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Sample records for malignant pancreatic tumors

  1. Radioimmunoassay for human pancreatic ribonuclease and measurement of serum immunoreactive pancreatic ribonuclease in patients with malignant tumors

    SciTech Connect

    Kurihara, M.; Ogawa, M.; Ohta, T.; Kurokawa, E.; Kitahara, T.; Murata, A.; Matsuda, K.; Kosaki, G.; Watanabe, T.; Wada, H.

    1984-05-01

    A method for radioimmunoassay of human pancreatic RNase was developed. The method is sensitive, reproducible, and specific. Almost no cross-reactivity exists between human pancreatic and liver RNases. A good correlation was observed between the serum concentration of pancreatic RNase as measured by radioimmunoassay and its enzymatic activity using polycytidylic acid as substrate. The concentration of serum pancreatic RNase correlates well with age, blood urea nitrogen, and albumin contents but does not correlate with serum amylase activity. Using the data of 52 patients with malignant tumors except pancreatic cancer, serum RNase level could be expressed by a multiple regression equation: Immunoreactive RNase content in pancreatic cancer was elevated in patients with complications from renal failure. Serum pancreatic RNase contents in patients with pancreatic cancer measured by radioimmunoassay agreed well with the values calculated using the equation derived from the data of patients with other malignant tumors.

  2. Pancreatic Candidiasis That Mimics a Malignant Pancreatic Cystic Tumor on Magnetic Resonance Imaging: A Case Report in an Immunocompetent Patient.

    PubMed

    Seong, Minjung; Kang, Tae Wook; Ha, Sang Yun

    2015-01-01

    Candida is a commensal organism that is frequently found in the human gastrointestinal tract. It is the most common organism that causes pancreatic fungal infections. However, magnetic resonance imaging findings of Candida infection in the pancreas have not been described. We report imaging findings of pancreatic candidiasis in a patient in immunocompetent condition. It presented as a multi-septated cystic mass with a peripheral solid component in the background of pancreatitis and restricted diffusion on diffusion-weighted image that mimicked a malignant pancreatic cystic tumor.

  3. Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD

    PubMed Central

    Cortez, Eliane; Gladh, Hanna; Braun, Sebastian; Bocci, Matteo; Cordero, Eugenia; Björkström, Niklas K.; Miyazaki, Hideki; Michael, Iacovos P.; Eriksson, Ulf; Folestad, Erika; Pietras, Kristian

    2016-01-01

    Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis. PMID:26831065

  4. Histopathologically Proven Autoimmune Pancreatitis Mimicking Neuroendocrine Tumor or Pancreatic Cancer

    PubMed Central

    Onda, Shinji; Okamoto, Tomoyoshi; Kanehira, Masaru; Fujioka, Shuichi; Harada, Tohru; Hano, Hiroshi; Fukunaga, Masaharu; Yanaga, Katsuhiko

    2012-01-01

    Autoimmune pancreatitis (AIP) can be difficult to distinguish from pancreatic cancer. We report a case of histopathologically proven AIP mimicking neuroendocrine tumor (NET) or pancreatic cancer in a 53-year-old man. He was referred to our hospital for further evaluation of a pancreatic mass detected on ultrasonography at a medical check-up. Abdominal ultrasonography showed a 15-mm hypoechoic mass located in the pancreatic body. Computed tomography revealed a tumor without any contrast enhancement, and magnetic resonance imaging demonstrated the mass to be hyperintense on diffusion-weighted image. Endoscopic retrograde cholangiopancreatography revealed slight dilatation of a branch of the pancreatic duct without stricture of the main pancreatic duct. The common bile duct seemed intact. Under suspicion of a non-functioning NET or malignant neoplasm, laparotomy was performed. At laparotomy, an elastic firm and well-circumscribed mass was found suggestive of a non-functioning NET, thus enucleation was performed. Histopathologically, the lesion corresponded to AIP. PMID:22423237

  5. Is metastatic pancreatic cancer an untargetable malignancy?

    PubMed Central

    Kourie, Hampig Raphael; Gharios, Joseph; Elkarak, Fadi; Antoun, Joelle; Ghosn, Marwan

    2016-01-01

    Metastatic pancreatic cancer (MPC) is one of the most aggressive malignancies, known to be chemo-resistant and have been recently considered resistant to some targeted therapies (TT). Erlotinib combined to gemcitabine is the only targeted therapy that showed an overall survival benefit in MPC. New targets and therapeutic approaches, based on new-TT, are actually being evaluated in MPC going from immunotherapy, epigenetics, tumor suppressor gene and oncogenes to stromal matrix regulators. We aim in this paper to present the major causes rendering MPC an untargetable malignancy and to focus on the new therapeutic modalities based on TT in MPC. PMID:26989465

  6. Clinicopathologic Review of 31 Cases of Solid Pseudopapillary Pancreatic Tumors: Can We Use the Scoring System of Microscopic Features for Suggesting Clinically Malignant Potential?

    PubMed

    Kim, Jang-Hee; Lee, Jae-Myeong

    2016-04-01

    A solid pseudopapillary tumor (SPT) is a pancreatic neoplasm of low malignant potential. The potentially malignant pathologic features of SPTs were regarded as angioinvasion, perineural invasion, deep invasion of the surrounding acinar tissue, and nuclear pleomorphism. We retrospectively reviewed 31 cases of SPTs (25 female and 6 male patients, with an average age of 35 ± 14 years). The mean follow-up period was 132.0 ± 55.9 months. To evaluate the clinical impact of above pathological parameters, we analyzed their correlation with actually observed clinical malignancy. In three cases, the SPTs were clearly clinically malignant: one patient had recurrences three times, one showed lymph node metastases, and one deep soft tissue invasion around the gastroduodenal artery. Tumor infiltration to the peripancreatic soft tissue was observed in 17 cases (54.8%). The pathologic features considered suggestive of malignant potential were angioinvasion (25.8%), perineural invasion (6.5%), presence of mitosis in 10 high-power fields (16.1%), and moderate nuclear pleomorphism (19.4%). The presence of at least three of these features was not correlated with clinically confirmed malignant behavior (P = 0.570). Microscopic pathologic features of SPTs cannot be reliably associated with aggressive clinical behavior. Moreover, the absence of these microscopic features cannot exclude clinical malignancy. PMID:27097622

  7. Pancreatic endocrine tumors: recent advances.

    PubMed

    Jensen, R T

    1999-01-01

    Pancreatic endocrine tumors (PET's) can be divided on a clinical and pathologic basis into ten classes [insulinomas, gastrinomas (Zollinger-Ellison syndrome), VIPomas (Verner-Morrison syndrome, WDHA, pancreatic cholera), glucagonomas, somatostatinomas, ACTH-releasing tumors (ACTHomas), growth hormone-releasing factor secreting tumors (GRFomas), nonfunctioning or pancreatic polypeptide secreting tumors (non-functioning PET), PET's causing carcinoid syndrome and PET's causing hypercalcemia)]. Recent reports suggest calcitonin-secreting PET's also rarely occur but whether they cause a distinct clinical syndrome is unclear. PET's resemble carcinoid tumors histologically; in their ability to synthesize and frequently secrete multiple peptides such as neuroendocrine cell markers (chromogranins); their biologic behavior and their tumor growth patterns. Both groups of tumors are highly vascular, have high densities of somatostatin receptors and similar tumor localization studies including somatostatin receptor scintigraphy are used for both. PET's, similar to carcinoids causing the carcinoid syndrome, require two separate treatment options be considered: treatment directed against the hormone-excess state and treatment directed against the tumor per se because of their malignant nature. In the last few years there have been advances in tumor diagnosis, localization methods, treatment approaches particularly related to the use of synthetic somatostatin analogues, and the definition of the role of surgical procedures in these diseases. Important other advances include insights into the long-term natural history of PET's particularly from studies of gastrinomas, which allow prognostic factors to be identified and the timing of treatment options to better planned, as well as insights into the molecular basis of these disorders. The latter includes both a description of the molecular basis of the genetic inherited syndromes associated with PET's or carcinoid tumors, as well as

  8. Minimally invasive surgical approach to pancreatic malignancies.

    PubMed

    Bencini, Lapo; Annecchiarico, Mario; Farsi, Marco; Bartolini, Ilenia; Mirasolo, Vita; Guerra, Francesco; Coratti, Andrea

    2015-12-15

    Pancreatic surgery for malignancy is recognized as challenging for the surgeons and risky for the patients due to consistent perioperative morbidity and mortality. Furthermore, the oncological long-term results are largely disappointing, even for those patients who experience an uneventfully hospital stay. Nevertheless, surgery still remains the cornerstone of a multidisciplinary treatment for pancreatic cancer. In order to maximize the benefits of surgery, the advent of both laparoscopy and robotics has led many surgeons to treat pancreatic cancers with these new methodologies. The reduction of postoperative complications, length of hospital stay and pain, together with a shorter interval between surgery and the beginning of adjuvant chemotherapy, represent the potential advantages over conventional surgery. Lastly, a better cosmetic result, although not crucial in any cancerous patient, could also play a role by improving overall well-being and patient self-perception. The laparoscopic approach to pancreatic surgery is, however, difficult in inexperienced hands and requires a dedicated training in both advanced laparoscopy and pancreatic surgery. The recent large diffusion of the da Vinci(®) robotic platform seems to facilitate many of the technical maneuvers, such as anastomotic biliary and pancreatic reconstructions, accurate lymphadenectomy, and vascular sutures. The two main pancreatic operations, distal pancreatectomy and pancreaticoduodenectomy, are approachable by a minimally invasive path, but more limited interventions such as enucleation are also feasible. Nevertheless, a word of caution should be taken into account when considering the increasing costs of these newest technologies because the main concerns regarding these are the maintenance of all oncological standards and the lack of long-term follow-up. The purpose of this review is to examine the evidence for the use of minimally invasive surgery in pancreatic cancer (and less aggressive tumors

  9. [Surgery for pancreatic neuroendocrine tumors].

    PubMed

    Shibata, Chikashi; Egawa, Shin-Ichi; Motoi, Fuyuhiko; Morikawa, Takanori; Naitoh, Takeshi; Unno, Michiaki; Sasaki, Iwao

    2012-11-01

    Approximately half of pancreatic neuroendocrine tumors (PNETs) are nonfunctioning, and insulinoma and gastrinoma are frequent forms of functioning tumors. The treatment of patients with PNETs should be based on the consideration that more than half are malignant except for insulinomas. Multiple endocrine neoplasia type 1 (MEN1) is often complicated with gastrinoma. Endoscopic ultrasound and somatostain receptor scintigraphy are useful in diagnosing PNETs, and the selective arterial secretagogue injection test is performed if necessary. WHO2010 is available as a histopathologic grading system of malignancy. Although surgical resection should first be considered as a treatment for PNETs, liver metastasis is a major factor hindering resection. In Japan, the choices of drugs to treat liver metastases are too few. In patients with MEN1 in whom PNETS are frequently multiple, we should perform procedures that preserve pancreatic function, although some patients may require total pancreatectomy for the complete resection of tumors. The indications for total pancreatectomy should be determined individually based on the tumor status and patient age. PMID:23330458

  10. Pancreatic paracoccidioidomycosis simulating malignant neoplasia: case report.

    PubMed

    Lima, Talles Bazeia; Domingues, Maria Aparecida Custódio; Caramori, Carlos Antonio; Silva, Giovanni Faria; de Oliveira, Cássio Vieira; Yamashiro, Fábio da Silva; Franzoni, Letícia de Campos; Sassaki, Lígia Yukie; Romeiro, Fernando Gomes

    2013-09-14

    Paracoccidioidomycosis is a systemic granulomatous disease caused by fungus, and must be considered in the differential diagnosis of intra-abdominal tumors in endemic areas. We report a rare case of paracoccidioidomycosis in the pancreas. A 45-year-old man was referred to our institution with a 2-mo history of epigastric abdominal pain that was not diet-related, with night sweating, inappetence, weight loss, jaundice, pruritus, choluria, and acholic feces, without signs of sepsis or palpable tumors. Abdominal ultrasonography (US) showed a solid mass of approximately 7 cm × 5.5 cm on the pancreas head. Abdominal computerized tomography showed dilation of the biliary tract, an enlarged pancreas (up to 4.5 in the head region), with dilation of the major pancreatic duct. The patient underwent exploratory laparotomy, and the surgical description consisted of a tumor, measuring 7 to 8 cm with a poorly-defined margin, adhering to posterior planes and mesenteric vessels, showing an enlarged bile duct. External drainage of the biliary tract, Roux-en-Y gastroenteroanastomosis, lymph node excision, and biopsies were performed, but malignant neoplasia was not found. Microscopic analysis showed chronic pancreatitis and a granulomatous chronic inflammatory process in the choledochal lymph node. Acid-alcohol resistant bacillus and fungus screening were negative. Fine-needle aspiration of the pancreas was performed under US guidance. The smear was compatible with infection by Paracoccidioides brasiliensis. We report a rare case of paracoccidioidomycosis simulating a malignant neoplasia in the pancreas head. PMID:24039371

  11. Radiological description of cystic pancreatic tumors.

    PubMed

    Rodríguez Torres, C; Larrosa López, R

    2016-01-01

    Although most cystic pancreatic lesions are pseudocysts, it is important to do a thorough differential diagnosis with true cystic tumors because cystic tumors are potentially malignant. Sometimes computed tomography and magnetic resonance imaging cannot establish the definitive diagnosis, making it necessary to perform other imaging tests such as endoscopic ultrasound, which in addition to morphological information, can also enable cytologic and biochemical analysis of the lesion through puncture and aspiration of its contents. Combining all these findings nearly always provides enough diagnostic information to allow the appropriate approach in each case. This article describes the specific morphological characteristics for each cystic pancreatic tumor on computed tomography, magnetic resonance imaging, and endoscopic ultrasound and reviews the guidelines for managing these types of lesions.

  12. Endoscopic approach to the diagnosis of pancreatic cystic tumor

    PubMed Central

    Kawaguchi, Yoshiaki; Mine, Tetsuya

    2016-01-01

    Because of the aging of the population, prevalence of medical checkups, and advances in imaging studies, the number of pancreatic cystic lesions detected has increased. Once these lesions are detected, neoplastic cysts should be differentiated from non-neoplastic cysts. Furthermore, because of the malignant potential of some neoplastic pancreatic cysts, further differentiation between benign and malignant cysts should be made regardless of their size. Although endoscopic ultrasound (EUS) has a very high diagnostic performance for pancreatic cystic lesions among the various imaging modalities, EUS findings alone are insufficient for the differentiation of pancreatic cysts and diagnosis of malignancy. In addition, cytology by EUS-guided fine-needle aspiration (FNA) has a high specificity but a low sensitivity for diagnosing malignancy in pancreatic cystic tumors. The levels of amylase, lipase, and tumor markers in pancreatic cystic fluid are considered auxiliary parameters for diagnosis of benign and malignant cysts, and a definitive diagnosis of malignancy using these parameters is difficult. Thus, in addition to EUS, cytology by EUS-FNA, and cystic fluid analysis, new techniques based on EUS-guided through-the-needle imaging, such as confocal laser endomicroscopy and cystoscopy, have been explored in recent years. PMID:26909130

  13. Pancreatic neuroendocrine tumors: biology, diagnosis, and treatment

    PubMed Central

    Ro, Cynthia; Chai, Wanxing; Yu, Victoria E.; Yu, Run

    2013-01-01

    Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are somewhat understood, but their molecular pathogenesis remains unknown. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is unpredictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally indicate a less favorable prognosis. Endocrine testing, imaging, and histological evidence are necessary to accurately diagnose PNETs. A 4-pronged aggressive treatment approach consisting of surgery, locoregional therapy, systemic therapy, and complication control has become popular in academic centers around the world. The optimal application of the multiple systemic therapeutic modalities is under development; efficacy, safety, availability, and cost should be considered when treating a specific patient. The clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including the novel Mahvash disease, are summarized. PMID:23237225

  14. Pancreatic islet cell tumor

    MedlinePlus

    Complications of these tumors include: Diabetes Hormone crises (if the tumor releases certain types of hormones) Severe low blood sugar (from insulinomas) Severe ulcers in the stomach and small intestine (from gastrinomas) Spread of the tumor to the liver

  15. Update on pancreatic neuroendocrine tumors

    PubMed Central

    McKenna, Logan R.

    2014-01-01

    Pancreatic neuroendocrine tumors (pNETs) are relatively rare tumors comprising 1-2% of all pancreas neoplasms. In the last 10 years our understanding of this disease has increased dramatically allowing for advancements in the treatment of pNETs. Surgical excision remains the primary therapy for localized tumors and only potential for cure. New surgical techniques using laparoscopic approaches to complex pancreatic resections are a major advancement in surgical therapy and increasingly possible. With early detection being less common, most patients present with metastatic disease. Management of these patients requires multidisciplinary care combining the best of surgery, chemotherapy and other targeted therapies. In addition to surgical advances, recently, there have been significant advances in systemic therapy and targeted molecular therapy. PMID:25493258

  16. Imaging probe for tumor malignancy

    NASA Astrophysics Data System (ADS)

    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.

  17. Malignant Peripheral Nerve Sheath Tumor.

    PubMed

    James, Aaron W; Shurell, Elizabeth; Singh, Arun; Dry, Sarah M; Eilber, Fritz C

    2016-10-01

    Malignant peripheral nerve sheath tumor (MPNST) is the sixth most common type of soft tissue sarcoma. Most MPNSTs arise in association with a peripheral nerve or preexisting neurofibroma. Neurofibromatosis type is the most important risk factor for MPNST. Tumor size and fludeoxyglucose F 18 avidity are among the most helpful parameters to distinguish MPNST from a benign peripheral nerve sheath tumor. The histopathologic diagnosis is predominantly a diagnosis of light microscopy. Immunohistochemical stains are most helpful to distinguish high-grade MPNST from its histologic mimics. Current surgical management of high-grade MPNST is similar to that of other high-grade soft tissue sarcomas. PMID:27591499

  18. Postirradiation malignant salivary gland tumor.

    PubMed

    Rice, D H; Batsakis, J G; McClatchey, K D

    1976-11-01

    Information concerning the relationship between salivary gland tumors and prior exposure to radiation for benign conditions or by accident is slowly being gathered. As yet, no statistical confidence can be established in this relationship. Very likely, this confidence will require studies akin to those done on the problem of thyroid cancer and irradiation. Including the case reported here, 50 tumors of the salivary glands have been reported to have followed prior radiation exposure. Twenty-three of these tumors have been malignant, with the mucoepidermoid carcinoma the most frequent histological type. The latent period in salivary tissues is 20 or more years.

  19. An unusual presentation of a solid pseudopapillary pancreatic tumor.

    PubMed

    Månsson, Christopher; Karlson, Britt-Marie

    2012-01-01

    Solid pseudopapillary pancreatic tumor (SPPT) is a rare tumor that constitutes 1-2% of all pancreatic tumors and most of the patients are young females. SPPT has low malignancy potential and radical resection is associated with good results and a high survival rate, even in cases with large tumors: the 5-year survival rate is estimated as 95%. This paper describes an unusual presentation of an SPPT discovered after blunt trauma to the abdomen during a basketball game. Computed tomography revealed a large tumor in the pancreatic head and the patient was operated by pylorus-preseving pancreaticoduodenectomy. The histopathologic examination indicated an SPPT with R0-resection and after 4 years there were no signs of recurrence.

  20. Malignant Solitary Fibrous Tumor of the Pancreas.

    PubMed

    Estrella, Jeannelyn S; Wang, Huamin; Bhosale, Priya R; Evans, Harry L; Abraham, Susan C

    2015-08-01

    Solitary fibrous tumor (SFT) arising in the pancreas is exceedingly rare, with only 11 cases reported in the English literature. All cases described thus far have exhibited benign histology. We report the first case of malignant SFT of the pancreas. The patient was a 52-year-old woman who presented with obstructive jaundice and a 15-cm pancreatic head mass. The mass showed areas with typical histologic features for SFT including small fibroblastlike cells arranged in the well-characterized "patternless pattern" of architecture, hemangiopericytomalike vessels, areas with dense collagen and infrequent mitoses (0-2 per 10 high-power fields [HPFs]). In addition, multiple areas with an overtly sarcomatous morphology were present, containing large spindle and epithelioid cells with nuclear pleomorphism, marked cellularity, up to17 mitoses per 10 HPFs, and necrosis. Immunohistochemical stains were positive for CD34 and B-cell CLL/lymphoma 2 (Bcl-2) in both benign and malignant components and showed strong, diffuse p53 and p16 staining in the malignant component. At last follow-up (40 months), the patient was alive and well without evidence of disease. However, given that the presence of a malignant component in extrapancreatic SFT has been associated with recurrence/metastasis and death, complete surgical resection and close long-term follow-up is required.

  1. Malignant Solitary Fibrous Tumor of the Pancreas.

    PubMed

    Estrella, Jeannelyn S; Wang, Huamin; Bhosale, Priya R; Evans, Harry L; Abraham, Susan C

    2015-08-01

    Solitary fibrous tumor (SFT) arising in the pancreas is exceedingly rare, with only 11 cases reported in the English literature. All cases described thus far have exhibited benign histology. We report the first case of malignant SFT of the pancreas. The patient was a 52-year-old woman who presented with obstructive jaundice and a 15-cm pancreatic head mass. The mass showed areas with typical histologic features for SFT including small fibroblastlike cells arranged in the well-characterized "patternless pattern" of architecture, hemangiopericytomalike vessels, areas with dense collagen and infrequent mitoses (0-2 per 10 high-power fields [HPFs]). In addition, multiple areas with an overtly sarcomatous morphology were present, containing large spindle and epithelioid cells with nuclear pleomorphism, marked cellularity, up to17 mitoses per 10 HPFs, and necrosis. Immunohistochemical stains were positive for CD34 and B-cell CLL/lymphoma 2 (Bcl-2) in both benign and malignant components and showed strong, diffuse p53 and p16 staining in the malignant component. At last follow-up (40 months), the patient was alive and well without evidence of disease. However, given that the presence of a malignant component in extrapancreatic SFT has been associated with recurrence/metastasis and death, complete surgical resection and close long-term follow-up is required. PMID:26166470

  2. Surgical management of pancreatic neuroendocrine tumors.

    PubMed

    Kimura, Wataru; Tezuka, Koji; Hirai, Ichiro

    2011-10-01

    This study outlines the surgical management and clinicopathological findings of pancreatic neuroendocrine tumors (P-NETs). There are various surgical options, such as enucleation of the tumor, spleen-preserving distal pancreatectomy, distal pancreatectomy with splenectomy, pancreatoduodenectomy, and duodenum-preserving pancreas head resection. Lymph node dissection is performed for malignant cases. New guidelines and classifications have been proposed and are now being used in clinical practice. However, there are still no clear indications for organ-preserving pancreatic resection or lymph node dissection. Hepatectomy is the first choice for liver metastases of well-differentiated neuroendocrine carcinoma without extrahepatic metastases. On the other hand, cisplatin-based combination therapy is performed as first-line chemotherapy for metastatic poorly differentiated neuroendocrine carcinoma. Other treatment options are radiofrequency ablation, transarterial chemoembolization/embolization, and liver transplantation. Systematic chemotherapy and biotherapy, such as that with somatostatin analogue and interferon-α, are used for recurrence after surgery. The precise surgical techniques for enucleation of the tumor and spleen-preserving distal pancreatectomy are described. PMID:21922354

  3. General Information about Pancreatic Neuroendocrine Tumors (Islet Cell Tumors)

    MedlinePlus

    ... Islet Cell Tumors) Treatment (PDQ®)–Patient Version General Information About Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Go ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

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

    PubMed

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

    2016-03-28

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

  5. [Splenoportography in pancreatic tumors and retroperitoneal neoplasms].

    PubMed

    Roshchektaev, N V

    1975-01-01

    Along with other methods of investigation splenoportography was performed in 29 patients with tumors and in 2 patients with cystic affection of the pancreas. Moreover, in 5 cases splenoportography was performed due to a suspicion to pancreatic tumor, and also in 6 patients with retroperitoneal tumors and in 7-with renal tumors. In all these patients with pancreatic tumors splenoportograms have shown changes on the part of a splenoportal trunk, which corresponded to the localization and degree of spread of a tumor in most cases. Splenoportography is felt to be rational in retroperitoneal tumors. In such cases splenoportography would contribute to a detailed determination of tumor localization and its relation with the liver.

  6. Fundamental differences in the neural invasion behavior of pancreatic endocrine tumors: relevance for local recurrence rates?

    PubMed

    Bergmann, Frank; Ceyhan, Güralp O; Rieker, Ralf J; Esposito, Irene; Fischer, Lars; Herpel, Esther; Friess, Helmut; Schirmacher, Peter; Kern, Michael A

    2009-01-01

    Neural invasion represents an important prognostic factor in pancreatic cancer, and it is thought to be one of the main causes for the high rate of postoperative local recurrences in pancreatic ductal adenocarcinomas. In contrast to the latter, systematic investigations of the mode and extent of neural invasion in pancreatic endocrine tumors have not yet been carried out, although this process represents an important feature in the classification of these tumors. In the present study, a total of 48 pancreatic endocrine tumors were analyzed including 10 well-differentiated endocrine tumors of uncertain behavior, 33 well-differentiated endocrine carcinomas, and 5 poorly differentiated endocrine carcinomas. Neural invasion was found in a large subset (73%) of pancreatic endocrine tumors. The frequency of neural invasion correlated with the grade of malignancy but occurred irrespective of functional activity, hormone phenotype, or histomorphology. Analogous to pancreatic ductal adenocarcinoma, the expression of epidermal growth factor receptor and nerve growth factor, which were expressed in 50% and 100% of the tumors, respectively, seemed to be associated with the frequency of neural invasion. However, in contrast to pancreatic ductal adenocarcinoma, neural invasion in pancreatic endocrine tumors was only detected within the tumor boundaries and did not reach beyond the tumor invasion front. This phenomenon may explain the low rate of local relapses after tumor resection in pancreatic endocrine tumors despite the high frequency of neural invasion.

  7. Malignant Peripheral Nerve Sheath Tumors.

    PubMed

    Durbin, Adam D; Ki, Dong Hyuk; He, Shuning; Look, A Thomas

    2016-01-01

    Malignant peripheral nerve sheath tumors (MPNST) are tumors derived from Schwann cells or Schwann cell precursors. Although rare overall, the incidence of MPNST has increased with improved clinical management of patients with the neurofibromatosis type 1 (NF1) tumor predisposition syndrome. Unfortunately, current treatment modalities for MPNST are limited, with no targeted therapies available and poor efficacy of conventional radiation and chemotherapeutic regimens. Many murine and zebrafish models of MPNST have been developed, which have helped to elucidate the genes and pathways that are dysregulated in MPNST tumorigenesis, including the p53, and the RB1, PI3K-Akt-mTOR, RAS-ERK and Wnt signaling pathways. Preclinical results have suggested that new therapies, including mTOR and ERK inhibitors, may synergize with conventional chemotherapy in human tumors. The discovery of new genome editing technologies, like CRISPR-cas9, and their successful application to the zebrafish model will enable rapid progress in the faithful modeling of MPNST molecular pathogenesis. The zebrafish model is especially suited for high throughput screening of new targeted therapeutics as well as drugs approved for other purposes, which may help to bring enhanced treatment modalities into human clinical trials for this devastating disease. PMID:27165368

  8. Retroperitoneal bronchogenic cyst as a differential diagnosis of pancreatic mucinous cystic tumor.

    PubMed

    Andersson, Roland; Lindell, Gert; Cwikiel, Wojciech; Dawiskiba, Sigmund

    2003-01-01

    Cystic tumors of the pancreas where a pseudocyst has not been able to be excluded has been considered potentially proliferative and pre-malignant or malignant and thus aggressive surgical approach has been advocated. Retroperitoneal cystic tumors are rare and among these bronchogenic cysts are extremely infrequent. The present paper describes a case of bronchogenic cyst in association with the pancreas in which diagnostic work-up was not able to exclude a proliferative pancreatic cystic tumor.

  9. Utility of preoperative dynamic magnetic resonance imaging of the pancreas in diagnosing tumor-forming pancreatitis that mimics pancreatic cancer: report of a case.

    PubMed

    Kuroki, Tamotsu; Tajima, Yoshitsugu; Tsuneoka, Noritsugu; Adachi, Tomohiko; Kanematsu, Takashi

    2010-01-01

    The differential diagnosis of pancreatic carcinoma and tumor-forming pancreatitis remains difficult, and this situation can cause serious problems because the management and prognosis of these two focal pancreatic masses are entirely different. We herein report a case of tumor-forming pancreatitis that mimics pancreatic carcinoma in an 80-year-old woman. Computed tomography showed a solid mass in the head of the pancreas, and endoscopic retrograde cholangiopancreatography showed a complete obstruction of the main pancreatic duct in the head of the pancreas. Dynamic contrastenhanced magnetic resonance imaging (MRI) demonstrated a time-signal intensity curve (TIC) with a slow rise to a peak (1 min after the administration of the contrast material), followed by a slow decline at the pancreatic mass, indicating a fibrotic pancreas. Under the diagnosis of tumor-forming pancreatitis, the patient underwent a segmental pancreatectomy instead of a pancreaticoduodenectomy. The histopathology of the pancreatic mass was chronic pancreatitis without malignancy. The pancreatic TIC obtained from dynamiccontrast MRI can be helpful to differentiate tumor-forming pancreatitis from pancreatic carcinoma and to avoid any unnecessary major pancreatic surgery.

  10. Pancreatic metastasis from mycosis fungoides mimicking primary pancreatic tumor

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Uehlinger, E

    1976-01-01

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

  12. Extracorporeal Irradiation in Malignant Bone Tumors.

    PubMed

    Bhandari, R B; Jha, A K; Neupane, P; Chaurasia, P P; Sigdel, A

    2015-01-01

    Extracorporeal irradiation (ECI) is relatively a rare method used in the management of malignant bone tumors (MBT). It consists of en block removal of the tumor bearing bone segment, removal of the tumor from the bone, irradiation and re implantation back in the body. PMID:27549504

  13. Malignant tumor emboli to the peripheral vessels.

    PubMed

    Vo, N M; Sakurai, H; Gambarini, A J

    1981-01-01

    The first case of tumor emboli trapped in a popliteal aneurysm and the longest survivor for this condition are reported. The characteristics of 25 cases reported in the literature since 1940 and the mechanism of tumor spread are reviewed. Tumor emboli represent the late stage of a malignancy and treatment does not seem to affect long-term survival. PMID:7017284

  14. Malignant tumors in an ancient Egyptian population.

    PubMed

    Zink, A; Rohrbach, H; Szeimies, U; Hagedorn, H G; Haas, C J; Weyss, C; Bachmeier, B; Nerlich, A G

    1999-01-01

    Since it is still an open debate whether malignant tumors are mainly influenced by environmental factors, the frequency of such malignant tumors in historic populations with different living conditions is of particular interest. In the present study, we investigated the occurrence of malignant tumors affecting bone tissue in a population of mumrnies and skeletons, which had been excavated from the large necropolis of Thebes-West, Upper Egypt. Our study material comprised a series of at least 415 individuals (thereof 325 adults) dating from approx. 1500-500 B.C. All individuals had been mummified, but were severely damaged and partially broken by grave robbers, so that often only parts of the mummies/skeletons were available for investigation. The available specimens were subjected to careful macroscopic examination, while isolated findings were radiologically analyzed. Using this approach, we identified at least 4 cases showing malignant tumors affecting the skeleton. In two cases, multiple mixed osteolytic-osteoblastic lesions suggested multiple metastases from carcinomas. Two further individuals presented with multiple osteolyses (vertebra, pelvis, skull) most suggestive of multiple myeloma. The observation of at least 4 cases of malignant tumors with osseous manifestation in a series of 325 adult individuals provides clear evidence that malignant tumors were not a rare event in the ancient Egyptian study population, particularly when the limitations of a study of tumors manifested only in osseous remnants are taken into consideration. A calculation of the age- and sex-adjusted tumor frequency in our material in comparison with a recent model for such a material by Waldron (1996) indicates that the rate of malignant tumors with bone affection in our series is higher than in an English population from 1901-1905, although lower than in a comparable present day population. This clearly indicates that important factors affecting malignant tumors were effective even

  15. Capecitabine, Temozolomide and Bevacizumab for Metastatic or Unresectable Pancreatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2016-09-21

    Gastrinoma; Glucagonoma; Insulinoma; Pancreatic Polypeptide Tumor; Recurrent Islet Cell Carcinoma; Recurrent Pancreatic Cancer; Somatostatinoma; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  16. [CHEMOPERFUSION TECHNOLOGIES IN TREATMENT FOR MALIGNANT TUMORS].

    PubMed

    Belyaev, A M; Gafton, G I; Levchenko, E V; Karachun, A M; Gulyaev, A V; Senchik, K Yu; Bespalov, V G; Berlev, I V; Urmancheeva, A F; Guseinov, K D; Semiletova, Yu V; Mamontov, O N; Kalinin, P V; Kireeva, G S; Belyaeva, O A; Alexeev, V V

    2015-01-01

    The data of literature on possibility of the use of perfusion technologies in combined treatment for malignant tumors of different sites are presented. Possible complications during hyperthermic chemoperfusion are discussed and the effectiveness of this method is analyzed. PMID:26242165

  17. Irreversible Electroporation of Hepatic and Pancreatic Malignancies: Radiologic-Pathologic Correlation.

    PubMed

    Gonzalez-Beicos, Aldo; Venkat, Shree; Songrug, Tanakorn; Poveda, Julio; Garcia-Buitrago, Monica; Poozhikunnath Mohan, Prasoon; Narayanan, Govindarajan

    2015-09-01

    Irreversible electroporation (IRE) is a novel therapy that has shown to be a feasible and promising alternative to conventional ablative techniques when treating tumors near vital structures or blood vessels. The clinical efficacy of IRE has been evaluated using established imaging criteria. This study evaluates the histologic and imaging response of hepatic and pancreatic malignancies that were surgically resected after IRE. In total, 12 lesions ablated with IRE were included, including 3 pancreatic carcinomas, 5 primary tumors of the liver, and 4 metastatic tumors of the liver. The rate of complete response to IRE was 25% based on the histologic evaluation of the resected tumors. Although treatment-related vessel wall changes were noted in several cases in histologic findings, there was no evidence of vascular luminal narrowing or obliteration in any of the specimens. The imaging response to IRE before surgical resection usually resulted in underestimation of disease burden when compared with the histologic response seen on the resected specimens.

  18. Malignant mixed tumor of the lacrimal gland.

    PubMed

    Ludwig, M E; LiVolsi, V A; McMahon, R T

    1979-10-01

    This paper reports a case of carcinoma arising in a benign mixed tumor of lacrimal gland following multiple recurrences. The patient had eight recurrences of the benign lesion and after 32 years developed an adenocarcinoma associated with recurrent nodules of still recognizable benign mixed tumor. The literature on malignant mixed tumors of the lacrimal gland is reviewed noting the confusion in diagnostic terminology in early reports. Our patient illustrates the resemblance between malignant mixed tumor (carcinoma arising in pleomorphic adenoma) of lacrimal and salivary gland both clinically and pathologically.

  19. Pancreatic mixed ductal-islet tumors. Is this an entity?

    PubMed

    Permert, J; Mogaki, M; Andrén-Sandberg, A; Kazakoff, K; Pour, P M

    1992-02-01

    Thirty-eight human pancreatic cancer specimens were studied for the reactivity of cancer cells with monoclonal antibodies against insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP), gastrin, calcitonin, and with argyrophilic reactivity. Immunoreactivity with one or several antibodies or argyrophilic reactivity were found in 30 (79%) cases. In 17 cases, the number of endocrine cells was excessive and morphologically consistent with the mixed ductal-islet tumor. Although most immunoreactive cells were located at the base of the malignant glands, some had intraepithelial location and were also present in the invasive portion of cancers, indicating their malignant nature. Endocrine cell proliferation were found in the pancreatic tissue adjacent to the carcinoma in 8 out of 12 specimens examined. In these cases, the immunoreactive cells were either distributed among the acinar cells or ductal cells. More endocrine cells were found in the hyperplastic ducts; however, no correlation was found between the degree of hyperplasia and the occurrence of any type of immunoreactive cells. Although several types of endocrine cells occurred in different pancreatic regions (head, body, and tail), PP cells were restricted to tissues taken from the head of the pancreas. Experimental data and similar observations by other investigators led us to conclude that participation of endocrine cells in ductal-type carcinomas is a general phenomenon and does not justify the classification of these lesions to mixed ductal-islet entity. However, because immunoreactive cells were more common and numerous in well-differentiated carcinomas, they may have some prognostic values. PMID:1316418

  20. Genetics of Bladder Malignant Tumors in Childhood.

    PubMed

    Zangari, Andrea; Zaini, Johan; Gulìa, Caterina

    2016-02-01

    Bladder masses are represented by either benign or malignant entities. Malignant bladder tumors are frequent causes of disease and death in western countries. However, in children they are less common. Additionally, different features are found in childhood, in which non epithelial tumors are more common than epithelial ones. Rhabdomyosarcoma is the most common pediatric bladder tumor, but many other types of lesions may be found, such as malignant rhabdoid tumor (MRT), inflammatory myofibroblastic tumor and neuroblastoma. Other rarer tumors described in literature include urothelial carcinoma and other epithelial neoplasms. Rhabdomyosarcoma is associated to a variety of genetic syndromes and many genes are involved in tumor development. PAX3-FKHR and PAX7-FKHR (P-F) fusion state has important implications in the pathogenesis and biology of RMS, and different genes alterations are involved in the pathogenesis of P-F negative and embryonal RMS, which are the subsets of tumors most frequently affecting the bladder. These genes include p53, MEF2, MYOG, Ptch1, Gli1, Gli3, Myf5, MyoD1, NF1, NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB1, FBXW7, IGF1R, PDGFRA, ERBB2/4, MET, BCOR. Malignant rhabdoid tumor (MRT) usually shows SMARCB1/INI1 alterations. Anaplastic lymphoma kinase (ALK) gene translocations are the most frequently associated alterations in inflammatory myofibroblastic tumor (IMT). Few genes alterations in urothelial neoplasms have been reported in the paediatric population, which are mainly related to deletion of p16/lnk4, overexpression of CK20 and overexpression of p53. Here, we reviewed available literature to identify genes associated to bladder malignancies in children and discussed their possible relationships with these tumors. PMID:27013922

  1. Genetics of Bladder Malignant Tumors in Childhood

    PubMed Central

    Zangari, Andrea; Zaini, Johan; Gulìa, Caterina

    2016-01-01

    Bladder masses are represented by either benign or malignant entities. Malignant bladder tumors are frequent causes of disease and death in western countries. However, in children they are less common. Additionally, different features are found in childhood, in which non epithelial tumors are more common than epithelial ones. Rhabdomyosarcoma is the most common pediatric bladder tumor, but many other types of lesions may be found, such as malignant rhabdoid tumor (MRT), inflammatory myofibroblastic tumor and neuroblastoma. Other rarer tumors described in literature include urothelial carcinoma and other epithelial neoplasms. Rhabdomyosarcoma is associated to a variety of genetic syndromes and many genes are involved in tumor development. PAX3-FKHR and PAX7-FKHR (P-F) fusion state has important implications in the pathogenesis and biology of RMS, and different genes alterations are involved in the pathogenesis of P-F negative and embryonal RMS, which are the subsets of tumors most frequently affecting the bladder. These genes include p53, MEF2, MYOG, Ptch1, Gli1, Gli3, Myf5, MyoD1, NF1, NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB1, FBXW7, IGF1R, PDGFRA, ERBB2/4, MET, BCOR. Malignant rhabdoid tumor (MRT) usually shows SMARCB1/INI1 alterations. Anaplastic lymphoma kinase (ALK) gene translocations are the most frequently associated alterations in inflammatory myofibroblastic tumor (IMT). Few genes alterations in urothelial neoplasms have been reported in the paediatric population, which are mainly related to deletion of p16/lnk4, overexpression of CK20 and overexpression of p53. Here, we reviewed available literature to identify genes associated to bladder malignancies in children and discussed their possible relationships with these tumors. PMID:27013922

  2. Malignant triton tumor (MTT) of the neck.

    PubMed

    Sørensen, Kristine Bjørndal; Godballe, Christian; Krogdahl, Annelise

    2006-03-01

    Malignant Triton Tumor (MTT) is a rare, malignant periphere nerve sheath tumor with rhabdomyoblastic differentiation. One third of described MTT's were located at the head and neck region. One third of these are associated with neurofibromatosis type 1. MTT most often appears in the third decade. MTT's are very aggressive tumors with early metastases and the overall survival is poor (26%). Therefore, early diagnosis and correct treatment is of utmost importance. We report a case of MTT of the left supraclavicular region in a 41-year-old man. We present the pathological findings, both light and immunohistochemically. PMID:16185834

  3. Malignant thyroid tumors after iodine-131 therapy

    SciTech Connect

    Holm, L.E.; Dahlqvist, I.; Israelsson, A.; Lundell, G.

    1980-07-24

    We studied the incidence of malignant thyroid tumors after /sup 131/l therapy in 2727 patients with hyperthyroidism and in 273 euthyroid patients with cardiac disease. The patients were all adults, with a mean age of 57 years. The /sup 131/l therapy was given between 1951 and 1965. The mean follow-up period was 13 years for the hyperthyroid patients (15 years for the 85 per cent surviving for more than five years) and six years for the cardiac patients (12 years for the 41 per cent surviving for more than five years). The incidence of malignant thyroid tumors was based on a search of the Swedish Cancer Registry for the occurrence of such tumors in any of the 3000 patients. At present there is no increased incidence of malignant thyroid tumors after /sup 131/l therapy (four cases observed versus 3.2 cases expected).

  4. Tumor initiating cells in malignant gliomas

    PubMed Central

    Hadjipanayis, Costas G.; Van Meir, Erwin G.

    2009-01-01

    A rare subpopulation of cells within malignant gliomas, which shares canonical properties with neural stem cells (NSCs), may be integral to glial tumor development and perpetuation. These cells, also known as tumor initiating cells (TICs), have the ability to self-renew, develop into any cell in the overall tumor population (multipotency), and proliferate. A defining property of TICs is their ability to initiate new tumors in immunocompromised mice with high efficiency. Mounting evidence suggests that TICs originate from the transformation of NSCs and their progenitors. New findings show that TICs may be more resistant to chemotherapy and radiation than the bulk of tumor cells, thereby permitting recurrent tumor formation and accounting for the failure of conventional therapies. The development of new therapeutic strategies selectively targeting TICs while sparing NSCs may provide for more effective treatment of malignant gliomas. PMID:19189072

  5. Cerebral malignant nerve sheath tumor, triton tumor variant: case report.

    PubMed

    Bornstein-Quevedo, Leticia; Peralta-Olvera, Fabiola; Marhx-Bracho, Alfonso; Rodríguez-Jurado, Rodolfo; De Leon-Bojorge, Beatriz

    2003-01-01

    A case of a cerebral malignant triton tumor in a 3-year-old boy with a 2-month history of frontal headache and no clinical evidence of neurofibromatosis is reported. The computed tomography (CT) scan showed a large, irregular tumor in the right parietooccipital lobe. A partial surgical resection was performed. Histologically, the tumor was highly cellular and consisted of spindle cells with hyperchromatic and pleomorphic nuclei. Focally, neoplastic cells with rhabdomyoblastic features were found. The immunohistochemical study showed that tumor cells were positive for S-100 protein and CD57, and the rhabdomyoblasts expressed desmin, Myo-D1, and myoglobin. During the postoperative period, a massive intraparenchymal hemorrhage was identified and surgical drainage was performed. The patient worsened and died 10 days after the first surgery. Postmortem study was not authorized. Six cases of cerebral malignant nerve sheath tumor have been described; however, primary intraparenchymal malignant triton tumor has not been previously described.

  6. Prostate-Specific Membrane Antigen (PSMA) Avid Pancreatic Neuroendocrine Tumor.

    PubMed

    Vamadevan, Shankar; Shetty, Deepa; Le, Ken; Bui, Chuong; Mansberg, Robert; Loh, Han

    2016-10-01

    Ga-PSMA PET/CT is increasingly used to evaluate recurrent prostatic malignancy due to its high specificity. A 75-year-old man with a previous history of treated prostate cancer 3 years earlier presented with rising prostate-specific antigen (PSA) level and underwent Ga-PSMA PET/CT which demonstrated a PSMA-avid focus in the neck of the pancreas. Triple-phase abdominal CT demonstrated enhancement in the arterial phase and to a lesser extent the venous phase of a soft tissue mass in the neck of the pancreas. Cytological and histopathological examination of the soft tissue mass confirmed a low-grade pancreatic neuroendocrine tumor.

  7. Benign retroperitoneal schwannoma mimicking a pancreatic cystic tumor: case report and literature review.

    PubMed

    Hsiao, W C; Lin, P W; Chang, K C

    1998-01-01

    A rare case of benign retroperitoneal schwannoma mimicking a pancreatic cystic tumor is reported herein. The tumor mass, based on a computed tomography scan and an abdominal echo examination, was initially suspected to be a mucinous cystadenoma or cystadenocarcinoma of the pancreas. However, the surgical and pathohistological findings made a final diagnosis of benign pancreatic schwannoma. The patient is doing well at a 2-year follow-up. The tumor, 18x17x15 cm in size, represented the largest among reported pancreatic schwannomas. Furthermore, a comprehensive review of reported cases of pancreatic schwannoma was carried out to summarize corresponding findings, including benign or malignant forms, adherence to other tissues, cystic change of the tumor, as well as relation to von Recklinghausen's neurofibromatosis.

  8. Autocrine growth factors and solid tumor malignancy.

    PubMed Central

    Walsh, J. H.; Karnes, W. E.; Cuttitta, F.; Walker, A.

    1991-01-01

    The ability of malignant cells to escape the constraint that normally regulate cell growth and differentiation has been a primary focus of attention for investigators of cancer cell biology. An outcome of this attention has been the discovery that the protein products of oncogenes play a role in the activation of growth signal pathways. A second outcome, possibly related to abnormal oncogene expression, has been the discovery that malignant cells frequently show an ability to regulate their own growth by the release of autocrine growth modulatory substances. Most important, the growth of certain malignant cell types has been shown to depend on autocrine growth circuits. A malignant tumor whose continued growth depends on the release of an autocrine growth factor may be vulnerable to treatment with specific receptor antagonists or immunoneutralizing antibodies designed to break the autocrine circuit. Information is rapidly emerging concerning autocrine growth factors in selected human solid tissue malignancy. Images PMID:1926844

  9. Malignant transformation of orbital solitary fibrous tumor.

    PubMed

    Wang, Xiangning; Qian, Jiang; Bi, Yingwen; Ping, Bo; Zhang, Rui

    2013-06-01

    Orbital solitary fibrous tumor (SFT) is a rare tumor and may recur or undergo malignant transformation without complete excision. We present a case of orbital SFT which recurred twice and underwent malignant transformation. The patient was treated with en bloc excision via a lateral orbitotomy. The postoperative histopathologic diagnosis of this case was an adult fibrosarcoma. Postoperative adjuvant radiation therapy was given. In 18 months of further follow-up, there has been no evidence of recurrence, both clinically and in regular imaging studies.

  10. Malignant Peripheral Nerve Sheath Tumor -A Rare Malignancy in Mandible.

    PubMed

    Majumdar, Sumit; Kotina, Sreekanth; Mahesh, Nirujogi; Uppala, Divya; Kumar, Singam Praveen

    2016-06-01

    Malignant Peripheral Nerve Sheath Tumor (MPNST) is biologically an aggressive tumor that is usually found in the extremities, trunk and infrequently found in the head and neck area particularly in the jaws, arising from the cells allied with nerve sheath. Mandibular MPNST may either arise from a preexisting neurofibroma or develop de novo. Because of the greater variability from case to case in overall appearance both clinically and histologically, a case of MPNST of the mandible in a 25-year-old female patient is reported. The lesion was excised and immunohistological studies (S-100 & Neuron specific enolase) were conducted to confirm the neural origin.

  11. Malignant Peripheral Nerve Sheath Tumor -A Rare Malignancy in Mandible

    PubMed Central

    Majumdar, Sumit; Kotina, Sreekanth; Uppala, Divya; Kumar, Singam Praveen

    2016-01-01

    Malignant Peripheral Nerve Sheath Tumor (MPNST) is biologically an aggressive tumor that is usually found in the extremities, trunk and infrequently found in the head and neck area particularly in the jaws, arising from the cells allied with nerve sheath. Mandibular MPNST may either arise from a preexisting neurofibroma or develop de novo. Because of the greater variability from case to case in overall appearance both clinically and histologically, a case of MPNST of the mandible in a 25-year-old female patient is reported. The lesion was excised and immunohistological studies (S-100 & Neuron specific enolase) were conducted to confirm the neural origin. PMID:27504425

  12. MSX2 in pancreatic tumor development and its clinical application for the diagnosis of pancreatic ductal adenocarcinoma

    PubMed Central

    Satoh, Kennichi; Hamada, Shin; Shimosegawa, Tooru

    2012-01-01

    MSX2, a member of the homeobox genes family, is demonstrated to be the downstream target for ras signaling pathway and is expressed in a variety of carcinoma cells, suggesting its relevance to the development of ductal pancreatic tumors since pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary-mucinous neoplasia (IPMN) harbor frequent K-ras gene mutations. Recent studies revealed the roles of MSX2 in the development of carcinoma of various origins including pancreas. Among gastrointestinal tumors, PDAC is one of the most malignant. PDAC progresses rapidly to develop metastatic lesions, frequently by the time of diagnosis, and these tumors are usually resistant to conventional chemotherapy and radiation therapy. The molecular mechanisms regulating the aggressive behavior of PDAC still remain to be clarified. On the other hand, IPMN of the pancreas is distinct from PDAC because of its intraductal growth in the main pancreatic duct or secondary branches with rare invasion and metastasis to distant organs. However, recent evidence indicated that once IPMN showed stromal invasion, it progresses like PDAC. Therefore, it is important to determin how IPMN progresses to malignant phenotype. In this review, we focus on the involvement of MSX2 in the enhancement of malignant behavior in PDAC and IPMN, and further highlight the clinical approach to differentiate PDAC from chronic pancreatitis by evaluating MSX2 expression level. PMID:23162473

  13. Malignant solitary fibrous tumor of the meninges.

    PubMed

    Ogawa, Kumiko; Tada, Toyohiro; Takahashi, Satoru; Sugiyama, Naotake; Inaguma, Shingo; Takahashi, Seishiro S; Shirai, Tomoyuki

    2004-05-01

    Increasing numbers of solitary fibrous tumors (SFTs) in the meninges have been reported since this entity was first recognized. While most cases previously reported were considered to be benign, the malignant potential of extrathoracic SFTs has not been excluded. The authors report a rare case of a meningeal SFT with malignant behavior occurring in a Japanese female patient, initially resected when she was 44 years old and recurring in the same place four times during a 26-year follow-up period. A metastatic tumor to the right lung arose 25 years after the resection of the first meningeal tumor and focal invasion into the cerebellum was also observed with her last (5th) meningeal tumor. Immunohistochemical analysis showed all tumors to be diffusely positive for CD34 and negative for EMA, with a so-called "patternless" histological pattern, featuring thin collagen fibers between tumor cells. A focal "staghorn" vascular pattern was also observed. Ki67 (MIB-1) labeling indices and mitosis rates were 3.1+/-1.2% and less than 1/10 high power fields (HPF) in the first meningeal tumor and 16.1+/-6.4% and 6/10HPF in the last (5th) one, respectively. Thus, the present case suggests that meningeal SFTs possess malignant potential so that careful long-term follow up is required.

  14. Malignant solitary fibrous tumor of the esophagus.

    PubMed

    Lococo, Filippo; Cesario, Alfredo; Mulè, Antonino; Margaritora, Stefano

    2011-04-01

    Solitary fibrous tumor (SFT) of the esophagus has been very rarely reported in literature. Herein, we report a case of a successful surgically treated malignant solitary fibrous tumor of the esophagus. A 36-year-old woman was admitted at our hospital with an erroneous ultrasound-based diagnosis of cervico-mediastinal goiter. Surprisingly, the preoperative diagnostic work-up, including a computed tomographic chest scan, endoscopy, and endoscopic ultrasonography, revealed a pedunculated intraluminal mass in the esophagus. The tumor was radically removed through left antero-lateral cervicotomy. Pathologic and immunohistochemical examination was concluded for a malignant SFT, a rare variant not previously described in relation to the esophagus. The patient underwent adjuvant radiotherapy and is alive with no signs of tumor recurrence 32 months after surgery.

  15. [Intraoperative radiotherapy in malignant bone tumors].

    PubMed

    Yamamuro, T; Kotoura, Y

    1993-06-01

    When a bone tumor is confirmed to be malignant by biopsy and has not expanded into the soft tissue, intraoperative radiation therapy (IORT) is indicated for most parts of the four extremities. The irradiation area is exposed through an extensive skin incision, and the soft tissues are opened and retracted away from the irradiation area, leaving a layer of normal tissue directly covering the tumor. The irradiation is performed with 12-26 MeV electron beams from a betatron at a dose of 50-100 Gy, depending on the radiosensitivity of each tumor. The multifocal bilateral irradiation method is the best for minimizing complications of the soft tissues. Since 1978, we have performed IORT in combination with chemotherapy in 41 cases of malignant bone tumors and experienced only five cases of tumor recurrence one in the irradiated area and four in the non-irradiated area. Joint function in the irradiated limb was excellent. However, due to the high incidence of pathological fracture after IORT in osteolytic tumors, the limb eventually had to be replaced by a prosthesis. After 1984 when cisplatinum was introduced to our chemotherapy protocol, the cumulative 5 year survival rate increased to 81%, with the irradiated lesion preserved in situ in osteoblastic tumors and replaced with a prosthesis in osteolytic tumors.

  16. Prognostic Significance of p27, Ki-67, and Topoisomerase lla Expression in Clinically Nonfunctioning Pancreatic Endocrine Tumors.

    PubMed

    Chang, Hee Jin; Batts, Kenneth P.; Lloyd, Ricardo V.; Sebo, Thomas J.; Thompson, Geoffrey B.; Lohse, Christine M.; Pankratz, Shane V.

    2000-01-01

    Nonfunctioning islet cell tumors or pancreatic endocrine tumors are the most common type of malignant islet cell tumor. Although previously detected usually at an advanced stage because of mass effect, the early detection rate of small localized disease has been increasing. To date it has been difficult to predict the clinical behavior in localized regional nonfunctioning tumors. To investigate potential markers predicting malignancy and poor prognosis in nonfunctioning pancreatic endocrine tumors, we analyzed the expression of Ki-67, topoisomerase Ila (Topolla), and p27, as well as a variety of clinicopathologic parameters in 76 cases of nonfunctioning islet cell tumors (23 benign cases and 53 malignant cases). Ki-67, Topolla. and p27 labeling indices were significantly different between benign and malignant tumors. Expression of Ki-67, Topolla, and p27 were associated with survival in patients with a malignant tumor in a univariate setting. However, only p27 and Topolla were jointly associated with survival in multivariate analysis. Immunohistochemical staining for p27, Topolla, and Ki-67 can be helpful in the diagnosis of nonfunctioning pancreatic endocrine tumor. Analysis of p27 and Topolla may also have potential utility as prognostic factors for malignant tumors.

  17. Malignant metastatic carcinoid presenting as brain tumor

    PubMed Central

    Sundar, I. Vijay; Jain, S. K.; Kurmi, Dhrubajyoti; Sharma, Rakesh; Chopra, Sanjeev; Singhvi, Shashi

    2016-01-01

    Carcinoid tumors are rarely known to metastasise to the brain. It is even more rare for such patients to present with symptoms related to metastases as the initial and only symptom. We present a case of a 60-year-old man who presented with hemiparesis and imaging features suggestive of brain tumor. He underwent surgery and the histopathology revealed metastatic malignant lesion of neuroendocrine origin. A subsequent work up for the primary was negative. Patient was treated with adjuvant radiotherapy. We present this case to highlight the pathophysiological features, workup and treatment options of this rare disease and discuss the methods of differentiating it from more common brain tumors. PMID:27366273

  18. Outcome of stenting in biliary and pancreatic benign and malignant diseases: A comprehensive review

    PubMed Central

    Mangiavillano, Benedetto; Pagano, Nico; Baron, Todd H; Luigiano, Carmelo

    2015-01-01

    Endoscopic stenting has become a widely method for the management of various malignant and benign pancreatico-biliary disorders. Biliary and pancreatic stents are devices made of plastic or metal used primarily to establish patency of an obstructed bile or pancreatic duct and may also be used to treat biliary or pancreatic leaks, pancreatic fluid collections and to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis. In this review, relevant literature search and expert opinions have been used to evaluate the outcome of stenting in biliary and pancreatic benign and malignant diseases. PMID:26290631

  19. General Information about Ovarian Low Malignant Potential Tumors

    MedlinePlus

    ... Malignant Potential Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Low Malignant Potential Tumors Go to ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  20. An intracranial malignant solitary fibrous tumor.

    PubMed

    Choi, Chan-Young; Han, Seong-Rok; Yee, Gi-Taek; Joo, Mee

    2011-04-01

    Intracranial malignant solitary fibrous tumor (SFT) is very rare. It was identified in a 39-year-old female patient who underwent malignant transformation over 6 months. MRI revealed an 8 × 5 × 6 cm mass with heterogenous strong enhancement in the left occipital lobe. Histologic findings and immunophenotype (positive for CD34, bcl-2 and vimentin, and negative for epithelial membrane antigen or S100 protein) of the primary tumor were typical of SFT. However, there was a focal area (<10% of tumor volume) showing hypercellularity, nuclear pleomorphism and increased Ki-67 labeling index (LI) of 10% (average, 1%). At the second operation, the recurrent tumor revealed full-blown histologic features of malignant SFT, such as infiltrative brain invasion, marked nuclear pleomorphism, frequent mitotic figures (15/10 high power fields), and high Ki-67 LI (25%). The presence of atypical histologic finding or increased Ki-67 LI in the typical SFT, although it is focal, needs to be mentioned in the diagnosis and also may require more aggressive surgical management.

  1. Pancreatic pseudocyst or a cystic tumor of the pancreas?

    PubMed Central

    Rabie, Mohammad Ezzedien; El Hakeem, Ismail; Al Skaini, Mohammad Saad; El Hadad, Ahmad; Jamil, Salim; Tahir Shah, Mian; Obaid, Mahmoud

    2014-01-01

    Pancreatic pseudocysts are the most common cystic lesions of the pancreas and may complicate acute pancreatitis, chronic pancreatitis, or pancreatic trauma. While the majority of acute pseudocysts resolve spontaneously, few may require drainage. On the other hand, pancreatic cystic tumors, which usually require extirpation, may disguise as pseudocysts. Hence, the distinction between the two entities is crucial for a successful outcome. We conducted this study to highlight the fundamental differences between pancreatic pseudocysts and cystic tumors so that relevant management plans can be devised. We reviewed the data of patients with pancreatic cystic lesions that underwent intervention between June 2007 and December 2010 in our hospital. We identified 9 patients (5 males and 4 females) with a median age of 40 years (range, 30–70 years). Five patients had pseudocysts, 2 had cystic tumors, and 2 had diseases of undetermined pathology. Pancreatic pseudocysts were treated by pseudocystogastrostomy in 2 cases and percutaneous drainage in 3 cases. One case recurred after percutaneous drainage and required pseudocystogastrostomy. The true pancreatic cysts were serous cystadenoma, which was treated by distal pancreatectomy, and mucinous cystadenocarcinoma, which was initially treated by drainage, like a pseudocyst, and then by distal pancreatectomy when its true nature was revealed. We conclude that every effort should be exerted to distinguish between pancreatic pseudocysts and cystic tumors of the pancreas to avoid the serious misjudgement of draining rather than extirpating a pancreatic cystic tumor. Additionally, percutaneous drainage of a pancreatic pseudocyst is a useful adjunct that may substitute for surgical drainage. PMID:23958054

  2. Pancreatic neuroendocrine tumor with ectopic adrenocorticotropin production: a case report and review of literature.

    PubMed

    Patel, Forum B; Khagi, Simon; Daly, Kevin P; Lechan, Ronald M; Ummaritchot, Vorawan; Saif, Muhammad W

    2013-09-01

    Pancreatic neuroendocrine tumors (p-NETs) entail a vast array of tumors, which can vary from benign neoplastic growths to rapidly aggressive malignancies. Such is the case with ectopic adrenocorticotropic hormone (ACTH)-producing p-NETs. These tumors have been found to be quite aggressive and a challenge to treat, especially due to the occurrence of metastatic disease even after resection of the primary tumor. We discuss the case of a 44-year-old female who initially presented with vague, non-specific symptoms, in which a malignant p-NET was found to be the cause of her clinical presentation. Although resection of the pancreatic mass was performed, the patient presented again with metastatic disease to the liver. PMID:24023341

  3. Malignant Tumors of Tongue in Iranian Population

    PubMed Central

    Akbari, Mohammad Esmaeil; Atarbashi Moghadam, Saede; Atarbashi Moghadam, Fazele; Bastani, Zahra

    2016-01-01

    Background The incidence of oral cancers varies from one country to another, which can be clarified by the difference in the distribution of the risk factors and the possible etiologies. Tongue is a main segment of oral cavity and malignant lesions of this region accounts for nearly 30% of all oral cancers. Objectives In the present study, we evaluated the pattern of tongue cancer in Iranian population and compared these findings with those previously reported in the other countries. Methods In this multicenter, retrospective cross-sectional study recorded cases of the malignant tongue tumors in the cancer research center (CRC) of Shahid Beheshti University of Medical Sciences were extracted. The patient records and their microscopic reports were retrieved from the archives and age, sex and microscopic types were evaluated. It is to be noted that the CRC has been serving as a cancer registry center for major hospitals all over the country since the year of 2003. Thus, the obtained statistics are highly reliable. Results During the years 2003 to 2008, a total number of 952 new cases of the tongue cancer were recorded in the CRC. Most cases are diagnosed in the sixth and seventh decades of life. 450 cases (47.2%) occurred in men and 489 cases (51.36%) in women. Four different types of malignant lesions (epithelial, salivary gland, hematopoietic and mesenchymal) were diagnosed. Epithelial tumors were the most prevalent malignancies (93%) of which squamous cell carcinoma (SCC) made up 87.39% of all lesions. Salivary gland tumors had the second place with 3.15% of the total lesions. Conclusions In Iranian population, squamous cell carcinoma is the most prevalent malignancy of tongue and it is notable that the ratio of female to male population was equal. These lesions were prevalent in the sixth and seventh decades of life. Thus screening examination of tongue by dentist especially in elderly patients is necessary for early detection of cancerous lesions. PMID:27761209

  4. Malignant Solitary Fibrous Tumor of the Scalp.

    PubMed

    Shirley, Brett M; Kang, David R; Sakamoto, Aya Hamao

    2016-07-01

    Solitary fibrous tumors are an uncommon slow growing benign neoplasm originally described as a pleural neoplasm but can also be found in the lung, mediastinum, peritoneum, or any other sites including the head and neck. Malignant solitary fibrous tumors (MSFT) are extremely rare and only few cases have been published in the literature. There have been 19 cases reported of MSFT in the head and neck, but there are no reports of MSFT located within the scalp in the English language literature. We present a case of MSFT arising in the scalp and describe our experience with the clinical presentation, surgical management, and outcome in this pathological condition. PMID:27408445

  5. A large retroperitoneal malignant solitary fibrous tumor.

    PubMed

    Yoh, Tomoaki; Sata, Ritsuko; Kobayashi, Atsushi; Wada, Seidai; Nakamura, Yuya; Kato, Tatsushi; Nakayama, Hiroyuki; Okamura, Ryuji

    2014-01-01

    We report on a large, retroperitoneal, malignant, solitary fibrous tumor (SFT) with high proliferation activity. A 43-year-old man was admitted to our department complaining of a palpable mass. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large retroperitoneal tumor occupying the entire abdominal cavity. A laparotomy was performed for diagnosis and treatment, which revealed a tumor in the retroperitoneum but with no invasion to the surrounding organs, thereby allowing safe macroscopic excision. Histologically, the tumor was composed of spindle-shaped cells with patternless pattern and a hemangiopericytomatous appearance. Moreover, immunohistochemical staining was positive for CD34, vimentin, Bcl-2, and CD99 and negative for desmin, S-100p, and smooth muscle actin (AMA). The tumor exhibited high cellularity, moderate mitotic activity, pleomorphism, necrosis, and hemorrhagic changes. In addition, the Ki-67 labeling index was 37%. These findings confirmed the diagnosis of malignant SFT with high proliferation activity. Subsequently, adjuvant doxorubicin plus ifosfamide chemotherapy was performed. No signs of recurrence were observed 12 months after the surgery.

  6. Tumor M2 pyruvate kinase: a tumor marker and its clinical application in gastrointestinal malignancy.

    PubMed

    Hardt, Philip D; Ewald, Nils

    2008-09-01

    Proliferating cells, in particular tumor cells, express a dimeric isoenzyme of pyruvate kinase, termed Tumor M2 pyruvate kinase. In the last few years, much attention has been paid to this novel tumor marker that can be determined in EDTA-plasma and in the feces. It has been used in diagnosis and surveillance of a variety of malignant diseases. As compared with the established tumor markers, Tumor M2-PK in EDTA-plasma proves to have at least equal sensitivity in pancreatic, gastric, esophageal, colorectal and cholangiocellular cancer. In combination with established tumor markers, EDTA-plasma M2-PK is a useful tool in diagnosis and surveillance of gastrointestinal tumors. In colorectal cancer, M2-PK in EDTA-plasma even proves superiority as compared with CEA. Fecal Tumor M2-PK testing resembles a good noninvasive screening parameter for colorectal cancer with a reported sensitivity of 68.8-91.0% and a specificity of 71.9-100%. It is superior to fecal occult blood testing in colorectal cancer screening. Since it is effective, easy to handle and bears rather low costs, fecal Tumor M2-PK testing is recommended for large-scale CRC screening.

  7. Surgical Treatment and Clinical Outcome of Nonfunctional Pancreatic Neuroendocrine Tumors

    PubMed Central

    Yang, Min; Zeng, Lin; Zhang, Yi; Su, An-ping; Yue, Peng-ju; Tian, Bo-le

    2014-01-01

    Abstract Our primary aim of the present study was to analyze the clinical characteristics and surgical outcome of nonfunctional pancreatic neuroendocrine tumors (non-F-P-NETs), with an emphasis on evaluating the prognostic value of the newly updated 2010 grading classification of the World Health Organization (WHO). Data of 55 consecutive patients who were surgically treated and pathologically diagnosed as non-F-P-NETs in our single institution from January 2000 to December 2013 were retrospectively collected. This entirety comprised of 55 patients (31 males and 24 females), with a mean age of 51.24 ± 12.95 years. Manifestations of non-F-P-NETs were nonspecific. Distal pancreatectomy, pancreaticoduodenectomy, and local resection of pancreatic tumor were the most frequent surgical procedures, while pancreatic fistula was the most common but acceptable complication (30.3%). The overall 5-year survival rate of this entire cohort was 41.0%, with a median survival time of 60.4 months. Patients who underwent R0 resections obtained a better survival than those who did not (P < 0.005). As for the prognostic analysis, tumor size and lymph invasion were only statistically significant in univariate analysis (P = 0.046 and P < 0.05, respectively), whereas the newly updated 2010 grading classification of WHO (G1 and G2 vs G3), distant metastasis, and surgical margin were all meaningful in both univariate and multivariate analysis (P = 0.045, 0.001, and 0.042, respectively). Non-F-P-NETs are a kind of rare neoplasm, with mostly indolent malignancy. Patients with non-F-P-NETs could benefit from the radical resections. The new WHO criteria, distant metastasis and surgical margin, might be independent predictors for the prognosis of non-F-P-NETs. PMID:25396335

  8. Multiple pancreatic metastases from malignant melanoma: Conclusive diagnosis with endoscopic ultrasound-guided fine needle aspiration.

    PubMed

    Jana, Tanima; Caraway, Nancy P; Irisawa, Atsushi; Bhutani, Manoop S

    2015-01-01

    Pancreatic metastases are rare, ranging from 2% to 5% of pancreatic malignancies. Differentiating a primary pancreatic malignancy from a metastasis can be difficult due to similarities on imaging findings, but is crucial to ensure proper treatment. Although transabdominal ultrasound, computed tomography, and magnetic resonance imaging provide useful images, endoscopic ultrasound (EUS) with fine needle aspiration (FNA) is often needed to provide a cytologic diagnosis. Here, we present a unique case of malignant melanoma with pancreatic metastases. It is important for clinicians to recognize the possibility of melanoma metastasizing to the pancreas and the role of EUS with FNA in providing cytological confirmation.

  9. Multiple pancreatic metastases from malignant melanoma: Conclusive diagnosis with endoscopic ultrasound-guided fine needle aspiration.

    PubMed

    Jana, Tanima; Caraway, Nancy P; Irisawa, Atsushi; Bhutani, Manoop S

    2015-01-01

    Pancreatic metastases are rare, ranging from 2% to 5% of pancreatic malignancies. Differentiating a primary pancreatic malignancy from a metastasis can be difficult due to similarities on imaging findings, but is crucial to ensure proper treatment. Although transabdominal ultrasound, computed tomography, and magnetic resonance imaging provide useful images, endoscopic ultrasound (EUS) with fine needle aspiration (FNA) is often needed to provide a cytologic diagnosis. Here, we present a unique case of malignant melanoma with pancreatic metastases. It is important for clinicians to recognize the possibility of melanoma metastasizing to the pancreas and the role of EUS with FNA in providing cytological confirmation. PMID:26020050

  10. Dominant Expression of DCLK1 in Human Pancreatic Cancer Stem Cells Accelerates Tumor Invasion and Metastasis

    PubMed Central

    Ito, Hiromitsu; Tanaka, Shinji; Akiyama, Yoshimitsu; Shimada, Shu; Adikrisna, Rama; Matsumura, Satoshi; Aihara, Arihiro; Mitsunori, Yusuke; Ban, Daisuke; Ochiai, Takanori; Kudo, Atsushi; Arii, Shigeki; Yamaoka, Shoji; Tanabe, Minoru

    2016-01-01

    Patients with pancreatic cancer typically develop tumor invasion and metastasis in the early stage. These malignant behaviors might be originated from cancer stem cells (CSCs), but the responsible target is less known about invisible CSCs especially for invasion and metastasis. We previously examined the proteasome activity of CSCs and constructed a real-time visualization system for human pancreatic CSCs. In the present study, we found that CSCs were highly metastatic and dominantly localized at the invading tumor margins in a liver metastasis model. Microarray and siRNA screening assays showed that doublecortin-like kinase 1 (DCLK1) was predominantly expressed with histone modification in pancreatic CSCs with invasive and metastatic potential. Overexpression of DCLK1 led to amoeboid morphology, which promotes the migration of pancreatic cancer cells. Knockdown of DCLK1 profoundly suppressed in vivo liver metastasis of pancreatic CSCs. Clinically, DCLK1 was overexpressed in the metastatic tumors in patients with pancreatic cancer. Our studies revealed that DCLK1 is essential for the invasive and metastatic properties of CSCs and may be a promising epigenetic and therapeutic target in human pancreatic cancer. PMID:26764906

  11. Carcinoma of the pancreatic head and periampullary region. Tumor staging with laparoscopy and laparoscopic ultrasonography.

