; Talebpour, Alireza

    2017-01-01

    Automatic diagnosis tool helps physicians to evaluate capsule endoscopic examinations faster and more accurate. The purpose of this study was to evaluate the validity and reliability of an automatic post-processing method for identifying and classifying wireless capsule endoscopic images, and investigate statistical measures to differentiate normal and abnormal images. The proposed technique consists of two main stages, namely, feature extraction and classification. Primarily, 32 features incorporating four statistical measures (contrast, correlation, homogeneity and energy) calculated from co-occurrence metrics were computed. Then, mutual information was used to select features with maximal dependence on the target class and with minimal redundancy between features. Finally, a trained classifier, adaptive neuro-fuzzy interface system was implemented to classify endoscopic images into tumor, healthy and unhealthy classes. Classification accuracy of 94.2% was obtained using the proposed pipeline. Such techniques are valuable for accurate detection characterization and interpretation of endoscopic images. PMID:28959000

  1. Detection of small bowel tumor in wireless capsule endoscopy images using an adaptive neuro-fuzzy inference system.

    Science.gov (United States)

    Alizadeh, Mahdi; Maghsoudi, Omid Haji; Sharzehi, Kaveh; Reza Hemati, Hamid; Kamali Asl, Alireza; Talebpour, Alireza

    2017-09-26

    Automatic diagnosis tool helps physicians to evaluate capsule endoscopic examinations faster and more accurate. The purpose of this study was to evaluate the validity and reliability of an automatic post-processing method for identifying and classifying wireless capsule endoscopic images, and investigate statistical measures to differentiate normal and abnormal images. The proposed technique consists of two main stages, namely, feature extraction and classification. Primarily, 32 features incorporating four statistical measures (contrast, correlation, homogeneity and energy) calculated from co-occurrence metrics were computed. Then, mutual information was used to select features with maximal dependence on the target class and with minimal redundancy between features. Finally, a trained classifier, adaptive neuro-fuzzy interface system was implemented to classify endoscopic images into tumor, healthy and unhealthy classes. Classification accuracy of 94.2% was obtained using the proposed pipeline. Such techniques are valuable for accurate detection characterization and interpretation of endoscopic images.

  2. Are there parameters that predict a nondiagnostic biopsy outcome taken during laparoscopic-assisted cryoablation of small renal tumors?

    NARCIS (Netherlands)

    Barwari, Kurdo; Beemster, Patricia W. T.; Hew, Miki N.; Wijkstra, Hessel; de la Rosette, Jean; Laguna, M. Pilar

    2011-01-01

    The histopathologic diagnosis of a small renal mass (SRM) that is managed with cryoablation relies on preoperative or intraoperative biopsies. Because a considerable number of these SRMs are benign, accurate diagnosis has prognostic and follow-up implications. The main problem in SRMs is the high

  3. Pituitary Tumors

    Science.gov (United States)

    ... nursing, or cause a man to lose his sex drive or lower his sperm count. Pituitary tumors often go undiagnosed because their symptoms resemble those of so many other more common diseases. × Definition The pituitary is a small, bean-sized gland ...

  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. 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.

  6. Hollow silica and silica-boron nano/microparticles for contrast-enhanced ultrasound to detect small tumors.

    Science.gov (United States)

    Liberman, Alexander; Martinez, H Paul; Ta, Casey N; Barback, Christopher V; Mattrey, Robert F; Kono, Yuko; Blair, Sarah L; Trogler, William C; Kummel, Andrew C; Wu, Zhe

    2012-07-01

    Diagnosing tumors at an early stage when they are easily curable and may not require systemic chemotherapy remains a challenge to clinicians. In order to improve early cancer detection, gas filled hollow boron-doped silica particles have been developed, which can be used for ultrasound-guided breast conservation therapy. The particles are synthesized using a polystyrene template and subsequently calcinated to create hollow, rigid nanoporous microspheres. The microshells are filled with perfluoropentane vapor. Studies were performed in phantoms to optimize particle concentration, injection dose, and the ultrasound settings such as pulse frequency and mechanical index. In vitro studies have shown that these particles can be continuously imaged by US up to 48 min and their signal lifetime persisted for 5 days. These particles could potentially be given by intravenous injection and, in conjunction with contrast-enhanced ultrasound, be utilized as a screening tool to detect smaller breast cancers before they are detectible by traditional mammography. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Chlorella sorokiniana induces mitochondrial-mediated apoptosis in human non-small cell lung cancer cells and inhibits xenograft tumor growth in vivo.

    Science.gov (United States)

    Lin, Ping-Yi; Tsai, Ching-Tsan; Chuang, Wan-Ling; Chao, Ya-Hsuan; Pan, I-Horng; Chen, Yu-Kuo; Lin, Chi-Chen; Wang, Bing-Yen

    2017-02-01

    Lung cancer is one of the leading causes of cancer related deaths worldwide. Marine microalgae are a source of biologically active compounds and are widely consumed as a nutritional supplement in East Asian countries. It has been reported that Chlorella or Chlorella extracts have various beneficial pharmacological compounds that modulate immune responses; however, no studies have investigated the anti-cancer effects of Chlorella sorokiniana (CS) on non-small cell lung cancer (NSCLC). In this study, we evaluated the anti-cancer effects of CS in two human NSCLC cell lines (A549 and CL1-5 human lung adenocarcinoma cells), and its effects on tumor growth in a subcutaneous xenograft tumor model. We also investigated the possible molecular mechanisms governing the pharmacological function of CS. Our results showed that exposure of the two cell lines to CS resulted in a concentration-dependent reduction in cell viability. In addition, the percentage of apoptotic cells increased in a dose-dependent manner, suggesting that CS might induce apoptosis in human NSCLC cells. Western blot analysis revealed that exposure to CS resulted in increased protein expression of the cleaved/activated forms of caspase-3, caspase-9, and PARP, except caspase-8. ZDEVD (caspase-3 inhibitor) and Z-LEHD (caspase-9 inhibitor) were sufficient at preventing apoptosis in both A549 and CL1-5 cells, proving that CS induced cell death via the mitochondria-mediated apoptotic pathway. Exposure of A549 and CL1-5 cells to CS for 24 h resulted in decreased expression of Bcl-2 protein and increased expression of Bax protein as well as decreased expression of two IAP family proteins, survivin and XIAP. We demonstrated that CS induces mitochondrial-mediated apoptosis in NSCLC cells via downregulation of Bcl-2, XIAP and survivin. In addition, we also found that the tumors growth of subcutaneous xenograft in vivo was markedly inhibited after oral intake of CS.

  8. 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.

  9. Paracrine signaling by VEGF-C promotes non-small cell lung cancer cell metastasis via recruitment of tumor-associated macrophages.

    Science.gov (United States)

    Deng, Yanchao; Yang, Yang; Yao, Bei; Ma, Lei; Wu, Qipeng; Yang, Zhicheng; Zhang, Luyong; Liu, Bing

    2018-03-15

    High expression of tumoral vascular endothelial growth factor C (VEGF-C) is correlated with clinical non-small cell lung cancer (NSCLC) metastasis and patient survival. Nevertheless, the comprehensive mechanisms accounting for VEGF-C-mediated cancer progression remain largely unclear. The present study found that VEGF-C expression was upregulated in various NSCLC cell lines. By utilizing transwell migration assay, we found that both recombinant VEGF-C protein and overexpression of VEGF-C in NSCLC cells (A549 and H441 cell lines) could efficiently enhance RAW264.7 cell (murine macrophages) migration. However, recombinant VEGF-C treatment had no effects on both CD206 (an M2 macrophage marker) expression and M1/M2 cytokine profiles of macrophages. Furthermore, additional treatment of recombinant Flt-4/Fc, the specific VEGFR-3 inhibitor or the specific VEGFR-2 inhibitor significantly suppressed macrophage migration compared with A549-CM (conditioned medium) or H441-CM alone group, confirming that NSCLC cells-derived VEGF-C is sufficient to promote macrophage migration. Interestingly, VEGF-C could stimulate the Src/p38 signaling via VEGFR-2/3 axis in macrophages, and inhibition of Src/p38 signaling obviously reversed the enhancement effect of VEGF-C on macrophage migration. Finally, the functional importance of macrophage infiltration induced by tumoral VEGF-C in promoting metastasis was established in a mouse model. In conclusion, our results highlight a novel function of tumoral VEGF-C that paracrinely induces macrophage recruitment, and resultantly promotes NSCLC cell metastasis. Therefore, VEGF-C/VEGFR-2/3 axis may be a promising microenvironmental target against progression of NSCLC. Copyright © 2018 Elsevier Inc. All rights reserved.

  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. 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.

  12. SU-F-J-207: Non-Small Cell Lung Cancer Patient Survival Prediction with Quantitative Tumor Textures Analysis in Baseline CT

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    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.

  13. 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.

  14. The Role of Canonical and Non-Canonical Hedgehog Signaling in Tumor Progression in a Mouse Model of Small Cell Lung Cancer

    Science.gov (United States)

    Szczepny, Anette; Rogers, Samuel; Jayasekara, W. Samantha N.; Park, Kwon; McCloy, Rachael A.; Cochrane, Catherine R.; Ganju, Vinod; Cooper, Wendy A.; Sage, Julien; Peacock, Craig D.; Cain, Jason E.; Burgess, Andrew; Watkins, D. Neil

    2017-01-01

    Hedgehog (Hh) signaling regulates cell fate and self-renewal in development and cancer. Canonical Hh signaling is mediated by Hh ligand binding to the receptor Patched (Ptch), which in turn activates Gli-mediated transcription through Smoothened (Smo), the molecular target of the Hh pathway inhibitors used as cancer therapeutics. Small cell lung cancer (SCLC) is a common, aggressive malignancy with universally poor prognosis. Although preclinical studies have shown that Hh inhibitors block the self-renewal capacity of SCLC cells, the lack of activating pathway mutations have cast doubt over the significance of these observations. In particular, the existence of autocrine, ligand-dependent Hh signaling in SCLC has been disputed. In a conditional Tp53;Rb1 mutant mouse model of SCLC, we now demonstrate a requirement for the Hh ligand Sonic Hedgehog (Shh) for the progression of SCLC. Conversely, we show that conditional Shh overexpression activates canonical Hh signaling in SCLC cells, and markedly accelerates tumor progression. When compared to mouse SCLC tumors expressing an activating, ligand-independent Smo mutant, tumors overexpressing Shh exhibited marked chromosomal instability and Smoothened-independent upregulation of Cyclin B1, a putative non-canonical arm of the Hh pathway. In turn, we show that overexpression of Cyclin B1 induces chromosomal instability in mouse embryonic fibroblasts lacking both Tp53 and Rb1. These results provide strong support for an autocrine, ligand-dependent model of Hh signaling in SCLC pathogenesis, and reveal a novel role for non-canonical Hh signaling through the induction of chromosomal instability. PMID:28581526

  15. 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

  16. 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

  17. 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.

  18. 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

  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. A small molecule disruptor of Rb/Raf-1 interaction inhibits cell proliferation, angiogenesis, and growth of human tumor xenografts in nude mice.

    Science.gov (United States)

    Kinkade, Rebecca; Dasgupta, Piyali; Carie, Adam; Pernazza, Daniele; Carless, Melanie; Pillai, Smitha; Lawrence, Nicholas; Sebti, Said M; Chellappan, Srikumar

    2008-05-15

    Although it is well established that cyclin-dependent kinases phosphorylate and inactivate Rb, the Raf-1 kinase physically interacts with Rb and initiates the phosphorylation cascade early in the cell cycle. We have identified an orally active small molecule, Rb/Raf-1 disruptor 251 (RRD-251), that potently and selectively disrupts the Rb/Raf-1 but not Rb/E2F, Rb/prohibitin, Rb/cyclin E, and Rb/HDAC binding. The selective inhibition of Rb/Raf-1 binding suppressed the ability of Rb to recruit Raf-1 to proliferative promoters and inhibited E2F1-dependent transcriptional activity. RRD-251 inhibited anchorage-dependent and anchorage-independent growth of human cancer cells and knockdown of Rb with short hairpin RNA or forced expression of E2F1 rescued cells from RRD-251-mediated growth arrest. P.o. treatment of mice resulted in significant tumor growth suppression only in tumors with functional Rb, and this was accompanied by inhibition of angiogenesis, inhibition of proliferation, decreased phosphorylated Rb levels, and inhibition of Rb/Raf-1 but not Rb/E2F1 binding in vivo. Thus, selective targeting of Rb/Raf-1 interaction seems to be a promising approach for developing novel chemotherapeutic agents.

  1. A small molecule disruptor of Rb-Raf-1 interaction inhibits cell proliferation, angiogenesis and growth of human tumor xenografts in nude mice

    Science.gov (United States)

    Kinkade, Rebecca; Dasgupta, Piyali; Carie, Adam; Pernazza, Daniele; Carless, Melanie; Pillai, Smitha; Lawrence, Nicholas; Sebti, Said M.; Chellappan, Srikumar

    2011-01-01

    Though it is well established that cyclin-dependent kinases phosphorylate and inactivate Rb, the Raf-1 kinase physically interacts with Rb and initiates the phosphorylation cascade early in the cell cycle. We have identified an orally-active small molecule, RRD-251 (Rb – Raf-1 Disruptor 251), that potently and selectively disrupts the Rb/Raf-1 but not Rb/E2F, Rb/Prohibitin, Rb/Cyclin E and Rb/HDAC binding. The selective inhibition of Rb/Raf-1 binding suppressed the ability of Rb to recruit Raf-1 to proliferative promoters and inhibited E2F1-dependent transcriptional activity. RRD-251 inhibited anchorage-dependent and –independent growth of human cancer cells; and knockdown of Rb with shRNA or forced expression of E2F1 rescued from RRD251-mediated growth arrest. Oral treatment of mice resulted in significant tumor growth suppression only in tumors with functional Rb; and this was accompanied by inhibition of angiogenesis, inhibition of proliferation, decreased phospho-Rb levels, and inhibition of Rb/Raf-1 but not Rb/E2F1 binding in vivo. Thus, selective targeting of Rb-Raf-1 interaction appears to be a promising approach for developing novel chemotherapeutic agents. PMID:18483265

  2. 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

    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. 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. 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, 0.81 and 0.65 for lung window

  3. 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

  4. Tumor necrosis factor receptor 1-dependent depletion of mucus in immature small intestine: a potential role in neonatal necrotizing enterocolitis.

    Science.gov (United States)

    McElroy, Steven J; Prince, Lawrence S; Weitkamp, Jörn-Hendrik; Reese, Jeff; Slaughter, James C; Polk, D Brent

    2011-10-01

    Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. NEC is believed to occur when intestinal bacteria invade the intestinal epithelial layer, causing subsequent inflammation and tissue necrosis. Mucins are produced and secreted by epithelial goblet cells as a key component of the innate immune system and barrier function of the intestinal tract that help protect against bacterial invasion. To better understand the role of mucins in NEC, we quantified the number of mucus-containing small intestinal goblet cells present in infants with NEC and found they had significantly fewer goblet cells and Paneth cells compared with controls. To test whether inflammation has a developmentally dependent effect on intestinal goblet cells, TNF-α was injected into mice at various stages of intestinal development. TNF-α caused a loss of mucus-containing goblet cells only in immature mice and induced Muc2 and Muc3 mRNA upregulation only in mature ileum. Only minimal changes were seen in apoptosis and in expression of markers of goblet cell differentiation. TNF-α increased small intestinal mucus secretion and goblet cell hypersensitivity to prostaglandin E2 (PGE(2)), a known mucus secretagogue produced by macrophages. These TNF-α-induced changes in mucus mRNA levels required TNF receptor 2 (TNFR2), whereas TNF-α-induced loss of mucus-positive goblet cells required TNFR1. Our findings of developmentally dependent TNF-α-induced alterations on intestinal mucus may help explain why NEC is predominantly found in premature infants, and TNF-α-induced alterations of the intestinal innate immune system and barrier functions may play a role in the pathogenesis of NEC itself.

  5. Effect of p53-targeted small molecular reactivator of p53 and induction of tumor apoptosis (RITA combined with temozolomide (TMZ on the glioma cell growth in vitro

    Directory of Open Access Journals (Sweden)

    Tao Jiang

    2017-05-01

    Full Text Available Objective: To study the effect of p53-targeted small molecular reactivator of p53 and induction of tumor apoptosis (RITA combined with temozolomide (TMZ on the glioma cell growth in vitro. Methods: Human glioma cell lines U87 were cultured and randomly divided into RITA+TMZ group (treated with 5 μmol/L RITA and 10 μmol/L TMZ, TMZ group (treated with 10 μmol/L TMZ and control group (treated with drug-free DMEM. After 24 h of treatment, the expression of p53 downstream cell cycle molecules, apoptosis molecules and invasion molecules in cells were measured. Results: p21cip1, Per2, ATM and E-cadherin protein expression in RITA+TMZ group and TMZ group were significantly higher than those in control group while CDK4, CDK6, p-Rb, E2F, MDM2, c-myc, ILK, Snail and Slug protein expression were significantly lower than those in control group; p21cip1, Per2, ATM and E-cadherin protein expression in RITA+TMZ group were significantly higher than those in TMZ group while CDK4, CDK6, p-Rb, E2F, MDM2, c-myc, ILK, Snail and Slug protein expression were significantly lower than those in TMZ group. Conclusion: p53-targeted small molecular RITA combined with temozolomide treatment of glioma cells can induce p53- mediated cell cycle arrest, cell apoptosis activation and cell invasion inhibition.

  6. Usefulness of automatic quantification of immunochemical staining on whole tumor sections for correlation with oncological small animal PET studies: an example with cell proliferation, glucose transporter 1 and FDG.

    Science.gov (United States)

    Aide, Nicolas; Labiche, Alexandre; Herlin, Paulette; Paciencia, Maria; Poulain, Laurent; Dutoit, Soizic; Montravers, Françoise; Gauduchon, Pascal; Chasle, Jacques

    2008-09-01

    To highlight the use of automatic quantification of immunochemical staining on digitized images of whole tumor sections in preclinical positron emission tomography (PET) studies. Xenografted human testicular tumors (36) were imaged with 2-deoxy-2[F-18]fluoro-D: -glucose (FDG) small animal PET (SA-PET). Tumor cell proliferation and glucose transportation were assessed with cyclin A and Glut-1 immunostaining. Tumor slides were digitized and processed with PixCyt software enabling whole slide quantification, then compared with junior and senior pathologist manual scoring. Manual and automatic quantification results were correlated to FDG uptake. For cyclin A, inter- and intra-observer agreement for manual scoring was 0.52 and 0.72 and concordance between senior pathologist and automatic quantification was 0.84. Correlations between Tumor/Background ratio and tumor cell proliferation assessed by automatic quantification, junior and senior pathologists were 0.75, 0.55, and 0.61, respectively. Correlation between Tumor/Background ratio and Glut-1 assessed by automatic quantification was 0.74. Automatic quantification of immunostaining is a valuable tool to overcome inter- and intra-observer variability for correlation of cell proliferation or other markers with tumor tracer uptake.

  7. Inhibition of platelet-derived growth factor receptor α by MEDI-575 reduces tumor growth and stromal fibroblast content in a model of non-small cell lung cancer.

