EUS-FNA for the Diagnosis of Retroperitoneal Primitive Neuroectodermal Tumor

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Aijaz A. Sofi

2011-01-01

Full Text Available Primitive neuroectodermal tumor (PNET is a rare “small round blue cell tumor” that is diagnosed by open biopsy or percutaneous biopsy of the lesion under radiologic guidance. In this case report, we present a novel approach to the diagnosis of a retroperitoneal PNET by endoscopic ultrasound- (EUS- guided fine needle aspiration (FNA. A 35-year-old man presented with the history of left-sided flank pain and swelling of 3-weeks duration. Computerized tomography (CT scan of his abdomen revealed a 12.8 × 13 × 12.5 cm cystic and solid mass arising from the retroperitoneum and displacing the third and fourth portions of the duodenum. He underwent EUS which revealed a well-circumscribed heterogeneous mass abutting the inferior portion of the stomach. EUS-FNA of the mass revealed malignant cells consistent with primitive neuroectodermal tumor (PNET/Ewing's sarcoma. EUS-guided FNA is an appropriate technique for diagnosing retroperitoneal PNET/Ewing's sarcoma.

Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors

NARCIS (Netherlands)

Vermeulen, Jeroen F; van Hecke, Wim; Spliet, Wim G M; Villacorta Hidalgo, José; Fisch, Paul; Broekhuizen, Roel; Bovenschen, Niels

2016-01-01

BACKGROUND: Central nervous system (CNS) primitive neuroectodermal tumors (PNETs) are malignant primary brain tumors that occur in young infants. Using current standard therapy, up to 80% of the children still dies from recurrent disease. Cellular immunotherapy might be key to improve overall

Postoperative Paraplegia as a Result of Undiagnosed Primitive Neuroectodermal Tumor, Not Epidural Analgesia

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Pei-Ching Hung

2007-10-01

Full Text Available Postoperative paraplegia is a rare complication after epidural analgesia and often occurs with spinal hematoma or cord injury. We present the case of a 16-year-old girl who suffered from a tumor mass in the neck and abdomen who underwent gynecologic operation. Preoperatively, liver metastasis was found by computed tomography. Pathologic findings revealed that the abdominal mass was an ovarian dermoid cyst. After the operation, the patient complained of paraplegia while receiving epidural analgesia for postoperative pain control. A peripheral primitive neuroectodermal tumor in the thoracic and lumbar spines with spinal cord compression was later detected using magnetic resonance imaging. Learning from this case, we suggest that when a patient is preoperatively diagnosed with tumor metastasis, back pain and soreness, spinal cord compression from tumor metastasis should be excluded before epidural analgesia is implemented.

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

DEFF Research Database (Denmark)

Stecher, Chalotte Willemann; Grønbaek, Kirsten; Hasle, Henrik

2008-01-01

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

Identification of novel biomarkers in pediatric primitive neuroectodermal tumors and ependymomas by proteome-wide analysis

NARCIS (Netherlands)

de Bont, Judith M.; den Boer, Monique L.; Kros, Johan M.; Passier, Monique M. C. J.; Reddinglus, Roel E.; Smitt, Peter A. E. Sillevis; Luider, Theo M.; Pieters, Rob

The aim of this study was to identify aberrantly expressed proteins in pediatric primitive neuroectodermal tumors (PNETs) and ependymornas. Tumor tissue of 29 PNET and 12 ependymoma patients was subjected to 2-dimensional difference gel electrophoresis. Gel analysis resulted in 79 protein spots

Peripheral primitive neuroectodermal tumor of the urinary bladder in an Arab woman with history of squamous cell carcinoma: a case report.

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Al Meshaan, Mohd Khaled; Nayef, Marwan; Kwaider, Talal; Otto, Wolfgang; Katchy, Ken C

2009-04-29

Peripheral primitive neuroectodermal tumors of the urinary bladder are rare and tend to occur in an older age group than do their counterparts in bones and soft tissue. We report a case of peripheral primitive neuroectodermal tumor of the urinary bladder in a 67-year-old woman of Arab origin. She had undergone transurethral resection followed by chemotherapy because of pulmonary metastasized muscle-invasive squamous cell carcinoma of the bladder in 2005. One year later, she first presented with a history of repeated hematuria in our institution. Performing cystoscopy any tumor could be detected. Control cystoscopy two months later showed a tumor mass of 3 cm in diameter at another location than described for the first tumor. After perforating by transurethral resection partial bladder resection had to be done. Tissue specimen after pathological analysis revealed a peripheral primitive neuroectodermal tumor with tumor cells reactive to cluster of differentiation 99, neuron-specific enolase and S100 protein and stained negative for other markers such as cytokeratins, epithelial membrane antigen, desmin, smooth muscle actin, chromogranin and leucocyte common antigen. Staging computerized tomography was especially free from any hint on organ metastasis, but the patient died due to a cardiac problem only a few months later. To the best of our knowledge, we report the eighth case of bladder peripheral primitive neuroectodermal tumors in literature and the first concerning an Arab patient. It is also the first presentation of a peripheral primitive neuroectodermal tumor patient with a history of squamous cell carcinoma of the bladder. As in other cases, expression of single-chain-type 1 glycoprotein and neural markers was positive and the disease was at an advanced stage at the time of diagnosis.

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

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Pradnya S Bhadarge

2017-01-01

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

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

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Toshiki Etani

2015-04-01

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

Primitive neuroectodermal tumor of the zygomaticoorbital complex: a rare location and ways of surgical repair of the area

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Ch. R. Ragimov

2015-01-01

Full Text Available Primitive neuroectodermal tumor in the zygomaticoorbital region is a rare neoplasm of the head and neck. Due to the necessity for wide radical excision of a primary tumor, there may be serious functional and cosmetic disorders that substantially affect quality of life in patients. Restoration of this region is one of the challenges of reconstructive surgery because of the specific features of the relief of bone structures. The paper describes a clinical case of the site of primitive neuroectodermal tumor in the zygomaticoorbital complex and a method for repairing postresectional defect and completely recovering the function of the organ of vision and aesthetic parameters of the face.

Primitive neuroectodermal tumors of kidney: Our experience in a tertiary care center.

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Seth, A; Mahapatra, S K; Nayak, B; Saini, A K; Biswas, B

2016-01-01

Primitive neuroectodermal tumors (PNET) are rare highly aggressive neoplasms. The diagnosis is made by histopathology with the support of immunohistochemistry (IHC) and cytogenetics. The aggressive multimodality treatment is recommended for the management of these tumors. The purpose of our study is to review our experiences in the diagnoses and treatment of PNET of the kidneys. We retrospectively reviewed the data of all the patients, who were treated for the PNET of the kidneys at our institute between April and March 2011 and compared with the available literature. A total of eight patients were treated for PNET of the kidney. Out of the eight patients, four were males and four females. Nearly 50% of our patients had inferior vena caval thrombus at the time of presentation. The diagnosis was made on histopathology supported by IHC. Out of the eight patients, one patient had intraoperative death due to massive pulmonary thromboembolism and another died on the 7th post-operative day due to disseminated intravascular coagulation and multiorgan failure. Rest six patients were treated with post-operative chemotherapy or a combination of chemotherapy and radiotherapy. For these six patients, overall median survival was 45 months with a 3 year disease-free survival of 66% and 5 year survival of 44%. PNET of the kidneys are rare peripheral neuroectodermal tumors with an aggressive clinical course. These tumors carry a very poor prognosis. An aggressive treatment approach using a combination of surgery, chemotherapy and radiotherapy is recommended for a reasonable survival in these tumors.

Primary Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Stomach

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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.

Clinical analysis of primary primitive neuroectodermal tumors in the female genital tract.

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Xiao, Changji; Zhao, Jing; Guo, Peng; Wang, Dan; Zhao, Dachun; Ren, Tong; Yang, Jiaxin; Shen, Keng; Lang, Jinghe; Xiang, Yang; Cui, Quancai

2014-03-01

The aim of the study was to investigate the clinical manifestations, diagnosis, treatment, and prognosis of primitive neuroectodermal tumors (PNETs) in the female genital tract. From April 2001 to May 2013, the clinicopathologic characteristics, treatments, outcomes, and prognosis of 11 patients with PNET in the female genital tract were analyzed retrospectively at our hospital. The location of PNET in the 11 patients presented here included vulva (2 patients), cervix (2 patients), uterus and its ligament (5 patients), and the ovaries (2 patients). Ages ranged from 18 to 59 years (median, 31 years).The main clinical manifestations of PNET in the female genital tract are irregular vaginal bleeding (6 patients), pelvic mass, uterine enlargement, and rapidly increasing vulvar mass (8 patients), and vulvar pain and lower abdominal pain (5 patients). The CA125 levels of 8 patients were elevated before the operations and reduced to normal when the diseases were controlled, while the levels increased as the tumor was progressive. Results for the most commonly used immunohistochemistry studies revealed CD99 in 11 of the 11 tumors, synaptophysin in 6 of the 7 positive tumors, and neuron-specific enolase in 6 of the 6 tumors. Ten patients underwent surgical resection. Nine of them underwent preoperative or/and postoperative combination chemotherapy. The follow-up of 10 patients were available and ranged from 1 to 145 months (median, 30.5 months), 3 of whom experiencing recurrence. Primitive neuroectodermal tumor is very rare and can originate from any part of the female genital tract. The tumors had different manifestations but the same pathologic features. CA125 may be an important marker for prognosis and follow-up of PNET of the female internal genital tract.

CT and MR findings of primitive neuroectodermal tumor

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Kook, Shin Ho; Kim, In One; Chang, Kee Hyun; Han, Moon Hee; Cho, Byung Kyu

1991-01-01

Cerebral primitive neuroectodermal tumor (PNET), consisting of undifferentiated primitive cells, is a neoplasm of children and young adults that occurs predominantly in the supratentorial compartment. In this report, we retrospectively reviewed and analyzed 18 CT and 6 MR findings in 18 patients with pathologically-proven PNET to discover the characteristic findings, if may. The most characteristic feature of the PNETs was a well-defined multilobular oval or round large mass with components of peripheral cystic change or calcification in the cerebral hemisphere, especially in the parietal lobe. Usually there was only minimal surrounding edema. The CT density of the tumor was iso - or slightly high density with homogeneous contrast enhancement in the solid portion and low density in the cystic area. MR findings demonstrated iso - signal intensity on both T1 - weighted (T1WI) and T2-weighted (T2WI) images and dense enhancement in the solid element. The cystic portion revealed low intensity on T1WI and high intensity on T2WI

Primary Vaginal Extraosseous Ewing Sarcoma/Primitive Neuroectodermal Tumor with Cranial Metastasis

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Chi-Man Yip

2009-06-01

Full Text Available Extraosseous Ewing sarcoma is now regarded as a member of the Ewing sarcoma/primitive neuroectodermal tumor (PNET family. It typically involves the soft tissues of the chest wall, pelvis, paravertebral region, abdominal wall, retroperitoneal region and extremities of children, adolescents and young adults, but it seldom occurs in the female genital tract. We report an extremely rare case of retrospective diagnosis of vaginal extraosseous Ewing sarcoma/PNET which metastasized to the right frontoparietal scalp, skull, and dura. Surgical resection, followed by adjuvant radiotherapy and chemotherapy resulted in a favourable clinical outcome. Both the vaginal and head tumors had similar light microscopic features supporting the diagnosis.

Congenital peripheral primitive neuroectodermal tumor: A case treated successfully with multimodality treatment

International Nuclear Information System (INIS)

Goyal, Sh.; Biswas, A.; Mohanti, B.K.; Gupta, R.

2014-01-01

Neonatal tumors comprise less than two percent of childhood malignancies. Most are solid tumors, most common histologies being teratoma and neuroblastoma. We encountered a child who was detected to have a right arm mass on antenatal sonogram, which was diagnosed to be a primitive neuroectodermal tumor involving the triceps on fine needle aspiration cytology performed in the post-natal period. The child was successfully treated with multimodality treatment consisting of surgery, chemotherapy and radiotherapy. We also discuss briefly the problems associated with therapy in neonatal period. A review of all cases reported to have congenital Ewing’s sarcoma family of tumors is presented. Novel therapies are needed to improve efficacy and decrease the devastating side effects of treatment in this age group.

Primitive neuroectodermal tumor of adrenal: Clinical presentation and outcomes

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Deep Dutta

2013-01-01

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

Molecular analysis of childhood primitive neuroectodermal tumors defines markers associated with poor outcome

DEFF Research Database (Denmark)

Scheurlen, W G; Schwabe, G C; Joos, S

1998-01-01

PURPOSE: The diagnostic and prognostic significance of well-defined molecular markers was investigated in childhood primitive neuroectodermal tumors (PNET). MATERIALS AND METHODS: Using microsatellite analysis, Southern blot analysis, and fluorescence in situ hybridization (FISH), 30 primary tumors......: In our study, amplification of c-myc was a poor-prognosis marker in PNET. LOH of chromosome 17p was associated with metastatic disease. Molecular analysis of primary tumors using these markers may be useful for stratification of children with PNET in future prospective studies. The other aberrations...... investigated were not of significant prognostic value, but may provide an entry point for future large-scale molecular studies....

Multiple Ewing Sarcoma/Primitive Neuroectodermal Tumors in the Mediastinum

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Bae, Sung Hwan; Hwang, Jung Hwa; Da Nam, Bo; Kim, Hyun Jo; Kim, Ki-Up; Kim, Dong Won; Choi, In Ho

2016-01-01

Abstract Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are high-grade malignant neoplasms. These malignancies present very rare tumors of thoracopulmonary area and even rarer in the mediastinum. In our knowledge, ES/PNET presented with multiple mediastinal masses has not been reported previously. We experienced a case of a 42-year-old man presented with gradual onset of left-side pleuritic chest pain. A contrast-enhanced chest computed tomography (CT) scan showed separate 2 large heterogeneously enhancing masses in each anterior and middle mediastinum of the left hemithorax. Positron emission tomography-computed tomography (PET-CT) scan revealed high fluorodeoxyglucose (FDG) uptake in the mediastinal masses. After surgical excision for the mediastinal masses, both of the masses were diagnosed as the ES/PNET group of tumors on the histopathologic examination. The patient refused postoperative adjuvant chemotherapy and came back with local tumor recurrence and distant metastasis on 4-month follow-up after surgical resection. We report this uncommon form of ES/PNET. We are to raise awareness that this rare malignancy should be considered as a differential diagnosis of the malignant mediastinal tumors and which can be manifested as multiple masses in a patient. Understanding this rare entity of extra-skeletal ES/PNET and characteristic imaging findings can help radiologists and clinicians to approach proper diagnosis and better management for this highly malignant tumor. PMID:26886614

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

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Shu-Guang Jin

2016-10-01

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

Clinical and pathological characteristics of primitive neuroectodermal tumor of the cerebral

International Nuclear Information System (INIS)

Fu Jun; Zhou Youxin; Xu Feng; Ye Ming; Zhou Dai; Bao Yaodong; Kang Suya

2004-01-01

Objective: To study the features of the cerebral primitive neuroectodermal tumor (PNET) in the clinical manifestation and in the histogenesis, morphology. Methods: Seven cases of cerebral PNET was analyzed with their clinical manifestations, histologic and immunohistochemical results. Results: Five patients of this group were children or young adults. Seven tumors were composed of primitive cells with focal evidence of glial or neuronal differentiation. Five out seven expressed NSE, one out seven expressed Syn, two out seven expressed CD99 and only one case expressed Vimentin, None expressed GFAP and S-100. CT findings were a homogeneous high density or heterogeneous mass. MR findings were high signal intensity both on T1 and T2 images. Conclusion: To diagnose the cerebral PNET depends on pathology and cerebral PNET have poor prognosis

Melanotic neuroectodermal tumor of infancy (progonoma): a case report emphasizing the computed tomography findings and literature review

International Nuclear Information System (INIS)

Araujo Junior, Cyrillo Rodrigues de; Carvalho, Tarcisio Nunes; Fraguas Filho, Sergio Roberto; Costa, Marlos Augusto Bitencourt; Borba, Ana Olivia Cardoso; Figueiredo, Sizenildo da Silva; Machado, Marcio Martins; Teixeira, Kim-Ir-Sen Santos

2004-01-01

The melanotic neuroectodermal tumor of infancy, also known as progonoma, is a rare benign disease of neural crest origin that occurs within the first year of life and affects mainly the maxilla. The authors report a case of a 10-month-old child presenting with this uncommon tumor in the maxilla, emphasizing the diagnostic findings on computed tomography, and present a literature review. (author)

Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Kidney: Two Unusual Presentations of a Rare Tumor

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E. C. Castro

2012-01-01

Full Text Available Only few cases of primary renal Ewing's sarcoma have been reported in the literature to date. We present here two cases of renal ES/PNET with an uncanny presentation. The first case was discovered after the patient presented clinically with irradiating flank pain, mimicking the pain related with kidney stones. The second case had clinical presentation of pulmonary thromboembolism after the patient was involved in an automobilist accident. The tumors were mainly composed of small blue cells which by immunohistochemical were positive for neural markers, and FISH revealed the translocation 22q12 for the EWSR1 gene. The diagnosis of renal primitive neuroectodermal tumor/EWING tumor is very rare and usually involves several different diagnostic techniques. The differential diagnosis is usually broad with frequent overlapping features between the entities. The cases presented in this paper illustrated the difficulties with which routine anatomical pathologist is faced when dealing with rare renal poorly differentiated neoplasm in adults.

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

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

2016-10-01

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

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

International Nuclear Information System (INIS)

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

2002-01-01

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

Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

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2013-10-07

Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Primitive Neuroectodermal Tumor (PNET) of the kidney: a case report

International Nuclear Information System (INIS)

Pomara, Giorgio; Cappello, Francesco; Cuttano, Maria G; Rappa, Francesca; Morelli, Girolamo; Mancini, Pierantonio; Selli, Cesare

2004-01-01

A case of Primitive Neuroectodermal Tumor (PNET) of the kidney in a 27-year-old woman is presented. Few cases are reported in the literature with a variable, nonspecific presentation and an aggressive behaviour. In our case, a radical nephrectomy with lymphadenectomy was performed and there was no residual or recurrent tumour at 24-month follow-up. The surgical specimens were formalin-fixed and paraffin embedded. The sections were stained with routinary H&E. Immunohistochemistry was performed. The immunohistochemical evaluation revealed a diffuse CD99 positivity in the cytoplasm of the neoplastic cells. Pankeratin, cytokeratin AE1/AE3, vimentin, desmin, S100, cromogranin were negative. The clinical presentation and the macroscopic aspect, together with the histological pattern, the cytological characteristic and the cellular immunophenotype addressed the diagnosis towards primary PNET of kidney. Since sometimes it is difficult to discriminate between PNET and Ewing's tumour, we reviewed the difficulties in differential diagnosis. These tumors have a common precursor but the stage of differentiation in which it is blocked is probably different. This could also explain their different biological behaviour and prognosis

Melanotic neuroectodermal tumor of infancy in an African-indigenous patient from the Amazon: a case report.

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Pinheiro, Thiago Pastor da Silva; Carneiro, José Thiers; de Melo Alves, Sérgio; de Jesus Viana Pinheiro, João; Tuji, Fabrício Mesquita

2013-11-25

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare condition that occurs normally in the anterior maxilla of infants aged Amazon residency, who presented to our unit in 2009 with a history of an expanding mass involving the anterior maxilla. Clinical and computerized tomography scans were used to diagnose the mass as MNTI, which was removed by total excision. A biopsy later confirmed the MNTI diagnosis.

Heavy Metal Bioaccumulation in an Atypical Primitive Neuroectodermal Tumor of the Abdominal Wall.

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Roncati, Luca; Gatti, Antonietta Morena; Capitani, Federico; Barbolini, Giuseppe; Maiorana, Antonio; Palmieri, Beniamino

2015-01-01

Heavy metals are able to interfere with the function of vital cellular components. Besides in trace heavy metals, which are essential at low concentration for humans, there are heavy metals with a well-known toxic and oncogenic potential. In this study, for the first time in literature, we report the unique adulthood case of an atypical primitive neuroectodermal tumor of the abdominal wall, diagnosed by histology and immunohistochemistry, with the molecular hybridization support. The neoplasia occurred in a patient chronically exposed to a transdermal delivery of heavy metal salts (aluminum and bismuth), whose intracellular bioaccumulation has been revealed by elemental microanalysis.

Peripheral primitive neuroectodermal tumor of the kidney in a 51-year-old female following breast cancer: A case report and review of the literature

OpenAIRE

ZHONG, JINJING; CHEN, NI; CHEN, XUEQIN; GONG, JING; NIE, LING; XU, MIAO; ZHOU, QIAO

2014-01-01

Peripheral primitive neuroectodermal tumor/Ewing’s sarcoma (pPNET/EWS) is an aggressive type of sarcoma that is rarely observed in the kidney. pPNET of the kidney principally occurs in young patients (

Primitive neuroectodermal tumor arising 8 years after chemotherapy and radiotherapy for acute lymphoblastic leukemia. Case report

International Nuclear Information System (INIS)

Yoshida, Yuya; Toma, Yasuo; Arai, Masayuki; Higashi, Ryo; Kashihara, Kengo; Kaizaki, Yasuharu

2005-01-01

We report a case of primitive neuroectodermal tumor (PNET) arising 8 years after chemotherapy and radiotherapy for acute lymphoblastic leukemia. A 15-year-old boy with a history of acute lymphoblastic leukemia, at the age of 7, underwent chemotherapy and 14 Gy of radiotherapy to the whole brain. He was admitted to our department due to the development of aphasia, right hemiparesis and generalized convulsive seizure. MRI showed an irregularly enhanced mass in the left frontal lobe. A gross total removal of the tumor was performed and histological examination showed it to be PNET. Postoperatively, the patient underwent 20 Gy of radiotherapy to the whole brain and 42 Gy of local radiotherapy. Follow-up MRI showed no evidence of recurrent tumor 4 months after the radiotherapy. This tumor was thought to be a secondary brain tumor arising in this survivor of childhood acute lymphoblastic leukemia and it is a rare complication of successful leukemia treatment. (author)

A general aspect on soft-tissue sarcoma and c-kit expression in primitive neuroectodermal tumor and Ewings sarcoma

International Nuclear Information System (INIS)

Kara, Ismail O.; Sahin, B.; Gonlusen, G.; Ergin, M.; Erdogan, S.

2005-01-01

Within soft-tissue sarcoma, primitive neuroectodermal tumors have been shown to cover a wide spectrum of small round cell sarcomas, including Ewings sarcomas (Es) and primitive neuroectodermal tumors (PET). The role of the stem cell factor/kit pathway has been investigated in different human tumors especially in chronic metallically leukemia and gastrointestinal stromal tumor and an autocrine loop has been assumed in small cell lung carcinoma, and recently in Es and PET. Our aim is to investigate the c-kit expression in Es and PET and also to assessed if c-kit has any role in disease process. We thoroughly searched the archives of the Department of Pathology, Faculty of Medicine, Cukurova University Turkey, between 2000 and 2004; and found 14 ES and 14 PNET paraffin embedded tissues. We carried out the detection of the c-kit expression by immunohistochemical staining. The patients median age was 23.7 +/-14.6 (12 male and 16 female). Five were diagnosed as metastatic disease whereas 23 were diagnosed as non-metastatic disease at admission. The mean follow up period was 38.9 +/- 22.3 months. The main localization of the disease was lower extremity (32.1%), and others were as follows: head and neck 25%, thorax and abdomen 14.3%, pelvic and upper extremity 7.1% (11 were localized skeletal and 17 were extraskeletal). According to treatment modalities, 10 were treated with surgery alone, 11 with surgery and chemotherapy, and 7 with surgery, radiation therapy and also with chemotherapy. The primary tumor was lower than 5 cm in its dimension in 21 patients. While in 5 patients, tumor was more than 5 cm but did not exceed 10 cm, it was >10 cm in 2 patients. The c-kit expression was positive in 7 patients both cytoplasmic and membranously, whereas 8 patients were positive cytoplasmically. In 5 PNET patients, c-kit expression were stained immunohistochemically in over 50% and in 3 of ES patients. There was no significant correlation between c-kit expression and gender

Treatment Outcome and Prognostic Molecular Markers of Supratentorial Primitive Neuroectodermal Tumors.

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Seo Hee Choi

Full Text Available To identify prognostic factors and define the optimal management of patients with supratentorial primitive neuroectodermal tumors (sPNETs, we investigated treatment outcomes and explored the prognostic value of specific molecular markers.A total of 47 consecutive patients with pathologically confirmed sPNETs between May 1985 and June 2012 were included. Immunohistochemical analysis of LIN28, OLIG2, and Rad51 expression was performed and correlated with clinical outcome.With a median follow-up of 70 months, 5-year overall survival (OS and progression-free survival (PFS was 55.5% and 40%, respectively, for all patients. Age, surgical extent, and radiotherapy were significant prognostic factors for OS and PFS. Patients who received initially planned multimodal treatment without interruption (i.e., radiotherapy and surgery (≥subtotal resection, with or without chemotherapy showed significantly higher 5-year OS (71.2% and PFS (63.1%. In 29 patients with available tumor specimens, tumors with high expression of either LIN28 or OLIG2 or elevated level of Rad51 were significantly associated with poorer prognosis.We found that multimodal treatment improved outcomes for sPNET patients, especially when radiotherapy and ≥subtotal resection were part of the treatment regimen. Furthermore, we confirmed the prognostic significance of LIN28 and OLIG2 and revealed the potential role of Rad51 in sPNETs.

Solitary epidural brain metastasis of Neuroepithelioma (a Primitive Neuroectodermal Tumor: case report

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Farnaz Farshidfar

2008-08-01

Full Text Available A 14 years old male was referred to Computerized tomography scan (CT of our hospital for evaluation of headache. The patient was known case of cervical soft tissue Primitive neuroectodermal tumor (PNET which has undergone surgery and radiotherapy 4 years ago. The CT scan showed large solitary extra axial, epidural lesion in right parietal region, with mass effect and bony involvement. Then surgery was done for him and the resultant biopsy was Neuroepithelioma. After diagnosis the patient has undergone chemotherapy and radiotherapy. He has no signs or symptoms of malignancy, and also follow up CT scan of the brain, chest, and abdomen were normal after two years of surgery. This is the first reported case of epidural metastasis of a head and neck PNET in an adolescent.

Rare case of undifferentiated uterine sarcoma with neuroectodermal differentiation and osteoclast-like giant cells

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Chiu-Hsuan Cheng

2018-06-01

Conclusion: UUSs are rare high-grade tumors observed in elderly women. These women typically present with postmenopausal bleeding and extrauterine diseases and have a poor prognosis. Neuroectodermal differentiation in UUSs has a müllerian origin. The presence of OGCs may suggest a poor prognosis; however, further studies are necessary to determine the exact nature of such neoplasms.

Primary Ewing's sarcoma-primitive neuroectodermal tumor of the uterus: a case report and literature review.

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Park, Jeong-Yeol; Lee, Sun; Kang, Hyoung Jin; Kim, Hy-Sook; Park, Sang-Yoon

2007-08-01

Primary Ewing's sarcoma-primitive neuroectodermal tumor (ES-PNET) of the uterus is an extremely rare malignancy. A 30-year-old Korean woman presented with abnormal uterine bleeding with uterine enlargement. A computed tomography (CT) scan and magnetic resonance imaging (MRI) of the abdomen and pelvis showed a huge uterine mass measuring 18 x 20 x 21 cm, metastasis to both pelvic and para-aortic lymph nodes, and omental infiltration. The pathology report of the uterine mass described a uniformly hypercellular tumor, which was arranged in diffuse solid sheets of uniform, small, rounded, and sometimes spindle-shaped cells, with scanty cytoplasm. Immunohistochemically, the mass tested positive for vimentin, CD99, and chromogranin. The patient received several courses of combination chemotherapy and radiotherapy but died from tumor progression 16 months after the initial diagnosis. This is a rare case of primary uterine ES-PNET in a woman of reproductive age. A review of the literature indicates that primary uterine ES-PNET requires early diagnosis and multimodality treatment including surgery, chemotherapy, and radiotherapy. The behavior of this tumor is potentially aggressive.

Local recurrence and distant metastasis of supratentorial primitive neuro-ectodermal tumor in an adult patient successfully treated with intensive induction chemotherapy and maintenance temozolomide

NARCIS (Netherlands)

Terheggen, F.; Troost, D.; Majoie, C. B.; Leenstra, S.; Richel, D. J.

2007-01-01

Supratentorial primitive neuro-ectodermal tumors (PNET) in adults are very rare. Extraneural metastasis are unusual and the optimal palliative chemotherapy regimen is not established. We present a 26-year-old patient with local recurrence and distant metastasis of supratentorial PNET successfully

Extraosseous Ewing's sarcoma / primitive neuroectodermal tumor of the sacral nerve plexus

International Nuclear Information System (INIS)

Narula, MK; Gupta, Nishant; Anand, Rama; Kapoor, Sudhir

2009-01-01

We report an unusual case of Ewing's sarcoma / primitive neuroectodermal tumor (PNET) of the sacral nerve plexus in a 9-year-old boy who presented with a soft tissue swelling and severe piercing pain in the lower back region. MRI of the lumbosacral spine showed a lobulated soft tissue mass with clubbed finger-like projections along the path of the sacral nerves, which had caused widening of the spinal canal and the sacral foramina (S2–S4 level). There was presacral extension and posterior scalloping of the sacral vertebrae. Histopathology of the lesion confirmed Ewing's sarcoma / PNET of the sacral spinal nerve plexus. The patient responded favorably to chemotherapy and radiotherapy, showing clinical and radiological improvement

Computed tomography and magnetic resonance imaging findings of peripheral primitive neuroectodermal tumors of the head and neck

International Nuclear Information System (INIS)

Zhang Weidong; Chen Yanfeng; Li Chuanxing; Zhang Liang; Xu Zhibin; Zhang Fujun

2011-01-01

Purpose: We aimed to analyze the computed tomography (CT) and magnetic resonance imaging (MRI) findings of peripheral primitive neuroectodermal tumor (pPNET) of the head and neck. Methods: Eight patients with pPNET of the head and neck confirmed by histopathological examination were analyzed retrospectively. Results: The average patient age was 8 years. The tumor location in the 8 patients was as follows: maxillofacial region (right, 2; left, 1), left maxillary sinus (1), right masticator space (1), left carotid space (1), right infratemporal fossa (1), and left parotid gland (1). All 5 patients who underwent CT demonstrated ill-defined soft masses and no calcification. Three patients with tumors in the maxillofacial region showed homogeneous small masses and a mild enhancement. The patient with left maxillary sinus tumor showed a heterogeneous mass with patchy, necrotic foci and mild heterogeneous enhancement. The patient with right masticator space tumor showed a heterogeneous mass, and marked heterogeneous enhancement. The T1-weighted images of the patients with right infratemporal fossa, left carotid space, and left parotid gland tumors were isointense. The T2-weighted images were heterogeneous and mildly hyperintense in 2 patients and hyperintense in 1 patient. Heterogeneous intermediate enhancement was demonstrated in 2 patients and mild ring enhancement in 1 patient. Conclusion: The imaging features of pPNET of the head and neck are non-specific. An ill-defined, aggressive mass and variable enhancement on CT and MR images may suggest the diagnosis of pPNET. Peripheral PNET should be included in the differential diagnosis of children and adolescents' regional tumors.

Computed tomography and magnetic resonance imaging findings of peripheral primitive neuroectodermal tumors of the head and neck

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Zhang Weidong [State Key Laboratory of Oncology in South China, Department of Radiology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060 (China); Chen Yanfeng [State Key Laboratory of Oncology in South China, Department of Head and Neck Surgery, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060 (China); Li Chuanxing; Zhang Liang; Xu Zhibin [State Key Laboratory of Oncology in South China, Department of Radiology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060 (China); Zhang Fujun, E-mail: drzhangfj@163.com [State Key Laboratory of Oncology in South China, Department of Radiology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060 (China)

2011-11-15

Purpose: We aimed to analyze the computed tomography (CT) and magnetic resonance imaging (MRI) findings of peripheral primitive neuroectodermal tumor (pPNET) of the head and neck. Methods: Eight patients with pPNET of the head and neck confirmed by histopathological examination were analyzed retrospectively. Results: The average patient age was 8 years. The tumor location in the 8 patients was as follows: maxillofacial region (right, 2; left, 1), left maxillary sinus (1), right masticator space (1), left carotid space (1), right infratemporal fossa (1), and left parotid gland (1). All 5 patients who underwent CT demonstrated ill-defined soft masses and no calcification. Three patients with tumors in the maxillofacial region showed homogeneous small masses and a mild enhancement. The patient with left maxillary sinus tumor showed a heterogeneous mass with patchy, necrotic foci and mild heterogeneous enhancement. The patient with right masticator space tumor showed a heterogeneous mass, and marked heterogeneous enhancement. The T1-weighted images of the patients with right infratemporal fossa, left carotid space, and left parotid gland tumors were isointense. The T2-weighted images were heterogeneous and mildly hyperintense in 2 patients and hyperintense in 1 patient. Heterogeneous intermediate enhancement was demonstrated in 2 patients and mild ring enhancement in 1 patient. Conclusion: The imaging features of pPNET of the head and neck are non-specific. An ill-defined, aggressive mass and variable enhancement on CT and MR images may suggest the diagnosis of pPNET. Peripheral PNET should be included in the differential diagnosis of children and adolescents' regional tumors.

Diagnostic Study of Tumor Characteristics in Patients With Ewing's Sarcoma

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2013-06-20

Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

Primitive neuroectodermal tumor of the maxillary sinus in an elderly male: A case report and literature review

International Nuclear Information System (INIS)

Shah, Saiquat; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul

2014-01-01

Primitive neuroectodermal tumor (PNET), which belongs to the Ewing's sarcoma (ES) family of tumors, is mainly seen in children and young adults. PNETs are extremely rare in the maxilla. Here, we report a case of PNET of the left maxillary sinus in an elderly male. Magnetic resonance imaging (MRI) revealed a slightly enhanced solid mass occupying the left maxillary sinus and infiltrating into the retroantral space. A partial maxillectomy was performed. Despite postoperative chemotherapy, follow-up computed tomography (CT) and MRI revealed a nodal metastasis in the submandibular space. Neck dissection was performed. However, the patient died 10 months after the second surgery because of distant metastasis to the liver. MRI and CT were particularly useful in detecting the extent of the tumor, recurrence, and metastasis. Further, a literature review of the previously reported PNET cases of the maxilla was carried out. In this paper, we also discuss the current approach for the diagnosis and management of these tumors.

Primitive neuroectodermal tumor of the maxillary sinus in an elderly male: A case report and literature review

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Shah, Saiquat [Dept. of Dental Public Health, Bangladesh Dental College, Dhaka (Bangladesh); Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul [Dept. of Oral and Maxillofacial Radiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul (Korea, Republic of)

2014-12-15

Primitive neuroectodermal tumor (PNET), which belongs to the Ewing's sarcoma (ES) family of tumors, is mainly seen in children and young adults. PNETs are extremely rare in the maxilla. Here, we report a case of PNET of the left maxillary sinus in an elderly male. Magnetic resonance imaging (MRI) revealed a slightly enhanced solid mass occupying the left maxillary sinus and infiltrating into the retroantral space. A partial maxillectomy was performed. Despite postoperative chemotherapy, follow-up computed tomography (CT) and MRI revealed a nodal metastasis in the submandibular space. Neck dissection was performed. However, the patient died 10 months after the second surgery because of distant metastasis to the liver. MRI and CT were particularly useful in detecting the extent of the tumor, recurrence, and metastasis. Further, a literature review of the previously reported PNET cases of the maxilla was carried out. In this paper, we also discuss the current approach for the diagnosis and management of these tumors.

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

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

2012-12-01

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

RASSF1A promoter is highly methylated in primitive neuroectodermal tumors of the central nervous system.

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Inda, María-del-Mar; Castresana, Javier S

2007-08-01

Although cancer is rare in children, primary brain tumors constitute the most frequent location of solid tumors in childhood. Primitive neuroectodermal tumors (PNET) of the central nervous system can be divided into infratentorial PNET or medulloblastoma (MB), and supratentorial (sPNET) tumors. Although MB and sPNET are histologically similar, clinical evolution differs, sPNET being more aggressive than MB. Some studies have suggested that MB and sPNET present different molecular genetic aberrations. The RASSF1A (Ras Association Domain Family Protein 1) gene, located at 3p21.3, is highly methylated in multiple primary tumor samples, including neuroblastoma. In order to define whether there are genetic differences in the methylation frequency of RASSF1A between MB and sPNET, we analyzed 32 PNET paraffin-embedded samples (23 MB and 9 sPNET) by methylation specific polymerase chain reaction (MSP). We also analyzed RASSF1A expression by reverse transcription polymerase chain reaction in five PNET cell lines. All PNET cell lines showed lack of RASSF1A expression that was correlated with RASSF1A promoter hypermethylation. RASSF1A methylation was detected in 19 of 21 MB cases (91%) and in five of six sPNET samples (83%). Although the methylation frequency found in MB was slightly higher than in sPNET, no statistical differences were found for the RASSF1A hypermethylation frequency (P > 0.05) presented at MB versus sPNET. Therefore, the inactivation of the RASSF1A gene seems to be an important step in the tumorigenesis of PNET of the central nervous sytem. More studies should be performed in order to determine genetic differences between MB and sPNET.

Melanotic neuroectodermal tumor of infancy (progonoma): a case report emphasizing the computed tomography findings and literature review; Tumor neuroectodermico melanocitico da infancia (progonoma): relato de caso enfatizando os aspectos tomograficos e revisao da literatura

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Araujo Junior, Cyrillo Rodrigues de; Carvalho, Tarcisio Nunes; Fraguas Filho, Sergio Roberto; Costa, Marlos Augusto Bitencourt; Borba, Ana Olivia Cardoso; Figueiredo, Sizenildo da Silva; Machado, Marcio Martins; Teixeira, Kim-Ir-Sen Santos [Goias Univ., Goiania, GO (Brazil). Hospital das Clinicas. Servico de Diagnostico por Imagem]. E-mail: radiologia@brturbo.com

2004-12-01

The melanotic neuroectodermal tumor of infancy, also known as progonoma, is a rare benign disease of neural crest origin that occurs within the first year of life and affects mainly the maxilla. The authors report a case of a 10-month-old child presenting with this uncommon tumor in the maxilla, emphasizing the diagnostic findings on computed tomography, and present a literature review. (author)

Recurrent spinal primitive neuroectodermal tumor with brain and bone metastases: A case report.

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Chen, Frank; Chiou, Shyh-Shin; Lin, Sheng-Fung; Lieu, Ann-Shung; Chen, Yi-Ting; Huang, Chih-Jen

2017-11-01

Primary spinal primitive neuroectodermal tumor (PNET) is relatively rare in all age groups, and the prognosis in most cases of spinal PNETs appears to be poor, with a median patient survival of 1 to 2 years. We present a case with recurrent spinal PNET with brain and bone metastases that was successfully treated by multimodality treatment. A 14-year-old teenage girl had suffered from progressive left upper back pain with bilateral lower legs weakness and numbness for 1 year. After treatment, left neck mass was noted 3 years later. Initially, magnetic resonance imaging (MRI) showed neurogenic tumor involving intradural extramedullary space of T5-T10. Pathology report showed PNET (World Health Organization grade IV) featuring lobules of neoplastic cells with round regular nuclei, high nucleus-to-cytoplasm ratio, and fibrillary cytoplasm. At the time of tumor recurrence, chest MRI then showed recurrent tumor at T2-T3 level of the epidural space with right neural foramina invasion. Brain MRI showed extensive bilateral calvarial metastases and leptomeningeal metastases in the right frontoparietal regions. Bone scan showed multiple bone metastases. T-spine tumor removal and adjuvant radiotherapy (RT) to T-spine tumor bed were performed in the initial treatment. After clinical tumor recurrence, tumor removal was done again. She then received chemotherapy followed by whole brain irradiation with hippocampal sparing with 35 gray in 20 fractions. After treatment, follow-up images showed that the disease was under control. There was no neurological sequela. She has survived more than 7 years from diagnosis and more than 4 years from recurrence to date. Multimodality treatments including operation, RT, and chemotherapy should be considered in the initial treatment planning, and salvage chemotherapy was useful in this case.

Multiple Ewing Sarcoma/Primitive Neuroectodermal Tumors in the Mediastinum: A Case Report and Literature Review.

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Bae, Sung Hwan; Hwang, Jung Hwa; Da Nam, Bo; Kim, Hyun Jo; Kim, Ki-Up; Kim, Dong Won; Choi, In Ho

2016-02-01

Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are high-grade malignant neoplasms. These malignancies present very rare tumors of thoracopulmonary area and even rarer in the mediastinum. In our knowledge, ES/PNET presented with multiple mediastinal masses has not been reported previously. We experienced a case of a 42-year-old man presented with gradual onset of left-side pleuritic chest pain. A contrast-enhanced chest computed tomography (CT) scan showed separate 2 large heterogeneously enhancing masses in each anterior and middle mediastinum of the left hemithorax. Positron emission tomography-computed tomography (PET-CT) scan revealed high fluorodeoxyglucose (FDG) uptake in the mediastinal masses. After surgical excision for the mediastinal masses, both of the masses were diagnosed as the ES/PNET group of tumors on the histopathologic examination. The patient refused postoperative adjuvant chemotherapy and came back with local tumor recurrence and distant metastasis on 4-month follow-up after surgical resection. We report this uncommon form of ES/PNET. We are to raise awareness that this rare malignancy should be considered as a differential diagnosis of the malignant mediastinal tumors and which can be manifested as multiple masses in a patient. Understanding this rare entity of extra-skeletal ES/PNET and characteristic imaging findings can help radiologists and clinicians to approach proper diagnosis and better management for this highly malignant tumor.

Primitive Neuroectodermal Tumor E wing's Sarcoma Arising from the Cigomatic Arch and the Masticator y Space. A Case Report

International Nuclear Information System (INIS)

Arango Bonnet, German; Andres Narvaez, Jorge; Garcia, Sara Eugenia

2008-01-01

Peripheral primitive neuroectodermic tumor (PNET) or peripheral neuro epithelioma is a malignant neoplasia consisting of round small blue cells, which derive from the neural crest. Amongst malignant tumors it is one the least differentiated histological types. Ewings sarcoma and PNET are morphologically impossible to differentiate; they are also very similar pathologically in terms of their imagining appearance. Due to these similarities we will consider them as a single entity. These can appear in infants, but are more common in adolescents. Treatment includes hemo therapy,surgery and radiotherapy. We present a case of an 8 year old female patient, diagnosed with Ewing Sarcoma, confirmed by histopathology and immunohistochemistry, we will also present a brief review of the literature.

Dynamic contrast enhanced MRI study of primary primitive neuroectodermal tumor in the thoracic spine

International Nuclear Information System (INIS)

Chen Yu; Xu Jianmin; Li Ying; Zhang Jingzhong; Zhu Jing

2004-01-01

Objective: To investigate the value of dynamic contrast-enhanced MR imaging in the diagnosis and differentiation of primitive neuroectodermal tumor (PNET) in the thoracic spine. Methods: The dynamic contrast-enhanced MR imaging of 2 patients (3 times) with PNET in the thoracic spine proved by surgery and pathology were prospectively studied. Results: In the curves of SI-time and CER-time, PNET in the thoracic spine showed a rapid rise to the peak between 60 s and 120 s, then the flat level was kept and no obvious decline was detected after about 3.5 minute. Conclusion: Dynamic contrast-enhanced MRI can help to make the diagnosis and differential diagnosis for PNET in the thoracic spine, offer reliable information for the choice of clinical management, and predict the prognosis

PTEN and DMBT1 homozygous deletion and expression in medulloblastomas and supratentorial primitive neuroectodermal tumors.

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Inda, María Mar; Mercapide, Javier; Muñoz, Jorge; Coullin, Philippe; Danglot, Giséle; Tuñon, Teresa; Martínez-Peñuela, José María; Rivera, José María; Burgos, Juan J; Bernheim, Alain; Castresana, Javier S

2004-12-01

Medulloblastoma, which accounts for 20-25% of all childhood brain tumors, is defined as a primitive neuroectodermal tumor (PNET) located in the cerebellum. Supratentorial PNET are less frequent than medulloblastoma. But their clinical outcome is worse than in medulloblastomas. Chromosome 10q contains at least 2 tumor suppressor genes that might play a role in brain tumor development: PTEN and DMBT1. The aim of this study was to compare the status of homozygous deletion and expression of PTEN and DMBT1 genes in PNET primary tumor samples and cell lines. Homozygous deletions of PTEN and DMBT1 were studied in 32 paraffin-embedded PNET samples (23 medulloblastomas and 9 supratentorial PNET) and in 7 PNET cell lines, by differential PCR and by FISH. PTEN homozygous losses were demonstrated in 7 medulloblastomas (32%) and in no supratentorial PNET, while homozygous deletions of DMBT1 appeared in 1 supratentorial PNET (20%) and in 7 medulloblastomas (33%). No homozygous deletion of PTEN or DMBT1 was detected in any of the PNET cell lines either by differential PCR or by FISH. Expression study of the 2 genes was performed in the 7 PNET cell lines by RT-PCR. One PNET cell line lacked PTEN and DMBT1 expression, while 2 medulloblastoma cell lines did not express DMBT1. Our results add some positive data to the hypothesis that supratentorial PNETs and medulloblastomas might be genetically different.

Tissue Reactivity of the 14F7 Mab Raised against N-Glycolyl GM3 Ganglioside in Tumors of Neuroectodermal, Mesodermal, and Epithelial Origin

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Blanco, Rancés; Quintana, Yisel; Blanco, Damián; Cedeño, Mercedes; Rengifo, Charles E.; Frómeta, Milagros; Ríos, Martha; Rengifo, Enrique; Carr, Adriana

2013-01-01

The expression of N-glycolylneuraminic acid forming the structure of gangliosides and/or other glycoconjugates (Hanganutziu-Deicher antigen) in human has been considered as a tumor-associated antigen. Specifically, some reports of 14F7 Mab (a highly specific Mab raised against N-glycolyl GM3 ganglioside) reactivity in human tumors have been recently published. Nevertheless, tumors of epithelial origin have been mostly evaluated. The goal of the present paper was to evaluate the immunohistochemical recognition of 14F7 Mab in different human tumors of neuroectodermal, mesodermal, and epithelial origins using an immunoperoxidase staining method. Samples of fetal, normal, and reactive astrocytosis of the brain were also included in the study. In general, nontumoral tissues, as well as, low-grade brain tumors showed no or a limited immunoreaction with 14F7 Mab. Nevertheless, high-grade astrocytomas (III-IV) and neuroblastomas, as well as, sarcomas and thyroid carcinomas were mostly reactive with 14F7. No reaction was evidenced in medulloblastomas and ependymoblastomas. Our data suggest that the expression of N-glycolyl GM3 ganglioside could be related to the aggressive behavior of malignant cells, without depending on the tumor origin. Our data could also support the possible use of N-glycolyl GM3 as a target for both active and passive immunotherapies of malignancies expressing this molecule. PMID:26317019

Primary Ewing's sarcoma/primitive neuroectodermal tumor of the ileum: case report of a 16-year-old Chinese female and literature review.

Science.gov (United States)

Li, Teng; Zhang, Fang; Cao, Yarui; Ning, Shoubin; Bi, Yongmin; Xue, Weicheng; Ren, Li

2017-05-04

Ewing's sarcoma (ES) and primitive neuroectodermal tumors (PNET) are closely related tumors. Although soft tissue ES/PNET are common in clinical practice, they are rare in the small intestine. Because of the absence of characteristic clinical symptoms, they are easily misdiagnosed as other benign or malignant diseases. Here, we present the case of a 16-year-old female who complained of anemia and interval hematochezia. Her serum test results showed only a slight elevation of CA-125 and a low level of hemoglobin. Computer tomography and magnetic resonance imaging revealed a cystic and solid mass in the lower abdominal quadrant and pelvic region, which prompted suspicion of a malignant gastrointestinal stromal tumor of the small intestine. After resection, the tumor's histology and immunohistochemistry (positive for CD99, vimentin and synaptophysin) results suggested ES/PNET. Fluorescent in situ hybridization tests proved the breakpoint rearrangement of the EWSR1 gene in chr 22.Ultrastructural analysis revealed neurosecretory and glycogen granules in the tumor cell cytoplasm. Together, these data supported the diagnosis of a rare case of localized ES/PNET in the small intestine without adjuvant chemo- or radiotherapy. To our knowledge, this is the first report from China of a primary small bowel ES/PNET in the English-language literature. In addition, on the basis of findings from previous publications and the current case, the optimal treatment for localized gastrointestinal ES/PNET is discussed.

Melanotic neuroectodermal tumour of infancy: Case report of an unusual tumor

Directory of Open Access Journals (Sweden)

Agarwal P

2003-01-01

Full Text Available The melanotic neuroectodermal tumour of infancy is a rare, pigmented neoplasm of neural crest origin occurring in infants before 1 year of age. We report a 6-month-old male baby with a similar tumour involving superior maxillary alveolar ridge and most of the hard palate. A partial maxillectomy was performed by oral approach. One-year follow-up of the patient showed no recurrence.

Integrated bioinformatic analysis unveils significant genes and pathways in the pathogenesis of supratentorial primitive neuroectodermal tumor

Directory of Open Access Journals (Sweden)

Wang G

2018-04-01

Full Text Available Guang-Yu Wang,1,* Ling Li,2,* Bo Liu,1 Xiao Han,1 Chun-Hua Wang,1 Ji-Wen Wang3 1Department of Neurosurgery, 2Department of Pediatrics, Qilu Children’s Hospital of Shandong University, Jinan, Shandong, 3Department of Neurology, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Pudong New District, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: This study aimed to explore significant genes and pathways involved in the pathogenesis of supratentorial primitive neuroectodermal tumor (sPNET. Materials and methods: Gene expression profile of GSE14295 was downloaded from publicly available Gene Expression Omnibus (GEO database. Differentially expressed genes (DEGs were screened out in primary sPNET samples compared with normal fetal and adult brain reference samples (sPNET vs fetal brain and sPNET vs adult brain. Pathway enrichment analysis of these DEGs was conducted, followed by protein–protein interaction (PPI network construction and significant module selection. Additionally, transcription factors (TFs regulating the common DEGs in the two comparison groups were identified, and the regulatory network was constructed. Results: In total, 526 DEGs (99 up- and 427 downregulated in sPNET vs fetal brain and 815 DEGs (200 up- and 615 downregulated in sPNET vs adult brain were identified. DEGs in sPNET vs fetal brain and sPNET vs adult brain were associated with calcium signaling pathway, cell cycle, and p53 signaling pathway. CDK1, CDC20, BUB1B, and BUB1 were hub nodes in the PPI networks of DEGs in sPNET vs fetal brain and sPNET vs adult brain. Significant modules were extracted from the PPI networks. In addition, 64 upregulated and 200 downregulated overlapping DEGs were identified in both sPNET vs fetal brain and sPNET vs adult brain. The genes involved in the regulatory network upon overlapping DEGs and the TFs were correlated with calcium signaling pathway

FOETAL ULTRASOUND - NEUROECTODERMAL ANOMALIES IN RURAL PREGNANT WOMEN

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Mala Venkata

2016-06-01

Full Text Available BACKGROUND A prospective clinical study to know the various types of congenital Neuroectodermal Anomalies on obstetric Ultrasound, in rural pregnant women. To reduce the maternal morbidity and mortality by early detection of these Congenital Neuroectodermal Anomalies. To calculate the incidence and prevalence of different types of Congenital Neuroectodermal Anomalies, in these rural pregnant women. To assist the obstetrician in taking decisions regarding the termination or continuation of the pregnancy in relation to the type of malformation and its prognosis. METHODS A prospective clinical study of Congenital Neuroectodermal Anomalies in 22,000 rural pregnant women coming to the Santhiram Medical College, Radiology Department for a routine obstetric scan. 44 cases of neuroectodermal anomalies were detected out of the 22000 cases, within an incidence of 2 per 1000 cases. Approximately 1 in every 500 cases showed an anomaly. RESULTS The most common lesions detected were hydrocephalus, and spina bifida followed by anencephaly. Association of these lesions with consanguinity, previous history of similar anomaly and intake of iron and folic acid tablets was noted. CONCLUSION Ultrasound is an excellent modality for the diagnosis and characterisation of the neuroectodermal anomalies. Its multiplanar imaging property along with real time image visualisation make it an excellent tool for the diagnosis and characterisation of these anomalies

MRI diagnosis of supratentorial and intraspinal primitive neuroectodermal tumors

International Nuclear Information System (INIS)

Liu Meili; Cui Shimin; Han Tong; Li Tao; Liu Li; Lei Jing; Qing Jingxi; Yan Xiaoling; Kong Fanming

2004-01-01

Objective: To analyze the MRI features of supratentorial and intraspinal primitive neuroectodermal tumors (PNET) and improve the diagnostic accuracy. Methods: MRI manifestations of 9 PNET diagnosed via operation and pathological examination were analyzed. There were 6 men and 3 women, and the mean age was 32.6 years. In all 9 cases, conventional plain MR scans were performed, including spin echo (SE), fast spin echo (FSE), and fluid attenuated inversion recovery (FLAIR) sequences. Diffusion weighted images (DWIs) and postcontrast MR images were obtained in 2 and 4 cases, respectively. Results: The 8 cases with supratentorial lesions included fronto-temporal lesion in 2 cases, occipital lesion in 2 cases, fronto-parietal lobe, parietal lobe, frontal lobe lesion in each 1 case, and posterior part of third ventricle in 1 case, and the lesion located in the thoracic spinal canal in 1 case. All the lesions were quite large in volume, and the largest one was 6.0 cm x 6.9 cm x 4.9 cm. Except for the round-like lesion in the posterior part of third ventricle, the other 7 supratentorial lesions were irregular in shape, well demarked, and often with solid consistency and slight peritumoral edema. The lesions demonstrated long T 1 and long or slightly long T 2 signal intensity in 4 cases, mixed signal intensity on T 1 WI, T 2 WI, and FLAIR images in 4 cases. Small cystic degeneration could be seen in 2 cases, hemorrhage in 4 cases, and flow void vessels in 3 cases. 3 cases demonstrated irregular ring-like enhancement and ependymal dissemination. The lesion in the thoracic canal demonstrated as a slightly enhanced soft tissue mass with adjacent bony destruction and muscle infiltration. Conclusion: MR findings of PNET are rather characteristic, but the final diagnosis relies on pathology

Primitive Neuroectodermal Tumors of the Female Genital Tract: A Morphologic, Immunohistochemical, and Molecular Study of 19 Cases.