    PubMed Central

    John, T G; Greig, J D; Carter, D C; Garden, O J

    1995-01-01

    OBJECTIVE: The authors performed a prospective evaluation of staging laparoscopy with laparoscopic ultrasonography in predicting surgical resectability in patients with carcinomas of the pancreatic head and periampullary region. SUMMARY BACKGROUND DATA: Pancreatic resection with curative intent is possible in a select minority of patients who have carcinomas of the pancreatic head and periampullary region. Patient selection is important to plan appropriate therapy and avoid unnecessary laparotomy in patients with unresectable disease. Laparoscopic ultrasonography is a novel technique that combines the proven benefits of staging laparoscopy with high resolution intraoperative ultrasound of the liver and pancreas, but which has yet to be evaluated critically in the staging of pancreatic malignancy. METHODS: A cohort of 40 consecutive patients referred to a tertiary referral center and with a diagnosis of potentially resectable pancreatic or periampullary cancer underwent staging laparoscopy with laparoscopic ultrasonography. The diagnostic accuracy of staging laparoscopy alone and in conjunction with laparoscopic ultrasonography was evaluated in predicting tumor resectability (absence of peritoneal or liver metastases; absence of malignant regional lymphadenopathy; tumor confined to pancreatic head or periampullary region). RESULTS: "Occult" metastatic lesions were demonstrated by staging laparoscopy in 14 patients (35%). Laparoscopic ultrasonography demonstrated factors confirming unresectable tumor in 23 patients (59%), provided staging information in addition to that of laparoscopy alone in 20 patients (53%), and changed the decision regarding tumor resectability in 10 patients (25%). Staging laparoscopy with laparoscopic ultrasonography was more specific and accurate in predicting tumor resectability than laparoscopy alone (88% and 89% versus 50% and 65%, respectively). CONCLUSIONS: Staging laparoscopy is indispensable in the detection of "occult" intra

  12. Diagnosing Pancreatic Tumors Using Contrast-enhanced Harmonic Endoscopic Ultrasonography with Sonazoid.

    PubMed

    Yamamoto, Naoki; Kato, Hironari; Mizukawa, Sho; Muro, Shinichiro; Akimoto, Yutaka; Uchida, Daisuke; Tomoda, Takeshi; Matsumoto, Kazuyuki; Horiguchi, Shigeru; Tsutsumi, Koichiro; Okada, Hiroyuki

    2016-08-01

    Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with contrast agent enabled us to assess the hemodynamics closely, despite limited data in pancreatic tumors. We have initiated a prospective, single arm, and non-randomized study to clarify the accuracy and safety of CH-EUS with Sonazoid and time-intensity curve (TIC) analysis for diagnosing benign or malignant pancreatic tumors. A total of 200 patients will undergo CH-EUS and TIC analysis. Receiver operating characteristic (ROC) analysis will be used to determine the optimal parameter cutoff values for TIC analysis. This will clarify whether CH-EUS and TIC can further improve the diagnosis of pancreatic tumors over conventional EUS. PMID:27549682

  13. A retroperitoneal neuroendocrine tumor in ectopic pancreatic tissue.

    PubMed

    Okasha, Hussein Hassan; Al-Bassiouni, Fahim; El-Ela, Monir Abo; Al-Gemeie, Emad Hamza; Ezzat, Reem

    2013-07-01

    Ectopic pancreas is the relatively uncommon presence of pancreatic tissue outside the normal location of the pancreas. We report a case of abdominal pain due to retroperitoneal neuroendocrine tumor arising from heterotopic pancreatic tissue between the duodenal wall and the head of the pancreas. Patient underwent surgical enucleation of the tumor.

  14. A Retroperitoneal Neuroendocrine Tumor in Ectopic Pancreatic Tissue

    PubMed Central

    Okasha, Hussein Hassan; Al-Bassiouni, Fahim; El-Ela, Monir Abo; Al-Gemeie, Emad Hamza; Ezzat, Reem

    2013-01-01

    Ectopic pancreas is the relatively uncommon presence of pancreatic tissue outside the normal location of the pancreas. We report a case of abdominal pain due to retroperitoneal neuroendocrine tumor arising from heterotopic pancreatic tissue between the duodenal wall and the head of the pancreas. Patient underwent surgical enucleation of the tumor. PMID:24949389

  15. Irreversible electroporation for the treatment of pancreatic neuroendocrine tumors

    PubMed Central

    Papamichail, Michail; Ali, Amir; Pizanias, Michail; Peddu, Praveen; Karani, John

    2016-01-01

    Backgrounds/Aims Resection or enucleation is currently the treatment of choice for small pancreatic neuroendocrine tumors (NETs). Irreversible electroporation is a novel ablative method that is used for locally advanced pancreatic adenocarcinoma, but little data exists for its use for pancreatic NETs. We report an early experience of IRE for early pancreatic NETs. Methods Between April 2014 and March 2015, 3 patients with small (<2 cm) pancreatic NETs were treated with percutaneous IRE. Results There were no adverse effects during the procedure. Mean hospital stay was 2.6 days. All patients remained disease free on 12-19 months follow up. One patient developed recurrent pancreatitis with pseudocyst formation. Conclusions IRE for small tumors of the pancreas is practical and may offer advantages over other thermal ablative techniques, since it preserves vital structures such as blood vessels, bile and pancreatic ducts. Further data regarding the long term disease free interval is required to establish efficacy.

  16. Irreversible electroporation for the treatment of pancreatic neuroendocrine tumors

    PubMed Central

    Papamichail, Michail; Ali, Amir; Pizanias, Michail; Peddu, Praveen; Karani, John

    2016-01-01

    Backgrounds/Aims Resection or enucleation is currently the treatment of choice for small pancreatic neuroendocrine tumors (NETs). Irreversible electroporation is a novel ablative method that is used for locally advanced pancreatic adenocarcinoma, but little data exists for its use for pancreatic NETs. We report an early experience of IRE for early pancreatic NETs. Methods Between April 2014 and March 2015, 3 patients with small (<2 cm) pancreatic NETs were treated with percutaneous IRE. Results There were no adverse effects during the procedure. Mean hospital stay was 2.6 days. All patients remained disease free on 12-19 months follow up. One patient developed recurrent pancreatitis with pseudocyst formation. Conclusions IRE for small tumors of the pancreas is practical and may offer advantages over other thermal ablative techniques, since it preserves vital structures such as blood vessels, bile and pancreatic ducts. Further data regarding the long term disease free interval is required to establish efficacy. PMID:27621748

  17. Photodynamic Therapy for Malignant Brain Tumors

    PubMed Central

    AKIMOTO, Jiro

    2016-01-01

    Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women’s Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area. PMID:26888042

  18. Photodynamic Therapy for Malignant Brain Tumors.

    PubMed

    Akimoto, Jiro

    2016-01-01

    Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women's Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area. PMID:26888042

  19. Photodynamic therapy of advanced malignant tumors

    NASA Astrophysics Data System (ADS)

    Wang, Lian-xing; Dai, Lu-pin; Lu, Wen-qin

    1993-03-01

    Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T1, 5 cases of T2, and 35 cases of T2 - T3. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

  20. Gastrointestinal stromal tumors (GISTs) and second malignancies

    PubMed Central

    Rodriquenz, Maria Grazia; Rossi, Sabrina; Ricci, Riccardo; Martini, Maurizio; Larocca, Mario; Dipasquale, Angelo; Quirino, Michela; Schinzari, Giovanni; Basso, Michele; D’Argento, Ettore; Strippoli, Antonia; Barone, Carlo; Cassano, Alessandra

    2016-01-01

    Abstract Several evidences showed that patients with gastrointestinal stromal tumors (GISTs) develop additional malignancies. However, thorough incidence of second tumors remains uncertain as the possibility of a common molecular pathogenesis. A retrospective series of 128 patients with histologically proven GIST treated at our institution was evaluated. Molecular analysis of KIT and PDGFR-α genes was performed in all patients. Following the involvement of KRAS mutation in many tumors’ pathogenesis, analysis of KRAS was performed in patients with also second neoplasms. Forty-six out of 128 GIST patients (35.9%) had a second neoplasm. Most second tumors (52%) raised from gastrointestinal tract and 19.6% from genitourinary tract. Benign neoplasms were also included (21.7%). Molecular analysis was available for 29/46 patients with a second tumor: wild-type GISTs (n. 5), exon 11 (n. 16), exon 13 (n. 1), exon 9 (n. 1) KIT mutations, exon 14 PDGFR-α mutation (n. 2) and exon 18 PDGFR-α mutation (n. 4). KIT exon 11 mutations were more frequent between patients who developed a second tumor (P = 0.0003). Mutational analysis of KRAS showed a wild-type sequence in all cases. In metachronous cases, the median time interval between GIST and second tumor was 21.5 months. The high frequency of second tumors suggests that an unknown common molecular mechanism might play a role, but it is not likely that KRAS is involved in this common pathogenesis. The short interval between GIST diagnosis and the onset of second neoplasms asks for a careful follow-up, particularly in the first 3 years after diagnosis. PMID:27661019

  1. Ultrastructural study of benign, low-malignant potential (LMP), and malignant ovarian tumors.

    PubMed

    Ishioka, Shin-ichi; Sagae, Satoru; Ito, Eiki; Kudo, Ryuichi

    2004-03-01

    Ultrastructural characteristics of benign, low-malignant potential (LMP), and malignant ovarian tumors were investigated, considering the aspects of histologic subtypes and histologic grading. In addition, the histogenesis of ovarian cancer was histologically investigated in an attempt to elucidate whether malignant tumor was generated from benign or LMP tumor, or whether it was generated de novo from normal tissues. Although all the benign, LMP, and malignant tumors appeared to be derived from Mullerian duct in serous tumors, the origin of endometrioid or mucinous tumor could not be ultrastructurally clarified. However, there was ultrastructural similarity between benign and malignant tumors among serous, endometrioid, and mucinous tumors, and it was suggested that benign adenoma may be the developmental origin of malignant tumors regardless of the histologic subtype. In addition, the investigation of endometrioid tumors revealed that the differences of histologic grading in malignant tumors reflected the ultrastructural differences, and that G1 tumor had an ultrastructure that was more similar to that of benign and LMP tumors than to that of G2 tumor.

  2. PTEN: Multiple Functions in Human Malignant Tumors

    PubMed Central

    Milella, Michele; Falcone, Italia; Conciatori, Fabiana; Cesta Incani, Ursula; Del Curatolo, Anais; Inzerilli, Nicola; Nuzzo, Carmen M. A.; Vaccaro, Vanja; Vari, Sabrina; Cognetti, Francesco; Ciuffreda, Ludovica

    2015-01-01

    PTEN is the most important negative regulator of the PI3K signaling pathway. In addition to its canonical, PI3K inhibition-dependent functions, PTEN can also function as a tumor suppressor in a PI3K-independent manner. Indeed, the PTEN network regulates a broad spectrum of biological functions, modulating the flow of information from membrane-bound growth factor receptors to nuclear transcription factors, occurring in concert with other tumor suppressors and oncogenic signaling pathways. PTEN acts through its lipid and protein phosphatase activity and other non-enzymatic mechanisms. Studies conducted over the past 10 years have expanded our understanding of the biological role of PTEN, showing that in addition to its ability to regulate proliferation and cell survival, it also plays an intriguing role in regulating genomic stability, cell migration, stem cell self-renewal, and tumor microenvironment. Changes in PTEN protein levels, location, and enzymatic activity through various molecular mechanisms can generate a continuum of functional PTEN levels in inherited syndromes, sporadic cancers, and other diseases. PTEN activity can indeed, be modulated by mutations, epigenetic silencing, transcriptional repression, aberrant protein localization, and post-translational modifications. This review will discuss our current understanding of the biological role of PTEN, how PTEN expression and activity are regulated, and the consequences of PTEN dysregulation in human malignant tumors. PMID:25763354

  3. More Complete Removal of Malignant Brain Tumors by Fluorescence-Guided Surgery

    ClinicalTrials.gov

    2016-05-13

    Benign Neoplasms, Brain; Brain Cancer; Brain Neoplasms, Benign; Brain Neoplasms, Malignant; Brain Tumor, Primary; Brain Tumor, Recurrent; Brain Tumors; Intracranial Neoplasms; Neoplasms, Brain; Neoplasms, Intracranial; Primary Brain Neoplasms; Primary Malignant Brain Neoplasms; Primary Malignant Brain Tumors; Gliomas; Glioblastoma

  4. PDT for malignant tumors: a clinical analysis of 152 cases

    NASA Astrophysics Data System (ADS)

    Zhuang, Shi-Zhang; Wang, Yun-Zhen; Li, Xin; Zhang, Changjun; Wang, Jian-Zhao; Zhang, Da-Ren

    1993-03-01

    Hematoporphyrin derivative (HPD) laser photodynamic therapy (PDT) was applied for the patients of 152 cases of malignant tumors, including tumors of the lip, tongue, esophagus, urinary bladder, skin, larynx, vagina, etc. Since early 1981 good results have been obtained.

  5. Dosimetric comparison of volumetric modulated arc therapy and intensity-modulated radiation therapy for pancreatic malignancies

    SciTech Connect

    Ali, Arif N.; Dhabaan, Anees H.; Jarrio, Christie S.; Siddiqi, Arsalan K.; Landry, Jerome C.

    2012-10-01

    Volumetric-modulated arc therapy (VMAT) has been previously evaluated for several tumor sites and has been shown to provide significant dosimetric and delivery benefits when compared with intensity-modulated radiation therapy (IMRT). To date, there have been no published full reports on the benefits of VMAT use in pancreatic patients compared with IMRT. Ten patients with pancreatic malignancies treated with either IMRT or VMAT were retrospectively identified. Both a double-arc VMAT and a 7-field IMRT plan were generated for each of the 10 patients using the same defined tumor volumes, organs at risk (OAR) volumes, dose, fractionation, and optimization constraints. The planning tumor volume (PTV) maximum dose (55.8 Gy vs. 54.4 Gy), PTV mean dose (53.9 Gy vs. 52.1 Gy), and conformality index (1.11 vs. 0.99) were statistically similar between the IMRT and VMAT plans, respectively. The VMAT plans had a statistically significant reduction in monitor units compared with the IMRT plans (1109 vs. 498, p < 0.001). In addition, the doses to the liver, small bowel, and spinal cord were comparable between the IMRT and VMAT plans. However, the VMAT plans demonstrated a statistically significant reduction in the mean left kidney V{sub 25} (9.4 Gy vs. 2.3 Gy, p = 0.018), mean right kidney V{sub 15} (53.4 Gy vs. 45.9 Gy, p = 0.035), V{sub 20} (32.2 Gy vs. 25.5 Gy, p = 0.016), and V{sub 25} (21.7 Gy vs. 14.9 Gy, p = 0.001). VMAT was investigated in patients with pancreatic malignancies and compared with the current standard of IMRT. VMAT was found to have similar or improved dosimetric parameters for all endpoints considered. Specifically, VMAT provided reduced monitor units and improved bilateral kidney normal tissue dose. The clinical relevance of these benefits in the context of pancreatic cancer patients, however, is currently unclear and requires further investigation.

  6. Synchronous benign and malignant tumors in the ipsilateral parotid gland.

    PubMed

    Roh, Jong-Lyel; Kim, Jin-Man; Park, Chan Il

    2007-01-01

    Synchronous benign and malignant tumors in the ipsilateral salivary glands are extremely rare. We report a unique case of synchronous unilateral parotid tumors in a 71-year-old man. The main parotid lesion was preoperatively suggested to be adenocarcinoma by fine needle aspiration cytology. A coexisting Warthin's tumor was also diagnosed on microscopic examination of total parotidectomy specimens. We describe this case of rare synchronous salivary gland tumors exhibiting both benign and malignant components with a review of the literature.

  7. TNM Staging of Pancreatic Neuroendocrine Tumors

    PubMed Central

    Yang, Min; Zeng, Lin; Zhang, Yi; Wang, Wei-guo; Wang, Li; Ke, Neng-wen; Liu, Xu-bao; Tian, Bo-le

    2015-01-01

    Abstract We aimed to analyze the clinical characteristics and compare the surgical outcome of pancreatic neuroendocrine tumors (p-NETs) using the 2 tumor-node-metastasis (TNM) systems by both the American Joint Committee on Cancer (AJCC) Staging Manual (seventh edition) and the European Neuroendocrine Tumor Society (ENETS). Moreover, we sought to validate the prognostic value of the new AJCC criterion. Data of 145 consecutive patients who were all surgically treated and histologically diagnosed as p-NETs from January 2002 to June 2013 in our single institution were retrospectively collected and analyzed. The 5-year overall survival (OS) rates for AJCC classifications of stages I, II, III, and IV were 79.5%, 63.1%, 15.0%, and NA, respectively, (P < 0.005). As for the ENETS system, the OS rates at 5 years for stages I, II, III, and IV were 75.5%, 72.7%, 29.0%, and NA, respectively, (P < 0.005). Both criteria present no statistically notable difference between stage I and stage II (P > 0.05) but between stage I and stages III and IV (P < 0.05), as well as those between stage II and stages III and IV (P < 0.05). Difference between stage III and IV by ENETS was significant (P = 0.031), whereas that by the AJCC was not (P = 0.144). What's more, the AJCC Staging Manual (seventh edition) was statistically significant in both uni- and multivariate analyses by Cox regression (P < 0.005 and P = 0.025, respectively). Our study indicated that the ENETS TNM staging system might be superior to the AJCC Staging Manual (seventh edition) for the clinical practice of p-NETs. Together with tumor grade and radical resection, the new AJCC system was also validated to be an independent predictor for p-NETs. PMID:25816036

  8. mir-329 restricts tumor growth by targeting grb2 in pancreatic cancer

    PubMed Central

    Wen, Chenlei; Shi, Minmin; Tang, Xiaomei; Chen, Hao; Peng, Chenghong; Li, Hongwei; Fang, Yuan; Deng, Xiaxing; Shen, Baiyong

    2016-01-01

    Pancreatic cancer is one of the most lethal malignancies worldwide. To illustrate the pathogenic mechanism(s), we looked into the expression and function of miR-329 associated with pancreatic cancer development. It was found that miR-329 expression was downregulated in the pancreatic cancer patients who demonstrated significantly shorter overall survival than the patients having upregulated expression. Also, more advanced pT stage cases were observed in the low miR-329 expression group of patients. Interestingly, our studies uncovered that miR-329 overexpression inhibited proliferation and induced apoptosis of pancreatic cancer cells, in contrast the miR-329 inhibitor reversed this phenomenon dramatically. Additionally, overexpression of miR-329 significantly limited tumor growth in the xenograft model. In the mechanistic study, we identified GRB2 as a direct target of miR-329 in pancreatic cancer cells, and expression of GRB2 was inversely correlated with miR-329 expression in pancreatic cancer patients. Furthermore, GRB2 overexpression in cell line and xenograft model dramatically diminished miR-329 mediated anti-proliferation and apoptosis induction, indicating that GRB2/pERK pathway was mainly downregulated by miR-329 expression. In general, our study has shed light on miR-329 regulated mechanism and, miR-329/GRB2/pERK is potential to be targeted for pancreatic cancer management. PMID:26885689

  9. Sternal Resection and Reconstruction for Malignant Phylloides Tumor.

    PubMed

    Selvakumar, Veda Padma Priya; Poonia, Dharmaram; Agrawal, Juhi; Goel, Ashish; Mehta, Sandeep; Kumar, Kapil

    2015-08-01

    Malignant phylloides tumor is a locally aggressive breast neoplasm constituting less than 1 % of all breast cancers. It has a tendency for local recurrence and management is multidisciplinary. We hereby report a case of total sternal resection and reconstruction using Biopore HDPE prosthesis for Malignant Phylloides tumor. PMID:26702245

  10. Neutralizing murine TGFβR2 promotes a differentiated tumor cell phenotype and inhibits pancreatic cancer metastasis.

    PubMed

    Ostapoff, Katherine T; Cenik, Bercin Kutluk; Wang, Miao; Ye, Risheng; Xu, Xiaohong; Nugent, Desiree; Hagopian, Moriah M; Topalovski, Mary; Rivera, Lee B; Carroll, Kyla D; Brekken, Rolf A

    2014-09-15

    Elevated levels of TGFβ are a negative prognostic indicator for patients diagnosed with pancreatic cancer; as a result, the TGFβ pathway is an attractive target for therapy. However, clinical application of pharmacologic inhibition of TGFβ remains challenging because TGFβ has tumor suppressor functions in many epithelial malignancies, including pancreatic cancer. In fact, direct neutralization of TGFβ promotes tumor progression of genetic murine models of pancreatic cancer. Here, we report that neutralizing the activity of murine TGFβ receptor 2 using a monoclonal antibody (2G8) has potent antimetastatic activity in orthotopic human tumor xenografts, syngeneic tumors, and a genetic model of pancreatic cancer. 2G8 reduced activated fibroblasts, collagen deposition, microvessel density, and vascular function. These stromal-specific changes resulted in tumor cell epithelial differentiation and a potent reduction in metastases. We conclude that TGFβ signaling within stromal cells participates directly in tumor cell phenotype and pancreatic cancer progression. Thus, strategies that inhibit TGFβ-dependent effector functions of stromal cells could be efficacious for the therapy of pancreatic tumors. Cancer Res; 74(18); 4996-5007. ©2014 AACR. PMID:25060520

  11. True malignant mixed tumors (carcinosarcoma) of salivary glands.

    PubMed

    Stephen, J; Batsakis, J G; Luna, M A; von der Heyden, U; Byers, R M

    1986-06-01

    True malignant mixed tumors (carcinosarcomas) of salivary glands are of a high grade of malignancy and are distinguishable from the more frequently occurring carcinomas ex pleomorphic adenoma. Having a putative origin from a benign pleomorphic adenoma, the true malignant mixed tumor is an aggressive, often rapidly lethal neoplasm in which the sarcomatous element is most often a chondrosarcoma and the epithelial element is most often a ductal carcinoma. The twelve cases in this report represent the largest recorded series to date.

  12. [Pelvic actinomycosis simulating adnexal malignant tumor].

    PubMed

    Benkiran, L; Gamra, L; Lamalmi, N; Essouyeh, M; Regragui, A; Amrani, M; Souadka, A; Melabbas, M A

    2002-01-01

    The purpose of this report is to describe the case of a 35-year-old patient admitted to the National Oncology Institute in Rabat, Morocco for pelvic pain and deteriorating general status ongoing for 8 months. Clinical and ultrasonographic examination showed a heterogenous mass measuring 7 cm in maximum width located inferior and lateral to the inferior aspect of the right side of the uterus. These findings were suggestive of a malignant tumor of the right ovary. Ovariectomy and omentectomy were performed. Histological examination of surgical specimens demonstrated right tubo-ovarian actinomycosis associated with peritonitis. Genital tract actinomycosis is an uncommon finding in women of childbearing age. It is due to colonization by a pyogenic bacteria (Actinomyces) usually secondary to a gastrointestinal infection, e.g. ileocecum, and sometimes in association with the presence of an intrauterine device or foreign body. Based on this case report, the authors discuss abdominopelvic actinomyocosis with emphasis on tumor-like findings that can lead to misdiagnosis by clinicians and radiologists. PMID:12038184

  13. Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

    ClinicalTrials.gov

    2016-04-12

    Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

  14. Immunohistochemical study of pancreatic neuroendocrine tumor in Panthera tigris tigris.

    PubMed

    Nyska, A; Goldstein, J; Eshkar, G; Klein, B

    1996-07-01

    The histological and immunohistochemical characteristics of a case of pancreatic neuroendocrine tumor are described in a 14-yr-old female Bengal tiger (Panthera tigris tigris) housed at the New Biblical Zoo of Jerusalem, Jerusalem, Israel, 1994. The neoplastic cells were immunohistochemically negative for insulin and glucagon, slightly positive for neuron-specific enolase, moderately positive for serotonin and somatostatin, and markedly positive for chromogranine A and gastrin. This is the first documentation of a pancreatic neuroendocrine tumor in the tiger.

  15. Immunohistochemical study of pancreatic neuroendocrine tumor in Panthera tigris tigris.

    PubMed

    Nyska, A; Goldstein, J; Eshkar, G; Klein, B

    1996-07-01

    The histological and immunohistochemical characteristics of a case of pancreatic neuroendocrine tumor are described in a 14-yr-old female Bengal tiger (Panthera tigris tigris) housed at the New Biblical Zoo of Jerusalem, Jerusalem, Israel, 1994. The neoplastic cells were immunohistochemically negative for insulin and glucagon, slightly positive for neuron-specific enolase, moderately positive for serotonin and somatostatin, and markedly positive for chromogranine A and gastrin. This is the first documentation of a pancreatic neuroendocrine tumor in the tiger. PMID:8827685

  16. Radiation-induced malignant and atypical peripheral nerve sheath tumors

    SciTech Connect

    Foley, K.M.; Woodruff, J.M.; Ellis, F.T.; Posner, J.B.

    1980-04-01

    The reported peripheral nerve complications of therapeutic irradiation in humans include brachial and lumbar plexus fibrosis and cranial and peripheral nerve atrophy. We have encountered 9 patients with malignant (7) and atypical (2) peripheral nerve tumors occurring in an irradiated site suggesting that such tumors represent another delayed effect of radiation treatment on peripheral nerve. In all instances the radio-theray was within an acceptable radiation dosage, yet 3 patients developed local radiation-induced skin and bony abnormalities. The malignant peripheral nerve sheath tumors developed only in the radiation port. Animal studies support the clinical observation that malignant peripheral nerve sheath tumors can occur as a delayed effect of irradiation.

  17. Surgical palliative treatment in bilio-pancreatic malignancy.

    PubMed

    Gouma, D J; van Geenen, R; van Gulik, T; de Wit, L T; Obertop, H

    1999-01-01

    Most patients with bilio-pancreatic malignancy are no candidate for curative resection and will need palliative treatment. Palliation in these patients is focussed on relief symptoms such as obstructive jaundice, duodenal obstruction and pain. It has been suggested that non surgical treatment (stenting) is the optimal palliation for patients with short survival and surgical bypass for those surviving more than 6 months. Unfortunately valid criteria for estimating survival are not available except for metastases. A prognostic score chart to predict survival probabilities for 3,6 and 9 months after diagnosis has been developed. The use of this prognostic score chart may help clinicians to select optimal palliative treatment for individual patients. Surgical biliary drainage can be performed by a simple cholecystoenterostomy; a choledochoduodenostomy or a choledocho/hepaticojejunostomy with Roux-Y jejunal limb reconstruction. The present data available in the literature do not give sufficient guidance to make a well deliberated selection between the different types of bypass surgery but choledochojejunostomy is generally preferred. Gastroentero-stomy is performed routinely during the biliary bypass procedure in our institution because gastric outlet obstruction has been described between 9-21% of the patients who underwent only a surgical biliary bypass but there is still controversy. Recently it was also suggested that there is an indication to perform palliative resections. No results are available to justify resections as a debulking procedure.

  18. [SURGICAL TREATMENT OF TUMORS OF THE LEFT PANCREATIC ANATOMICAL SEGMENT].

    PubMed

    Kopchak, V M; Tkachuk, O S; Kopchak, K V; Duvalko, O V; Khomyak, I V; Pererva, L O; Kvasivka, O O; Andronik, S V; Shevkolenko, G G; Khanenko, V V; Romaniv, Ya V; Grebihn, R M

    2015-04-01

    The results of treatment of 231 patients, suffering tumoral affection of pancreatic left anatomical segment in period of 2009-2013 yrs were analyzed. Individualized approach, using modern technologies, was applied. Radical operations were performed in 129 patients, ageing 14-81 yrs old, including pancreatic distal resections in various modifications, central resection and tumoral enucleation. Possibilities of the extended pancreatic resection performance were studied in conditions of tumoral invasion of adjacent organs, regional vessels, as well as impact of such interventions on postoperative complications and lethality rate. While performing pancreatic subtotal distal resection with simultant resection of affected main venous vessels and adjacent organs the operative intervention risk is enhanced, but possibilities of a radical operations performance in previously considered inoperable patients are expanding.

  19. Penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis

    PubMed Central

    Ranjan, Alok; Srivastava, Sanjay K.

    2016-01-01

    Pancreatic tumors exhibit enhanced autophagy as compared to any other cancer, making it resistant to chemotherapy. We evaluated the effect of penfluridol against pancreatic cancer. Penfluridol treatment induced apoptosis and inhibited the growth of Panc-1, BxPC-3 and AsPC-1, pancreatic cancer cells with IC50 ranging between 6–7 μM after 24 h of treatment. Significant autophagy was induced by penfluridol treatment in pancreatic cancer cells. Punctate LC3B and autophagosomes staining confirmed autophagy. Inhibiting autophagy by chloroquine, bafilomycin, 3-methyladenine or LC3BsiRNA, significantly blocked penfluridol-induced apoptosis, suggesting that autophagy lead to apoptosis in our model. Penfluridol treatment suppressed the growth of BxPC-3 tumor xenografts by 48% as compared to 17% when treated in combination with chloroquine. Similarly, penfluridol suppressed the growth of AsPC-1 tumors by 40% versus 16% when given in combination with chloroquine. TUNEL staining and caspase-3 cleavage revealed less apoptosis in the tumors from mice treated with penfluridol and chloroquine as compared to penfluridol alone. Penfluridol treatment also suppressed the growth of orthotopically implanted Panc-1 tumors by 80% by inducing autophagy-mediated apoptosis in the tumors. These studies established that penfluridol inhibits pancreatic tumor growth by autophagy-mediated apoptosis. Since penfluridol is already in clinic, positive findings from our study will accelerate its clinical development. PMID:27189859

  20. Alisertib and Gemcitabine Hydrochloride in Treating Patients With Solid Tumors or Pancreatic Cancer

    ClinicalTrials.gov

    2016-08-09

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

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

    PubMed Central

    Diacovo, Maria Julia

    2016-01-01

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

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

    PubMed Central

    Diacovo, Maria Julia

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  4. Caveolin-1 overexpression in benign and malignant salivary gland tumors.

    PubMed

    Jaafari-Ashkavandi, Zohreh; Ashraf, Mohammad Javad; Nazhvani, Ali Dehghani; Azizi, Zahra

    2016-02-01

    Caveolin-1, a tyrosine-phosphorylated protein, is supposed to have different regulatory roles as promoter or suppressor in many human cancers. However, no published study concerned its expression in benign and malignant salivary gland tumors. The aim of this study was to evaluate and compare the expression of Cav-1 in the most common benign and malignant salivary gland tumors and evaluate its correlation with proliferation activity. In this cross-sectional retrospective study, immunohistochemical expression of caveolin-1 and Ki67 were evaluated in 49 samples, including 11 normal salivary glands, 15 cases of pleomorphic adenoma (PA), 13 adenoid cystic carcinomas (AdCC), and 10 mucoepidermoid carcinomas (MEC). The expression of Cav-1 was seen in 18 % of normal salivary glands and 85 % of tumors. The immunoreaction in the tumors was significantly higher than normal tissues (P = 0.001), but the difference between benign and malignant tumors was not significant (P = 0.07). Expression of Cav-1 was correlated with Ki67 labeling index in PAs, but not in malignant tumors. Cav-1 expression was not in association with tumor size and stage. Overexpression of Cav-1 was found in salivary gland tumors in comparison with normal tissues, but no significant difference was observed between benign and malignant tumors. Cav-1 was inversely correlated with proliferation in PA. Therefore, this marker may participate in tumorigenesis of salivary gland tumors and may be a potential biomarker for cancer treatments.

  5. Hypercalcemia from metastatic pancreatic neuroendocrine tumor secreting 1,25-dihydroxyvitamin D

    PubMed Central

    Zhu, Viola; de las Morenas, Antonio; Janicek, Milos

    2014-01-01

    Malignant hypercalcemia occurs in about 20-30% of patients with cancer, both solid tumors and hematologic malignancies. The secretion of parathyroid hormone-related protein (PTH-rP) is the most common cause and has been shown to be the etiology of hypercalcemia associated with neuroendocrine tumors. Here we report the case of a patient with metastatic pancreatic neuroendocrine tumor who developed hypercalcemia more than 4 years after the initial diagnosis as a result of secretion of 1,25-dihydroxyvitamin D, a mechanism only commonly seen in lymphomas. The successful control of the patient’s disease with capecitabine and temozolomide led to the alleviation of this paraneoplastic syndrome. PMID:25083313

  6. L1CAM promotes enrichment of immunosuppressive T cells in human pancreatic cancer correlating with malignant progression.

    PubMed

    Grage-Griebenow, Evelin; Jerg, Elfi; Gorys, Artur; Wicklein, Daniel; Wesch, Daniela; Freitag-Wolf, Sandra; Goebel, Lisa; Vogel, Ilka; Becker, Thomas; Ebsen, Michael; Röcken, Christoph; Altevogt, Peter; Schumacher, Udo; Schäfer, Heiner; Sebens, Susanne

    2014-07-01

    Regulatory T cell (T-reg) enrichment in the tumor microenvironment is regarded as an important mechanism of tumor immune escape. Hence, the presence of T-regs in highly malignant pancreatic ductal adenocarcinoma (PDAC) is correlated with short survival. Likewise, the adhesion molecule L1CAM is upregulated during PDAC progression in the pancreatic ductal epithelium also being associated with poor prognosis. To investigate whether L1CAM contributes to enrichment of T-regs in PDAC, human CD4(+)CD25(+)CD127(-)CD49d(-) T-regs and CD4(+)CD25(-) T-effector cells (T-effs) were isolated by magnetic bead separation from blood of healthy donors. Their phenotype and functional behavior were analyzed in dependence on human premalignant (H6c7) or malignant (Panc1) pancreatic ductal epithelial cells, either exhibiting or lacking L1CAM expression. T cells derived from blood and tumors of PDAC patients were analyzed by flow cytometry and findings were correlated with clinical parameters. Predominantly T-regs but not T-effs showed an increased migration on L1CAM expressing H6c7 and Panc1 cells. Whereas proliferation of T-regs did not change in the presence of L1CAM, T-effs proliferated less, exhibited a decreased CD25 expression and an increased expression of CD69. Moreover, these T-effs exhibited a regulatory phenotype as they inhibited proliferation of autologous T cells. Accordingly, CD4(+)CD25(-)CD69(+) T cells were highly abundant in PDAC tissues compared to blood being associated with nodal invasion and higher grading in PDAC patients. Overall, these data point to an important role of L1CAM in the enrichment of immunosuppressive T cells in particular of a CD4(+)CD25(-)CD69(+)-phenotype in PDAC providing a novel mechanism of tumor immune escape which contributes to tumor progression. PMID:24746181

  7. Pancreatic solitary fibrous tumor causing ectopic adrenocorticotropic hormone syndrome.

    PubMed

    Murakami, Keigo; Nakamura, Yasuhiro; Felizola, Saulo J A; Morimoto, Ryo; Satoh, Fumitoshi; Takanami, Kentaro; Katakami, Hideki; Hirota, Seiichi; Takeda, Yoshiyu; Meguro-Horike, Makiko; Horike, Shin-Ichi; Unno, Michiaki; Sasano, Hironobu

    2016-11-15

    Solitary fibrous tumors occasionally present with hypoglycemia because of the excessive release of insulin-like growth factor II. We report the first case of pancreatic solitary fibrous tumor causing ectopic adrenocorticotropic hormone syndrome. An 82-year-old Japanese man presented with lower limb edema, uncontrolled hypertension, hypokalemia, and baseline hypercortisolism. Distal pancreatectomy was performed after the clinical diagnosis of a neuroendocrine tumor with ectopic secretion of adrenocorticotropic hormone. On histological examination, the tumor showed spindle cells in a fascicular arrangement. The diagnosis of the solitary fibrous tumor was confirmed by the identification of the NAB2-STAT6 fusion gene and positive immuno-histochemical staining for STAT6 and CD34. Using quantitative real-time polymerase chain reaction, mRNA that encoded proopiomelanocortin, precursor of adrenocorticotropic hormone, was detected. Proopiomelanocortin production through the demethylation of the promoter region Domain IV was detected. Pancreatic solitary fibrous tumors represent a new cause of ectopic adrenocorticotropic hormone syndrome. PMID:27585487

  8. Transformation of benign fibroadenoma to malignant phyllodes tumor

    PubMed Central

    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. PMID:26331090

  9. Transformation of benign fibroadenoma to malignant phyllodes tumor.

    PubMed

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

    2015-07-01

    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. PMID:26331090

  10. Rare Malignant Tumors of the Breast

    PubMed Central

    Miller, Trevor; Albarracin, Constance; Carkaci, Selin; Whitman, Gary J; Adrada, Beatriz E

    2015-01-01

    While the more common forms of breast cancer are well understood and recognized, there are many important rare malignancies that are less appreciated. Many of these cancers have imaging findings that, when understood, help to formulate a more educated differential diagnosis. In this article, the clinical features, imaging, and pathologic findings of rare breast malignancies will be discussed. PMID:26664775

  11. Disseminated malignant solitary fibrous tumor of the pleura.

    PubMed

    Zhang, Hongquan; Lucas, David R; Pass, Harvey I; Che, Mingxin

    2004-02-01

    Solitary fibrous tumor (SFT) of the pleura typically forms a localized pleura-based mass, and most are benign. A rare case of disseminated malignant SFT of the pleura is reported. The patient was a 71-year-old man who presented with complaints of shortness of breath to his primary care physician. A diagnosis of malignant mesothelioma was suspected, based on clinical, radiological and needle biopsy findings. He was referred to our institution for surgery. An extrapleural pneumonectomy, encompassing all pleural masses, was performed. Gross examination of the resected specimen was remarkable for numerous masses, ranging in size from 0.2 to 13.5 cm, covering the majority of the visceral pleura. Histologically, the tumor was composed of short spindle cells admixed with variable proportions of collagenous stroma. There were great intra- and intertumoral heterogeneity in tumor growth pattern, cellularity, pleomorphism and mitoses. Histologically malignant areas were present in all of the masses examined. The neoplastic cells were diffusely and intensely positive for bcl-2. Most tumor cells were also strongly stained for CD34 and CD99. Staining for cytokeratin was negative. The tumor also revealed p53 over-expression. Thus, the histological and immunohistochemical features of the tumor were consistent with a disseminated malignant SFT. This report shows that SFT rarely presents with disseminated pleural involvement, and a panel with CD34, bcl-2 and cytokeratin are valuable for differentiating SFT from malignant mesothelioma and other malignant spindle cell neoplasms of the pleura.

  12. Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor.

    PubMed

    Valetti, Sabrina; Maione, Federica; Mura, Simona; Stella, Barbara; Desmaële, Didier; Noiray, Magali; Vergnaud, Juliette; Vauthier, Christine; Cattel, Luigi; Giraudo, Enrico; Couvreur, Patrick

    2014-10-28

    Chemotherapy for pancreatic cancer is hampered by the tumor's physio-pathological complexity. Here we show a targeted nanomedicine using a new ligand, the CKAAKN peptide, which had been identified by phage display, as an efficient homing device within the pancreatic pathological microenvironment. Taking advantage of the squalenoylation platform, the CKAAKN peptide was conjugated to squalene (SQCKAAKN) and then co-nanoprecipitated with the squalenoyl prodrug of gemcitabine (SQdFdC) giving near monodisperse nanoparticles (NPs) for safe intravenous injection. By interacting with a novel target pathway, the Wnt-2, the CKAAKN functionalization enabled nanoparticles: (i) to specifically interact with both tumor cells and angiogenic vessels and (ii) to simultaneously promote pericyte coverage, thus leading to the normalization of the vasculature likely improving the tumor accessibility for therapy. All together, this approach represents a unique targeted nanoparticle design with remarkable selectivity towards pancreatic cancer and multiple mechanisms of action.

  13. Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: An update

    PubMed Central

    Gurzu, Simona; Turdean, Sabin; Kovecsi, Attila; Contac, Anca Otilia; Jung, Ioan

    2015-01-01

    Epithelial-to-mesenchymal transition (EMT) represents conversion of an epithelial cell in an elongated cell with mesenchymal phenotype, which can occur in physiologic and pathologic processes such as embryogenesis (type 1 EMT), wound healing and/or fibrosis (type 2 EMT) and malignant tumors (type 3 EMT). The proliferation rate, metastasizing and recurrence capacity, as also the individualized response at chemotherapics, in both epithelial and mesenchymal malignant tumors is known to be influenced by reversible switch between EMT and mesenchymal-to-epithelial transition (MET). Although much research work has already been done in these fields, the specific molecular pathways of EMT, relating to the tumor type and tumor localization, are yet to be elucidated. In this paper, based on the literature and personal experience of the authors, an update in the field of EMT vs MET in epithelial and mesenchymal tumors is presented. The authors tried to present the latest data about the particularities of these processes, and also of the so-called endothelial-to-mesenchymal transition, based on tumor location. The EMT-angiogenesis link is discussed as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management. The paper begins with presentation of the basic aspects of EMT, its classification and assessment possibilities, and concludes with prognostic and therapeutic perspectives. The particularities of EMT and MET in gastric and colorectal carcinomas, pancreatic cancer, hepatocellular and cholangiocarcinomas, and lung, breast and prostate cancers, respectively in sarcomas and gastrointestinal stromal tumors are presented in detail. PMID:25984514

  14. Rare Malignant and Benign Salivary Gland Epithelial Tumors.

    PubMed

    Seethala, Raja R; Barnes, E Leon

    2011-12-01

    Although at least 24 distinct histologic salivary gland carcinomas exist, many of them are rare, comprising only 1% to 2% of all salivary gland tumors. These include epithelial-myoepithelial carcinoma, (hyalinizing) clear cell carcinoma, basal cell adenocarcinoma, cystadenocarcinoma, low-grade salivary duct carcinoma (low-grade cribriform cystadenocarcinoma), oncocytic carcinoma, and adenocarcinoma not otherwise specified. Few tumors (clear cell carcinoma and basal cell adenocarcinoma) have unique molecular correlates. Benign tumors, although histologically less diverse, are far more common, with pleomorphic adenoma and Warthin tumor the most common salivary gland tumors. Many benign tumors have malignant counterparts for which histologic distinction can pose diagnostic challenge.

  15. The Role of Tumor Cell-Derived Connective Tissue Growth Factor (CTGF/CCN2) in Pancreatic Tumor Growth

    PubMed Central

    Bennewith, Kevin L.; Huang, Xin; Ham, Christine M.; Graves, Edward E.; Erler, Janine T.; Kambham, Neeraja; Feazell, Jonathan; Yang, George P.; Koong, Albert

    2009-01-01

    Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CCN2 derived from either tumor cells or stromal cells as it affects the growth of pancreatic tumors is unknown. Using genetic inhibition of CCN2, we have discovered that CCN2 derived from tumor cells is a critical regulator of pancreatic tumor growth. Pancreatic tumor cells derived from CCN2 shRNA-expressing clones showed dramatically reduced growth in soft agar and when implanted subcutaneously. We also observed a role for CCN2 in the growth of pancreatic tumors implanted orthotopically, with tumor volume measurements obtained by PET imaging. Mechanistically, CCN2 protects cells from hypoxia-mediated apoptosis, providing an in vivo selection for tumor cells that express high levels of CCN2. We found that CCN2 expression and secretion was increased in hypoxic pancreatic tumor cells in vitro, and we observed co-localization of CCN2 and hypoxia in pancreatic tumor xenografts and clinical pancreatic adenocarcinomas. Furthermore, we found increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal cells surrounding the tumor, supporting our assertion that tumor cell-derived CCN2 is important for pancreatic tumor growth. Taken together, these data improve our understanding of the mechanisms responsible for pancreatic tumor growth and progression, and also indicate that CCN2 produced by tumor cells represents a viable therapeutic target for the treatment of pancreatic cancer. PMID:19179545

  16. Inhibition of pancreatic tumoral cells by snake venom disintegrins

    PubMed Central

    Lucena, Sara; Castro, Roberto; Lundin, Courtney; Hofstetter, Amanda; Alaniz, Amber; Suntravat, Montamas; Sánchez, Elda Eliza

    2014-01-01

    Pancreatic cancer often has a poor prognosis, even when diagnosed early. Pancreatic cancer typically spreads rapidly and is rarely detected in its early stages, which is a major reason it is a leading cause of cancer death. Signs and symptoms may not appear until pancreatic cancer is quite advanced, and complete surgical removal is not possible. Furthermore, pancreatic cancer responds poorly to most chemotherapeutic agents. The importance of integrins in several cell types that affect tumor progression has made them an appealing target for cancer therapy. Some of the proteins found in the snake venom present a great potential as anti-tumor agents. In this study, we summarize the activity of two integrins antagonist, recombinant disintegrins mojastin 1 and viridistatin 2, on human pancreatic carcinoma cell line (BXPC-3). Both recombinant disintegrins inhibited some essential aspects of the metastasis process such as proliferation, adhesion, migration, and survival through apoptosis, making these proteins prominent candidates for the development of drugs for the treatment of pancreatic cancer. PMID:25450798

  17. Applications of Nanomaterials in Radiotherapy for Malignant Tumors.

    PubMed

    Wang, Yanchao; Liang, Ruichao; Fang, Fang

    2015-08-01

    Malignant tumors are tremendous heath problems facing by the medical world. In order to achieve the purpose of curing malignant tumor, numerous therapeutic strategies have been developed. Radiotherapy is one of the main therapeutic strategies for malignant tumors. Current imaging strategies cannot display exact infiltrating margins, radio-resistance generated by irradiated tissue, and intercurrent damage to healthy tissues during radiotherapy. Therefore, novel strategies to solve these problems are urgently needed. Nanomaterials have specific physical and biological properties that can help clinician to distinguish margins of infiltrating tumors as a novel contrast agent. Besides, nanoparticles can significantly enhance the effect of radiotherapy by generating reactive oxygen species (ROS) or influence cell cycle. In addition, nanomaterials can also help in diminishing the intercurrent damage caused by radiotherapy. So nanomaterials have very promising prospect in the radiotherapy of malignant tumors. This review mainly focuses on the applications of nanomaterials in radiotherapy for malignant tumors; especially it applies to lesion imaging and their radiosensitizing effects. PMID:26369108

  18. Transcriptional co-factor Transducin beta-like (TBL) 1 acts as a checkpoint in pancreatic cancer malignancy

    PubMed Central

    Stoy, Christian; Sundaram, Aishwarya; Rios Garcia, Marcos; Wang, Xiaoyue; Seibert, Oksana; Zota, Annika; Wendler, Susann; Männle, David; Hinz, Ulf; Sticht, Carsten; Muciek, Maria; Gretz, Norbert; Rose, Adam J; Greiner, Vera; Hofmann, Thomas G; Bauer, Andrea; Hoheisel, Jörg; Berriel Diaz, Mauricio; Gaida, Matthias M; Werner, Jens; Schafmeier, Tobias; Strobel, Oliver; Herzig, Stephan

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer fatalities in Western societies, characterized by high metastatic potential and resistance to chemotherapy. Critical molecular mechanisms of these phenotypical features still remain unknown, thus hampering the development of effective prognostic and therapeutic measures in PDAC. Here, we show that transcriptional co-factor Transducin beta-like (TBL) 1 was over-expressed in both human and murine PDAC. Inactivation of TBL1 in human and mouse pancreatic cancer cells reduced cellular proliferation and invasiveness, correlating with diminished glucose uptake, glycolytic flux, and oncogenic PI3 kinase signaling which in turn could rescue TBL1 deficiency-dependent phenotypes. TBL1 deficiency both prevented and reversed pancreatic tumor growth, mediated transcriptional PI3 kinase inhibition, and increased chemosensitivity of PDAC cells in vivo. As TBL1 mRNA levels were also found to correlate with PI3 kinase levels and overall survival in a cohort of human PDAC patients, TBL1 was identified as a checkpoint in the malignant behavior of pancreatic cancer and its expression may serve as a novel molecular target in the treatment of human PDAC. PMID:26070712

  19. Malignant solitary fibrous tumor of the urinary bladder.

    PubMed

    Cheng, Shih-Hao; Wang, Shian-Shiang; Lee, Chen-Hui; Ou, Yen-Chung; Cheng, Chen-Li

    2012-09-01

    A 67-year-old man was examined for persistent pain over his lower abdomen and was found to have a large pelvic tumor. During surgery, we detected a 16 × 9 × 9 cm(3) urinary bladder tumor with small intestinal adhesions, and performed partial cystectomy and segmental resection. Histological and immunohistochemical examinations established the diagnosis of malignant solitary fibrous tumor (SFT). Only 10 cases of urinary bladder SFT have been reported in the English literature; our patient is the second one with malignancy and had a longer follow-up period than the other case.

  20. A multicenter study of oral malignant tumors from Thailand

    PubMed Central

    Dhanuthai, Kittipong; Rojanawatsirivej, Somsri; Subarnbhesaj, Ajiravudh; Thosaporn, Watcharaporn; Kintarak, Sompid

    2016-01-01

    Background: Oral malignant tumors in Thailand have not been extensively studied. Hence the following study was conducted. Aims: To determine the prevalence and clinicopathologic data of the oral malignant tumors from Thailand. Subjects and Methods: Biopsy records of the Oral Pathology Department, Chulalongkorn University; Department of Oral Biology and Diagnostic Sciences, Chiang Mai University; Department of Oral Diagnosis, Khon Kaen University and Department of Stomatology, Prince of Songkla University, were reviewed for lesions diagnosed in the category of oral malignant tumors from 2005–2014. Demographic data and site of the lesions were collected. Statistical Analysis Used: Data were analyzed by descriptive statistics using SPSS software version 17.0. Results: Of the 22,639 accessioned cases, 1411 cases (6.23%) were diagnosed as oral malignant tumors. The mean age of the patients was 59.13 ± 17.32 years. A total of 651 cases (46.14%) were diagnosed in males, whereas 759 cases (53.79%) were diagnosed in females. The male-to-female ratio was 0.86:1. The sites of predilection for oral malignant tumors were the gingiva, followed by tongue and alveolar mucosa. The three most common oral malignant tumors in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Conclusions: This study provides extensive data on the oral malignant tumors from several university biopsy services located in virtually all parts of Thailand. The data from the present study show some similarities with previous studies; however, differences such as gender and site of predilection still exist. PMID:27721612

  1. Carcinomas ex pleomorphic adenoma and malignant mixed tumors. Histomorphologic indexes.

    PubMed

    Tortoledo, M E; Luna, M A; Batsakis, J G

    1984-03-01

    Clinical and pathologic differences exist between the several neoplasms encompassed by the term malignant mixed tumors of salivary glands. The majority of the neoplasms are carcinomas ex pleomorphic adenoma. True malignant mixed tumors (carcinosarcomas) are rare, and even more rare are the benign metastasizing mixed tumors. This study of 40 malignant mixed tumors indicates that two previously unreported variables, measured invasion in millimeters and histologic subclassifications of the malignant neoplasm, are valuable guides to prognosis and biologic behavior. All patients whose malignant neoplasm extended for more than 8 mm beyond residual capsule or benign residual tumor died of their disease. The extent of invasion also correlated with perineurial invasion, involvement of bone, and metastases to lymph nodes. Histologic subclassification points out that there is no prototypical carcinoma ex pleomorphic adenoma and that high- and low-grade carcinomas can be found. Only one of the patients with low-grade (terminal duct) carcinomas died of his disease during follow-up periods extending to over 20 years.

  2. APC promoter is frequently methylated in pancreatic juice of patients with pancreatic carcinomas or periampullary tumors

    PubMed Central

    Ginesta, Mireia M.; Diaz-Riascos, Zamira Vanessa; Busquets, Juli; Pelaez, Núria; Serrano, Teresa; Peinado, Miquel Àngel; Jorba, Rosa; García-Borobia, Francisco Javier; Capella, Gabriel; Fabregat, Joan

    2016-01-01

    Early detection of pancreatic and periampullary neoplasms is critical to improve their clinical outcome. The present authors previously demonstrated that DNA hypermethylation of adenomatous polyposis coli (APC), histamine receptor H2 (HRH2), cadherin 13 (CDH13), secreted protein acidic and cysteine rich (SPARC) and engrailed-1 (EN-1) promoters is frequently detected in pancreatic tumor cells. The aim of the present study was to assess their prevalence in pancreatic juice of carcinomas of the pancreas and periampullary area. A total of 135 pancreatic juices obtained from 85 pancreatic cancer (PC), 26 ampullary carcinoma (AC), 10 intraductal papillary mucinous neoplasm (IPMN) and 14 chronic pancreatitis (CP) patients were analyzed. The methylation status of the APC, HRH2, CDH13, SPARC and EN-1 promoters was analyzed using methylation specific-melting curve analysis (MS-MCA). Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were also tested with allele-specific quantitative polymerase chain reaction amplification. Out of the 5 promoters analyzed, APC (71%) and HRH2 (65%) were the most frequently methylated in PC juice. APC methylation was also detected at a high frequency in AC (76%) and IPMN (80%), but only occasionally observed in CP (7%). APC methylation had a high sensitivity (71–80%) for all types of cancer analyzed. The panel (where a sample scored as positive when ≥2 markers were methylated) did not outperform APC as a single marker. Finally, KRAS detection in pancreatic juice offered a lower sensitivity (50%) and specificity (71%) for detection of any cancer. APC hypermethylation in pancreatic juice, as assessed by MS-MCA, is a frequent event of potential clinical usefulness in the diagnosis of pancreatic and periampullary neoplasms.

  3. APC promoter is frequently methylated in pancreatic juice of patients with pancreatic carcinomas or periampullary tumors

    PubMed Central

    Ginesta, Mireia M.; Diaz-Riascos, Zamira Vanessa; Busquets, Juli; Pelaez, Núria; Serrano, Teresa; Peinado, Miquel Àngel; Jorba, Rosa; García-Borobia, Francisco Javier; Capella, Gabriel; Fabregat, Joan

    2016-01-01

    Early detection of pancreatic and periampullary neoplasms is critical to improve their clinical outcome. The present authors previously demonstrated that DNA hypermethylation of adenomatous polyposis coli (APC), histamine receptor H2 (HRH2), cadherin 13 (CDH13), secreted protein acidic and cysteine rich (SPARC) and engrailed-1 (EN-1) promoters is frequently detected in pancreatic tumor cells. The aim of the present study was to assess their prevalence in pancreatic juice of carcinomas of the pancreas and periampullary area. A total of 135 pancreatic juices obtained from 85 pancreatic cancer (PC), 26 ampullary carcinoma (AC), 10 intraductal papillary mucinous neoplasm (IPMN) and 14 chronic pancreatitis (CP) patients were analyzed. The methylation status of the APC, HRH2, CDH13, SPARC and EN-1 promoters was analyzed using methylation specific-melting curve analysis (MS-MCA). Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were also tested with allele-specific quantitative polymerase chain reaction amplification. Out of the 5 promoters analyzed, APC (71%) and HRH2 (65%) were the most frequently methylated in PC juice. APC methylation was also detected at a high frequency in AC (76%) and IPMN (80%), but only occasionally observed in CP (7%). APC methylation had a high sensitivity (71–80%) for all types of cancer analyzed. The panel (where a sample scored as positive when ≥2 markers were methylated) did not outperform APC as a single marker. Finally, KRAS detection in pancreatic juice offered a lower sensitivity (50%) and specificity (71%) for detection of any cancer. APC hypermethylation in pancreatic juice, as assessed by MS-MCA, is a frequent event of potential clinical usefulness in the diagnosis of pancreatic and periampullary neoplasms. PMID:27602165

  4. Paradoxical Role of HMGB1 in Pancreatic Cancer: Tumor Suppressor or Tumor Promoter?

    PubMed

    Cebrián, María José García; Bauden, Monika; Andersson, Roland; Holdenrieder, Stefan; Ansari, Daniel

    2016-09-01

    Pancreatic cancer has a dismal prognosis and there is an increasing and unmet need to identify better diagnostic and therapeutic targets in order to ameliorate the course of the disease. HMGB1, a nuclear DNA-binding protein that acts as a transcription factor, is currently in the limelight. HMGB1 exhibits a dual role in pancreatic cancer; when intracellular, it acts as an anti-tumor protein stabilizing the genome, whereas extracellular HMGB1 behaves as a pro-tumor protein with cytokine, chemokine and growth factor functions. Although the exact mechanisms of HMGB1 in pancreatic cancer are still to be elucidated, the significance of this protein for processes, such as autophagy, immunogenic cell death, tumor growth, metastasis and resistance to chemotherapy, have become increasingly clear. In this review, we provide a systematic summary and review of the biological and clinical relevance of HMGB1 in pancreatic cancer. PMID:27630273

  5. Malignant solitary fibrous tumor of the right atrium.

    PubMed

    Zhao, Xiao-Gang; Wang, Hao; Wang, Yan-Li; Chen, Gang; Jiang, Ge-Ning

    2012-11-01

    Cardiac solitary fibrous tumors (SFTs) are extremely rare, with only 4 cases described to date. Here, we describe the case of a 55-year-old man with a primary, malignant SFT that arose in the right atrium of his heart. His presenting complaint was of chest distress and shortness of breath. Physical examination revealed jugular venous engorgement. Computed tomography showed a tumor of 15 × 10 × 8 cm in the anterior mediastinum. The tumor was surgically resected under cardiopulmonary bypass. A grayish white neoplasm was discovered lying within the right atrium. The histological appearance of the tumor was of a hypercellular distribution of spindle cells with nuclear atypia, arranged in a storiform pattern and intermixed with collagenous stroma. Immunohistochemistry showed that the tumor was positive for CD34. Based on the aforementioned features, the diagnosis of malignant SFT was made. The patient subsequently died as a result of respiratory and circulatory failure.

  6. Immunotherapy of Malignancy by in vivo Gene Transfer into Tumors

    NASA Astrophysics Data System (ADS)

    Plautz, Gregory E.; Yang, Zhi-Yong; Wu, Bei-Yue; Gao, Xiang; Huang, Leaf; Nabel, Gary J.

    1993-05-01

    The immune system confers protection against a variety of pathogens and contributes to the surveillance and destruction of neoplastic cells. Several cell types participate in the recognition and lysis of tumors, and appropriate immune stimulation provides therapeutic effects in malignancy. Foreign major histocompatibility complex (MHC) proteins also serve as a potent stimulus to the immune system. In this report, a foreign MHC gene was introduced directly into malignant tumors in vivo in an effort to stimulate tumor rejection. In contrast to previous attempts to induce tumor immunity by cell-mediated gene transfer, the recombinant gene was introduced directly into tumors in vivo. Expression of the murine class I H-2K^s gene within the CT26 mouse colon adenocarcinoma (H-2K^d) or the MCA 106 fibrosarcoma (H-2K^b) induced a cytotoxic T-cell response to H-2K^s and, more importantly, to other antigens present on unmodified tumor cells. This immune response attenuated tumor growth and caused complete tumor regression in many cases. Direct gene transfer in vivo can therefore induce cell-mediated immunity against specific gene products, which provides an immunotherapeutic effect for malignancy, and potentially can be applied to the treatment of cancer and infectious diseases in man.

  7. KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic cancer cells in vitro

    SciTech Connect

    Laurila, Eeva; Vuorinen, Elisa; Savinainen, Kimmo; Rauhala, Hanna; Kallioniemi, Anne

    2014-03-10

    Pancreatic cancer is an aggressive malignancy and one of the leading causes of cancer deaths. The high mortality rate is mostly due to the lack of appropriate tools for early detection of the disease and a shortage of effective therapies. We have previously shown that karyopherin alpha 7 (KPNA7), the newest member of the alpha karyopherin family of nuclear import receptors, is frequently amplified and overexpressed in pancreatic cancer. Here, we report that KPNA7 expression is absent in practically all normal human adult tissues but elevated in several pancreatic cancer cell lines. Inhibition of KPNA7 expression in AsPC-1 and Hs700T pancreatic cancer cells led to a reduction in cell growth and decreased anchorage independent growth, as well as increased autophagy. The cell growth effects were accompanied by an induction of the cell cycle regulator p21 and a G1 arrest of the cell cycle. Interestingly, the p21 induction was caused by increased mRNA synthesis and not defective nuclear transport. These data strongly demonstrate that KPNA7 silencing inhibits the malignant properties of pancreatic cancer cells in vitro and thereby provide the first evidence on the functional role for KPNA7 in human cancer. - Highlights: • KPNA7 expression is elevated in several pancreatic cancer cell lines. • KPNA7 silencing in high expressing cancer cells leads to growth inhibition. • The cell growth reduction is associated with p21 induction and G1 arrest. • KPNA7 silencing is also accompanied with increased autophagy.

  8. Concise review: genetically engineered stem cell therapy targeting angiogenesis and tumor stroma in gastrointestinal malignancy.

    PubMed

    Keung, Emily Z; Nelson, Peter J; Conrad, Claudius

    2013-02-01

    Cell-based gene therapy holds considerable promise for the treatment of human malignancy. Genetically engineered cells if delivered to sites of disease could alleviate symptoms or even cure cancer through expression of therapeutic or suicide transgene products. Mesenchymal stem cells (MSCs), nonhematopoietic multipotent cells found primarily in bone marrow, have garnered particular interest as potential tumor-targeting vehicles due to their innate tumortropic homing properties. However, recent strategies go further than simply using MSCs as vehicles and use the stem cell-specific genetic make-up to restrict transgene expression to tumorigenic environments using tumor-tissue specific promoters. This addresses one of the concerns with this novel therapy that nonselective stem cell-based therapy could induce cancer rather than treat it. Even minimal off-target effects can be deleterious, motivating recent strategies to not only enhance MSC homing but also engineer them to make their antitumor effect selective to sites of malignancy. This review will summarize the advances made in the past decade toward developing novel cell-based cancer therapies using genetically engineered MSCs with a focus on strategies to achieve and enhance tumor specificity and their application to targeting gastrointestinal malignancies such as hepatocellular carcinoma and pancreatic adenocarcinoma.

  9. [In vitro evaluation of the chemosensitivity of malignant gastrointestinal tumors by stem cell assay].

    PubMed

    Scheithauer, W; Temsch, E M; Schieder, H; Funovics, J; Schiessel, R; Grabner, G

    1984-01-01

    The Human Tumor Stem Cell Assay, originally described by Hamburger and Salmon, was shown to be a useful in-vitro technique for predicting response or lack of response in individual patients' tumors. In the present study 34 GI-tumors were assayed for evaluation of in-vitro growth characteristics and sensitivity-patterns to standard chemotherapeutic drugs as well as to recombinant interferon alpha-2(rIF). Sufficient growth for evaluation of anticancer drug activity (greater than 30 colonies/control plate) was obtained in 56% of specimens: 2/9 colorectal, 0/3 stomach, 0/3 pancreatic tumors and 1/4 hepatomas revealed a 50% (or more) decrease of TCFUs, that was considered the minimum for in-vitro efficacy. Our results suggest a very limited overall activity of rIF in gastrointestinal malignancies. Only 1 pancreatic cancer (of 18 evaluable specimens) showed a significant decrease of colony formation (70%), when 100 U of interferon/ml were added to the culture system.

  10. [The observatory of rare malignant gynecologic tumors].

    PubMed

    Devouassoux-Shisheboran, Mojgan; Vacher-Lavenu, Marie-Cécile

    2014-02-01

    The observatory of gynecological rare tumors (TMRG) has been initially created for ovarian rare neoplasms (TMRO). Because of the similarities between ovarian and other gynecological tumors, this observatory has been then extended to all gynecological rare tumors. The recognition by INCa of three national expert centers (centre Léon-Bérard, hôpitaux de Paris, institut Gustave-Roussy) in rare gynecological cancers and a network of regional expert centers in 2010, expend the experience of the website "Observatoire francophone des tumeurs rares de l'ovaire". The major goals of this gynecology rare tumors experts network, are to promote systematic second opinion for initial diagnostic by experts in gynecopathology, systematic multidisciplinary advice by surgeons and medical oncologist experts, to disseminate clinical guidelines dedicated to rare gynecological tumors, to promote specific fundamental and translational research within clinical trials dedicated to rare tumors. At the end, we would like to improve benefit in term of survival and/or fertility for all these potential young patients.

  11. Comparison of cytotoxic T lymphocyte responses against pancreatic cancer induced by dendritic cells transfected with total tumor RNA and fusion hybrided with tumor cell

    PubMed Central

    Chen, Jiang; Li, Hong-Yu; Wang, Di; Shao, Xiao-Dong

    2015-01-01

    Pancreatic cancer (PC) is a deadly human malignancy. Dendritic cell (DC)-based immunotherapy with whole tumor antigens demonstrates potential efficiency in cancer treatment. Tumor RNA and tumor fusion hybrid cells are sources of whole tumor antigens for preparing DC tumor vaccines. However, the efficacy of these sources in eliciting immune responses against PC has not yet to be directly compared. In the present study, patient-derived PC cells and DCs were fused (DC–tumor hybrids) and primary cultured PC cell-derived total RNA was electroporated into autologous DCs (DC–tumor RNA). The antitumor immune responses induced by DC–tumor hybrids and DC–tumor RNA were compared directly. The results showed that both RNA and hybrid methodologies could induce tumor-specific cytotoxic T lymphocyte (CTL) responses, but pulsing DCs with total tumor RNA could induce a higher frequency of activated CTLs and T-helper cells than fusing DCs with autologous tumor cells. In addition, DC–tumor RNA triggered stronger autologous tumor cell lysis than DC–tumor hybrids. It could be concluded that DCs pulsed with whole tumor RNA are superior to those fused with tumor cells in priming anti-PC CTL responses. Electroporation with total tumor RNA may be more suitable for DC-based PC vaccination. PMID:25736302

  12. Malignant solitary fibrous tumor of breast: a rare case report.

    PubMed

    Yang, Lian-He; Dai, Shun-Dong; Li, Qing-Chang; Xu, Hong-Tao; Jiang, Gui-Yang; Zhang, Yong; Wang, Liang; Fan, Chui-Feng; Wang, En-Hua

    2014-01-01

    Solitary fibrous tumor (SFT) is rare mesenchymal neoplasm that has been originally and most often documented in the pleura. Recently, the ubiquitous nature of the SFT has been recognized with reports of involvement of numerous sites all over the body such as: upper respiratory tract, somatic tissue, mediastinum, head, and neck. Less than 10 cases SFT of breast have been reported. Herein, we presented a 52-year-old Asian female with SFT of breast, this tumor showed predominant malignant features. To our knowledge, SFT of breast with such malignant evidence is extremely rare.

  13. Endoscopic diagnosis and treatment of pancreatic neuroendocrine tumors.

    PubMed

    Rustagi, Tarun; Farrell, James J

    2014-01-01

    Pancreatic neuroendocrine tumors (PNETs) are rare pancreatic neoplasms comprising only 1% to 2% of all pancreatic tumors. In recent years, the number of incidentally discovered PNETs has greatly increased given the widespread use of axial imaging. However, a significant proportion of PNETs may not be visualized on conventional imaging such as computed tomography, magnetic resonance imaging, and somatostatin receptor scintigraphy. Endoscopic ultrasound (EUS) has become an integral part of the diagnosis of PNETs because of its high sensitivity for detecting, localizing, and diagnosing PNETs. EUS-guided tissue acquisition provides histologic and immunologic confirmation, and may also allow prognostication about tumor behavior. In addition to preoperative assessment of these tumors, EUS has also been shown to have an important role in nonoperative management of small nonfunctional PNETs. Finally, recent developments suggest that interventional EUS may be used to aid intraoperative localization of PNETs and to deliver therapeutic agents for the treatment of PNETs. This review will discuss the endoscopic diagnosis and treatment of PNETs, with focus on recent advances in the utility of EUS in the clinical management of these tumors.

  14. CTHRC1 promotes angiogenesis by recruiting Tie2-expressing monocytes to pancreatic tumors

    PubMed Central

    Lee, Jaemin; Song, Jinhoi; Kwon, Eun-Soo; Jo, Seongyea; Kang, Min Kyung; Kim, Yeon Jeong; Hwang, Yeonsil; Bae, Hosung; Kang, Tae Heung; Chang, Suhwan; Cho, Hee Jun; Kim, Song Cheol; Kim, Seokho; Koh, Sang Seok

    2016-01-01

    CTHRC1 (collagen triple-helix repeat-containing 1), a protein secreted during the tissue-repair process, is highly expressed in several malignant tumors, including pancreatic cancer. We recently showed that CTHRC1 has an important role in the progression and metastasis of pancreatic cancer. Although CTHRC1 secretion affects tumor cells, how it promotes tumorigenesis in the context of the microenvironment is largely unknown. Here we identified a novel role of CTHRC1 as a potent endothelial activator that promotes angiogenesis by recruiting bone marrow-derived cells to the tumor microenvironment during tumorigenesis. Recombinant CTHRC1 (rCTHRC1) enhanced endothelial cell (EC) proliferation, migration and capillary-like tube formation, which was consistent with the observed increases in neovascularization in vivo. Moreover, rCTHRC1 upregulated angiopoietin-2 (Ang-2), a Tie2 receptor ligand, through ERK-dependent activation of AP-1 in ECs, resulting in recruitment of Tie2-expressing monocytes (TEMs) to CTHRC1-overexpressing tumor tissues. Treatment with a CTHRC1-neutralizing antibody-abrogated Ang-2 expression in the ECs in vitro. Moreover, administration of a CTHRC1-neutralizing antibody to a xenograft mouse model reduced the tumor burden and infiltration of TEMs in the tumor tissues, indicating that blocking the CTHRC1/Ang-2/TEM axis during angiogenesis inhibits tumorigenesis. Collectively, our findings support the hypothesis that CTHRC1 induction of the Ang-2/Tie2 axis mediates the recruitment of TEMs, which are important for tumorigenesis and can be targeted to achieve effective antitumor responses in pancreatic cancers. PMID:27686285

  15. Heterotopic gastrointestinal mucosa and pancreatic tissue in a retroperitoneal tumor.

    PubMed

    Hashimoto, Naoki; Hakamada, Kenichi; Narumi, Shunji; Totsuka, Eishi; Aoki, Kazunori; Kamata, Yoshimasa; Sasaki, Mutsuo

    2006-01-01

    We believe that this is the first report of a retroperitoneal tumor consisting of heterotopic gastrointestinal mucosa and pancreatic tissue. The patient was a 19-year-old woman with the chief complaint being occasional back pain. Abdominal computerized tomography demonstrated a 3.1 x 2.5 x 3.2-cm low-density solid and cystic lesion adjoining the left renal vein between the aorta and inferior vena cava. Angiography revealed that the inferior vena cava was displaced by the hypovascular tumor. The retroperitoneal lesion was diagnosed preoperatively as a benign tumor such as a neurogenic neoplasm or lymphangioma. At laparotomy, a cystic tumor was found, which existed behind the inferior vena cava and renal vessels, and contained reddish-brown fluid, suggesting hemorrhage in the past. The cut surface of the tumor showed a unilocular cyst with partially hypertrophic wall. Histopathological examination revealed a cystic tumor lined with heterotopic gastric and duodenal mucosa, with pancreatic tissue in the muscularis propria. In addition, evidence of bleeding from the gastric mucosa was observed in the cystic tumor. External secretion from these tissues could have triggered the hemorrhage and expanded the tumor, possibly resulting in the back pain.