    Science.gov (United States)

    Laing, Naomi; McDermott, Brenda; Wen, Shenghua; Yang, David; Lawson, Deborah; Collins, Mike; Reimer, Corinne; Hall, Peter A; Andersén, Harriet; Snaith, Michael; Wang, Xin; Bedian, Vahe; Cao, Zhu A; Blakey, David

    2013-06-01

    Platelet-derived growth factor receptor α (PDGFRα) is a receptor tyrosine kinase that promotes cell survival and is expressed in both the tumor and the stromal components of human cancers. We have developed a fully human monoclonal antibody, MEDI-575, that selectively binds to human PDGFRα with high affinity, with no observable affinity for murine PDGFRα. To more fully characterize the role of PDGFRα in the regulation of tumor stroma, we evaluated the in vivo antitumor effects of MEDI-575 in tumor-bearing severe combined immunodeficient (SCID) mice and in genetically altered SCID mice expressing human PDGFRα in place of murine PDGFRα. We used the Calu-6 non-small cell lung cancer model because it lacks an in vitro proliferative response to PDGFRα activation. Antitumor activity was observed when the study was performed in mice expressing the human receptor, but no activity was observed in the mice expressing the murine receptor. Immunohistologic analysis of the tumors from mice expressing human PDGFRα showed a highly significant reduction in stromal fibroblast content and only minor changes in tumor proliferative index in tumors exposed to MEDI-575 compared with the results seen in vehicle-treated tumors or in tumors from mice expressing murine PDGFRα. Additional in vitro studies indicated that exposure of primary cancer-associated fibroblasts to MEDI-575 can directly affect proliferation and key signaling pathways in these cells. These results highlight the potential for observing antitumor activity with MEDI-575 through modulation of the stromal component of tumors and confirm that the PDGFRα pathway can play a role in maintaining a tumor microenvironment conducive to tumor growth.

  8. Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group. Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors.

    Science.gov (United States)

    von Pawel, J; von Roemeling, R; Gatzemeier, U; Boyer, M; Elisson, L O; Clark, P; Talbot, D; Rey, A; Butler, T W; Hirsh, V; Olver, I; Bergman, B; Ayoub, J; Richardson, G; Dunlop, D; Arcenas, A; Vescio, R; Viallet, J; Treat, J

    2000-03-01

    A phase III trial, Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors (CATAPULT I), was designed to determine the efficacy and safety of tirapazamine plus cisplatin for the treatment of non-small-cell lung cancer (NSCLC). Patients with previously untreated NSCLC were randomized to receive either tirapazamine (390 mg/m(2) infused over 2 hours) followed 1 hour later by cisplatin (75 mg/m(2) over 1 hour) or 75 mg/m(2) of cisplatin alone, every 3 weeks for a maximum of eight cycles. A total of 446 patients with NSCLC (17% with stage IIIB disease and pleural effusions; 83% with stage IV disease) were entered onto the study. Karnofsky performance status (KPS) was >/= 60 for all patients (for 10%, KPS = 60; for 90%, KPS = 70 to 100). Sixty patients (14%) had clinically stable brain metastases. The median survival was significantly longer (34.6 v 27. 7 weeks; P =.0078) and the response rate was significantly greater (27.5% v 13.7%; P CATAPULT I study shows that tirapazamine enhances the activity of cisplatin in patients with advanced NSCLC and confirms that hypoxia is an exploitable therapeutic target in human malignancies.

  9. Tumor Delineation and Quantitative Assessment of Glucose Metabolic Rate within Histologic Subtypes of Non-Small Cell Lung Cancer by Using Dynamic18F 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 metabolic rate and 18 F-FDG phosphorylation rate were higher in squamous cell carcinoma (SCC) than in adenocarcinoma (AC), whereas V B was lower (Mann-Whitney U test or t test, P = .003, P = .036, and P = .019, respectively). Glucose metabolic rate, 18 F-FDG phosphorylation rate, and V B were less heterogeneous in AC than in SCC (Friedman analysis of variance). Conclusion Parametric images are not superior to static images for NSCLC delineation. FLAB-based segmentation on static 18 F-FDG 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.

  10. MiR-424 Promotes Non-Small Cell Lung Cancer Progression and Metastasis through Regulating the Tumor Suppressor Gene TNFAIP1

    Directory of Open Access Journals (Sweden)

    Ming Zhang

    2017-05-01

    Full Text Available Background/Aims: This study aimed to investigate the potential roles of miR-424 expression in non-small cell lung cancer (NSCLC metastasis and growth and its underlying mechanism. Methods: The expression of miR-424 in two NSCLC cell lines (A549 and H1975 was altered by transfection with miR-424 mimic and inhibitor. Effects of miR-424 overexpression and suppression on cells migration, invasion and colony formation were analyzed. Target genes for miR-424 were predicted using bioinformatics method and then verified using luciferase assay. Effects of miR-424 expression on cell migration, invasion and proliferation were reanalyzed on the condition of TNFAIP1 was silenced. Moreover, TNFAIP1 silencing and miR-424 modified A549 cells were subcutaneous injected into node BALB/c mice to confirm the regulation of miR-424 on TNFAIP1 in regulating tumor growth. Results: Compared with the control, miR-424 overexpression significantly increased the migrated and invaded cells, as well as the proliferated colonies. TNFAIP1 was a predicted target gene for miR-424, and was negatively regulated by miR-424. TNFAIP1 silence significantly increased the migrated and invaded cells compared to that in control, while these increases were abolished by miR-424 suppression. Animal experiment further evidenced miR-424 affected tumor growth by regulating TNFAIP1. Conclusions: These data demonstrate that miR-424 may be a contributor for NSCLC progression and metastasis through involving in cell migration, invasion and proliferation via inhibiting TNFAIP1. This study may provide theoretical basis for miR-424 in NSCLC target therapeutic treatment.

  11. 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.

  12. 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

  13. 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

  14. 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 ...

  15. 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

  16. Tumores neuroectodérmicos primitivos periféricos de localización en el área orocervical: presentación de dos casos clínicos Peripheral primitive neuroectodermal tumors located in orocervical area: presentation of two clinical cases

    Directory of Open Access Journals (Sweden)

    C. Sánchez Acedo

    2010-03-01

    characteristically reveal the presence of small round cells and a translocation of the gene EWS. The prognosis in overall is very poor. Due to the small numbers of cases published the best treatment is not well defined.

  17. 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

  18. Synergies of Targeting Tumor Angiogenesis and Immune Checkpoints in Non-Small Cell Lung Cancer and Renal Cell Cancer: From Basic Concepts to Clinical Reality.

    Science.gov (United States)

    Pircher, Andreas; Wolf, Dominik; Heidenreich, Axel; Hilbe, Wolfgang; Pichler, Renate; Heidegger, Isabel

    2017-10-31

    In recent years, considerable advances concerning therapeutic strategies in patients with metastatic cancer have been achieved. Particularly in renal cell cancer (RCC) and advanced stage non-small cell lung cancer (NSCLC), immune-activating and antiangiogenic (AA) drugs (i.e., checkpoint antibodies and vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR) targeting compounds, respectively) have been successfully developed. As immune-effector cells have to enter the tumor, it is tempting to speculate that the combination of immunotherapy with AA treatment may induce synergistic effects. In this short review, we explore the theoretical background and the therapeutic potential of this novel treatment option for patients with advanced RCC or NSCLC. We discuss the growing body of evidence that pro-angiogenic factors negatively modulate the T-cell-mediated immune response and examine the preclinical evidence for testing combined immune-activating and AA therapy concepts in clinical practice. Particular attention will also be paid to potential novel treatment-related adverse events induced by combination treatment.

  19. 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.

  20. Residual tumor after laser ablation of human non-small-cell lung cancer demonstrated by ex vivo staining: correlation with invasive temperature measurements.

    Science.gov (United States)

    Hoffmann, Christian Oliver Martin; Rosenberg, Christian; Linder, Albert; Hosten, Norbert

    2012-02-01

    Histology is the gold standard for confirming thermally induced necrosis. Generally, however, no specimen is obtained from thermal ablation therapy for pathological examination. The aim of this study was to provide evidence for the relationship between temperatures reached and resulting tissue coagulation during laser ablation in a near-physiological ex vivo lung tumor model by combining viability staining and direct temperature measurement. In all, 17 human lung specimens with primary non-small-cell lung cancer (NSCLC) were examined in this study. Organs were resected with curative intent from patients of either gender (5 female, 12 male) with an average age of 65 years (51-78). Here, 11/17 specimens were subjected to interstitial laser thermal ablation in an ex vivo lung perfusion and ventilation model after surgery. A control group of 6/17 specimens was tested for viability without laser ablation. Tissue temperature was measured invasively in real-time during the ablation process using thermocouples. Afterwards, representative slices of all 17 specimens were tested for viability with triphenyltetrazolium chloride (TTC). Maximum tissue temperature Tmax[°C] measured at a distance of 10 and 20 mm from the laser tip and time of temperature exposure were correlated with the diameter of the induced coagulation as ascertained with viability staining. CH evaluated the results. Mean maximum temperature was 75.9°C ± 14.4°C at a distance of 10 mm from the laser tip and 50.3°C ± 14.6°C at a distance of 20 mm, respectively. The mean distance between the coagulation margin and the laser tip was 17.8 mm ± 7.3 mm. We found that coagulation size correlated positively with temperature. There was a clear trend towards the correlation of time over 44°C and ablation depth. Maximum temperatures did not significantly correlate with coagulation size. Laser ablation of lung tumors using the IHLP (isolated human lung perfusion) model represents a possible method for evaluating

  1. 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

  2. Assessment of the tumor malignancy after immunotherapy combined with EGFR-TKIs drug treatment of EGFR-mutant advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Lu Bai1

    2017-04-01

    Full Text Available Objective: To study the effect of immunotherapy combined with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs drug therapy on the tumor malignancy in patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC. Methods: Patients with EGFR-mutant advanced NSCLC who were treated in Xi’an No.1 Hospital and Shaanxi Provincial Tumor Hospital between May 2014 and August 2015 were selected as the research subjects and randomly divided into DC-CIK group and control group, the former received immunotherapy combined with EGFR-TKI drug therapy, and the latter received EGFR-TKI drug therapy. Before and after treatment, the cancer cell viability-related marker levels in serum as well as the antitumor immune response marker molecule expression in peripheral blood mononuclear cells were determined respectively, and the proliferation-related gene expression in lung cancer lesions were determined after treatment. Results: 2 weeks and 4 weeks after treatment, serum CEA, Cyfra21-1 and SCCA levels of both groups were significantly lower than those before treatment and serum CEA, Cyfra21-1 and SCCA levels of DC-CIK group were significantly lower than those of control group, CD3, CD4 and CD8 fluorescence intensity in peripheral blood mononuclear cells of DC-CIK group were significantly higher than those before treatment, and the CD3, CD4 and CD8 fluorescence intensity in peripheral blood mononuclear cells of control group were not significantly different from those before treatment; TCF3, MEF2D and cFLIP(L expression in lung cancer lesions of DC-CIK group were significantly lower than those of control group while FRMD8, PDCD5, caspase-3 and caspase-8 expression were significantly higher than those of control group. Conclusion: Immunotherapy combined with EGFR-TKI drug treatment of EGFR-mutant advanced nonsmall cell lung cancer (NSCLC can enhance the antitumor immune response and promote cancer cell apoptosis.

  3. Mediastinal tumor

    Science.gov (United States)

    Thymoma - mediastinal; Lymphoma - mediastinal ... mediastinal tumors in adults occur in the anterior mediastinum. They are usually cancerous (malignant) lymphomas, germ cell tumors, or thymomas. These tumors are ...

  4. Tumors and tumor-like lesions

    International Nuclear Information System (INIS)

    Koesling, S.; Stoevesandt, D.; Knipping, S.

    2007-01-01

    Tumors and tumor-like lesions are rare diseases in the paranasal sinuses. There is a great variety of histological types, but only a small number of morphological patterns on imaging. Histology is an important point in therapeutic planning. In most cases it is obtained by sampling, which is not as difficult in the sinonasal area as in other regions of the body. The main task of imaging is an exact estimation of the extent and spread of a lesion. This article discusses the possibilities and limitations of CT and MRI in the assessment of the dignity and spread of paranasal tumors and tumor-like lesions in consideration of necessary therapeutic information. Additionally, an overview of features on imaging of different paranasal tumors and tumor-like lesions is given. (orig.)

  5. 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

  6. Prognostic and predictive value of tumor-infiltrating lymphocytes for clinical therapeutic research in patients with non-small cell lung cancer

    Science.gov (United States)

    Zeng, Dong-Qiang; Yu, Yun-Fang; Ou, Qi-Yun; Li, Xiao-Yin; Zhong, Ru-Zhi; Xie, Chuan-Miao; Hu, Qiu-Gen

    2016-01-01

    Background Previous preclinical and clinical studies have shown that levels of tumor-infiltrating lymphocytes (TILs) significantly correlated with prognosis in non-small cell lung cancer (NSCLC), and survival after therapy; however, this finding remains controversial. We performed a meta-analysis, to evaluate, systematically, the clinical utilization of TIL subtypes in patients with NSCLC. Methods The PubMed, ISI Web of Science, EMBASE, and Cochrane Library databases were searched to identify relevant studies. We pooled estimates of treatment effects, and hazards were summarized using random or fixed effects models to evaluate survival outcomes. Results A total of 24 relevant studies involving 7,006 patients were eligible. The median percentage of lymph node positivity was 45.7% (95% confidence interval [CI], 37.1–56.4%). Pooled analysis shows that high levels of CD8+ TILs had a good prognostic effect on survival with a hazard ratio (HR) of 0.91 (P = 0.013) for death and 0.74 (P = 0.001) for recurrence, as did high levels of CD3+ and CD4+ TILs, with HRs of 0.77 (P = 0.009) and 0.78 (P = 0.005) for death, respectively. By contrast, high levels of FoxP3+ regulatory TILs had a worse prognostic effect for overall and recurrence-free survival, with HRs of 1.69 (P = 0.042) and 1.79 (P = 0.001), respectively. No individual study affected the results, and no publication bias was found. Conclusions Our findings support the hypothesis that TILs could be a prognostic marker in NSCLC. High-quality randomized studies are needed to verify statistically the effect of TILs on prognosis in future research. PMID:26871598

  7. 5'/ 3' imbalance strategy to detect ALK fusion genes in circulating tumor RNA from patients with non-small cell lung cancer.

    Science.gov (United States)

    Tong, Yongqing; Zhao, Zhijun; Liu, Bei; Bao, Anyu; Zheng, Hongyun; Gu, Jian; McGrath, Mary; Xia, Ying; Tan, Bihua; Song, Chunhua; Li, Yan

    2018-03-27

    Detecting an ALK fusion gene in patients with non-small cell lung cancer (NSCLC) could provide evidence to guide individualized therapy. The 5'/3' imbalance strategy for quantitative reverse transcription-PCR (RT-qPCR) was developed to detect ALK fusion genes in circulating tumor RNA (ctRNA) of NSCLC patients. This method was validated in patients with the ALK fusion gene confirmed by next generation sequencing (NGS). The amount of the ALK fusion gene detected by the new method ranged from 33.2 to 987.4, (mean 315.2), in the patients confirmed to have the ALK fusion gene (+). This is much higher than the amount of fusion gene detected in the patients who are negative for the ALK fusion gene (-). The amount detected in the ALK fusion gene (-) samples ranged from 0.36 to 13.04, (mean 4.58). In 188 NSCLC patients, the specificity and sensitivity of the method was compared to that of the FISH method. About 10.64% of the patients showed higher ALK fusion gene expression, and were classified as ALK fusion gene (+). This is identical to the percentage of patients detected by the FISH method to be ALK fusion gene (+). The cutoff value for diagnosis of ALK fusion (+) is 32.9 as determined by this method. A new RT-PCR method using a 5'/3' imbalance strategy was developed, with high specificity and sensitivity, for detection of the ALK fusion gene in ctRNA of NSCLC patients. This method can rapidly detect ALK fusion genes in patients, which will be helpful for guiding targeted therapy, particularly the individualized usage of TKIs in these patients.

  8. 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.

  9. 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

  10. The absence of HLA class I expression in non-small cell lung cancer correlates with the tumor tissue structure and the pattern of T cell infiltration.

    Science.gov (United States)

    Perea, Francisco; Bernal, Mónica; Sánchez-Palencia, Abel; Carretero, Javier; Torres, Cristina; Bayarri, Clara; Gómez-Morales, Mercedes; Garrido, Federico; Ruiz-Cabello, Francisco

    2017-02-15

    We wanted to analyze whether tumor HLA class I (HLA-I) expression influences the pattern of the immune cell infiltration and stromal cell reaction in the tumor microenvironment. Tumor tissues obtained from 57 patients diagnosed with lung carcinomas were analyzed for HLA expression and leukocyte infiltration. 28 patients out of the 57 were completely negative for HLA-I expression (49.1%) or showed a selective HLA-A locus downregulation (three patients, 5.2%). In 26 out of 57 tumors (47.8%) we detected a positive HLA-I expression but with a percentage of HLA-I negative cells between 10 and 25%. The HLA-I negative phenotype was produced by a combination of HLA haplotype loss and a transcriptional downregulation of β2-microglobulin (β2-m) and LMP2 and LMP7 antigen presentation machinery genes. The analysis and localization of different immune cell populations revealed the presence of two major and reproducible patterns. One pattern, which we designated "immune-permissive tumor microenvironment (TME)," was characterized by positive tumor HLA-I expression, intratumoral infiltration with cytotoxic T-CD8+ cells, M1-inflammatory type macrophages, and a diffuse pattern of FAP+ cancer-associated fibroblasts. In contrast, another pattern defined as "non-immune-permissive TME" was found in HLA-I negative tumors with strong stromal-matrix interaction, T-CD8+ cells surrounding tumor nests, a dense layer of FAP+ fibroblasts and M2/repair-type macrophages. In conclusion, this study revealed marked differences between HLA class I-positive and negative tumors related to tissue structure, the composition of leukocyte infiltration and stromal response in the tumor microenvironment. © 2016 UICC.

  11. Small molecule antagonists of the Wnt/β-catenin signaling pathway target breast tumor-initiating cells in a Her2/Neu mouse model of breast cancer.

    Directory of Open Access Journals (Sweden)

    Robin M Hallett

    Full Text Available BACKGROUND: Recent evidence suggests that human breast cancer is sustained by a minor subpopulation of breast tumor-initiating cells (BTIC, which confer resistance to anticancer therapies and consequently must be eradicated to achieve durable breast cancer cure. METHODS/FINDINGS: To identify signaling pathways that might be targeted to eliminate BTIC, while sparing their normal stem and progenitor cell counterparts, we performed global gene expression profiling of BTIC- and mammary epithelial stem/progenitor cell- enriched cultures derived from mouse mammary tumors and mammary glands, respectively. Such analyses suggested a role for the Wnt/Beta-catenin signaling pathway in maintaining the viability and or sustaining the self-renewal of BTICs in vitro. To determine whether the Wnt/Beta-catenin pathway played a role in BTIC processes we employed a chemical genomics approach. We found that pharmacological inhibitors of Wnt/β-catenin signaling inhibited sphere- and colony-formation by primary breast tumor cells and primary mammary epithelial cells, as well as by tumorsphere- and mammosphere-derived cells. Serial assays of self-renewal in vitro revealed that the Wnt/Beta-catenin signaling inhibitor PKF118-310 irreversibly affected BTIC, whereas it functioned reversibly to suspend the self-renewal of mammary epithelial stem/progenitor cells. Incubation of primary tumor cells in vitro with PKF118-310 eliminated their capacity to subsequently seed tumor growth after transplant into syngeneic mice. Administration of PKF118-310 to tumor-bearing mice halted tumor growth in vivo. Moreover, viable tumor cells harvested from PKF118-310 treated mice were unable to seed the growth of secondary tumors after transplant. CONCLUSIONS: These studies demonstrate that inhibitors of Wnt/β-catenin signaling eradicated BTIC in vitro and in vivo and provide a compelling rationale for developing such antagonists for breast cancer therapy.

