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Sample records for adult solid tumor

  1. Vaccine Therapy Plus Biological Therapy in Treating Adults With Metastatic Solid Tumors

    ClinicalTrials.gov

    2013-06-19

    Colorectal Cancer; Endometrial Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Melanoma (Skin); Pancreatic Cancer; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific

  2. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  3. A phase I trial of the HIV protease inhibitor nelfinavir in adults with solid tumors

    PubMed Central

    Blumenthal, Gideon M.; Gills, Joell J.; Ballas, Marc S.; Bernstein, Wendy B.; Komiya, Takefumi; Dechowdhury, Roopa; Morrow, Betsy; Root, Hyejeong; Chun, Guinevere; Helsabeck, Cynthia; Steinberg, Seth M.; LoPiccolo, Jaclyn; Kawabata, Shigeru; Gardner, Erin R.; Figg, William D.; Dennis, Phillip A.

    2014-01-01

    Nelfinavir is an HIV protease inhibitor being repurposed as an anti-cancer agent in preclinical models and in small oncology trials, yet the MTD of nelfinavir has not been determined. Therefore, we conducted a Phase Ia study to establish the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of nelfinavir in subjects with advanced solid tumors. Adults with refractory cancers were given oral nelfinavir twice daily with pharmacokinetic and pharmacodynamic analyses. Twenty-eight subjects were enrolled. Nelfinavir was generally well tolerated. Common adverse events included diarrhea, anemia, and lymphopenia, which were mostly mild. The DLT was rapid-onset neutropenia that was reversible. The MTD was established at 3125 mg twice daily. In an expansion cohort at the MTD, one of 11 (9%) evaluable subjects had a confirmed partial response. This, plus two minor responses, occurred in subjects with neuroendocrine tumors of the midgut or pancreatic origin. Thirty-six percent of subjects had stable disease for more than 6 months. In peripheral blood mononuclear cells, Nelfinavir inhibited AKT and induced markers of ER stress. In summary, nelfinavir is well tolerated in cancer patients at doses 2.5 times the FDA-approved dose for HIV management and showed preliminary activity in tumors of neuroendocrine origin. PMID:25327558

  4. Chemotherapy in Treating Patients With Solid Tumors

    ClinicalTrials.gov

    2013-07-01

    Bladder Cancer; Breast Cancer; Colorectal Cancer; Esophageal Cancer; Head and Neck Cancer; Kidney Cancer; Lung Cancer; Ovarian Cancer; Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  5. High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors

    ClinicalTrials.gov

    2013-03-06

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Ovarian Cancer; Retinoblastoma; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  6. Phase I clinical and pharmacokinetic study of titanocene dichloride in adults with advanced solid tumors.

    PubMed

    Korfel, A; Scheulen, M E; Schmoll, H J; Gründel, O; Harstrick, A; Knoche, M; Fels, L M; Skorzec, M; Bach, F; Baumgart, J; Sass, G; Seeber, S; Thiel, E; Berdel, W E

    1998-11-01

    This Phase I dose-escalation clinical trial of a lyophilized formulation of titanocene dichloride (MKT4) was conducted to determine the maximum tolerated dose, the dose-limiting toxicity (DLT), and pharmacokinetics of titanium (Ti) after a single i.v. infusion of MKT4. Forty patients with refractory solid malignancies were treated with a total of 78 courses. Using a modified Fibonacci scheme, 15 mg/m2 initial doses of titanocene dichloride were increased in cohorts of three patients up to level 11 (560 mg/m2) if DLT was not observed. The maximum tolerated dose was 315 mg/m2, and nephrotoxicity was DLT. Two minor responses (bladder carcinoma and non-small cell lung cancer) were observed. The pharmacokinetics of plasma Ti were assessed in 14 treatment courses by atomic absorption spectroscopy. The ratio for the area under the curve(0-infinity) in plasma and whole blood was 1.2. The following pharmacokinetic parameters were determined for plasma, as calculated in a two-compartment model: biological half-life t1/2beta in plasma was 22.8+/-11.2 h (xh +/- pseudo-SD), peak plasma concentration cmax approximately 30 microg/ml at a dose of 420 mg/m2, distribution volume Vss= 5.34+/-2.1 L (xa +/- SD), and a total clearance CItotal = 2.58+/-1.23 ml/min (xa +/- SD). There was a linear correlation between the area under the curve(0-infinity) of Ti in plasma and the titanocene dichloride dose administered with a correlation coefficient r2 of 0.8856. Plasma protein binding of Ti was in the 70-80% range. Between 3% and 16% of the total amount of Ti administered were renally excreted during the first 36 h. The recommended dose for Phase II evaluation is 240 mg/m2 given every 3 weeks with i.v. hydration to reduce renal toxicity. PMID:9829732

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

    PubMed Central

    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 <50% were excluded. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) methodology was utilized for this review (S1 PRISMA Checklist). Results 271 articles were identified for final review. There were 45% prospective studies and 52% retrospective. 264 had intermediate QA score (≥50% but <80%); Seven were adequate (80% -100%); A high CRP was predictive of prognosis in 90% (245/271) of studies—80% of the 245 studies by multivariate analysis, 20% by univariate analysis. Many (52%) of the articles were about gastrointestinal malignancies (GI) or kidney malignancies. A high CRP was prognostic in 90% (127 of 141) of the reports in those groups of tumors. CRP was also prognostic in most reports in other solid tumors primary sites. Conclusions A high CRP was associated with higher mortality in 90% of reports in people with solid tumors primary sites. This was particularly notable in GI malignancies and kidney malignancies. In other solid tumors (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

  8. Potential cytochrome P-450 drug–drug interactions in adults with metastatic solid tumors and effect on eligibility for Phase I clinical trials

    PubMed Central

    Wisinski, Kari B.; Cantu, Colby A.; Eickhoff, Jens; Osterby, Kurt; Tevaarwerk, Amye J.; Heideman, Jennifer; Liu, Glenn; Wilding, George; Johnston, Susan; Kolesar, Jill M.

    2015-01-01

    Purpose Potential cytochrome P-450 (CYP) drug–drug interactions in adults with metastatic solid tumors and their effect on eligibility for Phase I clinical trials were characterized. Methods This study included adult patients with metastatic solid tumors seen by a medical oncologist from January 2008 through July 2011. The medications used by these patients were identified. Each medication's potential for interacting with CYP isozymes was also characterized. Medication changes required to meet Phase I trial eligibility criteria were also reviewed. Results Data from 1773 patients were analyzed: 1489 were not enrolled in a Phase I trial and 284 were enrolled in a Phase I trial. Polypharmacy was significantly more prevalent in the group enrolled in a Phase I trial compared with those not enrolled (95% versus 80%, p < 0.001). The majority of patients not enrolled in a Phase I trial were taking at least one CYP isozyme inhibitor (87%) and at least one CYP isozyme inducer (45%). In a separate analysis, four Phase I trials were evaluated. Of 295 screened patients, 3.2% could not enroll due to concurrent medications. Charts from 74 enrolled patients revealed 655 concurrent medications—93 medications required further review for eligibility involving 51 (69%) of patients. Of the 93 medications, 38 (41%) were stopped and 41 (44%) were changed for the study. Conclusion Polypharmacy and the use of medications that interact with CYP isoyzmes were common in adult patients with metastatic solid tumors. Patients enrolling in Phase I studies often require medication changes to meet eligibility requirements. PMID:25987691

  9. High-Dose Chemotherapy, Total-Body Irradiation, and Autologous Stem Cell Transplantation or Bone Marrow Transplantation in Treating Patients With Hematologic Cancer or Solid Tumors

    ClinicalTrials.gov

    2013-05-07

    Breast Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  10. A Phase I Study of the SMAC-Mimetic Birinapant in Adults with Refractory Solid Tumors or Lymphoma.

    PubMed

    Amaravadi, Ravi K; Schilder, Russell J; Martin, Lainie P; Levin, Myron; Graham, Martin A; Weng, David E; Adjei, Alex A

    2015-11-01

    The inhibitor of apoptosis (IAP) family of antiapoptotic proteins has been identified as a target for small molecule inhibitors in cancer. Second mitochondrial-derived activator of caspases (SMAC) efficiently and naturally antagonizes IAPs, and preclinical studies have determined that SMAC mimetics have potent anticancer properties. Here, we report a first-in-human trial designed to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics/pharmacodynamics (PK/PD) of birinapant, a novel SMAC mimetic. Patients with advanced solid tumors or lymphoma were enrolled in a 3+3 dose escalation design with birinapant administered intravenously from 0.18 to 63 mg/m(2) once weekly every 3 of 4 weeks. Fifty patients were enrolled to 12 dose cohorts. Birinapant 47 mg/m(2) was determined to be the MTD. At 63 mg/m(2), dose-limiting toxicities included headache, nausea, and vomiting. Two cases of Bell's palsy (grade 2) also occurred at 63 mg/m(2). Birinapant had a plasma half-life of 30 to 35 hours and accumulated in tumor tissue. Birinapant suppressed cIAP1 and increased apoptosis in peripheral blood mononuclear cells and tumor tissue. Prolonged stable disease was observed in 3 patients: non-small cell lung cancer (5 months), colorectal cancer (5 months), and liposarcoma (9 months). Two patients with colorectal cancer had radiographic evidence of tumor shrinkage. In conclusion, birinapant was well tolerated with an MTD of 47 mg/m(2) and exhibited favorable PK and PD properties. Several patients demonstrated stable disease and evidence of antitumor activity. These results support the ongoing clinical trials of birinapant in patients with cancer. PMID:26333381