  16. [Treatment Strategy for Non-Functional Pancreatic Neuroendocrine Tumors (P-NETs) at Kurume University Hospital].

    PubMed

    Kawashima, Yusuke; Ishikawa, Hiroto; Hisaka, Toru; Okuda, Kouji; Akagi, Yoshito

    2016-01-01

    Pancreatic neuroendocrine tumors (P-NETs) are relatively rare. Approximately 50-90% of non-functioning P-NETs are malignant, and the only curative treatment is surgical resection. Liver and lymph node metastases often occur. In Japan, the mTOR inhibitor everolimus is now covered by the national health insurance for treatment of P-NETs, including advanced and unresectable tumors. We present a case of P-NETs with liver metastases seen at our hospital and discuss our treatment strategy for this disease. Patients with tumors≤1 cm receive follow-up observation. For G1 and G2 (other than G3) tumors, if their size is >1 cm when first discovered, resection of the primary lesion along with lymph node dissection (as for pancreatic cancer) is performed. In G1 and G2 tumors with synchronous distant metastases, the primary lesion is first resected, and depending on the pathological findings, chemotherapy (LAR plus everolimus) may be administered. After 4 courses of chemotherapy, the response is assessed, and if further resection is possible, resection is performed. When there are synchronous liver metastases, if partial resection and local treatment (such as RFA) are possible, the primary lesion and synchronous lesions are resected. If a major hepatic resection procedure such as a segmentectomy or lobectomy is possible, the primary lesion is resected, followed by chemotherapy. After 4 courses of chemotherapy, the response is assessed, and if further resection is possible, hepatic resection is performed. G3 tumors are usually highly malignant, advanced, and often associated with metastases at the time of diagnosis. Chemotherapy may be an option for treating patients with G3 tumors. PMID:26809536

  17. Malignant solitary fibrous tumor of the pleura with liposarcomatous differentiation.

    PubMed

    Bai, H; Aswad, B I; Gaissert, H; Gnepp, D R

    2001-03-01

    Pleural solitary fibrous tumors (SFTs) are uncommon tumors. Although these tumors have been well characterized, malignant pleural SFTs with liposarcomatous differentiation have not been reported. We report an unusual malignant pleural SFT intermixed with foci of well-differentiated liposarcoma. The patient was a 66-year-old, white man with a large, solid right pleural mass that measured 13.5 x 10.3 x 8.5 cm. The tumor was composed of spindle-shaped and plump cells embedded in dense collagenous stroma. The tumor cells were arranged in interlacing fascicles or in a patternless pattern. Marked nuclear atypia, a high mitotic rate (21 mitoses per 10 high-power fields), and areas of prominent necrosis were evident. In addition, numerous adipocytes mixed with typical lipoblasts were seen scattered throughout portions of the tumor. Immunohistochemistry revealed the tumor cells were strongly positive for CD34 and vimentin and negative for cytokeratin, desmin, smooth muscle actin (IA4), and S100. To the best of our knowledge, this case represents the first example of a malignant SFT with liposarcomatous differentiation.

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

    PubMed

    Khalil, Bassem D; El-Sibai, Mirvat

    2012-07-01

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

  19. Malignant Triton Tumors in Sisters with Clinical Neurofibromatosis Type 1

    PubMed Central

    Alina, Basnet; Sebastian, Jofre A.; Gerardo, Capo

    2015-01-01

    Malignant triton tumors (MTTs) are rare and aggressive sarcomas categorized as a subgroup of malignant peripheral nerve sheath tumors (MPNSTs). MTTs arise from Schwann cells of peripheral nerves or existing neurofibromas and have elements of rhabdomyoblastic differentiation. We report the occurrence of MTTs in two sisters. The first patient is a 36-year-old female who presented with left sided chest wall swelling. She also had clinical features consistent with neurofibromatosis type 1 (NF-1). Debulking of the mass showed high-grade malignant peripheral nerve sheath tumor with skeletal muscle differentiation (MTT). The patient was treated with ifosfamide and adriamycin along with radiation. Four years after treatment, she still has no evidence of disease recurrence. Her sister subsequently presented to us at the age of 42 with left sided lateral chest wall pain. Imaging showed a multicompartmental retroperitoneal cystic mass with left psoas involvement. The tumor was resected and, similarly to her sister, it showed high-grade malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation (MTT). The patient was started on chemotherapy and radiation as described above. PMID:26114002

  20. Ovarian mucinous tumor with malignant mural nodules: dedifferentiation or collision?

    PubMed

    Desouki, Mohamed M; Khabele, Dineo; Crispens, Marta A; Fadare, Oluwole

    2015-01-01

    Ovarian mucinous tumors with mural nodules are rare surface epithelial-stromal tumors. The mural nodules are divergent neoplasms that may be benign or malignant. The latter may be in the form of a sarcoma, carcinosarcoma, anaplastic carcinoma, or a variety of other recognized histotypes of carcinoma, which raises the question of whether malignant mural nodules represent a form of dedifferentiation in ovarian mucinous tumors or whether they represent collision tumors. We recently reported the K-RAS gene mutation status in a case of ovarian mucinous adenocarcinoma with mural nodule of high-grade sarcoma. The mucinous and sarcomatous components revealed a mutation in codon 12 of the K-RAS gene of a different nucleotide substitution, indicating that these 2 tumor components were different clones of the same tumor. Herein, we are reporting another case of a 20-yr-old woman who presented with 22 cm pelvic mass, omental caking, and ascites. A diagnosis of invasive mucinous carcinoma with mural nodules of anaplastic carcinoma was rendered. K-RAS gene mutation studies revealed p.G12V, c.35G>T mutation in the 2 components of the tumor, which is the most common mutation reported in mucinous tumors of the ovary. The fact that sarcomatous or anaplastic carcinomatous mural nodules in ovarian mucinous tumors display the same K-RAS mutations as their underlying mucinous neoplasms provides supportive evidence that at least some malignant mural nodules represent a form of dedifferentiation in ovarian mucinous tumors, rather than a collision of 2 divergent tumor types.

  1. A Rare Malignant Fetal Brain Tumor.

    PubMed

    Iruretagoyena, Jesus Igor; Heiser, Timothy; Iskandar, Bermans; Shah, Dinesh

    2016-01-01

    A gravida 4, para 3 female at 37 weeks' gestation presented for a routine ultrasound. She had an otherwise uncomplicated low-risk pregnancy. The sonographic evaluation of the fetus revealed a macrocephaly and a deviation of the brain midline structures with a mass effect as well as a massively dilated left cerebral ventricular system with ill-defined echogenic ventricular delineation. Multiple free intracavitary echogenicities and disruptions of the brain mantle were visible. Our images were suggestive of either an intracranial bleed with the presence of an underlying tumor or a spontaneous bleed. A postnatal MRI was consistent with our prenatal findings of a possible tumor. The postnatal biopsy revealed an anaplastic astroblastoma within a hemorrhagic background. The infant received multiple courses of chemotherapy and further tumor debulking. At present, the infant is 18 months old. This is only the 4th case of an astrocytoma identified in the fetal period, and our case has the longest known survival yet. PMID:26044034

  2. The therapy of infantile malignant brain tumors: current status?

    PubMed

    Kalifa, Chantal; Grill, Jacques

    2005-12-01

    Malignant brain tumors are not uncommon in infants as their occurrence before the age of three represents 20-25% of all malignant brain tumors in childhood [1]. Genetic predisposition to infantile malignant brain tumors are known in Gorlin syndrome for example who present with desmoplastic medulloblastoma in about 5% of the affected patients. In addition, sequelae from tumor and its treatment are more severe at this age [2]. Thus, malignant brain tumors represent a true therapeutic challenge in neuro-oncology. Before the era of modern imaging and modern neurosurgery these malignant brain tumors were misdiagnosed or could not benefit of the surgical procedures as well as older children because of increased risks in this age group. Since the end of the 80s, noninvasive imaging procedures produce accurate diagnosis of brain tumors and improvement in neurosurgery, neuroanesthesia and perioperative intensive care permit safe tumor resections or at least biopsies. Consequently, the pediatric oncologists are more often confronted with very young children who need a complementary treatment. Before the development of specific approaches for this age group, these children received the same kind of treatment than the older children did, but their survival and quality of life were significantly worse. The reasons of these poor results were probably due in part to the fear of late effects induced by radiation therapy, leading to decrease the necessary doses of irradiation which increased treatment failures without avoiding treatment related complications [3]. At the end of the 80s, pilot studies were performed using postoperative chemotherapy in young medulloblastoma patients. Van Eys treated 12 selected children with medulloblastoma with MOPP regimen and without irradiation; 8 of them were reported to be long term survivors [4]. Subsequently, the pediatric oncology cooperative groups studies have designed therapeutic trials for very young children with malignant brain tumors

  3. Primary Pancreatic Malignant Lymphoma Diagnosed from Endoscopic Ultrasound-guided Fine-needle Aspiration Findings.

    PubMed

    Fukuba, Nobuhiko; Moriyama, Ichiro; Ishihara, Shunji; Sonoyama, Hiroki; Yamashita, Noritsugu; Tada, Yasumasa; Oka, Akihiko; Oshima, Naoki; Yuki, Takafumi; Kawashima, Kousaku; Kinoshita, Yoshikazu

    2016-01-01

    A 60-year-old woman was admitted to our hospital with upper abdominal pain and jaundice. Computed tomography showed a 9-cm mass that was penetrated by the common hepatic artery in the pancreatic head area. Endoscopic retrograde pancreatography revealed no stenosis or obstruction of the main pancreatic duct, and a cytologic examination of the patient's pancreatic juice was negative. Next, endoscopic ultrasound-guided fine needle aspiration was performed. The immunohistological findings of the specimen revealed a diffuse large B-cell lymphoma. The size of the tumor was significantly reduced after 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). PMID:26726082

  4. Pancreatic mucinous cystic tumor in Turner syndrome: How a tumor bends to a genetic disease☆

    PubMed Central

    Pizzi, Marco; Pennelli, Gianmaria; Merante-Boschin, Isabella; Fassan, Matteo; Pelizzo, Maria Rosa; Rugge, Massimo

    2013-01-01

    INTRODUCTION Mucinous cystic neoplasms (MCN) are uncommon tumors of the pancreatic corpus/tail occurring mostly in middle-aged women, with a variable clinico-biological behavior. On histology, MCNs concurrently show an epithelial mucosecreting component with ovarian-type stromal cells. PRESENTATION OF CASE This report describes the first case of a pancreatic MCN with no ovarian-type stroma in a patient with Turner syndrome (TS). DISCUSSION The mesenchymal component of MCN presumably results from the intra-pancreatic entrapment of ovarian stroma during embryogenesis. In our case, the absence of such stromal component may relate to the “dysgenetic” changes in the ovary involved in TS. CONCLUSION The present case of primary pancreatic MCN arising in a TS-patient triggers some original speculation on the morphogenesis of pancreatic MCN, also expanding the current clinico-pathological knowledge of this extremely rare entity. PMID:24096346

  5. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

    PubMed

    Sunamura, Makoto; Duda, Dan G; Ghattas, Maivel H; Lozonschi, Lucian; Motoi, Fuyuhiko; Yamauchi, Jun-Ichiro; Matsuno, Seiki; Shibahara, Shigeki; Abraham, Nader G

    2003-01-01

    Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.

  6. Reconstruction after resection of malignant parapharyngeal space tumor

    PubMed Central

    Umezawa, Hiroki; Nakamizo, Munenaga; Yokoshima, Kazuhiko; Nara, Shimpei; Ogawa, Rei; Hyakusoku, Hiko

    2014-01-01

    Abstract Primary malignant tumor of the parapharyngeal space (PPS) is rare. After surgical resection, primary closure could be considered if the oropharynx mucosa remains. This report describes two patients who underwent reconstruction by free tissue transfer after the resection of PPS tumors. This report was presented at the 56th annual meeting of the Japanese Society of Plastic and Reconstructive Surgery, 4 April, 2013. PMID:27252950

  7. Suboccipital malignant solitary fibrous tumor: report of a case.

    PubMed

    Zuniga, M Geraldine; Orr, Brent A; Chang, Steven S; Tufano, Ralph P

    2012-02-01

    Solitary fibrous tumors (SFTs) are rare soft-tissue sarcomas usually arising in the pleura of the thoracic cavity. Thirty percent of SFTs present in extrapleural locations, and infrequently in the head and neck region. While the majority of SFTs are benign, aggressive variants have been described. We report a case of a patient with a malignant SFT arising in the suboccipital soft tissues of the neck. We elucidate the diagnostic and therapeutic challenges in managing this tumor in this unusual location.

  8. MTA1 Expression in Benign and Malignant Salivary gland Tumors

    PubMed Central

    Andisheh-Tadbir, Azadeh; Dehghani-Nazhvani, Ali; Ashraf, Mohammad Javad; Khademi, Bijan; Mirhadi, Hosein; Torabi-Ardekani, Shima

    2016-01-01

    Introduction: Salivary gland tumors (SGTs) are important parts of human neoplasms. The most common SGT is pleomorphic adenoma and the most common malignant SGTs are mucoepidermoid carcinoma and adenoid cystic carcinoma (ACC). Metastasis-associated genes 1 (MTA1), a member of the nucleosome remodeling and histone deacetylation complex, is one newly discovered gene which recruits histone deacetylation, causing ATP-dependent chromosome remodeling, and regulating transcription. MTA1 had been shown to be overexpressed in malignant tumors with the enhancement of invasion and metastasis. Materials and Methods: Fifty-six samples of salivary gland tumors from the Khalili Hospital archive, including 20 cases of pleomorphic adenoma, 17 cases of mucoepidermoid carcinoma, 19 cases of ACC, and 23 cases of normal salivary gland tissues were chosen for immunohistochemical analysis of MTA1. Results: MTA1 expression in the malignant tumors was significantly higher than that in pleomorphic adenoma (P<0.001), and higher in pleomorphic adenoma than the normal salivary glands(P< 0.001). In total, 69.6% of normal salivary gland tissues showed MTA1, but all cases of salivary gland tumors were positive for MTA1. High nuclear expression of MTA1 was detected in 83.3% (30/36) of the malignant salivary gland tumors and 45% (9/20) of pleomorphic adenoma, while low MTA1 expression was seen in all of the normal salivary gland tissues. No statistically significant correlation was found between MTA1 protein expression and any clinicopathological features (P>0.05). Conclusion: Our findings demonstrate that MTA1 was significantly overexpressed in malignant salivary gland neoplasm in comparison to a lower level in benign pleomorphic adenoma, suggesting that MTA1 protein might be involved in carcinogenesis. PMID:26878004

  9. Malignant mammary tumor in female dogs: environmental contaminants

    PubMed Central

    2010-01-01

    Mammary tumors of female dogs have greatly increased in recent years, thus demanding rapid diagnosis and effective treatment in order to determine the animal survival. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adjacent adipose tissue of canine mammary tumor. High Precision Liquid Chromatography - HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in nine female dogs, without predilection for breed or age. After surgery, masses were carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor were collected to detect of environmental contaminants. The identified pyrethroids were allethrin, cyhalothrin, cypermethrin, deltamethrin and tetramethrin, with a contamination level of 33.3%. Histopathology demonstrated six female dogs (66.7%) as having complex carcinoma and three (33.3%) with simple carcinoma. From these tumors, seven (77.8%) presented aggressiveness degree III and two (22.2%) degree I. Five tumors were positive for estrogen receptors in immunohistochemical analysis. The contamination level was observed in more aggressive tumors. This was the first report in which the level of environmental contaminants could be detected in adipose tissue of female dogs with malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis. Hence, the dog may be used as a sentinel animal for human breast cancer, since human beings share the same environment and basically have the same eating habits. PMID:20587072

  10. Targeting GIPC/Synectin in Pancreatic Cancer Inhibits Tumor Growth

    PubMed Central

    Muders, Michael H.; Vohra, Pawan K.; Dutta, Shamit K; Wang, Enfeng; Ikeda, Yasuhiro; Wang, Ling; Udugamasooriya, D. Gomika; Memic, Adnan; Rupashinghe, Chamila N.; Baretton, Gustavo B.; Aust, Daniela E.; Langer, Silke; Datta, Kaustubh; Simons, Michael; Spaller, Mark R.; Mukhopadhyay, Debabrata

    2009-01-01

    Translational Relevance The five year survival rate in patients with ductal adenocarcinoma of the pancreas is less than 4%. Accordingly, new targets for the treatment of this deadly disease are urgently needed. In this study, we show that targeting GAIP interacting protein C-terminal (GIPC, also known as Synectin) and its PDZ-domain reduces pancreatic cancer growth significantly in vitro and in vivo. Additionally, the blockage of GIPC/Synectin was accompanied by a reduction of IGF-1R protein levels. In summary, the use of a GIPC-PDZ domain inhibitor may be a viable option in the treatment of pancreatic adenocarcinoma in future. Purpose Various studies have demonstrated the importance of GAIP interacting protein, C-terminus (GIPC, also known as Synectin) as a central adaptor molecule in different signaling pathways and as an important mediator of receptor stability. GIPC/Synectin is associated with different growth promoting receptors like IGF-1R and integrins. These interactions were mediated through its PDZ domain. GIPC/Synectin has been shown to be overexpressed in pancreatic and breast cancer. The goal of this study was to demonstrate the importance of GIPC/Synectin in pancreatic cancer growth and to evaluate a possible therapeutic strategy by using a GIPC-PDZ domain inhibitor. Furthermore, the effect of targeting GIPC on the IGF-1 receptor as one of its associated receptors was tested. Experimental Design In vivo effects of GIPC/Synectin knockdown were studied after lentiviral transduction of luciferase-expressing pancreatic cancer cells with shRNA against GIPC/Synectin. Additionally, a GIPC-PDZ-targeting peptide was designed. This peptide was tested for its influence on pancreatic cancer growth in vitro and in vivo. Results Knockdown of GIPC/Synectin led to a significant inhibition of pancreatic adenocarcinoma growth in an orthotopic mouse model. Additionally, a cell-permeable GIPC-PDZ inhibitor was able to block tumor growth significantly without showing

  11. [Assay of urine cysteine proteinase in diagnosing gynecological malignant tumors].

    PubMed

    Peng, Z L

    1992-09-01

    Cysteine proteinases (CP) belong to the subclass of endopeptidase, and have been considered to play an important role in spreading cancer cells. Cysteine proteinases in urine (UCP) were determined in 71 healthy women, 76 patients with gynecological benign tumors and 125 cases (173 samples) with gynecological malignant tumors. Enzyme levels were assayed using the artificial substrate CSZ-Ala-Arg-AFC by detecting the release of free AFC with the aid of a fluorometer. The value ranged from upper 80% to 99% of UCP in 71 normal women and was calculated with the percentile method. The results showed that ROC curve displayed a highly sensitive character. The sensitivity and specificity for gynecological malignant tumor were 91.8%, and 71.7% respectively. The sensitivities of UCP for ovarian cancer, cervical cancer, carcinoma of endometrium and cancer of vulva were 96%, 91%, 85.7% and 72.7% respectively. Due to its high sensitivity. It was suggested that UCP assay can be a good screening test to distinguish gynecological malignancy from benign tumors. The accuracy of diagnosing gynecological malignancy may be improved if UCP assay is combined with other tests with higher specificity.

  12. Nucleolar organizer regions in malignant salivary gland tumors.

    PubMed

    Fujita, S; Takahashi, H; Okabe, H

    1992-10-01

    Proliferative activity of carcinomas arising from salivary glands was analyzed by enumeration of argyrophilic nucleolar organizer regions (AgNORs). The mean numbers of AgNORs in the various tumors were as follows: mucoepidermoid carcinoma, 2.20; acinic cell carcinoma, 2.51; adenoid cystic carcinoma (ACC), 2.57; carcinoma in pleomorphic adenoma, 1.00 (benign component) and 3.99 (cancer-bearing area); salivary duct carcinoma, 4.49; polymorphous low-grade adenocarcinoma, 3.37; sebaceous carcinoma, 2.57; oncocytic carcinoma, 4.63; adenocarcinoma, 4.53. Cells of most tumors showed heterogeneous activity within the same tumor. In mucoepidermoid carcinoma, the mucous cells had suppressed activity in comparison with the epidermoid cells and intermediate cells. In ACC, the activity of the tumor cells increased according to growth pattern in the order tubular, glandular and solid. In carcinoma in pleomorphic adenoma, vigorous proliferative activity was observed in the malignant component, whereas less active cells were seen in the myxoid or chondroid matrix. AgNOR staining was useful for distinguishing benign from malignant regions in carcinoma in pleomorphic adenoma. Our results suggest that mucoepidermoid carcinoma, acinic cell carcinoma and ACC, except for that with a solid growth pattern, may be considered as low-grade malignancies, whereas solid-type ACC, the cancer component in carcinoma in pleomorphic adenoma and some of the other carcinomas have high-grade malignant behavior.

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

    PubMed Central

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

    2015-01-01

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

  14. Repression of malignant tumor progression upon pharmacologic IGF1R blockade in a mouse model of insulinoma.

    PubMed

    Zumsteg, Adrian; Caviezel, Christoph; Pisarsky, Laura; Strittmatter, Karin; García-Echeverría, Carlos; Hofmann, Francesco; Christofori, Gerhard

    2012-06-01

    NVP-AEW541, a specific ATP-competitive inhibitor of the insulin-like growth factor-1 receptor (IGF1R) tyrosine kinase, has been reported to interfere with tumor growth in various tumor transplantation models. We have assessed the efficacy of NVP-AEW541 in repressing tumor growth and tumor progression in the Rip1Tag2 transgenic mouse model of pancreatic β-cell carcinogenesis. In addition, we have tested NVP-AEW541 in Rip1Tag2;RipIGF1R double-transgenic mice which show accelerated tumor growth and increased tumor malignancy compared with Rip1Tag2 single-transgenic mice. Previously, we have shown that high levels of IGF-2, a high-affinity ligand for IGF1R, are required for Rip1Tag2 tumor cell survival and tumor growth. Unexpectedly, treatment of Rip1Tag2 mice with NVP-AEW541 in prevention and intervention trials neither did affect tumor growth nor tumor cell proliferation and apoptosis. Yet, it significantly repressed progression to tumor malignancy, that is, the rate of the transition from differentiated adenoma to invasive carcinoma. Treatment of Rip1Tag2;RipIGF1R double-transgenic mice resulted in moderately reduced tumor volumes and increased rates of tumor cell apoptosis. Sustained expression of IGF-2 and of the IGF-2-binding form of insulin receptor (IR-A) in tumor cells suggests a compensatory role of IR-A upon IGF1R blockade. The results indicate that inhibition of IGF1R alone is not sufficient to efficiently block insulinoma growth and imply an overlapping role of IGF1R and insulin receptor in executing mitogenic and survival stimuli elicited by IGF-2. The reduction of tumor invasion upon IGF1R blockade on the other hand indicates a critical function of IGF1R signaling for the acquisition of a malignant phenotype.

  15. Malignant tumors in an area with an asbestos processing plant.

    PubMed

    Sarić, M; Vujović, M

    1994-01-01

    Incidence rate of malignant tumors of the lung/bronchus, pleura, larynx, pharynx, and peritoneum during the period 1974 to 1987 was studied in a Croatian coastal area with an asbestos processing plant which started to operate in 1954. The study area covers 169 km2 with 11,270 inhabitants: 5590 men and 5710 women (average number during the study period). The calculated number of inhabitants aged 35 and older was 4639 (41.1%), 11.5% were aged 60 or older, and the average age was 32 years. Over the observed 14-year period there were 51 cases of malignant tumors, 40 in men and 11 in women: lung/bronchus cancer, 36-29 men and 7 women; mesothelioma, 5-2 men and 3 women; laryngeal cancer, 5 men; pharyngeal cancer, 4-3 men and 1 women; and peritoneal cancer, 1 man. The results of the study showed that the incidence of lung/bronchus cancer in the studied population was half that in Croatia. There were also fewer malignant tumors of the pharynx and peritoneum in this area than in Croatia. On the other hand, the incidence of primary tumors of the pleura was more than 5 times as high and of laryngeal tumors more than 2 times as high as in Croatia. Evaluation of the data showed that distance from the source of emissions was not crucial for the development of tumors. The incidence of the tumors in the town with the asbestos factory was the lowest. Among and within different towns/villages the tumor incidence varied; in some the observed rate was higher than the expected rate. A more detailed analysis indicated a possible influence of the relief and prevailing wind direction on the environmental contamination with asbestos from the emissions source and consequently on an uneven distribution of the tumor incidence among separate settlements in the area under study.

  16. Three mutant genes cooperatively induce brain tumor formation in Drosophila malignant brain tumor.

    PubMed

    Riede, I

    1996-09-01

    The Drosophila melanogaster strain Malignant Brain Tumor reveals temperature-sensitive transformation of the larval brain tissue. Genetic analysis shows that three gene defects, spzMBT, yetiMBT, and tldMBT, cooperatively induce brain tumor formation. Whereas spz and tld belong to the genes inducing differentiation patterns in the embryo, yeti induces cell overgrowth. spzMBT-, yetiMBT-, and tldMBT-containing animals are larval lethal, whereas Malignant Brain Tumor is kept as a homozygous strain at a permissive temperature. This reveals that this tumor-forming strain is the result of a number of adaptive mutation events.

  17. Recurrent Intrapulmonary Solitary Fibrous Tumor With Malignant Transformation.

    PubMed

    Inoue, Takuya; Owada, Yuki; Watanabe, Yuzuru; Muto, Satoshi; Okabe, Naoyuki; Yonechi, Atsushi; Kanno, Ryuzo; Suzuki, Hiroyuki

    2016-07-01

    Intrapulmonary solitary fibrous tumor (SFT) of the pleura; the so-called inverted pattern, which appears to grow into the lung parenchyma, is extremely rare. We experienced a 66-year-old woman with an intrapulmonary SFT that recurred locally with malignant transformation 2 years after wedge resection of the left upper lobe for the primary tumor. Subsequently, she underwent a lobectomy of the residual left upper lobe. Six years after the second operation she was well, without rerecurrence. Complete excision and long-term follow-up of intrapulmonary SFTs of the pleura are important, even when the primary tumor displays benign histopathologic features.

  18. Recurrent Intrapulmonary Solitary Fibrous Tumor With Malignant Transformation.

    PubMed

    Inoue, Takuya; Owada, Yuki; Watanabe, Yuzuru; Muto, Satoshi; Okabe, Naoyuki; Yonechi, Atsushi; Kanno, Ryuzo; Suzuki, Hiroyuki

    2016-07-01

    Intrapulmonary solitary fibrous tumor (SFT) of the pleura; the so-called inverted pattern, which appears to grow into the lung parenchyma, is extremely rare. We experienced a 66-year-old woman with an intrapulmonary SFT that recurred locally with malignant transformation 2 years after wedge resection of the left upper lobe for the primary tumor. Subsequently, she underwent a lobectomy of the residual left upper lobe. Six years after the second operation she was well, without rerecurrence. Complete excision and long-term follow-up of intrapulmonary SFTs of the pleura are important, even when the primary tumor displays benign histopathologic features. PMID:27343529

  19. Immunocompetent cells in benign and malignant salivary gland tumors.

    PubMed

    Kärjä, V J; Syrjänen, K J; Syrjänen, S M

    1996-10-01

    IgA-, IgG, and IgM-producing plasma cells as well as 3- and T-lymphocytes were immunophenotyped and quantitated in a series of 216 benign and malignant salivary gland tumors, with special emphasis placed on the clinical behavior of the tumors. Highest number of plasma cells were found in mucoepidermoid carcinomas, where IgG-plasma cells were the sole Ig-class secreted. No IgA-immunoreactivity was found in adenoid cystic, undifferentiated, acinic cell, carcinoma in pleomorphic adenoma, and mucoepidermoid carcinomas. In squamous cell carcinomas, the number of IgM-plasma cells was higher than that in other salivary gland tumors. Basal cell adenomas contained only IgM-positive plasma cells. In logistic regression analysis, IgG- and IgM-producing plasma cells in malignant salivary gland tumors were related to an increased tumor diameter (p = 0.022 and 0.046, respectively). In benign tumors, neither clinical nor prognostic value could be attributed to the distribution of plasma cells. T-cells and B-cells were present in 63.9% and 33.8% of all tumors, found in 63.8% and 26.7% (p = 0.0048) of the benign tumors, and in 64.1% and 41.7% (not significant) of the malignant tumors, respectively. The presence of T- of B-lymphocytes was of no prognostic significance in malignant tumors. In benign tumors, however, the mean age of the patients was significantly higher (p = 0.010) and the mean time to recurrence significantly shorter (p = 0.018) in patients with tumors containing T-cells than in those devoid of these cells. In conclusion, the cell-mediated immunity (T-cells and their subsets) seems to play a more important role in pathogenesis and prognostication of salivary gland neoplasms than do the cells of the B-cell lineage, and, clearly, further studies are needed to elucidate these issues.

  20. Molecular subtypes of serous borderline ovarian tumor show distinct expression patterns of benign tumor and malignant tumor-associated signatures.

    PubMed

    Curry, Edward W J; Stronach, Euan A; Rama, Nona R; Wang, Yuepeng Y P; Gabra, Hani; El-Bahrawy, Mona A

    2014-03-01

    Borderline ovarian tumors show heterogeneity in clinical behavior. Most have excellent prognosis, although a small percentage show recurrence or progressive disease, usually to low-grade serous carcinoma. The aim of this study was to understand the molecular relationship between these entities and identify potential markers of tumor progression and therapeutic targets. We studied gene expression using Affymetrix HGU133plus2 GeneChip microarrays in 3 low-grade serous carcinomas, 13 serous borderline tumors and 8 serous cystadenomas. An independent data set of 18 serous borderline tumors and 3 low-grade serous carcinomas was used for validation. Unsupervised clustering revealed clear separation of benign and malignant tumors, whereas borderline tumors showed two distinct groups, one clustering with benign and the other with malignant tumors. The segregation into benign- and malignant-like borderline molecular subtypes was reproducible on applying the same analysis to an independent publicly available data set. We identified 50 genes that separate borderline tumors into their subgroups. Functional enrichment analysis of genes that separate borderline tumors to the two subgroups highlights a cell adhesion signature for the malignant-like subset, with Claudins particularly prominent. This is the first report of molecular subtypes of borderline tumors based on gene expression profiling. Our results provide the basis for identification of biomarkers for the malignant potential of borderline ovarian tumor and potential therapeutic targets for low-grade serous carcinoma.

  1. Malignant soft tissue tumors in children.

    PubMed

    Thacker, Mihir M

    2013-10-01

    Soft tissue masses are frequently seen in children. Although most are benign or reactive, soft tissue sarcomas (STS)-both rhabdomyosarcoma (most common) and non-rhabdo STS, do occur in the extremities. Appropriate evaluation of extremity soft tissue tumors often includes a biopsy as the clinical and imaging features may not be enough to establish a definitive diagnosis. Much needs to be done for improving the treatment of these rare but often devastating sarcomas. Given the small numbers of these cases seen at various centers, collaborative efforts should be made to further our understanding and improve the management of these challenging cases. PMID:24095080

  2. Malignant solitary fibrous tumor in the extremity: Cytopathologic findings.

    PubMed

    Khanchel, Fatma; Driss, Maha; Mrad, Karima; Romdhane, Khaled Ben

    2012-04-01

    Malignant solitary fibrous tumor (SFT) is an extremely rare neoplasm. There are only rare published accounts of the cytopathologic features of this tumor. We report a case of a 59-year-old woman presented with a 10-year history of a right thigh mass. A preoperative fine needle aspiration (FNA) was performed. Smears were hypercellular, with cohesive and crowded tissue fragments, haphazard cell arrangements and many single cells. The tumor cells were polymorphous, plump spindled or round with often indented or bare nuclei. A differential diagnosis of low grade sarcoma was favored. The diagnosis of malignant SFT is extremely difficult on FNA and must be included in the differential diagnosis of spindle cell neoplasms.

  3. Malignant solitary fibrous tumor of the nasal cavity.

    PubMed

    Zeitler, Daniel M; Kanowitz, Seth J; Har-El, Gady

    2007-07-01

    Solitary fibrous tumors (SFTs) are unusual mesenchymal tumors that were first described as primary spindle-cell neoplasms of the pleura. These tumors have been described in many other locations, including the urogenital system, orbit, mediastinum, and upper respiratory tract. Twenty-two cases of an SFT of the paranasal sinuses and nasal cavity have been reported, but none described a malignant SFT extending through the anterior skull base. A 70-year-old man had a 6-month history of unilateral left-sided epiphora and nasal obstruction. Computed tomography and magnetic resonance imaging showed a large left-sided nasal cavity mass with extension into the left extraconal orbit and intracranial extension through the left cribriform plate and ethmoid roof. The patient underwent preoperative embolization of the internal maxillary artery and a subsequent anterior craniofacial resection via a midfacial degloving approach and a left anterior craniotomy. Histopathological analysis of the specimen was consistent with a malignant SFT.

  4. Tumor type influences the effectiveness of pleurodesis in malignant effusions.

    PubMed

    Bielsa, Silvia; Hernández, Paula; Rodriguez-Panadero, Francisco; Taberner, Teresa; Salud, Antonieta; Porcel, José M

    2011-04-01

    Pleurodesis is commonly indicated for symptom relief in patients with malignant pleural effusions. A number of factors may influence pleurodesis outcome, but whether tumor type is one of them is a matter of debate. This study investigates the impact of tumor type on the efficacy of bedside doxycycline and thoracoscopic talc poudrage pleurodesis in order to determine which patients may benefit most from these procedures. A retrospective study of 138 and 450 doxycycline and talc poudrage pleurodesis procedures, respectively, evaluated their overall successes and failures, according to primary tumor types. In addition, a logistic regression model addressed whether the pleurodesis outcome in different tumor types was influenced by or attributable to pleural tumor burden. In the talc group, patients with lung cancer and mesothelioma had significantly lower complete response rates (63 and 61%, respectively) as compared with breast (77%) and other metastatic effusions (74%, p = 0.012). In the doxycycline group, the data followed the same trend in that complete response rates were lower in patients with lung carcinomas (31%) than in those with breast cancer (54%) or metastases from other primary sites (74%, p = 0.001). The regression analysis showed pleural burden and tumor type as independent predictors of pleurodesis failure in the talc group. The tumor type involving the pleural surfaces influences the success of a pleurodesis, regardless of the sclerosing agent used. Malignant effusions due to mesothelioma and lung cancer are particularly prone to a failed procedure.

  5. Tumor type influences the effectiveness of pleurodesis in malignant effusions.

    PubMed

    Bielsa, Silvia; Hernández, Paula; Rodriguez-Panadero, Francisco; Taberner, Teresa; Salud, Antonieta; Porcel, José M

    2011-04-01

    Pleurodesis is commonly indicated for symptom relief in patients with malignant pleural effusions. A number of factors may influence pleurodesis outcome, but whether tumor type is one of them is a matter of debate. This study investigates the impact of tumor type on the efficacy of bedside doxycycline and thoracoscopic talc poudrage pleurodesis in order to determine which patients may benefit most from these procedures. A retrospective study of 138 and 450 doxycycline and talc poudrage pleurodesis procedures, respectively, evaluated their overall successes and failures, according to primary tumor types. In addition, a logistic regression model addressed whether the pleurodesis outcome in different tumor types was influenced by or attributable to pleural tumor burden. In the talc group, patients with lung cancer and mesothelioma had significantly lower complete response rates (63 and 61%, respectively) as compared with breast (77%) and other metastatic effusions (74%, p = 0.012). In the doxycycline group, the data followed the same trend in that complete response rates were lower in patients with lung carcinomas (31%) than in those with breast cancer (54%) or metastases from other primary sites (74%, p = 0.001). The regression analysis showed pleural burden and tumor type as independent predictors of pleurodesis failure in the talc group. The tumor type involving the pleural surfaces influences the success of a pleurodesis, regardless of the sclerosing agent used. Malignant effusions due to mesothelioma and lung cancer are particularly prone to a failed procedure. PMID:21331598

  6. Quantification of Murine Pancreatic Tumors by High Resolution Ultrasound

    PubMed Central

    Sastra, Stephen A.; Olive, Kenneth P.

    2013-01-01

    Summary Ultrasonography is a powerful imaging modality that enables non-invasive, real time visualization of abdominal organs and tissues. This technology may be adapted for use in mice through the utilization of higher frequency transducers, allowing for extremely high resolution imaging of the mouse pancreas. This technique is particularly well-suited to pancreas imaging due to the ultrasonographic properties of the normal mouse pancreas, easily accessible imaging planes for the head and tail of the mouse pancreas, and the comparative difficulty in imaging the mouse pancreas with other technologies. A suite of measurements tools is available to characterize the normal and diseased states of tissues. Of particular utility for cancer applications is the ability to use tomography to construct a 3D tumor volume, enabling longitudinal imaging studies to track tumor development, or response to therapies. Here, we describe a detailed method for performing high resolution ultrasound to detect and measure pancreatic lesions in a genetically engineered mouse model of pancreatic ductal using the VisualSonics Vevo2100 High Resolution Ultrasound System. The method includes preparation of the animal for imaging, 2D and 3D image acquisition, and post-acquisition analysis of tumors volumes. The combined procedure has been utilized extensively by our group and others for the preclinical evaluation of novel therapeutic agents in the treatment of pancreatic ductal adenocarcinoma (1–4). PMID:23359158

  7. Opportunities and Challenges for Pancreatic Circulating Tumor Cells.

    PubMed

    Nagrath, Sunitha; Jack, Rhonda M; Sahai, Vaibhav; Simeone, Diane M

    2016-09-01

    Sensitive and reproducible platforms have been developed for detection, isolation, and enrichment of circulating tumor cells (CTCs)-rare cells that enter the blood from solid tumors, including those of the breast, prostate gland, lung, pancreas, and colon. These might be used as biomarkers in diagnosis or determination of prognosis. CTCs are no longer simply detected and quantified; they are now used in ex vivo studies of anticancer agents and early detection. We review what we have recently learned about CTCs from pancreatic tumors, describing advances in their isolation and analysis and challenges to their clinical utility. We summarize technologies used to isolate CTCs from blood samples of patients with pancreatic cancer, including immunoaffinity and label-free physical attribute-based capture. We explain methods of CTC analysis and how findings from these studies might be used to detect cancer at earlier stages, monitor disease progression, and determine prognosis. We review studies that have expanded CTCs for testing of anticancer agents and how these approaches might be used to personalize treatment. Advances in the detection, isolation, and analysis of CTCs have increased our understanding of the dissemination and progression of pancreatic cancer. However, standardization of methodologies and prospective studies are needed for this emerging technology to have a significant effect on clinical care. PMID:27339829

  8. Extracellular vesicles from malignant effusions induce tumor cell migration: inhibitory effect of LMWH tinzaparin.

    PubMed

    Gamperl, Hans; Plattfaut, Corinna; Freund, Annika; Quecke, Tabea; Theophil, Friederike; Gieseler, Frank

    2016-10-01

    Elevated levels of extracellular vesicles (EVs) have been correlated with inflammatory diseases as well as progressive and metastatic cancer. By presenting tissue factor (TF) on their membrane surface, cellular microparticles (MPs) activate both the coagulation system and cell-signaling pathways such as the PAR/ERK pathway. We have shown before that malignant effusions are a rich source of tumor cell-derived EVs. Here, we used EVs from malignant effusions from three different patients after serial low-speed centrifugation steps as recommended by the ISTH (lsEV). Significant migration of human pancreatic carcinoma cells could be induced by lsEVs and was effectively inhibited by pre-incubation with tinzaparin, a low-molecular-weight heparin. Tinzaparin induced tissue factor pathway inhibitor (TFPI) release from tumor cells, and recombinant TFPI inhibited EV-induced tumor cell migration. EVs also induced ERK phosphorylation, whereas inhibitors of PAR2 and ERK suppressed EV-induced tumor cell migration. LsEVs have been characterized by high-resolution flow cytometry and, after elimination of smaller vesicles including exosomes, by further high-speed centrifugation (hsEV). The remaining population consisting primarily of MPs is indeed the main migration-inducing population with tenase activity. Compared to other LMWHs, tinzaparin is suggested to have high potency to induce TFPI release from epithelial cells. The migration-inhibitory effect of TFPI and the interruption of tumor cell migration by inhibitors of PAR2 and ERK suggest that lsEVs induce tumor cell migration by activating the PAR2 signaling pathway. Tinzaparin might inhibit this process at least partly by inducing the release of TFPI from tumor cells, which blocks PAR-activating TF complexes. The clinical relevance of the results is discussed.

  9. Extracellular vesicles from malignant effusions induce tumor cell migration: inhibitory effect of LMWH tinzaparin.

    PubMed

    Gamperl, Hans; Plattfaut, Corinna; Freund, Annika; Quecke, Tabea; Theophil, Friederike; Gieseler, Frank

    2016-10-01

    Elevated levels of extracellular vesicles (EVs) have been correlated with inflammatory diseases as well as progressive and metastatic cancer. By presenting tissue factor (TF) on their membrane surface, cellular microparticles (MPs) activate both the coagulation system and cell-signaling pathways such as the PAR/ERK pathway. We have shown before that malignant effusions are a rich source of tumor cell-derived EVs. Here, we used EVs from malignant effusions from three different patients after serial low-speed centrifugation steps as recommended by the ISTH (lsEV). Significant migration of human pancreatic carcinoma cells could be induced by lsEVs and was effectively inhibited by pre-incubation with tinzaparin, a low-molecular-weight heparin. Tinzaparin induced tissue factor pathway inhibitor (TFPI) release from tumor cells, and recombinant TFPI inhibited EV-induced tumor cell migration. EVs also induced ERK phosphorylation, whereas inhibitors of PAR2 and ERK suppressed EV-induced tumor cell migration. LsEVs have been characterized by high-resolution flow cytometry and, after elimination of smaller vesicles including exosomes, by further high-speed centrifugation (hsEV). The remaining population consisting primarily of MPs is indeed the main migration-inducing population with tenase activity. Compared to other LMWHs, tinzaparin is suggested to have high potency to induce TFPI release from epithelial cells. The migration-inhibitory effect of TFPI and the interruption of tumor cell migration by inhibitors of PAR2 and ERK suggest that lsEVs induce tumor cell migration by activating the PAR2 signaling pathway. Tinzaparin might inhibit this process at least partly by inducing the release of TFPI from tumor cells, which blocks PAR-activating TF complexes. The clinical relevance of the results is discussed. PMID:27435911

  10. No Detectable Hypoxia in Malignant Salivary Gland Tumors: Preliminary Results

    SciTech Connect

    Wijffels, Karien; Hoogsteen, Ilse J.; Lok, Jasper; Rijken, Paulus F.J.W.; Marres, Henri A.M.; Wilde, Peter C.M. de; Kogel, Albert J. van der; Kaanders, Johannes H.A.M.

    2009-04-01

    Purpose: Hypoxia is detected in most solid tumors and is associated with malignant progression and adverse treatment outcomes. However, the oxygenation status of malignant salivary gland tumors has not been previously studied. The aim of this study was to investigate the potential clinical relevance of hypoxia in this tumor type. Methods and Materials: Twelve patients scheduled for surgical resection of a salivary gland tumor were preoperatively injected with the hypoxia marker pimonidazole and the proliferation marker iododeoxyuridine. Tissue samples of the dissected tumor were immunohistochemically stained for blood vessels, pimonidazole, carbonic anhydrase-IX, glucose transporters-1 and -3 (Glut-1, Glut-3), hypoxia-inducible factor-1{alpha}, iododeoxyuridine, and epidermal growth factor receptor. The tissue sections were quantitatively assessed by computerized image analysis. Results: The tissue material from 8 patients was of sufficient quality for quantitative analysis. All tumors were negative for pimonidazole binding, as well as for carbonic anhydrase-IX, Glut-1, Glut-3, and hypoxia-inducible factor-1{alpha}. The vascular density was high, with a median value of 285 mm{sup -2} (range, 209-546). The iododeoxyuridine-labeling index varied from <0.1% to 12.2% (median, 2.2%). Epidermal growth factor receptor expression levels were mostly moderate to high. In one-half of the cases, nuclear expression of epidermal growth factor receptor was observed. Conclusion: The absence of detectable pimonidazole binding, as well as the lack of expression of hypoxia-associated proteins in all tumors, indicates that malignant salivary gland tumors are generally well oxygenated. It is unlikely that hypoxia is a relevant factor for their clinical behavior and treatment responsiveness.

  11. De novo malignant solitary fibrous tumor of the kidney.

    PubMed

    Hsieh, Tsan-Yu; ChangChien, Yi-Che; Chen, Wen-Hsiang; Chen, Siu-Chung; Chang, Liang-Che; Hwang, Cheng-Cheng; Chein, Hui-Ping; Chen, Jim-Ray

    2011-01-01

    The kidney is a relatively infrequent site for solitary fibrous tumor (SFT). Among the previously reported cases, only two cases of malignant renal SFT developing via dedifferentiation from a pre-existing benign SFT have been reported. Here we reported a case of de novo malignant renal SFT clinically diagnosed as renal cell carcinoma in a 50-year-old woman. The tumor was circumscribed but unencapsulated and showed obvious hemorrhagic necrosis. Microscopically, the tumor was composed of patternless sheets of alternating hypercellular and hypocellular areas of spindle cells displaying mild to moderate nuclear atypia, frequent mitoses up to 8 per 10 high power fields, and a 20% Ki-67 proliferative index. Immunohistochemical studies revealed reactivity for CD34, CD99 and vimentin, with no staining for all other markers, confirming the diagnosis of SFT. No areas of dedifferentiation were seen after extensive sampling. Based on the pathologic and immunohistochemical features, a diagnosis of de novo malignant renal SFT was warranted. Our report expands the spectrum of malignant progression in renal SFTs. Even though this patient has been disease-free for 30 months, long-term follow-up is still mandatory.

  12. Boron Neutron Capture Therapy for Malignant Brain Tumors

    PubMed Central

    MIYATAKE, Shin-Ichi; KAWABATA, Shinji; HIRAMATSU, Ryo; KUROIWA, Toshihiko; SUZUKI, Minoru; KONDO, Natsuko; ONO, Koji

    2016-01-01

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID:27250576

  13. Boron Neutron Capture Therapy for Malignant Brain Tumors.

    PubMed

    Miyatake, Shin-Ichi; Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Suzuki, Minoru; Kondo, Natsuko; Ono, Koji

    2016-07-15

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting.

  14. Boron Neutron Capture Therapy for Malignant Brain Tumors.

    PubMed

    Miyatake, Shin-Ichi; Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Suzuki, Minoru; Kondo, Natsuko; Ono, Koji

    2016-07-15

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID:27250576

  15. Simian virus 40 transformation, malignant mesothelioma and brain tumors

    PubMed Central

    Qi, Fang; Carbone, Michele; Yang, Haining; Gaudino, Giovanni

    2011-01-01

    Simian virus 40 (SV40) is a DNA virus isolated in 1960 from contaminated polio vaccines, that induces mesotheliomas, lymphomas, brain and bone tumors, and sarcomas, including osteosarcomas, in hamsters. These same tumor types have been found to contain SV40 DNA and proteins in humans. Mesotheliomas and brain tumors are the two tumor types that have been most consistently associated with SV40, and the range of positivity has varied about from 6 to 60%, although a few reported 100% of positivity and a few reported 0%. It appears unlikely that SV40 infection alone is sufficient to cause human malignancy, as we did not observe an epidemic of cancers following the administration of SV40-contaminated vaccines. However, it seems possible that SV40 may act as a cofactor in the pathogenesis of some tumors. In vitro and animal experiments showing cocarcinogenicity between SV40 and asbestos support this hypothesis. PMID:21955238

  16. Tumor-associated macrophages: unwitting accomplices in breast cancer malignancy

    PubMed Central

    Williams, Carly Bess; Yeh, Elizabeth S; Soloff, Adam C

    2016-01-01

    Deleterious inflammation is a primary feature of breast cancer. Accumulating evidence demonstrates that macrophages, the most abundant leukocyte population in mammary tumors, have a critical role at each stage of cancer progression. Such tumor-associated macrophages facilitate neoplastic transformation, tumor immune evasion and the subsequent metastatic cascade. Herein, we discuss the dynamic process whereby molecular and cellular features of the tumor microenvironment act to license tissue-repair mechanisms of macrophages, fostering angiogenesis, metastasis and the support of cancer stem cells. We illustrate how tumors induce, then exploit trophic macrophages to subvert innate and adaptive immune responses capable of destroying malignant cells. Finally, we discuss compelling evidence from murine models of cancer and early clinical trials in support of macrophage-targeted intervention strategies with the potential to dramatically reduce breast cancer morbidity and mortality. PMID:26998515

  17. True malignant mixed tumor of the submandibular gland.

    PubMed

    Yamashita, T; Kameda, N; Katayama, K; Hiruta, N; Nakada, M; Takeda, Y

    1990-02-01

    A case of true malignant mixed tumor of the submandibular gland is reported. The submandibular tumor, occurring in a 52-year-old man, started to grow rapidly after a long history without any change in size. Surgical resection was carried out and the resected tumor measured 5.5 cm with a cut surface showing mixed solid structures. Microscopically, the tumor had both carcinomatous and sarcomatous elements, the former consisting of poorly differentiated adenocarcinoma with squamous cell differentiation and the latter consisting of osteosarcoma with chondrosarcomatous and fibrosarcomatous elements. A remnant of benign pleomorphic adenoma could also be identified. Immunohistochemical study demonstrated keratin and epithelial membrane antigen in the carcinoma cells and vimentin in all elements of the osteosarcoma. It is assumed from these clinical and histological findings that the tumor had transformed from a pre-existing benign pleomorphic adenoma.

  18. Phase II Study of Intraventricular Methotrexate in Children With Recurrent or Progressive Malignant Brain Tumors

    ClinicalTrials.gov

    2016-06-30

    Recurrent Childhood Medulloblastoma; Recurrent Childhood Ependymoma; Childhood Atypical Teratoid/Rhabdoid Tumor; Embryonal Tumor With Abundant Neuropil and True Rosettes; Metastatic Malignant Neoplasm to the Leptomeninges

  19. Identification of peptides that bind to irradiated pancreatic tumor cells

    SciTech Connect

    Huang Canhui; Liu, Xiang Y.; Rehemtulla, Alnawaz; Lawrence, Theodore S. . E-mail: tsl@med.umich.edu

    2005-08-01

    Purpose: Peptides targeting tumor vascular cells or tumor cells themselves have the potential to be used as vectors for delivering either DNA in gene therapy or antitumor agents in chemotherapy. We wished to determine if peptides identified by phage display could be used to target irradiated pancreatic cancer cells. Methods and Materials: Irradiated Capan-2 cells were incubated with 5 x 10{sup 12} plaque-forming units of a phage display library. Internalized phage were recovered and absorbed against unirradiated cells. After five such cycles of enrichment, the recovered phage were subjected to DNA sequencing analysis and synthetic peptides made. The binding of both phage and synthetic peptides was evaluated by fluorescence staining and flow cytometry in vitro and in vivo. Results: We identified one 12-mer peptide (PA1) that binds to irradiated Capan-2 pancreatic adenocarcinoma cells but not to unirradiated cells. The binding of peptide was significant after 48 h incubation with cells. In vivo experiments with Capan-2 xenografts in nude mice demonstrated that these small peptides are able to penetrate tumor tissue after intravenous injections and bind specifically to irradiated tumor cells. Conclusion: These data suggest that peptides can be identified that target tumors with radiation-induced cell markers and may be clinically useful.

  20. Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms

    PubMed Central

    Honda, Kazufumi; Kobayashi, Michimoto; Okusaka, Takuji; Rinaudo, Jo Ann; Huang, Ying; Marsh, Tracey; Sanada, Mitsuaki; Sasajima, Yoshiyuki; Nakamori, Shoji; Shimahara, Masashi; Ueno, Takaaki; Tsuchida, Akihiko; Sata, Naohiro; Ioka, Tatsuya; Yasunami, Yohichi; Kosuge, Tomoo; Miura, Nami; Kamita, Masahiro; Sakamoto, Takako; Shoji, Hirokazu; Jung, Giman; Srivastava, Sudhir; Yamada, Tesshi

    2015-01-01

    We recently reported that circulating apolipoprotein AII (apoAII) isoforms apoAII-ATQ/AT (C-terminal truncations of the apoAII homo-dimer) decline significantly in pancreatic cancer and thus might serve as plasma biomarkers for the early detection of this disease. We report here the development of novel enzyme-linked immunosorbent assays (ELISAs) for measurement of apoAII-ATQ/AT and their clinical applicability for early detection of pancreatic cancer. Plasma and serum concentrations of apoAII-ATQ/AT were measured in three independent cohorts, which comprised healthy control subjects and patients with pancreatic cancer and gastroenterologic diseases (n = 1156). These cohorts included 151 cases of stage I/II pancreatic cancer. ApoAII-ATQ/AT not only distinguished the early stages of pancreatic cancer from healthy controls but also identified patients at high risk for pancreatic malignancy. AUC values of apoAII-ATQ/AT to detect early stage pancreatic cancer were higher than those of CA19–9 in all independent cohorts. ApoAII-ATQ/AT is a potential biomarker for screening patients for the early stage of pancreatic cancer and identifying patients at risk for pancreatic malignancy (161 words). PMID:26549697

  1. Solitary fibrous tumor with malignant potential arising in sublingual gland.

    PubMed

    Ogawa, Ikuko; Sato, Sunao; Kudo, Yasusei; Miyauchi, Mutsumi; Sugiyama, Masaru; Suei, Yoshikazu; Takata, Takashi

    2003-01-01

    A rare case is described of a solitary fibrous tumor (SFT) with malignant potential arising in the sublingual gland. A 59-year-old man presented with a 4-month history of a slowly enlarging painless mass in the center of the floor of the mouth. The tumor was a well-demarcated, firm mass with a multicystic lesion. The tumor exhibited highly cellular areas of spindle cells with patternless architecture alternating with hypocellular areas. The tumor cells were positive for CD34 and bcl-2 as well as vimentin, and negative for epithelial, myogenic, neurogenic and histiocytic markers. The tumor cells formed multiple satellite nodules around dilated ducts in the multicystic lesion, indicating infiltrative growth. In addition, areas exhibiting higher cellularity with increased mitoses were noticed in the satellite nodules, although cellular atypia was not obvious. These findings led to a final diagnosis of SFT with malignant potential. There has been no recurrence or metastasis for 27 months after the surgery. Solitary fibrous tumor of the salivary gland must be differentiated from various spindle cell neoplasms including myogenic, peripheral nerve sheath, fibroblastic and fibro-histiocytic spindle cell neoplasms, hemangiopericytoma and myoepithelioma. In addition to characteristic morphological features, an immunohistochemical positivity for CD34 and bcl-2 may aid in the diagnosis of SFT.

  2. Ovarian tumors of low malignant potential (borderline tumors): immune morphology and current status.

    PubMed

    Neunteufel, W; Gitsch, G; Schieder, K; Kölbl, H; Breitenecker, G

    1989-01-01

    CA 125, CA 19-9 and CEA were demonstrated in tissue samples of 30 ovarian borderline tumors by immunohistochemistry. Of the 21 serous and 9 mucinous borderline tumors, 23 were in stage I and 7 stage III. None of the patients died of disease. All mucinous borderline tumors were CA 125 negative, 89% CA 19-9 positive and 44% CEA positive. 62% of the serous borderline tumors were CA 125 positive, 52% CA 19-9 and 19% CEA positive. Tumors of low malignant potential responded to CA 19-9 like invasive carcinomas. The incidence of positive responses to CA 125 ands CEA fell between that of benign and malignant tumors. The marker pattern did not correlate with tumor stage and cytological grading. The biological behavior of ovarian borderline tumors ranges between that of benign tumors and invasive carcinomas and cannot be classified as definitely belonging to either group. It is plausible that they are primarily of the borderline type, and not benign tumors that undergo malignant degeneration.

  3. Origin of induced pancreatic islet tumors: a radioautographic study

    SciTech Connect

    Michels, J.E.; Bauer, G.E.; Dixit, P.K.

    1987-02-01

    Endocrine tumors of the pancreas are induced in a high percentage of young rats by injections of streptozotocin and nicotinamide (SZ/NA). Benign tumors first appear 20 to 36 weeks after drug injections. To determine the possible site of their origin, the incorporation of (/sup 3/H)thymidine into islets, ducts, acini, microtumors, and gross tumors was examined by radioautography of histologic sections at 1 to 36 weeks after drug injection. Drug treatment led to early (1- to 6-week) increases in nuclear /sup 3/H labeling of exocrine pancreatic structures (ductal and acinar cells), which may involve DNA repair processes. A secondary increase in labeling of duct cells during the period of tumor emergence supports the assumption that SZ/NA-induced tumors are of ductal origin. Microtumors and gross tumors also exhibited markedly elevated rates of (/sup 3/H)thymidine incorporation compared to control islets. Nontumorous islet tissue, which exhibited a gradual decrease in volume due to B-cell destruction by the drug injection, showed about 10-fold higher /sup 3/H labeling than islets of controls at all time points. The results suggest that in addition to ductal precursors, islets that survive SZ/NA-induced injury may also provide sites of focal endocrine cell differentiation to tumor tissue. Once established, both microtumors and gross tumors continue to grow by accelerated cell division.

  4. [Synchronous tumors of the female genital tract: triple malignant and one benign tumor].

    PubMed

    Dudnyikova, Anna; Vereczkey, Ildikó; Pete, Imre

    2012-03-01

    Synchronous tumors of the female genital tract are rare, accounting for 0.7-1.8% of all cases. Double synchronous tumors are most often mentioned in the literature. Reviewing the English literature on this topic, we have found only one case report of a triple synchronous tumor. The 55-year-old patient mentioned in our case has had advanced diabetes mellitus, and has been treated with corticosteroid therapy for a long time because of chronic obstructive pulmonary disease (COPD). She was examined because of her vulvar tumor. During the diagnostic procedure, cervical and endometrial malignant tumors and a benign ovarian cyst have also been found. This event brings to our attention the fact that we should be prepared to manage synchronous even triple malignant gynecological tumors.

  5. Malignant tumors in two ancient populations: An approach to historical tumor epidemiology.

    PubMed

    Nerlich, Andreas G; Rohrbach, Helmut; Bachmeier, Beatrice; Zink, Albert

    2006-07-01

    The actual increase in the rate of malignant tumors has been ascribed to a higher life expectancy and the influence of various environmental factors. Herein, we present data on the frequency of malignant tumors in paleopathologically well-defined historic populations. Thereby, we looked for malignant growth affecting the skeleton in three study populations of 905 individuals that have been excavated from the necropoles of Thebes-West and Abydos, Upper Egypt covering the time period between 3200 and 500 BC and 2547 individuals that have been buried in a Southern German ossuary dating from between AD 1400 and 1800. The tissue preservation of both the Egyptian and Southern German material was excellent. All available specimens were subjected to a very careful macroscopic examination; isolated findings were also radiologically investigated. In parallel, anthropological data, such as gender and age at death, were recorded. We identified 5 cases of malignant tumors affecting the skeleton in the Egyptian material and 13 cases affecting the skeletal material from Southern Germany. In most instances, multiple osteolytic lesions with slight osteoblastic reaction are strongly suggestive for metastatic carcinoma. Few cases with poorly reactive osteolyses were most compatible with plasmacytoma. Relative tumor frequencies on an age- and sex-adjusted population basis (using a mathematic model of skeletal involvement of malignant tumors in a well-defined English study population from AD 1901 to 1905) indicated that the tumor rates were not statistically different between ancient Egyptian, the historical Southern German and the recent English reference population. These observations indicate that malignant tumors were present in spatially and temporarily different populations over the last 4000 years with an age- and gender-adjusted frequency not different from Western industrial populations of c. 100 years ago. Therefore, we conclude that the current rise in tumor frequencies in

  6. Malignant giant solitary fibrous tumor of the mediastinum.

    PubMed

    De Raet, Jan; Sacré, Robert; Hoorens, Anne; Fletcher, Christopher; Lamote, Jan

    2008-09-01

    Malignant giant solitary fibrous tumor (SFT) of the mediastinum is a rare neoplasm derived from mesenchymal tissue. Owing to its large size, a complete resection of the tumor can present many challenges, particularly given its proximity to vital neighboring structures. We report a successful en-bloc resection of a massive mediastinal SFT, which was compressing the inferior trachea and heart, by means of a median sternotomy and an anterior left thoracotomy. We emphasize the rarity of this uncommon mediastinal mass. Key points of mediastinal SFT are discussed.

  7. Training stem cells for treatment of malignant brain tumors

    PubMed Central

    Li, Shengwen Calvin; Kabeer, Mustafa H; Vu, Long T; Keschrumrus, Vic; Yin, Hong Zhen; Dethlefs, Brent A; Zhong, Jiang F; Weiss, John H; Loudon, William G

    2014-01-01

    The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for patients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution (i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system. PMID:25258664

  8. [Nuclear morphometry and DNA cytometry in the grading of malignant tumors of the salivary gland].

    PubMed

    Zhang, W Z

    1992-05-01

    Nuclear morphometry and DNA cytometry were performed in 6 normal salivary glands and 37 malignant tumors of the salivary gland. Multivariate discrimination analysis was used to grade the malignant salivary gland tumors. The discrimination rate was 100% for normal salivary gland, benign tumor, high malignant carcinoma and low malignant carcinoma. It was 66.7% for borderline malignancies. These results indicate that quantitative cytological analysis is effective and reproducible in the grading of salivary gland tumors. Stepwise multivariate regression analysis showed that there was a very complicated correlation between DNA content and nuclear morphometric parameters of salivary gland tumors.

  9. Measles may be a Risk Factor for Malignant Brain Tumors

    PubMed Central

    Green, Sheryl; Rendo, Angela; Rosenzweig, Kenneth E.

    2015-01-01

    Background A possible risk factor for brain tumor might be measles, since late neurologic sequelae are part of measles pathology. Subacute sclerosing panencephalitis, a devastating neurologic illness, is prone to develop years after measles infection. Methods Because measles damage to the brain might increase the risk of brain tumor, we examined the relationship of measles incidence in 1960 and brain tumor incidence in 50 US States and the District of Columbia, 2004-2007. Data on number of cases of measles by state in 1960 are from the Morbidity and Mortality Weekly Report. In 1960 measles was a childhood illness. We calculated measles incidence by obtaining the population of each state from the 1960 US Census and then age adjusting our results to the cumulative percent of the state population under age 21, since this would have been the measles-infected group. Data on the percentage white population by state are from the US Census (www.census.gov). Age-adjusted incidence (to the 2000 US standard population) of brain tumors is from the Central Brain Tumor Registry of the United States 2011 report. Results There was a significant correlation between 1960 measles incidence and incidence of malignant brain tumors in persons 20 and older in 2004-2007 (r=0.321, p=0.026). Because glioblastoma is more frequent in whites and males, multivariate linear regression was performed with tumor incidence as the dependent variable, measles incidence, percent white population, and sex ratio by state as independent variables. Measles incidence was significantly correlated with malignant brain tumor incidence (β=0.361, p<0.001) and independent of the effect of race (β=0.734, p<0.001) and sex ratio m/f (β=-0.478, p<0.001). There was no correlation of measles incidence with brain tumor incidence in persons younger than 20. Conclusion Inflammation is a critical component of tumor development. The inflammation of measles-induced subacute sclerosing panencephalitis, even subclinical

  10. Pancreatic acinar cells produce, release, and respond to tumor necrosis factor-alpha. Role in regulating cell death and pancreatitis.

    PubMed Central

    Gukovskaya, A S; Gukovsky, I; Zaninovic, V; Song, M; Sandoval, D; Gukovsky, S; Pandol, S J

    1997-01-01

    The aim of this study was to determine whether tumor necrosis factor-alpha (TNFalpha) and receptors for TNFalpha are expressed in the exocrine pancreas, and whether pancreatic acinar cells release and respond to TNFalpha. Reverse transcription PCR, immunoprecipitation, and Western blot analysis demonstrated the presence of TNFalpha and 55- and 75-kD TNFalpha receptors in pancreas from control rats, rats with experimental pancreatitis induced by supramaximal doses of cerulein, and in isolated pancreatic acini. Immunohistochemistry showed TNFalpha presence in pancreatic acinar cells. ELISA and bioassay measurements of TNFalpha indicated its release from pancreatic acinar cells during incubation in primary culture. Acinar cells responded to TNFalpha. TNFalpha potentiated NF-kappaB translocation into the nucleus and stimulated apoptosis in isolated acini while not affecting LDH release. In vivo studies demonstrated that neutralization of TNFalpha with an antibody produced a mild improvement in the parameters of cerulein-induced pancreatitis. However, TNFalpha neutralization greatly inhibited apoptosis in a modification of the cerulein model of pancreatitis which is associated with a high percentage of apoptotic cell death. The results indicate that pancreatic acinar cells produce, release, and respond to TNFalpha. This cytokine regulates apoptosis in both isolated pancreatic acini and experimental pancreatitis. PMID:9312187

  11. Pancreatic Tumor Cell Secreted CCN1/Cyr61 Promotes Endothelial cell migration and Aberrant Neovascularization

    PubMed Central

    Maity, Gargi; Mehta, Smita; Haque, Inamul; Dhar, Kakali; Sarkar, Sandipto; Banerjee, Sushanta K.; Banerjee, Snigdha

    2014-01-01

    The complex signaling networks between cancer cells and adjacent endothelial cells make it challenging to unravel how cancer cells send extracellular messages to promote aberrant vascularization or tumor angiogenesis. Here, in vitro and in vivo models show that pancreatic cancer cell generated unique microenvironments can underlie endothelial cell migration and tumor angiogenesis. Mechanistically, we find that pancreatic cancer cell secreted CCN1/Cyr61 matricellular protein rewires the microenvironment to promote endothelial cell migration and tumor angiogenesis. This event can be overcome by Sonic Hedgehog (SHh) antibody treatment. Collectively, these studies identify a novel CCN1 signaling program in pancreatic cancer cells which activates SHh through autocrine-paracrine circuits to promote endothelial cell migration and tumor angiogenesis and suggests that CCN1 signaling of pancreatic cancer cells is vital for the regulation of tumor angiogenesis. Thus CCN1 signaling could be an ideal target for tumor vascular disruption in pancreatic cancer. PMID:24833309

  12. Optically measured microvascular blood flow contrast of malignant breast tumors.

    PubMed

    Choe, Regine; Putt, Mary E; Carlile, Peter M; Durduran, Turgut; Giammarco, Joseph M; Busch, David R; Jung, Ki Won; Czerniecki, Brian J; Tchou, Julia; Feldman, Michael D; Mies, Carolyn; Rosen, Mark A; Schnall, Mitchell D; DeMichele, Angela; Yodh, Arjun G

    2014-01-01

    Microvascular blood flow contrast is an important hemodynamic and metabolic parameter with potential to enhance in vivo breast cancer detection and therapy monitoring. Here we report on non-invasive line-scan measurements of malignant breast tumors with a hand-held optical probe in the remission geometry. The probe employs diffuse correlation spectroscopy (DCS), a near-infrared optical method that quantifies deep tissue microvascular blood flow. Tumor-to-normal perfusion ratios are derived from thirty-two human subjects. Mean (95% confidence interval) tumor-to-normal ratio using surrounding normal tissue was 2.25 (1.92-2.63); tumor-to-normal ratio using normal tissues at the corresponding tumor location in the contralateral breast was 2.27 (1.94-2.66), and using normal tissue in the contralateral breast was 2.27 (1.90-2.70). Thus, the mean tumor-to-normal ratios were significantly different from unity irrespective of the normal tissue chosen, implying that tumors have significantly higher blood flow than normal tissues. Therefore, the study demonstrates existence of breast cancer contrast in blood flow measured by DCS. The new, optically accessible cancer contrast holds potential for cancer detection and therapy monitoring applications, and it is likely to be especially useful when combined with diffuse optical spectroscopy/tomography. PMID:24967878

  13. [What is new in the pathology of pancreatic neuroendocrine tumors?].

    PubMed

    Komminoth, P; Perren, A

    2015-05-01

    The diagnostics of pancreatic neuroendocrine tumors (PanNEN) have changed in recent years especially concerning the World Health Organization (WHO) classification, TNM staging and grading. Furthermore, some new prognostic and predictive immunohistochemical markers have been introduced. Most progress, however, has been made in the molecular pathogenesis of these neoplasms. Using next generation sequencing techniques, the mammalian target of rapamycin (mTOR) pathway, hypoxia and epigenetic changes were identified as key players in tumorigenesis. In this article the most important developments of morphological as well as immunohistochemical diagnostics together with the molecular background of PanNEN are summarized.

  14. Pancreatic neuroendocrine tumors: clinical features, diagnosis and medical treatment: advances

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato; Jensen, Robert T.