  12. 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.

  13. Mechanisms of action and resistance to anti-angiogenic small-molecule tyrosine kinase inhibitors in preclinical breast cancer and pancreatic neuroendocrine tumor mouse models

    OpenAIRE

    Bill, Ruben

    2015-01-01

    „Cancer“ – this one term is used to name a large spectrum of different syndromes, ranging from the relatively indolent chronic lymphocytic leukemia to highly lethal cancer types such as glioblastoma multiforme with a median survival of about 15 months even when treated with upfront treatment schedules. Based on the notion that tumors critically rely on their own blood supply, targeting the tumor blood vasculature by anti-angiogenic therapeutics has been implemented as an important treatment m...

  14. 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

  15. 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

  16. Circulating Tumor Cells Enriched by the Depletion of Leukocytes with Bi-Antibodies in Non-Small Cell Lung Cancer: Potential Clinical Application.

    Directory of Open Access Journals (Sweden)

    Jian Yin

    Full Text Available It has been considered that the detection methods for circulating tumor cells (CTCs based on epithelial cell adhesion molecule (EpCAM underestimate the number of CTCs and may miss a metastatic subpopulation with cancer stem cell (CSC properties. Therefore, we investigated EpCAM-positive and -negative CTCs in non-small cell lung cancer (NSCLC patients at different stages, assessed the clinical value of these CTCs and explored their capacity in the following CSC model.CTCs were enriched by the depletion of leukocytes with bi-antibodies using a magnetic bead separation technique and then identified by the expression of EpCAM and cytokeratin 7 and 8 using multi-parameter flow cytometry. We determined the distribution of CTCs classified by the expression of EpCAM in 46 NSCLC patients with stages I to IV, assessed the diagnostic value of these CTCs by longitudinal monitoring in 4 index patients during adjuvant therapy and characterized the stemness of these CTCs by the expression of CXCR4 and CD133 in 10 patients.EpCAM-negative (E- CTCs were detected to be significantly higher than EpCAM-positive (E+ CTCs in stage IV (p = 0.003. The patients with the percentage of E-CTCs more than 95% (r > 95% were detected to be significantly increased from 13.3% in stage I-II to 61.1% in stage IV (p = 0.006. Kaplan-Meier analysis indicated that the patients with r > 95% had significantly shorter survival time than those with r ≤ 0.95 (p = 0.041. Longitudinal monitoring of CTCs indicated that the patients with a high percentage of E-CTCs in the blood were not responsive to either chemotherapy or targeted therapy. Further characterization of CTCs revealed that a stem-like subpopulation of CXCR4+CD133+ CTCs were detected to be significantly more prevalent in E-CTCs than that in E+CTCs (p = 0.005.The enrichment of CTCs by the depletion of leukocytes with bi-antibodies is a valuable method for estimating the number of CTCs, which can be potentially applied in

  17. Trapping effect on a small molecular drug with vascular-disrupting agent CA4P in rodent H22 hepatic tumor model: in vivo magnetic resonance imaging and postmortem inductively coupled plasma atomic emission spectroscopy.

    Science.gov (United States)

    Gao, Meng; Yao, Nan; Huang, Dejian; Jiang, Cuihua; Feng, Yuanbo; Li, Yue; Lou, Bin; Peng, Fei; Sun, Ziping; Ni, Yicheng; Zhang, Jian

    2015-06-01

    The aim of the present study is to verify the trapping effect of combretastatin A-4-phosphate (CA4P) on small molecular drugs in rodent tumors. Mice with H22 hepatocarcinoma were randomized into groups A and B. Magnetic resonance imaging (MRI) of T1WI, T2WI, and DWI was performed as baseline. Mice in group A were injected with Gd-DTPA and PBS. Mice in group B were injected with Gd-DTPA and CA4P. All mice undergo CE-T1WI at 0 h, 3 h, 6 h, 12 h, and 24 h. Enhancing efficacy of the two groups on CE-T1WI was compared with the signal-to-noise ratio (SNR) calculated. Concentrations of gadolinium measured by ICP-AES in the tumor were compared between groups. On the early CE-T1WI, tumors were equally enhanced in both groups. On the delayed CE-T1WI, the enhancing effect of group A was weaker than that of group B. The SNR and the concentration of gadolinium within the tumor of group A were lower than that of group B at 6 h, 12 h, and 24 h after administration. This study indicates that CA4P could improve the retention of Gd-DTPA in the tumor and MRI allowed dynamically monitoring trapping effects of CA4P on local retention of Gd-DTPA as a small molecular drug.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. Survival Model Established by Combined Serum Tumor Markers in Predicating the Effect of Erlotinib on Patients with Recurrent Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Lan Shao

    2013-12-01

    Full Text Available Objective: To investigate the relationship of serum pulmonary surfactant-associated pretein (SP-D, transforming growth factor-α (TGF-α, matrix metalloproteinases-9 (MMP-9, tissue polypeptide specific antigen (TPS and lung adenocarcinoma-related antigen (KL-6 with the effect and survival of treating advanced recurrent non-small cell lung cancer (NSCLC, and to establish a survival predication model. Methods: ELISA was applied to detect peripheral serum SP-D, TGF-α, MMP-9, TPS and KL-6 levels in 114 patients with recurrent NSCLC, and to analyze their relationship with the effect of erlotinib by combining with clinical symptoms, while one-way and multi-way analysis of variances were analyzed with Kaplan-Meier survival curve and Cox multi-way survival analysis model in order to establish the survival predication model. Results: The total effective rate and stability rate of erlotinib in 114 patients were 22.8% and 72.8% with progression-free survival (PFS and 1-year survival rate being 5.13 months and 69.3%, respectively, and they were higher in SP-D > 110 ng/mL group than in ≤ 110 ng/mL group (P= 0.011, P = 0.017. The stability rate in MMP-9 ≤ 535 ng/mL and TPS < 80 U/L groups were higher than in MMP-9 > 535 ng/mL (P = 0.009 and TPS ≥80 U/L groups (P = 0.002 respectively, while mPFS in SP-D > 110 ng/mL, MMP-9 ≤ 535 ng/mL, KL-6 < 500 U/mL and TPS < 80 U/L groups were longer than in SP-D ≤ 110 ng/mL (5.95 months vs. 3.25 months, P =0.009, MMP-9 > 535 ng/mL (5.83 months vs. 3.47 months, P = 0.046, KL-6 ≥500 U/mL (6.03 months vs. 3.40 months, P = 0.040 and TPS ≥80 U/L groups (6.15 months vs. 2.42 months, P= 0.014, respectively. Cox multi-way analysis showed that smoking history, wild EGFR genes, effective progression of terminal chemotherapy, free-of-rash during erlotinib treatment, increased LDH and TPS ≥80 U/L were independent risk factors for PFS. Additionally, patients were divided into 4 groups according to the

  4. 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

  5. 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.

  6. 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.

  7. Hu-antigen receptor (HuR) and cyclooxygenase-2 (COX-2) expression in human non-small-cell lung carcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients' survival.

    Science.gov (United States)

    Giaginis, Constantinos; Alexandrou, Paraskevi; Tsoukalas, Nikolaos; Sfiniadakis, Ioannis; Kavantzas, Nikolaos; Agapitos, Emmanuel; Patsouris, Efstratios; Theocharis, Stamatios

    2015-01-01

    Hu-antigen R (HuR) is considered to play a central role in tumor formation, growth, and metastasis by binding to messenger RNAs (mRNAs) encoding proteins such as cyclooxygenase-2 (COX-2) and inducing their expression via mRNA stabilization and/or altered translation. The present study aimed to evaluate the clinical significance of HuR and COX-2 protein expression in non-small-cell lung carcinoma (NSCLC). HuR and COX-2 expression was assessed immunohistochemically on tissue microarrays of 81 surgically resected NSCLC and was analyzed in relation with clinicopathological characteristics and patients' survival. Enhanced total HuR expression was significantly associated with tumor histological type and presence of lymph node metastases, as well as with increased tumor proliferative capacity and poor patients' outcome (p = 0.039, p = 0.017, p = 0.033, and p = 0.022, respectively). Enhanced COX-2 expression was significantly associated with the presence of lymphovascular invasion and increased tumor proliferative capacity (p = 0.031 and p = 0.023, respectively). Concomitant elevated HuR/COX-2 expression levels were significantly associated with tumor histological type and increased proliferative capacity (p = 0.002 and p = 0.045, respectively). Enhanced total HuR expression, as well as its cytoplasmic localization, was significantly associated with increased COX-2 expression (p = 0.015 and p = 0.001, respectively). The present study supported evidence that HuR may participate in malignant transformation of NSCLC, reinforcing its usefulness as potential therapeutic target in this type of neoplasia.

  8. 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.

  9. 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.

  10. DNA repair rate and etoposide (VP16) resistance of tumor cell subpopulations derived from a single human small cell lung cancer

    DEFF Research Database (Denmark)

    Hansen, Lasse Tengbjerg; Lundin, Cecilia; Helleday, Thomas

    2003-01-01

    sublines both in vivo and in vitro. Here we measured the etoposide (VP16) sensitivity together with the induction and repair of VP16- and IR-induced DNA double-strand breaks (DSBs). The two subpopulations were found to differ significantly in sensitivity to VP16, with the radioresistant 54B subline also......, a significant difference in repair of both VP16- and IR-induced DSBs, together with a difference in the levels of the DSB repair proteins DNA-dependent protein kinase (DNA-PK(cs)) and RAD51 was observed. The VP16- and radioresistant 54B subline exhibited a pronounced higher repair rate of DSBs and higher...... protein levels of both DNA-PK(cs) and RAD51 compared with the sensitive 54A subline. We suggest, that different DSB repair rates among tumor cell subpopulations of individual SCLC tumors may be a major determinant for the variation in clinical treatment effect observed in human SCLC tumors of identical...

  11. 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

  12. Small putative NANOG, SOX2, and SSEA-4-positive stem cells resembling very small embryonic-like stem cells in sections of ovarian tissue in patients with ovarian cancer.

    Science.gov (United States)

    Virant-Klun, Irma; Kenda-Suster, Natasa; Smrkolj, Spela

    2016-03-03

    In previous studies it has been found that in cell cultures of human adult ovaries there is a population of small stem cells with diameters of 2-4 μm, which are present mainly in the ovarian surface epithelium and are comparable to very small embryonic-like stem cells (VSELs) from bone marrow. These cells are not observed by histopathologists in the ovarian tissue due to their small size and unknown clinical significance. Because these cells express a degree of pluripotency, they might be involved in the manifestation of ovarian cancer. Therefore we studied the ovarian tissue sections in women with borderline ovarian cancer and serous ovarian carcinoma to perhaps identify the small putative stem cells in situ. In 27 women with borderline ovarian cancer and 20 women with high-grade serous ovarian carcinoma the ovarian tissue sections were stained, per standard practice, with eosin and hematoxylin staining and on NANOG, SSEA-4 and SOX2 markers, related to pluripotency, using immunohistochemistry. We focused on the presence and localization of small putative stem cells with diameters of up to 5 μm and with the nuclei spread over nearly the full cell volume. In ovarian sections of both borderline ovarian cancer and serous ovarian carcinoma patients we were able to identify the presence of small round cells complying with the above criteria. Some of these small cells were NANOG-positive, were located among epithelial cells in the ovarian surface epithelium and as a single cell or groups of cells/clusters in typical "chambers", were found only in the presence of ovarian cancer and not in healthy ovaries and are comparable to those in fetal ovaries. We envision that these small cells could be related to NANOG-positive tumor-like structures and oocyte-like cells in similar "chambers" found in sections of cancerous ovaries, which could support their stemness and pluripotency. Further immunohistochemistry revealed a similar population of SSEA-4 and SOX2-positive cells. We

  13. Distribution of CD4(+) and CD8(+) T cells in tumor islets and stroma from patients with non-small cell lung cancer in association with COPD and smoking.

    Science.gov (United States)

    Jackutė, Jurgita; Žemaitis, Marius; Pranys, Darius; Šitkauskienė, Brigita; Miliauskas, Skaidrius; Bajoriūnas, Vytis; Sakalauskas, Raimundas

    2015-11-01

    The immune system plays an important role in non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the infiltration patterns of CD4(+) and CD8(+) T cells in NSCLC and to analyze their relation to COPD, smoking status and other clinicopathologic variables. Lung tissue specimens from 50 patients who underwent surgery for NSCLC (stages I-III) and 10 control group subjects were analyzed immunohistochemically. NSCLC patients had a greater number of CD4(+) and CD8(+) T cells infiltrating the lung tissue than the control group (P=0.001) with predominant infiltration in the tumor stroma. We found a significant association between the number of total and tumor stroma-infiltrating CD4(+) and CD8(+) T cells, and smoking status (Psmoking seems to be associated with higher infiltration of CD8(+) T cells in the tumor stroma of patients with NSCLC. It allows us to hypothesize that NSCLC patients with coexisting COPD may have a more favorable outcome due to anticancer properties of stromal CD8(+) T cells. Copyright © 2015 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. 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...

  15. 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.

  16. Comparison of different methods for detecting epidermal growth factor receptor mutations in peripheral blood and tumor tissue of non-small cell lung cancer as a predictor of response to gefitinib

    Directory of Open Access Journals (Sweden)

    Xu F

    2012-12-01

    Full Text Available Fei Xu,1,* Jingxun Wu,2,* Cong Xue,1,* Yuanyuan Zhao,1 Wei Jiang,3 Liping Lin,4 Xuan Wu,5 Yachao Lu,6 Hua Bai,7 Jiasen Xu,8 Guanshan Zhu,6 Li Zhang11State Key Laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China; 2Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People's Republic of China; 3Department of Medical Oncology, Cancer Hospital of Guangxi Medical University and Guangxi Autonomous Regional Cancer Hospital, Nanning, Guangxi, People's Republic of China; 4Department of Oncology and Hemotology, Panyu Central Hospital, Guangzhou, Guangdong, People's Republic of China; 5Department of Chemotherapy, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China; 6Innovation Center China, AstraZeneca Global R&D, Shanghai, People's Republic of China; 7Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China; 8SurExam Bio-Tech Co, Ltd, Science City, Guangzhou, People's Republic of China *These authors contributed equally to this workBackground: Previous studies have reported that epidermal growth factor receptor (EGFR mutation in tumor tissue and peripheral blood can predict the response to EGFR tyrosine kinase inhibitor (TKI in non-small cell lung cancer (NSCLC. However, the heterogeneity of the sample sources makes it difficult to evaluate the detecting methodologies. The goal of this study is to compare different methods for analyzing EGFR mutation in blood and tumor tissue.Materials and methods: Fifty-one advanced NSCLC patients treated with gefitinib were included in the study. The EGFR mutation status of each patients' blood was analyzed by denaturing high-performance liquid chromatography (DHPLC, mutant-enriched liquidchip (ME-Liquidchip, and Scorpion

  17. MicroRNA-184 Deregulated by the MicroRNA-21 Promotes Tumor Malignancy and Poor Outcomes in Non-small Cell Lung Cancer via Targeting CDC25A and c-Myc.

    Science.gov (United States)

    Lin, Tsang-Chi; Lin, Po-Lin; Cheng, Ya-Wen; Wu, Tzu-Chin; Chou, Ming-Chih; Chen, Chih-Yi; Lee, Huei

    2015-12-01

    MicroRNA (miR)-184 has been reported to have a dual role in human cancers. However, the role of miR-184 in non-small cell lung cancer (NSCLC) remains unclear. Wild-type or mutant CDC25A promoters were constructed by PCR and site-directed mutagenesis to verify whether miR-184 could inhibit CDC25A expression at post-transcription level. Boyden chamber assay was used to assess whether miR-184 could modulate cell invasiveness via targeting CDC25A and c-Myc. We utilized 124 tumors from NSCLC patients to determine miR-184, miR-21, PDCD4 mRNA, c-Myc mRNA, and CDC25A mRNA expression levels by means of real-time PCR analysis. The prognostic value of CDC25A, c-Myc, and miR-184 on overall survival (OS) and relapse-free survival (RFS) was evaluated by Kaplan-Meier and Cox regression analysis. MiR-184 suppressed CDC25A expression by enhancing the instability of its mRNA as a result of miR-184 binding to its coding region. An increase in CDC25A expression by means of a reduction in miR-184 promotes cell invasiveness. Moreover, a concomitant increase in CDC25A and c-Myc expression as a result of decreased miR-184 via the miR-21-mediated PDCD4 reduction is responsible for cell invasiveness. Among patients, miR-184 expression in lung tumors was found to correlate negatively with CDC25A mRNA, c-Myc mRNA, and miR-21 expression, but was positively related to PDCD4 mRNA expression. High-miR-184, High-CDC25A, or high-c-Myc mRNA tumors exhibited shorter OS and RFS periods than their counterparts. The worst OS and RFS were observed in low-miR-184/high-CDC25A/high-c-Myc tumors, followed by low-miR-184 /high-CDC25A, low-miR-184/high-c-Myc, high-c-Myc, and high-CDC25A tumors. MiR-184 as a tumor suppressor miR inhibits cell proliferation and invasion capability via targeting CDC25A and c-Myc. Low miR-184 level may predict worse prognosis in NSCLC patients.

  18. 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.

    Science.gov (United States)

    Su, ShengFa; Li, Tao; Lu, Bing; Wang, XiaoHu; Li, JianCheng; Chen, Ming; Lu, You; Bai, YuJu; Hu, YinXiang; Ouyang, WeiWei; Ma, Zhu; Li, QingSong; Li, HuiQin; Wang, Yu

    2015-11-15

    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). 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. 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 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. 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 predicted survival in these patients with limited-metastasis NSCLC. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. 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

  20. Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors.

    Science.gov (United States)

    Hendry, Shona; Salgado, Roberto; Gevaert, Thomas; Russell, Prudence A; John, Tom; Thapa, Bibhusal; Christie, Michael; van de Vijver, Koen; Estrada, M V; Gonzalez-Ericsson, Paula I; Sanders, Melinda; Solomon, Benjamin; Solinas, Cinzia; Van den Eynden, Gert G G M; Allory, Yves; Preusser, Matthias; Hainfellner, Johannes; Pruneri, Giancarlo; Vingiani, Andrea; Demaria, Sandra; Symmans, Fraser; Nuciforo, Paolo; Comerma, Laura; Thompson, E A; Lakhani, Sunil; Kim, Seong-Rim; Schnitt, Stuart; Colpaert, Cecile; Sotiriou, Christos; Scherer, Stefan J; Ignatiadis, Michail; Badve, Sunil; Pierce, Robert H; Viale, Giuseppe; Sirtaine, Nicolas; Penault-Llorca, Frederique; Sugie, Tomohagu; Fineberg, Susan; Paik, Soonmyung; Srinivasan, Ashok; Richardson, Andrea; Wang, Yihong; Chmielik, Ewa; Brock, Jane; Johnson, Douglas B; Balko, Justin; Wienert, Stephan; Bossuyt, Veerle; Michiels, Stefan; Ternes, Nils; Burchardi, Nicole; Luen, Stephen J; Savas, Peter; Klauschen, Frederick; Watson, Peter H; Nelson, Brad H; Criscitiello, Carmen; O'Toole, Sandra; Larsimont, Denis; de Wind, Roland; Curigliano, Giuseppe; André, Fabrice; Lacroix-Triki, Magali; van de Vijver, Mark; Rojo, Federico; Floris, Giuseppe; Bedri, Shahinaz; Sparano, Joseph; Rimm, David; Nielsen, Torsten; Kos, Zuzana; Hewitt, Stephen; Singh, Baljit; Farshid, Gelareh; Loibl, Sibylle; Allison, Kimberly H; Tung, Nadine; Adams, Sylvia; Willard-Gallo, Karen; Horlings, Hugo M; Gandhi, Leena; Moreira, Andre; Hirsch, Fred; Dieci, Maria V; Urbanowicz, Maria; Brcic, Iva; Korski, Konstanty; Gaire, Fabien; Koeppen, Hartmut; Lo, Amy; Giltnane, Jennifer; Rebelatto, Marlon C; Steele, Keith E; Zha, Jiping; Emancipator, Kenneth; Juco, Jonathan W; Denkert, Carsten; Reis-Filho, Jorge; Loi, Sherene; Fox, Stephen B

    2017-11-01

    Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

  1. 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.

