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Sample records for extracranial solid tumor

  1. Brain metastasis in pediatric extracranial solid tumors: survey and literature review.

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    Kebudi, Rejin; Ayan, Inci; Görgün, Omer; Ağaoğlu, Fulya Yaman; Vural, Sema; Darendeliler, Emin

    2005-01-01

    Brain is a rare site of metastasis in most extracranial pediatric solid tumors. The aim of this study is to investigate the incidence, treatment, prognosis of brain metastasis in extracranial pediatric malignant tumors in a single institution and to review the literature. From September 1989 to December 2002, 1100 children Pediatric Oncology, Oncology Institute, Istanbul University. Patients with parenchymal metastases in the brain were assessed. Sixteen (10 female, 6 male) of 1100 patients (1.45%) with extracranial solid tumors developed brain metastases. The median age of the patients was 10.5 (1-16) years. The diagnosis was sarcomas in 12 patients: 5 osteosarcomas, 4 Ewing's sarcoma family tumors, 1 rhabdomyosarcoma, 1 clear cell sarcoma of the soft tissue, 1 alveolar soft part sarcoma. Two patients had Wilms' tumor and two had germ cell tumors. Four patients (25%) had brain metastasis at diagnosis. Twelve (75%) developed brain metastasis during therapy or relapse at a median duration of 16 (1-70) months from initial diagnosis. All patients had metastases to various sites, mostly lung, at the time the brain metastases were detected. Treatment included surgery, followed by postoperative radiotherapy (RT) and chemotherapy (CT) in 1, S and RT in 1, S in 1, RT and CT in 6, RT in 1, CT in 1 and no treatment in 5. Only one patient with alveolar soft part sarcoma is alive with disease 20 months from diagnosis of brain metastasis. All other patients died at a median time of 2 months (2 days-6 months) from the time of brain metastasis. Children with metastatic cancer who develop headaches or any other neurologic symptom should be investigated for possible brain metastasis. Although, the outcome for these patients is dismal in this series and in the literature; reports of long term survival in a few cases with Wilms' tumor, osteosarcoma and alveolar soft part sarcoma who had isolated brain metastasis, suggest that a subset of patients may benefit from therapy.

  2. [Four cases of extracranial trigeminal benign neurogenic tumors].

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    Mada, Yusuke; Ueki, Yuji; Konno, Akiyoshi

    2014-11-01

    Extracranial trigeminal schwannomas are rare tumors accounting for about 10% of all trigeminal schwannomas. We report herein on four cases of extracranial trigeminal benign neurogenic tumors. The patients were aged between 39 and 75 years; they consisted of one male and three females. The origins of the schwannomas consisted of the maxillary nerve in two cases and the mandibular nerve in two cases. All cases were surgically treated using a transmaxillary approach in three cases, and a combination of the transcervical-parotid approach with a midline mandibulotomy in one case. In two cases, the schwannomas located in the pterygopalatine fossa were removed using a transmaxillary approach with the endoscope and the surgical microscope. Two patients underwent selective intravascular embolization of the feeding artery to reduce intraoperative bleeding, and they were less invasively treated via the transmaxillary approach.

  3. Chemotherapy-related neuropathic symptoms and functional impairment in adult survivors of extracranial solid tumors of childhood: results from the St. Jude Lifetime Cohort Study.

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    Ness, Kirsten K; Jones, Kendra E; Smith, Webb A; Spunt, Sheri L; Wilson, Carmen L; Armstrong, Gregory T; Srivastava, Deo Kumar; Robison, Leslie L; Hudson, Melissa M; Gurney, James G

    2013-08-01

    To ascertain prevalence of peripheral sensory and motor neuropathy, and to evaluate impairments in relation to function. St. Jude Lifetime Cohort Study, a clinical follow-up study designed to evaluate adverse late effects in adult survivors of childhood cancer. A children's research hospital. Eligibility required treatment for an extracranial solid malignancy between 1962 and 2002, age ≥ 18 years, ≥ 10 years postdiagnosis, and no history of cranial radiation. Survivors (N=531) were included in the evaluation with a median age of 32 years and a median time from diagnosis of 25 years. Not applicable. Primary exposure measures were cumulative doses of vinca-alkaloid and platinum-based chemotherapies. Survivors with scores ≥ 1 on the sensory subscale of the Modified Total Neuropathy Score were classified with prevalent sensory impairment. Those with sex-specific z scores of ≤-1.3 for dorsiflexion strength were classified with prevalent motor impairment. Participants completed the 6-minute walk test (endurance), the Timed Up & Go test (mobility), and the Sensory Organization Test (balance). The prevalence of sensory and motor impairment was 20% and 17.5%, respectively. Vinca-alkaloid exposure was associated with an increased risk of motor impairment (adjusted odds ratio [OR]=1.66; 95% confidence interval [CI], 1.04-2.64) without evidence for a dose response. Platinum exposure was associated with increased risk of sensory impairment (adjusted OR=1.62; 95% CI, .97-2.72) without evidence of a dose response. Sensory impairment was associated with poor endurance (OR=1.99; 95% CI, .99-4.0) and mobility (OR=1.65; 95% CI, .96-2.83). Vincristine and cisplatin exposure may increase risk for long-term motor and sensory impairment, respectively. Survivors with sensory impairment are at increased risk for functional performance limitations. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  4. Stages of Childhood Extracranial Germ Cell Tumors

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    ... tumors include the following: Having certain genetic syndromes : Klinefelter syndrome may increase the risk of germ cell ... and procedures may be used: Physical exam and history : An exam of the body to check general ...

  5. Glomus jugulare tumor with intra- and extracranial extension. A case report with MRI study

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    Morisako, Toshitaka; Goya, Tomokazu; Wakisaka, Shinichiro; Kinoshita, Kazuo

    1987-11-01

    A case of glomus jugulare tumor with intra- and extracranial extension is described. The patient was a 63-year-old woman who complained of gait and memory disturbances. On admission neurological examination revealed recent memory disturbance, left deafness, left XI, XIIth cranial nerve palsies, and slight ataxic gait. Roentgenogram of the skull showed an enlarged left jugular foramen with bone erosion. Plain X-ray computerized tomography scan (X-CT) indicated obstructive hydrocephalus and X-CT with contrast enhancement revealed a mass lesion in the left posterior cranial fossa extending through enlarged left jugular foramen to the extracranial space toward the level of C/sub 2/. Cerebral angiography demonstrated a large mass with blood supply from branches of left external carotid and vertebral arteries. The tumor stain was not remarkable. Left internal jugular vein was completely obstructed at the level of the second cervical vertebral body. Magnetic resonance imaging (MRI) clearly showed the tumor extending from the anterolateral portion to the second cervical vertebral body through the enlarged jugular foramen to the posterior cranial fossa. Brain stem and cerebellar hemisphere which were markedly compressed by the mass were clearly visualized. At first a ventriculo-peritoneal shunt was made and four weeks later subtotal removal of the tumor was undertaken. Histopathology of tumor specimen showed typical glomus jugulare tumor. MRI was considered to be very useful for the diagnosis and treatment of the glomus jugulare tumor with intra- and extracranial extension

  6. General Information about Childhood Extracranial Germ Cell Tumors

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    ... tumors include the following: Having certain genetic syndromes : Klinefelter syndrome may increase the risk of germ cell ... and procedures may be used: Physical exam and history : An exam of the body to check general ...

  7. Treatment Options for Childhood Extracranial Germ Cell Tumors

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    ... tumors include the following: Having certain genetic syndromes : Klinefelter syndrome may increase the risk of germ cell ... and procedures may be used: Physical exam and history : An exam of the body to check general ...

  8. Routine surveillance imaging after end of therapy for pediatric extracranial tumors: A retrospective analysis.

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    Lakkis, Farah; Alaiwi, Sarah Abou; Naffaa, Lena; Atweh, Lamya; Khoury, Nabil; Abboud, Miguel; Muwakkit, Samar; Tarek, Nidale; El Solh, Hassan; Saab, Raya

    2017-07-20

    Frequent surveillance imaging is routine practice for pediatric patients after cancer therapy. This retrospective study evaluated the follow-up of 301 children with extracranial tumors diagnosed between 2002 and 2012, at a tertiary pediatric cancer center in Beirut, Lebanon. Recurrence occurred in 15% of patients, at a median of 12 months after end of primary therapy. Outcome was not different comparing patients with recurrence detected via imaging surveillance versus clinically. False positive findings in 55 patients led to further interventions. These results raise important questions regarding benefit of current surveillance practices as standard care, especially in countries with limited resources. © 2017 Wiley Periodicals, Inc.

  9. Extracranial metastasizing solitary fibrous tumors (SFT) of meninges: histopathological features of a case with long-term follow-up.

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    Gessi, Marco; Gielen, Gerrit H; Roeder-Geyer, Eva-Dorette; Sommer, Clemens; Vieth, Michael; Braun, Veit; Kuchelmeister, Klaus; Pietsch, Torsten

    2013-02-01

    Extrapleural solitary fibrous tumors are uncommon mesenchymal neoplasms frequently observed in middle-aged adults and are classified, according to the WHO classification of soft tissue tumors, as part of the hemangiopericytoma tumor group. However, these two entities remain separated in the WHO classification of tumors of the central nervous system. In fact, meningeal solitary fibrous tumors are believed to be benign lesion and only in a minority of cases local relapses have been described, although detailed survival clinical studies on solitary fibrous tumors of meninges are rare. In contrast to hemangiopericytoma, which frequently shows distant extracranial metastases, such an event is exceptional in patients with meningeal solitary fibrous tumors and has been clinically reported in a handful of cases only and their histopathological features have not been investigated in detail. In this report, we describe the detailed clinico-pathological features of a meningeal solitary fibrous tumor presenting during a 17-year follow-up period, multiple intra-, extracranial relapses and lung metastases.

  10. Importance of Extracranial Disease Status and Tumor Subtype for Patients Undergoing Radiosurgery for Breast Cancer Brain Metastases

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    Dyer, Michael A.; Kelly, Paul J. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Chen, Yu-Hui [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (United States); Pinnell, Nancy E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Claus, Elizabeth B. [Harvard Medical School, Boston, MA (United States); Department of Neurosurgery, Brigham and Women' s Hospital, Boston, MA (United States); Yale University School of Medicine, New Haven, CT (United States); Lee, Eudocia Q. [Harvard Medical School, Boston, MA (United States); Center for Neuro-Oncology, Dana-Farber/Brigham and Women' s Center, Boston, MA (United States); Weiss, Stephanie E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Arvold, Nils D. [Harvard Radiation Oncology Program, Boston, MA (United States); Lin, Nancy U. [Harvard Medical School, Boston, MA (United States); Department of Medical Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)

    2012-07-15

    Purpose: In this retrospective study, we report on outcomes and prognostic factors for patients treated with stereotactic radiosurgery (SRS) for breast cancer brain metastases. Methods and Materials: We identified 132 consecutive patients with breast cancer who were treated with SRS for brain metastases from January 2000 through June 2010. We retrospectively reviewed records of the 51 patients with adequate follow-up data who received SRS as part of the initial management of their brain metastases. Overall survival (OS) and time to central nervous system (CNS) progression from the date of SRS were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results: Triple negative subtype was associated with CNS progression on univariate analysis (hazard ratio [HR] = 5.0, p = 0.008). On multivariate analysis, triple negative subtype (HR = 8.6, p = 0.001), Luminal B subtype (HR = 4.3, p = 0.03), and omission of whole-brain radiation therapy (HR = 3.7, p = 0.02) were associated with CNS progression. With respect to OS, Karnofsky Performance Status (KPS) {<=} 80% (HR = 2.0, p = 0.04) and progressive extracranial disease (HR = 3.1, p = 0.002) were significant on univariate analysis; KPS {<=} 80% (HR = 4.1, p = 0.0004), progressive extracranial disease (HR = 6.4, p < 0.0001), and triple negative subtype (HR = 2.9, p = 0.04) were significant on multivariate analysis. Although median survival times were consistent with those predicted by the breast cancer-specific Graded Prognostic Assessment (Breast-GPA) score, the addition of extracranial disease status further separated patient outcomes. Conclusions: Tumor subtype is associated with risk of CNS progression after SRS for breast cancer brain metastases. In addition to tumor subtype and KPS, which are incorporated into the Breast-GPA, progressive extracranial disease may be an important prognostic factor for OS.

  11. CCCT - NCTN Steering Committees - Pediatric and Adolescent Tumor

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    The Pediatric and Adolescent Solid Tumor Steering Committee addresses the design, prioritization and evaluation of concepts for large phase 2 and phase 3 clinical trials in extracranial solid tumors of children and youth.

  12. Solid tumor cytogenetics: current perspectives.

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    Nanjangud, Gouri; Amarillo, Ina; Rao, P Nagesh

    2011-12-01

    Conventional cytogenetics in conjunction with Fluorescence in Situ Hybridization (FISH) continues to remain an important and integral component in the diagnosis and management of solid tumors. The ability to effectively detect the vast majority of clinically relevant chromosomal aberrations with a rapid-to-acceptable turnaround time makes them the most cost-effective screening/detection tool currently available in modern pathology. In this review, we describe a representative set of solid tumors in which chromosomal analysis and/or FISH plays a significant role in the routine clinical management of solid tumors.

  13. Current immunotherapy for solid tumors.

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    Barkholt, Lisbeth; Bregni, Marco

    2009-05-01

    Explorative knowledge of cellular and molecular mechanisms of immune function and regulation has provided optimism in developing cancer immunotherapy. However, three decades of experimental and clinical investigations to offer powerful immunotherapeutic strategies against solid tumors, with the possible exception of monoclonal antibody-targeted therapies, have not succeeded in significantly prolonging patient survival. Nonspecific immune approaches, including cytokine-based therapies and allogeneic hematopoietic stem cell transplantation, have so far produced consistent, although limited, results. In this review, we present the developments of cell transfer-based strategies that, in preclinical studies, have demonstrated potential efficacy, but have only established tumor regression in limited numbers of patients. The key to success demands creative combinations of tumor antigens, adjuvance, gene modification and various administration strategies in the development of cell-based therapies together with other cancer-treatment principles, often in a stepwise 'space-rocket-type' approach. Combined efforts of several scientific disciplines, such as tumor biology and immunology, as well as cell and gene research in transplantation, will open new venues. New regulation for clinical trials with advanced therapy medicine products to ensure patient safety will be highlighted.

  14. Tumor Control Outcomes After Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases From Renal Cell Carcinoma

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    Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Greco, Carlo [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Motzer, Robert [Solid Tumor Service, Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Magsanoc, Juan Martin; Pei Xin [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Lovelock, Michael; Mechalakos, Jim [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Zatcky, Joan; Fuks, Zvi; Yamada, Yoshiya [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-04-01

    Purpose: To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Patients and Methods: Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48). Results: The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a high single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008). Conclusion: High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking.

  15. Minimal invasive surgery in pediatric solid tumors.

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    Chan, Kin Wai; Lee, K H; Tam, Y H; Yeung, C K

    2007-12-01

    There is only limited experience of using the minimally invasive surgery (MIS) technique in resecting pediatric solid tumors. In this paper, we report our experience of using the MIS technique in the management of pediatric solid tumors. A retrospective review was undertaken on all children who had undergone MIS for their solid tumors between 1995 and 2005. Over a 10-year period, there were 38 patients who had undergone MIS for tumor resection. The mean age at the time of surgery was 7.5 years (range, 1 day to 15 years). There were 22 ovarian tumors, 4 sacrococcygeal tumors, 3 adrenal tumors, 3 retroperitoneal tumors, 1 kidney tumor, 1 liver mass, 1 intra-abdominal testicular tumor, and 3 intrathoracic masses. Thirty of 38 patients had undergone a successful resection using the MIS technique (78.9%). Eight patients required a conversion to the open procedure because of limited intraperitoneal space in 7 and excessive bleeding in 1. Of the 28 successfully MIS-resected intra-abdominal tumors, 18 required enlargement of the umbilical incision and 5 required an additional Pfannenstiel incision for tumor retrieval. Enlargement of the thoracic port site for specimen retrieval was required in the 2 successfully MIS-resected intrathoracic masses. The mean operation time was 171 minutes (range, 45-275). There was no postoperative complication encountered. On an average follow-up of 3.1 years, there was no recurrence observed, even in the 7 patients with malignant tumors, and all patients with successful MIS tumor excision had good cosmetic results. With the advance of laparoscopic instruments and techniques, a variety of pediatric solid tumors can be resected safely by the MIS technique. This has the potential benefit of a more rapid postoperative recovery and better cosmetic results. The role of the MIS technique in resecting malignant tumors is uncertain, as the number of cases in the current series is too small to draw any conclusion.

  16. Cancer Stem Cells and Pediatric Solid Tumors

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    Gregory K. Friedman

    2011-01-01

    Full Text Available Recently, a subpopulation of cells, termed tumor-initiating cells or tumor stem cells (TSC, has been identified in many different types of solid tumors. These TSC, which are typically more resistant to chemotherapy and radiation compared to other tumor cells, have properties similar to normal stem cells including multipotency and the ability to self-renew, proliferate, and maintain the neoplastic clone. Much of the research on TSC has focused on adult cancers. With considerable differences in tumor biology between adult and pediatric cancers, there may be significant differences in the presence, function and behavior of TSC in pediatric malignancies. We discuss what is currently known about pediatric solid TSC with specific focus on TSC markers, tumor microenvironment, signaling pathways, therapeutic resistance and potential future therapies to target pediatric TSC.

  17. Leptomeningeal Metastases in Solid Tumors

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    Marija Karakolevska-Ilova

    2014-12-01

    CONCLUSION: The prognostic factors associated with survival in patients with LM metastasis are not certain as well as right treatment for these patients which is still a big challenge. Due to the lack of randomized studies and especially of studies referring to one specific primary tumor, there is currently no generally accepted standard of care in the treatment of LM metastases.

  18. Solid Tumors of the Mediastinum in Adults.

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    Azizad, Shameem; Sannananja, Bhagya; Restrepo, Carlos S

    2016-06-01

    A wide spectrum of solid tumors can develop in the mediastinum of adults. Like for any other tumor evaluation, the location and morphology play equally important role for lesion characterization. Compartmentalizing the mediastinal masses greatly narrows the number of possible differential diagnosis. Cross sectional imaging mainly with computed tomography (CT) and magnetic resonance imaging (MRI) are the preferred modalities of choice as they can establish the presence, location and morphology of the lesion allowing to suggest a possible diagnosis.

  19. Improving drug delivery to solid tumors: priming the tumor microenvironment.

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    Khawar, Iftikhar Ali; Kim, Jung Ho; Kuh, Hyo-Jeong

    2015-03-10

    Malignant transformation and growth of the tumor mass tend to induce changes in the surrounding microenvironment. Abnormality of the tumor microenvironment provides a driving force leading not only to tumor progression, including invasion and metastasis, but also to acquisition of drug resistance, including pharmacokinetic (drug delivery-related) and pharmacodynamic (sensitivity-related) resistance. Drug delivery systems exploiting the enhanced permeability and retention (EPR) effect and active targeting moieties were expected to be able to cope with delivery-related drug resistance. However, recent evidence supports a considerable barrier role of tumors via various mechanisms, which results in imperfect or inefficient EPR and/or targeting effect. The components of the tumor microenvironment such as abnormal tumor vascular system, deregulated composition of the extracellular matrix, and interstitial hypertension (elevated interstitial fluid pressure) collectively or cooperatively hinder the drug distribution, which is prerequisite to the efficacy of nanoparticles and small-molecule drugs used in cancer medicine. Hence, the abnormal tumor microenvironment has recently been suggested to be a promising target for the improvement of drug delivery to improve therapeutic efficacy. Strategies to modulate the abnormal tumor microenvironment, referred to here as "solid tumor priming" (vascular normalization and/or solid stress alleviation leading to improvement in blood perfusion and convective molecular movement), have shown promising results in the enhancement of drug delivery and anticancer efficacy. These strategies may provide a novel avenue for the development of new chemotherapeutics and combination chemotherapeutic regimens as well as reassessment of previously ineffective agents. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Recurrence of Solid Pseudopapillary Tumor: A Rare Pancreatic Tumor

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    Chandra Punch

    2016-01-01

    Full Text Available Solid pseudopapillary tumor of the pancreas (SPTP is a rare disease of young females that does not usually recur after resection. Here we report a case of an elderly female with history of SPTP ten years ago who presented with anorexia and a palpable left lower quadrant abdominal mass. Imaging revealed metastatic disease and US-guided biopsy of the liver confirmed the diagnosis of SPTP. Due to her advanced age and comorbidities, she elected to undergo hospice care. The objective of this case report is to increase awareness of this tumor and its possibility of recurrence, necessitating further guidelines for follow-up.

  1. Study of the Glutaminase Inhibitor CB-839 in Solid Tumors

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    2016-08-18

    Solid Tumors; Triple-Negative Breast Cancer; Non Small Cell Lung Cancer; Renal Cell Carcinoma; Mesothelioma; Fumarate Hydratase (FH)-Deficient Tumors; Succinate Dehydrogenase (SDH)-Deficient Gastrointestinal Stromal Tumors (GIST); Succinate Dehydrogenase (SDH)-Deficient Non-gastrointestinal Stromal Tumors; Tumors Harboring Isocitrate Dehydrogenase-1 (IDH1) and IDH2 Mutations; Tumors Harboring Amplifications in the cMyc Gene

  2. Targeting BET bromodomain proteins in solid tumors.

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    Sahai, Vaibhav; Redig, Amanda J; Collier, Katharine A; Eckerdt, Frank D; Munshi, Hidayatullah G

    2016-08-16

    There is increasing interest in inhibitors targeting BET (bromodomain and extra-terminal) proteins because of the association between this family of proteins and cancer progression. BET inhibitors were initially shown to have efficacy in hematologic malignancies; however, a number of studies have now shown that BET inhibitors can also block progression of non-hematologic malignancies. In this Review, we summarize the efficacy of BET inhibitors in select solid tumors; evaluate the role of BET proteins in mediating resistance to current targeted therapies; and consider potential toxicities of BET inhibitors. We also evaluate recently characterized mechanisms of resistance to BET inhibitors; summarize ongoing clinical trials with these inhibitors; and discuss potential future roles of BET inhibitors in patients with solid tumors.

  3. Destruction of solid tumors by immune cells

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    López, Álvaro G.; Seoane, Jesús M.; Sanjuán, Miguel A. F.

    2017-03-01

    The fractional cell kill is a mathematical expression describing the rate at which a certain population of cells is reduced to a fraction of itself. In order to investigate the fractional cell kill that governs the rate at which a solid tumor is lysed by a cell population of cytotoxic CD8+ T cells (CTLs), we present several in silico simulations and mathematical analyses. When the CTLs eradicate efficiently the tumor cells, the models predict a correlation between the morphology of the tumors and the rate at which they are lysed. However, when the effectiveness of the immune cells is decreased, the mathematical function fails to reproduce the process of lysis. This limit is thoroughly discussed and a new fractional cell kill is proposed.

  4. Solid Tumors: Facts, Challenges and Solutions

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    Gavhane Y. N.

    2011-01-01

    Full Text Available In 2005, 7.6 million people died of cancer out of 58 million deaths worldwide. Based on projections, cancer deaths will continue to rise with an estimated 9 million people dying from cancer in 2015, and 11.4 million dying in 2030. The increasing trend of cancer incidence has forced the humanity to work more on the cancer prevention and treatments. It is important for the public health professionals to understand the dynamics and kinetics of tumor incidence for future strategies. Over here we have reviewed solid tumor modeling, their detail classification, treatment strategies available along with their merits and demerits. To overcome these limitations, design focus for future studies is suggested.

  5. Characterization of cell suspensions from solid tumors

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    Pallavicini, M.

    1985-07-10

    The desirable features of cells in suspension will necessarily be dependent upon the use for which the cells were prepared. Adequate cell yield or recovery is defined by the measurement to be performed. Retention of cellular morphology is important for microscopic identification of cell types in a heterogenous cell suspension, and may be used to determine whether the cells in suspension are representative of those in the tumor in situ. Different dispersal protocols may yield cells with different degrees of clonogenicity, as well as altered biochemical features, such as loss of cellular proteins, surface antigens, nucleotide pools, etc. The quality of the cell suspension can be judged by the degree of cell clumping and level of cellular debris, both of which impact on flow cytometric measurements and studies in which the number of cells be known accurately. Finally, if the data measured on the cells in suspension are to be extrapolated to phenomena occurring in the tumor in situ, it is desirable that the cells in suspension are representative of those in the solid tumor in vivo. This report compares characteristics of tumor cell suspensions obtained by different types of selected disaggregation methods. 33 refs., 2 figs., 4 tabs.

  6. Amplification of cellular oncogenes in solid tumors

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    Ozkan Bagci

    2015-01-01

    Full Text Available The term gene amplification refers to an increase in copy number of a gene. Upregulation of gene expression through amplification is a general mechanism to increase gene dosage. Oncogene amplifications have been shown in solid human cancers and they are often associated with progression of cancer. Defining oncogene amplification is useful since it is used as a prognostic marker in clinical oncology nowadays, especially v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (HER2 targeted agents are used in breast cancer patients with high level of HER2 overexpression as a therapeutic approach. However, patients without HER2 overexpression do not appear to benefit from these agents. We concluded that determination of oncogene amplification in solid tumors is an important factor in treatment of human cancers with many unknowns. We have referred to PubMed and some databases to prepare this article.

  7. Therapy of leptomeningeal metastasis in solid tumors.

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    Mack, F; Baumert, B G; Schäfer, N; Hattingen, E; Scheffler, B; Herrlinger, U; Glas, M

    2016-02-01

    Leptomeningeal metastasis (LM), i.e. the seeding of tumor cells to the cerebrospinal fluid (CSF) and the leptomeninges, is a devastating and mostly late-stage complication of various solid tumors. Clinical signs and symptoms may include cranial nerve palsies, radicular symptoms, signs of increased intracranial pressure such as headache, nausea and vomiting, and cognitive dysfunction. In cases of suspected LM, the highest diagnostic sensitivity is provided by the combination of CSF cytology and contrast-enhanced MRI (cranial as well as complete spine). The therapeutic spectrum includes radiotherapy of the clinically involved region as well as systemic and intrathecal chemotherapy. The choice of treatment modalities depends on the type of LM (non-adherent tumor cells in the CSF vs. nodular contrast-enhancing tumor growth), additional systemic involvement (uncontrolled vs. controlled systemic disease) and additional involvement of the CNS parenchyma (LM as the only CNS involvement vs. LM+parenchymal CNS metastases). Larger contrast-enhancing nodular LM or symptomatic lesions of the spine may be treated with radiotherapy. In case of uncontrolled systemic disease, the treatment regimen should include systemic chemotherapy. The choice of systemic treatment should take into account the histology of the primary tumor. Intrathecal chemotherapy is most important in cases of LM of the non-adherent type. There are three substances for routine use for intrathecal chemotherapy: methotrexate, cytarabine, and thiotepa. Liposomal cytarabine shows advantages in terms of longer injection intervals, a sufficient distribution in the entire subarachnoid space after lumbar administration and improved quality-of-life. The role of new agents (e.g. rituximab and trastuzumab) for intrathecal therapy is still unclear.

  8. Pineal germinoma with extracranial metastases: case report

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    Lee, Young Rang; Lee, Seung Ro; Park, Dong Woo; Hahm, Chang Kok; Park, Moon Hyang; Ko, Yong [College of Medicine, Hanyang Univ., Seoul (Korea, Republic of)

    2004-08-01

    Pineal germinoma is the commonest pineal region tumor of childhood and adolescence. Metastatic germinoma most commonly occurs via the cerebrospinal fluid (CSF), and it is usually limited to the cerebrospinal axis. ExtacraniaI hematogenous metastasis is known to be very rare. We report here on a case of pineal germinoma with gradual extracranial metastases that occurred both through the CSF pathway and by hematogenous spread. The patient had multifocal CSF seeding after his surgery for pineal germinoma, and the left iliac metastasis and lung metastasis then occurred.

  9. Warburg′s effect on solid tumors

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    Talal El Imad

    2014-01-01

    Full Text Available Lactic acidosis is the result of imbalance between the systemic formation of lactate and its hepatic metabolism. In cancer patients, lactic acidosis is mainly associated with hematologic malignancies (leukemia and lymphomas and the mechanism is known as Warburg′s effect. We report a 76-year-old male known to have hypertension and coronary artery disease, who presented with abdominal distension and lactic acidosis. His initial evaluation showed multiple liver masses that were biopsied and the patient was diagnosed with undifferentiated carcinoma of unknown primary, involving the liver. The patient had progression of lactic acidosis leading to his death on day-15. As the lactic acidosis was not in the setting of hypoxia or hemodynamic instability, we made the diagnosis of malignancy-associated type B lactic acidosis, also known as the Warburg′s effect. Warburg′s effect can occur in solid cancer if the tumor involves the liver. It has bad prognostic implications. The use of intravenous bicarbonate as a temporary measure is of controversial benefit, as it can potentially worsen the metabolic acidosis and its use should be limited to patients with very low pH. In cancer patients, the use of lactatebased intravenous fluids can be potentially harmful and can increase the risk of tumor metastasis, at least in animal malignancy models.

  10. Solid-pseudopapillary tumor of the pancreatic tail

    Institute of Scientific and Technical Information of China (English)

    Frank Eder; Hans-Ulrich Schulz; Christoph R(o)cken; Hans Lippert

    2005-01-01

    We report a case of the rare solid-pseudopapillary tumor of the pancreas. In contrast to other pancreatic tumors,the solid-pseudopapillary tumor has a favorable prognosis.The 60-year-old female patient we report on here was treated by left pancreatic resection combined with splenectomy for a non-metastasizing tumor of the pancreas. A solid-pseudopapillary tumor was found on histology. The patient had no signs of metastases at present.Since a microscopically invasive tumor growth is assumed,oncologically curative resection should be preferred vs the less radical enucleation. The rare solid-pseudopapillary tumor of the pancreas has a good prognosis after successful oncological resection.

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

    Science.gov (United States)

    2017-03-21

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

  12. Diversity of Dynamics and Morphologies of Invasive Solid Tumors

    CERN Document Server

    Jiao, Yang

    2012-01-01

    Complex tumor-host interactions can significantly affect the growth dynamics and morphologies of progressing neoplasms. The growth of a confined solid tumor induces mechanical pressure and deformation of the surrounding microenvironment, which in turn influences tumor growth. In this paper, we generalize a recently developed cellular automaton model for invasive tumor growth in heterogeneous microenvironments by incorporating the effects of pressure. Specifically, we explicitly consider pressure exerted on the growing tumor due to deformation of the microenvironment and model the local tumor-host interface instability. Both noninvasive proliferative growth and invasive growth with individual cells that detach themselves from the primary tumor and migrate into surrounding microenvironment are investigated. We find that while noninvasive tumors growing in "soft" homogeneous microenvironments develop almost isotropic shapes, high pressure and host heterogeneity can strongly enhance malignant behavior, leading to...

  13. Chromosome aberrations in solid tumors have a stochastic nature

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Mauro A.A. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil) and Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil) and Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil) and Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil)]. E-mail: mauro@ufrgs.br; Onsten, Tor G.H. [Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil); Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil); Moreira, Jose C.F. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil); Almeida, Rita M.C. de [Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil)

    2006-08-30

    An important question nowadays is whether chromosome aberrations are random events or arise from an internal deterministic mechanism, which leads to the delicate task of quantifying the degree of randomness. For this purpose, we have defined several Shannon information functions to evaluate disorder inside a tumor and between tumors of the same kind. We have considered 79 different kinds of solid tumors with 30 or more karyotypes retrieved from the Mitelman Database of Chromosome Aberrations in Cancer. The Kaplan-Meier cumulative survival was also obtained for each solid tumor type in order to correlate data with tumor malignance. The results here show that aberration spread is specific for each tumor type, with high degree of diversity for those tumor types with worst survival indices. Those tumor types with preferential variants (e.g. high proportion of a given karyotype) have shown better survival statistics, indicating that aberration recurrence is a good prognosis. Indeed, global spread of both numerical and structural abnormalities demonstrates the stochastic nature of chromosome aberrations by setting a signature of randomness associated to the production of disorder. These results also indicate that tumor malignancy correlates not only with karyotypic diversity taken from different tumor types but also taken from single tumors. Therefore, by quantifying aberration spread, we could confront diverse models and verify which of them points to the most likely outcome. Our results suggest that the generating process of chromosome aberrations is neither deterministic nor totally random, but produces variations that are distributed between these two boundaries.

  14. Solid tumor therapy by selectively targeting stromal endothelial cells.

    Science.gov (United States)

    Liu, Shihui; Liu, Jie; Ma, Qian; Cao, Liu; Fattah, Rasem J; Yu, Zuxi; Bugge, Thomas H; Finkel, Toren; Leppla, Stephen H

    2016-07-12

    Engineered tumor-targeted anthrax lethal toxin proteins have been shown to strongly suppress growth of solid tumors in mice. These toxins work through the native toxin receptors tumor endothelium marker-8 and capillary morphogenesis protein-2 (CMG2), which, in other contexts, have been described as markers of tumor endothelium. We found that neither receptor is required for tumor growth. We further demonstrate that tumor cells, which are resistant to the toxin when grown in vitro, become highly sensitive when implanted in mice. Using a range of tissue-specific loss-of-function and gain-of-function genetic models, we determined that this in vivo toxin sensitivity requires CMG2 expression on host-derived tumor endothelial cells. Notably, engineered toxins were shown to suppress the proliferation of isolated tumor endothelial cells. Finally, we demonstrate that administering an immunosuppressive regimen allows animals to receive multiple toxin dosages and thereby produces a strong and durable antitumor effect. The ability to give repeated doses of toxins, coupled with the specific targeting of tumor endothelial cells, suggests that our strategy should be efficacious for a wide range of solid tumors.

  15. Cancer stem cells in solid tumors: elusive or illusive?

    Directory of Open Access Journals (Sweden)

    Lehrach Hans R

    2010-05-01

    Full Text Available Abstract During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a a stringent definition of cancer stem cells in solid tumors (b specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare. In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.

  16. CT differentiation of solid ovarian tumor and uterine subserosal leiomyoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Rae; Cho, Kyoung Sik [Asan Medical Center, Ulsan Univ. College of Medicine, Seoul (Korea, Republic of); Sohn, Chul Ho [Dongsan Medical Center, Keimyung Univ. College of Medicine, Taegu (Korea, Republic of); Ji, Eun Kyung [Bombit Hospital, Seoul (Korea, Republic of)

    1999-06-01

    On the basis of CT findings, to differentiate between solid ovarian tumor and uterine subserosal myoma. In eight surgically proven cases of solid ovarian tumor and in ten uterine subserosal myoma patients, contrast-enhanced CT images were obtained. Two genitourinary radiologists reviewed the findings with regard to degree of enhancement of the mass as compared with enhancement of uterine myometrium, thickening of round ligaments, visualization of normal ovaries, contour of the mass, and the presence of ascites in the pelvic cavity. Six of eight ovarian tumors but only two of ten uterine myomas were less enhanced than normal uterine myometrium (p<0.05). Pelvic ascites were seen in six of eight ovarian tumors, but in only one of ten uterine myomas (P<0.05). Three of 16 ovaries in ovarian tumor patients, but 12 of 20 ovaries in uterine myoma patients, were normal (p<0.05). Six of 16 round ligaments of the uterus in ovarian tumor patients, were thichened but 11 of 20 round ligaments in uterine myoma patients, were thickened (p>0.05). The contour of the mass was lobulated in two of eight ovarian tumor patients, but in five of ten uterine myoma patients (p>0.05). CT findings suggestive of solid ovarian tumor were less contrast enhancement of the mass than of normal uterine myometrium, pelvic ascites, and nonvisualization of normal ovary.

  17. Irinotecan in Treating Children With Refractory Solid Tumors

    Science.gov (United States)

    2013-06-13

    Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  18. Tumor-infiltrating CD45RO(+) Memory T Lymphocytes Predict Favorable Clinical Outcome in Solid Tumors.

    Science.gov (United States)

    Hu, Guoming; Wang, Shimin

    2017-09-04

    The prognostic role of tumor-infiltrating CD45RO(+) memory T lymphocytes (CD45RO(+) T cells) in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 25 published studies with 4720 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating CD45RO(+) T cells in human solid tumors. We found that CD45RO(+) T cell infiltration was significantly associated with improved overall survival (OS) and disease-free survival (DFS) in all types of solid tumors. In stratified analyses, CD45RO(+) T cell infiltration significantly improved 1-year, 3-year and 5-year OS in colorectal, gastric and esophageal cancer, but only 5-year OS in hepatocellular carcinoma. And these cells were positively associated with 1-year, 3-year and 5-year DFS in hepatocellular, colorectal and esophageal cancer. In addition, high density of intratumoral CD45RO(+) T cells inversely correlated with TNM stage of solid tumor. In conclusion, CD45RO(+) memory T lymphocyte infiltration leads to a favorable clinical outcome in solid tumors, implicating that it is a valuable biomarker for prognostic prediction for human solid malignances.

  19. Characterization and differentiation of three solid tumors using quantitative ultrasound

    Science.gov (United States)

    Oelze, Michael L.; O'Brien, William D.; Zachary, James F.

    2004-05-01

    Three kinds of solid tumors were acquired and scanned in vivo ultrasonically. The first tumor series (fibroadenoma) was acquired from tumors that had spontaneously developed in rats. The second tumor series was acquired by culturing a carcinoma cell line (4T1-MMT) in culture media and injecting the cells into Balb/c mice. The third tumor was acquired by transplanting a soft-tissue sarcoma cell line (EHS) into C57BL mice. The tumors were allowed to grow to 1 cm in size and then scanned ultrasonically. The scatterer properties of average scatterer diameter and acoustic concentration were estimated using a Gaussian form factor from the backscattered ultrasound measured from the tumors. Parametric images of the tumors were constructed utilizing estimated scatterer properties for regions of interest inside the tumors. The parametric images showed distinct differences between the various tumor types. Quantitatively, the tumors could be distinguished through feature analysis plots of average scatterer size versus acoustic concentration. Comparison with photomicrographs of the tumors showed structures similar in size to the ultrasound estimates. [Work supported by NIH Grant F32 CA96419 to MLO and by the University of Illinois Research Board.

  20. Diversity of dynamics and morphologies of invasive solid tumors

    Directory of Open Access Journals (Sweden)

    Yang Jiao

    2012-03-01

    Full Text Available Complex tumor-host interactions can significantly affect the growth dynamics and morphologies of progressing neoplasms. The growth of a confined solid tumor induces mechanical pressure and deformation of the surrounding microenvironment, which in turn influences tumor growth. In this paper, we generalize a recently developed cellular automaton model for invasive tumor growth in heterogeneous microenvironments [Y. Jiao and S. Torquato, PLoS Comput. Biol. 7, e1002314 (2011] by incorporating the effects of pressure. Specifically, we explicitly model the pressure exerted on the growing tumor due to the deformation of the microenvironment and its effect on the local tumor-host interface instability. Both noninvasive-proliferative growth and invasive growth with individual cells that detach themselves from the primary tumor and migrate into the surrounding microenvironment are investigated. We find that while noninvasive tumors growing in “soft” homogeneous microenvironments develop almost isotropic shapes, both high pressure and host heterogeneity can strongly enhance malignant behavior, leading to finger-like protrusions of the tumor surface. Moreover, we show that individual invasive cells of an invasive tumor degrade the local extracellular matrix at the tumor-host interface, which diminishes the fingering growth of the primary tumor. The implications of our results for cancer diagnosis, prognosis and therapy are discussed.

  1. Effect of tumor shape and size on drug delivery to solid tumors

    Directory of Open Access Journals (Sweden)

    Soltani M

    2012-04-01

    Full Text Available Abstract Tumor shape and size effect on drug delivery to solid tumors are studied, based on the application of the governing equations for fluid flow, i.e., the conservation laws for mass and momentum, to physiological systems containing solid tumors. The discretized form of the governing equations, with appropriate boundary conditions, is developed for predefined tumor geometries. The governing equations are solved using a numerical method, the element-based finite volume method. Interstitial fluid pressure and velocity are used to show the details of drug delivery in a solid tumor, under an assumption that drug particles flow with the interstitial fluid. Drug delivery problems have been most extensively researched in spherical tumors, which have been the simplest to examine with the analytical methods. With our numerical method, however, more complex shapes of the tumor can be studied. The numerical model of fluid flow in solid tumors previously introduced by our group is further developed to incorporate and investigate non-spherical tumors such as prolate and oblate ones. Also the effects of the surface area per unit volume of the tissue, vascular and interstitial hydraulic conductivity on drug delivery are investigated.

  2. Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Thamm Reinhard

    2006-06-01

    Full Text Available Abstract Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical

  3. [Solid and papillary tumor of the pancreas].

    Science.gov (United States)

    Spay, G; Mosnier, J F; Mangnas, D

    A patient who was treated in 1978 by duodenopancreatectomy for a tumour of the second duodenum survived for 15 years before death caused by trauma. The pathology slides were therefore reassessed and led, a posteriori, to the diagnosis of solid papillary tumour of the pancreas according to the new criteria described by Kloppel. The 86 references found in the literature reported 139 cases although many were too vague to be retained. Precise diagnosis can only be obtained on the basis of immunohistochemistry and ultra-structure criteria as described here.

  4. Potential of epigenetic therapies in the management of solid tumors

    Directory of Open Access Journals (Sweden)

    Valdespino V

    2015-07-01

    Full Text Available Victor Valdespino,1 Patricia M Valdespino2 1Health Attention Department, Universidad Autónoma Metropolitana, Mexico; 2Bacterial Ecology and Epigenetics Laboratory, Universidad Nacional Autónoma de México, Mexico Abstract: Cancer is a complex disease with both genetic and epigenetic origins. The growing field of epigenetics has contributed to our understanding of oncogenesis and tumor progression, and has allowed the development of novel therapeutic drugs. First-generation epigenetic inhibitor drugs have obtained modest clinical results in two types of hematological malignancy. Second-generation epigenetic inhibitors are in development, and have intrinsically greater selectivity for their molecular targets. Solid tumors are more genetic and epigenetically complex than hematological malignancies, but the transcriptome and epigenome biomarkers have been identified for many of these malignancies. This solid tumor molecular aberration profile may be modified using specific or quasi-specific epidrugs together with conventional and innovative anticancer treatments. In this critical review, we briefly analyze the strategies to select the targeted epigenetic changes, enumerate the second-generation epigenetic inhibitors, and describe the main signs indicating the potential of epigenetic therapies in the management of solid tumors. We also highlight the work of consortia or academic organizations that support the undertaking of human epigenetic therapeutic projects as well as some examples of transcriptome/epigenome profile determination in clinical assessment of cancer patients treated with epidrugs. There is a good chance that epigenetic therapies will be able to be used in patients with solid tumors in the future. This may happen soon through collaboration of diverse scientific groups, making the selection of targeted epigenetic aberration(s more rapid, the design and probe of drug candidates, accelerating in vitro and in vivo assays, and

  5. Epigenetic Therapy for Solid Tumors: Highlighting the Impact of Tumor Hypoxia

    Directory of Open Access Journals (Sweden)

    Shaliny Ramachandran

    2015-09-01

    Full Text Available In the last few decades, epigenetics has emerged as an exciting new field in development and disease, with a more recent focus towards cancer. Epigenetics has classically referred to heritable patterns of gene expression, primarily mediated through DNA methylation patterns. More recently, it has come to include the reversible chemical modification of histones and DNA that dictate gene expression patterns. Both the epigenetic up-regulation of oncogenes and downregulation of tumor suppressors have been shown to drive tumor development. Current clinical trials for cancer therapy include pharmacological inhibition of DNA methylation and histone deacetylation, with the aim of reversing these cancer-promoting epigenetic changes. However, the DNA methyltransferase and histone deacetylase inhibitors have met with less than promising results in the treatment of solid tumors. Regions of hypoxia are a common occurrence in solid tumors. Tumor hypoxia is associated with increased aggressiveness and therapy resistance, and importantly, hypoxic tumor cells have a distinct epigenetic profile. In this review, we provide a summary of the recent clinical trials using epigenetic drugs in solid tumors, discuss the hypoxia-induced epigenetic changes and highlight the importance of testing the epigenetic drugs for efficacy against the most aggressive hypoxic fraction of the tumor in future preclinical testing.

  6. Neutron-Activatable Needles for Radionuclide Therapy of Solid Tumors.

    Science.gov (United States)

    Kim, Junghyun; Narayan, Roger J; Lu, Xiuling; Jay, Michael

    2017-08-14

    Various approaches have been undertaken to enhance the delivery of therapeutic agents, including tissue-killing radionuclides, into solid tumors. Here we describe the preparation of conical needles composed of Ti and Mo coated by pulsed laser deposition or chemical vapor deposition with elements (Ho and Re) that can readily yield radioactive isotopes following irradiation in a neutron flux. The radioactive needles, whose design were based on solid microneedle arrays used in transdermal drug delivery, can be produced with minimal handling of radioactivity and subsequently inserted into tumors as a means of internal radiation therapy. Ho and Re, were specifically chosen because of their large neutron capture cross-sections as well as the desirable radiotherapeutic properties of the resultant radionuclides. Neutron-absorbing shields were also developed to prevent the production of unwanted radionuclides after neutron irradiation of the needle base materials. Neutron activation calculations showed that therapeutically significant amounts of radionuclides can be produced for treating solid tumors. Stability studies demonstrated that Re did not leach off the Mo needles. These coated neutron-activatable needles offer a new approach to internal radiation therapy of tumors that allows precise tailoring of the absorbed radiation dose delivered to the tumor by controlling the coating thickness and the irradiation time. This article is protected by copyright. All rights reserved. © 2017 Wiley Periodicals, Inc.

  7. Surgical treatment of pulmonary metastases in pediatric solid tumors.

    Science.gov (United States)

    Heaton, Todd E; Davidoff, Andrew M

    2016-10-01

    Most children who succumb to solid malignancies do so because of the burden of metastatic disease or due to complications associated with the therapy administered to treat metastatic disease. Approximately one-quarter of children with solid tumors will present with metastatic disease, and an additional 20% ultimately develop metastatic disease, most commonly in the lung. The role of surgery in the treatment of metastatic solid tumors, given its disseminated nature, is not intuitive, yet there are circumstances in which surgical resection of metastatic disease can potentially be curative. However, the utility of surgery is very much dependent on histology, and generally is most appropriate for those malignancies with histologies that are refractory to other adjuvant therapies. Copyright © 2016. Published by Elsevier Inc.

  8. Bioengineered models of solid human tumors for cancer research

    Science.gov (United States)

    Marturano-Kruik, Alessandro; Villasante, Aranzazu; Vunjak-Novakovic, Gordana

    2016-01-01

    Summary The lack of controllable in vitro models that can recapitulate the features of solid tumors such as Ewing’s sarcoma limits our understanding of the tumor initiation and progression and impedes the development of new therapies. Cancer research still relies of the use of simple cell culture, tumor spheroids, and small animals. Tissue-engineered tumor models are now being grown in vitro to mimic the actual tumors in patients. Recently, we have established a new protocol for bioengineering the Ewing’s sarcoma, by infusing tumor cell aggregates into the human bone engineered from the patient’s mesenchymal stem cells. The bone niche allows crosstalk between the tumor cells, osteoblasts and supporting cells of the bone, extracellular matrix and the tissue microenvironment. The bioreactor platform used in these experiments also allows the implementation of physiologically relevant mechanical signals. Here, we describe a method to build an in vitro model of Ewing’s sarcoma that mimics the key properties of the native tumor and provides the tissue context and physical regulatory signals. PMID:27115504

  9. Prospective Clinical Study of Precision Oncology in Solid Tumors.

    Science.gov (United States)

    Sohal, Davendra P S; Rini, Brian I; Khorana, Alok A; Dreicer, Robert; Abraham, Jame; Procop, Gary W; Saunthararajah, Yogen; Pennell, Nathan A; Stevenson, James P; Pelley, Robert; Estfan, Bassam; Shepard, Dale; Funchain, Pauline; Elson, Paul; Adelstein, David J; Bolwell, Brian J

    2016-03-01

    Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact. Colorectal (25%), breast (18%), lung (13%), and pancreatobiliary (13%) cancers were the most common diagnoses. Median time from consent to result was 25 days (range = 3-140). Of 223 evaluable samples, 49% (n = 109) of patients were recommended a specific therapy, but only 11% (n = 24) received such therapy: 12 on clinical trials, nine off-label, three on-label. Lack of clinical trial access (n = 49) and clinical deterioration (n = 29) were the most common reasons for nonrecommendation/nonreceipt of genomics-driven therapy.

  10. A case of solid pseudopapillary tumor of the pancreas

    Institute of Scientific and Technical Information of China (English)

    Ozan Karatag; Gulden Yenice; Huseyin Ozkurt; Muzaffer Basak; Can Basaran; Banu Yilmaz

    2006-01-01

    We present ultrasound, computed tomography and magnetic resonance imaging findings in a case with pancreatic solid pseudopapillary tumor and their correlations with histopathology. Ultrasound revealed a hypoechogenic mass, and computed tomography revealed a hypodense mass at the pancreatic head minimally enhanced after intravenous contrast agent administration. Magnetic resonance imaging showed a hypointense mass on unenhanced T1-weighted images including a hyperintense focus representing the hemorrhage. The lesion was hyperintense on T2-weighted images. On the postcontrast images the lesion showed peripheral thin contrast enhancement in arterial phase and enhanced slightly diffusely in venous and equilibrium phases. The patient underwent elective resection of the mass and pancreatoduodenectomy with jejunostomy tube placement. A final diagnosis of solid pseudopapillary tumor was made histopathologically.Solid pseudopapillary tumor is a rare pancreatic tumor.It is important to make the diagnosis preoperatively because with an adequate surgical resection the prognosis is good. A multimodalitary approach, especially magnetic resonance imaging can suggest the diagnosis without the need for biopsy.

  11. Correlation between intra- and extracranial background EEG

    DEFF Research Database (Denmark)

    Duun-Henriksen, Jonas; Kjær, Troels Wesenberg; Madsen, Rasmus Elsborg

    2012-01-01

    Scalp EEG is the most widely used modality to record the electrical signals of the brain. It is well known that the volume conduction of these brain waves through the brain, cerebrospinal fluid, skull and scalp reduces the spatial resolution and the signal amplitude. So far the volume conduction...... has primarily been investigated by realistic head models or interictal spike analysis. We have set up a novel and more realistic experiment that made it possible to compare the information in the intra- and extracranial EEG. We found that intracranial EEG channels contained correlated patterns when...... placed less than 30 mm apart, that intra- and extracranial channels were partly correlated when placed less than 40 mm apart, and that extracranial channels probably were correlated over larger distances. The underlying cortical area that influences the extracranial EEG is found to be up to 45 cm2...

  12. Clonal evolution and therapeutic resistance in solid tumors

    Directory of Open Access Journals (Sweden)

    Elizabeth eLenkiewicz

    2013-01-01

    Full Text Available Tumors frequently arise as a result of an acquired genomic instability and the subsequent evolution of neoplastic populations with variable genomes. A barrier to the study of the somatic genetics of human solid tumors in vivo is the presence of admixtures of non-neoplastic cells with normal genomes in patient samples. These can obscure the presence of somatic aberrations including mutations, homozygous deletions, and breakpoints in biopsies of interest. Furthermore, clinical samples frequently contain multiple neoplastic populations that cannot be distinguished by morphology. Consequently, it is difficult to determine whether mutations detected in a sample of interest are concurrent in a single clonal population or if they occur in distinct cell populations in the same sample. The advent of targeted therapies increases the selection for preexisting populations. However the asymmetric distribution of therapeutic targets in clonal populations provides a mechanism for the rapid evolution of resistant disease. Thus, there is a need to not only isolate tumor from normal cells, but to also enrich distinct populations of clonal neoplastic cells in order to apply genome technologies to identify clinically relevant genomic aberrations that drive disease in patients in vivo. To address this we have applied single and multiparameter DNA content based flow assays to the study of solid tumors. Our work has identified examples of clonal resistance to effective therapies. This includes androgen withdrawal in advanced prostate cancer. In addition we demonstrate examples of co-existing clonal populations with highly aberrant genomes and ploidies in a wide variety of solid tumors. We propose that clonal analysis of tumors, based on flow cytometry and high resolution genome analyses of purified neoplastic populations, provides a unique approach to the study of therapeutic responses and the evolution of resistance.

  13. Effect of atorvastatin and methotrexate on solid Ehrlich tumor.

    Science.gov (United States)

    Kabel, Ahmed M; Abdel-Rahman, Mohamed Nabih; El-Sisi, Alaa El-Din E; Haleem, Mahmoud Said; Ezzat, Nadia M; El Rashidy, Mohamed A

    2013-08-05

    Hydroxymethyl glutaryl CoA reductase is the key enzyme in cholesterol synthesis. A relationship was found between cholesterol and the development of many types of cancer. Atorvastatin is a hypolipidemic drug that may have a role in treatment of cancer. Moreover, atorvastatin was reported to decrease the resistance of cancer cells to many chemotherapeutic agents. The aim of this work was to study the effect of each of methotrexate (MTX) and atorvastatin alone and in combination on solid Ehrlich carcinoma (SEC) in mice. Fifty BALB/c mice were divided into five equal groups: control untreated group, SEC, SEC+MTX, SEC+atorvastatin, SEC+MTX+atorvastatin. Tumor volume, tissue glutathione reductase (GR), catalase, malondialdehyde (MDA), cholesterol and tumor necrosis factor alpha (TNF-α) were determined. A part of the tumor was examined for histopathological and immunohistochemical study. MTX or atorvastatin alone or in combination induced significant increase in tissue catalase and GR with significant decrease in tumor volume, tissue MDA, cholesterol and TNF-α and alleviated the histopathological changes with significant increase in p53 expression and apoptotic index compared to SEC group. In conclusion, the combination of MTX and atorvastatin had a better effect than each of MTX or atorvastatin alone against solid Ehrlich tumor in mice. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Solid Pseudopapillary Tumor of the Pancreas: a Case Report

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Case Report Solid pseudopapillary tumors (SPT) of the pancreas are considered to be a rare low-grade malignancy that mainly appears in young women. It accounts for less than 1% of all pancreatic neoplasms and is pathologically distinctive from other types of pancreatic cancers. Curative resection is the optimal choice for SPT and the 5-year survival rate of SPT is about 95%. Here we report a case of a young girl who presented with this rare pancreatic tumor.This case involved a 21-year-old girl with a 3-month history of a slowly growing palpable mass in the right upper abdomen.

  15. Strategies to increase drug penetration in solid tumors

    Directory of Open Access Journals (Sweden)

    Il-Kyu eChoi

    2013-07-01

    Full Text Available Despite significant improvement in modalities for treatment of cancer that led to a longer survival period, the death rate of patients with solid tumors has not changed during the last decades. Emerging studies have identified several physical barriers that limit the therapeutic efficacy of cancer therapeutic agents such as monoclonal antibodies, chemotherapeutic agents, antitumor immune cells, and gene therapeutics. Most solid tumors are of epithelial origin and, although malignant cells are de-differentiated, they maintain intercellular junctions, a key feature of epithelial cells, both in the primary tumor as well as in metastatic lesions. Furthermore, nests of malignant epithelial tumor cells are shielded by layers of extracellular matrix (ECM proteins (e.g. collagen, elastin, fibronectin, laminin whereby tumor vasculature rarely penetrates into the tumor nests. In this chapter, we will review potential strategies to modulate the ECM and epithelial junctions to enhance the intratumoral diffusion and/or to remove physical masking of target receptors on malignant cells. We will focus on peptides that bind to the junction protein desmoglein 2 (DSG2 and trigger intracellular signaling, resulting in the transient opening of intercellular junctions. Intravenous injection of these junction openers increased the efficacy and safety of therapies with monoclonal antibodies, chemotherapeutics, and T-cells in mouse tumor models and was safe in non-human primates. Furthermore, we will summarize approaches to transiently degrade ECM proteins or downregulate their expression. Among these approaches is the intratumoral expression of relaxin or decorin after adenovirus (Ad- or stem cell-mediated gene transfer. We will provide examples that relaxin- based approaches increase the antitumor efficacy of oncolytic viruses, monoclonal antibodies, and T-cells.

  16. Cytogenetics in solid tumors: lessons from the Philadelphia Chromosome.

    Science.gov (United States)

    Sudoyo, Aru W; Hardi, Fransiska

    2011-01-01

    Although presently known as an environmentally-related disease and appears mostly sporadic, cancer is regarded as a genetic disease based on the presence of gene mutation as a consistent factor. The "Philadelphia Chromosome" found consistently among chronic myeloid leukemia (CML) patients was the first significant finding of a chromosomal abnormality specifically related to a particular disease. Starting from this point, cytogenetics as the study of chromosomes has become a valuable tool in the assessment of cancer - as an aid in diagnosis, thus guiding therapy, and as a prognostic marker. As is the nature of the proliferating marrow, chromosomal abnormalities were found mostly in hematologic malignancies, and the findings more pathognomonic. The situation is different in solid tumors, which when visible to the naked eye already will have complex chromosomal changes and thus pose technical difficulties to the cytogeneticist. However, scientists believe that the shift in chromosomal studies from conventional cytogenetics to molecular cytogenetics will provide further information regarding solid tumors.

  17. Anaesthetic management of a child with massive extracranial arteriovenous malformation

    Directory of Open Access Journals (Sweden)

    Faisal Shamim

    2012-01-01

    Full Text Available Vascular tumors affect the head and neck commonly but arteriovenous malformations are rare. Vascular malformations are often present at birth and grow with the patient, usually only becoming significant later in childhood. Embolization has been the mainstay of treatment in massive and complex arteriovenous malformations. We present a case of massive extracranial arteriovenous malformation in a 7-year-old boy causing significant workload on right heart and respiratory distress. The management of angioembolization under general anaesthesia and anaesthetic concerns are presented.

  18. Mathematical Based Calculation of Drug Penetration Depth in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Hamidreza Namazi

    2016-01-01

    Full Text Available Cancer is a class of diseases characterized by out-of-control cells’ growth which affect cells and make them damaged. Many treatment options for cancer exist. Chemotherapy as an important treatment option is the use of drugs to treat cancer. The anticancer drug travels to the tumor and then diffuses in it through capillaries. The diffusion of drugs in the solid tumor is limited by penetration depth which is different in case of different drugs and cancers. The computation of this depth is important as it helps physicians to investigate about treatment of infected tissue. Although many efforts have been made on studying and measuring drug penetration depth, less works have been done on computing this length from a mathematical point of view. In this paper, first we propose phase lagging model for diffusion of drug in the tumor. Then, using this model on one side and considering the classic diffusion on the other side, we compute the drug penetration depth in the solid tumor. This computed value of drug penetration depth is corroborated by comparison with the values measured by experiments.

  19. Decitabine: a promising epi-immunotherapeutic agent in solid tumors.

    Science.gov (United States)

    Li, Xiang; Mei, Qian; Nie, Jing; Fu, Xiaobing; Han, Weidong

    2015-03-01

    The incidence of malignancies is increasing worldwide. Despite early detection, surgical resection, chemotherapy and radiotherapy, numerous patients continue to die from metastasis or recurrence. The immune system has the capacity to eradicate cancer cells; however, many tumors, especially solid tumors, present considerable challenges that render immune cells ineffectual, making cancer cells almost 'invisible' to the immune system. Compelling evidence has demonstrated that DNA methylation is involved in tumor development and progression, leading to the impaired immunogenicity and immune recognition of cancer cells. The hypomethylating agent decitabine has been shown to have therapeutic effects in malignancies and exhibits an effective immune efficacy in eliminating cancer cells. Based on the hypomethylating and immune remodeling effects of decitabine, we propose in this review that decitabine can be considered an epi-immunotherapeutic agent. We summarize the results of recent preclinical studies and clinical trials for decitabine and discuss the connections among its hypomethylating effect, immune-activated mechanisms and clinical activity in solid tumors, keeping in mind the goal of optimizing dosing schedules.

  20. Targeting a single mismatched minor histocompatibility antigen with tumor-restricted expression eradicates human solid tumors

    NARCIS (Netherlands)

    L. Hambaeh (Lothar); M. Vermeij (Marcel); A. Buser (Andreas); Z. Aghai (Zohara); Th.H. van der Kwast (Theo); E. Goulmy (Els)

    2008-01-01

    textabstractRegressions of metastatic solid tumors after allogeneic human leukocyte antigen (HLA)-matched stem cell transplantation (SCT) are often associated with detrimental graft-versus-host disease (GVHD). The graft-versus-host reaction of the HLA-matched donor is directed mainly against the mul

  1. A tumor cord model for Doxorubicin delivery and dose optimization in solid tumors

    Directory of Open Access Journals (Sweden)

    Eikenberry Steffen

    2009-08-01

    Full Text Available Abstract Background Doxorubicin is a common anticancer agent used in the treatment of a number of neoplasms, with the lifetime dose limited due to the potential for cardiotoxocity. This has motivated efforts to develop optimal dosage regimes that maximize anti-tumor activity while minimizing cardiac toxicity, which is correlated with peak plasma concentration. Doxorubicin is characterized by poor penetration from tumoral vessels into the tumor mass, due to the highly irregular tumor vasculature. I model the delivery of a soluble drug from the vasculature to a solid tumor using a tumor cord model and examine the penetration of doxorubicin under different dosage regimes and tumor microenvironments. Methods A coupled ODE-PDE model is employed where drug is transported from the vasculature into a tumor cord domain according to the principle of solute transport. Within the tumor cord, extracellular drug diffuses and saturable pharmacokinetics govern uptake and efflux by cancer cells. Cancer cell death is also determined as a function of peak intracellular drug concentration. Results The model predicts that transport to the tumor cord from the vasculature is dominated by diffusive transport of free drug during the initial plasma drug distribution phase. I characterize the effect of all parameters describing the tumor microenvironment on drug delivery, and large intercapillary distance is predicted to be a major barrier to drug delivery. Comparing continuous drug infusion with bolus injection shows that the optimum infusion time depends upon the drug dose, with bolus injection best for low-dose therapy but short infusions better for high doses. Simulations of multiple treatments suggest that additional treatments have similar efficacy in terms of cell mortality, but drug penetration is limited. Moreover, fractionating a single large dose into several smaller doses slightly improves anti-tumor efficacy. Conclusion Drug infusion time has a significant

  2. A rare case of extracranial meningioma in parapharyngeal space presented as a neck mass

    Directory of Open Access Journals (Sweden)

    Nader Albsoul

    2015-01-01

    Conclusion: Extracranial meningiomas are quite rare. The diagnosis of these types of tumors is challenging due to the non specific nature of the symptoms. The anatomic complexity of the region of parapharyngeal space also makes their detection difficult. Imaging modalities can aid in the diagnosis, but pathological examinations are essential in confirming a definite diagnosis.

  3. Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors

    Directory of Open Access Journals (Sweden)

    Griffiths Gary L

    2009-06-01

    Full Text Available Abstract Background The existence of large pores in the blood-tumor barrier (BTB of malignant solid tumor microvasculature makes the blood-tumor barrier more permeable to macromolecules than the endothelial barrier of most normal tissue microvasculature. The BTB of malignant solid tumors growing outside the brain, in peripheral tissues, is more permeable than that of similar tumors growing inside the brain. This has been previously attributed to the larger anatomic sizes of the pores within the BTB of peripheral tumors. Since in the physiological state in vivo a fibrous glycocalyx layer coats the pores of the BTB, it is possible that the effective physiologic pore size in the BTB of brain tumors and peripheral tumors is similar. If this were the case, then the higher permeability of the BTB of peripheral tumor would be attributable to the presence of a greater number of pores in the BTB of peripheral tumors. In this study, we probed in vivo the upper limit of pore size in the BTB of rodent malignant gliomas grown inside the brain, the orthotopic site, as well as outside the brain in temporalis skeletal muscle, the ectopic site. Methods Generation 5 (G5 through generation 8 (G8 polyamidoamine dendrimers were labeled with gadolinium (Gd-diethyltriaminepentaacetic acid, an anionic MRI contrast agent. The respective Gd-dendrimer generations were visualized in vitro by scanning transmission electron microscopy. Following intravenous infusion of the respective Gd-dendrimer generations (Gd-G5, N = 6; Gd-G6, N = 6; Gd-G7, N = 5; Gd-G8, N = 5 the blood and tumor tissue pharmacokinetics of the Gd-dendrimer generations were visualized in vivo over 600 to 700 minutes by dynamic contrast-enhanced MRI. One additional animal was imaged in each Gd-dendrimer generation group for 175 minutes under continuous anesthesia for the creation of voxel-by-voxel Gd concentration maps. Results The estimated diameters of Gd-G7 dendrimers were 11 ± 1 nm and those of Gd-G8

  4. Malignant solid pseudopapillary tumor of pancreas causing sinistral portal hypertension

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    Nisar Ahmad Wani

    2011-01-01

    Full Text Available Solid pseudopapillary tumor (SPT of the pancreas is a rare benign or low-grade malignant epithelial tumor that occurs mainly in young females in second to fourth decades of life. Pathologic and imaging findings include a well-defined, encapsulated pancreatic mass with cystic and solid components with evidence of hemorrhage. We report a 23-year-old female who presented with upper abdominal pain of long duration and epigastric mass on palpation. Multidetector-row CT (MDCT demonstrated a large well-defined heterogeneous attenuation mass, containing hyperdense areas of hemorrhage mixed with solid enhancing and cystic non-enhancing areas, arising from the pancreatic body and tail. Splenic vein thrombosis was present with dilated splenoportal collateral vessels between splenic hilum and portal/superior mesenteric veins, with dilated vessels seen in the gastric wall, with patent portal vein, compatible with sinistral portal hypertension. Typical imaging features and age and sex of the patient suggested a diagnosis of SPT of pancreas complicated by segmental portal hypertension due to splenic vein thrombosis. Histopathology of the biopsy material was confirmatory.

  5. Clinical significance of serum biomarkers in pediatric solid mediastinal and abdominal tumors.

    Science.gov (United States)

    Sandoval, John A; Malkas, Linda H; Hickey, Robert J

    2012-01-01

    Childhood cancer is the leading cause of death by disease among U.S. children between infancy and age 15. Despite successes in treating solid tumors such as Wilms tumor, disappointments in the outcomes of high-risk solid tumors like neuroblastoma have precipitated efforts towards the early and accurate detection of these malignancies. This review summarizes available solid tumor serum biomarkers with a special focus on mediastinal and abdominal cancers in children.

  6. Clinical Significance of Serum Biomarkers in Pediatric Solid Mediastinal and Abdominal Tumors

    Directory of Open Access Journals (Sweden)

    Robert J. Hickey

    2012-01-01

    Full Text Available Childhood cancer is the leading cause of death by disease among U.S. children between infancy and age 15. Despite successes in treating solid tumors such as Wilms tumor, disappointments in the outcomes of high-risk solid tumors like neuroblastoma have precipitated efforts towards the early and accurate detection of these malignancies. This review summarizes available solid tumor serum biomarkers with a special focus on mediastinal and abdominal cancers in children.

  7. Diagnosis and Management of Extracranial Head and Neck Schwannomas: A Review of 27 Cases

    Directory of Open Access Journals (Sweden)

    Ryuji Yasumatsu

    2013-01-01

    Full Text Available Objectives. Clinical records of 27 patients with extracranial head and neck schwannoma were retrospectively reviewed. Methods. Ultrasonography (US was performed in all cases. Seven patients underwent CT. Twenty-five patients underwent MRI. Fine needle aspiration cytology (FNAC was performed for 12 of the 27 patients. Clinical history, surgical data, and postoperative morbidity were analyzed. Results. The images of US showed a well-defined, hypoechoic, primarily homogeneous solid mass. At CT, only one of 7 cases (14% was able to suggest the diagnosis of schwannoma. At MRI, twenty of 25 cases (80% suggested the diagnosis of schwannoma. Only three of 12 cases (25% displayed a specific diagnosis of schwannoma rendered on FNAC. The distribution of 27 nerves of origin was 10 (37% vagus nerves, 6 (22% sympathetic trunks, 5 (19% cervical plexuses, 3 (11% brachial plexuses, 2 (7% hypoglossal nerves, and 1 (4% accessory nerve. Complete tumor resection was performed in 11 patients, and intracapsular enucleation of the tumor was performed in 16 patients. The rate of nerve palsy was 100 (11/11 and 31% (5/16. Conclusions. MRI is sensitive and specific in the diagnosis of schwannoma. Intracapsular enucleation was an effective and feasible method for preserving the neurological functions.

  8. Monoclonal antibodies and Fc fragments for treating solid tumors

    Directory of Open Access Journals (Sweden)

    Eisenbeis AM

    2012-01-01

    Full Text Available Andrea M Eisenbeis, Stefan J GrauDepartment of Neurosurgery, University Hospital of Cologne, Cologne, GermanyAbstract: Advances in biotechnology, better understanding of pathophysiological processes, as well as the identification of an increasing number of molecular markers have facilitated the use of monoclonal antibodies and Fc fragments in various fields in medicine. In this context, a rapidly growing number of these substances have also emerged in the field of oncology. This review will summarize the currently approved monoclonal antibodies used for the treatment of solid tumors with a focus on their clinical application, biological background, and currently ongoing trials.Keywords: targeted therapy, monoclonal antibodies, cancer, biological therapy

  9. Solid Pancreatic Tumors with Unilocular Cyst-Like Appearance on CT: Differentiation from Unilocular Cystic Tumors Using CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ju Hee [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Department of Radiology, National Cancer Center, Goyang 410-769 (Korea, Republic of); Byun, Jae Ho; Kim, Jin Hee; Lee, Seung Soo; Kim, Hyoung Jung; Lee, Moon-Gyu [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of)

    2014-07-01

    To describe the computed tomography (CT) features of neuroendocrine tumors (NETs) and solid pseudopapillary tumors (SPTs) with unilocular cyst-like appearance, and to compare them with those of unilocular cystic tumors of the pancreas. This retrospective study was approved by our Institutional Review Board, and informed consent was waived. We included 112 pancreatic tumors with unilocular cyst-like appearance on CT (16 solid tumors [nine NETs and seven SPTs] and 96 cystic tumors [45 serous cystadenomas, 30 mucinous cystic neoplasms, and 21 branch-duct intraductal papillary mucinous neoplasms]). Two radiologists reviewed the CT images in consensus to determine tumor location, long diameter, morphological features, wall thicknesses, ratio of wall thickness to tumor size, wall enhancement patterns, intratumoral contents, and accompanying findings. Fisher's exact test was used to analyze the results. All 16 solid tumors had perceptible walls (mean thickness, 2.7 mm; mean ratio of wall thickness to tumor size, 7.7%) with variable enhancement. Four NETs and seven SPTs had hemorrhage, calcifications, and/or mural nodules. Six CT findings were specific for solid tumors with unilocular cyst-like appearance: a thick (> 2 mm) wall, uneven thickness of the wall, high ratio of wall thickness to tumor size, hyper- or hypo-attenuation of the wall in the arterial and portal phase, and heterogeneous internal contents. When three or more of the above criteria were used, 100% specificity and 87.5-92% accuracy were obtained for solid tumors with unilocular cyst-like appearance. A combination of CT features was useful for distinguishing solid tumors with unilocular cyst-like appearance from unilocular cystic tumors of the pancreas.