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Chiang, Sarah; Snuderl, Matija; Kojiro-Sanada, Sakiko; Quer Pi-Sunyer, Ariadna; Daya, Dean; Hayashi, Tohru; Bosincu, Luisanna; Ogawa, Fumihiro; Rosenberg, Andrew E; Horn, Lars-Christian; Wang, Lu; Iafrate, A John; Oliva, Esther

2017-06-01

Primary primitive neuroectodermal tumor (PNET) of the female genital tract is rare, and its proper classification remains unclear. The clinical, histologic, and immunophenotypic features as well as EWSR1 rearrangement status of 19 gynecologic PNETs, including 10 ovarian, 8 uterine, and 1 vulvar tumors, are herein reported. Patient age ranged from 12 to 68 years, with a median age of 20 and 51 years among those with ovarian and uterine PNETs, respectively. Morphologic features of central nervous system (CNS) tumors were seen in 15 PNETs, including 9 medulloblastomas, 3 ependymomas, 2 medulloepitheliomas, and 1 glioblastoma, consistent with central PNET. The remaining 4 PNETs were composed entirely of undifferentiated small round blue cells and were classified as Ewing sarcoma/peripheral PNET. Eight PNETs were associated with another tumor type, including 5 ovarian mature cystic teratomas, 2 endometrial low-grade endometrioid carcinomas, and a uterine carcinosarcoma. By immunohistochemistry, 17 PNETs expressed at least 1 marker of neuronal differentiation, including synaptophysin, NSE, CD56, S100, and chromogranin in 10, 8, 14, 8, and 1 tumors, respectively. GFAP was positive in 4 PNETs, all of which were of central type. Membranous CD99 and nuclear Fli-1 staining was seen in 10 and 16 tumors, respectively, and concurrent expression of both markers was seen in both central and Ewing sarcoma/peripheral PNETs. All tumors expressed vimentin, whereas keratin cocktail (CAM5.2, AE1/AE3) staining was only focally present in 4 PNETs. Fluorescence in situ hybridization was successful in all cases and confirmed EWSR1 rearrangement in 2 of 4 tumors demonstrating morphologic features of Ewing sarcoma/peripheral PNET and concurrent CD99 and Fli-1 expression. In conclusion, central and Ewing sarcoma/peripheral PNETs may be encountered in the female genital tract with central PNETs being more common. Central PNETs show a spectrum of morphologic features that overlaps with CNS

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.

[Undifferentiated soft tissue tumor with rhabdoid phenotype (extra-renal rhabdoid tumor). Report of a congenital case associated with medulloblastoma in a brother].

Science.gov (United States)

Costes, V; Medioni, D; Durand, L; Sarran, N; Marguerite, G; Baldet, P

1997-03-01

We report a case of congenital cervical rhabdoid tumor with association of a medulloblastoma in a brother. The immunohistochemical features of this tumor are compatible with a neuroectodermal differentiation (MIC 2+, Leu 7+). Extrarenal rhabdoid tumors share a common morphology but do not represent a single entity with only one histogenesis. Most of them are now considered to be of neuroectodermal origin. In our case, the association with a medulloblastoma in a brother seems to confirm this concept.

Imaging of brain tumors

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Gaensler, E H.L. [California Univ., San Francisco, CA (United States). Dept. of Radiology

1996-12-31

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.).

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.)

Peripheral primitive neuroendocrine tumor of the chest wall—A case report with pathological correlation

Directory of Open Access Journals (Sweden)

Jidi Gao, MD

2018-04-01

Full Text Available Primitive neuroectodermal tumor is a high-grade malignant tumor originating from the neural crest and neuroectoderm, which can be subdivided into central and peripheral categories. Peripheral primitive neuroectodermal tumor is thought to be identical to Ewing's sarcoma, and falls under a broader category of Ewing's sarcoma family of tumors. Very rarely, it may present without osseous involvement, known as extraosseous Ewing's sarcoma. Here we present a case of a 38-year-old woman, who presented with several-month history of a slow-growing chest wall mass, initially thought to be a breast mass. The mass was diagnosed as extraosseous Ewing's sarcoma upon tissue biopsy. The patient was started on a dose-intensified neoadjuvant therapy, based on protocol from pediatric population given rarity of this tumor in the adult population. While the patient was initially planned for surgical resection, the tumor showed excellent response to chemotherapy on follow-up imaging, and radiation therapy was elected in lieu of resection. Keywords: Chest wall tumors, Peripheral PNET, Ewing's sarcoma

High resolution array-based comparative genomic hybridisation of medulloblastomas and supra-tentorial primitive neuroectodermal tumours

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McCabe, Martin Gerard; Ichimura, Koichi; Liu, Lu; Plant, Karen; Bäcklund, L Magnus; Pearson, Danita M; Collins, Vincent Peter

2010-01-01

Medulloblastomas and supratentorial primitive neuroectodermal tumours are aggressive childhood tumours. We report our findings using array comparative genomic hybridisation (CGH) on a whole-genome BAC/PAC/cosmid array with a median clone separation of 0.97Mb to study 34 medulloblastomas and 7 supratentorial primitive neuroectodermal tumours. Array CGH allowed identification and mapping of numerous novel small regions of copy number change to genomic sequence, in addition to the large regions already known from previous studies. Novel amplifications were identified, some encompassing oncogenes, MYCL1, PDGFRA, KIT and MYB, not previously reported to show amplification in these tumours. In addition, one supratentorial primitive neuroectodermal tumour had lost both copies of the tumour suppressor genes CDKN2A & CDKN2B. Ten medulloblastomas had findings suggestive of isochromosome 17q. In contrast to previous reports using conventional CGH, array CGH identified three distinct breakpoints in these cases: Ch 17: 17940393-19251679 (17p11.2, n=6), Ch 17: 20111990-23308272 (17p11.2-17q11.2, n=4) and Ch 17: 38425359-39091575 (17q21.31, n=1). Significant differences were found in the patterns of copy number change between medulloblastomas and supratentorial primitive neuroectodermal tumours, providing further evidence that these tumours are genetically distinct despite their morphological and behavioural similarities. PMID:16783165

Detection of SYT and EWS gene rearrangements by dual-color break-apart CISH in liquid-based cytology samples of synovial sarcoma and Ewing sarcoma/primitive neuroectodermal tumor.

Science.gov (United States)

Kumagai, Arisa; Motoi, Toru; Tsuji, Kaori; Imamura, Tetsuo; Fukusato, Toshio

2010-08-01

To improve cytologic diagnostic accuracy for translocation-associated sarcomas, we explored dual-color break-apart (dc) chromogenic in situ hybridization (CISH) on liquid-based cytology (LBC) samples of 2 prototypic sarcomas: synovial sarcoma (SS) and Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET). LBC samples of 10 cases of SS and 9 cases of ES/PNET were subjected to dc-CISH using probes for the specifically rearranged genes in each tumor entity: SYT in SS and EWS in ES/PNET. Rearranged SYT was successfully detected in all SSs but not in any ES/PNETs. In contrast, EWS rearrangement was identified in all ES/PNETs but not in any SSs. These results were validated by dc-fluorescence in situ hybridization and reverse transcription-polymerase chain reaction. dc-CISH on LBC samples is a reliable modality to detect gene rearrangements in sarcomas. This system has a clear advantage over other methods, enabling simultaneous visualization of the genetic abnormality and well-preserved, nonoverlapping cytomorphologic features with clear background under bright-field microscope.

Collecting and Storing Blood and Brain Tumor Tissue Samples From Children With Brain Tumors

Science.gov (United States)

2017-12-11

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Newly Diagnosed Childhood Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

NARCIS (Netherlands)

Sturm, Dominik; Orr, Brent A.; Toprak, Umut H.; Hovestadt, Volker; Jones, David T. W.; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A.; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J.; Balasubramanian, Gnanaprakash; Worst, Barbara C.; Pajtler, Kristian W.; Brabetz, Sebastian; Johann, Pascal D.; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M.; Remke, Marc; Phillips, Joanna J.; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C.; Schniederjan, Matthew J.; Santi, Mariarita; Buccoliero, Anna M.; Dahiya, Sonika; Kramm, Christof M.; von Bueren, André O.; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C.; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V. Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U.; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S.; Taylor, Michael D.; Jones, Chris; Jabado, Nada; Karajannis, Matthias A.; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M.; Ellison, David W.; Korshunov, Andrey; Kool, Marcel

2016-01-01

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

NARCIS (Netherlands)

Sturm, Dominik; Orr, Brent A.; Toprak, Umut H.; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A.; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J.; Balasubramanian, Gnanaprakash; Worst, Barbara C.; Pajtler, Kristian W.; Brabetz, Sebastian; Johann, Pascal D.; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M.; Remke, Marc; Phillips, Joanna J.; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C.; Schniederjan, Matthew J.; Santi, Mariarita; Buccoliero, Anna M.; Dahiya, Sonika; Kramm, Christof M.; Von Bueren, André O.; Von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C.; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V. Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U.; Shalaby, Tarek; Grotzer, Michael; Van Meter, Timothy; Monoranu, Camelia Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; Van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S.; Taylor, Michael D.; Jones, Chris; Jabado, Nada; Karajannis, Matthias A.; Eils, Roland; Schlesner, Matthias; Lichter, Peter; Von Deimling, Andreas; Pfister, Stefan M.; Ellison, David W.; Korshunov, Andrey; Kool, Marcel

2016-01-01

Summary Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of

BNCT for malignant brain tumors in children

International Nuclear Information System (INIS)

Kageji, T.; Mizobuchi, Y.; Nagahiro, S.; Nakagawa, Y.; Kumada, Hiroaki

2006-01-01

BSH-based intra-operative BNCT as an initial treatment underwent in 4 children with malignant brain tumors since 1998. There were 2 glioblastomas, one primitive neuroectodermal tumor (PNET) and one anaplastic ependymoma patient. They included two children under 3-year-old. All GBM patients were died of CSF dissemination without tumor regrowth in the primary site. Another PNET and anaplastic ependymoma patients are still alive without tumor recurrence. We can consider BNCT is optimal treatment modality for malignant brain tumor in children. (author)

Atypical teratoid/rhabdoid tumors: challenges and search for solutions

International Nuclear Information System (INIS)

Biswas, Ahitagni; Kashyap, Lakhan; Kakkar, Aanchal; Sarkar, Chitra; Julka, Pramod Kumar

2016-01-01

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal central nervous system tumor commonly affecting children <3 years of age. It roughly constitutes 1%–2% of all pediatric central nervous system tumors. Recent data show that it is the most common malignant central nervous system tumor in children <6 months of age. Management of this aggressive tumor is associated with a myriad of diagnostic and therapeutic challenges. On the basis of radiology and histopathology alone, distinction of AT/RT from medulloblastoma or primitive neuroectodermal tumor is difficult, and hence this tumor has been commonly misdiagnosed as primitive neuroectodermal tumor for decades. Presence of a bulky heterogeneous solid-cystic mass with readily visible calcification and intratumor hemorrhage, occurring off-midline in children <3 years of age, should alert the radiologist toward the possibility of AT/RT. Presence of rhabdoid cells on histopathology and polyphenotypic immunopositivity for epithelial, mesenchymal, and neuroectodermal markers along with loss of expression of SMARCB1/INI1 or SMARCA4/BRG1 help in establishing a diagnosis of AT/RT. The optimal management comprises maximal safe resection followed by radiation therapy and multiagent intensive systemic chemotherapy. Gross total excision is difficult to achieve in view of the large tumor size and location and young age at presentation. Leptomeningeal spread is noted in 15%–30% of patients, and hence craniospinal irradiation followed by boost to tumor bed is considered standard in children older than 3 years. However, in younger children, craniospinal irradiation may lead to long-term neurocognitive and neuroendocrine sequel, and hence focal radiation therapy may be a pragmatic approach. In this age group, high-dose chemotherapy with autologous stem cell rescue may also be considered to defer radiation therapy, but this approach is also associated with significant treatment-related morbidity and mortality

[Bilateral anophthalmia and left-sided orbital tumor : case of an eight-month-old infant].

Science.gov (United States)

Hundertmark, P; Dierks, P; Gottschalk, J; Kreusch, T; Wiegand, W

2011-08-01

An 8-month-old infant from Russia with bilateral anophthalmia presented with an expanding orbital tumor. The tumor was extirpated and the histological examination revealed a non-malignant pseudocystic process with residual neuro-ectodermal structures.

Simultaneous occurrence of a supra- and an infratentorial glioma in a patient with Ollier's disease : more evidence for non-mesodermal tumor predisposition in multiple enchondromatosis

NARCIS (Netherlands)

Heeg, M; Klein, JP; Krikke, AP

1998-01-01

A case is presented in which two neuro-ectodermal tumors, an infra- and a supratentorial glioma, developed in a young man with multiple enchondromatosis of Ollier's disease. This is the third such case of multifocal low-grade glioma in Ollier's disease, suggesting a predisposition for non-mesodermal

Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

Science.gov (United States)

2018-05-15

Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

18F-FLT Positron Emission Tomography and Diffusion-Weighted Magnetic Resonance Imaging in Planning Surgery and Radiation Therapy and Measuring Response in Patients With Newly Diagnosed Ewing Sarcoma

Science.gov (United States)

2017-11-16

Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Ewing Sarcoma of Bone; Extraosseous Ewing Sarcoma; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

Malignant melanotic neuroectodermal tumour of infancy affecting the occipital squama.

Directory of Open Access Journals (Sweden)

Patankar T

1998-07-01

Full Text Available An unusual case of a melanotic neuroectodermal tumour of the occipital squama, which underwent malignant transformation in a nine-month-old infant is reported and pertinent literature reviewed.

Yoga Therapy in Treating Patients With Malignant Brain Tumors

Science.gov (United States)

2017-07-27

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

Enhanced anti-tumor activity of a new curcumin-related compound against melanoma and neuroblastoma cells

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Pastorino Fabio

2010-06-01

Full Text Available Abstract Background Sharing the common neuroectodermal origin, melanoma and neuroblastoma are tumors widely diffused among adult and children, respectively. Clinical prognosis of aggressive neuroectodermal cancers remains dismal, therefore the search for novel therapies against such tumors is warranted. Curcumin is a phytochemical compound widely studied for its antioxidant, anti-inflammatory and anti-cancer properties. Recently, we have synthesized and tested in vitro various curcumin-related compounds in order to select new anti-tumor agents displaying stronger and selective growth inhibition activity on neuroectodermal tumors. Results In this work, we have demonstrated that the new α,β-unsaturated ketone D6 was more effective in inhibiting tumor cells growth when compared to curcumin. Normal fibroblasts proliferation was not affected by this treatment. Clonogenic assay showed a significant dose-dependent reduction in both melanoma and neuroblastoma colony formation only after D6 treatment. TUNEL assay, Annexin-V staining, caspases activation and PARP cleavage unveiled the ability of D6 to cause tumor cell death by triggering apoptosis, similarly to curcumin, but with a stronger and quicker extent. These apoptotic features appear to be associated with loss of mitochondrial membrane potential and cytochrome c release. In vivo anti-tumor activity of curcumin and D6 was surveyed using sub-cutaneous melanoma and orthotopic neuroblastoma xenograft models. D6 treated mice exhibited significantly reduced tumor growth compared to both control and curcumin treated ones (Melanoma: D6 vs control: P and D6 vs curcumin P Neuroblastoma: D6 vs both control and curcumin: P . Conclusions Our data indicate D6 as a good candidate to develop new therapies against neural crest-derived tumors.

Hyperfractionated craniospinal radiotherapy and adjuvant chemotherapy for children with newly diagnosed medulloblastoma and other primitive neuroectodermal tumors

International Nuclear Information System (INIS)

Allen, Jeffrey C.; Donahue, Bernadine; DaRosso, Robert; Nirenberg, Anita

1996-01-01

Purpose: This single-institution Phase I/II study conducted from 1989 to 1995 evaluates the feasibility of a multi-modality protocol combining hyperfractionated craniospinal radiotherapy (HFRT) followed by adjuvant chemotherapy in 23 patients with newly diagnosed primitive neuroectodermal tumors (PNET) arising in the central nervous system. Methods and Materials: All 23 patients had a histologically confirmed PNET and were over 3 years of age at diagnosis. The eligibility criteria for PNET patients with cerebellar primaries (medulloblastoma) included either a high T stage (T3b or 4) or high M stage (M1-3). All patients with noncerebellar primaries were eligible regardless of T or M stage. The median age of the 23 patients was 9 years (mean 3-25); 11 were female. The primary tumor arose in the cerebellum in 19. Of these medulloblastoma patients, 15 had high T stages (T3b or T4) with large locally invasive tumors and no evidence of metastases (M0), constituting Group 1. Thirteen (86%) of these patients had gross total resections. Four other medulloblastoma patients had both high T and high M stages, constituting Group 2. Group 3 consisted of four other patients with exocerebellar primaries (two brain, one brain stem, and one cauda equina), three of whom were M3. Hyperfractionated radiotherapy was administered within 4 weeks of surgery. Twice-daily 1-Gy fractions were administered separated by 4-6 h. The total dose to the primary intracranial tumor and other areas of measurable intracranial disease was 72 Gy. The prophylactic craniospinal axis dose was 36 Gy, and boosts of 44-56 Gy were administered to metastatic spinal deposits. Following radiotherapy, monthly courses of multiagent chemotherapy were administered sequentially (cyclophosphamide-vincristine followed by cisplatin-etoposide followed by carboplatin-vincristine) for a total of 9 months. Results: All patients completed radiotherapy as planned. Only three patients lost >10% of their body weight. One patient

ERK inhibition promotes neuroectodermal precursor commitment by blocking self-renewal and primitive streak formation of the epiblast.

Science.gov (United States)

Yu, Yang; Wang, Xiaoxiao; Zhang, Xiaoxin; Zhai, Yanhua; Lu, Xukun; Ma, Haixia; Zhu, Kai; Zhao, Tongbiao; Jiao, Jianwei; Zhao, Zhen-Ao; Li, Lei

2018-01-05

Pluripotent stem cells hold great promise for regenerative medicine. However, before clinical application, reproducible protocols for pluripotent stem cell differentiation should be established. Extracellular signal-regulated protein kinase (ERK) signaling plays a central role for the self-renewal of epiblast stem cells (EpiSCs), but its role for subsequent germ layer differentiation is still ambiguous. We proposed that ERK could modulate differentiation of the epiblast. PD0325901 was used to inhibit ERK activation during the differentiation of embryonic stem cells and EpiSCs. Immunofluorescence, western blot analysis, real-time PCR and flow cytometry were used to detect germ layer markers and pathway activation. We demonstrate that the ERK phosphorylation level is lower in neuroectoderm of mouse E7.5 embryos than that in the primitive streak. ERK inhibition results in neural lineage commitment of epiblast. Mechanistically, PD0325901 abrogates the expression of primitive streak markers by β-catenin retention in the cytoplasm, and inhibits the expression of OCT4 and NANOG during EpiSC differentiation. Thus, EpiSCs differentiate into neuroectodermal lineage efficiently under PD0325901 treatment. These results suggest that neuroectoderm differentiation does not require extrinsic signals, supporting the default differentiation of neural lineage. We report that a single ERK inhibitor, PD0325901, can specify epiblasts and EpiSCs into neural-like cells, providing an efficient strategy for neural differentiation.

Hanging drop culture enhances differentiation of human adipose-derived stem cells into anterior neuroectodermal cells using small molecules.

Science.gov (United States)

Amirpour, Noushin; Razavi, Shahnaz; Esfandiari, Ebrahim; Hashemibeni, Batoul; Kazemi, Mohammad; Salehi, Hossein

2017-06-01

Inspired by in vivo developmental process, several studies were conducted to design a protocol for differentiating of mesenchymal stem cells into neural cells in vitro. Human adipose-derived stem cells (hADSCs) as mesenchymal stem cells are a promising source for this purpose. At current study, we applied a defined neural induction medium by using small molecules for direct differentiation of hADSCs into anterior neuroectodermal cells. Anterior neuroectodermal differentiation of hADSCs was performed by hanging drop and monolayer protocols. At these methods, three small molecules were used to suppress the BMP, Nodal, and Wnt signaling pathways in order to obtain anterior neuroectodermal (eye field) cells from hADSCs. After two and three weeks of induction, the differentiated cells with neural morphology expressed anterior neuroectodermal markers such as OTX2, SIX3, β-TUB III and PAX6. The protein expression of such markers was confirmed by real time, RT-PCR and immunocytochemistry methods According to our data, it seems that the hanging drop method is a proper approach for neuroectodermal induction of hADSCs. Considering wide availability and immunosuppressive properties of hADSCs, these cells may open a way for autologous cell therapy of neurodegenerative disorders. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Treatment of Children With Central Nervous System Primitive Neuroectodermal Tumors/Pinealoblastomas in the Prospective Multicentric Trial HIT 2000 Using Hyperfractionated Radiation Therapy Followed by Maintenance Chemotherapy

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Gerber, Nicolas U., E-mail: nicolas.gerber@kispi.uzh.ch [Department of Pediatric Oncology, University Children' s Hospital, Zurich (Switzerland); Hoff, Katja von; Resch, Anika [Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Ottensmeier, Holger [Department of Pediatric Oncology, University of Wuerzburg, Wuerzburg (Germany); Kwiecien, Robert; Faldum, Andreas [Institute of Biostatistics and Clinical Research, University of Muenster (Germany); Matuschek, Christiane [Department of Radiation Oncology, Medical Faculty, Heinrich Heine University of Duesseldorf, Duesseldorf (Germany); Hornung, Dagmar [Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Bremer, Michael [Institute for Radiation Therapy and Special Oncology, Hannover Medical School, Hannover (Germany); Benesch, Martin [Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz (Austria); Pietsch, Torsten [Department of Neuropathology, University of Bonn, Bonn (Germany); Warmuth-Metz, Monika [Department of Neuroradiology, University of Wuerzburg, Wuerzburg (Germany); Kuehl, Joachim [Department of Pediatric Oncology, University of Wuerzburg, Wuerzburg (Germany); Rutkowski, Stefan [Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Kortmann, Rolf D. [Department of Radiation Oncology, University of Leipzig, Leipzig (Germany)

2014-07-15

Purpose: The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4. Methods and Materials: After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine). Results: Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (±standard error [SE]) were each 58% (±10%) for the entire cohort: CNS-PNET was 53% (±13); pinealoblastoma was 64% (±15%; P=.524 and P=.627, respectively). Conclusions: Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.

The usefulness of I-131 MIBG scintigraphy in assessing the staging of neuroectodermal tumors in children - Our experience

International Nuclear Information System (INIS)

Budlewski, T.; Rogowski, F.; Luczynski, W.; Krawczuk-Rybak, M.

2004-01-01

metastases in mediastinum, abdominal cavity and bone marrow. The child was prepared for autotransplantation of parent cells. MIBG scintigraphy showed high activity in liver hilus. Clinical test pointed to the progress of the disease. O.P. 3-year-old child with a Kinsbournea syndrome without a primary focus. MIBG study showed higher radioactivity in the right submandibular gland. The biopsy showed neoplastic infiltration. HP-neuroblastoma. The results of tests performed after chemotherapy were good, pointing to a total remission of the disease. M.A. 2 year old child having a tumor on the skin under the right scapula. In MIBG scan, a hyperactivity area in the right kidney region was found. The first CT scan was negative. A CT study three months later was positive. The child was successfully operated on. The MIBG control study showed hyperactivity area in the right chest. Clinically a subcutaneous tissue inflammation in the region of vascular port was diagnosed. Currently, a total remission of the disease. J.G. 10-year-old child having tumor in the right iliac fossa. The first MIBG study showed hyperactivity focus in the right iliac fossa. HP-pheochromocytoma. Post operation MIBG study was negative. Clinically total remission without a chemotherapy. K.K. 15-months-old: tumor of the posterior mediastinum. HP-neuroblastoma. MIBG study performed after operation and chemotherapy was negative. Clinically: total remission. Z.T. 13-year-old child with primary tumor in vertebral canal in the level L1-L4. HP-neuroblastoma with marrow bone infiltration. MIBG study negative. Clinical test pointed to the progress of the disease. To sum up, in most cases the MIBG study was positive and very useful to asses the staging and prognosis in neuroectodermal tumors in children. If the results of MIBG are positive after an operation and chemotherapy the prognosis is bad, and vice versa, if they are negative, the prognosis for these children is good. However, one must remember that these were very

Ewing’s sarcoma: an uncommon breast tumor

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Sawsen Meddeb

2014-10-01

Full Text Available Ewing’s sarcoma/primitive neuroectodermal tumors (EWS/PNET are rare malignant and aggressive tumors, usually seen in the trunk and lower limbs of children and young adults. They are uncommon in the breast. We report a case of a 43-year-old woman who developed a painless breast mass. An initial core needle biopsy concluded to a fibrocystic dystrophy contrasting with a rapidly growing mass; thus a large lumpectomy was done. Diagnosis of primary PNET of the breast was established, based on both histopathological examination and immunohistochemical findings. Surgical margins were positive, therefore, left modified radical mastectomy with axillary lymph nodes dissection was performed. The patient was given 6 cycles of adjuvant chemotherapy containing cyclophosphamide, adriamycin and vincristine. Twenty months later, she is in life without recurrence or metastasis. EWS/PNET may impose a diagnostic challenge. Indeed, mammography and ultrasonography features are non specific. The histopathological pattern is variable depending on the degree of neuroectodermal differentiation. Immuno-phenotyping is necessary and genetic study is the only confirmatory tool of diagnosis showing a characteristic cytogenetic anomaly; t (11; 22 translocation.

Primitive neuroectodermal tumour of the kidney: radiologic-pathological correlations.

Science.gov (United States)

Chea, Y W; Agrawal, Rashi; Poh, Angeline C C

2008-06-01

A primitive neuroectodermal tumour of the kidney is a rare malignancy. We report the computed tomographic features and the histopathological correlation of such a tumour occurring in a middle-aged man. Although the radiological appearance has significant overlap with other renal tumours, this tumour should be included in the differential diagnosis of a large renal mass in younger patients.

Proton Radiation Therapy for Pediatric Medulloblastoma and Supratentorial Primitive Neuroectodermal Tumors: Outcomes for Very Young Children Treated With Upfront Chemotherapy

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Jimenez, Rachel B., E-mail: rbjimenez@partners.org [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Sethi, Roshan [Harvard Medical School, Boston, Massachusetts (United States); Depauw, Nicolas [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Pulsifer, Margaret B. [Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts (United States); Adams, Judith [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); McBride, Sean M. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Ebb, David [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Fullerton, Barbara C.; Tarbell, Nancy J.; Yock, Torunn I.; MacDonald, Shannon M. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2013-09-01

Purpose: To report the early outcomes for very young children with medulloblastoma or supratentorial primitive neuroectodermal tumor (SPNET) treated with upfront chemotherapy followed by 3-dimensional proton radiation therapy (3D-CPT). Methods and Materials: All patients aged <60 months with medulloblastoma or SPNET treated with chemotherapy before 3D-CPT from 2002 to 2010 at our institution were included. All patients underwent maximal surgical resection, chemotherapy, and adjuvant 3D-CPT with either craniospinal irradiation followed by involved-field radiation therapy or involved-field radiation therapy alone. Results: Fifteen patients (median age at diagnosis, 35 months) were treated with high-dose chemotherapy and 3D-CPT. Twelve of 15 patients had medulloblastoma; 3 of 15 patients had SPNET. Median time from surgery to initiation of radiation was 219 days. Median craniospinal irradiation dose was 21.6 Gy (relative biologic effectiveness); median boost dose was 54.0 Gy (relative biologic effectiveness). At a median of 39 months from completion of radiation, 1 of 15 was deceased after a local failure, 1 of 15 had died from a non-disease-related cause, and the remaining 13 of 15 patients were alive without evidence of disease recurrence. Ototoxicity and endocrinopathies were the most common long-term toxicities, with 2 of 15 children requiring hearing aids and 3 of 15 requiring exogenous hormones. Conclusions: Proton radiation after chemotherapy resulted in good disease outcomes for a small cohort of very young patients with medulloblastoma and SPNET. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and late toxicity.

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

Directory of Open Access Journals (Sweden)

Adriano A. De Paula

2006-10-01

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

Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast

OpenAIRE

Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

2013-01-01

Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.

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

Science.gov (United States)

Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

2013-06-21

Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.

A Phase II Study of Preradiotherapy Chemotherapy Followed by Hyperfractionated Radiotherapy for Newly Diagnosed High-Risk Medulloblastoma/Primitive Neuroectodermal Tumor: A Report From the Children's Oncology Group (CCG 9931)

International Nuclear Information System (INIS)

Allen, Jeffrey; Donahue, Bernadine; Mehta, Minesh; Miller, Douglas C.; Rorke, Lucy B.; Jakacki, Regina; Robertson, Patricia; Sposto, Richard; Holmes, Emi; Vezina, Gilbert; Muraszko, Karin; Puccetti, Diane; Prados, Michael; Chan, K.-W.

2009-01-01

Purpose: To verify feasibility and monitor progression-free survival and overall survival in children with high-risk medulloblastoma and noncerebellar primitive neuroectodermal tumors (PNETs) treated in a Phase II study with preradiotherapy chemotherapy (CHT) followed by high-dose, hyperfractionated craniospinal radiotherapy (CSRT). Methods and Materials: Eligibility criteria included age >3 years at diagnosis, medulloblastoma with either high M stage and/or >1.5 cm 2 postoperative residual disease, and all patients with noncerebellar PNET. Treatment was initiated with five alternating monthly cycles of CHT (A [cisplatin, cyclophosphamide, etoposide, and vincristine], B [carboplatin and etoposide], A, B, and A) followed by hyperfractionated CSRT (40 Gy) with a boost to the primary tumor (72 Gy) given in twice-daily 1-Gy fractions. Results: The valid study group consisted of 124 patients whose median age at diagnosis was 7.8 years. Eighty-four patients (68%) completed the entire protocol according to study guidelines (within 9 months), and the median time to complete CSRT was 1.6 months. Major reasons for failure to complete CHT included progressive disease (17%) and toxic death (2.4%). The 5-year progression-free survival and overall survival rates were 43% ± 5% and 52% ± 5%, respectively. No significant differences were detected in subset analysis related to response to CHT, site of primary tumor, postoperative residual disease, or M stage. Conclusions: The feasibility of this intensive multimodality protocol was confirmed, and response to pre-RT CHT did not impact on survival. Survival data from this protocol can not be compared with data from other studies, given the protocol design.

Atypical teratoid/rhabdoid tumor: an unusual presentation

International Nuclear Information System (INIS)

Gandhi, Chirag D.; Krieger, Mark D.; McComb, J. Gordon

2004-01-01

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

BMPs regulate msx gene expression in the dorsal neuroectoderm of Drosophila and vertebrates by distinct mechanisms.

Science.gov (United States)

Esteves, Francisco F; Springhorn, Alexander; Kague, Erika; Taylor, Erika; Pyrowolakis, George; Fisher, Shannon; Bier, Ethan

2014-09-01

In a broad variety of bilaterian species the trunk central nervous system (CNS) derives from three primary rows of neuroblasts. The fates of these neural progenitor cells are determined in part by three conserved transcription factors: vnd/nkx2.2, ind/gsh and msh/msx in Drosophila melanogaster/vertebrates, which are expressed in corresponding non-overlapping patterns along the dorsal-ventral axis. While this conserved suite of "neural identity" gene expression strongly suggests a common ancestral origin for the patterning systems, it is unclear whether the original regulatory mechanisms establishing these patterns have been similarly conserved during evolution. In Drosophila, genetic evidence suggests that Bone Morphogenetic Proteins (BMPs) act in a dosage-dependent fashion to repress expression of neural identity genes. BMPs also play a dose-dependent role in patterning the dorsal and lateral regions of the vertebrate CNS, however, the mechanism by which they achieve such patterning has not yet been clearly established. In this report, we examine the mechanisms by which BMPs act on cis-regulatory modules (CRMs) that control localized expression of the Drosophila msh and zebrafish (Danio rerio) msxB in the dorsal central nervous system (CNS). Our analysis suggests that BMPs act differently in these organisms to regulate similar patterns of gene expression in the neuroectoderm: repressing msh expression in Drosophila, while activating msxB expression in the zebrafish. These findings suggest that the mechanisms by which the BMP gradient patterns the dorsal neuroectoderm have reversed since the divergence of these two ancient lineages.

BMPs regulate msx gene expression in the dorsal neuroectoderm of Drosophila and vertebrates by distinct mechanisms.

Directory of Open Access Journals (Sweden)

Francisco F Esteves

2014-09-01

Full Text Available In a broad variety of bilaterian species the trunk central nervous system (CNS derives from three primary rows of neuroblasts. The fates of these neural progenitor cells are determined in part by three conserved transcription factors: vnd/nkx2.2, ind/gsh and msh/msx in Drosophila melanogaster/vertebrates, which are expressed in corresponding non-overlapping patterns along the dorsal-ventral axis. While this conserved suite of "neural identity" gene expression strongly suggests a common ancestral origin for the patterning systems, it is unclear whether the original regulatory mechanisms establishing these patterns have been similarly conserved during evolution. In Drosophila, genetic evidence suggests that Bone Morphogenetic Proteins (BMPs act in a dosage-dependent fashion to repress expression of neural identity genes. BMPs also play a dose-dependent role in patterning the dorsal and lateral regions of the vertebrate CNS, however, the mechanism by which they achieve such patterning has not yet been clearly established. In this report, we examine the mechanisms by which BMPs act on cis-regulatory modules (CRMs that control localized expression of the Drosophila msh and zebrafish (Danio rerio msxB in the dorsal central nervous system (CNS. Our analysis suggests that BMPs act differently in these organisms to regulate similar patterns of gene expression in the neuroectoderm: repressing msh expression in Drosophila, while activating msxB expression in the zebrafish. These findings suggest that the mechanisms by which the BMP gradient patterns the dorsal neuroectoderm have reversed since the divergence of these two ancient lineages.

Medulloblastomas - primitive neuroectodermal tumours in the adult population

International Nuclear Information System (INIS)

Smee, R.I.; Williams, J.R.

2008-01-01

Medulloblastomas - primitive neuroectodermal tumours are rare in adults. This review will evaluate a single centre's experience with this malignancy. The medulloblastoma - primitive neuroectodermal tumour database was evaluated for all patients aged more than 18 years who were referred for management. Relevant information from the database was abstracted to provide a descriptive record of this malignancy. Between 1977-2004 there were 11 patients referred, 1 with persistent disease and 10 were eligible, presenting with initial diagnosis. There was increased intracranial pressure in 50% of patients. Most patients had symptoms >3 months, with three having symptoms 1-3 months before diagnosis and one patient having thoracic dural metastases at presentation. Complete resection was recorded in four patients and six had 50-90% resection. All patients completed craniospinal radiotherapy (35-36 Gy at 1.8-2.0 Gy fractions) barring one patient, who died of surgical complications during his radiotherapy. Chemotherapy was given in five of the nine patients postradiotherapy. There were two posterior fossa recurrences, with associated supratentorial and extra central nervous system disease. Of the 10 primary patients 7 are alive with no evidence of diease, 2 died because of disease, with 1 intercurrent death. One patient developed a second malignancy. The outcome for adults matches that of the more common paediatric patients. Radiotherapy could control local disease even where complete resection was not achieved.

Primitive neuroectodermal tumour of the kidney with vena caval and atrial tumour thrombus: a case report

Directory of Open Access Journals (Sweden)

Ong Poh

2008-08-01

Full Text Available Abstract Introduction Renal primitive neuroectodermal tumour is an extremely rare malignancy. Case presentation A 21-year-old woman presented with microscopic haematuria, a palpable right loin mass, dyspnoea, dizziness and fatigue. Initial ultrasound scan of the kidneys revealed an 11 cm right renal mass with venous extension into the inferior vena cava. Computed tomography of the thorax and abdomen revealed an extension of the large renal mass into the right renal vein, inferior vena cava and up to the right atrium. A small paracaval lymph node was noted and three small metastatic nodules were identified within the lung parenchyma. The patient underwent a radical nephrectomy and inferior vena caval tumour (level IV thrombectomy with cardiopulmonary bypass and deep hypothermic circulatory arrest. Immunohistochemical staining of the specimen showed a highly specific cluster of differentiation (CD 99, thus confirming the diagnosis of a primitive neuroectodermal tumour. Conclusion It is important that a renal primitive neuroectodermal tumour be considered, particularly in young patients with a renal mass and extensive thrombus.

Synovial sarcoma with radiological appearances of primitive neuroectodermal tumour/Ewing sarcoma: differentiation by molecular genetic studies

International Nuclear Information System (INIS)

O'Donnell, P.; Diss, T.C.; Whelan, J.; Flanagan, A.M.

2006-01-01

Synovial sarcoma (SS) arises in soft tissues but may invade adjacent bone. We describe a case of SS presenting as aggressive lysis of the proximal ulna, the imaging of which suggested a primary bone lesion. Needle biopsy showed a 'small round blue cell tumour', and a primitive neuroectodermal tumour (PNET)/Ewing sarcoma was suggested on the basis of the imaging appearances. The definitive diagnosis of synovial sarcoma was made following molecular genetic studies, which demonstrated a fusion product incorporating the genes SYT and SSX1. The importance of correct diagnosis to guide appropriate management, and, therefore, the necessity for molecular genetic studies, is discussed. (orig.)

Ewing's sarcoma: a neuroectodermal tumor of the chest wall

International Nuclear Information System (INIS)

Alcaraz, M. J.; Lorente, M. L.; Martin, A. M.; Gonzalez, I.

2000-01-01

Ewing's sarcoma is the second most common malignant bone tumor in children and young adults. It is most prevalent between the ages of 10 and 15 years. There are present two cases of Ewing's sarcoma of the chest wall. The clinical, radiological and pathological features are described and the therapeutic options are discussed. (Author)

Complete clinical response to neoadjuvant chemotherapy in a 54-year-old male with Askin tumor.

LENUS (Irish Health Repository)

Mulsow, J

2012-02-01

Askin tumor is a tumor of the thoracopulmonary region that most commonly affects children and adolescents. These rare tumors are a form of primitive neuroectodermal tumor and typically carry a poor prognosis. Treatment is multimodal and consists of a combination of neoadjuvant chemotherapy, radical resection, and adjuvant chemo- and radiotherapy or all of the above. Surgery is advocated in most cases. We report a case of Askin tumor in a 54-year-old male who showed rapid and complete response to neoadjuvant chemotherapy. This allowed potentially radical surgery to be avoided. At one-year follow-up he remains disease-free.

Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors

Science.gov (United States)

2017-09-27

Childhood Choroid Plexus Tumor; Childhood Ependymoblastoma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor

How specific is the MRI appearance of supratentorial atypical teratoid rhabdoid tumors?

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Au Yong, Kong Jung; Jaremko, Jacob L.; Bhargava, Ravi [University of Alberta Hospital, Department of Radiology and Diagnostic Imaging, Edmonton (Canada); Jans, Lennart [Ghent University Hospital, Department of Radiology and Medical Imaging, Gent (Belgium); Coleman, Lee T. [University of Melbourne and Murdoch Children' s Research Institute, Department of Radiology and Pediatrics, Melbourne (Australia); Medical Imaging, Royal Children' s Hospital, Parkville (Australia); Mehta, Vivek [University of Alberta Hospital, Department of Neurosurgery, Edmonton (Canada); Ditchfield, Michael R. [Monash Children' s and Monash University, Monash Medical Centre, Diagnostic Imaging, Clayton (Australia)

2013-03-15

Supratentorial atypical teratoid rhabdoid tumor (ATRT) in many cases has a distinctive appearance on post-gadolinium MRI. We sought to determine whether this is a unique appearance allowing ATRT to be distinguished accurately from other types of pediatric supratentorial tumors. Retrospective review of all available preoperative MRI of pediatric supratentorial tumors at two tertiary children's hospitals, and systematic literature review of case series and reports describing the MRI imaging appearances of supratentorial ATRT. We had 61 supratentorial tumors, including 32 gliomas, 6 ATRT, 8 ependymomas, 6 gangliogliomas, 2 pilomyxoid astrocytomas, 3 primitive neuro-ectodermal tumors, 2 choroid plexus papillomas, and 2 meningiomas. ATRT presented in significantly younger patients than astrocytomas (mean age 2.6 years vs. 9.9 years, P < 0.05). The visual pattern of a thick, wavy (irregular) heterogeneously enhancing wall around a cystic center was seen in 5/6 (83%) ATRTs and only 3/55 (5.4%) other tumors (P < 0.0001), for specificity of 95%, sensitivity of 83%, positive predictive value of 63% and a negative predictive value of 95%. A supratentorial tumor with a thick, wavy (irregular) heterogeneously enhancing wall surrounding a central cystic region is suggestive of ATRT in the appropriate clinical setting, especially in a child of preschool age. (orig.)

How specific is the MRI appearance of supratentorial atypical teratoid rhabdoid tumors?

International Nuclear Information System (INIS)

Au Yong, Kong Jung; Jaremko, Jacob L.; Bhargava, Ravi; Jans, Lennart; Coleman, Lee T.; Mehta, Vivek; Ditchfield, Michael R.

2013-01-01

Supratentorial atypical teratoid rhabdoid tumor (ATRT) in many cases has a distinctive appearance on post-gadolinium MRI. We sought to determine whether this is a unique appearance allowing ATRT to be distinguished accurately from other types of pediatric supratentorial tumors. Retrospective review of all available preoperative MRI of pediatric supratentorial tumors at two tertiary children's hospitals, and systematic literature review of case series and reports describing the MRI imaging appearances of supratentorial ATRT. We had 61 supratentorial tumors, including 32 gliomas, 6 ATRT, 8 ependymomas, 6 gangliogliomas, 2 pilomyxoid astrocytomas, 3 primitive neuro-ectodermal tumors, 2 choroid plexus papillomas, and 2 meningiomas. ATRT presented in significantly younger patients than astrocytomas (mean age 2.6 years vs. 9.9 years, P < 0.05). The visual pattern of a thick, wavy (irregular) heterogeneously enhancing wall around a cystic center was seen in 5/6 (83%) ATRTs and only 3/55 (5.4%) other tumors (P < 0.0001), for specificity of 95%, sensitivity of 83%, positive predictive value of 63% and a negative predictive value of 95%. A supratentorial tumor with a thick, wavy (irregular) heterogeneously enhancing wall surrounding a central cystic region is suggestive of ATRT in the appropriate clinical setting, especially in a child of preschool age. (orig.)

Malignant peripheral nerve sheath tumor arisen from plexiform Neurofibromatosis type 1

International Nuclear Information System (INIS)

Kirova, G.; Penkov, M.; Hadjidekov, G.; Parvanova, V.

2005-01-01

Neurofibromatosis type 1 is multisystemic neurocutaneous disorder involving both neuroectodermal and mesenchymal texture and the most common familial cancer predisposing syndrome in humans. Tumors occurring in patients with NF1 are primarily peripheral neurofibromas. They can continue to develop throughout life and the rate of appearance may vary greatly from year to year. At the same time any new and rapid change noted at clinical examination - increase volume, pain or neurological deficit, requires biopsy because of potential malignant transformation of the neurofibroma into neurofibrosarcoma. The definitive treatment depends on the respectable character of the tumor. In this case the authors document two cases of malignant peripheral nerve sheath tumor occurring in the association with NF type l

Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

Science.gov (United States)

2017-04-27

Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood

{sup 68}Ga-labelled peptides in the management of neuroectodermal tumours

Energy Technology Data Exchange (ETDEWEB)

Naji, Meeran [Maidstone and Tunbridge Wells NHS Trust, Departments of Nuclear Medicine and Radiology, Maidstone (United Kingdom); Al-Nahhas, Adil [Hammersmith Hospital, Imperial College NHS Trust, Department of Nuclear Medicine, London (United Kingdom)

2012-02-15

Neuroectodermal tumours arise from chromaffin cells and possess the ability to secrete catecholamines. They are generally rare and may occur in association with a variety of hereditary syndromes such as MEN-2A and 2B, neurofibromatosis type 1 and von Hippel-Lindau disease. The most common types are phaeochromocytoma arising from the adrenal medulla and paraganglioma of extra-adrenal origin. Phaeochromocytomas tend to be benign and are often associated with a gene mutation if the disease is bilateral, while paragangliomas are often malignant, have a more aggressive nature and tend to metastasize. There are no specific histological or immunohistochemical features that indicate the malignant potential and the diagnosis of malignancy can only be established by the presence of distant metastases. Therefore, imaging can play a vital role in the diagnosis, localization, staging and assessment of spread. Traditionally, this is achieved with a combination of cross-sectional (CT and MRI) and functional ({sup 123}I-MIBG or {sup 111}In-octreotide) imaging. However, these modalities are not adequate and achieve moderate sensitivity. The introduction of {sup 68}Ga-DOTA peptide in PET/CT imaging has led to improved receptor targeting and superb PET resolution, as well as accurate localization of lesions. The use of this technique in neuroectodermal tumours has been shown to be superior to all available modalities, but the available data are limited and larger studies are awaited to establish its role in the management of these tumours. (orig.)

Engineered Herpes Simplex Viruses for the Treatment of Malignant Peripheral Nerve Sheath Tumors

Science.gov (United States)

2015-11-01

lines). This is an entry receptor usually limited to lymphoid cells has not been previously identified in neuroectodermal tissue. Year 3: As a... innate and adaptive immune 327 response. However, resistance is common in vitro and therefore, to the extent that tumor cell lines 328 maintain the...Handgretinger R, et al. Innate immune 461 defense defines susceptibility of sarcoma cells to measles vaccine virus-based oncolysis. J Virol. 462 2013;87

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

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Sturm, Dominik; Orr, Brent A; Toprak, Umut H; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J; Balasubramanian, Gnanaprakash; Worst, Barbara C; Pajtler, Kristian W; Brabetz, Sebastian; Johann, Pascal D; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M; Remke, Marc; Phillips, Joanna J; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C; Schniederjan, Matthew J; Santi, Mariarita; Buccoliero, Anna M; Dahiya, Sonika; Kramm, Christof M; von Bueren, André O; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S; Taylor, Michael D; Jones, Chris; Jabado, Nada; Karajannis, Matthias A; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Ellison, David W; Korshunov, Andrey; Kool, Marcel

2016-02-25

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

Cross-sectional imaging with CT and/or MRI of pediatric chest tumors

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Wyttenbach, R.; Vock, P.; Tschaeppeler, H.

1998-01-01

The purpose of this study was to provide an overview of the spectrum of pediatric chest masses, to present the results of cross-sectional imaging with CT and/or MRI, and to define diagnostic criteria to limit differential diagnosis. Seventy-eight children with thoracic mass lesions were retrospectively evaluated using CT (72 patients) and/or MR imaging (12 patients). All masses were evaluated for tissue characteristics (attenuation values or signal intensity, enhancement, and calcification) and were differentiated according to age, gender, location, and etiology. Twenty-eight of 38 (74 %) mediastinal masses were malignant (neuroblastoma, malignant lymphoma). Thirty of 38 (79 %) pulmonary masses were metastatic in origin, all with an already known primary tumor (osteosarcoma, Wilms tumor). With one exception, all remaining pulmonary lesions were benign. Seventeen of 21 (81 %) chest wall lesions were malignant (Ewing sarcoma, primitive neuroectodermal tumor). The majority of mediastinal and chest wall tumors in children is malignant. Lung lesions are usually benign, unless a known extrapulmonary tumor suggests pulmonary metastases. Cross-sectional imaging with CT and/or MRI allows narrowing of the differential diagnosis of pediatric chest masses substantially by defining the origin and tissue characteristics. Magnetic resonance imaging is preferred for posterior mediastinal lesions, whereas CT should be used for pulmonary lesions. For the residual locations both modalities are complementary. (orig.)

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

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Mamot, Christoph; Krasniqi, Fatime; Metternich, Frank

2016-01-01

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

Neuro image in neuroectodermal disorders. Part III: angiomatous and melanotic syndromes

International Nuclear Information System (INIS)

Marti-Bonmati, L.; Menor, F.; Poyatos, C.; Cortina, H.; Esteban, M.J.; Vilar, J.

1994-01-01

Twenty-eight consecutive patients affected by these rare angiomatous melanotic neuroectodermal disorders are assessed. The diagnostics value and clinical correlation of neuroimaging methods, both CT and MR, are established. Patients with Sturge-Weber syndrome (15 cases), Klippel-Trenaunay syndrome (1 case), Rendu-Osler disease (3 cases), multiple hemangiomatosis (4 cases), von Hippel-Lindau syndrome (3 cases), neuro cutaneous melanosis (1 case) and hypo melanosis of Ito (1 case) are included. In vascular phacomatosis, neuroimaging methods usually contribute to the positive diagnosis. In melanotic disorders, the neuroradiological findings most often are unspecific and do not contribute to the diagnosis of the disease

Clinical results of BNCT for malignant brain tumors in children

International Nuclear Information System (INIS)

Nakagawa, Yoshinobu; Kageji, Teruyoshi; Mizobuchi, Yoshifumi; Kumada, Hiroaki; Nakagawa, Yoshiaki

2009-01-01

It is very difficult to treat the patients with malignant brain tumor in children, especially under 3 years, because the conventional irradiation cannot be applied due to the damage of normal brain tissue. However, boron neutron capture therapy (BNCT) has tumor selectivity such that it can make damage only in tumor cells. We evaluated the clinical results and courses in patients with malignant glioma under 15 years. Among 183 patients with brain tumors treated by our group using BSH-based intra-operative BNCT, 23 patients were under 15 years. They included 4 patients under 3 years. There were 3 glioblastomas (GBM), 6 anaplastic astrocytomas(AAS), 7 primitive neuroectodermal tumors (PNET), 6 pontine gliomas and 1 anaplastic ependymoma. All GBM and PNET patients died due to CSF and/or CNS dissemination without local tumor regrowth. All pontine glioma patients died due to regrowth of the tumor. Four of 6 anaplastic astrocytoma and 1 anaplastic ependymoma patients alive without tumor recurrence. BNCT can be applied to malignant brain tumors in children, especially under 3 years instead of conventional radiation. Although it can achieve the local control in the primary site, it cannot prevent CSF dissemination in patients with glioblastoma.