    2013-01-01

    Pancreatic neuroendocrine tumors (pNETs) comprise with gastrointestinal carcinoids, the main groups of gastrointestinal neuroendocrine tumors (GI-NETs). Although these two groups of GI-NETs share many features including histological aspects; over-/ectopic expression of somatostatin receptors; the ability to ectopically secrete hormones/peptides/amines which can result in distinct functional syndromes; similar approaches used for tumor localization and some aspects of treatment, it is now generally agreed they should be considered separate. They differ in their pathogenesis, hormonal syndromes produced, many aspects of biological behavior and most important, in their response to certain anti-tumor treatment (chemotherapy, molecular targeted therapies). In this chapter the clinical features of the different types of pNETs will be considered as well as aspects of their diagnosis and medical treatment of the hormone-excess state. Emphasis will be on controversial areas or recent advances. The other aspects of the management of these tumors (surgery, treatment of advanced disease, tumor localization) are not dealt with here, because they are covered in other chapters in this volume. PMID:23582916

  15. Molecular biology of malignant melanoma and other cutaneous tumors.

    PubMed

    Pons, M; Quintanilla, M

    2006-07-01

    Skin cancer is the most common cancer worldwide. Its incidence is doubling every 15-20 years likely because of an aging population, changes in behaviour towards sun exposure, and increased UV light fluency at the earth surface due to ozone depletion. In this review, we summarize the most important genetic changes contributing to the development of malignant melanoma, basal cell carcinoma and squamous cell carcinoma, the main tumor entities arising in the skin. While our understanding of the oncogenes and tumor suppressor genes involved in the development and progression of skin tumors is still fragmentary, recent advances have shown alterations affecting conserved signalling pathways that control cellular proliferation and viability. These pathways include INK4alpha/Rb, ARF/p53, RAS/MAPKs, and sonic hedgehog/Gli. PMID:16870533

  16. Tet1 is a tumor suppressor of hematopoietic malignancy

    PubMed Central

    Cimmino, Luisa; Dawlaty, Meelad M.; Ndiaye-Lobry, Delphine; Yap, Yoon Sing; Bakogianni, Sofia; Yu, Yiting; Bhattacharyya, Sanchari; Shaknovich, Rita; Geng, Huimin; Lobry, Camille; Mullenders, Jasper; King, Bryan; Trimarchi, Thomas; Aranda-Orgilles, Beatriz; Liu, Cynthia; Shen, Steven; Verma, Amit K.; Jaenisch, Rudolf; Aifantis, Iannis

    2015-01-01

    The TET methylcytosine dioxygenase 1 (TET1) enzyme is an important regulator of 5-hydroxymethylcytosine (5hmC) in embryonic stem cells. Decreased expression of TET proteins and loss of 5hmC in many tumors suggests a critical role for the maintenance of this epigenetic modification. Here we show that deletion of Tet1 promoted the development of B cell lymphoma in mice. Tet1 was required for maintaining normal content of 5hmC, preventing DNA hypermethylation and in the regulation of B cell lineage, chromosome maintenance and DNA repair genes. Whole-exome sequencing of Tet1-deficient tumors revealed mutations frequently found in Non-Hodgkin B cell lymphoma, where TET1 was hypermethylated and transcriptionally silenced. These findings provide in vivo evidence of TET1 function as a tumor suppressor of hematopoietic malignancy. PMID:25867473

  17. Cytology Findings in Pancreatic Heterotopia, a Potential Pitfall For Malignancy: A Case Report and Literature Review

    PubMed Central

    Raddaoui, Emad; Al-Sharabi, Abdulsalam; Almadi, Majid A.

    2015-01-01

    Pancreatic heterotopia is a rare congenital disorder occurring at a variety of sites in the gastrointestinal tract. It is rarely symptomatic. Despite advances in diagnostic techniques, it still remains a challenge to the clinician to differentiate it from a neoplasm. Cytologic characteristics of pancreatic heterotopia in general are rarely described in the literature. We report the cytologic characteristics of heterotopic pancreatic tissue at the gastric outlet in a 48-year-old female. The patient underwent surgical excision due to symptoms related to the lesion. Endoscopic ultrasound fine-needle aspiration is increasingly used for the diagnosis of gastrointestinal tumors, which makes the recognition of certain endoscopically unreachable lesions an important step in optimal patient management. PMID:25843199

  18. miRNA dynamics in tumor-infiltrating myeloid cells modulating tumor progression in pancreatic cancer.

    PubMed

    Mühlberg, Leonie; Kühnemuth, Benjamin; Costello, Eithne; Shaw, Victoria; Sipos, Bence; Huber, Magdalena; Griesmann, Heidi; Krug, Sebastian; Schober, Marvin; Gress, Thomas M; Michl, Patrick

    2016-06-01

    Myeloid cells including tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC) are known as important mediators of tumor progression in solid tumors such as pancreatic cancer. Infiltrating myeloid cells have been identified not only in invasive tumors, but also in early pre-invasive pancreatic intraepithelial precursor lesions (PanIN). The functional dynamics of myeloid cells during carcinogenesis is largely unknown. We aimed to systematically elucidate phenotypic and transcriptional changes in infiltrating myeloid cells during carcinogenesis and tumor progression in a genetic mouse model of pancreatic cancer. Using murine pancreatic myeloid cells isolated from the genetic mouse model at different time points during carcinogenesis, we examined both established markers of macrophage polarization using RT-PCR and FACS as well as transcriptional changes focusing on miRNA profiling. Myeloid cells isolated during carcinogenesis showed a simultaneous increase of established markers of M1 and M2 polarization during carcinogenesis, indicating that phenotypic changes of myeloid cells during carcinogenesis do not follow the established M1/M2 classification. MiRNA profiling revealed distinct regulations of several miRNAs already present in myeloid cells infiltrating pre-invasive PanIN lesions. Among them miRNA-21 was significantly increased in myeloid cells surrounding both PanIN lesions and invasive cancers. Functionally, miRNA-21-5p and -3p altered expression of the immune-modulating cytokines CXCL-10 and CCL-3 respectively. Our data indicate that miRNAs are dynamically regulated in infiltrating myeloid cells during carcinogenesis and mediate their functional phenotype by facilitating an immune-suppressive tumor-promoting micro-milieu. PMID:27471627

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

    PubMed

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

    2007-03-01

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

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

    PubMed

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

    2014-01-01

    Intraperitoneal (IP) chemotherapy confers significant survival benefits in cancer patients. However, several problems, including local toxicity and ineffectiveness against bulky tumors, have prohibited it from becoming a standard of care. We have developed drug-loaded, polymeric tumor-penetrating microparticles (TPM) to address these problems. Initial studies showed that TPM provides tumor-selective delivery and is effective against ovarian SKOV3 tumors of relatively small size (<50 mg). The present study evaluated whether the TPM activity extends to other tumor types that are more bulky and have different morphologies and disease presentation. We evaluated TPM in mice bearing two IP human pancreatic tumors with different growth characteristics and morphologies (rapidly growing, large and porous Hs766T vs. slowly growing, smaller and densely packed MiaPaCa2), and at different disease stage (early stage with smaller tumors vs. late stage with larger tumors plus peritoneal carcinomatosis). Comparison of treatments with TPM or paclitaxel in Cremophor micelles, at equi-toxic doses, shows, in all tumor types: (a) higher paclitaxel levels in tumors (up to 55-fold) for TPM, (b) greater efficacy for TPM, including significantly longer survival and higher cure rate, and (c) a single dose of TPM was equally efficacious as multiple doses of paclitaxel/Cremophor. The results indicate tumor targeting property and superior antitumor activity of paclitaxel-loaded TPM are generalizable to small and large peritoneal tumors, with or without accompanying carcinomatosis.

  1. Pancreatic neuroendocrine tumor accompanied with multiple liver metastases

    PubMed Central

    Hori, Tomohide; Takaori, Kyoichi; Uemoto, Shinji

    2014-01-01

    Pancreatic neuroendocrine tumor (P-NET) is rare and slow-growing. Current classifications predict its prognosis and postoperative recurrence. Curative resection is ideal, although often difficult, because over 80% of patients have unresectable multiple liver metastases and extrahepatic metastasis. Aggressive surgery for liver metastases is important to improve survival. Aggressive or cytoreductive surgery for liver metastases is indicated to reduce hormone levels and improve symptoms and prognosis. Liver transplantation was originally conceived as an ideal therapy for unresectable liver metastases. Unfortunately, there is no clear consensus on the role and timing of surgery for primary tumor and liver metastases. Surgeons still face questions in deciding the best surgical scenario in patients with P-NET with unresectable liver metastases. PMID:25232452

  2. Total Humeral Endoprosthetic Replacement following Excision of Malignant Bone Tumors

    PubMed Central

    Kotwal, Suhel; Moon, Bryan; Lin, Patrick; Satcher, Robert; Lewis, Valerae

    2016-01-01

    Humerus is a common site for malignant tumors. Advances in adjuvant therapies and reconstructive methods provide salvage of the upper limb with improved outcomes. Reports of limb salvage with total humeral replacement in extensive humeral tumors are sparse. We undertook a retrospective study of 20 patients who underwent total humeral endoprosthetic replacement as limb salvage following excision of extensile malignant tumor from 1990 to 2011. With an average followup of 42.9, functional and oncological outcomes were analyzed. Ten patients were still alive at the time of review. Mean estimated blood loss was 1131 mL and duration of surgery was 314 minutes. Deep infection was encountered in one patient requiring debridement while mechanical loosening of ulnar component was identified in one patient. Subluxation of prosthetic humeral head was noted in 3 patients. Mean active shoulder abduction was 12.5° and active flexion was 15°. Incompetence of abduction mechanism was the major determinant of poor active functional outcome. Mean elbow flexion was 103.5° with 30.5° flexion contracture in 10 patients with good and useful hand function. Average MSTS score was 71.5%. Total humeral replacement is a reliable treatment option in restoring mechanical stability and reasonable functional results without compromising patient survival, with low complication rate. PMID:27042158

  3. The Immunohistochemical Evaluation of Solid Pseudopapillary Tumors of the Pancreas and Pancreatic Neuroendocrine Tumors Reveals ERO1Lβ as a New Biomarker.

    PubMed

    Xie, Junjie; Zhu, Yi; Chen, Hao; Shi, Minmin; Gu, Jiangning; Zhang, Jiaqiang; Shen, Baiyong; Deng, Xiaxing; Zhan, Xi; Peng, Chenghong

    2016-01-01

    Solid pseudopapillary tumor of the pancreas (SPTP) is a class of low-grade malignant tumors that carry a favorable prognosis after surgery. Our group has reported that dysfunctions in the endoplasmic reticulum (ER) protein processing pathway may play a role in tumor development. However, alterations of this pathway in other pancreatic tumors had not been well investigated. In this study, we collected 35 SPTP and pancreatic neuroendocrine tumor (PNET) specimens and described the clinicopathological features of them. We performed immunohistochemistry (IHC) for 6 representative proteins (ERO1Lβ, TRAM1, GRP94, BIP, P4HB, and PDIA4) involved in the ER pathway in both SPTP and PNET specimens. We compared the IHC scoring results of tumors and matched normal pancreas tissues and demonstrated that these proteins were downregulated in SPTP specimens. Five of these proteins (TRAM1, GRP94, BIP, P4HB, and PDIA4) did not display significant changes between PNET and normal pancreas tissue. However, ERO1Lβ was upregulated in PNET tissues compared to the normal tissues, which could be used as a pathological biomarker in the future.

  4. Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy.

    PubMed

    Morrone, Fernanda B; Gehring, Marina P; Nicoletti, Natália F

    2016-09-01

    Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies, which include the combination of surgery and radio/chemotherapy, the average survival rate remains poor. Altered regulation of ion channels is part of the neoplastic transformation, which suggests that ion channels are involved in cancer. Distinct classes of calcium-permeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth. Specifically, cytosolic Ca(2+) activity plays an important role in the regulation of cell proliferation, and Ca(2+) signaling is altered in proliferating tumor cells. A series of previous studies emphasized the importance of the T-type low-voltage-gated calcium channels (VGCC) in different cancer types, including gliomas, and remarkably, pharmacologic inhibition of T-type VGCC caused antiproliferative effects and triggered apoptosis of human glioma cells. Other calcium permeable channels, such as transient receptor potential (TRP) channels, contribute to changes in Ca(2+) by modulating the driving force for Ca(2+) entry, and some TRP channels are required for proliferation and migration in gliomas. Furthermore, recent evidence shows that TRP channels contribute to the progression and survival of the glioblastoma patients. Likewise, the purinergic P2X7 receptor acts as a direct conduit for Ca(2+)-influx and an indirect activator of voltage-gated Ca(2+)-channel. Evidence also shows that P2X7 receptor activation is linked to elevated expression of inflammation promoting factors, tumor cell migration, an increase in intracellular mobilization of Ca(2+), and membrane depolarization in gliomas. Therefore, this review summarizes the recent findings on calcium channels and associated receptors as potential targets to treat malignant gliomas. PMID:27418672

  5. Ultrafast magnetic resonance imaging improves the staging of pancreatic tumors.

    PubMed Central

    Trede, M; Rumstadt, B; Wendl, K; Gaa, J; Tesdal, K; Lehmann, K J; Meier-Willersen, H J; Pescatore, P; Schmoll, J

    1997-01-01

    OBJECTIVE: This prospective study was undertaken to evaluate the accuracy of a noninvasive "all-in-one" staging method in predicting surgical resectability in patients with pancreatic or periampullary tumors. SUMMARY BACKGROUND DATA: Despite progress in imaging techniques, accurate staging and correct prediction of resectability remains one of the chief problems in the management of pancreatic tumors. Staging algorithms designed to separate operable from inoperable patients to save the latter an unnecessary laparotomy are becoming increasingly complex, expensive, time-consuming, invasive, and not without risks for the patient. METHODS: Between August 1996 and February 1997, 58 consecutive patients referred for operation of a pancreatic or periampullary tumor were examined clinically and by 5 staging methods: 1) percutaneous ultrasonography (US); 2) ultrafast magnetic resonance imaging (UMRI); 3) dual-phase helical computed tomography (CT); 4) selective visceral angiography; and 5) endoscopic cholangiopancreatography (ERCP). The assessment of resectability by each procedure was verified by surgical exploration and histologic examination. RESULTS: The study comprised 40 male and 18 female patients with a median age of 63 years. Thirty-five lesions were located in the pancreatic head (60%), 11 in the body (19%), and 1 in the tail of the gland (2%); there were 9 tumors of the ampulla (16%) and 2 of the distal common duct (3%). All five staging methods were completed in 36 patients. For reasons ranging from metallic implants to contrast medium allergy or because investigations already had been performed elsewhere, US was completed in 57 (98%), UMRI in 54 (93%), CT in 49 (84%), angiography in 48 (83%), and ERCP in 49 (84%) of these 58 patients. Signs of unresectability found were vascular involvement in 22 (38%), extrapancreatic tumor spread in 16 (26%), liver metastases in 10 (17%), lymph node involvement in 6 (10%), and peritoneal nodules in only 2 patients (3%). These

  6. Pancreatic Neuroendocrine Tumor in the Setting of Dorsal Agenesis of the Pancreas

    PubMed Central

    2016-01-01

    Dorsal agenesis of the pancreas (DAP) is an uncommon embryological abnormality where there is absence of the distal pancreas. DAP is mostly asymptomatic, but common presenting symptoms include diabetes mellitus, abdominal pain, pancreatitis, enlarged pancreatic head, and, in a few cases, polysplenia. MRCP and ERCP are the gold standard imaging techniques to demonstrate the absence of the dorsal pancreatic duct. The literature on the association of pancreatic neoplasia and DAP is limited. We present the case of a pancreatic neuroendocrine tumor in a patient with dorsal agenesis of the pancreas, with a review of the related literature. PMID:27738535

  7. Midkine expression in malignant salivary gland tumors and its role in tumor angiogenesis.

    PubMed

    Ota, Tomoko; Ota, Kazutoshi; Jono, Hirofumi; Fujimori, Hiromi; Ueda, Mitsuharu; Shinriki, Satoru; Sueyoshi, Takanao; Shinohara, Masanori; Ando, Yukio

    2010-09-01

    The aims of this study were to investigate midkine (MK) expression patterns in salivary gland tumors (SGTs) and to evaluate the correlation between MK expression and the degree of malignancy. We performed immunohistochemistry to examine MK expression in specimens of adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), and pleomorphic adenoma (PA). In addition, we performed immunohistochemistry for CD31 and measured microvessel density (MVD), which is an indicator of angiogenesis. Immunohistochemistry showed that MK protein expression was significantly higher in specimens of malignant SGTs (ACC [P<0.01] and MEC [P<0.001]) than in benign SGT (PA) samples. Furthermore, MVD values tended to be higher in cases that exhibited high expression of MK, which indicated a significant correlation between the degree of MK expression and MVD (P<0.001). These results suggest that MK may play important roles in malignant transformation and tumor angiogenesis in SGTs.

  8. Primary malignant peripheral nerve sheath tumor at unusual location

    PubMed Central

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

    2013-01-01

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

  9. Diabetic Ketoacidosis with Concurrent Pancreatitis, Pancreatic β Islet Cell Tumor, and Adrenal Disease in an Obese Ferret (Mustela putorius furo)

    PubMed Central

    Phair, Kristen A; Carpenter, James W; Schermerhorn, Thomas; Ganta, Chanran K; DeBey, Brad M

    2011-01-01

    A 5.5-y-old spayed female ferret (Mustela putorius furo) with a history of adrenal disease, respiratory disease, and chronic obesity was evaluated for progressive lethargy and ataxia, diminished appetite, and possible polyuria and polydipsia. Physical examination revealed obesity, lethargy, tachypnea, dyspnea, a pendulous abdomen, significant weakness and ataxia of the hindlimbs, prolonged skin tenting, and mild tail-tip alopecia. Clinicopathologic analysis revealed severe hyperglycemia, azotemia, an increased anion gap, glucosuria, ketonuria, proteinuria, and hematuria. Abdominal ultrasonography showed hyperechoic hepatomegaly, bilateral adrenomegaly, splenic nodules, mild peritoneal effusion, and thickened and mildly hypoechoic limbs of the pancreas with surrounding hyperechoic mesentery. Fine-needle aspirates of the liver were highly suggestive of hepatic lipidosis. In light of a diagnosis of concurrent diabetic ketoacidosis and pancreatitis, the ferret was treated with fluid therapy, regular and long-acting insulin administration, and pain medication. However, electrolyte derangements, metabolic acidosis, dyspnea, and the clinical appearance of the ferret progressively worsened despite treatment, and euthanasia was elected. Necropsy revealed severe hepatic lipidosis, severe suppurative pancreatitis and vacuolar degeneration of pancreatic islet cells, a pancreatic β islet cell tumor, bilateral adrenal cortical adenomas, and myocardial fibrosis. To our knowledge, this case represents the first report of concurrent diabetes mellitus, pancreatitis, pancreatic β islet cell tumor (insulinoma), and adrenal disease in a domestic ferret. The simultaneous existence of 3 endocrine diseases, pancreatitis, and their associated complications is a unique and clinically challenging situation. PMID:21838985

  10. [Positron emission tomography (PET) in malignant ovarian tumors].

    PubMed

    Fularz, Maciej; Adamiak, Paulina; Czepczyński, Rafał; Jarzabek-Bielecka, Grazyna; Kedzia, Witold; Ruchała, Marek

    2013-08-01

    Accessibility of positron emission tomography integrated with computed tomography (PET/CT) has improved significantly in recent years. PET/CT with the use of 18F-deoxyglucose (FDG) is widely used in patients with ovarian malignancies at different stages of the management. FDG PET/CT shows high diagnostic accuracy in the differentiation of benign and malignant ovarian lesions with the exception of borderline tumors that may cause false negative results. Moreover FDG PET/CT is used in some centers for preoperative staging and determining the prognosis of ovarian cancer However further studies including larger groups of patients are needed to confirm the applicability of FDG PET/CT in case of the two abovementioned indications. Until now, the best documented indication for FDG PET/ CT in patients with ovarian cancer has been the detection of recurrence, especially in subjects with elevated CA 125 marker and negative results of other imaging techniques. This review focuses on the applicability of PET with the use of FDG in ovarian malignancies and points out to the limitations of this method.

  11. A case of diffused malignant pleural mesothelioma forming small multiple disseminations with intraoperatively suspicious carcinoid tumors.

    PubMed

    Suemitsu, Ryuichi; Takeo, Sadanori; Hamatake, Motoharu; Furuya, Kiyomi; Uesugi, Noriko

    2011-01-01

    A 65-year-old male, having symptoms suggestive of pulmonary malignant tumor, underwent video-assisted thoracic surgery (VATS). Surgery revealed a solid tumor originating from the thoracic wall, with many small solid tumors in the thoracic wall and diaphragm near the tumor. The intraoperative observation of a frozen section typed the tumor as carcinoid; however, hematoxylin-eosin staining and immunohistological findings provided the definitive diagnosis of diffused, malignant pleural mesothelioma (MPM).

  12. Malignant transformation in concurrent benign mixed tumors of the parotid and submaxillary glands.

    PubMed

    McGrath, M H

    1980-05-01

    This patient is the only reported case of concomitant mixed tumors of the parotid and contralateral submaxillary gland. Each lesion had histologic changes consistent with different stages in the transformation of a benign to a malignant mixed tumor. Identifying premalignant disease in the parotid tumor and early preinvasive carcinoma in the submaxillary tumor lends support to the concept of malignant progression in salivary gland mixed tumors.

  13. Malignant pleomorphic adenoma (malignant mixed tumor) of the trachea: a case report and review of the literature.

    PubMed

    Demirağ, Funda; Topçu, Salih; Kurul, Cüneyt; Memiş, Leyla; Altinok, Tamer

    2003-02-01

    A case of malignant mixed tumor of the trachea in a 56-year-old man is described. His tumor was removed by segmental tracheal resection, and end-to-end anastomosis was performed. Histologically, the tumor was characterized by a biphasic composition showing admixtures of epithelial elements in varying proportions; these were cytologically atypical with prominent mitotic figures. However, stromal elements were osteoid and mixoid with a benign appearance. The patient had no evidence of disease in the head and neck region and had no history of previous surgery for a salivary gland tumor. These findings were interpreted as indicative of malignant pleomorphic adenoma of the trachea.

  14. Tumor malignancy is engaged to prokaryotic homolog toolbox.

    PubMed

    Fernandes, Janaina; Guedes, Patrícia G; Lage, Celso Luiz S; Rodrigues, Juliany Cola F; Lage, Claudia de Alencar S

    2012-04-01

    Cancer cells display high proliferation rates and survival provided by high glycolysis, chemoresistance and radioresistance, metabolic features that appear to be activated with malignancy, and seemed to have arisen as early in evolution as in unicellular/prokaryotic organisms. Based on these assumptions, we hypothesize that aggressive phenotypes found in malignant cells may be related to acquired unicellular behavior, launched within a tumor when viral and prokaryotic homologs are overexpressed performing likely robust functions. The ensemble of these expressed viral and prokaryotic close homologs in the proteome of a tumor tissue gives them advantage over normal cells. To assess the hypothesis validity, sequences of human proteins involved in apoptosis, energetic metabolism, cell mobility and adhesion, chemo- and radio-resistance were aligned to homologs present in other life forms, excluding all eukaryotes, using PSI-BLAST, with further corroboration from data available in the literature. The analysis revealed that selected sequences of proteins involved in apoptosis and tumor suppression (as p53 and pRB) scored non-significant (E-value>0.001) with prokaryotic homologs; on the other hand, human proteins involved in cellular chemo- and radio-resistance scored highly significant with prokaryotic and viral homologs (as catalase, E-value=zero). We inferred that such upregulated and/or functionally activated proteins in aggressive malignant cells represent a toolbox of modern human homologs evolved from a similar key set that have granted survival of ancient prokaryotes against extremely harsh environments. According to what has been discussed along this analysis, high mutation rates usually hit hotspots in important conserved protein domains, allowing uncontrolled expansion of more resistant, death-evading malignant clones. That is the case of point mutations in key viral proteins affording viruses escape to chemotherapy, and human homologs of such retroviral

  15. Tumor-Derived Tissue Factor-Bearing Microparticles are Associated with Venous Thromboembolic Events in Malignancy

    PubMed Central

    Zwicker, Jeffrey I.; Liebman, Howard A.; Neuberg, Donna; Lacroix, Romaric; Bauer, Kenneth A.; Furie, Barbara C.; Furie, Bruce

    2009-01-01

    Purpose Despite the strong association between malignant disease and thromboembolic disorders, the molecular and cellular basis of this relationship remains uncertain. We evaluated the hypothesis that tumor-derived tissue factor-bearing microparticles in plasma contribute to cancer-associated thrombosis. Experimental Design We developed impedance-based flow cytometry to detect, quantitate and size microparticles in platelet-poor plasma. We evaluated the number of tissue factor-bearing microparticles in a cohort of cancer patients of different histologies (N=96) and performed a case control study of 30 cancer patients diagnosed with an acute venous thromboembolic event (VTE) compared to 60 cancer patients of similar age, stage, sex, diagnosis without known VTE as well as 22 patients with an idiopathic VTE. Results Tissue factor-bearing microparticles were detected in patients with advanced malignancy including two thirds of patients with pancreatic carcinoma. Elevated levels of tissue factor-bearing microparticles were associated VTE in cancer patients (adjusted OR 3.72, 95% CI 1.18-11.76, P=0.01). In cancer patients without VTE, a retrospective analysis revealed a one-year cumulative incidence of VTE of 34.8% in patients with tissue factor-bearing microparticles versus 0% those without detectable tissue factor-bearing microparticles (Gray test p-value=0.002). The median number of tissue factor-bearing microparticles in the cancer VTE cohort (7.1 × 104 microparticles/μl) was significantly greater than both the idiopathic VTE and cancer-no VTE groups (P=0.002 and P=0.03, respectively). Pancreatectomy in three patients eliminated or nearly eliminated these microparticles which co-expressed the epithelial tumor antigen, MUC-1. Conclusion We conclude that tumor-derived tissue factor-bearing microparticles are associated with VTE in cancer patients and may be central to the pathogenesis of cancer-associated thrombosis. PMID:19861441

  16. Malignant tumor formation at the site of previously irradiated acanthomatous epulides in four dogs

    SciTech Connect

    Thrall, D.E.; Goldschmidt, M.H.; Biery, D.N.

    1981-01-15

    The radiation response of acanthomatous epulis in 32 dogs was good, with an estimated median survival time of 21 months. Of the 32 patients, 14 have died. In 4 of those 14, malignant tumors developed at the site of the acanthomatous epulis. The tumors were of epithelial origin in 3 patients and of mesenchymal origin in 1 patient. Possibilities explaining the appearance of the malignancies included spontaneous malignant transformation, radiation induction of neoplasms, and radiation induction of malignant transformation. This uncommon complication was not considered contradictory to radiotherapy of acanthomatous epulides, because of their excellent response to irradiation and the long latent period between irradiation and appearance of the malignant tumor.

  17. Modulation of the Leptin Receptor Mediates Tumor Growth and Migration of Pancreatic Cancer Cells

    PubMed Central

    Chalfant, Madeleine C.; Gorden, Lee D.

    2015-01-01

    Obesity has been implicated as a significant risk factor for development of pancreatic cancer. In the setting of obesity, a systemic chronic inflammatory response is characterized by alterations in the production and secretion of a wide variety of growth factors. Leptin is a hormone whose level increases drastically in the serum of obese patients. High fat diet induced obesity in mice leads to an overall increased body weight, pancreatic weight, serum leptin, and pancreatic tissue leptin levels. Here we report the contribution of obesity and leptin to pancreatic cancer growth utilizing an in vivo orthotopic murine pancreatic cancer model, which resulted in increased tumor proliferation with concomitant increased tumor burden in the diet induced obese mice compared to lean mice. Human and murine pancreatic cancer cell lines were found to express the short as well as the long form of the leptin receptor and functionally responded to leptin induced activation through an increased phosphorylation of AKT473. In vitro, leptin stimulation increased cellular migration which was blocked by addition of a PI3K inhibitor. In vivo, depletion of the leptin receptor through shRNA knockdown partially abrogated increased orthotopic tumor growth in obese mice. These findings suggest that leptin contributes to pancreatic tumor growth through activation of the PI3K/AKT pathway, which promotes pancreatic tumor cell migration. PMID:25919692

  18. Histological and clinical characteristics of malignant giant cell tumor of bone.

    PubMed

    Gong, Lihua; Liu, Weifeng; Sun, Xiaoqi; Sajdik, Constantin; Tian, Xinxia; Niu, Xiaohui; Huang, Xiaoyuan

    2012-03-01

    Malignant giant cell tumors of bone (MGCTB) are rare, and the diagnosis can be difficult due to the occurrence of a variety of malignant tumors containing giant cells. To better understand its clinicopathological features, we have reviewed our experience with 17 cases of MGCTB. Five cases were primary malignant giant cell tumor of bone (PMGCTB), and 12 cases were giant cell tumors of bone initially diagnosed as benign but malignant in a recurrent lesion (secondary MGCTB, SMGCTB). The patients included six women and 11 men (age ranged from 17 to 52 years; mean, 30.5 years). The tumor arose in the femur (six cases), the tibia (seven cases), the humerus (three cases), and the fibula (one case). Microscopically, PMGCTB showed both conventional giant cell tumor and malignant sarcoma features. SMGCTB were initially diagnosed as conventional giant cell tumor of bone, the recurrent lesion showing malignant features. Histologically, the malignant components included osteosarcoma (11 cases), undifferentiated high-grade pleomorphic sarcoma (two cases), and fibrosarcoma (four cases). SMGCTB cases showed strong expression of p53. Follow-up information revealed that four patients died of lung metastasis, two patients are alive with lung metastases, and 11 patients are alive without tumor. MGCTB should be considered as a high-grade sarcoma. It must be distinguished from GCTB and other malignant tumors containing giant cells. p53 might play a role in the malignant transformation of GCTB. PMID:22350004

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

    PubMed

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

    2011-01-01

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

  20. Prognostic value of immunohistochemical markers in malignant thymic epithelial tumors

    PubMed Central

    Leisibach, Priska; Schneiter, Didier; Soltermann, Alex; Yamada, Yoshi; Weder, Walter

    2016-01-01

    Background Thymic epithelial tumors (TET) are rare neoplasms with inconsistent treatment strategies. When researching for molecular pathways to find new therapies, the correlation between specific molecular markers and outcome has only rarely been investigated. The aim of this study was to investigate the correlation between survival, metastatic potential and invasiveness of aggressive subtypes of TET and immunohistochemical markers. Methods Overall survival (OS), disease-free survival (DFS), progression-free survival (PFS) and metastasis-free survival (MFS) of patients with WHO type B2/B3 mixed type thymoma (MT), thymoma type B3 (B3) and thymic carcinoma (TC), undergoing surgery [1998–2013] were determined. Tumor specimens were stained using a tissue microarray (TMA) (CD117, CD5, p63, p40, p21, p27, p53, Bcl-2, Ki67, podoplanin, synaptophysin, PTEN and Pax8). Invasive behavior of primary tumors and the presence of extrathoracic metastases were assessed. Results We found in 23 patients included into this study (four MT, ten B3, nine TC) that (I) p21 expression in the cytoplasm significantly correlated with a decrease of OS (P=0.016), PFS (P=0.034) and MFS (P=0.005); (II) MFS was significantly shorter when the combination of p21-low p27-low p53-high was present (P=0.029); and (III) nuclear p27 (P=0.042), Ki-67 (P=0.024) and podoplanin (P=0.05) expression correlated with the presence of extrathoracic metastases. Conclusions The main finding of this study is that cytoplasmic p21 expression negatively influences the outcome of malignant TETs and correlates with metastatic activity. Additionally, selected immunohistochemical markers correlate with the distant metastatic potential of TETs. These results may contribute to the stratification of diagnosis and improvement of treatment strategies for thymic malignancies. PMID:27747012

  1. A Pilot Study Treatment of Malignant Tumors Using [18F] Fluorodeoxyglucose (FDG)

    ClinicalTrials.gov

    2016-08-18

    Radiosensitive Stage IV Solid and Hematological Tumors With High FDG Uptake Not Responding to Standard of Care; Lung Cancer, Head and Neck Cancer, Breast Cancer, Gastric Cancer, Pancreatic Cancer, Colon Cancer, Lymphomas, Sarcomas, Etc

  2. MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors.

    PubMed

    Cros, J; Hentic, O; Rebours, V; Zappa, M; Gille, N; Theou-Anton, N; Vernerey, D; Maire, F; Lévy, P; Bedossa, P; Paradis, V; Hammel, P; Ruszniewski, P; Couvelard, A

    2016-08-01

    Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease. PMID:27353036

  3. MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors.

    PubMed

    Cros, J; Hentic, O; Rebours, V; Zappa, M; Gille, N; Theou-Anton, N; Vernerey, D; Maire, F; Lévy, P; Bedossa, P; Paradis, V; Hammel, P; Ruszniewski, P; Couvelard, A

    2016-08-01

    Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease.

  4. Computed tomography-guided percutaneous core needle biopsy in pancreatic tumor diagnosis

    PubMed Central

    Tyng, Chiang J; Almeida, Maria Fernanda A; Barbosa, Paula NV; Bitencourt, Almir GV; Berg, José Augusto AG; Maciel, Macello S; Coimbra, Felipe JF; Schiavon, Luiz Henrique O; Begnami, Maria Dirlei; Guimarães, Marcos D; Zurstrassen, Charles E; Chojniak, Rubens

    2015-01-01

    AIM: To evaluate the techniques, results, and complications related to computed tomography (CT)-guided percutaneous core needle biopsies of solid pancreatic lesions. METHODS: CT-guided percutaneous biopsies of solid pancreatic lesions performed at a cancer reference center between January 2012 and September 2013 were retrospectively analyzed. Biopsy material was collected with a 16-20 G Tru-Core needle (10-15 cm; Angiotech, Vancouver, CA) using a coaxial system and automatic biopsy gun. When direct access to the lesion was not possible, indirect (transgastric or transhepatic) access or hydrodissection and/or pneumodissection maneuvers were used. Characteristics of the patients, lesions, procedures, and histologic results were recorded using a standardized form. RESULTS: A total of 103 procedures included in the study were performed on patients with a mean age of 64.8 year (range: 39-94 year). The mean size of the pancreatic lesions was 45.5 mm (range: 15-195 mm). Most (75/103, 72.8%) procedures were performed via direct access, though hydrodissection and/or pneumodissection were used in 22.2% (23/103) of cases and indirect transhepatic or transgastric access was used in 4.8% (5/103) of cases. Histologic analysis was performed on all biopsies, and diagnoses were conclusive in 98.1% (101/103) of cases, confirming 3.9% (4/103) of tumors were benign and 94.2% (97/103) were malignant; results were atypical in 1.9% (2/103) of cases, requiring a repeat biopsy to diagnose a neuroendocrine tumor, and surgical resection to confirm a primary adenocarcinoma. Only mild/moderate complications were observed in 9/103 patients (8.7%), and they were more commonly associated with biopsies of lesions located in the head/uncinate process (n = 8), than of those located in the body/tail (n = 1) of the pancreas, but this difference was not significant. CONCLUSION: CT-guided biopsy of a pancreatic lesion is a safe procedure with a high success rate, and is an excellent option for minimally

  5. Postoperative irradiation in malignant epithelial tumors of the parotid

    SciTech Connect

    McNaney, D.; McNeese, M.D.; Guillamondegui, O.M.; Fletcher, G.H.; Oswald, M.J.

    1983-09-01

    From 1954 through 1979, 77 patients with malignant tumors of the parotid gland were referred from the Department of Head and Neck Surgery for postoperative irradiation. The analysis has been made by grouping the patients according to the estimated amount of disease left after the surgical procedure and by the histological types. There were no local failures in the low-grade tumors, and there were 6 in the 63 patients with high-grade tumors. With gross residual disease or potential residual disease the patients received slightly higher doses than those without. Although there were only 6 failures in the various histological types, there was perhaps a trend to more failures in the adenocarcinomas. There was no difference in the failure rates in patients having had a total resection of the facial nerve or partial resection or no resection. The preferred treatment has been a combination of 20 MeV photons and 18 MeV electrons. Five neck failures were essentially a result of lack of electrive irradiation of the neck. Severe complications appeared only in the patients irradiated either for gross residual disease or excision of a recurrence with a high risk of widespread microscopic residual disease.

  6. Phyllodes Tumor of the Breast With Malignant Melanoma Component: A Case Report.

    PubMed

    Vergine, Marco; Guy, Catherine; Taylor, Mark R

    2015-09-01

    Phyllodes tumors of the breast display a wide variation in histological appearance and are classified into benign, borderline, and malignant categories based on a combination of histological parameters. These tumors may include a malignant heterologous component that is believed to originate through a process of multidirectional differentiation from a cancer stem cell. In these cases, the tumor is classified as a malignant phyllodes tumor. Among the heterologous elements that have been described in malignant phyllodes tumors are rhabdomyosarcoma, chondrosarcoma, osteosarcoma, liposarcoma and angiosarcoma. We present the first case of a phyllodes tumor with a malignant melanoma component in the breast of a 71-year-old lady, discussing the clinical implications of this diagnosis. PMID:26113664

  7. [Primary pancreatic plasmacytoma].

    PubMed

    Sánchez Acevedo, Z; Pomares Rey, B; Alpera Tenza, M R; Andrada Becerra, E

    2014-01-01

    Extramedullary plasmacytomas are uncommon malignant plasma cell tumors that present outside the bone marrow; 80% of extramedullary plasmacytomas are located in the upper respiratory tract, and gastrointestinal plasmacytomas are rare. We present the case of an asymptomatic 65-year-old man in whom a pancreatic mass was found incidentally. The lesion was determined to be a pancreatic plasmacytoma after fine-needle aspiration cytology and surgical resection. No clinical, laboratory, or imaging findings indicative of multiple myeloma or association with other plasmacytomas were found, so the tumor was considered to be a primary pancreatic plasmacytoma. PMID:22738942

  8. GLP1 and glucagon co-secreting pancreatic neuroendocrine tumor presenting as hypoglycemia after gastric bypass

    PubMed Central

    Guimarães, Marta; Rodrigues, Pedro; Pereira, Sofia S; Nora, Mário; Gonçalves, Gil; Albrechtsen, Nicolai Wewer; Hartmann, Bolette; Holst, Jens Juul

    2015-01-01

    Summary Post-prandial hypoglycemia is frequently found after bariatric surgery. Although rare, pancreatic neuroendocrine tumors (pNET), which occasionally are mixed hormone secreting, can lead to atypical clinical manifestations, including reactive hypoglycemia. Two years after gastric bypass surgery for the treatment of severe obesity, a 54-year-old female with previous type 2 diabetes, developed post-prandial sweating, fainting and hypoglycemic episodes, which eventually led to the finding by ultrasound of a 1.8-cm solid mass in the pancreatic head. The 72-h fast test and the plasma chromogranin A levels were normal but octreotide scintigraphy showed a single focus of abnormal radiotracer uptake at the site of the nodule. There were no other clinical signs of hormone secreting pNET and gastrointestinal hormone measurements were not performed. The patient underwent surgical enucleation with complete remission of the hypoglycemic episodes. Histopathology revealed a well-differentiated neuroendocrine carcinoma with low-grade malignancy with positive chromogranin A and glucagon immunostaining. An extract of the resected tumor contained a high concentration of glucagon (26.707 pmol/g tissue), in addition to traces of GLP1 (471 pmol/g), insulin (139 pmol/g) and somatostatin (23 pmol/g). This is the first report of a GLP1 and glucagon co-secreting pNET presenting as hypoglycemia after gastric bypass surgery. Although pNET are rare, they should be considered in the differential diagnosis of the clinical approach to the post-bariatric surgery hypoglycemia patient. Learning points pNETs can be multihormonal-secreting, leading to atypical clinical manifestations.Reactive hypoglycemic episodes are frequent after gastric bypass.pNETs should be considered in the differential diagnosis of hypoglycemia after bariatric surgery. PMID:26266036

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

    PubMed Central

    2014-01-01

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

  10. Acute Pancreatitis and Gastroduodenal Intussusception Induced by an Underlying Gastric Gastrointestinal Stromal Tumor: A Case Report

    PubMed Central

    Doğan, Ahmet; Koparan, Ibrahim Halil; Adin, Mehmet Emin

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal system and comprise only 1% to 3% of all gastrointestinal tract tumors, with the majority of them arising in the stomach. In this report, we present the unique findings of a case of gastroduodenal intussusception caused by an underlying gastric GIST and complicated with severe acute pancreatitis. PMID:27104028

  11. Immunotherapy with autologous dendritic cells and tumor antigens for children with refractory malignant solid tumors.

    PubMed

    Suminoe, Aiko; Matsuzaki, Akinobu; Hattori, Hiroyoshi; Koga, Yuhki; Hara, Toshiro

    2009-09-01

    Immature DCs were generated from the peripheral blood monocytes from five children with refractory solid tumors (Ewing sarcoma, synovial sarcoma, neuroblastoma) using GM-CSF and IL-4. These DCs were then pulsed with tumor-specific synthetic peptides or tumor lysates in the presence of the immunogenic protein KLH for 12 h. Pulsed DCs were administered subcutaneously every one or two weeks in an outpatient setting without any toxicity. In one patient with Ewing sarcoma, the residual tumor disappeared following autologous PBSCT and DC therapy, and a complete remission has been maintained for 77 months. In two patients with synovial sarcoma or with neuroblastoma, growth of the tumors was temporally suppressed for one and 10 months, respectively, followed by their exacerbation. A DTH response was detected against KLH in all five patients and against the tumor lysate in one patient. In the patients with a possible DC-mediated anti-tumor effect, the number of CD8(+) HLA-DR(+) lymphocytes and INF-gamma(+)CD8(+) lymphocytes increased and an elevation of the NK cell cytotoxic activity was observed during and/or after DC therapy. DC-based immunotherapy may therefore be a feasible, well-tolerated and promising approach in the treatment of children with refractory malignant tumors.

  12. Paclitaxel tumor priming promotes delivery and transfection of intravenous lipid-siRNA in pancreatic tumors.

    PubMed

    Wang, Jie; Lu, Ze; Wang, Junfeng; Cui, Minjian; Yeung, Bertrand Z; Cole, David J; Wientjes, M Guillaume; Au, Jessie L-S

    2015-10-28

    The major barrier for using small interfering RNA (siRNA) as cancer therapeutics is the inadequate delivery and transfection in solid tumors. We have previously shown that paclitaxel tumor priming, by inducing apoptosis, expands the tumor interstitial space, improves the penetration and dispersion of nanoparticles and siRNA-lipoplexes in 3-dimensional tumor histocultures, and promotes the delivery and transfection efficiency of siRNA-lipoplexes under the locoregional setting in vivo (i.e., intraperitoneal treatment of intraperitoneal tumors). The current study evaluated whether tumor priming is functional for systemically delivered siRNA via intravenous injection, which would subject siRNA to several additional delivery barriers and elimination processes. We used the same pegylated cationic (PCat)-siRNA lipoplexes as in the intraperitoneal study to treat mice bearing subcutaneous human pancreatic Hs766T xenograft tumors. The target gene was survivin, an inducible chemoresistance gene. The results show single agent paclitaxel delayed tumor growth but also significantly induced the survivin protein level in residual tumors, whereas addition of PCat-siSurvivin completely reversed the paclitaxel-induced survivin and enhanced the paclitaxel activity (p<0.05). In comparison, PCat-siSurvivin alone did not yield survivin knockdown or antitumor activity, indicating the in vivo effectiveness of intravenous siRNA-mediated gene silencing requires paclitaxel cotreatment. Additional in vitro studies showed that paclitaxel promoted the cytoplasmic release of siGLO, a 22 nucleotide double-stranded RNA that has no mRNA targets, from its PCat lipoplex and/or endosomes/lysosomes. Taken together, our earlier and current data show paclitaxel tumor priming, by promoting the interstitial transport and cytoplasmic release, is critical to promote the delivery and transfection of siRNA in vivo. In addition, because paclitaxel has broad spectrum activity and is used to treat multiple types

  13. Methionine dependency of malignant tumors: a possible approach for therapy.

    PubMed

    Breillout, F; Antoine, E; Poupon, M F

    1990-10-17

    When methionine (Met), an essential amino acid, was substituted for by its precursor homocysteine (Hcy) in the culture medium, normal cells such as fibroblasts proliferated normally. In contrast, many tumor cells failed to grow or grew at a lower rate. Met dependency is acquired simultaneously with cell transformation, as observed with HBL 100, a human mammary epithelial cell line that acquired increased malignancy as a function of in vitro passage number, and NIH/3T3 (J10), a mouse fibroblast line transformed by transfection with the human HRAS oncogene. A relationship was observed between Met dependency and metastatic potential of the RMS-21, RMS-S4T, and RMS-J1 sublines derived from RMS-0, a rat rhabdomyosarcoma cell line: the higher the metastatic potential of the cell line, the higher the concentration of Met required to maintain its proliferation. Met-independent cells derived from the RMS-0 line, obtained by a progressive decrease of Met in the culture medium lost their tumorigenicity when injected into rats fed with Met-deprived diets. In addition, the in vitro motility of RMS-S4T tumor cells, a marker of metastatic capability, decreased in Met-free Hcy-complemented (Met- Hcy+) medium. Similarly, RMS-0 tumor cells, preincubated in a Met- Hcy+ culture medium for 24 hours, evidenced a decreased capacity to form lung colonies when injected into syngeneic rats: the median number of lung colonies was 27 and 3 (P less than .05) for cells cultivated in Met+ Hcy- and Met- Hcy+ media, respectively. An amino acid-defined mixture reproducing casein composition was used as a protein source in the diets fed to RMS-J1 tumor-bearing rats. Dietary substitution of Hcy for Met (i.e., met deprivation) resulted in decreased tumor growth (from 44.4 +/- 1.0 to 40.6 +/- 1.4; P less than .05) and prevention of metastatic spread (from 37 to 0; P less than .05). In conclusion, exogenous Met can be substituted for Hcy to maintain the survival of normal cells but is essential for

  14. Epithelioid angiosarcoma of the skin. A malignant tumor mimicking many different neoplasms.

    PubMed

    Santos-Juanes1, Jorge; Vivanco-Allende, Blanca; Galache, Cristina Galache

    2016-01-01

    Epithelioid angiosarcomas are rare malignant mesenchymal tumors. The main problem of these tumors is the complicate clinical and histological diagnosis. We report a case with an immunohistochemical panel. We propose the use of CD31 in the immunohistochemical panel of an undifferenciated tumor with epithelioid features, because it appears to be the only endothelial marker these tumors constantly express. PMID:27617941

  15. Preoperative Folfirinox for Resectable Pancreatic Adenocarcinoma - A Phase II Study

    ClinicalTrials.gov

    2016-02-16

    Pancreatic Adenocarcinoma; Poorly Differentiated Malignant Neoplasm; Resectable Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Undifferentiated Pancreatic Carcinoma

  16. MicroRNA-199a and -214 as potential therapeutic targets in pancreatic stellate cells in pancreatic tumor

    PubMed Central

    Kuninty, Praneeth R.; Bojmar, Linda; Tjomsland, Vegard; Larsson, Marie; Storm, Gert; Östman, Arne; Sandström, Per; Prakash, Jai

    2016-01-01

    Pancreatic stellate cells (PSCs) are the key precursor cells for cancer-associated fibroblasts (CAFs) in pancreatic tumor stroma. In this study, we explored miRNA as therapeutic targets in tumor stroma and found miR-199a-3p and miR-214-3p induced in patient-derived pancreatic CAFs and TGF-β-activated human PSCs (hPSCs). Inhibition of miR-199a/-214 using hairpin inhibitors significantly inhibited TGFβ-induced differentiation markers (e.g. α-SMA, collagen, PDGFβR), migration and proliferation. Furthermore, heterospheroids of Panc-1 and hPSCs attained smaller size with hPSCs transfected with anti-miR-199a/-214 compared to control anti-miR. The conditioned medium obtained from TGFβ-activated hPSCs induced tumor cell growth and endothelial cell tube formation. Interestingly, these inductions were abrogated in hPSCs transfected with anti-miR-199a or miR-214. Moreover, IPA analyses revealed signaling pathways related to miR-199a (TP53, mTOR, Smad1) and miR-214 (PTEN, Bax, ING4). Taken together, this study reveals miR-199a-3p and miR-214-3p as major regulators of PSC activation and PSC-induced pro-tumoral effects, representing them as key therapeutic targets in pancreatic cancer. PMID:26918939

  17. Discrimination of benign versus malignant mixed tumors of the salivary gland using digital image analysis.

    PubMed

    Layfield, L J; Hall, T L; Fu, Y S

    1989-03-01

    Seven benign and four malignant mixed tumors of the salivary gland, biopsied using fine-needle aspiration, were analyzed using digital image analysis. Mean nuclear form factor, perimeter, and area were significantly increased in malignant cases. Better separation between diagnostic categories, however, was achieved by utilizing the coefficient of variation (CV) within a case rather than mean value. Form factor CV alone divided cases into nonoverlapping diagnostic categories. This quantitative analog of "pleomorphism" provided a useful marker for malignancy in mixed tumors.

  18. Subacute brain atrophy after radiation therapy for malignant brain tumor

    SciTech Connect

    Asai, A.; Matsutani, M.; Kohno, T.; Nakamura, O.; Tanaka, H.; Fujimaki, T.; Funada, N.; Matsuda, T.; Nagata, K.; Takakura, K.

    1989-05-15

    Brain atrophy with mental and neurologic deterioration developing a few months after radiation therapy in patients without residual or recurrent brain tumors has been recognized. Two illustrative case reports of this pathologic entity are presented. Six autopsy cases with this entity including the two cases were reviewed neurologically, radiographically, and histopathologically. All patients presented progressive disturbances of mental status and consciousness, akinesia, and tremor-like involuntary movement. Computerized tomography (CT) demonstrated marked enlargement of the ventricles, moderate widening of the cortical sulci, and a moderately attenuated CT number for the white matter in all six patients. Four of the six patients had CSF drainage (ventriculoperitoneal shunt or continuous lumbar drainage), however, none of them improved. Histologic examination demonstrated swelling and loss of the myelin sheath in the white matter in all patients, and reactive astrocytosis in three of the six patients. Neither prominent neuronal loss in the cerebral cortex or basal ganglia, nor axonal loss in the white matter was generally identified. The blood vessels of the cerebral cortex and white matter were normal. Ependymal layer and the surrounding brain tissue were normal in all patients. These findings suggested that this pathologic condition results from demyelination secondary to direct neurotoxic effect of irradiation. The authors' previous report was reviewed and the differential diagnoses, the risk factors for this pathologic entity, and the indication for radiation therapy in aged patients with a malignant brain tumor are discussed.

  19. Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer.

    PubMed

    Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E

    2008-11-01

    Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer.

  20. Somatostatin Receptor-1 Induces Cell Cycle Arrest and Inhibits Tumor Growth in Pancreatic Cancer

    PubMed Central

    Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F. Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E.

    2010-01-01

    Functional somatostatin receptors (SSTRs) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G0/G1 growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n=5, p<0.05, t-test), and inhibited tumor weight by 69% and 47%, (n=5, p<0.05, t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer. PMID:18823376

  1. Mucoepidermoid Carcinoma Associated with Osteosarcoma in a True Malignant Mixed Tumor of the Submandibular Region

    PubMed Central

    Marcotullio, Dario; de Vincentiis, Marco; Iannella, Giannicola; Cerbelli, Bruna; Magliulo, Giuseppe

    2015-01-01

    Introduction. True malignant mixed tumor, also known as carcinosarcoma, is a rare tumor of the salivary gland composed of both malignant epithelial and malignant mesenchymal elements. Frequently carcinosarcoma arises in the background of a preexisting pleomorphic adenoma; however, if no evidence of benign mixed tumor is present, the lesion is known as carcinosarcoma “de novo.” We reported the first case of true malignant mixed tumor of the submandibular gland composed of high grade mucoepidermoid carcinoma associated with osteosarcoma. Case Presentation. A 69-year-old Caucasian male came to our department complaining of the appearance of an asymptomatic left submandibular neoformation progressively increasing in size over 3 months. We opted for surgical treatment. Histological examination confirmed the diagnosis of carcinosarcoma with the coexistence of high grade mucoepidermoid carcinoma and osteosarcoma. Conclusion. To the best of our knowledge, in the true malignant mixed tumor of the submandibular gland, mucoepidermoid carcinoma associated with osteosarcoma has never been previously reported. PMID:26600963

  2. Mucoepidermoid Carcinoma Associated with Osteosarcoma in a True Malignant Mixed Tumor of the Submandibular Region.

    PubMed

    Marcotullio, Dario; de Vincentiis, Marco; Iannella, Giannicola; Cerbelli, Bruna; Magliulo, Giuseppe

    2015-01-01

    Introduction. True malignant mixed tumor, also known as carcinosarcoma, is a rare tumor of the salivary gland composed of both malignant epithelial and malignant mesenchymal elements. Frequently carcinosarcoma arises in the background of a preexisting pleomorphic adenoma; however, if no evidence of benign mixed tumor is present, the lesion is known as carcinosarcoma "de novo." We reported the first case of true malignant mixed tumor of the submandibular gland composed of high grade mucoepidermoid carcinoma associated with osteosarcoma. Case Presentation. A 69-year-old Caucasian male came to our department complaining of the appearance of an asymptomatic left submandibular neoformation progressively increasing in size over 3 months. We opted for surgical treatment. Histological examination confirmed the diagnosis of carcinosarcoma with the coexistence of high grade mucoepidermoid carcinoma and osteosarcoma. Conclusion. To the best of our knowledge, in the true malignant mixed tumor of the submandibular gland, mucoepidermoid carcinoma associated with osteosarcoma has never been previously reported.

  3. The matricellular protein CYR61 interferes with normal pancreatic islets architecture and promotes pancreatic neuroendocrine tumor progression.

    PubMed

    Huang, Yu-Ting; Lan, Qiang; Ponsonnet, Lionel; Blanquet, Marisa; Christofori, Gerhard; Zaric, Jelena; Rüegg, Curzio

    2016-01-12

    The significance of matricellular proteins during development and cancer progression is widely recognized. However, how these proteins actively contribute to physiological development and pathological cancer progression is only partially elucidated. In this study, we investigated the role of the matricellular protein Cysteine-rich 61 (CYR61) in pancreatic islet development and carcinogenesis. Transgenic expression of CYR61 in β cells (Rip1CYR mice) caused irregular islets morphology and distorted sorting of α cells, but did not alter islets size, number or vascularization. To investigate the function of CYR61 during carcinogenesis, we crossed Rip1CYR mice with Rip1Tag2 mice, a well-established model of β cell carcinogenesis. Beta tumors in Rip1Tag2CYR mice were larger, more invasive and more vascularized compared to tumors in Rip1Tag2 mice. The effect of CYR61 on angiogenesis was fully abrogated by treating mice with the anti-VEGFR2 mAb DC101. Results from in vitro assays demonstrated that CYR61 modulated integrin α6β1-dependent invasion and adhesion without altering its expression. Taken together, these results show that CYR61 expression in pancreatic β cells interferes with normal islet architecture, promotes islet tumor growth, invasion and VEGF/VERGFR-2-dependent tumor angiogenesis. Taken together, these observations demonstrate that CYR61 acts as a tumor-promoting gene in pancreatic neuroendocrine tumors.

  4. Hyponatremia with intracranial malignant tumor resection in children

    PubMed Central

    Williams, Cydni; Simon, Tamara D.; Riva-Cambrin, Jay; Bratton, Susan L.

    2012-01-01

    Object Intracranial neoplasms are the second most common childhood cancer, and lead to significant morbidity and mortality. Hyponatremia is a complication associated with neurosurgical procedures, but children undergoing intracranial tumor resection have not been selectively studied. In this study, the authors aimed to determine the incidence and risk factors associated with hyponatremia among children undergoing intracranial neoplasm resection. Methods A retrospective cohort was compiled using the 2006 Kids' Inpatient Database to identify children younger than 21 years of age who underwent intracranial neoplasm resection. Hyponatremia was ascertained by diagnosis codes. Bivariate analyses were conducted using chi-square and Mann-Whitney U-tests. Logistic regression models were developed to evaluate factors associated with hyponatremia in bivariate analyses. Results Hyponatremia occurred in 205 (8.7%) of 2343 annual weighted cases, and was independently associated with tumor location in the deep brain structures and ventricles compared with the cortical area (adjusted odds ratio [aOR] 2.4; 95% CI 1.17–5.3). Hyponatremia was also associated with obstructive hydrocephalus (aOR 2.7; 95% CI 1.7–4.3) and emergency department admission (aOR 1.7; 95% CI 1.1–2.4). Hyponatremia was significantly associated with mechanical ventilation, ventriculostomy placement, ventriculoperitoneal shunt placement, and sepsis. Hyponatremia was also associated with a significantly longer average length of stay (24.6 vs 10.2 days), higher average charges ($191,000 vs $92,000), and a higher percentage of discharges to intermediate-care facilities. Conclusions Hyponatremia commonly occurs with resection of intracranial malignant tumors, especially for lesions located in the deep brain and in patients with obstructive hydrocephalus. Hyponatremia was associated with higher morbidity. Further research is needed to develop targeted monitoring and intervention strategies to decrease

  5. Impact of APE1/Ref-1 redox inhibition on pancreatic tumor growth.

    PubMed

    Fishel, Melissa L; Jiang, Yanlin; Rajeshkumar, N V; Scandura, Glenda; Sinn, Anthony L; He, Ying; Shen, Changyu; Jones, David R; Pollok, Karen E; Ivan, Mircea; Maitra, Anirban; Kelley, Mark R

    2011-09-01

    Pancreatic cancer is especially a deadly form of cancer with a survival rate less than 2%. Pancreatic cancers respond poorly to existing chemotherapeutic agents and radiation, and progress for the treatment of pancreatic cancer remains elusive. To address this unmet medical need, a better understanding of critical pathways and molecular mechanisms involved in pancreatic tumor development, progression, and resistance to traditional therapy is therefore critical. Reduction-oxidation (redox) signaling systems are emerging as important targets in pancreatic cancer. AP endonuclease1/Redox effector factor 1 (APE1/Ref-1) is upregulated in human pancreatic cancer cells and modulation of its redox activity blocks the proliferation and migration of pancreatic cancer cells and pancreatic cancer-associated endothelial cells in vitro. Modulation of APE1/Ref-1 using a specific inhibitor of APE1/Ref-1's redox function, E3330, leads to a decrease in transcription factor activity for NFκB, AP-1, and HIF1α in vitro. This study aims to further establish the redox signaling protein APE1/Ref-1 as a molecular target in pancreatic cancer. Here, we show that inhibition of APE1/Ref-1 via E3330 results in tumor growth inhibition in cell lines and pancreatic cancer xenograft models in mice. Pharmacokinetic studies also show that E3330 attains more than10 μmol/L blood concentrations and is detectable in tumor xenografts. Through inhibition of APE1/Ref-1, the activity of NFκB, AP-1, and HIF1α that are key transcriptional regulators involved in survival, invasion, and metastasis is blocked. These data indicate that E3330, inhibitor of APE1/Ref-1, has potential in pancreatic cancer and clinical investigation of APE1/Ref-1 molecular target is warranted.

  6. Ligand stimulation of ErbB4 and a constitutively-active ErbB4 mutant result in different biological responses in human pancreatic tumor cell lines

    SciTech Connect

    Mill, Christopher P.; Gettinger, Kathleen L.; Riese, David J.

    2011-02-15

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Indeed, it has been estimated that 37,000 Americans will die from this disease in 2010. Late diagnosis, chemoresistance, and radioresistance of these tumors are major reasons for poor patient outcome, spurring the search for pancreatic cancer early diagnostic and therapeutic targets. ErbB4 (HER4) is a member of the ErbB family of receptor tyrosine kinases (RTKs), a family that also includes the Epidermal Growth Factor Receptor (EGFR/ErbB1/HER1), Neu/ErbB2/HER2, and ErbB3/HER3. These RTKs play central roles in many human malignancies by regulating cell proliferation, survival, differentiation, invasiveness, motility, and apoptosis. In this report we demonstrate that human pancreatic tumor cell lines exhibit minimal ErbB4 expression; in contrast, these cell lines exhibit varied and in some cases abundant expression and basal tyrosine phosphorylation of EGFR, ErbB2, and ErbB3. Expression of a constitutively-dimerized and -active ErbB4 mutant inhibits clonogenic proliferation of CaPan-1, HPAC, MIA PaCa-2, and PANC-1 pancreatic tumor cell lines. In contrast, expression of wild-type ErbB4 in pancreatic tumor cell lines potentiates stimulation of anchorage-independent colony formation by the ErbB4 ligand Neuregulin 1{beta}. These results illustrate the multiple roles that ErbB4 may be playing in pancreatic tumorigenesis and tumor progression.

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

    SciTech Connect

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

    2009-07-01

    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.

  8. Functional Expression of TWEAK and the Receptor Fn14 in Human Malignant Ovarian Tumors: Possible Implication for Ovarian Tumor Intervention

    PubMed Central

    Zhu, Jing; Ding, Chuanwei; Xu, Hai-bo; Qiu, Lihua; Di, Wen

    2013-01-01

    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. PMID:23469193

  9. Multiple recurrent malignant solitary fibrous tumors: long-term follow-up of 24 years.

    PubMed

    Park, Chang Kwon; Lee, Deok Heon; Park, Ji Young; Park, Sun Hwa; Kwon, Kun Young

    2011-04-01

    Solitary fibrous tumor (SFT) of the pleura is a rare, generally benign, neoplasm that accounts for less than 5% of all pleural tumors. However, 10% to 30% of SFTs display aggressive behavior with local recurrence, malignant transformation, and distant metastasis. We report a case of multiple recurrent SFTs of the thorax in a 77-year-old Korean woman. During a 24-year period, she underwent six surgical resections for six recurrent SFTs. The tumor eventually underwent morphologically malignant transformation. This unique case highlights the necessity of long-term follow-up in cases of SFT because of the potentially malignant biological behavior of this type of tumor.

  10. Differentiation of solid pancreatic tumors by using dynamic contrast-enhanced MRI

    NASA Astrophysics Data System (ADS)

    Choi, Seung Joon; Kim, Hyung Sik; Park, Hyunjin

    2014-01-01

    Distinguishing among different solid pancreatic tumor types, pancreatic ductal adenocarcinomas, neuroendocrine tumors (NETs), and solid pseudopapillary tumors (SPTs) is important, as the treatment options are vastly different. This study compared characteristics of solid pancreatic tumors by using dynamic contrast enhanced magnetic resonance imaging (MRI). Fifty patients underwent MR imaging of pancreatic masses with a histopathology that was later confirmed as an adenocarcinoma (n = 27), a NET (n = 16), and a SPT (n = 7). For qualitative analysis, two reviewers evaluated the morphologic features of the tumors: locations, margins, shapes, contained products, pancreatic ductal dilatation, and grade of signal intensity (SI). For the quantitative analysis, all phases of the MR images were co-registered using proprietary image registration software; thus, a region of interest (ROI) defined on one phase could be re-applied in other phases. The following four ratios were considered: tumor-to-uninvolved pancreas SI ratio, percent SI change, tumor-touninvolved pancreas enhancement index, and arterial-to-delayed washout rate. The areas under the receiver operating characteristic (ROC) curves were assessed for the four ratios. Adenocarcinomas had ill-defined margins, irregular shapes, and ductal dilatation compared with NETs and SPTs (P < 0.001). The tumor-to-uninvolved pancreas ratio on all dynamic phases was significantly higher for NETs than for both adenocarcinomas and SPTs (P < 0.05). Percentage SI changes of pancreatic tumors on the pancreatic and the portal venous phases were significantly higher for NETs than for both adenocarcinomas and SPTs (P < 0.05). A significant difference between NETs and adenocarcinomas was also found with respect to the tumor-to-uninvolved pancreas enhancement index and arterial-to-delayed washout rate. The percentage SI changes in the pancreatic phase and the arterial-to-delayed washout rate best distinguished between adenocarcinomas and

  11. MICROBIAL DRIVEN TLR5-DEPENDENT SIGNALING GOVERNS DISTAL MALIGNANT PROGRESSION THROUGH TUMOR-PROMOTING INFLAMMATION

    PubMed Central

    Rutkowski, Melanie R.; Stephen, Tom L.; Svoronos, Nikolaos; Allegrezza, Michael J.; Tesone, Amelia J.; Perales-Puchalt, Alfredo; Brencicova, Eva; Escovar-Fadul, Ximena; Nguyen, Jenny M.; Cadungog, Mark G.; Zhang, Rugang; Salatino, Mariana; Tchou, Julia; Rabinovich, Gabriel A.; Conejo-Garcia, Jose R.

    2014-01-01

    The dominant TLR5R392X polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extra-mucosal locations by increasing systemic IL-6, which drives mobilization of myeloid derived suppressor cells (MDSCs). Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5-responsive tumors to secrete galectin-1, dampening anti-tumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently up-regulated in TLR5-unresponsive tumor-bearing mice, but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, anti-tumor immunity and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism. PMID:25533336

  12. Magnetic nanoparticles: an emerging technology for malignant brain tumor imaging and therapy

    PubMed Central

    Wankhede, Mamta; Bouras, Alexandros; Kaluzova, Milota; Hadjipanayis, Costas G

    2012-01-01

    Magnetic nanoparticles (MNPs) represent a promising nanomaterial for the targeted therapy and imaging of malignant brain tumors. Conjugation of peptides or antibodies to the surface of MNPs allows direct targeting of the tumor cell surface and potential disruption of active signaling pathways present in tumor cells. Delivery of nanoparticles to malignant brain tumors represents a formidable challenge due to the presence of the blood–brain barrier and infiltrating cancer cells in the normal brain. Newer strategies permit better delivery of MNPs systemically and by direct convection-enhanced delivery to the brain. Completion of a human clinical trial involving direct injection of MNPs into recurrent malignant brain tumors for thermotherapy has established their feasibility, safety and efficacy in patients. Future translational studies are in progress to understand the promising impact of MNPs in the treatment of malignant brain tumors. PMID:22390560

  13. In-vivo NIR autofluorescence of rat mammary tumors discriminates pathological malignancy

    NASA Astrophysics Data System (ADS)

    Fournier, Laure S.; Lucidi, Vincenzo; Rosenau, Werner; Demos, Stavros G.; Brasch, Robert C.

    2003-10-01

    Benign and malignant mammary tumors were induced in rats using a potent carcinogen, N-ethyl-N-nitrosurea (ENU). Induced tumors were examined under near-infrared (NIR) fluorescence imaging (excitation wavelength 670 to 730 nm, detection wavelength 750 and 800 nm) to search for a difference in the photophysical properties of the tumors reflecting their pathologic status. Three benign and eight malignant tumors were examined optically and pathologically. The non-enhanced optical images showed a significantly lower (P<0.05) spontaneous fluorescent signal in the benign tumors than in their malignant counterparts. The precise chemical origin for the observed differences in tumor autofluorescence remains undetermined. It can be hypothesized that the reported high concentration of porphyrins, NIR-fluorescing compounds, in the malignant lesions, could account for the observed increased autofluorescence.

  14. Malignant proliferating pilar tumors arising in KID syndrome: a report of two patients.

    PubMed

    Nyquist, Gurston G; Mumm, Christina; Grau, Renee; Crowson, A Neil; Shurman, Daniel L; Benedetto, Paul; Allen, Pamela; Lovelace, Kelli; Smith, David W; Frieden, Ilona; Hybarger, C Patrick; Richard, Gabriele

    2007-04-01

    We report on two young adults with KID syndrome and follicular hyperkeratosis, hidradenitis suppurativa of the groin, progressive development of proliferative pilar cysts and dissecting cellulitis of the scalp, who developed metastatic malignant pilar tumors. Based on our findings, we believe that cancer surveillance in patients with KID syndrome should include screening for pilar tumors and their early removal to avoid development of malignant proliferating pilar tumors with poor prognosis. PMID:17330861

  15. Tumor-associated macrophages exhibit pro- and anti-inflammatory properties by which they impact on pancreatic tumorigenesis.

    PubMed

    Helm, Ole; Held-Feindt, Janka; Grage-Griebenow, Evelin; Reiling, Norbert; Ungefroren, Hendrik; Vogel, Ilka; Krüger, Uwe; Becker, Thomas; Ebsen, Michael; Röcken, Christoph; Kabelitz, Dieter; Schäfer, Heiner; Sebens, Susanne

    2014-08-15

    Pancreatic ductal adenocarcinoma (PDAC) still ranking 4th in the order of fatal tumor diseases is characterized by a profound tumor stroma with high numbers of tumor-associated macrophages (TAMs). Driven by environmental factors, monocytes differentiate into M1- or M2-macrophages, the latter commonly regarded as being protumorigenic. Because a detailed analysis of TAMs in human PDAC development is still lacking, freshly isolated PDAC-derived TAMs were analyzed for their phenotype and impact on epithelial-mesenchymal-transition (EMT) of benign (H6c7) and malignant (Colo357) pancreatic ductal epithelial cells. TAMs exhibited characteristics of M1-macrophages (expression of HLA-DR, IL-1β, or TNF-α) and M2-macrophages (expression of CD163 and IL-10). In the presence of TAMs, H6c7, and Colo357 cells showed an elongated cell shape along with an increased expression of mesenchymal markers such as vimentin and reduced expression of epithelial E-cadherin. Similar to TAMs, in vitro generated M1- and M2-macrophages both mediated EMT in H6c7 and Colo357 cells. M1-macrophages acquired M2-characteristics during coculture that could be prevented by GM-CSF treatment. However, M1-macrophages still potently induced EMT in H6c7 and Colo357 cells although lacking M2-characteristics. Overall, these data demonstrate that TAMs exhibit anti- as well as proinflammatory properties that equally contribute to EMT induction in PDAC initiation and development. PMID:24458546

  16. Everolimus in advanced pancreatic neuroendocrine tumors: the clinical experience.

    PubMed

    Yao, James C; Phan, Alexandria T; Jehl, Valentine; Shah, Gaurav; Meric-Bernstam, Funda

    2013-03-01

    The incidence of neuroendocrine tumors (NET) has increased dramatically in the past 30 years. This information has revitalized basic and clinical research into the molecular biology of NET and has resulted in the recent approval of new therapies for pancreatic NET (pNET), including the oral inhibitor of the mTOR everolimus. Everolimus significantly improved progression-free survival among patients with pNET in the phase III RADIANT-3 study. Here, we review the clinical studies showing the efficacy of everolimus in pNET and summarize the translational science from these studies. To understand the mechanisms of resistance and cause of treatment failure, we compared the type of progression events observed in the everolimus and placebo arms of the RADIANT-3 study. Comparison of the everolimus arm to the placebo arm indicated the fractions of progression events due to new metastasis only (21% vs. 22%), growth of preexisting lesions only (54% vs. 49%), and new metastasis along with growth of preexisting lesions (24% vs. 27%) were similar. These results suggest that although everolimus delays disease progression in patients with pNET, patients who experience disease progression while on everolimus do not appear to have a more aggressive metastatic phenotype than those whose disease progresses while on placebo.

  17. Whole-genome sequencing of a malignant granular cell tumor with metabolic response to pazopanib

    PubMed Central

    Wei, Lei; Liu, Song; Conroy, Jeffrey; Wang, Jianmin; Papanicolau-Sengos, Antonios; Glenn, Sean T.; Murakami, Mitsuko; Liu, Lu; Hu, Qiang; Conroy, Jacob; Miles, Kiersten Marie; Nowak, David E.; Liu, Biao; Qin, Maochun; Bshara, Wiam; Omilian, Angela R.; Head, Karen; Bianchi, Michael; Burgher, Blake; Darlak, Christopher; Kane, John; Merzianu, Mihai; Cheney, Richard; Fabiano, Andrew; Salerno, Kilian; Talati, Chetasi; Khushalani, Nikhil I.; Trump, Donald L.; Johnson, Candace S.; Morrison, Carl D.