  10. Increased IMP dehydrogenase gene expression in solid tumor tissues and tumor cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Collart, F.R.; Chubb, C.B.; Mirkin, B.L.; Huberman, E.

    1992-07-10

    IMP dehydrogenase, a regulatory enzyme of guanine nucleotide biosynthesis, may play a role in cell proliferation and malignancy. To assess this possibility, we examined IMP dehydrogenase expression in a series of human solid tumor tissues and tumor cell lines in comparison with their normal counterparts. Increased IMP dehydrogenase gene expression was observed in brain tumors relative to normal brain tissue and in sarcoma cells relative to normal fibroblasts. Similarly, in several B- and T-lymphoid leukemia cell lines, elevated levels of IMP dehydrogenase mRNA and cellular enzyme were observed in comparison with the levels in peripheral blood lymphocytes. These results are consistent with an association between increased IMP dehydrogenase expression and either enhanced cell proliferation or malignant transformation.

  11. Evaluation of the effects of methotrexate released from polymeric implants in solid Ehrlich tumor.

    Science.gov (United States)

    de Fátima Pereira, Adriana; Mara da Costa, Vivian; Cristina Magalhães Santos, Millene; Maciel de A Ribeiro, Rosy Iara; Gabriela Silva, Ana; Carmo Horta Pinto, Flávia; Vieira Teixeira Vidigal, Paula; Rodrigues Da Silva, Gisele

    2014-04-01

    In this study, the effects of the controlled and sustained release of methotrexate from poly(ɛ-caprolactone) implants were evaluated in the solid Ehrlich tumor. The drug locally leached from the implantable devices was capable of reducing the tumor growth and the necrotic areas of the tumor site. Furthermore, the methotrexate exerted its anti-tumor effect probably by the recruitment of neutrophils at the tumor site, which assisted in modulating the growth of the tumor. The polymeric implants containing methotrexate could be a chemotherapic alternative to treat locally solid tumors with lower systemic side effects. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Temporal fossa intra-extracranial dumbbell schwannoma.

    LENUS (Irish Health Repository)

    Wong, Limy

    2011-02-01

    Intra-extracranial schwannomas arising unrelated to major cranial nerves are exceedingly rare neoplasms. We report the case of a 23-year-old male who presented with a 9 month history of progressive temporal swelling which was excised and found histologically to be a schwannoma. A succinct review of the relevant literature is presented.

  13. Management of Extracranial Carotid Artery Aneurysm

    NARCIS (Netherlands)

    Welleweerd, J. C.; den Ruijter, H. M.; Nelissen, B. G. L.; Bots, M. L.; Kappelle, L. J.; Rinkel, G. J. E.; Moll, F. L.; de Borst, G. J.

    2015-01-01

    Introduction: Aneurysms of the extracranial carotid artery (ECAA) are rare. Several treatments have been developed over the last 20 years, yet the preferred method to treat ECAA remains unknown. This paper is a review of all available literature on the risk of complications and long-term outcome aft

  14. Temporal fossa intra-extracranial dumbbell schwannoma.

    LENUS (Irish Health Repository)

    Wong, Limy

    2012-02-01

    Intra-extracranial schwannomas arising unrelated to major cranial nerves are exceedingly rare neoplasms. We report the case of a 23-year-old male who presented with a 9 month history of progressive temporal swelling which was excised and found histologically to be a schwannoma. A succinct review of the relevant literature is presented.

  15. Extracranial stereotactic radiotherapy: evaluation of PTV coverage and dose conformity.

    Science.gov (United States)

    Hädinger, Ulrich; Thiele, Wibke; Wulf, Jörn

    2002-01-01

    During the past few years the concept of cranial stereotactic radiotherapy has been successfully extended to extracranial tumoral targets. In our department, hypofractionated treatment of tumours in lung, liver, abdomen, and pelvis is performed in the Stereotactic Body Frame (ELEKTA Instrument AB) since 1997. We present the evaluation of 63 consecutively treated targets (22 lung, 21 liver, 20 abdomen/pelvis) in 58 patients with respect to dose coverage of the planning target volume (PTV) as well as conformity of the dose distribution. The mean PTV coverage was found to be 96.3% +/- 2.3% (lung), 95.0% +/- 4.5% (liver), and 92.1% +/- 5.2% (abdomen/pelvis). For the so-called conformation number we obtained values of 0.73 +/- 0.09 (lung), 0.77 +/- 0.10 (liver), and 0.70 +/- 0.08 (abdomen/pelvis). The results show that highly conformal treatment techniques can be applied also in extracranial stereotactic radiotherapy. This is primarily due to the relatively simple geometrical shape of most of the targets. Especially lung and liver targets turned out to be approximately spherically/cylindrically shaped, so that the dose distribution can be easily tailored by rotational fields.

  16. Ultrasonic enhancement of drug penetration in solid tumors

    Directory of Open Access Journals (Sweden)

    Chun-yen eLai

    2013-08-01

    Full Text Available Increasing the penetration of drugs within solid tumors can be accomplished through multiple ultrasound-mediated mechanisms. The application of ultrasound can directly change the structure or physiology of tissues or can induce changes in a drug or vehicle in order to enhance delivery and efficacy. With each ultrasonic pulse, a fraction of the energy in the propagating wave is absorbed by tissue and results in local heating. When ultrasound is applied to achieve mild hyperthermia, the thermal effects are associated with an increase in perfusion or the release of a drug from a temperature-sensitive vehicle. Higher ultrasound intensities locally ablate tissue and result in increased drug accumulation surrounding the ablated region of interest. Further, the mechanical displacement induced by the ultrasound pulse can result in the nucleation, growth and collapse of gas bubbles. As a result of such cavitation, the permeability of a vessel wall or cell membrane can be increased. Finally, the radiation pressure of the propagating pulse can translate particles or tissues. In this perspective, we will review recent progress in ultrasound-mediated tumor delivery and the opportunities for clinical translation.

  17. SOLID CYSTIC PAPILLARY TUMOR OF PANCREAS IN EIGHT CHILDREN

    Institute of Scientific and Technical Information of China (English)

    Ke-ren Zhang; Hui-min Jia; Hong Shu; Xin-yuan Li

    2007-01-01

    Objective To estimate the clinical and pathological features of pancreatic solid cystic papillary tumor (SCPT) in children.Methods From 2000 to 2005 , 8 cases with SCPT of the pancreas were analyzed retrospectively. All cases but one were females. Average age was 12.8 years. By case review, we discussed the clinical and pathological features of SCPT in children.Results The chief complains were abdominal pain and palpable mass. There were 3 cases in the head, 1 case in the body, and 4 cases in the tail of pancreas. The procedures employed included local resection (1 case), distal pancre-atectomy (5 cases) , pancreaticoduodenectomy (1 case) , and biopsy (1 case). Histological examination showed solid with cystic areas and papillary protrusions in the 8 cases; as for immunohistochemical examinations, the positive rate was 100% for ct-antitrypsin (AACT) , 87.5% for vinmentin, and 62.5% for neuron-specific enolase (NSE). The patients were followed up for 2 months to 4 years but one was lost by follow-up and all were alive postoperatively. SCPT in 2 cases relapsed.Conclusion Occurring predominantly in young females, SCPT is usually curable by surgical resection with a favorable prognosis.

  18. Busulfan, Melphalan, Topotecan Hydrochloride, and a Stem Cell Transplant in Treating Patients With Newly Diagnosed or Relapsed Solid Tumor

    Science.gov (United States)

    2016-11-04

    Solid Tumor; Adult Central Nervous System Germ Cell Tumor; Adult Rhabdomyosarcoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Soft Tissue Sarcoma; Ewing Sarcoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Ovarian Mixed Germ Cell Tumor; Previously Untreated Childhood Rhabdomyosarcoma; Recurrent Adult Brain Tumor; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Extragonadal Germ Cell Tumor; Recurrent Extragonadal Non-seminomatous Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Neuroblastoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  19. Pharmacokinetic study of aldoxorubicin in patients with solid tumors.

    Science.gov (United States)

    Mita, Monica M; Natale, Ronald B; Wolin, Edward M; Laabs, Brenda; Dinh, Hillary; Wieland, Scott; Levitt, Daniel J; Mita, Alain C

    2015-04-01

    Introduction Aldoxorubicin, a prodrug of doxorubicin, binds covalently to serum albumin in the bloodstream and accumulates in tumors. Aldoxorubicin can be administered at doses several-fold higher than doxorubicin can, without associated acute cardiotoxicity. Purpose This study fully evaluated the pharmacokinetic profile of aldoxorubicin (serum and urine). Methods Eighteen patients with advanced solid tumors received aldoxorubicin 230 or 350 mg/m(2) (equivalent in drug load to doxorubicin at doses of 170 or 260 mg/m(2), respectively) once every 21 days. Blood samples were taken in cycle 1 before aldoxorubicin infusion, and at 5, 15, 30, and 60 min, and at 2, 4, 8, 12, 16, 24, 48, and 72 h after infusion. Urine samples were taken in cycle 1 at 24, 48, and 72 h after infusion. Limited blood sampling was done in cycle 3, before aldoxorubicin infusion, and at 60 min and at 2, 4, and 8 h after infusion. Results The long mean half-life (20.1-21.1 h), narrow mean volume of distribution (3.96-4.08 L/m(2)), and slow mean clearance rate (0.136-0.152 L/h/m(2)) suggest that aldoxorubicin is stable in circulation and does not accumulate readily in body compartments outside of the bloodstream. Very little doxorubicin and its major metabolite doxorubicinol, which has been implicated in doxorubicin-associated cardiotoxicity, are excreted in urine. This might explain the lack of cardiotoxicity observed thus far with aldoxorubicin. Conclusions Our findings support dosing and administration schemas used in an ongoing phase 3 clinical study of aldoxorubicin in soft tissue sarcoma, and phase 2 clinical studies in small cell lung cancer, glioblastoma, and Kaposi's sarcoma.

  20. Supratentorial tumors; Supratentorielle Tumoren

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-06-15

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

  1. Predicting the presence of extracranial metastases in patients with brain metastases upon first diagnosis of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rades, D. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); Segedin, B. [Institute of Oncology, Department of Radiation Oncology, Ljubljana (Slovenia); Nagy, V. [Oncology Institute Ion Ciricuta, Department of Radiotherapy, Cluj-Napoca (Romania); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Arizona (United States); Trang, N.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Khoa, M.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Hanoi Medical University, Department of Nuclear Medicine, Hanoi (Viet Nam)

    2014-04-15

    This study aimed to determine factors allowing the prediction of extracranial metastases in patients presenting with brain metastases at the first diagnosis of cancer. Data from 659 patients with brain metastases upon first diagnosis of cancer were retrospectively analyzed. The parameters age, gender, Karnofsky performance score (KPS), primary tumor type and number of brain metastases were compared between 359 patients with extracranial metastases and 300 patients without extracranial metastases. Additional analyses were performed for patients with the most unfavorable and those with the most favorable characteristics. The comparison of patients with versus without extracranial metastases revealed significant differences between the groups in terms of KPS (p < 0.001) and number of brain metastases (p < 0.001). Of the study patients, 113 had both most unfavorable characteristics, i.e. KPS ≤ 50 and ≥ 4 brain metastases. The sensitivity for identifying patients with extracranial metastases was 82 %; specificity was 51 %. A total of 50 patients had KPS ≥ 90 and only one brain metastasis. The sensitivity for identifying patients without extracranial metastases was 86 %; specificity was 58 %. The combination of KPS and the number of brain metastases can help to predict the presence or absence of extracranial metastases. (orig.) [German] Diese Studie soll zur Abschaetzung des Vorliegens extrakranieller Metastasen bei Patienten mit primaer zerebral metastasierter Tumorerkrankung beitragen. Daten von 659 Patienten mit primaer zerebral metastasierter Tumorerkrankung wurden retrospektiv analysiert. Insgesamt 359 Patienten mit extrakraniellen Metastasen wurden mit 300 Patienten ohne extrakranielle Metastasierung hinsichtlich Alter, Geschlecht, Karnofsky-Performance-Score (KPS), Art des Primaertumors und der Anzahl der Hirnmetastasen miteinander verglichen. Weitere Analysen erfolgten bei Patienten mit den unguenstigsten und bei Patienten mit den guenstigsten

  2. Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting

    Science.gov (United States)

    Kharya, Parul; Jain, Ashish; Gulbake, Arvind; Shilpi, Satish; Jain, Ankit; Hurkat, Pooja; Majumdar, Subrata; Jain, Sanjay K.

    2013-11-01

    The purpose of this study is to investigate the targeting potential of amino acid (phenylalanine)-coupled solid lipid nanoparticles (SLN) loaded with ionically complexed doxorubicin HCl (Dox). Ionic complexation was used to enhance the loading efficiency and release characteristics of water soluble form of Dox. l-Type amino acid transporters (LAT1) are highly expressed on blood brain barrier as well as on many brain cancer cells, thus targeting LAT1 using phenylalanine improved anticancer activity of prepared nanocarrier. The phenylalanine-coupled SLN were characterized by fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, particle size, zeta potential, entrapment efficiency and in vitro release. The particle size of the resulting SLN was found to be in the range of 163.3 ± 5.2 to 113.0 ± 2.6 nm, with a slightly negative surface charge. In ex vivo study on C6 glioma cell lines, the cellular cytotoxicity of the SLN was highly increased when coupled with phenylalanine. In addition, stealthing sheath of PEG present on the surface of the SLN enhanced the cellular uptake of the SLN on C6 glioma cell line. Results of biodistribution and fluorescence studies clearly revealed that phenylalanine-coupled SLN could deliver high amount of drug into the brain tumor cells and showed the brain-targeting potential.

  3. Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting

    Energy Technology Data Exchange (ETDEWEB)

    Kharya, Parul; Jain, Ashish; Gulbake, Arvind; Shilpi, Satish; Jain, Ankit; Hurkat, Pooja [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India); Majumdar, Subrata [Bose Institute, Division of Molecular Medicine (India); Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2013-11-15

    The purpose of this study is to investigate the targeting potential of amino acid (phenylalanine)-coupled solid lipid nanoparticles (SLN) loaded with ionically complexed doxorubicin HCl (Dox). Ionic complexation was used to enhance the loading efficiency and release characteristics of water soluble form of Dox. l-Type amino acid transporters (LAT1) are highly expressed on blood brain barrier as well as on many brain cancer cells, thus targeting LAT1 using phenylalanine improved anticancer activity of prepared nanocarrier. The phenylalanine-coupled SLN were characterized by fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, particle size, zeta potential, entrapment efficiency and in vitro release. The particle size of the resulting SLN was found to be in the range of 163.3 ± 5.2 to 113.0 ± 2.6 nm, with a slightly negative surface charge. In ex vivo study on C6 glioma cell lines, the cellular cytotoxicity of the SLN was highly increased when coupled with phenylalanine. In addition, stealthing sheath of PEG present on the surface of the SLN enhanced the cellular uptake of the SLN on C6 glioma cell line. Results of biodistribution and fluorescence studies clearly revealed that phenylalanine-coupled SLN could deliver high amount of drug into the brain tumor cells and showed the brain-targeting potential.

  4. Phase I studies of porfiromycin (NSC--56410) in solid tumors.

    Science.gov (United States)

    Grage, T B; Weiss, A J; Wilson, W; Reynolds, V

    1975-01-01

    Porfiromycin was given to a group of patients with a variety of solid tumors. Of 114 patients admitted to the study, 103 yielded evaluable data. The following dosage schedules were used to determine the toxicity of porfiromycin when given in multiple doses by intravenous injection: 0.2 mg/kg x 5 days, 0.3 mg/kg x 5 days, 0.35 mg/kg x 5 days, 0.4 mg/kg x 5 days, 0.24 mg/kg x 10 days and 0.6 mg/kg weekly. Toxic effects noted were mainly leukopenia, thrombocytopenia, and, when injected paravenously, local tissue necrosis. Biological effects were noted at all dosage levels and were more severe at the higher dosages. The data suggest that profiromycin administered intravenously at a dose of 0.35 mg/kg daily for 5 days results in moderate hermatological toxicity and clinical evaluation in a Phase II study at this dosage level is indicated.

  5. HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea Pession

    2011-06-01

    Full Text Available Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing’s sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an eventfree survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemo therapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA-mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results.

  6. Growth delay effect of combined interstitial hyperthermia and brachytherapy in a rat solid tumor model.

    Science.gov (United States)

    Papadopoulos, D; Kimler, B F; Estes, N C; Durham, F J

    1989-01-01

    The rat mammary AC33 solid tumor model was used to investigate the efficacy of interstitial hyperthermia and/or brachytherapy. Subcutaneous flank tumors were heated with an interstitial microwave (915 MHz) antenna to a temperature of 43 +/- 0.5 degrees C for 45 min for two treatments, three days apart, and/or implanted with Ir-192 seeds for three days (-25 Gy tumor dose). Following treatments, tumors were measured 2 to 3 times per week. Hyperthermia alone produced a modest delay in tumor volume regrowth, while brachytherapy was substantially more effective. The combination produced a improvement in tumor regrowth delay compared to brachytherapy alone.

  7. Flavopiridol in Treating Children With Relapsed or Refractory Solid Tumors or Lymphomas

    Science.gov (United States)

    2013-07-01

    Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Retinoblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  8. Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors

    Science.gov (United States)

    2015-03-18

    Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Childhood Hepatoblastoma; Childhood Synovial Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adrenocortical Carcinoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive; Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Retinoblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors

  9. Ascitic and solid Ehrlich tumor inhibition by Chenopodium ambrosioides L. treatment.

    Science.gov (United States)

    Nascimento, Flávia R F; Cruz, Gustavo V B; Pereira, Paulo Vitor S; Maciel, Márcia C G; Silva, Lucilene A; Azevedo, Ana Paula S; Barroqueiro, Elizabeth S B; Guerra, Rosane N M

    2006-04-25

    The leaves of Chenopodium ambrosioides L. [Chenopodiaceae] ('mastruz') have been indicated for the treatment of several diseases, among which the cancer. There are no results focusing the effect of C. ambrosioides treatment on tumor development in vivo. The aim of this study was to investigate the effect of treatment with C. ambrosioides on Ehrlich tumor development. Swiss mice were treated by intraperitoneal route (i.p.) with hydroalcoholic extract from leaves of C. ambrosioides (5 mg/kg) or with PBS (control group) 48 h before or 48 h later the Ehrlich tumor implantation. The tumor cells were implanted on the left footpad (solid tumor) or in the peritoneal cavity (ascitic tumor). To determine the solid tumor growth, footpad was measured each 2 days until the fourteenth day, when the feet were weighed. Ascitic tumor development was evaluated after 8 days of tumor implantation by quantification of the ascitic fluid volume and tumor cell number. The i.p. administration of C. ambrosioides extract before or after the tumor implantation significantly inhibited the solid and ascitic Ehrlich tumor forms. This inhibition was observed in ascitic tumor cell number, in the ascitic volume, in the tumor-bearing foot size and foot weight when compared to control mice. The treatments also increased the survival of tumor-bearing mice. In conclusion, C. ambrosioides has a potent anti-tumoral effect which was evident with a small dose and even when the treatment was given two days after the tumor implantation. This effect is probably related with anti-oxidant properties of C. ambrosioides.

  10. Numerical simulation of blood flow and interstitial fluid pressure in solid tumor microcirculation based on tumor-induced angiogenesis

    Science.gov (United States)

    Zhao, Gaiping; Wu, Jie; Xu, Shixiong; Collins, M. W.; Long, Quan; König, Carola S.; Jiang, Yuping; Wang, Jian; Padhani, A. R.

    2007-10-01

    A coupled intravascular transvascular interstitial fluid flow model is developed to study the distributions of blood flow and interstitial fluid pressure in solid tumor microcirculation based on a tumor-induced microvascular network. This is generated from a 2D nine-point discrete mathematical model of tumor angiogenesis and contains two parent vessels. Blood flow through the microvascular network and interstitial fluid flow in tumor tissues are performed by the extended Poiseuille’s law and Darcy’s law, respectively, transvascular flow is described by Starling’s law; effects of the vascular permeability and the interstitial hydraulic conductivity are also considered. The simulation results predict the heterogeneous blood supply, interstitial hypertension and low convection on the inside of the tumor, which are consistent with physiological observed facts. These results may provide beneficial information for anti-angiogenesis treatment of tumor and further clinical research.

  11. Extracranial arterial aneurysms: a cause of crescendo transient ischaemic attacks.

    Science.gov (United States)

    Paterson, H M; Holdsworth, R J

    2000-12-01

    Crescendo transient ischaemic attacks (TIAs) should be regarded as a medical emergency. Patients require hospitalisation with urgent assessment and symptom control with anticoagulant therapy. We report on three patients, all of whom had atherosclerotic aneurysmal disease of the extracranial arterial circulation who presented with crescendo TIAs. The possibility of extracranial aneurysmal disease should always be considered and excluded.

  12. Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs.

    Science.gov (United States)

    Kirson, Eilon D; Giladi, Moshe; Gurvich, Zoya; Itzhaki, Aviran; Mordechovich, Daniel; Schneiderman, Rosa S; Wasserman, Yoram; Ryffel, Bernhard; Goldsher, Dorit; Palti, Yoram

    2009-01-01

    Tumor treating fields (TTFields) are low intensity, intermediate frequency, alternating electric fields used to treat cancerous tumors. This novel treatment modality effectively inhibits the growth of solid tumors in vivo and has shown promise in pilot clinical trials in patients with advanced stage solid tumors. TTFields were tested for their potential to inhibit metastatic spread of solid tumors to the lungs in two animal models: (1) Mice injected with malignant melanoma cells (B16F10) into the tail vein, (2) New Zealand White rabbits implanted with VX-2 tumors within the kidney capsule. Mice and rabbits were treated using two-directional TTFields at 100-200 kHz. Animals were either monitored for survival, or sacrificed for pathological and histological analysis of the lungs. The total number of lung surface metastases and the absolute weight of the lungs were both significantly lower in TTFields treated mice then in sham control mice. TTFields treated rabbits survived longer than sham control animals. This extension in survival was found to be due to an inhibition of metastatic spread, seeding or growth in the lungs of TTFields treated rabbits compared to controls. Histologically, extensive peri- and intra-tumoral immune cell infiltration was seen in TTFields treated rabbits only. These results raise the possibility that in addition to their proven inhibitory effect on the growth of solid tumors, TTFields may also have clinical benefit in the prevention of metastatic spread from primary tumors.

  13. Continuation Study of Entinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumors

    Science.gov (United States)

    2016-09-16

    Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Carcinoma, Non-Small-Cell Lung; Lung Diseases; Breast Diseases; Renal Neoplasm; Solid Tumors

  14. Liver Metastasis Four Years after Whipple's Resection for Solid-Pseudopapillary Tumor of the Pancreas

    Directory of Open Access Journals (Sweden)

    Srikrishna Nagri

    2007-03-01

    Full Text Available Context Solid-pseudopapillary tumor of the pancreas is a rare tumor which usually affects young females in their second and third decade of life. Metastasis is very rare after a resection of curative intent. Case report We report a case of a 65-yearold white female who presented with metastasis to the liver four years after Whipple’s resection for a solid-pseudopapillary tumor of the pancreas. Conclusions Solid-pseudopapillary tumors of the pancreas can present with metastasis a long time after resection of the primary tumor. Long term close follow up of these patients should be done. The survival rate even after liver metastasis is good.

  15. Clinical observation of intrathecal chemotherapy combined with concurrent radiotherapy for leptomeningeal metastases from malignant solid tumors

    Institute of Scientific and Technical Information of China (English)

    潘振宇

    2014-01-01

    Objective To investigate the efficacy and safety of intrathecal chemotherapy combined with concurrent radiotherapy in patients with leptomeningeal metastases from solid tumors.Methods The clinical and follow-up data of 29 patients with leptomeningeal metastases frommalignant solid tumor who had intrathecal chemotherapy combined with concurrent radiotherapy were retrospectively analyzed.The treatment regimen was that 12.5-15.0 mg of methotrexate intrathecal injection once a week for 8

  16. Role of constitutive behavior and tumor-host mechanical interactions in the state of stress and growth of solid tumors.

    Directory of Open Access Journals (Sweden)

    Chrysovalantis Voutouri

    Full Text Available Mechanical forces play a crucial role in tumor patho-physiology. Compression of cancer cells inhibits their proliferation rate, induces apoptosis and enhances their invasive and metastatic potential. Additionally, compression of intratumor blood vessels reduces the supply of oxygen, nutrients and drugs, affecting tumor progression and treatment. Despite the great importance of the mechanical microenvironment to the pathology of cancer, there are limited studies for the constitutive modeling and the mechanical properties of tumors and on how these parameters affect tumor growth. Also, the contribution of the host tissue to the growth and state of stress of the tumor remains unclear. To this end, we performed unconfined compression experiments in two tumor types and found that the experimental stress-strain response is better fitted to an exponential constitutive equation compared to the widely used neo-Hookean and Blatz-Ko models. Subsequently, we incorporated the constitutive equations along with the corresponding values of the mechanical properties - calculated by the fit - to a biomechanical model of tumor growth. Interestingly, we found that the evolution of stress and the growth rate of the tumor are independent from the selection of the constitutive equation, but depend strongly on the mechanical interactions with the surrounding host tissue. Particularly, model predictions - in agreement with experimental studies - suggest that the stiffness of solid tumors should exceed a critical value compared with that of the surrounding tissue in order to be able to displace the tissue and grow in size. With the use of the model, we estimated this critical value to be on the order of 1.5. Our results suggest that the direct effect of solid stress on tumor growth involves not only the inhibitory effect of stress on cancer cell proliferation and the induction of apoptosis, but also the resistance of the surrounding tissue to tumor expansion.

  17. FAU in Treating Patients With Advanced Solid Tumors or Lymphoma

    Science.gov (United States)

    2014-01-06

    Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  18. Chimeric Antigen Receptor-Modified T Cells for Solid Tumors: Challenges and Prospects

    Directory of Open Access Journals (Sweden)

    Yelei Guo

    2016-01-01

    Full Text Available Recent studies have highlighted the successes of chimeric antigen receptor-modified T- (CART- cell-based therapy for B-cell malignancies, and early phase clinical trials have been launched in recent years. The few published clinical studies of CART cells in solid tumors have addressed safety and feasibility, but the clinical outcome data are limited. Although antitumor effects were confirmed in vitro and in animal models, CART-cell-based therapy still faces several challenges when directed towards solid tumors, and it has been difficult to achieve the desired outcomes in clinical practice. Many studies have struggled to improve the clinical responses to and benefits of CART-cell treatment of solid tumors. In this review, the status quo of CART cells and their clinical applications for solid tumors will be summarized first. Importantly, we will suggest improvements that could increase the therapeutic effectiveness of CART cells for solid tumors and their future clinical applications. These interventions will make treatment with CART cells an effective and routine therapy for solid tumors.

  19. Ispinesib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Lymphoma

    Science.gov (United States)

    2013-01-15

    Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Unspecified Childhood Solid Tumor, Protocol Specific

  20. Mitochondrial D310 mutation as clonal marker for solid tumors

    NARCIS (Netherlands)

    W.R.R. Geurts-Giele (Ina); G.H.G.K. Gathier (Gerard H. G. K.); P.N. Atmodimedjo; H.J. Dubbink (Erik Jan); W.N.M. Dinjens (Winand)

    2015-01-01

    textabstractPatients with multiple tumors, either synchronous or metachronous, can have metastatic disease or suffer from multiple independent primary tumors. While proper diagnosis of these patients is important for prognosis and treatment, this can be challenging using only clinical and histologic

  1. Targets for active immunotherapy against pediatric solid tumors.

    NARCIS (Netherlands)

    Jacobs, J.F.M.; Coulie, P.G.; Figdor, C.G.; Adema, G.J.; Vries, I.J.M. de; Hoogerbrugge, P.M.

    2009-01-01

    The potential role of antibodies and T lymphocytes in the eradication of cancer has been demonstrated in numerous animal models and clinical trials. In the last decennia new strategies have been developed for the use of tumor-specific T cells and antibodies in cancer therapy. Effective anti-tumor im

  2. New strategies to enhance photodynamic therapy for solid tumors

    NARCIS (Netherlands)

    Broekgaarden, M.

    2016-01-01

    Photodynamic therapy for cancer uses laser light to specifically activate anti-cancer drugs at the tumor site. However, this potentially effective and patient-friendly therapy has seen limited clinical application due to the inability of these drugs to accumulate at the tumor site and the subsequent

  3. Rare Solid Tumors of the Pancreas as Differential Diagnosis of Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Sabine Kersting

    2012-05-01

    Full Text Available Context Rare solid tumors of the pancreas can be misinterpreted as primary pancreatic cancer. Objective The aim of this study was to report our experience in the treatment of patients with rare tumor lesions of the pancreas and to discuss clinical and pathological characteristics in the context of the role of surgery. Design Data from patients of our prospective data-base with rare benign and malignant tumors of the pancreas, treated in our division from January 2004 to August 2010, were analyzed retrospectively. Results One-thousand and ninety-eight patients with solid tumors of the pancreas underwent pancreatic surgery. In 19 patients (10 women, 9 men with a mean age of 57 years (range: 20-74 years rare pancreatic tumors (metastasis, solid pseudopapillary tumor, teratoma, hemangioma, accessory spleen, lymphoepithelial cyst, hamartoma, sarcoidosis, yolk sac tumor were the reason for surgical intervention. Conclusion If rare benign and malignant pancreatic tumors, intrapancreatic metastasis, as well as pancreatic malformations or other abnormalities, present themselves as solid masses of the pancreas, they constitute an important differential diagnosis to primary pancreatic neoplasia, e.g. pancreatic ductal adenocarcinoma. Clinical imaging techniques cannot always rule out malignancy, thus operative exploration often remains the treatment of choice to provide the correct diagnosis and initiate adequate surgical therapy.

  4. Tumor

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008479 Preliminary study of MR elastography in brain tumors. XU Lei(徐磊), et al.Neurosci Imaging Center, Beijing Tiantan Hosp, Capital Med Univ, Beijing 100050.Chin J Radiol 2008;42(6):605-608. Objective To investigate the potential values of magnetic resonance elastography (MRE) for evaluating the brain tumor consistency in vivo. Methods Fourteen patients with known solid brain tumor (5 male, 9 female; age range: 16-63 years)

  5. In-vivo photoacoustic microscopy of nanoshell extravasation from solid tumor vasculature

    OpenAIRE

    Li, Meng-Lin; Wang, James Chunjay; Schwartz, Jon A.; Gill-Sharp, Kelly L.; Stoica, George; Lihong V. Wang

    2009-01-01

    In this study, high resolution backward-mode photoacoustic microscopy (PAM) is used to noninvasively image progressive extravasation and accumulation of nanoshells within a solid tumor in vivo. PAM takes advantage of the strong near-infrared absorption of nanoshells and their extravasation tendency from leaky tumor vasculatures for imaging. Subcutaneous tumors are grown on immunocompetent BALB/c mice. Polyethylene glycol (PEGylated) nanoshells with a peak optical absorption at ∼800nm are intr...

  6. Qa-2 expression levels is related with tumor-infiltrating lymphocytes profile during solid Ehrlich tumor development.

    Science.gov (United States)

    da Silva, Istéfani Luciene; Veloso, Emerson Soares; Gonçalves, Ivy Nayra Nascimento; Braga, Ariadne Duarte; Lopes, Miriam Teresa Paz; Cassali, Geovanni Dantas; Quintanilla, Miguel; Simões, Renata Toscano; Ferreira, Enio

    2017-08-01

    The Qa-2 has been described as Human Leucocyte Antigen G (HLA-G) murine homolog. This homology is well accepted to gene and protein structure, in different pathology process and embryos implantation. However, in some neoplasm, this homology is questioned, where Qa-2 has been proposed as an immunogenic molecule, associated to tumor rejection. In this way, the aim of this study was to describe the pattern of Qa-2 expression and its relationship with the profile of tumor-infiltrating lymphocytes in solid Ehrlich tumor. The Ehrlich tumor growth was evaluated in Balb/c female mice in different tumor stages. The inflammatory infiltration features were determined by histopathology and, both lymphocyte type and tissue Qa-2 expression by immunohistochemistry. ELISA kit was used to determine soluble Qa-2 in the serum from the animals. We observed that Qa-2 in neoplastic cells increases in intermediate tumor development stages, while, serum Qa-2 increases in the late stage. Qa-2 increasing is correlated with CD3+ increase. Our results suggest that Qa-2 has a role opposite to HLA-G in Ehrlich solid carcinoma, and may be modulating the immune response by attracting the inflammatory infiltrate, especially T CD8+ Lymphocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma

    Science.gov (United States)

    2013-07-01

    Childhood Burkitt Lymphoma; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Medulloepithelioma; Childhood Meningioma; Childhood Mixed Glioma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Oligodendroglioma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  8. Integrin α5β1, the Fibronectin Receptor, as a Pertinent Therapeutic Target in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Monique Dontenwill

    2013-01-01

    Full Text Available Integrins are transmembrane heterodimeric proteins sensing the cell microenvironment and modulating numerous signalling pathways. Changes in integrin expression between normal and tumoral cells support involvement of specific integrins in tumor progression and aggressiveness. This review highlights the current knowledge about α5β1 integrin, also called the fibronectin receptor, in solid tumors. We summarize data showing that α5β1 integrin is a pertinent therapeutic target expressed by tumoral neovessels and tumoral cells. Although mainly evaluated in preclinical models, α5β1 integrin merits interest in particular in colon, breast, ovarian, lung and brain tumors where its overexpression is associated with a poor prognosis for patients. Specific α5β1 integrin antagonists will be listed that may represent new potential therapeutic agents to fight defined subpopulations of particularly aggressive tumors.

  9. Oxaliplatin and Irinotecan in Treating Young Patients With Refractory Solid Tumors or Lymphomas

    Science.gov (United States)

    2013-06-04

    Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma; Recurrent Colon Cancer; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Melanoma; Recurrent Nasopharyngeal Cancer; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  10. Integrin α5β1, the Fibronectin Receptor, as a Pertinent Therapeutic Target in Solid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schaffner, Florence; Ray, Anne Marie; Dontenwill, Monique, E-mail: monique.dontenwill@unistra.fr [UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Tumoral signaling and therapeutic targets, Université de Strasbourg, Faculté de Pharmacie, 67401 Illkirch (France)

    2013-01-15

    Integrins are transmembrane heterodimeric proteins sensing the cell microenvironment and modulating numerous signalling pathways. Changes in integrin expression between normal and tumoral cells support involvement of specific integrins in tumor progression and aggressiveness. This review highlights the current knowledge about α5β1 integrin, also called the fibronectin receptor, in solid tumors. We summarize data showing that α5β1 integrin is a pertinent therapeutic target expressed by tumoral neovessels and tumoral cells. Although mainly evaluated in preclinical models, α5β1 integrin merits interest in particular in colon, breast, ovarian, lung and brain tumors where its overexpression is associated with a poor prognosis for patients. Specific α5β1 integrin antagonists will be listed that may represent new potential therapeutic agents to fight defined subpopulations of particularly aggressive tumors.

  11. Plexin D1 is ubiquitously expressed on tumor vessels and tumor cells in solid malignancies.

    NARCIS (Netherlands)

    Roodink, I.; Verrijp, K.; Raats, J.; Leenders, W.P.J.

    2009-01-01

    BACKGROUND: Plexin D1 is expressed on both tumor-associated endothelium and malignant cells in a number of clinical brain tumors. Recently we demonstrated that Plexin D1 expression is correlated with tumor invasion level and metastasis in a human melanoma progression series. The objective of this st

  12. Rocking the foundations of solid tumor growth by attacking the tumor's blood supply

    NARCIS (Netherlands)

    Molema, G; Griffioen, AW

    1998-01-01

    Deprivation of tumor vascularization is a promising way to prevent tumor outgrowth. Various approaches are under investigation to achieve this, ranging from inhibition of endothelial cell growth or migration to selective tumor vascular targeting of chemotherapeutics. The rapid progress in the field

  13. New generations of targeted therapies fighting the resistance in solid tumors.

    Science.gov (United States)

    Barthélémy, Philippe; Aftimos, Philippe; Awada, Ahmad

    2015-05-01

    The identification of molecular alterations that drive tumor growth and spread of solid tumors has led to the development of multiple targeted therapies considered as first-generation agents that have improved clinical benefit. However, tumor cells are able to rapidly develop resistance to these agents. The growing understanding of the biology of the resistance mechanisms has spurred ongoing development of second-generation and third-generation targeted therapies aiming at new strategies to overcome resistance. Several generations of targeted therapies have been developed in order to prevent, delay or overcome tumor resistance. Some agents have already been approved, and others are currently under active clinical investigation in several cancer subtypes, including breast cancer, nonsmall cell lung cancer, head and neck squamous cell cancer and colorectal cancer. In the present review, we will discuss in solid tumors, the recent development of next generation anticancer-targeted therapies and new strategies including combination agents currently under active clinical investigation.

  14. Cytogenetics of solid tumors Revisión de tema Citogenética de tumores sólidos

    Directory of Open Access Journals (Sweden)

    José Luis Ramírez Castro

    2002-02-01

    Full Text Available Cytogenetic analysis of tumors has provided valuable information on the biology of cancer. It has been established that more than half of solid tumors show chromosomal anomalies; therefore, cytogenetic analysis is of great usefulness for diagnostic and prognostic purposes. Identification of recurrent chromosomal anomalies in numerous tumors has been considered as an indicador of clinical importance. Cytogenetic studies in tissue tumors have revealed near 100,000 clonal chromosome abnormalities belonging to more that 30,000 human neoplasms. However, due to technical difficulties in cell cultures, only one third of solid tumors have been cytogenetically characterized. Conventional cytogenetics has been very useful for molecular characterization of new oncogenes and tumor-suppressor genes involved in human tumorigenesis. In this review, some important issues related with tumors of chromosomal etiology, the diverse types of chromosomal anomalies with their frequencies, modern diagnostic techniques as well as their impact on the diagnosis and prognosis of cancer are presented. EL análisis citogenético de tumores ha proporcionado valiosa información sobre la biología del cáncer. Se ha establecido que más de la mitad de los tumores sólidos presentan alteraciones cromosómicas; por lo tanto, el análisis citogenético es de gran utilidad para el diagnóstico y el pronóstico. La identificación de cambios cromosómicos específicos recurrentes en numerosos tumores se considera un indicador de importancia clínica. Los estudios en este campo han revelado cerca de 100.000 alteraciones cromosómicas en más de 30.000 neoplasias humanas. Sin embargo, los tumores sólidos son los menos caracterizados citogenéticamente, sólo una tercera parte del total de ellos, debido a problemas técnicos en los cultivos celulares. La citogenética convencional ha sido muy útil para la posterior caracterización molecular de nuevos oncogenes y genes supresores de

  15. FR901228 in Treating Children With Refractory or Recurrent Solid Tumors or Leukemia

    Science.gov (United States)

    2013-01-15

    Blastic Phase Chronic Myelogenous Leukemia; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Chronic Myelogenous Leukemia; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  16. Fusion genes in solid tumors:an emerging target for cancer diagnosis and treatment

    Institute of Scientific and Technical Information of China (English)

    Brittany C. Parker; Wei Zhang

    2013-01-01

    Studies over the past decades have uncovered fusion genes, a class of oncogenes that provide immense diagnostic and therapeutic advantages because of their tumor-specific expression. Originally associated with hemotologic cancers, fusion genes have recently been discovered in a wide array of solid tumors, including sarcomas, carcinomas, and tumors of the central nervous system. Fusion genes are attractive as both therapeutic targets and diagnostic tools due to their inherent expression in tumor tissue alone. Therefore, the discovery and elucidation of fusion genes in various cancer types may provide more effective therapies in the future for cancer patients.

  17. Radioresistance in murine solid tumors induced by interleukin-1

    Energy Technology Data Exchange (ETDEWEB)

    Braunschweiger, P.G.; Basrur, V.; Santos, O.; Adessa, A.; Houdek, P.; Markoe, A.M. [Univ. of Miami School of Medicine, Miami, FL (United States)

    1996-02-01

    Interleukin-1 (IL-1) has radioprotective activity in hematopoietic lineages and in other normal cell renewal systems, but little is known about the effects of IL-1{alpha} on the radiosensitivity of tumor cell populations. The present studies were conducted to investigate the effects of IL-1{alpha} on the radiosensitivity of clonogenic cells in RIF-1 and SCC-7 tumors. Radioresistance was detected within 2-4 h after administration of IL-1{alpha} (0.5 {mu}g/mouse, ip) and characterized by increases in D{sub 0}, D{sub q}, {alpha}/{Beta} and SF2. This radioresistance was similar to that seen in tumors rendered totally hypoxic before X irradiation. Tirapazamine, a hypoxic cell cytotoxin, and IL-1{alpha} had synergistic schedule-dependent antitumor activity in vivo, suggesting that IL-1-induced radioresistance in vivo is due to hypoxia. Radioresistance induced by IL-1{alpha} was transient, and the data suggested reoxygenation within 12 h. In vitro, IL-1{alpha} had no direct effect on the radiosensitivity of SCC-7 cells in tissue culture under aerobic conditions. However, an increase in D{sub 0}, {alpha}/{Beta} and SF2 was seen in clonogenic tumor cells from primary cultures treated with IL-1{alpha} under aerobic conditions. Superoxide dismutase and catalase prevented the induction of radioresistance by IL-1{alpha} in vitro, suggesting that oxidative responses from tumor macrophages after administration of IL-1{alpha} may be responsible for induced radioresistance by IL-1 in vitro. Although oxidant stress induced by IL-1 may play an important role in the activity of IL-1{alpha} both in vivo and in vitro in our models, the mechanisms by which such responses modulate tumor radiosensitivity in vivo and in vitro are likely quite different. 32 refs., 6 figs., 1 tab.

  18. Targeting the epidermal growth factor receptor in solid tumor malignancies

    DEFF Research Database (Denmark)

    Nedergaard, Mette K; Hedegaard, Chris J; Poulsen, Hans S

    2012-01-01

    The epidermal growth factor receptor (EGFR) is over-expressed, as well as mutated, in many types of cancers. In particular, the EGFR variant type III mutant (EGFRvIII) has attracted much attention as it is frequently and exclusively found on many tumor cells, and hence both EGFR and EGFRvIII have...... been proposed as valid targets in many cancer therapy settings. Different strategies have been developed in order to either inhibit EGFR/EGFRvIII activity or to ablate EGFR/EGFRvIII-positive tumor cells. Drugs that inhibit these receptors include monoclonal antibodies (mAbs) that bind...

  19. Bacteria-mediated in vivo delivery of quantum dots into solid tumor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ying [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Zhou, Mei [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Luo, Dan; Wang, Lijun; Hong, Yuankai [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Yang, Yepeng, E-mail: yangyepeng@bjmu.edu.cn [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Sha, Yinlin, E-mail: shyl@hsc.pku.edu.cn [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Biomed-X Center, Peking University, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. Black-Right-Pointing-Pointer Bifidobacterium bifidum delivery system has intrinsic biocompatibility. Black-Right-Pointing-Pointer The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.

  20. Glucocorticoid receptor expression in 20 solid tumor types using immunohistochemistry assay

    Science.gov (United States)

    Block, Thaddeus S; Murphy, Tiffany I; Munster, Pamela N; Nguyen, Dat P; Lynch, Frank J

    2017-01-01

    Background Glucocorticoid receptor (GR) activity plays a role in many aspects of human physiology and may play a crucial role in chemotherapy resistance in a wide variety of solid tumors. A novel immunohistochemistry (IHC) based assay has been previously developed and validated in order to assess GR immunoreactivity in triple-negative breast cancer. The current study investigates the standardized use of this validated assay to assess GR expression in a broad range of solid tumor malignancies. Methods Archived formalin-fixed paraffin-embedded tumor bank samples (n=236) from 20 different solid tumor types were analyzed immunohistochemically. Nuclear staining was reported based on the H-score method using differential intensity scores (0, 1+, 2+, or 3+) with the percent stained (out of at least 100 carcinoma cells) recorded at each intensity. Results GR was expressed in all tumor types that had been evaluated. Renal cell carcinoma, sarcoma, cervical cancer, and melanoma were those with the highest mean H-scores, indicating high levels of GR expression. Colon, endometrial, and gastric cancers had lower GR staining percentages and intensities, resulting in the lowest mean H-scores. Conclusion A validated IHC assay revealed GR immunoreactivity in all solid tumor types studied and allowed for standardized comparison of reactivity among the different malignancies. Impact Baseline expression levels of GR may be a useful biomarker when pharmaceutically targeting GR in research or clinical setting. PMID:28293120

  1. Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors.

    Science.gov (United States)

    Yu, Man; Lee, Carol; Wang, Marina; Tannock, Ian F

    2015-10-01

    Cellular causes of resistance and limited drug distribution within solid tumors limit therapeutic efficacy of anticancer drugs. Acidic endosomes in cancer cells mediate autophagy, which facilitates survival of stressed cells, and may contribute to drug resistance. Basic drugs (e.g. doxorubicin) are sequestered in acidic endosomes, thereby diverting drugs from their target DNA and decreasing penetration to distal cells. Proton pump inhibitors (PPIs) may raise endosomal pH, with potential to improve drug efficacy and distribution in solid tumors. We determined the effects of the PPI lansoprazole to modify the activity of doxorubicin. To gain insight into its mechanisms, we studied the effects of lansoprazole on endosomal pH, and on the spatial distribution of doxorubicin, and of biomarkers reflecting its activity, using in vitro and murine models. Lansoprazole showed concentration-dependent effects to raise endosomal pH and to inhibit endosomal sequestration of doxorubicin in cultured tumor cells. Lansoprazole was not toxic to cancer cells but potentiated the cytotoxicity of doxorubicin and enhanced its penetration through multilayered cell cultures. In solid tumors, lansoprazole improved the distribution of doxorubicin but also increased expression of biomarkers of drug activity throughout the tumor. Combined treatment with lansoprazole and doxorubicin was more effective in delaying tumor growth as compared to either agent alone. Together, lansoprazole enhances the therapeutic effects of doxorubicin both by improving its distribution and increasing its activity in solid tumors. Use of PPIs to improve drug distribution and to inhibit autophagy represents a promising strategy to enhance the effectiveness of anticancer drugs in solid tumors.

  2. Nanoparticles carry chemotherapy drug deeper into solid tumors

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ CAS researchers have developed a new drug delivery method using nano-sized molecules to carry the chemotherapy drug doxorubicin to tumors, improving the effectiveness of the drug in mice and increasing their survival time. Their work has been reported online June 26 in the Journal of the National Cancer Institute.

  3. Criteria to define HLA haplotype loss in human solid tumors

    NARCIS (Netherlands)

    Ramal, LM; van der Zwan, AW; Collado, A; Lopez-Nevot, MA; Tilanus, M; Garrido, F

    2000-01-01

    Short tandem repeat (STR) markers are currently used to define loss of heterozygosity (LOH) of genes and chromosomes in tumors. Chromosome 6 and chromosome 15 STR markers are applied to define loss of HLA and related genes (e.g. TAP and beta(2)m) The number of STR identified in the HLA region is sti

  4. Some epidemiological and clinical characteristics of solid malignant tumors in children from Las Tunas

    Directory of Open Access Journals (Sweden)

    Silvio Laffita Estévez

    2015-11-01

    Full Text Available Background: cancer has kept up as the second cause of death in Las Tunas pediatric population.Objective: to characterize clinical and epidemiological variables of the cases diagnosed with solid malignant tumors in children seen and treated in the onco-pediatric consultation of “Mártires de Las Tunas” Pediatric Hospital from 2010 to 2014.Methods: a descriptive and retrospective study was carried out in 62 patients with solid malignant tumors in the pediatric population of Las Tunas province, from January, 2010 to December, 2014. The variables considered were: presumptive diagnosis, age, family history of tumors, clinical signs of alarm related to the tumor at the moment of diagnosis and investigations to confirm the diagnosis.  Results: non-Hodgkin lymphoma was the most frequently diagnosed tumor, with a 19, 35% of the patients. The most affected age group was between 11 and 14 years old, with a 33, 87%. The 16, 13% of the patients had family history of solid malignant tumors. The most frequent form of presentation was the abdominal tumor, with 29, 03 %. Abdominal ultrasound and computerized axial tomography were the most used complementary diagnostic means, both in the 17, 74% of the patients. Biopsy was used to confirm the 96, 77% of the cases.Conclusions: the clinical and epidemiological variables were characterized in pediatric patients diagnosed with solid malignant tumors in Las Tunas. Children between 11 and 14 years old and family history of malignant tumors were the most significant findings.

  5. Propranolol Hydrochloride in Treating Patients With Locally Recurrent or Metastatic Solid Tumors That Cannot Be Removed By Surgery

    Science.gov (United States)

    2016-09-28

    Male Breast Cancer; Recurrent Melanoma; Stage IV Breast Cancer; Stage IV Melanoma; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Hepatocellular Carcinoma

  6. Chromosomal aberrations related to metastasis of human solid tumors

    Institute of Scientific and Technical Information of China (English)

    Lun-Xiu Qin

    2002-01-01

    The central role of sequential accumulation of genetic alterations during the development of cancer has been firmly established since the pioneering cytogenetic studies successfully defined recurrent chromosome changes in spedfic types of tumor. In the course of carcinogenesis, cells experience several genetic alterations that are associated with the transition from a preneoplastic lesion to an invasive tumor and finally to the metastatic state. Tumor progression is characterized by stepwise accumulation of genetic alterations.So does the dominant metastatic clone. Modern molecular genetic analyses have clarified that genomic changes accumulate during the development and progression of cancers. In comparison with the corresponding primary tumor,additional events of chromosomal aberrations (including gains or allelic losses) are frequently found in metastases, and the incidence of combined chromosomal alterations in the primary tumor, plus the occurrence of additional aberrations inthe distant metastases, correlated significantly with decreased postmetastatic survival. The deletions at 3p, 4p, 6q, 8p, 10q,11p, 11q, 12p, 13q, 16q, 17p, 18q, 21q, and 22q, as well as the over-representations at 1q, 8q, 9q, 14q and 15q, have been found to associate preferentially with the metastatic phenotype of human cancers. Among of them, the deletions on chromosomes 8p, 17p, 11p and 13p seem to be more significant, and more detail fine regions of them, including 8p11, 8p21-12, 8p22, 8p23, 17p13.3, 11p15.5, and 13q12-13 have been suggested harboring metastasis-suppressor genes.During the past decade, several human chromosomes have been functionally tested through the use of microcell-mediated chromosome transfer (MMCT), and metastasis-suppressor activities have been reported on chromosomes 1, 6, 7, 8, 10,11, 12, 16, and 17. However, it is not actually known at what stage of the metastatic cascade these alterations have occurred.There is still controversial with the association

  7. An overview of viral oncology in Italy - report from the Pavia meeting on solid tumors.

    Science.gov (United States)

    Perfetti, Vittorio; Ricotti, Mattia; Buonaguro, Franco; Tirelli, Umberto; Pedrazzoli, Paolo

    2012-09-05

    This is a report on some of the research activities currently ongoing in Italy as outlined at the "Viruses and solid tumors" meeting jointly organized by the Oncology Sections of IRCCS Policlinico "San Matteo" (Pavia) and IRCCS National Cancer Institute (Aviano), held in Pavia, Italy, on October 2011. Experts from the various disciplines involved in the study of the complex relationships between solid tumors and viruses met to discuss recent developments in the field and to report their personal contributions to the specified topics. Secondary end point was to establish a multidisciplinary work group specifically devoted to solid tumors and infectious agents, aimed to identify areas of common interest, promoting and establishing collaborative projects and programs, and to coordinate clinical and research activities. The group, which will be named IVOG (Italian Viral Oncology Group), will operate under the patronage of the various scientific societies of interest.

  8. A case of primary extracranial meningioma of the forearm with bone invasion

    Energy Technology Data Exchange (ETDEWEB)

    Murata, Hideki [Self-Defense Force Fuji Hospital, Division of Orthopaedic Surgery, Oyama-cho, Sunto-gun, Shizuoka (Japan); Takahashi, Mitsuru; Takagi, Tatsuya; Katagiri, Hirohisa [Shizuoka Cancer Center Hospital, Division of Orthopaedic Oncology, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Ito, Ichiro [Shizuoka Cancer Center Hospital, Division of Pathology, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Ishida, Tsuyoshi [Kohnodai Hospital, Department of Pathology and Laboratory Medicine, National Center of Neurology and Psychiatry, Ichikawa, Chiba (Japan)

    2007-06-15

    We report here a rare case of primary extracranial meningioma in a 73-year-old woman with an asymptomatic mass located in the left distal-dorsal forearm. MRI revealed the lesion to be poorly circumscribed and unclear, with iso-signal intensity to muscle on T1 and with a relatively high signal intensity on T2-weighted imaging. The histopathology of the specimen from incision biopsy was typical of meningioma, showing bland spindle cell proliferation with a whorling pattern. Immunohistochemically, the tumor cells were positive for epithelial membrane antigen and vimentin, and negative for S-100 expression. (orig.)

  9. Extrapulmonary small cell sarcinoma: involvement of the brain without evidence of extracranial malignancy by serial PET/CT scans

    Directory of Open Access Journals (Sweden)

    Havlioglu Necat

    2008-09-01

    Full Text Available Abstract Background Extrapulmonary small cell carcinoma (EPSCC involving the brain is a rare manifestation of an uncommon tumor type. Case presentation We report a 59 year-old Caucasian female diagnosed with an EPSCC involving the left parietal lobe without detectable extracranial primary tumor followed by serial positron emission tomography/computed tomography (PET/CT imaging. Histopathological examination at both initial presentation and recurrence revealed small cell carcinoma. Serial PET/CT scans of the entire body failed to reveal any extracranial [18F]2-fluoro-2-deoxy-D-glucose (FDG avid lesions at either diagnosis or follow-up. Conclusion Chemotherapy may show a transient response in the treatment of EPSCC. Further studies are needed to help identify optimal treatment strategies. Combination PET/CT technology may be a useful tool to monitor EPSCC and assess for an occult primary malignancy.

  10. Favorable alteration of tumor microenvironment by immunomodulatory cytokines for efficient T-cell therapy in solid tumors.

    Science.gov (United States)

    Tähtinen, Siri; Kaikkonen, Saija; Merisalo-Soikkeli, Maiju; Grönberg-Vähä-Koskela, Susanna; Kanerva, Anna; Parviainen, Suvi; Vähä-Koskela, Markus; Hemminki, Akseli

    2015-01-01

    Unfavorable ratios between the number and activation status of effector and suppressor immune cells infiltrating the tumor contribute to resistance of solid tumors to T-cell based therapies. Here, we studied the capacity of FDA and EMA approved recombinant cytokines to manipulate this balance in favor of efficient anti-tumor responses in B16.OVA melanoma bearing C57BL/6 mice. Intratumoral administration of IFN-α2, IFN-γ, TNF-α, and IL-2 significantly enhanced the anti-tumor effect of ovalbumin-specific CD8+ T-cell (OT-I) therapy, whereas GM-CSF increased tumor growth in association with an increase in immunosuppressive cell populations. None of the cytokines augmented tumor trafficking of OT-I cells significantly, but injections of IFN-α2, IFN-γ and IL-2 increased intratumoral cytokine secretion and recruitment of endogenous immune cells capable of stimulating T-cells, such as natural killer and maturated CD11c+ antigen-presenting cells. Moreover, IFN-α2 and IL-2 increased the levels of activated tumor-infiltrating CD8+ T-cells concomitant with reduction in the CD8+ T-cell expression of anergy markers CTLA-4 and PD-1. In conclusion, intratumoral administration of IFN-α2, IFN-γ and IL-2 can lead to immune sensitization of the established tumor, whereas GM-CSF may contribute to tumor-associated immunosuppression. The results described here provide rationale for including local administration of immunostimulatory cytokines into T-cell therapy regimens. One appealing embodiment of this would be vectored delivery which could be advantageous over direct injection of recombinant molecules with regard to efficacy, cost, persistence and convenience.

  11. Favorable alteration of tumor microenvironment by immunomodulatory cytokines for efficient T-cell therapy in solid tumors.

    Directory of Open Access Journals (Sweden)

    Siri Tähtinen

    Full Text Available Unfavorable ratios between the number and activation status of effector and suppressor immune cells infiltrating the tumor contribute to resistance of solid tumors to T-cell based therapies. Here, we studied the capacity of FDA and EMA approved recombinant cytokines to manipulate this balance in favor of efficient anti-tumor responses in B16.OVA melanoma bearing C57BL/6 mice. Intratumoral administration of IFN-α2, IFN-γ, TNF-α, and IL-2 significantly enhanced the anti-tumor effect of ovalbumin-specific CD8+ T-cell (OT-I therapy, whereas GM-CSF increased tumor growth in association with an increase in immunosuppressive cell populations. None of the cytokines augmented tumor trafficking of OT-I cells significantly, but injections of IFN-α2, IFN-γ and IL-2 increased intratumoral cytokine secretion and recruitment of endogenous immune cells capable of stimulating T-cells, such as natural killer and maturated CD11c+ antigen-presenting cells. Moreover, IFN-α2 and IL-2 increased the levels of activated tumor-infiltrating CD8+ T-cells concomitant with reduction in the CD8+ T-cell expression of anergy markers CTLA-4 and PD-1. In conclusion, intratumoral administration of IFN-α2, IFN-γ and IL-2 can lead to immune sensitization of the established tumor, whereas GM-CSF may contribute to tumor-associated immunosuppression. The results described here provide rationale for including local administration of immunostimulatory cytokines into T-cell therapy regimens. One appealing embodiment of this would be vectored delivery which could be advantageous over direct injection of recombinant molecules with regard to efficacy, cost, persistence and convenience.

  12. Pregnancy following Radical Resection of Solid Pseudopapillary Tumor of the Pancreas

    Directory of Open Access Journals (Sweden)

    James M. O’Brien

    2014-01-01

    Full Text Available Solid pseudopapillary tumor of the pancreas is a rare tumor seen in predominately young women and carries a low malignant potential. We discuss a patient, who presented to our high risk clinic, with a clinical history of solid pseudopapillary tumor of the pancreas, predating her pregnancy. The patient had undergone previous surgery and imaging which had excluded recurrence of disease; however, increased attention was paid to the patient during her pregnancy secondary to elevated hormonal levels of progesterone, which any residual disease would have a heightened sensitivity to. In cases of pregnant patients with a history of pancreatic tumors, a multidisciplinary approach with maternal fetal medicine, medicine, and general surgery is appropriate and can result in a healthy mother and healthy term infant.

  13. Use of Arsenic Trioxide as an Antivascular and Thermosensitizing Agent in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Robert J. Griffin

    2000-01-01

    Full Text Available Arsenic trioxide, As2O3 (ATO, has been found to be an effective chemotherapy drug for acute promyelocytic leukemia but its effect on solid tumors has not been fully explored. In the present report, we describe our observation that ATO is a potent antivascular agent and that it markedly enhances the effect of hyperthermia on tumors. The tumor blood perfusion in SCK tumors of A/J mice and FSall tumors of C3H mice was significantly suppressed for up to 24 hours after an i.p. injection of 8 mg/kg ATO. ATO was also found to be able to increase the thermosensitivity of tumor cells in vitro. As a probable consequence of these effects, ATO treatment markedly increased the tumor growth delay caused by hyperthermia at 41.5-42.5°C. Immunohistochemical staining of tumor tissue revealed that the expression levels of several adhesion molecules and TNFa are noticeably increased in tumors 2–6 hours after systemic ATO treatment. It is concluded that ATO is potentially useful to enhance the effect of hyperthermia on tumors at a clinically relevant temperature.

  14. Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice

    Directory of Open Access Journals (Sweden)

    C.M. Souza

    2014-10-01

    Full Text Available Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106 cells in 0.05mL. After tumor inoculation, the animals were separated into two groups (n = 10. The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker and for CD31 (blood vessel marker. Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy.

  15. Four cases of solid pseudopapillary tumors of pancreas: Imaging findings and pathological correlations

    Energy Technology Data Exchange (ETDEWEB)

    Vargas-Serrano, Blanca [Servicio de Radiologia, Hospitales Universitarios Virgen del Rocio, Avda Manuel Siurot s/n, Sevilla 41013 (Spain); Dominguez-Ferreras, Esther [Servicio de Radiologia, Hospitales Universitarios Virgen del Rocio, Avda Manuel Siurot s/n, Sevilla 41013 (Spain)]. E-mail: blancavargas@terra.es; Chinchon-Espino, David [Servicio de Anatomia Patologica, Hospitales Universitarios Virgen del Rocio, Avda Manuel Siurot s/n, Sevilla 41013 (Spain)

    2006-04-15

    Objective: Solid pseudopapillary tumor of the pancreas (SPTP tumor) is a rare pancreatic neoplasm with low malignant potential, which usually affects female patients in the second or third decades of life. It is a non-functional, slow-growing neoplasm that very often reaches considerable size before the first symptoms appear. Symptomatology is frequently related to tumor size. Surgical excision is usually curative in most cases. Infrequently the tumor can appear in male patients or in aged women, which can make the diagnosis more difficult. Some patients develop liver metastases in the follow-up that can be resected. Our purpose is to review the radiological and pathological findings of SPTP with emphasis on these infrequent cases. Subjects and methods: The medical records and radiological findings of patients who underwent surgery for SPTP between 2000 and 2005 were retrospectively reviewed. Study eligibility required that patients had undergone surgical resection and that a SPTP had been pathologically proved. Results: Four cases of solid pseudopapillary tumor of the pancreas were diagnosed and treated in our institution in the study period. Two of the patients, developed on follow-up liver metastases, and peritoneal, hepatic, and nodal metastases, respectively. Conclusion: Solid pseudopapillary tumors are well-encapsulated neoplasms that usually have a good prognosis after surgical excision. A malignant behavior is uncommon and in this case lymph node involvement, hepatic metastases and occasionally peritoneal invasion may also occur. Resection of liver metastases can prolong the long-term survival of the patients.

  16. Co-Encapsulation of Doxorubicin With Galactoxyloglucan Nanoparticles for Intracellular Tumor-Targeted Delivery in Murine Ascites and Solid Tumors

    Directory of Open Access Journals (Sweden)

    Manu M. Joseph

    2014-10-01

    Full Text Available Doxorubicin (Dox treatment is limited by severe toxicity and frequent episodes of treatment failure. To minimize adverse events and improve drug delivery efficiently and specifically in cancer cells, encapsulation of Dox with naturally obtained galactoxyloglucan polysaccharide (PST001, isolated from Tamarindus indica was attempted. Thus formed PST-Dox nanoparticles induced apoptosis and exhibited significant cytotoxicity in murine ascites cell lines, Dalton’s lymphoma ascites and Ehrlich’s ascites carcinoma. The mechanism contributing to the augmented cytotoxicity of nanoconjugates at lower doses was validated by measuring the Dox intracellular uptake in human colon, leukemic and breast cancer cell lines. PST-Dox nanoparticles showed rapid internalization of Dox into cancer cells within a short period of incubation. Further, in vivo efficacy was tested in comparison to the parent counterparts - PST001 and Dox, in ascites and solid tumor syngraft mice models. Treatment of ascites tumors with PST-Dox nanoparticles significantly reduced the tumor volume, viable tumor cell count, and increased survival and percentage life span in the early, established and prophylactic phases of the disease. Administration of nanoparticles through intratumoral route delivered more robust antitumor response than the intraperitoneal route in solid malignancies. Thus, the results indicate that PST-Dox nanoparticles have greater potential compared to the Dox as targeted drug delivery nanocarriers for loco regional cancer chemotherapy applications.

  17. Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Xiaonan Zhang

    2015-11-01

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

  18. Hydrodynamics and convection enhanced macromolecular fluid transport in soft biological tissues: Application to solid tumor.

    Science.gov (United States)

    Dey, Bibaswan; Sekhar, G P Raja

    2016-04-21

    This work addresses a theoretical framework for transvascular exchange and extravascular transport of solute macromolecules through soft interstitial space inside a solid tumor. Most of the soft biological tissues show materialistic properties similar to deformable porous material. They exhibit mechanical behavior towards the fluid motion since the solid phase of the tumor tissue gets compressed by the drag force that is associated with the extracellular fluid flow. This paper presents a general view about the transvascular and interstitial transport of solute nutrients inside a tumor in the macroscopic level. Modified Starling׳s equation is used to describe transvascular nutrient transport. On the macroscopic level, motion of extracellular fluid within the tumor interstitium is modeled with the help of biphasic mixture theory and a spherical symmetry solution is given as a simpler case. This present model describes the average interstitial fluid pressure (IFP), extracellular fluid velocity (EFV) and flow rate of extracellular fluid, as well as the deformation of the solid phase of the tumor tissue as an immediate cause of extracellular fluid flow. When the interstitial transport is diffusion dominated, an analytical treatment of advection-diffusion-reaction equation finds the overall nutrient distribution. We propose suitable criteria for the formation of necrosis within the tumor interstitium. This study introduces some parameters that represent the nutrient supply from tumor blood vessels into the tumor extracellular space. These transport parameters compete with the reversible nutrient metabolism of the tumor cells present in the interstitium. The present study also shows that the effectiveness factor corresponding to a first order nutrient metabolism may reach beyond unity if the strength of the distributive solute source assumes positive non-zero values.

  19. Biopsy of solid liver tumors:adverse consequences

    Institute of Scientific and Technical Information of China (English)

    Dhya Al-Leswas; Derek A O'Reilly; Graeme J Poston

    2008-01-01

    BACKGROUND:Percutaneous radiologically-guided liver biopsy is used routinely worldwide in all secondary-level hospital centers. While it has an undoubted role in the investigation and management of acute and chronic inlfammatory conditions of the liver, its role in hepatic oncology is doubtful and probably dangerous. METHOD:We report on two patients who underwent preoperative biopsy of potentially resectable liver tumors. RESULTS:At the time of surgery, there was evidence of seeding at the biopsy site in both cases. In case 1, potentially curative liver resection was rendered incurable because of gross peritoneal carcinomatosis lying adjacent to the site of liver biopsy. In case 2, the patient underwent curative liver resection, but there was histopathological evidence of peritoneal disease beyond the liver capsule along the falciform ligament at the site of the previous biopsy. CONCLUSIONS:No patient with a suspicious liver tumor which is thought to be malignant and has any possibility of being a potential candidate for liver surgery, should be subjected to pre-operative diagnostic biopsy in a non-specialist center.

  20. Strategies for improving chemotherapeutic delivery to solid tumors mediated by vascular permeability modulation

    Science.gov (United States)

    Roy Chaudhuri, Tista

    An essential mode of distribution of blood-borne chemotherapeutic agents within a solid tumor is via the micro-circulation. Poor tumor perfusion, because of a lack of functional vasculature or a lack of microvessels, as well as low tumor vascular permeability, can prevent adequate deposition of even low molecular-weight agents into the tumor. The modulation of tumor vascular function and density can provides numerous strategies for improving intratumor deposition of chemotherapeutic agents. Here we investigated strategies to improve drug delivery to two tumor types that share in common poor drug delivery, but differ in the underlying cause. First, in an angiogenesis-driven brain tumor model of Glioblastoma, the vascular permeability barrier, along with poorly-functional vasculature, hinders drug delivery. A strategy of nanoparticle-based tumor 'priming' to attack the vascular permeability barrier, employing sterically stabilized liposomal doxorubicin (SSL-DXR), was investigated. Functional and histological evaluation of tumor vasculature revealed that after an initial period of depressed vascular permeability and vascular pruning 3--4 days after SSL-DXR administration, vascular permeability and perfusion were restored and then elevated after 5--7 days. As a result of tumor priming, deposition of subsequently-administered nanoparticles was enhanced, and the efficacy of temozolomide (TMZ), if administered during the window of elevated permeability, was increased. The sequenced regimen resulted in a persistent reduction of the tumor proliferative index and a 40% suppression of tumor volume, compared to animals that received both agents simultaneously. Second, in a hypovascular, pancreatic ductal adenocarcinoma model, disruption of tumor-stromal communication via sonic hedgehog (sHH) signaling pathway inhibition mediated an indirect vascular proliferation and a more than 2-fold increase in intratumor nanoparticle deposition. Enhanced delivery of SSL-DXR in tumors pre

  1. A hybrid cellular automaton model of solid tumor growth and bioreductive drug transport.

    Science.gov (United States)

    Kazmi, Nabila; Hossain, M A; Phillips, Roger M

    2012-01-01

    Bioreductive drugs are a class of hypoxia selective drugs that are designed to eradicate the hypoxic fraction of solid tumors. Their activity depends upon a number of biological and pharmacological factors and we used a mathematical modeling approach to explore the dynamics of tumor growth, infusion, and penetration of the bioreductive drug Tirapazamine (TPZ). An in-silico model is implemented to calculate the tumor mass considering oxygen and glucose as key microenvironmental parameters. The next stage of the model integrated extra cellular matrix (ECM), cell-cell adhesion, and cell movement parameters as growth constraints. The tumor microenvironments strongly influenced tumor morphology and growth rates. Once the growth model was established, a hybrid model was developed to study drug dynamics inside the hypoxic regions of tumors. The model used 10, 50 and 100 \\mu {\\rm M} as TPZ initial concentrations and determined TPZ pharmacokinetic (PK) (transport) and pharmacodynamics (cytotoxicity) properties inside hypoxic regions of solid tumor. The model results showed that diminished drug transport is a reason for TPZ failure and recommend the optimization of the drug transport properties in the emerging TPZ generations. The modeling approach used in this study is novel and can be a step to explore the behavioral dynamics of TPZ.

  2. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

  3. Elucidating the Uptake and Distribution of Nanoparticles in Solid Tumors via a Multilayered Cell Culture Model

    Institute of Scientific and Technical Information of China (English)

    Darren Yohan; Charmainne Cruje; Xiaofeng Lu; Devika Chithrani

    2015-01-01

    Multicellular layers (MCLs) have previously been used to determine the pharmacokinetics of a variety of different cancer drugs including paclitaxel, doxorubicin, methotrexate, and 5-fluorouracil across a number of cell lines. It is not known how nanoparticles (NPs) navigate through the tumor microenvironment once they leave the tumor blood vessel. In this study, we used the MCL model to study the uptake and penetration dynamics of NPs. Gold nanoparticles (GNPs) were used as a model system to map the NP distribution within tissue-like structures. Our results show that NP uptake and transport are dependent on the tumor cell type. MDA-MB-231 tissue showed deeper penetration of GNPs as compared to MCF-7 one. Intracellular and extracellular distributions of NPs were mapped using CytoViva imaging. The ability of MCLs to mimic tumor tissue characteristics makes them a useful tool in assessing the efficacy of particle distribution in solid tumors.