  11. Levofloxacin to Prevent Infection Following Chemotherapy in Treating Patients With Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-08-01

    Brain and Central Nervous System Tumors; Breast Cancer; Extragonadal Germ Cell Tumor; Infection; Lung Cancer; Lymphoma; Ovarian Cancer; Small Intestine Cancer; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific

  12. Decitabine in Treating Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2013-02-06

    Male Breast Cancer; Recurrent Bladder Cancer; Recurrent Breast Cancer; Recurrent Melanoma; Stage III Melanoma; Stage IV Bladder Cancer; Stage IV Breast Cancer; Stage IV Melanoma; Unspecified Adult Solid Tumor, Protocol Specific

  13. A first-in-human study of AMG 208, an oral MET inhibitor, in adult patients with advanced solid tumors

    PubMed Central

    Hong, David S.; Rosen, Peter; Lockhart, A. Craig; Fu, Siqing; Janku, Filip; Kurzrock, Razelle; Khan, Rabia; Amore, Benny; Caudillo, Isaac; Deng, Hongjie; Hwang, Yuying C.; Loberg, Robert; Ngarmchamnanrith, Gataree; Beaupre, Darrin M.; Lee, Peter

    2015-01-01

    Background This first-in-human study evaluated AMG 208, a small-molecule MET inhibitor, in patients with advanced solid tumors. Methods Three to nine patients were enrolled into one of seven AMG 208 dose cohorts (25, 50, 100, 150, 200, 300, and 400 mg). Patients received AMG 208 orally on days 1 and days 4–28 once daily. The primary objectives were to evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of AMG 208. Results Fifty-four patients were enrolled. Six dose-limiting toxicities were observed: grade 3 increased aspartate aminotransferase (200 mg), grade 3 thrombocytopenia (200 mg), grade 4 acute myocardial infarction (300 mg), grade 3 prolonged QT (300 mg), and two cases of grade 3 hypertension (400 mg). The MTD was not reached. The most frequent grade ≥3 treatment-related adverse event was anemia (n = 3) followed by hypertension, prolonged QT, and thrombocytopenia (two patients each). AMG 208 exposure increased linearly with dose; mean plasma half-life estimates were 21.4–68.7 hours. One complete response (prostate cancer) and three partial responses (two in prostate cancer, one in kidney cancer) were observed. Conclusions In this study, AMG 208 had manageable toxicities and showed evidence of antitumor activity, particularly in prostate cancer. PMID:26155941

  14. Brain and Spinal Cord Tumors in Adults

    MedlinePlus

    ... saved articles window. My Saved Articles » My ACS » Brain and Spinal Cord Tumors in Adults Download Printable ... the topics below to get started. What Is Brain/CNS Tumors In Adults? What are adult brain ...

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

    ClinicalTrials.gov

    2016-04-18

    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

  16. Adult Wilms tumor: Case report

    PubMed Central

    Morabito, V.; Guglielmo, N.; Melandro, F.; Mazzesi, G.; Alesini, F.; Bosco, S.; Berloco, P.B.

    2014-01-01

    Wilms tumor (WT) occurs infrequently in adults. Even rarer is adult WT with extension by direct intravascular spread into the right side of the heart. The present report describes a WT with intracaval and intracardiac extension in a 38-year-young man. In addition, thrombus extension above the infrahepatic IVC represents a major technical topic for surgeons because of the possible occurrence of uncontrollable hemorrhages and tumor fragmentation. We report the results of a surgical approach to caval thrombosis including the isolation of the IVC from the liver as routinely performed during liver harvesting. The morphologic and immune-histochemical findings confirmed the diagnosis. PMID:25553532

  17. Irinotecan and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases From Solid Tumors

    ClinicalTrials.gov

    2010-03-15

    Brain and Central Nervous System Tumors; Cognitive/Functional Effects; Long-term Effects Secondary to Cancer Therapy in Adults; Long-term Effects Secondary to Cancer Therapy in Children; Poor Performance Status; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

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

    ClinicalTrials.gov

    2016-05-04

    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. Potential Biomarkers for Bevacizumab-Induced High Blood Pressure in Patients With Solid Tumor

    ClinicalTrials.gov

    2012-02-23

    Breast Cancer; Cardiovascular Complications; Colorectal Cancer; Fallopian Tube Cancer; Head and Neck Cancer; Lung Cancer; Ovarian Cancer; Peritoneal Cavity Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  20. Phase I and Clinical Pharmacology Study of Bevacizumab, Sorafenib, and Low-dose Cyclophosphamide in Children and Young Adults with Refractory/Recurrent Solid Tumors

    PubMed Central

    Navid, Fariba; Baker, Sharyn D.; McCarville, M. Beth; Stewart, Clinton F.; Billups, Catherine A.; Wu, Jianrong; Davidoff, Andrew M.; Spunt, Sheri L.; Furman, Wayne L.; McGregor, Lisa M.; Hu, Shuiying; Panetta, John C.; Turner, David; Fofana, Demba; Reddick, Wilburn E.; Leung, Wing; Santana, Victor M.

    2012-01-01

    Purpose To determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics (PK), and pharmacodynamics (PD) of sorafenib, bevacizumab, and low-dose oral cyclophosphamide in children and young adults with recurrent/refractory solid tumors. Patients and Methods Sorafenib dose was escalated from 90 mg/m2 to 110 mg/m2 twice daily with fixed doses of bevacizumab at 5 mg/kg every 3 weeks and cyclophosphamide at 50 mg/m2 daily. Once sorafenib’s MTD was established, bevacizumab dose was escalated. Each course was 21 days. PK and PD studies were performed during the first course. Results Nineteen patients (11 males; median age, 9.2 years) received a median of 4 courses (range, 1 to 23). DLTs during course 1 included grade 3 rash (2), increased lipase (1), anorexia (1), and thrombus (1). With an additional 71 courses of therapy, the most common toxicities ≥ grade 3 included neutropenia (9), lymphopenia (9), and rashes (4). Five of 17 evaluable patients had partial tumor responses, and 5 had disease stabilization (>2 courses). Median day 1 cyclophosphamide apparent oral clearance was 3.13 L/h/m2. Median day 1 sorafenib apparent oral clearance was 44 and 39 ml/min/m2 at the 2 dose levels evaluated, and steady-state concentrations ranged from1.64 to 4.8 mg/L. Inhibition of serum VEGFR2 was inversely correlated with sorafenib steady-state concentrations (p=0.019). Conclusion The recommended phase II doses are sorafenib, 90 mg/m2 twice daily; bevacizumab, 15 mg/kg q3 weeks; and cyclophosphamide, 50 mg/m2 once daily. This regimen is feasible with promising evidence of antitumor activity that warrants further investigation. PMID:23143218

  1. Hepatic metastatic disease in pediatric and adolescent solid tumors

    PubMed Central

    Fernandez-Pineda, Israel; Sandoval, John A; Davidoff, Andrew M

    2015-01-01

    The management of hepatic metastatic disease from solid tumors in adults has been extensively described and resection of metastatic liver lesions from colorectal adenocarcinoma, renal adenocarcinoma, breast cancer, testicular cancer, and neuroendocrine tumors (NET) have demonstrated therapeutic benefits in select patients. However, there are few reports in the literature on the management of hepatic metastatic disease in the pediatric and adolescent populations and the effectiveness of hepatic metastasectomy. This may be due to the much lower incidence of pediatric malignancies and the higher chemosensitivity of childhood tumors which make hepatic metastasectomy less likely to be required. We review liver involvement with metastatic disease from the main pediatric solid tumors, including neuroblastoma and Wilms tumor focusing on the management and treatment options. We also review other solid malignant tumors which may have liver metastases including germ cell tumors, gastrointestinal stromal tumors, osteosarcoma, desmoplastic small round cell tumors and NET. However, these histological subtypes are so rare in the pediatric and adolescent populations that the exact incidence and best management of hepatic metastatic disease are unknown and can only be extrapolated from adult series. PMID:26207162

  2. ABT-751 in Treating Young Patients With Refractory Solid Tumors

    ClinicalTrials.gov

    2012-03-14

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  3. [Companion Diagnostics for Solid Tumors].