Primary Ewing's Sarcoma/Primitive Neuroectodermal Tumor of Kidney with Caval Involvement in a Pregnant Woman.

Science.gov (United States)

Ding, Yinghui; Huang, Zhenlin; Ding, Yafei; Jia, Zhankui; Gu, Chaohui; Xue, Rui; Yang, Jinjian

2016-01-01

In this article, we report the case of a woman in whom was found an abdominal mass during pregnancy and who underwent nephrectomy and extraction of the emboli after delivery. The kidney had a volume of 15 × 10 × 8 cm and pathological diagnosis was primary Ewing's sarcoma. The patient was treated with conventional chemotherapy for 1 year after surgery, at which time multiple metastases were found. From this case, we surmise that hormonal changes that occur during pregnancy may accelerate the growth of Ewing's sarcoma of the kidney, suggesting that renal tumors in pregnant women demand serious attention and that anti-cancer treatment should begin as soon as possible. © 2016 S. Karger AG, Basel.

Exome Sequencing of Bilateral Testicular Germ Cell Tumors Suggests Independent Development Lineages

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Sigmund Brabrand

2015-02-01

Full Text Available Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs, is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors, of these three patients in whom both tumors were available (six tumors and two patients each with only one available tumor (two tumors. Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21, some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA, and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients.

Primitive neuroectodermal tumour (PNET) of the kidney: a rare renal tumour in adolescents with seemingly characteristic radiological features

International Nuclear Information System (INIS)

Chu, Winnie C.; Reznikov, Boris; Lee, Edward Y.; Grant, Ronald M.; Cheng, Frankie W.T.; Babyn, Paul

2008-01-01

Primitive neuroectodermal tumours (PNETs) constitute a family of neoplasms of presumed neuroectodermal origin that predominantly present as bone or soft-tissue masses in adolescents and young adults. PNET arising in the kidney is rare. To describe the radiological features in three patients with primary renal PNET. The radiological features of primary renal PNET in three adolescent patients (age 10, 14 and 16 years) are described. Tumour thrombus extending into the renal vein and inferior vena cava was noted in all three patients. In addition, further tumour extension into the atrium was seen in two patients with extension into a pulmonary artery in one patient. Neural foraminal and intraspinal extension close to the origin of the tumour was identified in two patients. Liver, bone and lung metastases were identified. While rare, one should consider the diagnosis of PNET when encountering a renal mass with aggressive features such as inferior vena cava tumour thrombus, direct intraspinal invasion and distant metastasis. (orig.)

Exome sequencing of bilateral testicular germ cell tumors suggests independent development lineages.

Science.gov (United States)

Brabrand, Sigmund; Johannessen, Bjarne; Axcrona, Ulrika; Kraggerud, Sigrid M; Berg, Kaja G; Bakken, Anne C; Bruun, Jarle; Fosså, Sophie D; Lothe, Ragnhild A; Lehne, Gustav; Skotheim, Rolf I

2015-02-01

Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs) or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors), of these three patients in whom both tumors were available (six tumors) and two patients each with only one available tumor (two tumors). Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21), some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA), and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

Single cell cultures of Drosophila neuroectodermal and mesectodermal central nervous system progenitors reveal different degrees of developmental autonomy.

Science.gov (United States)

Lüer, Karin; Technau, Gerhard M

2009-08-03

The Drosophila embryonic central nervous system (CNS) develops from two sets of progenitor cells, neuroblasts and ventral midline progenitors, which behave differently in many respects. Neuroblasts derive from the neurogenic region of the ectoderm and form the lateral parts of the CNS. Ventral midline precursors are formed by two rows of mesectodermal cells and build the CNS midline. There is plenty of evidence that individual identities are conferred to precursor cells by positional information in the ectoderm. It is unclear, however, how far the precursors can maintain their identities and developmental properties in the absence of normal external signals. To separate the respective contributions of autonomous properties versus extrinsic signals during their further development, we isolated individual midline precursors and neuroectodermal precursors at the pre-mitotic gastrula stage, traced their development in vitro, and analyzed the characteristics of their lineages in comparison with those described for the embryo. Although individually cultured mesectodermal cells exhibit basic characteristics of CNS midline progenitors, the clones produced by these progenitors differ from their in situ counterparts with regard to cell numbers, expression of molecular markers, and the separation of neuronal and glial fate. In contrast, clones derived from individually cultured precursors taken from specific dorsoventral zones of the neuroectoderm develop striking similarities to the lineages of neuroblasts that normally delaminate from these zones and develop in situ. This in vitro analysis allows for the first time a comparison of the developmental capacities in situ and in vitro of individual neural precursors of defined spatial and temporal origin. The data reveal that cells isolated at the pre-mitotic and pre-delamination stage express characteristics of the progenitor type appropriate to their site of origin in the embryo. However, presumptive neuroblasts, once

Detection of EWS/FLI-1 fusion in non-Ewing soft tissue tumors.

Science.gov (United States)

Trancău, I O; Huică, R; Surcel, M; Munteanu, A; Ursaciuc, C

2015-01-01

EWS/FLI-1 fusion mainly appears in Ewing's sarcoma or the primitive neuroectodermal tumors and represents a genomic marker for these tumors. However, it can appear with lower frequency in other soft tissue tumors. The paper investigates the presence of EWS/FLI-1 fusion in clinically diagnosed sarcoma belonging to different non-Ewing connective tissue tumors in order to search for a possible new biomarker valuable for investigators. 20 patients with soft tissue tumors, who underwent surgery, were tested. Intra-operative samples of normal and tumor tissue were collected for histopathological diagnosis and genetics determinations. The patients' RNA from tumor and normal peritumoral tissue was extracted and EWS/FLI-1 fusion screened by quantitative real-time PCR. The relative expression of the fusion in the tumor sample was compared to the similar expression in normal tissue. The amplification in the threshold zone was shown by 5 samples (25%): 2 clear cell sarcoma, 1 fibrosarcoma, 1 malignant tumor of nerve sheath, 1 metastatic adenocarcinoma. We differentiated between the unspecific amplification and concluded that these are weak positive results. Genomic investigation may establish the tumor malignancy and its possible affiliation earlier than histopathology. It can support the screening of EWS/FLI-1 fusion in a larger variety of clinically diagnosed soft tissue tumors.

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

Boron neutron capture therapy for children with malignant brain tumor

International Nuclear Information System (INIS)

Nakagawa, Yoshinobu; Komatsu, Hisao; Kageji, Teruyoshi; Tsuji, Fumio; Matsumoto, Keizo; Kitamura, Katsuji; Hatanaka, Hiroshi; Minobe, Takashi.

1993-01-01

Among the 131 cases with brain tumors treated by boron-neutron capture therapy (BNCT), seventeen were children. Eight supratentorial tumors included five astrocytomas(grade 2-4), two primitive neuroectodermal tumors (PNET) and one rhabdomyosarcoma. Seven pontine tumors included one astrocytoma, one PNET and 5 unverified gliomas. Two cerebellar tumors (PNET and astrocytoma) were also treated. All pontine tumors showed remarkable decrease in size after BNCT. However, most of them showed regrowth of the tumors because the neutrons were insufficient due to the depth. Four cases with cerebral tumor died of remote cell dissemination, although they all responded to BNCT. One of them survived 7 years after repeated BNCTs. An 11 years old girl with a large astrocytoma in the right frontal lobe has lived more than 11 years and is now a draftswoman at a civil engineering company after graduating from a technical college. An 8 years old girl with an astrocytoma in the left occipital lobe has no recurrence of the tumor for 2 years and attends on elementary school without mental and physical problems. Two children (one year old girl and four years old boy) with cerebellar tumors have shown showed an excellent growth after BNCT and had no neurological deficits. Mental and physical development in patients treated by BNCT is usually better than that in patients treated by conventional radiotherapy. (author)

N-cadherin Expression in Testicular Germ Cell and Gonadal Stromal Tumors

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Daniel J. Heidenberg, Joel H. Barton, Denise Young, Michael Grinkemeyer, Isabell A. Sesterhenn

2012-01-01

Full Text Available Neural-cadherin is a member of the cadherin gene family encoding the N-cadherin protein that mediates cell adhesion. N-cadherin is a marker of Sertoli cells and is also expressed in germ cells of varying stages of maturation. The purpose of this study was to determine the presence and distribution of this protein by immunohistochemistry in 105 germ cell tumors of both single and mixed histological types and 12 gonadal stromal tumors. Twenty-four germ cell tumors consisted of one cell type and the remaining were mixed. Of the 23 seminomas in either pure or mixed tumors, 74% were positive. Two spermatocytic seminomas were positive. Of the 83 cases with yolk sac tumor, 99% were positive for N-cadherin. The teratomas were positive in 73% in neuroectodermal and / or glandular components. In contrast, 87% of embryonal carcinomas did not express N-cadherin. Only 17% of the syncytiotrophoblastic cells were positive for N-cadherin. In conclusion, N-cadherin expression is very helpful in the identification of yolk sac tumors. In addition to glypican-3 and Sal-like protein 4, N-cadherin can be beneficial for the diagnosis and classification of this subtype of testicular germ cell tumor. Nine of the 12 gonadal stromal tumors were positive to a variable extent.

Congenital tumors of the central nervous system

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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

GLI1 is a central mediator of EWS/FLI1 signaling in Ewing tumors.

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Jay Joo

2009-10-01

Full Text Available The Ewing Sarcoma Family Tumors (ESFT consist of the classical pathologic entities of Ewing Sarcoma and peripheral Primitive Neuroectodermal Tumor. Occurring largely in the childhood through young adult years, these tumors have an unsurpassed propensity for metastasis and have no defined cell of origin. The biology of these aggressive malignancies centers around EWS/FLI1 and related EWS/ETS chimeric transcription factors, which are largely limited to this tumor class. Much progress has been made in the identification of a network of loci whose expression is modulated by EWS/FLI1 and its congeners. To date, little progress has been made in reconstructing the sequence of direct and indirect events that produce this network of modulated loci. The recent identification of GLI1 as an upregulated target of EWS/ETS transcription factors suggests a target which may be a more central mediator in the ESFT signaling network. In this paper, we further define the relationship of EWS/FLI1 expression and GLI1 upregulation in ESFT. This relationship is supported with data from primary tumor specimens. It is consistently observed across multiple ESFT cell lines and with multiple means of EWS/FLI1 inhibition. GLI1 inhibition affects tumor cell line phenotype whether shRNA or endogenous or pharmacologic inhibitors are employed. As is seen in model transformation systems, GLI1 upregulation by EWS/FLI1 appears to be independent of Hedgehog stimulation. Consistent with a more central role in ESFT pathogenesis, several known EWS/FLI1 targets appear to be targeted through GLI1. These findings further establish a central role for GLI1 in the pathogenesis of Ewing Tumors.

Comparative expression analysis reveals lineage relationships between human and murine gliomas and a dominance of glial signatures during tumor propagation in vitro.

Science.gov (United States)

Henriquez, Nico V; Forshew, Tim; Tatevossian, Ruth; Ellis, Matthew; Richard-Loendt, Angela; Rogers, Hazel; Jacques, Thomas S; Reitboeck, Pablo Garcia; Pearce, Kerra; Sheer, Denise; Grundy, Richard G; Brandner, Sebastian

2013-09-15

Brain tumors are thought to originate from stem/progenitor cell populations that acquire specific genetic mutations. Although current preclinical models have relevance to human pathogenesis, most do not recapitulate the histogenesis of the human disease. Recently, a large series of human gliomas and medulloblastomas were analyzed for genetic signatures of prognosis and therapeutic response. Using a mouse model system that generates three distinct types of intrinsic brain tumors, we correlated RNA and protein expression levels with human brain tumors. A combination of genetic mutations and cellular environment during tumor propagation defined the incidence and phenotype of intrinsic murine tumors. Importantly, in vitro passage of cancer stem cells uniformly promoted a glial expression profile in culture and in brain tumors. Gene expression profiling revealed that experimental gliomas corresponded to distinct subclasses of human glioblastoma, whereas experimental supratentorial primitive neuroectodermal tumors (sPNET) correspond to atypical teratoid/rhabdoid tumor (AT/RT), a rare childhood tumor. ©2013 AACR.

Single cell cultures of Drosophila neuroectodermal and mesectodermal central nervous system progenitors reveal different degrees of developmental autonomy

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Technau Gerhard M

2009-08-01

Full Text Available Abstract Background The Drosophila embryonic central nervous system (CNS develops from two sets of progenitor cells, neuroblasts and ventral midline progenitors, which behave differently in many respects. Neuroblasts derive from the neurogenic region of the ectoderm and form the lateral parts of the CNS. Ventral midline precursors are formed by two rows of mesectodermal cells and build the CNS midline. There is plenty of evidence that individual identities are conferred to precursor cells by positional information in the ectoderm. It is unclear, however, how far the precursors can maintain their identities and developmental properties in the absence of normal external signals. Results To separate the respective contributions of autonomous properties versus extrinsic signals during their further development, we isolated individual midline precursors and neuroectodermal precursors at the pre-mitotic gastrula stage, traced their development in vitro, and analyzed the characteristics of their lineages in comparison with those described for the embryo. Although individually cultured mesectodermal cells exhibit basic characteristics of CNS midline progenitors, the clones produced by these progenitors differ from their in situ counterparts with regard to cell numbers, expression of molecular markers, and the separation of neuronal and glial fate. In contrast, clones derived from individually cultured precursors taken from specific dorsoventral zones of the neuroectoderm develop striking similarities to the lineages of neuroblasts that normally delaminate from these zones and develop in situ. Conclusion This in vitro analysis allows for the first time a comparison of the developmental capacities in situ and in vitro of individual neural precursors of defined spatial and temporal origin. The data reveal that cells isolated at the pre-mitotic and pre-delamination stage express characteristics of the progenitor type appropriate to their site of origin in

Pathology, treatment and management of posterior fossa brain tumors in childhood

International Nuclear Information System (INIS)

Bonner, K.; Siegel, K.R.

1988-01-01

Brain tumors are the second most common childhood malignancy. Between 1975 and 1985, 462 newly diagnosed patients were treated at the Children's Hospital of Philadelphia; 207 (45%) tumors arose in the posterior fossa and 255 (55%) appeared supratentorially. A wide variety of histological subtypes were seen, each requiring tumor-specific treatment approaches. These included primitive neuroectodermal tumor (n = 86, 19%), astrocytoma (n = 135, 30%), brainstem glioma (n = 47, 10%), anaplastic astrocytoma (n = 32, 7%), and ependymoma (n = 30, 6%). Because of advances in diagnostic abilities, surgery, radiotherapy, and chemotherapy, between 60% and 70% of these patients are alive today. Diagnostic tools such as computed tomography and magnetic resonance imaging allow for better perioperative management and follow-up, while the operating microscope, CO 2 laser, cavitron ultrasonic aspirator and neurosurgical microinstrumentation allow for more extensive and safer surgery. Disease specific treatment protocols, utilizing radiotherapy and adjuvant chemotherapy, have made survival common in tumors such as medulloblastoma. As survival rates increase, cognitive, endocrinologic and psychologic sequelae become increasingly important. The optimal management of children with brain tumors demands a multidisciplinary approach, best facilitated by a neuro-oncology team composed of multiple subspecialists. This article addresses incidence, classification and histology, clinical presentation, diagnosis, pre-, intra- and postoperative management, long-term effects and the team approach in posterior fossa tumors in childhood. Management of specific tumor types is included as well. 57 references

Melanotic neuroectodermal tumour of infancy: CT and MR findings

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Haque, Saira; Sebire, Neil; McHugh, Kieran [Great Ormond Street Hospital, Department of Radiology, London (United Kingdom); McCarville, Mary Beth [St. Jude Children' s Research Hospital, Memphis, TN (United States)

2012-06-15

Melanotic neuroectodermal tumour of infancy (MNTI) is a rare neoplasm of neural crest origin. To describe three further cases of MNTI, with emphasis on CT and MRI findings. Data for children with histologically confirmed MNTI following biopsy or surgery were retrieved. Three children with available imaging at the time of diagnosis were included in the study. All three children had primary tumour in the head and neck region: one in the maxilla, one in the occipital bone (extra-axial but with intracranial extension) and one with an unusual tumour growing exophytically from the subcutaneous tissues adjacent to the occipital bone. All tumours were iso/hypointense both on T1- and T2-weighted MRI, and showed marked contrast enhancement in their non-ossified components. CT allowed identification of bone destruction and remodelling. Our findings are consistent with previously reported cases of MNTI regarding age at presentation and location in the head and neck region. Our MR findings did not demonstrate the typical pattern of T1-shortening expected from melanin deposition. (orig.)

Central nervous system tumors: Radiologic pathologic correlation and diagnostic approach

Directory of Open Access Journals (Sweden)

Ishita Pant

2015-01-01

Full Text Available Objective: This study was conducted to formulate location-wise radiologic diagnostic algorithms and assess their concordance with the final histopathological diagnosis so as to evaluate their utility in a rural setting where only basic facilities are available. Materials and Methods: A retrospective analysis to assess the concordance of radiology (primarily MRI with final histopathology report was done. Based on the most common incidence of tumor location and basic radiology findings, diagnostic algorithms were prepared. Results: For supratentorial intraaxial parenchymal location concordance was seen in all high-grade astrocytomas, low- and high-grade oligodendrogliomas, metastatic tumors, primitive neuroectodermal tumors, high-grade ependymomas, neuronal and mixed neuro-glial tumors and tumors of hematopoietic system. Lowest concordance was seen in low-grade astrocytomas. In the supratentorial intraaxial ventricular location, agreement was observed in choroid plexus tumors, ependymomas, low-grade astrocytomas and meningiomas; in the supratentorial extraaxial location, except for the lack of concordance in the only case of metastatic tumor, concordance was observed in meningeal tumors, tumors of the sellar region, tumors of cranial and paraspinal nerves; the infratentorial intraaxial parenchymal location showed agreement in low- as well as high-grade astrocytomas, metastatic tumors, high-grade ependymoma, embryonal tumors and hematopoietic tumors; in the infratentorial intraaxial ventricular location, except for the lack of concordance in one case of low-grade astrocytoma and two cases of medulloblastomas, agreement was observed in low- and high-grade ependymoma; infratentorial extraaxial tumors showed complete agreement in all tumors of cranial and paraspinal nerves, meningiomas, and hematopoietic tumors. Conclusion: A location-based approach to central nervous system (CNS tumors is helpful in establishing an appropriate differential diagnosis.

The Combination of the Tumor Markers Suggests the Histological Diagnosis of Lung Cancer

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Linjie Liu

2017-01-01

Full Text Available Tumor markers are beneficial for the diagnosis and therapy monitoring of lung cancer. However, the value of tumor markers in lung cancer histological diagnosis is unknown. In this study, we analyzed the serum levels of six tumor markers (CEA, CYFRA21-1, SCC, NSE, ProGRP, and CA125 in 2097 suspected patients with lung cancer and determined whether the combination of the tumor markers was useful for histological diagnosis of lung cancer. We found that CYFRA21-1 was the most sensitive marker in NSCLC. ProGRP showed a better clinical performance than that of NSE in discriminating between SCLC and NSCLC. The serum level of CYFRA21-1 or SCC was significantly higher in squamous carcinoma (p<0.05, and the levels of ProGRP and NSE were significantly higher in SCLC (p<0.05. According to the criteria established, SCLC and NSCLC were discriminated with sensitivity of 87.12 and 62.63% and specificity of 64.61 and 99.5%, respectively. The sensitivity and specificity in the differentiation of adenocarcinoma and squamous carcinoma were 68.1 and 81.63% and 70.73 and 65.93%, with NPV of 46.03 and 68.97% and PPV of 85.82 and 79.47%, respectively. Our results suggested the combination of six tumor markers could discriminate the histological types of lung cancer.

Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)

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2017-06-20

Lymphoma; Childhood Lymphoma; Solid Tumor; Childhood Solid Tumor; Neuroblastoma; Ewing Sarcoma; Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Medulloblastoma; Germ Cell Tumor; Wilms Tumor; Brain Neoplasms; Medulloblastoma, Childhood; Neuroectodermal Tumors, Primitive

EXTRAOSSEOUS EWINGS/PNET-A CASE REPORT BY FNAC

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Bharath; Rakesh

2013-01-01

INTRODUCTION: Ewing sarcoma is one of the most common primary tumo r of the bone, but extra-skeletal type is rare. Ewing's sarcoma (ES) and primitive neuroectodermal t umor (PNET) are small round cell tumors showing varying (usuall y minimal) neuroectodermal differentiation [1] .These tumors occur predominately in adolescents and young adults,but rare below four years of age. The cytomorphologic feature s may be confused with other small round cell tu...

Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages

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Caiazzo, Massimiliano; Colucci-D'Amato, Luca; Esposito, Maria T.; Parisi, Silvia; Stifani, Stefano; Ramirez, Francesco; Porzio, Umberto di

2010-01-01

Previous gene targeting studies in mice have implicated the nuclear protein Krueppel-like factor 7 (KLF7) in nervous system development while cell culture assays have documented its involvement in cell cycle regulation. By employing short hairpin RNA (shRNA)-mediated gene silencing, here we demonstrate that murine Klf7 gene expression is required for in vitro differentiation of neuroectodermal and mesodermal cells. Specifically, we show a correlation of Klf7 silencing with down-regulation of the neuronal marker microtubule-associated protein 2 (Map2) and the nerve growth factor (NGF) tyrosine kinase receptor A (TrkA) using the PC12 neuronal cell line. Similarly, KLF7 inactivation in Klf7-null mice decreases the expression of the neurogenic marker brain lipid-binding protein/fatty acid-binding protein 7 (BLBP/FABP7) in neural stem cells (NSCs). We also report that Klf7 silencing is detrimental to neuronal and cardiomyocytic differentiation of embryonic stem cells (ESCs), in addition to altering the adipogenic and osteogenic potential of mouse embryonic fibroblasts (MEFs). Finally, our results suggest that genes that are key for self-renewal of undifferentiated ESCs repress Klf7 expression in ESCs. Together with previous findings, these results provide evidence that KLF7 has a broad spectrum of regulatory functions, which reflect the discrete cellular and molecular contexts in which this transcription factor operates.

Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages

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Caiazzo, Massimiliano, E-mail: caiazzo@igb.cnr.it [Institute of Genetics and Biophysics ' A. Buzzati-Traverso,' CNR, 80131 Naples (Italy); Istituto di diagnosi e cura ' Hermitage Capodimonte,' 80131 Naples (Italy); Colucci-D' Amato, Luca, E-mail: luca.colucci@unina2.it [Institute of Genetics and Biophysics ' A. Buzzati-Traverso,' CNR, 80131 Naples (Italy); Dipartimento di Scienze della Vita, Seconda Universita di Napoli, 81100 Caserta (Italy); Esposito, Maria T., E-mail: maria_teresa.esposito@kcl.ac.uk [CEINGE Biotecnologie Avanzate, 80145 Naples (Italy); Parisi, Silvia, E-mail: parisi@ceinge.unina.it [CEINGE Biotecnologie Avanzate, 80145 Naples (Italy); Stifani, Stefano, E-mail: stefano.stifani@mcgill.ca [Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4 (Canada); Ramirez, Francesco, E-mail: francesco.ramirez@mssm.edu [Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029 (United States); Porzio, Umberto di, E-mail: diporzio@igb.cnr.it [Institute of Genetics and Biophysics ' A. Buzzati-Traverso,' CNR, 80131 Naples (Italy)

2010-08-15

Previous gene targeting studies in mice have implicated the nuclear protein Krueppel-like factor 7 (KLF7) in nervous system development while cell culture assays have documented its involvement in cell cycle regulation. By employing short hairpin RNA (shRNA)-mediated gene silencing, here we demonstrate that murine Klf7 gene expression is required for in vitro differentiation of neuroectodermal and mesodermal cells. Specifically, we show a correlation of Klf7 silencing with down-regulation of the neuronal marker microtubule-associated protein 2 (Map2) and the nerve growth factor (NGF) tyrosine kinase receptor A (TrkA) using the PC12 neuronal cell line. Similarly, KLF7 inactivation in Klf7-null mice decreases the expression of the neurogenic marker brain lipid-binding protein/fatty acid-binding protein 7 (BLBP/FABP7) in neural stem cells (NSCs). We also report that Klf7 silencing is detrimental to neuronal and cardiomyocytic differentiation of embryonic stem cells (ESCs), in addition to altering the adipogenic and osteogenic potential of mouse embryonic fibroblasts (MEFs). Finally, our results suggest that genes that are key for self-renewal of undifferentiated ESCs repress Klf7 expression in ESCs. Together with previous findings, these results provide evidence that KLF7 has a broad spectrum of regulatory functions, which reflect the discrete cellular and molecular contexts in which this transcription factor operates.

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

International Nuclear Information System (INIS)

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

1985-01-01

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

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

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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

MicroRNA Signatures as Biomarkers and Therapeutic Target for CNS Embryonal Tumors: The Pros and the Cons

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Tarek Shalaby

2014-11-01

Full Text Available Embryonal tumors of the central nervous system represent a heterogeneous group of childhood cancers with an unknown pathogenesis; diagnosis, on the basis of histological appearance alone, is controversial and patients’ response to therapy is difficult to predict. They encompass medulloblastoma, atypical teratoid/rhabdoid tumors and a group of primitive neuroectodermal tumors. All are aggressive tumors with the tendency to disseminate throughout the central nervous system. The large amount of genomic and molecular data generated over the last 5–10 years encourages optimism that new molecular targets will soon improve outcomes. Recent neurobiological studies have uncovered the key role of microRNAs (miRNAs in embryonal tumors biology and their potential use as biomarkers is increasingly being recognized and investigated. However the successful use of microRNAs as reliable biomarkers for the detection and management of pediatric brain tumors represents a substantial challenge. This review debates the importance of miRNAs in the biology of central nervous systemembryonal tumors focusing on medulloblastoma and atypical teratoid/rhabdoid tumors and highlights the advantages as well as the limitations of their prospective application as biomarkers and candidates for molecular therapeutic targets.

Molecular-Guided Therapy for Childhood Cancer

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2017-07-07

Neuroblastoma; Medulloblastoma; Glioma; Ependymoma; Choroid Plexus Neoplasms; Craniopharyngioma; Dysembryoplastic Neuroepithelial Tumor; Meningioma; Primitive Neuroectodermal Tumors (PNETs); Germ Cell Tumors; Rhabdomyosarcoma; Non-rhabdomyosarcoma; Ewings Sarcoma; Osteosarcoma; Wilms Tumor; Renal Cell Carcinoma; Malignant Rhabdoid Tumor; Clear Cell Sarcoma; Liver Tumors

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

Energy Technology Data Exchange (ETDEWEB)

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

1985-09-01

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

Tumor disease and associated congenital abnormalities on prenatal MRI.

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Nemec, Stefan F; Horcher, Ernst; Kasprian, Gregor; Brugger, Peter C; Bettelheim, Dieter; Amann, Gabriele; Nemec, Ursula; Rotmensch, Siegfried; Rimoin, David L; Graham, John M; Prayer, Daniela

2012-02-01

Fetal tumors can have a devastating effect on the fetus, and may occur in association with congenital malformations. In view of the increasing role of fetal magnetic resonance imaging (MRI) as an adjunct to prenatal ultrasonography (US), we sought to demonstrate the visualization of fetal tumors, with regard to congenital abnormalities, on MRI. This retrospective study included 18 fetuses with tumors depicted on fetal MRI after suspicious US findings. An MRI standard protocol was used to diagnose tumors judged as benign or malignant. All organ systems were assessed for tumor-related complications and other congenital malformations. Available US results and histopathology were compared with MRI. There were 13/18 (72.2%) benign and 5/18 (27.8%) malignant tumors diagnosed: a cerebral primitive neuroectodermal tumor in 1/18, head-neck teratomas in 4/18; ventricular rhabdomyomas in 4/18; a cardiac teratoma in 1/18; a hepatoblastoma in 1/18; neuroblastomas in 2/18; a cystic hemorrhagic adrenal hyperplasia in 1/18; a pelvic leiomyoma in 1/18; sacrococcygeal teratomas in 3/18. Tumor-related complications were present in 13/18 (72.2%) cases; other congenital abnormalities in 3/18 (16.7%). MRI diagnosis and histology were concordant in 8/11 (72.7%) cases. In 6/12 (50%) cases, US and MRI diagnoses were concordant, and, in 6/12 (50%) cases, additional MRI findings changed the US diagnosis. Our MRI results demonstrate the visualization of fetal tumors, with frequently encountered tumor-related complications, and other exceptional congenital abnormalities, which may provide important information for perinatal management. Compared to prenatal US, MRI may add important findings in certain cases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Tumor disease and associated congenital abnormalities on prenatal MRI

International Nuclear Information System (INIS)

Nemec, Stefan F.; Horcher, Ernst; Kasprian, Gregor; Brugger, Peter C.; Bettelheim, Dieter; Amann, Gabriele; Nemec, Ursula; Rotmensch, Siegfried; Rimoin, David L.; Graham, John M. Jr.; Prayer, Daniela

2012-01-01

Objective: Fetal tumors can have a devastating effect on the fetus, and may occur in association with congenital malformations. In view of the increasing role of fetal magnetic resonance imaging (MRI) as an adjunct to prenatal ultrasonography (US), we sought to demonstrate the visualization of fetal tumors, with regard to congenital abnormalities, on MRI. Materials and methods: This retrospective study included 18 fetuses with tumors depicted on fetal MRI after suspicious US findings. An MRI standard protocol was used to diagnose tumors judged as benign or malignant. All organ systems were assessed for tumor-related complications and other congenital malformations. Available US results and histopathology were compared with MRI. Results: There were 13/18 (72.2%) benign and 5/18 (27.8%) malignant tumors diagnosed: a cerebral primitive neuroectodermal tumor in 1/18, head–neck teratomas in 4/18; ventricular rhabdomyomas in 4/18; a cardiac teratoma in 1/18; a hepatoblastoma in 1/18; neuroblastomas in 2/18; a cystic hemorrhagic adrenal hyperplasia in 1/18; a pelvic leiomyoma in 1/18; sacrococcygeal teratomas in 3/18. Tumor-related complications were present in 13/18 (72.2%) cases; other congenital abnormalities in 3/18 (16.7%). MRI diagnosis and histology were concordant in 8/11 (72.7%) cases. In 6/12 (50%) cases, US and MRI diagnoses were concordant, and, in 6/12 (50%) cases, additional MRI findings changed the US diagnosis. Conclusion: Our MRI results demonstrate the visualization of fetal tumors, with frequently encountered tumor-related complications, and other exceptional congenital abnormalities, which may provide important information for perinatal management. Compared to prenatal US, MRI may add important findings in certain cases.

Survival of very young children with medulloblastoma (primitive neuroectodermal tumor of the posterior fossa) treated with craniospinal irradiation

International Nuclear Information System (INIS)

Saran, Frank H.; Driever, Pablo Herniz; Thilmann, Christoph; Mose, Stephan; Wilson, Paula; Sharpe, Geoff; Adamietz, Irenaeus A.; Boettcher, Heinz D.

1998-01-01

Purpose: Very young children with medulloblastoma are considered to have a worse prognosis than older children. As radiotherapy remains an important part of the treatment, the adverse prognosis could be due to inadequate radiation treatment rather than biological factors. We analyzed the published literature to examine the impact of radiotherapy on survival in this group. Methods and Materials: A Medline search was performed and we reviewed studies of treatment of medulloblastoma where radiotherapy was delivered using megavoltage equipment and the minimum follow-up allowed the calculation of 5-year survival rates. Results: Thirty-nine studies were published between 1979 and 1996 with a treatment including craniospinal irradiation and boost to the posterior fossa. Eleven studies comprising 1366 patients analyzed survival by age at diagnosis. Eight of 11 studies showed a worse 5-year survival for the younger patient group which reached statistical significance in two. There is also a suggestion of a higher proportion of children with metastatic disease at presentation in the very young age group. The usual policy in younger children was to give a lower dose of radiotherapy to the craniospinal axis (CSA) and posterior fossa (PF) with reduction of dose in the range of 15 to 25% compared to standard treatment. As dose reduction to the posterior fossa is associated with worse survival and local recurrence is the predominant site of failure, the major determinant of worse survival in very young children with medulloblastoma may be suboptimal radiotherapy. Protocols including postoperative chemotherapy with delayed, omitted, or only local tumor irradiation do not reach survival rates of protocols with standard radiotherapy, also suggesting a continued importance for irradiation. Conclusion: Very young children with medulloblastoma have a worse prognosis than older children. Inadequate radiation dose and technique to the primary tumor region may be a major contributing

Suv4-20h histone methyltransferases promote neuroectodermal differentiation by silencing the pluripotency-associated Oct-25 gene.

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Dario Nicetto

Full Text Available Post-translational modifications (PTMs of histones exert fundamental roles in regulating gene expression. During development, groups of PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells into differentiated somatic cell lineages. Repressive histone modifications such as H3K9me3 or H3K27me3 have been investigated in detail, but the role of H4K20me3 in development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2 histone methyltransferases (HMTases are essential for induction and differentiation of the neuroectoderm. Morpholino-mediated knockdown of the two HMTases leads to a selective and specific downregulation of genes controlling neural induction, thereby effectively blocking differentiation of the neuroectoderm. Global transcriptome analysis supports the notion that these effects arise from the transcriptional deregulation of specific genes rather than widespread, pleiotropic effects. Interestingly, morphant embryos fail to repress the Oct4-related Xenopus gene Oct-25. We validate Oct-25 as a direct target of xSu4-20h enzyme mediated gene repression, showing by chromatin immunoprecipitaton that it is decorated with the H4K20me3 mark downstream of the promoter in normal, but not in double-morphant, embryos. Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos, we conclude that the epistatic relationship between Suv4-20h enzymes and Oct-25 controls the transit from pluripotent to differentiation-competent neural cells. Consistent with these results in Xenopus, murine Suv4-20h1/h2 double-knockout embryonic stem (DKO ES cells exhibit increased Oct4 protein levels before and during EB formation, and reveal a compromised and biased capacity for in vitro differentiation, when compared to normal ES cells. Together, these results suggest a regulatory mechanism, conserved

Prognostic value of proton MR spectroscopy of cerebral hemisphere tumors in children

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Girard, N. [Department of Neuroradiology and Vascular Radiology, Hopital de la Timone, Marseille (France); Wang, Z.J.; Zimmerman, R.A. [Department of Radiology, Children`s Hospital of Philadelphia, PA (United States); Erbetta, A. [Department of Neuroradiology, Istituto Nazionale Neurologico C. Besta, Milan (Italy); Sutton, L.N. [Division of Neurosurgery, Children`s Hospital of Philadelphia, PA (United States); Phillips, P.C. [Neurooncology Program, Children`s Hospital of Philadelphia, PA (United States); Rorke, L.B. [Department of Neuropathology, Children`s Hospital of Philadelphia, PA (United States)

1998-02-01

We studied 14 young people with newly diagnosed hemisphere tumors, aged from 3 to 20 years (average 10 years). All underwent surgery following MR imaging (MRI) and spectroscopy (MRS). The tumors studied were three glioblastomas, one each of ganglio-glioblastoma, primitive neuroectodermal tumor (PNET), rhabdoid teratoid tumor, pilocytic astrocytoma, ependymoma, anaplastic ependymoma, and gliomatosis cerebri, and four gangliogliomas. Four patients died; ten patients are alive (five with stable residual tumor, five with no evident tumor). Images and spectra were acquired on a 1.5-T imager. Proton MRS was performed before gadolinium injection in all but one case. Single-voxel techniques were utilized in all cases, using a spin-echo or STEAM sequence with a long echo time (135 or 270 ms). Peak areas of N -acetyl aspartate (NAA), choline (Cho), and creatine and phosphocreatine (Cr) were assessed. The NAA/Cho peak-area ratio was very low in the patients who died (mean {+-} s. d. 0.20 {+-} 0.14), and higher in the patients who are alive (0.74 {+-} 0.47; P = 0.007 by two-tailed t -test). The Cr/Cho peak-area ratio also followed a similar trend for the two groups (mean {+-} s. d. 0.17 {+-} 0.07 and 0.49 {+-} 0.30, respectively; P = 0.01 by two-tailed t -test). (orig.) With 4 figs., 3 tabs., 22 refs.

Analysis of limb function after various reconstruction methods according to tumor location following resection of pediatric malignant bone tumors

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Tokuhashi Yasuaki

2010-05-01

Full Text Available Abstract Background In the reconstruction of the affected limb in pediatric malignant bone tumors, since the loss of joint function affects limb-length discrepancy expected in the future, reconstruction methods that not only maximally preserve the joint function but also maintain good limb function are necessary. We analysis limb function of reconstruction methods by tumor location following resection of pediatric malignant bone tumors. Patients and methods We classified the tumors according to their location into 3 types by preoperative MRI, and evaluated reconstruction methods after wide resection, paying attention to whether the joint function could be preserved. The mean age of the patients was 10.6 years, Osteosarcoma was observed in 26 patients, Ewing's sarcoma in 3, and PNET(primitive neuroectodermal tumor and chondrosarcoma (grade 1 in 1 each. Results Type I were those located in the diaphysis, and reconstruction was performed using a vascularized fibular graft(vascularized fibular graft. Type 2 were those located in contact with the epiphyseal line or within 1 cm from this line, and VFG was performed in 1, and distraction osteogenesis in 1. Type III were those extending from the diaphysis to the epiphysis beyond the epiphyseal line, and a Growing Kotz was mainly used in 10 patients. The mean functional assessment score was the highest for Type I (96%: n = 4 according to the type and for VFG (99% according to the reconstruction method. Conclusion The final functional results were the most satisfactory for Types I and II according to tumor location. Biological reconstruction such as VFG and distraction osteogenesis without a prosthesis are so high score in the MSTS rating system. Therefore, considering the function of the affected limb, a limb reconstruction method allowing the maximal preservation of joint function should be selected after careful evaluation of the effects of chemotherapy and the location of the tumor.

Maternal xNorrin, a canonical Wnt signaling agonist and TGF-β antagonist, controls early neuroectoderm specification in Xenopus.

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Suhong Xu

Full Text Available Dorsal-ventral specification in the amphibian embryo is controlled by β-catenin, whose activation in all dorsal cells is dependent on maternal Wnt11. However, it remains unknown whether other maternally secreted factors contribute to β-catenin activation in the dorsal ectoderm. Here, we show that maternal Xenopus Norrin (xNorrin promotes anterior neural tissue formation in ventralized embryos. Conversely, when xNorrin function is inhibited, early canonical Wnt signaling in the dorsal ectoderm and the early expression of the zygotic neural inducers Chordin, Noggin, and Xnr3 are severely suppressed, causing the loss of anterior structures. In addition, xNorrin potently inhibits BMP- and Nodal/Activin-related functions through direct binding to the ligands. Moreover, a subset of Norrin mutants identified in humans with Norrie disease retain Wnt activation but show defective inhibition of Nodal/Activin-related signaling in mesoderm induction, suggesting that this disinhibition causes Norrie disease. Thus, xNorrin is an unusual molecule that acts on two major signaling pathways, Wnt and TGF-β, in opposite ways and is essential for early neuroectoderm specification.

[Pineal anlage tumor in a 8-month-old boy. The first case reported in Spanish language].

Science.gov (United States)

Rodríguez-Velasco, Alicia; Ramírez-Reyes, Alma Griselda

2014-01-01

The pineal anlage tumor is a very infrequent malign neoplasm. Even though it has been documented in literature, it is not listed yet in the World Health Organization's last nervous system classification (2007). It is a primitive pineal tumor with neuroepithelial and ectomesenchyme differentiation. Due to its low frequency, the understanding of its biological behavior and a suitable treatment are incomplete. In a search performed in PubMed with the term pineal anlage tumor, only seven informed cases were identified between 1989 and 2011. An 8-month-old infant was brought to medical attention because he had a progressive enlargement of the cephalic perimeter, and convergent strabismus of two months of evolution. A pineal tumor was identified. The histology showed glial tissue, ganglia cells, pigmented neuroepithelium and striate muscle cells. A ventriculoperitoneal derivation was done to diminish hydrocephalic pressure and also to led the complete surgical resection. The patient was treated with two courses of chemotherapy with carboplatine, ifosfamide and mesna. One year after the treatment, the patient is asymptomatic. This is the first case reported in Spanish language. Given that it is a really infrequent tumor, it could be misdiagnosed as teratome, melanotic or mesoblastic medulloblastoma, or a melanotic neuroectodermal tumor of childhood (melanotic prognoma).

Experiment list: SRX821477 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available see NEUROECTODERMAL TUMOR, PRIMITIVE). The tumor occurs most frequently in the first decade of life with the... most typical location being the cerebellar vermis. Histologic features include a

Ewing sarcoma

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Bone cancer - Ewing sarcoma; Ewing family of tumors; Primitive neuroectodermal tumors (PNET); Bone neoplasm - Ewing sarcoma ... to the lungs and other bones. At the time of diagnosis, spread is seen in about one- ...

A dual role of the extracellular domain of Drosophila Crumbs for morphogenesis of the embryonic neuroectoderm

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Shradha Das

2018-01-01

Full Text Available Epithelia are highly polarised tissues and several highly conserved polarity protein complexes serve to establish and maintain polarity. The transmembrane protein Crumbs (Crb, the central component of the Crb protein complex, is required, among others, for the maintenance of polarity in most epithelia in the Drosophila embryo. However, different epithelia exhibit different phenotypic severity upon loss of crb. Using a transgenomic approach allowed us to more accurately define the role of crb in different epithelia. In particular, we provide evidence that the loss of epithelial tissue integrity in the ventral epidermis of crb mutant embryos is due to impaired actomyosin activity and an excess number of neuroblasts. We demonstrate that the intracellular domain of Crb could only partially rescue this phenotype, while it is able to completely restore tissue integrity in other epithelia. Based on these results we suggest a dual role of the extracellular domain of Crb in the ventral neuroectoderm. First, it is required for apical enrichment of the Crb protein, which in turn regulates actomyosin activity and thereby ensures tissue integrity; and second, the extracellular domain of Crb stabilises the Notch receptor and thereby ensures proper Notch signalling and specification of the correct number of neuroblasts.

General Information about Ewing Sarcoma

Science.gov (United States)

... adults. Ewing sarcoma has also been called peripheral primitive neuroectodermal tumor, Askin tumor (Ewing sarcoma of the ... Ewing sarcoma are usually done at the same time. The following tests and procedures may be used ...

Stages of Ewing Sarcoma

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... adults. Ewing sarcoma has also been called peripheral primitive neuroectodermal tumor, Askin tumor (Ewing sarcoma of the ... Ewing sarcoma are usually done at the same time. The following tests and procedures may be used ...

Affinity cytochemistry of vascular endothelia in brain tumors by biotinylated Ulex europaeus type I lectin (UEA I).

Science.gov (United States)

Weber, T; Seitz, R J; Liebert, U G; Gallasch, E; Wechsler, W

1985-01-01

The vascularization of 50 tumors of the central nervous system (CNS) including 17 meningiomas, 25 neuroectodermal tumors, i.e., astrocytomas, oligodendrogliomas, mixed gliomas, glioblastomas, medulloblastomas, seven metastatic carcinomas, and one malignant hemangioendothelioma were investigated using biotinylated Ulex europaeus type I lectin (UEA I) in an indirect avidinbiotin-peroxidase procedure. The cytochemical staining pattern of UEA I on paraffin sections was compared with that of biotinylated Dolichos biflorus lectin (DBA), and with the immunocytochemical staining of factor VIII related antigen (F VIII/RAG) by polyclonal antisera using the PAP technique. UEA I visualized the endothelia of blood vessels with equal intensity, sensitivity, and reliability in normal brain and in tumor tissue with neovascularization. While large, medium, and small vessels were equally well demonstrated by UEA I and antibodies against FVIII/RAG, capillaries and endothelial sprouts were stained more consistently and intensely by UEA I. No reliable cytochemical staining could be obtained by DBA regardless of tissue or cell type investigated. It is concluded that UEA I is a highly useful cytochemical marker for the identification of vascular endothelia in paraffin sections of human brain tumors.

Radiotherapy for pediatric brain tumors: Standards of care, current clinical trials, and new directions

International Nuclear Information System (INIS)

Goldwein, Joel W.

1995-01-01

The objectives of the course are to evaluate the role of radiation therapy in the treatment of pediatric brain tumors. Areas where the role is evolving will be identified, and the results of clinical trials which been mounted to clarify radiotherapy's role will be reviewed. Brain tumors are the second most common malignancy of childhood after leukemias and lymphomas. However, they remain the most common group of childhood tumors to require radiation therapy. Therefore, a thorough understanding of these tumors, and the appropriate role of surgery, radiation and chemotherapy is critical. Issues surrounding the management of sequelae are no less important. The role of radiotherapy for the treatment of these tumors is far different from that for adults. These differences relate to the profound potential for sequelae from therapy, the higher overall cure rates, and the utility of multimodality therapies. In addition, the rarity of childhood brain tumors compared with adults' makes them more difficult to study. In this session, the following issues will be reviewed; 1. Incidence of pediatric brain tumors, 2. General issues regarding symptoms, diagnosis, diagnostic tests and evaluation, 3. Importance of a team approach, 4. General issues regarding treatment sequelae, 5. Specific tumor types/entities; a. Cerebellar Astrocytomas b. Benign and malignant Gliomas including brainstem and chiasmatic lesions c. Primitive Neuroectodermal Tumors (PNET) and Medulloblastoma d. Ependymomas e. Craniopharyngiomas f. Germ cell tumors g. Miscellaneous and rare pediatric brain tumors 6. Management of sequelae 7. New and future directions a. Treatment of infants b. The expanding role of chemotherapy c. Advances in radiotherapy. The attendees will complete the course with a better understanding of the role that radiation therapy plays in the treatment of pediatric brain tumors. They will be knowledgeable in the foundation for that role, and the changes which are likely to take place in the

Are clinical parameters valuable prognostic factors in childhood primitive neuroectodermal tumors? A multivariate analysis of 105 cases

NARCIS (Netherlands)

Michiels, E. M.; Heikens, J.; Jansen, M. J.; Oldenburger, F.; Voûte, T.

2000-01-01

Medulloblastoma is one of the most frequent brain tumors in children. Long-term survivors are often confronted with serious late sequelae, caused by the therapy. Therefore, prognostic markers must be identified that allow the children to be assigned to different treatment schedules according to

Infant brain tumors: incidence, survival, and the role of radiation based on Surveillance, Epidemiology, and End Results (SEER) Data.

Science.gov (United States)

Bishop, Andrew J; McDonald, Mark W; Chang, Andrew L; Esiashvili, Natia

2012-01-01

To evaluate the incidence of infant brain tumors and survival outcomes by disease and treatment variables. The Surveillance, Epidemiology, and End Results (SEER) Program November 2008 submission database provided age-adjusted incidence rates and individual case information for primary brain tumors diagnosed between 1973 and 2006 in infants less than 12 months of age. Between 1973 and 1986, the incidence of infant brain tumors increased from 16 to 40 cases per million (CPM), and from 1986 to 2006, the annual incidence rate averaged 35 CPM. Leading histologies by annual incidence in CPM were gliomas (13.8), medulloblastoma and primitive neuroectodermal tumors (6.6), and ependymomas (3.6). The annual incidence was higher in whites than in blacks (35.0 vs. 21.3 CPM). Infants with low-grade gliomas had the highest observed survival, and those with atypical teratoid rhabdoid tumors (ATRTs) or primary rhabdoid tumors of the brain had the lowest. Between 1979 and 1993, the annual rate of cases treated with radiation within the first 4 months from diagnosis declined from 20.5 CPM to incidence of infant brain tumors has been stable since 1986. Survival outcomes varied markedly by histology. For infants with medulloblastoma and ATRTs, improved survival was observed in patients treated with both surgery and early radiation compared with those treated with surgery alone. Copyright © 2012 Elsevier Inc. All rights reserved.

Causation of nervous system tumors in children: insights from traditional and genetically engineered animal models

International Nuclear Information System (INIS)

Rice, Jerry M.

2004-01-01

Pediatric neurogenic tumors include primitive neuroectodermal tumors (PNETs), especially medulloblastoma; ependymomas and choroid plexus papillomas; astrocytomas; retinoblastoma; and sympathetic neuroblastoma. Meningiomas and nerve sheath tumors, although uncommon in childhood, are also significant because they can result from exposures of children to ionizing radiation. Specific chromosomal loci and specific genes are related to each of these tumor types. Virtually all these genes appear to act as tumor suppressor genes, which are inactivated in tumor cells by mutations or by chromosomal loss. In genetically engineered mice, some genes that are clearly associated with specific human tumors (e.g., RB1 in retinoblastoma and NF2 in meningiomas and schwannomas) have no such effect. Other genetic constructs in mice involving the genes p53, ptc1, and Nf1 have produced tumors remarkably similar to some of the human pediatric neoplasms. Some of these tumors become clinically apparent after only a few weeks, while the mice are still juveniles, especially when two or more tumor suppressor genes are inactivated in the same genetic construct. Conversely, at least one genetic pathway in rodents involving point mutation in the coding region of a transforming gene (neu in malignant schwannomas) does not appear to operate in any human tumors. The nervous system is markedly susceptible to experimental carcinogenesis during early life in rodents, dogs, primates, and other nonhuman species, and there is no obvious reason why this generalization should not also apply to humans. However, except for therapeutic ionizing radiation, no physical, chemical, or biological cause of human pediatric nervous system tumors is known. The failure of experimental transplacental carcinogenesis to mirror human pediatric experience more closely may reflect the need for multiple mutational events in target cells, and for experimental carcinogens that are capable of causing the full spectrum of

Childhood Esthesioneuroblastoma Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Esthesioneuroblastoma (olfactory neuroblastoma) is a small round-cell tumor arising from the nasal neuroepithelium that is distinct from primitive neuroectodermal tumors. Get detailed information about esthesioneuroblastoma including symptoms, diagnosis, prognosis, Kadish staging system, and treatment in this summary for clinicians.

The cellular and molecular biology of medulloblastoma

NARCIS (Netherlands)

Peringa, A; Fung, KM; Muragaki, Y; Trojanowski, JQ

1995-01-01

Medulloblastomas are prototypical of primitive neuroectodermal tumors which are some of the most frequent malignant brain tumors of childhood. The cell biology of medulloblastomas is still poorly understood, but recent studies of the expression of trophic factors and their receptors in

A case-control study of childhood brain tumors and fathers' hobbies: a Children's Oncology Group study.

Science.gov (United States)

Rosso, Andrea L; Hovinga, Mary E; Rorke-Adams, Lucy B; Spector, Logan G; Bunin, Greta R

2008-12-01

A comprehensive case-control study was conducted to evaluate parental risk factors for medulloblastoma (MB) and primitive neuroectodermal tumor (PNET). This analysis was conducted to evaluate associations between fathers' hobbies and risk of their children developing MB/PNET. The hobbies chosen for study were those with similar exposures as occupations associated with childhood cancers. Cases were 318 subjects under six years of age at diagnosis between 1991 and 1997 and registered with the Children's Cancer Group. An equal number of controls were selected through random digit dialing and individually matched to cases. In multivariate analyses, a significant association was seen for lawn care with pesticides [during pregnancy: odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.5; after birth: OR = 1.8, 95% CI: 1.2, 2.8] and a weak association was seen for stripping paint [during pregnancy: OR = 1.4, 95% CI: 0.8, 2.6; after birth: OR = 1.4, 95% CI: 0.7, 2.6]. This study suggests that household exposures from hobbies, particularly pesticides, may increase risk of MB/PNET in children; previous research has been mostly limited to occupational exposures.

Pathological features of olfactory neuroblastoma in an axolotl (Ambystoma mexicanum).

Science.gov (United States)

Shioda, Chieko; Uchida, Kazuyuki; Nakayama, Hiroyuki

2011-08-01

A one-year-old, female Mexican axolotl (Ambystoma mexicanum) had a rough-surfaced, polypoid, pink tumor mass of approximately 10 mm in diameter in the oral cavity. Histologically, the tumor extended from the ethmoturbinate region and into the oral cavity and had replaced some of the maxillary bone tissue. The tumor mass was composed of a lobular architecture of small round-shaped tumor cells with occasional Flexner-Wintersteiner-like rosette formation. There were no metastatic lesions in the other organs. Immunohistochemically, the tumor cells were partly positive for several neural markers (class III beta-tubulin, S-100 protein, and doublecortin) and intensely positive for an epithelial marker (cytokeratin AE1/AE3). These results suggest that the present tumor originated from neuroectodermal tissue. Considering the location and histological and immunohistochemical features of the tumor, a diagnosis of olfactory neuroblastoma was made.