    2015-01-01

    Granular cell tumors are an uncommon soft tissue neoplasm. Malignant granular cell tumors comprise <2% of all granular cell tumors, are associated with aggressive behavior and poor clinical outcome, and are poorly understood in terms of tumor etiology and systematic treatment. Because of its rarity, the genetic basis of malignant granular cell tumor remains unknown. We performed whole-genome sequencing of one malignant granular cell tumor with metabolic response to pazopanib. This tumor exhibited a very low mutation rate and an overall stable genome with local complex rearrangements. The mutation signature was dominated by C>T transitions, particularly when immediately preceded by a 5′ G. A loss-of-function mutation was detected in a newly recognized tumor suppressor candidate, BRD7. No mutations were found in known targets of pazopanib. However, we identified a receptor tyrosine kinase pathway mutation in GFRA2 that warrants further evaluation. To the best of our knowledge, this is only the second reported case of a malignant granular cell tumor exhibiting a response to pazopanib, and the first whole-genome sequencing of this uncommon tumor type. The findings provide insight into the genetic basis of malignant granular cell tumors and identify potential targets for further investigation. PMID:27148567

  18. Whole-genome sequencing of a malignant granular cell tumor with metabolic response to pazopanib.

    PubMed

    Wei, Lei; Liu, Song; Conroy, Jeffrey; Wang, Jianmin; Papanicolau-Sengos, Antonios; Glenn, Sean T; Murakami, Mitsuko; Liu, Lu; Hu, Qiang; Conroy, Jacob; Miles, Kiersten Marie; Nowak, David E; Liu, Biao; Qin, Maochun; Bshara, Wiam; Omilian, Angela R; Head, Karen; Bianchi, Michael; Burgher, Blake; Darlak, Christopher; Kane, John; Merzianu, Mihai; Cheney, Richard; Fabiano, Andrew; Salerno, Kilian; Talati, Chetasi; Khushalani, Nikhil I; Trump, Donald L; Johnson, Candace S; Morrison, Carl D

    2015-10-01

    Granular cell tumors are an uncommon soft tissue neoplasm. Malignant granular cell tumors comprise <2% of all granular cell tumors, are associated with aggressive behavior and poor clinical outcome, and are poorly understood in terms of tumor etiology and systematic treatment. Because of its rarity, the genetic basis of malignant granular cell tumor remains unknown. We performed whole-genome sequencing of one malignant granular cell tumor with metabolic response to pazopanib. This tumor exhibited a very low mutation rate and an overall stable genome with local complex rearrangements. The mutation signature was dominated by C>T transitions, particularly when immediately preceded by a 5' G. A loss-of-function mutation was detected in a newly recognized tumor suppressor candidate, BRD7. No mutations were found in known targets of pazopanib. However, we identified a receptor tyrosine kinase pathway mutation in GFRA2 that warrants further evaluation. To the best of our knowledge, this is only the second reported case of a malignant granular cell tumor exhibiting a response to pazopanib, and the first whole-genome sequencing of this uncommon tumor type. The findings provide insight into the genetic basis of malignant granular cell tumors and identify potential targets for further investigation. PMID:27148567

  19. Circulating tumor cells in pancreatic cancer patients: Enrichment and cultivation

    PubMed Central

    Bobek, Vladimir; Gurlich, Robert; Eliasova, Petra; Kolostova, Katarina

    2014-01-01

    AIM: To investigate the feasibility of separation and cultivation of circulating tumor cells (CTCs) in pancreatic cancer (PaC) using a filtration device. METHODS: In total, 24 PaC patients who were candidates for surgical treatment were enrolled into the study. Peripheral blood samples were collected before an indicated surgery. For each patient, approximately 8 mL of venous blood was drawn from the antecubital veins. A new size-based separation MetaCell® technology was used for enrichment and cultivation of CTCs in vitro. (Separated CTCs were cultured on a membrane in FBS enriched RPMI media and observed by inverted microscope. The cultured cells were analyzed by means of histochemistry and immunohistochemistry using the specific antibodies to identify the cell origin. RESULTS: CTCs were detected in 16 patients (66.7%) of the 24 evaluable patients. The CTC positivity did not reflect the disease stage, tumor size, or lymph node involvement. The same percentage of CTC positivity was observed in the metastatic and non-metastatic patients (66.7% vs 66.7%). We report a successful isolation of CTCs in PaC patients capturing proliferating cells. The cells were captured by a capillary action driven size-based filtration approach that enabled cells cultures from the viable CTCs to be unaffected by any antibodies or lysing solutions. The captured cancer cells displayed plasticity which enabled some cells to invade the separating membrane. Further, the cancer cells in the “bottom fraction”, may represent a more invasive CTC-fraction. The CTCs were cultured in vitro for further downstream applications. CONCLUSION: The presented size-based filtration method enables culture of CTCs in vitro for possible downstream applications. PMID:25493031

  20. Breast tumor malignancy modelling using evolutionary neural logic networks.

    PubMed

    Tsakonas, Athanasios; Dounias, Georgios; Panagi, Georgia; Panourgias, Evangelia

    2006-01-01

    The present work proposes a computer assisted methodology for the effective modelling of the diagnostic decision for breast tumor malignancy. The suggested approach is based on innovative hybrid computational intelligence algorithms properly applied in related cytological data contained in past medical records. The experimental data used in this study were gathered in the early 1990s in the University of Wisconsin, based in post diagnostic cytological observations performed by expert medical staff. Data were properly encoded in a computer database and accordingly, various alternative modelling techniques were applied on them, in an attempt to form diagnostic models. Previous methods included standard optimisation techniques, as well as artificial intelligence approaches, in a way that a variety of related publications exists in modern literature on the subject. In this report, a hybrid computational intelligence approach is suggested, which effectively combines modern mathematical logic principles, neural computation and genetic programming in an effective manner. The approach proves promising either in terms of diagnostic accuracy and generalization capabilities, or in terms of comprehensibility and practical importance for the related medical staff.

  1. Neutrophil-Derived Proteases in the Microenvironment of Pancreatic Cancer -Active Players in Tumor Progression

    PubMed Central

    Felix, Klaus; Gaida, Matthias M.

    2016-01-01

    A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the fibro-inflammatory microenvironment, consisting of activated pancreatic stellate cells, extracellular matrix proteins, and a variety of inflammatory cells, such as T cells, macrophages, or neutrophils. Tumor-infiltrating immune cells, which are found in nearly all cancers, including PDAC, often fail to eliminate the tumor, but conversely can promote its progression by altering the tumor microenvironment. Pancreatic cancer cells are able to attract polymorphonuclear neutrophils (PMN) via tumor secreted chemokines and in human PDAC, PMN infiltrates can be observed in the vicinity of tumor cells and in the desmoplastic tumor stroma, which correlate with undifferentiated tumor growth and poor prognosis. The behavior of tumor-infiltrating neutrophils in the tumor micromilieu is not yet understood at a mechanistic level. It has been shown that PMN have the potential to kill tumor cells, either directly or by antibody-dependent cell-mediated cytotoxicity, but on the other side various adverse effects of PMN, such as promotion of aggressive tumor growth with epithelial-to-mesenchymal transition and increased metastatic potential, have been described. Recent therapeutic approaches for PDAC focus not only the tumor cell itself, but also elements of the tumor microenvironment. Therefore, the role of PMN and their derived products (e.g. cytokines, proteases) as a new vein for a therapeutic target should be critically evaluated in this context. This review summarizes the current understanding of the interplay between proteases of tumor-infiltrating neutrophils and pancreatic tumor cells and elements of the desmoplastic stroma. PMID:26929737

  2. Procedure for quantitative determination of effectiveness of photoinduced destruction of malignant tumors

    NASA Astrophysics Data System (ADS)

    Bizyuk, S. A.; Istomin, Yu. P.; Dzhagarov, B. M.

    2006-07-01

    We have developed a procedure for analysis of the functional status of blood vessels in tumor tissues using computer-assisted color scanning of tumor slices and also for a quantitative assessment of the effectiveness of photoinduced destruction of tumor tissues in animal experiments. Its major advantage is direct determination of the size of the tumor necrosis zone. The procedure has been tested in an experiment on three strains of malignant tumors with different morphologies.

  3. Case report of malignant pulmonary parenchymal glomus tumor: imaging features and review of the literature.

    PubMed

    Cunningham, Jane D; Plodkowski, Andrew J; Giri, Dilip D; Hwang, Sinchun

    2016-01-01

    Glomus tumor is rare tumor which arises from glomus body and is most frequently found in the soft tissue of the extremities. The lung is a rare ectopic site, and a malignant glomus tumor arising from pulmonary parenchyma is particularly uncommon. To deepen our understanding on their imaging features, we report a case of malignant glomus tumor of pulmonary parenchyma confirmed with surgical histopathology and immunochemistry and review the medical literature on pulmonary parenchymal glomus tumors with emphasis on their imaging features. PMID:26498485

  4. Small Cell Carcinoma of the Ovary (Hypercalcemic Type): Malignant Rhabdoid Tumor

    PubMed Central

    Kascak, Peter; Zamecnik, Michal; Bystricky, Branislav

    2016-01-01

    We present a rare case of malignant rhabdoid tumor (ovarian small cell carcinoma of hypercalcemic type) in a 24-year-old female with fulminant course. Clinically, hypercalcemia was not found at the time of primary diagnosis. However, it appeared later during the course of tumor progression. Histologically, the tumor showed classical features of small cell carcinoma of hypercalcemic type. Therapy included radical surgery with adjuvant chemotherapy. Despite this intensive therapy, the disease recurred and the patient died 10 months after the diagnosis. We discuss the diagnosis and therapy of this tumor, as well as its recent classification as malignant rhabdoid tumor. PMID:27462229

  5. Expression and mutation patterns of p53 in benign and malignant salivary gland tumors.

    PubMed

    Nordkvist, A; Röijer, E; Bang, G; Gustafsson, H; Behrendt, M; Ryd, W; Thoresen, S; Donath, K; Stenman, G

    2000-03-01

    The expression and mutation patterns of p53 were studied in a series of 68 benign pleomorphic adenomas and 237 malignant salivary gland tumors. p53 overexpression (nuclear staining exceeding 10%) was detected in 20% of the malignant salivary gland tumors, with the highest prevalence observed in polymorphous low grade adenocarcinoma, squamous cell carcinoma, and carcinoma ex pleomorphic adenoma and the lowest in adenoid cystic carcinoma and acinic cell carcinoma. In contrast, none of the 68 benign pleomorphic adenomas had nuclear staining exceeding 10%. SSCP and nucleotide sequence analysis of exons 4 to 9 of p53 in 19 malignant tumors revealed 9 mutations in 7 tumors. Our findings indicate that p53 may be a useful marker to help discriminate between benign and malignant salivary gland tumors.

  6. Dual FISH analysis of benign and malignant tumors of the salivary glands and paranasal sinuses.

    PubMed

    Götte, Karl; Ganssmann, Stefan; Affolter, Annette; Schäfer, Carsten; Riedel, Frank; Arens, Norbert; Finger, Sonja; Hörmann, Karl

    2005-11-01

    To date, the underlying genomic changes in benign and malignant tumors of salivary-gland and paranasal-sinus origin are poorly understood. This is due in part to the low incidence of these tumors and the enormous histological variety of tumors within this head and neck region. We examined 58 of these tumors (14 adenoid cystic carcinomas, 9 adenocarcinomas, 5 cylindrical carcinomas, 11 pleomorphic adenomas, and 19 inverted papillomas) by dual fluorescence in situ hybridization (FISH) with centromere-specific probes on six chromosomes (3, 7, 9, 11, 17, and 18) for numerical changes. In adenoid cystic carcinomas, monosomy of chromosome 17 and polysomy of chromosomes 3, 9 and 11 were most frequently encountered. In adenocarcinomas, monosomy of chromosome 17 and polysomy of chromosomes 7 and 11 were most frequent. In cylindrical cell carcinomas, polysomy of chromosomes 7, 9, 11 and 17 was present in the majority of tumors. Disomy is rare, even in benign tumors. Polysomy is more frequent in malignant tumors than in benign. Tetrasomy is found almost only in malignant tumors. In summary, the occurrence of polysomy might reflect a step towards malignancy in tumors of the salivary glands and paranasal mucosa. Polysomy of chromosome 11 could be defined as typical for all investigated histological types of malignant tumor in this region of the head and neck. PMID:16211271

  7. Brg1 promotes both tumor-suppressive and oncogenic activities at distinct stages of pancreatic cancer formation

    PubMed Central

    Roy, Nilotpal; Malik, Shivani; Villanueva, Karina E.; Urano, Atsushi; Lu, Xinyuan; Von Figura, Guido; Seeley, E. Scott; Dawson, David W.; Collisson, Eric A.

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDA) develops predominantly through pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) precursor lesions. Pancreatic acinar cells are reprogrammed to a “ductal-like” state during PanIN-PDA formation. Here, we demonstrate a parallel mechanism operative in mature duct cells during which functional cells undergo “ductal retrogression” to form IPMN-PDA. We further identify critical antagonistic roles for Brahma-related gene 1 (Brg1), a catalytic subunit of the SWI/SNF complexes, during IPMN-PDA development. In mature duct cells, Brg1 inhibits the dedifferentiation that precedes neoplastic transformation, thus attenuating tumor initiation. In contrast, Brg1 promotes tumorigenesis in full-blown PDA by supporting a mesenchymal-like transcriptional landscape. We further show that JQ1, a drug that is currently being tested in clinical trials for hematological malignancies, impairs PDA tumorigenesis by both mimicking some and inhibiting other Brg1-mediated functions. In summary, our study demonstrates the context-dependent roles of Brg1 and points to potential therapeutic treatment options based on epigenetic regulation in PDA. PMID:25792600

  8. SU-E-J-07: A Functional MR Protocol for the Pancreatic Tumor Delineation

    SciTech Connect

    Andreychenko, A; Heerkens, H; Meijer, G; Vulpen, M van; Lagendijk, J; Berg, C van den

    2014-06-01

    Purpose: Pancreatic cancer is one of the cancers with the poorest survival prognosis. At the time of diagnosis most of pancreatic cancers are unresectable and those patients can be treated by radiotherapy. Radiotherapy for pancreatic cancer is limited due to uncertainties in CT-based delineations. MRI provides an excellent soft tissue contrast. Here, an MR protocol is developed to improve delineations for radiotherapy treatment of pancreatic cancer. In a later stage this protocol can also be used for on-line visualization of the pancreas during MRI guided treatments. Methods: Nine pancreatic cancer patients were included. The MR protocol included T2 weighted(T2w), T1 weighted(T1w), diffusion weighted(DWI) and dynamic contrast enhanced(DCE) techniques. The tumor was delineated on T2w and T1w MRI by an experienced radiation oncologist. Healthy pancreas or pancreatitis (assigned by the oncologist based on T2w) areas were also delineated. Apparent diffusion coefficient(ADC), and area under the curve(AUC)/time to peak(TTP) maps were obtained from DWI and DCE scans, respectively. Results: A clear demarcation of tumor area was visible on b800 DWI images in 5 patients. ADC maps of those patients characterized tumor as an area with restricted water diffusion. Tumor delineations based on solely DCE were possible in 7 patients. In 6 of those patients AUC maps demonstrated tumor heterogeneity: a hypointense area with a hyperintense ring. TTP values clearly discriminated the tumor and the healthy pancreas but could not distinguish tumor and the pancreatitis accurately. Conclusion: MR imaging results in a more pronounced tumor contrast than contrast enhanced CT. The addition of quantitative, functional MRI provides valuable, additional information to the radiation oncologist on the spatial tumor extent by discriminating tumor from the healthy pancreas(TTP, DWI) and characterizing the tumor(ADC). Our findings indicate that tumor delineation in pancreatic cancer can greatly

  9. Ipsilateral kidney sparing in treatment of pancreatic malignancies using volumetric-modulated arc therapy avoidance sectors

    SciTech Connect

    Chan, Raymond W. Podgorsak, Matthew B.

    2015-10-01

    Recent research has shown treating pancreatic cancer with volumetric-modulated arc therapy (VMAT) to be superior to either intensity-modulated radiation therapy or 3-dimensional conformal radiotherapy (3D-CRT), with respect to reducing normal tissue toxicity, monitor units, and treatment time. Furthermore, using avoidance sectors with RapidArc planning can further reduce normal tissue dose while maintaining target conformity. This study looks at the methods in reducing dose to the ipsilateral kidney, in pancreatic head cases, while observing dose received by other critical organs using avoidance sectors. Overall, 10 patients were retrospectively analyzed. Each patient had preoperative/unresectable pancreatic tumor and were selected based on the location of the right kidney being situated within the traditional 3D-CRT treatment field. The target planning target volume (286.97 ± 85.17 cm{sup 3}) was prescribed to 50.4 Gy using avoidance sectors of 30°, 40°, and 50° and then compared with VMAT as well as 3D-CRT. Analysis of the data shows that the mean dose to the right kidney was reduced by 11.6%, 15.5%, and 21.9% for avoidance angles of 30°, 40°, and 50°, respectively, over VMAT. The mean dose to the total kidney also decreased by 6.5%, 8.5%, and 11.0% for the same increasing angles. Spinal cord maximum dose, however, increased as a function of angle by 3.7%, 4.8%, and 6.1% compared with VMAT. Employing avoidance sector angles as a complement to VMAT planning can significantly reduce high dose to the ipsilateral kidney while not greatly overdosing other critical organs.

  10. Acute pancreatitis following granulosa cell tumor removal in a mare

    PubMed Central

    Gomez, Diego E.; Radtke, Catherine L.; Russell, Lauren A.; Lopez, Alfonso; Wichtel, Maureen W.

    2015-01-01

    Acute pancreatitis is a rare disease in horses and is often associated with gastrointestinal disorders. Accurate diagnosis is challenging due to the presence of nonspecific clinical signs. This case represents the first documentation of acute pancreatitis in a horse following surgery of the reproductive tract. PMID:26483579

  11. Flow cytometric analysis of benign and malignant tumors of the oral and maxillofacial region.

    PubMed

    Chen, R B

    1989-06-01

    One hundred eight fresh tissue samples obtained from normal tissues, benign tumors, and malignant tumors of the oral and maxillofacial region were analyzed for nuclear DNA content and cell kinetics by flow cytometric analysis (FCM). Mean DNA indices for 22 normal tissues and 18 benign tumors were 1.00 and 1.02, respectively, and all samples but one showed diploid pattern. On the other hand, the value for 68 malignant tumors was 1.38, and 66% of them showed an aneuploid pattern. The S phase and G2 + M phase cell populations for malignant tumors were 17.2% and 7.0%, respectively. With the exception of G2 + M phase cell population, all values for malignant tumors were significantly higher than those of normal tissue and benign tumors. Although statistical differences were not observed in most of the values, they were higher in squamous cell carcinomas than in malignant salivary gland tumors. The incidence of aneuploidy and DNA index showed a tendency to increase with the increase of T classification, in N2 and N3 tumors, and in the group of patients with recurrence or who died. The DNA index and the type of DNA ploidy were well correlated to malignancy grade determined by six histologic parameters, whereas the S phase cell population was correlated to mitosis. The analysis by the two-dimensional diagnostic supporting system showed that more than 80% of malignant tumors can be correctly diagnosed by combined values of DNA index and S phase cell population. The results indicate that nuclear DNA analysis by FCM is quite useful as a supplement to histologic diagnosis and evaluation of malignancy grade.

  12. Challenges in detecting pre-malignant pancreatic lesions during acute pancreatitis using a serum microRNA assay: a study based on KrasG12D transgenic mice

    PubMed Central

    Hong, Xiafei; Zhang, Jie; Wu, Qiao; Wang, Wenze; Ye, Adam Yongxin; Song, Wei; Dai, Hongmei; Wang, Xianze; Wu, Fan; You, Lei; Wu, Wenming; Zhao, Yupei

    2016-01-01

    Caerulein-induced acute pancreatitis accelerates the progression of pancreatic intraepithelial neoplasia (PanIN) lesions in a pancreas-specific KrasG12D mouse model. The purpose of this study was to explore whether serum microRNAs (miRNAs) can serve as sensitive biomarkers to detect occult PanIN in the setting of acute pancreatitis. Serum miRNA profiles were quantified by an array-based method and normalized by both Variance Stabilization Normalization (VSN) and invariant methods. Individual miRNAs were validated by TaqMan real-time PCR with synthetic spike-in C. elegans miRNAs as external controls. Serum miRNA profiles distinguished KrasG12D mice with pancreatitis from wild-type mice without pancreatitis, but failed to differentiate KrasG12D mice with pancreatitis from wild-type mice with pancreatitis. Most individual miRNAs that increased in KrasG12D mice with pancreatitis were not significantly different between KrasG12D mice without pancreatitis and wild-type mice without pancreatitis. Mechanistically, Gene Set Enrichment Analysis (GSEA) of the mRNA array data and immunohistochemical assays showed that caerulein-induced acute pancreatitis involved acinar cell loss and immune cell infiltration, which might contribute to serum miRNA profile changes. This study highlighted the challenges in using sensitive serum miRNA biomarker screening for the early detection of pancreatic malignancies during acute pancreatitis. PMID:27009811

  13. Malignant fibrous histiocytoma (giant cell type) associated with a malignant mixed tumor in the salivary gland of a dog.

    PubMed

    Pérez-Martínez, C; García Fernández, R A; Reyes Avila, L E; Pérez-Pérez, V; González, N; García-Iglesias, M J

    2000-07-01

    A 12-year-old male Boxer dog presented with a 5 x 5 x 7-cm partially encapsulated mass in the right mandibular salivary gland. Histologically, the mass was composed of neoplastic epithelial and mesenchymal cells. The mesenchymal component consisted of two cell populations arranged in different patterns: coalescing nodules of neoplastic mononuclear cells with rare osteoid and numerous osteoclastlike giant cells; and sheets of neoplastic spindle cells intermingled with neoplastic epithelial cells and containing osteoid and well-formed bone trabeculae lined by osteoblasts and few osteoclastlike giant cells. On the basis of these histological features, two malignant salivary tumors were diagnosed: a malignant fibrous histiocytoma (giant cell type) and a malignant mixed tumor. Immunohistochemical studies demonstrated keratin 5 and 8 expression by the neoplastic epithelial cells, indicating a probable salivary ductal origin, and vimentin expression by all mesenchymal elements, suggesting a fibroblastic line of differentiation.

  14. Malignant chondroblastoma presenting as a recurrent pelvic tumor with DNA aneuploidy and p53 mutation as supportive evidence of malignancy.

    PubMed

    Ostrowski, M L; Johnson, M E; Truong, L D; Hicks, M J; Smith, F E; Spjut, H J

    1999-11-01

    We report a rare case of malignant chondroblastoma, which presented in a 47-year-old man as a recurrent tumor, 18 years following wide excision of a typical pelvic chondroblastoma. Radiologic studies of the recurrent tumor showed a large, lytic, destructive lesion of the right pelvic bones and femur, with a pathologic fracture of the latter, a large pelvic soft tissue mass, and multiple pulmonary metastases. Biopsy tissue showed typical features of chondroblastoma, but also increased nuclear atypia, hyperchromasia, and pleomorphism, compared to the original tumor, and, most significantly, abnormal mitotic figures. Immunohistochemical studies of the recurrent tumor revealed p53 mutation and extensive proliferative activity, and flow cytometric studies showed DNA aneuploidy, none of which was present in the original tumor. The patient received chemotherapy and radiation, but died of disease eight months after presentation. We also review chondroblastoma in general, to assign this unusual lesion to a tumor subtype.

  15. Surgical treatment and clinical outcome of nonfunctional pancreatic neuroendocrine tumors: a 14-year experience from one single center.

    PubMed

    Yang, Min; Zeng, Lin; Zhang, Yi; Su, An-Ping; Yue, Peng-Ju; Tian, Bo-le

    2014-11-01

    Our primary aim of the present study was to analyze the clinical characteristics and surgical outcome of nonfunctional pancreatic neuroendocrine tumors (non-F-P-NETs), with an emphasis on evaluating the prognostic value of the newly updated 2010 grading classification of the World Health Organization (WHO).Data of 55 consecutive patients who were surgically treated and pathologically diagnosed as non-F-P-NETs in our single institution from January 2000 to December 2013 were retrospectively collected.This entirety comprised of 55 patients (31 males and 24 females), with a mean age of 51.24 ± 12.95 years. Manifestations of non-F-P-NETs were nonspecific. Distal pancreatectomy, pancreaticoduodenectomy, and local resection of pancreatic tumor were the most frequent surgical procedures, while pancreatic fistula was the most common but acceptable complication (30.3%). The overall 5-year survival rate of this entire cohort was 41.0%, with a median survival time of 60.4 months. Patients who underwent R0 resections obtained a better survival than those who did not (P < 0.005). As for the prognostic analysis, tumor size and lymph invasion were only statistically significant in univariate analysis (P = 0.046 and P < 0.05, respectively), whereas the newly updated 2010 grading classification of WHO (G1 and G2 vs G3), distant metastasis, and surgical margin were all meaningful in both univariate and multivariate analysis (P = 0.045, 0.001, and 0.042, respectively).Non-F-P-NETs are a kind of rare neoplasm, with mostly indolent malignancy. Patients with non-F-P-NETs could benefit from the radical resections. The new WHO criteria, distant metastasis and surgical margin, might be independent predictors for the prognosis of non-F-P-NETs. PMID:25396335

  16. Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer.

    PubMed

    Takai, Erina; Totoki, Yasushi; Nakamura, Hiromi; Morizane, Chigusa; Nara, Satoshi; Hama, Natsuko; Suzuki, Masami; Furukawa, Eisaku; Kato, Mamoru; Hayashi, Hideyuki; Kohno, Takashi; Ueno, Hideki; Shimada, Kazuaki; Okusaka, Takuji; Nakagama, Hitoshi; Shibata, Tatsuhiro; Yachida, Shinichi

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. The genomic landscape of the PDAC genome features four frequently mutated genes (KRAS, CDKN2A, TP53, and SMAD4) and dozens of candidate driver genes altered at low frequency, including potential clinical targets. Circulating cell-free DNA (cfDNA) is a promising resource to detect and monitor molecular characteristics of tumors. In the present study, we determined the mutational status of KRAS in plasma cfDNA using multiplex picoliter-droplet digital PCR in 259 patients with PDAC. We constructed a novel modified SureSelect-KAPA-Illumina platform and an original panel of 60 genes. We then performed targeted deep sequencing of cfDNA and matched germline DNA samples in 48 patients who had ≥1% mutant allele frequencies of KRAS in plasma cfDNA. Importantly, potentially targetable somatic mutations were identified in 14 of 48 patients (29.2%) examined by targeted deep sequencing of cfDNA. We also analyzed somatic copy number alterations based on the targeted sequencing data using our in-house algorithm, and potentially targetable amplifications were detected. Assessment of mutations and copy number alterations in plasma cfDNA may provide a prognostic and diagnostic tool to assist decisions regarding optimal therapeutic strategies for PDAC patients. PMID:26669280

  17. Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer

    PubMed Central

    Takai, Erina; Totoki, Yasushi; Nakamura, Hiromi; Morizane, Chigusa; Nara, Satoshi; Hama, Natsuko; Suzuki, Masami; Furukawa, Eisaku; Kato, Mamoru; Hayashi, Hideyuki; Kohno, Takashi; Ueno, Hideki; Shimada, Kazuaki; Okusaka, Takuji; Nakagama, Hitoshi; Shibata, Tatsuhiro; Yachida, Shinichi

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. The genomic landscape of the PDAC genome features four frequently mutated genes (KRAS, CDKN2A, TP53, and SMAD4) and dozens of candidate driver genes altered at low frequency, including potential clinical targets. Circulating cell-free DNA (cfDNA) is a promising resource to detect and monitor molecular characteristics of tumors. In the present study, we determined the mutational status of KRAS in plasma cfDNA using multiplex picoliter-droplet digital PCR in 259 patients with PDAC. We constructed a novel modified SureSelect-KAPA-Illumina platform and an original panel of 60 genes. We then performed targeted deep sequencing of cfDNA and matched germline DNA samples in 48 patients who had ≥1% mutant allele frequencies of KRAS in plasma cfDNA. Importantly, potentially targetable somatic mutations were identified in 14 of 48 patients (29.2%) examined by targeted deep sequencing of cfDNA. We also analyzed somatic copy number alterations based on the targeted sequencing data using our in-house algorithm, and potentially targetable amplifications were detected. Assessment of mutations and copy number alterations in plasma cfDNA may provide a prognostic and diagnostic tool to assist decisions regarding optimal therapeutic strategies for PDAC patients. PMID:26669280

  18. [Predictors of malignancy in the management of parotid tumors: about 76 cases].

    PubMed

    Bouaity, Brahim; Darouassi, Youssef; Chihani, Mehdi; Touati, Mohamed Mliha; Ammar, Haddou

    2016-01-01

    Salivary gland tumor pathology is complex and poses a diagnostic and therapeutic problem. A good analysis of predictive factors for malignancy in parotid tumors seems currently necessary for better therapeutic planning. The aim of this study was to investigate the predictive factors for malignancy in parotid tumors through a retrospective study of 76 cases of parotid tumor treated in a service of Otorhinolaryngology and Cervico Facial Surgery of Avicenne military hospital of Marrakech between January 2000 and December 2012. The study involved 40 women and 36 men. The average age was 44 years for benign tumours whereas it was 50 years for malignant tumours. The median of consultation time was 24 months for benign tumors and 16 month for malignant tumours. Swelling in the area of the parotid was always a patient detecting sign. Malignancy is clinically suspected based on pain, facial paralysis, surface structure and deeper structure fixity and on the presence of adenopathy. MRI has become the methodology of choice for evaluating parotid tumors due to its good diagnostic value in the assessment of benignity and malignancy. Fine needle aspiration biopsy has no value unless it is positive. Explorative parotidectomy with extemporaneous anatomopathological examination remains the key to positive diagnosis. Parotid benign tumors represent the most frequent entity (80%) and pleomorphic adenoma remains the predominant histologic type (61%). With regard to malignant tumors, they are rare, mainly dominated by mucoepidermoid carcinomas (6,5%). Surgical treatment is the first choice and it is often associated with lymph node dissection and radiation therapy for malignant tumors. Facial paralysis is the most common complication of parotid surgery. PMID:27279939

  19. [Predictors of malignancy in the management of parotid tumors: about 76 cases].

    PubMed

    Bouaity, Brahim; Darouassi, Youssef; Chihani, Mehdi; Touati, Mohamed Mliha; Ammar, Haddou

    2016-01-01

    Salivary gland tumor pathology is complex and poses a diagnostic and therapeutic problem. A good analysis of predictive factors for malignancy in parotid tumors seems currently necessary for better therapeutic planning. The aim of this study was to investigate the predictive factors for malignancy in parotid tumors through a retrospective study of 76 cases of parotid tumor treated in a service of Otorhinolaryngology and Cervico Facial Surgery of Avicenne military hospital of Marrakech between January 2000 and December 2012. The study involved 40 women and 36 men. The average age was 44 years for benign tumours whereas it was 50 years for malignant tumours. The median of consultation time was 24 months for benign tumors and 16 month for malignant tumours. Swelling in the area of the parotid was always a patient detecting sign. Malignancy is clinically suspected based on pain, facial paralysis, surface structure and deeper structure fixity and on the presence of adenopathy. MRI has become the methodology of choice for evaluating parotid tumors due to its good diagnostic value in the assessment of benignity and malignancy. Fine needle aspiration biopsy has no value unless it is positive. Explorative parotidectomy with extemporaneous anatomopathological examination remains the key to positive diagnosis. Parotid benign tumors represent the most frequent entity (80%) and pleomorphic adenoma remains the predominant histologic type (61%). With regard to malignant tumors, they are rare, mainly dominated by mucoepidermoid carcinomas (6,5%). Surgical treatment is the first choice and it is often associated with lymph node dissection and radiation therapy for malignant tumors. Facial paralysis is the most common complication of parotid surgery.

  20. PIM kinases: an overview in tumors and recent advances in pancreatic cancer.

    PubMed

    Xu, Jianwei; Zhang, Taiping; Wang, Tianxiao; You, Lei; Zhao, Yupei

    2014-04-01

    The PIM kinases represent a family of serine/threonine kinases, which is composed of three different members (PIM1, PIM2 and PIM3). Aberrant expression of PIM kinases is observed in variety of tumors, including pancreatic cancer. The PIM kinases play pivotal roles in the regulation of cell cycle, apoptosis, properties of stem cells, metabolism, autophagy, drug resistance and targeted therapy. The roles of PIM kinases in pancreatic cancer include the regulation of proliferation, apoptosis, cell cycle, formation, angiogenesis and prediction prognosis. Blocking the activities of PIM kinases could prevent pancreatic cancer development. PIM kinases may be a novel target for cancer therapy. PMID:24799066

  1. Harmonic motion imaging for abdominal tumor detection and high-intensity focused ultrasound ablation monitoring: an in vivo feasibility study in a transgenic mouse model of pancreatic cancer.

    PubMed

    Chen, Hong; Hou, Gary Y; Han, Yang; Payen, Thomas; Palermo, Carmine F; Olive, Kenneth P; Konofagou, Elisa E

    2015-09-01

    Harmonic motion imaging (HMI) is a radiationforce- based elasticity imaging technique that tracks oscillatory tissue displacements induced by sinusoidal ultrasonic radiation force to assess the resulting oscillatory displacement denoting the underlying tissue stiffness. The objective of this study was to evaluate the feasibility of HMI in pancreatic tumor detection and high-intensity focused ultrasound (HIFU) treatment monitoring. The HMI system consisted of a focused ultrasound transducer, which generated sinusoidal radiation force to induce oscillatory tissue motion at 50 Hz, and a diagnostic ultrasound transducer, which detected the axial tissue displacements based on acquired radio-frequency signals using a 1-D cross-correlation algorithm. For pancreatic tumor detection, HMI images were generated for pancreatic tumors in transgenic mice and normal pancreases in wild-type mice. The obtained HMI images showed a high contrast between normal and malignant pancreases with an average peak-to-peak HMI displacement ratio of 3.2. Histological analysis showed that no tissue damage was associated with HMI when it was used for the sole purpose of elasticity imaging. For pancreatic tumor ablation monitoring, the focused ultrasound transducer was operated at a higher acoustic power and longer pulse length than that used in tumor detection to simultaneously induce HIFU thermal ablation and oscillatory tissue displacements, allowing HMI monitoring without interrupting tumor ablation. HMI monitoring of HIFU ablation found significant decreases in the peak-to-peak HMI displacements before and after HIFU ablation with a reduction rate ranging from 15.8% to 57.0%. The formation of thermal lesions after HIFU exposure was confirmed by histological analysis. This study demonstrated the feasibility of HMI in abdominal tumor detection and HIFU ablation monitoring.

  2. Harmonic Motion Imaging for Abdominal Tumor Detection and High-intensity Focused Ultrasound Ablation Monitoring: A Feasibility Study in a Transgenic Mouse Model of Pancreatic Cancer

    PubMed Central

    Chen, Hong; Hou, Gary Y.; Han, Yang; Payen, Thomas; Palermo, Carmine F.; Olive, Kenneth P.; Konofagou, Elisa E.

    2015-01-01

    Harmonic motion imaging (HMI) is a radiation force-based elasticity imaging technique that tracks oscillatory tissue displacements induced by sinusoidal ultrasonic radiation force to assess relative tissue stiffness. The objective of this study was to evaluate the feasibility of HMI in pancreatic tumor detection and high-intensity focused ultrasound (HIFU) treatment monitoring. The HMI system consisted of a focused ultrasound transducer, which generated sinusoidal radiation force to induce oscillatory tissue motion at 50 Hz, and a diagnostic ultrasound transducer, which detected the axial tissue displacements based on acquired radiofrequency signals using a 1D cross-correlation algorithm. For pancreatic tumor detection, HMI images were generated for pancreatic tumors in transgenic mice and normal pancreases in wild-type mice. The obtained HMI images showed a high contrast between normal and malignant pancreases with an average peak-to-peak HMI displacement ratio of 3.2. Histological analysis showed that no tissue damage was associated with HMI when it was used for the sole purpose of elasticity imaging. For pancreatic tumor ablation monitoring, the focused ultrasound transducer was operated with a higher acoustic power and longer pulse length than that used in tumor detection to simultaneously induce HIFU thermal ablation and oscillatory tissue displacements, allowing HMI monitoring without interrupting tumor ablation. HMI monitoring of HIFU ablation found significant decreases in the peak-to-peak HMI displacements before and after HIFU ablation with a reduction rate ranging from 15.8% to 57.0%. The formation of thermal lesions after HIFU exposure was confirmed by histological analysis. This study demonstrated the feasibility of HMI in abdominal tumor detection and HIFU ablation monitoring. PMID:26415128

  3. Capacity of tumor necrosis factor to augment lymphocyte-mediated tumor cell lysis of malignant mesothelioma

    SciTech Connect

    Bowman, R.V.; Manning, L.S.; Davis, M.R.; Robinson, B.W. )

    1991-01-01

    Recombinant human tumor necrosis factor (rHuTNF) was evaluated both for direct anti-tumor action against human malignant mesothelioma and for its capacity to augment the generation and lytic phases of lymphocyte-mediated cytotoxicity against this tumor. rHuTNF was directly toxic by MTT assay to one of two mesothelioma cell lines evaluated, but had no effect on susceptibility to subsequent lymphocyte-mediated lysis of either line. TNF alone was incapable of generating anti-mesothelioma lymphokine-activated killer cell (LAK) activity. Furthermore, it did not augment the degree or LAK activity produced by submaximal interleukin-2 (IL-2) concentrations nor did it augment lysis of mesothelioma cells by natural killer (NK) or LAK effector cells during the 4-hr 51chromium release cytolytic reaction. The studies also suggest that mesothelioma targets are less responsive to TNF plus submaximal IL-2 concentrations than the standard LAK sensitive target Daudi, raising the possibility that intermediate LAK sensitive tumors such as mesothelioma may require separate and specific evaluation in immunomodulation studies. This in vitro study indicates that use of low-dose rHuTNF and IL-2 is unlikely to be an effective substitute for high-dose IL-2 in generation and maintenance of LAK activity in adoptive immunotherapy for mesothelioma.

  4. Molecular beacon imaging of tumor marker gene expression in pancreatic cancer cells.

    PubMed

    Yang, Lily; Cao, Zehong; Lin, Yiming; Wood, William C; Staley, Charles A

    2005-05-01

    We have developed a fluorescence imaging-based approach to detect expression of tumor marker genes in pancreatic cancer cells using molecular beacons (MBs). MBs are short hairpin oligonucleotide probes that bind to specific oligonucleotide sequences and produce fluorescent signals. MBs targeting transcripts of two tumor marker genes, mutant K-ras and survivin, were synthesized and their specificity in detection of the expression of those genes in pancreatic cancer cells was examined. We found that K-ras MBs differentially bind to mutant K-ras mRNAs, resulting in strong fluorescent signals in pancreatic cancer cells with specific mutant K-ras genes but not in normal cells or cancer cells expressing either wild type or a different mutation of the K-ras gene. Additionally, MBs targeting survivin mRNA produced a bright fluorescent signal specifically in pancreatic cancer cells. We also demonstrated that MBs labeled with different fluorophores could detect survivin and mutant K-ras mRNAs simultaneously in single cancer cells. Furthermore, we showed that survivin and K-ras MBs have a high specificity in identifying cancer cells on frozen sections of pancreatic cancer tissues. In conclusion, molecular beacon-based imaging of expression of tumor marker genes has potential for the development of novel approaches for the detection of pancreatic cancer cells.

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

    PubMed

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

    2015-01-01

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

  6. High ROR2 expression in tumor cells and stroma is correlated with poor prognosis in pancreatic ductal adenocarcinoma

    PubMed Central

    Huang, Jianfei; Fan, Xiangjun; Wang, Xudong; Lu, Yuhua; Zhu, Huijun; Wang, Wei; Zhang, Shu; Wang, Zhiwei

    2015-01-01

    RTK-like orphan receptor 2 (ROR2) is overexpressed in several cancers and has tumorigenic activity. However, the expression of ROR2 and its functional and prognostic significance have yet to be evaluated in pancreatic ductal adenocarcinoma (PDAC). Quantitative real-time polymerase chain reaction was used to characterize the expression of ROR2 mRNA in PDAC, corresponding peritumoral tissues, and PDAC cell lines. Immunohistochemical analysis with tissue microarrays was used to evaluate ROR2 expression in PDAC and to investigate the relationship of this expression to clinicopathological factors and prognosis. The expression of ROR2 mRNA and protein was significantly higher in PDAC than in normal pancreatic tissues. High cytoplasmic ROR2 expression in cancer cells was significantly associated with a primary tumor, distant metastasis, and TNM stage, and high stromal ROR2 expression was significantly associated with regional lymph node metastasis and TNM stage. The Kaplan–Meier method and Cox regression analyses showed that high ROR2 expression in tumor cytoplasm or stromal cells was significantly associated with malignant attributes and reduced survival in PDAC. We present strong evidence that ROR2 could be used as an indicator of poor prognosis and could represent a novel therapeutic target for PDAC. PMID:26259918

  7. Secondary malignant giant-cell tumor of bone. Clinicopathological assessment of nineteen patients

    SciTech Connect

    Rock, M.G.; Sim, F.H.; Unni, K.K.; Witrak, G.A.; Frassica, F.J.; Schray, M.F.; Beabout, J.W.; Dahlin, D.C.

    1986-09-01

    Twenty-six patients who had a malignant giant-cell tumor of bone--a sarcoma either juxtaposed to a zone of typical benign giant-cell tumor or occurring at the site of a previously documented benign giant-cell tumor--have been seen at the Mayo Clinic. Of the twenty-six tumors, nineteen were secondary to a previous attempt at local control of a benign giant-cell tumor. All but one of these nineteen patients with a secondary tumor had received therapeutic irradiation four to thirty-nine years earlier. The nature and duration of the symptoms and the sites of predilection of the malignant giant-cell tumors were the same as for benign giant-cell tumor. Fibrosarcoma occurred three times as frequently as osteosarcoma. The best results of treatment of the secondary sarcoma were obtained with early ablation.

  8. Benign and malignant mammary tumors induced by DMBA in female Wistar rats.

    PubMed

    Dias, M; Cabrita, S; Sousa, E; França, B; Patrício, J; Oliveira, C

    1999-01-01

    This study pretends to characterize 7, 12-dimetylbenz[a]anthracene-induced benign and malignant tumors. One hundred and twenty female Wistar rats were randomly allocated to two groups: Control Group and Induction Group; IG animals were given a single dose of DMBA and killed 24 weeks after. Other tumors besides breast tumors were diagnosed, mainly tumors of the salivary glands and ovarian benign epithelial tumors. Incidence of breast disorders was about 60%. Macroscopic mammary tumors varied in dimension from 2 mm to 55 mm. Malignant breast tumors (n = 56) were essentially invasive ductal carcinomas (91.1%), G1 (92.2%), presenting histologic characteristics of good prognosis. Predominant benign breast disorders consisted of glandular (68.6%) and atypical (20%) hyperplasias reproducing histologic types of human breast diseases. Different individual susceptibility to DMBA apparently occurs; while some rats never developed neoplasias, others exhibited several tumors.

  9. [Application of the puncture biopsy in diagnosis of malignant tumors of suprarenal glands].

    PubMed

    Komissarenko, I V; Rybakov, S I; Rodzaevskiĭ, S A; Kvacheniuk, A N

    2004-10-01

    Possibilities of application of the fine-needle aspiration puncture biopsy (FNAPB) in diagnosis of suprarenal glands tumors were studied. Of 43 patients, to whom FNAPB was performed, in 27 the suprarenal gland tumor was diagnosed, in 11--renal tumor, in 5--the puncture biopsy material occurred noninformative. Of 27 patients with tumor of suprarenal gland in 15 it was malignant, in 11--benign adenoma and cyst of suprarenal gland were revealed. FNAPB of the suprarenal gland tumor is a safe, informative and in some situations curative method. FNAPB is recommended for diagnosis of primarily revealed tumors of suprarenal glands more than 2 cm in diameter. The procedure should be performed by specially trained physician, who determines technical conditions of its conduction by himself and possesses the method o fultrasonography. Data of cytological investigationspermits to differentiate benign and malignant tumor, to determine the tumor type, what constitutes diagnostic background for the tactic choice of surgical intervention and the disease prognosis.

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

    SciTech Connect

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

    1985-05-01

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

  11. Hemostatic alterations are unrelated to the stage of tumor in untreated malignant melanoma and breast carcinoma.

    PubMed

    Mannucci, P M; Vaglini, M; Maniezzo, M; Magni, E; Mari, D; Cascinelli, N

    1985-06-01

    A study of hemostatic variables was carried out in 80 untreated patients with breast adenocarcinoma or malignant melanoma, chosen as examples of tumors that can be accurately staged for localization or spread. The most marked abnormalities were high levels of clotting factors V and VIII, plasminogen, von Willebrand factor and fibrogen-fibrin degradation products. These abnormalities occurred in both types of tumors, albeit slightly more markedly in melanomas, and were also present in localized tumors. Our data indicate that in tumors, abnormalities of the hemostatic system are an early phenomenon unrelated to the presence of widespread malignancy.

  12. Malignant Potential of Murine Stromal Cells after Transplantation of Human Tumors into Nude Mice

    NASA Astrophysics Data System (ADS)

    Goldenberg, David M.; Pavia, Rose A.

    1981-04-01

    Human malignant cancer tumors grafted into nude mice produce tumors containing both human cancer cells and the host's stromal cells. After short-term propagation of these tumors in vitro, the murine mesenchymal cells appear transformed and are tumorigenic in nude mice. However, established human cancer cell lines fail to similarly alter adjacent murine stromal cells when used to produce tumors in nude mice. These experiments suggest that cancer cells may recruit normal cells to become malignant, qualifying the view of the clonal (unicellular) origin of cancer.

  13. A recurrent solitary fibrous tumor of the thigh with malignant transformation: A case report

    PubMed Central

    Yoshimura, Yasuo; Sano, Kenji; Isobe, Ken-ichi; Aoki, Kaoru; Kito, Munehisa; Kato, Hiroyuki

    2016-01-01

    Introduction We describe an unusual case of a uniformly high-grade malignant solitary fibrous tumor (SFT) of the thigh with recurrence after wide resection in a 31-year-old man. Presentation of case Our current case showed a long-term benign course before the operation, although the subcutaneous tumor was larger than 10 cm at presentation. The SFT was diagnosed by needle biopsy, and wide resection was performed. Histological findings showed proliferation of capillaries surrounded by masses of spindle-shaped cells without any cytologic atypia, and the percentage of MIB-1-positive nuclei was 2.1%. However, a rapidly enlarging recurrent tumor was observed 11 months after the operation. A second wide resection for the recurrent tumor was performed. Histologically, the tumor cells uniformly displayed significant cytologic atypia and pleomorphism, and had 40–50 mitoses per 10 high-power fields. The proportion of MIB-1-positive nuclei was 48%. Consequently, the tumor was diagnosed as a SFT with malignant transformation. Discussion The malignant transformation described in past studies showed high-grade areas within benign, low-grade, or intermediate-grade SFTs. Therefore, in contrast to our case, uniformly high-grade malignant histological findings at recurrence were not described. Conclusion Even if a tumor is non-malignant during the clinical course, as confirmed by tissue biopsy, the possibility of tumor progression to high-grade sarcoma at recurrence should be considered, and the treatment strategy should be determined carefully. PMID:26967903

  14. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast.

    PubMed

    Gatalica, Zoran; Vranic, Semir; Ghazalpour, Anatole; Xiu, Joanne; Ocal, Idris Tolgay; McGill, John; Bender, Ryan P; Discianno, Erin; Schlum, Aaron; Sanati, Souzan; Palazzo, Juan; Reddy, Sandeep; Pockaj, Barbara

    2016-01-12

    Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin-2, VCAM1, PDGFRA, and PTTG1. EGFR protein overexpression was observed in 26/27 (96%) of cases with amplification of the EGFR gene in 8/24 (33%) cases. Two EGFR mutations were identified including EGFRvIII and a presumed pathogenic V774M mutation, respectively. The most common pathogenic mutations included TP53 (50%) and PIK3CA (15%). Cases with matched primary and metastatic tumors harbored identical mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Tumor expression of PD-L1 immunoregulatory protein was observed in 3/22 (14%) of cases. Overexpression of molecular biomarkers of increased angiogenesis, EGFR and immune checkpoints provides novel targeted therapy options in malignant phyllodes tumors of the breast.

  15. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast

    PubMed Central

    Gatalica, Zoran; Vranic, Semir; Ghazalpour, Anatole; Xiu, Joanne; Ocal, Idris Tolgay; McGill, John; Bender, Ryan P.; Discianno, Erin; Schlum, Aaron; Sanati, Souzan; Palazzo, Juan; Reddy, Sandeep; Pockaj, Barbara

    2016-01-01

    Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin-2, VCAM1, PDGFRA, and PTTG1. EGFR protein overexpression was observed in 26/27 (96%) of cases with amplification of the EGFR gene in 8/24 (33%) cases. Two EGFR mutations were identified including EGFRvIII and a presumed pathogenic V774M mutation, respectively. The most common pathogenic mutations included TP53 (50%) and PIK3CA (15%). Cases with matched primary and metastatic tumors harbored identical mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Tumor expression of PD-L1 immunoregulatory protein was observed in 3/22 (14%) of cases. Overexpression of molecular biomarkers of increased angiogenesis, EGFR and immune checkpoints provides novel targeted therapy options in malignant phyllodes tumors of the breast. PMID:26625196

  16. Extrathoracic solitary fibrous tumor of the pelvic peritoneum with central malignant degeneration on CT and MRI.

    PubMed

    Vossough, Arastoo; Torigian, Drew A; Zhang, Paul J; Siegelman, Evan S; Banner, Marc P

    2005-11-01

    We describe a 61-year-old man who presented with an extrathoracic solitary fibrous tumor (SFT) of the pelvic peritoneum with central malignant degeneration as seen on computed tomography (CT), magnetic resonance imaging (MRI), and histopathology. When a central focus of heterogeneity and variable contrast enhancement are identified within a fibrous tumor of the pelvis on CT or MRI, malignant degeneration of an extrathoracic SFT, although rare, should be considered as a diagnostic possibility.

  17. A Prospective, Multi-Institutional Study of Adjuvant Radiotherapy After Resection of Malignant Phyllodes Tumors

    PubMed Central

    Barth, Richard J.; Wells, Wendy A.; Mitchell, Sandra E.; Cole, Bernard F.

    2016-01-01

    Background Malignant phyllodes tumors of the breast are unusual neoplasms, with an incidence of approximately 500 cases annually in the United States. Published local recurrence rates after margin-negative breast-conserving resections of borderline malignant and malignant phyllodes tumors are unacceptably high, at 24 and 20%, respectively. It is uncertain whether radiotherapy after resection of phyllodes tumors is beneficial. Methods We prospectively enrolled patients who were treated with a margin-negative breast-conserving resection of borderline malignant or malignant phyllodes tumors to adjuvant radiotherapy. The primary endpoint was local recurrence. Results Forty-six women were treated at 30 different institutions. The mean patient age was 49 years (range, 18–76 years). Thirty patients (65%) had malignant phyllodes tumors; the rest were borderline malignant. The mean tumor diameter was 3.7 cm (range, .8–11 cm). Eighteen patients had a negative margin on the first excision. The median size of the negative margin was .35 cm (range, <.1–2 cm). Twenty-eight patients underwent a re-excision because of positive margins in the initial resection. Two patients died of metastatic phyllodes tumor. During a median follow-up of 56 months (range, 12–129 months), none of the 46 patients developed a local recurrence (local recurrence rate, 0%; 95% confidence interval, 0–8). Conclusions Margin-negative resection combined with adjuvant radiotherapy is very effective therapy for local control of borderline and malignant phyllodes tumors. The local recurrence rate with adjuvant radiotherapy was significantly less than that observed in reported patients treated with margin-negative resection alone. PMID:19424757

  18. Divergent differentiation in malignant soft tissue neoplasms: the paradigm of liposarcoma and malignant peripheral nerve sheath tumor.

    PubMed

    Pytel, Peter; Taxy, Jerome B; Krausz, Thomas

    2005-01-01

    In tumors clonality does not always translate into morphologic uniformity. While most sarcomas exhibit only one line of histologic differentiation, a minority may display a strikingly diverse phenotype in addition to the main lineage. This phenomenon not only presents a diagnostic problem but also raises questions about the commitment of tumor cells toward a specific phenotype. Among sarcomas, malignant peripheral nerve sheath tumor (MPNST) and dedifferentiated liposarcoma are two entities in which divergent differentiation is a relatively frequent event. Diagnostically it is crucial to recognize the "primary" sarcoma in such tumors correctly and distinguish it from the "secondary" divergent elements. The presence of the latter could be the first morphologic clue to a specific sarcoma type. Even though it may be difficult to explain the pathogenesis of divergent differentiation, divergence still illustrates that the phenotype of a tumor cell is not set in stone but can be modulated or switched by a number of factors.

  19. The Tumor Suppressor rpl36 Restrains KRASG12V-Induced Pancreatic Cancer

    PubMed Central

    Provost, Elayne; Bailey, Jennifer M.; Aldrugh, Sumar; Liu, Shu; Iacobuzio-Donahue, Christine

    2014-01-01

    Abstract Ribosomal proteins are known to be required for proper assembly of mature ribosomes. Recent studies indicate an additional role for ribosomal proteins as candidate tumor suppressor genes. Pancreatic acinar cells, recently identified as effective cells of origin for pancreatic adenocarcinoma, display especially high-level expression of multiple ribosomal proteins. We, therefore, functionally interrogated the ability of two ribosomal proteins, rpl36 and rpl23a, to alter the response to oncogenic Kras in pancreatic acinar cells using a newly established model of zebrafish pancreatic cancer. These studies reveal that rpl36, but not rpl23a, acts as a haploinsufficient tumor suppressor, as manifested by more rapid tumor progression and decreased survival in rpl36hi1807/+;ptf1a:gal4VP16Tg;UAS:GFP-KRASG12V fish compared with their rpl36+/+;ptf1a:gal4VP16;UAS:GFP-KRASG12V siblings. These results suggest that rpl36 may function as an effective tumor suppressor during pancreatic tumorigenesis. PMID:25380065

  20. WT1 immunoprofiling and comparison of malignant Mullerian mixed tumors of the female genital tract.

    PubMed

    Franko, Angela; Magliocco, Anthony M; Duan, Quili; Duggan, Máire A

    2010-09-01

    A malignant Mullerian mixed tumor (MMMT) is a biphasic homologous or heterologous malignancy of the female genital tract. WT1 (Wilms tumor 1) is both a tumor suppressor gene and oncogene overexpressed in the nuclei of some gynecologic carcinomas. Expression in MMMT is incompletely described. Whole sections from 16 MMMTs were stained with WT1 (N terminus) using a standard immunoperoxidase technique. There were 7 heterologous and 9 homologous tumors and 10 were endometrial, 5 were ovarian, and 1 was of peritoneal origin. The tissue and cell staining pattern and score (intensity by amount) were evaluated and correlated with the tumor subtype and anatomic location. Among the 16 tumors, 81.3% showed mostly stromal and cytoplasmic staining and a score of 3 or 6. Staining was positive in 80% of the endometrial and ovarian tumors and the 1 peritoneal tumor and in all heterologous and 66.7% of the homologous tumors. The immunoprofile correlated with tumor subtype but not with anatomic location. Stromal and epithelial staining was more frequent (83.3%) in homologous tumors and differed significantly (P=0.009) from the heterologous types where stromal staining prevailed (85.7%). MMMT is another genital tract malignancy which can over express WT1 and the immunoprofile may assist in tumor subtyping.

  1. Malignant mixed salivary tumor presenting as a mandibular metastasis.

    PubMed

    Mellor, T K; Scott, J

    1985-11-01

    A rare case of a central mandibular metastatic mixed salivary gland tumor is reported which presented following a 45-year history of recurrent benign mixed salivary gland tumor of the parotid gland on the same side. The mandibular tumor included a predominantly benign mixed salivary gland component as well as frankly invasive adenocarcinoma. The clinicopathologic features of the mandibular and residual parotid tumors suggested that the metastatic event may have occurred prior to the development of frank carcinoma in the parotid tumor.

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

    PubMed Central

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

    2013-01-01

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

  3. [Extracting and study of biochemical properties of thiamine pyrophosphokinase from non-malignant and tumor tissue of myometrium].

    PubMed

    Orishaka, O V; Vovchuk, I L; Petrov, S A

    2014-01-01

    The method of extraction and purification of thiamine pyrophosphokinase from non-malignant and tumor tissue of myometrium has been elaborated. Kinetic characteristics of T-kinase from non-malignant and tumor tissue of women myometrium have been studied. It has been shown, that malignization of myometrium is accompanied by a decrease in affinity of thiamine pyrophosphokinase from tumor to thiamine and by an increase in sensitivity of the enzyme from tumor to thiochrome.

  4. Genetic methylation and lymphoid malignancies: biomarkers of tumor progression and targeted therapy

    PubMed Central

    2013-01-01

    Lymphoid malignancies, mainly including lymphocytic leukemia and lymphoma, are a group of heterogeneous diseases. Although the clinical outcome of patients has been significantly improved with current immuno-chemotherapy, definitive biomarkers remain to be investigated, particularly those reflecting the malignant behavior of tumor cells and those helpful for developing optimal targeted therapy. Recently, genome-wide analysis reveals that altered genetic methylations play an important role in tumor progression through regulation of multiple cellular transduction pathways. This review describes the pathogenetic effect of the aberrant genetic methylation in lymphoid malignancies, with special emphasis on potential therapeutic strategies targeting key signaling networks. PMID:24252620

  5. Solitary fibrous tumor: histological and immunohistochemical spectrum of benign and malignant variants presenting at different sites.

    PubMed

    Hanau, C A; Miettinen, M

    1995-04-01

    Twenty-nine tumors (from 26 patients, including two with recurrent disease) diagnosed as solitary fibrous tumor (SFT) of the pleura (n = 23), mediastinum (n = 4), abdominal cavity (n = 1), and parotid gland (n = 1) were studied immunohistochemically. Three histologically malignant tumors showed areas of high cellularity and mitotic activity (more than 4 mitoses/10 high-power fields) with features resembling malignant fibrous histiocytoma, malignant hemangiopericytoma, or fibrosarcoma, together with areas typical of benign solitary fibrous tumor. Formaldehyde-fixed, paraffin-embedded tissues and avidin-biotin-complex immunostaining were used. All of the tumors showed vimentin positivity and did not stain for cytokeratin, glial fibrillary acidic protein, or muscle cell markers, except for focal desmin reactivity in seven tumors, mostly seen in frozen sections, and focal keratin reactivity in one histologically malignant tumor. The neoplastic cells were positive for CD34 and negative for CD31; these patterns also were seen in the three histologically malignant cases. In nine of the cases acetone-fixed frozen sections showed variable focal positivity for neurofilament proteins of 68 kd. We conclude that SFT is a neoplasm of fibroblasts/primitive mesenchymal cells with features of multidirectional differentiation. We also report the finding of a novel site for SFT, the parotid gland.

  6. Distinct Malignant Behaviors of Mouse Myogenic Tumors Induced by Different Oncogenetic Lesions

    PubMed Central

    Hettmer, Simone; Bronson, Roderick T.; Wagers, Amy J.

    2015-01-01

    Rhabdomyosarcomas (RMS) are heterogeneous cancers with myogenic differentiation features. The cytogenetic and mutational aberrations in RMS are diverse. This study examined differences in the malignant behavior of two genetically distinct and disease-relevant mouse myogenic tumor models. Kras; p1619null myogenic tumors, initiated by expression of oncogenic Kras in p16p19null mouse satellite cells, were metastatic to the lungs of the majority of tumor-bearing animals and repopulated tumors in seven of nine secondary recipients. In contrast, SmoM2 tumors, initiated by ubiquitous expression of a mutant Smoothened allele, did not metastasize and repopulated tumors in 2 of 18 recipients only. In summary, genetically distinct myogenic tumors in mice exhibit marked differences in malignant behavior. PMID:25759794

  7. Metachronous Malignant Solitary Fibrous Tumor of Kidney: Case Report and Review of Literature.

    PubMed

    Cheung, Felix; Talanki, Varun R; Liu, Jingxuan; Davis, James E; Waltzer, Wayne C; Corcoran, Anthony T

    2016-01-01

    Solitary fibrous tumors are well described in the pleura, but rare extra-pleural neoplasms have been reported. We describe a patient with a solitary left renal fibrous tumor who after undergoing a nephrectomy, presented 8 years later with a contralateral metachronous solitary fibrous tumor. Malignant metastatic extra-pleural solitary fibrous tumors are extremely rare, and to our knowledge, this is the first case of contralateral recurrence of solitary renal fibrous tumor. The patient underwent a robotic assisted partial nephrectomy of the right renal mass. Both tumors showed overlapping histopathology.

  8. Metachronous Malignant Solitary Fibrous Tumor of Kidney: Case Report and Review of Literature.

    PubMed

    Cheung, Felix; Talanki, Varun R; Liu, Jingxuan; Davis, James E; Waltzer, Wayne C; Corcoran, Anthony T

    2016-01-01

    Solitary fibrous tumors are well described in the pleura, but rare extra-pleural neoplasms have been reported. We describe a patient with a solitary left renal fibrous tumor who after undergoing a nephrectomy, presented 8 years later with a contralateral metachronous solitary fibrous tumor. Malignant metastatic extra-pleural solitary fibrous tumors are extremely rare, and to our knowledge, this is the first case of contralateral recurrence of solitary renal fibrous tumor. The patient underwent a robotic assisted partial nephrectomy of the right renal mass. Both tumors showed overlapping histopathology. PMID:26793578

  9. Basic FGF and Ki-67 proteins useful for immunohistological diagnostic evaluations in malignant solitary fibrous tumor.

    PubMed

    Sun, Yuliang; Naito, Zenya; Ishiwata, Toshiyuki; Maeda, Shotaro; Sugisaki, Yuichi; Asano, Goro

    2003-05-01

    Solitary fibrous tumor (SFT) is an uncommon soft tissue tumor initially reported in the pleura but recently described in other sites in the body. Morphological distinction between benign and malignant SFT is often difficult. An immunohistochemical study was performed in pleural and extrapleural sites. The aim of this study was to determine if an immunohistochemical method is helpful in distinguishing benign SFT from malignant SFT, and providing valid information to predict the prognosis associated with malignant SFT. Twenty-four cases of benign (14 patients) and malignant (10 patients) SFT in the pleura, pelvic space, prostate and other sites of soft tissue were analyzed. Tumors from 10 patients were diagnosed as malignant on the basis of markedly increased cellularity, mitotic activity (>4/10 high-power fields), nuclear pleomorphism and areas of necrosis. Immunohistochemically, we found a mean basic fibroblast growth factor (bFGF) labeling index of 48.67% (48.67 +/- 8.52%) for benign SFT and 74.5% (74.5 +/- 6.92%) for malignant SFT (P < 0.05). We also found a mean Ki-67 labeling index of 1.9% (1.9 +/- 0.43%) for benign SFT and 6.11% (6.11 +/- 1.05%) for malignant SFT (P < 0.05). Our results suggest that bFGF and Ki-67 are diagnostically relevant to the evaluation of malignant SFT and these proteins are thought to be potentially useful markers for prognosis of SFT.

  10. Infrared absorption spectra of human malignant tumor tissues

    NASA Astrophysics Data System (ADS)

    Skornyakov, I. V.; Tolstorozhev, G. B.; Butra, V. A.

    2008-05-01

    We used infrared spectroscopy methods to study the molecular structure of tissues from human organs removed during surgery. The IR spectra of the surgical material from breast, thyroid, and lung are compared with data from histological examination. We show that in malignant neoplasms, a change occurs in the hydrogen bonds of protein macromolecules found in the tissue of the studied organs. We identify the spectral signs of malignant pathology.

  11. Mucin-producing pancreatic tumors: historical review of its nosological concept.

    PubMed

    Shimizu, M; Manabe, T

    1994-08-01

    A brief historic outline of the problem of mucin-producing pancreatic tumors is presented. Based on the authors' observations, clinical aspects and pathomorphology of these tumors have been described. The authors propose their own classification of this tumor type which is based on the literature published so far. Their classification also takes into account the localization of lesions. Reference is made to the concept described by the term "mucinous ductetatic/cystic lesions" (MDCL) and it is also pointed out that mucinous carcinoma may develop on the background of MDCL. Since the appearance of the term "mucus secreting pancreatic cancer" or "mucin-producing pancreatic tumor", many similar and/or related conditions have been described especially in Japan under the same or different names. However, there seems to be some confusion about the concept of this condition not only among clinicians but also among pathologists. In addition, another entity, mucinous cystic neoplasms of the pancreas, was proposed and may have provided some overlap with the former conditions in its concept. Furthermore, definitions of these two conditions varied according to the authors. In this paper, therefore, we review and critically analyze cases of mucin-producing pancreatic tumor (MPPT) as well as mucinous cystic neoplasm (MCN) of the pancreas, and intend to classify them under a generic term, i.e. "mucinous ductectatic/cystic lesions (MDCL) of the pancreas". PMID:7947630

  12. Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts.

    PubMed

    José, Anabel; Sobrevals, Luciano; Miguel Camacho-Sánchez, Juan; Huch, Meritxell; Andreu, Núria; Ayuso, Eduard; Navarro, Pilar; Alemany, Ramon; Fillat, Cristina

    2013-01-01

    Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p less than 0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.

  13. Intraductal Delivery of Adenoviruses Targets Pancreatic Tumors in Transgenic Ela-myc Mice and Orthotopic Xenografts

    PubMed Central

    José, Anabel; Sobrevals, Luciano; Camacho-Sánchez, Juan Miguel; Huch, Meritxell; Andreu, Núria; Ayuso, Eduard; Navarro, Pilar; Alemany, Ramon; Fillat, Cristina

    2013-01-01

    Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p<0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors. PMID:23328228

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

    PubMed Central

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

    2012-01-01

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

  15. Circulating tumor DNA as a liquid biopsy target for detection of pancreatic cancer

    PubMed Central

    Takai, Erina; Yachida, Shinichi

    2016-01-01

    Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The “liquid biopsy” addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA (ctDNA) could provide diagnostic information. In this review, we provide an overview of the current status of blood-based tests for diagnosis of pancreatic cancer and the potential utility of ctDNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ctDNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer. PMID:27784960

  16. Dasatinib in Treating Patients With Recurrent or Metastatic Malignant Salivary Gland Tumors

    ClinicalTrials.gov

    2016-05-26

    High-grade Salivary Gland Mucoepidermoid Carcinoma; Low-grade Salivary Gland Mucoepidermoid Carcinoma; Recurrent Salivary Gland Cancer; Salivary Gland Acinic Cell Tumor; Salivary Gland Adenocarcinoma; Salivary Gland Adenoid Cystic Carcinoma; Salivary Gland Anaplastic Carcinoma; Salivary Gland Malignant Mixed Cell Type Tumor; Salivary Gland Poorly Differentiated Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IV Salivary Gland Cancer

  17. TLR5 signaling, commensal microbiota and systemic tumor promoting inflammation: the three parcae of malignant progression

    PubMed Central

    Rutkowski, Melanie R; Conejo-Garcia, Jose R

    2015-01-01

    We have reported that TLR5-mediated recognition of commensal microbiota modulates systemic tumor-promoting inflammation and malignant progression of tumors at distal locations. Approximately 7–10% of the general population harbors a deleterious single nucleotide polymorphism in TLR5, implicating a novel role for genetic variation during the initiation and progression of cancer. PMID:26405577

  18. Fully Covered Self-Expandable Metal Stents for Treatment of Malignant Biliary Strictures due to Pancreatic Carcinoma

    PubMed Central

    Samie, Ahmed Abdel; Stumpf, Michael; Theilmann, Lorenz

    2012-01-01

    Background Transpapillary stents are used to treat malignant biliary strictures. However, there are different stent types and data are controversial in respect to success and complications. Recently, completely covered self-expandable metal stents (CSEMS) have become available. The aim of this study is to present a consecutive series of CSEMS placed to decompress the bile duct in malignant stenosis due to pancreatic carcinoma and to evaluate the effectiveness, complication rate and extractability of these devices. Methods We retrospectively reviewed the courses of 27 consecutive patients who received CSEMS due to malignant biliary strictures because of pancreatic carcinoma regardless of presumed resectability between January 2010 and May 2012 in our endoscopic unit. Results A total of 27 patients (12 male and 15 female) were included in the study. The mean age of the patients was 75 years. Endoscopic retrograde cholangiopancreatography (ERCP), endoscopic sphincterotomy (ES) and stent placement were successful at first attempt in all cases. The mean length of the stenosis was 20 mm. In 24 patients (89%) a stent length of 4 cm was sufficient to bridge the stenosis. In three cases a stent length of 6 cm was necessary. Drainage was achieved as monitored by a significant decrease or normalization of bilirubin in all cases (mean bilirubin 8.5 mg/dL and 1.5 mg/dL before and after stent placement respectively), 15 patients underwent surgery with pylorus preserving duodenopancreatectomy. In all patients who underwent surgery stents could be removed during the operation without difficulties. Leakage of the biliodigestive anastomosis occurred in one patient (6.6%). Four (15%) of the 27 patients developed complications related to the endoscopic procedure and/or stent placement respectively (cholecystitis in two patients, stent occlusion in one patient, and post-sphincterotomy bleeding in one patient). Conclusion The prolonged patency, extractability, and low complication rate

  19. Efficient targeting and tumor retardation effect of pancreatic adenocarcinoma up-regulated factor (PAUF)-specific RNA replacement in pancreatic cancer mouse model.

    PubMed

    Kim, Yun-Hee; Moon, Ju Young; Kim, Eun-Ok; Lee, Sang-Jin; Kang, Se Hun; Kim, Seok Ki; Heo, Kyun; Lee, Yusun; Kim, Hana; Kim, Kyung-Tae; Kim, Daehong; Song, Min Sun; Lee, Seoung-Wook; Lee, Yangsoon; Koh, Sang Seok; Kim, In-Hoo

    2014-03-28

    The soluble protein pancreatic adenocarcinoma up-regulated factor (PAUF) plays an important role in pancreatic tumor progression and has begun to attract attention as a therapeutic target for pancreatic cancer. We herein present PAUF RNA-targeting gene therapy strategies with both targeting and therapeutic function using trans-splicing ribozyme (TSR) in pancreatic cancer. We developed adenoviral PAUF-targeting TSR (Rz) containing a PAUF-specific internal guide sequence (IGS) determined by library screening. This Rz harbors suicide gene, herpes simplex virus thymidine kinase (HSV-tk) or firefly luciferase (Luc) as a transgene for 3' exon replacement of PAUF RNAs. Ad-Rz-TK, Rz harboring the HSV-tk, showed significant inhibition of tumor growth in vivo as well as PAUF-dependent cell death in vitro via a successful trans-splicing reaction. Selective induction of Rz-controlled transgene in PAUF-expressing pancreatic cancer was confirmed through noninvasive in vivo imaging; a luminescence signal from Rz harboring Luc (Ad-Rz-Luc) was detectable only in pancreatic tumor sites, not in normal mice. In addition, a [(125)I] FIAU signal reflecting thymidine kinase expression through SPECT and ex vivo biodistribution was co-localized with the tumor sites when we treated with Ad-Rz-TK in orthotopic xenograft model. Taken together, these results imply that PAUF-targeting TSR can contribute to successful targeted gene therapy for pancreatic cancer.