    PubMed

    Watanabe, Atsushi

    2015-11-01

    Companion diagnostics (CoDx) will likely continue to rapidly increase in number and application to disease areas including solid tumors, for example EGFR for gefitinib and ALK fusion gene for crizotinib in non-small-cell lung cancer; KRAS against the use of cetuximab and panitumumab in colorectal cancer; HER2 for trastuzumab in breast cancer. CoDx are an indispensable part of personalized medicine and pharmacogenomics. In CoDx development, there are still many challenges, such as the business model promoting cooperation between diagnostics and pharmaceutical companies, and also the regulations related to CoDx. The FDA notice on the development of CoDx in 2011 recommended the co-development of a new drug and CoDx as the best practice, and the Ministry of Health, Labour and Welfare in Japan also issued a statement in 2013. In addition, the recent discovery of many novel variants in the DNA sequence, advances in sequencing and genomic technology, and improved analytic methods have enabled the impact of germline and somatic mutations to be determined using multiplex diagnosis. The complex challenges to develop CoDx necessitate a close collaboration among academic institutions, regulatory authorities, and pharmaceutical companies. [Review]. PMID:26995877

  4. Temsirolimus, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2014-06-18

    Ovarian Sarcoma; Ovarian Stromal Cancer; Recurrent Endometrial Carcinoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Stage III Endometrial Carcinoma; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IV Endometrial Carcinoma; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific

  5. Adult granulosa cell tumor of the testis masquerading as hydrocele

    PubMed Central

    Vallonthaiel, Archana George; Kakkar, Aanchal; Singh, Animesh; Dogra, Prem N; Ray, Ruma

    2015-01-01

    ABSTRACT Adult testicular granulosa cell tumor is a rare, potentially malignant sex cord-stromal tumor, of which 30 cases have been described to date. We report the case of a 43-year-old male who complained of a left testicular swelling. Scrotal ultrasound showed a cystic lesion, suggestive of hydrocele. However, due to a clinical suspicion of a solid-cystic neoplasm, a high inguinal orchidectomy was performed, which, on pathological examination, was diagnosed as adult granulosa cell tumor. Adult testicular granulosa cell tumors have aggressive behaviour as compared to their ovarian counterparts. They may rarely be predominantly cystic and present as hydrocele. Lymph node and distant metastases have been reported in few cases. Role of MIB-1 labelling index in prognostication is not well defined. Therefore, their recognition and documentation of their behaviour is important from a diagnostic, prognostic and therapeutic point of view. PMID:26742984

  6. Cellular immunotherapy for pediatric solid tumors

    PubMed Central

    HEGDE, MEENAKSHI; MOLL, ALEXANDER; BYRD, TIARA T.; LOUIS, CHRYSTAL U.; AHMED, NABIL

    2015-01-01

    Substantial progress has been made in the treatment of pediatric solid tumors over the past 4 decades. However, children with metastatic and or recurrent disease continue to do poorly despite the aggressive multi-modality conventional therapies. The increasing understanding of the tumor biology and the interaction between the tumor and the immune system over the recent years have led to the development of novel immune-based therapies as alternative options for some of these high-risk malignancies. The safety and anti-tumor efficacy of various tumor vaccines and tumor-antigen specific immune cells are currently being investigated for various solid tumors. In early clinical trials, most of these cellular therapies have been well tolerated and have shown promising clinical responses. Although substantial work is being done in this field, the available knowledge for pediatric tumors remains limited. We review the contemporary early phase cell-based immunotherapy efforts for pediatric solid tumors and discuss the rationale and the challenges thereof. PMID:25082406

  7. Concepts in solid tumor evolution

    PubMed Central

    Sidow, Arend; Spies, Noah

    2015-01-01

    Evolutionary mechanisms in cancer progression give tumors their individuality. Cancer evolution is different from organismal evolution, however, and here we discuss where concepts from evolutionary genetics are useful or limited in facilitating an understanding of cancer. Based on these concepts we construct and apply the simplest plausible model of tumor growth and progression. Simulations using this simple model illustrate the importance of stochastic events early in tumorigenesis, highlight the dominance of exponential growth over linear growth and differentiation, and explain the clonal substructure of tumors. PMID:25733351

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

    PubMed

    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. PMID:25526702

  9. Emerging Trends for Radioimmunotherapy in Solid Tumors

    PubMed Central

    Gupta, Suprit; Kaur, Sukhwinder; Ponnusamy, Moorthy P.

    2013-01-01

    Abstract Due to its ability to target both known and occult lesions, radioimmunotherapy (RIT) is an attractive therapeutic modality for solid tumors. Poor tumor uptake and undesirable pharmacokinetics, however, have precluded the administration of radioimmunoconjugates at therapeutically relevant doses thereby limiting the clinical utility of RIT. In solid tumors, efficacy of RIT is further compromised by heterogeneities in blood flow, tumor stroma, expression of target antigens and radioresistance. As a result significant efforts have been invested toward developing strategies to overcome these impediments. Further, there is an emerging interest in exploiting short-range, high energy α-particle emitting radionuclides for the eradication of minimal residual and micrometastatic disease. As a result several modalities for localized therapy and models of minimal disease have been developed for preclinical evaluation. This review provides a brief update on the recent efforts toward improving the efficacy of RIT for solid tumors, and development of RIT strategies for minimal disease associated with solid tumors. Further, some of promising approaches to improve tumor targeting, which showed promise in the past, but have now been ignored are also discussed. PMID:23844555

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

    ClinicalTrials.gov

    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

  11. Radiofrequency Ablation Therapy for Solid Tumors

    SciTech Connect

    Kam, Anthony

    2002-12-04

    Surgical resection, systemic chemotherapy, and local radiation have been the conventional treatments for localized solid cancer. Because certain patients are not candidates for tumor resection and because many tumors are poorly responsive to chemotherapy and radiation, there has been an impetus to develop alternative therapies. Radiofrequency ablation (RFA) is a minimally invasive therapy for localized solid cancers that has gained considerable attention in the last 12 years. Advantages of minimally invasive therapies over surgery include less recovery time, lower morbidity and mortality, eligibility of more patients, and lower cost. RFA has been applied most extensively to inoperable hepatic tumors. It is investigational for tumors in the kidney, lung, bone, breast, and adrenal gland. This colloquium will review the mechanism, techniques, limitations, and clinical applications of RFA. The ultimate role that RFA will play in cancer therapy will depend on the results of long-term follow-up and prospective randomized trials.

  12. Irinotecan and Alisertib in Treating Patients With Advanced Solid Tumors or Colorectal Cancer

    ClinicalTrials.gov

    2016-02-16

    Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IIIA Colon Cancer; Unspecified Adult Solid Tumor, Protocol Specific

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

    ClinicalTrials.gov

    2016-08-09

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

  14. Chemotherapy in Treating Patients With Refractory Advanced Solid Tumors or Hematologic Cancer

    ClinicalTrials.gov

    2013-06-20

    Bladder Cancer; Breast Cancer; Colorectal Cancer; Gastric Cancer; Head and Neck Cancer; Kidney Cancer; Leukemia; Lung Cancer; Melanoma (Skin); Ovarian Cancer; Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

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

    ClinicalTrials.gov

    2016-01-16

    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

  16. Evolution of osmotic pressure in solid tumors

    PubMed Central

    Voutouri, Chysovalantis; Stylianopoulos, Triantafyllos

    2014-01-01

    The mechanical microenvironment of solid tumors includes both fluid and solid stresses. These stresses play a crucial role in cancer progression and treatment and have been analyzed rigorously both mathematically and experimentally. The magnitude and spatial distribution of osmotic pressures in tumors, however, cannot be measured experimentally and to our knowledge there is no mathematical model to calculate osmotic pressures in the tumor interstitial space. In this study, we developed a triphasic biomechanical model of tumor growth taking into account not only the solid and fluid phase of a tumor, but also the transport of cations and anions, as well as the fixed charges at the surface of the glycosaminoglycan chains. Our model predicts that the osmotic pressure is negligible compared to the interstitial fluid pressure for values of glycosaminoglycans (GAGs) taken from the literature for sarcomas, melanomas and adenocarcinomas. Furthermore, our results suggest that an increase in the hydraulic conductivity of the tumor, increases considerably the intratumoral concentration of free ions and thus, the osmotic pressure but it does not reach the levels of the interstitial fluid pressure. PMID:25287111

  17. Carcinomatous meningitis: Leptomeningeal metastases in solid tumors

    PubMed Central

    Le Rhun, Emilie; Taillibert, Sophie; Chamberlain, Marc C.

    2013-01-01

    Leptomeningeal metastasis (LM) results from metastatic spread of cancer to the leptomeninges, giving rise to central nervous system dysfunction. Breast cancer, lung cancer, and melanoma are the most frequent causes of LM among solid tumors in adults. An early diagnosis of LM, before fixed neurologic deficits are manifest, permits earlier and potentially more effective treatment, thus leading to a better quality of life in patients so affected. Apart from a clinical suspicion of LM, diagnosis is dependent upon demonstration of cancer in cerebrospinal fluid (CSF) or radiographic manifestations as revealed by neuraxis imaging. Potentially of use, though not commonly employed, today are use of biomarkers and protein profiling in the CSF. Symptomatic treatment is directed at pain including headache, nausea, and vomiting, whereas more specific LM-directed therapies include intra-CSF chemotherapy, systemic chemotherapy, and site-specific radiotherapy. A special emphasis in the review discusses novel agents including targeted therapies, that may be promising in the future management of LM. These new therapies include anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib in nonsmall cell lung cancer, anti-HER2 monoclonal antibody trastuzumab in breast cancer, anti-CTLA4 ipilimumab and anti-BRAF tyrosine kinase inhibitors such as vermurafenib in melanoma, and the antivascular endothelial growth factor monoclonal antibody bevacizumab are currently under investigation in patients with LM. Challenges of managing patients with LM are manifold and include determining the appropriate patients for treatment as well as the optimal route of administration of intra-CSF drug therapy. PMID:23717798

  18. Multistep, effective drug distribution within solid tumors

    PubMed Central

    Shemi, Amotz; Khvalevsky, Elina Zorde; Gabai, Rachel Malka; Domb, Abraham; Barenholz, Yechezkel

    2015-01-01

    The distribution of drugs within solid tumors presents a long-standing barrier for efficient cancer therapies. Tumors are highly resistant to diffusion, and the lack of blood and lymphatic flows suppresses convection. Prolonged, continuous intratumoral drug delivery from a miniature drug source offers an alternative to both systemic delivery and intratumoral injection. Presented here is a model of drug distribution from such a source, in a multistep process. At delivery onset the drug mainly affects the closest surroundings. Such ‘priming’ enables drug penetration to successive cell layers. Tumor ‘void volume’ (volume not occupied by cells) increases, facilitating lymphatic perfusion. The drug is then transported by hydraulic convection downstream along interstitial fluid pressure (IFP) gradients, away from the tumor core. After a week tumor cell death occurs throughout the entire tumor and IFP gradients are flattened. Then, the drug is transported mainly by ‘mixing’, powered by physiological bulk body movements. Steady state is achieved and the drug covers the entire tumor over several months. Supporting measurements are provided from the LODER™ system, releasing siRNA against mutated KRAS over months in pancreatic cancer in-vivo models. LODER™ was also successfully employed in a recent Phase 1/2 clinical trial with pancreatic cancer patients. PMID:26416413

  19. Sunitinib in Treating Young Patients With Refractory Solid Tumors

    ClinicalTrials.gov

    2014-01-27

    Central Nervous System Metastases; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; 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; Recurrent Childhood Central Nervous System Embryonal Tumor; Unspecified Childhood Solid Tumor, Protocol Specific

  20. Combination Chemotherapy in Treating Young Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2013-05-01

    Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; 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; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Unspecified Childhood Solid Tumor, Protocol Specific

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

    ClinicalTrials.gov

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

    PubMed Central

    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.