  4. Dynamic density functional theory of solid tumor growth: Preliminary models

    Directory of Open Access Journals (Sweden)

    Arnaud Chauviere

    2012-03-01

    Full Text Available Cancer is a disease that can be seen as a complex system whose dynamics and growth result from nonlinear processes coupled across wide ranges of spatio-temporal scales. The current mathematical modeling literature addresses issues at various scales but the development of theoretical methodologies capable of bridging gaps across scales needs further study. We present a new theoretical framework based on Dynamic Density Functional Theory (DDFT extended, for the first time, to the dynamics of living tissues by accounting for cell density correlations, different cell types, phenotypes and cell birth/death processes, in order to provide a biophysically consistent description of processes across the scales. We present an application of this approach to tumor growth.

  5. Targeting solid tumors : advances in treatment strategies for glioma and colorectal cancer

    NARCIS (Netherlands)

    van Houdt, W.J.

    2011-01-01

    Curative treatment of most solid tumors includes surgical interference. However, the incidence of local recurrence or distant micrometastases is significantly lower when patients are treated with systemic or locally administered chemo- or targeted therapy. In the last decade, many novel targeting st

  6. Prognostic value of programed death ligand 1 in patients with solid tumors: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Ying Jin

    2015-01-01

    Conclusion: With the available evidence, PD-L1 might serve as an efficient prognostic indicator in solid tumor and may represent the important new therapeutic target. More prospective studies are now needed to confirm the clinical utility of PD-L1 as an independent prognostic marker.

  7. Biochemical parameters of bone metabolism in bone metastases of solid tumors (Review)

    NARCIS (Netherlands)

    Meijer, Wilhelmus; van der Veer, E; Willemse, P H

    1998-01-01

    The role of biochemical markers of bone metabolism in the diagnosis and monitoring of bone metastases in solid tumors is reviewed. Emphasis is on the recently developed markers, which may provide a more accurate quantitation of bone metabolism. In metastatic bone disease, bone formation and resorpti

  8. Pharmacokinetics and excretion of 14C-omacetaxine in patients with advanced solid tumors

    NARCIS (Netherlands)

    Nijenhuis, Cynthia M.; Hellriegel, Edward; Beijnen, Jos H.; Hershock, Diane; Huitema, Alwin D R; Lucas, Luc; Mergui-Roelvink, Marja; Munteanu, Mihaela; Rabinovich-Guilatt, Laura; Robertson, Philmore; Rosing, Hilde; Spiegelstein, Ofer; Schellens, Jan H M

    2016-01-01

    Background Omacetaxine mepesuccinate is indicated in adults with chronic myeloid leukemia resistant and/or intolerant to ≥ 2 tyrosine kinase inhibitor treatments. This phase I study assessed the disposition, elimination, and safety of 14C-omacetaxine in patients with solid tumors. Methods The study

  9. Transient mild hyperthermia induces E-selectin mediated localization of mesoporous silicon vectors in solid tumors.

    Directory of Open Access Journals (Sweden)

    Dickson K Kirui

    Full Text Available BACKGROUND: Hyperthermia treatment has been explored as a strategy to overcome biological barriers that hinder effective drug delivery in solid tumors. Most studies have used mild hyperthermia treatment (MHT to target the delivery of thermo-sensitive liposomes carriers. Others have studied its application to permeabilize tumor vessels and improve tumor interstitial transport. However, the role of MHT in altering tumor vessel interfacial and adhesion properties and its relationship to improved delivery has not been established. In the present study, we evaluated effects of MHT treatment on tumor vessel flow dynamics and expression of adhesion molecules and assessed enhancement in particle localization using mesoporous silicon vectors (MSVs. We also determined the optimal time window at which maximal accumulation occur. RESULTS: In this study, using intravital microscopy analyses, we showed that temporal mild hyperthermia (∼1 W/cm(2 amplified delivery and accumulation of MSVs in orthotopic breast cancer tumors. The number of discoidal MSVs (1000×400 nm adhering to tumor vasculature increased 6-fold for SUM159 tumors and 3-fold for MCF-7 breast cancer tumors. By flow chamber experiments and Western blotting, we established that a temporal increase in E-selectin expression correlated with enhanced particle accumulation. Furthermore, MHT treatment was shown to increase tumor perfusion in a time-dependent fashion. CONCLUSIONS: Our findings reveal that well-timed mild hyperthermia treatment can transiently elevate tumor transport and alter vascular adhesion properties and thereby provides a means to enhance tumor localization of non-thermally sensitive particles such as MSVs. Such enhancement in accumulation could be leveraged to increase therapeutic efficacy and reduce drug dosing in cancer therapy.

  10. An overview of viral oncology in Italy - report from the Pavia meeting on solid tumors

    Directory of Open Access Journals (Sweden)

    Perfetti Vittorio

    2012-09-01

    Full Text Available Abstract This is a report on some of the research activities currently ongoing in Italy as outlined at the “Viruses and solid tumors” meeting jointly organized by the Oncology Sections of IRCCS Policlinico “San Matteo” (Pavia and IRCCS National Cancer Institute (Aviano, held in Pavia, Italy, on October 2011. Experts from the various disciplines involved in the study of the complex relationships between solid tumors and viruses met to discuss recent developments in the field and to report their personal contributions to the specified topics. Secondary end point was to establish a multidisciplinary work group specifically devoted to solid tumors and infectious agents, aimed to identify areas of common interest, promoting and establishing collaborative projects and programs, and to coordinate clinical and research activities. The group, which will be named IVOG (Italian Viral Oncology Group, will operate under the patronage of the various scientific societies of interest.

  11. Cytokine and Immuno-Gene Therapy for Solid Tumors

    Institute of Scientific and Technical Information of China (English)

    Chuan-Yuan Li; Qian Huang; Hsiang-Fu Kung

    2005-01-01

    Despite recent progress in our understanding of cancer biology and in many areas of cancer treatment, the success rate for cancer therapy remains dismal. Immunotherapy for cancer has long been an exciting field for many cancer researchers due to the possibility to mobilize the body's own immune system to eradicate cancer not only locally but also systemically. Since its initial discovery, cytokine-based immunotherapy has been vigorously and extensively investigated for cancer treatment due to the perception of it as a relatively easily purifiable, injectable form of cancer treatment agent. However, so far most cytokine-based therapy trials have fallen short of expectations. One of main obstacles is the difficulty to achieve therapeutically relevant dosage in patients without generating excessive normal tissue toxicity. The emergence of novel gene therapy approach to deliver therapeutic cytokine to tumors locally generated great excitement since it has the potential of generating sustained high local concentration of immunostimulatory cytokine without raising the systemic levels of the cytokines, which is responsible for most of the observed toxicity. In this review, we will attempt to provide an overview of the field and discuss some of the problems associated with cytokine-based immuno-gene therapy and potential solutions.Cellular & Molecular Immunology. 2005;2(2):81-91.

  12. Cytokine and Immuno-Gene Therapy for Solid Tumors

    Institute of Scientific and Technical Information of China (English)

    Chuan-YuanLi; QianHuang; Hsiang-FuKung

    2005-01-01

    Despite recent progress in our understanding of cancer biology and in many areas of cancer treatment, the success rate for cancer therapy remains dismal. Immunotherapy for cancer has long been an exciting field for many cancer researchers due to the possibility to mobilize the body's own immune system to eradicate cancer not only locally but also systemically. Since its initial discovery, cytokine-based immunotherapy has been vigorously and extensively investigated for cancer treatment due to the perception of it as a relatively easily purifiable, injectable form of cancer treatment agent. However, so far most cytokine-based therapy trials have fallen short ofexpectations. One of main obstacles is the difficulty to achieve therapeutically relevant dosage in patients without generating excessive normal tissue toxicity. The emergence of novel gene therapy approach to deliver therapeutic cytokine to tumors locally generated great excitement since it has the potential of generating sustained high local concentration of immunostimulatory cytokine without raising the systemic levels of the cytokines, which is responsible for most of the observed toxicity. In this review, we will attempt to provide an overview of the field and discuss some of the problems associated with cytokine-based immuno-gene therapy and potential solutions. Cellular & Molecular Immunology. 2005;2(2):81-91.

  13. Relaxin treatment of solid tumors: effects on electric field-mediated gene delivery.

    Science.gov (United States)

    Henshaw, Joshua; Mossop, Brian; Yuan, Fan

    2008-08-01

    Pulsed electric fields have been shown to enhance interstitial transport of plasmid DNA (pDNA) in solid tumors in vivo. However, the extent of enhancement is still limited partly due to the collagen component in extracellular matrix. To this end, effects of collagen remodeling on interstitial electrophoresis were investigated by pretreatment of tumor-bearing mice with a recombinant human relaxin (rh-Rlx). In the study, two tumor lines (4T1 and B16.F10) were examined and implanted s.c. to establish two murine models: dorsal skin-fold chamber (DSC) and hind leg. Effects of rh-Rlx on pDNA electrophoresis were measured either directly in the DSC model or indirectly in the hind leg model via reporter gene expression. It was observed that rh-Rlx treatment reduced collagen levels in the hind leg tumors but not in the DSC tumors. The observation correlated with the results from electromobility experiments, where rh-Rlx treatment enhanced transgene expression in 4T1 hind leg tumors but did not increase the electromobility of pDNA in the DSC tumors. In addition, it was observed that pDNA binding to collagen could block its diffusion in collagen gel in vitro. These observations showed that effects of rh-Rlx on the collagen content depended on microenvironment in solid tumors and that rh-Rlx treatment would enhance electric field-mediated gene delivery only if it could effectively reduce the collagen content in collagen-rich tumors.

  14. Modulation of macrophage cytokine profiles during solid tumor progression: susceptibility to Candida albicans infection

    Directory of Open Access Journals (Sweden)

    Venturini James

    2009-06-01

    Full Text Available Abstract Background In order to attain a better understanding of the interactions between opportunist fungi and their hosts, we investigated the cytokine profile associated with the inflammatory response to Candida albicans infection in mice with solid Ehrlich tumors of different degrees. Methods Groups of eight animals were inoculated intraperitoneally with 5 × 106 C. albicans 7, 14 or 21 days after tumor implantation. After 24 or 72 hours, the animals were euthanized and intraperitoneal lavage fluid was collected. Peritoneal macrophages were cultivated and the levels of IFN-γ, TNF-α, IL-12, IL-10 and IL-4 released into the supernatants were measured by ELISA. Kidney, liver and spleen samples were evaluated for fungal dissemination. Tumor-free animals and animals that had only been subjected to C. albicans infection were used as control groups. Results Our results demonstrated that the mice produced more IFN-γ and TNF-α and less IL-10, and also exhibited fungal clearance, at the beginning of tumor evolution. With the tumor progression, this picture changed: IL-10 production increased and IFN-γ and TNF-α release decreased; furthermore, there was extensive fungal dissemination. Conclusion Our results indicate that solid tumors can affect the production of macrophage cytokines and, in consequence, affect host resistance to opportunistic infections.

  15. Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

    Science.gov (United States)

    Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

    2016-02-01

    Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

  16. Phase I study of a systemically delivered p53 nanoparticle in advanced solid tumors.

    Science.gov (United States)

    Senzer, Neil; Nemunaitis, John; Nemunaitis, Derek; Bedell, Cynthia; Edelman, Gerald; Barve, Minal; Nunan, Robert; Pirollo, Kathleen F; Rait, Antonina; Chang, Esther H

    2013-05-01

    Selective delivery of therapeutic molecules to primary and metastatic tumors is optimal for effective cancer therapy. A liposomal nanodelivery complex (scL) for systemic, tumor-targeting delivery of anticancer therapeutics has been developed. scL employs an anti-transferrin receptor (TfR), scFv as the targeting molecule. Loss of p53 suppressor function, through mutations or inactivation of the p53 pathway, is present in most human cancers. Rather than being transiently permissive for tumor initiation, persistence of p53 dysfunction is a continuing requirement for maintaining tumor growth. Herein, we report results of a first-in-man Phase I clinical trial of restoration of the normal human tumor suppressor gene p53 using the scL nanocomplex (SGT-53). Minimal side effects were observed in this trial in patients with advanced solid tumors. Furthermore, the majority of patients demonstrated stable disease. One patient with adenoid cystic carcinoma had his status changed from unresectable to resectable after one treatment cycle. More significantly, we observed an accumulation of the transgene in metastatic tumors, but not in normal skin tissue, in a dose-related manner. These results show not only that systemically delivered SGT-53 is well tolerated and exhibits anticancer activity, but also supply evidence of targeted tumor delivery of SGT-53 to metastatic lesions.

  17. Preclinical evaluation of engineered oncolytic herpes simplex virus for the treatment of pediatric solid tumors.

    Directory of Open Access Journals (Sweden)

    Michael L Megison

    Full Text Available Recently, investigators showed that mice with syngeneic murine gliomas that were treated with a neuroattenuated oncolytic herpes simplex virus-1 (oHSV, M002, had a significant increase in survival. M002 has deletions in both copies of the γ134.5 gene, enabling replication in tumor cells but precluding infection of normal cells. Previous studies have shown antitumor effects of other oHSV against a number of adult tumors including hepatocellular carcinoma and renal cell carcinoma. The purpose of the current study was to investigate the oncolytic potential of M002 against difficult to treat pediatric liver and kidney tumors. We showed that the oHSV, M002, infected, replicated, and decreased cell survival in hepatoblastoma, malignant rhabdoid kidney tumor, and renal sarcoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly increased survival and decreased tumor growth. Finally, these studies showed that the primary entry protein for oHSV, CD111 (nectin-1 was present in human hepatoblastoma and malignant rhabdoid kidney tumor specimens. We concluded that M002 effectively targeted these rare aggressive tumor types and that M002 may have potential for use in children with unresponsive or relapsed pediatric solid tumors.

  18. Preclinical Evaluation of Engineered Oncolytic Herpes Simplex Virus for the Treatment of Pediatric Solid Tumors

    Science.gov (United States)

    Megison, Michael L.; Gillory, Lauren A.; Stewart, Jerry E.; Nabers, Hugh C.; Mroczek-Musulman, Elizabeth; Waters, Alicia M.; Coleman, Jennifer M.; Kelly, Virginia; Markert, James M.; Gillespie, G. Yancey; Friedman, Gregory K.; Beierle, Elizabeth A.

    2014-01-01

    Recently, investigators showed that mice with syngeneic murine gliomas that were treated with a neuroattenuated oncolytic herpes simplex virus-1 (oHSV), M002, had a significant increase in survival. M002 has deletions in both copies of the γ134.5 gene, enabling replication in tumor cells but precluding infection of normal cells. Previous studies have shown antitumor effects of other oHSV against a number of adult tumors including hepatocellular carcinoma and renal cell carcinoma. The purpose of the current study was to investigate the oncolytic potential of M002 against difficult to treat pediatric liver and kidney tumors. We showed that the oHSV, M002, infected, replicated, and decreased cell survival in hepatoblastoma, malignant rhabdoid kidney tumor, and renal sarcoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly increased survival and decreased tumor growth. Finally, these studies showed that the primary entry protein for oHSV, CD111 (nectin-1) was present in human hepatoblastoma and malignant rhabdoid kidney tumor specimens. We concluded that M002 effectively targeted these rare aggressive tumor types and that M002 may have potential for use in children with unresponsive or relapsed pediatric solid tumors. PMID:24497984

  19. Management of Facial Paralysis due to Extracranial Tumors.

    Science.gov (United States)

    Fritz, Michael; Rolfes, Bryan N

    2015-04-01

    Treatment of advanced parotid or cutaneous malignancies often requires sacrifice of the facial nerve as well as resection of the parotid gland and surrounding structures. In addition to considerations regarding reinnervation and dynamic reanimation, reconstruction in this setting must take into account unique factors such as soft tissue volume deficits and the high likelihood of adjunctive radiation therapy. Furthermore, considerations of patient comorbidities including advanced age and poor long-term prognosis often influence reconstructive modality. The optimal reconstructive technique would provide potential for restoration of facial tone and voluntary movement as well as immediate restoration of facial support and function. Beyond considerations of facial movement and rest position, restoration of lost soft tissue volume is critical to obtain facial symmetry. To control long-term volume in the setting of adjunctive radiation therapy, vascularized tissue is required. In this chapter, we describe a comprehensive approach to the management of radical parotidectomy and similar facial defects that addresses these concerns and also describes management strategies over time. Specific techniques employed include anterolateral thigh free flaps, nerve grafting utilizing motor nerves to the vastus lateralis muscle, and orthodromic temporalis tendon transfer. Further considerations relative to the eye, forehead, and long-term facial refinement are also discussed.

  20. Effect of microvascular distribution and its density on interstitial fluid pressure in solid tumors: A computational model.

    Science.gov (United States)

    Mohammadi, M; Chen, P

    2015-09-01

    Solid tumors with different microvascular densities (MVD) have been shown to have different outcomes in clinical studies. Other studies have demonstrated the significant correlation between high MVD, elevated interstitial fluid pressure (IFP) and metastasis in cancers. Elevated IFP in solid tumors prevents drug macromolecules reaching most cancerous cells. To overcome this barrier, antiangiogenesis drugs can reduce MVD within the tumor and lower IFP. A quantitative approach is essential to compute how much reduction in MVD is required for a specific tumor to reach a desired amount of IFP for drug delivery purposes. Here we provide a computational framework to investigate how IFP is affected by the tumor size, the MVD, and location of vessels within the tumor. A general physiologically relevant tumor type with a heterogenous vascular structure surrounded by normal tissue is utilized. Then the continuity equation, Darcy's law, and Starling's equation are applied in the continuum mechanics model, which can calculate IFP for different cases of solid tumors. High MVD causes IFP elevation in solid tumors, and IFP distribution correlates with microvascular distribution within tumor tissue. However, for tumors with constant MVD but different microvascular structures, the average values of IFP were found to be the same. Moreover, for a constant MVD and vascular distribution, an increase in tumor size leads to increased IFP.

  1. Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura

    DEFF Research Database (Denmark)

    Amin, Faisal Mohammad; Asghar, Mohammad Sohail; Hougaard, Anders

    2013-01-01

    Extracranial arterial dilatation has been hypothesised to be the cause of pain in patients who have migraine without aura. To test that hypothesis, we aimed to measure extracranial and intracranial arteries during attacks of migraine without aura.......Extracranial arterial dilatation has been hypothesised to be the cause of pain in patients who have migraine without aura. To test that hypothesis, we aimed to measure extracranial and intracranial arteries during attacks of migraine without aura....

  2. Primary extra-cranial meningioma following total hip replacement

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, T.J.; Beggs, I. [Royal Infirmary, Department of Radiology, Edinburgh (United Kingdom); Patton, J.T.; Porter, D. [Royal Infirmary, Department of Orthopaedics, Edinburgh (United Kingdom); Salter, D.M.; Al-Nafussi, A. [Royal Infirmary, Department of Pathology, Edinburgh (United Kingdom)

    2009-01-15

    A 61-year-old man presented with pain at the left hip and decreased mobility 10 years after total hip replacement. Imaging demonstrated a large destructive expansile mass adjacent to the prosthesis. Histological analysis confirmed the presence of an extra-cranial meningioma. Primary tumours after total hip replacement are rare and include soft tissue sarcomas, bone sarcomas and lymphomas. To our knowledge, no previous cases of primary extracranial meningioma have been identified. The imaging features, histology, pathogenesis and differential diagnosis are discussed. (orig.)

  3. Solid and Cystic Tumor (SCT of the Pancreas in an Adult Man

    Directory of Open Access Journals (Sweden)

    K. Ohiwa

    1997-01-01

    Full Text Available Solid and cystic tumor (SCT of the pancreas predominantly Occurs in women, and the occurrence in men is extremely rare. We experienced a male case of SCT. A 38-year-old man was admitted with the complaint of upper abdominal pain. CT scan showed the presence of a mass in the head of the pancreas. The mass was composed of high density areas and low density areas. Ultrasonograms revealed the mass being composed of high echoic areas and low echoic areas. The mass .was hypovascular on angiography. SCT was suspected and pancreaticoduodenectomy was performed. The cut surface of the tumor showed mainly cystic degenerative areas containing dark red hemorrhagic materials. Microscopically, there were solid areas in the periphery and pseudopapillary areas in the center. No metastasis was found in the removed lymph nodes. The tumor cells were not stained by Grimelius' silver stain. The tumor cells were positive for alpha-l-antitrypsin (AAT and neuron-specific enolase (NSE. Pancreatic hormones such as insulin, glucagon, and somatostatin were all negative. Electron micrograph showed that tumor cells were rich in mitochondria. Zymogen granules and neurosecretory granules were not detected. Estrogen receptor (ER and progesterone receptor (PR were both negative.

  4. Low energy scatter due to in-situ irradiation of solid tumors in laboratory rats

    Energy Technology Data Exchange (ETDEWEB)

    Ritenour, E.R. Jr.

    1980-01-01

    A study of the pattern of scattered radiation in laboratory rat cadavers during irradiation of solid tumors on the animals' flanks was performed. The animals were wrapped in a lead shield having a circular cutout through which the tumor protruded. Irradiations were performed with a 250 kVp 15ma X-ray machine with a measured half value layer of 1.39 mmCu. Lead shielding was of sufficient thickness to attenuate essentially all of the beam. The absorbed dose measured in the animal was then due to internal scatter from the tumor. Arrays of thermoluminescent dosimeters (TLDs) were placed beneath the skin of 17 animals bearing a solid tumor (hepatoma H-4-II-E). Absorbed dose was seen to vary isotropically, decreasing as the inverse distance squared from the tumor. Analysis of experimental error played a major role in this study. A pilot study resulted in standard errors that were 35% of the mean absorbed dose measurements. A careful reassessment of methods of manipulating the animals and the dosimetry system resulted in a reduction in standard error to 14% of the mean for small groups (less than 10 animals).

  5. Solid-Pseudopapillary Tumor of the Pancreas: One Case Report and Literatures Review

    Institute of Scientific and Technical Information of China (English)

    Shifu Hu; Naiqiang Cui; Erpeng Zhao

    2009-01-01

    @@ Introduction Solid-pseudopapillary tumor(SPT)is a very mre primary neoplasm of the pancreas.Franz first described it in 1959.It iS usually seen in young females.In spite of possible histological findings of malignancy,SPPT typically shows a benign clinical course and a low malignant potential.The pathogenesis of these tumors iS still controversial.It has been suggested that it might originate from ductal and acinar pancreatic cells,endocrine cells or pluripotential stem cells.

  6. Comparison of the EORTC criteria and PERCIST in solid tumors: a pooled analysis and review.

    Science.gov (United States)

    Kim, Jung Han

    2016-09-06

    Two sets of response criteria using PET are currently available to monitor metabolic changes in solid tumors: the criteria developed by the European Organization for Research and Treatment of Cancer (EORTC criteria) and the PET Response Criteria in Solid Tumors (PERCIST). We conducted this pooled study to investigate the strength of agreement between the EORTC criteria and PERCIST in the assessment of tumor response. We surveyed MEDLINE, EMBASE and PUBMED for articles with terms of the EORTC criteria and PERCIST between 2009 and January 2016. We searched for all the references of relevant articles and reviews using the 'related articles' feature in the PUBMED. There were six articles with the data on the comparison of the EORTC criteria and PERCIST. A total of 348 patients were collected; 190 (54.6%) with breast cancer, 81 with colorectal cancer, 45 with lung cancer, 14 with basal cell carcinoma in the skin, 12 with stomach cancer, and 6 with head and neck cancer. The agreement of tumor response between the EORTC criteria and PERCIST was excellent (k = 0.946). Of 348 patients, only 12 (3.4%) showed disagreement between the two criteria in the assessment of tumor response. The shift of tumor response between the EORTC criteria and PERCIST occurred mostly in patients with PMR and SMD. The estimated overall response rates were not significantly different between the two criteria (72.7% by EORTC vs. 73.6% by PERCIST). In conclusion, this pooled analysis demonstrates that the EORTC criteria and PERCIST showed almost perfect agreement in the assessment of tumor response.

  7. Comparison of the EORTC criteria and PERCIST in solid tumors: a pooled analysis and review

    Science.gov (United States)

    Kim, Jung Han

    2016-01-01

    Two sets of response criteria using PET are currently available to monitor metabolic changes in solid tumors: the criteria developed by the European Organization for Research and Treatment of Cancer (EORTC criteria) and the PET Response Criteria in Solid Tumors (PERCIST). We conducted this pooled study to investigate the strength of agreement between the EORTC criteria and PERCIST in the assessment of tumor response. We surveyed MEDLINE, EMBASE and PUBMED for articles with terms of the EORTC criteria and PERCIST between 2009 and January 2016. We searched for all the references of relevant articles and reviews using the ‘related articles’ feature in the PUBMED. There were six articles with the data on the comparison of the EORTC criteria and PERCIST. A total of 348 patients were collected; 190 (54.6%) with breast cancer, 81 with colorectal cancer, 45 with lung cancer, 14 with basal cell carcinoma in the skin, 12 with stomach cancer, and 6 with head and neck cancer. The agreement of tumor response between the EORTC criteria and PERCIST was excellent (k = 0.946). Of 348 patients, only 12 (3.4%) showed disagreement between the two criteria in the assessment of tumor response. The shift of tumor response between the EORTC criteria and PERCIST occurred mostly in patients with PMR and SMD. The estimated overall response rates were not significantly different between the two criteria (72.7% by EORTC vs. 73.6% by PERCIST). In conclusion, this pooled analysis demonstrates that the EORTC criteria and PERCIST showed almost perfect agreement in the assessment of tumor response. PMID:27517621

  8. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review.

    LENUS (Irish Health Repository)

    Shrotriya, Shiva

    2015-01-01

    A systematic literature review was done to determine the relationship between elevated CRP and prognosis in people with solid tumors. C-reactive protein (CRP) is a serum acute phase reactant and a well-established inflammatory marker. We also examined the role of CRP to predict treatment response and tumor recurrence.

  9. The Way that PEGyl-DSPC Liposomal Doxorubicin Particles Penetrate into Solid Tumor Tissue

    Directory of Open Access Journals (Sweden)

    Xing Qing Pan

    2006-01-01

    Full Text Available Background: For enhancement of drug effectiveness and reduction of drug toxicity, liposomal drugs have been studied in laboratories and clinics for decades. Although the results obtained from in vitro are encouraging, but the results from in vivo tests were not satisfactory. The main reasons for this situation were that we do not have enough information about the way how liposomal particles penetrating into solid tumor tissue, and what happening to the liposome particles after they got into the tumor tissue. In this paper, we are going to report the results from our observations on the way folic acid targeted and non-targeted PEGyl-DSPC liposomal doxorubicin particles penetrate into solid tumor tissue.Methods: Subcutaneous transplanted murine L1210JF solid tumors in mice were used as a model. PEGyl liposomal doxorubicins were injected through tail venue, and tumor tissue samples were collected at special time points. Cryosections were cut and dried by a fl owing of air after mounted on the slides right away. Then the dried cryosections were stained in water systems; the blood vessel cells were stained with green fluorescent FITC labeled antibody against CD31 antigen; the nuclei of the living cells were stained with a blue fluorescent dye DAPI. Since the whole procedure was carried out in aquatic system, the red color fluorescent liposomal doxorubicin particles remain visible under fl uorescence microscope.Results: Both folate conjugated and non-conjugated PEGyl-DSPC liposomal doxorubicin particles were only leaking out from the broken holes of blood vessels with a special direction and spread out for a limited distance, which was similar to the results showed before, in that observation a latex microsphere sample was used as a model.

  10. Chromosomal mapping of specific DNA gains and losses in solid tumors using comparative genomic hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Schrock, E.; Manoir, S. du; Speicher, M. [National Center for Human Genome Research, Bethesda, MD (United States)] [and others

    1994-09-01

    Comparative genomic hybridization (CGH) is a new molecular cytogenetic technique that is based on two color FISH and quantitative digital imaging microscopy. CGH is used to comprehensively survey tumor genomes for copy number changes and to determine the map position of amplification sites on normal reference chromosomes. CGH was used to analyze 107 different solid tumors, including 16 low grade astrocytomas, 15 recurrent astrocytic tumors, 13 high grade astrocytomas, 13 small cell lung cancers (SCLC), 14 breast cancer samples (7 diploid and 7 aneupoid tumors), 18 chromophobe renal cell carcinomas and 5 seminomas. Tumor DNA was extracted from frozen tissue, autopic material and formalin fixed, paraffin-embedded tissue samples. Our results revealed tumor specific gains and losses of certain chromosomes or chromosomal subregions (e.g., chromosomes 7 and 10 in glioblastomas, chromosomes 3 and 5 in SCLC). Numerous DNA-amplifications were mapped on reference metaphase and prometaphase chromosomes. The frequent amplification of the EGFR gene (malignant gliomas), protooncogenes of the myc family (SCLC) and of c-myc, int-2 and c-erbB2 (breast cancer) was confirmed. Many additional amplification sites, however, were mapped that were not described before. The results of CGH analysis were independently confirmed by means of cytogenetic banding analysis, interphase cytogenetics with region specific DNA-clones, Southern-Blot analysis, DNA-cytometry and studies of loss of heterozygosity.

  11. Computed tomography perfusion evaluation after extracranial-intracranial bypass surgery

    NARCIS (Netherlands)

    Vos, P.C.; Riordan, A.J.; Smit, E.J.; Jong, H.W. de; Zwan, A. van der; Velthuis, B.K.; Viergever, M.A.; Dankbaar, J.W.

    2015-01-01

    OBJECTIVE: Perfusion imaging is increasingly used for postoperative evaluation of extracranial to intracranial (EC-IC) bypass surgery. Altered hemodynamics and delayed arrival of the contrast agent in the area fed by the bypass can influence perfusion measurement. We compared perfusion asymmetry obt

  12. [Peripheral nerve injuries complicating extracranial vascular surgery (author's transl)].

    Science.gov (United States)

    Grobe, T; Raithel, D

    1978-10-01

    Peripheral nerve injuries may complicate extracranial vascular surgery. Pareses of the recurrent and hypoglossal nerves are clinically important. The nervus laryngeus superior, the ramus marginalis mandibulae of the facial nerve and the brachial plexus may be involved. Horner's syndrom indicating damage of sympathetic fibers may also appear. Lesions of the glossopharyngeal, vagus and phrenic nerves are rather seldom.

  13. [Neonatal subgaleal haemorrhage; a potential life-threatening extracranial haemorrhage

    NARCIS (Netherlands)

    Fuijkschot, J.; Antonius, T.A.J.; Meijers, P.W.; Vrancken, S.L.A.G.

    2008-01-01

    A female neonate delivered at term developed hypovolemic shock due to a subgaleal haemorrhage, i.e. extracranial bleeding between the galea aponeurotica and the cranial periosteum. The subgaleal haemorrhage was most likely the result of a traumatic vacuum extraction. The patient was treated with lar

  14. Computed tomography perfusion evaluation after extracranial-intracranial bypass surgery

    NARCIS (Netherlands)

    Vos, Pieter C.; Riordan, Alan J.; Smit, Ewoud J.; de Jong, Hugo W. A. M.; van der Zwan, Albert; Velthuis, BK; Viergever, Max A.; Dankbaar, Jan Willem

    2015-01-01

    Objective: Perfusion imaging is increasingly used for postoperative evaluation of extracranial to intracranial (EC-IC) bypass surgery. Altered hemodynamics and delayed arrival of the contrast agent in the area fed by the bypass can influence perfusion measurement. We compared perfusion asymmetry obt

  15. Emerging therapies targeting tumor vasculature in multiple myeloma and other hematologic and solid malignancies.

    Science.gov (United States)

    Podar, K; Anderson, K C

    2011-11-01

    Research on the formation of new blood vessels (angiogenesis) in general and vascular endothelial growth factor (VEGF) in particular is a major focus in biomedicine and has led to the clinical approval of the monoclonal anti- VEGF antibody bevazicumab; and the second-generation multitargeted receptor kinase inhibitors (RTKIs) sorafenib, sunitinib, and pazopanib. Although these agents show significant preclinical and clinical anti-cancer activity, they prolong overall survival of cancer patients for only months, followed by a restoration of tumor growth and progression. Therefore, there is a clear need to increase our understanding of tumor angiogenesis and the development of resistance. In this review we discuss up-to-date knowledge on mechanisms of tumor angiogenesis, and summarize preclinical and clinical data on existing and potential future anti-angiogenic agents and treatment strategies for Multiple Myeloma (MM) and other hematologic and solid malignancies.

  16. Clinicopathological study of solid and pseudopapillary tumor of pancreas: Emphasis on magnetic resonance imaging findings

    Institute of Scientific and Technical Information of China (English)

    Chi-Chang Yu; Jeng-Hwei Tseng; Chun-Nan Yeh; Tsann-Long Hwang; Yi-Yin Jan

    2007-01-01

    AIM:To report the Clinicopathological features and magnetic resonance imaging (MRI) findings of solid and pseudopapillary tumor (SPT) of pancreas.METHODS:From 1981 to 2005,26 surgically treated cases of SPT were retrospectively reviewed. MRI findings of the latest 11 consecutive SPT cases were investigated.RESULTS:There were 25 women and one man having SPT (median age:23 year) with a median tumor size of 7.5 cm. Among them,nine patients developed solid pseudopapillary carcinoma. During the median follow-up period of 66 mo,the 5-year survival rate of the 26 SPT patients was 96.2%. Three MRI features were proposed including Type 1 image,displaying SPT with completely solid part. All SPT patients with type 1 image were detected incidentally. Type 2 image displays of SPT with solid mass hemorrhage and type 3 image with massive hemorrhage. All the eight SPT patients with type 2 and 3 images suffered abdominal pain due to hemorrhage from SPT.CONCLUSION:SPT had a favorable survival rate irrespective of surgical procedures,malignancy,and MRI findings,however,MRI could reliably correlate with its Clinicopathological features.

  17. Effect of Arrabidaea chica extracts on the Ehrlich solid tumor development

    Directory of Open Access Journals (Sweden)

    Ana Flávia C. Ribeiro

    2012-04-01

    Full Text Available The aim of this study was to investigate the effect of Arrabidaea chica (Humb. & Bonpl. B. Verl., Bignoniaceae, extracts on Ehrlich solid tumor development in Swiss mice. Leaves of A. chica were extracted with two distinct solvents, ethanol and water. The phytochemical analysis of the extracts indicated different classes of secondary metabolites like as anthocyanidins, flavonoids, tannins and saponins. Ethanol (EE and aqueous (AE extracts at 30 mg/kg reduced the development of Ehrlich solid tumor after ten days of oral treatment. The EE group presented increase in neutrophil count, α1 and β globulin values, and decrease of α2 globulin values. Furthermore, EE reduced the percentage of CD4+ T cells in blood but did not alter the percentage of inflammatory mononuclear cells associated with tumor suggesting a direct action of EE on tumor cells. Reduced tumor development observed in AE group was accompanied by a lower percentage of CD4+ T lymphocytes in blood. At the tumor microenvironment, this treatment decreased the percentage of CD3+ T cells, especially due to a reduction of CD8+ T subpopulation and NK cells. The antitumor activity presented by the AE is possibly related to an anti-inflammatory activity. None of the extracts produced toxic effects in animals. In conclusion, the ethanol and aqueous extracts of A. chica have immunomodulatory and antitumor activities attributed to the presence of flavonoids, such as kaempferol. These effects appear to be related to different mechanisms of action for each extract. This study demonstrates the potential of A. chica as an antitumor agent confirming its use in traditional popular medicine.

  18. Bruton's tyrosine kinase (BTK) as a promising target in solid tumors.

    Science.gov (United States)

    Molina-Cerrillo, J; Alonso-Gordoa, T; Gajate, P; Grande, E

    2017-07-01

    Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells. Ibrutinib (PCI-32765) is an orally available small molecule that acts as an inhibitor of the BTK and is approved for the treatment of patients with some hematological malignancies. It has been suggested that ibrutinib may also have a potential antitumor activity in solid neoplasms. In this sense, ibrutinib has the ability to revert polarization of TCD4+ to Th1 lymphocytes to increase the cytotoxic ability of T CD8+ and to regulate tumor-induced immune tolerance by acting over tumor infiltrating cells activity and immunosuppressive cytokines release. Furthermore, based on its molecular activity and safety, ibrutinib has been considered as a partner for treatment combination with PI3K/AKT/mTOR inhibitors or with immune-checkpoint inhibitors, inhibiting immunosuppressive signals from the tumor microenvironment, and overcoming the immune resistance to current anti-PD1/PDL1 immunotherapeutic drugs by the CXCR4/CXCL2 pathway regulation. Currently, a broad range of different studies are evaluating the activity of ibrutinib either as single agent or in combination in patients with solid tumors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. The Prognostic Value of Decreased LKB1 in Solid Tumors: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Jian Xiao

    Full Text Available Liver kinase B1 (LKB1 is a protein kinase that regulates the growth, integrity and polarity of mammalian cells. Recent studies have reported the prognostic value of decreased LKB1 expression in different tumors. However, the results of these studies remain controversial. Therefore, this meta-analysis was performed to more accurately estimate the role of decreased LKB1 in the prognostication of human solid tumors.A systematic literature search in the electronic databases PubMed, Embase, Web of Science and CNKI (updated to October 15, 2015 was performed to identify eligible studies. The overall survival (OS, relapse-free survival (RFS, disease-free survival (DFS and clinicopathological features data were collected from these studies. The hazard ratios (HRs, odds ratios (ORs and 95% confidence intervals (CIs were calculated and pooled with a random-effects models using Stata12.0 software.A total of 14 studies covering 1915 patients with solid tumors were included in this meta-analysis. Decreased LKB1 was associated with poorer OS in both the univariate (HR: 1.86, 95%CI: 1.42-2.42, P<0.001 and multivariate (HR: 1.55, 95%CI: 1.09-2.21, P = 0.015 analyses. A subgroup analysis revealed that the associations between decreased LKB1 and poor OS were significant within the Asian region (HR 2.18, 95%CI: 1.66-2.86, P<0.001 and obvious for lung cancer (HR: 2.16, 95%CI: 1.47-3.18, P<0.001. However, the articles that involved analyses of both RFS and DFS numbered only 3, and no statistically significant correlations of decreased LKB1 with RFS or DFS were observed in this study. Additionally, the pooled odds ratios (ORs indicated that decreased LKB1 was associated with larger tumor size (OR: 1.60, 95%CI: 1.09-2.36, P = 0.017, lymph node metastasis (OR: 2.41, 95%CI: 1.53-3.78, P<0.001 and a higher TNM stage (OR: 3.35, 95%CI: 2.20-5.09, P<0.001.These results suggest that decreased LKB1 expression in patients with solid tumors might be related to poor prognosis and

  20. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 and Temsirolimus in Treating Patients With Advanced Solid Tumors

    Science.gov (United States)

    2014-05-29

    Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Recurrent Renal Cell Cancer; Stage III Endometrial Carcinoma; Stage III Renal Cell Cancer; Stage IV Endometrial Carcinoma; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  1. Chimeric antigen receptor T cells: a novel therapy for solid tumors.

    Science.gov (United States)

    Yu, Shengnan; Li, Anping; Liu, Qian; Li, Tengfei; Yuan, Xun; Han, Xinwei; Wu, Kongming

    2017-03-29

    The chimeric antigen receptor T (CAR-T) cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs) expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII) was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. The third generation of CAR-T demonstrates increased antitumor cytotoxicity and persistence through modification of CAR structure. In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2), and mesothelin (MSLN), as well as the challenges for CAR-T cell therapy.

  2. [High-dose chemotherapy as a strategy to overcome drug resistance in solid tumors].

    Science.gov (United States)

    Selle, Frédéric; Gligorov, Joseph; Soares, Daniele G; Lotz, Jean-Pierre

    2016-10-01

    The concept of high-doses chemotherapy was developed in the 1980s based on in vitro scientific observations. Exposure of tumor cells to increasing concentrations of alkylating agents resulted in increased cell death in a strong dose-response manner. Moreover, the acquired resistance of tumor cells could be overcome by dose intensification. In clinic, dose intensification of alkylating agents resulted in increased therapeutic responses, however associated with significant hematological toxicity. Following the development of autologous stem cells transplantation harvesting from peripheral blood, the high-doses of chemotherapy, initially associated with marked toxic effects, could be more easily tolerated. As a result, the approach was evaluated in different types of solid tumors, including breast, ovarian and germ cell tumors, small cell lung carcinoma, soft tissue sarcomas and Ewing sarcoma. To date, high-doses chemotherapy with hematopoietic stem cells support is only used as a salvage therapy to treat poor prognosis germ cell tumors patients with chemo-sensitive disease. Regarding breast and ovarian cancer, high-doses chemotherapy should be considered only in the context of clinical trials. However, intensive therapy as an approach to overcome resistance to standard treatments is still relevant. Numerous efforts are still ongoing to identify novel therapeutic combinations and active treatments to improve patients' responses.

  3. Clinicopathologic features and surgical outcome of solid pseudopapillary tumor of the pancreas: analysis of 17 cases

    Directory of Open Access Journals (Sweden)

    Wang Xiao-Guang

    2013-02-01

    Full Text Available Abstract Background We summarize our experience of the diagnosis, surgical treatment, and prognosis of solid pseudopapillary tumors (SPTs. Methods We carried out a retrospective study of clinical data from a series of 17 patients with SPT managed in two hospitals between October 2001 and November 2011. Results All of the 17 patients were female and the average age at diagnosis was 26.6 years (range 11 years to 55 years. The tumor was located in the body or tail in ten patients, the head in five patients, and the neck in two patients. The median tumor size was 5.5 cm (range 2 cm to 10 cm. All 17 patients had curative resections, including seven distal pancreatectomies, five local resections, four pancreaticoduodenectomies, and one central pancreatectomy. Two patients required concomitant splenic vein resection due to local tumor invasion. All patients were alive and disease-free at a median follow-up of 48.2 months (range 2 to 90 months. There were no significant associations between clinicopathologic factors and malignant potential of SPT. Ki-67 was detected in three patients with pancreatic parenchyma invasion. Conclusions The SPT is an infrequent tumor, typically affecting young women without notable symptoms. Surgical resection is justified even in the presence of local invasion or metastases, as patients demonstrate excellent long-term survival. Positive immunoreactivity for Ki-67 may predict the malignant potential of SPTs.

  4. Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.

    Directory of Open Access Journals (Sweden)

    Hamid R Molavian

    Full Text Available Hypoxia and acidity are two main microenvironmental factors intimately associated with solid tumors and play critical roles in tumor growth and metastasis. The experimental results of Helmlinger and colleagues (Nature Medicine 3, 177, 1997 provide evidence of a lack of correlation between these factors on the micrometer scale in vivo and further show that the distribution of pH and pO(2 are heterogeneous. Here, using computational simulations, grounded in these experimental results, we show that the lack of correlation between pH and pO(2 and the heterogeneity in their shapes are related to the heterogeneous concentration of buffers and oxygen in the blood vessels, further amplified by the network of blood vessels and the cell metabolism. We also demonstrate that, although the judicious administration of anti-angiogenesis agents (normalization process in tumors may lead to recovery of the correlation between hypoxia and acidity, it may not normalize the pH throughout the whole tumor. However, an increase in the buffering capacity inside the blood vessels does appear to increase the extracellular pH throughout the whole tumor. Based on these results, we propose that the application of anti-angiogenic agents and at the same time increasing the buffering capacity of the tumor extracellular environment may be the most efficient way of normalizing the tumor microenvironment. As a by-product of our simulation we show that the recently observed lack of correlation between glucose consumption and hypoxia in cells which rely on respiration is related to the inhomogeneous consumption of glucose to oxygen concentration. We also demonstrate that this lack of correlation in cells which rely on glycolysis could be related to the heterogeneous concentration of oxygen inside the blood vessels.

  5. Risk factors associated with recurrence in patients with solid pseudopapillary tumors of the pancreas.

    Science.gov (United States)

    Serrano, Pablo E; Serra, Stefano; Al-Ali, Hassan; Gallinger, Steven; Greig, Paul D; McGilvray, Ian D; Moulton, Carol-Anne; Wei, Alice C; Cleary, Sean P

    2014-11-28

    Solid pseudopapillary tumors (SPT) are rare, generally low grade pancreatic neoplasms that occasionally display malignant behavior. To analyze the clinical and pathological features associated with increased risk of recurrence of SPT. Cohort study of patients with SPT who underwent resection of the primary tumor and in selected cases resection of metastatic disease from 1999-2013 at a single tertiary care Hepatopancreatobiliary center. Risk factors for recurrence were statistically analyzed. There were 32 patients. The mean age was 35.65 years (standard deviation: 12.26), 26/32, 81.25% were female. Median size of resected tumors was 4.7 cm (1.1-14.5). Most were solid and cystic (22/32, 68.75%), encapsulated (27/32, 84.4%) and located in the pancreatic body or tail (22/32, 68.75%). All displayed strong β-catenin, cyclin D1, CD56, and progesterone receptor staining with loss of E-cadherin. Most stained positive for vimentin (15/16, 93.75%) and CD10 (17/18, 94.4%). Median follow-up was 43 months (range: 3-207); 3/32, 9.38% recurred (all after 5-years from curative resection) and 1 died by the end of the study period, 11 years after diagnosis. Patients who developed recurrences (n=3) more commonly had synchronous metastases at presentation (P=0.006), lymphovascular invasion (P=0.04) and invasion of tumor capsule (P=0.08) compared to those who did not have disease recurrence. Lymphovascular invasion, synchronous metastases and local invasion of tumor capsule are associated with aggressive behavior. Since recurrences may occur >5 years from resection, this high-risk group should undergo extended follow-up. Progression and recurrence is slow, therefore, resection of liver metastases can offer long-term survival.

  6. Preliminary evidence for biologic activity of toceranib phosphate (Palladia®) in solid tumors

    Science.gov (United States)

    London, Cheryl; Mathie, Tamra; Stingle, Nicole; Clifford, Craig; Haney, Siobhan; Klein, Mary K.; Beaver, Linda; Vickery, Kate; Vail, David M.; Hershey, Betsey; Ettinger, Susan; Vaughan, Andrew; Alvarez, Francisco; Hillman, Lorin; Kiselow, Mike; Thamm, Doug; Higginbotham, Mary Lynn; Gauthier, Meredith; Krick, Erika; Phillips, Brenda; LaDue, Tracy; Jones, Pam; Bryan, Jeffery; Gill, Virginia; Novasad, Andrew; Fulton, Lisa; Carreras, Janet; McNeill, Conor; Henry, Carolyn; Gillings, Sarah

    2013-01-01

    The purpose of this study was to provide an initial assessment of the potential biologic activity of toceranib phosphate (Palladia®) in select solid tumors in dogs. Cases in which toceranib was used to treat dogs with anal sac anal gland adenocarcinoma, metastatic osteosarcoma, thyroid carcinoma, head and neck carcinoma, and nasal carcinoma were included. Clinical benefit (CB) was observed in 63/85 (74%) dogs including 28/32 anal sac tumors (8PR, 20SD), 11/23 osteosarcomas (1PR, 10SD), 12/15 thyroid carcinomas (4PR, 8SD), 7/8 head and neck carcinomas (1CR, 5PR, 1SD) and 5/7 (1CR, 4SD) nasal carcinomas. For dogs experiencing CB, the median dose of toceranib was 2.8 mg/kg, 36/63 (58.7%) were dosed on a Monday/Wednesday/Friday basis, and 47/63 (74.6%) were treated 4 months or longer. While these data povide preliminary evidence that toceranib exhibits CB in dogs with certain solid tumors, future prospective studies are necessary to define its true activity. PMID:22236194

  7. INVESTIGATION ON EFFECT OF DRUG DOSING REGIMENTS ON DRUG DELIVERY IN SOLID TUMOR VIA LUMPED PARAMETER MODELING AND ANIMAL EXPERIMENTS

    Institute of Scientific and Technical Information of China (English)

    GAO Ci-xiu; XU Shi-xiong; JIANG Yu-ping; TU Jiang-long

    2009-01-01

    This work aims to investigate the effects of dosing regiments on drug delivery in solid tumors and to validate them with experiments on rats.The lumped parameter models of pharmacokinetics and of drug delivery in tumor were developed to simulate time courses of average drug concentration(Ct)of tumor interstitium in two types of dosing regiments(i.e.,single-shot and triple-shot ones).The two regiments were performed via antitumor drug,hydroxycamptothecin(HCPT),on rats,to measure the drug concentration in the tumor.The simulations of the drug concentration in the tumor of the two dosing regiments were conducted and compared with the experimental data on rats.The coefficients in the models were investigated.It is concluded that the triple-shot method is more effective than that of single-shot injection.The present lumped-parameter model is quantitatively competent for drug delivery in solid tumor.

  8. Novel and Expanded Oncology Drug Approvals of 2016-PART 1: New Options in Solid Tumor Management.

    Science.gov (United States)

    Knepper, Todd C; Saller, James; Walko, Christine M

    2017-02-15

    The nonradiologic medical management of solid tumors has evolved from the use of traditional cytotoxic agents to modern targeted therapies, monoclonal antibodies, and immunotherapies. Advances in the understanding of cancer biology and therapeutic strategies have resulted in increasing numbers of new drug applications and approvals. Consequently, practicing oncologists need to learn how the newly available agents function and what toxicities to watch for, as well as ways to optimize the use of both new drugs and previously approved drugs with new indications. In 2016, the US Food and Drug Administration approved three novel drugs for the treatment of solid malignancies-olaratumab in selected patients with soft-tissue sarcoma, atezolizumab for the treatment of bladder cancer, and rucaparib for the treatment of ovarian cancer; also in 2016, the use of previously approved anticancer agents (including atezolizumab) was expanded into 11 new patient populations. The diversity of options for patients is evident in the broad range of the 2016 approvals, which include immune checkpoint inhibitors, targeted therapies, monoclonal antibodies, and traditional cytotoxic agents. This article focuses on the new agents and indications that emerged in 2016 for solid tumor treatment. We review the drug indications, mechanisms of action, pivotal trial data, pertinent toxicities, use in special populations, and the appropriate clinical contexts for treatment planning.

  9. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

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

  10. The value of new high-throughput technologies for diagnosis and prognosis in solid tumors.

    Science.gov (United States)

    Pinto, Rosamaria; De Summa, Simona; Petriella, Daniela; Tudoran, Oana; Danza, Katia; Tommasi, Stefania

    2014-01-01

    Advances in our understanding of the molecular basis of tumors, as well as in the technology of DNA analysis, are rapidly changing the landscape of these diseases. Traditional approaches such as sequencing methods and arrays have too many limits. These have been overcome by the advent of next generation sequencing (NGS) methods which facilitate and accelerate the analysis of multiple genes and samples. These technologies allow new applications in molecular biology and medicine, for example precise analysis of RNA transcripts for gene expression; profiling of small RNAs, DNA methylation patterns and histone modification analysis; identification of splicing isoforms and of DNA regions that interact with regulatory proteins; pharmacogenomics studies and so on. In this review we describe recent applications of NGS in genomics, transcriptomics and epigenomics for a better comprehension of solid tumor metabolisms.

  11. Therapeutic potential and challenges of Natural killer cells in treatment of solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea eGras Navarro

    2015-04-01

    Full Text Available Natural killer (NK cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing requiring one–to-one target engagement and site directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME and augment adaptive immune responses by promoting differentiation, activation and/ or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach.

  12. Therapeutic Potential and Challenges of Natural Killer Cells in Treatment of Solid Tumors

    Science.gov (United States)

    Gras Navarro, Andrea; Björklund, Andreas T.; Chekenya, Martha

    2015-01-01

    Natural killer (NK) cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing, requiring one-to-one target engagement and site-directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells, and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME) and augment adaptive immune responses by promoting differentiation, activation, and/or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes, and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach. PMID:25972872

  13. Features of Extracranial Hemodynamics in Children with Bronchial Asthma

    Directory of Open Access Journals (Sweden)

    S.M. Nedelska

    2014-11-01

    Full Text Available The paper analyzes the performance of extracranial hemodynamics — volumetric and linear blood flow velocity, the state of peripheral vascular resistance and vascular reactivity at ultrasound Doppler examination of the internal carotid and vertebral arteries of 66 children with bronchial asthma and and 22 healthy children. Development of regional hypoperfusion in vertebrobasilar zone, disorders of the carotid system are proven, but these changes have not led to a decrease in the volumetric blood flow velocity in both internal carotid arteries and the total volume of cerebral blood flow, indicating the compensation of hemodynamic disturbances due to the influence of constant rates in volumetric blood flow in the carotid system. Changes in parameters of extracranial hemodynamics in children with bronchial asthma should be considered as predictor of cerebrovascular complications in this group of patients.

  14. Complications in the surgical management of children with malignant solid tumors.

    Science.gov (United States)

    Davidoff, Andrew M; Fernandez-Pineda, Israel

    2016-12-01

    With improvement in the outcomes for children with cancer has come an increasing focus on minimizing the morbidity from therapeutic interventions, including surgical procedures, while continuing to have a high likelihood of cure. Thus, an appreciation for the potential complications of surgery, both acute and long term, is critical when considering the risks and benefits of any procedure performed on a child with cancer. Although not meant to be an exhaustive review, here we discuss the most common and significant surgical complications that may occur when performing diagnostic, therapeutic, or supportive procedures in children with the most common malignant solid tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Targeting apoptosis in solid tumors: the role of bortezomib from preclinical to clinical evidence.

    Science.gov (United States)

    Russo, Antonio; Fratto, Maria E; Bazan, Viviana; Schiró, Valentina; Agnese, Valentina; Cicero, Giuseppe; Vincenzi, Bruno; Tonini, Giuseppe; Santini, Daniele

    2007-12-01

    The ubiquitin-proteasome pathway is the main proteolytic system present in the nucleus and cytoplasm of all eukaryotic cells. Apoptosis activation induced by ubiquitin-proteasome pathway inhibition makes the proteasome a new target of anticancer therapy. Bortezomib is the first proteasome inhibitor to be approved by the US FDA; in 2003 as a third line and in 2005 as a second line therapy for the treatment of multiple myeloma only. This review focuses on the use of bortezomib, not only in its therapeutic role but also, more specifically, in its biologic role and discusses the most recent applications of the drug in solid tumors, both at a preclinical and clinical level.

  16. Solid pseudopapillary tumor of the pancreas:A review of 553 cases in Chinese literature

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To sum up the clinical and pathological characte- ristics of solid pseudopapillary tumor (SPT) and the experience with it.METHODS: A total of 553 SPT patients reported in Chinese literature between January 1996 and January 2009 were retrospectively reviewed and analyzed. RESULTS: The mean age of the 553 SPT patients included in this review was 27.2 years, and the male to female ratio was 1:8.37. Their symptoms were non-specific, and nearly one third of the patients were asymptomatic. Computed tomography...

  17. Uncaria tomentosa (cat's claw) improves quality of life in patients with advanced solid tumors.

    Science.gov (United States)

    de Paula, Larissa Carvalho Lopes; Fonseca, Fernando; Perazzo, Fabio; Cruz, Felipe Melo; Cubero, Daniel; Trufelli, Damila Cristina; Martins, Suelen Patrícia Dos Santos; Santi, Patrícia Xavier; da Silva, Eliana Araújo; Del Giglio, Auro

    2015-01-01

    Cat's claw (Uncaria tomentosa) is a native Amazon plant that exhibits anti-inflammatory and antitumor properties. We wanted to assess its activity for symptom management of terminal cancer patients. This prospective phase II study assessed the effects of a 100-mg dose of a dry extract of U. tomentosa three times per day in patients with advanced solid tumors who had no further therapeutic options and a life expectancy of at least 2 months. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) and Functional Assessment of Chronic Illness Therapy - Fatigue questionnaires were used to assess the participants' quality of life, the Hospital Anxiety and Depression Scale questionnaire was used to assess anxiety and depression, and the Pittsburgh Sleep Quality Index was used to assess sleep quality. In addition, several biochemical and inflammatory parameters were analyzed. Fifty-one volunteers were recruited. Their median age was 64 (range, 33-85) years, and 47% of patients were female. More than 65% of patients had scores on the Karnofsky Performance Scale of 80% or less. Treatment improved the patients' overall quality of life (p=0.0411) and social functioning (p=0.0341), as assessed by the EORTC QLQ C-30, and reduced fatigue (p=0.0496) according to the Chalder Fatigue Questionnaire. None of the biochemical or inflammatory parameters assessed (interleukin-1 and -6, C-reactive protein, tumor necrosis factor-α, erythrocyte sedimentation rate, and α-1-acid glycoprotein) changed significantly. No tumor response was detected according to the Response Evaluation Criteria In Solid Tumors; however, the disease stabilized for more than 8 months in four participants. The medication was well tolerated by most patients. Use of cat's claw might be beneficial in patients with advanced cancer by improving their quality of life and reducing fatigue. The mechanism of action does not seem to be related to the anti

  18. Solid, non-skin, post-liver transplant tumors: Key role of lifestyle and immunosuppression management.

    Science.gov (United States)

    Carenco, Christophe; Faure, Stéphanie; Ursic-Bedoya, José; Herrero, Astrid; Pageaux, Georges Philippe

    2016-01-07

    Liver transplantation has been the treatment of choice for end-stage liver disease since 1983. Cancer has emerged as a major long-term cause of death for liver transplant recipients. Many retrospective studies that have explored standardized incidence ratio have reported increased rates of solid organ cancers post-liver transplantation; some have also studied risk factors. Liver transplantation results in a two to five-fold mean increase in the rate of solid organ cancers. Risk of head and neck, lung, esophageal, cervical cancers and Kaposi's sarcoma is high, but risk of colorectal cancer is not clearly demonstrated. There appears to be no excess risk of developing breast or prostate cancer. Environmental risk factors such as viral infection and tobacco consumption, and personal risk factors such as obesity play a key role, but recent data also implicate the role of calcineurin inhibitors, whose cumulative and dose-dependent effects on cell metabolism might play a direct role in oncogenesis. In this paper, we review the results of studies assessing the incidence of non-skin solid tumors in order to understand the mechanisms underlying solid cancers in post-liver transplant patients and, ultimately, discuss how to prevent these cancers. Immunosuppressive protocol changes, including a calcineurin inhibitor-free regimen, combined with dietary guidelines and smoking cessation, are theoretically the best preventive measures.

  19. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors.

    Science.gov (United States)

    Willingham, Stephen B; Volkmer, Jens-Peter; Gentles, Andrew J; Sahoo, Debashis; Dalerba, Piero; Mitra, Siddhartha S; Wang, Jian; Contreras-Trujillo, Humberto; Martin, Robin; Cohen, Justin D; Lovelace, Patricia; Scheeren, Ferenc A; Chao, Mark P; Weiskopf, Kipp; Tang, Chad; Volkmer, Anne Kathrin; Naik, Tejaswitha J; Storm, Theresa A; Mosley, Adriane R; Edris, Badreddin; Schmid, Seraina M; Sun, Chris K; Chua, Mei-Sze; Murillo, Oihana; Rajendran, Pradeep; Cha, Adriel C; Chin, Robert K; Kim, Dongkyoon; Adorno, Maddalena; Raveh, Tal; Tseng, Diane; Jaiswal, Siddhartha; Enger, Per Øyvind; Steinberg, Gary K; Li, Gordon; So, Samuel K; Majeti, Ravindra; Harsh, Griffith R; van de Rijn, Matt; Teng, Nelson N H; Sunwoo, John B; Alizadeh, Ash A; Clarke, Michael F; Weissman, Irving L

    2012-04-24

    CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.

  20. Magnetite nanoparticles inhibit tumor growth and upregulate the expression of p53/p16 in Ehrlich solid carcinoma bearing mice.

    Science.gov (United States)

    Bassiony, Heba; Sabet, Salwa; Salah El-Din, Taher A; Mohamed, Mona M; El-Ghor, Akmal A

    2014-01-01

    Magnetite nanoparticles (MNPs) have been widely used as contrast agents and have promising approaches in cancer treatment. In the present study we used Ehrlich solid carcinoma (ESC) bearing mice as a model to investigate MNPs antitumor activity, their effect on expression of p53 and p16 genes as an indicator for apoptotic induction in tumor tissues. MNPs coated with ascorbic acid (size: 25.0±5.0 nm) were synthesized by co-precipitation method and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day by day for 14 injections; intratumorally (IT) or intraperitoneally (IP). Tumor size, pathological changes and iron content in tumor and normal muscle tissues were assessed. We also assessed changes in expression levels of p53 and p16 genes in addition to p53 protein level by immunohistochemistry. Our results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor. A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor. This increase was accompanied with increase in p53 protein expression. It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group. MNPs might be more effective in breast cancer treatment if injected intratumorally to be directed to the tumor tissues.

  1. Magnetite nanoparticles inhibit tumor growth and upregulate the expression of p53/p16 in Ehrlich solid carcinoma bearing mice.

    Directory of Open Access Journals (Sweden)

    Heba Bassiony

    Full Text Available BACKGROUND: Magnetite nanoparticles (MNPs have been widely used as contrast agents and have promising approaches in cancer treatment. In the present study we used Ehrlich solid carcinoma (ESC bearing mice as a model to investigate MNPs antitumor activity, their effect on expression of p53 and p16 genes as an indicator for apoptotic induction in tumor tissues. METHOD: MNPs coated with ascorbic acid (size: 25.0±5.0 nm were synthesized by co-precipitation method and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day by day for 14 injections; intratumorally (IT or intraperitoneally (IP. Tumor size, pathological changes and iron content in tumor and normal muscle tissues were assessed. We also assessed changes in expression levels of p53 and p16 genes in addition to p53 protein level by immunohistochemistry. RESULTS: Our results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor. A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor. This increase was accompanied with increase in p53 protein expression. It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group. CONCLUSION: MNPs might be more effective in breast cancer treatment if injected intratumorally to be directed to the tumor tissues.

  2. Extracranial internal carotid artery aneurysm treated by combined endovascular - microsurgical techniques

    Directory of Open Access Journals (Sweden)

    Chiriac A.

    2015-09-01

    Full Text Available Extracranial internal carotid artery aneurysms are rare lesions that still represent a challenge from diagnosis and treatment point of view. Giant complex aneurysms of extracranial internal carotid artery are usually completely excluded by surgical approaches. We present a case of a patient with an extracranial internal carotid artery aneurysm treated by a combined treatment, along with a short review of this pathology.

  3. Clinical Analysis of Bisphosphonates Treatment on Bone Metastases and Hypercalcemia of Malignancy in Advanced Solid Tumor

    Institute of Scientific and Technical Information of China (English)

    MING Shu-hong; SUN Tie-ying

    2007-01-01

    Objective: To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods: Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores(NRS), Corrected serum calcium(CSC) and CSC effective rate. The vital signs, biochemical and hematological parameters were determined. Results: Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion(5.92 vs 3.25,P<0.01;6.13 vs 4.38, P<0.01, respectively). The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion: Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.

  4. Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature.

    Directory of Open Access Journals (Sweden)

    Qiong-wen Zhang

    Full Text Available PURPOSE: Tumor associated macrophages (TAMs are considered with the capacity to have both negative and positive effects on tumor growth. The prognostic value of TAM for survival in patients with solid tumor remains controversial. EXPERIMENTAL DESIGN: We conducted a meta-analysis of 55 studies (n = 8,692 patients that evaluated the correlation between TAM (detected by immunohistochemistry and clinical staging, overall survival (OS and disease free survival (DFS. The impact of M1 and M2 type TAM (n = 5 on survival was also examined. RESULTS: High density of TAM was significantly associated with late clinical staging in patients with breast cancer [risk ratio (RR  = 1.20 (95% confidence interval (CI, 1.14-1.28] and bladder cancer [RR = 3.30 (95%CI, 1.56-6.96] and with early clinical staging in patients with ovarian cancer [RR = 0.52 (95%CI, 0.35-0.77]. Negative effects of TAM on OS was shown in patients with gastric cancer [RR = 1.64 (95%CI, 1.24-2.16], breast cancer [RR = 8.62 (95%CI, 3.10-23.95], bladder cancer [RR = 5.00 (95%CI, 1.98-12.63], ovarian cancer [RR = 2.55 (95%CI, 1.60-4.06], oral cancer [RR = 2.03 (95%CI, 1.47-2.80] and thyroid cancer [RR = 2.72 (95%CI, 1.26-5.86],and positive effects was displayed in patients with colorectal cancer [RR = 0.64 (95%CI, 0.43-0.96]. No significant effect was showed between TAM and DFS. There was also no significant effect of two phenotypes of TAM on survival. CONCLUSIONS: Although some modest bias cannot be excluded, high density of TAM seems to be associated with worse OS in patients with gastric cancer, urogenital cancer and head and neck cancer, with better OS in patients with colorectal cancer.

  5. Prognostic significance of microRNA-100 in solid tumors: an updated meta-analysis

    Science.gov (United States)

    Wang, Jiangfeng; Yu, Miao; Guan, Shanghui; Zhang, Guangyu; Wang, Jianbo; Cheng, Yufeng

    2017-01-01

    Objective The aim of this study was to identify prognostic significance of microRNA-100 (miR-100) in solid tumor. Methods Literature search was conducted in databases such as PubMed, Embase, and Web of Science, using the following words “(microRNA-100 OR miR-100 OR mir100) AND (tumor OR neoplasm OR cancer OR carcinoma OR malignancy).” The search was updated up until July 10, 2016. Newcastle–Ottawa scale was used to evaluate the quality of studies. Pooled hazard ratio (HR) with 95% confidence interval (CI) for patients’ survival was calculated by using a fixed-effects or a random-effects model on the basis of heterogeneity. Subgroup analysis, sensitive analysis, and meta-regression were used to investigate the sources of heterogeneity. Publication bias was evaluated by using Begg’s and Egger’s tests. Results A total of 16 articles with 1,501 patients were included in the present meta-analysis. It was demonstrated that a lower expression of miR-100 plays a negative role in the overall survival (OS) of patients with solid tumor (HR =1.92; 95% CI =1.25–2.94). In addition, the association between miR-100 and prognosis was also revealed in the following subgroups: non-small-cell lung cancer (NSCLC; HR =2.46; 95% CI =1.98–3.06), epithelial ovarian cancer (EOC; HR =2.29, 95% CI =1.72–3.04), and bladder cancer (BC; HR =4.14, 95% CI =1.85–9.27). Conclusion This meta-analysis indicates that lower expression of miR-100 is related to poorer OS in patients with solid tumor, especially in those with NSCLC, EOC, and BC. MiR-100 is a promising prognosis predictor and may be a potential target for therapy in the future. PMID:28176958

  6. Solid tumors of the peritoneum, omentum, and mesentery in children: radiologic-pathologic correlation: from the radiologic pathology archives.

    Science.gov (United States)

    Chung, Ellen M; Biko, David M; Arzamendi, Aaron M; Meldrum, Jaren T; Stocker, J Thomas

    2015-01-01

    Intraperitoneal solid tumors are far less common in children than in adults, and the histologic spectrum of neoplasms of the peritoneum and its specialized folds in young patients differs from that in older patients. Localized masses may be caused by inflammatory myofibroblastic tumor, Castleman disease, mesenteric fibromatosis, or other mesenchymal masses. Inflammatory myofibroblastic tumor is a mesenchymal tumor of borderline biologic potential that appears as a solitary circumscribed mass, possibly with central calcification. Castleman disease is an idiopathic lymphoproliferative disorder that appears as a circumscribed, intensely enhancing mass in the mesentery. Mesenteric fibromatosis, or intra-abdominal desmoid tumor, is a benign tumor of mesenchymal origin associated with familial adenomatous polyposis. Mesenteric fibromatosis appears as a mildly enhancing, circumscribed solitary mass without metastases. Diffuse peritoneal disease may be due to desmoplastic small round cell tumor (DSRCT), non-Hodgkin lymphoma, or rhabdomyosarcoma. DSRCT is a rare member of the small round blue cell tumor family that causes diffuse peritoneal masses without a visible primary tumor. A dominant mass is typically found in the retrovesical space. Burkitt lymphoma is a pediatric tumor that manifests with extensive disease because of its short doubling time. The bowel and adjacent mesentery are commonly involved. Rhabdomyosarcoma may arise as a primary tumor of the omentum or may spread from a primary tumor in the bladder, prostate, or scrotum. Knowledge of this spectrum of disease allows the radiologist to provide an appropriate differential diagnosis and suggest proper patient management.

  7. Fate of orally administered {sup 15}N-labeled polyamines in rats bearing solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Masaki; Samejima, Keijiro; Goda, Hitomi; Niitsu, Masaru [Josai Univ., Sakado, Saitama (Japan). Faculty of Pharmaceutical Sciences; Xu Yongji [Qingdao Univ. of Science and Technology (China). Inst. of Chemical and Molecular Technology; Takahashi, Masakazu [Sasaki Inst., Tokyo (Japan); Hashimoto, Yoshiyuki [Kyoritsu Coll. of Pharmacy, Tokyo (Japan)

    2003-03-01

    We studied absorption, distribution, metabolism, and excretion of polyamines (putrescine, spermidine, and spermine) in the gastrointestinal tract using {sup 15}N-labeled polyamines as tracers and ionspray ionization mass spectrometry (IS-MS). The relatively simple protocol using rats bearing solid tumors provided useful information. Three {sup 15}N-labeled polyamines that were simultaneously administered were absorbed equally from gastrointestinal tract, and distributed within tissues at various concentrations. The uptake of {sup 15}N-spermidine seemed preferential to that of {sup 15}N-spermine since the concentrations of {sup 15}N-spermidine in the liver and tumors were higher, whereas those of {sup 15}N-spermine were higher in the kidney, probably due to the excretion of excess extracellular spermine. Most of the absorbed {sup 15}N-putrescine seemed to be lost, suggesting blood and tissue diamine oxidase degradation. Concentrations of {sup 15}N-spermidine and {sup 15}N-spermine in the tumor were low. We also describe the findings from two rats that were administered with {sup 15}N-spermine. The tissue concentrations of {sup 15}N-spermine were unusually high, and significant levels of {sup 15}N-spermidine were derived from {sup 15}N-spermine in these animals. (author)

  8. A Pancreatic Solid Pseudo-Papillary Tumor Detected After Abdominal Injury

    Science.gov (United States)

    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.

  9. Vascular Imaging of Solid Tumors in Rats with a Radioactive Arsenic-Labeled Antibody that Binds Exposed Phosphatidylserine

    Science.gov (United States)

    Jennewein, Marc; Lewis, Matthew A.; Zhao, Dawen; Tsyganov, Edward; Slavine, Nikolai; He, Jin; Watkins, Linda; Kodibagkar, Vikram D.; O'Kelly, Sean; Kulkarni, Padmakar; Antich, Peter P.; Hermanne, Alex; Roösch, Frank; Mason, Ralph P.; Thorpe, Philip E.