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

Directory of Open Access Journals (Sweden)

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.

Non-pineal supratentorial primitive neuro-ectodermal tumors (sPNET) in teenagers and young adults: Time to reconsider cisplatin based chemotherapy after cranio-spinal irradiation?

Science.gov (United States)

Biswas, Swethajit; Burke, Amos; Cherian, Sheen; Williams, Denise; Nicholson, James; Horan, Gail; Jefferies, Sarah; Williams, Michael; Earl, Helena M; Burnet, Neil G; Hatcher, Helen

2009-07-01

Supratentorial PNET (sPNET) are rare CNS tumors of embryonal origin arising in children and adults. The treatment of sPNET for all age groups at our cancer center has been based on the management of medulloblastoma (MB), involving neurosurgical debulking followed by cranio-spinal irradiation (CSI) and systemic chemotherapy. Medical records were reviewed to gather demographic and clinical data about all embryonal CNS tumors in children and adults from 2001 to 2007. Tumor pathology, clinical management and survival data were also assessed, particularly as regards those patients who received the Packer chemotherapy regimen for either sPNET or MB. Eleven patients (five children and six adults) were identified with non-pineal sPNET, three children with pineal sPNET, and 19 patients (18 children and 1 adult) with MB. There was no difference in overall survival (OS) rates between pediatric and adult sPNET. When all sPNET were compared to all MB, 5-year OS was 14% versus 73%, respectively, but was only 9% for non-pineal sPNET. When only considering those patients treated with the Packer chemotherapy regimen, the 5-year OS was 12% for sPNET versus 79% for MB. This retrospective study demonstrates that non-pineal sPNET are clinically distinct from MB and are resistant to the Packer chemotherapy regimen. We suggest that it is time to reconsider the use of this regimen in teenage and young adult non-pineal sPNET and to investigate the utility of alternative approaches. (c) 2009 Wiley-Liss, Inc.

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

International Nuclear Information System (INIS)

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

2007-01-01

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

A CASE-CONTROL STUDY OF CHILDHOOD BRAIN TUMORS AND FATHERS’ HOBBIES — A CHILDREN’S ONCOLOGY GROUP STUDY

Science.gov (United States)

Rosso, Andrea L.; Hovinga, Mary E.; Rorke-Adams, Lucy B.; Spector, Logan G.; Bunin, Greta R.

2009-01-01

Objective A comprehensive case-control study was conducted to evaluate parental risk factors for medulloblastoma (MB) and primitive neuroectodermal tumor (PNET). This analysis was conducted to evaluate associations between fathers’ hobbies and risk of their children developing MB/PNET. The hobbies chosen for study were those with similar exposures as occupations associated with childhood cancers. Methods Cases were 318 subjects under 6 years of age at diagnosis between 1991-1997 and registered with the Children’s Cancer Group. An equal number of controls were selected through random digit dialing and individually matched to cases. Results In multivariate analyses, a significant association was seen for lawn care with pesticides [during pregnancy: odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.5; after birth: OR = 1.8, 95% CI: 1.2, 2.8] and a weak association was seen for stripping paint [during pregnancy: OR = 1.4, 95% CI: 0.8, 2.6; after birth: OR = 1.4, 95% CI: 0.7, 2.6]. Conclusions This study suggests that household exposures from hobbies, particularly pesticides, may increase risk of MB/PNET in children; previous research has been mostly limited to occupational exposures. PMID:18560982

High-level expression of podoplanin in benign and malignant soft tissue tumors: immunohistochemical and quantitative real-time RT-PCR analysis.

Science.gov (United States)

Xu, Yongjun; Ogose, Akira; Kawashima, Hiroyuki; Hotta, Tetsuo; Ariizumi, Takashi; Li, Guidong; Umezu, Hajime; Endo, Naoto

2011-03-01

Podoplanin is a 38 kDa mucin-type transmembrane glycoprotein that was first identified in rat glomerular epithelial cells (podocytes). It is expressed in normal lymphatic endothelium, but is absent from vascular endothelial cells. D2-40 is a commercially available mouse monoclonal antibody which binds to an epitope on human podoplanin. D2-40 immunoreactivity is therefore highly sensitive and specific for lymphatic endothelium. Recent investigations have shown widespread applications of immunohistochemical staining with D2-40 in evaluating podoplanin expression as an immunohistochemical marker for diagnosis and prognosis in various tumors. To determine whether the podoplanin (D2-40) antibody may be useful for the diagnosis of soft tissue tumors, 125 cases, including 4 kinds of benign tumors, 15 kinds of malignant tumors and 3 kinds of tumor-like lesions were immunostained using the D2-40 antibody. Total RNA was extracted from frozen tumor tissue obtained from 41 corresponding soft tissue tumor patients and 12 kinds of soft tissue tumor cell lines. Quantitative real-time PCR reactions were performed. Immunohistochemical and quantitative real-time RT-PCR analyses demonstrated the expression of the podoplanin protein and mRNA in the majority of benign and malignant soft tissue tumors and tumor-like lesions examined, with the exception of alveolar soft part sarcoma, embryonal and alveolar rhabdomyosarcoma, extraskeletal Ewing's sarcoma/peripheral primitive neuro-ectodermal tumor and lipoma, which were completely negative for podoplanin. Since it is widely and highly expressed in nearly all kinds of soft tissue tumors, especially in spindle cell sarcoma, myxoid type soft tissue tumors and soft tissue tumors of the nervous system, podoplanin is considered to have little value in the differential diagnosis of soft tissue tumors.

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

Directory of Open Access Journals (Sweden)

Gallyas Ferenc

2007-12-01

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

Genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumours of the central nervous system.

Science.gov (United States)

Inda, M M; Perot, C; Guillaud-Bataille, M; Danglot, G; Rey, J A; Bello, M J; Fan, X; Eberhart, C; Zazpe, I; Portillo, E; Tuñón, T; Martínez-Peñuela, J M; Bernheim, A; Castresana, J S

2005-12-01

Medulloblastoma (MB), a kind of infratentorial primitive neuroectodermal tumour (PNET), is the most frequent malignant brain tumour in childhood. In contrast, supratentorial PNET (sPNET) are very infrequent tumours, but they are histologically similar to MB, although they present a worse clinical outcome. We investigated the differences in genetic abnormalities between sPNET and MB. We analysed 20 central PNET (14 MB and six sPNET) by conventional comparative genomic hybridization (CGH) in order to determine whether a different genetic profile for each tumour exists. Isochromosome 17q was detected in four of the 14 MB cases, but not in any sPNET. Gains at 17q and 7 happened more frequently in MB, and those at 1q in sPNET. Losses at chromosome 10 were detected only in MB, while losses at 16p and 19p happened more frequently in sPNET. A new amplification site, on 4q12, was detected in two MB. Central PNET are a heterogeneous group of tumours from the genetic point of view. The present and previous data, together with further results from larger series, might contribute to the establishment of specific treatments for supratentorial and infratentorial PNET.

Primary renal osteosarcoma: A case report

African Journals Online (AJOL)

C. Ahomadégbé

Primitive renal osteosarcoma is a rare sarcoma of the kidney with only 27 cases reported in the literature. Its histogenesis .... low-grade extraskeletal osteosarcoma. Skeletal ... et al. Primary Ewing's sarcoma/primitive neuroectodermal tumor of.

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.)

Curative treatment for central nervous system medulloepithelioma despite residual disease after resection. Report of two cases treated according to the GPHO protocol HIT 2000 and review of the literature

Energy Technology Data Exchange (ETDEWEB)

Mueller, Klaus [Leipzig Univ. (Germany). Dept. of Radiotherapy and Radiooncology; Zwiener, Isabella [University Medical Center Univ. Mainz (Germany). Inst. for Medical Biostatistics, Epidemiology and Informatics; Welker, Helmut [Katharinenhospital, Stuttgart (Germany). Dept. of Radiotherapy and Radiooncology; Maass, Eberhard [Klinikum Stuttgart - Olgahospital (DE). Pediatrics 5 (Oncology, Hematology, Immunology); Bongartz, Rudolf [Koeln Univ. (Germany). Dept. of Radiotherapy and Radiooncology; Berthold, Frank [Koeln Univ. (Germany). Dept. of Pediatric Oncology; Pietsch, Torsten [Bonn Univ. Medical Center (Germany). Dept. of Neuropathology; Warmuth-Metz, Monika [Wuerzburg Univ. (Germany). Dept. of Neuroradiology; Bueren, Andre von; Rutkowski, Stefan [University Medical Center Hamburg-Eppendorf, Hamburg (Germany). Dept. of Pediatric Hematology and Oncology

2011-11-15

Medulloepithelioma of the central nervous system (CNS) is an uncommon primitive neuroectodermal tumor (PNET) usually occurring in early childhood. It is characterized by highly malignant behavior with a propensity for progression, recurrence, and dissemination despite intensive therapy. Due to its rarity, the optimal management is still unknown. However, gross total resection (GTR) has been considered crucial to achieve cure. In this article, the authors report on 2 cases of CNS medulloepithelioma in which long-term survival (more than 6 years) could be achieved despite evidence of, or suspected postoperative residual disease with an otherwise dismal prognosis. The patients were treated according to different strata of the protocol for primitive neuroectodermal tumors (PNET) of the German-Austrian multicenter trial of the German Society for Pediatric Oncology and Hematology (GPOH) for childhood brain tumors (HIT 2000). Treatment included postoperative hyperfractionated radiotherapy of the craniospinal axis followed by a boost to the tumor site in combination with chemotherapy. A review of the 2 reported and 37 previously published cases confirmed GTR and older age as positive prognostic factors. (orig.)

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

Science.gov (United States)

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

2003-01-01

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

Human BCAS3 expression in embryonic stem cells and vascular precursors suggests a role in human embryogenesis and tumor angiogenesis.

Directory of Open Access Journals (Sweden)

Kavitha Siva

Full Text Available Cancer is often associated with multiple and progressive genetic alterations in genes that are important for normal development. BCAS3 (Breast Cancer Amplified Sequence 3 is a gene of unknown function on human chromosome 17q23, a region associated with breakpoints of several neoplasms. The normal expression pattern of BCAS3 has not been studied, though it is implicated in breast cancer progression. Rudhira, a murine WD40 domain protein that is 98% identical to BCAS3 is expressed in embryonic stem (ES cells, erythropoiesis and angiogenesis. This suggests that BCAS3 expression also may not be restricted to mammary tissue and may have important roles in other normal as well as malignant tissues. We show that BCAS3 is also expressed in human ES cells and during their differentiation into blood vascular precursors. We find that BCAS3 is aberrantly expressed in malignant human brain lesions. In glioblastoma, hemangiopericytoma and brain abscess we note high levels of BCAS3 expression in tumor cells and some blood vessels. BCAS3 may be associated with multiple cancerous and rapidly proliferating cells and hence the expression, function and regulation of this gene merits further investigation. We suggest that BCAS3 is mis-expressed in brain tumors and could serve as a human ES cell and tumor marker.

Broad in vitro efficacy of plant-derived betulinic acid against cell lines derived from the most prevalent human cancer types

NARCIS (Netherlands)

Kessler, Jan H.; Mullauer, Franziska B.; de Roo, Guido M.; Medema, Jan Paul

2007-01-01

Betulinic acid (BA) is a widely available plant-derived triterpene with reported activity against cancer cells of neuroectodermal origin and leukaemias. Treatment with BA was shown to protect mice against transplanted human melanoma and led to tumor regression. In contrast, cells from healthy

JMJD2A attenuation affects cell cycle and tumourigenic inflammatory gene regulation in lipopolysaccharide stimulated neuroectodermal stem cells

Energy Technology Data Exchange (ETDEWEB)

Das, Amitabh, E-mail: amitabhdas.kn@gmail.com [Department of Bionanotechnology, Hanyang University, Seoul 133-791 (Korea, Republic of); Chai, Jin Choul, E-mail: jincchai@gmail.com [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Jung, Kyoung Hwa, E-mail: khjung2@gmail.com [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Das, Nando Dulal, E-mail: nando.hu@gmail.com [Clinical Research Centre, Inha University School of Medicine, Incheon 400-711 (Korea, Republic of); Kang, Sung Chul, E-mail: gujiju11@gmail.com [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Lee, Young Seek, E-mail: yslee@hanyang.ac.kr [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Seo, Hyemyung, E-mail: hseo@hanyang.ac.kr [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Chai, Young Gyu, E-mail: ygchai@hanyang.ac.kr [Department of Bionanotechnology, Hanyang University, Seoul 133-791 (Korea, Republic of); Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of)

2014-11-01

JMJD2A is a lysine trimethyl-specific histone demethylase that is highly expressed in a variety of tumours. The role of JMJD2A in tumour progression remains unclear. The objectives of this study were to identify JMJD2A-regulated genes and understand the function of JMJD2A in p53-null neuroectodermal stem cells (p53{sup −/−} NE-4Cs). We determined the effect of LPS as a model of inflammation in p53{sup −/−} NE-4Cs and investigated whether the epigenetic modifier JMJD2A alter the expression of tumourigenic inflammatory genes. Global gene expression was measured in JMJD2A knockdown (kd) p53{sup −/−} NE-4Cs and in LPS-stimulated JMJD2A-kd p53{sup −/−} NE-4C cells. JMJD2A attenuation significantly down-regulated genes were Cdca2, Ccnd2, Ccnd1, Crebbp, IL6rα, and Stat3 related with cell cycle, proliferation, and inflammatory-disease responses. Importantly, some tumour-suppressor genes including Dapk3, Timp2 and TFPI were significantly up-regulated but were not affected by silencing of the JMJD2B. Furthermore, we confirmed the attenuation of JMJD2A also down-regulated Cdca2, Ccnd2, Crebbp, and Rest in primary NSCs isolated from the forebrains of E15 embryos of C57/BL6J mice with effective p53 inhibitor pifithrin-α (PFT-α). Transcription factor (TF) motif analysis revealed known binding patterns for CDC5, MYC, and CREB, as well as three novel motifs in JMJD2A-regulated genes. IPA established molecular networks. The molecular network signatures and functional gene-expression profiling data from this study warrants further investigation as an effective therapeutic target, and studies to elucidate the molecular mechanism of JMJD2A-kd-dependent effects in neuroectodermal stem cells should be performed. - Highlights: • Significant up-regulation of epigenetic modifier JMJD2A mRNA upon LPS treatment. • Inhibition of JMJD2A attenuated key inflammatory and tumourigenic genes. • Establishing IPA based functional genomics in JMJD2A-attenuated p53{sup �

MR imaging of the spine in children

Energy Technology Data Exchange (ETDEWEB)

Duthoy, M.J.; Lund, G.

1988-08-01

MR imaging was reviewed in 66 pediatric spinal cord patients with diagnoses of posterior fossa tumor, primary spinal cord tumor, metastatic disease, neuroectodermal disorder, congenital malformation, trauma, and demyelinating, neurodegenerative, or metabolic disorders. MR proved to be useful in delineating the extent of posterior fossa and cord tumor including metastasis to the cord. MR was of limited value in demyelinating and metabolic disorders. Arnold Chiari malformations, syringomyelia, tethered cord and meningoceles were all easily evaluated using MR.

A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood "resident" monocytes, and embryonic macrophages suggests common functions and developmental relationships.

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Pucci, Ferdinando; Venneri, Mary Anna; Biziato, Daniela; Nonis, Alessandro; Moi, Davide; Sica, Antonio; Di Serio, Clelia; Naldini, Luigi; De Palma, Michele

2009-07-23

We previously showed that Tie2-expressing monocytes (TEMs) have nonredundant proangiogenic activity in tumors. Here, we compared the gene expression profile of tumor-infiltrating TEMs with that of tumor-associated macrophages (TAMs), spleen-derived Gr1(+)Cd11b(+) neutrophils/myeloid-derived suppressor cells, circulating "inflammatory" and "resident" monocytes, and tumor-derived endothelial cells (ECs) by quantitative polymerase chain reaction-based gene arrays. TEMs sharply differed from ECs and Gr1(+)Cd11b(+) cells but were highly related to TAMs. Nevertheless, several genes were differentially expressed between TEMs and TAMs, highlighting a TEM signature consistent with enhanced proangiogenic/tissue-remodeling activity and lower proinflammatory activity. We validated these findings in models of oncogenesis and transgenic mice expressing a microRNA-regulated Tie2-GFP reporter. Remarkably, resident monocytes and TEMs on one hand, and inflammatory monocytes and TAMs on the other hand, expressed coordinated gene expression profiles, suggesting that the 2 blood monocyte subsets are committed to distinct extravascular fates in the tumor microenvironment. We further showed that a prominent proportion of embryonic/fetal macrophages, which participate in tissue morphogenesis, expressed distinguishing TEM genes. It is tempting to speculate that Tie2(+) embryonic/fetal macrophages, resident blood monocytes, and tumor-infiltrating TEMs represent distinct developmental stages of a TEM lineage committed to execute physiologic proangiogenic and tissue-remodeling programs, which can be co-opted by tumors.

Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors

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Xiaonan Zhang

2015-11-01

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

Blockade of Notch Signaling in Tumor-Bearing Mice May Lead to Tumor Regression, Progression, or Metastasis, Depending on Tumor Cell Types

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Xing-Bin Hu

2009-01-01

Full Text Available It has been reported that blocking Notch signaling in tumor-bearing mice results in abortive angiogenesis and tumor regression. However, given that Notch signaling influences numerous cellular processes in vivo, a comprehensive evaluation of the effect of Notch inactivation on tumor growth would be favorable. In this study, we inoculated four cancer cell lines in mice with the conditional inactivation of recombination signal-binding protein-Jκ (RBP-J, which mediates signaling from all four mammalian Notch receptors. We found that whereas three tumors including hepatocarcinoma, lung cancer, and osteogenic sarcoma grew slower in the RBP-J-deficient mice, at least a melanoma, B16, grew significantly faster in the RBP-J-deficient mice than in the controls, suggesting that the RBP-J-deficient hosts could provide permissive cues for tumor growth. All these tumors showed increased microvessels and up-regulated hypoxia-inducible factor 1α, suggesting that whereas defective angiogenesis resulted in hypoxia, different tumors might grow differentially in the RBP-J-deleted mice. Similarly, increased infiltration of Gr1+/Mac1+ cells were noticed in tumors grown in the RBP-J-inactivated mice. Moreover, we found that when inoculated in the RBP-J knockout hosts, the H22 hepatoma cells had a high frequency of metastasis and lethality, suggesting that at least for H22, deficiency of environmental Notch signaling favored tumor metastasis. Our findings suggested that the general blockade of Notch signaling in tumor-bearing mice could lead to defective angiogenesis in tumors, but depending on tumor cell types, general inhibition of Notch signaling might result in tumor regression, progression, or metastasis.

Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

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Jaehong Kim

2016-01-01

Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

Wilms tumor

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... suggested. Alternative Names Nephroblastoma; Kidney tumor - Wilms Images Kidney anatomy Wilms tumor References Babaian KN, Delacroix SE, Wood CG, Jonasch E. Kidney cancer. In: Skorecki K, Chertow GM, Marsden PA, ...

Ultrasound-guided core needle biopsy in diagnosis of abdominal and pelvic neoplasm in pediatric patients.

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Wang, Hailing; Li, Fangxuan; Liu, Juntian; Zhang, Sheng

2014-01-01

Ultrasound-guided core needle biopsy of abdominal and pelvic masses in adults has gained tremendous popularity. However, the application of the same treatment in children is not as popular because of apprehensions regarding inadequate tissues for the biopsy and accidental puncture of vital organs. Data of the application of ultrasound-guided core needle biopsy in 105 pediatric patients with clinically or ultrasound-diagnosed abdominopelvic masses were reviewed. Diagnostic procedures were conducted in our institution from May 2011 to May 2013. The biopsies were conducted on 86 malignant lesions and 19 benign lesions. 86 malignant tumors comprised neuroblastomas (30 cases), hepatoblastomas (15 cases), nephroblastomas (11 cases), and primitive neuroectodermal tumors/malignant small round cells (6 cases). Among malignant tumor cases, only a pelvic primitive neuroectodermal tumor did not receive a pathological diagnosis. Therefore, the biopsy accuracy was 98.8 % in malignant tumor. However, the biopsies for one neuroblastomas and one malignant small round cell tumor were inadequate for cytogenetic analysis. Therefore, 96.5 % of the malignant tumor patients received complete diagnosis via biopsy. 19 benign tumors comprised mature teratoma (10 cases), hemangioendothelioma (3 cases), paraganglioma (2 cases), and infection (2 cases). The diagnostic accuracy for benign neoplasm was 100 %. Five patients experienced postoperative complications, including pain (2 patients), bleeding from the biopsy site (2 patients), and wound infection (1 patient). Ultrasound-guided core needle biopsy is an efficient, minimally invasive, accurate, and safe diagnostic method that can be applied in the management of abdominal or pelvic mass of pediatric patients.

Infant Brain Tumors: Incidence, Survival, and the Role of Radiation Based on Surveillance, Epidemiology, and End Results (SEER) Data

International Nuclear Information System (INIS)

Bishop, Andrew J.; McDonald, Mark W.; Chang, Andrew L.; Esiashvili, Natia

2012-01-01

Purpose: To evaluate the incidence of infant brain tumors and survival outcomes by disease and treatment variables. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) Program November 2008 submission database provided age-adjusted incidence rates and individual case information for primary brain tumors diagnosed between 1973 and 2006 in infants less than 12 months of age. Results: Between 1973 and 1986, the incidence of infant brain tumors increased from 16 to 40 cases per million (CPM), and from 1986 to 2006, the annual incidence rate averaged 35 CPM. Leading histologies by annual incidence in CPM were gliomas (13.8), medulloblastoma and primitive neuroectodermal tumors (6.6), and ependymomas (3.6). The annual incidence was higher in whites than in blacks (35.0 vs. 21.3 CPM). Infants with low-grade gliomas had the highest observed survival, and those with atypical teratoid rhabdoid tumors (ATRTs) or primary rhabdoid tumors of the brain had the lowest. Between 1979 and 1993, the annual rate of cases treated with radiation within the first 4 months from diagnosis declined from 20.5 CPM to <2 CPM. For infants with medulloblastoma, desmoplastic histology and treatment with both surgery and upfront radiation were associated with improved survival, but on multivariate regression, only combined surgery and radiation remained associated with improved survival, with a hazard ratio for death of 0.17 compared with surgery alone (p = 0.005). For ATRTs, those treated with surgery and upfront radiation had a 12-month survival of 100% compared with 24.4% for those treated with surgery alone (p = 0.016). For ependymomas survival was higher in patients treated in more recent decades (p = 0.001). Conclusion: The incidence of infant brain tumors has been stable since 1986. Survival outcomes varied markedly by histology. For infants with medulloblastoma and ATRTs, improved survival was observed in patients treated with both surgery and early radiation

Essential contribution of tumor-derived perlecan to epidermal tumor growth and angiogenesis

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Jiang, Xinnong; Multhaupt, Hinke; Chan, En

2004-01-01

As a major heparan sulfate proteoglycan (PG) in basement membranes, perlecan has been linked to tumor invasion, metastasis, and angiogenesis. Here we produced epidermal tumors in immunocompromised rats by injection of mouse RT101 tumor cells. Tumor sections stained with species-specific perlecan...... factor. In vivo, antisense perlecan-transfected cells generated no tumors, whereas untransfected and vector-transfected cells formed tumors with obvious neovascularization, suggesting that tumor perlecan rather than host perlecan controls tumor growth and angiogenesis....

Tumor-associated fibrosis as a regulator of tumor immunity and response to immunotherapy.

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Jiang, Hong; Hegde, Samarth; DeNardo, David G

2017-08-01

Tumor-associated fibrosis is characterized by unchecked pro-fibrotic and pro-inflammatory signaling. The components of fibrosis including significant numbers of cancer-associated fibroblasts, dense collagen deposition, and extracellular matrix stiffness, are well appreciated regulators of tumor progression but may also be critical regulators of immune surveillance. While this suggests that the efficacy of immunotherapy may be limited in highly fibrotic cancers like pancreas, it also suggests a therapeutic opportunity to target fibrosis in these tumor types to reawaken anti-tumor immunity. This review discusses the mechanisms by which fibrosis might subvert tumor immunity and how to overcome these mechanisms.

[Outstanding problems of normal and pathological morphology of the diffuse endocrine system].

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Iaglov, V V; Iaglova, N V

2011-01-01

The diffuse endocrine system (DES)--a mosaic-cellular endoepithelial gland--is the biggest part of the human endocrine system. Scientists used to consider cells of DES as neuroectodermal. According to modem data cells of DES are different cytogenetic types because they develop from the different embryonic blastophyllum. So that any hormone-active tumors originated from DES of the digestive, respiratory and urogenital system shouldn't be considered as neuroendocrinal tumors. The basic problems of DES morphology and pathology are the creation of scientifically substantiated histogenetic classification of DES tumors.

Malignant Transformation in a Mature Teratoma with Metastatic Deposits in the Omentum: A Case Report

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Shramana Mandal

2012-01-01

Full Text Available Malignant transformation of a mature cystic teratoma (MCT is a very rare complication with an incidence of 0.17–2%;. The most common form of malignant transformation of the MCT is squamous cell carcinoma. Other tumors arising in MCT include basal cell carcinoma, sebaceous tumor, malignant melanoma, adenocarcinoma, sarcoma, and neuroectodermal tumor. However malignant transformation with metastatic deposits in the omentum is extremely rare. The present case highlights the rarity of the occurrence of an omental deposits in a case of mature cystic teratoma with malignant transformation.

Treatment outcomes and late toxicities in patients with embryonal central nervous system tumors

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Odagiri, Kazumasa; Omura, Motoko; Hata, Masaharu; Aida, Noriko; Niwa, Tetsu; Goto, Hiroaki; Ito, Susumu; Adachi, Masanori; Yoshida, Haruyasu; Yuki, Hiroko; Inoue, Tomio

2014-01-01

Standard treatment strategies for embryonal central nervous system (CNS) tumors have not yet been established. We treated these tumors using an original chemoradiation therapy protocol; the clinical outcomes and toxicities were retrospectively evaluated. Twenty-four patients were enrolled including sixteen with medulloblastoma, four with supratentorial primitive neuroectodermal tumor (sPNET), three with atypical teratoid/rhabdoid tumor, and one with pineoblastoma. Immediately after diagnosis, all patients underwent surgery initially. They were then categorized as high- or average-risk groups independent of tumor type/pathogenesis. The average-risk group included patients who were aged ≥3 years at diagnosis, had non-metastatic disease at diagnosis (M0), and had undergone gross total resection. Other patients were categorized as the high-risk group; this group received more intensive treatment than the average-risk group, including high-dose chemotherapy with autologous stem-cell transplantation. All patients received craniospinal irradiation (CSI). The CSI dose was 23.4 Gy for M0 patients aged ≥5 years, 18 Gy for M0 patients aged <5 years, and 30–36 Gy for all patients with M + disease. The total dose to the primary tumor bed was 54 Gy. The median follow-up time was 73.5 (range, 19–118) months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 71.1 and 88.9%, respectively in the average-risk group (n = 9) and 66.7 and 71.1%, respectively in the high-risk group (n = 15). The PFS and OS rates were not significantly different between the average- and high-risk groups. In patients with medulloblastoma only, these rates were also not significantly different between the average- and high-risk groups. Three of four patients with sPNET were disease free. The height standard deviation score (SDS) was significantly decreased at the last assessment relative to that at diagnosis (P < 0.0001). The latest median height SDS was -1.6 (range, 0

Congenital extraskeletal Ewing's sarcoma of chest wall--a rare case report.

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Atla, Bhagyalakshmi; Prasad, B Satya Vara; Sri, K Satya; Vandana, Geeta

2011-01-01

Congenital extraskeletal Ewing's sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing's sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing's sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing's sarcoma in neonates are reported in the literature.

The role of H1 linker histone subtypes in preserving the fidelity of elaboration of mesendodermal and neuroectodermal lineages during embryonic development.

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Giang D Nguyen

Full Text Available H1 linker histone proteins are essential for the structural and functional integrity of chromatin and for the fidelity of additional epigenetic modifications. Deletion of H1c, H1d and H1e in mice leads to embryonic lethality by mid-gestation with a broad spectrum of developmental alterations. To elucidate the cellular and molecular mechanisms underlying H1 linker histone developmental functions, we analyzed embryonic stem cells (ESCs depleted of H1c, H1d and H1e subtypes (H1-KO ESCs by utilizing established ESC differentiation paradigms. Our study revealed that although H1-KO ESCs continued to express core pluripotency genes and the embryonic stem cell markers, alkaline phosphatase and SSEA1, they exhibited enhanced cell death during embryoid body formation and during specification of mesendoderm and neuroectoderm. In addition, we demonstrated deregulation in the developmental programs of cardiomyocyte, hepatic and pancreatic lineage elaboration. Moreover, ectopic neurogenesis and cardiomyogenesis occurred during endoderm-derived pancreatic but not hepatic differentiation. Furthermore, neural differentiation paradigms revealed selective impairments in the specification and maturation of glutamatergic and dopaminergic neurons with accelerated maturation of glial lineages. These impairments were associated with deregulation in the expression profiles of pro-neural genes in dorsal and ventral forebrain-derived neural stem cell species. Taken together, these experimental observations suggest that H1 linker histone proteins are critical for the specification, maturation and fidelity of organ-specific cellular lineages derived from the three cardinal germ layers.

Congenital extraskeletal Ewing′s sarcoma of chest wall - A rare case report

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Bhagyalakshmi Atla; B Satya Vara Prasad; K Satya Sri; Geeta Vandana

2011-01-01

Congenital extraskeletal Ewing′s sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing′s sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing′s sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing′s sarcoma in neonates are reported in the li...

Congenital extraskeletal Ewing′s sarcoma of chest wall - A rare case report

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Bhagyalakshmi Atla

2011-01-01

Full Text Available Congenital extraskeletal Ewing′s sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing′s sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing′s sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing′s sarcoma in neonates are reported in the literature.

Tumor-Infiltrating Immune Cells Promoting Tumor Invasion and Metastasis: Existing Theories

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Yan-gao Man, Alexander Stojadinovic, Jeffrey Mason, Itzhak Avital, Anton Bilchik, Bjoern Bruecher, Mladjan Protic, Aviram Nissan, Mina Izadjoo, Xichen Zhang, Anahid Jewett

2013-01-01

Full Text Available It is a commonly held belief that infiltration of immune cells into tumor tissues and direct physical contact between tumor cells and infiltrated immune cells is associated with physical destructions of the tumor cells, reduction of the tumor burden, and improved clinical prognosis. An increasing number of studies, however, have suggested that aberrant infiltration of immune cells into tumor or normal tissues may promote tumor progression, invasion, and metastasis. Neither the primary reason for these contradictory observations, nor the mechanism for the reported diverse impact of tumor-infiltrating immune cells has been elucidated, making it difficult to judge the clinical implications of infiltration of immune cells within tumor tissues. This mini-review presents several existing hypotheses and models that favor the promoting impact of tumor-infiltrating immune cells on tumor invasion and metastasis, and also analyzes their strength and weakness.

Hemoglobins, Hemorphins, and 11p15.5 Chromosomal Region in Cancer Biology and İmmunity with Special Emphasis for Brain Tumors.

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Altinoz, Meric Adil; Elmaci, Ilhan; Ince, Bahri; Ozpinar, Aysel; Sav, Aydin Murat

2016-05-01

In systemic cancers, increased hemolysis leads to extracellular hemoglobin (HB), and experimental studies have shown its provoking role on tumor growth and metastasis. However, investigations have shown that HB chains presented by tumor vascular pericytes or serum protein complexes of HB could also induce antitumor immunity, which may be harnessed to treat refractory cancers and brain tumors. Mounting recent evidence shows that expression of HBs is not restricted to erythrocytes and that HBs exist in the cells of lung and kidney, in macrophages, and in neurons and glia of the central nervous system (CNS). HBs mediate coping with hypoxia and free radical stress in normal and tumor cells, and they are increased in certain tumors including breast, lung, colon, and squamous cell cancers. Recent studies showed HBs in meningioma, in the cyst fluid of craniopharyngioma, in the cerebrospinal fluid (CSF) of pediatric patients with posterior fossa tumors, and in glioblastoma cell lines. Hemorphins, abundant brain peptides formed via HB-chain cleavage, exert opioid activity and antiproliferative and immunomodifier effects. Hence mutations in HBs may modify brain tumorigenesis via influencing hemorphins and perturbing regulations of immune surveillance and cell growth in the neuroectodermal tissues. The β-globin gene cluster resides in the chromosome region 11p15.5, harboring important immunity genes and IGF2, H19, PHLDA2/TSSC3, TRIM3, and SLC22A18 genes associated with cancers and gliomas. 11p15.5 is a prominent region subject to epigenetic regulation. Thus the β-globin loci may exert haplotypal interactions with these. Some clues support this theory. It is well established that iron load induces liver cancer in thalassemia major; however iron load-independent associations also exist. Enhanced rates of hematologic malignancies are associated with HB Lepore, association of hemoglobin E with cholangiocarcinoma, and enhanced gastric cancer rates in the thalassemia trait. In

Brain Tumor Therapy-Induced Changes in Normal-Appearing Brainstem Measured With Longitudinal Diffusion Tensor Imaging

International Nuclear Information System (INIS)

Hua Chiaho; Merchant, Thomas E.; Gajjar, Amar; Broniscer, Alberto; Zhang, Yong; Li Yimei; Glenn, George R.; Kun, Larry E.; Ogg, Robert J.

2012-01-01

Purpose: To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI). Methods and Materials: We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.4–39.6 Gy) and a cumulative dose of 55.8 Gy to the primary site, followed by four cycles of high-dose chemotherapy. Patients with high-grade gliomas (n = 10) received erlotinib during and after irradiation (54–59.4 Gy). Parametric maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and spatially registered to three-dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age-related benchmark for comparison, 37 DTI studies from 20 healthy volunteers, aged 6 to 25 years, were included in the analysis. Results: The median DTI follow-up time was 3.5 years (range, 1.6–5.0 years). The median mean dose to the pons was 56 Gy (range, 7–59 Gy). Three patterns were seen in longitudinal FA and apparent diffusion coefficient changes: (1) a stable or normal developing time trend, (2) initial deviation from normal with subsequent recovery, and (3) progressive deviation without evidence of complete recovery. The maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long-term recovery patterns. Conclusions: Variations existed among individual patients after therapy in longitudinal evolution of brainstem white matter injury and recovery. Early response

Coexistence of meningioma and glioblastoma multiforme in a same patient: a case report

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Pereira, C.; Dumont, P.; Romero, P.C.; Lima, J.P.; Caldas, J.G.; Settanni, F.

1991-01-01

Tumoral collision has been defined as a coexistence of two or more central nervous system tumors histologically distinct, in a patient not harbouring a neuro-ectodermic disease (phakomatosis). Several theories exist for explaining this phenomenon but most of them assume that there is spacial proximity between the tumors and/or ionizing radiation effects. We report the case of coexistence of meningothelial meningioma and glioblastoma multiforme in a same patient, occurring in different hemispheres on different times. The tomographic aspects of the gliomatous lesion and the difficulty in differentiating by neuroimaging among high grade gliomas and recent hemorrhagic cerebral events are discussed. (author)

Ewing?s Sarcoma of the Adrenal Gland

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Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

2016-01-01

Ewing’s sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing’s sarcoma is very rare. Here we report a case of Ewing’s sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five mon...

Ewing's Sarcoma of the Adrenal Gland.

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Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

2016-01-01

Ewing's sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing's sarcoma is very rare. Here we report a case of Ewing's sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery.

Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

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Chanmee, Theerawut; Ontong, Pawared; Konno, Kenjiro; Itano, Naoki

2014-01-01

During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy

Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

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Chanmee, Theerawut [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Ontong, Pawared [Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Konno, Kenjiro [Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Itano, Naoki, E-mail: itanon@cc.kyoto-su.ac.jp [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan)

2014-08-13

During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy.

CT findings of parotid gland tumors: benign versus malignant tumors

International Nuclear Information System (INIS)

Lee, Moon Ok; Han, Chun Hwan; Kim, Mie Young; Yi, Jeong Geun; Park, Kyung Joo; Lee, Joo Hyuk; Bae, Sang Hoon; Kim, Jeung Sook

1994-01-01

The purpose of this study is to evaluate the characteristics of parotid gland tumors to help in the differentiation between benign and malignant lesions. The CT findings of 22 patients with surgically proven parotid gland tumors were reviewed. Analysis was focused on the density and margin characteristics of the tumors, and the relationship between the tumor and surrounding structures. Those tumors were pleomorphic adenoma (n = 8), Warthin's tumor (n = 5), basal cell adenoma (n = 1), lipoma (n = 1), dermoid cyst (n = 1), adenoid cystic carcinoma (n = 2), mucoepidermoid carcinoma (n 1), epidermoid carcinoma (n = 1), and carcinoma in pleomorphic adenoma (n 1). Most of benign and malignant tumors were heterogeneous in density on contrast enhanced CT scans. In 5 of 6 malignant cases, the tumors had irregular or ill-defined margin and a tendancy to involve or cross the superficial layer of deep cervical fascia with obliteration of subcutaneous fat. Two malignant tumors invaded surrounding structures. Although the heterogeneous density of tumor is not a specific finding for malignancy at CT, following findings, such as, irregular or blurred margin of the lesion, the involvement of fascial plane, and the infiltration of surrounding structures may suggest the possibility of malignant parotid tumor

An anterior signaling center patterns and sizes the anterior neuroectoderm of the sea urchin embryo.

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Range, Ryan C; Wei, Zheng

2016-05-01

Anterior signaling centers help specify and pattern the early anterior neuroectoderm (ANE) in many deuterostomes. In sea urchin the ANE is restricted to the anterior of the late blastula stage embryo, where it forms a simple neural territory comprising several types of neurons as well as the apical tuft. Here, we show that during early development, the sea urchin ANE territory separates into inner and outer regulatory domains that express the cardinal ANE transcriptional regulators FoxQ2 and Six3, respectively. FoxQ2 drives this patterning process, which is required to eliminate six3 expression from the inner domain and activate the expression of Dkk3 and sFRP1/5, two secreted Wnt modulators. Dkk3 and low expression levels of sFRP1/5 act additively to potentiate the Wnt/JNK signaling pathway governing the positioning of the ANE territory around the anterior pole, whereas high expression levels of sFRP1/5 antagonize Wnt/JNK signaling. sFRP1/5 and Dkk3 levels are rigidly maintained via autorepressive and cross-repressive interactions with Wnt signaling components and additional ANE transcription factors. Together, these data support a model in which FoxQ2 initiates an anterior patterning center that implements correct size and positions of ANE structures. Comparisons of functional and expression studies in sea urchin, hemichordate and chordate embryos reveal striking similarities among deuterostome ANE regulatory networks and the molecular mechanism that positions and defines ANE borders. These data strongly support the idea that the sea urchin embryo uses an ancient anterior patterning system that was present in the common ambulacrarian/chordate ancestor. © 2016. Published by The Company of Biologists Ltd.

Tumor stem cells: A new approach for tumor therapy (Review)

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MENG, MIN; ZHAO, XIN-HAN; NING, QIAN; HOU, LEI; XIN, GUO-HONG; LIU, LI-FENG

2012-01-01

Recent studies have demonstrated the existence of a minority of tumor cells possessing the stem cell properties of self-renewal and differentiation in leukemia and several solid tumors. However, these cells do not possess the normal regulatory mechanisms of stem cells. Following transplantation, they are capable of initiating tumorigenesis and are therefore known as ‘tumor stem cells’. Cellular origin analysis of tumor stem cells has resulted in three hypotheses: Embryonal rest hypothesis, anaplasia and maturation arrest. Several signaling pathways which are involved in carcinogenesis, including Wnt/β-catenin, Notch and Oct-4 signaling pathways are crucial in normal stem cell self-renewal decisions, suggesting that breakdown in the regulation of self-renewal may be a key event in the development of tumors. Thus, tumors can be regarded as an abnormal organ in which stem cells have escaped from the normal constraints on self-renewal, thus, leading to abnormally differentiated tumor cells that lose the ability to form tumors. This new model for maligancies has significance for clinical research and treatment. PMID:22844351

PNET Ewing's sarcoma: a case report of a 8-year-old child presenting with PNET Ewing sarcoma

International Nuclear Information System (INIS)

Bauskar, Pratibha; Bhalavat, Rajendra; Chandra, Manish; Bauskar, Dipak

2016-01-01

PNET (Primitive Neuro-Ectodermal) mostly present in younger children. PNET Ewing sarcoma Ewing's sarcomas are rare, aggressive tumors, growth from undeveloped brain cells, with a tendency towards recurrence. We report the case of a 8-year-old girl who presented with a one year history of pain in her lower neck region with single episode of un-consciousness associate with left side upper and lower limb weakness. Magnetic resonance imaging demonstrated an abnormal marrow changes involving C5 vertebra and involvement of posterior elements showing expansive changes. Biopsy showed malignant small round cell tumor identifying as PNET Ewing sarcoma. Laminectomy and Decompression of cervical tumor. (author)

Biological stoichiometry in tumor micro-environments.

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Irina Kareva

Full Text Available Tumors can be viewed as evolving ecological systems, in which heterogeneous populations of cancer cells compete with each other and somatic cells for space and nutrients within the ecosystem of the human body. According to the growth rate hypothesis (GRH, increased phosphorus availability in an ecosystem, such as the tumor micro-environment, may promote selection within the tumor for a more proliferative and thus potentially more malignant phenotype. The applicability of the GRH to tumor growth is evaluated using a mathematical model, which suggests that limiting phosphorus availability might promote intercellular competition within a tumor, and thereby delay disease progression. It is also shown that a tumor can respond differently to changes in its micro-environment depending on the initial distribution of clones within the tumor, regardless of its initial size. This suggests that composition of the tumor as a whole needs to be evaluated in order to maximize the efficacy of therapy.

Captopril improves tumor nanomedicine delivery by increasing tumor blood perfusion and enlarging endothelial gaps in tumor blood vessels.

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Zhang, Bo; Jiang, Ting; Tuo, Yanyan; Jin, Kai; Luo, Zimiao; Shi, Wei; Mei, Heng; Hu, Yu; Pang, Zhiqing; Jiang, Xinguo

2017-12-01

Poor tumor perfusion and unfavorable vessel permeability compromise nanomedicine drug delivery to tumors. Captopril dilates blood vessels, reducing blood pressure clinically and bradykinin, as the downstream signaling moiety of captopril, is capable of dilating blood vessels and effectively increasing vessel permeability. The hypothesis behind this study was that captopril can dilate tumor blood vessels, improving tumor perfusion and simultaneously enlarge the endothelial gaps of tumor vessels, therefore enhancing nanomedicine drug delivery for tumor therapy. Using the U87 tumor xenograft with abundant blood vessels as the tumor model, tumor perfusion experiments were carried out using laser Doppler imaging and lectin-labeling experiments. A single treatment of captopril at a dose of 100 mg/kg significantly increased the percentage of functional vessels in tumor tissues and improved tumor blood perfusion. Scanning electron microscopy of tumor vessels also indicated that the endothelial gaps of tumor vessels were enlarged after captopril treatment. Immunofluorescence-staining of tumor slices demonstrated that captopril significantly increased bradykinin expression, possibly explaining tumor perfusion improvements and endothelial gap enlargement. Additionally, imaging in vivo, imaging ex vivo and nanoparticle distribution in tumor slices indicated that after a single treatment with captopril, the accumulation of 115-nm nanoparticles in tumors had increased 2.81-fold with a more homogeneous distribution pattern in comparison to non-captopril treated controls. Finally, pharmacodynamics experiments demonstrated that captopril combined with paclitaxel-loaded nanoparticles resulted in the greatest tumor shrinkage and the most extensive necrosis in tumor tissues among all treatment groups. Taken together, the data from the present study suggest a novel strategy for improving tumor perfusion and enlarging blood vessel permeability simultaneously in order to improve

Radiation-induced nitric oxide mitigates tumor hypoxia and radioresistance in a murine SCCVII tumor model

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Nagane, Masaki; Yasui, Hironobu; Yamamori, Tohru; Zhao, Songji; Kuge, Yuji; Tamaki, Nagara; Kameya, Hiromi; Nakamura, Hideo; Fujii, Hirotada; Inanami, Osamu

2013-01-01

Highlights: •IR-induced NO increased tissue perfusion and pO 2 . •IR increased NO production in tumors without changes in the mRNA and protein levels of NOS isoforms. •NOS activity assay showed that IR upregulated eNOS activity in tumors. •IR-induced NO decreased tumor hypoxia and altered tumor radiosensitivity. -- Abstract: Tumor hypoxia, which occurs mainly as a result of inadequate tissue perfusion in solid tumors, is a well-known challenge for successful radiotherapy. Recent evidence suggests that ionizing radiation (IR) upregulates nitric oxide (NO) production and that IR-induced NO has the potential to increase intratumoral circulation. However, the kinetics of NO production and the responsible isoforms for NO synthase in tumors exposed to IR remain unclear. In this study, we aimed to elucidate the mechanism by which IR stimulates NO production in tumors and the effect of IR-induced NO on tumor radiosensitivity. Hoechst33342 perfusion assay and electron spin resonance oxymetry showed that IR increased tissue perfusion and pO 2 in tumor tissue. Immunohistochemical analysis using two different hypoxic probes showed that IR decreased hypoxic regions in tumors; treatment with a nitric oxide synthase (NOS) inhibitor, L-NAME, abrogated the effects of IR. Moreover, IR increased endothelial NOS (eNOS) activity without affecting its mRNA or protein expression levels in SCCVII-transplanted tumors. Tumor growth delay assay showed that L-NAME decreased the anti-tumor effect of fractionated radiation (10 Gy × 2). These results suggested that IR increased eNOS activity and subsequent tissue perfusion in tumors. Increases in intratumoral circulation simultaneously decreased tumor hypoxia. As a result, IR-induced NO increased tumor radiosensitivity. Our study provides a new insight into the NO-dependent mechanism for efficient fractionated radiotherapy

Tumor-reactive immune cells protect against metastatic tumor and induce immunoediting of indolent but not quiescent tumor cells.

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Payne, Kyle K; Keim, Rebecca C; Graham, Laura; Idowu, Michael O; Wan, Wen; Wang, Xiang-Yang; Toor, Amir A; Bear, Harry D; Manjili, Masoud H

2016-09-01

Two major barriers to cancer immunotherapy include tumor-induced immune suppression mediated by myeloid-derived suppressor cells and poor immunogenicity of the tumor-expressing self-antigens. To overcome these barriers, we reprogrammed tumor-immune cell cross-talk by combined use of decitabine and adoptive immunotherapy, containing tumor-sensitized T cells and CD25(+) NKT cells. Decitabine functioned to induce the expression of highly immunogenic cancer testis antigens in the tumor, while also reducing the frequency of myeloid-derived suppressor cells and the presence of CD25(+) NKT cells rendered T cells, resistant to remaining myeloid-derived suppressor cells. This combinatorial therapy significantly prolonged survival of animals bearing metastatic tumor cells. Adoptive immunotherapy also induced tumor immunoediting, resulting in tumor escape and associated disease-related mortality. To identify a tumor target that is incapable of escape from the immune response, we used dormant tumor cells. We used Adriamycin chemotherapy or radiation therapy, which simultaneously induce tumor cell death and tumor dormancy. Resultant dormant cells became refractory to additional doses of Adriamycin or radiation therapy, but they remained sensitive to tumor-reactive immune cells. Importantly, we discovered that dormant tumor cells contained indolent cells that expressed low levels of Ki67 and quiescent cells that were Ki67 negative. Whereas the former were prone to tumor immunoediting and escape, the latter did not demonstrate immunoediting. Our results suggest that immunotherapy could be highly effective against quiescent dormant tumor cells. The challenge is to develop combinatorial therapies that could establish a quiescent type of tumor dormancy, which would be the best target for immunotherapy. © The Author(s).

Lapatinib Plasma and Tumor Concentrations and Effects on HER Receptor Phosphorylation in Tumor.

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Neil L Spector

Full Text Available The paradigm shift in cancer treatment from cytotoxic drugs to tumor targeted therapies poses new challenges, including optimization of dose and schedule based on a biologically effective dose, rather than the historical maximum tolerated dose. Optimal dosing is currently determined using concentrations of tyrosine kinase inhibitors in plasma as a surrogate for tumor concentrations. To examine this plasma-tumor relationship, we explored the association between lapatinib levels in tumor and plasma in mice and humans, and those effects on phosphorylation of human epidermal growth factor receptors (HER in human tumors.Mice bearing BT474 HER2+ human breast cancer xenografts were dosed once or twice daily (BID with lapatinib. Drug concentrations were measured in blood, tumor, liver, and kidney. In a randomized phase I clinical trial, 28 treatment-naïve female patients with early stage HER2+ breast cancer received lapatinib 1000 or 1500 mg once daily (QD or 500 mg BID before evaluating steady-state lapatinib levels in plasma and tumor.In mice, lapatinib levels were 4-fold higher in tumor than blood with a 4-fold longer half-life. Tumor concentrations exceeded the in vitro IC90 (~ 900 nM or 500 ng/mL for inhibition of HER2 phosphorylation throughout the 12-hour dosing interval. In patients, tumor levels were 6- and 10-fold higher with QD and BID dosing, respectively, compared to plasma trough levels. The relationship between tumor and plasma concentration was complex, indicating multiple determinants. HER receptor phosphorylation varied depending upon lapatinib tumor concentrations, suggestive of changes in the repertoire of HER homo- and heterodimers.Plasma lapatinib concentrations underestimated tumor drug levels, suggesting that optimal dosing should be focused on the site of action to avoid to inappropriate dose escalation. Larger clinical trials are required to determine optimal dose and schedule to achieve tumor concentrations that maximally

Macrophage content of murine tumors: Associations with TD50 and tumor radiocurability

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Wike, J.; Hunter, N.; Volpe, J.; Milas, L.

1987-01-01

The experiments were designed to investigate whether the tumor-associated macrophage (TAM) content of murine solid tumors correlates with tumor response to ionizing radiation and with the clonogenic ability of tumor cells to establish s.c. tumors. Of 13 tumors studied, 6 were sarcomas and 7 were carcinomas; all tumors were of spontaneous origin in C/sub 3/Hf/Kam mice, with the exception of one sarcoma that was induced by 3-methylcholanthrene. Tumors were growing in the hind thighs of syngeneic mice, and their TAM content was determined when they were 8 mm in diameter. Their macrophage content varied greatly, ranging from 9 to 83%. Radiocurability of 8 mm tumors, determined by TCD50, ranged from 42 Gy (fibrosarcoma FSA) to > 80 Gy (hepatocarcinoma HCA-I). There was an obvious trend toward positive correlation (r = 0.43) between TAM content and reduced local tumor radiocurability. However, there was a significant negative correlation between TAM content and TD50 values, implying that cells from tumors with higher macrophage content were more clonogenic. TAM from the NFSA sarcoma, a tumor with a low TD50 value and poorly responsive to radiation, stimulated the in vitro growth of NFSA tumor cells. These observations suggest that high TAM content could be conducive to tumor cell proliferation and could be a factor in poor tumor radioresponse

Promotion of Tumor Invasion by Cooperation of Granulocytes and Macrophages Activated by Anti-tumor Antibodies

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Emilio Barbera-Guillem

1999-11-01

Full Text Available We investigated the potential role of anti-tumor antibodies and tumor antigens in the formation of immune complexes which promote matrix degradation and angiogenesis. B-cell deficient or B-cell depleted mice showed a reduction in tumor invasion and metastasis. In vitro invasion assays and in vivo models of metastasis showed that anti-sTn antibodies and sTn tumor antigens form complexes which induce granulocytes and macrophages together to mediate tumor invasion and metastasis by processes including extracellular matrix degradation and angiogenesis. These results suggest the existence of a tumor promoting role of a B-cell immune response induced by shed tumor associated antigens of solid, nonlymphoid tumors.

Genomic Heterogeneity of Breast Tumor Pathogenesis

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Ellsworth, Rachel E.; Hooke, Jeffrey A.; Shriver, Craig D.; Ellsworth, Darrell L.