    2014-01-01

    Objective To ascertain prevalence of peripheral sensory and motor neuropathy; to evaluate impairments in relation to function. Design St. Jude Lifetime Cohort Study, a clinical follow-up study designed to evaluate adverse late effects in adult survivors of childhood cancer. Setting St. Jude Children’s Research Hospital (SJCRH). Participants Eligibility required treatment for an extracranial solid malignancy between 1962 and 2002, age ≥18 years, ≥10 years post-diagnosis, no history of cranial radiation. 531 survivors were included in the evaluation: median age 32 years, median time from diagnosis 25 years. Interventions Not applicable. Main Outcome Measures 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 and go test (mobility), and the sensory organization test (balance). Results 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: 0.97–2.72) without evidence of a dose response. Sensory impairment was associated with poor endurance (OR=1.99, 95% CI: 0.99–4.00) and mobility (OR=1.65, 95% CI: 0.96–2.83). Conclusion 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. PMID:23537607

  3. Ixabepilone in Treating Young Patients With Refractory Solid Tumors

    ClinicalTrials.gov

    2014-11-13

    Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Alveolar Childhood Rhabdomyosarcoma; Childhood Synovial Sarcoma; Embryonal Childhood Rhabdomyosarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors

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

    ClinicalTrials.gov

    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

  5. Patterns of Chromosomal Aberrations in Solid Tumors

    PubMed Central

    Grade, Marian; Difilippantonio, Michael J.

    2016-01-01

    Chromosomal abnormalities are a defining feature of solid tumors. Such cytogenetic alterations are mainly classified into structural chromosomal aberrations and copy number alterations, giving rise to aneuploid karyotypes. The increasing detection of these genetic changes allowed the description of specific tumor entities and the associated patterns of gene expression. In fact, tumor-specific landscapes of gross genomic copy number changes, including aneuploidies of entire chromosome arms and chromosomes result in a global deregulation of the transcriptome of cancer cells. Furthermore, the molecular characterization of cytogenetic abnormalities has provided insights into the mechanisms of tumorigenesis and has, in a few instances, led to the clinical implementation of effective diagnostic and prognostic tools, as well as treatment strategies that target a specific genetic abnormality. PMID:26376875

  6. Patterns of Chromosomal Aberrations in Solid Tumors.

    PubMed

    Grade, Marian; Difilippantonio, Michael J; Camps, Jordi

    2015-01-01

    Chromosomal abnormalities are a defining feature of solid tumors. Such cytogenetic alterations are mainly classified into structural chromosomal aberrations and copy number alterations, giving rise to aneuploid karyotypes. The increasing detection of these genetic changes allowed the description of specific tumor entities and the associated patterns of gene expression. In fact, tumor-specific landscapes of gross genomic copy number changes, including aneuploidies of entire chromosome arms and chromosomes result in a global deregulation of the transcriptome of cancer cells. Furthermore, the molecular characterization of cytogenetic abnormalities has provided insights into the mechanisms of tumorigenesis and has, in a few instances, led to the clinical implementation of effective diagnostic and prognostic tools, as well as treatment strategies that target a specific genetic abnormality. PMID:26376875

  7. Geldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-12-13

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic 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 Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific

  8. Solid Tumor Therapy Using a Cannon and Pawn Combination Strategy.

    PubMed

    Song, Wantong; Tang, Zhaohui; Zhang, Dawei; Wen, Xue; Lv, Shixian; Liu, Zhilin; Deng, Mingxiao; Chen, Xuesi

    2016-01-01

    Nanocarrier-based anti-tumor drugs hold great promise for reducing side effects and improving tumor-site drug retention in the treatment of solid tumors. However, therapeutic outcomes are still limited, primarily due to a lack of drug penetration within most tumor tissues. Herein, we propose a strategy using a nanocarrier-based combination of vascular disrupting agents (VDAs) and cytotoxic drugs for solid tumor therapy. Specifically, combretastatin A-4 (CA4) serves as a "cannon" by eradicating tumor cells at a distance from blood vessels; concomitantly, doxorubicin (DOX) serves as a "pawn" by killing tumor cells in close proximity to blood vessels. This "cannon and pawn" combination strategy acts without a need to penetrate every tumor cell and is expected to eliminate all tumor cells in a solid tumor. In a murine C26 colon tumor model, this strategy proved effective in eradicating greater than 94% of tumor cells and efficiently inhibited tumor growth with a weekly injection. In large solid tumor models (C26 and 4T1 tumors with volumes of approximately 250 mm(3)), this strategy also proved effective for inhibiting tumor growth. These results showing remarkable inhibition of tumor growth provide a valuable therapeutic choice for solid tumor therapy. PMID:27217835

  9. Solid Tumor Therapy Using a Cannon and Pawn Combination Strategy

    PubMed Central

    Song, Wantong; Tang, Zhaohui; Zhang, Dawei; Wen, Xue; Lv, Shixian; Liu, Zhilin; Deng, Mingxiao; Chen, Xuesi

    2016-01-01

    Nanocarrier-based anti-tumor drugs hold great promise for reducing side effects and improving tumor-site drug retention in the treatment of solid tumors. However, therapeutic outcomes are still limited, primarily due to a lack of drug penetration within most tumor tissues. Herein, we propose a strategy using a nanocarrier-based combination of vascular disrupting agents (VDAs) and cytotoxic drugs for solid tumor therapy. Specifically, combretastatin A-4 (CA4) serves as a “cannon” by eradicating tumor cells at a distance from blood vessels; concomitantly, doxorubicin (DOX) serves as a “pawn” by killing tumor cells in close proximity to blood vessels. This “cannon and pawn” combination strategy acts without a need to penetrate every tumor cell and is expected to eliminate all tumor cells in a solid tumor. In a murine C26 colon tumor model, this strategy proved effective in eradicating greater than 94% of tumor cells and efficiently inhibited tumor growth with a weekly injection. In large solid tumor models (C26 and 4T1 tumors with volumes of approximately 250 mm3), this strategy also proved effective for inhibiting tumor growth. These results showing remarkable inhibition of tumor growth provide a valuable therapeutic choice for solid tumor therapy. PMID:27217835

  10. Nanoparticle ligand presentation for targeting solid tumors.

    PubMed

    Duskey, Jason T; Rice, Kevin G

    2014-10-01

    Among the many scientific advances to come from the study of nanoscience, the development of ligand-targeted nanoparticles to eliminate solid tumors is predicted to have a major impact on human health. There are many reports describing novel designs and testing of targeted nanoparticles to treat cancer. While the principles of the technology are well demonstrated in controlled lab experiments, there are still many hurdles to overcome for the science to mature into truly efficacious targeted nanoparticles that join the arsenal of agents currently used to treat cancer in humans. One of these hurdles is overcoming unwanted biodistribution to the liver while maximizing delivery to the tumor. This almost certainly requires advances in both nanoparticle stealth technology and targeting. Currently, it continues to be a challenge to control the loading of ligands onto polyethylene glycol (PEG) to achieve maximal targeting. Nanoparticle cellular uptake and subcellular targeting of genes and siRNA also remain a challenge. This review examines the types of ligands that have been most often used to target nanoparticles to solid tumors. As the science matures over the coming decade, careful control over ligand presentation on nanoparticles of precise size, shape, and charge will likely play a major role in achieving success. PMID:24927668

  11. Characterization of cell suspensions from solid tumors

    SciTech Connect

    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.