    2012-01-01

    Purpose We recently reported that anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of vascular endothelial cells in tumors, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we tested the hypothesis that a chimeric monoclonal antibody that binds phosphatidylserine could be labeled with radioactive arsenic isotopes and used for molecular imaging of solid tumors in rats. Experimental Design Bavituximab was labeled with 74As (β+,T1/2 17.8 days) or 77As (β−,T1/2 1.6 days) using a novel procedure. The radionuclides of arsenic were selected because their long half-lives are consistent with the long biological half lives of antibodies in vivo and because their chemistry permits stable attachment to antibodies. The radiolabeled antibodies were tested for the ability to image subcutaneous Dunning prostate R3227-AT1 tumors in rats. Results Clear images of the tumors were obtained using planar γ-scintigraphy and positron emission tomography. Biodistribution studies confirmed the specific localization of bavituximab to the tumors. The tumor-to-liver ratio 72 h after injection was 22 for bavituximab compared with 1.5 for an isotype-matched control chimeric antibody of irrelevant specificity. Immunohistochemical studies showed that the bavituximab was labeling the tumor vascular endothelium. Conclusions These results show that radioarsenic-labeled bavituximab has potential as a new tool for imaging the vasculature of solid tumors. PMID:18316558

  10. Tenascin-W is a better cancer biomarker than tenascin-C for most human solid tumors

    Directory of Open Access Journals (Sweden)

    Brellier Florence

    2012-09-01

    Full Text Available Abstract Background Tenascins are large glycoproteins found in the extracellular matrix of many embryonic and adult tissues. Tenascin-C is a well-studied biomarker known for its high overexpression in the stroma of most solid cancers. Tenascin-W, the least studied member of the family, is highly expressed in the stroma of colon and breast tumors and in gliomas, but not in the corresponding normal tissues. Other solid tumors have not been analyzed. The present study was undertaken to determine whether tenascin-W could serve as a cancer-specific extracellular matrix protein in a broad range of solid tumors. Methods We analyzed the expression of tenascin-W and tenascin-C by immunoblotting and by immunohistochemistry on multiple frozen tissue microarrays of carcinomas of the pancreas, kidney and lung as well as melanomas and compared them to healthy tissues. Results From all healthy adult organs tested, only liver and spleen showed detectable levels of tenascin-W, suggesting that tenascin-W is absent from most human adult organs under normal, non-pathological conditions. In contrast, tenascin-W was detectable in the majority of melanomas and their metastases, as well as in pancreas, kidney, and lung carcinomas. Comparing lung tumor samples and matching control tissues for each patient revealed a clear overexpression of tenascin-W in tumor tissues. Although the number of samples examined is too small to draw statistically significant conclusions, there seems to be a tendency for increased tenascin-W expression in higher grade tumors. Interestingly, in most tumor types, tenascin-W is also expressed in close proximity to blood vessels, as shown by CD31 co-staining of the samples. Conclusions The present study extends the tumor biomarker potential of tenascin-W to a broad range of solid tumors and shows its accessibility from the blood stream for potential therapeutic strategies.

  11. Imaging features of solid pseudopapillary tumor of the pancreas on multi-detector row computed tomography

    Institute of Scientific and Technical Information of China (English)

    Deng-Bin Wang; Qing-Bing Wang; Wei-Min Chai; Ke-Min Chen; Xia-Xing Deng

    2009-01-01

    AIM:To retrospectively analyze the imaging features of solid-pseudopapillary tumors (SPTs) of the pancreas on multi-detector row computed tomography (MDCT) and define the imaging findings suggestive of malignant potential.METHODS: A total of 24 consecutive cases with surgically and pathologically confirmed SPTs of the pancreas underwent preoperative abdominal MDCT studies in our hospital. All axial CT images, CT angiographic images, and coronally and sagittally reformed images were obtained. The images were retrospectively reviewed at interactive picture archiving and communication system workstations. RESULTS: Of the 24 cases of SPTs, 11 cases (45.8%) occurred in the pancreatic head and seven (29.1%) in the tail. Eighteen were pathologically diagnosed as benign and six as malignant. MDCT diagnosis of SPTs was well correlated with the surgical and pathological results (Kappa = 0.6, P < 0.05). The size of SPTs ranged from 3 to 15 cm (mean, 5.8 cm). When the size of the tumor was greater than 6 cm (including 6cm), the possibilities of vascular (8 vs 1) and capsular invasion (9 vs 0) increased significantly ( P < 0.05). Two pathologically benign cases with vascular invasion and disrupted capsule on MDCT presented with local recurrence and hepatic metastases during follow-up about 1 year after the resection of the primary tumors.CONCLUSION: Vascular and capsular invasion with superimposed spread into the adjacent pancreatic parenchyma and nearby structures in SPTs of the pancreas can be accurately revealed by MDCTpreoperatively. These imaging findings are predictive of the malignant potential associated with the aggressive behavior of the tumor, even in the pathologically benign cases.

  12. Valproic acid reduces the tolerability of temsirolimus in children and adolescents with solid tumors.

    Science.gov (United States)

    Coulter, Don W; Walko, Christine; Patel, Jai; Moats-Staats, Billie M; McFadden, Andrew; Smith, Scott V; Khan, Wasiuddin A; Bridges, Arlene S; Deal, Allison M; Oesterheld, Javier; Davis, Ian J; Blatt, Julie

    2013-04-01

    A pediatric study has established a maximum tolerated dose (MTD) for temsirolimus (Tem) of more than 150 mg/m intravenously/week. A phase I trial was conducted to establish the MTD for Tem in combination with valproic acid (VPA) in children and adolescents with refractory solid tumors. The secondary aims included expression of mammalian target of rapamycin (mTOR) markers on archival tumor tissue; Tem pharmacokinetics; assessment of histone acetylation (HA); and tumor response. Patients were treated with VPA (5 mg/kg orally three times daily) with a target serum level of 75-100 mcg/ml. Tem was started at an initial dose of 60 mg/m/week. Pharmacokinetics and HA measurements were performed during weeks 1 and 5. Two of the first three patients experienced dose-limiting toxicity (grade 3 mucositis). Tem at 35 mg/m/week was found to be tolerable. Peak Tem concentrations were higher in all patients compared with those in previously published reports of single agent Tem. Increases in HA are correlated with VPA levels. All tumor samples expressed mTORC1 and mTORC2. An objective response was observed in one patient (melanoma), whereas transient stable disease was observed in four other patients (spinal cord ependymoma, alveolar soft part sarcoma, medullary thyroid carcinoma, and hepatocellular carcinoma). The MTD of Tem when administered with VPA is considerably lower than when used as a single agent, with mucositis the major dose-limiting toxicity. The combination merits further study and may have activity in melanoma. Attention to drug-drug interactions will be important in future multiagent trials including Tem.

  13. Incidence of anemia in patients diagnosed with solid tumors receiving chemotherapy, 2010–2013

    Directory of Open Access Journals (Sweden)

    Xu H

    2016-04-01

    Full Text Available Hairong Xu,1 Lanfang Xu,2 John H Page,1 Kim Cannavale,2 Olivia Sattayapiwat,2 Roberto Rodriguez,3 Chun Chao2 1Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA; 2Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA; 3Department of Hematology Oncology, Los Angeles Medical Center, Kaiser Permanente Southern California, Psadena, CA, USA Purpose: The purpose of this study was to evaluate and characterize the risk of anemia during the course of chemotherapy among patients with five common types of solid tumors. Patients and methods: Patients diagnosed with incident cancers of breast, lung, colon/rectum, stomach, and ovary who received chemotherapy were identified from Kaiser Permanente Southern California Health Plan (2010–2012. All clinical data were collected from the health plan’s electronic medical records. Incidence proportions of patients developing anemia and 95% confidence intervals were calculated overall and by anemia severity and type, as well as by stage at cancer diagnosis, and by chemotherapy regimen and cycle. Results: A total of 4,426 patients who received chemotherapy were included. Across cancers, 3,962 (89.5% patients developed anemia during the course of chemotherapy (normocytic 85%, macrocytic 10%, microcytic 5%; normochromic 47%, hyperchromic 44%, hypochromic 9%. The anemia grades were distributed as follows: 58% were grade 1, 34% grade 2, 8% grade 3, and <1% grade 4. The incidence of grade 2+ anemia ranged from 26.3% in colorectal cancer patients to 59.2% in ovarian cancer patients. Incidence of grade 2+ anemia increased from 29% in stage I to 49% in stage IV. Incidence of grade 2+ anemia varied from 18.2% in breast cancer patients treated with cyclophosphamide + docetaxel regimen to 59.7% in patients with ovarian cancer receiving carboplatin + paclitaxel regimen. Conclusion: The incidence of moderate-to-severe anemia (hemoglobin <10 g/dL remained considerably

  14. Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

    Science.gov (United States)

    2014-11-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

  15. Risk of solid tumors and hematological malignancy in persons with Turner and Klinefelter syndromes: A national cohort study.

    Science.gov (United States)

    Ji, Jianguang; Zöller, Bengt; Sundquist, Jan; Sundquist, Kristina

    2016-08-15

    The risk of solid and hematological malignancy in patients with Turner syndrome, characterized by X chromosome monosomy in women, and Klinefelter syndrome, characterized with two and more X chromosomes in men, is not well established, but such evidence may have etiological implications on cancer development. We identified a total of 1,409 women with Turner syndrome and 1,085 men with Klinefelter syndrome from the Swedish Hospital Discharge and Outpatient Register. These individuals were further linked to the Swedish Cancer Register to examine the standardized incidence ratios (SIRs) of cancer using the general population without Turner and Klinefelter syndromes as reference. The overall risk of cancer was 1.34 for women with Turner syndrome; it was increased only for solid tumors. For a specific type of tumor, the risk of melanoma and central nervous system tumor was significantly increased. For persons with Klinefelter syndrome, the risk of solid tumors was decreased (SIR = 0.66), whereas the risk of hematological malignancy was increased (SIR = 2.72). Non-Hodgkin lymphoma and leukemia showed an increased SIR of 3.02 and 3.62, respectively. Our study supported the hypothesis that X chromosome plays an important role in the etiology of solid tumors. The underlying mechanisms for the increased incidence of non-Hodgkin lymphoma and leukemia in persons with Klinefelter syndrome need to be investigated further.

  16. Glucose transporter GLUT1 expression and clinical outcome in solid tumors: a systematic review and meta-analysis.

    Science.gov (United States)

    Wang, Ji; Ye, Chenyang; Chen, Cong; Xiong, Hanchu; Xie, Binbin; Zhou, Jichun; Chen, Yongxia; Zheng, Shu; Wang, Linbo

    2017-03-07

    Glucose transporter 1 (GLUT1), the uniporter protein encoded by the SLC2A1 gene, is a key rate-limiting factor in the transport of glucose in cancer cells, and frequently expressed in a significant proportion of human cancers. Numerous studies have reported paradoxical evidence of the relationship between GLUT1 expression and prognosis in solid human tumors. To address this discrepancy, we conducted a thorough search of Pubmed and Web of Science for studies evaluating the expression of GLUT1 and overall survival (OS) and disease-free survival (DFS) in patients with solid cancer from 1993 to April 2016. Data from published researches were extracted and computed into odds ratio (OR). A total of 26 studies including 2948 patients met our search criteria and were evaluated. Overexpression of GLUT1 was found to significantly correlate with poor 3-year OS (OR: 2.86; 95% CI, 1.90-4.32, P < 0.00001) and 5-year OS (OR: 2.52; 95% CI, 1.75-3.61, P < 0.00001) of solid tumors. Similar results were observed when analysis of DFS was performed. Subgroup analysis revealed that elevated GLUT1 expression was associated with worse prognosis of oral squamous cell carcinoma and breast cancer. Taken together, overexpression of GLUT1 is correlated with poor survival in most solid tumors, suggesting that the expression status of GLUT1 is a vital prognostic indicator and promising therapeutic target in solid tumors.

  17. Familial aggregation of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia with solid tumors and myeloid malignancies.

    Science.gov (United States)

    Kristinsson, Sigurdur Y; Goldin, Lynn R; Turesson, Ingemar; Björkholm, Magnus; Landgren, Ola

    2012-01-01

    Lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM) is a B-cell disorder resulting from the accumulation, predominantly in the bone marrow, of clonally related lymphoplasmacytic cells. LPL/WM is a very rare disease, with an incidence rate of 3-4 cases per million people per year.Currently, the causes of LPL/WM are poorly understood; however, there are emerging data to support a role for immune-related factors in the pathogenesis of LPL/WM. In addition, data show that genetic factors are of importance in the etiology of LPL/WM. In this paper, we will review the current knowledge about familiality of LPL/WM and provide novel data on solid tumors and myeloid malignancies in first-degree relatives of LPL/WM patients.

  18. Skull-base Ewing sarcoma with multifocal extracranial metastases

    Directory of Open Access Journals (Sweden)

    Sumit Thakar

    2012-01-01

    Full Text Available Intracranial occurrence of Ewing sarcoma (ES is unusual, with a skull-base location being anecdotal. We report a 29-year-old man who presented with rapidly progressive ophthalmoplegia, and was found to be harboring an infiltrative lesion involving the sphenoid sinus, sella, and clivus. He underwent trans-sphenoidal decompression of the lesion which was histologically suggestive of ES. He developed paraparesis 2 weeks after commencing adjuvant therapy. Imaging revealed two thoracic extradural lesions and florid vertebral and pulmonary metastases. This is the first report in indexed literature of a primary intracranial ES on the skull-base with disseminated extracranial disease.

  19. Endoplasmic reticulum stress in the proapoptotic action of edelfosine in solid tumor cells.

    Science.gov (United States)

    Nieto-Miguel, Teresa; Fonteriz, Rosalba I; Vay, Laura; Gajate, Consuelo; López-Hernández, Silvia; Mollinedo, Faustino

    2007-11-01

    The endoplasmic reticulum (ER) has been posited as a potential anticancer target. The synthetic antitumor alkyl-lysophospholipid analogue edelfosine accumulates in the ER of solid tumor cells. This ER accumulation of the drug leads to the inhibition of phosphatidylcholine and protein synthesis, G(2)-M arrest, depletion of ER-stored Ca(2+), Bax up-regulation and activation, transcriptional factor growth arrest and DNA damage-inducible gene 153 up-regulation, caspase-4 and caspase-8 activation, and eventually to apoptosis. Edelfosine prompted ER stress apoptotic signaling, but not the survival unfolded protein response. Edelfosine also induced persistent c-Jun NH(2)-terminal kinase (JNK) activation. Gene transfer-mediated overexpression of apoptosis signal-regulating kinase 1, which plays a crucial role in ER stress, enhanced edelfosine-induced JNK activation and apoptosis. Inhibition of JNK, caspase-4, or caspase-8 activation diminished edelfosine-induced apoptosis. Edelfosine treatment led to the generation of the p20 caspase-8 cleavage fragment of BAP31, directing proapoptotic signals between the ER and the mitochondria. bax(-/-)bak(-/-) double-knockout cells fail to undergo edelfosine-induced ER-stored Ca(2+) release and apoptosis. Wild-type and bax(-/-)bak(-/-) cells showed similar patterns of phosphatidylcholine and protein synthesis inhibition, despite their differences in drug sensitivity. Thus, edelfosine-induced apoptosis is dependent on Bax/Bak-mediated ER-stored Ca(2+) release, but phosphatidylcholine and protein synthesis inhibition is not critical. Transfection-enforced expression of Bcl-X(L), which localizes specifically in mitochondria, prevented apoptosis without inhibiting ER-stored Ca(2+) release. These data reveal that edelfosine induces an ER stress response in solid tumor cells, providing novel insights into the edelfosine-mediated antitumor activity. Our data also indicate that mitochondria are indispensable for this edelfosine-induced cell

  20. Engineering Chimeric Antigen Receptor T-Cells for Racing in Solid Tumors: Don’t Forget the Fuel

    Science.gov (United States)

    Irving, Melita; Vuillefroy de Silly, Romain; Scholten, Kirsten; Dilek, Nahzli; Coukos, George

    2017-01-01

    T-cells play a critical role in tumor immunity. Indeed, the presence of tumor-infiltrating lymphocytes is a predictor of favorable patient prognosis for many indications and is a requirement for responsiveness to immune checkpoint blockade therapy targeting programmed cell death 1. For tumors lacking immune infiltrate, or for which antigen processing and/or presentation has been downregulated, a promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell therapy. CARs are hybrid receptors that link the tumor antigen specificity and affinity of an antibody-derived single-chain variable fragment with signaling endodomains associated with T-cell activation. CAR therapy targeting CD19 has yielded extraordinary clinical responses against some hematological tumors. Solid tumors, however, remain an important challenge to CAR T-cells due to issues of homing, tumor vasculature and stromal barriers, and a range of obstacles in the tumor bed. Protumoral immune infiltrate including T regulatory cells and myeloid-derived suppressor cells have been well characterized for their ability to upregulate inhibitory receptors and molecules that hinder effector T-cells. A critical role for metabolic barriers in the tumor microenvironment (TME) is emerging. High glucose consumption and competition for key amino acids by tumor cells can leave T-cells with insufficient energy and biosynthetic precursors to support activities such as cytokine secretion and lead to a phenotypic state of anergy or exhaustion. CAR T-cell expansion protocols that promote a less differentiated phenotype, combined with optimal receptor design and coengineering strategies, along with immunomodulatory therapies that also promote endogenous immunity, offer great promise in surmounting immunometabolic barriers in the TME and curing solid tumors. PMID:28421069

  1. Engineering Chimeric Antigen Receptor T-Cells for Racing in Solid Tumors: Don't Forget the Fuel.

    Science.gov (United States)

    Irving, Melita; Vuillefroy de Silly, Romain; Scholten, Kirsten; Dilek, Nahzli; Coukos, George

    2017-01-01

    T-cells play a critical role in tumor immunity. Indeed, the presence of tumor-infiltrating lymphocytes is a predictor of favorable patient prognosis for many indications and is a requirement for responsiveness to immune checkpoint blockade therapy targeting programmed cell death 1. For tumors lacking immune infiltrate, or for which antigen processing and/or presentation has been downregulated, a promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell therapy. CARs are hybrid receptors that link the tumor antigen specificity and affinity of an antibody-derived single-chain variable fragment with signaling endodomains associated with T-cell activation. CAR therapy targeting CD19 has yielded extraordinary clinical responses against some hematological tumors. Solid tumors, however, remain an important challenge to CAR T-cells due to issues of homing, tumor vasculature and stromal barriers, and a range of obstacles in the tumor bed. Protumoral immune infiltrate including T regulatory cells and myeloid-derived suppressor cells have been well characterized for their ability to upregulate inhibitory receptors and molecules that hinder effector T-cells. A critical role for metabolic barriers in the tumor microenvironment (TME) is emerging. High glucose consumption and competition for key amino acids by tumor cells can leave T-cells with insufficient energy and biosynthetic precursors to support activities such as cytokine secretion and lead to a phenotypic state of anergy or exhaustion. CAR T-cell expansion protocols that promote a less differentiated phenotype, combined with optimal receptor design and coengineering strategies, along with immunomodulatory therapies that also promote endogenous immunity, offer great promise in surmounting immunometabolic barriers in the TME and curing solid tumors.

  2. Phase 1 and pharmacokinetic study of intravenous irinotecan in refractory solid tumor patients with hepatic dysfunction.

    Science.gov (United States)

    Schaaf, Larry J; Hammond, Lisa A; Tipping, Stuart J; Goldberg, Richard M; Goel, Rakesh; Kuhn, John G; Miller, Langdon L; Compton, Linda D; Cisar, Laura A; Elfring, Gary L; Gruia, Gabriela; McGovren, J Patrick; Pirotta, Nicoletta; Yin, Donghua; Sharma, Amarnath; Duncan, Barbara A; Rothenberg, Mace L

    2006-06-15

    To determine the recommended starting doses and pharmacokinetics of irinotecan in cancer patients with impaired liver function treated on a weekly schedule. Patients with solid tumors who had impaired liver function were enrolled into four groups based on baseline serum total bilirubin and aspartate aminotransferase (AST)/alanine aminotransferase (ALT): Group 1 (n = 19): total bilirubin 1.5 to 3.0 x institutional upper limit of normal (IULN) and ALT/AST vomiting (5%, grades 3/4). Two patients died from drug-induced neutropenic sepsis. Two patients had objective tumor responses (complete response, liver metastases from unknown primary; partial response, colon cancer). Hepatic dysfunction reduced irinotecan clearance while increasing relative exposure to the active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). SN-38 exposures in patients receiving doses of 40 to 75 mg/m(2) were comparable to exposures in patients with normal liver function treated with a starting dose of 125 mg/m(2). Irinotecan starting doses that seem to be safe for hepatically impaired patients treated with the weekly schedule are 60, 50, 60, and 40 mg/m(2) for groups 1 to 4, respectively. At these starting doses, exposure to SN-38 and the adverse event profile are similar to that observed in patients with normal liver function and antitumor activity can be observed.

  3. Identification and Validation of Commonly Overexpressed Genes in Solid Tumors by Comparison of Microarray Data

    Directory of Open Access Journals (Sweden)

    Christian Pilarsky

    2004-11-01

    Full Text Available Cancers originating from epithelial cells are the most common malignancies. No common expression profile of solid tumors compared to normal tissues has been described so far. Therefore we were interested if genes differentially expressed in the majority of carcinomas could be identified using bioinformatic methods. Complete data sets were downloaded for carcinomas of the prostate, breast, lung, ovary, colon, pancreas, stomach, bladder, liver, and kidney, and were subjected to an expression analysis using SAM. In each experiment, a gene was scored as differentially expressed if the q value was below 25%. Probe identifiers were unified by comparing the respective probe sequences to the Unigene build 155 using BIastN. To obtain differentially expressed genes within the set of analyzed carcinomas, the number of experiments in which differential expression was observed was counted. Differential expression was assigned to genes if they were differentially expressed in at least eight experiments of tumors from different origin. The identified candidate genes ADRM1, EBNA1BP2, FDPS, FOXM1, H2AFX, HDAC3, IRAK1, and YY1 were subjected to further validation. Using this comparative approach, 100 genes were identified as upregulated and 21 genes as downregulated in the carcinomas.

  4. Bortezomib in combination with celecoxib in patients with advanced solid tumors: a phase I trial

    Directory of Open Access Journals (Sweden)

    Salzer Shanta

    2007-12-01

    Full Text Available Abstract Background COX-2 inhibitors, such as celecoxib, and ubiquitin-proteasome pathway inhibitors, such as bortezomib, can down-regulate NF-κB, a transcription factor implicated in tumor growth. The objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of bortezomib in combination with celecoxib in patients with advanced solid tumors. Methods Patients received escalating doses of bortezomib either on a weekly schedule (days 1, 8, 15, 22, and 29 repeated every 42 days or on a twice-weekly administration schedule (days 1, 4, 8, and 11 repeated every 21 days, in combination with escalating doses of celecoxib twice daily throughout the study period from 200 mg to 400 mg twice daily. Results No dose-limiting toxicity was observed during the study period. Two patients had stable disease lasting for four and five months each, and sixteen patients developed progressive disease. Conclusion The combination of bortezomib and celecoxib was well tolerated, without dose limiting toxicities observed throughout the dosing ranges tested, and will be studied further at the highest dose levels investigated. Trial registration number NCT00290680.

  5. Clinical development of VEGF signaling pathway inhibitors in childhood solid tumors.

    Science.gov (United States)

    Glade Bender, Julia; Yamashiro, Darrell J; Fox, Elizabeth

    2011-01-01

    Angiogenesis is a target shared by both adult epithelial cancers and the mesenchymal or embryonal tumors of childhood. Development of antiangiogenic agents for the pediatric population has been complicated by largely theoretical concern for toxicities specific to the growing child and prioritization among the many antiangiogenic agents being developed for adults. This review summarizes the mechanism of action and preclinical data relevant to childhood cancers and early-phase clinical trials in childhood solid tumors. Single-agent adverse event profiles in adults and children are reviewed with emphasis on cardiovascular, bone health, and endocrine side effects. In addition, pharmacological factors that may be relevant for prioritizing clinical trials of these agents in children are reviewed. Considerations for further clinical evaluation should include preclinical data, relative potency, efficacy in adults, and the current U.S. Food and Drug Administration approval status. Toxicity profiles of vascular endothelial growth factor (VEGF) signaling pathway inhibitors may be age dependent and ultimately, their utility in the treatment of childhood cancer will require combination with standard cytotoxic drugs or other molecularly targeted agents. In combination studies, toxicity profiles, potential drug interactions, and late effects must be considered. Studies to assess the long-term impact of VEGF signaling pathway inhibitors on cardiovascular, endocrine, and bone health in children with cancer are imperative if these agents are to be administered to growing children and adolescents with newly diagnosed cancers.

  6. Pancreatic neuroendocrine tumor and solid-pseudopapillary neoplasm: Key immunohistochemical profiles for differential diagnosis

    Science.gov (United States)

    Ohara, Yusuke; Oda, Tatsuya; Hashimoto, Shinji; Akashi, Yoshimasa; Miyamoto, Ryoichi; Enomoto, Tsuyoshi; Satomi, Kaishi; Morishita, Yukio; Ohkohchi, Nobuhiro

    2016-01-01

    AIM To reveal better diagnostic markers for differentiating neuroendocrine tumor (NET) from solid-pseudopapillary neoplasm (SPN), focusing primarily on immunohistochemical analysis. METHODS We reviewed 30 pancreatic surgical specimens of NET (24 cases) and SPN (6 cases). We carried out comprehensive immunohistochemical profiling using 9 markers: Synaptophysin, chromogranin A, pan-cytokeratin, E-cadherin, progesterone receptor, vimentin, α-1-antitrypsin, CD10, and β-catenin. RESULTS E-cadherin staining in NETs, and nuclear labeling of β-catenin in SPNs were the most sensitive and specific markers. Dot-like staining of chromogranin A might indicate the possibility of SPNs rather than NETs. The other six markers were not useful because their expression overlapped widely between NETs and SPNs. Moreover, two cases that had been initially diagnosed as NETs on the basis of their morphological features, demonstrated SPN-like immunohistochemical profiles. Careful diagnosis is crucial as we actually found two confusing cases showing disagreement between the tumor morphology and immunohistochemical profiles. CONCLUSION E-cadherin, chromogranin A, and β-catenin were the most useful markers which should be employed for differentiating between NET and SPN.

  7. Phase I Study of Capecitabine, Oxaliplatin, Bevacizumab, and Everolimus in Advanced Solid Tumors

    Science.gov (United States)

    Rangwala, F.; Bendell, J.; Kozloff, M.; Arrowood, C.; Dellinger, A.; Meadows, J.; Tourt-Uhlig, S.; Murphy, J.; Meadows, K.L.; Starr, A.; Broderick, S.; Brady, J.C.; Cushman, S. M.; Morse, M.; Uronis, H.; Hsu, S.D.; Zafar, S.Y.; Wallace, J.; Starodub, A.; Strickler, J.; Pang, H.; Nixon, A.B.; Hurwitz, H.

    2014-01-01

    Purpose To define maximum tolerated dose (MTD), toxicities, and pharmacodynamics of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumor patients. Design This was a standard “3+3” dose-escalation trial. All subjects received bevacizumab 7.5mg/kg on day one of each cycle. Doses for capecitabine, oxaliplatin and everolimus were modified per dose limiting toxicity (DLT). Baseline and on-treatment plasma biomarkers were analyzed. Archived tumor mRNA levels were evaluated for NRP1, NRP2 and VEGF-A isoforms. Results Twenty-nine patients were evaluable for toxicity and 30 for efficacy. Two DLTs were observed in cohort 1 and one DLT each was observed in cohort -1 and -1b. Grade ≥3 toxicities included neutropenia, hypertension, perforation/fistula/hemorrhage, hypertriglyceridemia, diarrhea, and thromboembolism. Twelve subjects experienced partial response (PR); 12 had stable disease as best response. Three of seven chemorefractory metastatic colorectal cancer (mCRC) subjects experienced PR; eight of 15 chemonaive mCRC subjects experienced PR. Plasma TβRIII and IL-6 increased on treatment but without correlation to outcome. Increased VEGF165 levels significantly correlated with longer progression free survival. Conclusions Everolimus with full dose capecitabine, oxaliplatin, and bevacizumab had unacceptable toxicity. MTD was: everolimus 5mg daily; capecitabine 680mg/m2 BID days 1-14; oxaliplatin 100mg/m2 and bevacizumab 7.5mg/kg, day one. Activity was noted in mCRC. PMID:24711126

  8. Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia

    Science.gov (United States)

    2014-06-16

    Childhood Acute Promyelocytic Leukemia (M3); Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Juvenile Myelomonocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  9. Molecular cytogenetics in solid tumors: laboratorial tool for diagnosis, prognosis, and therapy.

    Science.gov (United States)

    Varella-Garcia, Marileila

    2003-01-01

    The remarkable progress in the understanding of leukemogenesis was soundly sustained by methodological developments in the cytogenetic field. Nonrandom chromosomal abnormalities frequently associated with specific types of hematological disease play a major role in their diagnosis and have been demonstrated as independent prognostic indicators. Molecular pathways altered by chimeric or deregulated proteins as a consequence of chromosomal abnormalities have also significantly contributed to the development of targeted therapies, and cytogenetic assays are valuable for selecting patients for treatment and monitoring outcome. In solid tumors, significantly high levels of chromosome abnormalities have been detected, but distinction between critical and irrelevant events has been a major challenge. Consequently, the application of cytogenetic technology as diagnostic, prognostic, or therapeutic tools for these malignancies remains largely under appreciated. The emergence of molecular-based techniques such as fluorescence in situ hybridization was particularly useful for solid malignancies, and the spectrum of their application is rapidly expanding to improve efficiency and sensitivity in cancer prevention, diagnosis, prognosis, and therapy selection, alone or in combination with other diagnostic methods. This overview illustrates current uses and outlines potential applications for molecular cytogenetics in clinical oncology.

  10. Extracranial soft-tissue swelling: a normal postmortem radiographic finding or a sign of trauma?

    Energy Technology Data Exchange (ETDEWEB)

    Strouse, P.J. [Section of Pediatric Radiology, University of Michigan Medical Center, Ann Arbor (United States); Caplan, M. [Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan (United States); Owings, C.L. [Department of Pediatrics and Communicable Diseases, C. S. Mott Children`s Hospital, Ann Arbor, Michigan (United States)

    1998-08-01

    Objective. To determine if extracranial soft-tissue swelling is an expected postmortem finding or a sign of trauma. Materials and methods. Extracranial soft-tissue thickness was measured at 5 standardized locations on postmortem skull films obtained of 18 infants with no evidence of trauma on autopsy. The same measurements were performed on the skull films of 100 living children, all less than 3 years old and without clinical history of trauma. Results. Extracranial soft tissues measured only slightly greater in the postmortem group than on films of living children; however, the difference did achieve statistical significance. Conclusion. Minimal extracranial soft-tissue swelling is a normal finding on a postmortem skeletal survey. The presence of substantial or asymmetric extracranial soft-tissue swelling should be viewed with suspicion for trauma. (orig.) With 2 tabs., 5 refs.

  11. The role of cancer-associated fibroblasts, solid stress and other microenvironmental factors in tumor progression and therapy resistance.

    Science.gov (United States)

    Kharaishvili, Gvantsa; Simkova, Dana; Bouchalova, Katerina; Gachechiladze, Mariam; Narsia, Nato; Bouchal, Jan

    2014-01-01

    Tumors are not merely masses of neoplastic cells but complex tissues composed of cellular and noncellular elements. This review provides recent data on the main components of a dynamic system, such as carcinoma associated fibroblasts that change the extracellular matrix (ECM) topology, induce stemness and promote metastasis-initiating cells. Altered production and characteristics of collagen, hyaluronan and other ECM proteins induce increased matrix stiffness. Stiffness along with tumor growth-induced solid stress and increased interstitial fluid pressure contribute to tumor progression and therapy resistance. Second, the role of immune cells, cytokines and chemokines is outlined. We discuss other noncellular characteristics of the tumor microenvironment such as hypoxia and extracellular pH in relation to neoangiogenesis. Overall, full understanding of the events driving the interactions between tumor cells and their environment is of crucial importance in overcoming treatment resistance and improving patient outcome.

  12. AFP464 in Treating Patients With Metastatic or Refractory Solid Tumors That Cannot Be Removed By Surgery

    Science.gov (United States)

    2014-02-21

    Male Breast Cancer; Recurrent Breast Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Recurrent Renal Cell Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  13. PNU-145156E, a novel angiogenesis inhibitor, in patients with solid tumors : A phase I and pharmacokinetic study

    NARCIS (Netherlands)

    Groen, HJM; de Vries, EGE; Wynendaele, W; van der Graaf, WTA; Lechuga, EFMJ; Poggesi, [No Value; Dirix, LY; van Oosterom, AT

    2001-01-01

    Our aim was to establish, in patients with solid tumors, the dose-limiting toxicity, maximum tolerated dose (MTD), and pharmacology of PNU-145156E, a new sulfonated distamycin A derivative that blocked circulating angiogenesis-promoting growth factors in animal studies and exhibited an antitumor eff

  14. Impact of TROP2 expression on prognosis in solid tumors: A Systematic Review and Meta-analysis

    Science.gov (United States)

    Zeng, Ping; Chen, Min-Bin; Zhou, Li-Na; Tang, Min; Liu, Chao-Ying; Lu, Pei-Hua

    2016-01-01

    Over-expression of TROP2 (the trophoblast cell surface antigen 2) was reported to predict poor prognosis in various solid tumors in number of studies. However, the results remained not comprehensive. Therefore, we here carried out this meta-analysis of relevant studies published on this topic to quantitatively evaluate the clinicopathological significance of TROP2 in solid tumors. Relevant articles were identified through searching the PubMed, Web of Science and Embase database. The primary outcomes were overall survival (OS) and disease-free survival (DFS). In this meta-analysis, 16 studies involving 2,569 participants were included, and we drew the conclusion that TROP2 overexpression was significantly associated with poor OS (pooled HR = 1.896, 95% CI = 1.599–2.247, P genital system neoplasms, as well in gastrointestine neoplasms. In addition, subgroup analysis found no difference HR across populations of different descent.Taken together, TROP2 overexpression was associated with poor survival in human solid tumors. TROP2 may be a valuable prognosis predictive biomarker and a potential therapeutic target in human solid tumors. PMID:27645103

  15. Beyond breast and ovarian cancers: PARP inhibitors for BRCA mutation-associated and BRCA-like solid tumors

    Directory of Open Access Journals (Sweden)

    Ciara C. O'Sullivan

    2014-02-01

    Full Text Available Poly(ADP-ribose polymerase inhibitors (PARPi have shown clinical activity in patients with germline BRCA1/2 mutation (gBRCAm-associated breast and ovarian cancers. Accumulating evidence suggests that PARPi may have a wider application in the treatment of cancers defective in DNA damage repair pathways, such as prostate, lung, endometrial, and pancreatic cancers. Several PARPi are currently in phase I/II clinical investigation, as single agents and/or in combination therapy in these solid tumors. Understanding more about the molecular abnormalities involved in BRCA-like phenotype in solid tumors beyond breast and ovarian cancers, exploring novel therapeutic trial strategies and drug combinations, and defining potential predictive biomarkers, are critical to expanding the field of PARPi therapy. This will improve clinical outcome in advanced solid tumors. Here we briefly review the preclinical data and clinical development of PARPi, and discuss its future of development in solid tumors beyond gBRCAm associated breast and ovarian cancers.

  16. Genetically modified T cells targeting neovasculature efficiently destroy tumor blood vessels, shrink established solid tumors and increase nanoparticle delivery.

    Science.gov (United States)

    Fu, Xinping; Rivera, Armando; Tao, Lihua; Zhang, Xiaoliu

    2013-11-15

    Converting T cells into tumor cell killers by grafting them with a chimeric antigen receptor (CAR) has shown promise as a cancer immunotherapeutic. However, the inability of these cells to actively migrate and extravasate into tumor parenchyma has limited their effectiveness in vivo. Here we report the construction of a CAR containing an echistatin as its targeting moiety (eCAR). As echistatin has high binding affinity to αvβ3 integrin that is highly expressed on the surface of endothelial cells of tumor neovasculature, T cells engrafted with eCAR (T-eCAR) can efficiently lyse human umbilical vein endothelial cells and tumor cells that express αvβ3 integrin when tested in vitro. Systemic administration of T-eCAR led to extensive bleeding in tumor tissues with no evidence of damage to blood vessels in normal tissues. Destruction of tumor blood vessels by T-eCAR significantly inhibited the growth of established bulky tumors. Moreover, when T-eCAR was codelivered with nanoparticles in a strategically designed temporal order, it dramatically increased nanoparticle deposition in tumor tissues, pointing to the possibility that it may be used together with nanocarriers to increase their capability to selectively deliver antineoplastic drugs to tumor tissues.

  17. Is the NBN gene mutation I171V a potential risk factor for malignant solid tumors in children?

    Science.gov (United States)

    Nowak, Jerzy; Mosor, Maria; Nowicka, Karina; Rembowska, Jolanta; Januszkiewicz, Danuta

    2011-08-01

    NBN gene is considered as one of the low-to-moderate cancer susceptibility gene. At least 4 germline NBN mutations have been found in several malignancies in adults. In our studies, we observed the high incidence of germline mutation I171V of NBN gene in breast, colorectal, larynx cancer, and in multiple primary tumors. In this study, we would like to answer the question whether I171V germline mutation of NBN gene may constitute risk factor for solid tumors in children. The frequency of this mutation has been analyzed in patients with neuroblastoma (n=66), Wilms tumor (n=54), medulloblastoma (n=57), and rhabdomyosarcoma (n=82) hospitalized in Pediatric Oncology, Hematology and Bone Marrow Transplantation Department in the years between 1987 and 2010. About 2947 anonymous blood samples collected on Guthrie cards drawn from the newborn screening program of the Wielkopolska region have been used as controls. All the patients and controls came from the same geographical region. I171V mutation of the NBN gene has been observed in 5 controls. Among children with solid tumors only in 1 child with medulloblastoma I171V variant has been found. In conclusion, I171V germline mutation in contrary to adults cannot be considered as a risk factor for children malignancies. However, owing to low number of patients with solid tumors the possibility of a Type II error may exist.

  18. A facile route to core-shell nanoparticulate formation of arsenic trioxide for effective solid tumor treatment

    Science.gov (United States)

    Zhang, Zongjun; Liu, Hanyu; Zhou, Hualu; Zhu, Xianglong; Zhao, Zhenghuan; Chi, Xiaoqin; Shan, Hong; Gao, Jinhao

    2016-02-01

    Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a ``one-pot'' method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core-shell embedding method endows nanodrugs with high loading capacity (57.9 wt%) and a prolonged pH-responsive releasing profile, which is crucial to increase the drug concentration at tumor sites and improve the drug efficacy. Based on these unique features, the nanodrugs significantly inhibit the growth of solid tumors without adverse side effects. Therefore, we anticipate that the arsenic-based nanodrugs generated by this facile synthetic route may be a powerful and alternative strategy for solid tumor therapy.Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a ``one-pot'' method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core-shell embedding method endows nanodrugs with high loading capacity

  19. A phase I study assessing the safety and pharmacokinetics of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with gemcitabine and cisplatin in patients with solid tumors

    NARCIS (Netherlands)

    Gietema, J. A.; Hoekstra, R.; de Vos, F. Y. F. L.; Uges, D. R. A.; van der Gaast, A.; Groen, H. J. M.; Loos, W. J.; Knight, R. A.; Carr, R. A.; Humerickhouse, R. A.; Eskens, F. A. L. M.

    2006-01-01

    Background: The aim of the study was to determine the safety profile, pharmacokinetics and potential drug interactions of the angiogenesis inhibitor ABT-510 combined with gemcitabine-cisplatin chemotherapy in patients with solid tumors. Patients and methods: Patients with advanced solid tumors recei

  20. Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors.

    Science.gov (United States)

    Milowsky, Matthew I; Nanus, David M; Kostakoglu, Lale; Sheehan, Christine E; Vallabhajosula, Shankar; Goldsmith, Stanley J; Ross, Jeffrey S; Bander, Neil H

    2007-02-10

    Based on prostate-specific membrane antigen (PSMA) expression on the vasculature of solid tumors, we performed a phase I trial of antibody J591, targeting the extracellular domain of PSMA, in patients with advanced solid tumor malignancies. This was a proof-of-principle evaluation of PSMA as a potential neovascular target. The primary end points were targeting,toxicity, maximum-tolerated dose, pharmacokinetics (PK), and human antihuman antibody (HAHA) response. Patients had advanced solid tumors previously shown to express PSMA on the neovasculature. They received 111Indium (111ln)-J591 for scintigraphy and PK, followed 2 weeks later by J591 with a reduced amount of 111In for additional PK measurements. J591 dose levels were 5, 10, 20, 40, and 80 mg. The protocol was amended for six weekly administrations of unchelated J591. Patients with a response or stable disease were eligible for re-treatment. Immunohistochemistry assessed PSMA expression in tumor tissues. Twenty-seven patients received monoclonal antibody (mAb) J591. Treatment was well tolerated. Twenty (74%) of 27 patients had at least one area of known metastatic disease targeted by 111In-J591, with positive imaging seen in patients with kidney, bladder, lung, breast, colorectal, and pancreatic cancers, and melanoma. Seven of 10 patient specimens available for immunohistochemical assessment of PSMA expression in tumor-associated vasculature demonstrated PSMA staining. No HAHA response was seen. Three patients of 27 with stable disease received re-treatment. Acceptable toxicity and excellent targeting of known sites of metastases were demonstrated in patients with multiple solid tumor types, highlighting a potential role for the anti-PSMA antibody J591 as a vascular-targeting agent.

  1. Dextran-functionalized magnetic fluid mediating magnetohyperthermia for treatment of Ehrlich-solid-tumor-bearing mice: toxicological and histopathological evaluations.

    Science.gov (United States)

    Miranda-Vilela, Ana Luisa; Yamamoto, Kelly Reis; Miranda, Kely Lopes Caiado; Matos, Breno Noronha; de Almeida, Marcos Célio; Longo, João Paulo Figueiró; de Souza Filho, José; Fernandes, Juliana Menezes Soares; Sartoratto, Patrícia Pommé Confessori; Lacava, Zulmira Guerrero Marques

    2014-04-01

    Dextran-functionalized maghemite fluid (DexMF) has been tested to treat Ehrlich-solid-tumor-bearing mice, evidencing its potential use in mediating magnetohyperthermia in breast cancer treatment. However, although magnetic nanoparticles tend to accumulate in tumor tissues, part of the nanomaterial can reach the blood stream, and then the organism. The aim of this study was to investigate the acute systemic effects of the intratumoral injection of DexMF mediating magnetohyperthermia in the treatment of an advanced clinical Ehrlich-solid-tumor, assessed through histopathological analyses of liver, kidneys, heart and spleen, comet assay, micronucleus test, hemogram, and serum levels of bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, creatinine, and urea. The tumor's histopathology and morphometry were used to assess its aggressiveness and regression. DexMF mediating hyperthermia was effective in containing tumor aggressiveness and in inducing tumor regression, besides showing no toxic effects. Its physical characteristics also suggest that it is safe to use in other biomedical applications.

  2. Tumor pseudopapilar sólido del páncreas: Reporte de un caso Solid pseudopapillary tumor of the pancreas: case report

    Directory of Open Access Journals (Sweden)

    Blas Gastón Vittore

    2010-04-01

    Full Text Available El tumor pseudopapilar sólido de páncreas es una neoplasia poco común que representa solo el 1-2% de los tumores del páncreas. En este reporte se presenta el caso de una paciente de sexo femenino de 13 años que consultó por un cuadro de dolor abdominal. Se le realizó una ecografía en la que se identificó una masa heterogénea pancreática, la que posteriormente fue estudiada con tomografía computada (TC. Se le extirpó quirúrgicamente la cola del páncreas y el bazo, revelando el informe de anatomía patológica la existencia de un tumor sólido-quístico del páncreas. Con la finalidad de plantear un correcto diagnóstico diferencial entre esta lesión y otros tumores pancreáticos, se realizó una revisión de la literatura existente, analizando el aporte de los distintos métodos de imágenes en los tumores de esta estirpe, con sus variables características y comportamientos.The solid pseudopapillary tumor of the pancreas is a rare disease, accounting for only 1-2% of pancreatic cystic tumors. We report on a 13-year-old female patient who complained of abdominal pain. An ultrasound was performed, which revealed a heterogeneous pancreatic mass, which was further analyzed with computed tomography (CT. The spleen and pancreas tail were surgically removed. The pathology report described the existence of a solid cystic tumor of the pancreas. In order to make a proper differential diagnosis between this lesion and other pancreatic tumors, a literature review was carried out. We further analyzed the contribution of different imaging methods to the excised tumors, which presented diverse characteristics and behaviors.

  3. Interleukin-12 in Treating Patients With Hematologic Cancers or Solid Tumors

    Science.gov (United States)

    2014-09-09

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  4. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review

    Science.gov (United States)

    Shrotriya, Shiva; Walsh, Declan; Bennani-Baiti, Nabila; Thomas, Shirley; Lorton, Cliona

    2015-01-01

    Purpose A systematic literature review was done to determine the relationship between elevated CRP and prognosis in people with solid tumors. C-reactive protein (CRP) is a serum acute phase reactant and a well-established inflammatory marker. We also examined the role of CRP to predict treatment response and tumor recurrence. Methods MeSH (Medical Subject Heading) terms were used to search multiple electronic databases (PubMed, EMBASE, Web of Science, SCOPUS, EBM-Cochrane). Two independent reviewers selected research papers. We also included a quality Assessment (QA) score. Reports with QA scores lung, pancreas, hepatocellular cancer, and bladder) an elevated CRP also predicted prognosis. In addition there is also evidence to support the use of CRP to help decide treatment response and identify tumor recurrence. Better designed large scale studies should be conducted to examine these issues more comprehensively. PMID:26717416

  5. Response Rate as a Regulatory End Point in Single-Arm Studies of Advanced Solid Tumors

    Science.gov (United States)

    Oxnard, Geoffrey R.; Wilcox, Katharine H.; Gonen, Mithat; Polotsky, Mikhael; Hirsch, Bradford R.; Schwartz, Lawrence H.

    2017-01-01

    IMPORTANCE Objective response rate (ORR) is an increasingly important end point for accelerated development of highly active anticancer therapies, yet its relationship to regulatory approval is not well characterized. OBJECTIVE To identify circumstances in which a high ORR is associated with regulatory approval, and therefore might be an appropriate end point for definitive single-arm studies of anticancer therapies. DATA SOURCE A database of all oncology clinical trials registered at clinicaltrials.gov between October 1, 2007, and September 30, 2010. STUDY SELECTION Trials of palliative systemic therapies for 4 measurable solid tumor types, limited to those with trial arms of at least 20 patients reporting ORR per Response Evaluation Criteria in Solid Tumors (RECIST). DATA EXTRACTION AND SYNTHESIS A systematic search was used to identify the reported ORR for each eligible treatment arm that had been presented publicly. MAIN OUTCOMES AND MEASURES For each treatment regimen, defined as a single-agent or unique combination of agents for 1 cancer type, the mean ORR and the maximum ORR statistically exceeded were calculated, and their association with regulatory approval was studied. A regimen was considered approved for a specific cancer type if it had received regulatory approval in any country for treatment of advanced cancer of that type. RESULTS From 1800 trials, 874 eligible trial arms in 578 eligible trials were identified; 542 arms had ORR data available for 294 regimens. Maximum ORR and mean ORR were significantly associated with regulatory approval (τ = 0.27, P < .001; τ = 0.12, P = .01); this relationship was stronger for single-agent therapies (τ = 0.49; τ = 0.41) than for combination regimens (τ = 0.28; τ = 0.17). Evaluation of ORR thresholds between 20% and 60% as potential trial end points demonstrated that ORR statistically exceeding 30% with a single agent had 98% specificity and 89% positive predictive value for identifying regimens achieving

  6. Pharmacokinetic characteristics of vincristine sulfate liposomes in patients with advanced solid tumors

    Institute of Scientific and Technical Information of China (English)

    Zhao YAN; Zhong-ling ZHU; Zheng-zi QIAN; Ge HU; Hua-qing WANG; Wan-hui LIU; Guang CHENG

    2012-01-01

    Aim:To evaluate the single- and multiple-dose pharmacokinetics of vincristine sulfate liposomes (VSLI) in patients with advanced solid tumors.Methods:In single-dose pharmacokinetic study,16 patients were administered VSLI (1.5,2.0,or 2.3 mg.m-2) through intravenous infusion.Another 6 patients receiving vincristine sulfate (VCR,2.0 mg) were taken as the control.In multiple-dose pharmacokinetic study,12 patients were administered VSLI (1.5 or 1.8 mg.m-2) through intravenous infusion weekly for 4 consecutive weeks.The plasma concentration of VSLI was determined using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.Results:After intravenous infusion of the single dose of VSLI,the plasma concentrations were characterized by bi-exponential decline curves.No statistically significant differences were observed between the main pharmacokinetic parameters in the 3 dose groups.Compared with the patients receiving VCR,the patients treated with VSLI displayed an increase in the area under the plasma concentration vs time curve (AUC),and a decrease in plasma clearance rates.On the 4th cycle in the multiple-dose study,the plasma concentration of VCR in all subjects prior to the weekly administration was below the lower limit of quantification (LLOQ).The calculated pharmacokinetic parameters from the subjects in the multiple-and single-dose (1.5 mgm-2) groups had no significant differences.Although the administration of liposomal VCR may significantly elevate the plasma concentration of VCR,VSLI-associated adverse events were similar to those associated with conventional VCR.Conclusion:VSLI exhibits a lower clearance and a higher AUC compared with conventional VCR.No accumulation was observed in patients exposed to VSLI for 4 consecutive weeks.VSLI was generally tolerated in the subjects.The phase Ⅱ dose of VSLI may be recommended as 4 doses of 1.5 mg·m-2 for treatment of patients with advanced solid tumors.

  7. Solid pseudopapillary tumors of the pancreas. Case report and review of the literature.

    Science.gov (United States)

    Leggio, Samuele; Orofino, Antonio; Anzillotto, Maria Paola L; Zullino, Francesca; Di Napoli, Geremia; Paradies, Guglielmo

    2014-07-21

    I Tumori solidi pseudopapillari del pancreas rappresentano una rara forma di tumori pancreatici: caratterizzati da un basso grado di malignità ed una lenta crescita, essi colpiscono più frequentemente donne giovani adulte ma anche, in circa il 20% dei casi descritti in letteratura, bambini ed adolescenti, epoca in cui viene riferita una minore aggressività biologica rispetto all’adulto. Nella maggior parte dei casi pediatrici la neoplasia è asintomatica e viene scoperta solo occasionalmente; diversamente, in altri casi, si manifesta come una massa addominale palpabile, talora dolente, oppure esordisce con dolore improvviso e con i segni ed i sintomi dovuti alla compressione degli organi vicini. Riportiamo il recente caso di una ragazza di 15 anni, giunta alla nostra osservazione per il riscontro di una massa interessante il corpo e la coda del pancreas, scoperta incidentalmente nel corso di un esame ecografico Published online (EP) 18 July 2014 - Ann. Ital. Chir 5 Solid pseudopapillary tumors of the pancreas. Case report and review of the literature dell’addome eseguito dopo un lieve trauma.Gli ulteriori successivi esami diagnostici cui veniva sottoposta la ragazza, confermavano la presenza della lesione pancreatica che appariva ben delimitata, apparentemente capsulata, a struttura disomogenea ,strettamente aderente alla vena splenica. Posto il sospetto diagnostico di un tumore solido pseudo-papillare del pancreas, si procedeva chirurgicamente alla sua enucleazione. L’esame istolopatologico della massa confermava la diagnosi preoperatoria. Il caso ,che viene presentato nei suoi aspetti clinico-diagnostici e terapeutici, offre l’occasione per ricercare e discutere alcuni interessanti aspetti di questa rara patologia, ancora ampiamente dibattuti in Letteratura.

  8. Phase I study of gemcitabine, docetaxel and imatinib in refractory and relapsed solid tumors

    Science.gov (United States)

    Chugh, Rashmi; Karantza, Vassiliki; Mehnert, Janice; Moss, Rebecca A.; Savkina, Nelli; Stein, Mark N.; Baker, Laurence H.; Chenevert, Thomas; Poplin, Elizabeth A.

    2017-01-01

    Summary Purpose In a phase I study, the combination of gemcitabine and imatinib was well tolerated with broad anticancer activity. This phase I trial evaluated the triplet of docetaxel, gemcitabine and imatinib. Experimental Design Imatinib was administered at 400 mg daily on days 1–5, 8–12 and 15–19. Gemcitabine was started at 600 mg/m2 at a rate of 10 mg/min on days 3 and 10 and docetaxel at 30 mg/m2 on day 10, on a 21-day cycle. Diffusion and dynamic contrast-enhanced perfusion MRI was performed in selected patients. Results Twenty patients with relapsed/ refractory solid tumors were enrolled in this IRB-approved study. The mean age was 64, and mean ECOG PS was 1. Two patients were evaluated by diffusion/perfusion MRI. After two grade 3 hematological toxicities at dose level 1, the protocol was amended to reduce the dose of imatinib. MTDs were 600 mg/ m2 on days 3 and 10 for gemcitabine, 30 mg/ m2 on day 10 for docetaxel, and 400 mg daily on days 1–5 and 8–12 for imatinib. Dose limiting toxicities after one cycle were neutropenic fever, and pleural and pericardial effusions. The best response achieved was stable disease, for six cycles, in one patient each with mesothelioma and non small cell lung cancer (NSCLC) at the MTD. Two patients with NSCLC had stable disease for four cycles. Discussion An unexpectedly low MTD for this triplet was identified. Our results suggest drug-drug interactions that amplify toxicities with little evidence of improved tumor control. PMID:20697775

  9. Spatial morphological and molecular differences within solid tumors may contribute to the failure of vascular disruptive agent treatments

    Directory of Open Access Journals (Sweden)

    Nguyen Linh

    2012-11-01

    Full Text Available Abstract Background Treatment of solid tumors with vascular disrupting agent OXi4503 results in over 90% tumor destruction. However, a thin rim of viable cells persists in the tumor periphery following treatment, contributing to subsequent recurrence. This study investigates inherent differences in the microenvironment of the tumor periphery that contribute to treatment resistance. Methods Using a murine colorectal liver metastases model, spatial morphological and molecular differences within the periphery and the center of the tumor that may account for differences in resistance to OXi4503 treatment were investigated. H&E staining and immunostaining were used to examine vessel maturity and stability, hypoxia and HIF1α levels, accumulation of immune cells, expression of proangiogenic factors/receptors (VEGF, TGF-β, b-FGF, and AT1R and expression of EMT markers (ZEB1, vimentin, E-cadherin and β-catenin in the periphery and center of established tumors. The effects of OXi4503 on tumor vessels and cell kinetics were also investigated. Results Significant differences were found between tumor periphery and central regions, including association of the periphery with mature vessels, higher accumulation of immune cells, increased growth factor expression, minimal levels of hypoxia and increased evidence of EMT. OXi4503 treatment resulted in collapse of vessels in the tumor center; however vasculature in the periphery remained patent. Similarly, tumor apoptosis and proliferation were differentially modulated between centre and periphery after treatment. Conclusions The molecular and morphological differences between tumor periphery and center may account for the observed differential resistance to OXi4503 treatment and could provide targets for drug development to totally eliminate metastases.

  10. Humanized mouse model of ovarian cancer recapitulates patient solid tumor progression, ascites formation, and metastasis.

    Directory of Open Access Journals (Sweden)

    Richard B Bankert

    Full Text Available Ovarian cancer is the most common cause of death from gynecological cancer. Understanding the biology of this disease, particularly how tumor-associated lymphocytes and fibroblasts contribute to the progression and metastasis of the tumor, has been impeded by the lack of a suitable tumor xenograft model. We report a simple and reproducible system in which the tumor and tumor stroma are successfully engrafted into NOD-scid IL2Rγ(null (NSG mice. This is achieved by injecting tumor cell aggregates derived from fresh ovarian tumor biopsy tissues (including tumor cells, and tumor-associated lymphocytes and fibroblasts i.p. into NSG mice. Tumor progression in these mice closely parallels many of the events that are observed in ovarian cancer patients. Tumors establish in the omentum, ovaries, liver, spleen, uterus, and pancreas. Tumor growth is initially very slow and progressive within the peritoneal cavity with an ultimate development of tumor ascites, spontaneous metastasis to the lung, increasing serum and ascites levels of CA125, and the retention of tumor-associated human fibroblasts and lymphocytes that remain functional and responsive to cytokines for prolonged periods. With this model one will be able to determine how fibroblasts and lymphocytes within the tumor microenvironment may contribute to tumor growth and metastasis, and will make it possible to evaluate the efficacy of therapies that are designed to target these cells in the tumor stroma.

  11. Doppler sonography of extracranial and intracranial vessels in patients with thrombotic stroke

    Directory of Open Access Journals (Sweden)

    Farhad Iranmanesh

    2006-12-01

    Full Text Available INTRODUCTION: The results of intracranial and extracranial vessel color Doppler sonography, which is now an inseparable part of patient evaluation, vary in different studies. The objective of this study was to evaluate the pattern of vascular involvement in thrombotic stroke and its relationship with risk factors of stroke. METHODS: One-hundred patients (45 males and 55 females with thrombotic stroke underwent transcranial sonography and color Doppler sonography of extracranial vessels. The pattern of vascular involvement was analyzed. The risk factors of stroke were also evaluated. RESULTS: Forty-seven percent of the studied individuals had some variations in their color Doppler sonography of extracranial vessels, 27% had changes in the intracranial vessels and 26% showed changes in both. The most frequently involved vessels among the intracranial and extracranial vessels were the middle cerebral artery and the internal carotid artery, respectively. The pattern of vascular involvement was unrelated to hypertension, cigarette smoking, diabetes mellitus, dyslipidemia or history of ischemic heart disease. Extracranial involvement in patients with positive history of MI was more prevalent than in those without such history. CONCLUSIONS: Extracranial vessel involvement in thrombotic stroke was found to be more prevalent than intracranial vessel involvement in the city of Rafsanjan; however, intracranial vessel involvement was more prevalent than in western countries. KEY WORDS: Thrombotic stroke, color Doppler sonography, intracranial vessels, extracranial, cerebrovascular risk factors

  12. Serum cross-linked n-telopeptides of type 1 collagen (NTx in patients with solid tumors

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    Fernando Jablonka

    Full Text Available CONTEXT AND OBJECTIVE: Cross-linked N-telopeptides of type I collagen (NTx increase in concentration in situations in which bone resorption is increased, such as osteoporosis and bone metastasis (BM. We aimed to evaluate the serum concentrations of NTx in a sample of patients with several types of solid tumors. DESIGN AND SETTING: Cross-sectional analytical study with a control group in a tertiary public hospital. METHODS: We performed the quantitative enzyme-linked immunosorbent assay (ELISA on serum NTx levels in 19 subjects without a history of cancer and 62 patients with various solid tumors who had been referred for a bone scan. Three experienced analysts read all bone scans. RESULTS: The serum NTx levels in patients with cancer and BM, with cancer but without BM and without cancer were 46.77 ± 2.58, 32.85 ± 2.05 and 22.32 ± 2.90 respectively (P < 0.0001. We did not find any significant correlations of serum NTx with age, gender, history of bone pain, tumor type and bone alkaline phosphatase levels. We found a significant correlation between serum NTx and alkaline phosphatase levels (R² = 0.08; P = 0.022. CONCLUSIONS: Serum NTx levels are significantly higher in patients with solid tumors and bone metastases than they are in patients without bone metastases and in normal controls.

  13. Incidence of anemia in patients diagnosed with solid tumors receiving chemotherapy, 2010–2013

    Science.gov (United States)

    Xu, Hairong; Xu, Lanfang; Page, John H; Cannavale, Kim; Sattayapiwat, Olivia; Rodriguez, Roberto; Chao, Chun

    2016-01-01

    Purpose The purpose of this study was to evaluate and characterize the risk of anemia during the course of chemotherapy among patients with five common types of solid tumors. Patients and methods Patients diagnosed with incident cancers of breast, lung, colon/rectum, stomach, and ovary who received chemotherapy were identified from Kaiser Permanente Southern California Health Plan (2010–2012). All clinical data were collected from the health plan’s electronic medical records. Incidence proportions of patients developing anemia and 95% confidence intervals were calculated overall and by anemia severity and type, as well as by stage at cancer diagnosis, and by chemotherapy regimen and cycle. Results A total of 4,426 patients who received chemotherapy were included. Across cancers, 3,962 (89.5%) patients developed anemia during the course of chemotherapy (normocytic 85%, macrocytic 10%, microcytic 5%; normochromic 47%, hyperchromic 44%, hypochromic 9%). The anemia grades were distributed as follows: 58% were grade 1, 34% grade 2, 8% grade 3, and anemia ranged from 26.3% in colorectal cancer patients to 59.2% in ovarian cancer patients. Incidence of grade 2+ anemia increased from 29% in stage I to 49% in stage IV. Incidence of grade 2+ anemia varied from 18.2% in breast cancer patients treated with cyclophosphamide + docetaxel regimen to 59.7% in patients with ovarian cancer receiving carboplatin + paclitaxel regimen. Conclusion The incidence of moderate-to-severe anemia (hemoglobin anemia was greater in patients with distant metastasis. PMID:27186078

  14. Prevalence of Café-au-Lait Spots in children with solid tumors.

    Science.gov (United States)

    Santos, Anna Claudia Evangelista Dos; Heck, Benjamin; Camargo, Beatriz De; Vargas, Fernando Regla

    2016-05-24

    Cafe-au-lait maculae (CALM) are frequently observed in humans, and usually are present as a solitary spot. Multiple CALMs are present in a smaller fraction of the population and are usually associated with other congenital anomalies as part of many syndromes. Most of these syndromes carry an increased risk of cancer development. Previous studies have indicated that minor congenital anomalies may be more prevalent in children with cancer. We investigated the prevalence of CALMs in two samples of Brazilian patients with childhood solid tumors, totaling 307 individuals. Additionally, 176 school children without diagnosis of cancer, or of a cancer predisposing syndrome, were investigated for the presence of CALMs. The prevalence of solitary CALM was similar in both study groups (18% and 19%) and also in the group of children without cancer. Multiple CALMs were more frequently observed in one of the study groups (Z = 2.1). However, when both groups were analyzed together, the significance disappeared (Z = 1.5). The additional morphological abnormalities in children with multiple CALMs were analyzed and compared to the findings observed in the literature. The nosologic entities associated with CALMs are reviewed.

  15. Paclitaxel and Carboplatin in Treating Patients With Metastatic or Recurrent Solid Tumors and HIV Infection

    Science.gov (United States)

    2017-08-23

    HIV Infection; Recurrent Anal Cancer; Recurrent Breast Cancer; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Anal Cancer; Stage IV Breast Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Unspecified Adult Solid Tumor, Protocol Specific

  16. Development and Validation of a Small Animal Immobilizer and Positioning System for the Study of Delivery of Intracranial and Extracranial Radiotherapy Using the Gamma Knife System.

    Science.gov (United States)

    Awan, Musaddiq J; Dorth, Jennifer; Mani, Arvind; Kim, Haksoo; Zheng, Yiran; Mislmani, Mazen; Welford, Scott; Yuan, Jiankui; Wessels, Barry W; Lo, Simon S; Letterio, John; Machtay, Mitchell; Sloan, Andrew; Sohn, Jason W

    2017-04-01

    The purpose of this research is to establish a process of irradiating mice using the Gamma Knife as a versatile system for small animal irradiation and to validate accurate intracranial and extracranial dose delivery using this system. A stereotactic immobilization device was developed for small animals for the Gamma Knife head frame allowing for isocentric dose delivery. Intercranial positional reproducibility of a reference point from a primary reference animal was verified on an additional mouse. Extracranial positional reproducibility of the mouse aorta was verified using 3 mice. Accurate dose delivery was validated using film and thermoluminescent dosimeter measurements with a solid water phantom. Gamma Knife plans were developed to irradiate intracranial and extracranial targets. Mice were irradiated validating successful targeted radiation dose delivery. Intramouse positional variability of the right mandible reference point across 10 micro-computed tomography scans was 0.65 ± 0.48 mm. Intermouse positional reproducibility across 2 mice at the same reference point was 0.76 ± 0.46 mm. The accuracy of dose delivery was 0.67 ± 0.29 mm and 1.01 ± 0.43 mm in the coronal and sagittal planes, respectively. The planned dose delivered to a mouse phantom was 2 Gy at the 50% isodose with a measured thermoluminescent dosimeter dose of 2.9 ± 0.3 Gy. The phosphorylated form of member X of histone family H2A (γH2AX) staining of irradiated mouse brain and mouse aorta demonstrated adjacent tissue sparing. In conclusion, our system for preclinical studies of small animal irradiation using the Gamma Knife is able to accurately deliver intracranial and extracranial targeted focal radiation allowing for preclinical experiments studying focal radiation.

  17. A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors.

    Science.gov (United States)

    Bacac, Marina; Fauti, Tanja; Sam, Johannes; Colombetti, Sara; Weinzierl, Tina; Ouaret, Djamila; Bodmer, Walter; Lehmann, Steffi; Hofer, Thomas; Hosse, Ralf J; Moessner, Ekkehard; Ast, Oliver; Bruenker, Peter; Grau-Richards, Sandra; Schaller, Teilo; Seidl, Annette; Gerdes, Christian; Perro, Mario; Nicolini, Valeria; Steinhoff, Nathalie; Dudal, Sherri; Neumann, Sebastian; von Hirschheydt, Thomas; Jaeger, Christiane; Saro, Jose; Karanikas, Vaios; Klein, Christian; Umaña, Pablo

    2016-07-01

    CEA TCB is a novel IgG-based T-cell bispecific (TCB) antibody for the treatment of CEA-expressing solid tumors currently in phase I clinical trials (NCT02324257). Its format incorporates bivalent binding to CEA, a head-to-tail fusion of CEA- and CD3e-binding Fab domains and an engineered Fc region with completely abolished binding to FcγRs and C1q. The study provides novel mechanistic insights into the activity and mode of action of CEA TCB. CEA TCB activity was characterized on 110 cell lines in vitro and in xenograft tumor models in vivo using NOG mice engrafted with human peripheral blood mononuclear cells. Simultaneous binding of CEA TCB to tumor and T cells leads to formation of immunologic synapses, T-cell activation, secretion of cytotoxic granules, and tumor cell lysis. CEA TCB activity strongly correlates with CEA expression, with higher potency observed in highly CEA-expressing tumor cells and a threshold of approximately 10,000 CEA-binding sites/cell, which allows distinguishing between high- and low-CEA-expressing tumor and primary epithelial cells, respectively. Genetic factors do not affect CEA TCB activity confirming that CEA expression level is the strongest predictor of CEA TCB activity. In vivo, CEA TCB induces regression of CEA-expressing xenograft tumors with variable amounts of immune cell infiltrate, leads to increased frequency of activated T cells, and converts PD-L1 negative into PD-L1-positive tumors. CEA TCB is a novel generation TCB displaying potent antitumor activity; it is efficacious in poorly infiltrated tumors where it increases T-cell infiltration and generates a highly inflamed tumor microenvironment. Clin Cancer Res; 22(13); 3286-97. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. TCR-engineered T cells meet new challenges to treat solid tumors: choice of antigen, T cell fitness and sensitisation of tumor milieu (review

    Directory of Open Access Journals (Sweden)

    Andre eKunert

    2013-11-01

    Full Text Available Adoptive transfer of T cells gene-engineered with antigen-specific T cell receptors (TCRs has proven its feasibility and therapeutic potential in the treatment of malignant tumors. To ensure further clinical development of TCR gene therapy, it is necessary to target immunogenic epitopes that are related to oncogenesis and selectively expressed by tumor tissue, and implement strategies that result in optimal T cell fitness. In addition, in particular for the treatment of solid tumors, it is equally necessary to include strategies that counteract the immune-suppressive nature of the tumor micro-environment. Here, we will provide an overview of the current status of TCR gene therapy, and redefine the following three challenges of improvement: ‘choice of target antigen’; ‘fitness of T cells’; and ‘sensitisation of tumor milieu’. We will categorize and discuss potential strategies to address each of these challenges, and argue that advancement of clinical TCR gene therapy critically depends on developments towards each of the three challenges.

  19. Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network.

    Directory of Open Access Journals (Sweden)

    M Soltani

    Full Text Available Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor's surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy's law for tissue, and simplified Navier-Stokes equation for blood flow through capillaries are used for simulating interstitial and intravascular flows and Starling's law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.

  20. Low-Dose Decitabine-Based Chemoimmunotherapy for Patients with Refractory Advanced Solid Tumors: A Phase I/II Report

    Directory of Open Access Journals (Sweden)

    Hui Fan

    2014-01-01

    Full Text Available Aberrant DNA methylation is one of the main drivers of tumor initiation and progression. The reversibility of methylation modulation makes it an attractive target for novel anticancer therapies. Clinical studies have demonstrated that high-dose decitabine, a hypomethylating agent, results in some clinical benefits in patients with refractory advanced tumors; however, they are extremely toxic. Low doses of decitabine minimize toxicity while potentially improving the targeted effects of DNA hypomethylation. Based on these mechanisms, low-dose decitabine combined with chemoimmunotherapy may be a new treatment option for patients with refractory advanced tumors. We proposed the regimen of low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors. A favorable adverse event profile was observed in our trial that was highlighted by the finding that most of these adverse events were grades 1-2. Besides, the activity of our cohort was optimistic and the clinical benefit rate was up to 60%, and the median PFS was prolonged compared with PFS to previous treatment. We also identified a significant correlation between the PFS to previous treatment and clinical response. The low-dose DAC decitabine-based chemoimmunotherapy might be a promising protocol for improving the specificity and efficiency of patients with refractory advanced solid tumors. This trial is registered in the ClinicalTrials.gov database (identifier NCT01799083.