  20. Increased mast cell counts in benign and malignant salivary gland tumors.

    PubMed

    Jaafari-Ashkavandi, Zohreh; Ashraf, Mohammad-Javad

    2014-01-01

    Background and aims. Mast cells are one of the characteristic factors in angiogenesis, growth, and metastatic spread of tumors. The distribution and significance of mast cells in many tumors have been demonstrated. However, few studies have evaluated mast cell infiltration in salivary gland tumors. In this study, mast cell counts were evaluated in benign and malig-nant salivary gland tumors. Materials and methods. This descriptive and cross-sectional study assessed 30 cases of pleomorphic adenoma, 13 cases of adenoid cystic carcinoma, 7 cases of mucoepidermoid carcinoma (diagnosed on the basis of 2005 WHO classifica-tion), with adequate stroma in peritumoral and intratumoral areas, and 10 cases of normal salivary glands. The samples were stained with 5% diluted Giemsa solution and the average stained cell counts were calculated in 10 random microscopic fields in peri- and intra-tumoral areas. Data were analyzed by t-test and Mann-Whitney and Krusskal-Wallis tests. Results. The average mast cell counts increased in the tumors compared to normal salivary glands. There was no signifi-cant difference between benign and malignant tumors and also between different malignant tumors. Infiltration was signifi-cantly denser in peri-tumoral stroma in both tumoral groups (P = 0.001). Minor salivary glands contained significantly more numerous mast cells. Conclusion. Although mast cell counts increased in benign and malignant salivary gland tumors, there were no signifi-cant differences between the tumoral groups. Further studies are suggested to determine the type of these cells which might be useful in the assessment of biological nature of the tumor and its future treatment modality.

  1. Pancreatitis.

    PubMed

    Mitchell, R M S; Byrne, M F; Baillie, J

    2003-04-26

    In the past decade, our understanding of the genetic basis, pathogenesis, and natural history of pancreatitis has grown strikingly. In severe acute pancreatitis, intensive medical support and non-surgical intervention for complications keeps patients alive; surgical drainage (necrosectomy) is reserved for patients with infected necrosis for whom supportive measures have failed. Enteral feeding has largely replaced the parenteral route; controversy remains with respect to use of prophylactic antibiotics. Although gene therapy for chronic pancreatitis is years away, our understanding of the roles of gene mutations in hereditary and sporadic pancreatitis offers tantalising clues about the disorder's pathogenesis. The division between acute and chronic pancreatitis has always been blurred: now, genetics of the disorder suggest a continuous range of disease rather than two separate entities. With recognition of pancreatic intraepithelial neoplasia, we see that chronic pancreatitis is a premalignant disorder in some patients. Magnetic resonance cholangiopancreatography and endoscopic ultrasound are destined to replace endoscopic retrograde cholangiopancreatography for many diagnostic indications in pancreatic disease.

  2. Pancreatitis

    MedlinePlus

    ... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...

  3. Successful Preoperative Chemoembolization in the Treatment of a Giant Malignant Phyllodes Tumor.

    PubMed

    Hashimoto, Kazuki; Mimura, Hidefumi; Arai, Yasunori; Doi, Masatomo; Kojima, Yasuyuki; Tsugawa, Koichiro; Nakajima, Yasuo

    2016-07-01

    The malignant phyllodes tumor is a relatively rare neoplasm and has not previously been a therapeutic target of interventional radiology. Herein, we report a successful case of preoperative chemoembolization of a giant malignant phyllodes tumor. The objective was to achieve sufficient tumor shrinkage before surgery to avoid the requirement for skin grafting after resection. Intra-arterial epirubicin infusion and subsequent embolization with Embosphere Microspheres (BioSphere Medical, Rockland, MA, USA) was undertaken three times over the course of 6 weeks and was well tolerated. The patient underwent surgery without skin grafting. Neither local recurrence nor distant metastasis was observed at 6 months after surgery. PMID:26916453

  4. Intraductal papillary tumors of the major salivary glands: case reports of benign and malignant variants.

    PubMed

    Nagao, T; Sugano, I; Matsuzaki, O; Hara, H; Kondo, Y; Nagao, K

    2000-02-01

    Intraductal papilloma is an extremely rare benign salivary gland tumor that occurs most commonly in the minor salivary glands. To our knowledge, a malignant counterpart of intraductal papilloma has not been described previously. We report one case each of benign and malignant intraductal papillary tumors. The benign tumor occurred in the sublingual gland and was a typical example of intraductal papilloma, with the exception that we found no previously published reports of this type of tumor in this location. The other patient had a left parotid gland tumor that was architecturally similar to the intraductal papilloma, with the addition of cytologic atypia, intraductal extension, microinvasion, and lymph node metastases. This tumor was diagnosed as intraductal papillary adenocarcinoma with an invasive component. Both patients were alive and well without evidence of recurrence 2 years and 6 months (case 1) and 6 years (case 2) after surgery. Immunohistochemical examination revealed that the tumor cells resembled duct luminal cells in both cases. The 2 tumors had different immunoreactivities for carcinoembryonic antigen, p53, and Ki-67. The malignant counterpart of intraductal papilloma should be considered in the differential diagnosis of salivary gland tumors with a predominantly papillary structure, even though this tumor is extremely rare.

  5. Congenital renal tumor: metanephric adenoma, nephrogenic rest, or malignancy?

    PubMed

    Yin, Minzhi; Cai, Jiaoyang; Thorner, Paul Scott

    2015-01-01

    We report a renal tumor detected by prenatal ultrasound and resected at 2 months of age. This 9-cm, solid mass was composed of tubular and papillary structures lined by small, uniform epithelial cells. There was local invasion into renal parenchyma and a tumor deposit in a hilar lymph node. The tumor was immunopositive for WT1, pankeratin, and CD10; focally positive for CK7; and negative for EMA and TFE3. Based on morphology and immunophenotype, the favored diagnosis was metanephric adenoma over Wilms tumor, renal cell carcinoma, and nephrogenic rest. However, metanephric adenoma only occasionally occurs in children and has never been reported prenatally. Alternatively, this tumor might be a congenital Wilms tumor that differentiated completely. Although the nature of the tumor remains unconfirmed, resection appears to have been curative; the patient remains disease-free 18 months following surgery alone. PMID:25734608

  6. CRABP1 provides high malignancy of transformed mesenchymal cells and contributes to the pathogenesis of mesenchymal and neuroendocrine tumors

    PubMed Central

    Kainov, Yaroslav; Favorskaya, Irina; Delektorskaya, Vera; Chemeris, Galina; Komelkov, Andrei; Zhuravskaya, Anna; Trukhanova, Lyubov; Zueva, Elina; Tavitian, Bertrand; Dyakova, Natalya; Zborovskaya, Irina; Tchevkina, Elena

    2014-01-01

    CRABP1 (cellular retinoic acid binding protein 1) belongs to the family of fatty acid binding proteins. Retinoic acid binding is the only known functional activity of this protein. The role of CRABP1 in human carcinogenesis remains poorly understood. Here, for the first time we demonstrated pro-metastatic and pro-tumorigenic activity of CRABP1 in mesenchymal tumors. Further functional analysis revealed that the pro-tumorigenic effect of CRABP1 does not depend on retinoic acid binding activity. These results suggest that CRABP1 could have an alternative intracellular functional activity that contributes to the high malignancy of transformed mesenchymal cells. Microarray analysis detected CRABP1-mediated alterations in the expression of about 100 genes, including those encoding key regulatory proteins. CRABP1 is ubiquitously expressed in monophasic synovial sarcomas, while in biphasic synovial sarcomas it is expressed uniquely by the spindle cells of the aggressive mesenchymal component. High level of CRABP1 expression is associated with lymph node metastasis and poor differentiation/high grade of pancreatic neuroendocrine tumors (pNETs). Presented data suggest CRABP1 as a promising biomarker of pNETs’ clinical behavior. Our results give the first evidence of pro-tumorigenic and pro-metastatic activity of CRABP1 in mesenchymal and neuroendocrine tumors. PMID:24626200

  7. Localized malignant pleural sarcomatoid mesothelioma misdiagnosed as benign localized fibrous tumor

    PubMed Central

    Vo, Hong-Phuc

    2016-01-01

    Localized malignant pleural mesothelioma (LMPM) is a rare tumor with good prognosis by surgical resection. We report an atypical case of malignant pleural sarcomatoid mesothelioma (SM) in an asymptomatic 65-year-old woman, who had no history of exposure to asbestos. She presented with a small pleural mass without pleural effusion and was misdiagnosed as a benign localized fibrous tumor (BLFT) on pathologic examination through a surgical tumor specimen. However, seven months later, the patient returned with serious cancerous symptoms. A large recurrent tumor mass was found within the chest wall invading at the old surgical resection site. SM, a subtype of LMPM, was confirmed with histopathogy and immunohistochemisty. In conclusion, malignant pleural mesothelioma (MPM) can present with typical radiologic finding similar to a BLFT, and has a wide histopathologic presentation in biopsy specimen. A thorough pathologic investigation should be attempted even when a pleural mass resembles benign, localized, and small on radiologic studies. PMID:27293862

  8. Localized malignant pleural sarcomatoid mesothelioma misdiagnosed as benign localized fibrous tumor.

    PubMed

    Kim, Kwan-Chang; Vo, Hong-Phuc

    2016-06-01

    Localized malignant pleural mesothelioma (LMPM) is a rare tumor with good prognosis by surgical resection. We report an atypical case of malignant pleural sarcomatoid mesothelioma (SM) in an asymptomatic 65-year-old woman, who had no history of exposure to asbestos. She presented with a small pleural mass without pleural effusion and was misdiagnosed as a benign localized fibrous tumor (BLFT) on pathologic examination through a surgical tumor specimen. However, seven months later, the patient returned with serious cancerous symptoms. A large recurrent tumor mass was found within the chest wall invading at the old surgical resection site. SM, a subtype of LMPM, was confirmed with histopathogy and immunohistochemisty. In conclusion, malignant pleural mesothelioma (MPM) can present with typical radiologic finding similar to a BLFT, and has a wide histopathologic presentation in biopsy specimen. A thorough pathologic investigation should be attempted even when a pleural mass resembles benign, localized, and small on radiologic studies. PMID:27293862

  9. Agenesis of the dorsal pancreas and its association with pancreatic tumors.

    PubMed

    Sakpal, Sujit Vijay; Sexcius, Lucretia; Babel, Nitin; Chamberlain, Ronald Scott

    2009-05-01

    Morphogenesis of the pancreas is a complex process; nevertheless, congenital anomalies are rare. At embryogenesis, the pancreas develops from the endoderm-lined dorsal and ventral buds of the duodenum. The ventral bud gives rise to the lower head and uncinate process of the pancreas; whereas, the dorsal bud gives rise to the upper head, isthmus, body, and tail of the pancreas. Rarely, developmental failure of the dorsal pancreatic bud at embryogenesis results in the agenesis of the dorsal pancreas--neck, body, and tail. Even rarer is the association of pancreatic tumors with agenesis of the dorsal pancreas. In addition to citing our case, we provide a comprehensive review on agenesis of the dorsal pancreas and its association with pancreatic tumors.

  10. The impact of additional malignancies in patients diagnosed with gastrointestinal stromal tumors.

    PubMed

    Smith, Myles J; Smith, Henry G; Mahar, Alyson L; Law, Calvin; Ko, Yoo-Joung

    2016-10-15

    A higher incidence of additional malignancies has been described in patients diagnosed with gastrointestinal stromal tumors (GIST). This study aimed to identify risk factors for developing additional malignancies in patients diagnosed with GIST and evaluate the impact on survival. Individuals diagnosed with GIST from 2001 to2009 were identified from the SEER database. Logistic regression was used to identify predictors of additional malignancies and Cox-proportional hazards regression used to identify predictors of survival. In the study period, 1705 cases of GIST were identified, with 181 (10.6%) patients developing additional malignancies. Colorectal cancer was the most common cancer developing within 6 months of GIST diagnosis (30%). The median time to diagnosis of a malignancy after 6 months of GIST diagnosis was 21.9 months. Older age (p < 0.0001) and extraoesophagogastric GIST (p = 0.0027) were significant prognostic factors associated with additional malignancies. The overall 5-year survival was 65%, with the presence of additional malignancies within 6 months of GIST diagnosis associated with poor overall survival (54%, HR 1.55 1.05-2.3 95% CI, p = 0.04). Predictive factors of additional malignancies in patients diagnosed with GIST are increasing age and the primary disease site. Developing additional malignancies within 6 months of GIST diagnosis is associated with poorer overall survival. Targeted surveillance may be warranted in patients diagnosed with GIST that are at high risk of developing additional malignancies. PMID:27299364

  11. Chronic increased serum lipase without evidence of pancreatitis: tumor-derived lipase?

    PubMed

    Donnelly, J G; Ooi, D S; Burns, B F; Goel, R

    1996-03-01

    A 51-year-old man developed a large retroperitoneal tumor with liver and lymph node metastases; there was no radiological evidence of pancreatic involvement. Despite the progression of disease, results of laboratory tests, notably serum amylase, were normal except for minor increases in aspartate aminotransferase and gamma-glutamyltransferase and a marked increase in lipase. The increased lipase was not attributable to formation of macroenzyme. To determine the source of the lipase, we fractionated serum and a tumor biopsy homogenate, using electrophoresis. The lipase pattern obtained from the patient's serum differed from that seen in serum from a patient with acute pancreatitis. Additionally, the lipase pattern obtained from a homogenate of biopsy sample from the retroperitoneal tumor did not match the pattern observed for normal pancreas. Apparently, the source of this increased serum lipase activity was the nonpancreatic tumor.

  12. A murine tumor progression model for pancreatic cancer recapitulating the genetic alterations of the human disease

    PubMed Central

    Wagner, Martin; Greten, Florian R.; Weber, Christoph K.; Koschnick, Stefan; Mattfeldt, Torsten; Deppert, Wolfgang; Kern, Horst; Adler, Guido; Schmid, Roland M.

    2001-01-01

    This study describes a tumor progression model for ductal pancreatic cancer in mice overexpressing TGF-α. Activation of Ras and Erk causes induction of cyclin D1-Cdk4 without increase of cyclin E or PCNA in ductal lesions. Thus, TGF-α is able to promote progression throughout G1, but not S phase. Crossbreeding with p53 null mice accelerates tumor development in TGF-α transgenic mice dramatically. In tumors developing in these mice, biallelic deletion of Ink4a/Arf or LOH of the Smad4 locus is found suggesting that loci in addition to p53 are involved in antitumor activities. We conclude that these genetic events are critical for pancreatic tumor formation in mice. This model recapitulates pathomorphological features and genetic alterations of the human disease. PMID:11159909

  13. Atypical features in salivary gland mixed tumors: their relationship to malignant transformation.

    PubMed

    Auclair, P L; Ellis, G L

    1996-06-01

    Although criteria for distinction between the benign and malignant elements in carcinoma ex mixed tumor have been adequately described, there have not been any attempts to identify clinical or histologic features in benign mixed tumors that indicate increased risk of malignant change. For this reason, 65 mixed tumors of the major and minor salivary glands that exhibited atypical histologic features were examined in an attempt to analyze which, if any, of these features might indicate a greater likelihood of malignant transformation. The atypical features evaluated were hypercellularity, capsule violation, hyalinization, necrosis, and cellular anaplasia. The mitotic rate was also analyzed. The age of the patient, and the site, size, and prediagnostic duration of the tumor were recorded and, together with the histologic findings, were correlated with follow-up information. Nine (13.8%) of the 65 tumors underwent malignant transformation. Five of these patients died of the tumor, two others had distant metastases and were alive with the disease, and two were free of disease. Benign mixed tumors that showed prominent zones of hyalinization or at least moderate mitotic activity were more likely to develop carcinoma than those that did not. chi 2 analysis indicated that only hyalinization was significant (P < 0.05), but, with Fisher's exact test (two-tailed), this and all of the other features evaluated revealed a P value greater than 0.05. The other atypical features failed to correlate with malignant change. Clinical findings at the initial diagnosis that indicated a greater likelihood of malignant transformation were occurrence in the submandibular gland, older patient age, and large tumor size.

  14. Pancreatic adenocarcinoma: Outstanding problems

    PubMed Central

    Zakharova, Olga P; Karmazanovsky, Grigory G; Egorov, Viacheslav I

    2012-01-01

    Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%. Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma. About 40% of patients have locally advanced nonresectable disease. In the past, determination of pancreatic cancer resectability was made at surgical exploration. The development of modern imaging techniques has allowed preoperative staging of patients. Institutions disagree about the criteria used to classify patients. Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis. There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition of borderline resectable pancreatic cancer is also lacking. Thus, there is much room for improvement in all aspects of treatment for pancreatic cancer. Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer. With improved surgical techniques and advanced perioperative management, vascular resection and reconstruction are performed more frequently; patients thought once to be unresectable are undergoing radical surgery. However, when attempting heroic surgery, a realistic approach concerning the patient’s age and health status, probability of recovery after surgery, perioperative morbidity and mortality and life quality after tumor resection is necessary. PMID:22655124

  15. LDL Receptor: An open route to feed pancreatic tumor cells

    PubMed Central

    Vasseur, Sophie; Guillaumond, Fabienne

    2016-01-01

    ABSTRACT The role of altered lipid metabolism in pancreatic ductal adenocarcinoma (PDAC) is poorly appreciated. We recently identified the lipid signature of PDAC and revealed low-density lipoprotein receptor (Ldlr) as a metabolic driver of this disease. Here, we comment our findings that disruption of Ldlr leads to intratumoral cholesterol imbalance and improves chemotherapy efficiency. PMID:27308549

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

    SciTech Connect

    Hirano, Tsuneo; Otake, Hidenori; Shibasaki, Takashi

    1997-01-01

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

  17. Pharmacokinetically Guided Everolimus in Patients With Breast Cancer, Pancreatic Neuroendocrine Tumors, or Kidney Cancer

    ClinicalTrials.gov

    2016-01-12

    Estrogen Receptor-positive Breast Cancer; Gastrinoma; Glucagonoma; HER2-negative Breast Cancer; Insulinoma; Mucositis; Oral Complications; Pancreatic Polypeptide Tumor; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Recurrent Islet Cell Carcinoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Renal Cell Cancer

  18. [Carcinoma with low malignant potential (borderline tumor) of the ovary: immunomorphology and clinical aspects].

    PubMed

    Neunteufel, W; Gitsch, G; Schieder, K; Kölbl, H; Breitenecker, G

    1989-01-01

    Four of 28 patients with borderline tumors of the ovary died of intercurrent disease. Twenty-four are alive without clinical evidence of disease, despite the fact that six of them were stage III; joined with the invasive carcinomas they would distort the survival rates. The development of monoclonal antibodies specific to borderline tumors could improve the value of immunohistochemistry in the diagnosis of borderline tumors. Our results show that the rates of expression of CA 125, CA 19-9, and CEA indicate that borderline tumors are an independent group between benign and malignant ovarian tumors.

  19. Clear Cell “Sugar” Tumor of the Lung: Benign or Malignant?

    PubMed Central

    Olivencia-Yurvati, Albert H.; Rodriguez, Abraham Elias

    2015-01-01

    Clear cell “sugar” tumors of the lung are rare pulmonary tumors. This case study illustrates a patient who was found to have a persistent nodule in the left-upper lobe of the lung. Positron emission tomographic scanning showed mild-moderate 18-fluorodeoxyglucose uptake. Based on these findings, a video-assisted resection of the tumor was undertaken. The mass was identified histologically, as a clear cell “sugar” tumor of the lung. This case report discusses the benign versus malignant nature of this rare tumor. PMID:26011217

  20. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    ClinicalTrials.gov

    2015-07-27

    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

  1. Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells

    PubMed Central

    2014-01-01

    Introduction Although breast phyllodes tumors are rare, there is no effective therapy other than surgery. Little is known about their tumor biology. A malignant phyllodes tumor contains heterologous stromal elements, and can transform into rhabdomyosarcoma, liposarcoma and osteosarcoma. These versatile properties prompted us to explore their possible relationship to mesenchymal stem cells (MSCs) and to search for the presence of cancer stem cells (CSCs) in phyllodes tumors. Methods Paraffin sections of malignant phyllodes tumors were examined for various markers by immunohistochemical staining. Xenografts of human primary phyllodes tumors were established by injecting freshly isolated tumor cells into the mammary fat pad of non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. To search for CSCs, xenografted tumor cells were sorted into various subpopulations by flow cytometry and examined for their in vitro mammosphere forming capacity, in vivo tumorigenicity in NOD-SCID mice and their ability to undergo differentiation. Results Immunohistochemical analysis revealed the expression of the following 10 markers: CD44, CD29, CD106, CD166, CD105, CD90, disialoganglioside (GD2), CD117, Aldehyde dehydrogenase 1 (ALDH), and Oct-4, and 7 clinically relevant markers (CD10, CD34, p53, p63, Ki-67, Bcl-2, vimentin, and Globo H) in all 51 malignant phyllodes tumors examined, albeit to different extents. Four xenografts were successfully established from human primary phyllodes tumors. In vitro, ALDH+ cells sorted from xenografts displayed approximately 10-fold greater mammosphere-forming capacity than ALDH- cells. GD2+ cells showed a 3.9-fold greater capacity than GD2- cells. ALDH+/GD2+cells displayed 12.8-fold greater mammosphere forming ability than ALDH-/GD2- cells. In vivo, the tumor-initiating frequency of ALDH+/GD2+ cells were up to 33-fold higher than that of ALDH+ cells, with as few as 50 ALDH+/GD2+ cells being sufficient for engraftment. Moreover, we

  2. Characterization of highly proliferative secondary tumor clusters along host blood vessels in malignant glioma.

    PubMed

    Wang, Ting-Chung; Cheng, Chun-Yu; Yang, Wei-Hsun; Chen, Wen-Cheng; Chang, Pey-Jium

    2015-11-01

    The aim of the present study was to investigate the extensive invasion of tumor cells into normal brain tissue, a life‑threatening feature of malignant gliomas. How invasive tumor cells migrate into normal brain tissue and form a secondary tumor structure remains to be elucidated. In the present study, the morphological and phenotypic changes of glioma cells during invasion in a C6 glioma model were investigated. C6 glioma cells were stereotactically injected into the right putamen region of adult Sprague‑Dawley rats. The brain tissue sections were then subjected to hematoxylin and eosin, immunohistochemical or immunofluorescent staining. High magnification views of the tissue sections revealed that C6 cells formed tumor spheroids following implantation and marked invasion was observed shortly after spheroid formation. In the later stages of invasion, certain tumor cells invaded the perivascular space and formed small tumor clusters. These small tumor clusters exhibited certain common features, including tumor cell multilayers surrounding an arteriole, which occurred up to several millimeters away from the primary tumor mass; a high proliferation rate; and similar gene expression profiles to the primary tumor. In conclusion, the present study revealed that invading tumor cells are capable of forming highly proliferative cell clusters along arterioles near the tumor margin, which may be a possible cause of the recurrence of malignant glioma.

  3. Characterization of highly proliferative secondary tumor clusters along host blood vessels in malignant glioma

    PubMed Central

    WANG, TING-CHUNG; CHENG, CHUN-YU; YANG, WEI-HSUN; CHEN, WEN-CHENG; CHANG, PEY-JIUM

    2015-01-01

    The aim of the present study was to investigate the extensive invasion of tumor cells into normal brain tissue, a life-threatening feature of malignant gliomas. How invasive tumor cells migrate into normal brain tissue and form a secondary tumor structure remains to be elucidated. In the present study, the morphological and phenotypic changes of glioma cells during invasion in a C6 glioma model were investigated. C6 glioma cells were stereotactically injected into the right putamen region of adult Sprague-Dawley rats. The brain tissue sections were then subjected to hematoxylin and eosin, immunohistochemical or immunofluorescent staining. High magnification views of the tissue sections revealed that C6 cells formed tumor spheroids following implantation and marked invasion was observed shortly after spheroid formation. In the later stages of invasion, certain tumor cells invaded the perivascular space and formed small tumor clusters. These small tumor clusters exhibited certain common features, including tumor cell multilayers surrounding an arteriole, which occurred up to several millimeters away from the primary tumor mass; a high proliferation rate; and similar gene expression profiles to the primary tumor. In conclusion, the present study revealed that invading tumor cells are capable of forming highly proliferative cell clusters along arterioles near the tumor margin, which may be a possible cause of the recurrence of malignant glioma. PMID:26299849

  4. Endoscopic Ultrasonography-Guided Ethanol Ablation for Small Pancreatic Neuroendocrine Tumors: Results of a Pilot Study

    PubMed Central

    Choi, Jun-Ho; Oh, Dongwook; Lee, Sang Soo; Seo, Dong-Wan; Lee, Sung Koo; Kim, Myung-Hwan

    2015-01-01

    Background/Aims Endoscopic ultrasonography (EUS)-guided ethanol ablation is gaining popularity for the treatment of focal pancreatic lesions. The aim of this study was to evaluate the safety, feasibility, and treatment response after EUS-guided ethanol injection for small pancreatic neuroendocrine tumors (p-NETs). Methods This was a retrospective analysis of a prospectively collected database including 11 consecutive patients with p-NETs who underwent EUS-guided ethanol injection. Results EUS-guided ethanol injection was successfully performed in 11 patients with 14 tumors. The final diagnosis was based on histology and clinical signs as follows: 10 non-functioning neuroendocrine tumors and four insulinomas. During follow-up (median, 370 days; range, 152 to 730 days), 10 patients underwent clinical follow-up after treatment, and one patient was excluded because of loss to follow-up. A single treatment session with an injection of 0.5 to 3.8 mL of ethanol resulted in complete responses (CRs) at the 3-month radiologic imaging for seven of 13 tumors (response rate, 53.8%). Multiple treatment sessions performed in three tumors with residual viable enhancing tissue increased the number of tumors with CRs to eight of 13 (response rate, 61.5%). Mild pancreatitis occurred in three of 11 patients. Conclusions EUS-guided ethanol injection appears to be a safe, feasible, and potentially effective method for treating small p-NETs in patients who are poor surgical candidates. PMID:25844345

  5. Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

    SciTech Connect

    Gu Yongpeng; Li Hongzhen; Miki, Jun; Kim, Kee-Hong; Furusato, Bungo; Sesterhenn, Isabell A.; Chu, Wei-Sing; McLeod, David G.; Srivastava, Shiv; Ewing, Charles M.; Isaacs, William B.; Rhim, Johng S. . E-mail: jrhim@cpdr.org

    2006-04-01

    In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferative capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents.

  6. [Results of surgical treatment of malignant brain tumors].

    PubMed

    Goldhahn, W E

    1987-05-29

    Although surgical treatment seldom cures any malignant brain tumours, it remains the basis of the management of these tumours. Studies by others and our own statistical studies demonstrate the absence of any real or significant improvement in survival time for most of the patients. Hence we must await progress in other oncological disciplines to provide a solution.

  7. Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma.

    PubMed

    Zeeberg, Katrine; Cardone, Rosa Angela; Greco, Maria Raffaella; Saccomano, Mara; Nøhr-Nielsen, Asbjørn; Alves, Frauke; Pedersen, Stine Falsig; Reshkin, Stephan Joel

    2016-07-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a very poor prognosis, due to the influence of the tumor stroma, which promotes tumor growth, early invasion and chemoradiation resistance. Efforts to develop models for identifying novel anticancer therapeutic compounds have been hampered by the limited ability of in vitro models to mimic these in vivo tumor-stroma interactions. This has led to the development of various three-dimensional (3D) culture platforms recapitulating the in vivo tumor-stroma crosstalk and designed to better understand basic cancer processes and screen drug action. However, a consensus for different experimental 3D platforms is still missing in PDAC. We compared four PDAC cell lines of different malignancy grown in 2D monolayers to three of the more commonly used 3D techniques (ultralow adhesion concave microwells, Matrigel inclusion and organotypic systems) and to tumors derived from their orthotopic implantation in mice. In these 3D platforms, we observed that cells grow with very different tumor morphologies and the organotypic setting most closely resembles the tumor cytoarchitecture obtained by orthotopically implanting the four cell lines in mice. We then analyzed the molecular and cellular responses of one of these cell lines to epidermal growth factor receptor (EGFR) stimulation with EGF and inhibition with erlotinib and found that only in the 3D platforms, and especially the organotypic, cells: i) responded to EGF by changing the expression of signalling components underlying cell-stroma crosstalk and tissue architecture, growth, invasion and drug resistance (E-cadherin, EGFR, ezrin, β1 integrin, NHERF1 and HIF-1α) similar to those reported in vivo; ii) had stimulated growth and increased erlotinib sensitivity in response to EGF, more faithfully mimicking their known in vivo behaviour. Altogether, these results, indicate the organotypic as the most relevant physiological 3D system to study the

  8. Endoscopic Ultrasound-Guided Radiofrequency Ablation of the Pancreatic Tumors: A Promising Tool in Management of Pancreatic Tumors

    PubMed Central

    2016-01-01

    Objective. Radiofrequency ablation is a well-established antitumor treatment and is recognized as one of the least invasive therapeutic modalities for pancreatic neoplasm. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) delivery can be used to treat both pancreatic cancer and asymptomatic premalignant pancreatic neoplasms and may serve as a less invasive alternative to surgical resection. This is an appealing option that may result in less morbidity and mortality. The aim of this review was to summarize and evaluate the clinical and technical effectiveness of EUS-guided RFA of pancreatic neoplasms. Methods. A through literature review was performed to identify the studies describing this novel technique. In this review article, we have summarized human case series. The indications, techniques, limitations, and complications reported are discussed. Results. A total of six studies were included. Overall, a 100% technical success rate was reported in human studies. Complications related to endoscopic ultrasound-guided radiofrequency ablation delivery have been described; however, few cases have presented life-threatening outcomes. Conclusion. We believe that this novel technique can be a safe and effective alternative approach in the management of selected patients. PMID:27478820

  9. SU-D-201-04: Study On the Impact of Tumor Shape and Size On Drug Delivery to Pancreatic Tumors

    SciTech Connect

    Soltani, M; Bazmara, H; Sefidgar, M; Subramaniam, R; Rahmim, A

    2015-06-15

    Purpose: Drug delivery to solid tumors can be expressed physically using transport phenomena such as convection and diffusion for the drug of interest within extracellular matrices. We aimed to carefully model these phenomena, and to investigate the effect of tumor shape and size on drug delivery to solid tumors in the pancreas. Methods: In this study, multiple tumor geometries as obtained from clinical PET/CT images were considered. An advanced numerical method was used to simultaneously solve fluid flow and solute transport equations. Data from n=45 pancreatic cancer patients with non-resectable locoregional disease were analyzed, and geometrical information from the tumors including size, shape, and aspect ratios were classified. To investigate effect of tumor shape, tumors with similar size but different shapes were selected and analyzed. Moreover, to investigate effect of tumor size, tumors with similar shapes but different sizes, ranging from 1 to 77 cm{sup 3}, were selected and analyzed. A hypothetical tumor similar to one of the analyzed tumors, but scaled to reduce its size below 0.2 cm{sup 3}, was also analyzed. Results: The results showed relatively similar average drug concentration profiles in tumors with different sizes. Generally, smaller tumors had higher absolute drug concentration. In the hypothetical tumor, with volume less than 0.2 cm{sup 3}, the average drug concentration was 20% higher in comparison to its counterparts. For the various real tumor geometries, however, the maximum difference between average drug concentrations was 10% for the smallest and largest tumors. Moreover, the results demonstrated that for pancreatic tumors the shape is not significant. The negligible difference of drug concentration in different tumor shapes was due to the minimum effect of convection in pancreatic tumors. Conclusion: In tumors with different sizes, smaller tumors have higher drug delivery; however, the impact of tumor shape in the case of pancreatic

  10. [Advance in Research of Angiotensin II and Its Receptor and Malignant Tumor].

    PubMed

    Sun, Lulu; Shi, Jian

    2016-09-20

    Angiotensin AngII, a linear small peptide,which is composed of eight amino acids, is the main effectors of renin-angiotensin systen (Renin-angiotensin system, RAS). AngII, a main biopolypeptide of the RAS, has important pathophysiologic in effects participating in cardiac hypertrophy, vascular cell proproliferation, inflammation and tissue remodeling through G-protein-coupled receptors. In recent years, Ang II can promote tumor cell proliferation, tumor vessel formation and inhibit the differentiation of the tumor cells. This suggests that inhibit the production of AngII or block its effect is expected to become a new measure for the treatment of malignant tumors. This article reviews the advances in research on the relationship between AngII and its receptor and malignant tumor in recent years. PMID:27666553

  11. Interleukin-33 Expression Indicates a Favorable Prognosis in Malignant Salivary Gland Tumors.

    PubMed

    Rössle, Matthias; Cathomas, Gieri; Bonapace, Laura; Sachs, Melanie; Dehler, Silvia; Storz, Martina; Huber, Gerhard; Moch, Holger; Junt, Tobias; Mertz, Kirsten D

    2016-08-01

    The cytokine interleukin-33 (IL-33) is abundantly expressed in epithelial barrier tissues such as salivary glands. Here, we characterized nuclear IL-33 protein expression by immunohistochemistry in benign and malignant salivary gland tumors and associated it with disease outcome. Most benign salivary gland tumors expressed IL-33, and all Warthin's tumors showed strong and consistent IL-33 expression in the basally oriented cells of their bilayered epithelium. In the malignant group of neoplasms, nuclear IL-33 expression was limited to specific tumor entities-for example, to epithelial-myopepithelial carcinomas (n = 9/11), acinic cell carcinomas (n = 13/27), and oncocytic carcinomas (n = 2/2). IL-33 expression in the combined group of malignant salivary gland neoplasms was significantly associated with favorable histological parameters, lack of metastasis, and longer overall survival, compared with IL-33-negative tumors. We conclude that IL-33 expression is a novel prognostic marker for malignant salivary gland tumors with potential use in clinical diagnostics.

  12. A subset of malignant phyllodes tumors harbors alterations in the Rb/p16 pathway.

    PubMed

    Cimino-Mathews, Ashley; Hicks, Jessica L; Sharma, Rajni; Vang, Russell; Illei, Peter B; De Marzo, Angelo; Emens, Leisha A; Argani, Pedram

    2013-11-01

    Breast phyllodes tumors are fibroepithelial neoplasms with variable risk of aggressive local recurrence and distant metastasis, and the molecular pathogenesis is unclear. Here, we systematically study p16 and Rb expression in 34 phyllodes tumors in relation to proliferation. Tissue microarrays were constructed from 10 benign, 10 borderline, and 14 malignant phyllodes (5 cores/tumor) and from 10 fibroadenomas (2 cores/tumor). Tissue microarrays were labeled by immunohistochemistry for p16, Rb, and Ki-67 and by in situ hybridization for high-risk human papillomavirus. Cytoplasmic and nuclear p16 were scored by percentage labeling (0%-100%, diffuse >95%) and intensity. Nuclear Rb was scored by percentage labeling (0%-100%, diffuse >75%) and intensity. p16 and Rb labeling were repeated on whole sections of cases with Rb loss on the tissue microarray. Twenty-nine percent (4/14) malignant phyllodes showed diffuse strong p16 labeling with Rb loss in malignant cells (diffuse p16+/Rb-), whereas 21% (3/14) malignant phyllodes showed the reverse pattern of p16 loss with diffuse strong Rb (p16-/diffuse Rb+). Results were consistent between tissue microarrays and whole sections. No borderline phyllodes, benign phyllodes, or fibroadenoma showed diffuse p16+/Rb- or p16-/diffuse Rb+ phenotypes. No cases contained high-risk human papillomavirus. Average Ki-67 proliferation indices were 15% in malignant phyllodes, 1.7% in borderline phyllodes, 0.5% in benign phyllodes, and 0% in fibroadenoma. Ki-67 was highest in malignant phyllodes with diffuse p16+/Rb- labeling. In summary, 50% malignant phyllodes display evidence of Rb/p16 pathway alterations, likely reflecting p16 or Rb inactivation. These and other mechanisms may contribute to the increased proliferation in malignant phyllodes relative to other fibroepithelial neoplasms.

  13. Pleural malignant solitary fibrous tumor with sarcomatous overgrowth showing PDGFRbeta mutation.

    PubMed

    Rossi, Giulio; Schirosi, Laura; Giovanardi, Filippo; Sartori, Giuliana; Paci, Massimiliano; Cavazza, Alberto

    2006-08-01

    Pleural malignant solitary fibrous tumors (SFTs) are uncommon, and little is known about their histogenesis and molecular features. We report a case of pleural SFT with sarcomatous overgrowth that showed expression for PDGFRbeta and a missense mutation on exon 18 of the PDGFRbeta gene. The involvement of the PDGFRbeta gene in SFT is compatible with a pericytic derivation, also supporting a possible role of this tyrosine kinase in malignant transformation and in the adoption of novel molecular therapies.

  14. Malignant and benign bone tumors that you are likely to see.

    PubMed

    Lewis, Valerae O; Morris, Carol D; Parsons, Theodore W

    2013-01-01

    Although primary malignancies of bone are rare, thousands of benign bone tumors are diagnosed annually. It is important to be able to distinguish benign lesions from malignant lesions and differentiate those lesions that can be watched versus lesions that require further treatment and referral to an orthopaedic oncologist. Learning to distinguish these entities and their appropriate treatment or triage will positively affect the patient and the surgeon's practice. PMID:23395056

  15. Clobenpropit enhances anti-tumor effect of gemcitabine in pancreatic cancer

    PubMed Central

    Paik, Woo Hyun; Ryu, Ji Kon; Jeong, Kyoung-Sin; Park, Jin Myung; Song, Byeong Jun; Lee, Sang Hyub; Kim, Yong-Tae; Yoon, Yong Bum

    2014-01-01

    AIM: To evaluate the anti-tumor effect of clobenpropit, which is a specific H3 antagonist and H4 agonist, in combination with gemcitabine in a pancreatic cancer cell line. METHODS: Three kinds of human pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and AsPC-1) were used in this study. Expression of H3 and H4 receptors in pancreatic cancer cells was identified with Western blotting. Effects of clobenpropit on cell proliferation, migration and apoptosis were evaluated. Alteration of epithelial and mesenchymal markers after administration of clobenpropit was analyzed. An in vivo study with a Panc-1 xenograft mouse model was also performed. RESULTS: H4 receptors were present as 2 subunits in human pancreatic cancer cells, while there was no expression of H3 receptor. Clobenpropit inhibited cell migration and increased apoptosis of pancreatic cancer cells in combination with gemcitabine. Clobenpropit up-regulated E-cadherin, but down-regulated vimentin and matrix metalloproteinase 9 in real-time polymerase chain reaction. Also, clobenpropit inhibited tumor growth (gemcitabine 294 ± 46 mg vs combination 154 ± 54 mg, P = 0.02) and enhanced apoptosis in combination with gemcitabine (control 2.5%, gemcitabine 25.8%, clobenpropit 9.7% and combination 40.9%, P = 0.001) by up-regulation of E-cadherin and down-regulation of Zeb1 in Panc-1 xenograft mouse. CONCLUSION: Clobenpropit enhanced the anti-tumor effect of gemcitabine in pancreatic cancer cells through inhibition of the epithelial-mesenchymal transition process. PMID:25024609

  16. [Prevalence and trend of gastrointestinal malignant tumors in the elderly over 75 years old in China].

    PubMed

    Zheng, Ying; Wu, Chunxiao

    2016-05-01

    Gastrointestinal malignant tumors are the most common malignant neoplasms among the elderly people over 75 years old in China. There are 122.1 thousand new gastric cases and 78.2 thousand new colorectal cancer cases diagnosed each year in China, which accounts for 42.73% and 18.08% respectively of the cases with same age in the world. The gastric cancer accounts for 25.13% and colorectal cancer accounts for 28.86%of all the malignancies in the elderly. The gastric cancer death accounts for 36.38% and colorectal cancer death accounts for 44.68% in those people over 75 years old in China. It was estimated that the risk of developing gastrointestinal malignant tumors of these elderly people was about 5-6 times and the risk of death of gastrointestinal malignant tumors was about 7-8 times of the general population. Compared with the general population and the people of 55-74 years old, the incidence of gastric cancer in the elderly decreased more slowly and the incidence of colorectal cancer increased more quickly over the past 40 years, which brought significant double burden. The survival rate of gastrointestinal malignant tumors in these elderly was lower than that of the general population. We summarized the incidence, mortality, survival and trend of gastrointestinal malignant tumors in the Chinese elderly, in order to provide data for predicting the age distribution and disease burden in the future, to improve the awareness for cancer prevention and control among these elderly, and to call attention to epidemiology, preclinical and clinical medicine for the elderly, especially in the field of study on the influence between comorbidity and cancer treatment, with the aim of improving survival and quality of life among the elderly.

  17. Influence of the Implantation Site on the Sensitivity of Patient Pancreatic Tumor Xenografts to Apo2L/TRAIL Therapy

    PubMed Central

    Sharma, R; Buitrago, S; Pitoniak, R; Gibbs, JF; Curtin, L; Seshadri, M; Repasky, EA; Hylander, BL

    2015-01-01

    Objectives We have previously demonstrated activity of Apo2L/TRAIL against patient pancreatic tumor xenografts. Here, we have examined the influence of the tumor implantation site on therapeutic response of orthotopic tumors and their metastases to Apo2L/TRAIL. Methods Sensitivity of six patient pancreatic tumor xenografts to Apo2L/TRAIL was determined in a subcutaneous model. To compare the response of orthotopic tumors, cells from subcutaneous xenografts were injected into the pancreas. Tumor growth was confirmed by histological examination of selected mice and then treatment was started. When all control mice developed externally palpable tumors, the experiment was terminated and pancreatic weights compared between control and treated groups. Magnetic resonance imaging was used to quantitate the response of orthotopic and metastatic tumors. Results The sensitivity to Apo2L/TRAIL observed in subcutaneous tumors was maintained in orthotopic tumors. Metastatic spread was observed with orthotopic tumor implantation. In an orthotopic model of a sensitive tumor, primary and metastatic tumor burden was significantly reduced and median survival significantly extended by Apo2L/TRAIL therapy. Conclusions Our data provide evidence that the site of tumor engraftment does not alter the inherent sensitivity of patient xenografts to Apo2L/TRAIL and these results highlight the potential of Apo2/TRAIL therapy against primary and metastatic pancreatic cancer. PMID:24518511

  18. [Rare malignant tumors of the ovaries in adolescents--clinical aspects in deciding therapeutic aggressiveness].

    PubMed

    Schröder, W; Bau, O

    1990-01-01

    4 patients below the age of 20 years have been treated for a malignant tumor of the ovary during the period November 1, 1984 until April 30, 1988. Dysgerminoma was the diagnosis in two cases, as the third patient suffered from a bilateral malignant teratoma. Burkitt's Lymphoma involved both ovaries primarily in an 17-year-old girl. Retrospectively we analyzed diagnosis, therapy and clinical course of these young patients. Regarding the different histological types of the tumors that have been found we discuss critically current recommendations in therapeutic managements referring chemotherapy and/or radiotherapy. Defined conditions provided surgical treatment, that preserves fertility in early stages of malignant germ cell tumors of adolescent women, may be justified, especially for dysgerminomas. A real benefit relate to survival and quality of life by using chemotherapeutic agents can only be expected, if all prognostic factors are regarded.

  19. Malignant solitary fibrous tumor of the pleura: report of a case with cytogenetic analysis.

    PubMed

    de Leval, Laurence; Defraigne, Jean-Olivier; Hermans, Gilberte; Dôme, Florence; Boniver, Jacques; Herens, Christian

    2003-04-01

    The majority of solitary fibrous tumors (SFTs) of the pleura are benign, but 10-30% locally recur or metastasize. Pathogenic factors relevant to the determinism of their biological properties are largely unknown. Cytogenetic data on SFTs of the pleura are sparse. We report herein a case of a malignant SFT of the pleura where successful karyotyping was obtained from the primary and recurrent tumors. The initial karyotype showed two abnormal clones: 48, XY; +8; +8; del(9)(q22; q32) [19] and 46, XY, t(1;16)(q25;p12) [7]. Culture of the recurrent tumor yielded one clone identical to the dominant clone of the initial karyotype. Demonstration of a recurrent abnormal karyotype largely supports its relevance to the malignant clone and suggests a role of supernumerary chromosome(s) 8 in the determinism of malignant behavior in SFT.

  20. Postoperative Radiotherapy for the Treatment of Solitary Fibrous Tumor With Malignant Transformation of the Pelvic

    PubMed Central

    Gao, Chao; Zhang, Yong; Jing, Ming; Qu, Wei; Li, Jia; Zhao, Xiang-Rong; Yu, Yong-Hua

    2016-01-01

    Abstract Solitary fibrous tumor of the pelvic is an uncommon neoplasm with nonspecific symptoms. Reports of malignant transformation are especially rare. We report a case of solitary fibrous tumor in pelvic. A unique feature of our case compared with previously reported is that this patient relapsed with malignant transformation and had significant response to radiotherapy. The patient was initially treated with surgery, followed by postoperative dimensional conformal intensity modulated radiation therapy (dynamic MLC VRIAN 23EX Linac, inversely optimized by the Eclipse system) to provide a radical cure for residual tumor. In this case, there were no signs of recurrence after six and a half years of further follow-up, indicating that postoperation radiotherapy may be an effective treatment for SFT with malignant transformation in pelvic. PMID:26765426

  1. miR-21 induces myofibroblast differentiation and promotes the malignant progression of breast phyllodes tumors.

    PubMed

    Gong, Chang; Nie, Yan; Qu, Shaohua; Liao, Jian-You; Cui, Xiuying; Yao, Herui; Zeng, Yunjie; Su, Fengxi; Song, Erwei; Liu, Qiang

    2014-08-15

    Phyllodes tumors of breast, even histologically diagnosed as benign, can recur locally and have metastatic potential. Histologic markers only have limited value in predicting the clinical behavior of phyllodes tumors. It remains unknown what drives the malignant progression of phyllodes tumors. We found that the expression of myofibroblast markers, α-smooth muscle actin (α-SMA), fibroblast activation protein (FAP), and stromal cell-derived factor-1 (SDF-1), is progressively increased in the malignant progression of phyllodes tumors. Microarray showed that miR-21 was one of the most significantly upregulated microRNAs in malignant phyllodes tumors compared with benign phyllodes tumors. In addition, increased miR-21 expression was primarily localized to α-SMA-positive myofibroblasts. More importantly, α-SMA and miR-21 are independent predictors of recurrence and metastasis, with their predictive value of recurrence better than histologic grading. Furthermore, miR-21 mimics promoted, whereas miR-21 antisense oligos inhibited, the expression of α-SMA, FAP, and SDF-1, as well as the proliferation and invasion of primary stromal cells of phyllodes tumors. The ability of miR-21 to induce myofibroblast differentiation was mediated by its regulation on Smad7 and PTEN, which regulate the migration and proliferation, respectively. In breast phyllodes tumor xenografts, miR-21 accelerated tumor growth, induced myofibroblast differentiation, and promoted metastasis. This study suggests an important role of myofibroblast differentiation in the malignant progression of phyllodes tumors that is driven by increased miR-21.

  2. [Von Hippel-Lindau disease type 2-related pancreatic neuroendocrine tumor and adrenal myelolipoma].

    PubMed

    Dolzhansky, O V; Morozova, M M; Korostelev, S A; Kanivets, I V; Chardarov, N K; Shatveryan, G A; Pal'tseva, E M; Fedorov, D N

    2016-01-01

    The paper describes a case of von Hippel--Lindau-related pancreatic neuroendocrine tumor and adrenal myelolipoma in a 44-year-old woman. The pancreatic tumor and a left retroperitoneal mass were removed in the women in July 2014 and May 2015. Histological examination of the pancreatic tumor revealed that the latter consisted of clear cells forming tubular and tubercular structures showing the expression of chromogranin A, synaptophysin, and cytokeratins 18 and 19 and a negative response to CD10 and RCC. The adrenal medullary mass presented as clear-cell alveolar structures with inclusions of adipose tissue mixed with erythroid, myeloid, and lymphoid cells. The clear-cell component of the adrenal gland expressed neuroendocrine markers with a negative response to cytokeratins, CD10, and RCC. Molecular genetic examination yielded a signal corresponding to two copies of the VHL gene. No deletions or amplifications of the gene were detected. Cases of von Hippel--Lindau disease concurrent with adrenal pheochromocytoma and myelolipoma and simultaneous pancreatic involvement were not found in the literature. PMID:26978235

  3. A Pancreatic Solid Pseudo-Papillary Tumor Detected After Abdominal Injury

    PubMed Central

    Ishii, Atsushi; Yoshimura, Kazuko; Ideguchi, Hiroshi; Hirose, Shinichi

    2013-01-01

    Solid pseudo-papillary tumor (SPT) of the pancreas is a relatively benign tumor that is more frequently reported in females. Most patients usually present with abdominal pain or mass. We experienced the girl who identified SPT with the injury. We diagnosed SPT in a previously healthy 14-year-old Asian girl after abdominal injury. She experienced upper abdominal pain and vomiting after being hit by a basketball. Blood examination revealed a high serum amylase level. Abdominal radiography indicated abnormal bowel gases. Contrast-enhanced computed tomography revealed a smooth, peripheral and unilocular mass approximately 55 mm in diameter in the pancreatic tail. Based on these observations, acute pancreatitis complicated by a pancreatic mass was initially diagnosed. Therapy for acute pancreatitis was instituted, while we simultaneously investigated the mass. Levels of tumor markers were not profoundly elevated in serum. Dynamic contrast-enhanced magnetic resonance imaging (MRI) revealed moderate and gradual increase in contrast-enhanced imaging, consistent with findings of SPT of the pancreas. We thus elected surgical resection for her. Pathological examination of the surgical specimen confirmed our diagnosis of SPT. SPT of the pancreas should be considered as a differential diagnosis of acute abdomen disorders, especially in instances after minor abdominal injuries in young women, and diagnoses must be confirmed with MRIs.

  4. CA19-9: A promising tumor marker for pancreatic carcinoma

    SciTech Connect

    Sakahara, H.; Endo, K.; Nakajima, K.; Hidaka, A.; Nakashima, T.; Ohta, H.; Torizuka, K.; Naito, A.; Suzuki, T.

    1984-01-01

    In order to evaluate CA19-9 as a tumor marker for pancreatic carcinoma (PC), serum levels of CA19-9 were compared with those of CEA and elastase-1 in 56 patients, consisted of 43 cases with histologically proven adenocarcinomas and 13 cases with chronic pancreatitis. Serum levels were determined by using RIA kit obtained from CIS, France (CA19-9 and CEA) and Abbot (elastase-1). CA19-9 gave the highest accuracy among tumor markers the authors have studied and serum levels were markedly elevated over 100U/ml in 30 (70%) cases with PC, whereas none in chronic pancreatitis. CA19-9 values were closely related to the tumor size and the presence or absence of metastsis on CT findings. Small tumors of less than 3cm in diameter, although the site of tumor was limited to the head of the pancreas, showed positive results in 2 out of 5 cases. Furthermore, CA19-9 was at a level of less than 22U/ml in 98 normal controls and was found to be elevated in only 4 (3%) out of 124 patients with benign diseases, including liver diseases, gastric ulcer, cholelithiasis, and so on. These results indicate that CA19-9 is much better in diagnosis and management of PC than is CEA.

  5. A Sporadic Desmoid Tumor: an Exceptional Pancreatic Cystic-Solid Mass.

    PubMed

    Ardakani, Jalal Vahedian; Mehrjardi, Ali Zare; Wadji, Massoud Baghai; Saraee, Amir

    2016-08-01

    Desmoid tumors are locally aggressive and non-metastatic neoplasms with a high rate of recurrence. Desmoid tumors of the pancreas are, however, very rare, and only a few cases have been reported in the literature. This paper reports an anecdotal case of a diffuse pancreatic desmoid tumor with the involvement of the pancreatic head, body, and-partially-tail. The patient underwent the Whipple procedure and subtotal pancreatectomy. Histopathological assessment showed that the tissues were partly positive for smooth muscle actin, but not for S100 or PanCK. The Ki67 index of the cells was only 1 %. Unfortunately, the patient died on the 10th postoperative day due to massive upper gastrointestinal bleeding. PMID:27574352

  6. Malignant giant cell tumor in the carpal tunnel: a case report and review of literature.

    PubMed

    Theunissen, Carla I J M; Bras, Johannes; Lienden, Krijn P van; Obdeijn, Miryam C

    2013-08-01

    Background Malignant tenosynovial giant cell tumors (GCTs) are extremely rare, and their etiology is unknown. However, this type of malignancy is associated with high metastasis and mortality rates. Therefore, the treatment of choice is wide excision. Case Description A 66-year-old man complained of tingling and loss of sensation in the left hand, caused by a tumor that compressed the median nerve. The tumor was excised. Histopathologic examination revealed a ganglion cyst. Two years later, the patient visited our clinic with recurrent and similar complaints of the left hand. This time, however, the lesion turned out to be a malignant tenosynovial GCT and was treated by amputation of the forearm. Literature Review Since 1979, only 37 malignant tenosynovial GCTs have been reported in literature. Follow-up of these patients showed that 11 patients died of the disease, 4 patients were still living with the disease, and 14 patients had no evidence of disease after treatment. The other seven patients were lost to follow-up, and one patient died of other causes. In these 37 patients, a high incidence of lymph node metastasis (41%) and a high mortality rate (30%) were seen. Clinical Relevance Although this malignant tenosynovial GCT is very rare, high mortality rates have been observed because of the high incidence of lymph node metastases. Therefore, more awareness has to be created, to recognize and treat this tumor timely. PMID:24436827

  7. Warburg metabolism in tumor-conditioned macrophages promotes metastasis in human pancreatic ductal adenocarcinoma.

    PubMed

    Penny, Hweixian Leong; Sieow, Je Lin; Adriani, Giulia; Yeap, Wei Hseun; See Chi Ee, Peter; San Luis, Boris; Lee, Bernett; Lee, Terence; Mak, Shi Ya; Ho, Ying Swan; Lam, Kong Peng; Ong, Choon Kiat; Huang, Ruby Y J; Ginhoux, Florent; Rotzschke, Olaf; Kamm, Roger D; Wong, Siew Cheng

    2016-08-01

    Patients with pancreatic ductal adenocarcinoma (PDAC) face a clinically intractable disease with poor survival rates, attributed to exceptionally high levels of metastasis. Epithelial-to-mesenchymal transition (EMT) is pronounced at inflammatory foci within the tumor; however, the immunological mechanisms promoting tumor dissemination remain unclear. It is well established that tumors exhibit the Warburg effect, a preferential use of glycolysis for energy production, even in the presence of oxygen, to support rapid growth. We hypothesized that the metabolic pathways utilized by tumor-infiltrating macrophages are altered in PDAC, conferring a pro-metastatic phenotype. We generated tumor-conditioned macrophages in vitro, in which human peripheral blood monocytes were cultured with conditioned media generated from normal pancreatic or PDAC cell lines to obtain steady-state and tumor-associated macrophages (TAMs), respectively. Compared with steady-state macrophages, TAMs promoted vascular network formation, augmented extravasation of tumor cells out of blood vessels, and induced higher levels of EMT. TAMs exhibited a pronounced glycolytic signature in a metabolic flux assay, corresponding with elevated glycolytic gene transcript levels. Inhibiting glycolysis in TAMs with a competitive inhibitor to Hexokinase II (HK2), 2-deoxyglucose (2DG), was sufficient to disrupt this pro-metastatic phenotype, reversing the observed increases in TAM-supported angiogenesis, extravasation, and EMT. Our results indicate a key role for metabolic reprogramming of tumor-infiltrating macrophages in PDAC metastasis, and highlight the therapeutic potential of using pharmacologics to modulate these metabolic pathways. PMID:27622062

  8. Pancreatic Cancer Tumor Size on CT Scan Versus Pathologic Specimen: Implications for Radiation Treatment Planning

    SciTech Connect

    Arvold, Nils D.; Niemierko, Andrzej; Mamon, Harvey J.; Hong, Theodore S.

    2011-08-01

    Purpose: Pancreatic cancer primary tumor size measurements are often discordant between computed tomography (CT) and pathologic specimen after resection. Dimensions of the primary tumor are increasingly relevant in an era of highly conformal radiotherapy. Methods and Materials: We retrospectively evaluated 97 consecutive patients with resected pancreatic cancer at two Boston hospitals. All patients had CT scans before surgical resection. Primary endpoints were maximum dimension (in millimeters) of the primary tumor in any direction as reported by the radiologist on CT and by the pathologist for the resected gross fresh specimen. Endoscopic ultrasound (EUS) findings were analyzed if available. Results: Of the patients, 87 (90%) had preoperative CT scans available for review and 46 (47%) had EUS. Among proximal tumors (n = 69), 40 (58%) had pathologic duodenal invasion, which was seen on CT in only 3 cases. The pathologic tumor size was a median of 7 mm larger compared with CT size for the same patient (range, -15 to 43 mm; p < 0.0001), with 73 patients (84%) having a primary tumor larger on pathology than CT. Endoscopic ultrasound was somewhat more accurate, with pathologic tumor size being a median of only 5 mm larger compared with EUS size (range, -15 to 35 mm; p = 0.0003). Conclusions: Computed tomography scans significantly under-represent pancreatic cancer tumor size compared with pathologic specimens in resectable cases. We propose a clinical target volume expansion formula for the primary tumor based on our data. The high rate of pathologic duodenal invasion suggests a risk of duodenal undercoverage with highly conformal radiotherapy.

  9. Malignant thyroid teratoma: report of an aggressive tumor in a 64-year-old man.

    PubMed

    Vilallonga, R; Zafon, C; Ruiz-Marcellan, C; Obiols, G; Fort, J M; Baena, J A; Villanueva, B; Garcia, A; Sobrinho-Simões, M

    2013-09-01

    Malignant teratoma of the thyroid is a rare and aggressive tumor, frequent in children than in adults. Histologically, thyroid teratomas usually show a predominance of a neuroectodermal component. Mature cartilage and bone may be present. We present the case of primary malignant teratoma of the thyroid in a 64-year-old man. Histologically, the tumor displayed a predominant neuroectodermal component. The diagnosis was confirmed by immunohistochemistry. The patient underwent a radical thyroidectomy with central neck dissection as primary treatment and radioiodine treatment afterwards. The patient had local and distant recurrence. A second surgery was performed with poor results and the patient died 3 months afterwards.

  10. True malignant mixed tumor (carcinosarcoma) of palatal minor salivary gland origin.

    PubMed

    Takeda, Y

    1991-01-01

    True malignant mixed tumor (carcinosarcoma) of salivary gland origin is exceedingly rare and is distinguishable from the more frequently occurring carcinoma ex pleomorphic adenoma. This paper reports a case of true malignant mixed tumor originating from a palatal minor salivary gland of a 55-year-old male. Histologically, nests of poorly differentiated adenocarcinoma were scattered in a sarcomatous background which partially showed an unequivocal chondrosarcoma. Clinical course of the present patient suggested that a pre-existing benign minor salivary gland lesion developed to a carcinosarcoma.

  11. Modern chemoradiation practices for malignant tumors of the trachea: An institutional experience.

    PubMed

    Joshi, N; Mallick, S; Haresh, K P; Gandhi, A; Prabhakar, R; Laviraj, M A; Sharma, D N; Julka, P K; Rath, G K

    2014-01-01

    Background: Malignant tumors of the trachea are rare. A multimodality treatment approach is often necessary. Outcomes of radical non-surgical approaches are sparse. Radiation combined with sequential or concurrent chemotherapy is an important treatment option. Materials and Methods: We present an analysis of outcomes using modern radiotherapy and chemotherapy for tracheal tumors. Results: Radiation dose escalation using modern techniques is of benefit for these tumors. The results with chemotherapy are encouraging. Conclusions: Radiation plays a distinct role and should be a part of treatment for these tumors. The role of chemotherapy needs to be studied further. PMID:25494113

  12. Metastatic Malignant Ovarian Steroid Cell Tumor: A Case Report and Review of the Literature

    PubMed Central

    Lee, Jessica; John, Veena S.; Liang, Sharon X.; D'Agostino, Catherine A.; Menzin, Andrew W.

    2016-01-01

    We report a case of malignant ovarian steroid cell tumor not otherwise specified (NOS) in a 47-year-old female who presented with hirsutism, virilization, and amenorrhea. At the time of laparotomy, the tumor had already spread to the pelvic cul-de-sac. She underwent a total hysterectomy, bilateral salpingo-oophorectomy, and tumor resection with no residual disease. She received three cycles of bleomycin, etoposide, and cisplatin (BEP) and is now free of disease 24 months after surgery. Literature review of ovarian steroid cell tumors NOS including clinicopathological features and clinical management was performed. PMID:27375912

  13. Applications of a novel tumor-grading-metastasis staging system for pancreatic neuroendocrine tumors

    PubMed Central

    Yang, Min; Tan, Chun-Lu; Zhang, Yi; Ke, Neng-Wen; Zeng, Lin; Li, Ang; Zhang, Hao; Xiong, Jun-Jie; Guo, Zi-Heng; Tian, Bo-Le; Liu, Xu-Bao

    2016-01-01

    Abstract The ability to stratify patients with pancreatic neuroendocrine tumors (p-NETs) into prognostic groups has been hindered by the absence of a commonly accepted staging system. Both the 7th tumor-node-metastasis (TNM) staging guidelines by the American Joint Committee on Cancer (AJCC) and the 2010 grading classifications by the World Health Organization (WHO) were validated to be unsatisfactory. We aim to evaluate the feasibility of combining the latest AJCC and WHO criteria to devise a novel tumor-grading-metastasis (TGM) staging system. We also sought to examine the stage-specific survival rates and the prognostic value of this new TGM system for p-NETs. Data of 120 patients with surgical resection and histopathological diagnosis of p-NETs from January 2004 to February 2014 in our institution were retrospectively collected and analyzed. Based on the AJCC and WHO criteria, we replaced the stage N0 and N1 with stage Ga (NET G1 and NET G2) and Gb (NET G3 and MANEC) respectively, without changes of the definition of T or M stage. The present novel TGM staging system was grouped as follows: stage I was defined as T1–2, Ga, M0; stage II as T3, Ga, M0 or as T1–3, Gb, M0; stage III as T4, Ga–b, M0 and stage IV as any T, M1. The new TGM staging system successfully distributed 55, 42, 12, and 11 eligible patients in stage I to IV, respectively. Differences of survival compared stage I with III and IV for patients with p-NETs were both statistically significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001). Patients in stage I showed better a survival than those in stage II, whereas difference between stages III and IV was not notable (P = 0.001, P = 0.286, respectively). In multivariate models, when the TGM staging system was evaluated in place of the individual T, G, and M variables, this new criteria were proven to be an independent predictor of survival for surgically resected p-NETs (P < 0.05). Stratifying patients well

  14. [Relation between location of elements in periodic table and affinity for the malignant tumor (author's transl)].

    PubMed

    Ando, A; Hisada, K; Ando, I

    1977-10-01

    Affinity of many inorganic compounds for the malignant tumor was examined, using the rats which were subcutaneously transplanted with Yoshida sarcoma. And the relations between the uptake rate into the malignant tumor and in vitro binding power to the protein were investigated in these compounds. In these experiments, the bipositive ions and anions had not affinity for the tumor tissue with a few exceptions. On the other hand, Hg, Au and Bi, which have strong binding power to the protein, showed high uptake rate into the malignant tumor. As Hg++, Au+ and Bi+++ are soft acids according to classification of Lewis acids, it was thought that these elements would bind strongly to soft base (R-SH, R-S-) present in the tumor tissue. In many hard acids (according to classification of Lewis acids), the uptake rate into the tumor was shown as a function of ionic potentials (valency/ionic radii) of the metal ions. It is presumed that the chemical bond of these hard acids in the tumor tissue is ionic bond to hard base (R-COO-, R-PO3(2-), R-SO3-, R-NH2).

  15. Identification of Genes Differentially Expressed in Benign versus Malignant Thyroid Tumors

    PubMed Central

    Prasad, Nijaguna B.; Somervell, Helina; Tufano, Ralph P.; Dackiw, Alan P.B.; Marohn, Michael R.; Califano, Joseph A.; Wang, Yongchun; Westra, William H.; Clark, Douglas P.; Umbricht, Christopher B.; Libutti, Steven K.; Zeiger, Martha A.

    2011-01-01

    Purpose Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30% of fine-needle aspiration biopsy cytology samples reported as “suspicious” or “indeterminate.” Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions. Experimental Design In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician. Results Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73% sensitivity and 82% specificity in predicting malignancy. Real-time reverse transcription – PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription – PCR data. Conclusions Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions. PMID:18519760

  16. [Recurrent malignant solitary fibrous tumor of the orbit].

    PubMed

    Manousaridis, K; Stropahl, G; Guthoff, R F

    2011-03-01

    A 53-year-old female patient presented with a palpable mass in the right medial orbit which had been present for 18 months. The left eye had been enucleated in childhood due to a perforating injury. An orbital biopsy performed ex domo showed unspecific inflammatory tissue but no definite diagnosis was made and systemic therapy with corticosteroids was unsuccessful. A second orbital biopsy was performed in our clinic and revealed a solitary fibrous tumor (SFT) of the orbit. Medial orbitotomy with tumor excision followed and the histological examination of the excised tumor established the diagnosis of SFT of the orbit with focal sarcomatous transformation. The patient presented 3 years later with a new orbital mass in a control MRI examination. Relapse was suspected and orbitotomy with excision of the mass was performed. The histological examination revealed a relapse of the SFT with sarcomatous transformation in the whole extent of the tumor. Radiotherapy with a dosis of 59.4 Gy was subsequently performed. The patient remained tumor-free in the most recent control examination 3 years later.

  17. Liquid cooled brassiere and method of diagnosing malignant tumors therewith

    NASA Technical Reports Server (NTRS)

    Elkins, W.; Williams, B. A.; Tickner, E. G. (Inventor)

    1976-01-01

    A device for enhancing the detection of malignant tissue in the breasts of a woman was described. A brassiere-like garment which is fitted with a pair of liquid-perfused cooling panels which completely and compliantly cover the breasts and upper torso was studied. The garment is connected by plastic tubing to a liquid cooling system comprising a fluid pump, a solenoid control valve for controlling the flow of fluid to either the cooling unit or the heating unit, a fluid reservoir, a temperature sensor in the reservoir, and a restrictor valve to control the pressure in the garment inlet cooling line.

  18. Characteristics and Patterns of Rare Malignancies Published in Rare Tumors.

    PubMed

    Habboush, Jacob; Hollant, Laeticia; Smart, Brigit; Single, Megan; Gaines, Katherine; Patel, Ajaykumar; Miller, Robert

    2016-06-28

    Rare Tumors is an international peer-reviewed medical journal established in 2009. The journal is focused on rare cancers and aims to expand upon current knowledge on their presentation, diagnosis, management, and outcomes. We reviewed the 335 case reports published from 2009 to 2015. We found great diversity in both the country of origin as well as specialty of first authors. Outside of the United States (US) and European Union (EU), there were 20 countries with contributions to the journal. Similarly, there was representation from twelve medical specialties with first authorship of reports. Rare Tumors continues to encourage involvement from physicians across the globe and from all medical disciplines. PMID:27441071

  19. Characteristics and Patterns of Rare Malignancies Published in Rare Tumors

    PubMed Central

    Habboush, Jacob; Hollant, Laeticia; Smart, Brigit; Single, Megan; Gaines, Katherine; Patel, Ajaykumar; Miller, Robert

    2016-01-01

    Rare Tumors is an international peer-reviewed medical journal established in 2009. The journal is focused on rare cancers and aims to expand upon current knowledge on their presentation, diagnosis, management, and outcomes. We reviewed the 335 case reports published from 2009 to 2015. We found great diversity in both the country of origin as well as specialty of first authors. Outside of the United States (US) and European Union (EU), there were 20 countries with contributions to the journal. Similarly, there was representation from twelve medical specialties with first authorship of reports. Rare Tumors continues to encourage involvement from physicians across the globe and from all medical disciplines. PMID:27441071

  20. Angiomyolipoma and Malignant PEComa: Discussion of Two Rare Adrenal Tumors

    PubMed Central

    Kwazneski II, Douglas; Merrill, Megan; Young, Jessica; Sell, Harry

    2016-01-01

    Angiomyolipoma and PEComa are rare tumors descending from perivascular epithelial cells (PECs), with distinctive IHC, morphological, and ultrastructural features. The kidney is the most frequent site of origin, but not the only one; however, adrenal gland angiomyolipomas are extremely rare. We describe two cases being found in the adrenal glands. Given the paucity of literature on the subject, more information on this disease is necessary for diagnosis and treatment. Here, we describe two complete case reports, from presentation to treatment and follow-up, along with imaging and microscopic pathology samples, and provide a comprehensive review as to the history and current literature available regarding these extremely rare tumors. PMID:26998374

  1. Large Malignant Phyllodes Tumor of the Breast with Metastases to the Lungs.

    PubMed

    Augustyn, Alexander; Sahoo, Sunati; Wooldridge, Rachel D

    2015-05-01

    Phyllodes tumors of the breast account for less than 0.5% of breast cancers and present most commonly in women 45 to 49 years old. The importance in managing fibroepithelial lesions lies in distinguishing fibroadenomas, which are benign, from phyllodes tumors, which can be malignant and require complete surgical excision. We report the case of a 56-year-old female who presented with a rapidly enlarging mass in her right breast 18 cm in maximum dimension that completely effaced the breast and distorted the nipple. The patient underwent a successful total mastectomy after core biopsy revealed a diagnosis of phyllodes tumor. Surgical resection is the primary treatment modality; neoadjuvant and adjuvant therapies remain controversial. Here, we report the case of a large malignant phyllodes tumor metastatic to the lungs, review the literature, and discuss diagnostic modalities and adjunct nonsurgical therapies.

  2. Large Malignant Phyllodes Tumor of the Breast with Metastases to the Lungs

    PubMed Central

    Augustyn, Alexander; Sahoo, Sunati; Wooldridge, Rachel D.