  12. Suprasellar Primitive Neuroectodermal Tumor in an Adult.

    PubMed

    Espino Barros Palau, Angelina; Khan, Khurrum; Morgan, Michael L; Powell, Suzanne Z; Lee, Andrew G

    2016-09-01

    Primitive neuroectodermal tumors (PNET) of the central nervous system (CNS) are a heterogeneous group of embryonal malignancies that are composed of undifferentiated or poorly differentiated neuroepithelial cells. Supratentorial PNET is the second most common CNS embryonal malignancy in children, but it is rare in adults. We report the case of a 31-year-old woman with bilateral vision loss and a bitemporal hemianopia. Neuroimaging revealed a suprasellar mass, and pathology was consistent with PNET. After surgical debulking of the tumor followed by radiation therapy and chemotherapy, the patient had significant visual recovery and remained stable over 14 months of follow-up. PMID:26517622

  13. Therapy of leptomeningeal metastasis in solid tumors.

    PubMed

    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. PMID:26827696

  14. Gamma-Secretase Inhibitor RO4929097 and Cediranib Maleate in Treating Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2014-12-22

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Solid Neoplasm; Male Breast Carcinoma; Recurrent Adult Brain Neoplasm; Recurrent Breast Carcinoma; Recurrent Colon Carcinoma; Recurrent Melanoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Carcinoma; Recurrent Rectal Carcinoma; Recurrent Renal Cell Carcinoma; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Skin Melanoma; Stage IIIB Breast Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Skin Melanoma; Stage IIIC Breast Cancer; Stage IIIC Colon Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC Skin Melanoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  15. Safety Study of AMG 228 to Treat Solid Tumors

    ClinicalTrials.gov

    2016-06-01

    Advanced Malignancy; Advanced Solid Tumors; Cancer; Oncology; Oncology Patients; Tumors; Melanoma; Non-small Cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Transitional Cell Carinoma of Bladder; Colorectal Cancer

  16. Bloodstream Infections in Patients With Solid Tumors

    PubMed Central

    Marín, Mar; Gudiol, Carlota; Garcia-Vidal, Carol; Ardanuy, Carmen; Carratalà, Jordi

    2014-01-01

    Abstract Current information regarding bloodstream infection (BSI) in patients with solid tumors is scarce. We assessed the epidemiology, antibiotic therapy, and outcomes of BSI in these patients. We also compared patients who died with those who survived to identify risk factors associated with mortality. From January 2006 to July 2012 all episodes of BSI in patients with solid tumors at a cancer center were prospectively recorded and analyzed. A total of 528 episodes of BSI were documented in 489 patients. The most frequent neoplasms were hepatobiliary tumors (19%), followed by lung cancer (18%) and lower gastrointestinal malignancies (16%). Many patients had received corticosteroid therapy (41%), and 15% had neutropenia (<500 neutrophils/μL) at the time of BSI. The most common source of BSI was cholangitis (21%), followed by other abdominal (19.5%) and urinary tract infections (17%). Gram-negative BSI occurred in 55% of cases, mainly due to Escherichia coli (55%), Pseudomonas aeruginosa (18%), and Klebsiella pneumoniae (16%). Among gram-positive BSI (35%), viridans group streptococci were the most frequent causative organisms (22%), followed by Staphylococcus aureus (21%) and Enterococcus species (18%). We identified 61 multidrug-resistant (MDR) organisms (13%), mainly extended-spectrum β-lactamase-producing Enterobacteriaceae (n = 20) and AmpC-producing Enterobacteriaceae (n = 13). The majority of patients with BSI caused by MDR organisms had received antibiotics (70%), and they had been previously hospitalized (61.4%) more frequently than patients with BSI caused by susceptible strains. Inadequate empirical antibiotic therapy was given to 23% of patients, with a higher proportion in those with BSI due to a MDR strain (69%). Early (<48 h) and overall (30 d) case-fatality rates were 7% and 32%, respectively. The overall case-fatality rate was higher among cases caused by MDR organisms (39.3%). The only independent risk factors for the early case-fatality rate

  17. GTI-2040, Oxaliplatin, and Capecitabine in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer or Other Solid Tumors

    ClinicalTrials.gov

    2013-03-26

    Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Unspecified Adult Solid Tumor, Protocol Specific

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

    ClinicalTrials.gov

    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

  19. Autocrine growth factors and solid tumor malignancy.

    PubMed Central

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

    1991-01-01

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

  20. Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors

    ClinicalTrials.gov

    2015-04-28

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  1. MORAb-004 in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2016-01-07

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  2. Oblimersen and Gemcitabine in Treating Patients With Advanced Solid Tumor or Lymphoma

    ClinicalTrials.gov

    2013-01-24

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell 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 Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific

  3. Cilengitide (EMD 121974) in Treating Patients With Advanced Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-01-23

    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

  4. Radioimmunotherapy of Solid Tumors: Searching for the Right Target

    PubMed Central

    Song, Hong; Sgouros, George

    2015-01-01

    Radioimmunotherapy of solid tumors remains a challenge despite the tremendous success of 90Y ibritumomab tiuxetan (Zevalin) and 131I Tositumomab (Bexxar) in treating non-Hodgkin’s lymphoma. For a variety of reasons, clinical trials of radiolabeled antibodies against solid tumors have not led to responses equivalent to those seen against lymphoma. In contrast, promising responses have been observed with unlabeled antibodies that target solid tumor receptors associated with cellular signaling pathways. These observations suggest that anti-tumor efficacy of the carrier antibody might be critical to achieving clinical responses. Here, we review and compare tumor antigens targeted by radiolabeled antibodies and unlabeled antibodies used in immunotherapy. The review shows that the trend for radiolabeled antibodies under pre-clinical development is to also target antigens associated with signaling pathways that are essential for the growth and survival of the tumor. PMID:21034423

  5. Trebananib And Temsirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2015-10-05

    Adult Solid Neoplasm; Lung Carcinoid Tumor; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Renal Cell Carcinoma; Recurrent Uterine Corpus Sarcoma; Stage III Renal Cell Cancer; Stage IIIB Uterine Sarcoma; Stage IIIC Uterine Sarcoma; Stage IV Renal Cell Cancer; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma

  6. Immunotherapeutics for Pediatric Solid Tumors | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute’s Pediatric Oncology Branch seeks partners interested in licensing or collaborative research to co-develop new immunotherapeutic agents based on chimeric antigen receptor (CARs) for the treatment of pediatric solid tumors.

  7. Veliparib, Oxaliplatin, and Capecitabine in Treating Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2014-04-01

    Adenocarcinoma of the Pancreas; Adenocarcinoma of the Stomach; BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Ovarian Mucinous Cystadenocarcinoma; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gastric Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  8. Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors

    ClinicalTrials.gov

    2016-04-12

    Diffuse Intrinsic Pontine Glioma; Brain Tumor, Recurrent; Solid Tumor, Recurrent; Neuroblastoma, Recurrent, Refractory; Ewing Sarcoma, Recurrent, Refractory; Rhabdomyosarcoma, Recurrent, Refractory; Osteosarcoma, Recurrent, Refractory; Rhabdoid Tumor, Recurrent, Refractory

  9. Solid Tumor Differentiation Therapy – Is It Possible?

    PubMed Central

    Dela Cruz, Filemon; Matushansky, Igor

    2012-01-01

    Genetic and epigenetic events within a cell which promote a block in normal development or differentiation coupled with unregulated proliferation are hallmarks of neoplastic transformation. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells. The promise of differentiation-based therapy as a viable treatment modality is perhaps best characterized by the addition of retinoids in the treatment of acute promyelocytic leukemia (APML) revolutionizing the management of APML and dramatically improving survival. However, interest and application of differentiation-based therapy for the treatment of solid malignancies have lagged due to deficiencies in our understanding of differentiation pathways in solid malignancies. Over the past decade, a differentiation-based developmental model for solid tumors has emerged providing insights into the biology of various solid tumors as well as identification of targetable pathways capable of re-activating blocked terminal differentiation programs. Furthermore, a variety of agents including retinoids, histone deacetylase inhibitors (HDACI), PPARγ agonists, and others, currently in use for a variety of malignancies, have been shown to induce differentiation in solid tumors. Herein we discuss the relevancy of differentiation-based therapies in solid tumors, using soft tissue sarcomas (STS) as a biologic and clinical model, and review the preclinical data to support its role as a promising modality of therapy for the treatment of solid tumors. PMID:22643847

  10. Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors

    ClinicalTrials.gov

    2016-08-10

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Lymphoma; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor; Unspecified Childhood Solid Tumor, Protocol Specific

  11. In Vitro, Matrix-Free Formation Of Solid Tumor Spheroids

    NASA Technical Reports Server (NTRS)

    Gonda, Steve R.; Marley, Garry M.

    1993-01-01

    Cinostatic bioreactor promotes formation of relatively large solid tumor spheroids exhibiting diameters from 750 to 2,100 micrometers. Process useful in studying efficacy of chemotherapeutic agents and of interactions between cells not constrained by solid matrices. Two versions have been demonstrated; one for anchorage-independent cells and one for anchorage-dependent cells.

  12. Wilms Tumor: An Uncommon Entity in the Adult Patient

    PubMed Central

    Mahmoud, Fade; Allen, M Brandon; Cox, Roni; Davis, Rodney

    2016-01-01

    Wilms tumor, the most common kidney tumor in children, is rarely seen in adults, making it a challenge for the adult oncologist to diagnose and treat. Unlike with renal cell carcinoma, patients with Wilms tumor should receive adjuvant chemotherapy with or without radiation therapy. Adult oncologists may not be familiar with pediatric oncology protocols, so it is important to consult with pediatric oncologists who have more experience in this disease. Multimodal therapy based on pediatric protocols improved the outcomes of adults with Wilms tumor worldwide. We report a rare case of a 24-year-old woman with a slow-growing mass of the left kidney during a 4-year period. The mass was surgically removed and final diagnosis confirmed by pathology to be Wilms tumor. The patient received adjuvant chemotherapy and has been free of disease since 2014. PMID:27043834

  13. The Childhood Solid Tumor Network: A new resource for the developmental biology and oncology research communities.

    PubMed

    Stewart, Elizabeth; Federico, Sara; Karlstrom, Asa; Shelat, Anang; Sablauer, Andras; Pappo, Alberto; Dyer, Michael A