  1. Spatial dose distributions in solid tumors from {sup 186}Re transported by liposomes using HS radiochromic media

    Energy Technology Data Exchange (ETDEWEB)

    Medina, Luis A.; Rodriguez-Villafuerte, Mercedes; Martinez-Davalos, Arnulfo; Galvan, Olga O.; Brandan, Maria-Ester [Instituto de Fisica, UNAM, A.P. 20-364, Mexico (Mexico); Goins, Beth; Awasthi, Vibhudutta; Santoyo, Cristina; Phillips, William T. [University of Texas Health Science Center at San Antonio, Department of Radiology, San Antonio, TX (United States); Bao, Ande [University of Texas Health Science Center at San Antonio, Department of Radiology, San Antonio, TX (United States); University of Texas Health Science Center at San Antonio, Department of Otolaryngology-Head and Neck Surgery, San Antonio, TX (United States)

    2007-07-15

    A procedure for the measurement of spatial dose rate distribution of beta particles emitted by {sup 186}Re-liposomes in tumoral tissue, using HS GafChromic films, is presented. HNSCC xenografts were intratumorally injected with 3.7 or 11.1 MBq of {sup 186}Re-liposomes, and planar gamma camera images were acquired to determine the liposome retention in the tumor. After imaging, rats were sacrificed and tumors were excised and processed in slices; HS film sections were placed between slices and the tumor lobe was reassembled. Tumors and films were kept in the dark at 4 C for 18 h. After irradiation, films were removed and response was read using a transmission scanner. Films were analyzed to determine two-dimensional spatial dose rate distributions and cumulative dose volume histograms. Dose rate distributions were quantified using a {sup 60}Co calibration curve, the {sup 186}Re physical half-life, and a perturbation factor that takes into account the effect of the film protective layer. Dose rate distributions are highly heterogeneous with maximal dose rates about 0.4 Gy h{sup -1} in tumors injected with 3.7 MBq and 1.3 Gy h{sup -1} in tumors injected with 11.1 MBq. Dose volume histograms showed dose distributed in more than 95% and 80% of the tumor when injected with the lower and the higher activity, respectively. The described procedures and techniques have shown the potential and utility of HS GafChromic film for determination of dose rate distributions in solid tumors injected intratumorally with {sup 186}Re-liposomes. The film's structure and the liposomes' biodistribution must be taken into account to obtain quantitative dose measurements. (orig.)

  2. Extracranially located PICA aneurysm presenting with supratentorial IVH: A rare event with diagnostic pitfalls

    Directory of Open Access Journals (Sweden)

    Amey Savardekar

    2013-01-01

    Full Text Available Extracranially located posterior inferior cerebellar artery (PICA aneurysms are rare with only 21 cases reported till date. They may arise either from the proximal segment of an extracranially originating PICA or from the tip of its caudal loop when it dips below the foramen magnum. A 16-year-old female presenting with sudden onset severe headache and intraventricular hemorrhage (IVH in the occipital horns of the lateral ventricle and the fourth ventricles, was diagnosed to have an extracranial proximal segment PICA aneurysm on a four vessel digital subtraction angiography (DSA, after initially missing it on the brain magnetic resonance imaging (MRI with angiogram (MRA because of its extracranial location. During surgery, the aneurysm was clipped following a far lateral suboccipital craniectomy with C1-C2 hemilaminectomy. The patient showed good recovery. Thus, we emphasize the need for a dedicated four vessel angiography to diagnose such lesions.

  3. Recanalization of extracranial internal carotid artery occlusion A 12-year retrospective study

    National Research Council Canada - National Science Library

    Liqun Jiao Gang Song Yang Hua Yan Ma Yanfei Chen Yabing Wang Feng Ling

    2013-01-01

    ... internal carotid artery occlusion. The study included 65 patients with extracranial internal ca- rotid artery occlusion who underwent carotid endarterectomy, carotid endarterectomy combined with Fogarty catheter embotectomy, or hybrid...

  4. Establishment of Primary Cell Culture From Ascitic Fluid and Solid Tumor Obtained From Epithelial Ovarian Carcinoma Patients.

    Science.gov (United States)

    Kar, Rajarshi; Chawla, Diwesh; Gupta, Bindiya; Mehndiratta, Mohit; Wadhwa, Neelam; Agarwal, Rachna

    2017-08-16

    Ovarian cancer is the seventh leading cause of cancer death worldwide. This is mainly due to late diagnosis and high rate of relapse and resistance following chemotherapy. In the present study, we describe simple and cost-effective method to establish primary culture from ascitic fluid and solid tumor obtained from epithelial ovarian carcinoma patient, which may provide a better tool for in vitro testing of drug sensitivity and designing individualized treatment protocol. Complete Dulbecco modified Eagle medium (DMEM) was prepared by supplementing DMEM with 10% fetal bovine serum and antibiotics (ciprofloxacin and amphotericin B). Establishment of primary culture of ovarian cancer cells from ascites fluid and solid tumor was done by using complete DMEM media. Primary cultures of ovarian cancer cells were established from ascitic fluid and solid tumor tissue. Of the 7 ascitic fluid samples, we were able to establish 5 primary cultures of ovarian cancer cells. All the 7 samples were diagnosed as serous papillary adenocarcinoma. Some fibroblasts were also attached to culture flask on day 4; they were removed by exposing them to trypsin for a brief period. On day 7, grape-like clusters were visualized under inverted microscope. The cells became confluent on the 10th and 11th day and showed cobblestone appearance, which is a hallmark of ovarian cancer cells. Senescent irregularly shaped cells that have ceased dividing were seen after 8 to 10 passages. This study highlights the fact that establishing primary cultures from ascitic fluid or solid tumor tissue may help us to understand the molecular profile of the cancer cells, which allow us to select the best chemotherapeutic agent for ovarian cancer patients and thus take a step toward patient-tailored therapy so that patients are not exposed to drugs to which they are not likely to respond.

  5. Effect of food on the pharmacokinetics of TAS‐102 and its efficacy and safety in patients with advanced solid tumors

    OpenAIRE

    Yoshino, Takayuki; Kojima, Takashi; Bando, Hideaki; YAMAZAKI, Tomoko; Naito, Yoichi; Mukai, Hirofumi; Fuse, Nozomu; Goto, Koichi; Ito, Yuko; Doi, Toshihiko; Ohtsu, Atsushi

    2016-01-01

    TAS‐102, a novel oral antitumor agent, consists of trifluridine and tipiracil hydrochloride (molar ratio, 1:0.5). We investigated the effects of food on trifluridine and tipiracil hydrochloride. The efficacy and safety of TAS‐102 were evaluated in patients with advanced solid tumors. We analyzed drug pharmacokinetics using a randomized, single‐dose, two‐treatment (fed versus fasting), two‐period, two‐sequence cross‐over design, followed by repeated administration. Patients were given single d...

  6. Tumor de Frantz-Gruber, un tumor sólido pseudopapilar del páncreas poco frecuente Frantz-Gruber Tumor, An Infrecuent Solid Pseudopapillary Tumor Of The Pancreas

    Directory of Open Access Journals (Sweden)

    Humberto Álvarez-Pertuz

    2011-09-01

    Full Text Available El tumor de Frantz - Gruber es una masa sólida pseudopapilar del páncreas, poco común y con bajo potencial de malignidad, descrita por primera vez por Franz en 1959.¹ Predomina en mujeres entre la 3era y 4ta década de vida. La sintomatología está dada principalmente por efecto de masa y se caracteriza por dolor vago y sensación de plenitud. El diagnóstico radiológico incluye estudios como tomografía axial computarizada (TAC y resonancia magnética, y los estudios histológicos confirman la sospecha clínica. El abordaje es quirúrgico en la mayoría de los casos e incluye una resección completa del tumor. La presencia de metástasis hepática no es infrecuente. La sobrevida a 5 años es por arriba del 90%.² Se reporta el caso de un paciente de 15 años, sin antecedentes patológicos o quirúrgicos, visto en el Servicio de Emergencias por epigastralgia y vómitos. Un ultrasonido (US abdominal demostró una lesión en la cola pancreática, luego por TAC y US endoscópico se logró documentar una masa de aspecto quístico y contenido denso que abarca también el cuerpo del páncreas. Se recomendó abordaje quirúrgico; durante la laparotomía exploratoria se halla tumoración mixta sólidoquística. Se practicó pancreatectomía distal y esplenectomía. La evolución y manejo postoperatorio fueron sin complicaciones.The Frantz-Gruber tumor is a rare solid pseudopapilar mass of the pancreas characterized for its low malignant potential, first described by Franz in 1959.1 It occurs mainly in women between the third and fourth decades of life. Symptoms are determined by a mass effect, commonly non-specific abdominal pain and fullness sensation. Radiological diagnosis is mainly based on CT scan and Magnetic Resonance, while the histological findings confirm the clinical suspicion. Surgical management is recommended in most of the cases and implies complete resection of the tumor. Liver metastasis are not uncommon. Five year survival rates

  7. Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

    Directory of Open Access Journals (Sweden)

    Hyun-Kyoung Kim

    Full Text Available BACKGROUND: The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs, which are abundant in solid tumors, can be utilized for identification of rearranged ends. METHOD: As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP microarray method entailing CNB-region refinement by competitor DNA. RESULT: Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9% were identified, and two polymerase chain reaction (PCR-amplifiable rearrangements were obtained in six cases (66.7%. And significantly, TNGS-CNB, with its high positive identification rate (82.6% of PCR-amplifiable rearrangements at candidate sites (19/23, just from filtering of aligned sequences, requires little effort for validation. CONCLUSION: Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

  8. Clinical analysis of solid-pseudopapillar y tumor of the pancreas:repor t of 15 cases

    Institute of Scientific and Technical Information of China (English)

    Shao-Qin Chen; Sheng-Quan Zou; Qi-Bao Dai; Hong Li

    2008-01-01

    BACKGROUND:Solid-pseudopapillary tumor of the pancreas (SPTP) is an uncommon and enigmatic pancreatic neoplasm that occurs mainly in young women. Although more and more cases have been reported in recent years, misdiagnosis and incorrect treatment still frequently take place. This study was designed to stimulate consideration of this tumor. METHODS: We retrospectively reviewed the experience of diagnosis and treatment of 15 patients with SPTP and compared them with 516 patients with pancreatic cancer from January 1997 to March 2007. RESULTS: Most of the SPTP cases were asymptomatic except for one palpable mass. Almost all SPTPs demonstrated a solid structure with hypo- or iso-attenuation, cystic structure with hypo-attenuation on pre-contrast CT scan, and enhancement of solid portions on post-contrast CT scan. By contrast, most cases of pancreatic carcinoma had multiple symptoms and abnormal blood results. The tumors showed hypo-attenuation on both pre-contrast and post-contrast CT scan, and only a few showed iso-attenuation on post-contrast CT scan. All cases of SPTP in our group were cured by surgical resection, while only 16.86%of patients with pancreatic carcinoma could undergo a radical resection. CONCLUSIONS:Clinical features and CT scans were helpful to differentiate SPTP from pancreatic carcinoma. Radical surgical resection was the most effective and safe method for the treatment of SPTP.

  9. Experience of off-label use of Eltrombopag in the treatment of thrombocytopenia associated with solid tumors

    Directory of Open Access Journals (Sweden)

    María Henar García Lagunar

    2015-02-01

    Full Text Available Purpose: To describe the results of the off-label use of eltrombopag in patients with solid tumors and thrombocytopenia that limits chemotherapy. Methods: Retrospective observational study including all patients with solid tumors who were treated with eltrombopag for thrombocytopenia during the chemotherapy treatment between January 2012 and December 2014. Results: Six patients, with solid tumors and thrombocytopenia that limits chemotherapy treatment, received eltrombopag during the study and it was observed a decrease in the delay of chemotherapy cycles (4.83 ± 4.79 delayed cycles before starting eltrombopag vs 2.50 ± 4.32 delayed cycles during the treatment with eltrombopag, p=0.492 and an increase in the percentage of administrated dosage (89.29 ± 13.36% vs 91.43 ± 10.69%, p=0.682. Also, there was an increase in platelet nadir (55.29 ± 16.45x109/L vs 76.14 ± 36.38x109/L, p=0.248 without platelet transfusion support in any patient during treatment with eltrombopag. Conclusions: eltrombopag has resulted to be an alternative in the treatment of patients with thrombocytopenia that limits chemotherapy, clinical trials with more number or patients are needed to confirm these results

  10. Tanespimycin in Treating Young Patients With Recurrent or Refractory Leukemia or Solid Tumors

    Science.gov (United States)

    2013-06-03

    Childhood Chronic Myelogenous Leukemia; Childhood Desmoplastic Small Round Cell Tumor; Disseminated Neuroblastoma; Metastatic Childhood Soft Tissue Sarcoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

  11. Solid tumors "melt" from the inside after successful CD8 T cell attack.

    NARCIS (Netherlands)

    Blohm, U.; Potthoff, D.; Kogel, A.J. van der; Pircher, H.

    2006-01-01

    Adoptive transfer of tumor-specific T cells represents a promising approach for cancer immunotherapy. Here, we visualized the anti-tumor response of CD8 T cells from P14 TCR-transgenic mice specific for the model antigen GP33 by immunohistology. P14 T cells, adoptively transferred into tumor-bearing

  12. Erlotinib and Temozolomide in Treating Young Patients With Recurrent or Refractory Solid Tumors

    Science.gov (United States)

    2013-06-04

    Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

  13. Extracranial vascular malformation: value of antenatal and postnatal MRI in management

    Energy Technology Data Exchange (ETDEWEB)

    Roche, C.J.; Pilling, D.W. [Dept. of Radiology, Royal Liverpool Children' s Hospital NHS Trust (United Kingdom); Walkinshaw, S.A. [Dept. of Fetal Medicine, Liverpool Women' s Hospital (United Kingdom); May, P.L. [Dept. of Neurosurgery, Royal Liverpool Children' s Hospital NHS Trust (United Kingdom)

    2001-10-01

    We report a case where fetal MRI using a low-field-strength magnet (0.5 T) accurately confirmed a large extracranial vascular malformation, which was suspected on antenatal US. Fetal MRI enabled better counselling of the parents and allowed suitable plans to be made regarding method of delivery and early management of the neonate. To our knowledge this is the first case of an extracranial vascular malformation imaged using fetal MRI. (orig.)

  14. Herpes simplex virus lower respiratory tract infection in patients with solid tumors.

    Science.gov (United States)

    Aisenberg, Gabriel M; Aisenberg, Galbiel; Torres, Harrys A; Torres, Harrys; Tarrand, Jeffrey; Safdar, Amar; Bodey, Gerald; Chemaly, Roy F

    2009-01-01

    The clinical significance of herpes simplex virus (HSV) isolated in lower respiratory tract specimens (LRTS) of patients with solid tumors (ST) is unknown. In the current study, the authors attempted to determine the clinical relevance of this finding among ST patients. The authors reviewed records of ST patients admitted to the study institution between April 2000 and April 2004 with clinical and radiologic evidence of pneumonia, and HSV identified in LRTS by culture alone or culture and cytology. Patients were categorized as having proven (HSV identified by culture and cytology from the LRTS), probable (HSV as the sole pathogen by culture alone), and possible (HSV along with copathogens identified by culture) HSV pneumonia. Forty-five ST patients with either proven (6 patients), probable (25 patients), or possible (14 patients) HSV pneumonia were identified. When compared with patients with probable or possible HSV pneumonia, more patients with proven infection were on mechanical ventilation (40% vs 50% vs 100%, respectively; P=.03), and had longer length of stay in the intensive care unit (12 days vs 13 days vs 26 days, respectively; P=.05). The overall mortality rate was 22% (10 patients). Four of 25 (16%) patients who received HSV-directed antiviral therapy died during their hospital stay versus 6 of 20 (30%) who were not treated (P=.3). None of the 6 patients with proven HSV pneumonia who were treated with acyclovir died. On univariate analysis, risk factors for mortality included underlying breast cancer, an Acute Physiology and Chronic Health Evaluation (APACHE) II score>15, admission to the intensive care unit, and use of mechanical ventilation and vasopressors (all P15 being found to be independent predictors of death by multiple logistic regression analysis (all P

  15. Pharmacokinetics and excretion of (14)C-omacetaxine in patients with advanced solid tumors.

    Science.gov (United States)

    Nijenhuis, Cynthia M; Hellriegel, Edward; Beijnen, Jos H; Hershock, Diane; Huitema, Alwin D R; Lucas, Luc; Mergui-Roelvink, Marja; Munteanu, Mihaela; Rabinovich-Guilatt, Laura; Robertson, Philmore; Rosing, Hilde; Spiegelstein, Ofer; Schellens, Jan H M

    2016-10-01

    Background Omacetaxine mepesuccinate is indicated in adults with chronic myeloid leukemia resistant and/or intolerant to ≥ 2 tyrosine kinase inhibitor treatments. This phase I study assessed the disposition, elimination, and safety of (14)C-omacetaxine in patients with solid tumors. Methods The study comprised a 7-days pharmacokinetic assessment followed by a treatment period of ≤ six 28-days cycles. A single subcutaneous dose of 1.25 mg/m(2) (14)C-omacetaxine was administered to six patients. Blood, urine, and feces were collected through 168 h or until radioactivity excreted within 24 h was <1 % of the dose. Total radioactivity (TRA) was measured in all matrices and concentrations of omacetaxine, 4'-desmethylhomoharringtonine (4'-DMHHT), and cephalotaxine were measured in plasma and urine. For each treatment cycle, patients received 1.25 mg/m(2) omacetaxine twice daily for 7 days. Results Mean TRA recovered was approximately 81 % of the dose, with approximately half of the radioactivity recovered in feces and half in urine. Approximately 20 % of the dose was excreted unchanged in urine; cephalotaxine (0.4 % of dose) and 4' DMHHT (9 %) were also present. Plasma concentrations of TRA were higher than the sum of omacetaxine and known metabolites, suggesting the presence of other (14)C-omacetaxine-derived compounds. Fatigue and anemia were common, consistent with the known toxicity profile of omacetaxine. Conclusion Renal and hepatic processes contribute to the elimination of (14)C-omacetaxine-derived radioactivity in cancer patients. In addition to omacetaxine and its known metabolites, other (14)C-omacetaxine-derived materials appear to be present in plasma and urine. Omacetaxine was adequately tolerated, with no new safety signals.

  16. Prognostic value of long non-coding RNA UCA1 in human solid tumors

    Science.gov (United States)

    Liu, Fang-teng; Zhu, Pei-qian; Luo, Hong-liang; Zhang, Yi; Qiu, Cheng

    2016-01-01

    Background Numerous studies have shown that the expression of UCA1 was aberrantly upregulated in various cancer types. High expression of UCA1 was reported to be associated with unfavorable prognosis in cancer patients. Results A total of 1240 patients from 15 articles were included. The results indicated that a significantly shorter OS was observed in patients with high expression level of UCA1 (HR = 1.71, 95% CI: 1.43–1.99), in the subgroup analysis, the association was also observed in patients with cancers of digestive system (HR = 2.12, 95% CI: 1.59–2.66). Statistical significance was also observed in subgroup meta-analysis stratified by the cancer type, cut-off value, analysis type and sample size. Furthermore, poorer DFS was observed in patients with high expression level of UCA1 (HR = 2.54; 95% CI: 1.09–4.00). Additionally, the pooled odds ratios (ORs) showed that increased UCA1 was also related to positive lymph node metastasis (OR = 2.98, 95% CI: 2.06–4.30), distant metastasis (OR = 3.14, 95% CI: 1.77–5.58) and poor clinical stage (OR = 2.76, 95% CI: 2.08–3.68). Materials and Methods A comprehensive retrieval was conducted in multiple databases, including PubMed, Embase, Web of Science and CNKI. We collected relevant articles to explore the association between the expression levels of UCA1 and prognosis. Conclusions High expression level of UCA1 was associated with poor clinical outcome. UCA1 could serve as a novel biomarker for prognosis and might be a potential predictive factor for clinicopathological characteristics in various cancers. Further studies should be performed to verify the clinical utility of UCA1 in human solid tumors. PMID:27517147

  17. Phase 1 study of cardiac safety of TAS-102 in patients with advanced solid tumors.

    Science.gov (United States)

    Bendell, Johanna C; Patel, Manish R; Yoshida, Kenichiro; Seraj, Jabed; Weaver, Racquel; Lemech, Charlotte; Todaro, Thomas G; Pant, Shubham; Arkenau, Hendrik-Tobias

    2016-06-01

    TAS-102 is a novel oral agent combining the antineoplastic thymidine-based nucleoside analogue, trifluridine, and the thymidine phosphorylase inhibitor, tipiracil (molar ratio 1:0.5). TAS-102 has shown good activity in refractory metastatic colorectal cancer with acceptable safety. No QT prolongation was seen in clinical studies. This study aimed to investigate TAS-102 cardiac safety for regulatory requirements. This was a phase 1, non-randomized study in adults with advanced solid tumors. Intensive QT assessments were conducted at baseline, placebo, and following single and multiple doses of TAS-102 during a 28-day cycle. Following single- and multiple-dose administration (N = 30), the upper bounds of the one-sided 95 % confidence intervals for the difference between TAS-102 and placebo in time-matched baseline-subtracted 12-lead Holter QT intervals did not exceed 20 ms at any prespecified time point. One patient had a change from baseline in QTcI interval ≥60 ms, and one patient had a QTcI interval >500 ms following multiple-dose TAS-102 administration. No patient had an uncorrected QT, QTcF, or QTcB interval >500 ms. Based on the exposure-response analysis between TAS-102 plasma concentrations and the placebo-adjusted QTc intervals, none of the upper bounds of the one-sided 95 % prediction intervals exceeded 20 ms. There were no significant morphological changes for T or U waves. No cardiovascular AEs were reported in cycle 1. Across all cycles, no patient experienced an AE of ventricular tachycardia, ventricular fibrillation, syncope, or seizure. There was no clinically relevant relationship between TAS-102 plasma concentrations and QTc interval; TAS-102 had no clinically relevant effects on cardiac repolarization. ClinicalTrials.gov study number: NCT01867879.

  18. BRAFV600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study

    Directory of Open Access Journals (Sweden)

    Cohn AL

    2017-02-01

    Full Text Available Allen L Cohn,1 Bann-Mo Day,2 Sarang Abhyankar,3 Edward McKenna,2 Todd Riehl,4 Igor Puzanov5 1Medical Research, Rocky Mountain Cancer Centers, Denver, CO, 2US Medical Affairs, 3Global Safety and Risk Management, 4Product Development Oncology, Genentech, Inc., South San Francisco, CA, 5Melanoma Section, Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Background: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer or multiple myeloma harboring activating BRAFV600 mutations for enrollment in a vemurafenib clinical study.Methods: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAFV600 mutations by bidirectional direct Sanger sequencing.Results: Overall incidence of BRAFV600E mutation in evaluable patients (n=548 was 3% (95% confidence interval [CI], 1.7–4.7: 11% in colorectal tumors (n=75, 6% in biliary tract tumors (n=16, 3% in non-small cell lung cancers (n=71, 2% in other types of solid tumors (n=180, and 3% in multiple myeloma (n=31. There were no BRAFV600 mutations in this cohort of patients with ovarian tumors (n=68, breast cancer (n=86, or prostate cancer (n=21.Conclusion: This multicenter, national screening study confirms previously reported incidences of BRAFV600 mutations from single-center studies. Patients identified with BRAFV600 mutations were potentially eligible for enrollment in the VE-BASKET study. Keywords: genetic testing, proto-oncogene proteins B-raf, PLX4032

  19. Solid tumors provide niche-specific conditions that lead to preferential growth of Salmonella

    Science.gov (United States)

    Silva-Valenzuela, Cecilia A.; Desai, Prerak T.; Molina-Quiroz, Roberto C.; Pezoa, David; Zhang, Yong; Porwollik, Steffen; Zhao, Ming; Hoffman, Robert M.; Contreras, Inés; Santiviago, Carlos A.; McClelland, Michael

    2016-01-01

    Therapeutic attenuated strains of Salmonella Typhimurium target and eradicate tumors in mouse models. However, the mechanism of S. Typhimurium for tumor targeting is still poorly understood. We performed a high-throughput screening of single-gene deletion mutants of S. Typhimurium in an orthotopic, syngeneic murine mammary model of breast cancer. The mutants under selection in this system were classified into functional categories to identify bacterial processes involved in Salmonella accumulation within tumors. Niche-specific genes involved in preferential tumor colonization were identified and exemplars were confirmed by competitive infection assays. Our results show that the chemotaxis gene cheY and the motility genes motAB confer an advantage for colonization of Salmonella within orthotopic syngeneic breast tumors. In addition, eutC, a gene belonging to the ethanolamine metabolic pathway, also confers an advantage for Salmonella within tumors, perhaps by exploiting either ethanolamine or an alternative nutrient in the inflamed tumor environment. PMID:27145267

  20. Computed Tomography Imaging of Solid Tumors Using a Liposomal-Iodine Contrast Agent in Companion Dogs with Naturally Occurring Cancer.

    Directory of Open Access Journals (Sweden)

    Ketan B Ghaghada

    Full Text Available Companion dogs with naturally occurring cancer serve as an important large animal model in translational research because they share strong similarities with human cancers. In this study, we investigated a long circulating liposomal-iodine contrast agent (Liposomal-I for computed tomography (CT imaging of solid tumors in companion dogs with naturally occurring cancer.The institutional animal ethics committees approved the study and written informed consent was obtained from all owners. Thirteen dogs (mean age 10.1 years with a variety of masses including primary and metastatic liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after intravenous administration of Liposomal-I (275 mg/kg iodine dose. Conventional contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained for each dog prior to admission into the study.Liposomal-I resulted in significant (p 1 cm demonstrated a heterogeneous pattern of intra-tumoral signal with visibly higher signal enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors, including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung tumors, were visualized with a heterogeneous enhancement pattern in the post-24 hour scan.The long circulating liposomal-iodine contrast agent enabled prolonged visualization of small and large tumors in companion dogs with naturally occurring cancer. The study warrants future work to assess the sensitivity and specificity of the Liposomal-I agent in various types of naturally occurring canine tumors.

  1. Distinct expression profiles of Notch-1 protein in human solid tumors: Implications for development of targeted therapeutic monoclonal antibodies

    Directory of Open Access Journals (Sweden)

    Yuan Li

    2010-06-01

    Full Text Available Yuan Li1, Janine A Burns1, Carol A Cheney1, Ningyan Zhang1, Salvatore Vitelli1, Fubao Wang1, Andrew Bett2, Michael Chastain2, Laurent P Audoly1, Zhi-Qiang Zhang1,31Department of Biologics Research, 2Department of Vaccine Research, Merck Research Laboratories, West Point, PA, USA; 3Clinical Development Laboratory, Merck Research Laboratories, Rahway, NJ, USAAbstract: Biological therapies, such as monoclonal antibodies (mAbs that target tumor-associated antigens have been considered an effective therapeutic approach in oncology. In considering Notch-1 receptor as a potential target, we performed immunohistochemistry on tissue microarrays to determine 1 whether the receptor is overexpressed in tumor cells as compared to their corresponding normal tissues and 2 the clinical significance of its expression levels in human breast, colorectal, lung and prostate cancers. We found that the expression of Notch-1 protein was overexpressed in primary colorectal adenocarcinoma and nonsmall cell lung carcinoma (NSCLC, but not in primary ductal breast carcinoma or prostate adenocarcinoma. Further analysis revealed that higher levels of Notch-1 protein expression were significantly associated with poorer differentiation of breast and prostate tumors. Strikingly, for NSCLC, the expression levels of Notch-1 protein were found to be inversely correlated with tumor differentiation and progression. For colorectal tumors, however, no correlation of Notch-1 protein expression was found with any tumor clinicopathological parameters, in spite of its overexpression in tumor cells. Our data demonstrated the complexity of Notch-1 protein expression in human solid tumors and further supported the notion that the roles of Notch-1 expression in tumorigenesis are highly context-dependent. The findings could provide the basis for development of distinct therapeutic strategies of Notch-1 mAbs for its applications in the treatment of suitable types of human cancers.Keywords: Notch

  2. Metastasis-associated protein 1 as a new prognostic marker for solid tumors: a meta-analysis of cohort studies.

    Science.gov (United States)

    Luo, Haiqing; Li, Hongjiao; Yao, Na; Hu, Liren; He, Taiping

    2014-06-01

    Metastasis-associated protein 1 (MTA1) is a molecular marker in various solid tumors that has recently been investigated. The prognostic significance of MAT1 expression remains controversial. In this work, we aimed to determine the relationship between immunohistochemistry-detected MAT1 expression and survival of patients with solid tumors by conducting a meta-analysis of cohort studies. Relevant studies were identified via an electronic database search updated on October 28, 2013. We included cohort studies that reported hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (CIs) to determine the association of high MTA1 expression with overall survival (OS) and clinicopathological characteristics. Heterogeneity was quantified using I (2) statistics, and publication bias was evaluated using funnel plots. Sensitivity analysis was conducted to evaluate the robustness of meta-analysis findings. We identified 16 cohort studies that focused on MTA1 overexpression and prognosis involving 2,253 cancer patients. Overall, the combined HR for OS was 1.85 (95 % CI: 1.55-2.28, P<0.001). Omission of any single study had no significant effect on the pooled HR estimate. When the studies were stratified by tumor type, similar results of poor prognosis were observed in non-small cell lung cancer (HR=2.05, 95 % CI: 1.14-3.68, P=0.016) and esophageal squamous cell carcinoma (HR=1.86, 95 % CI: 1.44-2.39, P<0.001). Moreover, multivariate survival analysis showed that MTA1 overexpression was an independent predictor of poor prognosis (HR=1.90, 95 % CI: 1.53-2.37, P<0.001). In addtional, MTA1 overexpression was significantly associated with tumor size (OR=2.72, 95 % CI=1.44-5.14, P=0.002), tumor stage (OR=2.44, 95 % CI=1.67-3.57, P<0.001), depth of invasion (OR=2.63, 95 % CI=1.74-3.97, P<0.001), and lymph node metastasis (OR=2.57, 95 % CI=1.57-4.19, P<0.001). However, when age, sex, and tumor differentiation were considered, no obvious association was observed. This

  3. The ubiquitin+proteasome protein degradation pathway as a therapeutic strategy in the treatment of solid tumor malignancies.

    Science.gov (United States)

    Driscoll, James J; Minter, Alex; Driscoll, Daniel A; Burris, Jason K

    2011-02-01

    A concept that currently steers the development of cancer therapies has been that agents directed against specific proteins that facilitate tumorigenesis or maintain a malignant phenotype will have greater efficacy, less toxicity and a more sustained response relative to traditional cytotoxic chemotherapeutic agents. The clinical success of the targeted agent Imatinib mesylate as an inhibitor of the tyrosine kinase associated with the breakpoint cluster region-Abelson oncogene locus (BCR-ABL) in the treatment of Philadelphia-positive chronic myelogenous leukemia (CML) has served as a paradigm. While intellectually gratifying, the selective targeting of a single driver event by a small molecule, e.g., kinase inhibitor, to dampen a tumor-promoting pathway in the treatment of solid tumors is limited by many factors. Focus can alternatively be placed on targeting fundamental cellular processes that regulate multiple events, e.g., protein degradation, through the Ubiquitin (Ub)+Proteasome System (UPS). The UPS plays a critical role in modulating numerous cellular proteins to regulate cellular processes such as signal transduction, growth, proliferation, differentiation and apoptosis. Clinical success with the proteasome inhibitor bortezomib revolutionized treatment of B-cell lineage malignancies such as Multiple Myeloma (MM). However, many patients harbor primary resistance and do not respond to bortezomib and those that do respond inevitably develop resistance (secondary resistance). The lack of clinical efficacy of proteasome inhibitors in the treatment of solid tumors may be linked mechanistically to the resistance detected during treatment of hematologic malignancies. Potential mechanisms of resistance and means to improve the response to proteasome inhibitors in solid tumors are discussed.

  4. Combined detection of serum tumor markers for differential diagnosis of solid lesions located at the pancreatic head

    Institute of Scientific and Technical Information of China (English)

    Quan Liao; Yu-Pei Zhao; Ying-Chi Yang; Li-Jun Li; Xiao Long; Shao-Mei Han

    2007-01-01

    BACKGROUND:The differential diagnosis of solid lesions located at the pancreatic head is very important for choosing therapies and setting up surgical tactics. This study was designed to evaluate the clinical signiifcance of combined measurement of multiple serum tumor markers and the application of the receiver-operating characteristic (ROC) curves in the differential diagnosis of solid lesions located at the pancreatic head. METHODS:The serum levels of CA19-9, CA242, CA50 and carcinoembryonic antigen (CEA) in 112 patients with carcinoma of the pancreatic head and 38 patients with focal chronic pancreatitis in the pancreatic head were measured with ELISA. The sensitivity, speciifcity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of the four serum tumor markers were calculated. The ROC curves for the four serum tumor markers were constructed and the area under the curve (AUC) was calculated. RESULTS:The AUCs of CA19-9, CA242, CA50 and CEA were 0.805, 0.749, 0.738 and 0.705; the PLRs were 1.91, 3.43, 5.09 and 5.46; and the NLRs were 0.41, 0.56, 0.59 and 0.71, respectively. Combined measurements increased the diagnostic speciifcity, and parallel combined testing increased the diagnostic sensitivity. CONCLUSIONS:Combined measurement of serum tumor markers CA19-9, CA242, CA50 and CEA is valuable in differential diagnosis of solid lesions located at the pancreatic head, and CA19-9 has the best diagnostic ability. Combined measurements can increase the speciifcity of diagnosis. Evaluation with the ROC curve is better than the sensitivity or speciifcity alone and the results are more integrated and objective.

  5. Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature.

    Science.gov (United States)

    Sills, A K; Williams, J I; Tyler, B M; Epstein, D S; Sipos, E P; Davis, J D; McLane, M P; Pitchford, S; Cheshire, K; Gannon, F H; Kinney, W A; Chao, T L; Donowitz, M; Laterra, J; Zasloff, M; Brem, H

    1998-07-01

    The novel aminosterol, squalamine, inhibits angiogenesis and tumor growth in multiple animal models. This effect is mediated, at least in part, by blocking mitogen-induced proliferation and migration of endothelial cells, thus preventing neovascularization of the tumor. Squalamine has no observable effect on unstimulated endothelial cells, is not directly cytotoxic to tumor cells, does not alter mitogen production by tumor cells, and has no obvious effects on the growth of newborn vertebrates. Squalamine was also found to have remarkable effects on the primitive vascular bed of the chick chorioallantoic membrane, which has striking similarities to tumor capillaries. Squalamine may thus be well suited for treatment of tumors and other diseases characterized by neovascularization in humans.

  6. Applications of lipid nanocarriers for solid tumors therapy: literature review; Aplicacoes das nanoparticulas lipidicas no tratamento de tumores solidos: revisao de literatura

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Fac. de Farmacia; Taveira, Eliseu Jose Fleury, E-mail: stephaniafleury@gmail.com [Hospital Erasto Gaertner, Curitiba, PR (Brazil). Oncologia Clinica

    2012-07-01

    Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed{sup R} database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

  7. Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors

    Science.gov (United States)

    2017-02-08

    Childhood Hepatoblastoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

  8. Blunt Traumatic Extracranial Cerebrovascular Injury and Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Paul M. Foreman

    2017-04-01

    Full Text Available Background: Ischemic stroke occurs in a significant subset of patients with blunt traumatic cerebrovascular injury (TCVI. The patients are victims of motor vehicle crashes, assaults or other high-energy collisions, and suffer ischemic stroke due to injury to the extracranial carotid or vertebral arteries. Summary: An increasing number of patients with TCVI are being identified, largely because of the expanding use of computed tomography angiography for screening patients with blunt trauma. Patients with TCVI are particularly challenging to manage because they often suffer polytrauma, that is, numerous additional injuries including orthopedic, chest, abdominal, and head injuries. Presently, there is no consensus about optimal management. Key Messages: Most literature about TCVI and stroke has been published in trauma, general surgery, and neurosurgery journals; because of this, and because these patients are managed primarily by trauma surgeons, patients with stroke due to TCVI have been essentially hidden from view of neurologists. This review is intended to bring this clinical entity to the attention of clinicians and investigators with specific expertise in neurology and stroke.

  9. Erlotinib in Treating Patients With Solid Tumors and Liver or Kidney Dysfunction

    Science.gov (United States)

    2013-01-15

    ; Stage III Pancreatic Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Bladder Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Pancreatic Cancer; Stage IV Prostate Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Unspecified Adult Solid Tumor, Protocol Specific; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  10. The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition

    Directory of Open Access Journals (Sweden)

    Peddaboina Chander

    2012-11-01

    Full Text Available Abstract Background It has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. Mcl-1 is a critical survival protein in a variety of cell lineages and is critically regulated via ubiquitination. Methods The Mcl-1, Bcl-xL and USP9X expression patterns in human lung and colon adenocarcinomas were evaluated via immunohistochemistry. Interaction between USP9X and Mcl-1 was demonstrated by immunoprecipitation-western blotting. The protein expression profiles of Mcl-1, Bcl-xL and USP9X in multiple cancer cell lines were determined by western blotting. Annexin-V staining and cleaved PARP western blotting were used to assay for apoptosis. The cellular toxicities after various treatments were measured via the XTT assay. Results In our current analysis of colon and lung cancer samples, we demonstrate that Mcl-1 and Bcl-xL are overexpressed and also co-exist in many tumors and that the expression levels of both genes correlate with the clinical staging. The downregulation of Mcl-1 or Bcl-xL via RNAi was found to increase the sensitivity of the tumor cells to chemotherapy. Furthermore, our analyses revealed that USP9X expression correlates with that of Mcl-1 in human cancer tissue samples. We additionally found that the USP9X inhibitor WP1130 promotes Mcl-1 degradation and increases tumor cell sensitivity to chemotherapies. Moreover, the combination of WP1130 and ABT-737, a well-documented Bcl-xL inhibitor, demonstrated a chemotherapeutic synergy and promoted apoptosis in different tumor cells. Conclusion Mcl-1, Bcl-xL and USP9X overexpression are tumor survival mechanisms protective against chemotherapy. USP9X inhibition increases tumor cell sensitivity to various chemotherapeutic agents including Bcl-2/Bcl-xL inhibitors.

  11. Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors.

    Science.gov (United States)

    Shimizu, Toshio; Seto, Takashi; Hirai, Fumihiko; Takenoyama, Mitsuhiro; Nosaki, Kaname; Tsurutani, Junji; Kaneda, Hiroyasu; Iwasa, Tsutomu; Kawakami, Hisato; Noguchi, Kazuo; Shimamoto, Takashi; Nakagawa, Kazuhiko

    2016-06-01

    Background This phase I study evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics, immunogenicity, and antitumor activity of pembrolizumab in Japanese patients with advanced solid tumors. Methods Following an initial dose and a 28-day rest (cycle 1), pembrolizumab was administered as an intravenous infusion at escalating doses (2 or 10 mg/kg) every 2 weeks (Q2W) until disease progression or unacceptable toxicity. Adverse events (AEs) were assessed using CTCAE v4.0, and tumor response was assessed using both RECIST v1.1 and immune-related response criteria (irRC). Full pharmacokinetic sampling was performed during cycle 1. Results Three patients received pembrolizumab at 2.0 mg/kg and seven at 10 mg/kg. No dose-limiting toxicities were observed during cycle 1. Eighty percent of patients experienced drug-related AEs (mostly grade 1 or 2); the most common drug-related AEs were nausea, malaise, pyrexia, and aspartate aminotransferase/alanine transaminase (AST/ALT) elevations (n = 2 each). No drug-related grade 4 or 5 AEs occurred. Immune-related AEs comprised grade 3 ALT elevation (n = 1), grade 3 AST elevation (n = 1), grade 1 pneumonitis (n = 1), and grade 1 thyroid-stimulating hormone elevation (n = 1). The safety and pharmacokinetic profiles of Japanese patients were similar to those previously reported for Caucasian patients. A partial tumor response was observed in one patient with non-small-cell lung cancer (NSCLC) and in one patient with melanoma. Conclusions Pembrolizumab at both 2 and 10 mg/kg Q2W was well tolerated in Japanese patients with advanced solid tumors and showed encouraging anti-tumor activity against melanoma and NSCLC.

  12. Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.

    Directory of Open Access Journals (Sweden)

    Maciej H Swat

    Full Text Available Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution. Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

  13. Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors

    Science.gov (United States)

    2017-03-16

    Childhood Brain Stem Neoplasm; Childhood Lymphoma; Childhood Solid Neoplasm; Pineal Region Neoplasm; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Visual Pathway Glioma; Refractory Central Nervous System Neoplasm

  14. Neoplastic Meningitis from Solid Tumors: A Prospective Clinical Study in Lombardia and a Literature Review on Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    A. Silvani

    2013-01-01

    Full Text Available Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC and liposomal antitumor agents (liposomal AraC. Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported.

  15. Hematemesis, a very rare presentation of solid pseudo-papillary tumors of the pancreas: a case report

    Directory of Open Access Journals (Sweden)

    Apostolidis Stylianos

    2008-08-01

    Full Text Available Abstract Introduction Solid pseudo-papillary tumors of the pancreas are rare and typically present in young female patients. They are slowly growing masses that may attain large size, and are of low malignant potential. Surgical resection is usually curative. Case presentation A 71-year-old woman presented to the emergency department with an episode of hematemesis but was otherwise hemodynamically stable. Emergency gastroscopy revealed a bleeding mass projecting to the duodenum. Fluid, blood and electrolyte resuscitation followed. Computed tomography revealed a small mass in the head of the pancreas. A Whipple operation was performed. Pathology revealed a solid pseudo-papillary tumor. The postoperative course of the patient was uneventful and no recurrence was present a year after the operation. Conclusion In our case, the most noteworthy observations concern the small size of the tumor, the age of the patient and the presenting symptom. However, pancreaticoduodenectomy in a 71-year-old woman is a major effort and should only be undertaken by centers and surgeons experienced in complex hepatobiliary surgery. Furthermore, the unique nature of this case reminds every clinician that each patient has to be considered separately and with extreme caution.

  16. Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia

    Science.gov (United States)

    2016-07-20

    Hepatoblastoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Kidney Neoplasm; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

  17. Molecular imaging using Cu-ATSM and FDG in solid canine tumors

    DEFF Research Database (Denmark)

    Hansen, Anders Elias

    glycolysis and blood perfu- sion. 3) To compare tumor uptake of 64 Cu-ATSM and [ 18 F]fluoro-D-glucose ( 18 FDG) (glycolytic activity) to pimonidazole (immunological hypoxia marker) immunohistochemistry. 4) To investigate 18 FDG PET as a diagnostic modality in canine cancer patients. The thesis contains....... Identification of hypoxic tumor and intratumoral hypoxic regions therefore hold the potential to serve as a basis for individualized treatment protocols, including image guided radiation therapy. The current PhD project was undertaken to study tumor hypoxia in cancer bearing dogs, with the aims of 1) identifying...... the potential of implementing canine cancer patients in translational research on tumor hypoxia. 2) Non- invasively evaluate the hypoxia positron emission tomography (PET) tracer 64 Copper(II)diacetyl-bis(N 4 -methylthiosemicarbazone) ( 64 Cu-ATSM), including the comparison to non-invasive measures of tumor...

  18. Temsirolimus and Vinorelbine Ditartrate in Treating Patients With Unresectable or Metastatic Solid Tumors

    Science.gov (United States)

    2016-06-09

    Extensive Stage Small Cell Lung Cancer; Hereditary Paraganglioma; Male Breast Cancer; Malignant Paraganglioma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Endometrial Carcinoma; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pheochromocytoma; Recurrent Prostate Cancer; Recurrent Renal Cell Cancer; Recurrent Small Cell Lung Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Regional Pheochromocytoma; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage III Uterine Sarcoma; Stage IIIA Breast Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Breast Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Endometrial Carcinoma; Stage IV Neuroendocrine Carcinoma of the Skin; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IV Uterine Sarcoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Thyroid Gland Medullary Carcinoma

  19. Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors.

    Science.gov (United States)

    Annunziata, Christina M; Kohn, Elise C; LoRusso, Patricia; Houston, Nicole D; Coleman, Robert L; Buzoianu, Manuela; Robbie, Gabriel; Lechleider, Robert

    2013-02-01

    Targeting the cell-surface receptor EphA2, which is highly expressed in some solid tumors, is a novel approach for cancer therapy. We aimed to evaluate the safety profile, maximum tolerated dose (MTD), pharmacokinetics, and antitumor activity of MEDI-547, an antibody drug conjugate composed of the cytotoxic drug auristatin (toxin) linked to a human anti-EphA2 monoclonal antibody (1C1), in patients with solid tumors relapsed/refractory to standard therapy. In this phase 1, open-label study with planned dose-escalation and dose-expansion cohorts, patients received a 1-h intravenous infusion of MEDI-547 (0.08 mg/kg) every 3 weeks. Six patients received 0.08 mg/kg; all discontinued treatment. Dose escalation was not pursued. The study was stopped before cohort 2 enrollment due to treatment-related bleeding and coagulation events (hemorrhage-related, n = 3; epistaxis, n = 2). Therefore, lower doses were not explored and an MTD could not be selected. The most frequently reported treatment-related adverse events (AEs) were increased liver enzymes, decreased hemoglobin, decreased appetite, and epistaxis. Three patients (50%) experienced treatment-related serious AEs, including conjunctival hemorrhage, pain (led to study drug discontinuation), liver disorder, and hemorrhage. Best response included progressive disease (n = 5; 83.3%) and stable disease (n = 1; 16.7%). Minimal or no dissociation of toxin from 1C1 conjugate occurred in the blood. Serum MEDI-547 concentrations decreased rapidly, ~70% by 3 days post-dose. No accumulation of MEDI-547 was observed at 0.08 mg/kg upon administration of a second dose 3 weeks following dose 1. The safety profile of MEDI-547 does not support further clinical investigation in patients with advanced solid tumors.

  20. [ICO-10 (Thy-1) and K-20 (gp 120/200) monoclonal antibodies in immunophenotyping of solid tumors in man].

    Science.gov (United States)

    Kadagidze, Z G; Tupitsyn, N N; Kadyrov, Kh P; Baryshnikov, A Iu; Mentkevich, G L; Matiakin, G G; Blinov, V M

    1990-01-01

    ICO - 10 (Thy-1 antigen) and K 20 (gp 120/200) monoclonal antibodies proved suitable for immunophenotyping solid tumors. The following typical antigen combinations were identified with regard to reaction with those antibodies: ICO - 10+ K 20- (neuroblastoma, malignant schwannoma, neurosarcoma and soft tissue sarcomas); K 20+ ICO - 10- (cancer of the tongue and esophagus, adenoma of the adrenal cortex, adenocarcinoma of the stomach, hepatoblastoma and nephroblastoma); ICO - 10+ K 20+ (immature teratoma and cervical and esophageal leiomyoma) and ICO - 10+ K 20- (malignant fibrous histiocytoma).

  1. Case of radiation induced aneurysm of extracranial carotid artery

    Energy Technology Data Exchange (ETDEWEB)

    Tashiro, Takashi; Ikota, Toshio; Yamashita, Kousuke; Kodama, Takao

    1988-08-01

    An unusual case of post-irradiation aneurysm of extracranial internal carotid artery is presented. A 70-year-old man, complaining of left cervical throbbing mass with focal pain, was admitted on February 8, 1985. It was noted, from his past history, that he had had surgery of the removal of cervical lymphnodes and that unknown dosage of irradiation had been added to the cervical region 30 years before. Left carotid angiography (on admission) demonstrated a giant aneurysm in the cervical portion of internal carotid artery. Right carotid angiography with compression of left carotid artery revealed good cross filling through anterior communicating artery. Computed tomography with contrast media showed a ring like enhanced mass, which was thought to suggest that a large part of the aneurysm was filled with intraluminal thrombosis. During 30 days of evaluation, the aneurysm grew larger and his cervical pain became untolerable. Operation, the resection of the aneurysm and the reconstruction (of circulation) with vein graft, was challenged on March 12. It was so difficult with meticulous work that the ligation of left common carotid artery was performed after all. Seven days after the operation, he suffered from the gastrointestinal bleeding, which was enough to lead him to hypovolemic shock. Thereafter, right hemiparesis and aphasia were brought about. Two months later, he died of pneumonia. On histological examination, it was demonstrated that the aneurysm communicated with the necrotic tissue and that the normal structure of the blood vessel was not observed in the aneurysmal wall and consisted of the collagenous fiber and granulated tissue. The aneurysm was interpreted as a false one.

  2. Anechoic halo in solid liver tumors: sonographic, microangiographic, and histologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Marchal, G.J.; Pylyser, K.; Tshibwabwa-Tumba, E.A.; Verbeken, E.K.; Oyen, R.H.; Baert, A.L.; Lauweryns, J.M.

    1985-08-01

    The origin of the sonographic halo sign in liver metastases was studied after autopsy in 33 livers with macroscopic tumoral involvement. For 20 lesions a detailed comparison of findings from high-resolution 7.5- and 10-MHz sonography, microangiography, and histology was carried out. Histologic study focused on the tumor periphery and its relationship to the adjacent liver parenchyma. In particular, the type of tumor infiltration, the presence or absence of peritumoral fibrosis, and the degree of liver cell compression were assessed. In all but two cases the halo was extratumoral and was caused by peritumoral liver cell compression. In the remaining two cases the halo was tumoral and was caused by irregular fibrosis or vascularization.

  3. FNAB cytology of extra-cranial metastasis of glioblastoma multiforme may resemble a lung primary: A diagnostic pitfall

    Directory of Open Access Journals (Sweden)

    Dincer HE

    2005-01-01

    Full Text Available Abstract Background As extra-cranial metastasis of glioblastoma multiforme (GBM is rare, it may create a diagnostic dilemma especially during interpretation of fine needle aspiration biopsy (FNAB cytology. Case presentation We present transbronchial FNAB findings in a 62-year-old smoker with lung mass clinically suspicious for a lung primary. The smears of transbronchial FNAB showed groups of cells with ill-defined cell margins and cytological features overlapping with poorly differentiated non-small cell carcinoma. The tumor cells demonstrated lack of immunoreactivity for cytokeratin, thyroid transcription factor-1, and usual neuroendocrine markers, synaptophysin and chromogranin in formalin-fixed cellblock sections. However, they were immunoreactive for the other neuroendocrine immunomarker, CD56, suggesting neural nature of the cells. Further scrutiny of clinical details revealed a history of GBM, 13 months status-post surgical excision with radiation therapy and systemic chemotherapy. The tumor recurred 7 months earlier and was debulked surgically and with intra-cranial chemotherapy. Additional evaluation of tumor cells for glial fibrillary acidic protein (GFAP immunoreactivity with clinical details resulted in final interpretation of metastatic GBM. Conclusion Lack of clinical history and immunophenotyping may lead to a diagnostic pitfall with possible misinterpretation of metastatic GBM as poorly differentiated non-small cell carcinoma of lung in a smoker.

  4. Heterogeneous delivery is a barrier to the translational advancement of oncolytic virotherapy for treating solid tumors

    Directory of Open Access Journals (Sweden)

    Miller AC

    2014-07-01

    Full Text Available Amber C Miller,1,2 Stephen J Russell2,3 1Mayo Graduate School, Mayo Clinic, Rochester, Minnesota, USA; 2Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA; 3Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA Abstract: Oncolytic viruses are a promising experimental anticancer therapy currently undergoing clinical translation. The development of oncolytic virotherapy offers a potential solution to the elusive “one-shot”cancer cure by providing targeted therapy to selectively infect and kill cancer cells while provoking adaptive anticancer immune responses as protection against distant metastasis and recurrent tumor challenge. While this technology has overcome barriers to safety and efficacy through cancer-specific targeting techniques, in order to reach full therapeutic potential, oncolytic therapies must still overcome barriers to intratumoral delivery and spread that result in heterogeneous intratumoral delivery and nonuniform response. This review will discuss barriers to oncolytic virotherapy translation related to mechanisms of delivering virus via tumor vasculature and distributing virus throughout the tumor microenvironment. Barriers include extravasation into the tumor that is dependent on adequate blood flow, tissue perfusion, and tumoral enhanced permeability and retention for transvascular transport. Subsequently, virions must undergo interstitial transport against dense stromal barriers and high interstitial fluid pressure to initiate infection. In order to achieve massive tumor regression, infection must spread to cover large volumes of tumor mass. Furthermore, virus bioavailability is quickly dampened upon systemic administration due to neutralization and sequestration. These barriers to delivery limit the amount of virus that effectively reaches and spreads within the tumor, forcing dose increases that impinge upon limits of production and increase possibility of adverse

  5. Alvespimycin Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors

    Science.gov (United States)

    2013-04-09

    and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer; Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Melanoma; Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Ovarian Epithelial Cancer; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Unspecified Adult Solid Tumor, Protocol Specific; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  6. Pembrolizumab and Ziv-aflibercept in Treating Patients With Advanced Solid Tumors

    Science.gov (United States)

    2016-09-09

    Adult Solid Neoplasm; Metastatic Melanoma; Metastatic Renal Cell Cancer; Recurrent Colorectal Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Ovarian Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

  7. Selumetinib and Cyclosporine in Treating Patients With Advanced Solid Tumors or Advanced or Metastatic Colorectal Cancer

    Science.gov (United States)

    2017-09-04

    Recurrent Colorectal Carcinoma; Solid Neoplasm; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  8. Prognostic factors in breast cancer with extracranial oligometastases and the appropriate role of radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Gyu Sang; Yu, Jeong Il; Park, Won; Huh, Seung Jae; Choi, Doo Ho [Dept. of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2015-12-15

    To identify prognostic factors for disease progression and survival of patients with extracranial oligometastatic breast cancer (EOMBC), and to investigate the role of radiation therapy (RT) for metastatic lesions. We retrospectively reviewed the medical records of 50 patients who had been diagnosed with EOMBC following standard treatment for primary breast cancer initially, and received RT for metastatic lesions, with or without other systemic therapy between January 2004 and December 2008. EOMBC was defined as breast cancer with five or less metastases involving any organs except the brain. All patients had bone metastasis (BM) and seven patients had pulmonary, hepatic, or lymph node metastasis. Median RT dose applied to metastatic lesions was 30 Gy (range, 20 to 60 Gy). The 5-year tumor local control (LC) and 3-year distant progression-free survival (DPFS) rate were 66.1% and 36.8%, respectively. High RT dose (> or =50 Gy10) was significantly associated with improved LC. The 5-year overall survival (OS) rate was 49%. Positive hormone receptor status, pathologic nodal stage of primary cancer, solitary BM, and whole-lesion RT (WLRT), defined as RT whose field encompassed entire extent of disease, were associated with better survival. On analysis for subgroup of solitary BM, high RT dose was significantly associated with improved LC and DPFS, shorter metastasis-to-RT interval (< or =1 month) with improved DPFS, and WLRT with improved DPFS and OS, respectively. High-dose RT in solitary BM status and WLRT have the potential to improve the progression-free survival and OS of patients with EOMBC.

  9. Vascular Pathology in the Extracranial Vertebral Arteries in Patients with Acute Ischemic Stroke

    DEFF Research Database (Denmark)

    Bentsen, L; Nygård, A; Ovesen, C;

    2014-01-01

    INTRODUCTION: Vascular pathology in the extracranial vertebral arteries remains among the possible causes in cryptogenic stroke. However, the diagnosis is challenged by the great variety in the anatomy of the vertebral arteries, clinical symptoms and difficulties in the radiological assessments....... The aim of this study was to assess the prevalence of CT angiography (CTA)-detected pathological findings in the extracranial vertebral arteries in an acute stroke population and secondly to determine the frequency of posterior pathology as probable cause in patients with otherwise cryptogenic stroke...... scans systematically, assessing the four segments of the extracranial vertebral arteries. First, the frequency of pathological findings including stenosis, plaques, dissection, kinked artery and coiling was assessed. Subsequently, we explored the extent of the pathological findings that were the most...

  10. Classical surgical approach and treatment with clips of extracranial internal carotid artery berry aneurysm

    Directory of Open Access Journals (Sweden)

    Haris Vukas

    2016-06-01

    Full Text Available Introduction: We can define extracranial carotid artery aneurysm (ECAA as bulb dilatation greater than 200% of the diameter of the internal carotid artery (ICA or in a case of common carotid artery (CCA greater than 150% of the diameter. Surgical intervention is required for the treatment of this disease.Case report: This study presents an open vascular surgical procedure to resolve ECAA. We report a case of 61 years old woman with an extracranial internal carotid artery berry aneurysm, presented with a headache and dizziness when turning the head aside. Classic open surgery was performed and the lumen of berry aneurysm was separated with three clips from the lumen of ICA.Conclusions: The open surgical approach is the method of choice for the treatment of extracranial internal carotid artery pathological conditions.

  11. Extracranial Vertebral Artery Aneurysm Presenting as a Chronic Cervical Mass Lesion

    Directory of Open Access Journals (Sweden)

    Lampis C. Stavrinou

    2010-01-01

    Full Text Available Background. Aneurysms of the extracranial vertebral artery are rare and can provide a diagnostic and therapeutic challenge. Methods. We reviewed the clinical history of a patient presenting with cervical radiculopathy, who harboured an extracranial vertebral artery aneurysm eroding the cervical spine. Results. CT Angiography and MR Angiography set the diagnosis, by revealing a left C5-C6 vertebral artery aneurysm with cervical root impingement. Bony reconstruction depicted enlargement of the C6 transverse foramen and a marked enlargement of the C6-C7 intravertebral foramen. The lesion was treated by intravascular proximal vertebral artery occlusion. Conclusions. Extracranial vertebral artery aneurysms require a high index of clinical suspicion. This is the first report of a vertebral artery pseudoaneurysm presenting with bony erosion, which supports a less minacious portrayal of vertebral artery aneurysms.

  12. Alterations of Lymphoid Enhancer Factor-1 Isoform Expression in Solid Tumors and Acute Leukemias

    Institute of Scientific and Technical Information of China (English)

    Wenbing WANG; Carsten M(U)LLER-TIDOW; Ping JI; Bj(o)rn STEFFEN; Ralf METZGER; Paul M. SCHNEIDER; Hartmut HALFTER; Mark SCHRADER; Wolfgang E. BERDEL; Hubert SERVE

    2005-01-01

    Two major transcripts of lymphoid enhancer factor-1 (LEF-1) have been described. The long isoform with β-catenin binding domain functions as a transcriptional enhancer factor. The short isoform derives from an intronic promoter and exhibits dominant negative activity. Recently, alterations of LEF- 1isoforms distribution have been described in colon cancer. In the current study we employed a quantitative real-time reverse transcription PCR method (TaqMan) to analyze expression of LEF-1 isoforms in a large cohort of human tumor (n=304) and tumor-free control samples (n=56). The highest expression level of LEF-1 was found in carcinoma samples whereas brain cancer samples expressed little. Expression of LEF1 was different in distinct cancer types. For example, the mRNA level of LEF-1 was lower in testicular tumor samples compared with tumor-free control samples. Besides epithelial cancers, significant LEF-1expression was also found in hematopoietic cells. In hematological malignancies, overall LEF-1 level was higher in lymphocytic leukemias compared with myeloid leukemias and normal hematopoiesis. However,acute myeloid leukemia and acute lymphocytic leukemia showed a significantly increased fraction of the oncogenic LEF-1 compared with chronic lymphocytic leukemia and chronic myeloid leukemia. Taken together,these data suggest that LEF-1 is abundantly expressed in human tumors and the ratio of the oncogenic and the dominant negative short isoform altered not only in carcinomas but also in leukemia.

  13. Pre-targeted radioimmunotherapy of solid tumors: A multidisciplinary approach; La radio-immunotherapie preciblee des tumeurs solides: une demarche pluridisciplinaire

    Energy Technology Data Exchange (ETDEWEB)

    Barbet, J.; Kraber-Bodere, F.; Faivre-Chauvet, A.; Gestin, J.F.; Bardies, M.; Chatal, J.F. [Institut National de la Sante et de la Recherche Medicale (INSERM), U601, Institut de Biologie, Dept. de Recherche en Cancerologie, 44 - Nantes (France); Nantes Univ., U601, Dept. de Recherche en Cancerologie, 44 (France); Campion, L. [Institut National de la Sante et de la Recherche Medicale (INSERM), U601, Institut de Biologie, Dept. de Recherche en Cancerologie, 44 - Nantes (France); Centre de lutte contre le cancer Rene-Gauducheau, 44 - Saint-Herblain (France)

    2007-09-15

    No effective therapy is currently available for the management of patients with metastases of most solid tumors. Thus, pre targeted radioimmunotherapy approaches have been developed that have shown promises. One of these techniques uses bi specific monoclonal antibody and radiolabeled bivalent haptens injected sequentially. In two clinical trials, 29 patients with advanced, progressive medullary thyroid carcinoma, as documented by short serum calcitonin doubling times, received an anti-carcinoembryonic antigen x anti-diethylenetriamine pentaacetic acid (DTPA)-indium) bi specific monoclonal antibody, followed four to five days later by an {sup 131}I-labeled bivalent hapten. Overall survival was significantly longer in high-risk, treated patients than in high-risk, untreated patients (110 versus 61 months; P < 0.030). Forty-seven percent of patients, defined as biologic responders by a more than 100% increase in calcitonin doubling time, experienced significantly longer survival than non-responders (159 versus 109 months; P < 0.035) and untreated patients (159 versus 61 months; P < 0.010). Toxicity was mainly hematologic and related to bone/bone-marrow tumor spread. Various multidisciplinary aspects of this long-term endeavor that resulted in long-term disease stabilization and a significantly longer survival in high-risk patients are described and discussed with respect to future directions of research on pre targeted radioimmunotherapy. (authors)

  14. Symptoms, Quality of Life, and Daily Activities in People With Newly Diagnosed Solid Tumors Presenting to a Medical Oncologist.

    Science.gov (United States)

    Thomas, Shirley; Walsh, Declan; Shrotriya, Shiva; Aktas, Aynur; Hullihen, Barbara; Estfan, Bassam; Budd, G Thomas; Hjermstad, Marianne Jensen; O'Connor, Brenda

    2017-08-01

    Symptom and Quality of Life (QOL) data are important patient reported outcomes. Early identification of these is critical for appropriate interventions. Data collection may be helped by modern information technology. This study examined symptoms and QOL in people with solid tumors at their first visit to a medical oncologist. We also evaluated the clinical utility of tablet computers (TC) to collect this data. This was a prospective study of 105 consecutive patients in the cancer outpatient clinic of a tertiary level academic medical center. Symptom and QOL data was collected by TC with wireless database upload. One-third participants had moderate to severe pain; almost half clinically significant pain that interfered with daily activities. Tiredness, anxiety, and drowsiness were common (prevalence - 79%, 63% and 50% respectively). One-third of those who had items identified from the Edmonton System Assessment System also volunteered other symptoms, mostly gastrointestinal problems. Many of those affected also reported impaired Global Wellbeing and low Overall QOL. There was a 98% completion rate, which took on average ten minutes. Direct observation and informal feedback from patients and physicians regarding the acceptability of TC in this setting was uniformly positive. Amongst people with newly diagnosed solid tumors clinically important psychological and physical symptoms, QOL problems and difficulties with daily activities were commonly present in the 24-hour period and in the week before a first Medical Oncology visit. Symptom and QOL data collection by TC in busy outpatient clinics showed good clinical utility.

  15. Solid-pseudopapillary tumor of the pancreas: Clinical experience and literature review

    Institute of Scientific and Technical Information of China (English)

    Hsueh-Lien Huang; Shou-Chuan Shih; Wen-Hsiung Chang; Tsang-En Wang; Ming-Jen Chen; Yu-Jan Chan

    2005-01-01

    AIM: To evaluate the clinical presentations of solidpseudopapillary tumor of the pancreas (SPT) and examine the diagnosis, treatment, low grade malignant potential of this rare disease.METHODS: We retrospectively reviewed a series of seven patients with SPT managed in our hospital between July 1990 and October 2003. Six females and one male with mean age of 31 years (range 13 to 50 years) were diagnosed with SPT at our institution.RESULTS: Clinical presentation included a palpable abdominal mass in two patients and vague abdominal discomfort in another two. Two patients were asymptomatic;their tumors were found incidentally on abdominal sonographic examination for other reasons. The final patient was admitted with hemoperitoneum secondary to tumor rupture. The mean diameter of the tumors in the seven patients was 10.5 cm (range 5 to 20 cm). The lesions were located in the body and tail in five cases and in the head of the pancreas in two. Surgical procedures included distal pancreatectomy (3), distal pancreatectomy with splenectomy (2), pancreaticoduodenectomy (1) and a pylorus-preserving Whipple procedure (1). There were gross adhesions or histological evidence of infiltration to the adjacent pancreas and/or splenic capsule in four cases. None of the patients received adjuvant therapy.The mean follow up was 7 years (range 0.5 to 14 years).One patient developed multiple liver metastases after 14 years of follow up.CONCLUSION: SPT is a rare tumor that behaves less aggressively than other pancreatic tumor. However, in cases with local invasion, long-term follow up is advisable.

  16. Optimizing the Delivery of Short-Lived Alpha Particle-Emitting Isotopes to Solid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Gregory P.

    2004-11-24

    The underlying hypothesis of this project was that optimal alpha emitter-based radioimmunotherapy (RAIT) could be achieved by pairing the physical half-life of the radioisotope to the biological half-life of the targeting vehicle. The project had two specific aims. The first aim was to create and optimize the therapeutic efficacy of 211At-SAPS-C6.5 diabody conjugates. The second aim was to develop bispecific-targeting strategies that increase the specificity and efficacy of alpha-emitter-based RAIT. In the performance of the first aim, we created 211At-SAPS-C6.5 diabody conjugates that specifically targeted the HER2 tumor associated antigen. In evaluating these immunoconjugates we determined that they were capable of efficient tumor targeting and therapeutic efficacy of established human tumor xenografts growing in immunodeficient mice. We also determined that therapeutic doses were associated with late renal toxicity, likely due to the role of the kidneys in the systemic elimination o f these agents. We are currently performing more studies focused on better understanding the observed toxicity. In the second aim, we successfully generated bispecific single-chain Fv (bs-scFv) molecules that co-targeted HER2 and HER3 or HER2 and HER4. The in vitro kinetics and in vivo tumor-targeting properties of these molecules were evaluated. These studies revealed that the bs-scFv molecules selectively localized in vitro on tumor cells that expressed both antigens and were capable of effective tumor localization in in vivo studies.

  17. Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy.

    Science.gov (United States)

    Siemann, Dietmar W; Mercer, Emma; Lepler, Sharon; Rojiani, Amyn M

    2002-05-01

    The utility of combining the vascular targeting agents 5,6-dimethyl-xanthenone-4 acetic acid (DMXAA) and combretastatin A-4 disodium phosphate (CA4DP) with the anticancer drugs cisplatin and cyclophosphamide (CP) was evaluated in experimental rodent (KHT sarcoma), human breast (SKBR3) and ovarian (OW-1) tumor models. Doses of the vascular targeting agents that led to rapid vascular shutdown and subsequent extensive central tumor necrosis were identified. Histologic evaluation showed morphologic damage of tumor cells within a few hours after treatment, followed by extensive hemorrhagic necrosis and dose-dependent neoplastic cell death as a result of prolonged ischemia. Whereas these effects were induced by a range of CA4DP doses (10-150 mg/kg), the dose response to DMXAA was extremely steep; doses or = 20 mg/kg were toxic. DMXAA also enhanced the tumor cell killing of cisplatin, but doses > 15 mg/kg were required. In contrast, CA4DP increased cisplatin-induced tumor cell killing at all doses studied. This enhancement of cisplatin efficacy was dependent on the sequence and interval between the agents. The greatest effects were achieved when the vascular targeting agents were administered 1-3 hr after cisplatin. When CA4DP (100 mg/kg) or DMXAA (17.5 mg/kg) were administered 1 hr after a range of doses of cisplatin or CP, the tumor cell kill was 10-500-fold greater than that seen with chemotherapy alone. In addition, the inclusion of the antivascular agents did not increase bone marrow stem cell toxicity associated with these anticancer drugs, thus giving rise to a therapeutic gain.

  18. Agent-Based Modeling of Cancer Stem Cell Driven Solid Tumor Growth.

    Science.gov (United States)

    Poleszczuk, Jan; Macklin, Paul; Enderling, Heiko

    2016-01-01

    Computational modeling of tumor growth has become an invaluable tool to simulate complex cell-cell interactions and emerging population-level dynamics. Agent-based models are commonly used to describe the behavior and interaction of individual cells in different environments. Behavioral rules can be informed and calibrated by in vitro assays, and emerging population-level dynamics may be validated with both in vitro and in vivo experiments. Here, we describe the design and implementation of a lattice-based agent-based model of cancer stem cell driven tumor growth.

  19. STAT3 as a target for inducing apoptosis in solid and hematological tumors

    Institute of Scientific and Technical Information of China (English)

    Khandaker Al Zaid Siddiquee; James Turkson

    2008-01-01

    Studies in the past few years have provided compelling evidence for the critical role of aberrant Signal Transducer and Activator of Transcription 3 (STAT3) in malignant transformation and tumorigenesis. Thus, it is now generally accepted that STAT3 is one of the critical players in human cancer formation and represents a valid target for novel anticancer drug design. This review focuses on aberrant STAT3 and its role in promoting tumor cell survival and supporting the malignant phenotype. A brief evaluation of the current strategies targeting STAT3 for the development of novel anticancer agents against human tumors harboring constitutively active STAT3 will also be presented.

  20. Wortmannin potentiates roscovitine-induced growth inhibition in human solid tumor cells by repressing PI3K/Akt pathway.

    Science.gov (United States)

    Zhang, Feng; Zhang, Tao; Jiang, Tao; Zhang, Rong; Teng, Zeng-hui; Li, Chen; Gu, Zhong-Ping; Mei, Qibing

    2009-12-28

    Roscovitine has been reported to have anti-tumor effects in some cancer cell lines. The phosphatidylinositol-3-kinase (PI3K) signaling, which activates protein kinase B (PKB)/Akt, is known to mediate cell survival. The current study examined the role of wortmannin, a PI3K inhibitor, as a chemosensitizer for roscovitine and its proposed mechanism of action. The results showed that wortmannin significantly chemosensitized three human tumor cell lines (A549, HCT116 and HeLa cells). In A549 cells, wortmannin increased roscovitine-induced apoptosis in a dose-dependent manner, which was correlated with the inhibition of phosphorylated PKB/Akt level. Wortmannin enhanced the effects of roscovitine by causing pronounced reduction of mitochondrial transmembrane potential (MMP) and increases of cytochrome c release and active caspase-3, as well as enhanced activation of Bax and Bad, including Bax oligomerization and mitochondrial translocation of Bax and Bad. Taken together, these results provide evidence for the potential application of roscovitine/wormannin combination in clinical treatment for solid tumors.