    2015-01-01

    Phyllodes tumors of the breast account for less than 0.5% of breast cancers and present most commonly in women 45 to 49 years old. The importance in managing fibroepithelial lesions lies in distinguishing fibroadenomas, which are benign, from phyllodes tumors, which can be malignant and require complete surgical excision. We report the case of a 56-year-old female who presented with a rapidly enlarging mass in her right breast 18 cm in maximum dimension that completely effaced the breast and distorted the nipple. The patient underwent a successful total mastectomy after core biopsy revealed a diagnosis of phyllodes tumor. Surgical resection is the primary treatment modality; neoadjuvant and adjuvant therapies remain controversial. Here, we report the case of a large malignant phyllodes tumor metastatic to the lungs, review the literature, and discuss diagnostic modalities and adjunct nonsurgical therapies. PMID:26266007

  3. MED12 mutations occurring in benign and malignant mammalian smooth muscle tumors.

    PubMed

    Markowski, Dominique Nadine; Huhle, Sonja; Nimzyk, Rolf; Stenman, Göran; Löning, Thomas; Bullerdiek, Jörn

    2013-03-01

    Mutations of the mediator subcomplex 12 gene (MED12) recently have been described in a large group of uterine leiomyomas (UL) but only in a single malignant uterine smooth muscle tumor. To further address the occurrence of fibroid-type MED12 mutations in smooth muscle tumors, we have analyzed samples from 34 leiomyosarcomas (LMS), 21 UL, two extrauterine leiomyomas (EL), and 10 canine genital leiomyomas for the presence of MED12 mutations of the UL-type. Interestingly, besides UL MED12 mutations were found in one uterine LMS, one EL, and two canine vaginal leiomyomas. The results confirm the occurrence of fibroid-type MED12 mutations in malignant uterine smooth muscle tumors thus suggesting a rare but existing leiomyoma-LMS sequence. In addition, for the first time MED12 mutations are reported in smooth muscle tumors in a non-primate mammalian species. PMID:23225304

  4. Large Malignant Phyllodes Tumor of the Breast with Metastases to the Lungs.

    PubMed

    Augustyn, Alexander; Sahoo, Sunati; Wooldridge, Rachel D

    2015-05-01

    Phyllodes tumors of the breast account for less than 0.5% of breast cancers and present most commonly in women 45 to 49 years old. The importance in managing fibroepithelial lesions lies in distinguishing fibroadenomas, which are benign, from phyllodes tumors, which can be malignant and require complete surgical excision. We report the case of a 56-year-old female who presented with a rapidly enlarging mass in her right breast 18 cm in maximum dimension that completely effaced the breast and distorted the nipple. The patient underwent a successful total mastectomy after core biopsy revealed a diagnosis of phyllodes tumor. Surgical resection is the primary treatment modality; neoadjuvant and adjuvant therapies remain controversial. Here, we report the case of a large malignant phyllodes tumor metastatic to the lungs, review the literature, and discuss diagnostic modalities and adjunct nonsurgical therapies. PMID:26266007

  5. Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations.

    PubMed

    Sawai, Yugo; Kodama, Yuzo; Shimizu, Takahiro; Ota, Yuji; Maruno, Takahisa; Eso, Yuji; Kurita, Akira; Shiokawa, Masahiro; Tsuji, Yoshihisa; Uza, Norimitsu; Matsumoto, Yuko; Masui, Toshihiko; Uemoto, Shinji; Marusawa, Hiroyuki; Chiba, Tsutomu

    2015-08-15

    Pancreatic ductal adenocarcinoma (PDAC) develops via an accumulation of various gene mutations. The mechanism underlying the mutations in PDAC development, however, is not fully understood. Recent insight into the close association between the mutation pattern of various cancers and specific mutagens led us to investigate the possible involvement of activation-induced cytidine deaminase (AID), a DNA editing enzyme, in pancreatic tumorigenesis. Our immunohistochemical findings revealed AID protein expression in human acinar ductal metaplasia, pancreatic intraepithelial neoplasia, and PDAC. Both the amount and intensity of the AID protein expression increased with the progression from precancerous to cancerous lesions in human PDAC tissues. To further assess the significance of ectopic epithelial AID expression in pancreatic tumorigenesis, we analyzed the phenotype of AID transgenic (AID Tg) mice. Consistent with our hypothesis that AID is involved in the mechanism of the mutations underlying pancreatic tumorigenesis, we found precancerous lesions developing in the pancreas of AID Tg mice. Using deep sequencing, we also detected Kras and c-Myc mutations in our analysis of the whole pancreas of AID Tg mice. In addition, Sanger sequencing confirmed the presence of Kras, c-Myc, and Smad4 mutations, with the typical mutational footprint of AID in precancerous lesions in AID Tg mice separated by laser capture microdissection. Taken together, our findings suggest that AID contributes to the development of pancreatic precancerous lesions by inducing tumor-related gene mutations. Our new mouse model without intentional manipulation of specific tumor-related genes provides a powerful system for analyzing the mutations involved in PDAC.

  6. Deregulation of miR-183 and KIAA0101 in Aggressive and Malignant Pituitary Tumors

    PubMed Central

    Roche, Magali; Wierinckx, Anne; Croze, Séverine; Rey, Catherine; Legras-Lachuer, Catherine; Morel, Anne-Pierre; Fusco, Alfredo; Raverot, Gérald; Trouillas, Jacqueline; Lachuer, Joel

    2015-01-01

    Changes in microRNAs (miRNAs) expression in many types of cancer suggest that they may be involved in crucial steps during tumor progression. Indeed, miRNAs deregulation has been described in pituitary tumorigenesis, but few studies have described their role in pituitary tumor progression toward aggressiveness and malignancy. To assess the role of miRNAs within the hierarchical cascade of events in prolactin (PRL) tumors during progression, we used an integrative genomic approach to associate clinical–pathological features, global miRNA expression, and transcriptomic profiles of the same human tumors. We describe the specific down-regulation of one principal miRNA, miR-183, in the 8 aggressive (A, grade 2b) compared to the 18 non-aggressive (NA, grades 1a, 2a) PRL tumors. We demonstrate that it acts as an anti-proliferative gene by directly targeting KIAA0101, which is involved in cell cycle activation and inhibition of p53–p21-mediated cell cycle arrest. Moreover, we show that miR-183 and KIAA0101 expression significantly correlate with the main markers of pituitary tumors aggressiveness, Ki-67 and p53. These results confirm the activation of proliferation in aggressive and malignant PRL tumors compared to non-aggressive ones. Importantly, these data also demonstrate the ability of such an integrative genomic strategy, applied in the same human tumors, to identify the molecular mechanisms responsible for tumoral progression even from a small cohort of patients. PMID:26322309

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

    PubMed

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

    2014-04-01

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

  8. Prognostication and response assessment in liver and pancreatic tumors: The new imaging

    PubMed Central

    De Robertis, Riccardo; Tinazzi Martini, Paolo; Demozzi, Emanuele; Puntel, Gino; Ortolani, Silvia; Cingarlini, Sara; Ruzzenente, Andrea; Guglielmi, Alfredo; Tortora, Giampaolo; Bassi, Claudio; Pederzoli, Paolo; D’Onofrio, Mirko

    2015-01-01

    Diffusion-weighted imaging (DWI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) are technical improvements of morphologic imaging that can evaluate functional properties of hepato-bilio-pancreatic tumors during conventional MRI or CT examinations. Nevertheless, the term “functional imaging” is commonly used to describe molecular imaging techniques, as positron emission tomography (PET) CT/MRI, which still represent the most widely used methods for the evaluation of functional properties of solid neoplasms; unlike PET or single photon emission computed tomography, functional imaging techniques applied to conventional MRI/CT examinations do not require the administration of radiolabeled drugs or specific equipments. Moreover, DWI and DCE-MRI can be performed during the same session, thus providing a comprehensive “one-step” morphological and functional evaluation of hepato-bilio-pancreatic tumors. Literature data reveal that functional imaging techniques could be proposed for the evaluation of these tumors before treatment, given that they may improve staging and predict prognosis or clinical outcome. Microscopic changes within neoplastic tissues induced by treatments can be detected and quantified with functional imaging, therefore these techniques could be used also for post-treatment assessment, even at an early stage. The aim of this editorial is to describe possible applications of new functional imaging techniques apart from molecular imaging to hepatic and pancreatic tumors through a review of up-to-date literature data, with a particular emphasis on pathological correlations, prognostic stratification and post-treatment monitoring. PMID:26078555

  9. Genotypic alterations in benign and malignant salivary gland tumors: histogenetic and clinical implications.

    PubMed

    el-Naggar, A K; Hurr, K; Kagan, J; Gillenwater, A; Callender, D; Luna, M A; Batsakis, J G

    1997-06-01

    Loss of heterozygosity (LOH) and microsatellite instability (MI) were examined at 24 microsatellite loci in 46 primary benign and malignant salivary gland tumors. Among the 27 benign tumors, 11 (40.7%), manifested microsatellite alterations in at least one locus; of these, five (18.5%) showed LOH and four (14.8%) had microsatellite instability at two or more loci. Four of 11 pleomorphic adenomas (36.4%) had allele loss on the long arm of chromosome 8. Among the 19 malignant neoplasms examined, 10 (52.6%) and one (5.2%) had allele losses and MI, respectively, at multiple loci; three tumors showed MI at only one locus. Frequent LOH was detected at D8S166 (8q11-12), D17S799, and D17S122 (17p-17p11-2) loci, with an incidence of 40%, 37.5%, and 43%, respectively. In general, malignant neoplasms with LOH exhibited aggressive tumor characteristics. Statistically significant correlation's were found between LOH and pathologic classification (chi 2, p = 0.05), higher grade (p = 0.02), DNA aneuploidy (p = 0.005), and a proliferative index of > 6% (p = 0.005) of the malignant tumors. Carcinomas with 17p loci alterations, including two carcinomas expleomorphic adenoma with concurrent 8q LOH, showed more aggressive features. The results suggested that (a) loci on chromosome 8q may harbor a tumor suppressor gene or genes associated with the development or progression of some salivary neoplasms; (b) alterations on the short arm of chromosome 17 may represent an event related to tumor progression; and (c) tumors with LOH at multiple loci have aggressive biologic characteristics.

  10. Nuances in the Treatment of Malignant Tumors of the Clival and Petroclival Region

    PubMed Central

    Mohyeldin, Ahmed; Prevedello, Daniel M.; Jamshidi, Ali O.; Filho, Leo F.S. Ditzel; Carrau, Ricardo L.

    2014-01-01

    Introduction Malignancies of the clivus and petroclival region are mainly chordomas and chondrosarcomas. Although a spectrum of malignancies may present in this area, a finite group of commonly encountered malignant pathologies will be the focus of this review, as they are recognized to be formidable pathologies due to adjacent critical neurovascular structures and challenging surgical approaches. Objectives The objective is to review the literature regarding medical and surgical management of malignant tumors of the clival and petroclival region with a focus on clinical presentation, diagnostic identification, and associated adjuvant therapies. We will also discuss our current treatment paradigm using endoscopic, open, and combined approaches to the skull base. Data Synthesis A literature review was conducted, searching for basic science and clinical evidence from PubMed, Medline, and the Cochrane Database. The selection criteria encompassed original articles including data from both basic science and clinical literature, case series, case reports, and review articles on the etiology, diagnosis, treatment, and management of skull base malignancies in the clival and petroclival region. Conclusions The management of petroclival malignancies requires a multidisciplinary team to deliver the most complete surgical resection, with minimal morbidity, followed by appropriate adjuvant therapy. We advocate the combination of endoscopic and open approaches (traditional or minimally invasive) as required by the particular tumor followed by radiation therapy to optimize oncologic outcomes. PMID:25992140

  11. CD14/TLR4 priming potentially recalibrates and exerts anti-tumor efficacy in tumor associated macrophages in a mouse model of pancreatic carcinoma

    PubMed Central

    Prakash, Hridayesh; Nadella, Vinod; Singh, Sandhya; Schmitz-Winnenthal, Hubertus

    2016-01-01

    Pancreatic cancer is the fourth major cause of cancer related deaths in the world and 5 year survival is below 5%. Among various tumor directed therapies, stimulation of Toll-like receptors (TLR) has shown promising effects in various tumor models. However, pancreatic cancer cells frequently express these receptors themselves and their stimulation (TLR 2 and/or 4 particularly) within tumor microenvironment is known to potentially enhance tumor cell proliferation and cancer progression. Consistent stimulation of tumor associated macrophages (TAMs), in particular with tumor derived TLR ligand within the tumor microenvironment promotes cancer related inflammation, which is sterile, non-immunogenic and carcinogenic in nature. In view of this, recalibrating of TAM has the potential to induce immunogenic inflammation. Consistent with this, we provide experimental evidence for the first time in this study that priming of TAMs with TLR4 ligend (LPS) alone or in combination with IFN-γ not only recalibrates pancreatic tumor cells induced M2 polarization, but also confers anti-tumor potential in TAMs. Most interestingly, reduced tumor growth in macrophage depleted animals suggests that macrophage directed approaches are important for the management of pancreatic tumors. PMID:27511884

  12. Barriers Prevent Patient Access to Personalized Therapies Identified by Molecular Tumor Profiling of Gynecologic Malignancies

    PubMed Central

    Hillman, R. Tyler; Ward, Kristy; Saenz, Cheryl; McHale, Michael; Plaxe, Steven

    2015-01-01

    Objective. This study was designed to evaluate the ability of commercial molecular tumor profiling to discover actionable mutations and to identify barriers that might prevent patient access to personalized therapies. Methods. We conducted an IRB-approved retrospective review of 26 patients with gynecologic malignancies who underwent commercial tumor profiling at our institution during the first 18 months of test availability. Tumor profiles reported targeted therapies and clinical trials matched to patient-specific mutations. Data analysis consisted of descriptive statistics. Results. Most patients who underwent tumor profiling had serous epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (46%). Patients underwent profiling after undergoing a median of two systemic therapies (range 0 to 13). A median of one targeted therapy was suggested per patient profile. Tumor profiling identified no clinically actionable mutations for seven patients (27%). Six patients sought insurance approval for a targeted therapy and two were declined (33%). One patient (4%) received a targeted therapy and this was discontinued due to tumor progression. Conclusions. There are formidable barriers to targeted therapy for patients with gynecologic malignancies. These barriers include a dearth of FDA-approved targeted agents for gynecologic malignancies, lack of third party insurance coverage and limited geographic availability of clinical trials. PMID:26011384

  13. Malignant granular cell tumor of the lateral femoral cutaneous nerve: report of a case with cytogenetic analysis.

    PubMed

    Di Tommaso, Luca; Magrini, Elisabetta; Consales, Alessandro; Poppi, Massimo; Pasquinelli, Gianandrea; Dorji, Tsering; Benedetti, Giovanni; Baccarini, Paola

    2002-12-01

    Malignant granular cell tumors (MGCTs) are rare neoplasms of uncertain histogenesis. We report a case of MGCT involving a peripheral nerve with peritoneal and omental dissemination in which cytogenetic findings are available. Our results show that MGCTs share some cytogenetic abnormalities with malignant peripheral nerve sheath tumors (MPNSTs), supporting the hypothesis that they may represent histogenetically related lesions.

  14. Malignant Small Bowel Tumors: Diagnosis, Management and Prognosis.

    PubMed

    Cardoso, Hélder; Rodrigues, João Tiago; Marques, Margarida; Ribeiro, Armando; Vilas-Boas, Filipe; Santos-Antunes, João; Rodrigues-Pinto, Eduardo; Silva, Marco; Maia, José Costa; Macedo, Guilherme

    2015-01-01

    Introdução: Apesar de entidades raras, a incidência dos tumores malignos do intestino delgado parece estar a aumentar. O desenvolvimento da cápsula endoscópica e da enteroscopia assistida por balão permitiram um avanço na avaliação das lesões do intestino delgado. Temos como objetivo descrever as características clínicas e patológicas dos doentes com cancro do intestino delgado e averiguar o papel que estas técnicas endoscópicas assumem atualmente. Material e Métodos: Foi realizado um estudo retrospetivo dos doentes diagnosticados com cancro do intestino delgado, desde janeiro de 2010 até outubro de 2014. Os dados foram submetidos a análise estatística. Resultados: Dos 28 doentes diagnosticados, 54% eram do sexo feminino. A idade média ao diagnóstico foi de 61 anos. O tumor mais frequente foi o adenocarcinoma (n = 11), seguido do sarcoma (n = 6), linfoma (n = 6) e tumores neuroendócrinos (n = 3). A principal forma de apresentação esteve relacionada com perdas hemáticas ou obstrução intestinal. Ao diagnóstico, 46% dos doentes tinhammetástases distantes/tumor irressecável. A maioria dos tumores foi diagnosticada por técnicas endoscópicas (41%) ou imagiológicas (35%). No primeiro ano após o diagnóstico, 29% dos doentes faleceram. Na análise multivariada, o adenocarcinoma permaneceu fator independente para pior sobrevida. Discussão: Os doentes com adenocarcinoma apresentaram-se em estádios tardios e com tumores irressecáveis, contribuindo para um pior prognóstico. Ã necessário um elevado grau de suspeita clínica para o diagnóstico de cancro do intestino delgado. Conclusão: As características dos doentes foram globalmente consistentes com o descrito na literatura. A cápsula endoscópica e a enteroscopia assistida por balão são úteis no diagnóstico, gestão e vigilância do cancro do intestino delgado.

  15. The Rho guanine nucleotide exchange factor ARHGEF5 promotes tumor malignancy via epithelial–mesenchymal transition

    PubMed Central

    Komiya, Y; Onodera, Y; Kuroiwa, M; Nomimura, S; Kubo, Y; Nam, J-M; Kajiwara, K; Nada, S; Oneyama, C; Sabe, H; Okada, M

    2016-01-01

    Epithelial tumor cells often acquire malignant properties, such as invasion/metastasis and uncontrolled cell growth, by undergoing epithelial–mesenchymal transition (EMT). However, the mechanisms by which EMT contributes to malignant progression remain elusive. Here we show that the Rho guanine nucleotide exchange factor (GEF) ARHGEF5 promotes tumor malignancy in a manner dependent on EMT status. We previously identified ARHGEF5, a member of the Dbl family of GEFs, as a multifunctional mediator of Src-induced cell invasion and tumor growth. In the present study, ARHGEF5 was upregulated during tumor growth factor-β-induced EMT in human epithelial MCF10A cells, and promoted cell migration by activating the Rho-ROCK pathway. ARHGEF5 was necessary for the invasive and in vivo metastatic activity of human colorectal cancer HCT116 cells. These findings underscore the crucial role of ARHGEF5 in cell migration and invasion/metastasis. An in vivo tumorigenesis assay revealed that ARHGEF5 had the potential to promote tumor growth via the phosphatidylinositol 3-kinase (PI3K) pathway. However, ARHGEF5 was not required for tumor growth in epithelial-like human colorectal cancer HCT116 and HT29 cells, whereas the growth of mesenchymal-like SW480 and SW620 cells depended on ARHGEF5. Induction of EMT by tumor necrosis factor-α or Slug in HCT116 cells resulted in the dependence of tumor growth on ARHGEF5. In these mesenchymal-like cells, Akt was activated via ARHGEF5 and its activity was required for tumor growth. Analysis of a transcriptome data set revealed that the combination of ARHGEF5 upregulation and E-cadherin downregulation or Snail upregulation was significantly correlated with poor prognosis in patients with colorectal cancers. Taken together, our findings suggest that EMT-induced ARHGEF5 activation contributes to the progression of tumor malignancy. ARHGEF5 may serve as a potential therapeutic target in a subset of malignant tumors that have undergone EMT. PMID

  16. The Rho guanine nucleotide exchange factor ARHGEF5 promotes tumor malignancy via epithelial-mesenchymal transition.

    PubMed

    Komiya, Y; Onodera, Y; Kuroiwa, M; Nomimura, S; Kubo, Y; Nam, J-M; Kajiwara, K; Nada, S; Oneyama, C; Sabe, H; Okada, M

    2016-01-01

    Epithelial tumor cells often acquire malignant properties, such as invasion/metastasis and uncontrolled cell growth, by undergoing epithelial-mesenchymal transition (EMT). However, the mechanisms by which EMT contributes to malignant progression remain elusive. Here we show that the Rho guanine nucleotide exchange factor (GEF) ARHGEF5 promotes tumor malignancy in a manner dependent on EMT status. We previously identified ARHGEF5, a member of the Dbl family of GEFs, as a multifunctional mediator of Src-induced cell invasion and tumor growth. In the present study, ARHGEF5 was upregulated during tumor growth factor-β-induced EMT in human epithelial MCF10A cells, and promoted cell migration by activating the Rho-ROCK pathway. ARHGEF5 was necessary for the invasive and in vivo metastatic activity of human colorectal cancer HCT116 cells. These findings underscore the crucial role of ARHGEF5 in cell migration and invasion/metastasis. An in vivo tumorigenesis assay revealed that ARHGEF5 had the potential to promote tumor growth via the phosphatidylinositol 3-kinase (PI3K) pathway. However, ARHGEF5 was not required for tumor growth in epithelial-like human colorectal cancer HCT116 and HT29 cells, whereas the growth of mesenchymal-like SW480 and SW620 cells depended on ARHGEF5. Induction of EMT by tumor necrosis factor-α or Slug in HCT116 cells resulted in the dependence of tumor growth on ARHGEF5. In these mesenchymal-like cells, Akt was activated via ARHGEF5 and its activity was required for tumor growth. Analysis of a transcriptome data set revealed that the combination of ARHGEF5 upregulation and E-cadherin downregulation or Snail upregulation was significantly correlated with poor prognosis in patients with colorectal cancers. Taken together, our findings suggest that EMT-induced ARHGEF5 activation contributes to the progression of tumor malignancy. ARHGEF5 may serve as a potential therapeutic target in a subset of malignant tumors that have undergone EMT. PMID

  17. Malignant peripheral nerve sheath tumor arising in a traumatic neuroma: a case report.

    PubMed

    Kos, Zuzana; Robertson, Susan J; Purgina, Bibianna M; Verma, Shailendra; Gravel, Denis H

    2013-10-01

    A 67-year-old woman with a history of breast cancer presented with a soft tissue mass at the site of a remote, non-neoplastic lumbar surgery. Excisional biopsy revealed a traumatic neuroma. Five years later she re-presented with a rapidly growing, tender nodule at the same site. An excisional biopsy was again performed and revealed a tumor composed of malignant epithelioid and spindle cells merging imperceptibly with residual traumatic neuroma. The malignant cells were positive for vimentin, S-100 and micropthalmia transcription factor. They were negative for cytokeratins, muscle markers, Melan-A, HMB45, glial fibrillary acidic protein, and myelin basic protein. Electron microscopy showed no melanosomes. The diagnosis of malignant peripheral nerve sheath tumor arising within a long-standing traumatic neuroma was rendered and represents a hitherto unreported origin of this rare, aggressive soft tissue sarcoma.

  18. Fluorescein Sodium-Guided Surgery of Malignant Brain Tumors: History, Current Concepts, and Future Project.

    PubMed

    Schebesch, Karl-Michael; Brawanski, Alexander; Hohenberger, Christoph; Hohne, Julius

    2016-01-01

    Fluorescein sodium (FL)-guided resection has become an important and beneficial treatment method for malignant brain tumors. FL-guided resection improves the rate of gross total resection in high-grade gliomas (HGG) and cerebral metastases (CM). FL sensitively visualizes the disruption of the blood-brain barrier in the area surrounding malignant lesions, similar to contrast-enhanced T1-weighted MR sequences. This review of the current literature summarizes the history of FL in neurosurgery from 1946 until today. We discuss the molecular mechanism of FL accumulation in cerebral malignant tumors and provide an overview of the current practice of using FL and applying a dedicated surgical microscope filter. Additionally, we outline and discuss ongoing trials and future projects. PMID:26956810

  19. The effects of "BAR" therapy on oral malignant tumors.

    PubMed

    Nagai, T; Sakaizumi, K; Asanami, S; Lian, S L; Tomita, O; Hirayama, T

    1978-05-01

    "BAR" therapy is a combined therapy with BUdR (Radiosensitizer), Antimetabolites (5-FU, FT-207 etc.) and Radiation for malignant tumours. How radiation can be reduced as far as possible and how the effects of treatment can be increased as much as possible are the objectives of this study of combining radiation and BUdR therapy. The authors attempted to irradiate 3-5 days after the BUdR and antimetabolite had been infused via the superficial temporal artery, in 12 malignant oral tumours (11 squamous cell carcinomas and 1 reticulum-cell sarcoma). BUdR 50-250 mg/day, antimetabolites (5-FU) 10-250 mg/day and a total irradiation dose of 6000 rads by 6 MeV Linac X-ray or Co-60 gamma ray, 200 rads/day were given. 9 marked responses, 2 moderate responses and 1 no response (2 cases were operated on by local resection) were obtained by the authors. Side effects of treatment were observed during the course of "BAR" therapy. Stomatitis was found in all patients and it occurred on the mucosa of the tumour-affected site especially. Dermatitis of the skin of the face was noted in 6 cases, resembling irradiation dermatitis. Fever was observed in 4 cases and it always occurred after irradiation. Diarrhoea was noted in 3 cases and occurred before irradiation, 2 out of 3 were given BUdR 0.1 g and the remaining one was given BUdR 1 g, and 5-FU lg. In addition, there were: 1 loss of appetite, 1 nausea and 1 exfoliation of nails. PMID:353211

  20. Synthesis and evaluation of boron compounds for neutron capture therapy of malignant brain tumors

    SciTech Connect

    Soloway, A.H.

    1991-01-01

    Current progress on this research includes the synthesis of chemical structures for malignant brain tumors. These structures include boron-containing derivatives of lipophilic anticonvulsants and CNS depressants; carboranyl precursors of nucleic acids and related structures; and carboranyl amino acids. Cellular uptake and persistence studies have also been carried out with F98 rat glioma cells. 1 fig., 1 tab.

  1. Advanced malignant solitary fibrous tumor in pelvis responding to radiation therapy.

    PubMed

    Kawamura, Shinobu; Nakamura, Takafumi; Oya, Takeshi; Ishizawa, Shin; Sakai, Yuta; Tanaka, Tomonori; Saito, Shigeru; Fukuoka, Junya

    2007-04-01

    Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm that is benign in most cases. Although SFT was first recognized to arise only in the pleura, recent reports indicate that SFT can involve a wide range of anatomical sites. To date, 17 cases of pelvic SFT have been reported. Herein is reported a case of a 74-year-old woman with a giant malignant SFT in the pelvis. Along with massive invasion to adjacent organs and multiple lung metastases detected on radiography, biopsy from the tumor through the vaginal wall showed malignant looking spindle-cell neoplasm with increased cellularity, areas of necrosis, and high mitotic activity (5/10 high-power fields). Immunohistochemically, the tumor cells were diffusely and strongly positive for CD34, CD99, and bcl-2. Based on pathological features and clinical presentation, diagnosis of malignant SFT was made. The patient received systemic and the intra-arterial chemotherapy followed by whole pelvic radiation therapy (50 Gy). Initial chemotherapies failed to control the tumor. Afterwards, improvement was observed radiologically and pathologically in the 12 months' follow up after the radiation therapy. This is the first report related to therapeutic remarks on advanced malignant SFT.

  2. Salivary gland-type tumors of the breast: a spectrum of benign and malignant tumors including "triple negative carcinomas" of low malignant potential.

    PubMed

    Foschini, Maria P; Krausz, Thomas

    2010-02-01

    Salivary gland-type neoplasms of the breast are uncommon and comprise numerous entities analogous to that more commonly seen in salivary glands. The clinicopathologic spectrum ranges from benign to malignant but there are important differences as compared with those of their salivary counterpart. In the breast, benign adenomyoepithelioma is recognized in addition to malignant one, whereas in the salivary gland a histologically similar tumor is designated as epithelial-myoepithelial carcinoma without a separate benign subgroup. Mammary adenoid cystic carcinoma is a low-grade neoplasm compared with its salivary equivalent. It is also important to appreciate that in contrast to "triple negative" conventional breast carcinomas with aggressive course, most salivary-type malignant breast neoplasms behave in a low-grade manner. Most of these tumors are capable of differentiating along both epithelial and myoepithelial lines, but the amount of each lineage-component varies from case to case, contributing to diagnostic difficulties. Well established examples of this group include pleomorphic adenoma, adenomyoepithelioma, and adenoid cystic carcinoma. Another family of salivary gland-type mammary epithelial neoplasms is devoid of myoepithelial cells. Key examples include mucoepidermoid carcinoma and acinic cell carcinoma. The number of cases of salivary gland-type mammary neoplasms in the published data is constantly increasing but some of the rarest subtypes like polymorphous low-grade adenocarcinoma and oncocytic carcinoma are "struggling" to become clinically relevant entities in line with those occurring more frequently in salivary glands.

  3. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma.

    PubMed

    Moffitt, Richard A; Marayati, Raoud; Flate, Elizabeth L; Volmar, Keith E; Loeza, S Gabriela Herrera; Hoadley, Katherine A; Rashid, Naim U; Williams, Lindsay A; Eaton, Samuel C; Chung, Alexander H; Smyla, Jadwiga K; Anderson, Judy M; Kim, Hong Jin; Bentrem, David J; Talamonti, Mark S; Iacobuzio-Donahue, Christine A; Hollingsworth, Michael A; Yeh, Jen Jen

    2015-10-01

    Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival rate of 4%. A key hallmark of PDAC is extensive stromal involvement, which makes capturing precise tumor-specific molecular information difficult. Here we have overcome this problem by applying blind source separation to a diverse collection of PDAC gene expression microarray data, including data from primary tumor, metastatic and normal samples. By digitally separating tumor, stromal and normal gene expression, we have identified and validated two tumor subtypes, including a 'basal-like' subtype that has worse outcome and is molecularly similar to basal tumors in bladder and breast cancers. Furthermore, we define 'normal' and 'activated' stromal subtypes, which are independently prognostic. Our results provide new insights into the molecular composition of PDAC, which may be used to tailor therapies or provide decision support in a clinical setting where the choice and timing of therapies are critical. PMID:26343385

  4. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma.

    PubMed

    Moffitt, Richard A; Marayati, Raoud; Flate, Elizabeth L; Volmar, Keith E; Loeza, S Gabriela Herrera; Hoadley, Katherine A; Rashid, Naim U; Williams, Lindsay A; Eaton, Samuel C; Chung, Alexander H; Smyla, Jadwiga K; Anderson, Judy M; Kim, Hong Jin; Bentrem, David J; Talamonti, Mark S; Iacobuzio-Donahue, Christine A; Hollingsworth, Michael A; Yeh, Jen Jen

    2015-10-01

    Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival rate of 4%. A key hallmark of PDAC is extensive stromal involvement, which makes capturing precise tumor-specific molecular information difficult. Here we have overcome this problem by applying blind source separation to a diverse collection of PDAC gene expression microarray data, including data from primary tumor, metastatic and normal samples. By digitally separating tumor, stromal and normal gene expression, we have identified and validated two tumor subtypes, including a 'basal-like' subtype that has worse outcome and is molecularly similar to basal tumors in bladder and breast cancers. Furthermore, we define 'normal' and 'activated' stromal subtypes, which are independently prognostic. Our results provide new insights into the molecular composition of PDAC, which may be used to tailor therapies or provide decision support in a clinical setting where the choice and timing of therapies are critical.

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

    NASA Astrophysics Data System (ADS)

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

    1996-12-01

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

  6. Malignant mixed tumors arising in salivary glands. I. Carcinomas arising in benign mixed tumors: a clinicopathologic study.

    PubMed

    LiVolsi, V A; Perzin, K H

    1977-05-01

    Forty-seven cases of malignant mixed tumor (MMT) arising in major and minor salivary glands are presented. By definition, all these lesions contained both a benign mixed tumor (BMT) as well as a malignant neoplasm, usually a poorly differentiated carcinoma. In some cases, the carcinoma developed in a previously untreated salivary gland mass which was known to have been present for many years, others evolved in a recurrent previously resected BMT and still others originated in a previously undetected BMT. Adverse prognostic factors included: carcinomatous involvement of the resection lines, perineural invasion, metastases in lymph nodes, and origin in a major salivary gland. Lesions arising in the palate had a better prognosis as compared to major salivary gland tumors. Some patients died of locally uncontrollable tumor and others because of metastatic disease. Local recurrences of MMT were seen frequently; 18 patients (38%) had a total of 32 local recurrences. Of patients followed five years or more, seven (35%) had died of tumor, 11 (55%) had no evidence of disease, and two (10%) had died of other causes. Prolonged follow-up is required because recurrences and death from tumor may be seen many years following the diagnosis of MMT. Recommendations for therapy are made. Criteria for differentiating MMT from recurrent BMT and from cylindromatous carcinoma are discussed.

  7. Skeletal sequelae of radiation therapy for malignant childhood tumors

    SciTech Connect

    Butler, M.S.; Robertson, W.W. Jr.; Rate, W.; D'Angio, G.J.; Drummond, D.S. )

    1990-02-01

    One hundred forty-three patients who received radiation therapy for childhood tumors, and survived to the age of skeletal maturity, were studied by retrospective review of oncology records and roentgenograms. Diagnoses for the patients were the following: Hodgkin's lymphoma (44), Wilms's tumor (30), acute lymphocytic leukemia (26), non-Hodgkin's lymphoma (18), Ewing's sarcoma (nine), rhabdomyosarcoma (six), neuroblastoma (six), and others (four). Age at the follow-up examination averaged 18 years (range, 14-28 years). Average length of follow-up study was 9.9 years (range, two to 18 years). Asymmetry of the chest and ribs was seen in 51 (36%) of these children. Fifty (35%) had scoliosis; 14 had kyphosis. In two children, the scoliosis was treated with a brace, while one developed significant kyphosing scoliosis after laminectomy and had spinal fusion. Twenty-three (16%) patients complained of significant pain at the radiation sites. Twelve of the patients developed leg-length inequality; eight of those were symptomatic. Three patients developed second primary tumors. Currently, the incidence of significant skeletal sequelae is lower and the manifestations are less severe than reported in the years from 1940 to 1970. The reduction in skeletal complications may be attributed to shielding of growth centers, symmetric field selection, decreased total radiation doses, and sequence changes in chemotherapy.

  8. Radionuclide salivary scan imaging of a "functioning" malignant parotid tumor (mucous-producing papillary adenocarcinoma).

    PubMed

    Noyek, A M; Greyson, N D; Fernandes, B J; Chapnik, J S

    1982-04-01

    To date, all "functioning" or "hot" tumors on salivary gland scan have been benign - either the not uncommon Warthin's tumor or the rare oncocytoma. A positive salivary scan was obtained in a functioning malignant tumor of the parotid gland (a mucous-producing papillary adenocarcinoma). This occurrence has not previously been reported. The pathologic findings and the radionuclide images are demonstrated in this elderly female. It is presumed that the Technetium Tc99m pertechnetate has been concentrated in the tumor. The functioning epithelial cell, however, is not the benign oncocyte associated with other previously reported benign functioning tumors. Clinical discretion is therefore suggested in interpreting the significance of a functioning salivary gland tumor if encountered in an elderly female.

  9. Hypoxia Responsive, Tumor Penetrating Lipid Nanoparticles for Delivery of Chemotherapeutics to Pancreatic Cancer Cell Spheroids.

    PubMed

    Kulkarni, Prajakta; Haldar, Manas K; Katti, Preeya; Dawes, Courtney; You, Seungyong; Choi, Yongki; Mallik, Sanku

    2016-08-17

    Solid tumors are often poorly irrigated due to structurally compromised microcirculation. Uncontrolled multiplication of cancer cells, insufficient blood flow, and the lack of enough oxygen and nutrients lead to the development of hypoxic regions in the tumor tissues. As the partial pressure of oxygen drops below the necessary level (10 psi), the cancer cells modulate their genetic makeup to survive. Hypoxia triggers tumor progression by enhancing angiogenesis, cancer stem cell production, remodeling of the extracellular matrix, and epigenetic changes in the cancer cells. However, the hypoxic regions are usually located deep in the tumors and are usually inaccessible to the intravenously injected drug carrier or the drug. Considering the designs of the reported nanoparticles, it is likely that the drug is delivered to the peripheral tumor tissues, close to the blood vessels. In this study, we prepared lipid nanoparticles (LNs) comprising the synthesized hypoxia-responsive lipid and a peptide-lipid conjugate. We observed that the resultant LNs penetrated to the hypoxic regions of the tumors. Under low oxygen partial pressure, the hypoxia-responsive lipid undergoes reduction, destabilizing the lipid membrane, and releasing encapsulated drugs from the nanoparticles. We demonstrated the results employing spheroidal cultures of the pancreatic cancer cells BxPC-3. We observed that the peptide-decorated, drug encapsulated LNs reduced the viability of pancreatic cancer cells of the spheroids to 35% under hypoxic conditions. PMID:27391789

  10. Imaging Tumor Variation in Response to Photodynamic Therapy in Pancreatic Cancer Xenograft Models

    SciTech Connect

    Samkoe, Kimberley S.; Chen, Alina; Rizvi, Imran; O'Hara, Julia A.; Hoopes, P. Jack; Pereira, Stephen P.; Hasan, Tayyaba; Pogue, Brian W.

    2010-01-15

    Purpose: A treatment monitoring study investigated the differential effects of orthotopic pancreatic cancer models in response to interstitial photodynamic therapy (PDT), and the validity of using magnetic resonance imaging as a surrogate measure of response was assessed. Methods and Materials: Different orthotopic pancreatic cancer xenograft models (AsPC-1 and Panc-1) were used to represent the range of pathophysiology observed in human beings. Identical dose escalation studies (10, 20, and 40J/cm) using interstitial verteporfin PDT were performed, and magnetic resonance imaging with T2-weighted and T1-weighted contrast were used to monitor the total tumor volume and the vascular perfusion volume, respectively. Results: There was a significant amount of necrosis in the slower-growing Panc-1 tumor using high light dose, although complete necrosis was not observed. Lower doses were required for the same level of tumor kill in the faster-growing AsPC-1 cell line. Conclusions: The tumor growth rate and vascular pattern of the tumor affect the optimal PDT treatment regimen, with faster-growing tumors being relatively easier to treat. This highlights the fact that therapy in human beings shows a heterogeneous range of outcomes, and suggests a need for careful individualized treatment outcomes assessment in clinical work.

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

    PubMed

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

    2015-05-01

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

  12. Patient-derived xenograft models for pancreatic adenocarcinoma demonstrate retention of tumor morphology through incorporation of murine stromal elements.

    PubMed

    Delitto, Daniel; Pham, Kien; Vlada, Adrian C; Sarosi, George A; Thomas, Ryan M; Behrns, Kevin E; Liu, Chen; Hughes, Steven J; Wallet, Shannon M; Trevino, Jose G

    2015-05-01

    Direct implantation of viable surgical specimens provides a representative preclinical platform in pancreatic adenocarcinoma. Patient-derived xenografts consistently demonstrate retained tumor morphology and genetic stability. However, the evolution of the tumor microenvironment over time remains poorly characterized in these models. This work specifically addresses the recruitment and incorporation of murine stromal elements into expanding patient-derived pancreatic adenocarcinoma xenografts, establishing the integration of murine cells into networks of invading cancer cells. In addition, we provide methods and observations in the establishment and maintenance of a patient-derived pancreatic adenocarcinoma xenograft model. A total of 25 histologically confirmed pancreatic adenocarcinoma specimens were implanted subcutaneously into nonobese diabetic severe combined immunodeficiency mice. Patient demographics, staging, pathological analysis, and outcomes were analyzed. After successful engraftment of tumors, histological and immunofluorescence analyses were performed on explanted tumors. Pancreatic adenocarcinoma specimens were successfully engrafted in 15 (60%) of 25 attempts. Successful engraftment does not appear to correlate with clinicopathologic factors or patient survival. Tumor morphology is conserved through multiple passages, and tumors retain metastatic potential. Interestingly, despite morphological similarity between passages, human stromal elements do not appear to expand with invading cancer cells. Rather, desmoplastic murine stroma dominates the xenograft microenvironment after the initial implantation. Recruitment of stromal elements in this manner to support and maintain tumor growth represents a novel avenue for investigation into tumor-stromal interactions.

  13. Molecular classification of breast phyllodes tumors: validation of the histologic grading scheme and insights into malignant progression.

    PubMed

    Ang, Mei Kim; Ooi, Aik Seng; Thike, Aye Aye; Tan, Patrick; Zhang, Zhongfa; Dykema, Karl; Furge, Kyle; Teh, Bin Tean; Tan, Puay Hoon

    2011-09-01

    Phyllodes tumors of the breast are rare fibroepithelial neoplasms with a potential for recurrence. Current histological classification is not always predictive of clinical behavior. The aim of this study was to identify genetic changes associated with the development of borderline and malignant phyllodes tumors in an Asian population, and to assess if genetic data supported the categorization of these tumors into the existing three grades of benign, borderline, and malignant. Expression profiling of 21 phyllodes tumors (6 benign, 10 borderline, 5 malignant) was performed using Affymetrix U133Plus 2.0 GeneChips(®). Gene expression among benign, borderline, and malignant tumors was compared and a 29 gene list was able to classify them according to their histologic grade. Among these 29 genes are those responsible for matrix formation, cell adhesion, epidermis formation, and cell proliferation. Comparative genomic microarray analysis showed that the most common chromosomal alteration associated with borderline and malignant tumors was 1q gain, and an increasing number of chromosomal changes was noted with increasing histological grade. Upregulation of HOXB13 was seen in malignant relative to borderline phyllodes tumors and further investigated by immunohistochemistry in a corresponding set of formalin-fixed, paraffin-embedded tumors. HOXB13 protein overexpression was found to be correlated with stromal hypercellularity and atypia (P = 0.03, P = 0.039, respectively) and may be implicated in the development of malignant phyllodes tumors.

  14. Altered PTEN, ATRX, CHGA, CHGB, and TP53 expression are associated with aggressive VHL-associated pancreatic neuroendocrine tumors.

    PubMed

    Weisbrod, Allison B; Zhang, Lisa; Jain, Meenu; Barak, Stephanie; Quezado, Martha M; Kebebew, Electron

    2013-06-01

    Von Hippel-Lindau (VHL) syndrome is an inherited cancer syndrome in which 8-17 % of germline mutation carriers develop pancreatic neuroendocrine tumors (PNETs). There is limited data on prognostic markers for PNETs other than Ki-67, which is included in the World Health Organization classification system. Recently, specific genes and pathways have been identified by whole exome sequencing which may be involved in the tumorigenesis of PNETs and may be markers of disease aggressiveness. The objective of this study was to identify molecular markers of aggressive disease in VHL-associated PNETs. The protein expression of eight genes (PTEN, CHGA, CHGB, ATRX, DAXX, CC-3, VEGF, and TP53) was analyzed in PNETs by immunohistochemistry and compared to clinical data, VHL genotype, functional imaging results, and pathologic findings. Subcellular distribution of phosphatase and tensin (PTEN), chromogranin A (CHGA), and alpha thalassemia/mental retardation syndrome X-linked (ATRX) were significantly different by WHO classifications (p ≤ 0.05). There was decreased PTEN nuclear to cytoplasmic ratio (p < 0.01) and decreased CHGA nuclear expression (p = 0.03) in malignant samples as compared to benign. Lower cytoplasmic chromogranin B (CHGB) expression (p = 0.03) was associated with malignant tumors and metastasis. Higher nuclear expression of PTEN was associated with VHL mutations in exon 3 (p = 0.04). Higher PTEN and CHGB expression was associated with higher FDG-PET avidity (p < 0.05). Cytoplasmic expression of CC-3 was associated with higher serum chromogranin A levels (ρ = 0.72, p = 0.02). Lastly, greater cytoplasmic expression of p53 was associated with metastasis. Our findings suggest that altered PTEN, ATRX, CHGA, and CHGB expression are associated with aggressive PNET phenotype in VHL and may serve as useful adjunct prognostic markers to Ki-67 in PNETs.

  15. CA 19-9 in pancreatic cancer: retrospective evaluation of patients with suspicion of pancreatic cancer.

    PubMed

    Molina, Victor; Visa, Laura; Conill, Carles; Navarro, Salvador; Escudero, Jose M; Auge, Jose M; Filella, Xavier; Lopez-Boado, Miguel A; Ferrer, Joana; Fernandez-Cruz, Laureano; Molina, Rafael

    2012-06-01

    CA 19.9 serum levels were prospectively determined in 573 patients admitted to hospital for suspicion of pancreatic cancer. The final diagnosis was 77 patients with no malignancy, 389 patients with pancreatic cancer, 37 neuroendocrine pancreatic cancer, 28 cholangiocarcinomas, 4 gallbladder cancer, 27 ampullary carcinomas, and 11 periampullary carcinomas. CA 19.9 was determined using a commercial assay from Roche Diagnostics, and 37 U/ml was considered as the upper limit of normality. Abnormal CA 19.9 serum levels were found in 27%, 81.5%, 85.7%, 59.3%, 63.6%, and 18.9% of patients with benign diseases, pancreatic cancer, cholangiocarcinomas, and ampullary, periampullary, or neuroendocrine tumors. Significantly higher concentrations of CA 19.9 were found in patients with than in those without malignancy or with neuroendocrine tumors. CA 19.9 serum levels were higher in pancreatic cancer or cholangiocarcinoma than in other malignancies (p < 0.0001). CA 19.9 serum levels were also correlated with tumor stage, treatment (significantly lower concentrations in resectable tumors), and tumor location (the highest in those located in the body, the lowest in those in the tail or uncinate) and site of metastases (highest in liver metastases). A trend to higher CA 19.9 serum concentrations was found in patients with jaundice, but only with statistical significance in the early stages. Using 50 or 100 U/ml in patients with jaundice, CA 19.9 was useful as an aid in the diagnosis of pancreatic cancer (sensitivity 77.9%, specificity 95.9%) as well as tumor resectability in pancreatic cancer with different cutoffs according to tumor location and bilirubin serum levels with specificities ranging from 90% to 100%. CA 19.9 is the tumor marker of choice in pancreatic adenocarcinomas, with a clear relationship with tumor location, stage, and resectability.

  16. Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST).

    PubMed

    Fujimoto, Takuya; Andoh, Tooru; Sudo, Tamotsu; Fujita, Ikuo; Fukase, Naomasa; Takeuchi, Tamotsu; Sonobe, Hiroshi; Inoue, Masayoshi; Hirose, Tkanori; Sakuma, Toshiko; Moritake, Hiroshi; Sugimoto, Tohru; Kawamoto, Teruya; Fukumori, Yoshinobu; Yamamoto, Satomi; Atagi, Shinji; Sakurai, Yoshinori; Kurosaka, Masahiro; Ono, Koji; Ichikawa, Hideki; Suzuki, Minoru

    2015-12-01

    Malignant peripheral nerve sheath tumors (MPNST) are relatively rare neoplasms with poor prognosis. At present there is no effective treatment for MPNST other than surgical resection. Nonetheless, the anti-tumor effect of boron neutron capture therapy (BNCT) was recently demonstrated in two patients with MPNST. Subsequently, tumor-bearing nude mice subcutaneously transplanted with a human MPNST cell line were injected with p-borono-L-phenylalanine (L-BPA) and subjected to BNCT. Pathological studies then revealed that the MPNST cells were selectively destroyed by BNCT.

  17. [The use of fast neutrons in treatment of malignant tumors of the head and neck].

    PubMed

    Gribova, O V; Musabaeva, L I; Choinzonov, E L; Novikov, V A; Lisin, V A

    2015-01-01

    The article presents issues of the application of neutron therapy in the combined and radiation therapy for head and neck tumors. There were developed methods of neutron and neutron-photon therapy in pre- and postoperative periods as well as in stand-alone option in unresectable tumors. The data obtained clearly demonstrate the superiority of new ways over standard methods of treatment. Neutron therapy is satisfactorily tolerated and allows improving the results of combined and radiation therapy patients with malignant tumors of the head and neck.

  18. Characterization of a pancreatic islet cell tumor in a polar bear (Ursus maritimus).

    PubMed

    Fortin, Jessica S; Benoit-Biancamano, Marie-Odile

    2014-01-01

    Herein, we report a 25-year-old male polar bear suffering from a pancreatic islet cell tumor. The aim of this report is to present a case of this rare tumor in a captive polar bear. The implication of potential risk factors such as high carbohydrate diet or the presence of amyloid fibril deposits was assessed. Necropsy examination revealed several other changes, including nodules observed in the liver, spleen, pancreas, intestine, and thyroid glands that were submitted for histopathologic analysis. Interestingly, the multiple neoplastic nodules were unrelated and included a pancreatic islet cell tumor. Immunohistochemistry of the pancreas confirmed the presence of insulin and islet amyloid polypeptide (IAPP) within the pancreatic islet cells. The IAPP gene was extracted from the paraffin-embedded liver tissue and sequenced. IAPP cDNA from the polar bear exhibits some differences as compared to the sequence published for several other species. Different factors responsible for neoplasms in bears such as diet, infectious agents, and industrial chemical exposure are reviewed. This case report raised several issues that further studies may address by evaluating the prevalence of cancers in captive or wild animals. PMID:25273481

  19. Optimizing 4-Dimensional Magnetic Resonance Imaging Data Sampling for Respiratory Motion Analysis of Pancreatic Tumors

    SciTech Connect

    Stemkens, Bjorn; Tijssen, Rob H.N.; Senneville, Baudouin D. de

    2015-03-01

    Purpose: To determine the optimum sampling strategy for retrospective reconstruction of 4-dimensional (4D) MR data for nonrigid motion characterization of tumor and organs at risk for radiation therapy purposes. Methods and Materials: For optimization, we compared 2 surrogate signals (external respiratory bellows and internal MRI navigators) and 2 MR sampling strategies (Cartesian and radial) in terms of image quality and robustness. Using the optimized protocol, 6 pancreatic cancer patients were scanned to calculate the 4D motion. Region of interest analysis was performed to characterize the respiratory-induced motion of the tumor and organs at risk simultaneously. Results: The MRI navigator was found to be a more reliable surrogate for pancreatic motion than the respiratory bellows signal. Radial sampling is most benign for undersampling artifacts and intraview motion. Motion characterization revealed interorgan and interpatient variation, as well as heterogeneity within the tumor. Conclusions: A robust 4D-MRI method, based on clinically available protocols, is presented and successfully applied to characterize the abdominal motion in a small number of pancreatic cancer patients.

  20. Characterization of a pancreatic islet cell tumor in a polar bear (Ursus maritimus).

    PubMed

    Fortin, Jessica S; Benoit-Biancamano, Marie-Odile

    2014-01-01

    Herein, we report a 25-year-old male polar bear suffering from a pancreatic islet cell tumor. The aim of this report is to present a case of this rare tumor in a captive polar bear. The implication of potential risk factors such as high carbohydrate diet or the presence of amyloid fibril deposits was assessed. Necropsy examination revealed several other changes, including nodules observed in the liver, spleen, pancreas, intestine, and thyroid glands that were submitted for histopathologic analysis. Interestingly, the multiple neoplastic nodules were unrelated and included a pancreatic islet cell tumor. Immunohistochemistry of the pancreas confirmed the presence of insulin and islet amyloid polypeptide (IAPP) within the pancreatic islet cells. The IAPP gene was extracted from the paraffin-embedded liver tissue and sequenced. IAPP cDNA from the polar bear exhibits some differences as compared to the sequence published for several other species. Different factors responsible for neoplasms in bears such as diet, infectious agents, and industrial chemical exposure are reviewed. This case report raised several issues that further studies may address by evaluating the prevalence of cancers in captive or wild animals.

  1. Epidemiologic and molecular characteristics of borderline and malignant epithelial ovarian tumors

    NASA Astrophysics Data System (ADS)

    Bastos, Eugenia Maria Chaves De Moraes

    Data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study were used to identify risk factors for epithelial ovarian cancer according to tumor behavior, histologic types, as well as p53 expression. Cases were women between 20 to 54 years old diagnosed with epithelial ovarian cancer from 1980 to 1982. Controls were women selected by random digit dialing. Tumor samples were analyzed for p53 overexpression using immunohistochemistry. Case-case and case-control conditional logistic regression models matched on age and diagnosing centers were used to calculate odds ratios (OR's) and 95% confidence intervals (CI's) for borderline, malignant, mucinous, and nonmucinous tumors, and p53 positive and p53 negative cases. The OR's for high number of lifetime ovulatory cycles (376-533 compared with less than 234) were 3.1 (95% CI 1.6-6.1) for malignant and 1.4 (95% CI 0.5-3.7) for borderline cases. The high number of ovulatory cycles was also a strong risk factor among nonmucinous cases. OR's for current and recent ex-smokers compared with never smokers were 2.8 (95% CI 1.7-4.8) for mucinous and 0.9 (95% CI 0.7-1.1) for nonmucinous types. Infertility showed a positive association with borderline ovarian cancer. Family history of ovarian or breast cancer was positively associated with malignant and nonmucinous cases. Parity had an inverse association with malignant ovarian cancer cases. When cases were subdivided by p53 results, the OR for tobacco smoking and p53 positive ovarian cancer was elevated for mucinous (OR = 3.9; 95% CI 0.8-18) at localized stage. Alcohol use showed a positive association with p53 positive malignant cases at advanced stage (OR = 2.0; 95% CI 1.2-3.2) and with p53 positive nonmucinous cases at advanced stage (OR = 2.1; 95% CI 1.2-3.4). A positive association between high number of ovulatory cycles and p53 positive malignant cases was observed in cases with localized stage (OR = 6.6; 95% CI 1.0-45) and advanced

  2. Hypoxia Drives Breast Tumor Malignancy through a TET-TNFα-p38-MAPK Signaling Axis.

    PubMed

    Wu, Min-Zu; Chen, Su-Feng; Nieh, Shin; Benner, Christopher; Ger, Luo-Ping; Jan, Chia-Ing; Ma, Li; Chen, Chien-Hung; Hishida, Tomoaki; Chang, Hong-Tai; Lin, Yaoh-Shiang; Montserrat, Nuria; Gascon, Pedro; Sancho-Martinez, Ignacio; Izpisua Belmonte, Juan Carlos

    2015-09-15

    Hypoxia is a hallmark of solid tumors that drives malignant progression by altering epigenetic controls. In breast tumors, aberrant DNA methylation is a prevalent epigenetic feature associated with increased risk of metastasis and poor prognosis. However, the mechanism by which hypoxia alters DNA methylation or other epigenetic controls that promote breast malignancy remains poorly understood. We discovered that hypoxia deregulates TET1 and TET3, the enzymes that catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), thereby leading to breast tumor-initiating cell (BTIC) properties. TET1/3 and 5hmC levels were closely associated with tumor hypoxia, tumor malignancy, and poor prognosis in breast cancer patients. Mechanistic investigations showed that hypoxia leads to genome-wide changes in DNA hydroxymethylation associated with upregulation of TNFα expression and activation of its downstream p38-MAPK effector pathway. Coordinate functions of TET1 and TET3 were also required to activate TNFα-p38-MAPK signaling as a response to hypoxia. Our results reveal how signal transduction through the TET-TNFα-p38-MAPK signaling axis is required for the acquisition of BTIC characteristics and tumorigenicity in vitro and in vivo, with potential implications for how to eradicate BTIC as a therapeutic strategy. PMID:26294212

  3. Current Understanding of Circulating Tumor Cells – Potential Value in Malignancies of the Central Nervous System

    PubMed Central

    Adamczyk, Lukasz A.; Williams, Hannah; Frankow, Aleksandra; Ellis, Hayley Patricia; Haynes, Harry R.; Perks, Claire; Holly, Jeff M. P.; Kurian, Kathreena M.

    2015-01-01

    Detection of circulating tumor cells (CTCs) in the blood via so-called “liquid biopsies” carries enormous clinical potential in malignancies of the central nervous system (CNS) because of the potential to follow disease evolution with a blood test, without the need for repeat neurosurgical procedures with their inherent risk of patient morbidity. To date, studies in non-CNS malignancies, particularly in breast cancer, show increasing reproducibility of detection methods for these rare tumor cells in the circulation. However, no method has yet received full recommendation to use in clinical practice, in part because of lack of a sufficient evidence base regarding clinical utility. In CNS malignancies, one of the main challenges is finding a suitable biomarker for identification of these cells, because automated systems, such as the widely used Cell Search system, are reliant on markers, such as the epithelial cell adhesion molecule, which are not present in CNS tumors. This review examines methods for CTC enrichment and detection, and reviews the progress in non-CNS tumors and the potential for using this technique in human brain tumors. PMID:26322014

  4. Malignant solitary fibrous tumor of the thyroid: a case-report and review of the literature.

    PubMed

    Alves Filho, Wellington; Mahmoud, Renata Regina da Graça Lorencetti; Ramos, Daniel Marin; Araujo-Filho, Vergilius José Furtado de; Lima, Patricia Picciarelli de; Cernea, Claudio Roberto; Brandão, Lenine Garcia

    2014-06-01

    Solitary fibrous tumor (SFT) is an uncommon spindle-cell neoplasm that most often involves the pleura, rarely occurring in extra-thoracic locations. Twenty-six cases of SFT arising in the thyroid gland have been described. We report a case of a 60-year-old woman presenting an 8-month history of enlargement of the neck associated with dysphagia. The patient underwent a right hemithyroidectomy and SFT of the thyroid was diagnosed. Immunohistochemistry showed positivity for CD34 marker, and the high number of mitoses and the presence of cellular atypia suggested that the tumor was malignant. To our knowledge, this is the second case of malignant SFT of the thyroid gland ever reported. Due to the rarity of these tumors, the indication of adjuvant therapy and prognosis are uncertain. Long-term follow-up after surgical resection seems to be advisable.

  5. Malignant peripheral nerve sheath tumor presenting as orbito temporal lump: Case report and review of literature

    PubMed Central

    Panigrahi, Souvagya; Mishra, Sudhansu S.; Mishra, Sanjib; Das, Srikant

    2016-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma. The most common anatomical sites include the upper and lower extremities and trunk and less commonly the head and neck. To our knowledge, few patients with a cranial or facial MPNST have been reported. We report such a lesion in a 35-year-old woman who presented with left sided rapidly progressive proptosis and visual loss due to an orbital lump extending up to the temporal lobe. Cranial imaging showed a huge mass invading the orbital wall and temporal bone. The presumptive diagnosis was a malignant orbital tumor. Preoperative fine needle aspiration cytology of the orbital mass came to be neurofibroma. Near total resection of the tumor was done. Histopathology revealed MPNST which was subsequently confirmed on the basis of immunopositivity for S-100. The patient recovered uneventfully and was discharged 8 days after surgery with an advice to attend cancer institute for possible radiotherapy. PMID:27057226

  6. Malignant peripheral nerve sheath tumor presenting as orbito temporal lump: Case report and review of literature.

    PubMed

    Panigrahi, Souvagya; Mishra, Sudhansu S; Mishra, Sanjib; Das, Srikant

    2016-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma. The most common anatomical sites include the upper and lower extremities and trunk and less commonly the head and neck. To our knowledge, few patients with a cranial or facial MPNST have been reported. We report such a lesion in a 35-year-old woman who presented with left sided rapidly progressive proptosis and visual loss due to an orbital lump extending up to the temporal lobe. Cranial imaging showed a huge mass invading the orbital wall and temporal bone. The presumptive diagnosis was a malignant orbital tumor. Preoperative fine needle aspiration cytology of the orbital mass came to be neurofibroma. Near total resection of the tumor was done. Histopathology revealed MPNST which was subsequently confirmed on the basis of immunopositivity for S-100. The patient recovered uneventfully and was discharged 8 days after surgery with an advice to attend cancer institute for possible radiotherapy. PMID:27057226

  7. Efficacy and Safety of Endoscopic Ultrasound-guided Ethanol Ablation Therapy for Pancreatic Neuroendocrine Tumors.

    PubMed

    Matsumoto, Kazuyuki; Kato, Hironari; Tsutsumi, Koichiro; Mizukawa, Sho; Yabe, Syuntaro; Seki, Hiroyuki; Akimoto, Yutaka; Uchida, Daisuke; Tomoda, Takeshi; Yamamoto, Naoki; Horiguchi, Shigeru; Okada, Hiroyuki

    2016-08-01

    Recently, endoscopic ultrasonography (EUS)-guided ethanol ablation for small pancreatic neuroendocrine tumors (p-NETs) has been reported. However, the efficacy and safety of the technique remain unclear. We have launched a prospective pilot study of EUS-guided ethanol ablation for p-NETs. The major eligibility criteria are the presence of a pathologically diagnosed grade (G) 1 or G2 p-NET, a tumor size of 2cm, and being a poor candidate for surgery. A total of 5 patients will be treated. The primary endpoint will be the complete ablation rate at 1 month after treatment. PMID:27549680

  8. Molecular analyses of the candidate tumor suppressor gene, PLAGL1, in benign and malignant salivary gland tumors.

    PubMed

    Enlund, Fredrik; Persson, Fredrik; Stenman, Göran

    2004-12-01

    Deletions affecting the long arm of chromosome 6 are a characteristic feature of all major subtypes of malignant salivary gland tumors. Moreover, a subgroup of adenoid cystic carcinomas have t(6;9)(q23-25;p21-24) translocations with breakpoints located within the commonly deleted region. Here we have examined the possible involvement of the candidate tumor suppressor gene, PLAGL1, in these deletions and translocations. Northern blot and fluorescence in situ hybridization (FISH) analyses of a series of 27 salivary gland tumors revealed no significant changes in the gene expression or rearrangements of PLAGL1. FISH analysis also demonstrated that the 6q translocation breakpoint in adenoid cystic carcinomas with t(6;9) is proximal to the PLAGL1 locus. Collectively, these results indicate that PLAGL1 is not likely to be the major target gene of the 6q rearrangements in salivary gland tumors.

  9. Bone morphogenetic protein modulator BMPER is highly expressed in malignant tumors and controls invasive cell behavior.

    PubMed

    Heinke, J; Kerber, M; Rahner, S; Mnich, L; Lassmann, S; Helbing, T; Werner, M; Patterson, C; Bode, C; Moser, M

    2012-06-14

    Bone morphogenetic proteins (BMPs) are growth factors that exert important functions in cell proliferation, migration and differentiation. Till date, multiple human tumors have been reported to display a dysregulation of several members of the BMP pathway that is associated with enhanced malignant tumor growth and metastasis. BMPER (BMP endothelial cell precursor-derived regulator) is a direct BMP modulator that is necessary for BMPs to exert their full-range signaling activity. Moreover, BMPER is expressed by endothelial cells and their progenitors, and has pro-angiogenic features in these cells. Here, we describe the expression of BMPER in human specimens of lung, colon and cervix carcinomas and cell lines derived from such carcinomas. In contrast to healthy tissues, BMPER is highly expressed upon malignant deterioration. Functionally, loss of BMPER in the lung tumor cell line A549 impairs proliferation, migration, invasion as well as tumor cell-induced endothelial cell sprout formation. In contrast, stimulation of A549 cells with exogenous BMPER had no further effect. We found that the BMPER effect may be transduced by regulation of the BMP target transcription factor inhibitor of DNA binding 1 (Id1) and matrix metalloproteinases (MMPs) 9 and 2. These facilitators of cell migration are downregulated when BMPER is absent. To prove the relevance of our in vitro results in vivo, we generated Lewis lung carcinoma cells with impaired BMPER expression and implanted them into the lungs of C57BL/6 mice. In this model, the absence of BMPER resulted in severely reduced tumor growth and tumor angiogenesis. Taken together, these data unequivocally demonstrate that the BMP modulator BMPER is highly expressed in malignant tumors and tumor growth is dependent on the presence of BMPER.

  10. Bone morphogenetic protein modulator BMPER is highly expressed in malignant tumors and controls invasive cell behavior

    PubMed Central

    Heinke, J; Kerber, M; Rahner, S; Mnich, L; Lassmann, S; Helbing, T; Werner, M; Patterson, C; Bode, C; Moser, M

    2012-01-01

    Bone morphogenetic proteins (BMPs) are growth factors that exert important functions in cell proliferation, migration and differentiation. Till date, multiple human tumors have been reported to display a dysregulation of several members of the BMP pathway that is associated with enhanced malignant tumor growth and metastasis. BMPER (BMP endothelial cell precursor-derived regulator) is a direct BMP modulator that is necessary for BMPs to exert their full-range signaling activity. Moreover, BMPER is expressed by endothelial cells and their progenitors, and has pro-angiogenic features in these cells. Here, we describe the expression of BMPER in human specimens of lung, colon and cervix carcinomas and cell lines derived from such carcinomas. In contrast to healthy tissues, BMPER is highly expressed upon malignant deterioration. Functionally, loss of BMPER in the lung tumor cell line A549 impairs proliferation, migration, invasion as well as tumor cell-induced endothelial cell sprout formation. In contrast, stimulation of A549 cells with exogenous BMPER had no further effect. We found that the BMPER effect may be transduced by regulation of the BMP target transcription factor inhibitor of DNA binding 1 (Id1) and matrix metalloproteinases (MMPs) 9 and 2. These facilitators of cell migration are down-regulated when BMPER is absent. To prove the relevance of our in vitro results in vivo, we generated Lewis lung carcinoma cells with impaired BMPER expression and implanted them into the lungs of C57BL/6 mice. In this model, the absence of BMPER resulted in severely reduced tumor growth and tumor angiogenesis. Taken together, these data unequivocally demonstrate that the BMP modulator BMPER is highly expressed in malignant tumors and tumor growth is dependent on the presence of BMPER. PMID:22020334

  11. Polyethylenimine-coated SPION exhibits potential intrinsic anti-metastatic properties inhibiting migration and invasion of pancreatic tumor cells.

    PubMed

    Mulens-Arias, Vladimir; Rojas, José Manuel; Pérez-Yagüe, Sonia; Morales, María del Puerto; Barber, Domingo F

    2015-10-28

    Due to its aggressive behavior, pancreatic cancer is one of the principal causes of cancer-related deaths. The highly metastatic potential of pancreatic tumor cells demands the development of more effective anti-metastatic approaches for this disease. Although polyethylenimine-coated superparamagnetic iron oxide nanoparticles (PEI-coated SPIONs) have been studied for their utility as transfection agents, little is known of their effect on tumor cell biology. Here we demonstrated that PEI-coated SPIONs have potent inhibitory effects on pancreatic tumor cell migration/invasion, through inhibition of Src kinase and decreased expression of MT1-MMP and MMP2 metalloproteinases. When treated with PEI-coated SPIONs, the pancreatic tumor cell line Pan02 showed reduced invadosome density and thus, a decrease in their ability to invade through basement membrane. These nanoparticles temporarily downmodulated microRNA-21, thereby upregulating the cell migration inhibitors PTEN, PDCD4 and Sprouty-1. PEI-coated SPIONs thus show intrinsic, possibly anti-metastatic properties for modulating pancreatic tumor cell migration machinery, which indicates their potential as anti-metastatic agents for treatment of pancreatic cancer.

  12. Malignant mixed tumors of the salivary gland: a study of loss of heterozygosity in tumor suppressor genes.

    PubMed

    Fowler, Melissa H; Fowler, Jason; Ducatman, Barbara; Barnes, Leon; Hunt, Jennifer L

    2006-03-01

    Carcinosarcomas and carcinoma ex pleomorphic adenoma of the salivary glands are rare tumors that fit into the broader category of malignant mixed tumors. Although most evidence has suggested that the different morphologic components arise from a common clonal origin, there are very few studies that have provided molecular evidence for this clonality. In this study, we examined a set of seven carcinosarcomas and four carcinomas ex pleomorphic adenoma for tumor suppressor gene loss of heterozygosity, in order to assess the clonal patterns in the varying components. Microdissection was performed to obtain each morphological component and tumor suppressor gene loci on 3p, 5q, 9p, 17p, 17q, and 18q were analyzed. The fractional allelic loss (FAL) was calculated for each area, and the different targets were compared for their molecular profile. The overall mean FAL of the malignant targets was 42%. In carcinosarcomas, the sarcomatous targets had a higher mean FAL than the carcinomatous targets (68 vs 46%, respectively) and in carcinomas ex pleomorphic adenoma, the mean FAL in the benign component was 11 vs 46% seen in the carcinomatous component. The most frequently lost genetic loci were p53 (17p13, 73%), nm23-H1 (17q21, 55%), and DCC (18q21, 50%). Loss of heterozygosity of 17q21 and 9p21 only occurred in carcinosarcomas and not in carcinomas ex pleomorphic adenoma. Within the carcinosarcomas, the mutational profiles were conserved between epithelial and sarcomatous areas. In carcinomas ex pleomorphic adenoma, loss of heterozygosity was uncommon in the benign component, but the mutations were conserved in the corresponding malignant areas. These results support the hypothesis that the carcinomatous and sarcomatous components of carcinosarcomas are clonally related. Furthermore, these data support prior studies that suggest a common clonal origin for the benign and malignant components of carcinomas ex pleomorphic adenoma.

  13. Mucin-producing pancreatic tumors: a study of nuclear DNA content by flow cytometry.

    PubMed

    Murakami, Y; Yokoyama, T; Kodama, T; Takesue, Y; Okita, M; Nakamitsu, A; Imamura, Y; Santo, T; Tsumura, H; Miyamoto, K

    1993-01-01

    Nuclear DNA content in eight surgically resected mucin-producing pancreatic tumors (MPPT) consisting of two mucinous intraductal adenocarcinomas (MIDAC), two mucinous intraductal adenomas (MIDA), one mucinous cyst-adenocarcinoma (MCAC), and three mucinous cystadenomas (MCA) were measured by flow cytometry using paraffin-embedded tissue samples. The technique of Shutte was used for the preparation of paraffin-embedded tissue into single dissociated nuclei, while the method of Vindelov was used for staining the isolated nuclei with propidium iodine. Clinicopathologically, the four patients with MIDAC or MIDA were all male and had cystic lesions with a dilated pancreatic duct at the head of the pancreas, while the four patients with MCAC or MCA were all females and had cystic tumors at either the body or tail of the pancreas. All eight patients with MPPT had no metastasis to the regional lymph nodes and were all still alive without recurrence. In an analysis of nuclear DNA content, seven of eight patients had DNA diploid tumors while one patient with a MIDAC perforating the duodenum and choledochus had a DNA aneuploid tumor. Thus, these findings suggest that DNA diploid patterns in MPPT might be associated with a favorable prognosis in MPPT although some patients whose MPPT invaded the surrounding organs might have DNA aneuploid tumors. PMID:8395265

  14. Partial dependence of breast tumor malignancy on ultrasound image features derived from boosted trees

    NASA Astrophysics Data System (ADS)

    Yang, Wei; Zhang, Su; Li, Wenying; Chen, Yaqing; Lu, Hongtao; Chen, Wufan; Chen, Yazhu

    2010-04-01

    Various computerized features extracted from breast ultrasound images are useful in assessing the malignancy of breast tumors. However, the underlying relationship between the computerized features and tumor malignancy may not be linear in nature. We use the decision tree ensemble trained by the cost-sensitive boosting algorithm to approximate the target function for malignancy assessment and to reflect this relationship qualitatively. Partial dependence plots are employed to explore and visualize the effect of features on the output of the decision tree ensemble. In the experiments, 31 image features are extracted to quantify the sonographic characteristics of breast tumors. Patient age is used as an external feature because of its high clinical importance. The area under the receiver-operating characteristic curve of the tree ensembles can reach 0.95 with sensitivity of 0.95 (61/64) at the associated specificity 0.74 (77/104). The partial dependence plots of the four most important features are demonstrated to show the influence of the features on malignancy, and they are in accord with the empirical observations. The results can provide visual and qualitative references on the computerized image features for physicians, and can be useful for enhancing the interpretability of computer-aided diagnosis systems for breast ultrasound.