2009-01-01

Pathological grade is a useful prognostic factor for stratifying breast cancer patients into favorable (low-grade, well-differentiated tumors) and less favorable (high-grade, poorly-differentiated tumors) outcome groups. Under the current system of tumor grading, however, a large proportion of tumors are characterized as intermediate-grade, making determination of optimal treatments difficult. In an effort to increase objectivity in the pathological assessment of tumor grade, differences in chromosomal alterations and gene expression patterns have been characterized in low-grade, intermediate-grade, and high-grade disease. In this review, we outline molecular data supporting a linear model of progression from low-grade to high-grade carcinomas, as well as contradicting genetic data suggesting that low-grade and high-grade tumors develop independently. While debate regarding specific pathways of development continues, molecular data suggest that intermediate-grade tumors do not comprise an independent disease subtype, but represent clinical and molecular hybrids between low-grade and high-grade tumors. Finally, we discuss the clinical implications associated with different pathways of development, including a new clinical test to assign grade and guide treatment options. PMID:20689613

Extra-skeletal Ewing's sarcoma resembling acute abdomen. Case report.

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Valdivia Gómez, Gilberto Guzmán; Soto Guerrero, María Teresa; Cedillo de la Cruz, María Isabel

2010-01-01

Extraosseous Ewing's sarcoma is a rare tumor of neuroectodermal origin. It presents mainly in the soft tissue of the extremities and thorax. Histologically, it is similar to Ewing's sarcoma of the bone. We present the case of a male who arrived at the emergency room with acute abdomen, leucocytosis and imaging techniques (abdominal ultrasound and computed tomography) suggestive of complicated diverticular disease. He was treated with emergency surgery. Intraoperative findings were an unsuspected tumor (20 x 15 x 15 cm). Treatment consisted of extirpation of the tumor, separating it from the adjacent viscera and followed by chemotherapy based on epirubicin, cyclophosphamide and vincristine for six cycles. Because the control abdominal CT demonstrated tumor activity in the retroperitoneum adjacent to the ascending colon and cecum, further resection was decided upon. In a review of the literature, no previous reports of extraosseous Ewing's sarcoma were found presenting as acute abdomen. Due to the rarity of this tumor, only case reports or series have been found in the literature without randomized or comparative studies. Surgery was the cornerstone of treatment, without reports of preoperative chemotherapy. If the patient's condition permits, percutaneous needle biopsy is mandatory to obtain optimum treatment as well as to improve prognosis.

Diagnosis and treatment of Ewing's sarcoma

International Nuclear Information System (INIS)

Iwamoto, Yukihide

2007-01-01

Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Ewing's sarcoma has retained the most unfavorable prognosis of all primary musculoskeletal tumors. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%. In addition, the preferred method of tumor resection has changed; limb salvage has nearly replaced amputation of the affected limb. Limb salvage procedures can be performed in place of amputation without compromising patient survival rates. Recent studies have revealed that the pathognomonic translocations involving the EWS gene on chromosome 22 and an ETS-type gene, which is most commonly the Fli1 gene on chromosome 11, are implicated in more than 95% of Ewing's sarcomas, primitive neuroectodermal tumors and Askin's tumors. Therefore, these lesions have become regarded as a single entity, dubbed the Ewing's family of tumors. Reverse transcription polymerase chain reaction (RT-PCR) to detect EWS-ETS gene arrangements is widely used to confirm the diagnosis of Ewing's family of tumors. Experimental results suggest that inhibition of the signaling pathway downstream of the EWS-ETS gene may lead to the development of molecularly targeted therapy in the future. (author)

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

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

2002-06-01

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

Imaging probe for tumor malignancy

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Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Hasahiro

2009-02-01

Solid tumors possess unique microenvironments that are exposed to chronic hypoxic conditions ("tumor hypoxia"). Although more than half a century has passed since it was suggested that tumor hypoxia correlated with poor treatment outcomes and contributed to cancer recurrence, a fundamental solution to this problem has yet to be found. Hypoxia-inducible factor (HIF-1) is the main transcription factor that regulates the cellular response to hypoxia. It induces various genes whose functions are strongly associated with malignant alteration of the entire tumor. The cellular changes induced by HIF-1 are extremely important targets of cancer therapy, particularly in therapy against refractory cancers. Imaging of the HIF-1-active microenvironment is therefore important for cancer therapy. To image HIF-1activity in vivo, we developed a PTD-ODD fusion protein, POHA, which was uniquely labeled with near-infrared fluorescent dye at the C-terminal. POHA has two functional domains: protein transduction domain (PTD) and VHL-mediated protein destruction motif in oxygen-dependent degradation (ODD) domain of the alpha subunit of HIF-1 (HIF-1α). It can therefore be delivered to the entire body and remain stabilized in the HIF-1-active cells. When it was intravenously injected into tumor-bearing mice, a tumor-specific fluorescence signal was detected in the tumor 6 h after the injection. These results suggest that POHA can be used an imaging probe for tumor malignancy.

Spinal drop metastasis

International Nuclear Information System (INIS)

Kramer, E.D.; Rafto, S.E.; Zimmerman, R.A.; Packer, R.J.

1989-01-01

Identifying subarachnoid metastatic disease (SAMD) in patients with primary central nervous system tumors is important in determining subsequent therapy. Myelography with CT follow-up has been the gold standard for this evaluation. It is an invasive procedure often performed with general anesthesia in children. Now that gadolinium MR imaging has become available, a comparison of these techniques has been initiated to determine their relative effectiveness in demonstrating SAMD in children. Ten children (seven male, aged 2-19 years) with primitive neuroectoderm tumor (n = 5), ependymoma (n = 2), glioblastoma multiforme (n = 1), diffuse low-grade astrocytoma (n = 1), and rhabdoid/teratoid tumors (n = 1) underwent simultaneous myelography/CT and gadolinium MR imaging. Results are presented

Multiparametric MR assessment of pediatric brain tumors

International Nuclear Information System (INIS)

Tzika, A.A.; Astrakas, L.G.; Zarifi, M.K.; Petridou, N.; Young-Poussaint, T.; Goumnerova, L.; Black, P.McL.; Zurakowski, D.; Anthony, D.C.

2003-01-01

MR assessment of pediatric brain tumors has expanded to include physiologic information related to cellular metabolites, hemodynamic and diffusion parameters. The purpose of this study was to investigate the relationship between MR and proton MR spectroscopic imaging in children with primary brain tumors. Twenty-one patients (mean age 9 years) with histologically verified brain tumors underwent conventional MR imaging, hemodynamic MR imaging (HMRI) and proton MR spectroscopic imaging (MRSI). Fourteen patients also had diffusion-weighted MR imaging (DWMRI). Metabolic indices including choline-containing compounds (Cho), total creatine (tCr) and lipids/lactate (L) were derived by proton MRSI, relative cerebral blood volume (rCBV) by HMRI, and apparent tissue water diffusion coefficients (ADC) by DWMRI. Variables were examined by linear regression and correlation as well as by ANOVA. Cho (suggestive of tumor cellularity and proliferative activity) correlated positively with rCBV, while the relationship between Cho and ADC (suggestive of cellular density) was inverse (P<0.001). The relationship between rCBV and ADC was also inverse (P=0.004). Cho and lipids (suggestive of necrosis and/or apoptosis) were not significantly correlated (P=0.51). A positive relationship was found between lipids and ADC (P=0.002). The relationships between Cho, rCBV, ADC and lipids signify that tumor physiology is influenced by the tumor's physical and chemical environment. Normalized Cho and lipids distinguished high-grade from low-grade tumors (P<0.05). Multiparametric MR imaging using MRSI, HMRI and DWMRI enhances assessment of brain tumors in children and improves our understanding of tumor physiology while promising to distinguish higher- from lower-malignancy tumors, a distinction that is particularly clinically important among inoperable tumors. (orig.)

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

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

2009-03-01

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

Inflammatory Myofibroblastic Tumor of the Nasal Septum

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Yuri Okumura

2013-01-01

Full Text Available We report an extremely rare case of inflammatory myofibroblastic tumor of the posterior edge of the nasal septum. An 11-year-old boy presented with frequent epistaxis and nasal obstruction persisting for one year. Based on the clinical presentation and imaging studies, juvenile angiofibroma was suspected, but angiography suggested the possibility of another type of tumor. Transnasal endoscopic surgery found that the tumor protruded into the nasopharynx from the posterior end of the nasal septum. Histological examination identified spindle cells with immunoreaction for vimentin, smooth muscle actin, and anaplastic lymphoma kinase (ALK, but not for desmin and cytokeratin. This is a report of inflammatory myofibroblastic tumor mimicking juvenile angiofibroma. This case suggests that angiography is helpful in the differential diagnosis of epipharyngeal tumor in adolescence.

99mTc-monoclonal antibody radiolabeled via hydrazino nicotinamide derivative for imaging disialoganglioside GD2-positive tumors

International Nuclear Information System (INIS)

Fonti, Rosa; Cheung, N.-K.V.; Bridger, Gary J.; Guo, H.-F.; Abrams, Michael J.; Larson, Steven M.

1999-01-01

3F8 is a murine IgG 3 monoclonal antibody (MAb) selective for the ganglioside G D2 . Previous studies using 131 I-3F8 have shown great potential in the imaging of neuroectodermal tumors and the therapy of human neuroblastoma. 131 I is commonly used in radioimmunodiagnosis, but its relatively long half-life (8 days) and its high energy γ-emission (364 KeV) are suboptimal for imaging purposes when compared with 99m Tc (6 h and 140 KeV, respectively). To label 3F8 with 99m Tc, the antibody was first coupled with a heterobifunctional linker, succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH), obtaining a hydrazinonicotinamide-antibody conjugate. Using 99m Tc-Tricine as the precursor complex, 3F8-SHNH was coupled efficiently to 99m Tc, resulting in >90% radiometal incorporation, with a specific activity >10 mCi/mg and retaining full immunoreactivity. Immunoscintigraphy at 6, 22, and 46 h after intravenous injection of 1 mCi of 99m Tc-3F8 showed selective neuroblastoma localization in xenografted nude mice, comparable to that obtained with the injection of 100 μCi of 131 I-3F8. Biodistribution studies of 131 I-3F8 and 99m Tc-3F8 in mice demonstrated comparable %ID/g uptake in tumor (with a T/B ratio: ∼2.5 at 24 h and ∼3.5 at 48 h) and normal organs, including blood, except for spleen and liver which had about a three times higher uptake of the 99m Tc conjugate. In conclusion, 99m Tc can be coupled conveniently at high specific activity to 3F8 without compromising immunoreactivity. SHNH appears to be a useful linker for 99m Tc in tumor diagnostic imaging and may have potential utility in coupling other radioisotopes (e.g., 94m Tc) for positron imaging and therapy

Pericytes limit tumor cell metastasis

DEFF Research Database (Denmark)

Xian, Xiaojie; Håkansson, Joakim; Ståhlberg, Anders

2006-01-01

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

Targeted delivery of immunotoxin by antibody to ganglioside GD3: a novel drug delivery route for tumor cells.

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Vanina Torres Demichelis

Full Text Available Gangliosides are sialic acid-containing glycolipids expressed on plasma membranes from nearly all vertebrate cells. The expression of ganglioside GD3, which plays essential roles in normal brain development, decreases in adults but is up regulated in neuroectodermal and epithelial derived cancers. R24 antibody, directed against ganglioside GD3, is a validated tumor target which is specifically endocytosed and accumulated in endosomes. Here, we exploit the internalization feature of the R24 antibody for the selective delivery of saporin, a ribosome-inactivating protein, to GD3-expressing cells [human (SK-Mel-28 and mouse (B16 melanoma cells and Chinese hamster ovary (CHO-K1 cells]. This immunotoxin showed a specific cytotoxicity on tumor cells grew on 2D monolayers, which was further evident by the lack of any effect on GD3-negative cells. To estimate the potential antitumor activity of R24-saporin complex, we also evaluated the effect of the immunotoxin on the clonogenic growth of SK-Mel-28 and CHO-K1(GD3+ cells cultured in attachment-free conditions. A drastic growth inhibition (>80-90% of the cell colonies was reached after 3 days of immunotoxin treatment. By the contrary, colonies continue to growth at the same concentration of the immuntoxin, but in the absence of R24 antibody, or in the absence of both immunotoxin and R24, undoubtedly indicating the specificity of the effect observed. Thus, the ganglioside GD3 emerge as a novel and attractive class of cell surface molecule for targeted delivery of cytotoxic agents and, therefore, provides a rationale for future therapeutic intervention in cancer.

A zebrafish transgenic model of Ewing’s sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis

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Stefanie W. Leacock

2012-01-01

Ewing’s sarcoma, a malignant bone tumor of children and young adults, is a member of the small-round-blue-cell tumor family. Ewing’s sarcoma family tumors (ESFTs, which include peripheral primitive neuroectodermal tumors (PNETs, are characterized by chromosomal translocations that generate fusions between the EWS gene and ETS-family transcription factors, most commonly FLI1. The EWS-FLI1 fusion oncoprotein represents an attractive therapeutic target for treatment of Ewing’s sarcoma. The cell of origin of ESFT and the molecular mechanisms by which EWS-FLI1 mediates tumorigenesis remain unknown, and few animal models of Ewing’s sarcoma exist. Here, we report the use of zebrafish as a vertebrate model of EWS-FLI1 function and tumorigenesis. Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewing’s sarcoma. The incidence of tumors increased in a p53 mutant background, suggesting that the p53 pathway suppresses EWS-FLI1-driven tumorigenesis. Gene expression profiling of the zebrafish tumors defined a set of genes that might be regulated by EWS-FLI1, including the zebrafish ortholog of a crucial EWS-FLI1 target gene in humans. Stable zebrafish transgenic lines expressing EWS-FLI1 under the control of the heat-shock promoter exhibit altered embryonic development and defective convergence and extension, suggesting that EWS-FLI1 interacts with conserved developmental pathways. These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene.

A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis.

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Leacock, Stefanie W; Basse, Audrey N; Chandler, Garvin L; Kirk, Anne M; Rakheja, Dinesh; Amatruda, James F

2012-01-01

Ewing's sarcoma, a malignant bone tumor of children and young adults, is a member of the small-round-blue-cell tumor family. Ewing's sarcoma family tumors (ESFTs), which include peripheral primitive neuroectodermal tumors (PNETs), are characterized by chromosomal translocations that generate fusions between the EWS gene and ETS-family transcription factors, most commonly FLI1. The EWS-FLI1 fusion oncoprotein represents an attractive therapeutic target for treatment of Ewing's sarcoma. The cell of origin of ESFT and the molecular mechanisms by which EWS-FLI1 mediates tumorigenesis remain unknown, and few animal models of Ewing's sarcoma exist. Here, we report the use of zebrafish as a vertebrate model of EWS-FLI1 function and tumorigenesis. Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewing's sarcoma. The incidence of tumors increased in a p53 mutant background, suggesting that the p53 pathway suppresses EWS-FLI1-driven tumorigenesis. Gene expression profiling of the zebrafish tumors defined a set of genes that might be regulated by EWS-FLI1, including the zebrafish ortholog of a crucial EWS-FLI1 target gene in humans. Stable zebrafish transgenic lines expressing EWS-FLI1 under the control of the heat-shock promoter exhibit altered embryonic development and defective convergence and extension, suggesting that EWS-FLI1 interacts with conserved developmental pathways. These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene.

Immune response to UV-induced tumors: mediation of progressor tumor rejection by natural killer cells

International Nuclear Information System (INIS)

Streeter, P.R.; Fortner, G.W.

1986-01-01

Skin tumors induced in mice by chronic ultraviolet (UV) irradiation are highly antigenic and can induce a state of transplantation immunity in syngeneic animals. In the present study, the authors compared the in vitro cytolytic activity of splenic lymphocytes from mice immunized with either regressor or progressor UV-tumors. The results of this comparison implicated tumor-specific cytolytic T (Tc) lymphocytes in rejection of regressor UV-tumors, and revealed that immunization with the progressor UV-tumor 2237 failed to elicit detectable levels of progressor tumor-specific Tc cells even as the tumors rejected. Following in vitro resensitization of spleen cells from either regressor or progressor tumor immune animals, the authors found NK-like lymphocytes with anti-tumor activity. As the authors had not detected cells with this activity in splenic lymphocyte preparations prior to in vitro resensitization, the authors examined lymphocytes from the local tumor environment during the course of progressor tumor rejection for this activity. This analysis revealed NK lymphocytes exhibiting significant levels of cytolytic activity against UV-tumors. These results implicate NK cells as potential effector cells in the rejection of progressor UV-tumors by immune animals, and suggests that these cells may be regulated by T lymphocytes

Molecular crosstalk between cancer cells and tumor microenvironment components suggests potential targets for new therapeutic approaches in mobile tongue cancer

International Nuclear Information System (INIS)

Dayan, Dan; Salo, Tuula; Salo, Sirpa; Nyberg, Pia; Nurmenniemi, Sini; Costea, Daniela Elena; Vered, Marilena

2012-01-01

We characterized tumor microenvironment (TME) components of mobile tongue (MT) cancer patients in terms of overall inflammatory infiltrate, focusing on the protumorigenic/anti-inflammatory phenotypes and on cancer-associated fibroblasts (CAFs) in order to determine their interrelations and associations with clinical outcomes. In addition, by culturing tongue carcinoma cells (HSC-3) on a three-dimensional myoma organotypic model that mimics TME, we attempted to investigate the possible existence of a molecular crosstalk between cancer cells and TME components. Analysis of 64 cases of MT cancer patients revealed that the overall density of the inflammatory infiltrate was inversely correlated to the density of CAFs (P = 0.01), but that the cumulative density of the protumorigenic/anti-inflammatory phenotypes, including regulatory T cells (Tregs, Foxp3+), tumor-associated macrophages (TAM2, CD163+), and potentially Tregs-inducing immune cells (CD80+), was directly correlated with the density of CAFs (P = 0.01). The hazard ratio (HR) for recurrence in a TME rich in CD163+ Foxp3+ CD80+ was 2.9 (95% CI 1.03–8.6, P = 0.043 compared with low in CD163+ Foxp3+ CD80+). The HR for recurrence in a TME rich in CAFs was 4.1 (95% confidence interval [CI] 1.3–12.8, P = 0.012 compared with low in CAFs). In vitro studies showed cancer-derived exosomes, epithelial–mesenchymal transition process, fibroblast-to-CAF-like cell transdifferentiation, and reciprocal interrelations between different cytokines suggesting the presence of molecular crosstalk between cancer cells and TME components. Collectively, these results highlighted the emerging need of new therapies targeting this crosstalk between the cancer cells and TME components in MT cancer

Oral treatment with a rattlesnake native polypeptide crotamine efficiently inhibits the tumor growth with no potential toxicity for the host animal and with suggestive positive effects on animal metabolic profile.

Science.gov (United States)

Campeiro, Joana D; Marinovic, Marcelo P; Carapeto, Fernando Cintra; Dal Mas, Caroline; Monte, Gabriela Guilherme; Carvalho Porta, Lucas; Nering, Marcela B; Oliveira, Eduardo B; Hayashi, Mirian A F

2018-02-01

The efficacy of crotamine as antitumoral was first demonstrated by daily intraperitoneal (IP) injections of low doses of this toxin in an animal model bearing melanoma tumors. Significant inhibition of tumor growth and increased lifespan of mice bearing tumor was also noticed after 21 consecutive days of this daily IP administration of crotamine. However, due to the limited acceptance of treatments by IP route in clinical conditions, herein, we evaluated the antitumor effect of this native polypeptide employing the oral route. The efficacy of crotamine in inhibiting the melanoma growth in vivo, even after passing through the gastrointestinal tract of the animal, was confirmed here. In addition, biochemical biomarkers and also histopathological analysis showed both the absence of any potential toxic effects in tissues or organs of the animal in which the highest accumulation of crotamine is expected. Interestingly, a reduction of weight gain was observed mainly in animals with tumor treated with crotamine by IP route, but not by oral administration. Albeit, oral administered crotamine was able to significantly decrease the body weight gain of healthy animals without tumor. Taking advantage of this same experimental animal models receiving crotamine by oral route, it was possible to show metabolic changes as the increased capacity of glucose clearance, which was accompanied by a reduction of the total cholesterol, and by increased high-density lipoprotein levels, both observed mainly in the absence of tumor. Triglycerides and low-density lipoprotein were also significantly decreased, but only in the absence of tumor. Taken together, these data suggest a clear trend for metabolic positive effects and mischaracterize unhealthy condition of animals, with or without tumors, treated with crotamine for 21 days. In addition, this study confirmed the efficacy of crotamine administered by oral route as antitumor agent, which besides the additional advantage of

Case of choroid plexus papilloma of the lateral ventricle presenting as a primary intracranial hemorrhage

Energy Technology Data Exchange (ETDEWEB)

Kurokawa, Hiroyuki; Kikuchi, Kenji; Gito, Yoji; Goto, Tsuneo; Ito, Yasunobu; Fujii, Satoshi

1988-04-01

A case of a choroid plexus papilloma of the lateral ventricle that was revealed by a massive intracranial hemorrhage in a 61-year-old man is presented. This patient had an intracranial hemorrhage at the onset. The presence of brain tumor was suspected after a radiologic evaluation using computerized tomography (CT) and angiography; the correctness of this histological diagnosis was confirmed by surgical specimens. Choroid plexus papillomas, rare tumors of neuroectodermal origin, account for 0.5 to 0.6 % of all intracranial tumors. They most frequently appear during the first 2 years of life. A case manifesting intracranial hemorrhage associated with choroid plexus papilloma in an adult is described, with a review of the literature. The importance of adequate radiological investigation is emphasized.

A case of choroid plexus papilloma of the lateral ventricle presenting as a primary intracranial hemorrhage

International Nuclear Information System (INIS)

Kurokawa, Hiroyuki; Kikuchi, Kenji; Gito, Yoji; Goto, Tsuneo; Ito, Yasunobu; Fujii, Satoshi

1988-01-01

A case of a choroid plexus papilloma of the lateral ventricle that was revealed by a massive intracranial hemorrhage in a 61-year-old man is presented. This patient had an intracranial hemorrhage at the onset. The presence of brain tumor was suspected after a radiologic evaluation using computerized tomography (CT) and angiography; the correctness of this histological diagnosis was confirmed by surgical specimens. Choroid plexus papillomas, rare tumors of neuroectodermal origin, account for 0.5 to 0.6 % of all intracranial tumors. They most frequently appear during the first 2 years of life. A case manifesting intracranial hemorrhage associated with choroid plexus papilloma in an adult is described, with a review of the literature. The importance of adequate radiological investigation is emphasized. (author)

Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

International Nuclear Information System (INIS)

Ahmed, Kamran A.; Fulp, William J.; Berglund, Anders E.; Hoffe, Sarah E.; Dilling, Thomas J.; Eschrich, Steven A.; Shridhar, Ravi; Torres-Roca, Javier F.

2015-01-01

Purpose: We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases. Methods and Materials: Patients were identified from our institutional review board–approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiation therapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026). Conclusions: Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a larger

Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

Energy Technology Data Exchange (ETDEWEB)

Ahmed, Kamran A. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Fulp, William J.; Berglund, Anders E. [Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Hoffe, Sarah E.; Dilling, Thomas J. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Eschrich, Steven A. [Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Shridhar, Ravi [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Torres-Roca, Javier F., E-mail: javier.torresroca@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States)

2015-07-15

Purpose: We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases. Methods and Materials: Patients were identified from our institutional review board–approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiation therapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026). Conclusions: Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a larger

Tumor sterilization dose and radiation induced change of the brain tissue in radiotherapy of brain tumors

International Nuclear Information System (INIS)

Yoshii, Yoshihiko; Maki, Yutaka; Takano, Shingo

1987-01-01

Ninety-seven patients with brain tumors (38 gliomas, 26 brain metastases, 18 sellar tumors, 15 others) were treated by cobalt gamma ray or proton radiotherapy. In this study, normal brain injury due to radiation was analysed in terms of time-dose-fractionation (TDF), nominal standard dose (NSD) by the Ellis formula and NeuNSD by a modification in which the N exponent was -0.44 and the T exponent was -0.06. Their calculated doses were analysed in relationship to the normal brain radiation induced change (RIC) and the tumor sterilization dose. All brain tumors with an exception of many patients with brain metastases were received a surgical extirpation subtotally or partially prior to radiotherapy. And all patients with glioma and brain metastasis received also immuno-chemotherapy in the usual manner during radiotherapy. The calculated dose expressed by NeuNSD and TDF showed a significant relationship between a therapeutic dose and a postradiation time in terms of the appearance of RIC. It was suggested that RIC was caused by a dose over 800 in NeuNSD and a dose over 70 in TDF. Furthermore, it was suggested that an aged patient and a patient who had the vulnerable brain tissue to radiation exposure in the irradiated field had the high risk of RIC. On the other hand, our results suggested that the tumor sterilization dose should be over 1,536 NeuNSD and the irradiated method should be further considered in addition to the radiobiological concepts for various brain tumors. (author)

Suggestions on technical guide of implantation of radioactive seeds

International Nuclear Information System (INIS)

Wang Zhongmin; Huang Gang; Lv Zhongwei; Liu Jianjun; Chen Kemin; Chen Yongde

2009-01-01

Implantation of radioactive seeds is an effective therapeutic option for the treatment of malignant tumors. With the development of imaging technique and the use of treatment planning system (TPS) it has been more and more employed in clinical settings. The technique has been widely practiced in various malignant tumors, such as prostate cancer, lung caner, pancreatic cancer, hepatocarcinoma, etc. In order to standardize the clinical application of this technology, the authors propose some suggestions concerning the management of radioactive seeds, the indications and contraindications as well as the method of operation as a technical guidance. (authors)

Suggestions on technical guide of implantation of radioactive seeds

Energy Technology Data Exchange (ETDEWEB)

Zhongmin, Wang; Gang, Huang; Zhongwei, Lv; Jianjun, Liu [Department of Radiology, Luwan Branch of Ruijin Hospital, School of Medicine, Shanghai Jiaotong Univ., Shanghai (China); Kemin, Chen; Yongde, Chen

2009-09-15

Implantation of radioactive seeds is an effective therapeutic option for the treatment of malignant tumors. With the development of imaging technique and the use of treatment planning system (TPS) it has been more and more employed in clinical settings. The technique has been widely practiced in various malignant tumors, such as prostate cancer, lung caner, pancreatic cancer, hepatocarcinoma, etc. In order to standardize the clinical application of this technology, the authors propose some suggestions concerning the management of radioactive seeds, the indications and contraindications as well as the method of operation as a technical guidance. (authors)

Multiple bone metastasis of medulloblastoma; a case report

International Nuclear Information System (INIS)

Oh, Jae Cheon; Lee, Seoung Ro; Kim, Yong Soo; Park, Dong Woo; Joo, Kyung Bin; Hahm, Chang Kok

1996-01-01

Medulloblastoma is one of the most undifferentiated primitive neuroectodermal tumors and represents about 30% of all posterior fossa tumors in children. Disseminated medulloblastoma, mainly involving cerebral surfaces, ventricles and the subarachnoid space can, in 50% of patients, be identified on intial imaging studies. One third of these lesions metastasize to an extracranial sity, primarily to bone. Osseous metastases, which occur mainly after craniectomy are typically lytic, but osteoblastic lesions also may occur. We experienced the case of a 14 year-old female patient with multiple bone metastases of medulloblastoma after craniectomy. Bone metastatic lesions were present in the right femur and thoracic spine and were osteoblastic or osteolytic

Tumor-associated antigens identified by mRNA expression profiling as tumor rejection epitopes

DEFF Research Database (Denmark)

Andersen, Marie; Ruhwald, Morten; Thorn, Mette

2003-01-01

, suggesting that SM7 thymoma cells are recognized by the adaptive immune system of the host. However, prophylactic vaccination with RAD23-31 and RAD24-31 peptides combined with anti-CTLA4 Ab treatment and did not improve tumor resistance. Our data would indicate that vaccination with immunogenic peptides......Thirteen H-2b-binding peptides derived from six potentially overexpressed proteins in p53-/- thymoma (SM7) cells were studied for immunogenecity and vaccine-induced prevention of tumor growth in mice inoculated with SM7 tumor cells. Six of the peptides generated specific CTL responses after...... immunization, but only two of these peptides (RAD23-31 and RAD24-31) were capable of generating a weak vaccination-induced protection against adoptive tumor growth. SM7 inoculated mice treated with a blocking antibody against the inhibitory T cell signal transducing molecule CTLA4 appeared to delay tumor take...

Pedunculated Pulmonary Artery Sarcoma Suggested by Transthoracic Echocardiography.

Science.gov (United States)

Wang, Xiaobing; Ren, Weidong; Yang, Jun

2016-04-01

Pulmonary artery sarcoma (PAS) is an extremely rare malignancy. It is usually found after it grows large enough to occupy almost the entire lumen of the pulmonary artery and causes serious clinical symptoms. Thus, it is usually difficult to distinguish PAS from pulmonary thromboembolism based on imaging examinations. Few case reports had shown the attachment of PAS to pulmonary artery, a key characteristic for diagnosis, and differential diagnosis of PAS. In this case, we found a PAS, which did not cause local obstruction and some tumor emboli, which obstructed the branches of the pulmonary arteries and caused pulmonary hypertension and clinical symptoms. Transthoracic echocardiography (TTE) revealed a part of the tumor attached to the intima of the main pulmonary artery with a peduncle and had obvious mobility, which was suggestive of PAS and differentiated it from the pulmonary thromboembolism. To our knowledge, this is the first case report of a pedunculated PAS suggested by TTE. Combined with pulmonary artery computed tomography angiography, the diagnosis of PAS is strongly suggested before the operation. This case indicates that TTE could reveal the attachment and mobility of PAS in the main pulmonary and may provide useful information for the diagnosis and differential diagnosis of PAS, especially a pedunculated PAS. © 2015, Wiley Periodicals, Inc.

Awake Craniotomy for Tumor Resection: Further Optimizing Therapy of Brain Tumors.

Science.gov (United States)

Mehdorn, H Maximilian; Schwartz, Felix; Becker, Juliane

2017-01-01

In recent years more and more data have emerged linking the most radical resection to prolonged survival in patients harboring brain tumors. Since total tumor resection could increase postoperative morbidity, many methods have been suggested to reduce the risk of postoperative neurological deficits: awake craniotomy with the possibility of continuous patient-surgeon communication is one of the possibilities of finding out how radical a tumor resection can possibly be without causing permanent harm to the patient.In 1994 we started to perform awake craniotomy for glioma resection. In 2005 the use of intraoperative high-field magnetic resonance imaging (MRI) was included in the standard tumor therapy protocol. Here we review our experience in performing awake surgery for gliomas, gained in 219 patients.Patient selection by the operating surgeon and a neuropsychologist is of primary importance: the patient should feel as if they are part of the surgical team fighting against the tumor. The patient will undergo extensive neuropsychological testing, functional MRI, and fiber tractography in order to define the relationship between the tumor and the functionally relevant brain areas. Attention needs to be given at which particular time during surgery the intraoperative MRI is performed. Results from part of our series (without and with ioMRI scan) are presented.

Novel PMS2 Pseudogenes Can Conceal Recessive Mutations Causing a Distinctive Childhood Cancer Syndrome

OpenAIRE

De Vos, Michel; Hayward, Bruce E.; Picton, Susan; Sheridan, Eamonn; Bonthron, David T.

2004-01-01

We investigated a family with an autosomal recessive syndrome of café-au-lait patches and childhood malignancy, notably supratentorial primitive neuroectodermal tumor. There was no cancer predisposition in heterozygotes; nor was there bowel cancer in any individual. However, autozygosity mapping indicated linkage to a region of 7p22 surrounding the PMS2 mismatch-repair gene. Sequencing of genomic PCR products initially failed to identify a PMS2 mutation. Genome searches then revealed a previo...

Metastatic Ewing's sarcoma to the right ventricle

OpenAIRE

Datrice, Nicole; Milliken, Jeffrey; Kirsh, M.; Abolhoda, Amir; Saremi, Farhood; Sender, Leonard

2011-01-01

Ewing's sarcoma is a round cell neoplasm derived from neural crest cells that is part of the primitive neuroectodermal tumor (PNET) family. It is a rare, aggressive malignancy that affects young people, most commonly in the second decade of life. The treatment of localized disease has improved greatly over the past four decades, but the prognosis for metastatic disease remains poor. Cardiac metastases of Ewing's sarcoma are exceedingly rare, with only a few reported cases. This...

Role of tumor necrosis factor in flavone acetic acid-induced tumor vasculature shutdown

International Nuclear Information System (INIS)

Mahadevan, V.; Malik, S.T.; Meager, A.; Fiers, W.; Lewis, G.P.; Hart, I.R.

1990-01-01

Flavone acetic acid (FAA), a novel investigational antitumor agent, has been shown to cause early vascular shutdown in several experimental murine tumors, and this phenomenon is believed to be crucial to FAA's antitumor effects. However, the basis of this FAA-induced tumor vascular shutdown is unknown. In this study a radioactive tracer-clearance technique has been used as an objective indication of tumor blood flow to show that i.p. administered FAA induces a progressive and sustained reduction in blood flow in a colon 26 tumor growing s.c. in syngeneic mice. As early as 1 h after administration, there was a significant increase in the t1/2 clearance value for intratumorally injected 133Xe, reaching a peak at 3 h (117.3 +/- 36.4 versus 7.8 +/- 0.85 min for controls). Significant inhibition of blood flow was still apparent 48 h after a single injection of drug. This FAA-induced vascular shutdown was virtually abolished in tumor-bearing mice pretreated with an antiserum against tumor necrosis factor, while no such effect was observed in controls pretreated with nonimmune serum (t1/2 of 10.8 +/- 1.2 versus 65.6 +/- 8.0 min for controls). Furthermore, in vitro FAA was seen to induce tumor necrosis factor secretion from murine peritoneal cells and splenocytes. These studies suggest that FAA-induced tumor vascular shutdown in the colon 26 tumor is mediated by tumor necrosis factor

Response of the tumor and organs of the tumor-bearing animal to the action of an ionizing radiation

International Nuclear Information System (INIS)

Burlakova, E.B.; Gaintseva, V.D.; Pal'mina, N.P.; Sezina, N.P.

1977-01-01

Changes in the antioxigenic activity (AOA) of the liver of the tumor-bearing animals and the tumor have been studied after a single whole-body exposure of animals to a dose of 600 R. AOA of the liver of animals having hepatoma 22-a and Ehrlich ascites tumor (EAT) was found to decrease immediately after irradiation while that of the tumor itself can both increase (hepatoma 22-a) and decrease (EAT). Proceeding from the assumption that AOA is connected with tissue radiosensitivity it is suggested that the observed variations in the response of tumor cells and normal tissue to the action of ionizing radiation should be taken into account when developing the schemes of radiation effect on the tumor

CT and MRI of germ-cell tumors with metastasis or multi-located tumors

International Nuclear Information System (INIS)

Miyagami, Mitsusuke; Tazoe, Makoto; Tsubokawa, Takashi

1989-01-01

Twenty-seven cases of germ-cell tumors were examined with a CT scan in our clinic. In the 11 cases of metastasis or multi-localized tumors, the CT findings were studied in connection with the MRI findings. There were 6 cases of germ-cell tumors which had broad infiltrating tumors with multiple lesions on first admission. Their tumor sites were different from that in cases of malignant glioma, being frequently localized in the pineal and/or the suprasellar region, on the wall of the third and/or lateral ventricle, and in the region of the basal ganglia. Five of the cases of germ-cell tumors had metastasis with various patterns connected to a remote area - that is, to spinal cords, to the ventricular wall and basal cistern of the brain stem by CSF dissemination, to a lung by hematogeneous metastasis, and to the peritoneal wall or organs by a V-P shunt. The CT findings of germ-cell tumors were correlated mainly with the results of the histological diagnosis; they were found not to differ with the tumor site. The germinoma in the suprasellar region had less calcification than in the pineal region. Cysts, calcification, and an enlargement of the lateral ventricle on the tumor side were frequently seen in the germinoma of the basal ganglia. On the MRI of 5 cases of germinoma, the T 1 -weighted image revealed a slightly low or iso signal intensity, while the T 2 -weighted image showed a high signal intensity. In the case of multiple tumor lesions, some cases demonstrated different CT findings and radiosensitivities for each tumor. The possibility of a multicentric origin for the tumors is thus suggested in some cases of germ-cell tumors. (author)

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

Science.gov (United States)

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

2017-09-01

3 cycles (HR for PFS, 0.46; 95% CI, 0.23-0.93; P = .03) and those without a bone sarcoma (ie, neither primitive neuroectodermal tumor nor osteosarcoma) (HR for PFS, 0.39; 95% CI, 0.18-0.81; P = .01) appeared to benefit from metronomic chemotherapy. Metronomic chemotherapy does not improve 6-month PFS, compared with placebo, among pediatric patients with extracranial progressive solid malignant tumors . However, patients without bone sarcoma and those able to tolerate therapy for more than 3 cycles (9 weeks) benefit. clinicaltrials.gov Identifier: NCT01858571.

Management of Renal Tumors by Image-Guided Radiofrequency Ablation: Experience in 105 Tumors

International Nuclear Information System (INIS)

Breen, David J.; Rutherford, Elizabeth E.; Stedman, Brian; Roy-Choudhury, Shuvro H.; Cast, James E. I.; Hayes, Matthew C.; Smart, Christopher J.

2007-01-01

Aims. In this article we present our experience with radiofrequency ablation (RFA) in the treatment of 105 renal tumors. Materials and Methods. RFA was performed on 105 renal tumors in 97 patients, with a mean tumor size of 32 mm (11-68 mm). The mean patient age was 71.7 years (range, 36-89 years). The ablations were carried out under ultrasound (n = 43) or CT (n = 62) guidance. Imaging follow-up was by contrast-enhanced CT within 10 days and then at 6-monthly intervals. Multivariate analysis was performed to determine variables associated with procedural outcome. Results. Eighty-three tumors were completely treated at a single sitting (79%). Twelve of the remaining tumors were successfully re-treated and a clinical decision was made not to re-treat seven patients. A patient with a small residual crescent of tumor is under follow-up and may require further treatment. In another patient, re-treatment was abandoned due to complicating pneumothorax and difficult access. One patient is awaiting further re-treatment. The overall technical success rate was 90.5%. Multivariate analysis revealed tumor size to be the only significant variable affecting procedural outcome. (p = 0.007, Pearson χ 2 ) Five patients had complications. There have been no local recurrences. Conclusion. Our experience to date suggests that RFA is a safe and effective, minimally invasive treatment for small renal tumors

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 Chiari malformation, 5 trauma, 1 meningitis, 1 hydrocephalus, 1 idiopathic) and 6 of which were associated with intramedullary tumor (3 ependymoma, 2 astrocytoma, 1 hemangioendothelioma). The syrinx showed low signal in all 26 cases on T1 weighted images (SE 600/40). All 6 cases with syrinx associated with intramedullary tumor showed high intensity on T2 weighted images (SE 2000/120). On the other hand, the syrinx of 19 of 20 cases with no tumor condition showed reduced intensity on T2 weighted images. Only one post-traumatic small syrinx showed high signal. This was quite different between the cases with spinal cord tumor and without tumor. Therefore, when the syrinx cavity shows high signal on T2 weighted images, an intramedullary tumor is strongly suggested.

Ketoconazole attenuates radiation-induction of tumor necrosis factor

Energy Technology Data Exchange (ETDEWEB)

Hallahan, D.E.; Virudachalam, S.; Kufe, D.W.; Weichselbaum, R.R. [Dana Farber Cancer Institute, Boston, MA (United States)

1994-07-01

Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation-induced arachidonic acid production, protein kinase C activation, and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, the authors analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cycloxygenase (indomethacine) were added to cell culture 1 h prior to irradiation. Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2 inhibitors (quinicrine, bromphenylbromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. The authors propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. 25 refs., 2 figs.

Effects of hyperthermia, radiotherapy and thermoradiotherapy on tumor microvasculature

International Nuclear Information System (INIS)

Fujiwara, Kouji

1987-01-01

The therapeutic effects of hyperthermia (immersion of tumor-bearing leg in a water bath at 46 deg C for 60 min), radiotherapy (500 rad or 1000 rad) and thermoradiotherapy on VX-2 tumors of the rabbits were studied morphologically. Especially, vascular morphological changes and vascular permeability to ferritin after treatment were investigated by electron microscopy. As assessed by decrease in tumor volume, local hyperthermia potentiated the destructive effect of radiotherapy. The light microscopic pictures invariably suggested prolonged necrotic tendency of tumor cells following thermoradiotherapy. Electron microscopically, 1 day and 3 days after thermoradiotherapy, small blood vessels in the tumors showed swelling and protrusion of endothelial cells in the lumen. Similar morphological changes were obtained only at 3 days after radiotherapy. When vascular permeability to ferritin was examined by electron microscopy, an increase in tumor vascular permeability was occured at 1 day after hyperthermia or thermoradiotherapy, while at 3 days after radiotherapy. These results suggest that the early reaction of tumor microvasculature may be a contributing factor to delayed cell death in tumors after hyperthermia or thermoradiotherapy. (author)

Demonstration of tumor-associated antigens in dogs

International Nuclear Information System (INIS)

Warren, R.P.; Tsoi, M.S.; Henderson, B.H.; Weiden, P.L.; Storb, R.

1975-01-01

Procedures for the 51 Cr release assay using labeled L cells or lymphocytes and the indirect leukocyte migration test are described. These assays appear capable of detecting cellular immunity against tumor associated antigens in dogs. In 8 of 14 instances, lymphocyte-mediated cytotoxicity to autochthonous L cells was found as measured by 51 Cr release, and lymphocytes from 12 of 24 dogs produced the migration inhibition factor (MIF) when cultured with autochthonous tumor cells. Chromium-51 release occurred with 4 h of exposure of effector cells to target cells, suggesting that the immunity detected in the tumor dogs against their tumors is also present in vivo. With the leukocyte migration test, however, consistent MIF production was achieved only after 3 to 6 days in culture, suggesting that in vitro sensitization may result in increased MIF production

Risk factors for oligodendroglial tumors: a pooled international study

DEFF Research Database (Denmark)

McCarthy, Bridget J; Rankin, Kristin M; Aldape, Ken

2011-01-01

Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate p...

Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy.

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Han, Kai; Zhang, Jin; Zhang, Weiyun; Wang, Shibo; Xu, Luming; Zhang, Chi; Zhang, Xianzheng; Han, Heyou

2017-03-28

Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rod-like nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing tumor microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery.

Disseminated Intracranial Ewing’s Sarcoma in an Adult:A Rare and Difficult Diagnosis

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Emil Lou

2012-06-01

Full Text Available The Ewing sarcoma family of tumors comprises a rare class of cancers of mesenchymal origin. Cases of Ewing’s sarcoma in the central nervous system – specifically, intracranial Ewing’s – are extremely rare. Almost all reported cases have occurred in children. However, this rare presentation can also occur in the adult population. It is important to distinguish these tumors from primitive neuroectodermal tumors at the time of diagnosis. Testing for EWSR1(22q12 gene rearrangement using fluorescence in situ hybridization is a useful tool for making the distinction between these 2 similar but distinct entities. We present here the case of a middle-aged male patient with intracranial Ewing’s sarcoma, and discuss diagnostic challenges and potential new treatment approaches for this rare disease.

Expression of the p16{sup INK4a} tumor suppressor gene in rodent lung tumors

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Swafford, D.S.; Tesfaigzi, J.; Belinsky, S.A.

1995-12-01

Aberrations on the short arm of chromosome 9 are among the earliest genetic changes in human cancer. p16{sup INK4a} is a candidate tumor suppressor gene that lies within human 9p21, a chromosome region associated with frequent loss of heterozygosity in human lung tumors. The p16{sup INK4a} protein functions as an inhibitor of cyclin D{sub 1}-dependent kinases that phosphorylate the retinoblastoma (Rb) tumor suppressor gene product enabling cell-cycle progression. Thus, overexpression of cyclin D{sub 1}, mutation of cyclin-dependent kinase genes, or loss of p16{sup INK4a} function, can all result in functional inactivation of Rb. Inactivation of Rb by mutation or deletion can result in an increase in p16{sup INK4a} transcription, suggesting that an increased p16{sup INK4a} expression in a tumor cell signals dysfunction of the pathway. The p16{sup (INK4a)} gene, unlike some tumor suppressor genes, is rarely inactivated by mutation. Instead, the expression of this gene is suppressed in some human cancers by hypermethylation of the CpG island within the first exon or by homozygous deletion: 686. Chromosome losses have been observed at 9p21 syntenic loci in tumors of the mouse and rat, two species often used as animal models for pulmonary carcinogenesis. Expression of p16{sup INK4a} is lost in some mouse tumor cell lines, often due to homozygous deletion. These observations indicate that p16{sup INK4a} dysfunction may play a role in the development of neoplasia in rodents as well as humans. The purpose of the current investigation was to define the extent to which p16{sup INK4a} dysfunction contributes to the development of rodent lung tumors and to determine the mechanism of inactivation of the gene. There is no evidence to suggest a loss of function of the p16{sup INK4a} tumor suppressor gene in these primary murine lung tumors by mutation, deletion, or methylation.

Ductuloinsular tumors of the pancreas - Endocrine tumors with entrapped nonneoplastic ductules

NARCIS (Netherlands)

van Eeden, Susanne; de Leng, Wendy W. J.; Offerhaus, G. Johan A.; Morsink, Folkert H.; Weterman, Marian A. J.; de Krijger, Ronald R.; Klöppel, Günter; Klimstra, David S.

2004-01-01

Rare pancreatic neoplasms have been reported that show both endocrine and exocrine differentiation in the neoplastic components. In addition, pancreatic endocrine tumors may contain small, cytologically bland ductules intimately admixed with the endocrine component. It was recently suggested that

Frontal recurrence of medulloblastoma five years after excision and craniospinal irradiation

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Roka Y

2009-07-01

Full Text Available Medulloblastomas were originally classified under gliomas of the cerebellum until Bailey and Cushing in 1925 named these tumors as medulloblastoma. At present these tumors are classified under primitive neuroectodermal tumor. Surgical excision followed by craniospinal irradiation is the treatment of choice. A 13-year-old-girl operated for posterior fossa medulloblastoma 5 years ago presented with history of headache and vomiting on and off for 4 days in late August 2008. The MRI showed left frontal tumor which on excision was reported as medulloblastoma. Even after optimal treatment reports of recurrence abound in literature. The most common location is in the posterior fossa, followed by spinal, supratentorial, and uncommonly, systemic metastases. We conclude that medulloblastomas are highly aggressive tumor with high local recurrences if the initial excision is incomplete and that recurrence in the supratentorial area although uncommon is still a possibility. This mandates regular follow up of these children till adulthood to catch early recurrences and metastatic disease.

Adult medulloblastoma with myogenic differentiation

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Xia-ling ZHANG

2015-09-01

labeling index was about 10% . Pathological diagnosis was medulloblastoma with myogenic differentiation (WHO Ⅳ. The patient was not given further treatment including chemotherapy or radiotherapy after surgery. Nine-month follow-up showed no tumor recurrence.  Conclusions Medulloblastoma is a malignant, invasive embryonal tumor commonly occuring in the cerebellum of children. Medulloblastoma with myogenic differentiation occurs very rarely in adult, which is characterized by containing primitive neuroectodermal and rhabdomyoblastic elements. The diagnosis should be differentiated from central nervous system primitive neuroectodermal tumor (PNET, atypical teratoid/rhabdoid tumor (AT/RT and rhabdomyosarcoma. DOI: 10.3969/j.issn.1672-6731.2015.09.009

Doranidazole (PR-350), a hypoxic cell radiosensitizer, radiosensitizes human lung tumors (RERF-LC- AI) and causes changes in tumor oxygenation

International Nuclear Information System (INIS)

Kubota, N.; Griffin, R.J.; Williams, B.W.; Song, C.W.; Yahiro, T.

2003-01-01

Full text: We previously have reported the radiosensitizing capability of Doranidazole (PR-350) on SCCVII cells and tumors (Puerto Rico, 2001). In the present study, we have investigated the efficacy of PR-350 as a hypoxic cell radiosensitizer using human lung cancer cells (RERF-LC-AI) in vitro and also RERF-LC-AI tumors grown s.c. in Balb/c nude mice. Using the micronucleus assay method, we determined the effect of PR-350 on the response of RERF-LC-AI cells to radiation under hypoxic conditions and enhancement ratios (ER) of 1.45∼2.26 were obtained. The in vivo radiosensitizing effect was studied by irradiating RERF-LC-AI tumors with 15 Gy at 20 min. after i.v. injection of PR-350 (200mg/kg) and measuring the tumor growth delay. Significant growth delay occurred after i.v. injection of PR-350 before irradiation compared to radiation alone. We measured tumor pO 2 at 3, 7 and 14 days after treatment using an Eppendorf pO 2 histograph. The frequency of pO 2 values 2 in tumors treated with radiation plus PR-350 were higher than that in tumors treated with radiation plus saline. These data suggest that the O 2 consumption in tumors treated with radiation plus PR-350 was less than that in tumors treated with radiation plus saline due to greater drug and radiation-induced cell death. This hypothesis is supported by the fact that the tumor size in the combined treatment group was smaller than in radiation alone. These results suggest that PR-350 may improve the response of tumors to radiotherapy not only by increasing the radiosensitivity of hypoxic cells but also by improving tumor oxygenation over many days during fractionated radiotherapy

Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

International Nuclear Information System (INIS)

Schmalz, Philip G.R.; Shen, Michael J.; Park, John K.

2011-01-01

Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed

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

Induction of mouse mammary tumor virus RNA in mammary tumors of BALB/c mice treated with urethane, x-irradiation, and hormones

International Nuclear Information System (INIS)

Michalides, R.; van Deemter, L.; Nusse, R.; Hageman, P.

1979-01-01

The involvement of mouse mammary tumor virus (MTV) in the development of mammary tumors of nonviral etiology in BALB/c mice was studied by measuring the levels of MTV RNA, MTV DNA, and MTV proteins in spontaneously arising and hormally, chemically, and/or physically induced mammary tumors of BALB/c females. The following results were obtained: (1) spontaneous mammary tumors contained very low levels of MTV RNA; 4 x 10 -6 % of the cytoplasmic RNA was MTV RNA. No MTV proteins could be demonstrated by using sensitive radioimmunoassays for MTV proteins p27 and gp52. (2) Mammary tumors induced by treatments with urethane or x-irradiation alone contained higher levels of MTV RNA; these tumors contained 3- and 19-fold more MTV RNA, respectively, compared with spontaneous mammary tumors. (3) Mammary tumors induced by combined treatment with urethane and x-irradiation expressed high levels of MTV RNA in the mammary tumors; a 1,724-fold increase in MTV RNA content compared with spontaneous mammary tumors was observed. However, very low levels of MTV proteins gp52 and p27 were detected, suggesting some kind of impairment at the translation of MTV RNA. MTV RNA was also induced by this treatment in mammary glands and spleens, but not in the livers of tumor-bearing animals. (4) BALB/c females continuously exposed to prolactin contained high levels of MTV RNA and MTV proteins in stimulated mammary glands and in the hormonally induced mammary tumors. These findings suggest that MTV is not responsible for the maintenance and probably also not for the development of all murine mammary cancers

Targeting tumor-associated macrophages by anti-tumor Chinese materia medica.

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Pu, Wei-Ling; Sun, Li-Kang; Gao, Xiu-Mei; Rüegg, Curzio; Cuendet, Muriel; Hottiger, Micheal O; Zhou, Kun; Miao, Lin; Zhang, Yun-Sha; Gebauer, Margaret

2017-10-01

Tumor-associated macrophages (TAMs) play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica (CMM) is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy.

Conjunctival Melanocytic Tumors-New Developments

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Hülya Gökmen Soysal

2014-09-01

Full Text Available Melanocytic lesions of the conjunctiva represent a wide spectrum of tumors that include benign, premalignant, and malignant tumors. There are many ongoing arguments about the definition, classification, and therapeutic options of the conjunctival melanocytic tumors with many different suggestions. Conjunctival nevi are the most common melanocytic tumors and their risk of malignant transformation is less than1%. Primary acquired melanosis (PAM histopathologically includes various types of lesions from increased melanin pigmentation without melanocyte proliferation to melanoma in situ and is accepted as a clinical definition, so that a new classification is recommended which is based on more objective criteria than before. Although conjunctival melanoma is seen rarely, it is associated with a high mortality rate. Management of these tumors mainly involves surgery and adjuvant topical chemotherapy, cryotherapy, and radiation therapy that help improving the survival, however, new options are being investigated related to genetic and molecular researches. (Turk J Ophthalmol 2014; 44: Supplement 15-21

67Ga-citrate incorporation and DNA synthesis in tumors

International Nuclear Information System (INIS)

Hammersley, P.A.G.; Taylor, D.M.