  2. 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.

  3. Ephrin (Eph) receptor A1, A4, A5 and A7 expression in human non-small cell lung carcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients' survival.

    Science.gov (United States)

    Giaginis, Constantinos; Tsoukalas, Nikolaos; Bournakis, Evangelos; Alexandrou, Paraskevi; Kavantzas, Nikolaos; Patsouris, Efstratios; Theocharis, Stamatios

    2014-02-04

    Ephrin (Eph) receptors are frequently overexpressed in a wide variety of human malignant tumors, being associated with tumor growth, invasion, metastasis and angiogenesis. The present study aimed to evaluate the clinical significance of EphA1, A4, A5 and A7 protein expression in non-small cell lung carcinoma (NSCLC). EphA1, A4, A5 and A7 protein expression was assessed immunohistochemically in tissue microarrays of 88 surgically resected NSCLC and was analyzed in relation with clinicopathological characteristics and patients' survival. Elevated EphA4 expression was significantly associated with low histopathological stage and presence of inflammation (p = 0.047 and p = 0.026, respectively). Elevated EphA7 expression was significantly associated with older patients' age, presence of fibrosis and smaller tumor size (p = 0.036, p = 0.029 and p = 0.018, respectively). EphA1, A5 and A7 expression were positively associated with tumor proliferative capacity (p = 0.047, p = 0.002 and p = 0.046, respectively). Elevated EphA4, A5 and A7 expression were identified as predictors of favourable patients' survival at both univariate (Log-rank test, 0 = 0.019, p = 0.006 and p = 0.012, respectively) and multivariate levels (Cox-regression analysis, p = 0.029, p = 0.068 and p = 0.044, respectively). The present study supported evidence that Ephs may be involved in lung cancer progression, reinforcing their utility as clinical biomarkers for patients' management and prognosis, as also as potential targets for future therapeutic interventions.

  4. 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.)

  5. Mammary tumors

    International Nuclear Information System (INIS)

    Weller, R.E.

    1988-10-01

    Mammary neoplasia is one of the more common malignancies affecting domestic species. Despite their importance, they are often over- diagnosed, undertreated and subject to several misconceptions propagated by veterinarians and pet owners alike. Mammary neoplasia is the most frequent tumor type encountered in the female accounting for almost half of all malignancies reported. The canine has the highest incidence of mammary tumors of all domestic species. In the dog, about 65 percent of mammary tumors are benign mixed tumors, and 25 percent are carcinomas. The rest are adenomas, myoepitheliomas, and malignant mixed tumors. The age distribution of mammary tumors closely follows the age distribution of most tumors in the dog. Mammary tumors are rare in dogs 2 years old, but incidence begins to increase sharply at approximately 6 years of age. Median age at diagnosis is about 10 years. No breed predilection has been consistently reported

  6. 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

  7. 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.

  8. 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 ...

  9. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

    DEFF Research Database (Denmark)

    Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas Tuxen

    2010-01-01

    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine de...

  10. 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

  11. Phyllodes Tumor in a Lactating Breast

    OpenAIRE

    Murthy, Sudha S.; Raju, K. V. V. N.; Nair, Haripreetha G.

    2016-01-01

    Phyllodes tumor is attributed to a small fraction of primary tumors of the breast. Such tumors occur rarely in pregnancy and lactation. We report a case of a 25-year-old lactating mother presenting with a lump in the left breast. Core needle biopsy was opined as phyllodes tumor with lactational changes, and subsequent wide local excision confirmed the diagnosis of benign phyllodes tumor with lactational changes. The characteristic gross and microscopic findings of a well-circumscribed lesion ...

  12. Askin's Tumor: A Dual Case Study

    Directory of Open Access Journals (Sweden)

    Bikash Shrestha

    2011-01-01

    Full Text Available Askin's tumor is a rare tumor arising from the chest wall. It is a subset of Ewing sarcoma characterized histologically by the presence of small round blue cells. It is a highly malignant tumor with guarded prognosis, which is dependent upon the extension of tumor at the time of diagnosis. A dual paper of Askin's tumors in young boys is being presented here.

  13. 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

  14. 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.

  15. Tumor vascular endothelium : Barrier or target in tumor directed drug delivery and immunotherapy

    NARCIS (Netherlands)

    Molema, Ingrid; de Leij, Lou; Meijer, D.K F

    The therapy of solid tumors with conventional chemotherapeutics, drug delivery preparations and immunomodulatory agents directed against the tumor cells is corrupted by a major barrier presented by the tumor vasculature. Permeability of the tumor blood vessels for transport of small molecules and

  16. Effects of MALAT1 on proliferation and apo- ptosis of human non-small cell lung cancer A549 cells in vitro and tumor xenograft growth in vivo by modulating autophagy.

    Science.gov (United States)

    Ma, Jun; Wu, Kaiming; Liu, Kuanzhi; Miao, Rong

    2018-01-29

    To explore the ability of MALAT1 to influence non-small cell lung cancer (NSCLC) A549 cells in vitro and tumor xenograft growth in vivo by modulating autophagy. LncRNA MALAT-1 in normal HBE cells and human NSCLC cells was measured. A549 cells were treated with si-MALAT-1, negative control and si-MALAT-1 + rapamycin. The mRNA levels of MALAT-1, P62 and LC3 was determined by the qRT-PCR and the protein levels of autophagy-related proteins by the western blotting. The CCK8 assay was performed for cell proliferation, the scratch test for cell migration, the Transwell assay for cell invasion, and the flow cytometry for cell cycle and apoptosis. Tumor xenograft in nude mice is performed to test tumorigenesis of the transfected A549 cells. The expression level of MALAT-1 in A549, SPC-A-1 and NCI-H460 cells was increased compared to HBE cells. And A549 with a high expression level of MALAT-1 were selected for cell transfection. si-MALAT-1 decreased cell proliferation, migration, invasion, and LC3-II/LC3-I ratio, reduced cell cycle progression, and increased cell apoptosis and P62 protein expression. No significant difference was found between A549 cells and A549 cells transfected with si-MALAT-1 + RAPA, A549 cells transfected with NC and A549 cells transfected with si-MALAT-1 + RAPA. Nude mice injected with A549 cells transfected with si-MALAT-1 had smallest tumor on size and weight among other nude mice. Downregulation of MALAT1 may promote apoptosis and suppress proliferation, migration and invasion of human NSCLC A549 cells by inhibiting autophagy, thereby suppressing the development of NSCLC.

  17. EGFR T790M mutation testing of non-small cell lung cancer tissue and blood samples artificially spiked with circulating cell-free tumor DNA: results of a round robin trial.

    Science.gov (United States)

    Fassunke, Jana; Ihle, Michaela Angelika; Lenze, Dido; Lehmann, Annika; Hummel, Michael; Vollbrecht, Claudia; Penzel, Roland; Volckmar, Anna-Lena; Stenzinger, Albrecht; Endris, Volker; Jung, Andreas; Lehmann, Ulrich; Zeugner, Silke; Baretton, Gustavo; Kreipe, Hans; Schirmacher, Peter; Kirchner, Thomas; Dietel, Manfred; Büttner, Reinhard; Merkelbach-Bruse, Sabine

    2017-10-01

    The European Commision (EC) recently approved osimertinib for the treatment of adult patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) harboring EGFR T790M mutations. Besides tissue-based testing, blood samples containing cell-free circulating tumor DNA (ctDNA) can be used to interrogate T790M status. Herein, we describe the conditions and results of a round robin trial (RRT) for T790M mutation testing in NSCLC tissue specimens and peripheral blood samples spiked with cell line DNA mimicking tumor-derived ctDNA. The underlying objectives of this two-staged external quality assessment (EQA) approach were (a) to evaluate the accuracy of T790M mutations testing across multiple centers and (b) to investigate if a liquid biopsy-based testing for T790M mutations in spiked blood samples is feasible in routine diagnostic. Based on a successfully completed internal phase I RRT, an open RRT for EGFR T790M mutation testing in tumor tissue and blood samples was initiated. In total, 48 pathology centers participated in the EQA. Of these, 47 (97.9%) centers submitted their analyses within the pre-defined time frame and 44 (tissue), respectively, 40 (plasma) successfully passed the test. The overall success rates in the RRT phase II were 91.7% (tissue) and 83.3% (blood), respectively. Thirty-eight out of 48 participants (79.2%) successfully passed both parts of the RRT. The RRT for blood-based EGFR testing initiated in Germany is, to the best of our knowledge, the first of his kind in Europe. In summary, our results demonstrate that blood-based genotyping for EGFR resistance mutations can be successfully integrated in routine molecular diagnostics complementing the array of molecular methods already available at pathology centers in Germany.

  18. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

    DEFF Research Database (Denmark)

    Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas Tuxen

    2010-01-01

    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine...... deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug. Experimental design: The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter insulinoma-associated 1 (INSM1...

  19. High-dose radiation improved local tumor control and overall survival in patients with inoperable/unresectable non-small-cell lung cancer: Long-term results of a radiation dose escalation study

    International Nuclear Information System (INIS)

    Kong, F.-M.; Haken, Randall K. ten; Schipper, Matthew J.; Sullivan, Molly A.; Chen, Ming; Lopez, Carlos; Kalemkerian, Gregory P.; Hayman, James A.

    2005-01-01

    Purpose: To determine whether high-dose radiation leads to improved outcomes in patients with non-small-cell lung cancer (NSCLC). Methods and Materials: This analysis included 106 patients with newly diagnosed or recurrent Stages I-III NSCLC, treated with 63-103 Gy in 2.1-Gy fractions, using three-dimensional conformal radiation therapy (3D-CRT) per a dose escalation trial. Targets included the primary tumor and any lymph nodes ≥1 cm, without intentionally including negative nodal regions. Nineteen percent of patients (20/106) received neoadjuvant chemotherapy. Patient, tumor, and treatment factors were evaluated for association with outcomes. Estimated median follow-up was 8.5 years. Results: Median survival was 19 months, and 5-year overall survival (OS) was 13%. Multivariate analysis revealed weight loss (p = 0.011) and radiation dose (p = 0.0006) were significant predictors for OS. The 5-year OS was 4%, 22%, and 28% for patients receiving 63-69, 74-84, and 92-103 Gy, respectively. Although presence of nodal disease was negatively associated with locoregional control under univariate analysis, radiation dose was the only significant predictor when multiple variables were included (p = 0.015). The 5-year control rate was 12%, 35%, and 49% for 63-69, 74-84, and 92-103 Gy, respectively. Conclusions: Higher dose radiation is associated with improved outcomes in patients with NSCLC treated in the range of 63-103 Gy

  20. The mouse small eye mutant, Del(2)Sey3H, which deletes the putative tumor suppressor region of the radiation-induced acute myeloid leukemia is susceptible to radiation

    International Nuclear Information System (INIS)

    Nitta, Yumiko; Yoshida, Kazuko; Tanaka, Kimio; Peters, Jo; Cattanach, Bruce M.

    2003-01-01

    Radiation-induced murine acute myeloid leukemia (AML) is characterized by the chromosome 2 deletions. Standing on the hypothesis that an AML suppressor gene would locate on the chromosome 2, a deletion-wide screen was performed on radiation-induced AMLs by the fluorescence in situ hybridization (FISH) method. The hemizugous deletion of the D2Mit15, a marker DNA at the 49.0cM region from the centromere, associated with the AMLs in 97 out of the 105 cases (92.4%). As the deletion region was close to the region of human WAGR syndrome (MIM194072), the mouse small eye mutants could be the animal model for radiation-induced AMLs. The mutant, Del(2)Sey3H (Sey3H) was found to delete around the 49.0cM region by the allelic loss mapping. The Sey3H showed high susceptibility to radiation to develop tumors including the myeloid leukemia with shorter latency. These finding support the existence of a putative tumor suppressor gene responsible for the radiation-leukemogenesis near the D2Mit15 region. (author)

  1. Enhanced detection of lymphovascular invasion in small rectal neuroendocrine tumors using D2-40 and Elastica van Gieson immunohistochemical analysis.

    Science.gov (United States)

    Kitagawa, Yoshiyasu; Ikebe, Dai; Hara, Taro; Kato, Kazuki; Komatsu, Teisuke; Kondo, Fukuo; Azemoto, Ryousaku; Komoda, Fumitake; Tanaka, Taketsugu; Saito, Hirofumi; Itami, Makiko; Yamaguchi, Taketo; Suzuki, Takuto

    2016-11-01

    Rectal neuroendocrine tumor (RNET) lymphovascular invasion (LVI) is regarded as an important predictor of nodal metastasis after endoscopic resection (ER). However, little is known about the frequency of immunohistochemical detection of LVI in RNETs. This study was performed to establish the actual detection of LVI rate in RNETs ≤10 mm and to evaluate associated clinical outcomes. We retrospectively reviewed the records for 98 consecutive patients treated by ER with a total of 102 RNETs ≤10 mm. Tissue sections were labeled with hematoxylin-eosin (HE) stain, the D2-40 monoclonal antibody to evaluate lymphatic invasion, and Elastica van Gieson (EVG) stain to detect venous invasion. LVI detection rate by HE versus immunohistochemical analysis was compared. Follow-up findings and clinical outcomes were also evaluated for 91 patients who were followed for ≥12 months. Lymphatic and venous invasion were detected using HE staining alone in 6.9% and 3.9% of patients, respectively, whereas they were detected using D2-40 and EVG staining in 20.6% and 47.1% of the patients, respectively. Thus, the LVI detection frequency using D2-40 and EVG staining (56.9%) was significantly higher than with HE (8.8%). Two out of seven patients who required additional surgery had regional lymph node metastases. However, among the 84 patients who were followed up without surgery, no distant metastases or recurrences were detected. Compared with HE staining, immunohistochemical analysis significantly increased the frequency of LVI detection in RNETs ≤10 mm. However, the clinical impact of LVIs detected using immunohistochemical analysis remains unclear. Clarification of the actual role of LVI using immunohistochemical analysis requires a patient long-term follow-up and outcomes. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  2. Tumor vaccines:

    OpenAIRE

    Frank, Mojca; Ihan, Alojz

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regirrcents. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tccmor aaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which imrrtune tol...

  3. WE-AB-207B-02: A Bayesian Network Approach for Joint Prediction of Tumor Control and Radiation Pneumonitis (RP) in Non-Small-Cell Lung Cancer (NSCLC)

    International Nuclear Information System (INIS)

    Luo, Y; McShan, D; Matuszak, M; Hobson, S; Jolly, S; Ten Haken, R; El Naqa, I

    2016-01-01

    Purpose: NSCLC radiotherapy treatment is a trade-off between controlling the tumor while limiting radiation-induced toxicities. Here we identify hierarchical biophysical relationships that could simultaneously influence both local control (LC) and RP by using an integrated Bayesian Networks (BN) approach. Methods: We studied 79 NSCLC patients treated on prospective protocol with 56 cases of LC and 21 events of RP. Beyond dosimetric information, each patient had 193 features including 12 clinical factors, 60 circulating blood cytokines before and during radiotherapy, 62 microRNAs, and 59 single-nucleotide polymorphisms (SNPs). The most relevant biophysical predictors for both LC and RP were identified using a Markov blanket local discovery algorithm and the corresponding BN was constructed using a score-learning algorithm. The area under the free-response receiver operating characteristics (AU-FROC) was used for performance evaluation. Cross-validation was employed to guard against overfitting pitfalls. Results: A BN revealing the biophysical interrelationships jointly in terms of LC and RP was developed and evaluated. The integrated BN included two SNPs, one microRNA, one clinical factor, three pre-treatment cytokines, relative changes of two cytokines between pre and during-treatment, and gEUDs of the GTV (a=-20) and lung (a=1). On cross-validation, the AUC prediction of independent LC was 0.85 (95% CI: 0.75–0.95) and RP was 0.83 (0.73–0.92). The AU-FROC of the integrated BN to predict both LC/RP was 0.81 (0.71–0.90) based on 2000 stratified bootstrap, indicating minimal loss in joint prediction power. Conclusions: We developed a new approach for multiple outcome utility application in radiotherapy based on integrated BN techniques. The BN developed from large-scale retrospective data is able to simultaneously predict LC and RP in NSCLC treatments based on individual patient characteristics. The joint prediction is only slightly compromised compared to

  4. Tumoral tracers

    International Nuclear Information System (INIS)

    Camargo, E.E.

    1979-01-01

    Direct tumor tracers are subdivided in the following categories:metabolite tracers, antitumoral tracers, radioactive proteins and cations. Use of 67 Ga-citrate as a clinically important tumoral tracer is emphasized and gallium-67 whole-body scintigraphy is discussed in detail. (M.A.) [pt

  5. Carcinoid Tumors

    Science.gov (United States)

    ... spread to other parts of the body. Doctors don't know what causes the mutations that can lead to carcinoid tumors. But they know that carcinoid tumors develop in neuroendocrine cells. Neuroendocrine cells are found in various organs throughout the body. They perform some nerve cell ...

  6. Animal tumors

    International Nuclear Information System (INIS)

    Gillette, E.L.

    1983-01-01

    There are few trained veterinary radiation oncologists and the expense of facilities has limited the extent to which this modality is used. In recent years, a few cobalt teletherapy units and megavoltage x-ray units have been employed in larger veterinary institutions. In addition, some radiation oncologists of human medical institutions are interested and willing to cooperate with veterinarians in the treatment of animal tumors. Carefully designed studies of the response of animal tumors to new modalities serve two valuable purposes. First, these studies may lead to improved tumor control in companion animals. Second, these studies may have important implications to the improvement of therapy of human tumors. Much remains to be learned of animal tumor biology so that appropriate model systems can be described for such studies. Many of the latter studies can be sponsored by agencies interested in the improvement of cancer management

  7. Monocyte to macrophage differentiation-associated (MMD) targeted by miR-140-5p regulates tumor growth in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weina, E-mail: liweina228@163.com [Department of Biomedical Engineering, Fourth Military Medical University, Xi’an 710032 (China); He, Fei, E-mail: hesili1027@163.com [Department of Hepatic Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032 (China)

    2014-07-18

    Highlights: • Expression of MMD is increased in lung cancer tissues. • Knockdown of MMD inhibits growth of A549 and LLC cells in vitro and in vivo. • MMD is a direct functional target of miR-140-5p. • MiR-140-5p/MMD axis regulates Erk1/2 signaling. - Abstract: Monocyte to macrophage differentiation-associated (MMD) is identified in macrophages as a gene associated with the differentiation from monocytes to macrophages. Recent microarray analysis for non-small cell lung cancer (NSCLC) suggests that MMD is an important signature associated with relapse and survival among patients with NSCLC. Therefore, we speculate that MMD likely plays a role in lung cancer. In this study, we found that the protein level of MMD was increased in lung cancer compared to benign lung tissues, and knockdown of MMD inhibited the growth of A549 and Lewis lung cancer cells (LLC) in vitro and in vivo. Integrated analysis demonstrated that MMD was a direct functional target of miR-140-5p. Furthermore, we found that miR-140-5p/MMD axis could affect the cell proliferation of lung cancer cells by regulating Erk signaling. Together, our results highlight the significance of miR-140-5p/MMD axis in lung cancer, and miR-140-5p/MMD axis could serve as new molecular targets for the therapy against lung cancer.