    2016-03-15

    Significant advances have been made over the past 25 years in our understanding of the most common adult solid tumors such as breast, colon, lung and prostate cancer. Much less is known about childhood solid tumors because they are rare and because they originate in developing organs during fetal development, childhood and adolescence. It can be very difficult to study the cellular origins of pediatric solid tumors in developing organs characterized by rapid proliferative expansion, growth factor signaling, developmental angiogenesis, programmed cell death, tissue reorganization and cell migration. Not only has the etiology of pediatric cancer remained elusive because of their developmental origins, but it also makes it more difficult to treat. Molecular targeted therapeutics that alter developmental pathway signaling may have devastating effects on normal organ development. Therefore, basic research focused on the mechanisms of development provides an essential foundation for pediatric solid tumor translational research. In this article, we describe new resources available for the developmental biology and oncology research communities. In a companion paper, we present the detailed characterization of an orthotopic xenograft of a pediatric solid tumor derived from sympathoadrenal lineage during development. PMID:26068307

  14. MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2013-01-23

    Adult Grade III Lymphomatoid Granulomatosis; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell 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

  15. 17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2013-01-24

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin 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; Waldenstr

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

    PubMed

    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. PMID:27357689

  17. Therapeutic attack of hypoxic cells of solid tumors: presidential address.

    PubMed

    Sartorelli, A C

    1988-02-15

    Hypoxic cells of solid tumors are relatively resistant to therapeutic assault. Studies have demonstrated that oxygen-deficient tumor cells exist in an environment conducive to reductive reactions making hypoxic cells particularly sensitive to bioreductive alkylating agents. Mitomycin C, the prototype bioreductive alkylating agent available for clinical use, is capable of preferentially killing oxygen-deficient cells both in vitro and in vivo. This phenomenon is at least in part the result of differences in the uptake and metabolism of mitomycin C by hypoxic and oxygenated tumor cells, with the ultimate critical lesion being the cross-linking of DNA by the mitomycin antibiotic. The combination of mitomycin C with X-irradiation, to attack hypoxic and oxygenated tumor cell populations, respectively, has led to enhanced antitumor effects in mice bearing solid tumor implants and in patients with cancer of the head and neck. More efficacious kill of hypoxic tumor cells may be possible by the use of dicoumarol in combination with mitomycin or by the use of the related antibiotic porfiromycin. The findings support the use of an agent with specificity for hypoxic tumor cells in potentially curative regimens for solid tumors. PMID:3123053

  18. Immune microenvironments in solid tumors: new targets for therapy

    PubMed Central

    Shiao, Stephen L.; Ganesan, A. Preethi; Rugo, Hope S.; Coussens, Lisa M.

    2011-01-01

    Leukocytes and their soluble mediators play important regulatory roles in all aspects of solid tumor development. While immunotherapeutic strategies have conceptually held clinical promise, with the exception of a small percentage of patients, they have failed to demonstrate effective, consistent, and durable anti-cancer responses. Several subtypes of leukocytes that commonly infiltrate solid tumors harbor immunosuppressive activity and undoubtedly restrict the effectiveness of these strategies. Several of these same immune cells also foster tumor development by expression of potent protumor mediators. Given recent evidence revealing that immune-based mechanisms regulate the response to conventional cytotoxic therapy, it seems reasonable to speculate that tumor progression could be effectively diminished by combining cytotoxic strategies with therapies that blunt protumor immune-based effectors and/or neutralize those that instead impede development of desired anti-tumor immunity, thus providing synergistic effects between traditional cytotoxic and immune-modulatory approaches. PMID:22190457

  19. Diversity of dynamics and morphologies of invasive solid tumors

    NASA Astrophysics Data System (ADS)

    Jiao, Yang; Torquato, Salvatore

    2012-03-01

    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 [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.

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

    NASA Astrophysics Data System (ADS)

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

    2001-05-01

    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.

  1. Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver Dysfunction

    ClinicalTrials.gov

    2014-02-21

    IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell 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

  2. Analysis of virotherapy in solid tumor invasion.

    PubMed

    Malinzi, Joseph; Sibanda, Precious; Mambili-Mamboundou, Hermane

    2015-05-01

    Cancer treatment is an inexact science despite traditional cancer therapies. The traditional cancer treatments have high levels of toxicity and relatively low efficacy. Current research and clinical trials have indicated that virotherapy, a procedure which uses replication-competent viruses to kill cancer cells, has less toxicity and a high efficacy. However, the interaction dynamics of the tumor host, the virus, and the immune response is poorly understood due to its complexity. We present a mathematical analysis of models that study tumor-immune-virus interactions in the form of differential equations with spatial effects. A stability analysis is presented and we obtained analytical traveling wave solutions. Numerical simulations were obtained using fourth order Runge-Kutta and Crank-Nicholson methods. We show that the use of viruses as a cancer treatment can reduce the tumor cell concentration to a very low cancer dormant steady state or possibly deplete all tumor cells in body tissue. The traveling waves indicated an exponential increase and decrease in the cytotoxic-T-lymphocytes (CTLs) density and tumor load in the long term respectively. PMID:25725123

  3. Irinotecan in Treating Children With Refractory Solid Tumors

    ClinicalTrials.gov

    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

  4. Barriers to drug delivery in solid tumors

    PubMed Central

    Sriraman, Shravan Kumar; Aryasomayajula, Bhawani; Torchilin, Vladimir P

    2014-01-01

    Over the last decade, significant progress has been made in the field of drug delivery. The advent of engineered nanoparticles has allowed us to circumvent the initial limitations to drug delivery such as pharmacokinetics and solubility. However, in spite of significant advances to tumor targeting, an effective treatment strategy for malignant tumors still remains elusive. Tumors possess distinct physiological features which allow them to resist traditional treatment approaches. This combined with the complexity of the biological system presents significant hurdles to the site-specific delivery of therapeutic drugs. One of the key features of engineered nanoparticles is that these can be tailored to execute specific functions. With this review, we hope to provide the reader with a clear understanding and knowledge of biological barriers and the methods to exploit these characteristics to design multifunctional nanocarriers, effect useful dosing regimens and subsequently improve therapeutic outcomes in the clinic. PMID:25068098

  5. Tanespimycin and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2014-02-21

    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

  6. PXD101 and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2013-05-01

    Lymphoma; Stage IV Adult Immunoblastic Large Cell 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

  7. Exome Sequencing of an Adult Pituitary Atypical Teratoid Rhabdoid Tumor

    PubMed Central

    Biswas, Swethajit; Wood, Madeleine; Joshi, Abhijit; Bown, Nick; Strain, Lisa; Martinsson, Tommy; Campbell, James; Ashworth, Alan; Swain, Amanda

    2015-01-01

    Atypical teratoid rhabdoid tumors (AT/RTs) are rare pediatric brain tumors characterized by bialleic loss of the SMARCB1 tumor suppressor gene. In contrast to pediatric AT/RT that has a simple genome, very little is known about the adult AT/RT genomic landscape. Using a combination of whole-exome sequencing and high-resolution SNP array in a single adult pituitary AT/RT, we identified a total of 47 non-synonymous mutations, of which 20 were predicted to cause non-conservative amino acid substitutions, in addition to a subclone of cells with trisomy 8. We suggest that adult AT/RT may not be markedly dissimilar to other adult brain tumors where mutations in a range of genes, reflecting the functional specialization of different brain regions, but including SMARCB1 inactivation, may be required for its pathogenesis. PMID:26557502

  8. Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK1/2/3, ROS1, or ALK Gene Rearrangements (Fusions)

    ClinicalTrials.gov

    2016-09-13

    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

  9. Genetic Testing Plus Irinotecan in Treating Patients With Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-01-23

    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

  10. 3-AP and Gemcitabine in Treating Patients With Advanced Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-09-27

    -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

  11. Chimeric antigen receptor T-cell therapy for solid tumors

    PubMed Central

    Newick, Kheng; Moon, Edmund; Albelda, Steven M

    2016-01-01

    Chimeric antigen receptor (CAR) T cells are engineered constructs composed of synthetic receptors that direct T cells to surface antigens for subsequent elimination. Many CAR constructs are also manufactured with elements that augment T-cell persistence and activity. To date, CAR T cells have demonstrated tremendous success in eradicating hematological malignancies (e.g., CD19 CARs in leukemias). This success is not yet extrapolated to solid tumors, and the reasons for this are being actively investigated. Here in this mini-review, we discuss some of the key hurdles encountered by CAR T cells in the solid tumor microenvironment. PMID:27162934

  12. Solid pseudopapillary tumor of the pancreas: emphasis on differential diagnosis from aggressive tumors of the pancreas.