  15. A pathology study of malignant and benign ovarian tumors among atomic-bomb survivors--case series report.

    PubMed

    Inai, Kouki; Shimizu, Yukiko; Kawai, Kioko; Tokunaga, Masayoshi; Soda, Midori; Mabuchi, Kiyohiko; Land, Charles E; Tokuoka, Shoji

    2006-03-01

    The present article describes the series of incident primary ovarian tumors in the Life Span Study (LSS) cohort of the Radiation Effects Research Foundation, with particular emphasis on case ascertainment and characterization of histological features of the tumors. We identified 723 ovarian tumors (260 malignant, 463 benign) in 648 individuals of about 70,000 female LSS subjects; 71 cases had more than one ovarian tumor. We histologically confirmed 601 tumors (182 malignant, 419 benign tumors). The most frequent histological type was common epithelial tumor (90.7% for malignant and 59.7% for benign tumors). The distributions of ovarian tumors by histological type were similar to those from other studies. Among malignancies, the frequency of common epithelial types relative to other tumor types increased with radiation dose (p = 0.02). Among benign tumors, the relative frequency of sex-cord stromal tumors increased with radiation dose (p = 0.04). The women with mucinous cancer had better survival than those with serous cancers (p = 0.03). Within tumor types, there was no consistent pattern of survival by radiation dose. Variations in histological types of ovarian tumors in response to radiation dose, suggested by the case series data need to be followed up by population-based incidence analysis.

  16. Expression of the ERBB2 protein in benign and malignant salivary gland tumors.

    PubMed

    Stenman, G; Sandros, J; Nordkvist, A; Mark, J; Sahlin, P

    1991-03-01

    Fifty-two primary human salivary gland tumors were analyzed for expression of the p185ERBB2 protein using immunohistochemical and immunoblotting techniques. About 63% (33/52) of the tumors expressed the ERBB2 protein. The highest expression levels were detected among the carcinomas, where 32% of the tumors showed intense membrane staining in 25-100% of the tumor cells. In benign pleomorphic adenomas, the corresponding figure was only 12%. Clinical follow-up data available for 18 of the 19 patients with carcinomas suggested an association between high ERBB2 protein levels and poor prognosis as measured by recurrence of disease and/or the appearance of metastases. These results indicate that ERBB2 activation and overexpression could be an important genetic event with possible prognostic implications in a subset of malignant salivary gland tumors.

  17. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma

    PubMed Central

    Moffitt, Richard A.; Marayati, Raoud; Flate, Elizabeth L.; Volmar, Keith E.; Loeza, S. Gabriela Herrera; Hoadley, Katherine A.; Rashid, Naim U.; Williams, Lindsay A.; Eaton, Samuel C.; Chung, Alexander H.; Smyla, Jadwiga K.; Anderson, Judy M.; Kim, Hong Jin; Bentrem, David J.; Talamonti, Mark S.; Iacobuzio-Donahue, Christine A.; Hollingsworth, Michael A.; Yeh, Jen Jen

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival of 4%. A key hallmark of PDAC is extensive stromal involvement, which makes capturing precise tumor-specific molecular information difficult. Here, we have overcome this problem by applying blind source separation to a diverse collection of PDAC gene expression microarray data, which includes primary, metastatic, and normal samples. By digitally separating tumor, stroma, and normal gene expression, we have identified and validated two tumor-specific subtypes including a “basal-like” subtype which has worse outcome, and is molecularly similar to basal tumors in bladder and breast cancer. Furthermore, we define “normal” and “activated” stromal subtypes which are independently prognostic. Our results provide new insight into the molecular composition of PDAC which may be used to tailor therapies or provide decision support in a clinical setting where the choice and timing of therapies is critical. PMID:26343385

  18. Over-expression of tetraspanin 8 in malignant glioma regulates tumor cell progression

    SciTech Connect

    Pan, Si-Jian; Wu, Yue-Bing; Cai, Shang; Pan, Yi-Xin; Liu, Wei; Bian, Liu-Guan; Sun, Bomin; Sun, Qing-Fang

    2015-03-13

    Tumor cell invasion and proliferation remain the overwhelming causes of death for malignant glioma patients. To establish effective therapeutic methods, new targets implied in these processes have to be identified. Tetraspanin 8 (Tspn8) forms complexes with a large variety of trans-membrane and/or cytosolic proteins to regulate several important cellular functions. In the current study, we found that Tspn8 was over-expressed in multiple clinical malignant glioma tissues, and its expression level correlated with the grade of tumors. Tspn8 expression in malignant glioma cells (U251MG and U87MG lines) is important for cell proliferation and migration. siRNA-mediated knockdown of Tspn8 markedly reduced in vitro proliferation and migration of U251MG and U87MG cells. Meanwhile, Tspn8 silencing also increased the sensitivity of temozolomide (TMZ), and significantly increased U251MG or U87MG cell death and apoptosis by TMZ were achieved with Tspn8 knockdown. We observed that Tspn8 formed a complex with activated focal adhesion kinase (FAK) in both human malignant glioma tissues and in above glioma cells. This complexation appeared required for FAK activation, since Tspn8 knockdown inhibited FAK activation in U251MG and U87MG cells. These results provide evidence that Tspn8 contributes to the pathogenesis of glioblastoma probably by promoting proliferation, migration and TMZ-resistance of glioma cells. Therefore, targeting Tspn8 may provide a potential therapeutic intervention for malignant glioma. - Highlights: • Tspn8 is over-expressed in multiple clinical malignant glioma tissues. • Tspn8 expression is correlated with the grade of malignant gliomas. • Tspn8 knockdown suppresses U251MG/U87MG proliferation and in vitro migration. • Tspn8 knockdown significantly increases TMZ sensitivity in U251MG/U87MG cells. • Tspn8 forms a complex with FAK, required for FAK activation.

  19. [Utility of hyperbaric oxygenation in radiotherapy for malignant brain tumors--a literature review].

    PubMed

    Beppu, Takaaki; Tanaka, Katsuyuki; Kohshi, Kiyotaka

    2009-06-01

    Over the past 50 years, hyperbaric oxygenation (HBO) therapy has been used in a wide variety of medical conditions; this theraphy causes an increase in oxygen tension in blood and tissues. In the treatment of malignant gliomas, HBO therapy is used for the radiosensitization of cells in combination with radiotherapy (RT). Further, HBO therapy is applied for the treatment and prevention of radiation-induced brain necrosis that is the most serious complication observed after radiosurgery. We reviewed the literature to evaluate the manner in which HBO therapy contributes to clinical fields in cases of RT administration for malignant brain tumors.

  20. Malignant mixed müllerian tumor of primary peritoneal origin☆

    PubMed Central

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

    2016-01-01

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

  1. Malignant mixed tumor of salivary gland with a solitary metastasis to the tibia.

    PubMed

    Aynaci, O; Onder, C; Yildiz, K

    2001-05-01

    A 23-year-old, male patient previously operated on four times for a recurring, benign, paranasal mass was admitted to our clinic with pain and swelling under the knee. Physical and radiological examination revealed a malignant process. The histopathological examination of the fine-needle biopsy specimen of the tibia was a malignant mixed tumor. Then. en-bloc resection, free fibular grafting, and fixation with blade plate was performed for one-third of the tibia, conserving the knee joint. Recurrences and metastasis were not observed after surgery and radiotherapy.

  2. Assessment of biophysical tumor response to PDT in pancreatic cancer using localized reflectance spectroscopy

    NASA Astrophysics Data System (ADS)

    Isabelle, Martin; Klubben, William; He, Ting; Laughney, Ashley M.; Glaser, Adam; Krishnaswamy, Venkataramanan; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

    2011-02-01

    Biophysical changes such as inflammation and necrosis occur immediately following PDT and may be used to assess the treatment response to PDT treatment in-vivo. This study uses localized reflectance measurements to quantify the scatter changes in tumor tissue occurring in response to verteporfin-based PDT treatment in xenograft pancreas tumors. Nude mice were implanted with subcutaneous AsPC-1 pancreatic tumors cells in matrigel, and allowed to establish solid tumors near 100mm3 volume. The mice were sensitized with 1mg/kg of the active component of verteporfin (benzoporphryin derivative, BPD), one hour before light delivery. The optical irradiation was performed using a 1 cm cylindrical interstitial diffusing tip fiber with 20J of red light (690nm). Tumor tissue was excised progressively and imaged, from 1 day to 4 weeks, after PDT treatment. The tissue sections were stained and analyzed by an expert veterinary pathologist, who provided information on tissue regions of interest. This information was correlated with variations in scattering and absorption parameters elucidated from the spectral images and the degree of necrosis and inflammation involvement was identified. Areas of necrosis and dead cells exhibited the lowest average scatter irradiance signature (3.78 and 4.07 respectively) compared to areas of viable pancreatic tumor cells and areas of inflammation (5.81 and 7.19 respectively). Bilirubin absorbance parameters also showed a lower absorbance value in necrotic tissue and areas of dead cells (0.05 and 0.1 respectively) compared to tissue areas for viable pancreatic tumor cells and areas of inflammation (0.28 and 0.35). These results demonstrate that localized reflectance spectroscopy is an imaging modality that can be used to identify tissue features associated with PDT treatment (e.g. necrosis and inflammation) that can be correlated with histopathologically-reviewed H&E stained slides. Further study of this technique may provide means for automated

  3. Kallikrein 4 and matrix metalloproteinase-20 immunoexpression in malignant, benign and infiltrative odontogenic tumors

    PubMed Central

    Crivelini, Marcelo Macedo; Oliveira, Denise Tostes; de Mesquita, Ricardo Alves; de Sousa, Suzana Cantanhede Orsini Machado; Loyola, Adriano Motta

    2016-01-01

    Context: Matrix metalloproteinase-20 (MMP20) (enamelysin) and kallikrein 4 (KLK4) are enzymes secreted by ameloblasts that play an important role in enamel matrix degradation during amelogenesis. However, studies have shown that neoplastic cells can produce such enzymes, which may affect the tumor infiltrative and metastatic behaviors. Aims: The aim of this study is to assess the biological role of MMP20 and KLK4 in odontogenic tumors. Materials and Methods: The enzymes were analyzed immunohistochemically in ameloblastoma, adenomatoid odontogenic tumor (AOT), calcifying epithelial odontogenic tumor, keratocystic odontogenic tumor with or without recurrence and odontogenic carcinoma. Statistical Analysis Used: Clinicopathological parameters were statistically correlated with protein expression using the Fisher's exact test. Kruskal–Wallis and Wilcoxon-independent methods were used to evaluate the differences in median values. Results: Positive Immunoexpression was detected in all benign lesions, with a prevalence of 75–100% immunolabeled cells. Patients were predominantly young, Caucasian, female, with slow-growing tumors located in the mandible causing asymptomatic swelling. No KLK4 expression was seen in carcinomas, and the amount of MMP20-positive cells varied between 20% and 80%. Rapid evolution, recurrence and age >60 years characterized the malignant nature of these lesions. Conclusions: Data showed that KLK4 and MMP20 enzymes may not be crucial to tumoral infiltrative capacity, especially in malignant tumors, considering the diversity and peculiarity of these lesions. The significant immunoexpression in benign lesions, remarkably in AOT, is likely associated with differentiated tumor cells that can produce and degrade enamel matrix-like substances. This would be expected since the histogenesis of odontogenic tumors commonly comes from epithelium that recently performed a secretory activity in tooth formation. PMID:27601817

  4. Genetic polymorphism of N-acetyltransferases, glutathione S-transferase M1 and NAD(P)H:quinone oxidoreductase in relation to malignant and benign pancreatic disease risk. The International Pancreatic Disease Study Group.

    PubMed

    Bartsch, H; Malaveille, C; Lowenfels, A B; Maisonneuve, P; Hautefeuille, A; Boyle, P

    1998-06-01

    Carcinogens present in cigarette smoke and diet have been associated with pancreatic cancer. We hypothesized that heterocyclic and aromatic amines implicated in these exposures could be involved as causative agents and that therefore genetic variation in enzymes metabolizing these carcinogens could modify the risk of developing malignant and benign pancreatic disease. The effect of the genetic polymorphism of acetyltransferases (NAT1) and NAT2), glutathione S-transferase M1 (GSTM1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) on the risk of pancreatic diseases (cancer, pancreatitis) was examined in a case-control study. PCR-based assays were used for genotype analysis of genomic DNA from whole blood cells. Samples collected from Caucasian patients with diagnosed pancreatic cancer (n = 81), with non-alcoholic (n = 41) and alcoholic pancreatitis (n = 73) and from asymptomatic control subjects (n = 78) were analysed. The prevalence of GSTM1 null genotype and of NAT2 fast and slow acetylator genotypes and the distribution of frequencies for NQO1 genotypes did not differ in subjects with pancreatic diseases vs controls. For NAT1 slow acetylators a non-significant excess (P = 0.18) was found among pancreatic cancer cases vs controls. There was a significant over-representation of the GSTM1 AB or B genotype in all pancreatic disease cases combined (OR = 2.6; P < 0.05). When concurrent controls were pooled with literature controls (n = 1427), OR was 1.4 (P = 0.08). The results of this study, requiring confirmation, suggest that the polymorphism of GSTM1 and NAT1 enzymes may be associated with a modest increase in susceptibility to pancreatic diseases.

  5. Orchestrating the Tumor Microenvironment to Improve Survival for Patients With Pancreatic Cancer Normalization, Not Destruction

    PubMed Central

    Whatcott, Clifford J.; Hanl, Haiyong; Von Hoff, Daniel D.

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. The microenvironment of pancreatic cancer could be one of the “perfect storms” that support the growth of a cancer. Indeed, pancreatic cancer may be the poster child of a problem with the microenvironment. In this article, we review the rationale and attempts to date on modifying or targeting structural proteins in the microenvironment including hyaluronan (HA) (in primary and metastases), collagen, and SPARC (secreted protein, acidic, and rich in cysteine). Indeed, working in this area has produced a regimen that improves survival for patients with advanced pancreatic cancer (nab-paclitaxel + gemcitabine). In addition, in initial clinical trials, PEGylated hyaluronidase appears promising. We also review a new approach that is different than targeting/destroying the microenvironment and that is orchestrating, reengineering, reprogramming, or normalizing the microenvironment (including normalizing structural proteins, normalizing an immunologically tumor-friendly environment to a less friendly environment, reversing epithelial-to-mesenchymal transition, and so on). We believe this will be most effectively done by agents that have global effects on transcription. There is initial evidence that this can be done by agents such as vitamin D derivatives and other new agents. There is no doubt these opportunities can now be tried in the clinic with hopefully beneficial effects. PMID:26222082

  6. Orchestrating the Tumor Microenvironment to Improve Survival for Patients With Pancreatic Cancer: Normalization, Not Destruction.

    PubMed

    Whatcott, Clifford J; Han, Haiyong; Von Hoff, Daniel D

    2015-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. The microenvironment of pancreatic cancer could be one of the "perfect storms" that support the growth of a cancer. Indeed, pancreatic cancer may be the poster child of a problem with the microenvironment. In this article, we review the rationale and attempts to date on modifying or targeting structural proteins in the microenvironment including hyaluronan (HA) (in primary and metastases), collagen, and SPARC (secreted protein, acidic, and rich in cysteine). Indeed, working in this area has produced a regimen that improves survival for patients with advanced pancreatic cancer (nab-paclitaxel + gemcitabine). In addition, in initial clinical trials, PEGylated hyaluronidase appears promising. We also review a new approach that is different than targeting/destroying the microenvironment and that is orchestrating, reengineering, reprogramming, or normalizing the microenvironment (including normalizing structural proteins, normalizing an immunologically tumor-friendly environment to a less friendly environment, reversing epithelial-to-mesenchymal transition, and so on). We believe this will be most effectively done by agents that have global effects on transcription. There is initial evidence that this can be done by agents such as vitamin D derivatives and other new agents. There is no doubt these opportunities can now be tried in the clinic with hopefully beneficial effects.

  7. Orchestrating the Tumor Microenvironment to Improve Survival for Patients With Pancreatic Cancer: Normalization, Not Destruction.

    PubMed

    Whatcott, Clifford J; Han, Haiyong; Von Hoff, Daniel D

    2015-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. The microenvironment of pancreatic cancer could be one of the "perfect storms" that support the growth of a cancer. Indeed, pancreatic cancer may be the poster child of a problem with the microenvironment. In this article, we review the rationale and attempts to date on modifying or targeting structural proteins in the microenvironment including hyaluronan (HA) (in primary and metastases), collagen, and SPARC (secreted protein, acidic, and rich in cysteine). Indeed, working in this area has produced a regimen that improves survival for patients with advanced pancreatic cancer (nab-paclitaxel + gemcitabine). In addition, in initial clinical trials, PEGylated hyaluronidase appears promising. We also review a new approach that is different than targeting/destroying the microenvironment and that is orchestrating, reengineering, reprogramming, or normalizing the microenvironment (including normalizing structural proteins, normalizing an immunologically tumor-friendly environment to a less friendly environment, reversing epithelial-to-mesenchymal transition, and so on). We believe this will be most effectively done by agents that have global effects on transcription. There is initial evidence that this can be done by agents such as vitamin D derivatives and other new agents. There is no doubt these opportunities can now be tried in the clinic with hopefully beneficial effects. PMID:26222082

  8. Portal vein-circulating tumor cells predict liver metastases in patients with resectable pancreatic cancer.

    PubMed

    Bissolati, Massimiliano; Sandri, Maria Teresa; Burtulo, Giovanni; Zorzino, Laura; Balzano, Gianpaolo; Braga, Marco

    2015-02-01

    Pancreatic cancer patients underwent surgical resection often present distant metastases early after surgery. Detection of circulating tumor cells (CTCs) has been correlated to a worse oncological outcome in patients with advanced pancreatic cancer. The objective of this pilot study is to investigate the possible prognostic role of CTCs in patients undergoing surgery for pancreatic cancer. In 20 patients undergoing pancreatic resection, 10 mL blood sample was collected intraoperatively from both systemic circulation (SC) and portal vein (PV). Blood sample was analyzed for CTCs with CellSearch® system. All patients underwent an oncologic follow-up for at least 3 years, quarterly. CTCs were detected in nine (45%) patients: five patients had CTCs in PV only, three patients in both SC and PV, and one patient in SC only. CTC-positive and CTC-negative patients were similar for demographics and cancer stage pattern. No significant differences were found in both overall and disease-free survival between CTC-positive and CTC-negative patients. At 3-year follow-up, portal vein CTC-positive patients presented a higher rate of liver metastases than CTC-negative patients (53 vs. 8%, p = 0.038). CTCs were found in 45% of the patients. No correlation between CTCs and survival was found. The presence of CTCs in portal vein has been associated to higher rate of liver metastases after surgery.

  9. MicroRNA142-3p promotes tumor-initiating and radioresistant properties in malignant pediatric brain tumors.

    PubMed

    Lee, Yi-Yen; Yang, Yi-Ping; Huang, Ming-Chao; Wang, Mong-Lien; Yen, Sang-Hue; Huang, Pin-I; Chen, Yi-Wei; Chiou, Shih-Hwa; Lan, Yuan-Tzu; Ma, Hsin-I; Shih, Yang-Hsin; Chen, Ming-Teh

    2014-01-01

    Primary central nervous system (CNS) atypical teratoid/rhabdoid tumor (ATRT) is an extremely malignant pediatric brain tumor observed in infancy and childhood. It has been reported that a subpopulation of CD133(+) cells isolated from ATRT tumors present with cancer stem-like and radioresistant properties. However, the exact biomolecular mechanisms of ATRT or CD133-positive ATRT (ATRT-CD133(+)) cells are still unclear. We have previously shown that ATRT-CD133(+) cells have pluripotent differentiation ability and the capability of malignant cells to be highly resistant to ionizing radiation (IR). By using microRNA array and quantitative RT-PCR in this study, we showed that expression of miR142-3p was lower in ATRT-CD133(+) cells than in ATRT-CD133(-) cells. miR142-3p overexpression significantly inhibited the self-renewal and tumorigenicity of ATRT-CD133(+) cells. On the contrary, silencing of endogenous miR142-3p dramatically increased the tumor-initiating and stem-like cell capacities in ATRT cells or ATRT-CD133(-) cells and further promoted the mesenchymal transitional and radioresistant properties of ATRT cells. Most importantly, therapeutic delivery of miR142-3p in ATRT cells effectively reduced its lethality by blocking tumor growth, repressing invasiveness, increasing radiosensitivity, and prolonging survival time in orthotropic-transplanted immunocompromised mice. These results demonstrate the prospect of developing novel miRNA-based strategies to block the stem-like and radioresistant properties of malignant pediatric brain cancer stem cells. PMID:24816458

  10. Benign, malignant salivary gland tumors: comparison of immunohistochemical expression of e-cadherin.

    PubMed

    Prabhu, Sudeendra; Kaveri, H; Rekha, K

    2009-07-01

    The aim of the present study was to assess any variation in the immunohistochemical expression of E-cadherin in benign and malignant salivary gland tumors. A total of 60 cases of benign and malignant salivary gland tumors were evaluated immunohistochemically for E-cadherin expression. These included 10 cases of pleomorphic adenoma (PA), 2 cases of canalicular adenoma (CA), 2 cases of myoepithelioma (MY), 24 cases of adenoid cystic carcinoma (ACC), 12 cases of mucoepidermoid carcinoma (MEC), 9 cases of adenocarcinoma (AC) and 1 case of carcinoma ex pleomorphic adenoma (Ca Ex PA). 48 cases (80%) showed positive expression, in which benign tumors exhibited relatively increased reactivity (85.7%) as compared to the malignant tumors (78.3%). 10 PA, 2 MY, 20 ACC, 9 MEC, 6 AC and 1 Ca Ex PA expressed E-cadherin. Negative expression was evident in CA, ACC, MEC and AC. Statistically significant reduction in reactivity was evident in mucoepidermoid carcinoma and adenocarcinoma, when compared to pleomorphic adenoma.

  11. Malignant tumors during the first 2 decades of life in the offspring of atomic bomb survivors

    SciTech Connect

    Yoshimoto, Y.; Neel, J.V.; Schull, W.J.; Kato, H.; Soda, M.; Eto, R.; Mabuchi, K. )

    1990-06-01

    The risk of cancer (incidence) prior to age 20 years has been determined for children born to atomic bomb survivors and to a suitable comparison group. Tumor ascertainment was through death certificates and the tumor registries maintained in Hiroshima and Nagasaki. The rationale for the study stemmed from the evidence that a significant proportion of such childhood tumors as retinoblastoma and Wilms tumor arise on the basis of a mutant gene inherited from one parent plus a second somatic cell mutation involving the allele of this gene. Gonadal radiation doses were calculated by the recently established DS86 system, supplemented by an ad hoc system for those children for one or both of whose parents a DS86 dose could not be computed but for whom an ad hoc dose could be developed on the basis of the available information. The total data set consisted of (1) a cohort of 31,150 live-born children one or both of whose parents received greater than 0.01 Sv of radiation at the time of the atomic bombings (average conjoint gonad exposure 0.43 Sv) and (2) two suitable comparison groups totaling 41,066 children. Altogether, 43 malignant tumors were ascertained in the children of exposed parents, and 49 malignant tumors were ascertained in the two control groups. A multiple linear regression analysis revealed no increase in malignancy in the children of exposed parents. However, examination of the data suggested that only 3.0-5.0% of the tumors of childhood that were observed in the comparison groups are associated with an inherited genetic predisposition that would be expected to exhibit an altered frequency if the parental mutation rate were increased. There is thus far no confirmation of the positive findings that Nomura found in a mouse system.

  12. Comparison of the expression of 5 heat shock proteins in benign and malignant salivary gland tumor tissues.

    PubMed

    Wang, Guilan; Gu, Xiaolin; Chen, Li; Wang, Yinmei; Cao, Bin; E, Qun

    2013-04-01

    The objective of this study was to analyze the significance and potential value of heat shock proteins (HSPs) in salivary gland tumors. We found that expression of HSP60, HSP70, HSP86 and HSP84 were all upregulated in both salivary gland benign tumors and malignant tumors, and that the expression of HSP70, HSP86 and HSP84 was more greatly overexpressed in the malignant tumors (each P<0.01). For HSP27, expression was upregulated both in malignant and benign tumors, with less expression observed in malignant tumors (P<0.01). In malignant tumors, expression of HSP27 was negatively correlated with the age of the patients, size of the tumor tissue, occurrence of neural invasion and metastasis (each P<0.05). Additionally, in malignant tumors, HSP70 and HSP86 were both positively correlated with occurrence site, neural invasion and metastasis (each P<0.05), while HSP60 was only negatively correlated with the age of the patients (P<0.05). HSP86 was also positively correlated with malignant degree (P<0.01). In malignant tumors, the proliferation index (PI), which was marked by proliferating cell nuclear antigen (PCNA; PCNA-PI) was 49.95±14.569, which was significantly higher compared with that in benign tumors (P<0.001), which was in accordance with the upregulation of HSP70, HSP86 or HSP84; however, an adverse correlation was found between HSP27 expression and PCNA (each P<0.05). In conclusion, these results suggest that HSPs are involved in the occurrence and development of salivary gland tumors. HSP70, HSP86 and HSP84 retained the higher multiplication capability of the malignant tumor cells, however, HSP27 did not. Thus, the upregulation of HSP70, HSP86 and HSP84 and the downregulation of HSP27 may all be used as biomarkers of the occurrence and development of malignant salivary gland tumors. Moreover, the extremely high expression of HSP86 and HSP84 in benign tumors indicates the malignant transformation potential.

  13. PAX2 Expression in Low Malignant Potential Ovarian Tumors and Low-Grade Ovarian Serous Carcinomas

    PubMed Central

    Tung, Celestine S.; Mok, Samuel C.; Tsang, Yvonne T.M.; Zu, Zhifei; Song, Huijuan; Liu, Jinsong; Deavers, Michael; Malpica, Anais; Wolf, Judith K.; Lu, Karen H.; Gershenson, David M.; Wong, Kwong-Kwok

    2009-01-01

    Ovarian tumors of low-malignant potential and low-grade ovarian serous carcinomas are thought to represent different stages on a tumorigenic continuum and to develop along pathways distinct from high-grade ovarian serous carcinoma. We performed gene expression profiling on 3 normal human ovarian surface epithelia samples, and 10 low-grade and 10 high-grade ovarian serous carcinomas. Analysis of gene expression profiles of these samples has identified 80 genes up-regulated and 232 genes down-regulated in low-grade ovarian serous carcinomas. PAX2 was found to be one of the most up-regulated genes in low-grade ovarian serous carcinoma. The up-regulation of PAX2 was validated by real-time quantitative RT-PCR, Western blot and immunohistochemical analyses. Real-time RT-PCR demonstrated a statistically significant difference in PAX2 mRNA expression (expressed as fold change in comparison to normal human ovarian surface epithelia) among ovarian tumors of low-malignant potential (1837.38, N=8), low-grade (183.12, N=17), and high-grade (3.72, N=23) carcinoma samples (p=0.015). Western blot analysis revealed strong PAX2 expression in ovarian tumors of low-malignant potential (67%, N=3) and low-grade carcinoma samples (50%, N=10) but no PAX2 protein expression in high-grade carcinomas (0%, N=10). Using immunohistochemistry, tumors of low-malignant potential (59%, N=17) and low-grade carcinoma (63%, N=16) samples expressed significantly stronger nuclear staining than high-grade ovarian carcinoma samples (9.1%, N=263). Furthermore, consistent with previous immunohistochemical findings, PAX2 expression was found to be expressed in the epithelial cells of fallopian tubes but not in normal ovarian surface epithelial cells. Our findings further support the two-tiered hypothesis that tumors of low-malignant potential and low-grade ovarian serous carcinoma are on a continuum and are distinct from high-grade ovarian carcinomas. Additionally, the absence of PAX2 expression in normal

  14. Prostatic Stromal Tumor of Uncertain Malignant Potential Which Was Difficult to Diagnose

    PubMed Central

    Matsuyama, Satoko; Nohara, Takahiro; Kawaguchi, Shohei; Seto, Chikashi; Nakanishi, Yuko; Uchiyama, Akio; Ishizawa, Shin

    2015-01-01

    Here, we report a case of stromal tumor of uncertain malignant potential (STUMP) that was difficult to diagnose. A 53-year-old male was found to have a hard nodule on digital rectal examination; magnetic resonance imaging revealed a large nodule on the left side of the prostate, indicating prostate cancer. However, pathological diagnosis of the biopsy specimen was benign prostatic hyperplasia. Although a papillary tumor in the prostatic urethra was also seen on urethrocystoscopy, the tumor specimen obtained from transurethral resection was not malignant. The tumor in the prostatic urethra recurred only 3 months after transurethral resection, and pathological findings revealed benign hyperplasia not only in the stromal tissue but also in the epithelium; therefore, the prostate tumor was suspected to be STUMP. It took many prostate pathologists a long time to reach the final diagnosis of STUMP. STUMP is a rare benign tumor, difficult to diagnose, and sometimes transforms into stromal sarcoma. Thus, we should consider radical resection in such cases. PMID:26839730

  15. Expression of β-adrenergic receptors in pediatric malignant brain tumors

    PubMed Central

    SARDI, IACOPO; GIUNTI, LAURA; BRESCI, CECILIA; BUCCOLIERO, ANNA MARIA; DEGL’INNOCENTI, DUCCIO; CARDELLICCHIO, STEFANIA; BARONI, GIANNA; CASTIGLIONE, FRANCESCA; ROS, MARTINA DA; FIORINI, PATRIZIO; GIGLIO, SABRINA; GENITORI, LORENZO; ARICÒ, MAURIZIO; FILIPPI, LUCA

    2013-01-01

    β-adrenergic receptors (β-ARs) are G protein-coupled receptors that activate signal transduction pathways involved in angiogenesis, resulting in enhanced tumor vascularization and more aggressive growth. In this study, we evaluated the expression of β-ARs in a population of 12 children affected by malignant primary brain tumors. We found a significant expression of β1- and β2-ARs in all 12 samples as well as the 3 cell lines tested (U87MG, T98G and DAOY). The mean absolute β1-AR mRNA level standardized to GAPDH was 5.81 (range, -7.91 to 11.29) for brain tumors and 8.59 (range, 6.046 to 12.59) for cell lines (U87MG, DAOY and T98G), respectively. The mean absolute β2-AR mRNA level was 4.74 (range, −9.30 to 8.45) for tumor specimens and 7.64 (range, 5.85 to 8.88) for cell lines. These real-time quantitative (qRT)-PCR expression data were confirmed by immunohistochemical analysis. Our study evaluated the presence of β1- and β2-ARs in malignant pediatric brain tumors and brain tumor cell lines. PMID:23255924

  16. Malignant glomus tumor with oncocytic features: an unusual presentation of dysphagia.

    PubMed

    Ugras, Nesrin; Yercİ, Ömer; Yalçınkaya, Ulviye; Gülcü, Barış; Öztürk, Ersin; Yıldırım, Çınar; Çavuşoğlu, İlkin

    2015-07-01

    Glomus tumors in the gastrointestinal tract are unusual, as the previous series in the literature have been mainly limited to the stomach. Less than 10 cases of esophageal glomus tumors have been described in the literature. Oncocytic glomus tumors are a recently identified, rare variant of the glomus tumor. We report a 47-year-old female who presented with an approximately 3-month history of dysphagia and weight loss. Upper gastrointestinal endoscopy showed a black-purple, hypervascular, protruding lesion measuring approximately 65 mm at the 37th cm of the esophagus. The patient underwent an Ivor Lewis operation via open thoracotomy. The resected specimen had a protuberant, ulcerated mass measuring 80 × 35 mm in the posterior wall of the esophagus. Based on the histopathological, immunohistochemical and electron microscope findings, the final diagnosis was a malignant glomus tumor with oncocytic features. To our knowledge, this is the first report of a malignant glomus tumor with oncocytic features in an esophageal location. PMID:25908295

  17. Pancreatic tumor cell metabolism: focus on glycolysis and its connected metabolic pathways.

    PubMed

    Guillaumond, Fabienne; Iovanna, Juan Lucio; Vasseur, Sophie

    2014-03-01

    Because of lack of effective treatment, pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of death by cancer in Western countries, with a very weak improvement of survival rate over the last 40years. Defeat of numerous conventional therapies to cure this cancer makes urgent to develop new tools usable by clinicians for a better management of the disease. Aggressiveness of pancreatic cancer relies on its own hallmarks: a low vascular network as well as a prominent stromal compartment (desmoplasia), which creates a severe hypoxic environment impeding correct oxygen and nutrients diffusion to the tumoral cells. To survive and proliferate in those conditions, pancreatic cancer cells set up specific metabolic pathways to meet their tremendous energetic and biomass demands. However, as PDAC is a heterogenous tumor, a complex reprogramming of metabolic processes is engaged by cancer cells according to their level of oxygenation and nutrients supply. In this review, we focus on the glycolytic activity of PDAC and the glucose-connected metabolic pathways which contribute to the progression and dissemination of this disease. We also discuss possible therapeutic strategies targeting these pathways in order to cure this disease which still until now is resistant to numerous conventional treatments.

  18. Malignant solitary fibrous tumor with high-grade nuclear atypia: an alternate entity for the undetermined tumor group.

    PubMed

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

    2015-02-01

    Recently, a novel fusion transcript, NAB2-STAT6, and its variants have also been reported to be specific diagnostic markers for solitary fibrous tumors (SFTs). In this study, we validated the existence of the NAB2-STAT6 fusion gene in SFTs and examined its relation with the pathological features. Frozen samples from 9 tumors were assessed for fusion gene. The detected fusion genes exhibited large intron sequences and the insertion of unknown and previously unreported sequences. The fusion genes were not detected in the 2 malignant cases with high-grade nuclear atypia, nuclear pleomorphism and necrosis, that was confirmed by multiplex PCR method. In addition, 1 of the 2 NAB2-STAT6 fusion gene-negative tumors showed amplification of the MDM2 and CDK4 genes. It was suggested that a certain proportion of tumors previously diagnosed as malignant SFTs with high-grade nuclear atypia lacking NAB2-STAT6 should be categorized into a special subtype of SFT, which is genetically different from conventional SFTs, and which cannot be apparently distinguished from dedifferentiated liposarcoma or undifferentiated pleomorphic sarcoma.

  19. A subset of malignant phyllodes tumors express p63 and p40: a diagnostic pitfall in breast core needle biopsies.

    PubMed

    Cimino-Mathews, Ashley; Sharma, Rajni; Illei, Peter B; Vang, Russell; Argani, Pedram

    2014-12-01

    Breast phyllodes tumors are rare fibroepithelial neoplasms of variable grade, and one key differential of malignant phyllodes on core biopsy is sarcomatoid carcinoma. p63 is reported to be sensitive and specific for sarcomatoid carcinoma, with rare expression in phyllodes in limited series. The p63 deltaNp63 isoform, p40, is postulated to be more specific for squamous differentiation but has not previously been evaluated in breast phyllodes or sarcomatoid carcinoma. Tissue microarrays containing 34 unambiguous phyllodes tumors (10 benign, 10 borderline, 14 malignant), 13 sarcomatoid carcinomas, and 10 fibroadenomas were labeled by immunohistochemistry for p63, p40, CD34, and cytokeratins AE1/AE3, 34betaE12, and CK8/18. No borderline phyllodes tumor, benign phyllodes tumor, or fibroadenoma labeled with p63, p40, or cytokeratin. However, p63 labeled 57% malignant phyllodes tumors and 62% sarcomatoid carcinomas, and p40 labeled 29% malignant phyllodes (focal) and 46% sarcomatoid carcinomas. Among established markers, cytokeratins labeled 21% malignant phyllodes tumors (focal) and 100% sarcomatoid carcinomas. CD34 labeled 57% malignant phyllodes tumors and no sarcomatoid carcinomas. Focal p63, p40, and cytokeratin labeling can be seen in malignant phyllodes tumors but not in lower-grade fibroepithelial lesions, and immunoreactivity with these markers alone is not diagnostic of sarcomatoid carcinoma on core needle biopsy. In the differential diagnosis of malignant phyllodes, p40 is a more specific but less sensitive marker of sarcomatoid carcinoma than p63. These results are consistent with the sarcoma literature in which p63 labeling has been increasingly reported and suggest caution in classifying malignant spindle cell tumors of the breast on core biopsy.

  20. Biokinetics and dosimetry with 177Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

    NASA Astrophysics Data System (ADS)

    Rodríguez-Cortés, J.; de Murphy, C. Arteaga; Ferro-Flores, Ge; Pedraza-López, M.; Murphy-Stack, E.

    Malignant pancreatic tumours induced in athymic mice are a good model for peptide receptor targeted radiotherapy. The objective of this research was to determine biokinetic parameters in mice, in order to estimate the induced pancreatic tumour absorbed doses and to evaluate an `in house' 177Lu-DOTA-TATE radiopharmaceutical as part of preclinical studies for targeted therapy in humans. AR42J murine pancreas cancer cells expressing somatostatin receptors, were implanted in athymic mice (nD22) to obtain biokinetic and dosimetric data of 177Lu-DOTA-TATE. The mean tumour uptake 2 h post injection was 14.76±1.9% I.A./g; kidney and pancreas uptake, at the same time, were 7.27±1.1% I.A./g (1.71±0.90%/organ) and 4.20±0.98% I.A./g (0.42±0.03%/organ), respectively. The mean absorbed dose to tumour, kidney and pancreas was 0.58±0.02 Gy/MBq; 0.23±0.01 Gy/MBq and 0.14±0.01 Gy/MBq, respectively. These studies justify further dosimetric estimations to ensure that 177Lu-DOTA-TATE will act as expected in humans.

  1. Neuroendocrine tumor targeting: study of novel gallium-labeled somatostatin radiopeptides in a rat pancreatic tumor model.

    PubMed

    Froidevaux, Sylvie; Eberle, Alex N; Christe, Martine; Sumanovski, Lazar; Heppeler, Axel; Schmitt, Jörg S; Eisenwiener, Klaus; Beglinger, Christoph; Mäcke, Helmut R

    2002-04-20

    Somatostatin analogs labeled with radionuclides are of considerable interest in the diagnosis and therapy of SSTR-expressing tumors, such as gastroenteropancreatic, small cell lung, breast and frequently nervous system tumors. In view of the favorable physical characteristics of the Ga isotopes (67)Ga and (68)Ga, enabling conventional tumor scintigraphy, PET and possibly internal radiotherapy, we focused on the development of a Ga-labeled somatostatin analog suitable for targeting SSTR-expressing tumors. For this purpose, 3 somatostatin analogs, OC, TOC and TATE were conjugated to the metal chelator DOTA and labeled with the radiometals (111)In, (90)Y and (67)Ga. They were then evaluated for their performance in the AR4-2J pancreatic tumor model by testing SSTR2-binding affinity, internalization/externalization in isolated cells and biodistribution in tumor-bearing nude mice. Surprisingly, we found that, compared to (111)In or (90)Y, labeling with (67)Ga considerably improved the biologic performance of the tested somatostatin analogs with respect to SSTR2 affinity and tissue distribution. (67)Ga-labeled DOTA-somatostatin analogs were rapidly excreted from nontarget tissues, leading to excellent tumor-to-nontarget tissue uptake ratios. Of interest for radiotherapeutic application, [(67)Ga]DOTATOC was strongly internalized by AR4-2J cells. Furthermore, our results suggest a link between the radioligand charge and its kidney retention. The excellent tumor selectivity of Ga-DOTA somatostatin analogs together with the different applications of Ga in nuclear oncology suggests that Ga-DOTA somatostatin analogs will become an important tool in the management of SSTR-positive tumors.

  2. Benign and malignant ovarian steroid cell tumors, not otherwise specified: case studies, comparison, and review of the literature.

    PubMed

    Jiang, Wei; Tao, Xiang; Fang, Fang; Zhang, Shaofen; Xu, Congjian

    2013-01-01

    Ovarian steroid cell tumors, not otherwise specified (NOS) are rare sex cord-stromal tumors of the ovary with malignant potential. So far only a few cases were reported in English literature through the Pubmed search. Here we report two cases of such tumor, one was benign (first case underwent laparoscopic cystectomy) and the other was malignant (died 10 months later after initial diagnosis), both presented with amenorrhea and clinical signs or symptoms of virilization. In malignant case, we provided evidence (tumor embolus) in addition to the reported five characteristics associated with malignancy. On further evaluation, laboratory investigations revealed hyperandrogenism in the male range, while follicle stimulating hormone (FSH) and luteinising hormone (LH) levels were within normal limits. Various aspects of the presentation, diagnosis, and treatment of these tumors are discussed.

  3. Targeting the mRNA-binding protein HuR impairs malignant characteristics of pancreatic ductal adenocarcinoma cells

    PubMed Central

    Jimbo, Masaya; Blanco, Fernando F.; Screnci, Brad A.; Cosma, Gabriela L.; Alexeev, Vitali; Gonye, Gregory E.; Yeo, Charles J.; Sawicki, Janet A.; Winter, Jordan M.; Brody, Jonathan R.

    2015-01-01

    Post-transcriptional regulation is a powerful mediator of gene expression, and can rapidly alter the expression of numerous transcripts involved in tumorigenesis. We have previously shown that the mRNA-binding protein HuR (ELAVL1) is elevated in human pancreatic ductal adenocarcinoma (PDA) specimens compared to normal pancreatic tissues, and its cytoplasmic localization is associated with increased tumor stage. To gain a better insight into HuR’s role in PDA biology and to assess it as a candidate therapeutic target, we altered HuR expression in PDA cell lines and characterized the resulting phenotype in preclinical models. HuR silencing by short hairpin and small interfering RNAs significantly decreased cell proliferation and anchorage-independent growth, as well as impaired migration and invasion. In comparison, HuR overexpression increased migration and invasion, but had no significant effects on cell proliferation and anchorage-independent growth. Importantly, two distinct targeted approaches to HuR silencing showed marked impairment in tumor growth in mouse xenografts. NanoString nCounter® analyses demonstrated that HuR regulates core biological processes, highlighting that HuR inhibition likely thwarts PDA viability through post-transcriptional regulation of diverse signaling pathways (e.g. cell cycle, apoptosis, DNA repair). Taken together, our study suggests that targeted inhibition of HuR may be a novel, promising approach to the treatment of PDA. PMID:26314962

  4. Targeting the mRNA-binding protein HuR impairs malignant characteristics of pancreatic ductal adenocarcinoma cells.

    PubMed

    Jimbo, Masaya; Blanco, Fernando F; Huang, Yu-Hung; Telonis, Aristeidis G; Screnci, Brad A; Cosma, Gabriela L; Alexeev, Vitali; Gonye, Gregory E; Yeo, Charles J; Sawicki, Janet A; Winter, Jordan M; Brody, Jonathan R

    2015-09-29

    Post-transcriptional regulation is a powerful mediator of gene expression, and can rapidly alter the expression of numerous transcripts involved in tumorigenesis. We have previously shown that the mRNA-binding protein HuR (ELAVL1) is elevated in human pancreatic ductal adenocarcinoma (PDA) specimens compared to normal pancreatic tissues, and its cytoplasmic localization is associated with increased tumor stage. To gain a better insight into HuR's role in PDA biology and to assess it as a candidate therapeutic target, we altered HuR expression in PDA cell lines and characterized the resulting phenotype in preclinical models. HuR silencing by short hairpin and small interfering RNAs significantly decreased cell proliferation and anchorage-independent growth, as well as impaired migration and invasion. In comparison, HuR overexpression increased migration and invasion, but had no significant effects on cell proliferation and anchorage-independent growth. Importantly, two distinct targeted approaches to HuR silencing showed marked impairment in tumor growth in mouse xenografts. NanoString nCounter® analyses demonstrated that HuR regulates core biological processes, highlighting that HuR inhibition likely thwarts PDA viability through post-transcriptional regulation of diverse signaling pathways (e.g. cell cycle, apoptosis, DNA repair). Taken together, our study suggests that targeted inhibition of HuR may be a novel, promising approach to the treatment of PDA.

  5. Malignant mesenchymoma: a very rare tumor of the peritoneum. Case report with a review of the literature.

    PubMed

    Hauser, H; Beham, A; Schmid, C; Uranüs, S

    1991-01-01

    We report the case of an 82-year-old male patient with a malignant mesenchymoma. The tumor arose from the parietal peritoneum closely attached to the ascending colon. It consisted of a larger liposarcomatous and a smaller leiomyosarcomatous component which was demonstrated by immunohistochemistry. To our knowledge this is the first report of a malignant mesenchymoma of this histological composition originating from the parietal peritoneum. The tumor was completely removed surgically, which is the treatment of choice for such tumors. In agreement with other authors, we believe that malignant mesenchymomas arise from a primitive mesenchymal cell with the capacity for totipotent differentiation.

  6. Thermal therapy of pancreatic tumors using endoluminal ultrasound: parametric and patient-specific modeling

    PubMed Central

    Adams, Matthew S.; Scott, Serena J.; Salgaonkar, Vasant A.; Sommer, Graham; Diederich, Chris J.

    2016-01-01

    Purpose To investigate endoluminal ultrasound applicator configurations for volumetric thermal ablation and hyperthermia of pancreatic tumors using 3D acoustic and biothermal finite element models. Materials and Methods Parametric studies compared endoluminal heating performance for varying applicator transducer configurations (planar, curvilinear-focused, or radial-diverging), frequencies (1–5 MHz), and anatomical conditions. Patient-specific pancreatic head and body tumor models were used to evaluate feasibility of generating hyperthermia and thermal ablation using an applicator positioned in the duodenal or stomach lumen. Temperature and thermal dose were calculated to define ablation (>240 EM43°C) and moderate hyperthermia (40–45 °C) boundaries, and to assess sparing of sensitive tissues. Proportional-integral control was incorporated to regulate maximum temperature to 70–80 °C for ablation and 45 °C for hyperthermia in target regions. Results Parametric studies indicated that 1–3 MHz planar transducers are most suitable for volumetric ablation, producing 5–8 cm3 lesion volumes for a stationary 5 minute sonication. Curvilinear-focused geometries produce more localized ablation to 20–45 mm depth from the GI tract and enhance thermal sparing (Tmax<42 °C) of the luminal wall. Patient anatomy simulations show feasibility in ablating 60.1–92.9% of head/body tumor volumes (4.3–37.2 cm3) with dose <15 EM43°C in the luminal wall for 18–48 min treatment durations, using 1–3 applicator placements in GI lumen. For hyperthermia, planar and radial-diverging transducers could maintain up to 8 cm3 and 15 cm3 of tissue, respectively, between 40–45 °C for a single applicator placement. Conclusions Modeling studies indicate the feasibility of endoluminal ultrasound for volumetric thermal ablation or hyperthermia treatment of pancreatic tumor tissue. PMID:27097663

  7. Metastatic testicular tumor presenting as a scrotal hydrocele: An initial manifestation of pancreatic adenocarcinoma

    PubMed Central

    KIM, YEON WOOK; KIM, JIN WON; KIM, JEE-HYUN; LEE, JUNGSIL; LEE, EUIJAE; KIM, MOON YOUNG; YANG, HYUN KYUNG; CHANG, HYUN

    2014-01-01

    Metastatic pancreatic adenocarcinoma involving the testis is a rare condition with a poor prognosis. The current study describes the case of a 69-year-old male who presented with a painful swelling of the left scrotum. Scrotal ultrasonography revealed hydroceles in the scrotal sacs, with the left one being larger in size. The patient underwent left hydrocelectomy and was eventually diagnosed with metastatic adenocarcinoma. Abdominal computed tomography, which was performed to detect the primary cancer, showed a pancreatic tail carcinoma with liver and multiple lymph node metastases, and peritoneal carcinomatosis. The patient received gemcitabine-based chemotherapy but resulted in progressive disease. This case shows that in a patient in whom a primary testicular tumor is unusual due to their age, a testicular mass or hydrocele should be a suspect for possible metastatic disease. PMID:24932235

  8. Breast malignant phyllodes tumor with rare pelvic metastases and long-term overall survival

    PubMed Central

    Shan, Jinlan; Zhang, Shizhen; Wang, Zhen; Fu, Yanbiao; Li, Ling; Wang, Xiaochen

    2016-01-01

    Abstract Background: Malignant phyllodes tumor (PT) is a rare fibro epithelial neoplasm of the breast, which is poor prognosis due to high risk of recurrence and distant metastasis. Methods: We report a case of malignant PT. It had recurred locally five times, and the sixth relapse was occurred 54 months after first diagnosis, presenting a huge pelvic mass (14 cm × 11 cm) by CT scan. Histopathological examination has demonstrated a metastatic phyllodes tumor. After postoperative chemotherapy treatment, a longer survival has been achieved, which is more than 72 months. Results: Our case report describes a breast PT with several local recurrences and a rare metastasis (pelvic cavity), but long-term overall survival was achieved after surgery and chemotherapy. Conclusion: We conclude that trustworthy prognosticators that identify patients with excessive potential of aggressive clinical course should be explored. Moreover, proper treatment could prolong overall survival of metastatic PT patients. PMID:27661051

  9. An aggressive solitary fibrous tumor with evidence of malignancy: a rare case report.

    PubMed

    Vimi, S; Punnya, V A; Kaveri, H; Rekha, K

    2008-09-01

    Solitary fibrous tumor (SFT) is rare mesenchymal neoplasm that has been originally and most often documented in the pleura. Recently, the ubiquitous nature of the SFT has been recognized with reports of involvement of numerous sites all over the body, i.e, upper respiratory tract, breast, somatic tissue, mediastinum, head, and neck, etc. The diagnosis of SFT still remains an enigma in our field. Furthermore, malignant SFT is extremely rare and only two cases have been reported in the oral cavity till date. Here, we present a rare case report of an aggressive solitary fibrous tumor which presented as a palatal mass and extended throughout the middle cranial fossa and exhibited features of malignancy.

  10. Lung and skeleton malignant tumor induction due to high let emitters

    SciTech Connect

    Buldakov, L.A.; Lyubchansky, E.R.; Kalmikova, Z.I.; Buhtoyarova, Z.M.

    1992-06-01

    Experimental studies show that malignant tumor induction is of primary importance in regard to the biological action of transuranium elements on the animal body. Clarification of quantitative relationship between these parameters for low-level radiation is aproblem to be solved by health physics. This report aims at analysis of the dose-response relationship following rat exposure to PU-239, Am-241, and NP-237 over a wide range of doses, and also at comparison between risk fact obtained experimentally and tose recommended by the ICRP. The biological effect of transuranium elements was investigated regarding malignant tumor incidence in rat bone for all the pathways of intake covered and in the lung for intakes of radionuclides into the respiratory system.

  11. Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies

    PubMed Central

    Bettegowda, Chetan; Sausen, Mark; Leary, Rebecca J.; Kinde, Isaac; Wang, Yuxuan; Agrawal, Nishant; Bartlett, Bjarne R.; Wang, Hao; Luber, Brandon; Alani, Rhoda M.; Antonarakis, Emmanuel S.; Azad, Nilofer S.; Bardelli, Alberto; Brem, Henry; Cameron, John L.; Lee, Clarence C.; Fecher, Leslie A.; Gallia, Gary L.; Gibbs, Peter; Le, Dung; Giuntoli, Robert L.; Goggins, Michael; Hogarty, Michael D.; Holdhoff, Matthias; Hong, Seung-Mo; Jiao, Yuchen; Juhl, Hartmut H.; Kim, Jenny J.; Siravegna, Giulia; Laheru, Daniel A.; Lauricella, Calogero; Lim, Michael; Lipson, Evan J.; Marie, Suely Kazue Nagahashi; Netto, George J.; Oliner, Kelly S.; Olivi, Alessandro; Olsson, Louise; Riggins, Gregory J.; Sartore-Bianchi, Andrea; Schmidt, Kerstin; Shih, le-Ming; Oba-Shinjo, Sueli Mieko; Siena, Salvatore; Theodorescu, Dan; Tie, Jeanne; Harkins, Timothy T.; Veronese, Silvio; Wang, Tian-Li; Weingart, Jon D.; Wolfgang, Christopher L.; Wood, Laura D.; Xing, Dongmei; Hruban, Ralph H.; Wu, Jian; Allen, Peter J.; Schmidt, C. Max; Choti, Michael A.; Velculescu, Victor E.; Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas; Diaz, Luis A.

    2014-01-01

    The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction–based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer. PMID:24553385

  12. Multifrequency solid state YAG:Nd laser for diagnosis of malignant tumors

    NASA Astrophysics Data System (ADS)

    Lalayan, Asatur A.; Aidinian, Lusine E.; Galstian, Hayro M.

    1998-09-01

    The possibility of laser fluorescence diagnosis of malignant tumors with the aid of multifrequency (355, 440, 446, 532, 660, 670 nm) solid state YAG:Nd laser and the rise in accuracy of this method were discussed. Permitted for clinical employment sodium fluorescein has been used as human tumor-localizing dye. The fluorescence spectra of sodium fluorescein containing human normal tissue and breast, stomach, intestine, skin cancer during excitation with the third harmonics of YAG:Nd and with help of multichannel fiber-optic spectrofluorometer were studied. The contrast accumulation of the dye in tumors of different localization was investigated. The fluorescence spectra of chlorine e6, containing animal tissues at different excitation wavelength (355, 532 and 660 nm) were obtained. The pharmacokinetic behavior of chlorine e6, containing different organs and tumor tissues of rats, infected with Sarcoma-45 has been investigated.

  13. Comparison of Percutaneous Ablation Technologies in the Treatment of Malignant Liver Tumors

    PubMed Central

    Yu, Hyeon; Burke, Charles T.

    2014-01-01

    Tumor ablation is a minimally invasive technique used to deliver chemical, thermal, electrical, or ultrasonic damage to a specific focal tumor in an attempt to achieve substantial tumor destruction or complete eradication. As the technology continues to advance, several image-guided tumor ablations have emerged to effectively manage primary and secondary malignancies in the liver. Percutaneous chemical ablation is one of the oldest and most established techniques for treating small hepatocellular carcinomas. However, this technique has been largely replaced by newer modalities including radiofrequency ablation, microwave ablation, laser-induced interstitial thermotherapy, cryoablation, high-intensity–focused ultrasound ablation, and irreversible electroporation. Because there exist significant differences in underlying technological bases, understanding each mechanism of action is essential for achieving desirable outcomes. In this article, the authors review the current state of each ablation method including technological and clinical considerations. PMID:25071303

  14. Tumor-induced solid stress activates β-catenin signaling to drive malignant behavior in normal, tumor-adjacent cells

    PubMed Central

    Ou, Guanqing; Weaver, Valerie Marie

    2016-01-01

    Recent work by Fernández-Sánchez and coworkers examining the impact of applied pressure on the malignant phenotype of murine colon tissue in vivo revealed that mechanical perturbations can drive malignant behavior in genetically normal cells. Their findings build upon an existing understanding of how the mechanical cues experienced by cells within a tissue become progressively modified as the tissue transforms. Using magnetically stimulated ultra-magnetic liposomes to mimic tumor growth -induced solid stress, Fernández-Sánchez and coworkers were able to stimulate β-catenin to promote the cancerous behavior of both a normal and genetically modified colon epithelium. In this perspective, we discuss their findings in the context of what is currently known regarding the role of the mechanical landscape in cancer progression and β-catenin as a mechanotransducer. We review data that suggest that mechanically regulated activation of β-catenin fosters development of a malignant phenotype in tissue and predict that mechanical cues may contribute to tumor heterogeneity. PMID:26439949

  15. A massive chondroblastoma in the proximal humerus simulating malignant bone tumors.

    PubMed

    Tonogai, Ichiro; Takahashi, Mitsuhiko; Manabe, Hiroaki; Nishisho, Toshihiko; Iwamoto, Seiji; Takao, Shoichiro; Kagawa, Seiko; Kudo, Eiji; Yasui, Natsuo

    2013-01-01

    Chondroblastoma is a mostly benign bone neoplasm that typically affects the second decade of life and exhibits a lytic lesion in the epiphysis of long bones. We report an extreme case of massive, destructive chondroblastoma of the proximal humerus in a 9-year-old girl. It was difficult to differentiate using imaging information the lesion from malignant bone tumors such as osteosarcoma. Histopathological examination from biopsy proved chondroblastoma. The tumor was resected after preoperative transcatheter embolization. Reconstructive procedure for the proximal humerus was not performed due to the local destruction. The present case demonstrates clinical and radiological differentiations of the massive chondroblastoma from the other lesions and histopathological understandings for this lesion.

  16. Detection and Identification of Hematologic Malignancies and Solid Tumors by an Electrochemical Technique

    PubMed Central

    Zhang, Bowen; Zhang, Xiaoping; Wang, Xuemei; Cheng, Jian; Chen, Baoan

    2016-01-01

    Purpose Develop and evaluate an electrochemical method to identify healthy individuals, malignant hematopathic patients and solid tumor patients by detecting the leukocytes in whole-blood. Methods A total of 114 individual blood samples obtained from our affiliated hospital in China (June 2015- August 2015) were divided into three groups: healthy individuals (n = 35), hematologic malignancies (n = 41) and solid tumors (n = 38). An electrochemical workstation system was used to measure differential pulse voltammetry due to the different electrochemical behaviors of leukocytes in blood samples. Then, one-way analysis of variance (ANOVA) was applied to analyze the scanning curves and to compare the peak potential and peak current. Results The scanning curve demonstrated the specific electrochemical behaviors of the blank potassium ferricyanide solution and that mixed with blood samples in different groups. Significant differences in mean peak potentials of mixture and shifts (ΔEp (mV)) were observed of the three groups (P< = 0.001). 106.00±9.00 and 3.14±7.48 for Group healthy individuals, 120.90±11.18 and 18.10±8.81 for Group hematologic malignancies, 136.84±11.53 and 32.89±10.50 for Group solid tumors, respectively. In contrast, there were no significant differences in the peak currents and shifts. Conclusions The newly developed method to apply the electrochemical workstation system to identify hematologic malignancies and solid tumors with good sensitivity and specificity might be effective, suggesting a potential utility in clinical application. PMID:27115355

  17. A Rare Case of Breast Malignant Phyllodes Tumor With Metastases to the Kidney

    PubMed Central

    Karczmarek-Borowska, Bożenna; Bukala, Agnieszka; Syrek-Kaplita, Karolina; Ksiazek, Mariusz; Filipowska, Justyna; Gradalska-Lampart, Monika

    2015-01-01

    Abstract Phyllodes tumors are rare breast neoplasms. Surgery is the treatment of choice. The role of postoperative radiotherapy and chemotherapy is still under dispute, as there are no equivocal prognostic factors. Treatment failure results in the occurrence of distant metastasis—mainly to the lungs, bones, liver, and brain. We have described the case of a woman with a malignant phyllodes tumor of the breast that was surgically treated. She did not receive adjuvant therapy because there is no consensus on the role of postoperative chemotherapy and radiotherapy. One year following the surgery, the patient had left-sided nephrectomy performed because of a rapidly growing tumor of the kidney. Renal cancer was suspected; however, a histopathological examination revealed that it was a metastatic phyllodes tumor. At the same time, the patient was diagnosed as having metastases in the other kidney, the lungs, liver, and bones. Our case report describes not only an unusual localization of the metastases (in the kidneys), but also failure of the chemotherapy and the aggressive course of malignant phyllodes tumor. Identification of patients with high risk for distant metastasis and the introduction of uniform rules for the management of adjuvant chemotherapy and radiotherapy would make planning treatment as efficacious as possible. PMID:26287414

  18. [Hormone dependence of malignant ovarian tumors--an in vitro model].

    PubMed

    Schieder, K; Bieglmayer, C; Kölbl, H

    1989-05-01

    The steroid hormone receptor content of 32 malignant ovarian tumors was compared with the in vitro effectiveness of 4 hydroxytamoxifen (OH-TAM) and medroxy-progesterone acetate (MPA) tested in the Human Tumor Colony Forming Assay (HTCFA). The sensitivity for the receptor determination was 5 fmol/mg cytosol protein. Estrogen receptors (ER) and progesterone receptors (PR) were found in 15 (47%) and 13 (41%) of the tumors respectively. As standard criteria for the HTCFA, a minimum of 30 colonies with a diameter of more than 60 microns and 100 microns was used in the control group. The in-vitro sensitivity of ovarian tumors to OH-TAM and MPA was independent on the ER or PR content, and amounted to 9% for OH-TAM and 6% for MPA. However, all 12 ER-PR-tumors proved resistant to OH-TAM and MPA. 18 ovarian tumors showed a sufficient colony growth, even in the size class exceeding 100 microns. With a minimum colony size of 60 microns and 100 microns, 17% and 33% respectively were sensitive to OH-TAM. A similar effect on the proliferative capacity of the Tumor Colony Forming Units (TCFUs), unrelated to PR, was observed with MPA. Dependent on colony size, we found an increasing sensitivity against MPA from 11% to 22%. The in-vitro effectiveness of both OH-TAM and MPA in the clonogenic assay of malignant ovarian tumors was certainly not as potent as suggested by the results obtained in biochemical steroid hormone receptor analysis. To prove the hormonal response in the HTCFA, it is necessary to determine number and size of the colonies as an expression of their proliferative potential.

  19. Multiorgan chronic inflammatory hepatobiliary pancreatic murine model deficient in tumor necrosis factor receptors 1 and 2

    PubMed Central

    Oz, Helieh S

    2016-01-01

    AIM: To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic tissues. METHODS: Tumor necrosis factor receptors 1 and 2 (TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride (DBTC) twice within 10 d by oral gavage delivery. Sham control animals received vehicle treatment and naïve animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological changes were examined postmortem in tissues. Collagen accumulation and fibrosis were confirmed with Sirius Red staining. RESULTS: Animals lost weight after oral administration of DBTC and developed persistent inflammatory abdominal and hindpaw hypersensitivity compared to sham-treated controls (P < 0.0001). These pain related secondary mechanical hypersensitivity responses increased more than 2-fold in DBTC-treated animals. The drastically diminished rearing and grooming rates persisted after DBTC administration throughout the study. Gross as well as micropathology at one month confirmed that animals treated with DBTC developed chronic hepatobiliary injuries evidenced with activation of stellate cells, multifocal necrosis, fatty degeneration of hepatocytes, periportal infiltration of inflammatory cells, and prominent biliary ductal dilation. The severity of hepatitis was scored 3.7 ± 0.2 (severe) in DBTC-treated animals vs score 0 (normal) in sham-treated animals. Fibrotic thickening was extensive around portal ducts, in hepatic parenchyma as well as in lobular pancreatic structures and confirmed with Sirius Red histopathology. In addition, pancreatic microarchitecture was presented with distortion of islets, and parenchyma, infiltration of

  20. Characteristics of Tumor Infiltrating Lymphocyte and Circulating Lymphocyte Repertoires in Pancreatic Cancer by the Sequencing of T Cell Receptors

    PubMed Central

    Bai, Xueli; Zhang, Qi; Wu, Song; Zhang, Xiaoyu; Wang, Mingbang; He, Fusheng; Wei, Tao; Yang, Jiaqi; Lou, Yu; Cai, Zhiming; Liang, Tingbo

    2015-01-01

    Pancreatic cancer has a poor prognosis and few effective treatments. The failure of treatment is partially due to the high heterogeneity of cancer cells within the tumor. T cells target and kill cancer cells by the specific recognition of cancer-associated antigens. In this study, T cells from primary tumor and blood of sixteen patients with pancreatic cancer were characterized by deep sequencing. T cells from blood of another eight healthy volunteers were also studied as controls. By analyzing the complementary determining region 3 (CDR3) gene sequence, we found no significant differences in the T cell receptor (TCR) repertoires between patients and healthy controls. Types and length of CDR3 were similar among groups. However, two clusters of patients were identified according to the degree of CDR3 overlap within tumor sample group. In addition, clonotypes with low frequencies were found in significantly higher numbers in primary pancreatic tumors compared to blood samples from patients and healthy controls. This study is the first to characterize the TCR repertoires of pancreatic cancers in both primary tumors and matched blood samples. The results imply that specific types of pancreatic cancer share potentially important immunological characteristics. PMID:26329277

  1. Expansion of Tumor-reactive T Cells From Patients With Pancreatic Cancer.

    PubMed

    Meng, Qingda; Liu, Zhenjiang; Rangelova, Elena; Poiret, Thomas; Ambati, Aditya; Rane, Lalit; Xie, Shanshan; Verbeke, Caroline; Dodoo, Ernest; Del Chiaro, Marco; Löhr, Matthias; Segersvärd, Ralf; Maeurer, Markus J

    2016-01-01

    Generation of T lymphocytes with reactivity against cancer is a prerequisite for effective adoptive cellular therapies. We established a protocol for tumor-infiltrating lymphocytes (TILs) from patients with pancreatic ductal adenocarcinoma. Tumor samples from 17 pancreatic cancer specimens were cultured with cytokines (IL-2, IL-15, and IL-21) to expand TILs. After 10 days of culture, TILs were stimulated with an anti-CD3 antibody (OKT3) and irradiated allogeneic peripheral blood mononuclear cells. Reactivity of TILs against tumor-associated antigens (mesothelin, survivin, or NY-ESO-1) was detected by intracellular cytokine production by flow cytometry. Cytotoxicity was measured using a Chromium 51 release assay, and reactivity of TILs against autologous tumor cells was detected by INF-[gamma] production (ELISA). TIL composition was tested by CD45RA, CCR7, 4-1BB, LAG-3, PD-1, TIM3, and CTLA-4 marker analysis. TCR V[beta] was determined by flow cytometry and TCR clonality was gauged measuring the CDR3 region length by PCR analysis and subsequent sequencing. We could reliably obtain TILs from 17/17 patients with a majority of CD8(+) T cells. CD3(+)CD8(+), CD3(+)CD4(+), and CD3(+)CD4(-)CD8(-)[double-negative (DN) T cells] resided predominantly in central (CD45RA(-)CCR7(+)) and effector (CD45RA-CCR7-) memory subsets. CD8(+) TILs tested uniformly positive for LAG-3 (about 100%), whereas CD4(+) TILs showed only up to 12% LAG-3(+) staining and PD-1 showed a broad expression pattern in TILs from different patients. TILs from individual patients recognized strongly (up to 11.9% and 8.2% in CD8(+)) NY-ESO-1, determined by ICS, or mesothelin, determined respectively by TNF-[alpha] and IFN-[gamma] production. Twelve of 17 of CD8(+) TILs showed preferential expansion of certain TCR V[beta] families (eg, 99.2% V[beta]13.2 in CD8(+) TILs, 77% in the V[beta]1, 65.9% in the V[beta]22, and 63.3% in the V[beta]14 family). TCR CDR3 analysis exhibited monoclonal or oligoclonal TCRs

  2. Malignant solitary fibrous tumor of tandem lesions in the skull and spine.

    PubMed

    Son, Seong; Lee, Sang-Gu; Jeong, Dong-Hae; Yoo, Chan Jong

    2013-09-01

    A Solitary Fibrous Tumor (Sft) Is A Rare Neoplasm Originated From The Pleura, But They Can Occur In A Variety Of Extrathoracic Regions. Although Many Cases Of Primary Sft Have Been Reported, There Are Extremely Rare Repots To Date Of A Malignant Sft In The Spine Or Skull. A 54-year-woman Visited Our Hospital Due To Low Back Pain And Both Leg Radiating Pain. Several Imaging Studies Including Magnetic Resonance Imaging And Computed Tomography Revealed Expansive Enhanced Lesions In The Occipital Bone, T8, S1-2, And Ilium, With Neural Tissue Compression. We Performed Surgical Resection Of The Tumor In Each Site, And Postoperative Radiosurgery And Chemotherapy Were Performed. However, After Six Months, Tumors Were Recurred And Metastasized In Multiple Regions Including Whole Spine And Lung. The Authors Report Here The First Case Of Patient With Malignant Sft Of Tandem Lesions In The Various Bony Structures, Including Skull, Thoracic Spine, And Sacral Spine, With A Rapid Recurrence And Metastasis. Although Malignant Sft Is Extremely Rare, It Should Be Considered In The Differential Diagnosis And Carful Follow-up Is Needed.

  3. Dynamic holographic endoscopy--ex vivo investigations of malignant tumors in the human stomach.

    PubMed

    Avenhaus, Wolfgang; Kemper, Björn; Knoche, Sabine; Domagk, Dirk; Poremba, Christopher; von Bally, Gert; Domschke, Wolfram

    2005-01-01

    Laser holographic interferometry is based on the superimposition of the holograms of different motional states of an object on a single holographic storing medium. Using a combination of holographic interferometry and endoscopic imaging, we tried to detect areas of focally disturbed tissue elasticity in gastric cancer preparations. By connecting a mobile electronic speckle pattern interferometry (ESPI) camera system (light source: double frequency Nd:YAG laser, lambda = 532 nm) to different types of endoscopes, ex vivo experiments were performed on ten formalin fixed human stomachs, nine containing adenocarcinomas and one with a gastric lymphoma. Linking the endoscopic ESPI camera complex to a fast image processing system, the method of double pulse exposure image subtraction was applied at a video frame rate of 12.5 Hz. Speckle correlation patterns and corresponding phase difference distributions resulting from gastric wall deformation by gentle touch with a guide wire were analyzed. Tumor-free gastric areas showed high-contrast concentric fringes around the point of stimulation. In contrast, fringe patterns and filtered phase difference distributions corresponding to the areas of malignancy in all the cases were characterized by largely parallel lines, indicating that stimulation of rigid tumor tissue primarily led to tilting. Our ex vivo investigations of malignant gastric tumors show that the application of dynamic holographic endoscopy makes it possible to distinguish areas of malignancy from surrounding healthy tissue based on the differences in tissue elasticity. PMID:15726298

  4. Tumor microenvironment (TME)-driven immune suppression in B cell malignancy.

    PubMed

    Nicholas, Nicole S; Apollonio, Benedetta; Ramsay, Alan G

    2016-03-01

    Immune checkpoint blockade antibodies and immunomodulatory drugs can unleash anti-tumor T cell immunity and mediate durable cancer regressions. However, only a fraction of patients currently respond to immunotherapy. Lymphoid malignancies are known to have clinically exploitable immune sensit