  8. Comparative intracellular uptake of adriamycin and 4'-deoxydoxorubicin by non-small cell lung tumor cells in culture and its relationship to cell survival.

    Science.gov (United States)

    Kerr, D J; Kerr, A M; Freshney, R I; Kaye, S B

    1986-08-15

    4'-Deoxydoxorubicin (4'-deoxy) is a new adriamycin analogue with a similar spectrum of antitumour activity but is significantly more lipophilic than the parent compound. We report the kinetics and uptake of the two drugs by human non-small cell lung tumour cells in monolayer culture and the relationship between intracellular drug levels and cytotoxicity. The rate and degree of cell uptake of 4'-deoxy (Vmax = 30 ng/10(5) cells/min) was greater than that of adriamycin (Vmax = 0.15 ng/10(5) cells/min). Although for a given intracellular drug concentration adriamycin was more lethal, on the basis of extracellular drug concentration, cell kill was virtually identical. The log cell survival vs intracellular drug concentration plot was linear for adriamycin but biphasic for 4'-deoxy. Intracellular distribution of the two drugs was followed by fluorescent microscopy and it was apparent that adriamycin was localized mainly within the nucleus whereas 4'-deoxy accumulated within the cytoplasm. Our results suggest that the relationship between intracellular distribution of the two drugs could reflect different modes of action for the drugs with respect to binding sites or could be a non-specific phenomenon, unrelated to lethal effects.

  9. Panels of tumor-derived RNA markers in peripheral blood of patients with non-small cell lung cancer: their dependence on age, gender and clinical stages.

    Science.gov (United States)

    Chian, Chih-Feng; Hwang, Yi-Ting; Terng, Harn-Jing; Lee, Shih-Chun; Chao, Tsui-Yi; Chang, Hung; Ho, Ching-Liang; Wu, Yi-Ying; Perng, Wann-Cherng

    2016-08-02

    Peripheral blood mononuclear cell (PBMC)-derived gene signatures were investigated for their potential use in the early detection of non-small cell lung cancer (NSCLC). In our study, 187 patients with NSCLC and 310 age- and gender-matched controls, and an independent set containing 29 patients for validation were included. Eight significant NSCLC-associated genes were identified, including DUSP6, EIF2S3, GRB2, MDM2, NF1, POLDIP2, RNF4, and WEE1. The logistic model containing these significant markers was able to distinguish subjects with NSCLC from controls with an excellent performance, 80.7% sensitivity, 90.6% specificity, and an area under the receiver operating characteristic curve (AUC) of 0.924. Repeated random sub-sampling for 100 times was used to validate the performance of classification training models with an average AUC of 0.92. Additional cross-validation using the independent set resulted in the sensitivity 75.86%. Furthermore, six age/gender-dependent genes: CPEB4, EIF2S3, GRB2, MCM4, RNF4, and STAT2 were identified using age and gender stratification approach. STAT2 and WEE1 were explored as stage-dependent using stage-stratified subpopulation. We conclude that these logistic models using different signatures for total and stratified samples are potential complementary tools for assessing the risk of NSCLC.

  10. Development of irradiation techniques and assessment of tumor response carbon ion radiotherapy in ultra-short fraction and time for a small lung cancer

    International Nuclear Information System (INIS)

    Baba, Masayuki; Miyamoto, Tadaaki; Sugawara, Toshiyuki

    2005-01-01

    For planning safety carbon therapy for lung cancer, the minimum (threshold) dose to generate lung reaction on CT image was investigated at each fraction regimen. From 1995 January to 2003 December, 44 patients with stage I non-small cell lung cancer who were treated with carbon ion beams of various fractions (1-12 fractions a port) and total doses (28-90 GyE). The 78 irradiated fields for the early reaction (within 6 months) and 67 for the late (1 year after) were divided into the two groups: the positive (+) and the negative (-) after the reactions on CT image were graded according to Libshits's criteria. The α/βvalue of biological effective dose (BED) responsive curve was determined by assuming the biserial correlation coefficient between positive rate of lung reaction and BED dose. From the BED responsive curve, in turn, the dose responsive curve for lung reaction rate at each fraction regimen was obtained. Based on the curve, D10 (to generate the lung reaction at 10% of the patients) in single fraction regimen was determined to be 10.6 GyE for the late reaction and 9.96 GyE for the early reaction, respectively. These doses seem to be very useful to estimate lung injuries in singe-dose irradiation. (author)

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

    Directory of Open Access Journals (Sweden)

    Jun Nishio

    2011-01-01

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

  12. Tumors and tumor-like lesions; Tumoren und tumoraehnliche Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Koesling, S.; Stoevesandt, D. [Klinik fuer Diagnostische Radiologie, Martin-Luther-Univ. Halle-Wittenberg, Halle (Germany); Knipping, S. [Universitaetsklinik und Poliklinik fuer Hals-, Nasen-, Ohrenheilkunde, Kopf- und Halschirurgie, Martin-Luther-Univ. Halle-Wittenberg, Halle (Germany)

    2007-07-15

    Tumors and tumor-like lesions are rare diseases in the paranasal sinuses. There is a great variety of histological types, but only a small number of morphological patterns on imaging. Histology is an important point in therapeutic planning. In most cases it is obtained by sampling, which is not as difficult in the sinonasal area as in other regions of the body. The main task of imaging is an exact estimation of the extent and spread of a lesion. This article discusses the possibilities and limitations of CT and MRI in the assessment of the dignity and spread of paranasal tumors and tumor-like lesions in consideration of necessary therapeutic information. Additionally, an overview of features on imaging of different paranasal tumors and tumor-like lesions is given. (orig.)

  13. Joint Serum Tumor Markers Serve as survival predictive model of Erlotinib in the treatment of recurrent Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Lan SHAO

    2014-05-01

    Full Text Available Background and objective Molecular targeting therapy is the direction of individualized treatment of lung cancer, scholars has been established targeted therapy prediction models which provide more guidance for clinical individual therapy. This study investigated the relationship among pulmonary surfactant-associated protein D (SP-D, transforming growth factor α (TGF-α, matrix metalloproteinase 9 (MMP-9, tissue polypeptide specific antigen (TPS, and Krebs von den Lungen-6 (KL-6 and response as well as survival in the patients with recurrent non-small cell lung cancer, which Erlotinib was as second line treatment after failure to chemotherapy. This study also established a predictive prognostic model. Methods Serum levels of SP-D, TGF-α, MMP-9, TPS, and KL-6 in 114 patients before erlotinib treatment were detected by ELISA method. Combined with clinical factors, these levels were used to investigate the relationship with efficacy in erlotinib treatment and construct a predicted prognostic model by Kaplan-Meier curve and Cox proportional hazard model multivariate analysis. Results The objective response rate (ORR and disease control rate (DCR in the 114 patients, were 22.8% (26/114 and 72.8% (83/114, to Erlotinib treatment respectively. The median progression-free survival (PFS and one year survival rate with Erlotinib treatment were 5.13 months and 69.3%, respectively. Patients in the SP-D>110 ng/mL group exhibited more ORR (33.3% vs 13.3%, P=0.011 and DCR (83.3% vs 63.3%, P=0.017 than those in the ≤110 ng/mL group. Patients in the MMP-9≤535 ng/mL group showed more DCR (83.9% than those in the >535 ng/mL group (62.1% (P=0.009. Patients in the TPS110 ng/mL (5.95 months vs 3.25 months, P=0.009, MMP-9≤535 ng/mL (5.83 months vs 3.47 months, P=0.046, KL-6<500 U/mL (6.03 months vs 3.40 months, P=0.040, and TPS<80 U/L (6.15 months vs 2.42 months, P=0.014 groups showed better PFS. Multivariate analysis showed that current or ever-smoker, wild

  14. Influence of Interfraction Interval on Local Tumor Control in Patients With Limited-Disease Small-Cell Lung Cancer Treated With Radiochemotherapy

    International Nuclear Information System (INIS)

    Jeremic, Branislav; Milicic, Biljana

    2007-01-01

    Purpose: To investigate the influence of interfraction interval (IFI) on local recurrence-free survival (LRFS) in patients with limited-disease small-cell lung cancer (LD SCLC) treated with accelerated hyperfractionated radiotherapy (Acc Hfx RT) and concurrent cisplatin and etoposide (PE). Methods and Materials: A total of 103 patients were treated with either 'early' (Cycle 1) or 'late' (Cycle 4) concurrent Acc Hfx RT/PE. Two daily fractions were nonrandomly given using an IFI of either 4.5-5.0 h ('shorter') (n = 52) or 5.5-6.0 h ('longer') (n = 51). Results: The median LRFS and 5-year LRFS rate for all 103 patients were 52 months and 48%, respectively. Besides gender, Karnofsky performance status, and treatment group, IFI also influenced LRFS, whereas age and weight loss did not. When a multivariate model was used, IFI was marginally insignificant (p = 0.0770) as a predictor of LRFS. In terms of individual treatment groups, IFI was not significant in 'early' Acc Hfx RT/PE but showed a strong trend in a 'late' Acc Hfx RT/PE regimen. Although a shorter IFI led to a higher incidence of high-grade (≥3) esophagitis, leukopenia, and infection, a correlation analysis of toxicities with all potential prognostic factors showed that a shorter IFI was not an independent predictor of any acute high-grade toxicity. Conclusion: 'Shorter' IFI had a marginally insignificant influence on LRFS. A strong trend favoring it was observed in patients treated with 'late' concurrent Acc Hfx RT/PE. This may be of interest because it could contribute to further understanding of potential biologic parameters influencing treatment outcome

  15. Adrenocortical tumors in children

    Directory of Open Access Journals (Sweden)

    R.C. Ribeiro

    2000-10-01

    Full Text Available Childhood adrenocortical tumors (ACT are rare. In the USA, only about 25 new cases occur each year. In Southern Brazil, however, approximately 10 times that many cases are diagnosed each year. Most cases occur in the contiguous states of São Paulo and Paraná. The cause of this higher rate has not been identified. Familial genetic predisposition to cancer (p53 mutations and selected genetic syndromes (Beckwith-Wiedemann syndrome have been associated with childhood ACT in general but not with the Brazilian counterpart. Most of the affected children are young girls with classic endocrine syndromes (virilizing and/or Cushing. Levels of urinary 17-ketosteroids and plasma dehydroepiandrosterone sulfate (DHEA-S, which are abnormal in approximately 90% of the cases, provide the pivotal clue to a diagnosis of ACT. Typical imaging findings of pediatric ACT consist of a large, well-defined suprarenal tumor containing calcifications with a thin capsule and central necrosis or hemorrhage. The pathologic classification of pediatric ACT is troublesome. Even an experienced pathologist can find it difficult to differentiate carcinoma from adenoma. Surgery is the single most important procedure in the successful treatment of ACT. The role of chemotherapy in the management of childhood ACT has not been established although occasional tumors are responsive to mitotane or cisplatin-containing regimens. Because of the heterogeneity and rarity of the disease, prognostic factors have been difficult to establish in pediatric ACT. Patients with incomplete tumor resection or with metastatic disease at diagnosis have a dismal prognosis. In patients with localized and completely resected tumors, the size of the tumor has predictive value. Patients with large tumors have a much higher relapse rate than those with small tumors.

  16. Application of serum microRNA-9-5p, 21-5p, and 223-3p combined with tumor markers in the diagnosis of non-small-cell lung cancer in Yunnan in southwestern China.

    Science.gov (United States)

    Yang, Yanlong; Chen, Kai; Zhou, Yongchun; Hu, Zaoxiu; Chen, Shuai; Huang, Yunchao

    2018-01-01

    Xuanwei City is located in late Permian coal-accumulating areas of the northeastern region of Yunnan Province. In China, morbidity and mortality from lung cancer are highest in Yunnan. Identifying useful circulating markers suitable for the diagnosis of lung cancer in this region is quite meaningful. In this study, we evaluated diagnostic roles of serum miR-9-5p, 21-5p, 223-3p, 135b-5p, 339-5p, and 501-5p in patients with non-small-cell lung cancer (NSCLC) in Yunnan. Moreover, we evaluated the diagnostic performance of several tumor markers, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA21-1), and squamous cell carcinoma-related antigen (SCC). Quantitative real-time polymerase chain reaction detected six miRNAs in the serum of 104 NSCLC patients and 50 cancer-free controls. Other markers, including CEA, CYFRA21-1, and SCC, in serum were also measured. The diagnostic ability of miRNAs and tumor markers was evaluated by receiver operating characteristic (ROC) curve analysis. The diagnostic performance of these serum markers was also evaluated in Xuanwei and non-Xuanwei subjects, because the etiological and the epidemiological characteristics of lung cancer in Xuanwei were quite different from those in other regions. Serum miR-9-5p, miR-21-5p, miR-223-3p, CEA, CYFRA21-1, and SCC were upregulated in NSCLC patients, compared with cancer-free controls. No significant difference was found in miR-135b-5p, miR-339-5p, and miR-501-5p expression. The area under ROC curves (AUCs) of miR-9-5p, miR-21-5p, miR-223-3p, CEA, CYFRA21-1, and SCC were 0.706, 0.765, 0.744, 0.749, 0.735, and 0.616, respectively. When combined, miRNAs and tumor markers yielded the highest diagnostic power, with AUC of 0.886, sensitivity of 82.69%, and specificity of 88.00%. In Xuanwei subjects, miR-223-3p and CEA may be suitable biomarkers to distinguish NSCLC from cancer-free states with AUCs of 0.752 and 0.791, respectively. The diagnostic power of the combination of mi

  17. The Oncogenic Small Tumor Antigen of Merkel Cell Polyomavirus Is an Iron-Sulfur Cluster Protein That Enhances Viral DNA Replication.

    Science.gov (United States)

    Tsang, Sabrina H; Wang, Ranran; Nakamaru-Ogiso, Eiko; Knight, Simon A B; Buck, Christopher B; You, Jianxin

    2016-02-01

    Merkel cell polyomavirus (MCPyV) plays an important role in Merkel cell carcinoma (MCC). MCPyV small T (sT) antigen has emerged as the key oncogenic driver in MCC carcinogenesis. It has also been shown to promote MCPyV LT-mediated replication by stabilizing LT. The importance of MCPyV sT led us to investigate sT functions and to identify potential ways to target this protein. We discovered that MCPyV sT purified from bacteria contains iron-sulfur (Fe/S) clusters. Electron paramagnetic resonance analysis showed that MCPyV sT coordinates a [2Fe-2S] and a [4Fe-4S] cluster. We also observed phenotypic conservation of Fe/S coordination in the sTs of other polyomaviruses. Since Fe/S clusters are critical cofactors in many nucleic acid processing enzymes involved in DNA unwinding and polymerization, our results suggested the hypothesis that MCPyV sT might be directly involved in viral replication. Indeed, we demonstrated that MCPyV sT enhances LT-mediated replication in a manner that is independent of its previously reported ability to stabilize LT. MCPyV sT translocates to nuclear foci containing actively replicating viral DNA, supporting a direct role for sT in promoting viral replication. Mutations of Fe/S cluster-coordinating cysteines in MCPyV sT abolish its ability to stimulate viral replication. Moreover, treatment with cidofovir, a potent antiviral agent, robustly inhibits the sT-mediated enhancement of MCPyV replication but has little effect on the basal viral replication driven by LT alone. This finding further indicates that MCPyV sT plays a direct role in stimulating viral DNA replication and introduces cidofovir as a possible drug for controlling MCPyV infection. MCPyV is associated with a highly aggressive form of skin cancer in humans. Epidemiological surveys for MCPyV seropositivity and sequencing analyses of healthy human skin suggest that MCPyV may represent a common component of the human skin microbial flora. However, much of the biology of the virus

  18. The early predictive value of a decrease of metabolic tumor volume in repeated {sup 18}F-FDG PET/CT for recurrence of locally advanced non-small cell lung cancer with concurrent radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Wei, E-mail: weihuang@mcw.com [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China); Liu, Bo; Fan, Min [Department of Internal Medicine Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Zhou, Tao [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China); Fu, Zheng [PET/CT center, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Zhang, Zicheng; Li, Hongsheng [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China); Li, Baosheng, E-mail: alvinbird@163.com [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China)

    2015-03-15

    Highlights: •The patients underwent the second FDG PET during the early stage of concurrent chemoradiotherapy (CCRT). •To our knowledge, this could be the first study showing that the repeated FDG PET during the early stage of CCRT has added value by being a prognostic factor for recurrence of the locally advanced NSCLC patients. •This is a result of continuous research. •The decrease of MTV was the only significant risk factor for recurrence. -- Abstract: Purpose: The aim of this study is to investigate the value of [{sup 18}F] fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F FDG PET/CT) to predict recurrence of patients with locally advanced non-small cell lung cancer (NSCLC) during the early stage of concurrent chemoradiotherapy (CCRT). Methods: A total of 53 stage III NSCLC patients without diabetics or undergoing surgery were enrolled in the prospective study. Those patients were evaluated by FDG PET before and following 40 Gy radiotherapy (RT) with a concurrent cisplatin-based heterogeneous chemotherapy regimen. Semiquantitative assessment was used to determine maximum and mean SUVs (SUVmax/SUVmean) and metabolic tumor volume (MTV) of the primary tumor. The prognostic significance of PET/CT parameters and other clinical variables was assessed using Cox regression analyses. The cutoffs of PET/CT parameters which have been determined by the previous study were used to separate the groups with Kaplan–Meier curves. Results: Recurrence rates at 1- and 2-years were 18.9% (10/53) and 50.9% (27/53) for all patients, respectively. Cox regression analysis showed that the only prognostic factor for recurrence was a decrease of MTV. Using the cutoff of 29.7%, a decrease of MTV can separate the patients into 2 groups with Kaplan–Meier curve successfully. Conclusion: The prospective study has reinforced the early predictive value of MTV in repeated {sup 18}F-FDG PET/CT for recurrence in a subgroup of locally advanced NSCLC who

  19. Tumor Grade

    Science.gov (United States)

    ... Peer Review and Funding Outcomes Step 4: Award Negotiation & Issuance Manage Your Award Grants Management Contacts Monitoring ... may require immediate or more aggressive treatment. The importance of tumor grade in planning treatment and determining ...

  20. Benign notochordal cell tumors.

    Science.gov (United States)

    Martínez Gamarra, C; Bernabéu Taboada, D; Pozo Kreilinger, J J; Tapia Viñé, M

    Benign notochordal cell tumors (TBCN) are lesions with notochordal differentiation which affect the axial skeleton. They are characterized by asymptomatic or non-specific symptomatology and are radiologically unnoticed because of their small size, or because they are mistaken with other benign bone lesions, such as vertebral hemangiomas. When they are large, or symptomatic, can be differential diagnosis with metastases, primary bone tumors and chordomas. We present a case of a TBCN in a 50-year-old woman, with a sacral lesion seen in MRI. A CT-guided biopsy was scheduled to analyze the lesion, finding that the tumor was not clearly recognizable on CT, so the anatomical references of MRI were used to select the appropriate plane. The planning of the approach and the radio-pathological correlation were determinant to reach the definitive diagnosis. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. A case of a pleomorphic hyalinizing angiectatic tumor of soft parts with intracytoplasmic hemosiderin pigment apparent upon fine-needle aspiration cytology.