    PubMed

    Aydiner, Fatma; Erinanç, Hilal; Savaş, Berna; Erden, Esra; Karayalçin, Kaan

    2006-09-01

    Solid pseudopapillary tumor is an unusual primary tumor of the pancreas with a low potential for malignancy and unknown cell origin, seen mostly in young women. Although it is discussed among pancreatic epithelial tumors, many cases do not express cytokeratin but show neuroendocrine differentiation. Three cases (2 female, 1 male, aged 24, 45 and 50 years, respectively) of solid pseudopapillary tumor localized in the pancreas are presented. All cases displayed a well-circumscribed tumor, with an average diameter of 6 cm and a red-brown colored, hemorrhagic, cystic cut surface. Microscopically they were encapsulated with large areas composed of thin papillary formations and solid areas focally. Tumor cells were dyscohesive with small, round- to-oval, central nuclei, and vacuolated, clear or eosinophilic cytoplasm without mitotic activity. NSE, vimentin, synaptophysin, ER, PR, Ki-67, S-100, Pan CK, a1-antitrypsin, a2-antichymotrypsin, and antibodies were used in the immunohistochemical study. Vimentin, synaptophysin, NSE, PR, and a1-antitrypsin showed expression in all cases, while Pan-CK was expressed in two cases. Ki-67 expression was below 1% in all cases. Morphologic features of solid pseudopapillary tumor may be confused with pancreatic endocrine neoplasm and ductal adenocarcinoma. All cases showed features of histiocytic and neuroendocrine differentiation. Epithelial differentiation was identified in two cases. We conclude that immunohistochemistry is incapable of giving additional information for the diagnosis of solid pseudopapillary tumor due to different lines of differentiation of tumor cells. We believe that macroscopic and microscopic features (using hematoxylin and eosin stain) are more important for the diagnosis and differential diagnosis of this tumor. PMID:16941259

  13. Myeloid Cells as Targets for Therapy in Solid Tumors.

    PubMed

    Cotechini, Tiziana; Medler, Terry R; Coussens, Lisa M

    2015-01-01

    It is well established that cancer development ensues based on reciprocal interactions between genomically altered neoplastic cells and diverse populations of recruited "host" cells co-opted to support malignant progression. Among the host cells recruited into tumor microenvironments, several subtypes of myeloid cells, including macrophages, monocytes, dendritic cells, and granulocytes contribute to tumor development by providing tumor-promoting factors as well as a spectrum of molecules that suppress cytotoxic activities of T lymphocytes. Based on compelling preclinical data revealing that inhibition of critical myeloid-based programs leads to tumor suppression, novel immune-based therapies and approaches are now entering the clinic for evaluation. This review discusses mechanisms underlying protumorigenic programming of myeloid cells and discusses how targeting of these has potential to attenuate solid tumor progression via the induction and of mobilization CD8 cytotoxic T cell immunity. PMID:26222088

  14. Myeloid Cells as Targets for Therapy in Solid Tumors

    PubMed Central

    Cotechini, Tiziana; Medler, Terry R.; Coussens, Lisa M.

    2016-01-01

    It is well established that cancer development ensues based on reciprocal interactions between genomically altered neoplastic cells and diverse populations of recruited “host” cells co-opted to support malignant progression. Among the host cells recruited into tumor microenvironments, several subtypes of myeloid cells, including macrophages, monocytes, dendritic cells, and granulocytes contribute to tumor development by providing tumor-promoting factors as well as a spectrum of molecules that suppress cytotoxic activities of T lymphocytes. Based on compelling preclinical data revealing that inhibition of critical myeloid-based programs leads to tumor suppression, novel immune-based therapies and approaches are now entering the clinic for evaluation. This review discusses mechanisms underlying protumorigenic programming of myeloid cells and discusses how targeting of these has potential to attenuate solid tumor progression via the induction and of mobilization CD8+ cytotoxic T cell immunity. PMID:26222088

  15. Dextran-doxorubicin/chitosan nanoparticles for solid tumor therapy.

    PubMed

    Bisht, Savita; Maitra, Amarnath

    2009-01-01

    Chemotherapy is a major therapeutic approach for the treatment of localized and metastasized cancers. Whereas potent chemotherapeutic agents seem promising in the test tube, clinical trials often fail due to unfavorable pharmacokinetics, poor delivery, low local concentrations, and limited accumulation in the target cell. The pathophysiology of the tumor vasculature and stromal compartment presents a major obstacle to effective delivery of agents to solid tumors. Poor perfusion of the tumor, arterio-venous shunting, necrotic and hypoxic areas, as well as a high interstitial fluid pressure work against favorable drug uptake. Thus, targeted drug delivery using long-circulating particulate drug carriers such as hydrogels of controlled size (<100 nm diameter) holds immense potential to improve the treatment of cancer by selectively providing therapeutically effective drug concentrations at the tumor site [through enhanced permeability and retention (EPR) effect] while reducing undesirable side effects. This review focuses on the progress of targeted delivery of nanoparticulated anticancer drug such as doxorubicin chemically conjugated with dextran and encapsulated in chitosan nanoparticles to solid tumor with reduced side effect of drug. Regulated particle size and long circulation of these hydrogel nanoparticles in blood help them accumulate in tumor tissue through EPR effect as evident from the significant regression of the tumor volume. The cardiotoxicity of doxorubicin can be minimized by coupling the drug with dextran and encapsulating it in chitosan nanoparticles. PMID:20049807

  16. Multipotent Mesenchymal Stromal Cells: Possible Culprits in Solid Tumors?

    PubMed Central

    Johann, Pascal David; Müller, Ingo

    2015-01-01

    The clinical use of bone marrow derived multipotent mesenchymal stromal cells (BM-MSCs) in different settings ranging from tissue engineering to immunotherapies has prompted investigations on the properties of these cells in a variety of other tissues. Particularly the role of MSCs in solid tumors has been the subject of many experimental approaches. While a clear phenotypical distinction of tumor associated fibroblasts (TAFs) and MSCs within the tumor microenvironment is still missing, the homing of bone marrow MSCs in tumor sites has been extensively studied. Both, tumor-promoting and tumor-inhibiting effects of BM-MSCs have been described in this context. This ambiguity requires a reappraisal of the different studies and experimental methods employed. Here, we review the current literature on tumor-promoting and tumor-inhibiting effects of BM-MSCs with a particular emphasis on their interplay with components of the immune system and also highlight a potential role of MSCs as cell of origin for certain mesenchymal tumors. PMID:26273308

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

    PubMed Central

    Ramachandran, Shaliny; Ient, Jonathan; Göttgens, Eva-Leonne; Krieg, Adam J.; Hammond, Ester M.

    2015-01-01

    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. PMID:26426056

  18. [Chemotherapy for brain tumors in adult patients].

    PubMed

    Weller, M

    2008-02-01

    Chemotherapy has become a third major treatment option for patients with brain tumors, in addition to surgery and radiotherapy. The role of chemotherapy in the treatment of gliomas is no longer limited to recurrent disease. Temozolomide has become the standard of care in newly diagnosed glioblastoma. Several ongoing trials seek to define the role of chemotherapy in the primary care of other gliomas. Some of these studies are no longer only based on histological diagnoses, but take into consideration molecular markers such as MGMT promoter methylation and loss of genetic material on chromosomal arms 1p and 19q. Outside such clinical trials chemotherapy is used in addition to radiotherapy, e.g., in anaplastic astrocytoma, medulloblastoma or germ cell tumors, or as an alternative to radiotherapy, e.g., in anaplastic oligodendroglial tumors or low-grade gliomas. In contrast, there is no established role for chemotherapy in other tumors such as ependymomas, meningiomas or neurinomas. Primary cerebral lymphomas are probably the only brain tumors which can be cured by chemotherapy alone and only by chemotherapy. The chemotherapy of brain metastases follows the recommendations for the respective primary tumors. Further, strategies of combined radiochemotherapy using mainly temozolomide or topotecan are currently explored. Leptomeningeal metastases are treated by radiotherapy or systemic or intrathecal chemotherapy depending on their pattern of growth. PMID:18253773

  19. Immunomagnetic separation can enrich fixed solid tumors for epithelial cells.

    PubMed Central

    Yaremko, M. L.; Kelemen, P. R.; Kutza, C.; Barker, D.; Westbrook, C. A.

    1996-01-01

    Immunomagnetic separation is a highly specific technique for the enrichment or isolation of cells from a variety of fresh tissues and microorganisms or molecules from suspensions. Because new techniques for molecular analysis of solid tumors are now applicable to fixed tissue but sometimes require or benefit from enrichment for tumor cells, we tested the efficacy of immunomagnetic separation for enriching fixed solid tumors for malignant epithelial cells. We applied it to two different tumors and fixation methods to separate neoplastic from non-neoplastic cells in primary colorectal cancers and metastatic breast cancers, and were able to enrich to a high degree of purity. Immunomagnetic separation was effective in unembedded fixed tissue as well as fixed paraffin-embedded tissue. The magnetically separated cells were amenable to fluorescence in situ hybridization and polymerase chain reaction amplification of their DNA with minimal additional manipulation. The high degree of enrichment achieved before amplification contributed to interpretation of loss of heterozygosity in metastatic breast cancers, and simplified fluorescence in situ hybridization analysis because only neoplastic cells were hybridized and counted. Immunomagnetic separation is effective for the enrichment of fixed solid tumors, can be performed with widely available commercial antibodies, and requires little specialized instrumentation. It can contribute to interpretation of results in situations where enrichment by other methods is difficult or not possible. Images Figure 1 Figure 2 Figure 3 PMID:8546231

  20. Strategies to Increase Drug Penetration in Solid Tumors

    PubMed Central

    Choi, Il-Kyu; Strauss, Robert; Richter, Maximilian; Yun, Chae-Ok; Lieber, André

    2013-01-01

    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, anti-tumor 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 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- or stem cell-mediated gene transfer. We will provide examples that relaxin-based approaches increase the anti-tumor efficacy of oncolytic viruses, monoclonal antibodies, and T cells. PMID:23898462

  1. Bioengineered models of solid human tumors for cancer research

    PubMed Central

    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

  2. A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies

    ClinicalTrials.gov

    2016-08-16

    Advanced Solid Tumors With Alterations of FGFR1, 2 and/or 3;; Squamous Lung Cancer With FGFR1 Amplification;; Bladder Cancer With FGFR3 Mutation or Fusion; Advanced Solid Tumors With FGFR1 Amplication,; Advanced Solid Tumors With FGFR2 Amplication,; Advanced Solid Tumors With FGFR3 Mutation

  3. SB-715992 in Treating Patients With Metastatic or Unresectable Solid Tumors or Hodgkin's or Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-01-11

    Adult Grade III Lymphomatoid Granulomatosis; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic 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 Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  4. ReCAP: Serum Tumor Marker Use in Patients With Advanced Solid Tumors

    PubMed Central

    Wright, Jason D.; Vasan, Sowmya; Neugut, Alfred I.; Tergas, Ana; Hu, Jim C.; Hershman, Dawn L.