1975-01-01

The results obtained in these studies suggest that in the tumors studied there is some form of relationship between 67 Ga uptake and the rate of DNA synthesis. However, the observations in the HP melanoma, in which small tumors showed a negative correlation between 67 Ga uptake and rate of DNA synthesis and larger tumors showed a positive correlation, coupled with the virtually constant uptake of 67 Ga over a wide range of rates of DNA synthesis in the drug- and radiation-treated tumors, suggest that the uptake of the radionuclide is not simply related to the rate of DNA synthesis per se. Studies in embryonic mouse tissues suggested that 67 Ga uptake was not related to the rate of DNA synthesis and regenerating liver does not show a greater 67 Ga uptake than normal liver. Phytohemagglutinin-treated human lymphocytes show increased 67 Ga uptake compared to unstimulated lymphocytes, and it has been suggested that this is related to the stimulus to divide rather than to events occurring in a specific phase of the cell cycle. This suggests that proliferating cells may exhibit membrane changes which either result in increased transport of 67 Ga into the cell or permit a greater degree of binding of the radionuclide to the cell membrane than can occur in resting cells. The membrane-binding hypothesis is supported by the observations on phytohemagglutinin-stimulated lymphocytes but not by observations of the subcellular distribution of 67 Ga in these tumors which confirm the suggestion that the radionuclide is concentrated in lysosomes. Thus it appears that although in tumor cells, at least, there is some correlation between 67 Ga uptake and the rate of DNA synthesis and hence by implication of cell proliferation, the nature of this link remains obscure, and more detailed studies are needed to increase our understanding of the relationship

Immunological tolerance and tumor rejection in embryo-aggregated chimeric mice – Lessons for tumor immunity

International Nuclear Information System (INIS)

Wagner, Alexander Y; Holle, Eric; Holle, Lori; Yu, Xianzhong; Schwamberger, Günter

2008-01-01

Rejection of transplanted tumors by the immune system is a rare event in syngeneic hosts, and is considered to be dependent on the local interaction of defensive immune reactions and tumor tolerance mechanisms. Here, we have enlisted the aid of a unique set of embryo-aggregated lineage chimeric mice derived from C57/BL6 and FVB donors to study the interplay between local and systemic tumor immunity and tolerance in rejection of mouse B16 melanoma cells, syngeneic to the C57/BL6 donor strain. Two variants of embryo-aggregated chimeric mice with either variable or no contribution of C57-derived cells to their skin were generated by the fusion of different ratios of morula stage blastomers. Chimeric mice were analyzed for s.c. growth of B16 tumors in comparison to their respective donor strains as well as normal F1 hybrids, and the relative frequencies of cellular components of the immune system by FACS analysis of peripheral blood or lymph node cells. B16 tumors grew significantly faster in mice with full chimerism in their skin as compared to syngeneic C57 or semi-syngeneic C57 × FVB F1 hosts. In contrast, s.c. tumor growth was either absent or significantly reduced in chimeric mice lacking C57-derived cells in their skin, but tolerant to C57 tissue in other organs. Comparison of the relative frequencies of various immune cells in the periphery via FACS-analysis did not reveal any significant differences between the two types of chimeric mice with respect to their donor strains. Our data suggest a complex interplay between mechanisms of local peripheral tolerance and innate antitumor mechanisms possibly involving NK cell allorecognition as a basis for the differential growth or rejection of B16 tumors in these unique chimeric mice, which we suggest to constitute a valuable new model system for the study of immune-mediated tumor rejection

Immunological tolerance and tumor rejection in embryo-aggregated chimeric mice – Lessons for tumor immunity

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Yu Xianzhong

2008-12-01

Full Text Available Abstract Background Rejection of transplanted tumors by the immune system is a rare event in syngeneic hosts, and is considered to be dependent on the local interaction of defensive immune reactions and tumor tolerance mechanisms. Here, we have enlisted the aid of a unique set of embryo-aggregated lineage chimeric mice derived from C57/BL6 and FVB donors to study the interplay between local and systemic tumor immunity and tolerance in rejection of mouse B16 melanoma cells, syngeneic to the C57/BL6 donor strain. Methods Two variants of embryo-aggregated chimeric mice with either variable or no contribution of C57-derived cells to their skin were generated by the fusion of different ratios of morula stage blastomers. Chimeric mice were analyzed for s.c. growth of B16 tumors in comparison to their respective donor strains as well as normal F1 hybrids, and the relative frequencies of cellular components of the immune system by FACS analysis of peripheral blood or lymph node cells. Results B16 tumors grew significantly faster in mice with full chimerism in their skin as compared to syngeneic C57 or semi-syngeneic C57 × FVB F1 hosts. In contrast, s.c. tumor growth was either absent or significantly reduced in chimeric mice lacking C57-derived cells in their skin, but tolerant to C57 tissue in other organs. Comparison of the relative frequencies of various immune cells in the periphery via FACS-analysis did not reveal any significant differences between the two types of chimeric mice with respect to their donor strains. Conclusion Our data suggest a complex interplay between mechanisms of local peripheral tolerance and innate antitumor mechanisms possibly involving NK cell allorecognition as a basis for the differential growth or rejection of B16 tumors in these unique chimeric mice, which we suggest to constitute a valuable new model system for the study of immune-mediated tumor rejection.

Targeted Imaging of Tumor-Associated Macrophages by Cyanine 7-Labeled Mannose in Xenograft Tumors

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Chong Jiang MD

2017-01-01

Full Text Available Mannose receptor is considered as a hallmark of M2-oriented tumor-associated macrophages (TAMs, but its utility in TAMs was rarely reported. Therefore, deoxymannose (DM, a high-affinity ligand of mannose receptor, was labeled with near-infrared dye cyanine 7 (Cy7, and its feasibility of targeted imaging on TAMs was evaluated in vitro and in vivo. The Cy7-DM was synthesized, and its binding affinity with induced TAMs in vitro, whole-body imaging in xenograft tumor mouse model in vivo, and the cellular localization in dissected tissues were evaluated. We demonstrated a high uptake of Cy7-DM by induced M2 macrophages and TAMs in tumor tissues. In vivo near-infrared live imaging visualized abundant TAMs in tumor lesions instead of inflammatory sites by Cy7-DM imaging, and the quantity of Cy7-DM signals in tumors was significantly higher than that shown in inflammatory sites from 1 to 8 hours of imaging. Our results suggest that mannose could rapidly and specifically target TAMs and is a promising candidate for targeted diagnosis of tumor with rich TAMs.

Combined cytotoxic effects of tumor necrosis factor-alpha with various cytotoxic agents in tumor cell lines that are drug resistant due to mutated p53

NARCIS (Netherlands)

Sleijfer, S; Le, T. K. P.; de Jong, S.; Timmer-Bosscha, H; Withoff, S; Mulder, NH

Several studies suggest that tumor necrosis factor-alpha (TNF) is able to overcome drug resistance in tumors. Whether TNF is able to do so in tumor cell lines that are drug resistant due to a mutation in the tumor suppressor gene p53 is unclear. Therefore, we studied the in vitro cytotoxic effects

Local and systemic tumor immune dynamics

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Enderling, Heiko

Tumor-associated antigens, stress proteins, and danger-associated molecular patterns are endogenous immune adjuvants that can both initiate and continually stimulate an immune response against a tumor. In retaliation, tumors can hijack intrinsic immune regulatory programs that are intended to prevent autoimmune disease, thereby facilitating continued growth despite the activated antitumor immune response. In metastatic disease, this ongoing tumor-immune battle occurs at each site. Adding an additional layer of complexity, T cells activated at one tumor site can cycle through the blood circulation system and extravasate in a different anatomic location to surveil a distant metastasis. We propose a mathematical modeling framework that incorporates the trafficking of activated T cells between metastatic sites. We extend an ordinary differential equation model of tumor-immune system interactions to multiple metastatic sites. Immune cells are activated in response to tumor burden and tumor cell death, and are recruited from tumor sites elsewhere in the body. A model of T cell trafficking throughout the circulatory system can inform the tumor-immune interaction model about the systemic distribution and arrival of T cells at specific tumor sites. Model simulations suggest that metastases not only contribute to immune surveillance, but also that this contribution varies between metastatic sites. Such information may ultimately help harness the synergy of focal therapy with the immune system to control metastatic disease.

Famine versus feast: understanding the metabolism of tumors in vivo.

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Mayers, Jared R; Vander Heiden, Matthew G

2015-03-01

To fuel unregulated proliferation, cancer cells alter metabolism to support macromolecule biosynthesis. Cell culture studies have revealed how different oncogenic mutations and nutrients impact metabolism. Glucose and glutamine are the primary fuels used in vitro; however, recent studies have suggested that utilization of other amino acids as well as lipids and protein can also be important to cancer cells. Early investigations of tumor metabolism are translating these findings to the biology of whole tumors and suggest that additional complexity exists beyond nutrient availability alone in vivo. Whole-body metabolism and tumor heterogeneity also influence the metabolism of tumor cells, and successful targeting of metabolism for cancer therapy will require an understanding of tumor metabolism in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tumor suppressors: enhancers or suppressors of regeneration?

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Pomerantz, Jason H.; Blau, Helen M.

2013-01-01

Tumor suppressors are so named because cancers occur in their absence, but these genes also have important functions in development, metabolism and tissue homeostasis. Here, we discuss known and potential functions of tumor suppressor genes during tissue regeneration, focusing on the evolutionarily conserved tumor suppressors pRb1, p53, Pten and Hippo. We propose that their activity is essential for tissue regeneration. This is in contrast to suggestions that tumor suppression is a trade-off for regenerative capacity. We also hypothesize that certain aspects of tumor suppressor pathways inhibit regenerative processes in mammals, and that transient targeted modification of these pathways could be fruitfully exploited to enhance processes that are important to regenerative medicine. PMID:23715544

Oat cell carcinoma of esophagus: a report of six British patients with a review of the literature

International Nuclear Information System (INIS)

Doherty, M.A.; McIntyre, M.; Arnott, S.J.

1984-01-01

This paper presents 6 British patients with a diagnosis of oat cell carcinoma of the esophagus. Sixty-six patients have previously been reported in the literature, the majority (30) being British. Approximately two-thirds of these tumors have been reported as pure oat cell carcinoma of the esophagus. Four other histological patterns have been described: oat cell carcinoma with squamous carcinoma in situ; oat cell carcinoma with squamous carcinoma; oat cell carcinoma with adenocarcinoma; and oat cell carcinoma with carcinoid differentiation. A preponderance of males has also been noted, although this series shows a 2:1 female:male ratio. The tumor arises most commonly in the mid or lower esophagus. The cell of origin of these tumors is considered to be the Kulchitsky or APUD cell of neuroectodermal derivation. They may show neurosecretory granules on electron microsopy. Polypeptides have been identified within the tumor cells. One previous report describes a patient with primary oat cell carcinoma of the esophagus and hypercalcemia. A patient with the syndrome of inappropriate anti-diuretic hormone secretion is described in this paper. Survival is poor following radiotherapy, with a median survival of 3 months in this series. On reviewing the records of the Radiation Oncology Unit in Edinburgh, no patient with oat cell carcinoma of the esophagus was reported before 1972. This suggests that awareness of this tumor is increasing and, although rare, its incidence is greater than previously reported

Costal chondrosarcoma requiring differential diagnosis from metastatic tumor.

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Matsuoka, Katsunari; Ueda, Mitsuhiro; Miyamoto, Yoshihiro

2017-02-01

Although chondrosarcoma is a common malignant bone tumor, cases arising in the rib are relatively rare. We experienced a case of chondrosarcoma arising in the right 10th rib during follow-up after lung cancer surgery. Although the finding of an osteolytic mass suggested a metastatic bone tumor, 18F-fluorodeoxyglucose positron-emission tomography demonstrated low fluorodeoxyglucose uptake, and a primary bone tumor was suspected. The bone tumor was resected and diagnosed as chondrosarcoma. Four years after resection, there has been no recurrence or metastasis. Positron-emission tomography was useful for differential diagnosis between a chondrosarcoma and a metastatic bone tumor.

Number and location of mouse mammary tumor virus proviral DNA in mouse DNA of normal tissue and of mammary tumors.

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Groner, B; Hynes, N E

1980-01-01

The Southern DNA filter transfer technique was used to characterize the genomic location of the mouse mammary tumor proviral DNA in different inbred strains of mice. Two of the strains (C3H and CBA) arose from a cross of a Bagg albino (BALB/c) mouse and a DBA mouse. The mouse mammary tumor virus-containing restriction enzyme DNA fragments of these strains had similar patterns, suggesting that the proviruses of these mice are in similar genomic locations. Conversely, the pattern arising from the DNA of the GR mouse, a strain genetically unrelated to the others, appeared different, suggesting that its mouse mammary tumor proviruses are located in different genomic sites. The structure of another gene, that coding for beta-globin, was also compared. The mice strains which we studied can be categorized into two classes, expressing either one or two beta-globin proteins. The macroenvironment of the beta-globin gene appeared similar among the mice strains belonging to one genetic class. Female mice of the C3H strain exogenously transmit mouse mammary tumor virus via the milk, and their offspring have a high incidence of mammary tumor occurrence. DNA isolated from individual mammary tumors taken from C3H mice or from BALB/c mice foster nursed on C3H mothers was analyzed by the DNA filter transfer technique. Additional mouse mammary tumor virus-containing fragments were found in the DNA isolated from each mammary tumor. These proviral sequences were integrated into different genomic sites in each tumor. Images PMID:6245257

Clinicopathological characteristics of duodenal epithelial neoplasms: Focus on tumors with a gastric mucin phenotype (pyloric gland-type tumors.

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Takehiro Mitsuishi

Full Text Available Epithelial tumors less commonly occur in the duodenum than in the stomach or large intestine. The clinicopathological characteristics of duodenal epithelial tumors remain a matter of debate. We therefore studied resected specimens to investigate the clinicopathological characteristics of duodenal epithelial tumors.Among duodenal epithelial tumors resected endoscopically or surgically in our hospital, we studied the clinicopathological characteristics of 110 adenomas or intramucosal carcinomas. The grade of atypia of all tumors was classified into 3 groups according to the World Health Organization (WHO 2010 classification. The tumors were immunohistochemically evaluated to determine the frequency of differentiation toward fundic glands.As for patient characteristics, there were 76 men (75.2% and 25 women (24.8%, with a median age of 65 years (range, 34 to 84. The tumors most commonly arose in the first to second part of the duodenum. Many lesions were flat, and the median tumor diameter was 8.0 mm. The lesions were classified into 2 types according to mucin phenotype: intestinal-type tumors (98 lesions, 89.1% and gastric-type tumors (12 lesions, 10.9%. Intestinal-type tumors were subdivided into 2 groups: tubular-type tumors (91 lesions, 82.7% and tubulovillous-type tumors (7 lesions, 6.4%. Gastric-type tumors were classified into 2 types: foveolar type (3 lesions, 2.7% and pyloric gland-type (PG tumors (9 lesions, 8.2%. The grade of atypia was significantly higher in gastric-type tumors (p<0.01. PG tumors were gastric-type tumors characterized by pyloric glands and findings suggesting differentiation toward fundic glands.About 10% of the duodenal tumors had a gastric-type mucin phenotype. Gastric-type tumors showed high-grade atypia. In particular, PG tumors showed similarities to PG tumors of the stomach, such as differentiation toward fundic glands.

Recurrent PAX3-MAML3 Fusion in Biphenotypic Sinonasal Sarcoma

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Wang, Xiaoke; Bledsoe, Krista L.; Graham, Rondell P.; Asmann, Yan W.; Viswanatha, David S.; Lewis, Jean E.; Lewis, Jason T.; Chou, Margaret M.; Yaszemski, Michael J.; Jen, Jin; Westendorf, Jennifer J.; Oliveira, André M.

2014-01-01

Biphenotypic sinonasal sarcoma (SNS) is a newly described tumor of the nasal and paranasal areas. Herein, we report the novel recurring chromosomal translocation t(2;4)(q35;q31.1) in SNS. The translocation results in the formation of the fusion protein PAX3-MAML3, which is a potent transcriptional activator of PAX3 response elements. The SNS phenotype is characterized by aberrant expression of genes involved in neuroectodermal and myogenic differentiation, which closely simulates the developmental roles of PAX3. PMID:24859338

Askin Tumour: Case Report

International Nuclear Information System (INIS)

Gomez, Carolina; Ramirez, Sandra Milena; Quesada, Diana Constanza; Unigarro Luz Adriana

2011-01-01

In this article we report a case of a 19 year-old woman with a final diagnosis of an extra skeletal Primitive Neuroectodermal Tumor/Ewing sarcoma of the chest, also known as Askin tumour. The histologic features and the immunohistochemical profile were consistent with this aggressive malignancy of the chest wall that affects young people. Because the low incidence of this entity, as well as the clear radiological findings, we considered it interesting to describe this documented case and undertake a review of the literature.

Extra skeletal Soft Tissue Ewing?s Sarcoma with Variant Translocation of Chromosome t (4; 22) (q35; q12)-A Case Report

OpenAIRE

Nagaraj, Prashanth; H, Srinivas C; Rao, Raghavendra; Manohar, Sandesh

2013-01-01

Introduction: Ewing’s sarcomas is a rare primitive neuroectodermal tumour (PNET) which has an annual incidence of 2.9 /million population in USA 1Jeffery Toretsky et al (2008) They are very uncommon in African and Asian population .lt is commonly associated with reciprocal translocation between chromosome 11 and 12 t (11:12) or less frequently the t(21 ;22)(q22;ql 2) translocation. It is highly aggressive tumor which is PAS- and CD99 (MIC2)-positive relatively few variant translocations have ...

Tumor-specific chromosome mis-segregation controls cancer plasticity by maintaining tumor heterogeneity.

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Yuanjie Hu

Full Text Available Aneuploidy with chromosome instability is a cancer hallmark. We studied chromosome 7 (Chr7 copy number variation (CNV in gliomas and in primary cultures derived from them. We found tumor heterogeneity with cells having Chr7-CNV commonly occurs in gliomas, with a higher percentage of cells in high-grade gliomas carrying more than 2 copies of Chr7, as compared to low-grade gliomas. Interestingly, all Chr7-aneuploid cell types in the parental culture of established glioma cell lines reappeared in single-cell-derived subcultures. We then characterized the biology of three syngeneic glioma cultures dominated by different Chr7-aneuploid cell types. We found phenotypic divergence for cells following Chr7 mis-segregation, which benefited overall tumor growth in vitro and in vivo. Mathematical modeling suggested the involvement of chromosome instability and interactions among cell subpopulations in restoring the optimal equilibrium of tumor cell types. Both our experimental data and mathematical modeling demonstrated that the complexity of tumor heterogeneity could be enhanced by the existence of chromosomes with structural abnormality, in addition to their mis-segregations. Overall, our findings show, for the first time, the involvement of chromosome instability in maintaining tumor heterogeneity, which underlies the enhanced growth, persistence and treatment resistance of cancers.

Extracellular vesicles as shuttles of tumor biomarkers and anti-tumor drugs.

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Zocco, Davide; Ferruzzi, Pietro; Cappello, Francesco; Kuo, Winston Patrick; Fais, Stefano

2014-01-01

Extracellular vesicles (EV) include vesicles released by either normal or tumor cells. EV may exceed the nanometric scale (microvesicles), or to be within the nanoscale, also called exosomes. Thus, it appears that only exosomes and larger vesicles may have the size for potential applications in nanomedicine, in either disease diagnosis or therapy. This is of particular interest for research in cancer, also because the vast majority of existing data on EV are coming from pre-clinical and clinical oncology. We know that the microenvironmental features of cancer may favor cell-to-cell paracrine communication through EV, but EV have been purified, characterized, and quantified from plasma of tumor patients as well, thus suggesting that EV may have a role in promoting and maintaining cancer dissemination and progression. These observations are prompting research efforts to evaluate the use of nanovesicles as tumor biomarkers. Moreover, EVs are emerging as natural delivery systems and in particular, exosomes may represent the ideal natural nanoshuttles for new and old anti-tumor drugs. However, much is yet to be understood about the role of EV in oncology and this article aims to discuss the future of EV in cancer on the basis of current knowledge.

Human neutrophils facilitate tumor cell transendothelial migration.

LENUS (Irish Health Repository)

Wu, Q D

2012-02-03

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

Updated results of a pilot study of low dose craniospinal irradiation plus chemotherapy for children under five with cerebellar primitive neuroectodermal tumors (medulloblastoma)

International Nuclear Information System (INIS)

Goldwein, Joel W.; Radcliffe, Jerilynn; Johnson, James; Moshang, Thomas; Packer, Roger J.; Sutton, Leslie N.; Rorke, Lucy B.; D'Angio, Giulio J.

1996-01-01

Purpose: Children under 5 years old with medulloblastoma (MB) have a poor prognosis. They are more susceptible to the deleterious effects of craniospinal irradiation (CSART) and have a higher relapse rate when treated with low-dose CSART alone. We, thus, embarked on a prospective trial testing the usefulness of very low dose CSART and adjuvant chemotherapy. This is an update of a previous report on these patients. Methods and Materials: Between January 1988 and March 1990, 10 patients with medulloblastoma were treated using 18 Gy radiation therapy (RT) to the craniospinal axis, a posterior fossa (PF) boost to 50.4-55.8 Gy and chemotherapy consisting of vincristine (VCR) weekly during RT. This was followed by VCR, cis-diamminedichloroplatinum (CDDP), and lomustine (CCNU) for eight, 6-week cycles. Patients between 18 and 60 months of age without evidence of tumor dissemination were eligible for study. Follow-up was available until September 1994 with a median follow-up for living patients of 6.3 years from diagnosis. Results: Actuarial survival at over 6 years is 70 ± 20%. Three of the 10 patients relapsed and died. In one patient, the relapse developed in the spine and brain outside the posterior fossa, in the second, concurrently in the posterior fossa, brain and spine, and the third, only in the spine. One surviving child developed a brain stem infarct 4.8 years after diagnosis and has since almost fully recovered. A mean intelligence quotient (IQ) score of 103 in six patients surviving at least 1 year is unchanged from the baseline group score of 107. Five children tested at baseline and 2 years following treatment had IQ scores of 101 and 102, respectively. Six children tested at baseline and at 3 years had IQ scores of 106 and 96, respectively. Excluding the child tested shortly after his brain stem infarct, baseline and 3 year IQ scores were 103 and 97, respectively. Five of the seven long-term survivors grew at rates significantly below their expected

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

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Tozeren Aydin

2006-11-01

Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

Neem leaf glycoprotein prophylaxis transduces immune dependent stop signal for tumor angiogenic switch within tumor microenvironment.

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Saptak Banerjee

Full Text Available We have reported that prophylactic as well as therapeutic administration of neem leaf glycoprotein (NLGP induces significant restriction of solid tumor growth in mice. Here, we investigate whether the effect of such pretreatment (25µg/mice; weekly, 4 times benefits regulation of tumor angiogenesis, an obligate factor for tumor progression. We show that NLGP pretreatment results in vascular normalization in melanoma and carcinoma bearing mice along with downregulation of CD31, VEGF and VEGFR2. NLGP pretreatment facilitates profound infiltration of CD8+ T cells within tumor parenchyma, which subsequently regulates VEGF-VEGFR2 signaling in CD31+ vascular endothelial cells to prevent aberrant neovascularization. Pericyte stabilization, VEGF dependent inhibition of VEC proliferation and subsequent vascular normalization are also experienced. Studies in immune compromised mice confirmed that these vascular and intratumoral changes in angiogenic profile are dependent upon active adoptive immunity particularly those mediated by CD8+ T cells. Accumulated evidences suggest that NLGP regulated immunomodulation is active in tumor growth restriction and normalization of tumor angiogenesis as well, thereby, signifying its clinical translation.

Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model.

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Jablonska, Jadwiga; Leschner, Sara; Westphal, Kathrin; Lienenklaus, Stefan; Weiss, Siegfried

2010-04-01

Angiogenesis is a hallmark of malignant neoplasias, as the formation of new blood vessels is required for tumors to acquire oxygen and nutrients essential for their continued growth and metastasis. However, the signaling pathways leading to tumor vascularization are not fully understood. Here, using a transplantable mouse tumor model, we have demonstrated that endogenous IFN-beta inhibits tumor angiogenesis through repression of genes encoding proangiogenic and homing factors in tumor-infiltrating neutrophils. We determined that IFN-beta-deficient mice injected with B16F10 melanoma or MCA205 fibrosarcoma cells developed faster-growing tumors with better-developed blood vessels than did syngeneic control mice. These tumors displayed enhanced infiltration by CD11b+Gr1+ neutrophils expressing elevated levels of the genes encoding the proangiogenic factors VEGF and MMP9 and the homing receptor CXCR4. They also expressed higher levels of the transcription factors c-myc and STAT3, known regulators of VEGF, MMP9, and CXCR4. In vitro, treatment of these tumor-infiltrating neutrophils with low levels of IFN-beta restored expression of proangiogenic factors to control levels. Moreover, depletion of these neutrophils inhibited tumor growth in both control and IFN-beta-deficient mice. We therefore suggest that constitutively produced endogenous IFN-beta is an important mediator of innate tumor surveillance. Further, we believe our data help to explain the therapeutic effect of IFN treatment during the early stages of cancer development.

Investigation of HIFU-induced anti-tumor immunity in a murine tumor model

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Lyerly H Kim

2007-07-01

Full Text Available Abstract Background High intensity focused ultrasound (HIFU is an emerging non-invasive treatment modality for localized treatment of cancers. While current clinical strategies employ HIFU exclusively for thermal ablation of the target sites, biological responses associated with both thermal and mechanical damage from focused ultrasound have not been thoroughly investigated. In particular, endogenous danger signals from HIFU-damaged tumor cells may trigger the activation of dendritic cells. This response may play a critical role in a HIFU-elicited anti-tumor immune response which can be harnessed for more effective treatment. Methods Mice bearing MC-38 colon adenocarcinoma tumors were treated with thermal and mechanical HIFU exposure settings in order to independently observe HIFU-induced effects on the host's immunological response. In vivo dendritic cell activity was assessed along with the host's response to challenge tumor growth. Results Thermal and mechanical HIFU were found to increase CD11c+ cells 3.1-fold and 4-fold, respectively, as compared to 1.5-fold observed for DC injection alone. In addition, thermal and mechanical HIFU increased CFSE+ DC accumulation in draining lymph nodes 5-fold and 10-fold, respectively. Moreover, focused ultrasound treatments not only caused a reduction in the growth of primary tumors, with tumor volume decreasing by 85% for thermal HIFU and 43% for mechanical HIFU, but they also provided protection against subcutaneous tumor re-challenge. Further immunological assays confirmed an enhanced CTL activity and increased tumor-specific IFN-γ-secreting cells in the mice treated by focused ultrasound, with cytotoxicity induced by mechanical HIFU reaching as high as 27% at a 10:1 effector:target ratio. Conclusion These studies present initial encouraging results confirming that focused ultrasound treatment can elicit a systemic anti-tumor immune response, and they suggest that this immunity is closely related to

Genetic ablation of soluble tumor necrosis factor with preservation of membrane tumor necrosis factor is associated with neuroprotection after focal cerebral ischemia

DEFF Research Database (Denmark)

Madsen, Pernille M; Clausen, Bettina H; Degn, Matilda

2016-01-01

Microglia respond to focal cerebral ischemia by increasing their production of the neuromodulatory cytokine tumor necrosis factor, which exists both as membrane-anchored tumor necrosis factor and as cleaved soluble tumor necrosis factor forms. We previously demonstrated that tumor necrosis factor...... reduced infarct volumes at one and five days after stroke. This was associated with improved functional outcome after experimental stroke. No changes were found in the mRNA levels of tumor necrosis factor and tumor necrosis factor-related genes (TNFR1, TNFR2, TACE), pro-inflammatory cytokines (IL-1β, IL-6...... knockout mice display increased lesion volume after focal cerebral ischemia, suggesting that tumor necrosis factor is neuroprotective in experimental stroke. Here, we extend our studies to show that mice with intact membrane-anchored tumor necrosis factor, but no soluble tumor necrosis factor, display...

Circulating tumor DNA functions as an alternative for tissue to overcome tumor heterogeneity in advanced gastric cancer.

Science.gov (United States)

Gao, Jing; Wang, Haixing; Zang, Wanchun; Li, Beifang; Rao, Guanhua; Li, Lei; Yu, Yang; Li, Zhongwu; Dong, Bin; Lu, Zhihao; Jiang, Zhi; Shen, Lin

2017-09-01

Overcoming tumor heterogeneity is a major challenge for personalized treatment of gastric cancer, especially for human epidermal growth factor receptor-2 targeted therapy. Analysis of circulating tumor DNA allows a more comprehensive analysis of tumor heterogeneity than traditional biopsies in lung cancer and breast cancer, but little is known in gastric cancer. We assessed mutation profiles of ctDNA and primary tumors from 30 patients with advanced gastric cancer, then performed a comprehensive analysis of tumor mutations by multiple biopsies from five patients, and finally analyzed the concordance of HER2 amplification in ctDNA and paired tumor tissues in 70 patients. By comparing with a single tumor sample, ctDNA displayed a low concordance of mutation profile, only approximately 50% (138/275) somatic mutations were found in paired tissue samples, however, when compared with multiple biopsies, most DNA mutations in ctDNA were also shown in paired tumor tissues. ctDNA had a high concordance (91.4%, Kappa index = 0.784, P < 0.001) of HER2 amplification with tumor tissues, suggesting it might be an alternative for tissue. It implied that ctDNA-based assessment could partially overcome the tumor heterogeneity, and might serve as a potential surrogate for HER2 analysis in gastric cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Morphologic classification of ductal breast tumors on ultrasound : differential diagnosis of benign and malignant tumors

International Nuclear Information System (INIS)

Won, Mi Sook; Chung, Soo Young; Yang, Ik; Lee, Yul; Park, Hai Jung; Lee, Myoung Hwan; Yoon, In Sook; Koh, Mi Gyoung

1997-01-01

To evaluate the morphologic differential diagnosis of benign and malignant ductal breast tumors, as seen on US US findings in 29 pathologically proven cases of ductal breast tumor were retrospectively reviewed. All patients were female and their mean age was 42 years. Nineteen tumors were benign and ten were malignant, and all ductal or cystic lesions showed solid masses. According to the location of the mural nodule, we classified the sonographic appearance of these tumors into three types:intraductal, intracystic and amorphic. The intraductal type was divided into three subtypes:incompletely obstructive, completely obstructive and multiple mural nodules. For the intracystic type, too, three subtypes were designated:the intracystic mural nodule (mural cyst), intracystic mural nodule with the duct (mural cyst+duct) and intracystic multiple mural nodules. The amorphic type is defined as an atypical ductal tumor with the mural nodule extending into adjacent parenchyma. The margin of the duct or cyst was smooth in 68.4% of benign, and irregular in 90% of malignant ductal tumors. Internal echogeneity of the duct or cyst usually showed homogeneity in both benign and malignant tumors. 73.7% of tumors connecting the duct were benign and 50% were malignant. In benign tumors, 52.6% of mural nodule had an irregular margin, while in malignant tumors, the corresponding proportion was 100%;both types usually showed heterogeneous hypoechogeneity. Among benign tumors, the most common morphologic type was the intraductal incompletely obstructive subtype (36.8%);among those that were malignant, the amorphic type was most common, accounting for 40% of tumors. No amorphic type was benign and no incompletely obstructive subtype was malignant. When ductal breast tumors are morphologically classified on the basis of sonographic findings, the intraductal incompletely obstructive subtype suggests benignancy, and the amorphic type, malignancy. The morphologic classification of ductal

NF-κB functions as a molecular link between tumor cells and Th1/Tc1 T cells in the tumor microenvironment to exert radiation-mediated tumor suppression

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Simon, Priscilla S.; Bardhan, Kankana; Chen, May R.; Paschall, Amy V.; Lu, Chunwan; Bollag, Roni J.; Kong, Feng-Chong; Jin, JianYue; Kong, Feng-Ming; Waller, Jennifer L.; Pollock, Raphael E.; Liu, Kebin

2016-01-01

Radiation modulates both tumor cells and immune cells in the tumor microenvironment to exert its anti-tumor activity; however, the molecular connection between tumor cells and immune cells that mediates radiation-exerted tumor suppression activity in the tumor microenvironment is largely unknown. We report here that radiation induces rapid activation of the p65/p50 and p50/p50 NF-κB complexes in human soft tissue sarcoma (STS) cells. Radiation-activated p65/p50 and p50/p50 bind to the TNFα promoter to activate its transcription in STS cells. Radiation-induced TNFα induces tumor cell death in an autocrine manner. A sublethal dose of Smac mimetic BV6 induces cIAP1 and cIAP2 degradation to increase tumor cell sensitivity to radiation-induced cell death in vitro and to enhance radiation-mediated suppression of STS xenografts in vivo. Inhibition of caspases, RIP1, or RIP3 blocks radiation/TNFα-induced cell death, whereas inhibition of RIP1 blocks TNFα-induced caspase activation, suggesting that caspases and RIP1 act sequentially to mediate the non-compensatory cell death pathways. Furthermore, we determined in a syngeneic sarcoma mouse model that radiation up-regulates IRF3, IFNβ, and the T cell chemokines CCL2 and CCL5 in the tumor microenvironment, which are associated with activation and increased infiltration of Th1/Tc1 T cells in the tumor microenvironment. Moreover, tumor-infiltrating T cells are in their active form since both the perforin and FasL pathways are activated in irradiated tumor tissues. Consequently, combined BV6 and radiation completely suppressed tumor growth in vivo. Therefore, radiation-induced NF-κB functions as a molecular link between tumor cells and immune cells in the tumor microenvironment for radiation-mediated tumor suppression. PMID:27014915

Commensal bacteria modulate the tumor microenvironment.

Science.gov (United States)

Poutahidis, Theofilos; Erdman, Susan E

2016-09-28

It has been recently shown that gut microbes modulate whole host immune and hormonal factors impacting the fate of distant preneoplastic lesions toward malignancy or regression. This raises the possibility that the tumor microenvironment interacts with broader systemic microbial-immune networks. These accumulated findings suggest novel therapeutic opportunities for holobiont engineering in emerging tumor microenvironments. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

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Shoya Shiromizu

2018-04-01

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

Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells.

Science.gov (United States)

Testa, Ugo; Pelosi, Elvira; Castelli, Germana

2018-04-13

Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20-30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse.

Mena deficiency delays tumor progression and decreases metastasis in polyoma middle-T transgenic mouse mammary tumors.

Science.gov (United States)

Roussos, Evanthia T; Wang, Yarong; Wyckoff, Jeffrey B; Sellers, Rani S; Wang, Weigang; Li, Jiufeng; Pollard, Jeffrey W; Gertler, Frank B; Condeelis, John S

2010-01-01

deficiency during development causes defects in invasive processes involved in mammary gland development. These findings suggest that functional intervention targeting Mena in breast cancer patients may provide a valuable treatment option to delay tumor progression and decrease invasion and metastatic spread leading to an improved prognostic outcome.

Fluorescent Nanoparticle Uptake for Brain Tumor Visualization

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Rachel Tréhin

2006-04-01

Full Text Available Accurate delineation of tumor margins is vital to the successful surgical resection of brain tumors. We have previously developed a multimodal nanoparticle CLIO-Cy5.5, which is detectable by both magnetic resonance imaging and fluorescence, to assist in intraoperatively visualizing tumor boundaries. Here we examined the accuracy of tumor margin determination of orthotopic tumors implanted in hosts with differing immune responses to the tumor. Using a nonuser-based signal intensity method applied to fluorescent micrographs of 9L gliosarcoma green fluorescent protein (GFP tumors, mean overestimations of 2 and 24 µm were obtained using Cy5.5 fluorescence, compared to the true tumor margin determined by GFP fluorescence, in nude mice and rats, respectively. To resolve which cells internalized the nanoparticle and to quantitate degree of uptake, tumors were disaggregated and cells were analyzed by flow cytometry and fluorescence microscopy. Nanoparticle uptake was seen in both CD11b+ cells (representing activated microglia and macrophages and tumor cells in both animal models by both methods. CD11b+ cells were predominantly found at the tumor margin in both hosts, but were more pronounced at the margin in the rat model. Additional metastatic (CT26 colon and primary (Gli36 glioma brain tumor models likewise demonstrated that the nanoparticle was internalized both by tumor cells and by host cells. Together, these observations suggest that fluorescent nanoparticles provide an accurate method of tumor margin estimation based on a combination of tumor cell and host cell uptake for primary and metastatic tumors in animal model systems and offer potential for clinical translation.

Colorectal cancer patient-derived xenografted tumors maintain characteristic features of the original tumors.

Science.gov (United States)

Cho, Yong Beom; Hong, Hye Kyung; Choi, Yoon-La; Oh, Ensel; Joo, Kyeung Min; Jin, Juyoun; Nam, Do-Hyun; Ko, Young-Hyeh; Lee, Woo Yong

2014-04-01

Despite significant improvements in colon cancer outcomes over the past few decades, preclinical development of more effective therapeutic strategies is still limited by the availability of clinically relevant animal models. To meet those clinical unmet needs, we generated a well-characterized in vivo preclinical platform for colorectal cancer using fresh surgical samples. Primary and metastatic colorectal tumor tissues (1-2 mm(3)) that originate from surgery were implanted into the subcutaneous space of nude mice and serially passaged in vivo. Mutation status, hematoxylin and eosin staining, short tandem repeat profiling, and array comparative genomic hybridization were used to validate the similarity of molecular characteristics between the patient tumors and tumors obtained from xenografts. From surgical specimens of 143 patients, 97 xenograft models were obtained in immunodeficient mice (establish rate = 67%). Thirty-nine xenograft models were serially expanded further in mice with a mean time to reach a size of 1000-1500 mm(3) of 90 ± 20 d. Histologic and immunohistochemical analyses revealed a high degree of pathologic similarity including histologic architecture and expression of CEA, CK7, and CD20 between the patient and xenograft tumors. Molecular analysis showed that genetic mutations, genomic alterations, and gene expression patterns of each patient tumor were also well conserved in the corresponding xenograft tumor. Xenograft animal models derived from fresh surgical sample maintained the key characteristic features of the original tumors, suggesting that this in vivo platform can be useful for preclinical development of novel therapeutic approaches to colorectal cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

WE-EF-BRA-11: Precision Partial-Tumor Irradiation of Dorsal Rodent Mammary Tumors

Energy Technology Data Exchange (ETDEWEB)

Malcolm, J [Duke Medical Physics Graduate Program, Durham, NC (United States); Boss, K [Department of Comparative Biomedical Sciences, North Carolina State University (United States); Dewhirst, M [Dpt of Radiation and Cancer Biology, Duke University, Durham, North Carolina (United States); Oldham, M [Dpt of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

2015-06-15

Purpose: To introduce a pre-clinical treatment technique on a micro-irradiator to treat specific volumes of dorsal mammary tumors in BALB/c mice while sparing lungs and spine. This technique facilitates pre-clinical investigation of tumor response to sub-optimal radiation treatments in which a portion of the tumor is unirradiated, known as a “marginal miss”. In-vitro data suggests that partial tumor radiations trigger a more aggressive phenotype in non-irradiated, regional tumor cells via bystander effects. As the lung tissue is spared, the impact of marginal miss on the development of pulmonary metastasis may be assessed. Methods: End to end test was performed on three BALB/c mice as proof of concept for larger studies. 1Gy was delivered on the micro-irradiator employing previously unexplored lateral parallel-opposed diamond and/or triangle-shaped beams. The margins of the treatment beam were defined using a combination of tumor palpation, barium fiducial markers, and real-time fluoroscopic images. The dose distribution was independently verified with kilovoltage beam Monte Carlo dose calculations with 7% statistical uncertainty and double exposure images. As a final step, the technique was used in a larger pre-clinical study (15Gy, 36 BALB/c mice) and lung metastasis in response to tumor irradiation of 100%, 50% and 0% was quantified. Results: For the Monte-Carlo dose calculations, the dose volume histograms established a maximum dose within the un-irradiated and radiated portions of the mammary tumor of 0.3Gy and 1.5Gy respectively, with a sharp gradient at the boundary. 100% of the lung volume received less than 0.5Gy. This technique proved suitable for a pre-clinical marginal miss study with 50% more lung metastases in partially-radiated mouse models compared to completely. Conclusion: We have developed a novel treatment technique for partial or full irradiation of dorsal mammary tumors incorporating lung sparing.The technique will be useful for exploring

Monoclonal antibodies reactive with common tumor antigens on UV-induced tumors also react with hyperplastic UV-irradiated skin

International Nuclear Information System (INIS)

Spellman, C.W.; Beauchamp, D.A.

1986-01-01

Most murine skin tumors induced by ultraviolet light (UVB, 280-340 nm) can be successfully transplanted only into syngeneic hosts that have received subcarcinogenic doses of UVB. The tumor susceptible state is long-lived and mediated by T suppressor cells that control effector responses against common antigens on UV-induced tumors. Because antigen specific suppression arises prior to the appearance of a tumor, questions arise about the source of the original antigen. They have previously reported transplantation studies indicating that UV-irradiated skin is antigenically cross-reactive with UV-induced tumors. They now report on flow cytometry analyses showing that a series of MoAb reactive with common antigens expressed by UV-induced tumors are also reactive on cells from UV-irradiated skin. Various antigens appear at different times in the UV irradiation scheme, and some persist while others are transient. They speculate that the common antigens detected may be the ones to which functional suppression is directed. If true, these results suggest that successful tumors need not escape host defenses to emerge. Rather, tumors may arise and grow progressively if they express antigens that cross-react with specificities to which the host has previously mounted a suppressive response

Imaging of non-central nervous system primitive neuroectodermal tumours: Diagnostic features and correlation with outcome

Energy Technology Data Exchange (ETDEWEB)

Dick, E.A.; McHugh, K.; Kimber, C.; Michalski, A

2001-03-01

AIM: To document the varied radiological features before, during, and after treatment of non-Central Nervous System Primitive Neuroectodermal Tumours (PNETs), which are rare tumours of childhood. MATERIALS AND METHODS: Thirty-three children with PNETs have been treated at our institution between 1990 and 1999. Full radiological and clinical follow-up was obtained in 29 (17 females, 12 males). Imaging was retrospectively reviewed, with particular attention to Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). RESULTS: Age range at diagnosis was 0-16 years old (mean 4.4 years). There were five main sites of tumour: head and neck (n = 7), scapula/axilla (n 2), chest (n = 11), abdomen (n = 3), and spinal/paraspinal (n = 6). Overall mortality was 62%. Tumours of the scapula or paraspinal region appear to show better survival than other sites. Of 23 patients who had Tc99m-methylene diphosphonate (MDP) bone scans at diagnosis, four patients showed widespread distant metastases, seven showed focal increased uptake in an adjacent bone only, and 12 had normal examinations. CT was performed in 25 patients and MRI in 20, both at diagnosis and follow-up. Average size of tumours at presentation was 4.5 cm in the paraspinal, head and neck and scapular regions and 7.5 cm in the chest and abdomen. Tumours were typically of soft tissue density on CT with the larger (>5 cm) masses tending to be more heterogeneous in character. The lesions were slightly higher signal than muscle on T1-weighted (T1W) MRI and all masses were heterogeneous on T2W sequences. Calcification was uncommon (n = 6) and generally sparse. Tumours tended to displace adjacent soft tissue structures such as vessels and bronchi rather than invade or encase them. Tumours rarely crossed the midline. Local or bony invasion was seen in 12 patients at diagnosis. Metastases were identified in the lung (n = 5), pleura (n = 2), brain (n = 4), bone (n = 4), lymph nodes (n = 2), liver (n = 2), subcutaneous tissues

Imaging of non-central nervous system primitive neuroectodermal tumours: Diagnostic features and correlation with outcome

International Nuclear Information System (INIS)

Dick, E.A.; McHugh, K.; Kimber, C.; Michalski, A.

2001-01-01

AIM: To document the varied radiological features before, during, and after treatment of non-Central Nervous System Primitive Neuroectodermal Tumours (PNETs), which are rare tumours of childhood. MATERIALS AND METHODS: Thirty-three children with PNETs have been treated at our institution between 1990 and 1999. Full radiological and clinical follow-up was obtained in 29 (17 females, 12 males). Imaging was retrospectively reviewed, with particular attention to Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). RESULTS: Age range at diagnosis was 0-16 years old (mean 4.4 years). There were five main sites of tumour: head and neck (n = 7), scapula/axilla (n 2), chest (n = 11), abdomen (n = 3), and spinal/paraspinal (n = 6). Overall mortality was 62%. Tumours of the scapula or paraspinal region appear to show better survival than other sites. Of 23 patients who had Tc99m-methylene diphosphonate (MDP) bone scans at diagnosis, four patients showed widespread distant metastases, seven showed focal increased uptake in an adjacent bone only, and 12 had normal examinations. CT was performed in 25 patients and MRI in 20, both at diagnosis and follow-up. Average size of tumours at presentation was 4.5 cm in the paraspinal, head and neck and scapular regions and 7.5 cm in the chest and abdomen. Tumours were typically of soft tissue density on CT with the larger (>5 cm) masses tending to be more heterogeneous in character. The lesions were slightly higher signal than muscle on T1-weighted (T1W) MRI and all masses were heterogeneous on T2W sequences. Calcification was uncommon (n = 6) and generally sparse. Tumours tended to displace adjacent soft tissue structures such as vessels and bronchi rather than invade or encase them. Tumours rarely crossed the midline. Local or bony invasion was seen in 12 patients at diagnosis. Metastases were identified in the lung (n = 5), pleura (n = 2), brain (n = 4), bone (n = 4), lymph nodes (n = 2), liver (n = 2), subcutaneous tissues

FIBROMATOSIS (DESMOID TUMOR OF THE BREAST. Fibromatosis (tumor desmoide de mama

Directory of Open Access Journals (Sweden)

Zhaneta P Boceska

2016-03-01

Full Text Available El tumor desmoide (fibromatosis es una entidad patológica extremadamente rara que se desarrolla de la fascia muscular y la aponeusorsis. Aunque sin potencial metastático, estos tumores son localmente muy agresivos y tienden a infiltrarse en los tejidos circundantes. Nosotros presentamos un caso de tumour desmoide de mama, que tuvo apariencias clínicas sugestivas a carcinoma. La paciente, de 56 años presentó una masa palpable de mama derecho. La citología por aspiracion con aguja fina (AGF no detectó ninguna célula maligna, por lo que se hizo una escisión local conservadora. La paciente no recibió ningun tratamiento postoperatorio adicional, y continúa viva y sana en los siguientes 18 meses. Desmoid tumor (fibromatosis is extremely rare benign pathological entity that develops from muscular fasciae and aponeuroses. Although without metastatic potential, these tumors are locally very aggressive and tend to infiltrate the surrounding tissues. We present a case of a desmoid tumor of the breast that had clinical appearance suggestive of carcinoma. The patient was 56 years old female with a previous history of surgical trauma who presented with a palpable mass in the right breast. A fine needle aspiration (FNA cytology did not reveal any malignant cells, thus conservative local excision was performed. The patient did not receive any additional postoperative treatment and was alive and free of disease after 18 months of follow-up. 

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

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

2013-07-12

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

An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells

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David A. Turner

2014-06-01

Full Text Available Embryonic Stem cells derived from the epiblast tissue of the mammalian blastocyst retain the capability to differentiate into any adult cell type and are able to self-renew indefinitely under appropriate culture conditions. Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains elusive. In this work, we have analysed in a systematic manner the interaction between the dynamics of loss of pluripotency and Activin/Nodal, BMP4 and Wnt signalling in fate assignment during the early stages of differentiation of mouse ES cells in culture. During the initial period of differentiation, cells exit from pluripotency and enter an Epi-like state. Following this transient stage, and under the influence of Activin/Nodal and BMP signalling, cells face a fate choice between differentiating into neuroectoderm and contributing to Primitive Streak fates. We find that Wnt signalling does not suppress neural development as previously thought and that it aids both fates in a context dependent manner. Our results suggest that as cells exit pluripotency they are endowed with a primary neuroectodermal fate and that the potency to become endomesodermal rises with time. We suggest that this situation translates into a “race for fates” in which the neuroectodermal fate has an advantage.

Simultaneous development of craniopharyngioma and choroid plexus carcinoma in the childhood -a clinical case

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Marinova, L.; Georgiev, R.; Mihaylova, I.

2014-01-01

We present a clinical case of 9 years old girl with concomitant brain tumors - choroid plexus carcinoma and craniopharyngioma diagnosed in 2009. After three operations, cranio-spinal irradiation with boost for the remaining tumor located in left ventricular trigonum to a total dose of 55 Gy and 7 courses chemotherapy, local tumor control was achieved for the choroid plexus carcinoma. Four years following the achievement of local tumor control of the choroid plexus carcinoma, an increase of the tumor formation located in the left side of the pituitary was reported. The diagnosis cystic craniopharyngeoma was found during the surgical operation. With this clinical case we would like to stress on the achieved local tumor control following the complex treatment of carcinoma of the choroid plexus, as well as on the slow growth of simultaneously diagnosed craniopharyngeoma. This case report raises the question of the genetic predisposition of the brain tumors in children, as well as possibility of malignant transformation of craniopharyngeoma following radiotherapy. The differential diagnosis of neuroectodermal brain tumors requires immunohistochemical analysis and if necessary genetic analysis. Key words: Complex treatment. Choroid plexus carcinoma. Craniopharyngioma. Radiotherapy. Malignant transformation. Simultaneity

Exploiting tumor shrinkage through temporal optimization of radiotherapy

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Unkelbach, Jan; Craft, David; Hong, Theodore; Papp, Dávid; Wolfgang, John; Bortfeld, Thomas; Ramakrishnan, Jagdish; Salari, Ehsan

2014-01-01

In multi-stage radiotherapy, a patient is treated in several stages separated by weeks or months. This regimen has been motivated mostly by radiobiological considerations, but also provides an approach to reduce normal tissue dose by exploiting tumor shrinkage. The paper considers the optimal design of multi-stage treatments, motivated by the clinical management of large liver tumors for which normal liver dose constraints prohibit the administration of an ablative radiation dose in a single treatment. We introduce a dynamic tumor model that incorporates three factors: radiation induced cell kill, tumor shrinkage, and tumor cell repopulation. The design of multi-stage radiotherapy is formulated as a mathematical optimization problem in which the total dose to the normal tissue is minimized, subject to delivering the prescribed dose to the tumor. Based on the model, we gain insight into the optimal administration of radiation over time, i.e. the optimal treatment gaps and dose levels. We analyze treatments consisting of two stages in detail. The analysis confirms the intuition that the second stage should be delivered just before the tumor size reaches a minimum and repopulation overcompensates shrinking. Furthermore, it was found that, for a large range of model parameters, approximately one-third of the dose should be delivered in the first stage. The projected benefit of multi-stage treatments in terms of normal tissue sparing depends on model assumptions. However, the model predicts large dose reductions by more than a factor of 2 for plausible model parameters. The analysis of the tumor model suggests that substantial reduction in normal tissue dose can be achieved by exploiting tumor shrinkage via an optimal design of multi-stage treatments. This suggests taking a fresh look at multi-stage radiotherapy for selected disease sites where substantial tumor regression translates into reduced target volumes. (paper)

Correlation of MRI Biomarkers with Tumor Necrosis in Hras5 Tumor Xenograft in Athymic Rats

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Daniel P. Bradley

2007-05-01

Full Text Available Magnetic resonance imaging (MRI can measure the effects of therapies targeting the tumor vasculature and has demonstrated that vascular-damaging agents (VDA induce acute vascular shutdown in tumors in human and animal models. However, at subtherapeutic doses, blood flow may recover before the induction of significant levels of necrosis. We present the relationship between changes in MRI biomarkers and tumor necrosis. Multiple MRI measurements were taken at 4.7 T in athymic rats (n = 24 bearing 1.94 ± 0.2-cm3 subcutaneous Hras5 tumors (ATCC 41000 before and 24 hours after clinically relevant doses of the VDA, ZD6126 (0-10 mg/kg, i.v.. We measured effective transverse relaxation rate (R2*, initial area under the gadolinium concentration-time curve (IAUGC60/150, equivalent enhancing fractions (EHF60/150, time constant (Ktrans, proportion of hypoperfused voxels as estimated from fit failures in Ktrans analysis, and signal intensity (SI in T2-weighted MRI (T2W. ZD6126 treatment induced < 90% dose-dependent tumor necrosis at 10 mg/kg; correspondingly, SI changes were evident from T2W MRI. Although R2* did not correlate, other MRI biomarkers significantly correlated with necrosis at doses of ≥ 5 mg/kg ZD6126. These data on Hras5 tumors suggest that the quantification of hypoperfused voxels might provide a useful biomarker of tumor necrosis.