    Science.gov (United States)

    Yorita, Kenji; Ishihara, Akira; Tokumitsu, Takako; Minematsu, Eiko; Ohno, Akinobu; Ikejiri, Hiroshi; Kataoka, Hiroaki

    2015-05-01

    Pleomorphic hyalinizing angiectatic tumors of soft parts are extremely rare low-grade mesenchymal lesions that frequently occur subcutaneously, especially in the lower extremity. The tumor is histologically characterized by sheets of plump, spindled or rounded cells, and clusters of ectatic blood vessels. It also has a number of previously characterized cytological features such as pleomorphic cells, intranuclear pseudoinclusion, and intracytoplasmic hemosiderin pigments. However, intracytoplasmic hemosiderin has not been carefully evaluated in cytology specimens. Here, we report the case of a 56-year-old Japanese man with an encapsulated pleomorphic hyalinizing angiectatic tumor of soft parts that included fine and coarse hemosiderin-laden tumor cells. The tumor was clinically followed up as a hematoma, but malignant tumors, including malignant melanoma, were suspected because aspiration cytology specimens contained pleomorphic cells with intracytoplasmic brown pigments. The tumor was closely associated with an intratumoral hematoma and a few microscopic satellite lesions. Pleomorphic hyalinizing angiectatic tumor of soft parts should be included in the differential cytological diagnosis of soft tissue tumors if the three cytological features described earlier are present. Enucleation therapy could facilitate local recurrence, as the tumor may have the potential to infiltrate surrounding soft tissue or form satellite lesions. © 2014 The Authors. Diagnostic Cytopathology Published by Wiley Periodicals, Inc.

  2. Computed tomography in gastrointestinal stromal tumors

    International Nuclear Information System (INIS)

    Ghanem, Nadir; Altehoefer, Carsten; Winterer, Jan; Schaefer, Oliver; Springer, Oliver; Kotter, Elmar; Langer, Mathias; Furtwaengler, Alex

    2003-01-01

    The aim of this study was to define the imaging characteristics of primary and recurrent gastrointestinal stromal tumors (GIST) in computed tomography with respect to the tumor size. Computed tomography was performed in 35 patients with histologically confirmed gastrointestinal stromal tumors and analyzed retrospectively by two experienced and independent radiologist. The following morphologic tumor characteristics of primary (n=20) and (n=16) recurrent tumors were evaluated according to tumor size, shape, homogeneity, density compared with liver, contrast enhancement, presence of calcifications, ulcerations, fistula or distant metastases and the anatomical relationship to the intestinal wall, and the infiltration of adjacent visceral organs. Small GIST ( 5-10 cm) demonstrated an irregular shape, inhomogeneous density on unenhanced and contrast-enhanced images, a combined intra- and extraluminal tumor growth with aggressive findings, and infiltration of adjacent organs in 9 primary diagnosed and 2 recurrent tumors. Large GIST (>10 cm), which were observed in 8 primary tumors and 11 recurrent tumors, showed an irregular margin with inhomogeneous density and aggressive findings, and were characterized by signs of malignancy such as distant and peritoneal metastases. Small recurrent tumors had a similar appearance as compared with large primary tumors. Computed tomography gives additional information with respect to the relationship of gastrointestinal stromal tumor to the gastrointestinal wall and surrounding organs, and it detects distant metastasis. Primary and recurrent GIST demonstrate characteristic CT imaging features which are related to tumor size. Aggressive findings and signs of malignancy are found in larger tumors and in recurrent disease. Computed tomography is useful in detection and characterization of primary and recurrent tumors with regard to tumor growth pattern, tumor size, and varied appearances of gastrointestinal stromal tumors, and indirectly

  3. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    Search Menu Facebook Twitter YouTube Flickr Instagram LinkedIn Brain Tumor Information | News & Blog Our Mission Our History Mission Leadership & Staff Financials Careers News & Blog Contact Us Donate Now Our Impact Our Impact Recent News News & ...

  4. Cryoablation for pulmonary tumor

    International Nuclear Information System (INIS)

    Kawamura, Masafumi; Izumi, Yotaro; Tsukada, Norimasa; Asakura, Keisuke; Nakatsuka, Seishi; Yashiro, Hideki; Inoue, Masanori; Kuribayashi, Sachio; Kobayashi, Koichi

    2008-01-01

    We have experienced more than 200 sessions for mainly metastatic lung tumor and small number of primary lung cancer since 2002. Cryo-probe is inserted percutaneously with local anesthesia under CT scan guide. Co-axial technique is adopted to prevent from hemorrhage and massive air leakage. The average of hospital stay after treatment is 2.6 days. Although pneumothorax was associated with more than half patients, 5% of them experienced chest tube insertion. Local recurrence 1 year after treatment was found 10% of tumors of 10 mm or less diameter, 30% of 11-20 mm diameter, and 40% of 20-30 mm diameter and 100% of 31 mm or more diameter. In case of large vessels (3 mm or more diameter) running within 4 mm from tumor, recurrence rate was higher compared with the same sized tumors without large vessels running nearby. We are eager for the development of 3D-simulation system considering the distribution of caloric value is strongly requested to improve the local control power of cryoablation for lung tumor. (author)

  5. Mediastinal tumors

    International Nuclear Information System (INIS)

    Canizares, Claudio; Araujo, Ivan; Rodriguez, Amparo; Robles, Wilson; Simba, Catalina

    2005-01-01

    In our practice the mediastinal tumors are infrequent. The mediastinum is the portion of the thoracic cavity that contains numerous organs and structures which makes a crossroad for the diagnostic process. Within which congenital cysts, inflammatory and benign tumors, malignant neoplasms may develop. In the superior compartment are found: thymoma and thymic cysts, germ cell tumors, thyroid lesions, parathyroid adenomas, malignant lymphomas, paragangliomas, hemangiomas, lipomas, and inflammatory lesions such as fibrosing mediastinitis. In the middle portion: pericardial cysts, bronchial cysts, malignant lymphomas. In the posterior region: neurogenic tumors such as Shawnomas, neurofibromas, ganglioneuroblastomas, neuroblastomas, paragangliomas, and gastro enteric cysts. We describe two cases. One of a female patient with a prominent tumor in the anterior compartment of the mediastinum, detected by the x-ray films. Initially a cardiac lesion was excluded by echographic, angiographic studies. The biopsy exhibited a prominent fibrosis that suggested fibrosing mediastinitis (sclerosing). Whoever the immunohistochemical phenotype was positive for lambda chains, determining the diagnosis of lymphoma. The other case is of a young male with a thymoma associated to a pure red cell aplasia, which was the initial clinical symptom. Computerized tomography and thyroid scintigraphy was used. (The author)

  6. Potent and selective small-molecule inhibitors of cIAP1/2 proteins reveal that the binding of Smac mimetics to XIAP BIR3 is not required for their effective induction of cell death in tumor cells.

    Science.gov (United States)

    Sun, Haiying; Lu, Jianfeng; Liu, Liu; Yang, Chao-Yie; Wang, Shaomeng

    2014-04-18

    Cellular inhibitor of apoptosis protein 1 and 2 (cIAP1/2) and X-linked inhibitor of apoptosis protein (XIAP) are key apoptosis regulators and promising new cancer therapeutic targets. This study describes a set of non-peptide, small-molecule Smac (second mitochondria-derived activator of caspases) mimetics that are selective inhibitors of cIAP1/2 over XIAP. The most potent and most selective compounds bind to cIAP1/2 with affinities in the low nanomolar range and show >1,000-fold selectivity for cIAP1 over XIAP. These selective cIAP inhibitors effectively induce degradation of the cIAP1 protein in cancer cells at low nanomolar concentrations and do not antagonize XIAP in a cell-free functional assay. They potently inhibit cell growth and effectively induce apoptosis at low nanomolar concentrations in cancer cells with a mechanism of action similar to that of other known Smac mimetics. Our study shows that binding of Smac mimetics to XIAP BIR3 is not required for effective induction of apoptosis in tumor cells by Smac mimetics. These potent and highly selective cIAP1/2 inhibitors are powerful tools in the investigation of the role of these IAP proteins in the regulation of apoptosis and other cellular processes.

  7. ERCC1 expression in circulating tumor cells (CTCs) using a novel detection platform correlates with progression-free survival (PFS) in patients with metastatic non-small-cell lung cancer (NSCLC) receiving platinum chemotherapy.

    Science.gov (United States)

    Das, Millie; Riess, Jonathan W; Frankel, Paul; Schwartz, Erich; Bennis, Robyn; Hsieh, H Ben; Liu, Xiaohe; Ly, Janey C; Zhou, Lisa; Nieva, Jorge J; Wakelee, Heather A; Bruce, Richard H

    2012-08-01

    To utilize a novel circulating tumor cell (CTC) technology to quantify ERCC1 expression on CTCs and determine whether ERCC1 expression levels predict efficacy of platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). ERCC1 expression was measured in 17 metastatic NSCLC patients who received platinum-based therapy and had ≥2 intact CTCs with acceptable ERCC1 expression assay results. ERCC1 levels were determined from average expression on individual CTCs in each sample. Progression-free survival (PFS) was calculated from the date of therapy initiation. PFS decreased with increasing ERCC1 expression (ptest, linear regression). Lack of ERCC1 expression was associated with longer PFS (266 days versus 172 days, log-rank, ptest (linear regression)). The hazard ratio is 4.38 (95% CI 1.76-10.9) for each log-change in CK value until progression was noted on imaging. Low expression of ERCC1 on CTCs correlates with PFS in patients with metastatic NSCLC receiving platinum-based therapy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Three-dimensional conformal radiation may deliver considerable dose of incidental nodal irradiation in patients with early stage node-negative non-small cell lung cancer when the tumor is large and centrally located

    International Nuclear Information System (INIS)

    Zhao Lujun; Chen Ming; Haken, Randall ten; Chetty, Indrin; Chapet, Olivier; Hayman, James A.; Kong Fengming

    2007-01-01

    Background and purpose: To determine the dose to regional nodal stations in patients with T 1-3 N 0 M 0 non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3DCRT) without intentional elective nodal irradiation (ENI). Materials and methods: Twenty-three patients with medically inoperable T 1-3 N 0 M 0 NSCLC were treated with 3DCRT without ENI. Hilar and mediastinal nodal regions were contoured on planning CT. The prescription dose was normalized to 70 Gy. Equivalent uniform dose (EUD) and other dosimetric parameters (e.g., V 40 ) were calculated for each nodal station. Results: The median EUD for the whole group ranged from 0.4 to 4.4 Gy for all elective nodal regions. Gross tumor volume (GTV) and the relationship between GTV and hilum were significantly correlated with irradiation dose to ipsilateral hilar nodal regions (P 3 (diameter ∼ 4 cm) and or having any overlap with hilum, the median EUDs were 9.6, 22.6, and 62.9 Gy for ipsilateral lower paratracheal, subcarinal, and ipsilateral hilar regions, respectively. The corresponding median V 40 were 32.5%, 39.3%, and 97.6%, respectively. Conclusions: Although incidental nodal irradiation dose is low in the whole group, the dose to high-risk nodal regions is considerable in patients with T 1-3 N 0 NSCLC when the primary is large and/or centrally located

  9. Scope of FNAC in the diagnosis of soft tissue tumors-A study from a tertiary cancer referral center in India

    Directory of Open Access Journals (Sweden)

    Rekhi Bharat

    2007-10-01

    Full Text Available Abstract Background Fine needle aspiration cytology (FNAC forms one of the first diagnostic tools in the evaluation of tumors. Its role in diagnosing soft tissue tumors (STT has been fairly documented, as well as debated. Present study was aimed at evaluating its scope in diagnosing 127 cases of soft tissue tumors. Methods Conventional Pap and MGG staining was available in all the cases. Immunocytochemistry (ICC was performed in 15 cases. Histopathological details were available in 115 cases. Results 50% cases were referred for a primary diagnosis, while 26.8% & 22.8% cases were evaluated for recurrent and metastatic lesions, respectively. Extremities were the commonest sites. On FNAC, 101 cases (79.5% were labeled as malignant, whereas 10 cases (7.9% were labeled as benign. The remaining 16 cases (11% were not categorized and were labeled as 'unsure/not specified'. Histopathological confirmation in 115 cases, gave a diagnostic accuracy of 98%, with a positive predictive value of 98% in malignant cases and a negative predictive value of 100% in benign cases. Two cases were false positive. Among the various cytological categories, 60 cases (47.2% were of spindle cell type, followed by 32 (25.2% of round cell type and 14 cases (11% of lipomatous type. Other 12 cases (9.4% were of pleomorphic type; 7 (5.5% cases of epithelioid type and remaining 2 cases were of myxoid type. All the round cell, pleomorphic and myxoid type of tumors were sarcomas, whereas 73.3% cases of spindle cell type were labeled as 'malignant'. Exact cytological sub typing was offered in 58 cases, with rhabdomyosarcoma (RMS as the most frequently sub typed tumor. The two false positive malignant cases were of fibromatosis and a pigmented schwannoma, on biopsy. Out of 28 metastatic lesions, lymph nodes were the commonest site for metastasis, with epithelioid tumors that formed highest percentage of metastatic cases. Conclusion FNAC is fairly specific and sensitive in STT

  10. Small cell glioblastoma or small cell carcinoma

    DEFF Research Database (Denmark)

    Hilbrandt, Christine; Sathyadas, Sathya; Dahlrot, Rikke H

    2013-01-01

    was admitted to the hospital with left-sided loss of motor function. A MRI revealed a 6 cm tumor in the right temporoparietal area. The histology was consistent with both glioblastoma multiforme (GBM) and small cell lung carcinoma (SCLC) but IHC was suggestive of a SCLC metastasis. PET-CT revealed...

  11. Imaging of brain tumors

    International Nuclear Information System (INIS)

    Gaensler, E.H.L.

    1995-01-01

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.)

  12. Nephrogenic tumors

    International Nuclear Information System (INIS)

    Wiesbauer, P.

    2008-01-01

    Nephroblastomas are the most common malignant renal tumors in childhood. According to the guidelines of the SIOP (Societe Internationale d'Oncologie Pediatrique) and GPOH (Gesellschaft fuer Paediatrische Onkologie und Haematologie) pre-operative chemotherapy can be started without histological confirmation and thus initial imaging studies, in particular ultrasound, play an outstanding role for diagnostic purposes

  13. PET-based analysis of tumor glucose metabolism and tumor hypoxia before and during anti-neoplastic treatment

    NARCIS (Netherlands)

    Bollineni, Vikram

    2015-01-01

    Tumor hypoxia is an important contributor to chemo-radiotherapy resistance. This has been demonstrated in several tumor types including non-small cell lung cancer and head and neck squamous cell carcinoma. Tumor hypoxia is a dynamic process, some parts of the tumor exhibit higher levels of hypoxia

  14. Pituitary gland tumors; Hypophysentumoren

    Energy Technology Data Exchange (ETDEWEB)

    Jesser, J.; Schlamp, K.; Bendszus, M. [Radiologische Klinik, Universitaetsklinikum Heidelberg, Abteilung fuer Neuroradiologie, Heidelberg (Germany)

    2014-10-15

    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.) [German] Diese Arbeit ist eine Uebersicht ueber die haeufigsten Hypophysentumoren und deren Differenzialdiagnosen mit Augenmerk auf die

  15. A genome-wide siRNA screen for regulators of tumor suppressor p53 activity in human non-small cell lung cancer cells identifies components of the RNA splicing machinery as targets for anticancer treatment.

    Science.gov (United States)

    Siebring-van Olst, Ellen; Blijlevens, Maxime; de Menezes, Renee X; van der Meulen-Muileman, Ida H; Smit, Egbert F; van Beusechem, Victor W

    2017-05-01

    Reinstating wild-type tumor suppressor p53 activity could be a valuable option for the treatment of cancer. To contribute to development of new treatment options for non-small cell lung cancer (NSCLC), we performed genome-wide siRNA screens for determinants of p53 activity in NSCLC cells. We identified many genes not previously known to be involved in regulating p53 activity. Silencing p53 pathway inhibitor genes was associated with loss of cell viability. The largest functional gene cluster influencing p53 activity was mRNA splicing. Prominent p53 activation was observed upon silencing of specific spliceosome components, rather than by general inhibition of the spliceosome. Ten genes were validated as inhibitors of p53 activity in multiple NSCLC cell lines: genes encoding the Ras pathway activator SOS1, the zinc finger protein TSHZ3, the mitochondrial membrane protein COX16, and the spliceosome components SNRPD3, SF3A3, SF3B1, SF3B6, XAB2, CWC22, and HNRNPL. Silencing these genes generally increased p53 levels, with distinct effects on CDKN1A expression, induction of cell cycle arrest and cell death. Silencing spliceosome components was associated with alternative splicing of MDM4 mRNA, which could contribute to activation of p53. In addition, silencing splice factors was particularly effective in killing NSCLC cells, albeit in a p53-independent manner. Interestingly, silencing SNRPD3 and SF3A3 exerted much stronger cytotoxicity to NSCLC cells than to lung fibroblasts, suggesting that these genes could represent useful therapeutic targets. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  16. A potential new enriching trial design for selecting non-small-cell lung cancer patients with no predictive biomarker for trials based on both histology and early tumor response: further analysis of a thalidomide trial.

    Science.gov (United States)

    Lee, Siow Ming; Hackshaw, Allan

    2013-06-01

    There are few predictive biomarkers for antiangiogenic trials in lung cancer. We examine a potential treatment strategy in which a patient group is enriched using both histology and an early assessment of response during standard chemotherapy, and where a new agent is given for the remainder of chemotherapy and as maintenance. We performed a retrospective analysis of 722 stage IIIB/IV non-small-cell lung cancer patients from a double-blind placebo-controlled trial of thalidomide or placebo 100-200 mg/day, combined with gemcitabine/carboplatin (for up to four cycles), then given as single agent maintenance therapy. There was a significant statistical interaction between treatment and histology, with a possible benefit among squamous cell cancer (SCC) patients. We examined 150 SCC patients who were "nonprogressors" (stable disease or complete/partial response) after completing the second chemotherapy cycle. Endpoints were progression-free survival (PFS) and overall survival (OS). Among the 150 patients nonprogressors after cycle 2 (thalidomide, n = 72; placebo, n = 78; baseline characteristics were similar), the hazard ratios (HRs) were: OS = 0.76 (95% CI: 0.54-1.07) and PFS = 0.69 (95% CI: 0.50-0.97). In 57 patients who had a complete/partial response, the HRs were: OS = 0.63 (95% CI: 0.34-1.15) and PFS = 0.50 (95% CI: 0.28-0.88). SCC patients who were nonprogressors after 2 cycles of standard chemotherapy showed evidence of a benefit from thalidomide when taken for the remainder of chemotherapy and as maintenance. This strategy based on histology and, importantly, early assessment of tumor response, as a means of patient enrichment, could be examined in other lung cancer studies. Such an approach might be suitable for trials where there are no predictive biomarkers.

  17. Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.