  1. Selective changes in expression of HLA class I polymorphic determinants in human solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Natali, P.G.; Nicotra, M.R.; Bigotti, A.; Venturo, I.; Giacomini, P. (Regina Elena Cancer Institute, Rome (Italy)); Marcenaro, L.; Russo, C. (Cornell Univ. Medical College, New York, NY (USA))

    1989-09-01

    Analysis of surgical biopsies with monoclonal antibodies (mAbs) to framework determinants of major histocompatibility complex class I antigens has shown that malignant transformation is frequently associated with a marked loss of these cell surface molecules. The present study sought to determine whether more selective losses of major histocompatibility complex class I expression occur. Multiple specimens from 13 different types of primary and metastatic tumors were tested utilizing mAb BB7.2, which recognizes a polymorphic HLA-A2 epitope. In each case, expression of HLA-A,B,C molecules was determined by testing with mAb W6/32 directed to a framework HLA class I determinant. The authors have found that in HLA-A2-positive patients, HLA-A2 products are not detectable or are reduced in their expression in 70-80% of endometrial, colorectal, mammary, and renal tumors; in 40-60% of soft-tissue, skin, ovary, urinary bladder, prostate, and stomach tumors; and in 25-30% of melanomas and lung carcinomas tested. All tumors expressed the framework HLA-A,B.C determinant. The HLA-A2 epitope recognized by mAb BB7.2 is located in a portion of the HLA-A2 molecule postulated to react with the T-cell receptor. The selective loss of an HLA class I polymorphic epitope shown in this study may explain the mechanism by which tumor cells escape both T-cell recognition and natural killer cell surveillance.

  2. Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy

    Science.gov (United States)

    2016-07-07

    Adult Solid Neoplasm; Bladder Carcinoma; Colon Carcinoma; Estrogen Receptor Negative; Head and Neck Squamous Cell Carcinoma; Hepatocellular Carcinoma; HER2/Neu Negative; Melanoma; Non-Small Cell Lung Carcinoma; Pancreatic Carcinoma; Progesterone Receptor Negative; Rectal Carcinoma; Renal Cell Carcinoma; Soft Tissue Sarcoma; Triple-Negative Breast Carcinoma

  3. Indole carboxylic acid esters of melampomagnolide B are potent anticancer agents against both hematological and solid tumor cells.

    Science.gov (United States)

    Bommagani, Shobanbabu; Ponder, Jessica; Penthala, Narsimha R; Janganati, Venumadhav; Jordan, Craig T; Borrelli, Michael J; Crooks, Peter A

    2017-08-18

    A series of novel, heteroaryl carboxylic acid conjugates of the sesquiterpene melampomagnolide-B (MMB, 3) has been evaluated as antitumor agents against an NCI panel of 64 human hematopoetic and solid tumor cell lines. The indole-3-acrylic acid conjugate 7j and the indole-3-carboxylic acid conjugate 7k were found to be the most potent analogs in the series. Compounds 7j and 7k exhibited remarkable growth inhibition, with GI50 values in the range 0.03-0.30 μM and 0.04-0.28 μM, respectively, against the cell lines in the leukemia sub-panel, and GI50 values of 0.05-0.40 μM and 0.04-0.61 μM, respectively, against 90% of the solid tumor cell lines in the NCI panel. Compound 7a was particularly effective against the sub-panel of breast cancer cell lines with GI50 values in the range <0.01-0.30 μM. Compounds 7j, 7a and its water soluble analog 7p also exhibited potent anticancer activity against rat 9L-SF gliosarcoma cells in culture. Compound 7j was the most potent compound in the series in the M9-ENL1 AML cell assay with a lethal dose concentration EC50 value of 720 nM, and exhibited the greatest cytotoxicity against a collection of primary AML stem cell specimens, which included a specimen that was unresponsive to PTL, affording EC50 values in the range 0.33-1.0 μM in three out of four specimens. The results from this study provide further evidence that analogs of the sesquiterpene MMB can be designed to afford molecules with significantly improved anticancer activity. Thus, both 7j and 7k are considered potential lead molecules in the search for new anticancer agents that can be used as treatments for both hematopoetic and solid tumors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors.

    Science.gov (United States)

    Dienstmann, R; Rodon, J; Prat, A; Perez-Garcia, J; Adamo, B; Felip, E; Cortes, J; Iafrate, A J; Nuciforo, P; Tabernero, J

    2014-03-01

    The fibroblast growth factor receptor (FGFR) cascade plays crucial roles in tumor cell proliferation, angiogenesis, migration and survival. Accumulating evidence suggests that in some tumor types, FGFRs are bona fide oncogenes to which cancer cells are addicted. Because FGFR inhibition can reduce proliferation and induce cell death in a variety of in vitro and in vivo tumor models harboring FGFR aberrations, a growing number of research groups have selected FGFRs as targets for anticancer drug development. Multikinase FGFR/vascular endothelial growth factor receptor (VEGFR) inhibitors have shown promising activity in breast cancer patients with FGFR1 and/or FGF3 amplification. Early clinical trials with selective FGFR inhibitors, which may overcome the toxicity constraints raised by multitarget kinase inhibition, are recruiting patients with known FGFR(1-4) status based on genomic screens. Preliminary signs of antitumor activity have been demonstrated in some tumor types, including squamous cell lung carcinomas. Rational combination of targeted therapies is expected to further increase the efficacy of selective FGFR inhibitors. Herein, we discuss unsolved questions in the clinical development of these agents and suggest guidelines for management of hyperphosphatemia, a class-specific mechanism-based toxicity. In addition, we propose standardized definitions for FGFR1 and FGFR2 gene amplification based on in situ hybridization methods. Extended access to next-generation sequencing platforms will facilitate the identification of diseases in which somatic FGFR(1-4) mutations, amplifications and fusions are potentially driving cancer cell viability, further strengthening the role of FGFR signaling in cancer biology and providing more possibilities for the therapeutic application of FGFR inhibitors.

  5. A Nanostructured Matrices Assessment to Study Drug Distribution in Solid Tumor Tissues by Mass Spectrometry Imaging

    Science.gov (United States)

    Giordano, Silvia; Pifferi, Valentina; Morosi, Lavinia; Morelli, Melinda; Falciola, Luigi; Cappelletti, Giuseppe; Visentin, Sonja; Licandro, Simonetta A.; Frapolli, Roberta; Zucchetti, Massimo; Pastorelli, Roberta; Brunelli, Laura; D’Incalci, Maurizio; Davoli, Enrico

    2017-01-01

    The imaging of drugs inside tissues is pivotal in oncology to assess whether a drug reaches all cells in an adequate enough concentration to eradicate the tumor. Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) is one of the most promising imaging techniques that enables the simultaneous visualization of multiple compounds inside tissues. The choice of a suitable matrix constitutes a critical aspect during the development of a MALDI-MSI protocol since the matrix ionization efficiency changes depending on the analyte structure and its physico-chemical properties. The objective of this study is the improvement of the MALDI-MSI technique in the field of pharmacology; developing specifically designed nanostructured surfaces that allow the imaging of different drugs with high sensitivity and reproducibility. Among several nanomaterials, we tested the behavior of gold and titanium nanoparticles, and halloysites and carbon nanotubes as possible matrices. All nanomaterials were firstly screened by co-spotting them with drugs on a MALDI plate, evaluating the drug signal intensity and the signal-to-noise ratio. The best performing matrices were tested on control tumor slices, and were spotted with drugs to check the ion suppression effect of the biological matrix. Finally; the best nanomaterials were employed in a preliminary drug distribution study inside tumors from treated mice. PMID:28336905

  6. Augmented lymphocyte expansion from solid tumors with engineered cells for costimulatory enhancement.

    Science.gov (United States)

    Friedman, Kevin M; Devillier, Laura E; Feldman, Steven A; Rosenberg, Steven A; Dudley, Mark E

    2011-01-01

    Treatment of patients with adoptive T-cell therapy requires expansion of unique tumor-infiltrating lymphocyte (TIL) cultures from single-cell suspensions processed from melanoma biopsies. Strategies which increase the expansion and reliability of TIL generation from tumor digests are necessary to improve access to TIL therapy. Previous studies have evaluated artificial antigen presenting cells for their antigen-specific and costimulatory properties. We investigated engineered cells for costimulatory enhancement (ECCE) consisting of K562 cells that express 4-1BBL in the absence of artificial antigen stimulation. ECCE accelerated TIL expansion and significantly improved TIL numbers (P=0.001) from single-cell melanoma suspensions. TIL generated with ECCE contain significantly more CD8CD62L and CD8CD27 T cells then comparable interleukin-2-expanded TIL and maintained antitumor reactivity. Moreover, ECCE improved TIL expansion from nonmelanoma-cell suspensions similar to that seen with melanoma tumors. These data demonstrate that the addition of ECCE to TIL production will enable the treatment of patients that are ineligible using current methods.

  7. Eosinophilia in routine blood samples as a biomarker for solid tumor development - A study based on the Copenhagen Primary Care Differential Count (CopDiff) Database.

    Science.gov (United States)

    Andersen, Christen Lykkegaard; Siersma, Volkert Dirk; Hasselbalch, Hans Carl; Lindegaard, Hanne; Vestergaard, Hanne; Felding, Peter; de Fine Olivarius, Niels; Bjerrum, Ole Weis

    2014-09-01

    Eosinophilia may represent an early paraclinical sign of malignant disease and a host anti-tumor effect. The association between eosinophilia and the development of solid tumors has never before been examined in an epidemiological setting. The aim of the present study was to investigate eosinophilia in routine blood samples as a potential biomarker of solid tumor development in a prospective design. From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356 196 individuals with at least one differential cell count (DIFF) encompassing the eosinophil count during 2000-2007. From these, one DIFF was randomly chosen and categorized according to no (eosinophilia. From the Danish Civil Registration System and the Danish Cancer Registry we ascertained all-cause death and solid tumors within the first three years following the DIFF. Using multivariable logistic regression, odds ratios (OR) were calculated and adjusted for previous eosinophilia, sex, age, year, month, C-reactive protein, previous cancer and Charlson's Comorbidity Index. The risk of bladder cancer was increased with mild eosinophilia [OR 1.93 (CI 1.29-2.89), p = 0.0013]. No associations with eosinophilia were observed for the remaining solid cancers. We demonstrate that eosinophilia in routine blood samples associates with an increased risk of bladder cancer. Our data emphasize that additional preclinical studies are needed in order to shed further light on the role of eosinophils in carcinogenesis, where it is still unknown whether the cells contribute to tumor immune surveillance or neoplastic evolution.

  8. Phosphodiesterase 4 D Gene Polymorphism in Relation to Intracranial and Extracranial Atherosclerosis in Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Jayantee Kalita

    2011-01-01

    Full Text Available In ischemic stroke, extracranial MR angiography (ECMRA is more frequently abnormal in Caucasians and intracranial (ICMRA in Asians which may have a genetic basis. We report phosphodiesterase (PDE4D gene polymorphism and its correlation with MRA findings in patients with ischemic stroke.

  9. Thrombolysis in patients with acute ischemic stroke due to arterial extracranial dissection

    NARCIS (Netherlands)

    M.D.I. Vergouwen; P.A.C.A. Beentjes; P.J. Nederkoorn

    2009-01-01

    No data of randomized controlled trials investigating the effect of thrombolysis in patients with ischemic stroke caused by an extracranial dissection are available. Previous case series suggested that thrombolysis in this group of patients is safe and improves outcome, however publication bias may

  10. An open-label study to investigate the cardiac safety profile of cabazitaxel in patients with advanced solid tumors

    DEFF Research Database (Denmark)

    Maison-Blanche, Pierre; Dakhil, Shaker; Baron, Ari;

    2014-01-01

    additional ECG parameters (QT, PR and QRS intervals, and heart rate), plasma pharmacokinetics of cabazitaxel and overall clinical safety. RESULTS: The pharmacodynamic (ECG) population included 94 patients. In 63 patients with a full 24-h ECG evaluation, the maximum upper bound of 90 % confidence interval (CI......PURPOSE: This study assessed the cardiovascular safety of cabazitaxel, based on thorough evaluation of QT and non-QT variables, and the relationship between pharmacokinetic and pharmacodynamic electrocardiographic (ECG) profiles and the occurrence of Grade ≥3 cardiovascular adverse events. METHODS......: Patients with advanced solid tumors were treated with cabazitaxel 25 mg/m(2) every 3 weeks. Digital ECG recordings were obtained during Cycle 1 over 24 h after dosing. The primary end point was effect of cabazitaxel on QT interval corrected by the Fridericia formula (QTcF). Secondary end points were...

  11. Experience with cefepime versus meropenem as empiric monotherapy for neutropenia and fever in pediatric patients with solid tumors.

    Science.gov (United States)

    Oguz, Aynur; Karadeniz, Ceyda; Citak, Elvan Caglar; Cil, Visal; Eldes, Nilufer

    2006-01-01

    A prospective, open-label, randomized, comparative study in pediatric cancer patients was conducted to evaluate the efficacy and safety of cefepime and meropenem in the empiric therapy of febrile neutropenic patients. Febrile episodes were classified as microbiologically documented infection, clinical documented infection, or fever of unknown origin. Clinical response to therapy was classified as success or failure. In this period 37 children with solid tumors including lymphoma, 25 males, 12 females, had neutropenia on 65 occasions. Microbiologically documented infections occurred in 21 episodes (32.31%). Frequency of positive bacteria isolated was higher than gram-negative bacteria. There was no infection-related death. There were no statistical differences between the cefepime and meropenem groups for duration of fever or neutropenia, response rate, and necessity for modification. Cefepime appears to be as effective and safe as meropenem for empiric treatment of febrile episodes in neutropenic pediatric cancer patients.

  12. Some implications of Scale Relativity theory in avascular stages of growth of solid tumors in the presence of an immune system response.

    Science.gov (United States)

    Buzea, C Gh; Agop, M; Moraru, Evelina; Stana, Bogdan A; Gîrţu, Manuela; Iancu, D

    2011-08-07

    We present a traveling-wave analysis of a reduced mathematical model describing the growth of a solid tumor in the presence of an immune system response in the framework of Scale Relativity theory. Attention is focused upon the attack of tumor cells by tumor-infiltrating cytotoxic lymphocytes (TICLs), in a small multicellular tumor, without necrosis and at some stage prior to (tumor-induced) angiogenesis. For a particular choice of parameters, the underlying system of partial differential equations is able to simulate the well-documented phenomenon of cancer dormancy and propagation of a perturbation in the tumor cell concentration by cnoidal modes, by depicting spatially heterogeneous tumor cell distributions that are characterized by a relatively small total number of tumor cells. This behavior is consistent with several immunomorphological investigations. Moreover, the alteration of certain parameters of the model is enough to induce soliton like modes and soliton packets into the system, which in turn result in tumor invasion in the form of a standard traveling wave. In the same framework of Scale Relativity theory, a very important feature of malignant tumors also results, that even in avascular stages they might propagate and invade healthy tissues, by means of a diffusion on a Newtonian fluid. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Role of denosumab in the management of skeletal complications in patients with bone metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Stopeck AT

    2012-04-01

    Full Text Available Ursa Brown-Glaberman, Alison T StopeckUniversity of Arizona Cancer Center, Tucson, AZ, USAAbstract: Skeletal-related events (SREs including pain, fractures, and hypercalcemia are a major source of morbidity for cancer patients with bone metastases. The receptor activator of NF-κB ligand (RANKL is a key mediator of osteoclast formation and activity in normal bone physiology as well as cancer-induced bone resorption. The first commercially available drug that specifically targets and inhibits the RANKL pathway is denosumab, a fully human monoclonal antibody that binds and neutralizes RANKL, thereby inhibiting osteoclast function. In this review, we summarize the major studies leading to the US Food and Drug Administration-approval of denosumab for the prevention of SREs in patients with bone metastases from solid tumors. Further, we discuss the role of denosumab in the prevention and treatment of SREs and bone loss in cancer patients. As a monoclonal antibody, denosumab has several advantages over bisphosphonates, including improved efficacy, better tolerability, and the convenience of administration by subcutaneous injection. In addition, as denosumab has no known renal toxicity, it may be the preferred choice over bisphosphonates in patients with baseline renal insufficiency or receiving nephrotoxic therapies. However, other toxicities, including osteonecrosis of the jaw and hypocalcemia, appear to be class effects of agents that potently inhibit osteoclast activity and are associated with both denosumab and bisphosphonate use. The data presented highlight the differences associated with intravenous bisphosphonate and denosumab use as well as confirm the essential role bone-modifying agents play in maintaining the quality of life for patients with bone metastases.Keywords: denosumab, bone metastases, solid tumor, breast cancer, prostate cancer, skeletal related events, skeletal complications 

  14. Somatic mutagenesis with a Sleeping Beauty transposon system leads to solid tumor formation in zebrafish.

    Directory of Open Access Journals (Sweden)

    Maura McGrail

    Full Text Available Large-scale sequencing of human cancer genomes and mouse transposon-induced tumors has identified a vast number of genes mutated in different cancers. One of the outstanding challenges in this field is to determine which genes, when mutated, contribute to cellular transformation and tumor progression. To identify new and conserved genes that drive tumorigenesis we have developed a novel cancer model in a distantly related vertebrate species, the zebrafish, Danio rerio. The Sleeping Beauty (SB T2/Onc transposon system was adapted for somatic mutagenesis in zebrafish. The carp ß-actin promoter was cloned into T2/Onc to create T2/OncZ. Two transgenic zebrafish lines that contain large concatemers of T2/OncZ were isolated by injection of linear DNA into the zebrafish embryo. The T2/OncZ transposons were mobilized throughout the zebrafish genome from the transgene array by injecting SB11 transposase RNA at the 1-cell stage. Alternatively, the T2/OncZ zebrafish were crossed to a transgenic line that constitutively expresses SB11 transposase. T2/OncZ transposon integration sites were cloned by ligation-mediated PCR and sequenced on a Genome Analyzer II. Between 700-6800 unique integration events in individual fish were mapped to the zebrafish genome. The data show that introduction of transposase by transgene expression or RNA injection results in an even distribution of transposon re-integration events across the zebrafish genome. SB11 mRNA injection resulted in neoplasms in 10% of adult fish at ∼10 months of age. T2/OncZ-induced zebrafish tumors contain many mutated genes in common with human and mouse cancer genes. These analyses validate our mutagenesis approach and provide additional support for the involvement of these genes in human cancers. The zebrafish T2/OncZ cancer model will be useful for identifying novel and conserved genetic drivers of human cancers.

  15. The effect of phosphoethanolamine intake on mortality and macrophage activity in mice with solid ehrlich tumors

    Directory of Open Access Journals (Sweden)

    Maria Sueli Parreira de Arruda

    2011-12-01

    Full Text Available The aim of the present study was to examine the effect of a diet rich in synthetic PEtn on the metabolism macrophages of tumor-bearing mice. The results demonstrated that PEtn increased the animals' survival time. In addition, the treated animals released smaller amounts of hydrogen peroxide (H2O2 and nitric oxide (NO than the non-treated animals, particularly after day 14. From the results it could be concluded that H2O2 and NO were important in the modulation of neoplastic growth, and pointed to a promising role of PEtn in the control of human neoplasms.

  16. Forebyggelse af skeletrelaterede hændelser hos patienter med knoglemetastaser ved solide tumorer

    DEFF Research Database (Denmark)

    Kamby, Claus; Tarp, Simon; Mellemgaard, Anders

    2015-01-01

    This article is based on a systematic literature search and meta-analyses of clinical data regarding effects of bisphosphonates (BP) and denosumab (DS) on preventing skeletal related events (SRE) in patients with bone metastases from solid tumours. Although there are pharmacological differences...... between the different types of BP no major differences were observed between BP in preventing SRE or in adverse events. Treatment with DS has in three randomised trials showed a greater effect than BP in preventing SRE. The optimal choice of bone-anti-resorptive agent should depend on the patient...

  17. Forebyggelse af skeletrelaterede hændelser hos patienter med knoglemetastaser ved solide tumorer

    DEFF Research Database (Denmark)

    Kamby, Claus; Tarp, Simon; Mellemgaard, Anders

    2014-01-01

    This article is based on a systematic literature search and meta-analyses of clinical data regarding effects of bisphosphonates (BP) and denosumab (DS) on preventing skeletal related events (SRE) in patients with bone metastases from solid tumours. Although there are pharmacological differences...... between the different types of BP no major differences were observed between BP in preventing SRE or in adverse events. Treatment with DS has in three randomised trials showed a greater effect than BP in preventing SRE. The optimal choice of bone-anti-resorptive agent should depend on the patient...

  18. Brain metastasis from non-small cell lung cancer (NSCLC). Prognostic importance of the number of involved extracranial organs

    Energy Technology Data Exchange (ETDEWEB)

    Gerdan, L. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); University of Luebeck, Section of Nuclear Medicine, Luebeck (Germany); Segedin, B. [Institute of Oncology, Department of Radiation Oncology, Ljubljana (Slovenia); Nagy, V. [Oncology Institute Ion Ciricuta, Department of Radiotherapy, Cluj-Napoca (Romania); Khoa, M.T. [Hanoi Medical University, Department of Nuclear Medicine, Hanoi (Viet Nam); Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Trang, N.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale, AZ (United States); Rades, D. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany)

    2014-01-15

    This study investigated the potential prognostic value of the number of involved extracranial organs in patients with brain metastasis from non-small cell lung cancer (NSCLC). A total of 472 patients who received whole-brain radiotherapy (WBRT) alone with 5 x 4 Gy or 10 x 3 Gy for brain metastasis from NSCLC were included in this retrospective study. In addition to the number of involved extracranial organs, 6 further potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), number of brain metastases, and the interval from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung+bone vs. lung+lymph nodes vs. other combinations) extracranial organs. The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3, and ≥4 extracranial organs were 52, 27, 17, 4, and 14%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs remained significant (risk ratio 1.32; 95% confidence interval 1.19-1.46; p<0.001). Age <65 years (p=0.004), KPS ≥70 (p<0.001), and only 1-3 brain metastases (p=0.022) were also significantly associated with survival in the multivariate analysis. In the separate analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the pattern of extracranial organ involvement. The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from NSCLC, irrespective of the pattern of extracranial organ involvement. (orig.)

  19. PLGA Nanoparticles for Ultrasound-Mediated Gene Delivery to Solid Tumors

    Directory of Open Access Journals (Sweden)

    Marxa Figueiredo

    2012-01-01

    Full Text Available This paper focuses on novel approaches in the field of nanotechnology-based carriers utilizing ultrasound stimuli as a means to spatially target gene delivery in vivo, using nanoparticles made with either poly(lactic-co-glycolic acid (PLGA or other polymers. We specifically discuss the potential for gene delivery by particles that are echogenic (amenable to destruction by ultrasound composed either of polymers (PLGA, polystyrene or other contrast agent materials (Optison, SonoVue microbubbles. The use of ultrasound is an efficient tool to further enhance gene delivery by PLGA or other echogenic particles in vivo. Echogenic PLGA nanoparticles are an attractive strategy for ultrasound-mediated gene delivery since this polymer is currently approved by the US Food and Drug Administration for drug delivery and diagnostics in cancer, cardiovascular disease, and also other applications such as vaccines and tissue engineering. This paper will review recent successes and the potential of applying PLGA nanoparticles for gene delivery, which include (a echogenic PLGA used with ultrasound to enhance local gene delivery in tumors or muscle and (b PLGA nanoparticles currently under development, which could benefit in the future from ultrasound-enhanced tumor targeted gene delivery.

  20. Tumor markers in clinical practice: a review focusing on common solid cancers.

    Science.gov (United States)

    Duffy, Michael J

    2013-01-01

    Tumor markers are playing an increasingly important role in cancer detection and management. These laboratory-based tests are potentially useful in screening for early malignancy, aiding cancer diagnosis, determining prognosis, surveillance following curative surgery for cancer, up front predicting drug response or resistance, and monitoring therapy in advanced disease. Clinically useful markers include fecal occult blood testing in screening for early colorectal cancer, carcinoembryonic antigen in the management of patients with colorectal cancer, both α-fetoprotein and human chorionic gonadotrophin in the management of patients with non-seminomatous germ cell tumors, CA 125 for monitoring therapy in patients with ovarian cancer, estrogen receptors for predicting response to hormone therapy in breast cancer, human epidermal growth factor receptor 2 for the identification of women with breast cancer likely to respond to trastuzumab (Herceptin) and KRAS mutational status for identifying patients with advanced colorectal cancer likely to benefit from treatment with the anti-epidermal growth factor receptor antibodies, cetuximab and panitumumab. Although widely used, the value of prostate-specific antigen screening in reducing mortality from prostate cancer is unclear.

  1. Evaluation of anterior mediastinal solid tumors by CT perfusion: a preliminary study.

    Science.gov (United States)

    Bakan, Selim; Kandemirli, Sedat Giray; Dikici, Atilla Süleyman; Erşen, Ezel; Yıldırım, Onur; Samancı, Cesur; Batur, Şebnem; Çebi Olgun, Deniz; Kantarcı, Fatih; Akman, Canan

    2017-01-01

    We aimed to assess the role of computed tomography (CT) perfusion in differentiation of thymoma from thymic hyperplasia, lymphoma, thymic carcinoma, and lung cancer invading anterior mediastinum. In this study, 25 patients with an anterior mediastinal lesion underwent CT perfusion imaging from January 2015 to February 2016. Diagnoses included thymoma (n=7), thymic hyperplasia (n=8), lymphoma (n=4), thymic carcinoma (n=3), and invasive lung cancer (n=3). Lymphoma, thymic carcinoma, and lung cancer were grouped as malignant tumors for statistical analysis. Values for blood flow, blood volume, and permeability surface were measured in CT perfusion. Blood flow and blood volume values were higher in thymoma in comparison to thymic hyperplasia; however, the difference was not statistically significant. Blood volume values were significantly higher in thymoma (mean, 11.4 mL/100 mL; range, 5.2-20.2 mL/100 mL) compared with lymphoma (mean, 5.3 mL/100 mL; range, 2.5-7.2 mL/100 mL) (P = 0.023). Blood flow and blood volume values were significantly higher in thymoma compared with non-thymoma malignant tumors (P = 0.025). CT perfusion is helpful in differentiating thymoma from non-thymoma malignancies including lymphoma, thymic carcinoma, and invasive lung cancer involving the anterior mediastinum.

  2. Barriers to the Access of Bevacizumab in Patients with Solid Tumors and the Potential Impact of Biosimilars: A Physician Survey.

    Science.gov (United States)

    Monk, Bradley J; Lammers, Philip E; Cartwright, Thomas; Jacobs, Ira

    2017-01-28

    Access to bevacizumab, an important component of oncology treatment regimens, may be limited. This survey of oncologists in the US (n = 150), Europe (n = 230), and emerging markets (EM: Brazil, Mexico, and Turkey; n = 130) examined use of and barriers to accessing bevacizumab as treatment of advanced solid tumors. We also assessed the likelihood that physicians would prescribe a bevacizumab biosimilar, if available. Bevacizumab was frequently used as early-line therapy in metastatic colorectal cancer, metastatic non-squamous non-small-cell lung cancer, and metastatic ovarian cancer (all markets), and as a second-line therapy in glioblastoma multiforme (US, EM). A greater percentage of EM-based physicians cited access-related issues as a barrier to prescribing bevacizumab versus US and EU physicians. Lack of reimbursement and high out-of-pocket costs were cited as predominant barriers to prescribing and common reasons for reducing the number of planned cycles. Overall, ~50% of physicians reported they "definitely" or "probably" would prescribe a bevacizumab biosimilar, if available. Efficacy and safety data in specific tumor types and lower cost were factors cited that would increase likelihood to prescribe a bevacizumab biosimilar. A lower cost bevacizumab biosimilar could address the unmet needs of patients and physicians worldwide, and may have the greatest impact on patient outcomes in EM.

  3. Volumetric response classification in metastatic solid tumors on MSCT: Initial results in a whole-body setting

    Energy Technology Data Exchange (ETDEWEB)

    Wulff, A.M., E-mail: a.wulff@rad.uni-kiel.de [Klinik für Diagnostische Radiologie, Arnold-Heller-Straße 3, Haus 23, 24105 Kiel (Germany); Fabel, M. [Klinik für Diagnostische Radiologie, Arnold-Heller-Straße 3, Haus 23, 24105 Kiel (Germany); Freitag-Wolf, S., E-mail: freitag@medinfo.uni-kiel.de [Institut für Medizinische Informatik und Statistik, Brunswiker Str. 10, 24105 Kiel (Germany); Tepper, M., E-mail: m.tepper@rad.uni-kiel.de [Klinik für Diagnostische Radiologie, Arnold-Heller-Straße 3, Haus 23, 24105 Kiel (Germany); Knabe, H.M., E-mail: h.knabe@rad.uni-kiel.de [Klinik für Diagnostische Radiologie, Arnold-Heller-Straße 3, Haus 23, 24105 Kiel (Germany); Schäfer, J.P., E-mail: jp.schaefer@rad.uni-kiel.de [Klinik für Diagnostische Radiologie, Arnold-Heller-Straße 3, Haus 23, 24105 Kiel (Germany); Jansen, O., E-mail: o.jansen@neurorad.uni-kiel.de [Klinik für Diagnostische Radiologie, Arnold-Heller-Straße 3, Haus 23, 24105 Kiel (Germany); Bolte, H., E-mail: hendrik.bolte@ukmuenster.de [Klinik für Nuklearmedizin, Albert-Schweitzer-Campus 1, Gebäude A1, 48149 Münster (Germany)

    2013-10-01

    Purpose: To examine technical parameters of measurement accuracy and differences in tumor response classification using RECIST 1.1 and volumetric assessment in three common metastasis types (lung nodules, liver lesions, lymph node metastasis) simultaneously. Materials and methods: 56 consecutive patients (32 female) aged 41–82 years with a wide range of metastatic solid tumors were examined with MSCT for baseline and follow up. Images were evaluated by three experienced radiologists using manual measurements and semi-automatic lesion segmentation. Institutional ethics review was obtained and all patients gave written informed consent. Data analysis comprised interobserver variability operationalized as coefficient of variation and categorical response classification according to RECIST 1.1 for both manual and volumetric measures. Continuous data were assessed for statistical significance with Wilcoxon signed-rank test and categorical data with Fleiss kappa. Results: Interobserver variability was 6.3% (IQR 4.6%) for manual and 4.1% (IQR 4.4%) for volumetrically obtained sum of relevant diameters (p < 0.05, corrected). 4–8 patients’ response to therapy was classified differently across observers by using volumetry compared to standard manual measurements. Fleiss kappa revealed no significant difference in categorical agreement of response classification between manual (0.7558) and volumetric (0.7623) measurements. Conclusion: Under standard RECIST thresholds there was no advantage of volumetric compared to manual response evaluation. However volumetric assessment yielded significantly lower interobserver variability. This may allow narrower thresholds for volumetric response classification in the future.

  4. Phase I study of LY2181308, an antisense oligonucleotide against survivin, in patients with advanced solid tumors.

    Science.gov (United States)

    Tanioka, M; Nokihara, H; Yamamoto, N; Yamada, Y; Yamada, K; Goto, Y; Fujimoto, T; Sekiguchi, R; Uenaka, K; Callies, S; Tamura, T

    2011-08-01

    LY2181308 is an antisense oligonucleotide that complementarily binds to survivin mRNA and inhibits its expression in tumor tissue. This phase I dose escalation study evaluated the tolerability, pharmacokinetics, and anticancer activity of LY2181308 in Japanese. Patients with solid tumors refractory to standard therapy received LY2181308 (400, 600, or 750 mg) as a 3-h intravenous infusion for 3 consecutive days and thereafter once a week. LY2181308 was administered to 14 patients, aged 44-73 (median 60) years. Flu-like syndrome, prolonged prothrombin time-international normalized ratio (PT-INR), thrombocytopenia, and fatigue were common reversible grade 1/2 toxicities. The dose-limiting toxicity was reversible grade 3 elevation of ALT/AST/γ-GTP in 1 patient treated at the 750-mg dose. Pharmacokinetic analysis showed a long terminal half-life of 21 days and an extensive tissue distribution of LY2181308. In 12 evaluable patients, one patient had stable disease, while the remaining 11 patients had progressive disease. LY2181308 monotherapy is well tolerated up to 750 mg with a manageable toxicity, the pharmacokinetic profile warrants further evaluation of LY2181308 in combination with cytotoxic agents or radiotherapy.

  5. A fluid biopsy as investigating technology for the fluid phase of solid tumors

    Science.gov (United States)

    Kuhn, Peter; Bethel, Kelly

    2012-02-01

    Reliable measurement of internal bodily substances and structures is one of the cornerstones of modern medicine. Progress in cancer medicine, like that in many medical fields, must encompass and take advantage of progress in the physical sciences. Historically, the development and refinement of physical sciences-based detection of biological entities precedes periods of great advancements in therapies. To treat broken limbs and arthritis, we are indebted to Conrad Roentgen's discovery of x-rays by which we can evaluate the bones; to apply gamma knife therapy for cancer, we are indebted to Marie Curie's discoveries about radioactivity by which we can eradicate tumors; to manage the complications of diabetes, we are indebted to Tom Clemens, Ames Pharmaceuticals and Dick Bernstein's refinement of direct blood glucose measurement technology by which we can count, hour-to-hour, the waxing and waning of blood sugar levels; to understand anything at all on the cellular level, we are indebted to Antonie van Leeuwenhoek's microscope, by which we can see our cells. The application of physical sciences perspectives to biological and medical problems has a long and productive history. As of late, however, the increasing compartmentalization of science and exponential increases of knowledge in both arenas has resulted in a rift between the two. The NCI has initiated a research network establishing multiple centers of investigation, the Physical Sciences in Oncology Centers (http://physics.cancer.gov), which seek to mend the rift. Each headed by a pair of investigators, one in the physical sciences and one in the biological sciences, the centers seek to bring the advances and breakthroughs of the physical sciences world to bear on the question of cancer. This issue of physical biology contains a series of articles exploring the utility and applicability of a new method for measuring cancer as it spreads, developed at the Scripps Physical Oncology Center. Although some progress

  6. Influência de Agaricus blazei Murrill sobre o tumor sólido de Ehrlich e linfonodos poplíteos de camundongos Influence of Agaricus blazei Murrill in solid Ehrlich tumor and popliteal lymph nodes in mice

    Directory of Open Access Journals (Sweden)

    D. Verçosa Junior

    2007-02-01

    Full Text Available Estudou-se a influência do tratamento diário com filtrado aquoso de Agaricus blazei Murrill (ABM (25mg/ml, via oral, por 17 e 57 dias, em camundongos inoculados com tumor sólido de Ehrlich (TSE por meio da curva de crescimento tumoral, do peso relativo do tumor, da contagem de regiões organizadoras de nucléolos (AgNORs e dos padrões histológicos das massas tumorais e linfonodos poplíteos. Os animais que ingeriram o extrato aquoso do ABM por 57 dias apresentaram menor (P0,05 entre os animais tratados e não tratados.The influence of daily administration of Agaricus blazei Murrill (ABM aqueous solution (25mg/ml during 17 and 57 days in mice bearing solid Ehrlich tumor was studied. Tumoral growth, tumoral and spleenic relative weights, nucleoly organization regions AgNORs values and tumor and popliteal lymph nodes histopathology were daily evaluated. The animals that received ABM during 57 days showed lower values (P0.05 between treated and non-treated animals. No difference in microscopic evaluation of the tumors in treated and non-treated animals was seen and metastasis in popliteal nodes of the tumor occurred in all the animals.

  7. Expression pattern of receptor activator of NFκB (RANK) in a series of primary solid tumors and related bone metastases.

    Science.gov (United States)

    Santini, Daniele; Perrone, Giuseppe; Roato, Ilaria; Godio, Laura; Pantano, Francesco; Grasso, Donatella; Russo, Antonio; Vincenzi, Bruno; Fratto, Maria Elisabetta; Sabbatini, Roberto; Della Pepa, Chiara; Porta, Camillo; Del Conte, Alessandro; Schiavon, Gaia; Berruti, Alfredo; Tomasino, Rosa Maria; Papotti, Mauro; Papapietro, Nicola; Onetti Muda, Andrea; Denaro, Vincenzo; Tonini, Giuseppe

    2011-03-01

    Receptor activator of NFκB ligand (RANKL), RANK, and osteoprotegerin (OPG) represent the key regulators of bone metabolism both in normal and pathological conditions, including bone metastases. To our knowledge, no previous studies investigated and compared RANK expression in primary tumors and in bone metastases from the same patient. We retrospectively examined RANK expression by immunohistochemistry in 74 bone metastases tissues from solid tumors, mostly breast, colorectal, renal, lung, and prostate cancer. For 40 cases, tissue from the corresponding primary tumor was also analyzed. Sixty-six (89%) of the 74 bone metastases were RANK-positive and, among these, 40 (59.5%) showed more than 50% of positive tumor cells. The median percentage of RANK-positive cells was 60% in primary tumors and metastases, without any statistically significant difference between the two groups (P=0.194). The same percentage was obtained by considering only cases with availability of samples both from primary and metastasis. Our study shows that RANK is expressed by solid tumors, with high concordance between bone metastasis and corresponding primary tumor. These data highlight the central role of RANK/RANKL/OPG pathway as potential therapeutic target not only in bone metastasis management, but also in the adjuvant setting.

  8. Development of near-infrared photoactivable phthalocyanine-loaded nanoparticles to kill tumor cells: An improved tool for photodynamic therapy of solid cancers.

    Science.gov (United States)

    Duchi, Serena; Ramos-Romero, Sara; Dozza, Barbara; Guerra-Rebollo, Marta; Cattini, Luca; Ballestri, Marco; Dambruoso, Paolo; Guerrini, Andrea; Sotgiu, Giovanna; Varchi, Greta; Lucarelli, Enrico; Blanco, Jeronimo

    2016-10-01

    Conventional photodynamic therapy has shown to be beneficial in the treatment of a variety of tumors. However, one of its major limitations is the inadequate penetration depth of visible light. In order to overcome this constraint, we developed 80nm poly-methylmethacrylate core-shell fluorescent nanoparticles (FNP) loaded with the photosensitizer tetrasulfonated aluminum phthalocyanine (Ptl). To demonstrate the efficacy of our Ptl@FNP we performed in vitro and in vivo studies using a human prostate tumor model. Our data reveal that Ptl@FNP are internalized by tumor cells, favour Ptl intracellular accumulation, and efficiently trigger cell death through the generation of ROS upon irradiation with 680nm light. When directly injected into tumors intramuscularly induced in SCID mice, Ptl@FNP upon irradiation significantly reduce tumor growth with higher efficiency than the bare Ptl. Collectively, these results demonstrate that the newly developed nanoparticles may be utilized as a delivery system for antitumor phototherapy in solid cancers.

  9. Not All Next Generation Sequencing Diagnostics are Created Equal: Understanding the Nuances of Solid Tumor Assay Design for Somatic Mutation Detection

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Phillip N., E-mail: pgray@ambrygen.com; Dunlop, Charles L.M.; Elliott, Aaron M. [Ambry Genetics, 15 Argonaut, Aliso Viejo, CA 92656 (United States)

    2015-07-17

    The molecular characterization of tumors using next generation sequencing (NGS) is an emerging diagnostic tool that is quickly becoming an integral part of clinical decision making. Cancer genomic profiling involves significant challenges including DNA quality and quantity, tumor heterogeneity, and the need to detect a wide variety of complex genetic mutations. Most available comprehensive diagnostic tests rely on primer based amplification or probe based capture methods coupled with NGS to detect hotspot mutation sites or whole regions implicated in disease. These tumor panels utilize highly customized bioinformatics pipelines to perform the difficult task of accurately calling cancer relevant alterations such as single nucleotide variations, small indels or large genomic alterations from the NGS data. In this review, we will discuss the challenges of solid tumor assay design/analysis and report a case study that highlights the need to include complementary technologies (i.e., arrays) and germline analysis in tumor testing to reliably identify copy number alterations and actionable variants.

  10. An Implantable Wireless Interstitial Pressure Sensor With Integrated Guyton Chamber: in vivo Study in Solid Tumors.

    Science.gov (United States)

    Song, Seung Hyun; Kim, Albert; Brown, Marcus; Jung, Chaeyong; Ko, S; Ziaie, Babak

    2016-11-01

    A wireless implantable interstitial fluid pressure (IFP) sensor with an integrated Guyton chamber is presented. This implantable device enables noninvasive and continuous measurements of IFP. The Guyton chamber allows for an accurate measurement of IFP without the interference from various cellular/tissue components. The sensor consists of a coil, an air chamber, a silicone membrane embedded with a nickel plate, and a Guyton chamber. The fabricated device is 3 mm in diameter and 1 mm in thickness. The sensor shows a linear response to the pressure with a sensitivity of 60 kHz/mmHg and a resolution of 1 mmHg. Experiments in human prostate cancer tumors grown in mice confirm the sensor's capability to operate in vivo and provide continuous wireless measurement of IFP, a surrogate parameter indicating the "window of opportunity" for delivering chemo- and radio-therapeutic agents.

  11. Claudin 3, 4, and 15 expression in solid tumors of lung adenocarcinoma versus malignant pleural mesothelioma.

    Science.gov (United States)

    Chaouche-Mazouni, Siham; Scherpereel, Arnaud; Zaamoum, Rima; Mihalache, Adriana; Amir, Zine-Charaf; Lebaïli, Nemcha; Delaire, Baptiste; Gosset, Pierre

    2015-08-01

    Epithelioid malignant pleural mesothelioma (MPM) can easily be confused with lung adenocarcinomas (ACAs). In serous effusion, claudin (cldn) 3 is shown to be useful in the diagnosis of mesothelioma vs ACAs. Cldn15 is reported to be overexpressed in epithelioid mesothelioma and absent in human airway epithelium. The aim was to assess the value of cldn3 and cldn4 compared to that of BerEp4 and thyroid transcription factor-1 (TTF1) in differentiating lung ACA from epithelioid MPM and to examine the expression of cldn15 in these tumors. The expression of cldn3, cldn4, cldn15, BerEp4, and TTF1 was examined by immunohistochemistry in a total of 62 human specimen including 28 epithelioid MPMs and 34 ACAs of the lung. In lung ACA, cldn4 was strongly expressed in all 34 (100%) specimens followed by cldn3 in 33 (97%) of 34. BerEp4 was expressed in 32 (94.1%) of 34. TTF1 reacted for only 20 (58.82%) of 34 cases of lung ACA. In MPM specimens, the expression of cldn3 and4 as well as that of TTF1 was completely absent. In contrast, BerEp4 was focally expressed in 5 (17.85%) of 28 cases of epithelioid MPM. Cldn15 was strongly expressed in 53% pf epithelioid MPMs but also in 50% of lung ACAs. Its expression was moderate in normal pleura and limited in normal lung. Cldn3 and cldn4 appear to be the best performing carcinoma markers in discriminating lung ACA from mesothelioma compared with BerEp4 and TTF1. There is no differential expression of cldn15 between the 2 pathologies. However, the limited cldn15 expression in normal tissues and high expression in tumors make it an attractive candidate for cancer therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Cyclamen exerts cytotoxicity in solid tumor cell lines: a step toward new anticancer agents?

    Science.gov (United States)

    Yildiz, Mustafa; Bozcu, Hakan; Tokgun, Onur; Karagur, Ege Riza; Akyurt, Oktay; Akca, Hakan

    2013-01-01

    Cyclamen coum is a traditional medicinal plant in the Turkey. Its anticancer properties and whether cyclamen extract induces any cytotoxicity in solid cancer cell lines have not been thoroughly investigated previously. Therefore we examined cytotoxic effects on cervical cancer, HeLa, and non small cell lung cancer cell, H1299, lines. Cyclamen extract induced cellular death of both HeLa and H1299 cells in a dose dependent manner. We also analyzed the capacity of cyclamen extract to induce apoptosis by the TUNEL method. Here, we for the first time report that the extract of Cyclamen coum, an endemic plant for Turkey, can induce cytotoxicity via apoptosis in HeLa and H1299 cells. These results imply that cyclamen extract can be further analyzed to potentially find novel anticancer compounds.

  13. Phase I pharmacokinetic and pharmacodynamic study of the first-in-class spliceosome inhibitor E7107 in patients with advanced solid tumors

    NARCIS (Netherlands)

    F.A.L.M. Eskens (Ferry); F.J. Ramos (Francisco); H. Burger (Herman); J.P. O'Brien (James); A. Piera (Adelaida); M.J.A. de Jonge (Maja); Y. Mizui (Yoshiharu); E.A.C. Wiemer (Erik); M.J. Carreras (Maria Josepa); J. Baselga (José); J. Tabernero (Josep)

    2013-01-01

    textabstractPurpose: To assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of E7107 administered as 5-minute bolus infusions on days 1, 8, and 15 in a 28-day schedule. Experimental Design: Patients with solid tumors refractory to standard therapies or with no

  14. First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors

    DEFF Research Database (Denmark)

    Abdul Razak, Albiruni R; Mau-Sørensen, Morten; Gabrail, Nashat Y

    2016-01-01

    PURPOSE: This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of selinexor (KPT-330), a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1), and determined the recommended phase II dose. PATIENTS AND METHODS: In total, 189 patients with advanced solid tumors...

  15. Phase I and pharmacologic study of oral ZD9331, a novel nonpolyglutamated thymidylate synthase inhibitor, in adult patients with solid tumors.

    NARCIS (Netherlands)

    Jonge, M.J.A. de; Punt, C.J.A.; Sparreboom, A.; Planting, A.S.T.; Peters, M.E.W.J.; Schraaf, J. van de; Jackman, A.; Smith, R.J.H.; Mulder, P.H.M. de; Verweij, J.

    2002-01-01

    PURPOSE: To assess the toxicity profile and dose-limiting toxicities (DLTs), to determine the maximum-tolerated dose, and to study the pharmacokinetics of ZD9331 when administered orally to patients with advanced solid tumors. PATIENTS AND METHODS: Patients were treated with oral ZD9331 given once d

  16. Systemic delivery of siRNA by aminated poly(α)glutamate for the treatment of solid tumors.

    Science.gov (United States)

    Polyak, Dina; Krivitsky, Adva; Scomparin, Anna; Eliyahu, Shay; Kalinski, Hagar; Avkin-Nachum, Sharon; Satchi-Fainaro, Ronit

    2016-06-26

    Small interfering RNA (siRNA) can silence the expression of a targeted gene in a process known as RNA interference (RNAi). As a consequence, RNAi has immense potential as a novel therapeutic approach in cancer targeted therapy. However, successful application of siRNA for therapeutic purposes is challenging due to its rapid renal clearance, degradation by RNases in the bloodstream, poor cellular penetration, immunogenicity and aggregation in the blood. In addition, the few oligonucleotide-based nanomedicines that reached clinical trials either go to the liver following systemic administration or are applied topically. Treatment of solid tumors requires selective distribution of siRNA to the target tissue, hence there is an unmet medical need for an efficacious and safe nano-sized delivery system for their clinical use. To overcome these hurdles, we have designed, synthesized and physico-chemically characterized a novel nanocarrier based on aminated poly(α)glutamate (PGAamine). This cathepsin B-biodegradable polymer interacts electrostatically with the siRNA to form a nano-sized polyplex stable in plasma. Treatment with PGAamine-Rac1 siRNA polyplex (siRac1-polyplex) caused specific gene silencing by 80% in HeLa and SKOV-3 human ovarian adenocarcinoma cells as opposed to PGAamine-control non-targeting siRNA polyplex (siCtrl-polyplex) leading to inhibition of cell migration and wound healing abilities. A stepwise dose escalation was performed in order to determine the in vivo maximum tolerated dose (MTD). This was followed by intraperitoneal administration of siRac1-polyplex to mCherry-labeled ovarian adenocarcinoma-bearing mice leading to preferred tumor accumulation of siRac1 (8-fold) which resulted in 38% Rac1 knockdown. Furthermore, the polyplex was administered intravenously to lung carcinoma-bearing mice in which it caused 33% Rac1 knockdown. These promising results led to efficacy studies administering systemic treatment with an anticancer siRNA, siPlk1

  17. The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer.

    Science.gov (United States)

    Travis, William D; Asamura, Hisao; Bankier, Alexander A; Beasley, Mary Beth; Detterbeck, Frank; Flieder, Douglas B; Goo, Jin Mo; MacMahon, Heber; Naidich, David; Nicholson, Andrew G; Powell, Charles A; Prokop, Mathias; Rami-Porta, Ramón; Rusch, Valerie; van Schil, Paul; Yatabe, Yasushi

    2016-08-01

    This article proposes codes for the primary tumor categories of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and a uniform way to measure tumor size in part-solid tumors for the eighth edition of the tumor, node, and metastasis classification of lung cancer. In 2011, new entities of AIS, MIA, and lepidic predominant adenocarcinoma were defined, and they were later incorporated into the 2015 World Health Organization classification of lung cancer. To fit these entities into the T component of the staging system, the Tis category is proposed for AIS, with Tis (AIS) specified if it is to be distinguished from squamous cell carcinoma in situ (SCIS), which is to be designated Tis (SCIS). We also propose that MIA be classified as T1mi. Furthermore, the use of the invasive size for T descriptor size follows a recommendation made in three editions of the Union for International Cancer Control tumor, node, and metastasis supplement since 2003. For tumor size, the greatest dimension should be reported both clinically and pathologically. In nonmucinous lung adenocarcinomas, the computed tomography (CT) findings of ground glass versus solid opacities tend to correspond respectively to lepidic versus invasive patterns seen pathologically. However, this correlation is not absolute; so when CT features suggest nonmucinous AIS, MIA, and lepidic predominant adenocarcinoma, the suspected diagnosis and clinical staging should be regarded as a preliminary assessment that is subject to revision after pathologic evaluation of resected specimens. The ability to predict invasive versus noninvasive size on the basis of solid versus ground glass components is not applicable to mucinous AIS, MIA, or invasive mucinous adenocarcinomas because they generally show solid nodules or consolidation on CT.

  18. Volumetric modulated arc therapy for treatment of solid tumors: current insights

    Directory of Open Access Journals (Sweden)

    Macchia G

    2017-07-01

    Full Text Available Gabriella Macchia,1 Francesco Deodato,1 Savino Cilla,2 Silvia Cammelli,3 Alessandra Guido,3 Martina Ferioli,3 Giambattista Siepe,3 Vincenzo Valentini,4 Alessio Giuseppe Morganti,3,* Gabriella Ferrandina5,6,* 1Radiation Oncology Unit, 2Medical Physics Unit, “Giovanni Paolo II” Foundation, Catholic University of the Sacred Heart, Campobasso, 3Radiation Oncology Unit, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, 4Department of Radiation Oncology, Catholic University of the Sacred Heart, Rome, 5Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, 6Department of Health Sciences and Medicine, University of Molise, Campobasso, Italy *These authors contributed equally to this work Aim: This article discusses the current use of volumetric modulated arc therapy (VMAT techniques in clinical practice and reviews the available data from clinical outcome studies in different clinical settings. An overview of available literature about clinical outcomes with VMAT stereotactic/radiosurgical treatment is also reported.Materials and methods: All published manuscripts reporting the use of VMAT in a clinical setting from 2009 to November 2016 were identified. The search was carried out in December 2016 using the National Library of Medicine (PubMed/Medline. The following words were searched: “volumetric arc therapy”[All Fields] OR “vmat”[All Fields] OR “rapidarc”[All Fields], AND “radiotherapy”[All Fields] AND “Clinical Trial”[All Fields].Results: Overall, 37 studies (21 prospective and 16 retrospective fulfilling inclusion criteria and thus included in the review evaluated 2,029 patients treated with VMAT; of these patients, ~30.8% had genitourinary (GU tumors (81% prostate, 19% endometrial, 26.2% head-and-neck cancer (H&NC, 13.9% oligometastases, 11.2% had anorectal cancer, 10.6% thoracic neoplasms (81% breast, 19% lung, and 7

  19. Vascular Pathology in the Extracranial Vertebral Arteries in Patients with Acute Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    L. Bentsen

    2014-01-01

    Full Text Available Introduction: Vascular pathology in the extracranial vertebral arteries remains among the possible causes in cryptogenic stroke. However, the diagnosis is challenged by the great variety in the anatomy of the vertebral arteries, clinical symptoms and difficulties in the radiological assessments. The aim of this study was to assess the prevalence of CT angiography (CTA-detected pathological findings in the extracranial vertebral arteries in an acute stroke population and secondly to determine the frequency of posterior pathology as probable cause in patients with otherwise cryptogenic stroke. Method: The analysis was based on 657 consecutive patients with symptoms of acute stroke and a final diagnosis of ischemic stroke or transient ischemic attack. On admission, a noncontrast CT cerebrum and CTA were performed. A senior consultant neuroradiologist, blinded to clinical data, reviewed all CTA scans systematically, assessing the four segments of the extracranial vertebral arteries. First, the frequency of pathological findings including stenosis, plaques, dissection, kinked artery and coiling was assessed. Subsequently, we explored the extent of the pathological findings that were the most plausible causes of stroke, namely either a possible dissection or a kinked artery. Results: Findings in the extracranial vertebral arteries included significant stenosis (0.8%, atherosclerotic plaque types (3.8%, possible dissections (2.6%, kinked arteries (2.6% and coiling (32.0%. Eighteen patients (2.8% with pathological findings had an unknown cause of stroke, likely posterior symptoms and no clinical stroke symptoms from the anterior circuit. Of these, 3 cases were kinked arteries (0.5% and 15 cases (2.3% were possible dissections. Conclusion: We found that in approximately 3% of the study population, the most plausible cause of the cryptogenic strokes was due to a pathological finding in the posterior extracranial vertebral arteries, being either a possible

  20. Targeting the epidermal growth factor receptor in solid tumors: focus on safety.

    Science.gov (United States)

    Lucchini, Eleonora; Pilotto, Sara; Spada, Elisa; Melisi, Davide; Bria, Emilio; Tortora, Giampaolo

    2014-05-01

    Inhibition of the EGFR has emerged as a promising anticancer strategy, offering improved efficacy and quality of life for patients affected by tumors. The overall level of toxicity associated with EGFR inhibitors is low compared to other chemotherapy drugs, although they are commonly associated with skin and gastrointestinal adverse events. Thus, patients' quality of life may be considerably affected both by a physical and a psychosocial perspective. Adverse events that lead to treatment interruption or cessation may significantly compromise their outcome. This review summarizes the characteristics of the distinctive toxicities of drugs targeting EGFR, addressing their incidence, pathophysiology and clinical presentation with a focus on the management of skin rash and other relevant adverse events, according to the available clinical evidence. Data regarding the correlation between the development of skin rash and clinical outcome are also reported. Drugs targeting EGFR are associated with a lower overall incidence of systemic side effects compared to standard chemotherapeutic agents; nevertheless, an increased risk of distinct toxicities that may affect patient's quality of life and anticancer treatment compliance is observed. Thus, clinical training projects directed toward a more accurate knowledge of such adverse events are essential to maximize the progress of targeted therapies against cancer.

  1. Multimodal approach to the management of metastatic epidural spinal cord compression (MESCC) due to solid tumors.

    Science.gov (United States)

    Tancioni, Flavio; Navarria, Pierina; Lorenzetti, Martin A; Pedrazzoli, Paolo; Masci, Giovanna; Mancosu, Pietro; Alloisio, Marco; Morenghi, Emanuela; Santoro, Armando; Rodriguez y Baena, Riccardo; Scorsetti, Marta

    2010-12-01

    To assess the impact of a multidisciplinary approach for treatment of patients with metastatic epidural spinal cord compression in terms of feasibility, local control, and survival. Eighty-nine consecutive patients treated between January 2004 and December 2007 were included. The most common primary cancers were lung, breast, and kidney cancers. Ninety-eight surgical procedures were performed. Radiotherapy was performed within the first month postoperatively. Clinical outcome was evaluated by modified visual analog scale for pain, Frankel scale for neurologic deficit, and magnetic resonance imaging or computed tomography scan. Nearly all patients (93%) had back pain before treatment, whereas major or minor preoperative neurologic deficit was present in 62 cases (63%). Clinical remission of pain was obtained in the vast majority of patients (91%). Improvement of neurologic deficit was observed in 45 cases (72.5%). Local relapse occurred in 10%. Median survival was 11 months (range, 0-46 months). Overall survival at 1 year was 43.6%. Type of primary tumor significantly affected survival. In patients with metastatic epidural spinal cord compression, the combination of surgery plus radiotherapy is feasible and provides clinical benefit in most patients. The discussion of each single case within a multidisciplinary team has been of pivotal importance in implementing the most appropriate therapeutic approach. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. Usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors: its independency of p53 status.

    Science.gov (United States)

    Masunaga, Shin-ichiro; Tano, Keizo; Nakamura, Jun; Watanabe, Masami; Kashino, Genro; Takahashi, Akihisa; Tanaka, Hiroki; Suzuki, Minoru; Ohnishi, Ken; Kinashi, Yuko; Liu, Yong; Ohnishi, Takeo; Ono, Koji

    2010-01-01

    The usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors and its dependency on the p53 status of tumor cells were examined. Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53), or with neo vector as a control (SAS/neo), were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. The tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. Then, they received hexamethylenetetramine (HMTA), intraperitoneally or continuously, combined with or without gamma-ray irradiation or cisplatin treatment. Immediately after treatment following HMTA, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The response of the total (= P + Q) tumor cells was determined from the BrdU non-treated tumors. A higher toxicity of HMTA to Q cells than total cells, especially in SAS/neo, was made less clear by continuous administration. There was no apparent difference in the radio- and cisplatin-sensitivity enhancing effects by HMTA combination between SAS/neo and SAS/mp53 tumors, with a slightly greater effect in SAS/mp53. In both SAS/neo and SAS/mp53 tumors, continuous HMTA administration produced higher radio- and cisplatin-sensitivity enhancing effects than intraperitoneal single administration. Therefore, the use of HMTA as an adjuvant to radiation or cisplatin might be promising in curing solid tumors with large fraction of hypoxic cells and also with frequent loss-of-function in p53.

  3. Preclinical development of a novel class of CXCR4 antagonist impairing solid tumors growth and metastases.

    Directory of Open Access Journals (Sweden)

    Luigi Portella

    Full Text Available The CXCR4/CXCL12 axis plays a role in cancer metastases, stem cell mobilization and chemosensitization. Proof of concept for efficient CXCR4 inhibition has been demonstrated in stem cell mobilization prior to autologous transplantation in hematological malignancies. Nevertheless CXCR4 inhibitors suitable for prolonged use as required for anticancer therapy are not available. To develop new CXCR4 antagonists a rational, ligand-based approach was taken, distinct from the more commonly used development strategy. A three amino acid motif (Ar-Ar-X in CXCL12, also found in the reverse orientation (X-Ar-Ar in the vMIP-II inhibitory chemokine formed the core of nineteen cyclic peptides evaluated for inhibition of CXCR4-dependent migration, binding, P-ERK1/2-induction and calcium efflux. Peptides R, S and I were chosen for evaluation in in vivo models of lung metastases (B16-CXCR4 and KTM2 murine osteosarcoma cells and growth of a renal cells xenograft. Peptides R, S, and T significantly reduced the association of the 12G5-CXCR4 antibody to the receptor and inhibited CXCL12-induced calcium efflux. The four peptides efficiently inhibited CXCL12-dependent migration at concentrations as low as 10 nM and delayed CXCL12-mediated wound healing in PES43 human melanoma cells. Intraperitoneal treatment with peptides R, I or S drastically reduced the number of B16-CXCR4-derived lung metastases in C57/BL mice. KTM2 osteosarcoma lung metastases were also reduced in Balb/C mice following CXCR4 inhibition. All three peptides significantly inhibited subcutaneous growth of SN12C-EGFP renal cancer cells. A novel class of CXCR4 inhibitory peptides was discovered. Three peptides, R, I and S inhibited lung metastases and primary tumor growth and will be evaluated as anticancer agents.

  4. Conditions of tumor-associated antigens as a proper target for therapeutic antibodies against solid cancers

    Directory of Open Access Journals (Sweden)

    Yoshikazu Kurosawa

    2011-01-01

    Full Text Available Since the success of rituximab and trastuzumab for treatment of non-Hodgkin’s lymphoma and breast cancer, respectively, a huge therapeutic potential of monoclonal antibodies (mAbs was realized and development of therapeutic mAbs has been widely tried against various cancers. However, the successful examples are still limited and therapeutic mAbs are not yet available for the majority of human cancers. We established a procedure for comprehensive identification of tumor-associated antigens (TAAs through the extensive isolation of human mAbs that may become therapeutic. Thirty-twoTAAs have been identified and 555 mAbs that bound to one of the TAAs have been isolated to date. Now we are trying to select TAAs as proper targets for therapy and candidate mAbs as drugs from among them. The immunohistochemical analysis using many fresh lung cancer specimens suggested probabilities of proper targets, and moreover, presence of cancer-specific epitopes that could be distinguished from normal epitopes on the same molecules by mAbs. For Abs to efficiently kill the cancer cells they should have the ability to induce immunological cytotoxicity such as ADCC and/or CDC. They should also be able to inhibit the function mediated by the target Ags. For clinical point of view, the continuous presence of the target molecule on the cell surface until cell death might be essential for successful treatment. Therefore, it will be required for targets TAAs to play essential roles in tumorigenesis. Otherwise the cancer cells that do not express them could selectively survive during treatment and finally become dominant. It was also suggested that even the same molecules could play different roles in tumorigenesis quite often in different patients. Therefore when we develop therapeutic Abs, we should obtain information about the conditions of patients including genetic background to whom the treatment will be effective. I will discuss how we can accomplish this purpose.

  5. Enhanced in Vitro Anti-Tumor Activity of 5-Azacytidine by Entrapment into Solid Lipid Nanoparticles

    Science.gov (United States)

    Jahanfar, Farhad; Hasani, Akbar; Shanebandi, Dariush; Rahmati, Mohammad; Hamishehkar, Hamed

    2016-01-01

    Purpose: In this study the effectiveness of encapsulating of 5-azacytidine into the lipid nanoparticles was investigated and in vitro effect of encapsulated 5-azacytidine studied on MCF-7 cell lines Methods: 5-azacytidine -loaded solid lipid nanoparticles were produced by double emulsification (w/o/w) method by using stearic acid as lipid matrix, soy lecithin and poloxamer 407 as surfactant and co-surfactant respectively. Particle size, zeta potential, surface morphology, entrapment efficiency and kinetic of drug release were studied. In vitro effect of 5-azacytidine on MCF-7 cell line studied by MTT assay, DAPI staining, Rhodamine B relative uptake, and also Real time RT-PCR was performed for studying difference effect of free and encapsulated drug on expression of RARß2 gene. Results: The formulation F5 with 55.84±0.46 % of entrapment efficiency shows zero order kinetic of drug release and selected for in vitro studies; the cytotoxicity of free drug and encapsulated drug in 48 h of incubation have significant difference. DAPI staining shows morphology of apoptotic nucleus in both free and encapsulated drug, Rhodamine B labeled SLNs show time dependency and accumulation of SLNs in cytoplasm. Real time qRT-PCR doesn’t show any significant difference (p>0.05) in expression of RARß2 gene in both cells treated with free or encapsulated drug. Conclusion: The results of the present study indicated that the entrapment of 5-azacytidine into SLNs enhanced its cytotoxicity performance and may pave a way for the future design of a desired dosage form for 5-azacytidine. PMID:27766220

  6. Delivery of kinesin spindle protein targeting siRNA in solid lipid nanoparticles to cellular models of tumor vasculature

    Energy Technology Data Exchange (ETDEWEB)

    Ying, Bo; Campbell, Robert B., E-mail: robert.campbell@mcphs.edu

    2014-04-04

    Highlights: • siRNA-lipid nanoparticles are solid particles not lipid bilayers with aqueous core. • High, but not low, PEG content can prevent nanoparticle encapsulation of siRNA. • PEG reduces cellular toxicity of cationic nanoparticles in vitro. • PEG reduces zeta potential while improving gene silencing of siRNA nanoparticles. • Kinesin spindle protein can be an effective target for tumor vascular targeting. - Abstract: The ideal siRNA delivery system should selectively deliver the construct to the target cell, avoid enzymatic degradation, and evade uptake by phagocytes. In the present study, we evaluated the importance of polyethylene glycol (PEG) on lipid-based carrier systems for encapsulating, and delivering, siRNA to tumor vessels using cellular models. Lipid nanoparticles containing different percentage of PEG were evaluated based on their physical chemical properties, density compared to water, siRNA encapsulation, toxicity, targeting efficiency and gene silencing in vitro. siRNA can be efficiently loaded into lipid nanoparticles (LNPs) when DOTAP is included in the formulation mixture. However, the total amount encapsulated decreased with increase in PEG content. In the presence of siRNA, the final formulations contained a mixed population of particles based on density. The major population which contains the majority of siRNA exhibited a density of 4% glucose, and the minor fraction associated with a decreased amount of siRNA had a density less than PBS. The inclusion of 10 mol% PEG resulted in a greater amount of siRNA associated with the minor fraction. Finally, when kinesin spindle protein (KSP) siRNA was encapsulated in lipid nanoparticles containing a modest amount of PEG, the proliferation of endothelial cells was inhibited due to the efficient knock down of KSP mRNA. The presence of siRNA resulted in the formation of solid lipid nanoparticles when prepared using the thin film and hydration method. LNPs with a relatively modest amount of

  7. Educational achievement, employment, smoking, marital, and insurance statuses in long-term survivors of childhood malignant solid tumors.

    Science.gov (United States)

    Yağci-Küpeli, Begül; Yalçin, Bilgehan; Küpeli, Serhan; Varan, Ali; Akyüz, Canan; Kutluk, Tezer; Büyükpamukçu, Münevver

    2013-03-01

    Survivors of childhood cancer experience many social adaptation problems. We aimed to identify social, educational, and occupational issues of this growing population. Survivors treated for childhood malignant solid tumors who were older than 18 years and in remission for at least 3 years were surveyed. The educational achievement, employment, type of habitation, marital status, parenthood, social insurance, and smoking status of the patients were inquired and recorded. Two hundred one patients (126 male patients/75 female patients) were included in the study between 2007 and 2009. The median ages at the time of diagnosis and at the time of study were 10 years (range, 0 to 19 y) and 23 years (range, 18 to 39 y), respectively. The median follow-up duration was 13.5 years (range, 3 to 31 y). Nearly half of the participants were lymphoma survivors. One hundred eleven (55.5%) survivors were high school graduates and 47 (23%) were university graduates. Unemployment rate was 36.8%. Public social insurance rate was 90.5%. Fifty-three (26.4%) survivors had independent habitation. Thirty percent of survivors were married and 7.5% had at least 1 child. Marriage rates were significantly higher in survivors who were older than 23 years, had a follow-up duration of >13 years, had a job, and lived independently (for each parameter P=0.001). University degree was significantly lower in survivors who were treated for central nervous system tumors. Our results have drawn a more marked picture with lower educational achievement and marital rates when compared with the results of large survivorship studies conducted in developed countries. However, they can be interpreted as intriguing when limited resources are taken into account.

  8. Safety, Antitumor Activity, and Immune Activation of Pegylated Recombinant Human Interleukin-10 (AM0010) in Patients With Advanced Solid Tumors.

    Science.gov (United States)

    Naing, Aung; Papadopoulos, Kyriakos P; Autio, Karen A; Ott, Patrick A; Patel, Manish R; Wong, Deborah J; Falchook, Gerald S; Pant, Shubham; Whiteside, Melinda; Rasco, Drew R; Mumm, John B; Chan, Ivan H; Bendell, Johanna C; Bauer, Todd M; Colen, Rivka R; Hong, David S; Van Vlasselaer, Peter; Tannir, Nizar M; Oft, Martin; Infante, Jeffrey R

    2016-10-10

    Purpose Interleukin-10 (IL-10) stimulates the expansion and cytotoxicity of tumor-infiltrating CD8+ T cells and inhibits inflammatory CD4+ T cells. Pegylation prolongs the serum concentration of IL-10 without changing the immunologic profile. This phase I study sought to determine the safety and antitumor activity of AM0010. Patients and Methods Patients with selected advanced solid tumors were treated with AM0010 in a dose-escalation study, which was followed by a renal cell cancer (RCC) dose-expansion cohort. AM0010 was self-administered subcutaneously at doses of 1 to 40 μg/kg once per day. Primary end points were safety and tolerability; clinical activity and immune activation were secondary end points. Results In the dose-escalation and -expansion cohorts, 33 and 18 patients, respectively, were treated with daily subcutaneous injection of AM0010. AM0010 was tolerated in a heavily pretreated patient population. Treatment-related adverse events (AEs) included anemia, fatigue, thrombocytopenia, fever, and injection site reactions. Grade 3 to 4 nonhematopoietic treatment-related AEs, including rash (n = 2) and transaminitis (n = 1), were observed in five of 33 patients. Grade 3 to 4 anemia or thrombocytopenia was observed in five patients. Most treatment-related AEs were transient or reversible. AM0010 led to systemic immune activation with elevated immune-stimulatory cytokines and reduced transforming growth factor beta in the serum. Partial responses were observed in one patient with uveal melanoma and four of 15 evaluable patients with RCC treated at 20 μg/kg (overall response rate, 27%). Prolonged stable disease of at least 4 months was observed in four patients, including one with colorectal cancer with disease stabilization for 20 months. Conclusion AM0010 has an acceptable toxicity profile with early evidence of antitumor activity, particularly in RCC. These data support the further evaluation of AM0010 both alone and in combination with other immune

  9. Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)

    Science.gov (United States)

    2016-10-12

    Breast Cancer; Cholangiocarcinoma; Colorectal Cancer; Head and Neck Neoplasms; Lymphoma, Large-Cell, Anaplastic; Melanoma; Neuroendocrine Tumors; Non-Small Cell Lung Cancer; Ovarian Cancer; Pancreatic Cancer; Papillary Thyroid Cancer; Primary Brain Tumors; Renal Cell Carcinoma; Sarcomas; Salivary Gland Cancers; Adult Solid Tumor

  10. Karnofsky Performance Status and Lactate Dehydrogenase Predict the Benefit of Palliative Whole-Brain Irradiation in Patients With Advanced Intra- and Extracranial Metastases From Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Partl, Richard, E-mail: richard.partl@medunigraz.at [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria); Richtig, Erika [Department of Dermatology, Medical University of Graz, Graz (Austria); Avian, Alexander; Berghold, Andrea [Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz (Austria); Kapp, Karin S. [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria)

    2013-03-01

    Purpose: To determine prognostic factors that allow the selection of melanoma patients with advanced intra- and extracerebral metastatic disease for palliative whole-brain radiation therapy (WBRT) or best supportive care. Methods and Materials: This was a retrospective study of 87 patients who underwent palliative WBRT between 1988 and 2009 for progressive or multiple cerebral metastases at presentation. Uni- and multivariate analysis took into account the following patient- and tumor-associated factors: gender and age, Karnofsky performance status (KPS), neurologic symptoms, serum lactate dehydrogenase (LDH) level, number of intracranial metastases, previous resection or stereotactic radiosurgery of brain metastases, number of extracranial metastasis sites, and local recurrences as well as regional lymph node metastases at the time of WBRT. Results: In univariate analysis, KPS, LDH, number of intracranial metastases, and neurologic symptoms had a significant influence on overall survival. In multivariate survival analysis, KPS and LDH remained as significant prognostic factors, with hazard ratios of 3.3 (95% confidence interval [CI] 1.6-6.5) and 2.8 (95% CI 1.6-4.9), respectively. Patients with KPS ≥70 and LDH ≤240 U/L had a median survival of 191 days; patients with KPS ≥70 and LDH >240 U/L, 96 days; patients with KPS <70 and LDH ≤240 U/L, 47 days; and patients with KPS <70 and LDH >240 U/L, only 34 days. Conclusions: Karnofsky performance status and serum LDH values indicate whether patients with advanced intra- and extracranial tumor manifestations are candidates for palliative WBRT or best supportive care.