Tumor associated CD70 expression is involved in promoting tumor migration and macrophage infiltration in GBM.

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Ge, Haitao; Mu, Luyan; Jin, Linchun; Yang, Changlin; Chang, Yifan Emily; Long, Yu; DeLeon, Gabriel; Deleyrolle, Loic; Mitchell, Duane A; Kubilis, Paul S; Lu, Dunyue; Qi, Jiping; Gu, Yunhe; Lin, Zhiguo; Huang, Jianping

2017-10-01

Tumor migration/metastasis and immunosuppression are major obstacles in effective cancer therapy. Incidentally, these 2 hurdles usually coexist inside tumors, therefore making therapy significantly more complicated, as both oncogenic mechanisms must be addressed for successful therapeutic intervention. Our recent report highlights that the tumor expression of a TNF family member, CD70, is correlated with poor survival for primary gliomas. In this study, we investigated how CD70 expression by GBM affects the characteristics of tumor cells and the tumor microenvironment. We found that the ablation of CD70 in primary GBM decreased CD44 and SOX2 gene expression, and inhibited tumor migration, growth and the ability to attract monocyte-derived M2 macrophages in vitro. In the tumor microenvironment, CD70 was associated with immune cell infiltrates, such as T cells; myeloid-derived suppressor cells; and monocytes/macrophages based on the RNA-sequencing profile. The CD163+ macrophages were far more abundant than T cells were. This overwhelming level of macrophages was identified only in GBM and not in low-grade gliomas and normal brain specimens, implying their tumor association. CD70 was detected only on tumor cells, not on macrophages, and was highly correlated with CD163 gene expression in primary GBM. Additionally, the co-expression of the CD70 and CD163 genes was found to correlate with decreased survival for patients with primary GBM. Together, these data suggest that CD70 expression is involved in promoting tumor aggressiveness and immunosuppression via tumor-associated macrophage recruitment/activation. Our current efforts to target this molecule using chimeric antigen receptor T cells hold great potential for treating patients with GBM. © 2017 UICC.

I-131 metaiodobenzylguanidine: diagnostic use in neuroblastoma patients in relapse

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Heyman, S.; Evans, A.E.; D'Angio, G.J.

1988-01-01

Metaiodobenzylguanidine (MIBG) has been used for the detection and treatment of neuroectodermal tumors, including neuroblastoma. We report our experience with 131 I-MIBG used diagnostically in neuroblastoma patients with relapse. Thirty-eight studies were performed in 26 patients. There were 24 children (range 3 months-14 years) and two adults. While the study was found to be both sensitive and specific for the presence of disease, there are instances of discordance. False-negative studies were found with a markedly anaplastic tumor and with two mature ganglioneuromas. A bone lesion was negative with 131 I-MIBG, but positive on bone scan. A biopsy confirmed the presence of neuroblastoma. Caution should be exercised when scanning pretreated patients, and perhaps with newly diagnosed patients as well

Medullomyoblastoma in an adult.

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Rao, C; Friedlander, M E; Klein, E; Anzil, A P; Sher, J H

1990-01-01

Medullomyoblastoma is a rare histologic variant of medulloblastoma. Of the 20 cases reported in the literature, 19 were in children ages 2.5 to 10.5 years and one was in a 26-year-old woman. In the reported adult case the myogenic component of the tumor was leiomyosarcomatous. The authors report a case of medullomyoblastoma with a rhabdomyosarcomatous component in a 40-year-old man with light microscopic, immunohistochemical, and ultrastructural findings. The histogenetic theories regarding this tumor include that it is a teratoma, or that the myogenic component arises from the perivascular or leptomeningeal ectomesenchyme, or pluripotential neuroectodermal cells, or endothelial cells. The authors' findings do not elucidate the histogenesis but argue against an endothelial origin of the rhabdomyoblastic component.

Spinal metastasis of medulloblastoma in adults: A case report

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Živković Nenad

2014-01-01

Full Text Available Introduction. Medulloblastoma is a primitive neuro-ectodermal malignant tumor most commonly seen in childhood and rarely and uncommonly in adult age. Treatment consists of surgery followed by radiotherapy. In the case of a relapse there is no overall accepted treatment. Tumor metastasis can be seen along the neural axis, lymph nodes, soft tissues, bones and distant organs. Case Outline. In this paper we present a 45-year-old female patient with a thoraco-spinal extramedullary metastatic medulloblastoma and progressive neurological deterioration seen 11 months after the first operation and description of magnetic resonance and intraoperative finding. Conclusion. Although rare, the presence of metastasis is a poor prognostic factor. The treatment options for patients with metastases are limited and their prognosis continues to remain poor.

Tumor associated osteoclast-like giant cells promote tumor growth and lymphangiogenesis by secreting vascular endothelial growth factor-C

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Hatano, Yu; Nakahama, Ken-ichi; Isobe, Mitsuaki; Morita, Ikuo

2014-01-01

Highlights: • M-CSF and RANKL expressing HeLa cells induced osteoclastogenesis in vitro. • We established OGC-containing tumor model in vivo. • OGC-containing tumor became larger independent of M-CSF or RANKL effect. • VEGF-C secreted from OGCs was a one of candidates for OGC-containing tumor growth. - Abstract: Tumors with osteoclast-like giant cells (OGCs) have been reported in a variety of organs and exert an invasive and prometastatic phenotype, but the functional role of OGCs in the tumor environment has not been fully clarified. We established tumors containing OGCs to clarify the role of OGCs in tumor phenotype. A mixture of HeLa cells expressing macrophage colony-stimulating factor (M-CSF, HeLa-M) and receptor activator of nuclear factor-κB ligand (RANKL, HeLa-R) effectively supported the differentiation of osteoclast-like cells from bone marrow macrophages in vitro. Moreover, a xenograft study showed OGC formation in a tumor composed of HeLa-M and HeLa-R. Surprisingly, the tumors containing OGCs were significantly larger than the tumors without OGCs, although the growth rates were not different in vitro. Histological analysis showed that lymphangiogenesis and macrophage infiltration in the tumor containing OGCs, but not in other tumors were accelerated. According to quantitative PCR analysis, vascular endothelial growth factor (VEGF)-C mRNA expression increased with differentiation of osteoclast-like cells. To investigate whether VEGF-C expression is responsible for tumor growth and macrophage infiltration, HeLa cells overexpressing VEGF-C (HeLa-VC) were established and transplanted into mice. Tumors composed of HeLa-VC mimicked the phenotype of the tumors containing OGCs. Furthermore, the vascular permeability of tumor microvessels also increased in tumors containing OGCs and to some extent in VEGF-C-expressing tumors. These results suggest that macrophage infiltration and vascular permeability are possible mediators in these tumors. These

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

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Shiromizu, Shoya; Kusunose, Naoki; Matsunaga, Naoya; Koyanagi, Satoru; Ohdo, Shigehiro

2018-04-01

Proliferation of acute lymphoblastic leukemic cells is nutritionally dependent on the external supply of asparagine. l-asparaginase, an enzyme hydrolyzing l-asparagine in blood, is used for treatment of acute lymphoblastic leukemic and other related blood cancers. Although previous studies demonstrated that l-asparaginase suppresses the proliferation of cultured solid tumor cells, it remains unclear whether this enzyme prevents the growth of solid tumors in vivo. In this study, we demonstrated the importance of optimizing dosing schedules for the anti-tumor activity of l-asparaginase in 4T1 breast tumor-bearing mice. Cultures of several types of murine solid tumor cells were dependent on the external supply of asparagine. Among them, we selected murine 4T1 breast cancer cells and implanted them into BALB/c female mice kept under standardized light/dark cycle conditions. The growth of 4T1 tumor cells implanted in mice was significantly suppressed by intravenous administration of l-asparaginase during the light phase, whereas its administration during the dark phase failed to show significant anti-tumor activity. Decreases in plasma asparagine levels due to the administration of l-asparaginase were closely related to the dosing time-dependency of its anti-tumor effects. These results suggest that the anti-tumor efficacy of l-asparaginase in breast tumor-bearing mice is improved by optimizing the dosing schedule. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Colorectal Mesenchymal Tumor: A Clinicopathologic Study of 25 Cases

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Chen-Hui Lee

2005-07-01

Conclusion: Two clinicopathologically different categories were identified from our colorectal mesenchymal tumors: intramural GISTs and polypoid submucosal leiomyomas. Our study suggests that GIST is a better categorization than smooth muscle tumor because of the malignant potential. Prognosis is strictly related to the number of mitoses. However, tumor size, nuclear atypia and tumor necrosis are probably also significant predictive factors of lethality. Future studies with DNA analysis and larger patient numbers are essential to evaluate the prognostic significance of our findings.

Revisiting the TCA cycle: signaling to tumor formation.

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Raimundo, Nuno; Baysal, Bora E; Shadel, Gerald S

2011-11-01

A role for mitochondria in tumor formation is suggested by mutations in enzymes of the TCA cycle: isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH) and fumarate hydratase (FH). Although they are all components of the TCA cycle, the resulting clinical presentations do not overlap. Activation of the hypoxia pathway can explain SDH phenotypes, but recent data suggest that FH and IDH mutations lead to tumor formation by repressing cellular differentiation. In this review, we discuss recent findings in the context of both mitochondrial and cytoplasmic components of the TCA cycle, and we propose that extrametabolic roles of TCA cycle metabolites result in reduced cellular differentiation. Furthermore, activation of the pseudohypoxia pathway likely promotes the growth of these neoplasias into tumors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Characterization of Pancreatic Tumor Motion Using Cine MRI: Surrogates for Tumor Position Should Be Used With Caution

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Feng, Mary; Balter, James M.; Normolle, Daniel; Adusumilli, Saroja; Cao Yue; Chenevert, Thomas L.; Ben-Josef, Edgar

2009-01-01

Purpose: Our current understanding of intrafraction pancreatic tumor motion due to respiration is limited. In this study, we characterized pancreatic tumor motion and evaluated the application of several radiotherapy motion management strategies. Methods and Materials: Seventeen patients with unresectable pancreatic cancer were enrolled in a prospective internal review board-approved study and imaged during shallow free-breathing using cine MRI on a 3T scanner. Tumor borders were agreed on by a radiation oncologist and an abdominal MRI radiologist. Tumor motion and correlation with the potential surrogates of the diaphragm and abdominal wall were assessed. These data were also used to evaluate planning target volume margin construction, respiratory gating, and four-dimensional treatment planning for pancreatic tumors. Results: Tumor borders moved much more than expected. To provide 99% geometric coverage, margins of 20 mm inferiorly, 10 mm anteriorly, 7 mm superiorly, and 4 mm posteriorly are required. Tumor position correlated poorly with diaphragm and abdominal wall position, with patient-level Pearson correlation coefficients of -0.18-0.43. Sensitivity and specificity of gating with these surrogates was also poor, at 53%-68%, with overall error of 35%-38%, suggesting that the tumor may be underdosed and normal tissues overdosed. Conclusions: Motion of pancreatic tumor borders is highly variable between patients and larger than expected. There is substantial deformation with breathing, and tumor border position does not correlate well with abdominal wall or diaphragmatic position. Current motion management strategies may not account fully for tumor motion and should be used with caution.

Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

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Stuckey, Ashley; Brodsky, Alexander S; Fischer, Andrew; Miller, Daniel H; Hillenmeyer, Sara; Kim, Kyu K; Ritz, Anna; Singh, Rakesh K; Raphael, Benjamin J; Brard, Laurent

2011-01-01

Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function in vivo. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c. In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth. These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival. We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number

Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression.

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Ma, Ruihua; Ji, Tiantian; Chen, Degao; Dong, Wenqian; Zhang, Huafeng; Yin, Xiaonan; Ma, Jingwei; Liang, Xiaoyu; Zhang, Yi; Shen, Guanxin; Qin, Xiaofeng; Huang, Bo

2016-04-01

Despite identification of macrophages in tumors (tumor-associated macrophages, TAM) as potential targets for cancer therapy, the origin and function of TAM in the context of malignancy remain poorly characterized. Here, we show that microparticles (MPs), as a by-product, released by tumor cells act as a general mechanism to mediate M2 polarization of TAM. Taking up tumor MPs by macrophages is a very efficient process, which in turn results in the polarization of macrophages into M2 type, not only leading to promoting tumor growth and metastasis but also facilitating cancer stem cell development. Moreover, we demonstrate that the underlying mechanism involves the activation of the cGAS/STING/TBK1/STAT6 pathway by tumor MPs. Finally, in addition to murine tumor MPs, we show that human counterparts also possess consistent effect on human M2 polarization. These findings provide new insights into a critical role of tumor MPs in remodeling of tumor microenvironment and better understanding of the communications between tumors and macrophages.

Management of hemorrhage in gastrointestinal stromal tumors: a review.

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Liu, Qi; Kong, Fanmin; Zhou, Jianping; Dong, Ming; Dong, Qi

2018-01-01

Gastrointestinal stromal tumors (GISTs) are relatively common mesenchymal tumors. They originate from the wall of hollow viscera and may be found in any part of the digestive tract. The prognosis of patients with stromal tumors depends on various risk factors, including size, location, presence of mitotic figures, and tumor rupture. Emergency surgery is often required for stromal tumors with hemorrhage. The current literature suggests that stromal tumor hemorrhage indicates poor prognosis. Although the optimal treatment options for hemorrhagic GISTs are based on surgical experience, there remains controversy with regard to optimum postoperative management as well as the classification of malignant potential. This article reviews the biological characteristics, diagnostic features, prognostic factors, treatment, and postoperative management of GISTs with hemorrhage.

Peritumoral edema associated with metastatic brain tumor

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Shirotani, Toshiki; Takiguchi, Hiroshi; Shima, Katsuji; Chigasaki, Hiroo; Tajima, Atsushi; Watanabe, Satoru.

1992-01-01

Computed tomographic (CT) examinations were performed in 94 lesions of 50 patients with metastatic brain tumors. Peritumoral edema (A E ) and tumor area (A T ) were measured using the planimetric method on the CT scan films that demonstrated maximum size of the tumor. Then, the volume of the peritumoral edema (V E ) and the surface area of the tumor (S T ) were claculated from these data. Eighty-three brain lesions from lung cancers were subdivided into 49 adenocarcinomas, 11 squamous cell carcinomas, 16 small cell carcinomas and 7 large cell carcinomas. Eleven metastatic tumors from breast cancers were all adenocarcinomas. There was statistical correlation between the surface area of tumor and the volume of the peritumoral edema for the adenocarcinoma (r=0.4043, p E /S T ratios in small cell carcinomas were smaller then those in non-small cell carcinomas, when the volume of the tumor was larger than 10 mm 3 . Accordingly, we suggest that the volume of the peritumoral edema in the small cell carcinoma is generally smaller than that in others. (author)

A Rare Gestational Trophoblastic Disease: Placental Site Trophoblastic Tumor

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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.

Dynamic association with donor cell filopodia and lipid-modification are essential features of Wnt8a during patterning of the zebrafish neuroectoderm.

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Marta Luz

Full Text Available BACKGROUND: Wnt proteins are conserved signaling molecules that regulate pattern formation during animal development. Many Wnt proteins are post-translationally modified by addition of lipid adducts. Wnt8a provides a crucial signal for patterning the anteroposterior axis of the developing neural plate in vertebrates. However, it is not clear how this protein propagates from its source, the blastoderm margin, to the target cells in the prospective neural plate, and how lipid-modifications might influence Wnt8a propagation and activity. RESULTS: We have dynamically imaged biologically active, fluorescently tagged Wnt8a in living zebrafish embryos. We find that Wnt8a localizes to membrane-associated, punctate structures in live tissue. In Wnt8a expressing cells, these puncta are found on filopodial cellular processes, from where the protein can be released. In addition, Wnt8a is found colocalized with Frizzled receptor-containing clusters on signal receiving cells. Combining in vitro and in vivo assays, we compare the roles of conserved Wnt8a residues in cell and non-cell-autonomous signaling activity and secretion. Non-signaling Wnt8 variants show these residues can regulate Wnt8a distribution in producing cell membranes and filopodia as well as in the receiving tissue. CONCLUSIONS: Together, our results show that Wnt8a forms dynamic clusters found on filopodial donor cell and on signal receiving cell membranes. Moreover, they demonstrate a differential requirement of conserved residues in Wnt8a protein for distribution in producing cells and receiving tissue and signaling activity during neuroectoderm patterning.

Dynamic association with donor cell filopodia and lipid-modification are essential features of Wnt8a during patterning of the zebrafish neuroectoderm.

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Luz, Marta; Spannl-Müller, Stephanie; Özhan, Günes; Kagermeier-Schenk, Birgit; Rhinn, Muriel; Weidinger, Gilbert; Brand, Michael

2014-01-01

Wnt proteins are conserved signaling molecules that regulate pattern formation during animal development. Many Wnt proteins are post-translationally modified by addition of lipid adducts. Wnt8a provides a crucial signal for patterning the anteroposterior axis of the developing neural plate in vertebrates. However, it is not clear how this protein propagates from its source, the blastoderm margin, to the target cells in the prospective neural plate, and how lipid-modifications might influence Wnt8a propagation and activity. We have dynamically imaged biologically active, fluorescently tagged Wnt8a in living zebrafish embryos. We find that Wnt8a localizes to membrane-associated, punctate structures in live tissue. In Wnt8a expressing cells, these puncta are found on filopodial cellular processes, from where the protein can be released. In addition, Wnt8a is found colocalized with Frizzled receptor-containing clusters on signal receiving cells. Combining in vitro and in vivo assays, we compare the roles of conserved Wnt8a residues in cell and non-cell-autonomous signaling activity and secretion. Non-signaling Wnt8 variants show these residues can regulate Wnt8a distribution in producing cell membranes and filopodia as well as in the receiving tissue. Together, our results show that Wnt8a forms dynamic clusters found on filopodial donor cell and on signal receiving cell membranes. Moreover, they demonstrate a differential requirement of conserved residues in Wnt8a protein for distribution in producing cells and receiving tissue and signaling activity during neuroectoderm patterning.

pH distribution in human tumors

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Thistlethwaite, A.J.; Leeper, D.B.; Moylan, D.J.; Nerlinger, R.E.

1984-01-01

pH distribution in human tumors is being determined to evaluate this parameter as a prognostic indicator of hyperthermia response. pH is measured by a modified glass pH electrode (21g, model MI 408, Microelectrodes, Inc., Londonderry, NH) inserted through an 18g open-ended Angiocath. Eight tumors have been evaluated to date; and of those, 3 were also assayed after the first heat treatment coincident with determination of blood flow. Tumors were between 2-5 cm, of various histologies, and of primary, recurrent, or metastatic origin. 2-4 measurements were made per tumor. Pretreatment readings were between 6.4 and 7.2 pH units. As tumor blood flow increased after 1 hr heating (41.5 - 43 0 ) pH rose 0.1 - 0.3 units. Normal rat muscle yields pH readings of 7.35 - 7.45. Although there was considerable heterogeneity of pH within tumors, accuracy and drift were not a problem. 5-15 min were required for pH stabilization after catheter insertion and <5 min after electrode insertion. A saline wheal was used for anesthesia to preclude modification of pH by anesthetics. Patient tolerance has not been a problems. This study suggests that human tumor tissue has a preponderance of areas more acidic than normal tissue. This may serve to sensitize tumor cells to hyperthermia and provide a prognostic indicator of tumor response

Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization.

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Daniel Y Joh

Full Text Available Successful treatment of brain tumors such as glioblastoma multiforme (GBM is limited in large part by the cumulative dose of Radiation Therapy (RT that can be safely given and the blood-brain barrier (BBB, which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs. GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ~1.3. Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature.

Avoiding Pitfalls in the Statistical Analysis of Heterogeneous Tumors

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Judith-Anne W. Chapman

2009-01-01

Full Text Available Information about tumors is usually obtained from a single assessment of a tumor sample, performed at some point in the course of the development and progression of the tumor, with patient characteristics being surrogates for natural history context. Differences between cells within individual tumors (intratumor heterogeneity and between tumors of different patients (intertumor heterogeneity may mean that a small sample is not representative of the tumor as a whole, particularly for solid tumors which are the focus of this paper. This issue is of increasing importance as high-throughput technologies generate large multi-feature data sets in the areas of genomics, proteomics, and image analysis. Three potential pitfalls in statistical analysis are discussed (sampling, cut-points, and validation and suggestions are made about how to avoid these pitfalls.

Differentiation of phyllodes tumors versus fibroadenomas

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Yilmaz, E.; Sal, S. [Dokuz Eyluel Univ. Hospital, Izmir (Turkey). Dept. of Radiology; Lebe, B. [Dokuz Eyluel Univ. Hospital, Izmir (Turkey). Dept. of Pathology

2002-04-01

Purpose: To determine if mammographic and sonographic findings allow discrimination between phyllodes tumor and large sized fibroadenoma, which mimic each other in the clinical, radiologic and histopathologic appearances. Material and Methods: Thirty-one histopathologically proven masses including 12 phyllodes tumors and 19 fibroadenomas 3 cm or greater in diameter were compared. In total 28 women were retrospectively evaluated by mammography and pre-operative sonography. Results: Mammography revealed a high-density mass compared with surrounding fibroglandular breast tissue to be present in 9 of the 12 (75%) phyllodes tumors and 7 of the 19 (37%) fibroadenomas. At sonography a mass, which had a round or lobulated shape, marked posterior acoustic enhancement and intramural cystic areas, were statistically significantly more likely to be phyllodes tumors than fibroadenomas. None of the other mammographic or sonographic characteristics proved to be useful in differentiating phyllodes tumors and fibroadenomas. Conclusion: Although masses of high density at mammography, circumscribed border associated with posterior acoustic enhancement and internal cystic areas at sonography should suggest the diagnosis of phyllodes tumors rather than large sized fibroadenomas, there was a substantial overlap in the mammographic and sonographic characteristics of these two tumors. Therefore, an excisional biopsy would be necessary for equivocal masses.

Differentiation of phyllodes tumors versus fibroadenomas

International Nuclear Information System (INIS)

Yilmaz, E.; Sal, S.; Lebe, B.

2002-01-01

Purpose: To determine if mammographic and sonographic findings allow discrimination between phyllodes tumor and large sized fibroadenoma, which mimic each other in the clinical, radiologic and histopathologic appearances. Material and Methods: Thirty-one histopathologically proven masses including 12 phyllodes tumors and 19 fibroadenomas 3 cm or greater in diameter were compared. In total 28 women were retrospectively evaluated by mammography and pre-operative sonography. Results: Mammography revealed a high-density mass compared with surrounding fibroglandular breast tissue to be present in 9 of the 12 (75%) phyllodes tumors and 7 of the 19 (37%) fibroadenomas. At sonography a mass, which had a round or lobulated shape, marked posterior acoustic enhancement and intramural cystic areas, were statistically significantly more likely to be phyllodes tumors than fibroadenomas. None of the other mammographic or sonographic characteristics proved to be useful in differentiating phyllodes tumors and fibroadenomas. Conclusion: Although masses of high density at mammography, circumscribed border associated with posterior acoustic enhancement and internal cystic areas at sonography should suggest the diagnosis of phyllodes tumors rather than large sized fibroadenomas, there was a substantial overlap in the mammographic and sonographic characteristics of these two tumors. Therefore, an excisional biopsy would be necessary for equivocal masses

Effects of exercise on tumor physiology and metabolism.

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Pedersen, Line; Christensen, Jesper Frank; Hojman, Pernille

2015-01-01

Exercise is a potent regulator of a range of physiological processes in most tissues. Solid epidemiological data show that exercise training can reduce disease risk and mortality for several cancer diagnoses, suggesting that exercise training may directly regulate tumor physiology and metabolism. Here, we review the body of literature describing exercise intervention studies performed in rodent tumor models and elaborate on potential mechanistic effects of exercise on tumor physiology. Exercise has been shown to reduce tumor incidence, tumor multiplicity, and tumor growth across numerous different transplantable, chemically induced or genetic tumor models. We propose 4 emerging mechanistic effects of exercise, including (1) vascularization and blood perfusion, (2) immune function, (3) tumor metabolism, and (4) muscle-to-cancer cross-talk, and discuss these in details. In conclusion, exercise training has the potential to be a beneficial and integrated component of cancer management, but has yet to fully elucidate its potential. Understanding the mechanistic effects of exercise on tumor physiology is warranted. Insight into these mechanistic effects is emerging, but experimental intervention studies are still needed to verify the cause-effect relationship between these mechanisms and the control of tumor growth.

Influence of WR-2721 on metastatic tumor spread after irradiation

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Ullrich, R.L.; Jernigan, M.C.; Yuhas, J.M.

1975-01-01

The Line 1 alveolar cell carcinoma is a transplantable murine tumor which, unlike most others, kills the host by means of metastatic spread. Attempts to cure this tumor with localized radiation therapy often fail, in spite of local tumor control, because the metastases evade the treatment. These facts suggest that host-tumor interactions may play a particularly important role in determining the ultimate survival of the tumor bearing animal. In order to initially evaluate the possible importance of normal regional tissues in host-tumor interactions the influence of WR-2721, a radioprotective drug, was examined for local tumor control and subsequent survival of the tumor bearing animal after localized radiation. Results indicated that WR-2721 can decrease metastasis. (U.S.)

Isolated tumor endothelial cells maintain specific character during long-term culture

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Matsuda, Kohei; Ohga, Noritaka; Hida, Yasuhiro; Muraki, Chikara; Tsuchiya, Kunihiko; Kurosu, Takuro; Akino, Tomoshige; Shih, Shou-Ching

2010-01-01

Tumor angiogenesis is necessary for solid tumor progression and metastasis. Increasing evidence indicates that tumor endothelial cells (TECs) are more relevant to the study of tumor angiogenesis than normal endothelial cells (NECs) because their morphologies and gene expression are different from NECs. However, it is challenging to isolate and culture large numbers of pure ECs from tumor tissue since the percentage of ECs is only about 1-2% and tumor cells and fibroblasts easily overgrow them. In addition, there has been concern that isolated TECs may lose their special phenotype once they are dissociated from tumor cells. In this study, we have successfully purified murine TECs from four different human tumor xenografts and NECs from murine dermal tissue. Isolated ECs expressed endothelial markers, such as CD31, VE-cadherin (CD144), and endoglin (CD105), for more than 3 months after isolation. TECs maintained tumor endothelial-specific markers, such as tumor endothelial marker 8 (TEM8) and aminopeptidase N (APN), as in tumor blood vessels in vivo. In addition, TECs were more proliferative and motile than NECs. TECs showed a higher response to VEGF and higher expression of VEGF receptors-1 and -2 than NECs did. Stem cell antigen-1 was up-regulated in all four TECs, suggesting that they have a kind of stemness. Cultured TECs maintain distinct biological differences from NECs as in vivo. In conclusion, it was suggested that TECs are relevant material for tumor angiogenesis research.

Supratentorial primary intra-axial tumors in children. MR and CT evaluation

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Higano, S.; Takahashi, S.; Kurihara, N.; Singh, L.N.; Yamada, S.; Ishii, K.; Matsumoto, K.; Shirane, R.; Katakura, R.

1997-01-01

Purpose: To evaluate the MR and CT features of pediatric supratentorial intra-axial tumors with respect to different diagnosis and the role of each investigation modality. Material and Methods: MR and CT findings in 40 children with 12 types of pathologically proven histological tumors were reviewed. Results: The location of tumors might be one clue to differential diagnosis. In our material, cysts (60%), calcifications (45%), and intratumoral hemorrhages (27%) were found in the tumors. Characteristic features noted in some lesions included: peritumoral hemosiderin deposition in cavernous angiomas; intratumoral flow void in a choroid plexus carcinoma and in glioblastomas; and hemicerebral atrophy in germinomas. A comparison between malignant and benign tumors showed perifocal edema and a mass effect to be signifcantly more common in malignant lesions. Homogeneous enhancement suggested a benign tumor and an inhomogeneous pattern represented malignancy, while the lack of obvious enhancement did not always suggest benignity. Intratumoral calcium deposition was a not uncommon finding in malignant tumors. Conclusion: In most cases, the exact diagnosis should be made hy histological examination but it is important for treatment planning that the appropriate depiction of tumor extension and tissue characterization be made by MR and CT. (orig.)

The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients

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Medrek, Catharina; Pontén, Fredrik; Jirström, Karin; Leandersson, Karin

2012-01-01

Tumor associated macrophages (TAMs) are alternatively activated macrophages that enhance tumor progression by promoting tumor cell invasion, migration and angiogenesis. TAMs have an anti-inflammatory function resembling M2 macrophages. CD163 is regarded as a highly specific monocyte/macrophage marker for M2 macrophages. In this study we evaluated the specificity of using the M2 macrophage marker CD163 as a TAM marker and compared its prognostic value with the more frequently used pan-macrophage marker CD68. We also analyzed the prognostic value of the localization of CD163 + and CD68 + myeloid cells in human breast cancer. The extent of infiltrating CD163 + or CD68 + myeloid cells in tumor nest versus tumor stroma was evaluated by immunohistochemistry in tissue microarrays with tumors from 144 breast cancer cases. Spearman’s Rho and χ 2 tests were used to examine the correlations between CD163 + or CD68 + myeloid cells and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the impact of CD163 + and CD68 + myeloid cells in tumor stroma and tumor nest, respectively, on recurrence free survival, breast cancer specific and overall survival. We found that infiltration of CD163 + and CD68 + macrophages into tumor stroma, but not into tumor nest, were of clinical relevance. CD163 + macrophages in tumor stroma positively correlated with higher grade, larger tumor size, Ki67 positivity, estrogen receptor negativity, progesterone receptor negativity, triple-negative/basal-like breast cancer and inversely correlated with luminal A breast cancer. Some CD163 + areas lacked CD68 expression, suggesting that CD163 could be used as a general anti-inflammatory myeloid marker with prognostic impact. CD68 + macrophages in tumor stroma positively correlated to tumor size and inversely correlated to luminal A breast cancer. More importantly, CD68 in tumor stroma was an independent prognostic factor for reduced breast cancer

Floating tumor debris. A cause of intermittent biliary obstruction.

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Roslyn, J J; Kuchenbecker, S; Longmire, W P; Tompkins, R K

1984-11-01

Tumor debris, free-floating in the major biliary ductal system, is a cause of intermittent biliary obstruction that has previously not been recognized. Six patients had hepatic neoplasms with episodic jaundice and/or cholangitis due to floating tumor debris. Diagnosis included metastatic adenocarcinoma of the colon (n = 3), cholangiocarcinoma (n = 1), hepatocellular carcinoma (n = 1), and cavernous hemangioma (n = 1). All patients underwent biliary exploration, with hepatic resection and transhepatic intubation in two and T-tube placement in four. One patient died in the early postoperative period, and the major complication rate in the five survivors was 0%. Four of the five survivors had no further episodes suggestive of major bile duct obstruction. Our experience emphasizes the importance of distinguishing extrahepatic obstruction secondary to tumor debris from the more common causes of jaundice in patients with tumors and suggests that safe and effective palliation can be achieved in these patients.

Guidelines for imaging retinoblastoma: imaging principles and MRI standardization

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Graaf, Pim de; Rodjan, Firazia; Castelijns, Jonas A. [VU University Medical Center, Department of Radiology, Amsterdam (Netherlands); Goericke, Sophia [University Hospital, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Galluzzi, Paolo [Azienda Ospedaliera e Universitaria Senese, Policlinico ' ' Le Scotte' ' , Unit of Diagnostic and Therapeutic Neuroradiology, Siena (Italy); Maeder, Philippe [CHUV, Service de Radiodiagnostic et Radiologie Interventionelle, Lausanne (Switzerland); Brisse, Herve J. [Institut Curie, Departement d' Imagerie, Paris (France)

2012-01-15

Retinoblastoma is the most common intraocular tumor in children. The diagnosis is usually established by the ophthalmologist on the basis of fundoscopy and US. Together with US, high-resolution MRI has emerged as an important imaging modality for pretreatment assessment, i.e. for diagnostic confirmation, detection of local tumor extent, detection of associated developmental malformation of the brain and detection of associated intracranial primitive neuroectodermal tumor (trilateral retinoblastoma). Minimum requirements for pretreatment diagnostic evaluation of retinoblastoma or mimicking lesions are presented, based on consensus among members of the European Retinoblastoma Imaging Collaboration (ERIC). The most appropriate techniques for imaging in a child with leukocoria are reviewed. CT is no longer recommended. Implementation of a standardized MRI protocol for retinoblastoma in clinical practice may benefit children worldwide, especially those with hereditary retinoblastoma, since a decreased use of CT reduces the exposure to ionizing radiation. (orig.)

Magnetic resonance imaging of nasopharyngeal malignant tumors

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Sakakihara, Junji; Kanoh, Naoyuki; Hayakawa, Katsumi.

1988-01-01

Magnetic Resonance Imaging (MRI) was used in the examination of three patients with nasopharyngeal malignant tumor and cranial nerve symptoms. Coronal and saggital sections were very useful for determining skull base invasion. Its high contrast resolution enabled us to visualize several cranial nerves directly. Differentiation between tumor and effusion in the paranasal sinuses was easy especially in T2 weighted images. Bone destruction could also be detected as bone marrow replacement by tumor or as interruption of the black line of compact bone. Local relationships of tumor and large blood vessels were visualized by MRI without invasive contrast enhancing methods. Despite such advantages, in one patient whose symptoms were highly suggestive of cranial invasion, no cranial invasion was detected by CT or MRI. (author)

Transformation of benign fibroadenoma to malignant phyllodes tumor

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Sanders, Linda M; Daigle, Megan E; Tortora, Matthew; Panasiti, Ryane

2015-01-01

The transformation of a benign fibroadenoma into a phyllodes tumor is uncommon and unpredictable. We report the case of a 40-year-old woman with a core biopsy proven fibroadenoma that underwent transformation into a malignant phyllodes tumor after 3 years of size stability. We present ultrasound and magnetic resonance images, as well as pathology slides from core biopsy and surgical excision, to illustrate this transformation. It has been suggested that phyllodes tumors may be misdiagnosed as fibroadenomas by core biopsy. However, in this case, pathology supports correct initial diagnosis of fibroadenoma and demonstrates a portion of the original fibroadenoma along the periphery of the malignant phyllodes tumor

Reduced glucocorticoid receptor expression predicts bladder tumor recurrence and progression.

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Ishiguro, Hitoshi; Kawahara, Takashi; Zheng, Yichun; Netto, George J; Miyamoto, Hiroshi

2014-08-01

To assess the levels of glucocorticoid receptor (GR) expression in bladder tumors because the status and its prognostic value remain largely unknown. We immunohistochemically stained for GR in bladder tumor and matched non-neoplastic bladder tissue specimens. Overall, GR was positive in 129 (87%) of 149 urothelial tumors, which was significantly (P=.026) lower than in non-neoplastic urothelium (90 [96%] of 94). Forty-two (79%) of 53 low-grade tumors vs 45 (47%) of 96 high-grade carcinomas (Pcancer-specific survival of MI tumors (P=.067). Multivariate analysis identified low GR expression as a strong predictor for recurrence of NMI tumors (P=.034). GR expression was downregulated in bladder tumors compared with nonneoplastic bladder tumors and in high-grade/MI tumors compared with low-grade/NMI tumors. Decreased expression of GR, as an independent prognosticator, predicted recurrence of NMI tumors. These results support experimental evidence suggesting an inhibitory role of GR signals in bladder cancer outgrowth. Copyright© by the American Society for Clinical Pathology.

Tumor of granular cells of esophagus

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Gonzalez Fabian, Licet; Diaz Anaya, Amnia; Perez de la Torre, Georgina

2010-01-01

Granular cells tumors are rare and asymptomatic lesions and by general, it is an incidental finding en high or low endoscopy. They were described for the first time by Abrikossoff in 1926. The more frequent locations are the buccal mucosa, dermis and subcutaneous cellular tissue, most of these tumors has a benign origin. This is the case of a woman aged 44 with a pyrosis history from a year ago; by high endoscopy it is noted a 8 mm lesion distal to esophagus and confirmed by histological study of granular cells tumor. Elective treatment of this lesion is the endoscopic polypectomy. Despite that the malign potential is low; we suggested a close clinical and endoscopic follow-up.

Tumor Suppression and Promotion by Autophagy

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Yenniffer Ávalos

2014-01-01

Full Text Available Autophagy is a highly regulated catabolic process that involves lysosomal degradation of proteins and organelles, mostly mitochondria, for the maintenance of cellular homeostasis and reduction of metabolic stress. Problems in the execution of this process are linked to different pathological conditions, such as neurodegeneration, aging, and cancer. Many of the proteins that regulate autophagy are either oncogenes or tumor suppressor proteins. Specifically, tumor suppressor genes that negatively regulate mTOR, such as PTEN, AMPK, LKB1, and TSC1/2 stimulate autophagy while, conversely, oncogenes that activate mTOR, such as class I PI3K, Ras, Rheb, and AKT, inhibit autophagy, suggesting that autophagy is a tumor suppressor mechanism. Consistent with this hypothesis, the inhibition of autophagy promotes oxidative stress, genomic instability, and tumorigenesis. Nevertheless, autophagy also functions as a cytoprotective mechanism under stress conditions, including hypoxia and nutrient starvation, that promotes tumor growth and resistance to chemotherapy in established tumors. Here, in this brief review, we will focus the discussion on this ambiguous role of autophagy in the development and progression of cancer.

Tumor suppression and promotion by autophagy.

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Ávalos, Yenniffer; Canales, Jimena; Bravo-Sagua, Roberto; Criollo, Alfredo; Lavandero, Sergio; Quest, Andrew F G

2014-01-01

Autophagy is a highly regulated catabolic process that involves lysosomal degradation of proteins and organelles, mostly mitochondria, for the maintenance of cellular homeostasis and reduction of metabolic stress. Problems in the execution of this process are linked to different pathological conditions, such as neurodegeneration, aging, and cancer. Many of the proteins that regulate autophagy are either oncogenes or tumor suppressor proteins. Specifically, tumor suppressor genes that negatively regulate mTOR, such as PTEN, AMPK, LKB1, and TSC1/2 stimulate autophagy while, conversely, oncogenes that activate mTOR, such as class I PI3K, Ras, Rheb, and AKT, inhibit autophagy, suggesting that autophagy is a tumor suppressor mechanism. Consistent with this hypothesis, the inhibition of autophagy promotes oxidative stress, genomic instability, and tumorigenesis. Nevertheless, autophagy also functions as a cytoprotective mechanism under stress conditions, including hypoxia and nutrient starvation, that promotes tumor growth and resistance to chemotherapy in established tumors. Here, in this brief review, we will focus the discussion on this ambiguous role of autophagy in the development and progression of cancer.

Risk interrelationship among multiple primary tumors

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Safi, Mohammed; Sun, Xiuhua; Wang, Lifen; Zhang, Xinwei; Song, Jicheng; Ameen, Mohammed

2018-01-01

Abstract Rationale: Along with advanced management in oncology, great progress has been recently achieved in the studies of multiple primary tumors. Several reports have studied the coexistence between lymphoma and either renal cell carcinoma (RCC) or Warthin tumor. However, the level of coexistence between these cases remains unclear due to the absence of a distinct link between them. Patient concerns: We present a unique case of multiple primary tumors (lymphoma, RCC, and Warthin tumor) in an 80-year-old man and a review of the literature on the coexistence of RCC with lymphoma and lymphoma with Warthin tumor. Diagnosis: With a history of RCC, the patient had a freely movable lump under his left ear, and the pathological report indicated Hodgkin lymphoma and Warthin tumor. Intervention: RCC and Warthin tumor of the patient were surgically treated, followed by 2 cycles (14 days per cycle) of Epirubicin 40 mg day 1, Bleomycin 8 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1. The chemotherapy protocol was then changed to Epirubicin 40 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1 for 7 cycles. Outcomes: After the last day of chemotherapy, the patient showed a complete response. Lessons: To the best of our knowledge, this paper is the first to report a case of multiple primary tumors with a complete response. For their early detection, favorable prognosis, and correlation identification, we suggest a transitive relation between these coexisting tumors. Therefore, similar studies should be conducted. PMID:29642151

The role of immunohistochemistry in medullomyoblastoma--a case series highlighting divergent differentiation.

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Sachdeva, Man Updesh S; Vankalakunti, Mahesha; Rangan, Aruna; Radotra, Bishan D; Chhabra, Rajesh; Vasishta, Rakesh K

2008-04-25

To analyse the histo-morphology of cases of medullomyoblastoma and identifying its divergent differentiation. A retrospective review of all cases reported as medulloblastoma between the period of Jan 2000 to Dec 2006 was carried out on Hematoxylin and eosin (H & E) stained slides. The cases were screened on light microscopy for primitive neuroectodermal component of a medulloblastoma accompanied by areas of "myoid" differentiation, identified on the basis of presence of strap cells (indicating a clear skeletal muscle differentiation) and/or large anaplastic cells with vescicular nuclei and moderate to abundant amount of eosinophilic cytoplasm. All these cases were subjected to a panel of immunohistochemical stains, including Desmin, GFAP, NFP, HMB45, SMA, S100, CK and EMA. Ultrastructural analysis was done on tissue obtained from paraffin blocks in 2 cases. Male predominance (M:F = 5:1) was noted with an incidence of five percent of all cases of medulloblastoma (6 out of 120 cases) over a period of 6 years. Primitive neuroectodermal areas were accompanied with areas of "myoid" differentiation, 5 cases showing strap cells. Two cases with epithelial and cartilaginous differentiation were seen. Three cases showed focal melanocytic differentiation, identified only on HMB45 immunostaining. Four cases showed glial differentiation. Neuronal differentiation again was very focally seen in two cases, of which one was identified only by NFP immunostain. Seventh case is included in the study, however it is not considered to calculate incidence as it occurred beyond the period of 6 years of records search. Medullomyoblastoma is a rare childhood tumor of cerebellum. Majority of cases reveal divergent differentiation, which are identified with the help of panel of immunostains indicating multi-potential nature of primitive neuroectodermal cells.

Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.

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Gao, Ning; Bozeman, Erica N; Qian, Weiping; Wang, Liya; Chen, Hongyu; Lipowska, Malgorzata; Staley, Charles A; Wang, Y Andrew; Mao, Hui; Yang, Lily

2017-01-01

The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

Determinates of tumor response to radiation: Tumor cells, tumor stroma and permanent local control

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Li, Wende; Huang, Peigen; Chen, David J.; Gerweck, Leo E.

2014-01-01

Background and purpose: The causes of tumor response variation to radiation remain obscure, thus hampering the development of predictive assays and strategies to decrease resistance. The present study evaluates the impact of host tumor stromal elements and the in vivo environment on tumor cell kill, and relationship between tumor cell radiosensitivity and the tumor control dose. Material and methods: Five endpoints were evaluated and compared in a radiosensitive DNA double-strand break repair-defective (DNA-PKcs −/− ) tumor line, and its DNA-PKcs repair competent transfected counterpart. In vitro colony formation assays were performed on in vitro cultured cells, on cells obtained directly from tumors, and on cells irradiated in situ. Permanent local control was assessed by the TCD 50 assay. Vascular effects were evaluated by functional vascular density assays. Results: The fraction of repair competent and repair deficient tumor cells surviving radiation did not substantially differ whether irradiated in vitro, i.e., in the absence of host stromal elements and factors, from the fraction of cells killed following in vivo irradiation. Additionally, the altered tumor cell sensitivity resulted in a proportional change in the dose required to achieve permanent local control. The estimated number of tumor cells per tumor, their cloning efficiency and radiosensitivity, all assessed by in vitro assays, were used to predict successfully, the measured tumor control doses. Conclusion: The number of clonogens per tumor and their radiosensitivity govern the permanent local control dose

A sequence-based survey of the complex structural organization of tumor genomes

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Collins, Colin; Raphael, Benjamin J.; Volik, Stanislav; Yu, Peng; Wu, Chunxiao; Huang, Guiqing; Linardopoulou, Elena V.; Trask, Barbara J.; Waldman, Frederic; Costello, Joseph; Pienta, Kenneth J.; Mills, Gordon B.; Bajsarowicz, Krystyna; Kobayashi, Yasuko; Sridharan, Shivaranjani; Paris, Pamela; Tao, Quanzhou; Aerni, Sarah J.; Brown, Raymond P.; Bashir, Ali; Gray, Joe W.; Cheng, Jan-Fang; de Jong, Pieter; Nefedov, Mikhail; Ried, Thomas; Padilla-Nash, Hesed M.; Collins, Colin C.

2008-04-03

The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using End Sequencing Profiling (ESP), which relies on paired-end sequencing of cloned tumor genomes. In this study, brain, breast, ovary and prostate tumors along with three breast cancer cell lines were surveyed with ESP yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization (FISH) confirmed translocations and complex tumor genome structures that include coamplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms (SNPs) revealed candidate somatic mutations and an elevated rate of novel SNPs in an ovarian tumor. These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than previously appreciated and that genomic fusions including fusion transcripts and proteins may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.

Does Tumor Development Follow a Programmed Path?

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Austin, Robert

2011-03-01

The initiation and progression of a tumor is a complex process, resembling the growth of a embryo in terms of the stages of development and increasing differentiation and somatic evolution of constituent cells in the community of cells that constitute the tumor. Typically we view cancer cells as rogue individuals violating the rules of the games played within an organism, but I would suggest that what we see is a programmed and algorithmic process. I will then question If tumor progression is dominated by the random acquisition of successive survival traits, or by a systematic and sequential unpacking of ``weapons'' from a pre-adapted ``toolkit'' of genetic and epigenetic potentialities? Can we then address this hypothesis by data mining solid tumors layer by layer? Support of the NSF and the NCI is gratefully acknowledged.

Suggestion for the prostatic fossa clinical target volume in adjuvant or salvage radiotherapy after a radical prostatectomy

International Nuclear Information System (INIS)

Park, Jun Su; Park, Won; Pyo, Hong Ryull; Park, Byung Kwan; Park, Sung Yoon; Choi, Han Yong; Lee, Hyun Moo; Jeon, Seong Soo; Seo, Seong Il; Jeong, Byong Chang; Jeon, Hwang Gyun

2014-01-01

Background and purpose: To assess the location of recurrent tumors and suggest the optimal target volume in adjuvant or salvage radiotherapy (RT) after a radical prostatectomy (RP). Material and methods: From January 2000 to December 2012, 113 patients had been diagnosed with suspected recurrent prostate cancer by MRI scan and received salvage RT in the Samsung Medical Center. This study assessed the location of the suspected tumor recurrences and used the inferior border of the pubic symphysis as a point of reference. Results: There were 118 suspect tumor recurrences. The most common site of recurrence was the anastomotic site (78.8%), followed by the bladder neck (15.3%) and retrovesical area (5.9%). In the cranial direction, 106 (87.3%) lesions were located within 30 mm of the reference point. In the caudal direction, 12 lesions (10.2%) were located below the reference point. In the transverse plane, 112 lesions (94.9%) were located within 10 mm of the midline. Conclusions: A MRI scan acquired before salvage RT is useful for the localization of recurrent tumors and the delineation of the target volume. We suggest the optimal target volume in adjuvant or salvage RT after RP, which includes 97% of suspected tumor recurrences

Tumor-Derived Exosomes and Their Role in Cancer Progression.

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Whiteside, Theresa L

2016-01-01

Tumor cells actively produce, release, and utilize exosomes to promote tumor growth. Mechanisms through which tumor-derived exosomes subserve the tumor are under intense investigation. These exosomes are information carriers, conveying molecular and genetic messages from tumor cells to normal or other abnormal cells residing at close or distant sites. Tumor-derived exosomes are found in all body fluids. Upon contact with target cells, they alter phenotypic and functional attributes of recipients, reprogramming them into active contributors to angiogenesis, thrombosis, metastasis, and immunosuppression. Exosomes produced by tumors carry cargos that in part mimic contents of parent cells and are of potential interest as noninvasive biomarkers of cancer. Their role in inhibiting the host antitumor responses and in mediating drug resistance is important for cancer therapy. Tumor-derived exosomes may interfere with cancer immunotherapy, but they also could serve as adjuvants and antigenic components of antitumor vaccines. Their biological roles in cancer development or progression as well as cancer therapy suggest that tumor-derived exosomes are critical components of oncogenic transformation. © 2016 Elsevier Inc. All rights reserved.

An inguinal hernia sac tumor of extrahepatic cholangiocarcinoma origin

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Yamazaki Hidehiro

2006-03-01

Full Text Available Abstract Background Metastatic hernia sac tumor from biliary malignancy is extremely rare with only one such case previously reported. We herein report an additional case of extrahepatic cholangiocarcinoma presenting as a hernia sac tumor. Case presentation A 78-year-old man presented with an irreducible right inguinal hernia associated with a firm tumor, 2.0 cm in diameter. A computed tomography scan demonstrated a soft tissue density mass with heterogeneous enhancement within the right inguinal canal. The patient underwent a hernia repair and the hernia sac tumor was resected. Histological examination of the tumor revealed a metastatic adenocarcinoma suggesting the tumor was of pancreato-biliary origin. Further investigation using imaging studies disclosed a primary tumor in the upper bile duct. The patient died of the disease nine months after the resection. Conclusion Hernia sac tumors should be considered when an irreducible, growing mass appears within an inguinal hernia. Computed tomography may be useful for the early detection of hernia sac tumors from undiagnosed intra-abdominal malignancies.

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

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Wagner LM

2017-04-01

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

Bone tumor

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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 ...

Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth.

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McIntyre, Alan; Hulikova, Alzbeta; Ledaki, Ioanna; Snell, Cameron; Singleton, Dean; Steers, Graham; Seden, Peter; Jones, Dylan; Bridges, Esther; Wigfield, Simon; Li, Ji-Liang; Russell, Angela; Swietach, Pawel; Harris, Adrian L

2016-07-01

Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extracellularly by CA9 could exacerbate the intracellular acidity produced by hypoxic conditions, perhaps compromising cell growth and viability as a result. In 8 of 10 cancer cell lines, we found that hypoxia induced the expression of at least one bicarbonate transporter. The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1α and HIF2α activity for their expression. In cancer cell spheroids, SLC4A4 or SLC4A9 disruption by either genetic or pharmaceutical approaches acidified intracellular pH and reduced cell growth. Furthermore, treatment of spheroids with S0859, a small-molecule inhibitor of sodium-driven bicarbonate transporters, increased apoptosis in the cell lines tested. Finally, RNAi-mediated attenuation of SLC4A9 increased apoptosis in MDA-MB-231 breast cancer spheroids and dramatically reduced growth of MDA-MB-231 breast tumors or U87 gliomas in murine xenografts. Our findings suggest that disrupting pH homeostasis by blocking bicarbonate import might broadly relieve the common resistance of hypoxic tumors to anticancer therapy. Cancer Res; 76(13); 3744-55. ©2016 AACR. ©2016 American Association for Cancer Research.