    Directory of Open Access Journals (Sweden)

    Ioannis Boukovinas

    Full Text Available BACKGROUND: Overexpression of RRM1 and RRM2 has been associated with gemcitabine resistance. BRCA1 overexpression increases sensitivity to paclitaxel and docetaxel. We have retrospectively examined the effect of RRM1, RRM2 and BRCA1 expression on outcome to gemcitabine plus docetaxel in advanced non-small-cell lung cancer (NSCLC patients. METHODOLOGY AND PRINCIPAL FINDINGS: Tumor samples were collected from 102 chemotherapy-naïve advanced NSCLC patients treated with gemcitabine plus docetaxel as part of a randomized trial. RRM1, RRM2 and BRCA1 mRNA levels were assessed by quantitative PCR and correlated with response, time to progression and survival. As BRCA1 levels increased, the probability of response increased (Odds Ratio [OR], 1.09: p = 0.01 and the risk of progression decreased (hazard ratio [HR], 0.99; p = 0.36. As RRM1 and RRM2 levels increased, the probability of response decreased (RRM1: OR, 0.97; p = 0.82; RRM2: OR, 0.94; p<0.0001 and the risk of progression increased (RRM1: HR, 1.02; p = 0.001; RRM2: HR, 1.005; p = 0.01. An interaction observed between BRCA1 and RRM1 allowed patients to be classified in three risk groups according to combinations of gene expression levels, with times to progression of 10.13, 4.17 and 2.30 months (p = 0.001. Low BRCA1 expression was the only factor significantly associated with longer time to progression in 31 patients receiving cisplatin-based second-line therapy. CONCLUSIONS: The mRNA expression of BRCA1, RRM1 and RRM2 is potentially a useful tool for selecting NSCLC patients for individualized chemotherapy and warrants further investigation in prospective studies.

  18. Tumor-induced osteomalacia

    Directory of Open Access Journals (Sweden)

    Pablo Florenzano

    2017-12-01

    Full Text Available Tumor-induced osteomalacia (TIO is a rare paraneoplastic syndrome clinically characterized by bone pain, fractures and muscle weakness. It is caused by tumoral overproduction of fibroblast growth factor 23 (FGF23 that acts primarily at the proximal renal tubule, decreasing phosphate reabsorption and 1α-hydroxylation of 25 hydroxyvitamin D, thus producing hypophosphatemia and osteomalacia. Lesions are typically small, benign mesenchymal tumors that may be found in bone or soft tissue, anywhere in the body. In up to 60% of these tumors, a fibronectin-1(FN1 and fibroblast growth factor receptor-1 (FGFR1 fusion gene has been identified that may serve as a tumoral driver. The diagnosis is established by the finding of acquired chronic hypophosphatemia due to isolated renal phosphate wasting with concomitant elevated or inappropriately normal blood levels of FGF23 and decreased or inappropriately normal 1,25-OH2-Vitamin D (1,25(OH2D. Locating the tumor is critical, as complete removal is curative. For this purpose, a step-wise approach is recommended, starting with a thorough medical history and physical examination, followed by functional imaging. Suspicious lesions should be confirmed by anatomical imaging, and if needed, selective venous sampling with measurement of FGF23. If the tumor is not localized, or surgical resection is not possible, medical therapy with phosphate and active vitamin D is usually successful in healing the osteomalacia and reducing symptoms. However, compliance is often poor due to the frequent dosing regimen and side effects. Furthermore, careful monitoring is needed to avoid complications such us secondary/tertiary hyperparathyroidism, hypercalciuria, and nephrocalcinosis. Novel therapeutical approaches are being developed for TIO patients, such as image-guided tumor ablation and medical treatment with the anti-FGF23 monoclonal antibody KRN23 or anti FGFR medications. The case of a patient with TIO is presented to

  19. Neuroendocrine Tumors of the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Fisseler-Eckhoff, Annette, E-mail: Annette.Fisseler-Eckhoff@hsk-wiesbaden.de; Demes, Melanie [Department of Pathology und Cytology, Dr. Horst-Schmidt-Kliniken (HSK), Wiesbaden 65199 (Germany)

    2012-07-31

    Neuroendocrine tumors may develop throughout the human body with the majority being found in the gastrointestinal tract and bronchopulmonary system. Neuroendocrine tumors are classified according to the grade of biological aggressiveness (G1–G3) and the extent of differentiation (well-differentiated/poorly-differentiated). The well-differentiated neoplasms comprise typical (G1) and atypical (G2) carcinoids. Large cell neuroendocrine carcinomas as well as small cell carcinomas (G3) are poorly-differentiated. The identification and differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. Pulmonary neuroendocrine tumors are characterized according to the proportion of necrosis, the mitotic activity, palisading, rosette-like structure, trabecular pattern and organoid nesting. The given information about the histopathological assessment, classification, prognosis, genetic aberration as well as treatment options of pulmonary neuroendocrine tumors are based on own experiences and reviewing the current literature available. Most disagreements among the classification of neuroendocrine tumor entities exist in the identification of typical versus atypical carcinoids, atypical versus large cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas versus small cell carcinomas. Additionally, the classification is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts in small biopsies which can be compressed in cytological specimens. Until now, pulmonary neuroendocrine tumors have been increasing in incidence. As compared to NSCLCs, only little research has been done with respect to new molecular targets as well as improving the classification and differential diagnosis of neuroendocrine tumors of the lung.

  20. A Rare Gestational Trophoblastic Disease: Placental Site Trophoblastic Tumor

    Directory of Open Access Journals (Sweden)

    Senem Yaman Tunç

    2016-12-01

    PSTT is a rare tumor. In contrast to other trophoblastic tumors, PSTT produces a small amount of ß-HCG and it is relatively insensitive to chemotherapy. Adjuvant chemotherapy is suggested to follow surgical treatment in the cases with metastasis.

  1. 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...... increased amounts of cholecystokinin, the concentrations being extremely high in two: 8281 and 13,453 pmol per gram as compared with less than 30 pmol per gram in normal pituitary glands. The cholecystokinin concentrations were moderately increased in adenomas from another 12 patients, of whom 5 had Cushing......'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....

  2. Peculiarities in the CT findings of germ cell tumors in various tumor localizations

    International Nuclear Information System (INIS)

    Tazoe, Makoto; Miyagami, Mitsusuke; Tsubokawa, Takashi

    1991-01-01

    The CT findings of 17 germ cell tumors were studied in relation to the locations of the tumor, the pathological diagnoses, and the tumor markers (AFP and HCG). Generally, the CT findings of germ cell tumors depended on the pathological diagnoses more strongly than on the location of the tumors. On plain CT of 7 germ cell tumors in the pineal region, all of them demonstrated heterogeneous findings. Hydrocephalus was seen in 6 cases (86%) and calcification in 6 cases (86%) of the germ cell tumors in the pineal region. Calcification and hydrocephalus that appeared more often than in other regions were characteristic of germ cell tumors of the pineal region. The germ cell tumors in the basal ganglia had a slightly homogenous high density, with small cysts and calcification in most of them on plain CT. On enhanced CT, the tumors were moderately enhanced in all cases located in the basal ganglia. Four cases of germ cell tumors located in the basal ganglia revealed the dilatation of lateral ventricle due to hemispheric atrophy in the tumor side. The germ cell tumors showing an increase in the tumor markers such as AFP and HCG, which were usually malignant germ cell tumors, were strongly enhanced on enhanced CT. (author)

  3. Adrenal Gland Tumors: Statistics

    Science.gov (United States)

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  4. Brain Tumor Symptoms

    Science.gov (United States)

    ... Brain Anatomy Brain Tumor Symptoms Headaches Seizures Memory Depression Mood Swings & Cognitive Changes Fatigue Other Symptoms Diagnosis Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning About Us ...

  5. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  6. Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

    Science.gov (United States)

    2018-01-12

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Melanoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Pheochromocytoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

  7. Strategic management of adrenal tumors.

    Science.gov (United States)

    Schmidt, N

    1994-02-01

    Adrenal tumors--large and small, symptomatic and asymptomatic, benign and malignant--are being diagnosed with increasing frequency. Patients presenting with endocrine syndromes symptomatic of adrenal tumors require meticulous, considerate history taking, thorough physical examination, and careful planning for medical management and/or surgical removal. Adrenal tumors discovered in the absence of endocrine syndromes, and which are greater than 5 cm in diameter, require careful biochemical and imaging investigation before removal, since their rate of malignancy increases with size. Adrenal masses less than 4 cm in diameter present in the absence of endocrine syndromes can, after full endocrine and imaging evaluation, be carefully observed. Even with optimal surgical/medical management, malignant disease of the adrenal glands presents a poor outcome. This paper reviews the broad management of adrenal tumors, including a personal experience with a challenging case of adrenal adenocarcinoma.

  8. Rare tumors of the rectum. Narrative review.

    Science.gov (United States)

    Errasti Alustiza, José; Espín Basany, Eloy; Reina Duarte, Angel

    2014-11-01

    Most rectal neoplasms are adenocarcinomas, but there is a small percentage of tumors which are of other histological cell lines such as neuroendocrine tumors, sarcomas, lymphomas and squamous cell carcinomas, which have special characteristics and different treatments. We have reviewed these rare tumors of the rectum from a clinical and surgical point of view. Copyright © 2013 AEC. Published by Elsevier Espana. All rights reserved.

  9. Comparison of the Intraperitoneal, Retroorbital and per Oral Routes for F 18 FDG Administration as Effective Alternatives to Intravenous Administration in Mouse Tumor Models Using Small Animal PET/CT Studies

    International Nuclear Information System (INIS)

    Kim, Chulhan; Kim, In Hye; Kim, Seo il; Kim, Young Sang; Kang, Se Hun; Moon, Seung Hwan; Kim, Tae Sung; Kim, Seok ki

    2011-01-01

    We compared alternative routes for 18F fluorodeoxyglucose (FDG) administration, such as the retroorbital (RO), intraperitoneal (IP) and per oral (PO) routes, with the intravenous (IV) route in normal tissues and tumors of mice. CRL 1642 (ATCC, Lewis lung carcinoma) cells were inoculated in female BALB/c nu/nu mice 6 to 10 weeks old. When the tumor grew to about 9mm in diameter, positron emission tomography (PET) scans were performed after FDG administration via the RO, IP, PO or IV route. Additional serial PET scans were performed using the RO, IV or IP route alternatively from 5 to 29 days after the tumor cell injection. There was no significant difference in the FDG uptake in normal tissues at 60 min after FDG administration via RO, IP and IV routes. PO administration, however, showed delayed distribution and unwanted high gastrointestinal uptake. Tumoral uptake of FDG showed a similar temporal pattern and increased until 60 min after FDG administration in the RO, IP and IV injection groups. In the PO administration group, tumoral uptake was delayed and reduced. There was no statistical difference among the RO, IP and IV administration groups for additional serial PET scans. RO administration is an effective alternative route to IV administration for mouse FDG PET scans using normal mice and tumor models. In addition, IP administration can be a practical alternative in the late phase, although the initial uptake is lower than those in the IV and RO groups.

  10. Ratio of mediastinal lymph node SUV to primary tumor SUV in {sup 18}F-FDG PET/CT for nodal staging in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jae Hyuk; Choe, Jae Gol; Pahk, Kisoo; Choi, Sun Ju; Kwon, Hye Ryeong; Kim, Sun Geun [Dept. of Nuclear Medicine, Korea University Anam Hospital, Seoul (Korea, Republic of); Eo, Jae Seon; Seo, Hyo Jung [Dept. of Nuclear Medicine, Korea University Guro Hospital, Seoul (Korea, Republic of); Kim, Chul Han [Dept. of Nuclear Medicine, Korea University Ansan Hospital, Ansan (Korea, Republic of)

    2017-06-15

    Following determination of the maximum standardized uptake values (SUVmax) of the mediastinal lymph nodes (SUV-LN) and of the primary tumor (SUV-T) on 18F-FDG PET/CT in patients with non-small-cell lung cancer (NSCLC), the aim of the study was to determine the value of the SUV-LN/SUV-T ratio in lymph node staging in comparison with that of SUV-LN. We retrospectively reviewed a total of 289 mediastinal lymph node stations from 98 patients with NSCLC who were examined preoperatively for staging and subsequently underwent pathologic studies of the mediastinal lymph nodes. We determined SUV-LN and SUV-R for each lymph node station on 18F-FDG PET/CT and then classified each station into one of three groups based on SUV-T (low, medium and high SUV-T groups). Diagnostic performance was assessed based on receiver operating characteristic (ROC) curve analysis, and the optimal cut-off values that would best discriminate metastatic from benign lymph nodes were determined for each method. The average of SUV-R of malignant lymph nodes was significantly higher than that of benign lymph nodes (0.79 ± 0.45 vs. 0.36 ± 0.23, P < 0.0001). In the ROC curve analysis, the area under the curve (AUC) of SUV-R was significantly higher than that of SUV-LN in the low SUV-T group (0.885 vs. 0.810, P = 0.019). There were no significant differences between the AUCs of SUV-LN and of SUV-R in the medium and high SUV-T groups. The optimal cut-off value for SUV-R in the low SUV-T group was 0.71 (sensitivity 87.5 %, specificity 85.9 %). The SUV-R performed well in distinguishing between metastatic and benign lymph nodes. In particular, SUV-R was found to have a better diagnostic performance than SUV-LN in the low SUV-T group.

  11. Activity of drug-loaded tumor-penetrating microparticles in peritoneal pancreatic tumors.

    Science.gov (United States)

    Lu, Ze; Tsai, Max; Wang, Jie; Cole, David J; Wientjes, M Guillaume; Au, Jessie L-S

    2014-01-01

    Intraperitoneal (IP) chemotherapy confers significant survival benefits in cancer patients. However, several problems, including local toxicity and ineffectiveness against bulky tumors, have prohibited it from becoming a standard of care. We have developed drug-loaded, polymeric tumor-penetrating microparticles (TPM) to address these problems. Initial studies showed that TPM provides tumor-selective delivery and is effective against ovarian SKOV3 tumors of relatively small size (TPM activity extends to other tumor types that are more bulky and have different morphologies and disease presentation. We evaluated TPM in mice bearing two IP human pancreatic tumors with different growth characteristics and morphologies (rapidly growing, large and porous Hs766T vs. slowly growing, smaller and densely packed MiaPaCa2), and at different disease stage (early stage with smaller tumors vs. late stage with larger tumors plus peritoneal carcinomatosis). Comparison of treatments with TPM or paclitaxel in Cremophor micelles, at equi-toxic doses, shows, in all tumor types: (a) higher paclitaxel levels in tumors (up to 55-fold) for TPM, (b) greater efficacy for TPM, including significantly longer survival and higher cure rate, and (c) a single dose of TPM was equally efficacious as multiple doses of paclitaxel/Cremophor. The results indicate tumor targeting property and superior antitumor activity of paclitaxel-loaded TPM are generalizable to small and large peritoneal tumors, with or without accompanying carcinomatosis.

  12. Childhood Central Nervous System Embryonal Tumors Treatment

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... are open only to patients who have not started treatment. Children who have CNS embryonal tumors should ...

  13. Brain and Spinal Tumors: Hope through Research

    Science.gov (United States)

    ... understand, diagnose, and treat CNS tumors. Several of today’s treatment regimens were experimental therapies only a decade ... up Meeting Now That You Are Funded Small Business Grants Overview Areas of Interest Budget Information Grant ...

  14. Neuroendocrine Tumor, diagnostic difficulties

    Directory of Open Access Journals (Sweden)

    Pedro Oliveira

    2017-06-01

    Full Text Available Ectopic adrenocorticotropic hormone (ACTH secretion is a rare disease. A 51 years old woman, with a Cushing syndrome secondary to ectopic ACTH secretion, diagnosed in 2009, with mediastinal lymphadenopathy, whose biopsy was compatible with lung small cell carcinoma, staged as IIIB using TNM classification. No other lesions were found in patient study. The patient was submitted to chemotherapy, associated to ketoconazole 200 mg twice daily, with partial remission of both conditions. Three years later was admitted with an aggravation of Cushing syndrome. There was no evidence of progression of pulmonary disease. A cystic lesion in the pancreatic uncinated process was found by abdominal CT scan and with avid uptake by DOTANOC PET discreet in anterior mediastinal lymphadenopathy. Biopsy of pancreatic mass revealed a neuroendocrine tumor. Pulmonary masses were biopsied again and was in favor of neuroendocrine tumor. It was assumed the diagnosis of pancreatic neuroendocrine tumor with mediastinal metastasis. The patient initiated lanreotid (120 mg, monthly, subcutaneous in association with ketoconazole. After 5 months of therapy, patient died with sepsis secondary to pneumonia. Neuroendocrine tumours are rare, difficult to diagnose and with poor prognosis when associated with ectopic ACTH secreting Cushing syndrome.

  15. Cytomorphometric analysis of keratinized round cells in human oral carcinoma

    Directory of Open Access Journals (Sweden)

    Abhimanyu Mohanta

    2015-01-01

    Conclusion: Cellular keratinization, hyperchromasia and increased N/C ratios in both LKRCs and SKRCs indicates the state of malignancy and thus the present finding has a practical value in early detection and diagnosis of OSCC patients.

  16. Cryospectrophotometric determination of tumor intravascular oxyhemoglobin saturations: dependence on vascular geometry and tumor growth.

    Science.gov (United States)

    Fenton, B M; Rofstad, E K; Degner, F L; Sutherland, R M

    1988-12-21

    To delineate the complex relationships between overall tumor oxygenation and vascular configuration, intravascular oxyhemoglobin (HbO2) saturation distributions were measured with cryospectrophotometric techniques. Four factors related to vascular morphometry and tumor growth were evaluated: a) vessel diameter, b) distance of vessel from the tumor surface, c) tumor volume, and d) vascular density. To measure intertumor heterogeneity, two murine sarcomas (RIF-1 and KHT) and two human ovarian carcinoma xenografts (OWI and MLS) were utilized. In contrast to skeletal muscle, a preponderance of very low HbO2 saturations was observed for both large and small tumors of all lines. Saturations up to about 90% were also generally present, however, even in very large tumors. Variations in vascular configuration were predominantly tumor-line dependent rather than due to inherent characteristics of the host vasculature, and widely disparate HbO2 distributions were found for alternate lines implanted in identical host mice. Although peripheral saturations remained fairly constant with tumor growth, HbO2 values were markedly lower for vessels nearer the tumor center and further decreased with increasing tumor volume. HbO2 saturations did not change substantially with increasing vascular density (except for KHT tumors), although density did decrease with increasing distance from tumor surface. Combined effects of vessel diameter, tumor volume, and vessel location on HbO2 saturations were complex and varied markedly with both tumor line and vessel class. For specific classes, HbO2 distributions correlated closely with radiobiological hypoxic fractions, i.e., for tumor lines in which hypoxic fraction increased substantially with tumor volume, corresponding HbO2 values decreased, while for lines in which hypoxic fraction remained constant, HbO2 values also were unchanged. Although these trends may also be a function of differing oxygen consumption rates between tumor lines

  17. Biopsy in Musculoskeletal Tumors

    Directory of Open Access Journals (Sweden)

    Mohammad Gharehdaghi

    2014-09-01

    other anatomic structures? (4 Carcinomas are homogeneous, and a simple CNB is usually sufficient for diagnosis, but in soft tissue sarcomas, the periphery of the tumor is the growing part and usually represents the authentic underlying malignancy. The center of the tumor may be hemorrhagic or necrotic, thus taking biopsy from this part may distract from the correct diagnosis.Extraosseus part of a bone sarcoma is as representative as bony component of the tumor. Violating the bone and weakening the cortex may predispose it to pathologic fracture, so biopsy of an extraosseus part is sufficient for the diagnosis if present (3. The biopsy tract “open or CNB” is contaminated by tumor cells and should be widely excised if a wide excision or amputation is performed. For this reason, excision of the biopsy incision or needle entrance should be planned along with the definitive tumor excision to prevent complications and the need for altering the treatment strategy (Figure A, B, C. Open incisional biopsy provides sufficient material for microscopic diagnosis as well as immune- histochemical, cytogenetic, or electron microscopic studies. It has some disadvantages such as wound healing problems, infection, tumor cell contamination, and nerve and vessel injuries (1. For open biopsies, the incision should be as small as necessary and longitudinal. Transverse incisions are not advisable. To perform an intraosseus biopsy, the window should be circular or oblong, and as small as needed to prevent a pathologic fracture. Closing this window by PMMA prevents tumor cell contamination. Compressing the PMMA exceeds the chance of metastasis. As a rule, culture what you biopsy and biopsy what you culture. Use of a tourniquet without exsanguinations helps better visualization and meticulous hemostasis which prevents spreading of the tumor cells in hematoma. Importantly, it should be deflated before closing the wound (3. The port of entry of drains, if necessary, must be in line and

  18. Diagnostic evaluatuin of gastrointestinal tumors

    International Nuclear Information System (INIS)

    Linke, R.; Tatsch, K.