  11. CDH1/E-cadherin and solid tumors. An updated gene-disease association analysis using bioinformatics tools.

    Science.gov (United States)

    Abascal, María Florencia; Besso, María José; Rosso, Marina; Mencucci, María Victoria; Aparicio, Evangelina; Szapiro, Gala; Furlong, Laura Inés; Vazquez-Levin, Mónica Hebe

    2016-02-01

    Cancer is a group of diseases that causes millions of deaths worldwide. Among cancers, Solid Tumors (ST) stand-out due to their high incidence and mortality rates. Disruption of cell-cell adhesion is highly relevant during tumor progression. Epithelial-cadherin (protein: E-cadherin, gene: CDH1) is a key molecule in cell-cell adhesion and an abnormal expression or/and function(s) contributes to tumor progression and is altered in ST. A systematic study was carried out to gather and summarize current knowledge on CDH1/E-cadherin and ST using bioinformatics resources. The DisGeNET database was exploited to survey CDH1-associated diseases. Reported mutations in specific ST were obtained by interrogating COSMIC and IntOGen tools. CDH1 Single Nucleotide Polymorphisms (SNP) were retrieved from the dbSNP database. DisGeNET analysis identified 609 genes annotated to ST, among which CDH1 was listed. Using CDH1 as query term, 26 disease concepts were found, 21 of which were neoplasms-related terms. Using DisGeNET ALL Databases, 172 disease concepts were identified. Of those, 80 ST disease-related terms were subjected to manual curation and 75/80 (93.75%) associations were validated. On selected ST, 489 CDH1 somatic mutations were listed in COSMIC and IntOGen databases. Breast neoplasms had the highest CDH1-mutation rate. CDH1 was positioned among the 20 genes with highest mutation frequency and was confirmed as driver gene in breast cancer. Over 14,000 SNP for CDH1 were found in the dbSNP database. This report used DisGeNET to gather/compile current knowledge on gene-disease association for CDH1/E-cadherin and ST; data curation expanded the number of terms that relate them. An updated list of CDH1 somatic mutations was obtained with COSMIC and IntOGen databases and of SNP from dbSNP. This information can be used to further understand the role of CDH1/E-cadherin in health and disease.

  12. Extracranial sources of S100B do not affect serum levels.

    Directory of Open Access Journals (Sweden)

    Nancy Pham

    Full Text Available S100B, established as prevalent protein of the central nervous system, is a peripheral biomarker for blood-brain barrier disruption and often also a marker of brain injury. However, reports of extracranial sources of S100B, especially from adipose tissue, may confound its interpretation in the clinical setting. The objective of this study was to characterize the tissue specificity of S100B and assess how extracranial sources of S100B affect serum levels. The extracranial sources of S100B were determined by analyzing nine different types of human tissues by ELISA and Western blot. In addition, brain and adipose tissue were further analyzed by mass spectrometry. A study of 200 subjects was undertaken to determine the relationship between body mass index (BMI and S100B serum levels. We also measured the levels of S100B homo- and heterodimers in serum quantitatively after blood-brain barrier disruption. Analysis of human tissues by ELISA and Western blot revealed variable levels of S100B expression. By ELISA, brain tissue expressed the highest S100B levels. Similarly, Western blot measurements revealed that brain tissue expressed high levels of S100B but comparable levels were found in skeletal muscle. Mass spectrometry of brain and adipose tissue confirmed the presence of S100B but also revealed the presence of S100A1. The analysis of 200 subjects revealed no statistically significant relationship between BMI and S100B levels. The main species of S100B released from the brain was the B-B homodimer. Our results show that extracranial sources of S100B do not affect serum levels. Thus, the diagnostic value of S100B and its negative predictive value in neurological diseases in intact subjects (without traumatic brain or bodily injury from accident or surgery are not compromised in the clinical setting.

  13. Sensitivity and specificity of serum cross-linked N-telopeptides of type 1 collagen (NTx in patients with solid tumors

    Directory of Open Access Journals (Sweden)

    Fernando Jablonka

    2009-03-01

    Full Text Available Objective: Cross-linked N-telopeptides of type I collagen (NTx increase in situations in which bone resorption is increased, such as osteoporosis and bone metastasis. It was evaluated the usefulness of NTx for the diagnosis of bone metastases in patients with solid tumors. Methods: It was conducted a prospective study, at a tertiary public hospital. A quantitative enzyme-linked immunosorbent assay (ELISA assay of serum NTx levels in 19 subjects without a history of cancer and 62 patients with various solid tumors referred for a bone scan was evaluated. Three specialists read all bone scans. Rresults: It was not found any significant correlations between serum NTx and age, sex, history of bone pain, tumor type and bone alkaline phosphatase levels. We found a significant correlation between serum NTx and alkaline phosphatase levels (r2 = 0.08, p  = 0.022. Serum NTx sensitivity, specificity, positive and negative predictive values and area under the receiver operating characteristic (ROC curve for the presence of bone metastases were 0.34, 0.92, 0.95, 0.22 and 0.59, respectively. Cconclusions: It was concluded that serum levels of NTx are highly sensitive for the diagnosis of bone metastases in patients with solid tumors.

  14. Cisplatin-induced ototoxicity in pediatric solid tumors: the role of glutathione S-transferases and megalin genetic polymorphisms.

    Science.gov (United States)

    Choeyprasert, Worawut; Sawangpanich, Rachchadol; Lertsukprasert, Krisna; Udomsubpayakul, Umaporn; Songdej, Duantida; Unurathapan, Usanarat; Pakakasama, Samart; Hongeng, Suradej

    2013-05-01

    Cisplatin-induced ototoxicity, an important dose-limiting side effect, has proven high interindividual variability. Glutathione S-transferases (GSTs) are isoenzymes involved in cellular detoxification processes. Megalin has been demonstrated to bind aminoglycosides, known to be similar to cisplatin for their ototoxicity. The GSTs and megalin expression is genetically polymorphic, which might be responsible for the variability in cisplatin-induced ototoxicity. The genotyping of GSTM1, GSTT1 polymorphisms, and 2 nonsynonymous single nucleotide polymorphisms (SNPs) at megalin genes, rs2075252 and rs2228171, were performed in 68 children diagnosed with solid tumors who received cisplatin-based chemotherapy. After the end of treatment, audiometry demonstrated hearing loss in 79.4% of patients according to Brock classification. The cumulative cisplatin dose >400 mg/m is associated with increased risk of cisplatin-induced ototoxicity [odds ratio (OR), 17.5; 95% confidence interval (CI), 3.09-98.62]. GSTT1 wild genotype and C-allele of rs2228171 SNPs of megalin gene occurred with higher frequency in patients with ototoxicity (P=0.023; OR, 10; 95% CI, 1.80-56.00 and P=0.034; OR, 2.67; 95% CI, 1.22-5.82, respectively). In conclusion, our results suggested that GSTT1 wild genotype and C-allele of rs2228171 SNPs might be risk factors for ototoxicity. The cumulative cisplatin dose ototoxicity.

  15. MCL1 and BCL-xL levels in solid tumors are predictive of dinaciclib-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Robert N Booher

    Full Text Available Dinaciclib is a potent CDK1, 2, 5 and 9 inhibitor being developed for the treatment of cancer. Additional understanding of antitumor mechanisms and identification of predictive biomarkers are important for its clinical development. Here we demonstrate that while dinaciclib can effectively block cell cycle progression, in vitro and in vivo studies, coupled with mouse and human pharmacokinetics, support a model whereby induction of apoptosis is a main mechanism of dinaciclib's antitumor effect and relevant to the clinical duration of exposure. This was further underscored by kinetics of dinaciclib-induced downregulation of the antiapoptotic BCL2 family member MCL1 and correlation of sensitivity with the MCL1-to-BCL-xL mRNA ratio or MCL1 amplification in solid tumor models in vitro and in vivo. This MCL1-dependent apoptotic mechanism was additionally supported by synergy with the BCL2, BCL-xL and BCL-w inhibitor navitoclax (ABT-263. These results provide the rationale for investigating MCL1 and BCL-xL as predictive biomarkers for dinaciclib antitumor response and testing combinations with BCL2 family member inhibitors.

  16. Consensus Contouring Guidelines for Postoperative Stereotactic Body Radiation Therapy for Metastatic Solid Tumor Malignancies to the Spine.

    Science.gov (United States)

    Redmond, Kristin J; Robertson, Scott; Lo, Simon S; Soltys, Scott G; Ryu, Samuel; McNutt, Todd; Chao, Samuel T; Yamada, Yoshiya; Ghia, Amol; Chang, Eric L; Sheehan, Jason; Sahgal, Arjun

    2017-01-01

    To develop consensus contouring guidelines for postoperative stereotactic body radiation therapy (SBRT) for spinal metastases. Ten spine SBRT specialists representing 10 international centers independently contoured the clinical target volume (CTV), planning target volume (PTV), spinal cord, and spinal cord planning organ at risk volume (PRV) for 10 representative clinical scenarios in postoperative spine SBRT for metastatic solid tumor malignancies. Contours were imported into the Computational Environment for Radiotherapy Research. Agreement between physicians was calculated with an expectation minimization algorithm using simultaneous truth and performance level estimation with κ statistics. Target volume definition guidelines were established by finding optimized confidence level consensus contours using histogram agreement analyses. Nine expert radiation oncologists and 1 neurosurgeon completed contours for all 10 cases. The mean sensitivity and specificity were 0.79 (range, 0.71-0.89) and 0.94 (range, 0.90-0.99) for the CTV and 0.79 (range, 0.70-0.95) and 0.92 (range, 0.87-0.99) for the PTV), respectively. Mean κ agreement, which demonstrates the probability that contours agree by chance alone, was 0.58 (range, 0.43-0.70) for CTV and 0.58 (range, 0.37-0.76) for PTV (Ppostoperative SBRT for spinal metastases. These consensus guidelines are subject to clinical validation. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. SU-E-I-84: Accuracy Comparison of Multi-Modality Image-Based Volumes of Rodent Solid Tumors Using In-Air Micro-CT Image Volume

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y [University of Kansas Hospital, Kansas City, KS (United States); Fullerton, G; Goins, B [University of Texas Health Science Center at San Antonio, San Antonio, TX (United States)

    2015-06-15

    Purpose: Tumor volume is considered as a better predictor for therapy response monitoring and tumor staging over Response Evaluation Criteria In Solid Tumors (RECIST) or World Health Organization (WHO) criteria. In this study, the accuracy of subcutaneous rodent tumor volumes using preclinical magnetic resonance imaging (MRI), micro-computed tomography (micro-CT) and ultrasound (US) equipment and with an external caliper was compared using in-air micro-CT image volume of excised tumors determined as reference tumor volume in our prior study. Methods: MR, US and micro-CT images of subcutaneous SCC4 head and neck tumor xenografts were acquired 4, 6, 9, 11 and 13 days after tumor cell inoculation. Before MR and US scans, caliper measurements were made. After tumors were excised, in-air micro-CT imaging and ex vivo caliper measurements were performed. Tumor volumes were calculated using formula V = (π/6)*a*b*c where a, b and c are the maximum diameters in three perpendicular dimensions determined by the three image modalities and caliper, and compared with reference tumor volume by linear regression analysis as well as Bland-Altman plots. A one-way Analysis of Variance (ANOVA) test was also performed to compare volumes among caliper measurements. Results: The correlation coefficients (R2) of the regression lines for tumor volumes measured by the three imaging modalities and caliper were 0.9939, 0.9669, 0.9806, 0.9274, 0.9619 and 0.9819 for MRI, US and micro-CT, caliperbeforeMRI, caliperbeforeUS and ex vivo caliper respectively. In Bland-Altman plots, the average of tumor volume difference from reference tumor volume (bias) was significant for caliper and micro- CT, but not for MRI and US. Comparison of caliper measurements showed a significant difference (p < 0.05). Conclusion: Using the in-air micro-CT image volume, tumor volume measured by MRI was the most accurate among the three imaging modalities. In vivo caliper volume measurements showed unreliability while ex

  18. Exposure and Tumor Fn14 Expression as Determinants of Pharmacodynamics of the Anti-TWEAK Monoclonal Antibody RG7212 in Patients with Fn14-Positive Solid Tumors

    DEFF Research Database (Denmark)

    Meulendijks, Didier; Lassen, Ulrik N; Siu, Lillian L;

    2016-01-01

    -TWEAK mAb, in patients with Fn14-expressing tumors. EXPERIMENTAL DESIGN: Patients with Fn14-positive tumors (IHC ≥ 1+) treated in a phase I first-in-human study with ascending doses of RG7212 were the basis for this analysis. Pharmacokinetics of RG7212 and dynamics of TWEAK were determined, as were......PURPOSE: The TWEAK-Fn14 pathway represents a novel anticancer target that is being actively investigated. Understanding the relationship between pharmacokinetics of anti-TWEAK therapeutics and tumor pharmacodynamics is critical. We investigated exposure-response relationships of RG7212, an anti......*h/mL). Significant reductions in tumor Ki-67 expression and early changes in serum concentrations of CCL-2 and MMP-9 were observed exclusively in patients with higher drug exposure who had high pretreatment tumor Fn14 expression. Pretreatment tumor Fn14 expression was not associated with outcome, but a trend toward...

  19. Pilot trial of EZN-2968, an antisense oligonucleotide inhibitor of hypoxia-inducible factor-1 alpha (HIF-1α), in patients with refractory solid tumors.

    Science.gov (United States)

    Jeong, Woondong; Rapisarda, Annamaria; Park, Sook Ryun; Kinders, Robert J; Chen, Alice; Melillo, Giovanni; Turkbey, Baris; Steinberg, Seth M; Choyke, Peter; Doroshow, James H; Kummar, Shivaani

    2014-02-01

    Hypoxia-inducible factor-1 (HIF-1) facilitates the adaptation of normal and tumor tissues to oxygen deprivation. HIF-1 is frequently overexpressed in cancer cells, where it is involved in the upregulation of many genes necessary for survival. EZN-2968 is an antisense oligodeoxynucleotide that specifically targets HIF-1α, one of the subunits of HIF-1. We conducted a trial of EZN-2968 in patients with refractory solid tumors to evaluate antitumor response and to measure modulation of HIF-1α mRNA and protein levels as well as HIF-1 target genes. Adult patients with refractory advanced solid tumors were administered EZN-2968 as a 2-h IV infusion at a dose of 18 mg/kg once a week for three consecutive weeks followed by 3-week off; in a 6-week cycle. Tumor biopsies and dynamic contrast enhanced MRI (DCE-MRI) were performed at baseline and after the third dose. Ten patients were enrolled, of whom all were evaluable for response; one patient with a duodenal neuroendocrine tumor had prolonged stabilization of disease (24 weeks). Reduction in HIF-1α mRNA levels compared to baseline was demonstrated in 4 of 6 patients with paired tumor biopsies. Reductions in levels of HIF-1α protein and mRNA levels of some target genes were observed in two patients. Quantitative analysis of DCE-MRI from two patients revealed changes in K (trans) and k ep. The trial was closed prematurely when the sponsor suspended development of this agent. This trial provides preliminary proof of concept for modulation of HIF-1α mRNA and protein expression and target genes in tumor biopsies following the administration of EZN-2968.

  20. Comparative therapeutic efficacy of rhenium-188 radiolabeled-liposome and 5-fluorouracil in LS-174T human colon carcinoma solid tumor xenografts.

    Science.gov (United States)

    Hsu, Chin-Wei; Chang, Ya-Jen; Chang, Chih-Hsien; Chen, Liang-Cheng; Lan, Keng-Li; Ting, Gann; Lee, Te-Wei

    2012-10-01

    Nanoliposomes are important carriers capable of packaging drugs for various delivery applications. Rhenium-188-radiolabeled liposome ((188)Re-liposome) has potential for radiotherapy and diagnostic imaging. To evaluate the targeting of (188)Re-liposome, biodistribution, microSPECT/CT, whole-body autoradiography (WBAR), and pharmacokinetics were performed in LS-174T human tumor-bearing mice. The comparative therapeutic efficacy of (188)Re-liposome and 5-fluorouracil (5-FU) was assessed according to inhibition of tumor growth and the survival ratio. The highest uptake of (188)Re-liposome in LS-174T tumor was found at 24 hours by biodistribution and microSPECT/CT imaging, showing a positive correlation for tumor targeting of (188)Re-liposome using the Pearson's correlation analysis (r=0.997). Pharmacokinetics of (188)Re-liposome showed the properties of high circulation time and high bioavailability (mean residence time [MRT]=18.8 hours, area under the curve [AUC]=1371%ID/g·h). For therapeutic efficacy, the tumor-bearing mice treated with (188)Re-liposome (80% maximum tolerated dose [MTD], 23.7 MBq) showed better tumor growth inhibition and longer survival time than those treated with 5-FU (80% MTD, 144 mg/kg). The median survival time for mice treated with (188)Re-liposome (58.5 days; p0.05) and normal saline-treated mice (43.63 days). Dosimetry study revealed that the (188)Re-liposome did not lead to high absorbed doses in normal tissue, but did in small tumors. These results of imaging and biodistribution indicated the highly specific accumulation of tumor after intravenous (i.v.) injection of (188)Re-liposome. The therapeutic efficacy of radiotherapeutics of (188)Re-liposome have been confirmed in a LS-174T solid tumor animal model, which points to the potential benefit and promise of passive nanoliposome delivered radiotherapeutics for cancer treatment.

  1. A Comparison of Entecavir and Lamivudine for the Prophylaxis of Hepatitis B Virus Reactivation in Solid Tumor Patients Undergoing Systemic Cytotoxic Chemotherapy.

    Directory of Open Access Journals (Sweden)

    Wen-Chi Chen

    Full Text Available Nucleos(tide analogues reduce the incidence of hepatitis B virus (HBV reactivation in cancer patients undergoing systemic cytotoxic chemotherapy but the experience of solid tumors remains limited. Aims. The aim of this study was to compare the efficacy of entecavir and lamivudine in the prophylaxis of HBV reactivation in solid tumor patients undergoing systemic cytotoxic chemotherapy.HBsAg seropositive patients undergoing systemic cytotoxic chemotherapy for solid tumors with prophylactic entecavir and lamivudine between January 2006 and June 2013 were retrospectively investigated. The incidence of HBV reactivation and outcome of the patients were analyzed. The risk factors of HBV reactivation were examined.A total of 213 patients (entecavir group, 70 patients; lamivudine group, 143 patients were evaluated. Less incidence of HBV reactivation was noticed in entecavir group than in lamivudine group (0% vs. 7.0%, P = 0.02. No HBV reactivation was noticed in the patients with a baseline HBV DNA level < 2000 IU/mL. A baseline HBV DNA level ≥ 2000 IU/mL, HBeAg, and lamivudine were significantly associated with HBV reactivation. Subgroup analysis of the patients with a baseline HBV DNA level ≥ 2000 IU/mL found that lamivudine was significantly associated with HBV reactivation. Most of the reactivation events were properly managed by using tenofovir disoproxil fumarate. The incidence of hepatitis during chemotherapy and disruption of chemotherapy was similar between patients using entecavir and lamivudine with a baseline HBV DNA level ≥ or < 2000 IU/mL.A baseline HBV DNA level ≥ 2000 IU/mL, HBeAg, and lamivudine were the risk factors of HBV reactivation during systemic cytotoxic chemotherapy in solid tumor patients. Entecavir was superior to lamivudine in terms of less incidence of reactivation in the patients with a baseline HBV DNA level ≥ 2000 IU/mL. Both agents were equally efficacious in the patients with HBV DNA levels < 2000 IU/mL.

  2. A phase 1 dose-escalation study of the oral histone deacetylase inhibitor abexinostat in combination with standard hypofractionated radiotherapy in advanced solid tumors

    Science.gov (United States)

    Deutsch, Eric; Moyal, Elizabeth Cohen-Jonathan; Gregorc, Vanesa; Zucali, Paolo Andrea; Menard, Jean; Soria, Jean-Charles; Kloos, Ioana; Hsu, Jeff; Luan, Ying; Liu, Emily; Vezan, Remus; Graef, Thorsten; Rivera, Sofia

    2017-01-01

    Current treatments for advanced solid tumors tend to be only palliative. Although radiotherapy is administered with a curative intent, radioresistance and dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation in various solid tumor cell lines. We conducted an exploratory, phase 1, dose-escalation study of abexinostat in combination with standard hypofractionated radiotherapy in patients with advanced solid tumors treated in a palliative setting. Among 58 treated patients, the median age was 61.5 years (range, 20-82); 47% of the patients had M1 stage disease, and 95% had received previous chemotherapy alone or chemotherapy in combination with surgery and/or radiotherapy. The recommended phase 2 dose was determined to be 90 mg/m2 (140 mg). Of the 51 patients evaluable for response, best overall response was 8% (1 complete response [CR], 3 partial responses [PRs]), and best loco-regional response was 12% (1 CR and 5 PRs) at a median follow-up of 16 weeks. Of note, patients with target or non-target brain lesions showed encouraging responses, with 1 patient achieving a best loco-regional response of CR. Treatment-emergent grade ≥3 adverse events (AEs) were few, with most common being thrombocytopenia (17%), lymphopenia (12%), and hypokalemia (7%). Six patients (10%) discontinued treatment due to AEs. No grade ≥3 prolongation of the QTc interval was observed, with no treatment discontinuations due to this AE. Oral abexinostat combined with radiotherapy was well tolerated in patients with advanced solid tumors. The combination may have potential for treatment of patients with brain lesions. PMID:28915584

  3. A phase 1 dose-escalation study of the oral histone deacetylase inhibitor abexinostat in combination with standard hypofractionated radiotherapy in advanced solid tumors.

    Science.gov (United States)

    Deutsch, Eric; Cohen-Jonathan Moyal, Elizabeth; Gregorc, Vanesa; Zucali, Paolo Andrea; Menard, Jean; Soria, Jean-Charles; Kloos, Ioana; Hsu, Jeff; Luan, Ying; Liu, Emily; Vezan, Remus; Graef, Thorsten; Rivera, Sofia

    2016-12-24

    Current treatments for advanced solid tumors tend to be only palliative. Although radiotherapy is administered with a curative intent, radioresistance and dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation in various solid tumor cell lines. We conducted an exploratory, phase 1, dose-escalation study of abexinostat in combination with standard hypofractionated radiotherapy in patients with advanced solid tumors treated in a palliative setting. Among 58 treated patients, the median age was 61.5 years (range, 20-82); 47% of the patients had M1 stage disease, and 95% had received previous chemotherapy alone or chemotherapy in combination with surgery and/or radiotherapy. The recommended phase 2 dose was determined to be 90 mg/m2 (140 mg). Of the 51 patients evaluable for response, best overall response was 8% (1 complete response [CR], 3 partial responses [PRs]), and best loco-regional response was 12% (1 CR and 5 PRs) at a median follow-up of 16 weeks. Of note, patients with target or non-target brain lesions showed encouraging responses, with 1 patient achieving a best loco-regional response of CR. Treatment-emergent grade ≥3 adverse events (AEs) were few, with most common being thrombocytopenia (17%), lymphopenia (12%), and hypokalemia (7%). Six patients (10%) discontinued treatment due to AEs. No grade ≥3 prolongation of the QTc interval was observed, with no treatment discontinuations due to this AE. Oral abexinostat combined with radiotherapy was well tolerated in patients with advanced solid tumors. The combination may have potential for treatment of patients with brain lesions.

  4. Expression of integrin alpha 10 is transcriptionally activated by pRb in mouse osteoblasts and is downregulated in multiple solid tumors.

    Science.gov (United States)

    Engel, B E; Welsh, E; Emmons, M F; Santiago-Cardona, P G; Cress, W D

    2013-11-28

    pRb is known as a classic cell cycle regulator whose inactivation is an important initiator of tumorigenesis. However, more recently, it has also been linked to tumor progression. This study defines a role for pRb as a suppressor of the progression to metastasis by upregulating integrin α10. Transcription of this integrin subunit is herein found to be pRb dependent in mouse osteoblasts. Classic pRb partners in cell cycle control, E2F1 and E2F3, do not repress transcription of integrin α10 and phosphorylation of pRb is not necessary for activation of the integrin α10 promoter. Promoter deletion revealed a pRb-responsive region between -108 bp to -55 bp upstream of the start of the site of transcription. pRb activation of transcription also leads to increased levels of integrin α10 protein and a greater concentration of the integrin α10 protein at the cell membrane of mouse osteoblasts. These higher levels of integrin α10 correspond to increased binding to collagen substrate. Consistent with our findings in mouse osteoblasts, we found that integrin α10 is significantly underexpressed in multiple solid tumors that have frequent inactivation of the pRb pathway. Bioinformatically, we identified data consistent with an 'integrin switch' that occurs in multiple solid tumors consisting of underexpression of integrins α7, α8, and α10 with concurrent overexpression of integrin β4. pRb promotes cell adhesion by inducing expression of integrins necessary for cell adhesion to a substrate. We propose that pRb loss in solid tumors exacerbates aggressiveness by debilitating cellular adhesion, which in turn facilitates tumor cell detachment and metastasis.

  5. Chromosomal differences between acute nonlymphocytic leukemia in patients with prior solid tumors and prior hematologic malignancies. A study of 14 cases with prior breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mamuris, Z.; Dumont, J.; Dutrillaux, B.; Aurias, A. (Institut Curie, Paris (France))

    1989-10-01

    A cytogenetic study of 14 patients with secondary acute nonlymphocytic leukemia (S-ANLL) with prior treatment for breast cancer is reported. The chromosomes recurrently involved in numerical or structural anomalies are chromosomes 7, 5, 17, and 11, in decreasing order of frequency. The distribution of the anomalies detected in this sample of patients is similar to that observed in published cases with prior breast or other solid tumors, though anomalies of chromosome 11 were not pointed out, but it significantly differs from that of the S-ANLL with prior hematologic malignancies. This difference is principally due to a higher involvement of chromosome 7 in patients with prior hematologic malignancies and of chromosomes 11 and 17 in patients with prior solid tumors. A genetic determinism involving abnormal recessive alleles located on chromosomes 5, 7, 11, and 17 uncovered by deletions of the normal homologs may be a cause of S-ANLL. The difference between patients with prior hematologic malignancies or solid tumors may be explained by different constitutional mutations of recessive genes in the two groups of patients.

  6. A Tumor-stroma Targeted Oncolytic Adenovirus Replicated in Human Ovary Cancer Samples and Inhibited Growth of Disseminated Solid Tumors in Mice

    Science.gov (United States)

    Lopez, M Veronica; Rivera, Angel A; Viale, Diego L; Benedetti, Lorena; Cuneo, Nicasio; Kimball, Kristopher J; Wang, Minghui; Douglas, Joanne T; Zhu, Zeng B; Bravo, Alicia I; Gidekel, Manuel; Alvarez, Ronald D; Curiel, David T; Podhajcer, Osvaldo L

    2012-01-01

    Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 1010 v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15–40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression. PMID:22948673

  7. Raising the bar for antineoplastic agents: how to choose threshold values for superiority trials in advanced solid tumors.

    Science.gov (United States)

    Sobrero, Alberto F; Pastorino, Alessandro; Sargent, Daniel J; Bruzzi, Paolo

    2015-03-01

    To establish the concept of minimum clinically meaningful outcome (mCMO) of treatment in advanced solid tumors, to establish its threshold and evaluate how many superiority trials of new antineoplastic agents pass this threshold. We chose overall survival as the primary indicator of patient benefit. Four conceptually different types of treatment effect can be identified in OS curves: HR, gains in median OS, proportional, and absolute increases at long-term OS. We postulated threshold levels for these four parameters defining the mCMO and set the bar at three different levels of required benefit: high, medium, and low. The postulated values were then studied by comparing our thresholds with the actual results of the pivotal superiority phase III trials on new drugs reporting on mature OS data. Forty-three trials on 35,419 patients in 12 cancer types on 23 novel agents met these criteria. Only two trials reached the postulated "high" thresholds for HR and median OS. The number of "positive trials" increased to eight and 15 when the bar was lowered to the "medium" and "low" levels, respectively. The same analysis was done for proportional and absolute increases in long-term OS. No trial satisfied the criteria for long-term benefit, whereas only two and nine trials satisfied both parameters for the "medium and low" required benefit levels, respectively. All four OS-related parameters contribute to define the mCMO. If the bar for the mCMO is raised too much, positive trials are exceptional. ©2014 American Association for Cancer Research.

  8. First-in-human study of the antibody DR5 agonist DS-8273a in patients with advanced solid tumors.

    Science.gov (United States)

    Forero, Andres; Bendell, Johanna C; Kumar, Prasanna; Janisch, Linda; Rosen, Michael; Wang, Qiang; Copigneaux, Catherine; Desai, Madhuri; Senaldi, Giorgio; Maitland, Michael L

    2017-06-01

    Background DR5 is a transmembrane receptor that transduces extracellular ligand-binding to activate apoptosis signaling cascades. This phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of a new monoclonal antibody potent DR5 agonist, DS-8273a, in subjects with advanced solid tumors. Methods The study comprised dose escalation and dose expansion cohorts. The dose escalation cohorts intended to determine the safety and to identify the maximum tolerated dose (MTD) or maximum administered dose (MAD) and to characterize the pharmacokinetics and pharmacodynamics by a conventional 3 + 3 design (starting at 2 mg/kg and escalating through 8, 16 and 24 mg/kg once every 3 weeks). In the dose expansion cohort, additional subjects were treated at the MAD for further evaluation of PK and safety. Results Thirty two subjects were enrolled and treated, 16 in the dose escalation cohorts and 16 in the dose expansion cohort. No subjects experienced a dose limiting toxicity (DLT). Treatment emergent adverse events were observed in 29 (91%) subjects, 14 (44%) of which were attributed to study-drug; all drug-related events were grade 1 and 2 in severity, and were mainly fatigue, nausea, vomiting and diarrhea. Measures of plasma exposure increased dose-proportionally and the mean terminal elimination half-life was 11 days. Blood samples available from a subset of patients treated at 24 mg/kg revealed declines in myeloid derived suppressor cells (MDSC) at 2 weeks. No objective responses were observed in any subjects. Conclusions DS-8273a was well tolerated and demonstrated linear pharmacokinetics. Decreases in MDSC were temporally associated with DS-8273a exposure. This agent could be studied further in combination with other agents, pending further proof-of-target-engagement.

  9. KIR Genes and Their Ligands Predict the Response to Anti-EGFR Monoclonal Antibodies in Solid Tumors.

    Science.gov (United States)

    Morales-Estevez, Cristina; De la Haba-Rodriguez, Juan; Manzanares-Martin, Barbara; Porras-Quintela, Ignacio; Rodriguez-Ariza, Antonio; Moreno-Vega, Alberto; Ortiz-Morales, Maria J; Gomez-España, Maria A; Cano-Osuna, Maria T; Lopez-Gonzalez, Javier; Chia-Delgado, Beatriz; Gonzalez-Fernandez, Rafael; Aranda-Aguilar, Enrique

    2016-01-01

    Killer-cell immunoglobulin-like receptors (KIRs) regulate the killing function of natural killer cells, which play an important role in the antibody-dependent cell-mediated cytotoxicity response exerted by therapeutic monoclonal antibodies (mAbs). However, it is unknown whether the extensive genetic variability of KIR genes and/or their human leukocyte antigen (HLA) ligands might influence the response to these treatments. This study aimed to explore whether the variability in KIR/HLA genes may be associated with the variable response observed to mAbs based anti-epidermal growth factor receptor (EGFR) therapies. Thirty-nine patients treated with anti-EGFR mAbs (trastuzumab for advanced breast cancer, or cetuximab for advanced colorectal or advanced head and neck cancer) were included in the study. All the patients had progressed to mAbs therapy and were grouped into two categories taking into account time to treatment failure (TTF ≤6 and ≥10 months). KIR genotyping (16 genetic variability) was performed in genomic DNA from peripheral blood by PCR sequence-specific primer technique, and HLA ligand typing was performed for HLA-B and -C loci by reverse polymerase chain reaction sequence-specific oligonucleotide methodology. Subjects carrying the KIR/HLA ligand combinations KIR2DS1/HLAC2C2-C1C2 and KIR3DS1/HLABw4w4-w4w6 showed longer TTF than non-carriers counterparts (14.76 vs. 3.73 months, p KIR/HLA ligand combinations predict better response of patients to anti-EGFR therapy. These findings increase the overall knowledge on the role of specific gene variants related to responsiveness to anti-EGFR treatment in solid tumors and highlight the importance of assessing gene polymorphisms related to cancer medications.

  10. Effect of food on the pharmacokinetics of TAS-102 and its efficacy and safety in patients with advanced solid tumors.

    Science.gov (United States)

    Yoshino, Takayuki; Kojima, Takashi; Bando, Hideaki; Yamazaki, Tomoko; Naito, Yoichi; Mukai, Hirofumi; Fuse, Nozomu; Goto, Koichi; Ito, Yuko; Doi, Toshihiko; Ohtsu, Atsushi

    2016-05-01

    TAS-102, a novel oral antitumor agent, consists of trifluridine and tipiracil hydrochloride (molar ratio, 1:0.5). We investigated the effects of food on trifluridine and tipiracil hydrochloride. The efficacy and safety of TAS-102 were evaluated in patients with advanced solid tumors. We analyzed drug pharmacokinetics using a randomized, single-dose, two-treatment (fed versus fasting), two-period, two-sequence cross-over design, followed by repeated administration. Patients were given single doses of TAS-102 (35 mg/m(2) ) in the pharmacokinetic phase and received twice-daily doses of TAS-102 in 28-day cycles in the repeated administration phase for evaluating efficacy and safety. Food showed no effect on the area under the curve from 0 to 12 h or 0 h-infinity values of trifluridine following administration of TAS-102 under fasting and fed conditions, whereas those of tipiracil hydrochloride decreased by approximately 40%. Maximum concentrations of both drugs decreased by approximately 40%, indicating that food influenced the absorption and bioavailability of trifluridine and tipiracil hydrochloride, respectively. During the repeated administration, stable disease was observed in nine patients with rectal, small-cell lung, breast, thymic, duodenal, and prostate cancers. Major adverse events were neutropenia, leukopenia, anemia, and nausea. Postprandial administration was optimal for TAS-102 because trifluridine's area under the curve was not changed by food, indicating that its clinical efficacy would not be affected. Additionally, postprandial administration was reasonable because the maximum concentration of trifluridine decreased in neutrophils, which correlated with previous studies. These results suggest that TAS-102 would be an effective treatment for small-cell lung, thymic, and colorectal cancers. This trial is registered with the Japan Pharmaceutical Information Center (no. JapicCTI-111482). © 2016 The Authors. Cancer Science published by John Wiley & Sons

  11. Double-echo gradient chemical shift MR imaging fails to differentiate minimal fat renal angiomyolipomas from other homogeneous solid renal tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ferré, R., E-mail: kn638@yahoo.fr [Department of Radiology, Necker Hospital, 149 rue de Sèvres, 75730 Paris (France); Cornelis, F. [Department of Radiology, Pellegrin Hospital, Place Amélie Raba Léon, 33076 Bordeaux (France); Verkarre, V. [Department of Pathology, Necker Hospital, 149 rue de Sèvres, 75730 Paris (France); Eiss, D.; Correas, J.M. [Department of Radiology, Necker Hospital, 149 rue de Sèvres, 75730 Paris (France); Grenier, N. [Department of Radiology, Pellegrin Hospital, Place Amélie Raba Léon, 33076 Bordeaux (France); Hélénon, O. [Department of Radiology, Necker Hospital, 149 rue de Sèvres, 75730 Paris (France)

    2015-03-15

    Highlights: •Diagnosis of AMLs with minimal fat (mfAMLs) is still challenging with MRI. •Drop of signal on opposed-phase MR imaging is not specific of mfAMLs. •Double-echo gradient-echo sequences cannot accurately differentiate renal mfAMLs from other renal tumors. -- Abstract: Objectives: The purpose of this retrospective study was to evaluate the diagnostic performance of double-echo gradient chemical shift (GRE) magnetic resonance (MR) imaging for the differentiation of angiomyolipomas with minimal fat (mfAML) from other homogeneous solid renal tumors. Methods: Between 2005 and 2010 in two institutions, all histologically proven homogenous solid renal tumors imaged with computed tomography and MR imaging, including GRE sequences, have been retrospectively selected. A total of 118 patients (mean age: 61 years; range: 20–87) with 119 tumors were included. Two readers measured independently the signal intensity (SI) on GRE images and calculated SI index (SII) and tumor-to-spleen ratio (TSR) on in-phase and opposed-phase images. Intra- and interreader agreement was obtained. Cut-off values were derived from the receiver operating characteristic (ROC) curve analysis. Results: Twelve mfAMLs in 11 patients were identified (mean size: 2.8 cm; range: 1.2–3.5), and 107 non-AML tumors (3.2 cm; 1–7.8) in 107 patients. The intraobserver reproducibility of SII and TSR was excellent with an intraclass correlation coefficient equal to 0.99 [0.98–0.99]. The coefficient of correlation between the readers was 0.99. The mean values of TSR for mfAMLs and non-mfAMLs were −7.0 ± 22.8 versus −8.2 ± 21.2 for reader 1 and −6.7 ± 22.8 versus −8.4 ± 20.9 for reader 2 respectively. No significant difference was noticed between the two groups for SII (p = 0.98) and TSR (p = 0.86). Only 1 out of 12 mfAMLs and 11 of 107 non-AML tumors presented with a TSR inferior to −30% (p = 0.83). Conclusion: In a routine practice, GRE sequences cannot be a confident tool to

  12. Nickel(II) diacetyl monoxime-2-pyridyl hydrazone complex can inhibit Ehrlich solid tumor growth in mice: A potential new antitumor drug.

    Science.gov (United States)

    Saad, Entsar A; Hassanien, Mohamed M; El-Lban, Faten W

    2017-03-11

    The chief chemotherapeutic drug, cisplatin had common bad effects such as nephrotoxicity, ototoxicity and bone marrow depression. This led us to develop a new potential anticancer drug based on nickel metal ion that may be less toxic. Nickel(II) diacetyl monoxime-2-pyridyl hydrazone complex cytoprotective effect, superoxide dismutase (SOD)-like activity and anticancer activities were studied. In vitro, the complex showed SOD-like activity of 86.62%. It was capable to kill 90.2% of Ehrlich ascites carcinoma (EAC) cells and to protect 92.48% of human RBCs. In vivo, the complex lowered the tumor burden markedly in a concentration-dependent manner. Noticeably, solid tumor growth was suppressed; tumor volume and weight were reduced and mice life span was lengthened. The hematological indices were improved, catalase activity was re-elevated and malondialdehyde (MDA) level was reversed towards normal. Nucleic acids, cholesterol, triglycerides, liver enzymes, urea and creatinine contents were reduced to near normal ranges. Glutathione (GSH), SOD, albumin and total protein levels were increased. In conclusion, our results revealed that the complex has the ability to suppress Ehrlich solid tumor growth in mice with minimal side effects. This may possibly via its redox activity. Surprisingly, nickel complex antitumor activities were more potent than those of cisplatin. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas

    Science.gov (United States)

    2016-10-18

    Ewing Sarcoma; Gastrointestinal Tumor; Germ Cell Tumor; Hepatic Tumor; Lymphoma; Wilms Tumor; Rhabdoid Tumor; Clear Cell Carcinoma; Renal Cell Carcinoma; Melanoma; Neuroblastoma; Rhabdomyosarcoma; Non-rhabdomyosarcoma

  14. Armed Oncolytic Adenovirus-Expressing PD-L1 Mini-Body Enhances Antitumor Effects of Chimeric Antigen Receptor T Cells in Solid Tumors.

    Science.gov (United States)

    Tanoue, Kiyonori; Rosewell Shaw, Amanda; Watanabe, Norihiro; Porter, Caroline; Rana, Bhakti; Gottschalk, Stephen; Brenner, Malcolm; Suzuki, Masataka

    2017-04-15

    Chimeric antigen receptor-modified T cells (CAR T cells) produce proinflammatory cytokines that increase expression of T-cell checkpoint signals such as PD-L1, which may inhibit their functionality against solid tumors. In this study, we evaluated in human tumor xenograft models the proinflammatory properties of an oncolytic adenovirus (Onc.Ad) with a helper-dependent Ad (HDAd) that expresses a PD-L1 blocking mini-antibody (mini-body; HDPDL1) as a strategy to enhance CAR T-cell killing. Coadministration of these agents (CAd-VECPDL1) exhibited oncolytic effects with production of PD-L1 mini-body locally at the tumor site. On their own, HDPDL1 exhibited no antitumor effect and CAd-VECPDL1 alone reduced tumors only to volumes comparable to Onc.Ad treatment. However, combining CAd-VECPDL1 with HER2.CAR T cells enhanced antitumor activity compared with treatment with either HER2.CAR T cells alone or HER2.CAR T cells plus Onc.Ad. The benefits of locally produced PD-L1 mini-body by CAd-VECPDL1 could not be replicated by infusion of anti-PD-L1 IgG plus HER2.CAR T cells and coadministration of Onc.Ad in an HER2(+) prostate cancer xenograft model. Overall, our data document the superiority of local production of PD-L1 mini-body by CAd-VECPDL1 combined with administration of tumor-directed CAR T cells to control the growth of solid tumors. Cancer Res; 77(8); 2040-51. ©2017 AACR. ©2017 American Association for Cancer Research.

  15. Extracranial aneurysms of the distal posterior inferior cerebellar artery: Resection and primary reanastomosis as the preferred management approach.

    Science.gov (United States)

    Chwajol, Markus; Hage, Ziad A; Amin-Hanjani, Sepideh; Charbel, Fady T

    2013-01-01

    Extracranial aneurysms of the posterior inferior cerebellar artery (PICA) are rare, with only 22 reported cases in the English literature. For saccular extracranial distal PICA aneurysms not amenable to coiling, a surgically placed clip is not protected by the cranium postoperatively, and can be subject to movement in the mobile cervical region. Furthermore, fusiform or complex aneurysms cannot be clipped primarily. Resection and primary reanastomosis is a useful surgical approach not previously described for these extracranial lesions. We report three cases of extracranially located distal PICA aneurysms successfully treated with this surgical strategy at our center. One patient harboring a broad necked saccular aneurysm originally underwent successful primary clipping of the aneurysm but sustained a second subarachnoid hemorrhage (SAH) on postoperative day 25 due to clip dislodgement from vigorous neck movement. The other two patients were found to have fusiform and complex aneurysms, respectively. All three patients were ultimately treated with resection and end-to-end PICA anastomosis, which successfully obliterated their aneurysms. Resection and primary reanastomosis of extracranial distal PICA aneurysms averts the risk of clip dislodgement due to neck movement and/or compression by soft tissues in the upper cervical region. It is a safe and efficacious technique, which we propose as the preferred management strategy for these rare vascular lesions.

  16. Natural Killer Cells and Neuroblastoma: tumor recognition, escape mechanisms and possible novel immunotherapeutic approaches

    Directory of Open Access Journals (Sweden)

    Cristina eBottino

    2014-02-01

    Full Text Available Neuroblastoma (NB is the most common extra-cranial solid tumor of childhood and arises from developing sympathetic nervous system. Most primary tumors localize in the abdomen, the adrenal gland or lumbar sympathetic ganglia. Amplification in tumor cells of MYCN, the major oncogenic driver, patients’ age over 18 months and the presence at diagnosis of a metastatic disease (stage IV, M identify NB at high risk of treatment failure. Conventional therapies did not significantly improve the overall survival of these patients. Moreover, the limited landscape of somatic mutations detected in NB is hampering the development of novel pharmacological approaches. Major efforts aim to identify novel NB-associated surface molecules that activate immune responses and/or direct drugs to tumor cells and tumor-associated vessels. PVR (Poliovirus Receptor and B7-H3 are promising targets, since they are expressed by most high-risk NB, are upregulated in tumor vasculature and are essential for tumor survival/invasiveness. PVR is a ligand of DNAM-1 activating receptor that triggers the cytolytic activity of Natural Killer (NK cells against NB. In animal models targeting of PVR with an attenuated oncolytic poliovirus induced tumor regression and elimination. Also B7-H3 was successfully targeted in preclinical studies and is now being tested in phase I/II clinical trials. B7-H3 down-regulates NK cytotoxicity, providing NB with a mechanism of escape from immune response. The immunosuppressive potential of NB can be enhanced by the release of soluble factors that impair NK cell function and/or recruitment. Among these, TGF-β1 modulates the cytotoxicity receptors and the chemokine receptor repertoire of NK cells.Here, we summarize the current knowledge on the main cell surface molecules and soluble mediators that modulate the function of NK cells in NB, considering the pros and cons that must be taken into account in the design of novel NK cell-based immunotherapeutic

  17. Clinical Analysis of stereotactic body radiation therapy using extracranial gamma knife for patients with mainly bulky inoperable early stage non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Tang Hanjun

    2011-07-01

    Full Text Available Abstract Purpose To evaluate the clinical efficacy and toxicity of stereotactic body radiation therapy (SBRT using extracranial gamma knife in patients with mainly bulky inoperable early stage non-small cell lung carcinoma (NSCLC. Materials and methods A total of 43 medically inoperable patients with mainly bulky Stage I/II NSCLC received SBRT using gamma knife were reviewed. The fraction dose and the total dose were determined by the radiation oncologist according to patients' general status, tumor location, tumor size and the relationship between tumor and nearby organ at risk (OAR. The total dose of 34~47.5 Gy was prescribed in 4~12 fractions, 3.5~10 Gy per fraction, one fraction per day or every other day. The therapeutic efficacy and toxicity were evaluated. Results The median follow-up was 22 months (range, 3-102 months. The local tumor response rate was 95.35%, with CR 18.60% (8/43 and PR 76.74% (33/43, respectively. The local control rates at 1, 2, 3, 5 years were 77.54%, 53.02%, 39.77%, and 15.46%, respectively, while the 1- and 2-year local control rates were 75% and 60% for tumor ≤3 cm; 84% and 71% for tumor sized 3~5 cm; 55% and 14.6% for tumor sized 5~7 cm; and 45%, 21% in those with tumor size of >7 cm. The overall survival rate at 1, 2, 3, 5 years were 92.04%, 78.04%, 62.76%, 42.61%, respectively. The toxicity of stereotactic radiation therapy was grade 1-2. Clinical stages were significantly important factor in local control of lung tumors (P = 0.000. Both clinical stages (P = 0.015 and chemotherapy (P = 0.042 were significantly important factors in overall survival of lung tumors. Conclusion SBRT is an effective and safe therapy for medically inoperable patients with early stage NSCLC. Clinical stage was the significant prognostic factors for both local tumor control and overall survival. The toxicity is mild. The overall local control for bulky tumors is poor. Tumor size is a poor prognostic factor, and the patients for

  18. Pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Poussaint, Tina Y. [Department of Radiology, Boston, MA (United States); Panigrahy, Ashok [Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States); Huisman, Thierry A.G.M. [Charlotte R. Bloomberg Children' s Center, Johns Hopkins Hospital, Division of Pediatric Radiology and Pediatric Neuroradiology, Baltimore, MD (United States)

    2015-09-15

    Among all causes of death in children from solid tumors, pediatric brain tumors are the most common. This article includes an overview of a subset of infratentorial and supratentorial tumors with a focus on tumor imaging features and molecular advances and treatments of these tumors. Key to understanding the imaging features of brain tumors is a firm grasp of other disease processes that can mimic tumor on imaging. We also review imaging features of a common subset of tumor mimics. (orig.)

  19. An Open-Label, Multicenter, Phase 1/2 Study of E7438 (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Advanced Solid Tumors or With B-cell Lymphomas

    Science.gov (United States)

    2016-09-01

    B-cell Lymphomas (Phase 1); Advanced Solid Tumors (Phase 1); Diffuse Large B-cell Lymphoma (Phase 2); Follicular Lymphoma (Phase 2); Transformed Follicular Lymphoma; Primary Mediastinal Large B-Cell Lymphoma

  20. The baboon (Papio anubis extracranial carotid artery: An anatomical guide for endovascular experimentation

    Directory of Open Access Journals (Sweden)

    Laufer Ilya

    2001-12-01

    Full Text Available Abstract Background As novel endovascular strategies are developed for treating neurological disease, there is an increasing need to evaluate these techniques in relevant preclinical models. The use of non-human primates is especially critical given their structural and physiological homology with humans. In order to conduct primate endovascular studies, a comprehensive understanding of the carotid anatomy is necessary. We therefore performed a detailed examination of the vessel lengths, lumen diameters and angles of origin of the baboon extracranial carotid system. Methods We characterized the extracranial carotid system often male baboons (Papio anubis, range 15.1–28.4 kg by early post-mortem dissection. Photographic documentation of vessel lengths, lumen diameters, and angles of origin were measured for each segment of the carotid bilaterally. Results The common carotid arteries averaged 94.7 ± 1.7 mm (left and 87.1 ± 1.6 mm (right in length. The average minimal common carotid lumen diameters were 3.0 ± 0.3 mm (left and 2.9 ± 0.2 mm (right. Each animal had a common brachiocephalic artery arising from the aorta which bifurcated into the left common carotid artery and right braciocephalic artery after 21.5 ± 1.6 mm. The vascular anatomy was found to be consistent among animals despite a wide range of animal weights. Conclusions The consistency in the Papio anubis extracranial carotid system may promote the use of this species in the preclinical investigation of neuro-interventional therapies.

  1. Intracranial cerebral artery stenosis with associated coronary artery and extracranial carotid artery stenosis in Turkish patients

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    Alkan, Ozlem [Department of Radiology, Baskent University, Faculty of Medicine, Ankara (Turkey)], E-mail: yalinozlem@hotmail.com; Kizilkilic, Osman; Yildirim, Tulin [Department of Radiology, Baskent University, Faculty of Medicine, Ankara (Turkey); Atalay, Hakan [Department of Cardiovascular Surgery, Baskent University, Faculty of Medicine, Ankara (Turkey)

    2009-09-15

    Purpose: Although it has been demonstrated that there is a high prevalence of extracranial carotid artery stenosis (ECAS) in patients with severe coronary artery disease, intracranial cerebral artery stenosis (ICAS) is rarely mentioned. We evaluated the prevalence of ICAS in patients with ECAS having elective coronary artery bypass grafting (CABG) surgery to determine the relations between ICAS, ECAS and atherosclerotic risk factors. Methods: We retrospectively reviewed the digital subtraction angiography findings of 183 patients with ECAS {>=} 50% preparing for CABG surgery. The analyses focused on the intracranial or extracranial location and degree of the stenosis. The degree of extracranial stenoses were categorized as normal, <50%, 50-69%, 70-89%, and 90-99% stenosis and occluded. The degree of intracranial stenosis was classified as normal or {<=}25%, 25-49%, and {>=}50% stenosis and occluded. Traditional atherosclerotic risk factors were recorded. Results: ECAS < 70% in 42 patients and ECAS {>=} 70% in 141 patients. ICAS was found in 51 patients and ICAS {>=} 50% in 30 patients. Regarding risk factors, we found hypertension in 135 patients, diabetes mellitus in 91 patients, hyperlipidemia in 84 patients, and smoking in 81 patients. No risk factor was significant predictors of intracranial atherosclerosis. The severity of ICAS was not significantly associated with that of the ECAS. Conclusions: We found ICAS in 27.8% of the patients with ECAS > 50% on digital subtraction angiography preparing for CABG. Therefore a complete evaluation of the neck vessels with magnetic resonance or catheter angiography seems to be indicated as well as intracranial circulation for the risk assessment of CABG.

  2. A phase I dose-escalation study of the safety and pharmacokinetics of a tablet formulation of voxtalisib, a phosphoinositide 3-kinase inhibitor, in patients with solid tumors.

    Science.gov (United States)

    Mehnert, Janice M; Edelman, Gerald; Stein, Mark; Camisa, Heather; Lager, Joanne; Dedieu, Jean-François; Ghuysen, Anne-Frédérique; Sharma, Jyoti; Liu, Li; LoRusso, Patricia M

    2017-04-17

    Background Voxtalisib, a PI3K/mTOR inhibitor, has shown antitumor activity in capsule formulation in patients with solid tumors. This Phase I study assessed safety and pharmacokinetics of voxtalisib administered as immediate-release tablets in patients with solid tumors (NCT01596270). Methods A "3 + 3" dose escalation design was used. Adverse events (AEs), pharmacokinetics (PK), food effect and tumor response were evaluated. Results Thirty-two patients received voxtalisib doses ranging from 50 mg to 70 mg once daily (QD) and 17 patients received voxtalisib doses ranging from 30 mg to 50 mg twice daily (BID), for two 28-day cycles. Dose-limiting toxicities (DLTs) were Grade 3 fatigue (two patients at 70 mg QD, one patient at 40 mg BID) and Grade 3 rash (two patients at 50 mg BID). The maximum tolerated dose (MTD) was 60 mg for QD and 40 mg for BID regimens. Common treatment-emergent AEs were diarrhea (41%), nausea (37%) and fatigue (33%). Voxtalisib appeared to follow linear PK, with a general increase in plasma exposure with dose and no significant accumulation. Administration with food caused a slight decrease in exposure; however, given the high variability observed in the exposure parameters, this should be interpreted with caution. Best response was stable disease in 29% and 50% of patients (QD and BID regimens, respectively). Conclusions The safety profile of voxtalisib tablets at the MTD in patients with solid tumors was consistent with that observed with voxtalisib capsules. Given the limited activity observed across multiple clinical trials, no further trials of voxtalisib are planned.

  3. Short-term results of carotid stenting for the treatment of extracranial carotid occlusive disease

    Institute of Scientific and Technical Information of China (English)

    FU Wei-guo; ZHU Ting; CHEN Bin; JIANG Jun-hao; YANG Jue; SHI Zhen-yu

    2006-01-01

    @@ Carotid artery angioplasty and stenting (CAS) has been performed with increasing frequency for the treatment of extracranial carotid occlusive diseases (ECOD) in recent years. Its feasibility and safety are supported by the Stenting and Angioplasty with Protection in Patient at High Risk for Endarterectomy (SAPPHIRE) trial,1 which revealed a lower incidence of death, stroke and myocardial infarction compared with carotid endarterectomy (CEA) in high-risk patients. However, it is a pity that up to now, initial results of this endovascular procedure have yet been infrequently documented in China. This retrospective study was to analyze the short-term results of CAS to treat ECOD in a single medical center.

  4. Extracranial internal carotid artery stenting in Moya-Moya syndrome: a case report.

    Science.gov (United States)

    Casana, R; Tolva, V; Guy Bianchi, P; Dalainas, I

    2012-12-01

    A 58-year-old Caucasian lady presented for severe left internal carotid artery (ICA) stenosis. Two months before she was operated for right carotid endarterectomy (CEA) in another Institution, complicated with internal carotid artery thrombosis and development of transient hemiplegia and aphasia. Postoperative selective DSA showed the development of an abnormal basal meshwork of collateral vessels with typical evidence for moyamoya disease. Preoperative workup in our Institution included cerebral MRI witch showed two ischemic right frontal and parietal lesions. The patient underwent successful stenting of the left ICA. This is the first report of extracranial ICA stenting in a patient with moyamoya syndrome.

  5. Childhood extracranial neoplasms: the role of imaging in drug development and clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Fowkes, Lucy A.; Koh, Dow-Mu; MacVicar, David [Royal Marsden NHS Foundation Trust, Department of Radiology, Sutton, Surrey (United Kingdom); Collins, David J.; Jerome, Neil P. [Institute of Cancer Research, Cancer Research UK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Chua, Sue C. [Royal Marsden NHS Foundation Trust, Nuclear Medicine and PET Department, Sutton, Surrey (United Kingdom); Pearson, Andrew D.J. [Royal Marsden NHS Foundation Trust, Paediatric Drug Development Unit, Children and Young People' s Unit, Sutton, Surrey (United Kingdom)

    2015-10-15

    Cancer is the leading cause of death in children older than 1 year of age and new drugs are necessary to improve outcomes. Imaging is crucial to the drug development process and assessment of therapeutic response. In adults, tumours are often assessed with CT using size criteria. Unfortunately, techniques established in adults are not necessarily applicable in children due to differing pathophysiology, ability to cooperate and increased susceptibility to ionising radiation. MRI, in particular quantitative MRI, has to date not been fully utilised in children with extracranial neoplasms. The specific challenges of imaging in children, the potential for functional imaging techniques to inform upon and their inclusion in clinical trials are discussed. (orig.)

  6. Multiple Spontaneous Intracranial-Extracranial Arterial Dissections in a Patient with Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Mehmet Kolukısa

    2017-01-01

    Full Text Available A 40-year-old male with osteogenesis imperfecta (OI was admitted to the hospital with an acute right monoparesis. Diffusion-weighted MRI showed infarction in the territory of the left anterior cerebral artery (ACA and in the left posterior cerebral artery (PCA. In his vascular imaging, occlusion of the left vertebral artery (VA starting from V2 segment was consistent with dissection and pseudoaneurysm in the right ACA. We presented this case because of the presence of spontaneous and simultaneous occurrence of both intracranial and extracranial arterial dissections in OI.

  7. Vascular reconstruction of a ruptured and infected aneurysm of extracranial carotid artery

    Institute of Scientific and Technical Information of China (English)

    SONG Jin-qiu; ZHANG Jian; YIN Ming-di; SHAN Shao-yin; WU Bin; DUAN Zhi-quan; XIN Shi-jie

    2008-01-01

    @@ Extracranial carotid artery aneurysm represents an uncommon vascular condition with relatively higher incidence in China than in the West.1 The complication with infection and rupture is even rarer,but potentially lethal.Management of mis condition is challenging but urgent because of high risks for embolization,generalized sepsis,further expansion,rupture,and life threatening.1,2 We present an exceptional case of carotid aneurysm at bifurcation complicated with rupture and infection and discuss the Dathogenesis and vailOUS aspects of diagnosis and surgical management.

  8. Identification of a panel of tumor-associated antigens from breast carcinoma cell lines, solid tumors and testis cDNA libraries displayed on lambda phage

    Directory of Open Access Journals (Sweden)

    Cianfriglia Maurizio

    2004-11-01

    Full Text Available Abstract Background Tumor-associated antigens recognized by humoral effectors of the immune system are a very attractive target for human cancer diagnostics and therapy. Recent advances in molecular techniques have led to molecular definition of immunogenic tumor proteins based on their reactivity with autologous patient sera (SEREX. Methods Several high complexity phage-displayed cDNA libraries from breast carcinomas, human testis and breast carcinoma cell lines MCF-7, MDA-MB-468 were constructed. The cDNAs were expressed in the libraries as fusion to bacteriophage lambda protein D. Lambda-displayed libraries were efficiently screened with sera from patients with breast cancer. Results A panel of 21 clones representing 18 different antigens, including eight proteins of unknown function, was identified. Three of these antigens (T7-1, T11-3 and T11-9 were found to be overexpressed in tumors as compared to normal breast. A serological analysis of the 21 different antigens revealed a strong cancer-related profile for at least five clones (T6-2, T6-7, T7-1, T9-21 and T9-27. Conclusions Preliminary results indicate that patient serum reactivity against five of the antigens is associated with tumor disease. The novel T7-1 antigen, which is overexpressed in breast tumors and recognized specifically by breast cancer patient sera, is potentially useful in cancer diagnosis.

  9. The influence of a human embryonic stem cell-derived microenvironment on targeting of human solid tumor xenografts.

    Science.gov (United States)

    Tzukerman, Maty; Rosenberg, Tzur; Reiter, Irena; Ben-Eliezer, Shoshana; Denkberg, Galit; Coleman, Raymond; Reiter, Yoram; Skorecki, Karl

    2006-04-01

    The awareness of the important role that the surrounding tissue microenvironment and stromal response play in the process of tumorigenesis has grown as a result of in vivo models of tumor xenograft growth in immunocompromised mice. In the current study, we used human embryonic stem cells in order to study the interactions of tumor cells with the surrounding microenvironment of differentiated human cell tissues and structures. Several cancer cell types stably expressing an H2A-green fluorescence protein fusion protein, which allowed tracking of tumor cells, were injected into mature teratomas and developed into tumors. The salient findings were: (a) the observation of growth of tumor cells with high proliferative capacity within the differentiated microenvironment of the teratoma, (b) the identification of invasion by tumor cells into surrounding differentiated teratoma structures, and (c) the identification of blood vessels of human teratoma origin, growing adjacent to and within the cancer cell-derived tumor. Mouse embryonic stem cell-derived teratomas also supported cancer cell growth, but provided a less suitable model for human tumorigenesis studies. Anticancer immunotherapy treatment directed against A431 epidermoid carcinoma cell-related epitopes induced the complete regression of A431-derived tumor xenografts following direct i.m. injection in immunocompromised mice, as opposed to corresponding tumors growing within a human embryonic stem cell-derived microenvironment, wherein remnant foci of viable tumor cells were detected and resulted in tumor recurrence. We propose using this novel experimental model as a preclinical platform for investigating and manipulating the stromal response in tumor cell growth as an additional tool in cancer research.

  10. Diagnostic accuracy of diffusion-weighted imaging with conventional MR imaging for differentiating complex solid and cystic ovarian tumors at 1.5T

    Directory of Open Access Journals (Sweden)

    Zhang Ping

    2012-11-01

    Full Text Available Abstract Background Preoperative characterization of complex solid and cystic adnexal masses is crucial for informing patients about possible surgical strategies. Our study aims to determine the usefulness of apparent diffusion coefficients (ADC for characterizing complex solid and cystic adnexal masses. Methods One-hundred and 91 patients underwent diffusion-weighted (DW magnetic resonance (MR imaging of 202 ovarian masses. The mean ADC value of the solid components was measured and assessed for each ovarian mass. Differences in ADC between ovarian masses were tested using the Student’s t-test. The receiver operating characteristic (ROC was used to assess the ability of ADC to differentiate between benign and malignant complex adnexal masses. Results Eighty-five patients were premenopausal, and 106 were postmenopausal. Seventy-four of the 202 ovarian masses were benign and 128 were malignant. There was a significant difference between the mean ADC values of benign and malignant ovarian masses (p -3 mm2/s may be the optimal one for differentiating between benign and malignant tumors. Conclusions A high signal intensity within the solid component on T2WI was less frequently in benign than in malignant adnexal masses. The combination of DW imaging with ADC value measurements and T2-weighted signal characteristics of solid components is useful for differentiating between benign and malignant ovarian masses.

  11. Clinical Evaluation of ErbB-Targeted CAR T-Cells, Following Intracavity Delivery in Patients with ErbB-Expressing Solid Tumors.

    Science.gov (United States)

    Papa, Sophie; van Schalkwyk, May; Maher, John

    2015-01-01

    Adoptive cell therapy using gene-modified T-cells has achieved impressive results in the treatment of B-cell malignancies. However, the development of similar strategies to treat solid tumors raises challenges with respect to tumor antigen selection and the achievement of efficient T-cell homing, survival and sustained effector function within the tumor microenvironment. To address these challenges, we have developed a gene-modified cellular therapy called T4 immunotherapy. To generate T4 immunotherapy, autologous T-cells are engineered by retroviral transduction to co-express two transgenes: (1) a chimeric antigen receptor (CAR), T1E28z, targeted against a range of ErbB homodimers and heterodimers and (2) a chimeric cytokine receptor, 4αβ, that allows the selective ex vivo expansion of engineered cells using interleukin-4. Targeting of the extended ErbB network using CAR T-cells is supported by prevalence of ErbB dysregulation in diverse solid tumors and the clinical impact of monoclonal antibody therapy directed against members of this family. However, the key obstacle to effective clinical translation is risk of on-target toxicity owing to the lower level expression of ErbB family members in many healthy tissues. To de-risk T4 immunotherapy in man, we are undertaking a trial in patients with locally advanced or recurrent head and neck squamous cell carcinoma. In that setting, engineered T-cells are injected directly into the tumor without prior lymphodepletion, an approach that we believe will minimize risk of toxicity. This chapter outlines how we plan to advance the development of T4 immunotherapy thereafter in Phase II clinical testing. In that setting, regional (intracavitary) approaches will be used to administer this therapy to patients with epithelial ovarian cancer and malignant pleural mesothelioma.

  12. Resource Utilization for Chemotherapy-Induced Nausea and Vomiting Events in Patients with Solid Tumors Treated with Antiemetic Regimens

    Science.gov (United States)

    Schwartzberg, Lee; Harrow, Brooke; Lal, Lincy S.; Radtchenko, Janna; Lyman, Gary H.

    2015-01-01

    Background Chemotherapy-induced nausea and vomiting (CINV) can lead to increased emergency department visits and hospitalizations, which may contribute to increased cost of care. Antiemetic agents, such as neurokinin-1 (NK1) receptor antagonists and 5-hydroxytryptamine (5-HT3) receptor antagonists, are prescribed for patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). The current guidelines recommend a 3-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone with HEC regimens and certain MEC regimens. Objective To compare the incidence of CINV and CINV-related resource utilization among patients who receive guideline-adherent HEC and MEC regimens and patients who receive non–guideline-adherent regimens. Methods In this retrospective, claims-based study, Inovalon's Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) Research Edition database was used to identify 8089 patients with solid tumors receiving therapy with anthracycline plus cyclophosphamide (AC), cisplatin, or carboplatin from June 2013 to December 2013. The patients were stratified according to the use of an NK1 receptor antagonist regimen. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify CINV events associated with hospital, emergency department, and outpatient office visits among patients in the NK1 receptor antagonist group and the non-NK1 receptor antagonist group. Results A total of 1059 patients were included in the analysis, of whom 51% (N = 536) used an NK1 receptor antagonist–based regimen and 49% (N = 523) used non-NK1 receptor antagonist therapy. A higher percentage of patients receiving AC (73%) than cisplatin (56%) or carboplatin (23%) received an NK1 receptor antagonist. The incidence rates of total CINV events and CINV-related emergency department visits were lower in the group receiving an NK1 receptor

  13. Interactions between three subpopulations of Ehrlich ascites tumor and a P388 murine leukemia in mixed solid tumors in immune competent mice

    DEFF Research Database (Denmark)

    Aabo, K; Vindeløv, L L; Christensen, I B

    1989-01-01

    of interaction required close cellular contact of viable cells, and no cellular immune response was elicited by the host animals. A third finding was that a faster growing Ehrlich cell line E1.95 dominated the tumors when inoculated in mixture with a slower growing subpopulation E1.80. This could be explained...... imposed by an immunogenic cell line on other cell lines require genetic and thereby close immunogenic resemblance between the cell lines. Another type of interaction was found between the E1.95 cell line and the P388 line which showed nearly identical growth characteristics as determined by tumor weight...

  14. Acute Effects of Vascular Modifying Agents in Solid Tumors Assessed by Noninvasive Laser Doppler Flowmetry and Near Infrared Spectroscopy

    Directory of Open Access Journals (Sweden)

    Michael Kragh

    2002-01-01

    Full Text Available The potential of noninvasive laser Doppler flowmetry (LDF and near infrared spectroscopy (NIRS to detect acute effects of different vascular-modifying agents on perfusion and blood volume in tumors was evaluated. C3H mouse mammary carcinomas (∼200 mm3 in the rear foot of CDF1 mice were treated with flavone acetic acid (FAA, 150 mg/kg, 5,6-dimethylxanthenone-4acetic acid (DMXAA, 20 mg/kg, combretastatin A-4 disodium phosphate (CAMP, 250 mg/kg, hydralazine (HDZ, 5 mg/kg, or nicotinamide (NTA, 500 mg/kg. Tumor perfusion before and after treatment was evaluated by noninvasive LDF, using a 41°C heated custombuilt LDF probe with four integrated laser/receiver units, and tumor blood volume was estimated by MRS, using light guide coupled reflectance measurements at 800±10 nm. FAA, DMXAA, CAMP, and HDZ significantly decreased tumor perfusion by 50%, 47%, 73%, and 78%, respectively. In addition, FAA, DMXAA, and HDZ significantly reduced the blood volume within the tumor, indicating that these compounds to some degree shunted blood from the tumor to adjacent tissue, HDZ being most potent. CAMP caused no change in the tumor blood volume, indicating that the mechanism of action of CAMP was vascular shut down with the blood pool trapped in the tumor. NTA caused no change in either tumor perfusion or tumor blood volume. We conclude that noninvasive LDF and MRS can determine acute effects of vascular modifying agents on tumor perfusion and blood volume.

  15. Concurrent radiotherapy and intrathecal methotrexate for treating leptomeningeal metastasis from solid tumors with adverse prognostic factors: A prospective and single-arm study.

    Science.gov (United States)

    Pan, Zhenyu; Yang, Guozi; He, Hua; Zhao, Gang; Yuan, Tingting; Li, Yu; Shi, Weiyan; Gao, Pengxiang; Dong, Lihua; Li, Yunqian

    2016-10-15

    The prognosis of leptomeningeal metastasis (LM) from solid tumors is extremely poor, especially for patients with adverse prognostic factors. In this phase II clinical trial, we evaluated the efficacy and safety of intrathecal chemotherapy (IC) combined with concomitant involved-field radiotherapy (IF-RT) for treating LM from solid tumors with adverse prognostic factors. Fifty-nine patients with LM from various solid tumors were enrolled between May 2010 and December 2014. Concurrent therapy consisted of concomitant IC (methotrexate 12.5-15 mg and dexamethasone 5 mg, weekly) and IF-RT (whole brain and/or spinal canal RT, 40 Gy/20f). For patients with low Karnofsky performance status (KPS) score and radiotherapy intolerance, induction IC (1-3 times) was given before concurrent therapy. Thirty-eight patients (64.4%) received subsequent treatments. All patients were followed up at least 6 months after LM diagnosis or until death. Primary endpoint evaluated was clinical response rate. Secondary endpoints were overall survival (OS) and safety. The pathological types included lung cancer (n = 42), breast cancer (n = 11) and others (n = 6). Median KPS score was 40 (range 20-70). Fifty-one patients (86.4%) completed concurrent therapy. The overall response rate was 86.4% (51/59). OS ranged from 0.4 to 36.7 months (median 6.5 months), and 1-year-survival rate was 21.3%. Treatment-related adverse events mainly included acute meningitis, chronic-delayed encephalopathy, radiculitis, myelosuppression and mucositis. Twelve patients (20.3%) had grade III-V toxic reactions. We concluded that IC combined with concomitant IF-RT, with significant efficacy and acceptable toxicity, may be an optimal therapeutic option for treatment of LM from solid tumors with adverse prognostic factors. LM, in which cancer cells spread to membranes enveloping the brain and spinal cord, is a devastating complication of solid cancers. Existing LM therapies center on IC. In this prospective

  16. Tumor Microenvironment in the Brain

    Energy Technology Data Exchange (ETDEWEB)

    Lorger, Mihaela [Leeds Institute of Molecular Medicine, University of Leeds, St. James’s University Hospital, Beckett Street, Leeds, LS9 7TF (United Kingdom)

    2012-02-22

    In addition to malignant cancer cells, tumors contain a variety of different stromal cells that constitute the tumor microenvironment. Some of these cell types provide crucial support for tumor growth, while others have been suggested to actually inhibit tumor progression. The composition of tumor microenvironment varies depending on the tumor site. The brain in particular consists of numerous specialized cell types such as microglia, astrocytes, and brain endothelial cells. In addition to these brain-resident cells, primary and metastatic brain tumors have also been shown to be infiltrated by different populations of bone marrow-derived cells. The role of different cell types that constitute tumor microenvironment in the progression of brain malignancies is only poorly understood. Tumor microenvironment has been shown to be a promising therapeutic target and diagnostic marker in extracranial malignancies. A better understanding of tumor microenvironment in the brain would therefore be expected to contribute to the development of improved therapies for brain tumors that are urgently required due to a poor availability of treatments for these malignancies. This review summarizes some of the known interactions between brain tumors and different stromal cells, and also discusses potential therapeutic approaches within this context.