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

Estrogen receptor beta, a possible tumor suppressor involved in ovarian carcinogenesis

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Lazennec, Gwendal

2006-01-01

Ovarian cancer is one of the leading cause of death from gynecological tumors in women. Several lines of evidence suggest that estrogens may play an important role in ovarian carcinogenesis, through their receptors, ERα and ERβ. Interestingly, malignant ovarian tumors originating from epithelial surface constitute about 90% of ovarian cancers and expressed low levels of ERβ, compared to normal tissues. In addition, restoration of ERβ in ovarian cancer cells, leads to strong inhibition of their proliferation and invasion, while apoptosis is enhanced. In this manuscript, recent data suggesting a possible tumor-suppressor role for ERβ in ovarian carcinogenesis are discussed. PMID:16399219

Tumor vascularity under hypertension induced by intravenous infusion of angiotensin II

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Kato, Toshio

1986-01-01

We studied whether or not the blood flow of tumors was increased by AT-II-induced hypertension in patients. Angiograms of 51 patients before and after intravenous infusion of AT-II were compared carefully from 5 points of view which suggested increased tumor blood flow. These were, 1) Contraction of small arteries feeding normal tissue, 2) Enhanced visualization of tumor vessels, 3) Enhanced visualization of tumor stain, 4) Increase of venous return from tumor-bearing region, and 5) Enhanced visualization of metastatic lymph nodes. The results were as follows. Contractions of small arteries feeding normal tissue [Finding 1)] were observed in 34 cases (66.6 %) and enhanced visualization of tumor vessels, tumor stain and so on [Finding 2)-5] were observed in 18 cases (35.3 %). Concequently, an increase of tumor blood flow was suggested in 40 cases (78.4 %). Blood flow of human tumors and normal tissue during the full course of induced hypertension with AT-II were measures by means of radionuclide angiography ( 99m Tc-RBC) and laser Doppler velocimetry. Activities of the tumor-bearing region and the mid-portion of the thigh (selected as normal tissue) were measured continuously by collimated scintillation detectors. In 26 measurements out of 31 (83.8 %), the activity in the thigh decreased promptly and returned to the baseline synchronously with the rise and fall of blood pressure. In contrast, in 11 measurements (34.4 %) the activity of the tumor-bearing region increased and returned to the baseline accompanying the change of blood pressure. Preliminary observations using laser Doppler velocimetry revealed an increase of blood flow in 5 tumors. In conclusion, the blood flow of human tumors was increased by AT-II, in agreement with the findings in animal tumors. (J.P.N.)

Hyperdensity liver tumor on plain CT

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Hirota, Shozo; Hanaguri, Katsuro [Kochi Municipal Central Hospital (Japan); Shimizu, Masahumi; Sako, Masao; Harada, Yasushi

1984-12-01

Most liver tumors on plain CT have been recognized as low density or iso-density masses. Sometimes calcified high density masses were shown on plain CT in case of cysts or metastatic liver tumors. However, hyperdensity mass of the liver on CT, of which the density was a little higher than surrounding tissues, was very rare. Recently 7 patients with hyperdensity liver masses on plain CT were experienced: 6 hepatocellular carcinomas and 1 hepatic cavernous hemangioma. A single hyperdensity mass was shown in 4 patients, a hyperdensity mass of multiple hepatic tumors was shown in 2 patients, and some hyperdensity masses of multiple hepatic tumors were shown in 1 patient. Lesions are classified in 3 types according to the appearance of hyperdensity masses: diffuse hyperdensity all over the mass, ring like hyperdensity, creascent like hyperdensity. Intravenous contrast enhancement was performed in 2 patients: one with a primary hepatocellular carcinoma, and another with a hepatic cavernous hemangioma. In the former case the tumor margin had changed unclear, in the latter case the tumor was markedly enhanced. Our results revealed that hyperdensity liver tumors were divided into 2 types: One type, shown in a cavernous hemangioma with fatty liver, demonstrated relative hyperdensity due to lower density of the surrounding tissue. Another type, shown in 6 hepatocellular carcinomas, showed hyperdensity since the density of the tumor was hyperdensity relative to the surrounding tissue of the liver. It was suggested that the tumor with the latter type had been strongly probable of malignant one, and been recommended to receive further examination. Cause of hyperdensity was thought to be due to hemorrhage, though microcalcification could not be denyed. In Japan, no hyperdensity liver tumor had been reported partly due to a wide window width with which CT photographs were taken.

Giant cell tumor of soft tissue: a case report with emphasis on MR imaging

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Lee, Moon Young; Jee, Won-Hee [The Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, School of Medicine, Seocho-gu, Seoul (Korea, Republic of); Jung, Chan Kwon [The Catholic University of Korea, Department of Pathology, Seoul St. Mary' s Hospital, College of Medicine, Seocho-gu, Seoul (Korea, Republic of); Yoo, Ie Ryung [The Catholic University of Korea, Department of Nuclear Medicine, Seoul St. Mary' s Hospital, College of Medicine, Seocho-gu, Seoul (Korea, Republic of); Chung, Yang-Guk [The Catholic University of Korea, Department of Orthopedic Surgery, Seoul St. Mary' s Hospital, College of Medicine, Seocho-gu, Seoul (Korea, Republic of)

2015-04-03

Giant cell tumor of soft tissue is a rare neoplasm, histologically resembling giant cell tumor of bone. In this report, we describe a deep and solid giant cell tumor of soft tissue interpreted as a benign soft tissue tumor based on magnetic resonance (MR) findings with hypointense to intermediate signals on T2-weighted images and impeded diffusivity (water movement) on diffusion-weighted imaging (DWI), which could suggest a giant-cell-containing benign soft tissue tumor, despite the malignancy suggested by {sup 18}F-fluorodeoxyglucose positron emission tomography-computed tomography in a 35-year-old male. To our knowledge, this report introduces the first deep, solid giant cell tumor of soft tissue with MR features of a giant-cell-containing benign soft tissue tumor, despite the malignancy-mimicking findings on {sup 18}F-FDG PET-CT. (orig.)

Regional cerebral blood flow in the patient with brain tumor

International Nuclear Information System (INIS)

Tsuchida, Shohei

1993-01-01

Regional cerebral blood flow (rCBF) was measured with xenon-enhanced CT (Xe-CT) in 21 cases of intracranial tumors (13 meningiomas, 5 gliomas, 3 metastatic brain tumors). Peritumoral edema was graded as mild, moderate or severe based on the extent of edema on CT and MRI. According to intratumoral blood flow distribution patterns, three patterns were classified as central type with relatively high blood flow at the center of the tumor, homogeneous type with an almost homogeneous blood flow distribution, and marginal type with relatively high blood flow at the periphery of the tumor. High grade astrocytoma and metastatic brain tumor showed marginal type blood flow and moderate or severe edema except in one case. Five meningiomas with severe peritumoral edema revealed marginal type blood flow and four with mild peritumoral edema showed central type blood flow, except for one case. No correlation was found between the extent of peritumoral edema and histological subtype, tumor size, location, duration of clinical history, vascularization on angiogram, and mean blood flow in the tumor. These results suggest that blood flow distribution patterns within the tumor may affect the extension of peritumoral edema. Pre- and postoperative rCBFs were evaluated with Xe-CT and IMP-SPECT in 7 cases, mean rCBF of peritumoral edema was 6.2 ml/100 g/min preoperatively, and discrepancy between rCBF on Xe-CT and that on IMP-SPECT was shown in the remote cortical region ipsilateral to the tumor. Postoperative rCBF revealed an improved blood flow in both adjacent and remote areas, suggesting that the decreased blood flow associated with brain tumors might be relieved after surgery. (author) 53 refs

Effect of host age on the transplantation, growth, and radiation response of EMT6 tumors

International Nuclear Information System (INIS)

Rockwell, S.

1981-01-01

The characteristics of EMT6 tumors in young adult and aged BALB/c KaRw mice were compared. The number of tumor cells implanted s.c. necessary to cause tumors in 50% of the injection sites was lower in aging than in young adult mice. The latent period of intradermally implanted tumors was shorter in aging mice than in young animals; however, the growth curves of established tumors were similar. The number and appearance of lung colonies after injection of cells i.v. and the pattern of spontaneous metastases were similar in young and aged animals. Radiation dose-response curves for the cells of tumors in young and aging mice were different and suggested that the proportion of hypoxic cells was higher in tumors on aging animals. These findings suggest that both immunological and nonimmunological tumor-host interactions differ in young and aged animals and that such factors may influence the natural history of the tumor and the response of the tumor to treatment

Teratoid Wilms′ tumor - A rare renal tumor

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Biswanath Mukhopadhyay

2011-01-01

Full Text Available Teratoid Wilms′ tumor is an extremely rare renal tumor. We report a case of unilateral teratoid Wilms′ tumor in a 4-year-old girl. The patient was admitted with a right-sided abdominal mass. The mass was arising from the right kidney. Radical nephrectomy was done and the patient had an uneventful recovery. Histopathology report showed teratoid Wilms′ tumor.

Tumor metabolism, the ketogenic diet and β-hydroxybutyrate: novel approaches to adjuvant brain tumor therapy

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Eric C. Woolf

2016-11-01

Full Text Available Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD. The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention.

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Liying Gu

Full Text Available The aim of this current study was to investigate the expression of the tumor necrosis factor (TNF-like weak inducer of apoptosis (TWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14 in human malignant ovarian tumors, and test TWEAK's potential role on tumor progression in cell models in-vitro. Using immunohistochemistry (IHC, we found that TWEAK and its receptor Fn14 were expressed in human malignant ovarian tumors, but not in normal ovarian tissues or in borderline/benign epithelial ovarian tumors. High levels of TWEAK expression was detected in the majority of malignant tumors (36 out of 41, 87.80%. Similarly, 35 out of 41 (85.37% malignant ovarian tumors were Fn14 positive. In these malignant ovarian tumors, however, TWEAK/Fn14 expression was not corrected with patients' clinical subtype/stages or pathological features. In vitro, we demonstrated that TWEAK only inhibited ovarian cancer HO-8910PM cell proliferation in combination with tumor necrosis factor-α (TNF-α, whereas either TWEAK or TNF-α alone didn't affect HO-8910PM cell growth. TWEAK promoted TNF-α production in cultured THP-1 macrophages. Meanwhile, conditioned media from TWEAK-activated macrophages inhibited cultured HO-8910PM cell proliferation and invasion. Further, TWEAK increased monocyte chemoattractant protein-1 (MCP-1 production in cultured HO-8910PM cells to possibly recruit macrophages. Our results suggest that TWEAK/Fn14, by activating macrophages, could be ovarian tumor suppressors. The unique expression of TWEAK/Fn14 in malignant tumors indicates that it might be detected as a malignant ovarian tumor marker.

Spinal tumors

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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

Radionecrosis after radiotherapy for brain tumor

International Nuclear Information System (INIS)

Yoshii, Yoshihiko; Maki, Yutaka; Tosa, Junichi; Tsuboi, Koji; Matsumura, Akira

1984-01-01

The neurological deterioration after radiotherapy of brain tumor may depend on radionecrosis or regrowth of the tumor. In the present study, five patients with brain tumor were irradiated with doses of 3,900 to 6,800 rads. The neurological deterioration appeared 3.5 to 46 months after radiotherapy in three patients, who received 5,000 to 5,680 rads, immediately after radiotherapy in one patient, who received 6,800 rads, and during radiotherapy in one patient, who received 3,900 rads. Ring enhancement was observed on sequential CT scans. This enhanced area was surgically removed and the correlation between histology and CT scans and superimposed dose distributions was studied in order to differentiate radionecrosis from regrowth of tumor. The radionecrosis was confirmed at the second operation in five patients, but regrowth of the tumor was also observed in the brain adjacent to radionecrosis in three out of five patients. Coagulation necrosis and fibrinoid necrosis were observed microscopically at the rim of the ring enhancement and necrotic and hyalinized debri were observed in the central low density area of the ring enhancement. Viable tumor cells were noted in the enhanced area adjacent to the ring enhancement on CT scans. Both radionecrosis and regrowth of tumor were observed in the dose distribution area of 3,500 to 6,120 rads on CT scans. This suggested that the superimposed dose distributions could not differentiate radionecrosis from tumor regrowth. Forty-eight cases of cerebral radionecrosis gathered from the literature were reviewed. (J.P.N.)

Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.

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Akhmetzyanova, Ilseyar; Zelinskyy, Gennadiy; Schimmer, Simone; Brandau, Sven; Altenhoff, Petra; Sparwasser, Tim; Dittmer, Ulf

2013-02-01

The important role of tumor-specific cytotoxic CD8(+) T cells is well defined in the immune control of the tumors, but the role of effector CD4(+) T cells is poorly understood. In the current research, we have used a murine retrovirus-induced tumor cell line of C57BL/6 mouse origin, namely FBL-3 cells, as a model to study basic mechanisms of immunological control and escape during tumor formation. This study shows that tumor-specific CD4(+) T cells are able to protect against virus-induced tumor cells. We show here that there is an expansion of tumor-specific CD4(+) T cells producing cytokines and cytotoxic molecule granzyme B (GzmB) in the early phase of tumor growth. Importantly, we demonstrate that in vivo depletion of regulatory T cells (Tregs) and CD8(+) T cells in FBL-3-bearing DEREG transgenic mice augments IL-2 and GzmB production by CD4(+) T cells and increases FV-specific CD4(+) T-cell effector and cytotoxic responses leading to the complete tumor regression. Therefore, the capacity to reject tumor acquired by tumor-reactive CD4(+) T cells largely depends on the direct suppressive activity of Tregs. We suggest that a cytotoxic CD4(+) T-cell immune response may be induced to enhance resistance against oncovirus-associated tumors.

Efficacy and complications of radiotherapy of anterior visual pathway tumors

International Nuclear Information System (INIS)

Capo, H.; Kupersmith, M.J.

1991-01-01

A progressive disturbance in visual acuity or visual field, along with an unexplained optic nerve atrophy, suggests the possibility of a tumor. Tumors that frequently affect the anterior visual pathway include primary optic nerve sheath meningiomas, intracranial meningiomas, optic gliomas, pituitary tumors, and craniopharyngiomas. The location of these tumors sometimes prohibits a complete surgical excision that might jeopardize the visual system. Radiation therapy, however, can be beneficial in these cases. This article reviews the indications for radiotherapy of tumors that involve the anterior visual pathway, along with the possible complications. Cases that present the effect of radiation therapy and radiation damage are presented.131 references

Tumor control probability after a radiation of animal tumors

International Nuclear Information System (INIS)

Urano, Muneyasu; Ando, Koichi; Koike, Sachiko; Nesumi, Naofumi

1975-01-01

Tumor control and regrowth probability of animal tumors irradiated with a single x-ray dose were determined, using a spontaneous C3H mouse mammary carcinoma. Cellular radiation sensitivity of tumor cells and tumor control probability of the tumor were examined by the TD 50 and TCD 50 assays respectively. Tumor growth kinetics were measured by counting the percentage of labelled mitosis and by measuring the growth curve. A mathematical analysis of tumor control probability was made from these results. A formula proposed, accounted for cell population kinetics or division probability model, cell sensitivity to radiation and number of tumor cells. (auth.)

Primary cardiac tumors associated with genetic syndromes. A comprehensive review

International Nuclear Information System (INIS)

Lee, Elizabeth; Agarwal, Prachi P.; Mahani, Maryam Ghadimi; Lu, Jimmy C.; Dorfman, Adam L.; Srinivasan, Ashok

2018-01-01

Various cardiac tumors occur in the setting of a genetic syndrome such as myxomas in Carney complex and rhabdomyomas in tuberous sclerosis. Tumor biology can be different in syndromic forms, and on imaging children sometimes demonstrate additional manifestations of the underlying syndrome. We discuss the imaging appearance of cardiac tumors occurring in the framework of a genetic syndrome, the findings that suggest an underlying syndrome, and the impact on management. (orig.)

Primary cardiac tumors associated with genetic syndromes. A comprehensive review

Energy Technology Data Exchange (ETDEWEB)

Lee, Elizabeth; Agarwal, Prachi P. [University of Michigan Health System, University Hospital Division of Cardiothoracic Radiology, Department of Radiology, Ann Arbor, MI (United States); Mahani, Maryam Ghadimi [University of Michigan Health System, University Hospital Division of Cardiothoracic Radiology, Department of Radiology, Ann Arbor, MI (United States); University of Michigan Health System, Section of Pediatric Radiology, C.S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); Lu, Jimmy C.; Dorfman, Adam L. [University of Michigan Health System, Section of Pediatric Radiology, C.S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); C.S. Mott Children' s Hospital, University of Michigan Health System, Section of Pediatric Cardiology, Department of Pediatrics, Ann Arbor, MI (United States); Srinivasan, Ashok [University of Michigan Health System, Division of Neuroradiology, Department of Radiology, Ann Arbor, MI (United States)

2018-02-15

Various cardiac tumors occur in the setting of a genetic syndrome such as myxomas in Carney complex and rhabdomyomas in tuberous sclerosis. Tumor biology can be different in syndromic forms, and on imaging children sometimes demonstrate additional manifestations of the underlying syndrome. We discuss the imaging appearance of cardiac tumors occurring in the framework of a genetic syndrome, the findings that suggest an underlying syndrome, and the impact on management. (orig.)

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

International Nuclear Information System (INIS)

Kim, Sung Mok; Kim, Ji Hye; Yoo, So Young; Park, Won Soon; Jang, Yun Sil; Shin, Hyung Jin; Suh, Yeon Lim

2008-01-01

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

Application of lectins to tumor imaging radiopharmaceuticals

International Nuclear Information System (INIS)

Kojima, Shuji; Jay, M.

1986-01-01

We investigated the in vitro binding of 125 I-lectins to Ehrlich ascites tumor (EAT) cells and in vivo uptake of 125 I-lectins in Ehrlich solid tumor (EST) bearing mice. In in vitro binding assays, phaseolus vulgaris agglutinin (PHA), pisum sativum agglutinin (PSA), and concanavalia agglutinin (Con A) showed a high affinity for EAT cells. The in vivo biodistribution of 125 I-lectins showed 125 I-PSA to be significantly taken up into EST tissues 24 h postinjection. After IV injection of 125 I-PSA, uptake of the radioactivity into the tumor tissues reached a maximum at 6 h, and thereafter decreased. Rapid disappearance of the radioactivity from blood and its excretion into kidney soon after injection of 125 I-PSA were observed. When compared with the biodistribution of 67 Ga-citrate in EST bearing mice 24 h postinjection, tumor to liver (T/B), tumor to muscle (T/M), and tumor to blood (T/B) ratios were superior for 125 I-PSA. At 6 h postinjection, the T/B-ratio of 125 I-PSA was 2.5, and this value may be sufficient to enable discernable diagnostic images. Our results suggest that PSA might be a useful tumor imaging radiopharmaceutical. (orig.)

Studies into the transplantation biology of ultraviolet light-induced tumors

International Nuclear Information System (INIS)

Daynes, R.A.; Spellman, C.W.; Woodward, J.G.; Stewart, D.A.

1977-01-01

The majority of skin tumors induced in mice by ultraviolet (uv) light are rejected when implanted into normal syngeneic recipients. Subcarcinogenic levels of uv light exposure render the normally resistant mice susceptible to tumor challenge. The immunoregulatory effect of uv light appears to be additive, since the growth rate of a tumor transplant is dependent upon the length of uv exposure administered prior to implantation. This suppressive influence does not appear to be directly mediated by the uv light, because the amputation of uv-irradiated tail skin allows for a retention of tumor resistance in otherwise tumor-susceptible hosts. uv-irradiated mice could also be immunized against uv tumors, which suggests that immune recognition of tumor-specific transplantation antigens has not been inhibited. The ability of uv exposure to alter normal immunological reactivity to uv-induced tumors is possibly an integral factor in the mechanism underlying uv carcinogenesis

An exceptional collision tumor: gastric calcified stromal tumor and ...

African Journals Online (AJOL)

The authors report an exceptional case of collision tumor comprised of a gastric calcified stromal tumor and a pancreatic adenocarcinoma. The pancreatic tumor was detected fortuitously on the histological exam of resection specimen. Key words: Collision tumor, stromal tumor, adenocarcinoma ...

Single and 30 fraction tumor control doses correlate in xenografted tumor models: implications for predictive assays

International Nuclear Information System (INIS)

Gerweck, Leo E.; Dubois, Willum; Baumann, Michael; Suit, Herman D.

1995-01-01

, the rank-order correlation coefficient between the single dose hypoxic versus fractionated dose TCD50s under hypoxic or aerobic conditions was 1.0. For all 5 tumors examined, a trend for rank correlation was observed between the single dose and the fractionated dose TCD50s performed under normal or clamp hypoxic conditions (r=0.7, p=0.16 in both cases). The linear correlation coefficients were 0.83, p=0.08 and 0.72, p=0.17, respectively. Failure to attain a rank correlation of 1.0 was due to one tumor exhibiting an insignificant fractionation effect. The rank correlation between the TCD50s for fractionated treatments under normal versus the extrapolated TCD50s under clamp hypoxic conditions was 1.00; the linear correlation coefficient was 0.97 (p=0.01). Conclusions: In the tumor models examined, factors controlling the single fraction tumor control dose, also impact the response to fractionated treatments. These results suggest that laboratory estimates of intrinsic radiosensitivity and tumor clonogen number at the onset of treatment, will be of use in predicting radiocurability for fractionated treatments, as has been observed for single dose treatments

The Yin and Yang of Invariant Natural Killer T Cells in Tumor Immunity—Suppression of Tumor Immunity in the Intestine

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Ying Wang

2018-01-01

Full Text Available CD1d-restricted invariant natural killer T (iNKT cells are known as early responding, potent regulatory cells of immune responses. Besides their established role in the regulation of inflammation and autoimmune disease, numerous studies have shown that iNKT cells have important functions in tumor immunosurveillance and control of tumor metastasis. Tumor-infiltrating T helper 1 (TH1/cytotoxic T lymphocytes have been associated with a positive prognosis. However, inflammation has a dual role in cancer and chronic inflammation is believed to be a driving force in many cancers as exemplified in patients with inflammatory bowel disease that have an increased risk of colorectal cancer. Indeed, NKT cells promote intestinal inflammation in human ulcerative colitis, and the associated animal model, indicating that NKT cells may favor tumor development in intestinal tissue. In contrast to other cancers, recent data from animal models suggest that iNKT cells promote tumor formation in the intestine by supporting an immunoregulatory tumor microenvironment and suppressing TH1 antitumor immunity. Here, we review the role of iNKT cells in suppression of tumor immunity in light of iNKT-cell regulation of intestinal inflammation. We also discuss suppression of immunity in other situations as well as factors that may influence whether iNKT cells have a protective or an immunosuppressive and tumor-promoting role in tumor immunity.

Big Bang Tumor Growth and Clonal Evolution.

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Sun, Ruping; Hu, Zheng; Curtis, Christina

2018-05-01

The advent and application of next-generation sequencing (NGS) technologies to tumor genomes has reinvigorated efforts to understand clonal evolution. Although tumor progression has traditionally been viewed as a gradual stepwise process, recent studies suggest that evolutionary rates in tumors can be variable with periods of punctuated mutational bursts and relative stasis. For example, Big Bang dynamics have been reported, wherein after transformation, growth occurs in the absence of stringent selection, consistent with effectively neutral evolution. Although first noted in colorectal tumors, effective neutrality may be relatively common. Additionally, punctuated evolution resulting from mutational bursts and cataclysmic genomic alterations have been described. In this review, we contrast these findings with the conventional gradualist view of clonal evolution and describe potential clinical and therapeutic implications of different evolutionary modes and tempos. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

eTumorType, An Algorithm of Discriminating Cancer Types for Circulating Tumor Cells or Cell-free DNAs in Blood

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Jinfeng Zou

2017-04-01

Full Text Available With the technology development on detecting circulating tumor cells (CTCs and cell-free DNAs (cfDNAs in blood, serum, and plasma, non-invasive diagnosis of cancer becomes promising. A few studies reported good correlations between signals from tumor tissues and CTCs or cfDNAs, making it possible to detect cancers using CTCs and cfDNAs. However, the detection cannot tell which cancer types the person has. To meet these challenges, we developed an algorithm, eTumorType, to identify cancer types based on copy number variations (CNVs of the cancer founding clone. eTumorType integrates cancer hallmark concepts and a few computational techniques such as stochastic gradient boosting, voting, centroid, and leading patterns. eTumorType has been trained and validated on a large dataset including 18 common cancer types and 5327 tumor samples. eTumorType produced high accuracies (0.86–0.96 and high recall rates (0.79–0.92 for predicting colon, brain, prostate, and kidney cancers. In addition, relatively high accuracies (0.78–0.92 and recall rates (0.58–0.95 have also been achieved for predicting ovarian, breast luminal, lung, endometrial, stomach, head and neck, leukemia, and skin cancers. These results suggest that eTumorType could be used for non-invasive diagnosis to determine cancer types based on CNVs of CTCs and cfDNAs.

Primary Tumor Thickness is a Prognostic Factor in Stage IV Melanoma: A Retrospective Study of Primary Tumor Characteristics.

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Luen, Stephen; Wong, Siew Wei; Mar, Victoria; Kelly, John W; McLean, Catriona; McArthur, Grant A; Haydon, Andrew

2018-01-01

Stage IV melanoma exhibits a diverse range of tumor biology from indolent to aggressive disease. Many important prognostic factors have already been identified. Despite this, the behavior of metastatic melanoma remains difficult to predict. We sought to determine if any primary tumor characteristics affect survival following the diagnosis of stage IV melanoma. All patients diagnosed with stage IV melanoma between January 2003 and December 2012 were identified from the Victorian Melanoma Service database. Retrospective chart review was performed to collect data on primary tumor characteristics (thickness, ulceration, mitotic rate, melanoma subtype, or occult primary). Known and suspected prognostic factors were additionally collected (time to diagnosis of stage IV disease, age, sex, stage, receipt of chemotherapy, and era of recurrence). The effect of primary tumor characteristics on overall survival from the date of diagnosis of stage IV disease was assessed. A total of 227 patients with a median follow-up of 5 years from diagnosis of stage IV disease were identified. Median overall survival of the cohort was 250 days.Of the primary tumor characteristics assessed, only tumor thickness affected survival from diagnosis of stage IV disease, hazard ratio=1.09 (1.02 to 1.16), P=0.008. This remained significant in multivariate analysis, P=0.007. Other primary tumor characteristics did not significantly influence survival. Primary tumor thickness is a significant prognostic factor in stage IV melanoma. Our data suggest that the biology of the primary melanoma may persist to influence the behavior of metastatic disease.

Non-resectable tumors of head and neck.Opportunities chemoradiotherapy

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Cjedakov, Yi.Je.; Semykoz, N.G.; Rogaljev, A.V.; Ostapenko, Yu.V.; Gonchar, O.G.; Bondar, A.V.; Gorovenko, R.Je.

2015-01-01

This article is concerned with the treatment of non-resectable epithelial tumors of the head and neck. It gives a detailed account of the experience of radiation therapy in combination with selective regional chemotherapy administration as a method of combined treatment. According to the study result the complete tumor response was demonstrated in 5.3 % cases, participial tumor response - in 80.4 %, stable disease - in 10.7 %, progression of the tumor process - in 3.6 %. The reported adheres events and their treatment details are described for all severity as per NCI-CTCAE. The performed analysis suggests the preliminary study treatment results and the advantages of the selected scheme

131I-MIBG Scintigraphy in the Evaluation of Suspected Pheochromocytoma

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Oh, Sei Jung; Yoo, Hyung Sik; Park, Chang Yun; Lee, So Jin

1992-01-01

Pheochromocytomas are catecholamine producing tumors of neuroectodermal origin. Diagnosis of pheochromocytoma is significant due to potentially curable hypertension. But they have a significant associated morbidity due to uncontrolled hypertension and mortality since 10% are malignant. From Aug. 1989 to Jul. 1992, 12 patients of our institution had 131 I-MIBG scan during work up of suspected primary or recurrent pheochromocytoma. In our studies conclude that 131 I-MIBG scan is recommended as the initial localizing study of choice (especially for the detection of extraadrenal disease and postoperative recurrence) as a guide for CT and/or MR and specific functional confirmation of their findings.

Bridging from Brain to Tumor Imaging: (S-(−- and (R-(+-[18F]Fluspidine for Investigation of Sigma-1 Receptors in Tumor-Bearing Mice

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Mathias Kranz

2018-03-01

Full Text Available Sigma-1 receptors (Sig1R are highly expressed in various human cancer cells and hence imaging of this target with positron emission tomography (PET can contribute to a better understanding of tumor pathophysiology and support the development of antineoplastic drugs. Two Sig1R-specific radiolabeled enantiomers (S-(−- and (R-(+-[18F]fluspidine were investigated in several tumor cell lines including melanoma, squamous cell/epidermoid carcinoma, prostate carcinoma, and glioblastoma. Dynamic PET scans were performed in mice to investigate the suitability of both radiotracers for tumor imaging. The Sig1R expression in the respective tumors was confirmed by Western blot. Rather low radiotracer uptake was found in heterotopically (subcutaneously implanted tumors. Therefore, a brain tumor model (U87-MG with orthotopic implantation was chosen to investigate the suitability of the two Sig1R radiotracers for brain tumor imaging. High tumor uptake as well as a favorable tumor-to-background ratio was found. These results suggest that Sig1R PET imaging of brain tumors with [18F]fluspidine could be possible. Further studies with this tumor model will be performed to confirm specific binding and the integrity of the blood-brain barrier (BBB.

MR findings of ovarian tumors with hormonal activity, with emphasis on tumors other than sex cord-stromal tumors

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Tanaka, Yumiko Oishi [Department of Radiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan)]. E-mail: ytanaka@md.tsukuba.ac.jp; Saida, Tsukasa Sasaki [Department of Diagnostic and Interventional Radiology, Tsukuba University Hospital (Japan); Minami, Rie [Department of Obstetrics and Gynecology, Graduate School of Comprehensive Human Sciences, University of Tsukuba (Japan); Yagi, Takako [Department of Diagnostic and Interventional Radiology, Tsukuba University Hospital (Japan); Tsunoda, Hajime [Department of Obstetrics and Gynecology, Kanto Medical Center, Nippon Telegraph and Telephone East Corporation (Japan); Yoshikawa, Hiroyuki [Department of Obstetrics and Gynecology, Graduate School of Comprehensive Human Sciences, University of Tsukuba (Japan); Minami, Manabu [Department of Radiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan)

2007-06-15

Sex cord-stromal tumors including granulosa cell tumor, thecoma, Sertoli stromal cell tumor and steroid cell tumor are noted for their hormonal activity. However, there are many kinds of ovarian tumors other than sex cord-stromal tumors and tumor-like conditions with endocrine manifestations. Cross-sectional imaging, especially MR, can provide precise features of ovarian tumors and uterine morphological change even in a clinically latent excess of estrogen. In this article, we demonstrate typical imaging findings of ovarian tumors with hormonal activity. We also shortly explain the mechanism of the virilization and hyperestrogenism caused by ovarian tumors and tumor-like conditions.

MR findings of ovarian tumors with hormonal activity, with emphasis on tumors other than sex cord-stromal tumors

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Tanaka, Yumiko Oishi; Saida, Tsukasa Sasaki; Minami, Rie; Yagi, Takako; Tsunoda, Hajime; Yoshikawa, Hiroyuki; Minami, Manabu

2007-01-01

Sex cord-stromal tumors including granulosa cell tumor, thecoma, Sertoli stromal cell tumor and steroid cell tumor are noted for their hormonal activity. However, there are many kinds of ovarian tumors other than sex cord-stromal tumors and tumor-like conditions with endocrine manifestations. Cross-sectional imaging, especially MR, can provide precise features of ovarian tumors and uterine morphological change even in a clinically latent excess of estrogen. In this article, we demonstrate typical imaging findings of ovarian tumors with hormonal activity. We also shortly explain the mechanism of the virilization and hyperestrogenism caused by ovarian tumors and tumor-like conditions

Tumor-specific loss of 11p15.5 alleles in del11p13 Wilms tumor and in familial adrenocortical carcinoma

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Henry, I.; Grandjouan, S.; Couillin, P.

1989-01-01

The authors have compared constitutional and tumor genotypes in nine cases of hereditary Wilms tumor (WT) and in three unrelated cases of familial adrenocortical carcinoma (ADCC). Since susceptibility to these tumors can be observed in malformation syndromes associated with a constitutional deletion of band 11p13 (WT) and with a constitutional duplication of band 11p15.5 (WT, ADCC), they investigated these two candidate regions by using 11p polymorphic markers. As expected, somatic chromosomal events, resulting in a loss of heterozygosity limited to region 11p15.5, were observed in the tumor of two familial cases of adrenocortical carcinoma. Surprisingly, however, analysis of the WT of two patients with a constitutional deletion of band 11p13, associated with aniridia, genitourinary abnormalities, and mental retardation (WAGR syndrome), revealed a loss of heterozygosity limited to region 11p15.5. These data therefore suggest that observation of a specific loss of heterozygosity may not necessarily point to the site of the initial germinal mutation. Together with previous similar observations of a loss of heterozygosity limited to 11p15.5 in breast cancer and in rhabdomyosarcoma, the data suggest that region 11p15.5 may carry a non-tissue-specific gene that could be involved in genetic predisposition, in tumor progression, or in both

Recurrent and multiple bladder tumors show conserved expression profiles

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Lindgren, David; Fioretos, Thoas; Månsson, Wiking; Höglund, Mattias; Gudjonsson, Sigurdur; Jee, Kowan Ja; Liedberg, Fredrik; Aits, Sonja; Andersson, Anna; Chebil, Gunilla; Borg, Åke; Knuutila, Sakari

2008-01-01

Urothelial carcinomas originate from the epithelial cells of the inner lining of the bladder and may appear as single or as multiple synchronous tumors. Patients with urothelial carcinomas frequently show recurrences after treatment making follow-up necessary. The leading hypothesis explaining the origin of meta- and synchronous tumors assumes a monoclonal origin. However, the genetic relationship among consecutive tumors has been shown to be complex in as much as the genetic evolution does not adhere to the chronological appearance of the metachronous tumors. Consequently, genetically less evolved tumors may appear chronologically later than genetically related but more evolved tumors. Forty-nine meta- or synchronous urothelial tumors from 22 patients were analyzed using expression profiling, conventional CGH, LOH, and mutation analyses. We show by CGH that partial chromosomal losses in the initial tumors may not be present in the recurring tumors, by LOH that different haplotypes may be lost and that detected regions of LOH may be smaller in recurring tumors, and that mutations present in the initial tumor may not be present in the recurring ones. In contrast we show that despite apparent genomic differences, the recurrent and multiple bladder tumors from the same patients display remarkably similar expression profiles. Our findings show that even though the vast majority of the analyzed meta- and synchronous tumors from the same patients are not likely to have originated directly from the preceding tumor they still show remarkably similar expressions profiles. The presented data suggests that an expression profile is established early in tumor development and that this profile is stable and maintained in recurring tumors

Increased Tumor Oxygenation and Drug Uptake During Anti-Angiogenic Weekly Low Dose Cyclophosphamide Enhances the Anti-Tumor Effect of Weekly Tirapazamine

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Doloff, J.C.; Khan, N.; Ma, J.; Demidenko, E.; Swartz, H.M.; Jounaidi, Y.

2010-01-01

Metronomic cyclophosphamide treatment is associated with anti-angiogenic activity and is anticipated to generate exploitable hypoxia using hypoxia-activated prodrugs. Weekly administration of tirapazamine (TPZ; 5 mg/kg body weight i.p.) failed to inhibit the growth of 9L gliosarcoma tumors grown s.c. in scid mice. However, the anti-tumor effect of weekly cyclophosphamide (CPA) treatment (140 mg/kg BW i.p.) was substantially enhanced by weekly TPZ administration. An extended tumor free period and increased frequency of tumor eradication without overt toxicity were observed when TPZ was given 3, 4 or 5 days after each weekly CPA treatment. Following the 2nd CPA injection, Electron Paramagnetic Resonance (EPR) Oximetry indicated significant increases in tumor pO2, starting at 48 hr, which further increased after the 3rd CPA injection. pO2 levels were, however, stable in growing untreated tumors. A strong negative correlation (−0.81) between tumor pO2 and tumor volume during 21 days of weekly CPA chemotherapy was observed, indicating increasing tumor pO2 with decreasing tumor volume. Furthermore, CPA treatment resulted in increased tumor uptake of activated CPA. CPA induced increases in VEGF RNA, which reached a maximum on day 1, and in PLGF RNA which was sustained throughout the treatment, while anti-angiogenic host thrombospondin-1 increased dramatically through day 7 post-CPA treatment. Weekly cyclophosphamide treatment was anticipated to generate exploitable hypoxia. However, our findings suggest that weekly CPA treatment induces a functional improvement of tumor vasculature, which is characterized by increased tumor oxygenation and drug uptake in tumors, thus counter-intuitively, benefiting intratumoral activation of TPZ and perhaps other bioreductive drugs. PMID:19754361

In vivo imaging of tumor vascular endothelial cells

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Zhao, Dawen; Stafford, Jason H.; Zhou, Heling; Thorpe, Philip E.

2013-02-01

Phosphatidylserine (PS), normally restricted to the inner leaflet of the plasma membrane, becomes exposed on the outer surface of viable (non-apoptotic) endothelial cells in tumor blood vessels, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we optically imaged exposed PS on tumor vasculature in vivo using PGN635, a novel human monoclonal antibody that targets PS. PGN635 F(ab')2 was labeled with the near infrared (NIR) dye, IRDye 800CW. Human glioma U87 cells or breast cancer MDA-MB-231 cells were implanted subcutaneously or orthotopically into nude mice. When the tumors reached ~5 mm in diameter, 800CW- PGN635 was injected via a tail vein and in vivo dynamic NIR imaging was performed. For U87 gliomas, NIR imaging allowed clear detection of tumors as early as 4 h later, which improved over time to give a maximal tumor/normal ratio (TNR = 2.9 +/- 0.5) 24 h later. Similar results were observed for orthotopic MDA-MB-231 breast tumors. Localization of 800CW-PGN635 to tumors was antigen specific since 800CW-Aurexis, a control probe of irrelevant specificity, did not localize to the tumors, and pre-administration of unlabeled PGN635 blocked the uptake of 800CW-PGN635. Fluorescence microscopy confirmed that 800CW-PGN635 was binding to PS-positive tumor vascular endothelium. Our studies suggest that tumor vasculature can be successfully imaged in vivo to provide sensitive tumor detection.

The Tumor Macroenvironment: Cancer-Promoting Networks Beyond Tumor Beds.

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Rutkowski, Melanie R; Svoronos, Nikolaos; Perales-Puchalt, Alfredo; Conejo-Garcia, Jose R

2015-01-01

During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the macroenvironment and the primary tumor will enable the design of specific therapies that have the potential to prevent dissemination and metastatic spread. This chapter will summarize recent findings detailing how the primary tumor and systemic tumor macroenvironment coordinate malignant progression. © 2015 Elsevier Inc. All rights reserved.

Bone tumors

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Unni, K.K.

1988-01-01

This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

Ellagic acid radiosensitizes tumor cells by evoking apoptotic pathway

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Ahire, Vidhula R.; Mishra, K.P.

2016-01-01

Cancer causes millions of deaths each year globally. In most patients, the cause of treatment failure is found associated with the resistance to chemotherapy and radiotherapy. The development of tumor cell resistance evokes multiple intracellular molecular pathways. In addition, the limitation in treatment outcome arises due to unintended cytotoxic effects of the synthetic anticancer drugs to normal cells and tissues. Considerable focus of research is, therefore, devoted to examine plant-based herbal compounds which may prove potential anticancer drug for developing effective cancer therapy. Research results from our laboratory have shown that ellagic acid (EA), a natural flavonoid displays enhanced tumor toxicity in combination with gamma radiation to many types of cancers in vitro as well as in vivo. Studies on the underlying mechanisms of toxicity suggest that EA employs the cellular signaling pathways in producing the observed effects. This paper gives an account of molecular mechanisms of EA-induced apoptosis process in tumor cytotoxicity. It is suggested that EA acts as a novel radiosensitizer for tumors and a radioprotector for normal cells which may offer a novel protocol for cancer treatment. (author)

Evaluation of [1-11C]-α-aminoisobutyric acid for tumor detection and amino acid transport measurement: Spontaneous canine tumor studies

International Nuclear Information System (INIS)

Bigler, R.E.; Zanzonico, P.B.; Schmall, B.; Conti, P.S.; Dahl, J.R.; Rothman, L.; Sgouros, G.

1985-01-01

Alpha-aminoisobutyric acid (AIB) or α-methyl alanine, is a nonmetabolized amino acid treansported into cells particularly malignant cells, predominantly by the ''A'' amino acid transport system. Since it is not metabolized, [1- 11 C]-AIB can be used to quantify A-type amino acid transport into cells using a relatively simple compartmental model and quantitative imaging procedures (e.g. positron tomography). The tissue distribution of [1- 11 C]-AIB was determined in six dogs bearing spontaneous tumors, including lymphosarcoma, osteogenic sarcoma, mammary carcinoma, and adenocarcinoma. Quantitative imaging with tissue radioassay confirmation at necropsy showed poor to excellent tumor localization. However, in all cases the concentrations achieved appear adequate for amino acid transport measurement at known tumor locations. The observed low normal brain (due to blood-brain barrier exclusion) and high (relative to brain) tumor concentrations of [1- 11 C]-AIB suggest that this agent may prove effective for the early detection of human brain tumors. (orig.)

Microdissecting the Genetic Events in Nephrogenic Rests and Wilms’ Tumor Development

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Charles, Adrian K.; Brown, Keith W.; Berry, P. Jeremy

1998-01-01

Nephrogenic rests are precursor lesions associated with about 40% of Wilms’ tumors. This study identifies genetic steps occurring in the development of Wilms’ tumor. Thirty-four Wilms’ tumors with nephrogenic rests and/or areas of anaplasia were microdissected from paraffin sections to determine whether and at what stage loss of heterozygosity (LOH) occurred, using polymerase chain reaction-based polymorphic markers at 11p13, 11p15, and 16q. LOH at these loci have been identified in Wilms’ tumors and are associated with identified or putative tumor suppressor genes. Three cystic nephromas/cystic partially differentiated nephroblastomas were also examined. LOH was detected in six cases at 11p13 and in six cases at 11p15, and two of these cases had LOH at both loci. All intralobar rests showing LOH also showed LOH in the tumor. A case with a small perilobar rest showed LOH of 11p13 only in the tumor. Five cases showing LOH at 16q were identified (this was identified only in the tumor, and not in the associated rest), and three of these had recurrence of the tumor. Two cases had a WT1 mutation (one germline and the other somatic), as well as LOH in both the intralobar rest and the tumor. A cystic partially differentiated nephroblastoma showed loss at 11p13 and 11p15, as well as at 16q. This study suggests that LOH at 11p13 and 11p15 and WT1 mutations are early events but that LOH at 16q occurs late in the pathogenesis of Wilms’ tumor. Intralobar and perilobar nephrogenic rests are known to have different biological behaviors, and this study suggests that they are genetically different. A multistep model of Wilms’ tumor pathogenesis is supported by these findings. PMID:9736048

X-ray sensitivity of human tumor cells in vitro

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Weichselbaum, R.R.; Nove, J.; Little, J.B.

1980-01-01

Clonally-derived cells from ten human malignant tumors considered radiocurable (breast, neuroblastoma, medulloblastoma) or non-radiocurable (osteosarcoma, hypernephroma, glioblastoma, melanoma) were studied in cell culture and their in vitro x-ray survival curve parameters determined (anti n, D 0 ). There were no significant differences among the tumor cell lines suggesting that survival parameters in vitro do not explain differences in clinical radiocurability. Preliminary investigation with density inhibited human tumor cells indicate that such an approach may yield information regarding inherent cellular differences in radiocurability

The problem: Tumor radioresistance in clinical radiotherapy

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Peters, L.J.; Withers, H.R.; Thames, H.D.; Fletcher, G.H.; M.D. Anderson Hospital and Tumor Inst., Houston, TX)

1983-01-01

Tumor radioresistance in clinical radiotherapy implies failure to achieve local-regional disease control with radiation doses producing an acceptable degree of morbidity. Such radioresistance may be due to many different causes (biological and technical) which are reviewed in terms of possible remedial actions. Dose-response relationships for human cancers suggest that, in many sites, tumors are heterogeneous with respect to their cure-limiting characteristics. The case is developed that unless the predominant cure-limiting factor can be predicted, little benefit may be seen in trials of new treatment strategies using heterogeneous tumor populations. The fundamental problem of clinical radioresistance is therefore perceived as the inability to identify predictively its cause in the individual patient

Regulatory T cells as suppressors of anti-tumor immunity: Role of metabolism.

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De Rosa, Veronica; Di Rella, Francesca; Di Giacomo, Antonio; Matarese, Giuseppe

2017-06-01

Novel concepts in immunometabolism support the hypothesis that glucose consumption is also used to modulate anti-tumor immune responses, favoring growth and expansion of specific cellular subsets defined in the past as suppressor T cells and currently reborn as regulatory T (Treg) cells. During the 1920s, Otto Warburg and colleagues observed that tumors consumed high amounts of glucose compared to normal tissues, even in the presence of oxygen and completely functioning mitochondria. However, the role of the Warburg Effect is still not completely understood, particularly in the context of an ongoing anti-tumor immune response. Current experimental evidence suggests that tumor-derived metabolic restrictions can drive T cell hyporesponsiveness and immune tolerance. For example, several glycolytic enzymes, deregulated in cancer, contribute to tumor progression independently from their canonical metabolic activity. Indeed, they can control apoptosis, gene expression and activation of specific intracellular pathways, thus suggesting a direct link between metabolic switches and pro-tumorigenic transcriptional programs. Focus of this review is to define the specific metabolic pathways controlling Treg cell immunobiology in the context of anti-tumor immunity and tumor progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Factors associated with tumor size of hepatocellular carcinoma

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Siregar, G. A.; Buulolo, B. A.

2018-03-01

Determining the association of age and laboratory parameters with tumor size of hepatocellular carcinoma (HCC). The study was at Adam Malik Hospital Medan from June- December 2016. 100 HCC patients were enrolled; those with excluding liver metastatic. Baseline characteristics of gender, age, obtaining etiology of HCC. Liver function tests, viral marker, and INR were done. Based on tumor size from abdomen CT, patients were three groups: tumor size below 3 cm, 3-5 cm, and above 5 cm size. Patients were also divided based on Child-Pugh class. Correlation of age and laboratory results with tumor size of HCC patients were analyzed. Age have negative correlation with tumor size in HCC patients (r=-0.297, p=0.032) while AFP have positive correlation with tumor size (r0.446, p=<0.001). Total bilirubin, AST, and ALT have negative correlation but non-significant (r=-0.045, -0.078, - 0.126 respectively). Albumin and INR have positive correlation but non-significant (r=0.021, 0.112 respectively). Our study suggests that older age correlates with smaller tumor size, while AFP level has a significant correlation with tumor size in HCC patients. AFP level may be a useful marker for determining the prognosis of HCC patients.

Nature and Nurture: What Determines Tumor Metabolic Phenotypes?

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Mayers, Jared R; Vander Heiden, Matthew G

2017-06-15

Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein. These differences in amino acid metabolism translate into distinct pathway dependencies, as genetic disruption of the enzymes responsible for utilization of BCAA nitrogen limits the growth of lung tumors, but not pancreatic tumors. These data argue that some cancer metabolic phenotypes are defined by cancer tissue-of-origin and environment and that these features constrain the influence of genetic mutations on metabolism. A better understanding of the factors defining tumor nutrient utilization could be exploited to help improve cancer therapy. Cancer Res; 77(12); 3131-4. ©2017 AACR . ©2017 American Association for Cancer Research.

The impact of stress on tumor growth: peripheral CRF mediates tumor-promoting effects of stress

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Stathopoulos Efstathios N

2010-09-01

Full Text Available Abstract Introduction Stress has been shown to be a tumor promoting factor. Both clinical and laboratory studies have shown that chronic stress is associated with tumor growth in several types of cancer. Corticotropin Releasing Factor (CRF is the major hypothalamic mediator of stress, but is also expressed in peripheral tissues. Earlier studies have shown that peripheral CRF affects breast cancer cell proliferation and motility. The aim of the present study was to assess the significance of peripheral CRF on tumor growth as a mediator of the response to stress in vivo. Methods For this purpose we used the 4T1 breast cancer cell line in cell culture and in vivo. Cells were treated with CRF in culture and gene specific arrays were performed to identify genes directly affected by CRF and involved in breast cancer cell growth. To assess the impact of peripheral CRF as a stress mediator in tumor growth, Balb/c mice were orthotopically injected with 4T1 cells in the mammary fat pad to induce breast tumors. Mice were subjected to repetitive immobilization stress as a model of chronic stress. To inhibit the action of CRF, the CRF antagonist antalarmin was injected intraperitoneally. Breast tissue samples were histologically analyzed and assessed for neoangiogenesis. Results Array analysis revealed among other genes that CRF induced the expression of SMAD2 and β-catenin, genes involved in breast cancer cell proliferation and cytoskeletal changes associated with metastasis. Cell transfection and luciferase assays confirmed the role of CRF in WNT- β-catenin signaling. CRF induced 4T1 cell proliferation and augmented the TGF-β action on proliferation confirming its impact on TGFβ/SMAD2 signaling. In addition, CRF promoted actin reorganization and cell migration, suggesting a direct tumor-promoting action. Chronic stress augmented tumor growth in 4T1 breast tumor bearing mice and peripheral administration of the CRF antagonist antalarmin suppressed this

Large mid-esophageal granular cell tumor: benign versus malignant

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Prarthana Roselil Christopher

2015-06-01

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

Epidermal growth factor receptor expression in radiation-induced dog lung tumors by immunocytochemical localization

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Leung, F.L.; Park, J.F.; Dagle, G.E.

1993-06-01

In studies to determine the role of growth factors in radiation-induced lung cancer, epidermal growth factor (EGFR) expression was examined by immunocytochemistry in 51 lung tumors from beagle dogs exposed to inhaled plutonium; 21 of 51 (41%) tumors were positive for EGFR. The traction of tumors positive for EGFR and the histological type of EGFR-positive tumors in the plutonium-exposed dogs were not different from spontaneous dog lung tumors, In which 36% were positive for EGFR. EGFR involvement in Pu-induced lung tumors appeared to be similar to that in spontaneous lung tumors. However, EGFR-positive staining was observed in only 1 of 16 tumors at the three lowest Pu exposure levels, compared to 20 of 35 tumors staining positive at the two highest Pu exposure levels. The results in dogs were in good agreement with the expression of EGFR reported in human non-small cell carcinoma of the lung, suggesting that Pu-induced lung tumors in the dog may be a suitable animal model to investigate the role of EGFR expression in lung carcinogenesis. In humans, EGFR expression in lung tumors has been primarily related to histological tumor types. In individual dogs with multiple primary lung tumors, the tumors were either all EGFR positive or EGFR negative, suggesting that EGFR expression may be related to the response of the individual dog as well as to the histological type of tumor.

Evaluation of technetium-99M labeled RGD-containing peptide as potential tumor imaging agents in tumor-bearing mice

International Nuclear Information System (INIS)

Hu Silong; Zeng Jun; Zhang Lihua

2004-01-01

Integrins (especially α v β 3 ) play a important role in angiogenesis, growth and metastasis of a solid tumor. Targeting tumor with radiolabeled ligands of the α V β 3 integrin may provide information about the receptor status and enable specific therapeutic strategy. A tripeptidic sequence Arg-Gly-Asp (RGD) is often the primary site of recognition by integrins. The aim of this study examine 99m Tc-labeled elevenfold peptide (GRGDSRGDSCY, GY11) that target the α V β 3 integrin to determine if this agent target tumors for diagnostic imaging and/or targeted radiotherapy of cancer. Methods: GY11 was radiolabelled with 99 Tc m via cystine residue by means of stannous chloride. 99 Tc m -GY11 was injected through tail vein into nude mice bearing A375 human melanoma. Biodistribution was investigated at 1,2,4 and 6 hours after injection. Percentage injected dose/gram of tissue (%ID/g) and tumor/non-tumor ratios were calculated. Planar images were acquired with SPECT at 1,2,4,6hrs, respectively. Results: 99 Tc m -GY11 was rapidly cleared from blood and excreted predominantly from the kidney. Tumor uptake at 2h postinjection was 3.1%ID/g. The ratios of tumor/blood and tumor/muscle increased from 0.9-6.2, 4.3-13.5 from 1-6hrs postinjection, respectively. Planar images confirmed that tumor could be visualized at 4h after administration of 99 Tc m -GY11. Conclusion: The results suggest that 99 Tc m -GY11 is a promising compound for noninvasive determining the α V β 3 integrin status. 99 Tc m -GY11 SPECT may be useful to imaging α V β 3 -positive tumor and also guide proper utility of α V β 3 antagonist therapy and radionuclide therapy for cancer. (authors)

Histopathological studies on the irradiated brain tumors

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Narita, Tadao