    1998-01-01

    Prior to surgery of gastrointestinal tumors exact information about tumor localization, extent and possible infiltration in adjacent structures are important. The task for radiological and scintigraphic methods is predominantly the preoperative tumor staging. The upper (esophagus, stomach, duodenum) and the lower (colon, rectum) gastrointestinal tract should be routinely investigated by endoscopy and endosonography. CT or MRI imaging may add information about tumor extent, infiltration in adjacent structures and pathologically enlarged lymph nodes. The latter may be detected with similar or higher sensitivity by PET as well. Furthermore, with PET it is possible to differentiate a tumor recurrence from postoperative scar tissue earlier than with conventional morphological imaging techniques, for example in colorectal cancer. Liver tumors should primarily be inspected sonographically followed by an MRI scan if dignity is uncertain. The receptor scintigraphy with radioactive ligands allows to further characterize a detected tumor. Benigne liver lesions can be distinguished from malignant tumors (metastasis, hepatocellular carcinoma [HCC]) by the neogalactoalbumin-(NGA-)scintigraphy, because NGA binds exclusively to the liver galactose receptors of normally functioning hepatocytes. For the differentiation between liver metastasis and HCC insulin scintigraphy can be used, since insulin binds significantly in HCC due to an overexpression of insulin receptors in these tumors. If a malignant process is suspected, additionally CT-arterioportography may be recommended, because this newer radiological technique is capable to visualize lesions smaller than 1 cm. In such cases PET is sensitive as well and due to increased glucose metabolism even small foci can be detected with comparably high sepcificity. The method of choice for the detection of a pancreatic tumor is endoscopic sonography. In most cases the dignity of the tumor can be verified by ERCP, but sometimes it is very

  19. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 11/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  20. Tumors and Pregnancy

    Science.gov (United States)

    Tumors during pregnancy are rare, but they can happen. Tumors can be either benign or malignant. Benign tumors aren't cancer. Malignant ones are. The most common cancers in pregnancy are breast cancer, cervical cancer, lymphoma, and melanoma. ...

  1. DCB - Tumor Metastasis Research

    Science.gov (United States)

    Tumor metastasis research examines the mechanisms that allow cancer cells to leave the primary tumor and spread to another part of the body. Learn about recent tumor metastasis research studies supported by the Division of Cancer Biology.

  2. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  3. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  4. Brainstem tumors: Current management and future directions

    Directory of Open Access Journals (Sweden)

    Pablo F Recinos

    2012-01-01

    Full Text Available Tumors arising in the brainstem comprise 10-20% of all pediatric central nervous system (CNS tumors and account for a small percentage in adults. The prognosis for these tumors was considered uniformly poor prior to the era of modern neuroimaging and the location was fraught with disaster being considered a ′no man′s land′ for neurosurgeons. Following the introduction of advanced imaging modalities and neurophysiological monitoring, striking progress has occurred in the management of these lesions. Brainstem tumors are presently classified based on their anatomic location, focality, and histopathology. This article reviews the current classification of brainstem tumors, current management options, and future directions in the treatment for these rare tumors.

  5. Recommendations for standardized diagnostics, treatment and following care in tumor diseases. Geriatric patient with tumor disease

    International Nuclear Information System (INIS)

    Hagmueller, E.; Neises, M.; Queisser, W.; Richter, H.; Schneider, G.

    2001-01-01

    The recommendations for the treatment of geriatric patients with tumor disease, presented in the paper, cover: surgery; chemotherapy; radiotherapy and immunotherapy. Radiotherapy is recommended for skin tumors, pain treatment in the bone metastases (40 - 50 Gy), system diseases (with reduction of the usual size of the irradiated area), small size tumors etc. It is considered as an appropriate method (excluding wide fields) for geriatric outpatients

  6. Congenital tumors of the central nervous system

    International Nuclear Information System (INIS)

    Severino, Mariasavina; Schwartz, Erin S.; Thurnher, Majda M.; Rydland, Jana; Nikas, Ioannis; Rossi, Andrea

    2010-01-01

    Congenital tumors of the central nervous system (CNS) are often arbitrarily divided into ''definitely congenital'' (present or producing symptoms at birth), ''probably congenital'' (present or producing symptoms within the first week of life), and ''possibly congenital'' (present or producing symptoms within the first 6 months of life). They represent less than 2% of all childhood brain tumors. The clinical features of newborns include an enlarged head circumference, associated hydrocephalus, and asymmetric skull growth. At birth, a large head or a tense fontanel is the presenting sign in up to 85% of patients. Neurological symptoms as initial symptoms are comparatively rare. The prenatal diagnosis of congenital CNS tumors, while based on ultrasonography, has significantly benefited from the introduction of prenatal magnetic resonance imaging studies. Teratomas constitute about one third to one half of these tumors and are the most common neonatal brain tumor. They are often immature because of primitive neural elements and, rarely, a component of mixed malignant germ cell tumors. Other tumors include astrocytomas, choroid plexus papilloma, primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and medulloblastomas. Less common histologies include craniopharyngiomas and ependymomas. There is a strong predilection for supratentorial locations, different from tumors of infants and children. Differential diagnoses include spontaneous intracranial hemorrhage that can occur in the presence of coagulation factor deficiency or underlying vascular malformations, and congenital brain malformations, especially giant heterotopia. The prognosis for patients with congenital tumors is generally poor, usually because of the massive size of the tumor. However, tumors can be resected successfully if they are small and favorably located. The most favorable outcomes are achieved with choroid plexus tumors, where aggressive surgical treatment leads to disease

  7. Congenital tumors of the central nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Severino, Mariasavina [G. Gaslini Children' s Hospital, Department of Neuroradiology, Genoa (Italy); Schwartz, Erin S. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Thurnher, Majda M. [Medical University of Vienna, Department of Radiology, Vienna (Austria); Rydland, Jana [MR Center, St. Olav' s Hospital HF, Trondheim (Norway); Nikas, Ioannis [Agia Sophia Children' s Hospital, Imaging Department, Athens (Greece); Rossi, Andrea [G. Gaslini Children' s Hospital, Department of Neuroradiology, Genoa (Italy); G. Gaslini Children' s Hospital, Department of Pediatric Neuroradiology, Genoa (Italy)

    2010-06-15

    Congenital tumors of the central nervous system (CNS) are often arbitrarily divided into ''definitely congenital'' (present or producing symptoms at birth), ''probably congenital'' (present or producing symptoms within the first week of life), and ''possibly congenital'' (present or producing symptoms within the first 6 months of life). They represent less than 2% of all childhood brain tumors. The clinical features of newborns include an enlarged head circumference, associated hydrocephalus, and asymmetric skull growth. At birth, a large head or a tense fontanel is the presenting sign in up to 85% of patients. Neurological symptoms as initial symptoms are comparatively rare. The prenatal diagnosis of congenital CNS tumors, while based on ultrasonography, has significantly benefited from the introduction of prenatal magnetic resonance imaging studies. Teratomas constitute about one third to one half of these tumors and are the most common neonatal brain tumor. They are often immature because of primitive neural elements and, rarely, a component of mixed malignant germ cell tumors. Other tumors include astrocytomas, choroid plexus papilloma, primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and medulloblastomas. Less common histologies include craniopharyngiomas and ependymomas. There is a strong predilection for supratentorial locations, different from tumors of infants and children. Differential diagnoses include spontaneous intracranial hemorrhage that can occur in the presence of coagulation factor deficiency or underlying vascular malformations, and congenital brain malformations, especially giant heterotopia. The prognosis for patients with congenital tumors is generally poor, usually because of the massive size of the tumor. However, tumors can be resected successfully if they are small and favorably located. The most favorable outcomes are achieved with choroid plexus tumors

  8. Primitive neuroectodermal tumor of prostate

    Directory of Open Access Journals (Sweden)

    Kumar Vikash

    2008-07-01

    Full Text Available Primitive neuroectodermal tumors (PNETs are malignant proliferations of small, undifferentiated neuroectodermal cells occurring mainly in children and share the same reciprocal translocation between chromosomes 11 and 22 and the same patterns of biochemical and oncogene expression as osseus and extraosseus Ewing′s sarcoma. Some PNETs occur in the brain, while others (the peripheral PNETs occur in sites outside the brain, such as in the extremities, pelvis and the chest wall. They mostly originate in the chest, pelvis and retroperitoneum; in rare cases, occurrence in the head and neck area has also been seen. We present a rare case of primitive neuroectodermal tumor arising in the prostate gland in a 25-year-old male. To the best of our knowledge, this is the first documentation of a primary peripheral primitive neuroectodermal tumor in the prostate gland of any patient from India and rarely reported in English literature.

  9. Unraveling tumor grading and genomic landscape in lung neuroendocrine tumors.

    Science.gov (United States)

    Pelosi, Giuseppe; Papotti, Mauro; Rindi, Guido; Scarpa, Aldo

    2014-06-01

    Currently, grading in lung neuroendocrine tumors (NETs) is inherently defined by the histological classification based on cell features, mitosis count, and necrosis, for which typical carcinoids (TC) are low-grade malignant tumors with long life expectation, atypical carcinoids (AC) intermediate-grade malignant tumors with more aggressive clinical behavior, and large cell NE carcinomas (LCNEC) and small cell lung carcinomas (SCLC) high-grade malignant tumors with dismal prognosis. While Ki-67 antigen labeling index, highlighting the proportion of proliferating tumor cells, has largely been used in digestive NETs for assessing prognosis and assisting therapy decisions, the same marker does not play an established role in the diagnosis, grading, and prognosis of lung NETs. Next generation sequencing techniques (NGS), thanks to their astonishing ability to process in a shorter timeframe up to billions of DNA strands, are radically revolutionizing our approach to diagnosis and therapy of tumors, including lung cancer. When applied to single genes, panels of genes, exome, or the whole genome by using either frozen or paraffin tissues, NGS techniques increase our understanding of cancer, thus realizing the bases of precision medicine. Data are emerging that TC and AC are mainly altered in chromatin remodeling genes, whereas LCNEC and SCLC are also mutated in cell cycle checkpoint and cell differentiation regulators. A common denominator to all lung NETs is a deregulation of cell proliferation, which represents a biological rationale for morphologic (mitoses and necrosis) and molecular (Ki-67 antigen) parameters to successfully serve as predictors of tumor behavior (i.e., identification of pathological entities with clinical correlation). It is envisaged that a novel grading system in lung NETs based on the combined assessment of mitoses, necrosis, and Ki-67 LI may offer a better stratification of prognostic classes, realizing a bridge between molecular alterations

  10. Aquaporins and Brain Tumors

    Directory of Open Access Journals (Sweden)

    Rosario Maugeri

    2016-06-01

    Full Text Available Brain primary tumors are among the most diverse and complex human cancers, and they are normally classified on the basis of the cell-type and/or the grade of malignancy (the most malignant being glioblastoma multiforme (GBM, grade IV. Glioma cells are able to migrate throughout the brain and to stimulate angiogenesis, by inducing brain capillary endothelial cell proliferation. This in turn causes loss of tight junctions and fragility of the blood–brain barrier, which becomes leaky. As a consequence, the most serious clinical complication of glioblastoma is the vasogenic brain edema. Both glioma cell migration and edema have been correlated with modification of the expression/localization of different isoforms of aquaporins (AQPs, a family of water channels, some of which are also involved in the transport of other small molecules, such as glycerol and urea. In this review, we discuss relationships among expression/localization of AQPs and brain tumors/edema, also focusing on the possible role of these molecules as both diagnostic biomarkers of cancer progression, and therapeutic targets. Finally, we will discuss the possibility that AQPs, together with other cancer promoting factors, can be exchanged among brain cells via extracellular vesicles (EVs.

  11. An Uncommon Presentation of Giant Cell Tumor

    Science.gov (United States)

    Al-Kindi, Hunaina; George, Mina; Malhotra, Gopal; Al-Muzahmi, Khamis

    2011-01-01

    Giant Cell Tumors commonly occur at the ends of long bones. However in rare cases, they can occur in the bones of the hands and feet. Tumors in these locations occur in younger patients; in addition, these tumors are more commonly multifocal and are associated with a higher risk for local recurrence than tumors at the ends of long bones. Since lesions in the small bones may be multifocal, a patient with a giant cell tumor of the small bones should undergo a skeletal survey to exclude similar lesions elsewhere. Primary surgical treatment ranges from curettage or excision with or without bone grafting to amputation. The success of surgical treatment depends on the completeness with which the tumor was removed. We are presenting a case report of a 34 year old female, who presented with a swelling in the right hand, following trauma. X-ray of the hand showed an osteolytic expansile lesion at the base of the 1st metacarpal bone. The lesion was initially curetted and then treated by local resection with bone grafting. Histological examination revealed a typical benign giant cell tumor composed of closely packed stromal cells with a variable admixture of giant cells. Follow up at the end of one year did not reveal any recurrence of the tumor. PMID:22125733

  12. In vivo trans-rectal ultrasound coupled trans-rectal near-infrared optical tomography of canine prostate bearing transmissible venereal tumor

    Science.gov (United States)

    Jiang, Zhen; Holyoak, G. Reed; Bartels, Kenneth E.; Ritchey, Jerry W.; Xu, Guan; Bunting, Charles F.; Slobodov, Gennady; Krasinski, Jerzy S.; Piao, Daqing

    2009-02-01

    In vivo trans-rectal near-infrared (NIR) optical tomography is conducted on a tumor-bearing canine prostate with the assistance of trans-rectal ultrasound (TRUS). The canine prostate tumor model is made possible by a unique round cell neoplasm of dogs, transmissible venereal tumor (TVT) that can be transferred from dog to dog regardless of histocompatibility. A characterized TVT cell line was homogenized and passed twice in subcutaneous tissue of NOD/SCID mice. Following the second passage, the tumor was recovered, homogenized and then inoculated by ultrasound guidance into the prostate gland of a healthy dog. The dog was then imaged with a combined trans-rectal NIR and TRUS imager using an integrated trans-rectal NIR/US applicator. The image was taken by NIR and US modalities concurrently, both in sagittal view. The trans-rectal NIR imager is a continuous-wave system that illuminates 7 source channels sequentially by a fiber switch to deliver sufficient light power to the relatively more absorbing prostate tissue and samples 7 detection channels simultaneously by a gated intensified high-resolution CCD camera. This work tests the feasibility of detecting prostate tumor by trans-rectal NIR optical tomography and the benefit of augmenting TRUS with trans-rectal NIR imaging.

  13. Malignant phyllodes breast tumor

    OpenAIRE

    Lisa R. Shah-Patel, MD

    2017-01-01

    Malignant phyllodes tumor is a rare tumor of the breast occurring in females usually between the ages of 35 and 55 years. It is often difficult to distinguish benign from malignant phyllodes tumors from other benign entities such as fibroadenomas. This case presentation demonstrates a woman with malignant phyllodes tumor treated with mastectomy with abdominal skin flap reconstruction.

  14. Malignant phyllodes breast tumor

    Directory of Open Access Journals (Sweden)

    Lisa R. Shah-Patel, MD

    2017-12-01

    Full Text Available Malignant phyllodes tumor is a rare tumor of the breast occurring in females usually between the ages of 35 and 55 years. It is often difficult to distinguish benign from malignant phyllodes tumors from other benign entities such as fibroadenomas. This case presentation demonstrates a woman with malignant phyllodes tumor treated with mastectomy with abdominal skin flap reconstruction.

  15. Liver Tumors (For Parents)

    Science.gov (United States)

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

  16. Endocrine tumors other than thyroid tumors

    International Nuclear Information System (INIS)

    Takeichi, Norio; Dohi, Kiyohiko

    1992-01-01

    This paper discusses the tendency for the occurrence of tumors in the endocrine glands, other than the thyroid gland, in A-bomb survivors using both autopsy and clinical data. ABCC-RERF sample data using 4136 autopsy cases (1961-1977) revealed parathyroid tumors in 13 A-bomb survivors, including 3 with the associated hyperparathyroidism, with the suggestion of dose-dependent increase in the occurrence of tumors. Based on clinical data from Hiroshima University, 7 (46.7%) of 15 parathyroid tumors cases were A-bomb survivors. Data (1974-1987) from the Tumor Registry Committee (TRC) in Hiroshima Prefecture revealed that a relative risk of parathyroid tumors was 5.6 times higher in the entire group of A-bomb survivors and 16.2 times higher in the group of heavily exposed A-bomb survivors, suggesting the dose-dependent increase in their occurrence. Adrenal tumors were detected in 47 of 123 cases from the TRC data, and 15 (31.5%) of these 47 were A-bomb survivors. Particularly, 11 cases of adrenal tumors associated with Cushing syndrome included 6 A-bomb survivors (54.5%). The incidence of multiple endocrine gonadial tumors (MEGT) tended to be higher with increasing exposure doses; and the 1-9 rad group, the 10-99 rad group, and the 100 or more rad group had a risk of developing MEGT of 4.1, 5.7, and 7.1, respectively, relative to both the not-in the city group and the 0 rad group. These findings suggested that there is a correlation between A-bomb radiation and the occurrence of parathyroid tumors (including hyperparathyroidism), adrenal tumors associated with Cushing syndrome and MEGT (especially, the combined thyroid and ovarian tumors and the combined thyroid and parathyroid tumors). (N.K.)

  17. Supratentorial tumors; Supratentorielle Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, I.; Dillmann, K.; Roth, C.; Backens, M.; Reith, W. [Universitaetsklinikum Saarland, Homburg (Germany). Klinik fuer Diagnostische und Interventionelle Neuroradiologie

    2007-06-15

    Magnetic resonance imaging is a routine diagnostic measure for a suspected intracerebral mass. Computed tomography is usually also indicated. Further diagnostic procedures as well as the interpretation of the findings vary depending on the tumor location. This contribution discusses the symptoms and diagnostics for supratentorial tumors separated in relation to their intra- or extracranial location. Supratentorial tumors include astrocytoma, differentiated by their circumscribed and diffuse growth, ganglioglioma, ependyoma, neurocytoma, primitive neuroectodermal tumors (PNET), oligodendroglioma, dysembryoplastic neuroepithelial tumors (DNET), meningoangiomatosis, pineal tumors, hamartoma, lymphoma, craniopharyngeoma and metastases. The supratentorial extracranial tumors include the choroid plexus, colloid cysts, meningeoma, infantile myofibromatosis and lipoma. The most common subforms, especially of astrocytoma, will also be presented. (orig.)

  18. Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

    Directory of Open Access Journals (Sweden)

    Yingjen Jeffrey Wu

    2009-02-01

    Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

  19. Magnetic resonance imaging of syrinx cavity. Differentiation between syrinx with spinal cord tumor and without tumor

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Teruo; Inoue, Yuichi; Nemoto, Yutaka

    1987-12-01

    Syrinx cavity may result from a number of intramedullary tumors or non-neoplastic conditions such as Chiari malformation, trauma and meningitis. The surgical procedure to repair the syrinx is quite different between the cases with spinal cord tumor and without tumor. Therefore, it is important to determine whether syrinx is associated with tumor or not before surgery. We reviewed MR images of 26 cases with syrinx cavity; 20 of which were not associated with tumor (12