  17. Usefulness of combined treatment with mild temperature hyperthermia and/or tirapazamine in the treatment of solid tumors. Its independence of p53 status

    Energy Technology Data Exchange (ETDEWEB)

    Masunaga, Shin-ichiro; Ono, Koji [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.; Takahashi Akihisa [Nara Medical Univ., Kashihara (Japan)] [and others

    2003-01-01

    induced a slightly greater enhancement effect in SAS/mp53 cells and Q cells. In view of the difficulty in controlling mutated p53 status tumors and intratumor Q cells, combination treatment with MTH and/or TPZ as a cooperative modality in cancer therapy is considered to have potential for controlling solid tumors as a whole. (author)

  18. Evaluation of the therapeutic efficacy of sequential therapy involving percutaneous microwave ablation in combination with 131I-hypericin using the VX2 rabbit breast solid tumor model.

    Directory of Open Access Journals (Sweden)

    Miao Zhu

    Full Text Available Combination of percutaneous microwave ablation (PMWA and intravenous injection of 131I-hypericin(IIIH may bear potential as a mini-invasive treatment for tumor. The objective of this study was to assess the effect of PMWA and IIIH in breast tumor growth.Ten New Zealand White rabbits bearing VX2 breast carcinomas were randomly divided into two groups (each 5 examples and processed using PMWA followed by IIIH and IIIH alone. The IIIH activity was evaluated using planar scintigraphy, autoradiography and biodistribution analysis. The maximum effective safe dose of IIIH was found through 48 rabbits with VX2 breast tumor, which were randomized into six groups (n=8 per group. Subsequently, a further 75 rabbits bearing VX2 breast solid tumors were randomly divided into five groups (each 15 examples and treated as follows: A, no treatment group; B, PMWA alone; C, IIIH alone; D, PMWA+IIIH×1 (at 8 h post-PMWA; and E, PMWA+IIIH×2 (at 8 h and at 8 days post-PMWA. The therapeutic effect was assessed by measurement of tumor size and performation of positron emission tomography/computed tomograph (PET/CT scans, liver and renal function tests and Kaplan-Meier survival analysis.The planar scintigraphy findings suggested a significant uptake of 131I in necrotic tumor tissue. The autoradiography gray scales indicated higher selective uptake of IIIH by necrotic tissue, with significant differences between the groups with and those without necrotic tumor tissue (P<0.05. The maximum effective safe dose of IIIH was 1 mCi/kg. The PET/CT scans and tumor size measurement suggested improvements in treatment groups at all time points (P<0.01. Significant differences were detected among Groups A, B, D and E (P<0.05. Lower levels of lung metastasis were detected in Groups D and E (P<0.05. There were no abnormalities in liver and renal functions tests or other reported side effects.IIIH exhibited selective uptake by necrotic tumor tissue. Sequential therapy involving PMWA

  19. Fluorescence-based codetection with protein markers reveals distinct cellular compartments for altered MicroRNA expression in solid tumors

    DEFF Research Database (Denmark)

    Sempere, Lorenzo F; Preis, Meir; Yezefski, Todd

    2010-01-01

    High-throughput profiling experiments have linked altered expression of microRNAs (miRNA) to different types of cancer. Tumor tissues are a heterogeneous mixture of not only cancer cells, but also supportive and reactive tumor microenvironment elements. To clarify the clinical significance of alt...

  20. EVALUATION OF CHIP (IPROPLATIN) IN RECURRENT PEDIATRIC MALIGNANT SOLID TUMORS - A PHASE-II STUDY (PEDIATRIC ONCOLOGY GROUP)

    NARCIS (Netherlands)

    NITSCHKE, R; PRATT, C; HARRIS, M; KRISCHER, J; VIETTI, TJ; GRIER, H; KAMPS, W; TOLEDANO, S

    1992-01-01

    CHIP (325 mg/M2), a second generation cisplatin derivative, was administered intravenously every 3 weeks to 85 pediatric patients with recurrent sarcomas (19), osteosarcomas (20), neuroblastoma (23), germ cell tumors (10), and other malignant tumors (7). Thirty-eight of them had been previously expo

  1. Novel systemic treatment options for advanced solid tumors with or without central nervous system metastases or malignant glioma

    NARCIS (Netherlands)

    Milojkovic Kerklaan, B.

    2015-01-01

    Chemotherapy is a very frequently used therapy in patients with advanced tumors with or without central nervous system (CNS) metastases or primary brain tumors. Despite the significant progress in drug development, the survival of patients is limited with an unmet need for more effective chemotherap

  2. TCR-engineered T cells meet new challenges to treat solid tumors: choice of antigen, t cell fitness, and sensitization of tumor milieu

    NARCIS (Netherlands)

    Straetemans, T.; Govers, C.C.F.M.

    2013-01-01

    Adoptive transfer of T cells gene-engineered with antigen-specific T cell receptors (TCRs) has proven its feasibility and therapeutic potential in the treatment of malignant tumors. To ensure further clinical development of TCR gene therapy, it is necessary to target immunogenic epitopes that are re

  3. Early Detection of Tumor Response by FLT/MicroPET Imaging in a C26 Murine Colon Carcinoma Solid Tumor Animal Model

    Directory of Open Access Journals (Sweden)

    Wan-Chi Lee

    2011-01-01

    Full Text Available Fluorine-18 fluorodeoxyglucose (18F-FDG positron emission tomography (PET imaging demonstrated the change of glucose consumption of tumor cells, but problems with specificity and difficulties in early detection of tumor response to chemotherapy have led to the development of new PET tracers. Fluorine-18-fluorothymidine (18F-FLT images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study, we evaluate the early response of colon carcinoma to the chemotherapeutic drug, lipo-Dox, in C26 murine colorectal carcinoma-bearing mice by 18F-FDG and 18F-FLT. The male BALB/c mice were bilaterally inoculated with 1×105 and 1×106 C26 tumor cells per flank. Mice were intravenously treated with 10 mg/kg lipo-Dox at day 8 after 18F-FDG and 18F-FLT imaging. The biodistribution of 18F-FDG and 18F-FLT were followed by the microPET imaging at day 9. For the quantitative measurement of microPET imaging at day 9, 18F-FLT was superior to 18F-FDG for early detection of tumor response to Lipo-DOX at various tumor sizes (<0.05. The data of biodistribution showed similar results with those from the quantification of SUV (standard uptake value by microPET imaging. The study indicates that 18F-FLT/microPET is a useful imaging modality for early detection of chemotherapy in the colorectal mouse model.

  4. Extracranial Venous abnormalities: A true pathological finding in patients with multiple sclerosis or an anatomical variant?

    Energy Technology Data Exchange (ETDEWEB)

    Torres, Carlos; Chakraborty, Santanu; Nguyen, Thanh; Thornhill, Rebecca; Lum, Cheemun [University of Ottawa, Department of Radiology, Ottawa, ON (Canada); The Ottawa Hospital, Department of Medical Imaging, Ottawa, ON (Canada); Ottawa Hospital Research Institute OHRI, Ottawa, ON (Canada); Hogan, Matthew; Freedman, Mark [Ottawa Hospital Research Institute OHRI, Ottawa, ON (Canada); University of Ottawa, Department of Medicine, Ottawa, ON (Canada); The Ottawa Hospital, Division of Neurology, Ottawa, ON (Canada); Patro, Satya [University of Ottawa, Department of Radiology, Ottawa, ON (Canada); The Ottawa Hospital, Department of Medical Imaging, Ottawa, ON (Canada); Bussiere, Miguel [University of Alberta, Department of Medicine, Division of Neurology, Edmonton (Canada); Dabirzadeh, Hamid [University of Saskatchewan, Neuroradiologist, Department of Radiology, Saskatoon (Canada); Schwarz, Betty Anne; Belanger, Stefanie; Legault-Kingstone, Lysa [The Ottawa Hospital, Department of Medical Imaging, Ottawa, ON (Canada); Schweitzer, Mark [Stony Brook School of Medicine, Department of Radiology, Stony Brook, NY (United States)

    2017-01-15

    To evaluate the extracranial venous anatomy with contrast-enhanced MR venogram (CE-MRV) in patients without multiple sclerosis (MS), and assess the prevalence of various venous anomalies such as asymmetry and stenosis in this population. We prospectively recruited 100 patients without MS, aged 18-60 years, referred for contrast-enhanced MRI. They underwent additional CE-MRV from skull base to mediastinum on a 3T scanner. Exclusion criteria included prior neck radiation, neck surgery, neck/mediastinal masses or significant cardiac or pulmonary disease. Two neuroradiologists independently evaluated the studies to document asymmetry and stenosis in the jugular veins and prominence of collateral veins. Asymmetry of internal jugular veins (IJVs) was found in 75 % of subjects. Both observers found stenosis in the IJVs with fair agreement. Most stenoses were located in the upper IJV segments. Asymmetrical vertebral veins and prominence of extracranial collateral veins, in particular the external jugular veins, was not uncommon. It is common to have stenoses and asymmetry of the IJVs as well as prominence of the collateral veins of the neck in patients without MS. These findings are in contrast to prior reports suggesting collateral venous drainage is rare except in MS patients. (orig.)

  5. [Cytological Study in vitro on Co-delivery of siRNA and Paclitaxel within Solid Lipid Nanoparticles to Overcome Multidrug Resistance in Tumors].

    Science.gov (United States)

    Huang, Rui; Yao, Xinyu; Chen, Yuan; Sun, Xun; Lin, Yunzhu

    2016-02-01

    Multidrug resistance (MDR) remains the major obstacle to the success of clinical cancer chemotherapy. P-glycoprotein (P-gp), encoded by the MDR1, is an important part with complex mechanisms associated with the MDR. In order to overcome the MDR of tumors, we in the present experimental design incorporated small interfering RNA (siRNA) targeting MDR1 gene and anticancer drug paclitaxel (PTX) into the solid lipid nanoparticles (SLNs) to achieve the combinational therapeutic effects of genetherapy and chemotherapy. In this study, siRNA-PTX-SLNs were successfully prepared. The cytotoxicity of blank SLNs and siRNA-PTX-SLNs in MCF-7 cells and MCF-7/ADR cells were detected by MTT; and the uptake efficiency of PTX in MCF-7/ADR cells were detected via HPLC method; quantitative real-time PCR and flow cytometry were performed to investigate the silencing effect of siRNA-PTX- SLNs on MDR1 gene in MCF-7/ADR cells. The results showed that PTX loaded SLNs could significantly inhibit the growth of tumor cells, and more importantly, the MDR tumor cells treated with siRNA-PTX-SLNs showed the lowest viability. HPLC study showed that SLNs could enhance the cellular uptake for PTX. Meanwhile, siRNA delivered by SLNs significantly decreased the P-gp expression in MDR tumor cells, thus increased the cellular accumulation of rhodamine123 as a P-gp substrate. In conclusion, the MDR1 gene could be silenced by siRNA-PTX-SLNs, which could promote the growth inhibition efficiency of PTX on tumor cells, leading to synergetic effect on MDR tumor therapy.

  6. Genetically modified bacteria as a tool to detect microscopic solid tumor masses with triggered release of a recombinant biomarker.

    Science.gov (United States)

    Panteli, Jan T; Forkus, Brittany A; Van Dessel, Nele; Forbes, Neil S

    2015-04-01

    Current tomographic methods of cancer detection have limited sensitivity and are unable to detect malignant masses smaller than half a centimeter in diameter. Mortality from tumor recurrence and metastatic disease would be reduced if small lesions could be detected earlier. To overcome this limitation, we created a detection system that combines the specificity of tumor-targeting bacteria with the sensitivity of a synthetic biomarker. Bacteria, specifically Salmonella, preferentially accumulate in tumors and microscopic metastases as small as five cell layers thick. To create tumor detecting bacteria, an attenuated strain of Salmonella was engineered to express and release the fluorescent protein ZsGreen. A single-layer antibody method was developed to measure low concentrations of ZsGreen. Engineered bacteria were administered to a microfluidic tumor-on-a-chip device to measure protein production. In culture, half of produced ZsGreen was released by viable bacteria at a rate of 87.6 fg bacterium(-1) h(-1). Single-layer antibody dots were able to detect bacterially produced ZsGreen at concentrations down to 4.5 ng ml(-1). Bacteria colonized in 0.12 mm(3) of tumor tissue in the microfluidic device released ZsGreen at a rate of 23.9 μg h(-1). This release demonstrates that ZsGreen readily diffuses through tissue and accumulates at detectable concentrations. Based on a mathematical pharmacokinetic model, the measured rate of release would enable detection of 0.043 mm(3) tumor masses, which is 2600 times smaller than the current limit of tomographic techniques. Tumor-detecting bacteria would provide a sensitive, minimally invasive method to detect tumor recurrence, monitor treatment efficacy, and identify the onset of metastatic disease.

  7. Radioiodination of 2,3-dimethyl-4H-furo[3,2-c]coumarin and biological evaluation in solid tumor bearing mice.

    Science.gov (United States)

    Abd Elhalim, S M; Ibrahim, I T

    2014-10-22

    Compound 2,3-dimethyl-4H-furo[3,2-c]coumarin is a coumarin derivative that could be labeled with (125)I. The process of labeling was started using 1mg of the compound, 50µg CAT oxidizing agent, 30min as reaction time at pH with a yield about 95%. The (125)I-coumarin derivative was stable for about 48h. Radiochemical purity of the labeled compound was performed by electrophoresis and HPLC. The labeled compound was separated with purity about 95%. Tumor transplantation to produce a solid tumor in the right leg of albino mice was made by intramuscular injection of 2×10(6) EAC (Ehrlish acittes carcinoma cells). Biodistribution study of (125)I-coumarin derivative revealed that the uptake in tumor bearing leg was over 5% at 1h and 4h post-injection. This uptake encourages the use of (123)I-coumarin derivative in imaging of tumor sites.

  8. Safety and Efficacy in Advanced Solid Tumors of a Targeted Nanocomplex Carrying the p53 Gene Used in Combination with Docetaxel: A Phase 1b Study.

    Science.gov (United States)

    Pirollo, Kathleen F; Nemunaitis, John; Leung, Po Ki; Nunan, Robert; Adams, Jana; Chang, Esther H

    2016-09-01

    Loss of p53 suppressor function, through mutations or inactivation of the p53 pathway, occurs in most human cancers. SGT-53 is a liposomal nanocomplex designed for systemic, tumor-targeting delivery of the wt p53 gene. In this nanodelivery system, an anti-transferrin receptor single-chain antibody fragment serves as the targeting moiety. In an initial phase 1 trial in patients with advanced solid tumors, SGT-53 demonstrated tumor-specific targeting, was shown to be well tolerated, and was associated with an antitumor effect in several patients. Our preclinical studies have also demonstrated enhanced antitumor activity with the combination of SGT-53 and docetaxel. Thus, this dose-escalation trial was undertaken to assess the combination of SGT-53 and docetaxel for safety and potential efficacy in 14 advanced cancer patients. Results reveal that the combination of SGT-53 (maximum dose, 3.6 mg DNA/infusion) and docetaxel (75 mg/m(2)/infusion) was well tolerated. Moreover, clinical activity involving 12 evaluable patients was observed. Three of these patients achieved RECIST-verified partial responses with tumor reductions of -47%, -51%, and -79%. Two others had stable disease with significant shrinkage (-25% and -16%). These results support phase 2 testing of SGT-53 in combination with docetaxel.

  9. Eosinophilia in routine blood samples as a biomarker for solid tumor development - A study based on the Copenhagen Primary Care Differential Count (CopDiff) Database

    DEFF Research Database (Denmark)

    Andersen, Christen Lykkegaard; Siersma, Volkert Dirk; Hasselbalch, Hans Carl;

    2014-01-01

    eosinophilia in routine blood samples as a potential biomarker of solid tumor development in a prospective design. MATERIAL AND METHODS: From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356 196 individuals with at least one differential cell count (DIFF) encompassing...... the eosinophil count during 2000-2007. From these, one DIFF was randomly chosen and categorized according to no (... was increased with mild eosinophilia [OR 1.93 (CI 1.29-2.89), p = 0.0013]. No associations with eosinophilia were observed for the remaining solid cancers. CONCLUSION: We demonstrate that eosinophilia in routine blood samples associates with an increased risk of bladder cancer. Our data emphasize...

  10. Barriers to effective treatment of pediatric solid tumors in middle-income countries: Can we make sense of the spectrum of non-biological factors that influence outcomes?

    Science.gov (United States)

    Friedrich, Paola; Ortiz, Roberta; Fuentes, Soad; Gamboa, Yéssica; Chu-Sanchez, María Sabina Ah; Arambú, Ingrid Carolina; Montero, Margarita; Báez, Fulgencio; Rodríguez-Galindo, Carlos; Antillón-Klussmann, Federico

    2013-01-01

    Background Delivery of effective treatment for pediatric solid tumors poses a particular challenge to centers in middle-income countries (MIC) already vigorously addressing pediatric cancer. This study aimed to improve our understanding of barriers to effective treatment of pediatric solid tumors in MICs. Methods An ecological model centering in pediatric sarcoma and expanding to country as the environment were used as benchmark for studying delivery of solid tumor care in MICs. Data on resources was gathered from seven centers members of the Central American Association of Pediatric Hematologists and Oncologists (AHOPCA) using an infrastructure assessment tool. Pediatric sarcoma outcomes data was available and retrieved from hospital-based cancer registries for six of the seven centers and analyzed by country. Patients diagnosed from 1/1/2000-12/31/2009 with osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, and other soft tissue sarcomas were included in the analysis. In order to explore correlations between resources and outcomes a pilot performance-index was created. Findings Results identified specific human resources, communication, quality and infrastructure deficits. Treatment abandonment rate, metastatic disease at diagnosis, relapse rate and 4-year abandonment-sensitive overall survival (AOS) varied considerably by country (1-38%, 15-54%, 24-52%, 21-51%, respectively). Treatment abandonment rate correlated inversely with health economic expenditure per capita (r= −0.86, p=0.03) and life expectancy at birth (r = −0.93, p=0.007). Four-year AOS correlated inversely with under-5 mortality rate (r= −0.80, p=0.05) and directly with the pilot performance-index (r =0.98, p=0.005). Interpretation Initiatives to improve treatment effectiveness of pediatric solid tumor care in MIC and pediatric sarcoma in particular are warranted. Building capacity and infrastructure, improving supportive care and communication, and fostering comprehensive multidisciplinary teams

  11. Acute effects of vascular modifying agents in solid tumors assessed by noninvasive laser Doppler flowmetry and near infrared spectroscopy

    DEFF Research Database (Denmark)

    Kragh, Michael; Quistorff, Bjørn; Horsman, Michael R;

    2002-01-01

    The potential of noninvasive laser Doppler flowmetry (LDF) and near infrared spectroscopy (NIRS) to detect acute effects of different vascular-modifying agents on perfusion and blood volume in tumors was evaluated. C3H mouse mammary carcinomas (approximately 200 mm(3)) in the rear foot of CDF1 mice...... were treated with flavone acetic acid (FAA, 150 mg/kg), 5,6-dimethylxanthenone-4-acetic acid (DMXAA, 20 mg/kg), combretastatin A-4 disodium phosphate (CA4DP, 250 mg/kg), hydralazine (HDZ, 5 mg/kg), or nicotinamide (NTA, 500 mg/kg). Tumor perfusion before and after treatment was evaluated by noninvasive...... LDF, using a 41 degrees C heated custom-built LDF probe with four integrated laser/receiver units, and tumor blood volume was estimated by NIRS, using light guide coupled reflectance measurements at 800+/-10 nm. FAA, DMXAA, CA4DP, and HDZ significantly decreased tumor perfusion by 50%, 47%, 73...

  12. Permanent occlusion of feeding arteries and draining veins in solid mouse tumors by vascular targeted photodynamic therapy (VTP with Tookad.

    Directory of Open Access Journals (Sweden)

    Noa Madar-Balakirski

    Full Text Available BACKGROUND: Antiangiogenic and anti-vascular therapies present intriguing alternatives to cancer therapy. However, despite promising preclinical results and significant delays in tumor progression, none have demonstrated long-term curative features to date. Here, we show that a single treatment session of Tookad-based vascular targeted photodynamic therapy (VTP promotes permanent arrest of tumor blood supply by rapid occlusion of the tumor feeding arteries (FA and draining veins (DV, leading to tumor necrosis and eradication within 24-48 h. METHODOLOGY/PRINCIPAL FINDINGS: A mouse earlobe MADB106 tumor model was subjected to Tookad-VTP and monitored by three complementary, non-invasive online imaging techniques: Fluorescent intravital microscopy, Dynamic Light Scattering Imaging and photosensitized MRI. Tookad-VTP led to prompt tumor FA vasodilatation (a mean volume increase of 70% with a transient increase (60% in blood-flow rate. Rapid vasoconstriction, simultaneous blood clotting, vessel permeabilization and a sharp decline in the flow rates then followed, culminating in FA occlusion at 63.2 sec+/-1.5SEM. This blockage was deemed irreversible after 10 minutes of VTP treatment. A decrease in DV blood flow was demonstrated, with a slight lag from FA response, accompanied by frequent changes in flow direction before reaching a complete standstill. In contrast, neighboring, healthy tissue vessels of similar sizes remained intact and functional after Tookad-VTP. CONCLUSION/SIGNIFICANCE: Tookad-VTP selectively targets the tumor feeding and draining vessels. To the best of our knowledge, this is the first mono-therapeutic modality that primarily aims at the larger tumor vessels and leads to high cure rates, both in the preclinical and clinical arenas.

  13. Distinct expression profiles of Notch-1 protein in human solid tumors: Implications for development of targeted therapeutic monoclonal antibodies

    OpenAIRE

    Li, Yuan; Burns, Janine A.; Carol A Cheney; Zhang, Ningyan; Vitelli, Salvatore; Wang, Fubao; Bett, Andrew; Chastain, Michael; Audoly, Laurent P.; Zhang, Zhi-Qiang

    2010-01-01

    Biological therapies, such as monoclonal antibodies (mAbs) that target tumor-associated antigens have been considered an effective therapeutic approach in oncology. In considering Notch-1 receptor as a potential target, we performed immunohistochemistry on tissue microarrays to determine 1) whether the receptor is overexpressed in tumor cells as compared to their corresponding normal tissues and 2) the clinical significance of its expression levels in human breast, colorectal, lung and prosta...

  14. Factors affecting the pharmacokinetics and pharmacodynamics of PEGylated liposomal irinotecan (IHL-305 in patients with advanced solid tumors

    Directory of Open Access Journals (Sweden)

    Wu H

    2015-02-01

    Full Text Available Huali Wu,1 Jeffrey R Infante,2 Vicki L Keedy,3 Suzanne F Jones,2 Emily Chan,3 Johanna C Bendell,2 Wooin Lee,4 Whitney P Kirschbrown,1 Beth A Zamboni,5 Satoshi Ikeda,6 Hiroshi Kodaira,6 Mace L Rothenberg,3 Howard A Burris III,2 William C Zamboni1,7–9 1UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 2Sarah Cannon Research Institute/Tennessee Oncology, PLLC, 3Vanderbilt University, Nashville, TN, 4Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 5Department of Mathematics, Carlow University, Pittsburgh, PA, USA; 6Yakult Honsha Co., Ltd., Medical Development Department, Tokyo, Japan; 7UNC Lineberger Comprehensive Cancer Center, 8UNC Institute for Pharmacogenomics and Individualized Therapy, 9Carolina Center for Cancer Nanotechology Excellence, University of North Carolina, Chapel Hill, NC, USA Abstract: IHL-305 is a PEGylated liposomal formulation of irinotecan (CPT-11. The objective of this study was to evaluate the factors associated with interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 in patients with advanced solid tumors. IHL-305 was administered intravenously once every 4 weeks as part of a Phase I study. Pharmacokinetic studies of the liposomal sum total CPT-11, released CPT-11, SN-38, SN-38G, 7-ethyl-10-[4-N-(5-aminopentanoic acid-1-piperidino]-carbonyloxycamptothecin, and 7-ethyl-10-[4-amino-1-piperidino]-carbonyloxycamptothecin in plasma were performed. Noncompartmental and compartmental pharmacokinetic analyses were conducted using pharmacokinetic data for sum total CPT-11. The pharmacokinetic variability of IHL-305 is associated with linear and nonlinear clearance. Patients whose age and body composition (ratio of total body weight to ideal body weight [TBW/IBW] were greater than the median age and TBW/IBW of the study had a 1.7-fold to 2.6-fold higher ratio of released CPT-11 area under the concentration versus time

  15. A polymer-based magnetic resonance tracer for visualization of solid tumors by 13C spectroscopic imaging.

    Directory of Open Access Journals (Sweden)

    Yoshikazu Suzuki

    Full Text Available Morphological imaging precedes lesion-specific visualization in magnetic resonance imaging (MRI because of the superior ability of this technique to depict tissue morphology with excellent spatial and temporal resolutions. To achieve lesion-specific visualization of tumors by MRI, we investigated the availability of a novel polymer-based tracer. Although the 13C nucleus is a candidate for a detection nucleus because of its low background signal in the body, the low magnetic resonance sensitivity of the nucleus needs to be resolved before developing a 13C-based tracer. In order to overcome this problem, we enriched polyethylene glycol (PEG, a biocompatible polymer, with 13C atoms. 13C-PEG40,000 (13C-PEG with an average molecular weight of 40 kDa emitted a single 13C signal with a high signal-to-noise ratio due to its ability to maintain signal sharpness, as was confirmed by in vivo investigation, and displayed a chemical shift sufficiently distinct from that of endogenous fat. 13C-PEG40,000 intravenously injected into mice showed long retention in circulation, leading to its effective accumulation in tumors reflecting the well-known phenomenon that macromolecules accumulate in tumors because of leaky tumor capillaries. These properties of 13C-PEG40,000 allowed visualization of tumors in mice by 13C spectroscopic imaging. These findings suggest that a technique based on 13C-PEG is a promising strategy for tumor detection.

  16. A phase I study of bortezomib, etoposide and carboplatin in patients with advanced solid tumors refractory to standard therapy

    NARCIS (Netherlands)

    Lieu, Christopher; Chow, Laura; Pierson, A. Scott; Eckhardt, S. Gail; O'Bryant, Cindy L.; Morrow, Mark; Tran, Zung Vu; Wright, John J.; Gore, Lia

    2009-01-01

    Purpose: To evaluate the toxicity, pharmacological, and biological properties of the combination of bortezomib, etoposide, and carboplatin in adults with advanced solid malignancies. Patients and methods: Patients received escalating doses of bortezomib, etoposide, and carboplatin every 21 days. Sur

  17. Phase I pharmacokinetic and pharmacodynamic study of triciribine phosphate monohydrate, a small-molecule inhibitor of AKT phosphorylation, in adult subjects with solid tumors containing activated AKT.

    Science.gov (United States)

    Garrett, Christopher R; Coppola, Domenico; Wenham, Robert M; Cubitt, Christopher L; Neuger, Anthony M; Frost, Timothy J; Lush, Richard M; Sullivan, Daniel M; Cheng, Jin Q; Sebti, Saïd M

    2011-12-01

    Triciribine phosphate is a potent, small-molecule inhibitor of activation of all three isoforms of AKT in vitro. AKT is an intracellular protein that, when activated, leads to cellular division; it is dysregulated in a large number of malignancies, and constitutively activating AKT mutations are present in a minority of cancers. In this phase I study triciribine phosphate monohydrate (TCN-PM) was administered to subjects whose tumors displayed evidence of increased AKT phosphorylation (p-AKT) as measured by immunohistochemical analysis (IHC). TCN-PM was administered over 30 min on days 1, 8 and 15 of a 28-day cycle. Tumor biopsy specimens, collected before treatment and on day +15, were assessed for p-AKT by IHC and western blot analyses. Nineteen subjects were enrolled; 13 received at least one cycle of therapy, and a total of 34 complete cycles were delivered. One subject was treated at the 45 mg/m(2) dose before the study was closed due to its primary objective having been met. No dose-limiting toxic effects were observed. Modest decreases in tumor p-AKT following therapy with TCN-PM were observed at the 35 mg/m(2) and 45 mg/m(2) dose levels, although definitive conclusions were limited by the small sample size. These preliminary data suggest that treatment with TCN-PM inhibits tumor p-AKT at doses that were tolerable. Although single agent activity was not observed in this enriched population, further combination studies of TCN-PM with other signal transduction pathway inhibitors in solid tumors is warranted.

  18. Aggressive behaviour of solid-pseudopapillary tumor of the pancreas in adults:A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Solid-pseudopapillary tumor (SPT) is a rare neoplasm of the pancreas that usually occurs in young females.It is generally considered a low-grade malignant tumor that can remain asymptomatic for several years.The occurrence of infiltrating varieties of 5PT is around 10%-15%.Between 1986 and 2006,282 cystic tumors of the pancreas were observed.Among them a SPT was diagnosed in 8 patients (2.8%) with only one infiltrating variety.This was diagnosed in a 49-year-old female 13 years after the sonographic evidence of a small pancreatic cystic lesion interpreted as a pseudocyst.The tumor invaded a long segment of the portalmesenteric vein confluence,and was removed with a total pancreatectomy,resection of the portal vein and reconstruction with the internal jugular vein.Histological examination confirmed the R-0 resection of the primary SPT,although a vascular invasion was demonstrated.The postoperative course was uneventful,but 32 mo after surgery the patient experienced diffuse liver metastases.Chemotherapy with different drugs was started.The patient is alive and symptom-free,with stable disease,75 mo after surgery.Twenty-five patients with invasion of the portal vein and/or of mesenteric vessels were retrieved from the literature,16 recent patients with tumor relapse after potentially curative resection were also retrieved.The best treatment remains a radical resection whenever possible,even in locally advanced or metastatic disease.The role of chemotherapy,and/or radiotherapy,is still to be defined.

  19. Adverse effect of mild temperature hyperthermia combined with hexamethylenetetramine compared to its effect combined with tirapazamine in the treatment of solid tumors.

    Science.gov (United States)

    Masunaga, Shin-Ichiro; Tano, Keizo; Nakamura, Jun; Watanabe, Masami; Kashino, Genro; Suzuki, Minoru; Kinashi, Yuko; Ono, Koji

    2010-01-01

    This study aimed to assess the effect on solid tumors of mild temperature hyperthermia (MTH) combined with hexamethylenetetramine (HMTA) or tirapazamine (TPZ). Squamous cell carcinoma (SCC VII) tumor-bearing mice were continuously administered 5-bromo-2'-deoxyuridine (BrdU) to label intratumor proliferating (P) cells. Mice received HMTA or TPZ through intraperitoneal single or subcutaneous continuous administration, with or without MTH (40°C, 60 min), followed or not by γ-ray irradiation or cisplatin treatment. After HMTA or TPZ administration without γ-ray irradiation or cisplatin treatment, immediately after γ-ray irradiation, or 1 h after cisplatin treatment, the response of quiescent (Q) cells was assessed in terms of micronucleus frequency using immunofluorescence staining for BrdU. The response of the total (P + Q) tumor cells was determined based on a comparison with non-BrdU-treated tumors. Without MTH, HMTA and TPZ had a nearly equal radiosensitizing and cisplatin sensitivity-enhancing effect on both total and Q cells. With MTH, radio- and cisplatin-sensitizing effects by HMTA were reduced, particularly in the Q cells. In contrast, the enhancing effects of TPZ were increased, particularly in the Q cells. Continuous administration of HMTA and TPZ resulted in higher radio- and cisplatin-sensitizing effects than intraperitoneal single administration. In terms of tumor cytotoxicity as a whole, including Q cells, the administration of γ-ray irradiation or cisplatin treatment combined with continuous HMTA administration is promising, taking into account the clinical use of HMTA. However, MTH should not be combined with HMTA administration.

  20. Inducible activation of MyD88 and CD40 in CAR T-cells results in controllable and potent antitumor activity in preclinical solid tumor models.

    Science.gov (United States)

    Mata, Melinda; Gerken, Claudia; Nguyen, Phuong; Krenciute, Giedre; Spencer, David M; Gottschalk, Stephen

    2017-08-11

    Adoptive immunotherapy with T-cells expressing chimeric antigen receptors (CARs) has had limited success for solid tumors in early phase clinical studies. We reasoned that introducing into CAR T-cells an inducible co-stimulatory (iCO) molecule consisting of a chemical inducer of dimerization (CID)-binding domain and the MyD88 and CD40 signaling domains would improve and control CAR T-cell activation. In the presence of CID, T-cells expressing HER2-CARζ and a MyD88/CD40-based iCO molecule (HER2ζ.iCO T-cells) had superior T-cell proliferation, cytokine production, and ability to sequentially kill targets in vitro relative to HER2ζ.iCO T-cells without CID and T-cells expressing HER2-CAR.CD28ζ. HER2ζ.iCO T-cells with CID also significantly improved survival in vivo in two xenograft models. Repeat injections of CID were able to further increase the antitumor activity of HER2ζ.iCO T-cells in vivo. Thus, expressing MyD88/CD40-based iCO molecules in CAR T-cells has the potential to improve the efficacy of CAR T-cell therapy approaches for solid tumors. Copyright ©2017, American Association for Cancer Research.

  1. The role of the insulin-like growth factor signaling pathway in non-small cell lung cancer and other solid tumors.

    Science.gov (United States)

    Scagliotti, Giorgio V; Novello, Silvia

    2012-06-01

    The type 1 insulin-like growth factor receptor (IGF-1R) and its downstream signaling components have become increasingly recognized as having a driving role in the development of malignancy, and consequently IGF-1R has become a potential target for cancer therapy. Several inhibitors of IGF-1R are in clinical development for the treatment of solid tumors, including non-small cell lung cancer (NSCLC). These IGF-1R-targeted agents include monoclonal antibodies such as cixutumumab (IMC-A12), AMG-479, AVE1642, BIIB022, dalotuzumab (MK-0646), and robatumumab (Sch717454), the ligand neutralizing antibody Medi-573, and the small molecule inhibitors BMS-754807, linsitinib (OSI-906), XL228, and AXL1717. Two phase III trials of the anti-IGF-1R monoclonal antibody, figitumumab (CP-751,871), were discontinued in 2010 as it was considered unlikely either trial would meet their primary endpoints. In light of disappointing clinical data with figitumumab and other targeted agents, it is likely that the use of molecular markers will become important in predicting response to treatment. This review outlines the role of IGF-1R signaling in solid tumors with a particular focus on NSCLC, and provides an overview of clinical data.

  2. Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma

    Science.gov (United States)

    2017-02-08

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

  3. Detección molecular de enfermedad mínima residual en melanoma y otros tumores sólidos Molecular detection of minimal residual disease in melanoma and solid tumors

    Directory of Open Access Journals (Sweden)

    Valeria Vázquez

    2009-02-01

    Full Text Available La disponibilidad de métodos altamente sensibles y específicos para la detección de enfermedad mínima residual en pacientes con tumores sólidos podría tener importantes consecuencias pronósticas y terapéuticas. Uno de los métodos más usados para la detección molecular de células cancerosas es la técnica de RT-PCR, que permite la amplificación de secuencias de ARNm específicas de distintos tejidos. La misma fue aplicada por primera vez en la detección de células tumorales circulantes en sangre periférica de pacientes con melanoma avanzado, poco tiempo después fue adaptada para la búsqueda de enfermedad mínima residual en otros tumores sólidos. El objetivo de la presente revisión es evaluar la información publicada desde el primer estudio sobre este tema en 1991 y analizar el valor clínico de los hallazgos obtenidos. Se discute también la importancia del manejo de la muestra y de la estandarización de los procedimientos de RT-PCR.The availability of highly sensitive and specific methods for the detection of minimal residual disease in patients with solid tumors may have important prognostic and therapeutic implications. One of the most widely used methods for the molecular detection of cancer cells is the RT-PCR technique, which leads to the amplification of tissue-specific mRNA. It was firstly applied in the detection of circulating tumor cells in peripheral blood of patients with advanced melanoma; and soon it was adapted for the detection of minimal residual disease in other solid tumors. The aim of the present review is to evaluate the published data since the first study in 1991 and to analyze the clinical value of the findings obtained. The importance of sample handling and standardization of RT-PCR procedures is also discussed.

  4. 实体瘤外周血循环肿瘤细胞与转移相关性的研究进展%Relationship between circulating tumor cells in peripheral blood of solid tumor and metastasis

    Institute of Scientific and Technical Information of China (English)

    任传利; 韩崇旭; 王大新

    2011-01-01

    目的:总结实体瘤外周血中循环肿瘤细胞(CTC)和转移相关性的研究进展.方法:以"循环肿瘤细胞、实体瘤、转移"为关键词,检索2000-01-2010-10PubMed、Science Direct、Ovid、Springer、CNKI和维普等数据库的相关文献.纳入标准:关于实体瘤CTC与转移密切相关的分子机制、临床相关性的文献.共纳入分析42篇文献.结果:随着分子生物学和材料技术的发展,越来越多的方法有效地富集和鉴定不同类型实体瘤外周血CTC.细胞基因水平证实CTC具有恶性生物学特性,CTC自身基因和转移相关蛋白谱的表达,肿瘤微环境、免疫系统等因素影响着CTC远处器官转移灶的形成.CTC数目、特定基因、蛋白的表达与治疗疗效、预后等具有相关性.结论:研究CTC参与血液播散转移的机制,为全面、准确地阐明恶性实体瘤转移的机制、个体化的治疗提供新的工具.%OBJECTIVE: To review of the studies the relationship between circulating tumor cells (CTC)in peripheral blood of solid tumors and the mechanism of metastasis. METHODS: Keyword: circulating tumor cell (CTC), solid tumors, metastasis. Retrieval system: PubMed, Ovid, Science Direct, Springer, CNKI,Weipu Data. The time limit: 2000-01- 2010-10. The enrolled criteria: about the relationship between CTC in peripheral blood of solid tumors and the mechanism of metastasis, its clinical relevance. Overall, 42 literatures were cited. RESULTS: As the development of the advanced technique of molecular biology and material,more and more methods can be used to enrich and identify CTC. It is reported that cytogenetic evidence that CTC in patients with carcinoma are malignant. The gene and related metastatic protein profile in CTC,tumor microenvironment, immune system can influence on tumor metastasis. The number of CTC, the expression of specific genes and proteins have a relationship with the effect of treatment and evaluation of prognosis. CONCLUSION: The study

  5. Tumor sólido pseudopapilar de pâncreas: relato de um caso com apresentação incomum Solid pseudopapillary tumor of the pancreas: report of one uncommon presentation case

    Directory of Open Access Journals (Sweden)

    Felipe Santos Xavier

    2009-10-01

    Full Text Available Caso clínico atípico de tumor sólido pseudopapilar de pâncreas (TSPPP acometendo paciente do sexo masculino, 37 anos, com quadro inicial de dor abdominal aguda. Após cirurgia e exame anatomopatológico com imuno-histoquímica, demonstrou padrão condizente com TSPPP e forte positividade para β-catenina. Dois anos após a cirurgia o paciente encontra-se livre de recidiva. O TSPPP é mais comum em mulheres jovens com quadro clínico de massa ou desconforto abdominal, podendo alguns casos ser assintomáticos. Apresenta crescimento lento e baixo potencial de malignidade, sendo a ressecção cirúrgica o tratamento de escolha com altos índices de cura.Atypical clinical case of solid pseudopapillary tumor (SPPT of the pancreas in a 37 year-old man with acute abdominal pain. After surgery, anatomopathologic investigation with immunohistochemistry showed pattern in keeping with SPPT and strong positivity for β-catenin. Two years post-surgery the patient does not present recurrence. The SPPT normally occurs in young women with a history of mass or abdominal discomfort, although in some cases it can be asymptomatic. The tumor has slow growth, low potential for malignancy and surgical resection yields high cure rates.

  6. EFFECTS OF LIMONENE, SALVIA MILTIORRHIZA AND TURMERIC DERIVATIVES ON H-RAS ONCOGENE EXPRESSION AND GAP JUNCTION INTERCELLULAR COMMUNICATION IN HUMAN SOLID TUMOR CELL LINES

    Institute of Scientific and Technical Information of China (English)

    Chen Xiaoguang; Taday oshi Hasuma; Yoshihisa Yano; Toshiko Yoshimata; Hiyoshi Kamoi; Shuzo Otani

    1998-01-01

    Objective: To study gap junction intercellular communication (GJIC), H-ras oncogene expression and ras oncogene product (P21 ras protein) expression in four human solid tumor cell lines, W1-38, CACO2, A549 and PaCa, and the effects of four compounds, Salvia miltiorrhiza derivative (SMD), d-Limonene, Turmeric derivative Ⅰ (TD-Ⅰ) and Turmeric derivative Ⅱ (TD-Ⅱ), on them. Methods: The abilities of the four solid tumor cell lines to transfer dye to adjacent cells were examined by the scrape-loading/dye transfer technique, and the Hras oncogene expression by Northern blotting and P21 ras protein expression by Western blotting. Results: The results showed the loss of intercellular coupling in PaCa cells, slight GJIC in A549 and CACO2 cells, and a good GJIC in W1-38 cells. The four compounds could improve the GJIC of PaCa to different extents. The amount of total and membrane associated P21 ras in PaCa cells were decreased after treatment with SMD, d-Limonene and TD-Ⅰ (2.5 μg/ml) for 48 h. Concomitantly, the growth of PaCa cells decreased in soft agar and had enhanced GJIC.The relative potency was found to be:d-Limonene>SMD >TD-Ⅰ=TD-Ⅱ. There was no significant effect of the four compounds on H-ras oncogene expression. Conclusion:It was suggested that there was an excellent correlation between loss of Lucifer Yellow dye transfer and ras gene mutation rate in the four solid tumor cell lines (ras gene mutation rate inversely correlated with average cell number coupled, r=0.98) i.e., the high ras gene mutation was closely correlated with loss of GJIC in these malignant human tumor cells; The antitumor effect of the monoterpene d-Limonene and the phenol compound,SMD, might be related to inhibition of P21 ras membrane association and enhancement of GJIC, whilst that of the others may be by a different mechanism; The inhibition of p21 ras membrane association was directly related to the enhancement of gap junction intercellular communication.

  7. The influence of ICRF-159 and levamisole on the incidence of metastases following local irradiation of a solid tumor

    Energy Technology Data Exchange (ETDEWEB)

    Baker, D.; Constable, W.; Elkon, D.; Rinehart, L.

    1981-11-15

    Courses of irradiation consisting of 6000 rad in ten equal fractions over 12 days delivered to KHT sarcomas in mice controlled 55% of the local tumors but 83% of the mice died from metastases. Three strategies to reduce the risk of metastatic spread were tested. The fractionation scheme was changed to deliver the same total dose using a large initial fraction followed by seven equal portions with the same overall time. ICRF-159 was used with the intention of partially synchronizing the tumor growth fraction in a radiosensitive state of the growth cycle and of promoting normalization of the tumor vasculature. Levamisole was used to stimulate the immune system. The combination of ICRF-159 with the eight-fraction radiation course proved to be effective for both increasing local control and decreasing the incidence of metastases. The addition of levamisole did not improve the results obtained with a combination of ICRF-159 and irradiation.

  8. Influence of ICRF-159 and levamisole on the incidence of metastases following local irradiation of a solid tumor

    Energy Technology Data Exchange (ETDEWEB)

    Baker, D.; Constable, W.; Elkon, D.; Rinehart, L.

    1981-11-15

    Courses of irradiation consisting of 6000 rad in ten equal fractions over 12 days delivered to KHT sarcomas in mice controlled 55% of the local tumors but 83% of the mice died from metastases. Three strategies to reduce the risk of metastatic spread were tested. The fractionation scheme was changed to deliver the same total dose using a large initial fraction followed by seven equal portions with the same overall time. ICRF-159 was used with the intention of partially synchronizing the tumor growth fraction in a radiosensitive state of the growth cycle and of promoting normalization of the tumor vasculature. Levamisole was used to stimulate the immune system. The combination of ICRF-159 with the eight-fraction radiation course proved to be effective for both increasing local control and decreasing the incidence of metastases. The addition of levamisole did not improve the results obtained with a combination of ICRF-159 and irradiation.

  9. Observed Effection of Solid Tumors by Percutaneous to Inject Anticancer Milk%实体瘤经皮注射抗癌乳疗效观察

    Institute of Scientific and Technical Information of China (English)

    温海华; 刘静

    2014-01-01

    目的进一步探索和观察抗癌乳的抗癌效果和临床应用安全性。拓宽其临床应用范围。方法我科对63例实体瘤经皮穿刺注射抗癌乳,4w后复查,用WHO对实体瘤的疗效评价标准,评判其疗效;再与文献报道的实体瘤经皮植入放射微粒125I的临床对应指标相比较。进一步明确抗癌乳对实体瘤的临床治疗价值和优势。结果本组63例中,RR 76.18%CBR 93.64%。获得平均6个月PFS。与125I微粒比较,两者有效率为76.18%VS(73.14%~77.8%),PFS、本组平均6个月,与文献报道的125I粒子植入术后,累计91.67%患者无进展生存期为6月比较,极为相近。差异无统计学意义。结论抗癌乳与125I微粒比较,两者有效率和无进展生存期极为相近,无统计学差异。但在更加廉价易得、保存储运和使用安全方便等方面,抗癌乳则更具优势。在基层医院更适合于无手术指征实体瘤患者的治疗。%Objective Further exploration and observation of anticancer milk anti-cancer ef ect and safety for clinical application. To broaden the scope of clinical application. Methods In our department, 63 patients with solid tumors by percutaneous injection of anticancer milk, after 4 weeks,the standard to evaluate the ef ect of solid tumors with WHO, to judge its curative ef ect; then with the reported solid tumor by clinical corresponding index skin implanted radioactive particles 125I compared. To further clarify the anticancer milk for solid tumors in the clinical value and advantages. Results The 63 patients, RR 76.18% CBR 93.64%. For an average of 6 months PFS. With 125I particles implantation compared, The RR of 76.18%VS (73.14%~77.8%),PFS,In this group, with an average of 6 months. Compared 125I particle implantation was reported in the literature, a total of 91.67% patients were progression free survival was June, very close. No significant differences. Conclusion Anticancer milk compared with 125I particles, both efficient

  10. Extracranial to intracranial bypass for the treatment of cerebral aneurysms in the pediatric population.

    Science.gov (United States)

    Strickland, Ben A; Attenello, Frank; Russin, Jonathan J

    2016-12-01

    Cerebral aneurysms are rare in the pediatric population, making a definitive treatment algorithm difficult. Microsurgical clipping is the first choice for treatment but is not always feasible, while high recurrence rates and radiation exposure make endovascular options less favorable. Extracranial-intracranial (EC-IC) bypass, though not commonly performed in the pediatric aneurysm population, has been reported in a small number of studies to be both safe and effective for the management of cerebral aneurysms. The authors present the case of a child with a distal middle cerebral artery (MCA) aneurysm in eloquent territory, successfully treated with a superficial temporal artery (STA) to MCA bypass and trapping. A review of the current literature on pediatric EC-IC bypass in the treatment of intracranial aneurysms is presented. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Endovascular Management of Extra-cranial Supra-aortic Vascular Injuries

    Energy Technology Data Exchange (ETDEWEB)

    Almazedi, Bahir, E-mail: b.almazedi@doctors.org.uk; Lyall, Harpreet; Bhatnagar, Priya [Leeds and West Yorkshire Radiology Academy, Leeds General Infirmary (United Kingdom); Kessel, David; McPherson, Simon; Patel, Jai V.; Puppala, Sapna [The Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary, Department of Vascular and Interventional Radiology (United Kingdom)

    2013-02-08

    Supra-aortic vessel injuries are uncommon but can be life-threatening and surgically challenging. Trauma to these vessels may be blunt or penetrating, including iatrogenic trauma following the insertion of central venous lines, which may be preventable. Recent advances in technology have resulted in endovascular therapy becoming a common first-line treatment, and interventional radiologists now play a major role in the management of these vascular injuries. We review the literature on the endovascular management of these types of injuries and describe a spectrum of case-based extra-cranial supra-aortic vascular injuries managed at our institution and the range of imaging appearances, including active contrast extravasation, traumatic vessel occlusion, true aneurysms, pseudoaneurysms, and arteriovenous fistulae.

  12. Hyperhomocysteinemia Presenting with Complete Unilateral Intracranial and Extracranial Carotid Occlusion in a Young Patient.

    Science.gov (United States)

    Niazi, Farheen; Rahman, Abdul; Batool, Uzma

    2017-09-01

    Hyperhomocysteinemia has been associated with premature peripheral vascular, cerebrovascular, and coronary artery disease. It has been associated with vascular diseases including cerebrovascular disease, particularly in subjects with significant carotid stenosis. However, hyperhomocysteinemia causing unilateral complete occlusion of whole of internal carotid, common carotid, and external carotid has been rarely reported. We report a case of an adult patient aged 35-year with complete occlusion of right common carotid, internal carotid, both intracranial and extracranial part, presented with recurrent TIAs and stroke and was found to be having hyperhomocysteinemia as the cause of this complete occlusion and showed marked clinical recovery with appropriate treatment. Prompt identification and treatment of hyperhomocysteinemia, as a vascular risk factor especially in young, is of utmost importance especially when its treatment is cost-effective and can save major disability from stroke.

  13. Telescoping Dual Covered Stent Graft Construct for Endovascular Treatment of a Giant Extracranial Carotid Artery Pseudoaneurysm.

    Science.gov (United States)

    Ding, Dale; Starke, Robert M; Moriarty, Maurice; Brew, Stefan

    2016-12-01

    Large pseudoaneurysms which compress the parent vessel are challenging lesions to successfully treat with endovascular therapy. We describe the endovascular treatment of a giant extracranial carotid artery (ECCA) pseudoaneurysm resulting in substantial mass effect on the common carotid artery (CCA) bifurcation using a telescoping dual covered stent graft construct. A 56-year-old male was diagnosed with an 8.5 cm × 13 cm pseudoaneurysm arising from the left CCA bifurcation, which was causing luminal narrowing of the CCA and proximal internal carotid artery (ICA). The patient underwent endovascular intervention, during which a balloon-expandable covered stent was deployed within a heparin-bonded covered stent, such that the overall construct spanned from the CCA to the lower cervical ICA. The employment of a telescoping dual covered stent technique can successfully treat appropriately selected patients with large or giant ECCA pseudoaneurysms, with the concomitant goals of excluding the pseudoaneurysm and restoring the luminal caliber of the parent artery.

  14. Validation and Application of a Custom-Designed Targeted Next-Generation Sequencing Panel for the Diagnostic Mutational Profiling of Solid Tumors.

    Science.gov (United States)

    Froyen, Guy; Broekmans, An; Hillen, Femke; Pat, Karin; Achten, Ruth; Mebis, Jeroen; Rummens, Jean-Luc; Willemse, Johan; Maes, Brigitte

    2016-01-01

    The inevitable switch from standard molecular methods to next-generation sequencing for the molecular profiling of tumors is challenging for most diagnostic laboratories. However, fixed validation criteria for diagnostic accreditation are not in place because of the great variability in methods and aims. Here, we describe the validation of a custom panel of hotspots in 24 genes for the detection of somatic mutations in non-small cell lung carcinoma, colorectal carcinoma and malignant melanoma starting from FFPE sections, using 14, 36 and 5 cases, respectively. The targeted hotspots were selected for their present or future clinical relevance in solid tumor types. The target regions were enriched with the TruSeq approach starting from limited amounts of DNA. Cost effective sequencing of 12 pooled libraries was done using a micro flow cell on the MiSeq and subsequent data analysis with MiSeqReporter and VariantStudio. The entire workflow was diagnostically validated showing a robust performance with maximal sensitivity and specificity using as thresholds a variant allele frequency >5% and a minimal amplicon coverage of 300. We implemented this method through the analysis of 150 routine diagnostic samples and identified clinically relevant mutations in 16 genes including KRAS (32%), TP53 (32%), BRAF (12%), APC (11%), EGFR (8%) and NRAS (5%). Importantly, the highest success rate was obtained when using also the low quality DNA samples. In conclusion, we provide a workflow for the validation of targeted NGS by a custom-designed pan-solid tumor panel in a molecular diagnostic lab and demonstrate its robustness in a clinical setting.

  15. Rhythmic Components in Extracranial Brain Signals Reveal Multifaceted Task Modulation of Overlapping Neuronal Activity.

    Directory of Open Access Journals (Sweden)

    Roemer van der Meij

    Full Text Available Oscillatory neuronal activity is implicated in many cognitive functions, and its phase coupling between sensors may reflect networks of communicating neuronal populations. Oscillatory activity is often studied using extracranial recordings and compared between experimental conditions. This is challenging, because there is overlap between sensor-level activity generated by different sources, and this can obscure differential experimental modulations of these sources. Additionally, in extracranial data, sensor-level phase coupling not only reflects communicating populations, but can also be generated by a current dipole, whose sensor-level phase coupling does not reflect source-level interactions. We present a novel method, which is capable of separating and characterizing sources on the basis of their phase coupling patterns as a function of space, frequency and time (trials. Importantly, this method depends on a plausible model of a neurobiological rhythm. We present this model and an accompanying analysis pipeline. Next, we demonstrate our approach, using magnetoencephalographic (MEG recordings during a cued tactile detection task as a case study. We show that the extracted components have overlapping spatial maps and frequency content, which are difficult to resolve using conventional pairwise measures. Because our decomposition also provides trial loadings, components can be readily contrasted between experimental conditions. Strikingly, we observed heterogeneity in alpha and beta sources with respect to whether their activity was suppressed or enhanced as a function of attention and performance, and this happened both in task relevant and irrelevant regions. This heterogeneity contrasts with the common view that alpha and beta amplitude over sensory areas are always negatively related to attention and performance.

  16. High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors

    Science.gov (United States)

    2016-11-07

    Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Neuroblastoma; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Regional Neuroblastoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  17. High prevalence of malnutrition among patients with solid non-hematological tumors as found by using skinfold and circumference measurements

    Directory of Open Access Journals (Sweden)

    Adriana Garófolo

    Full Text Available CONTEXT AND OBJECTIVE: Malnutrition in cancer patients has many causes. Nutritional status is usually assessed from weight/height indices. These present limitations for the nutritional assessment of cancer patients: their weights include tumor mass, and lean mass changes are not reflected in weight/height indices. The objective was to evaluate differences between two anthropometric methods and compare deficits, in non-hematological tumor patients and hematological disease patients. DESIGN AND SETTING: Cross-sectional study at Instituto de Oncologia Pediátrica, Universidade Federal de São Paulo. METHODS: Children and adolescents were evaluated between March 1998 and January 2000. Traditional anthropometric measurements were obtained in the first month of treatment (induction therapy, by weight-for-height (W/H using z-scores index for children and body mass index (BMI for adolescents. Body composition evaluations consisted of specific anthropometric measurements: triceps skinfold thickness (TSFT, mid-upper arm circumference (MUAC and arm muscle circumference (AMC. Data were analyzed to compare nutritional assessment methods for diagnosing malnutrition prevalence. The chi-squared test was used for comparative analyses between tumor patients and hematological disease patients. RESULTS: Analysis was done on 127 patients with complete data. Higher percentages of deficits were found among tumor patients, by W/H z-scores or BMI and by MUAC and AMC. Higher percentages of deficits were shown by TSFT (40.2% and MUAC (35.4% than by W/H z-scores or BMI (18.9%. CONCLUSION: Non-hematological tumor patients presented higher malnutrition prevalence than did hematological disease patients. Body composition measurements by TSFT and MUAC detected more patients with malnutrition than did W/H or BMI.

  18. A 3D microfluidic model for preclinical evaluation of TCR-engineered T cells against solid tumors

    Science.gov (United States)

    Tan, Anthony T.; Koh, Sarene; Chia, Adeline; Colombo, Marta; Antonecchia, Emanuele; Miccolis, Carlo; Raimondi, Manuela T.; Kamm, Roger D.

    2017-01-01

    The tumor microenvironment imposes physical and functional constraints on the antitumor efficacy of adoptive T cell immunotherapy. Preclinical testing of different T cell preparations can help in the selection of efficient immune therapies, but in vivo models are expensive and cumbersome to develop, while classical in vitro 2D models cannot recapitulate the spatiotemporal dynamics experienced by T cells targeting cancer. Here, we describe an easily customizable 3D model, in which the tumor microenvironment conditions are modulated and the functionality of different T cell preparations is tested. We incorporate human cancer hepatocytes as a single cell or as tumor cell aggregates in a 3D collagen gel region of a microfluidic device. Human T cells engineered to express tumor-specific T cell receptors (TCR–T cells) are then added in adjacent channels. The TCR–T cells’ ability to migrate and kill the tumor target and the profile of soluble factors were investigated under conditions of varying oxygen levels and in the presence of inflammatory cytokines. We show that only the 3D model detects the effect that oxygen levels and the inflammatory environment impose on engineered TCR–T cell function, and we also used the 3D microdevice to analyze the TCR–T cell efficacy in an immunosuppressive scenario. Hence, we show that our microdevice platform enables us to decipher the factors that can alter T cell function in 3D and can serve as a preclinical assay to tailor the most efficient immunotherapy configuration for a specific therapeutic goal. PMID:28614795

  19. A high-fat diet increases angiogenesis, solid tumor growth, and lung metastasis of CT26 colon cancer cells in obesity-resistant BALB/c mice.

    Science.gov (United States)

    Park, Heesook; Kim, Minhee; Kwon, Gyoo Taik; Lim, Do Young; Yu, Rina; Sung, Mi-Kyung; Lee, Ki Won; Daily, James W; Park, Jung Han Yoon

    2012-11-01

    We evaluated whether high-fat diet (HFD), in the absence of increased calorie intake, increases colon cancer growth and metastasis. Four-week-old male BALB/c mice were fed on an HFD (60 kcal% fat) or control diet (10 kcal% fat) for 16 wk, after which CT26 colon cancer cells were subcutaneously injected into the right flank. Solid tumor growth and the number and volume of tumor nodules in the lung were increased markedly in the HFD group with only a slight increase in body weight (5.9%). HFD feeding increased tumor tissue levels of Ki67, cyclin A, cyclin D1, CDK2, Bcl-xL, and Bcl-2; reduced p53 levels and TUNEL-positive apoptotic cells; increased the levels of CD45, CD68, CD31, VEGF, P-VEGF receptor-2, iNOS, and COX-2 as well as hemoglobin content; and increased the levels of HIF-1α, P-STAT3-Y705, P-STAT3-S727, P-IκB-α, P-p65, p65, P-c-Jun, P-Akt, P-ERK1/2, P-p38, and P-SAPK/JNK. HFD feeding increased the serum levels of EGF, insulin, IGF-I, IFN-γ, leptin, RANTES, MCP-1, IL-1ra, and SDF-1α and media conditioned by epididymal fat tissue explants from HFD-fed mice caused an increase in microvessel outgrowth from the mouse aorta and tube formation of human umbilical vein endothelial cells. These results indicate that the chronic consumption of an HFD increases colon cancer cell proliferation, tumor angiogenesis, and lung metastasis in mice in the absence of discernible weight gain. HFD feeding increases the levels of growth factors which activate transcription factors, thereby inducing the expression of many genes involved in the stimulation of inflammation, angiogenesis, and cellular proliferation. Copyright © 2011 Wiley Periodicals, Inc.

  20. Expression of stage-specific embryonic antigen-4 (SSEA-4) defines spontaneous loss of epithelial phenotype in human solid tumor cells.

    Science.gov (United States)

    Sivasubramaniyan, Kavitha; Harichandan, Abhishek; Schilbach, Karin; Mack, Andreas F; Bedke, Jens; Stenzl, Arnulf; Kanz, Lothar; Niederfellner, Gerhard; Bühring, Hans-Jörg

    2015-08-01

    Stage-specific embryonic antigen-4 (SSEA-4) is a glycosphingolipid, which is overexpressed in some cancers and has been linked to disease progression. However, little is known about the functions of SSEA-4 and the characteristics of SSEA-4 expressing tumor cells. Our studies identified SSEA-4 expression on a subpopulation of cells in many solid tumor cell lines but not in leukemic cell lines. Fluorescence-activated cell sorting-sorted SSEA-4(+) prostate cancer cells formed fibroblast-like colonies with limited cell-cell contacts, whereas SSEA-4(-) cells formed cobblestone-like epithelial colonies. Only colonies derived from SSEA-4(+) cells were enriched for pluripotent embryonic stem cell markers. Moreover, major epithelial cell-associated markers Claudin-7, E-cadherin, ESRP1 and GRHL2 were down-regulated in the SSEA-4(+) fraction of DU145 and HCT-116 cells. Similar to cell lines, SSEA-4(+) primary prostate tumor cells also showed down-regulation of epithelial cell-associated markers. In addition, they showed up-regulation of epithelial-to-mesenchymal transition as well as mesenchymal markers. Furthermore, SSEA-4(+) cells escape from adhesive colonies spontaneously and form invadopodia-like migratory structures, in which SSEA-4, cortactin as well as active pPI3K, pAkt and pSrc are enriched and colocalized. Finally, SSEA-4(+) cells displayed strong tumorigenic ability and stable knockdown of SSEA-4 synthesis resulted in decreased cellular adhesion to different extracellular matrices. In conclusion, we introduce SSEA-4 as a novel marker to identify heterogeneous, invasive subpopulations of tumor cells. Moreover, increased cell-surface SSEA-4 expression is associated with the loss of cell-cell interactions and the gain of a migratory phenotype, suggesting an important role of SSEA-4 in cancer invasion by influencing cellular adhesion to the extracellular matrix.

  1. Robust augmented reality registration method for localization of solid organs' tumors using CT-derived virtual biomechanical model and fluorescent fiducials.

    Science.gov (United States)

    Kong, Seong-Ho; Haouchine, Nazim; Soares, Renato; Klymchenko, Andrey; Andreiuk, Bohdan; Marques, Bruno; Shabat, Galyna; Piechaud, Thierry; Diana, Michele; Cotin, Stéphane; Marescaux, Jacques

    2017-07-01

    fiducials to propagate the deformation of solid organs' surface to their inner structures including tumors with good accuracy and automatized robust tracking.

  2. PolyHEMA spheroids are an inadequate model for the drug resistance of the intractable solid tumors

    DEFF Research Database (Denmark)

    Steadman, Kenneth; Stein, Wilfred D; Litman, Thomas;

    2008-01-01

    Cancers arising in pancreas, lung, liver and stomach are difficult to treat successfully. Wanting to understand the basis for such intractability, we previously performed comparative analyses of publicly available gene expression data from tumor biopsies. Expression of many cell adhesion genes...... correlated significantly with intractability of cancers, our surrogate of intractability being the SEER five-year survivals of patients with disseminated tumors. To model resistance mediated by cell adhesion, we evaluated HCT 116 cells grown in two modes differing in cell adhesion status: (i)as monolayers...... between these latter two conditions. We conclude that while spheroids (and confluent monolayer cells) show drug resistance, the mechanisms underlying this resistance diverge from those conferring resistance to intractable cancers....

  3. Distinct expression profiles of Notch-1 protein in human solid tumors: Implications for development of targeted therapeutic monoclonal antibodies

    OpenAIRE

    Yuan Li; Burns, Janine A.; Carol A Cheney; et al

    2010-01-01

    Yuan Li1, Janine A Burns1, Carol A Cheney1, Ningyan Zhang1, Salvatore Vitelli1, Fubao Wang1, Andrew Bett2, Michael Chastain2, Laurent P Audoly1, Zhi-Qiang Zhang1,31Department of Biologics Research, 2Department of Vaccine Research, Merck Research Laboratories, West Point, PA, USA; 3Clinical Development Laboratory, Merck Research Laboratories, Rahway, NJ, USAAbstract: Biological therapies, such as monoclonal antibodies (mAbs) that target tumor-associated antigens have been considered an effecti...

  4. [Experience of off-label use of Eltrombopag in the treatment of thrombocytopenia associated with solid tumors].

    Science.gov (United States)

    García Lagunar, María Henar; Cerezuela Fuentes, Pablo; Martínez Penella, Mónica; Gutiérrez-Meca Maestre, Dolores Paula; García Coronel, María; Martínez Ortiz, María José

    2015-05-01

    Objetivo: Describir los resultados del uso fuera de indicación de eltrombopag en pacientes con trombocitopenia limitante de tratamiento quimioterápico y tumores sólidos. Método: Estudio observacional retrospectivo en el que se incluyeron todos los pacientes con tumores sólidos tratados con eltrombopag por trombocitopenia durante el tratamiento con quimioterapia entre enero de 2012 y diciembre de 2014. Resultados: Seis pacientes, con tumores sólidos y trombocitopenia limitante de tratamiento, recibieron eltrombopag durante el periodo de estudio con una disminución en el retraso de ciclos de quimioterapia (4,83 ± 4,79 ciclos retrasados antes del inicio de eltrombopag vs 2,50 ± 4,32 ciclos durante el tratamiento con eltrombopag, p=0,492) y un aumento en el porcentaje de dosis real administrada (89,29 ± 13,36% vs 91,43 ± 10,69%, p=0,682). Así mismo, se produjo un aumento en el nadir de plaquetas (55,29 ± 16,45x109/L vs 76,14 ± 36,38x109/L, p=0,248) sin requerir en ningún paciente soporte transfusional con plaquetas durante el tratamiento con eltrombopag. Conclusiones: eltrombopag ha resultado ser una alternativa de tratamiento para pacientes con trombocitopenia limitante de tratamiento con quimioterapia, siendo necesarios ensayos clínicos con mayor número de pacientes que confirmen estos resultados.

  5. Nonenhanced hybridized arterial spin labeled magnetic resonance angiography of the extracranial carotid arteries using a fast low angle shot readout at 3 Tesla

    National Research Council Canada - National Science Library

    Ioannis Koktzoglou; Matthew T Walker; Joel R Meyer; Ian G Murphy; Robert R Edelman

    2016-01-01

    ... (MRA) of the extracranial carotid arteries using a fast low angle shot (FLASH) readout at 3 Tesla. Methods In this retrospective, institutional review board-approved and HIPAA-compliant study, we evaluated the image quality...

  6. A phase I and pharmacokinetics study of intravenous calcitriol in combination with oral dexamethasone and gefitinib in patients with advanced solid tumors

    Science.gov (United States)

    Muindi, Josephia R.; Johnson, Candace S.; Trump, Donald L.; Christy, Renee; Engler, Kristie L.

    2009-01-01

    Purpose The primary objective of this study was to determine the maximum tolerated dose (MTD) of intravenously (i.v.) calcitriol administered in combination with a fixed oral dose of dexamethasone and gefitinib in patients with refractory solid tumors. Methods A fixed oral dose of dexamethasone of 4 mg/day was given every 12 h × 3 doses starting 12 h prior to i.v. calcitriol administration. Calcitriol was administered i.v. over 1 h on weeks 1, 3, and weekly thereafter. The starting calcitriol dose level was 57 μg and escalation occurred in cohorts of three patients until the MTD was defined. Gefitinib was given at a fixed oral daily dose of 250 mg starting at week 2 (day 8). Serum calcitriol PK studies were performed on day 1 (calcitriol + dexamethasone) and on day 15 (calcitriol + dexamethasone + gefitinib). Results A total of 20 patients were treated. Dose-limiting hypercalcemia was observed in two out of the four patients receiving 163 mcg/week of calcitriol. Mean (±SE) peak serum calcitriol concentration (Cmax) at the MTD (125 μg/week calcitriol) was 11.17 ± 2.62 ng/ml and the systemic exposure (AUC0–72 h) of 53.30 ± 10.49 ng h/ml. The relationship between calcitriol dose and either Cmax or AUC was linear over the 57–163 μg dose range. Conclusions The addition of a low dose of dexamethasone allowed the safe escalation of calcitriol to the MTD of 125 μg/week. This dose level resulted in serum calcitriol concentrations that are associated with pre-clinical antitumor activity. However, no antitumor activity was noted clinically in patients with solid tumors. PMID:19396601

  7. Endoscopic ultrasound-guided fine-needle aspiration cytology diagnosis of solid pseudopapillary tumor of the pancreas:A case report and literature review

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    We describe the clinical, imaging and cytopathological features of solid pseudopapillary tumor of the pancreas (SPTP) diagnosed by endoscopic ultrasoundguided (EUS-guided) fine-needle aspiration (FNA). A 17-year-old woman was admitted to our hospital with complaints of an unexplained episodic abdominal pain for 2 mo and a short history of hypertension in the endocrinology clinic. Clinical laboratory examinations revealed polycystic ovary syndrome, splenomegaly and low serum amylase and carcinoembryonic antigen (CEA)levels. Computed tomography (CT) analysis revealed a mass of the pancreatic tail with solid and cystic consistency. EUS confirmed the mass, both in body and tail of the pancreas, with distinct borders, which caused dilation of the peripheral part of the pancreatic duct (major diameter 3.7 mm). The patient underwent EUS-FNA. EUS-FNA cytology specimens consisted of single cells and aggregates of uniform malignant cells,forming microadenoid structures, branching, papillary clusters with delicate fibrovascular cores and nuclear overlapping. Naked capillaries were also seen. The nuclei of malignant cells were round or oval, eccentric with fine granular chromatin, small nucleoli and nuclear grooves in some of them. The malignant cells were periodic acid Schiff (PAS)-Alcian blue (+) and immunocytochemically they were vimentin (+), CA 19.9 (+), synaptophysin (+), chromogranin (-), neuro-specific enolase (-), a1-antitrypsin and a1-antichymotrypsin focal positive.Cytologic findings were strongly suggestive of SPTP.Biopsy confirmed the above cytologic diagnosis. EUS-guided FNA diagnosis of SPTP is accurate. EUS findings,cytomorphologic feat