    2016-01-01

    QUESTION ASKED: The objective of this study is to evaluate the frequency of tumor marker use in patients with advanced solid tumors. SUMMARY ANSWER: Over a 1-year period, the mean number of any individual test per patient was seven tests, and the maximum number was 35 tests; the mean number of total tests per patient was 12 tests, and the maximum number was 70 tests. In a 1-year time frame, 16.3% of patients had more than 12 individual tests, and 34.3% had more than one individual test in a 1-month span. METHODS: For each patient with a diagnosis of advanced solid tumor who had outpatient visits between July 1, 2013, and June 30, 2014, at Columbia University Medical Center, we recorded the dates of the following tumor marker tests: α-fetoprotein, CA-125, CA 15-3, CA 19-9, CA 27-29, and carcinoembryonic antigen (CEA). BIAS, CONFOUNDING FACTOR(S), DRAWBACKS: This was a 1-year evaluation of tumor marker use at a single institution. As a result, our findings may be skewed by the practice patterns of a few individual providers. Our cancer center is an urban academic tertiary care center; as a result, our experience may not be applicable to the general population. REAL-LIFE IMPLICATIONS: We found a high rate of serum tumor marker testing overuse in patients with advanced solid tumors. There is currently a lack of evidence supporting the effectiveness of frequent tumor marker testing, and additional studies are needed to inform practice. Interventions to reduce overuse could help reduce the financial burden of cancer care. Future research should define the minimal frequency of testing. In the meantime, efforts should be made to limit use of tumor marker testing in patients with advanced solid tumors. FIG 2. Percentage of patients (N = 928) with solid tumors who had excessive tumor marker testing in 1 month (> one test in 1 month). (*) Maximum number of tests over 1-month period. AFP, α-fetoprotein; CEA, carcinoembryonic antigen. PMID:26374862

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

    ClinicalTrials.gov

    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

  6. Association between EZH2 expression, silencing of tumor suppressors and disease outcome in solid tumors

    PubMed Central

    Wassef, M.; Michaud, A.; Margueron, R.

    2016-01-01

    ABSTRACT EZH2, the main catalytic component of the Polycomb Repressive Complex 2 (PRC2) is apparently upregulated in most solid tumors. Furthermore its expression generally associates with poor prognosis. It was proposed that this correlation reflects a causal event, EZH2 mediating the silencing of key tumor suppressor loci. In contrast, we recently showed that EZH2 is dispensable for solid tumor development and that its elevated expression reflects the abnormally high proliferation rate of cancer cells. Here, we investigate the functional association between EZH2 expression and silencing of key tumor suppressor loci and further illustrate the confounding effect of proliferation on EZH2′s association to outcome. PMID:27419533

  7. Low Density Lipid Nanoparticles for Solid Tumor Targeting

    PubMed Central

    Shrivastava, Mayank; Jain, Aviral; Gulbake, Arvind; Hurkat, Pooja; Jain, Neeti; Vijayraghwan, R.; Jain, Sanjay K.

    2014-01-01

    Abstract One of the most significant characteristics of cancer cells is their rapid dividing ability and overexpression of LDL receptors, which offers an opportunity for the selective targeting of these cells. 5-Fluorouracil (5-FU)-encapsulated low density lipid nanoparticles (LDLN) were prepared by the emulsion congealing method which mimics the plasma-derived LDL by acquiring the apolipoprotein B-100 from the blood. The average particle size, transmission electron microscope (TEM), and drug content of the prepared LDLN dispersion were found to be 161±3.5 nm, with spherical shape, and 0.370±0.05 mg/mL, respectively. In vitro release studies revealed a sustained profile which decreased with a lapse of time. In vivo studies of 5-FU serum concentration and biodistribution revealed a 5-FU serum concentration of 8.5% in tumor cells and about 2.1% in the liver at the end of 24 hr from LDLN. Tumor growth suppression studies showed 185.42% average tumor growth and 89.76% tumor height as compared to the control exhibiting tumor growth at 1166.47% and tumor height at 176.07%. On the basis of these collective data, it is suggested that a higher accumulation of LDLN, when given as an IV, in solid tumors is attributed to the active uptake of LDLN via LDL receptors via apolipoprotein B-100. PMID:26279976

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

    PubMed Central

    Valdespino, Victor; Valdespino, Patricia M

    2015-01-01

    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 undertaking new cancer epigenetic-therapy clinical trails. PMID:26346546

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

    PubMed Central

    2012-01-01

    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. PMID:22947174

  10. Altered expression of natively glycosylated dystroglycan in pediatric solid tumors

    PubMed Central

    Martin, Laura T.; Glass, Matthew; Dosunmu, Eniolami; Martin, Paul T.

    2010-01-01

    Summary Altered glycosylation and/or expression of dystroglycan have been reported in forms of congenital muscular dystrophy as well as in cancers of the breast, colon, and oral epithelium. To date, however, there has been no study of the expression of dystroglycan in pediatric solid tumors. Using a combination of immunostaining on tissue microarrays and immunoblotting of snap-frozen unfixed tissues, we demonstrate a significant reduction in native α dystroglycan expression in pediatric alveolar rhabdomyosarcoma (RMS), embryonal RMS, neuroblastoma (NBL), and medulloblastoma, whereas expression of β dystroglycan, which is cotranslated with α dystroglycan, is largely unchanged. Loss of native α dystroglycan expression was significantly more pronounced in stage 4 NBL than in pooled samples of stage 1 and stage 2 NBL, suggesting that loss of native α dystroglycan expression increases with advancing tumor stage. Neuroblastoma and RMS samples with reduced expression of native α dystroglycan also showed reduced laminin binding in laminin overlay experiments. Expression of natively glycosylated α dystroglycan was not altered in several other pediatric tumor types when compared with appropriate normal tissue controls. These data provide the first evidence that α dystroglycan glycosylation and laminin binding to α dystroglycan are altered in certain pediatric solid tumors and suggest that aberrant dystroglycan glycosylation may contribute to tumor cell biology in patients with RMS, medulloblastoma, and NBL. PMID:17640712

  11. Extrapancreatic solid pseudopapillary tumors: A clinicopathological analysis of two cases

    PubMed Central

    GUO, XINGMEI; LI, NAN; REN, KAI; WU, LIGAO; MA, LI; WU, SHIWU; XIE, FENGMEI; FENG, ZHENZHONG

    2016-01-01

    Solid pseudopapillary tumors (SPTs) are unusual neoplasms that mostly occur in the pancreas, and predominantly affect young women. As a low-grade malignant neoplasm of the exocrine pancreas, they occasionally metastasize, usually to the liver or peritoneum. It has been reported that <1% of SPTs are primary extrapancreatic SPTs. In the present study, we present two rare, but conspicuous extrapancreatic SPTs. Both occurred in young women, and showed good prognoses following surgery. One was a recurrent SPT of the pancreas that metastasized to the ovary, and the other was a distinct primary neoplasm that arose in the retroperitoneal area. The pathological features of the two tumors, including solid and pseudopapillary growth patterns with pale or eosinophilic cytoplasm, were characteristic of SPTs of the pancreas. However, in the case of the metastatic ovarian tumor, focal necrosis and an increased nuclear-to-cytoplasmic ratio were observed. The presence of positive nuclear-cytoplasmic β-catenin, the loss of membranous E-cadherin expression, and a perinuclear punctate CD99 staining pattern on immunohistochemistical analysis, were essential features for diagnosis. The aim of the present study was to compare the morphological and immunohistochemical features of these tumors with those typical of pancreatic SPTs, and to raise awareness that SPTs are able to metastasize to unusual sites, and may also arise as primary tumors outside the pancreas, which may lead to diagnostic dilemmas. PMID:27123293

  12. Onivyde for the therapy of multiple solid tumors

    PubMed Central

    Zhang, Haijun

    2016-01-01

    Drug delivery system based on nanobiotechnology can improve the pharmacokinetics and therapeutic index of chemotherapeutic agents, which has revolutionized tumor therapy. Onivyde, also known as MM-398 or PEP02, is a nanoliposomal formulation of irinotecan which has demonstrated encouraging anticancer activity across a broad range of malignancies, including pancreatic cancer, esophago-gastric cancer, and colorectal cancer. This up-to-date review not only focuses on the structure, pharmacokinetics, and pharmacogenetics of Onivyde but also summarizes clinical trials and recommends Onivyde for patients with advanced solid tumors. PMID:27284250

  13. Onivyde for the therapy of multiple solid tumors.

    PubMed

    Zhang, Haijun

    2016-01-01

    Drug delivery system based on nanobiotechnology can improve the pharmacokinetics and therapeutic index of chemotherapeutic agents, which has revolutionized tumor therapy. Onivyde, also known as MM-398 or PEP02, is a nanoliposomal formulation of irinotecan which has demonstrated encouraging anticancer activity across a broad range of malignancies, including pancreatic cancer, esophago-gastric cancer, and colorectal cancer. This up-to-date review not only focuses on the structure, pharmacokinetics, and pharmacogenetics of Onivyde but also summarizes clinical trials and recommends Onivyde for patients with advanced solid tumors. PMID:27284250

  14. Biomodulatory Approaches to Photodynamic Therapy for Solid Tumors

    PubMed Central

    Anand, Sanjay; Ortel, Bernhard J.; Pereira, Stephen P.; Hasan, Tayyaba; Maytin, Edward V.

    2012-01-01

    Photodynamic Therapy (PDT) uses a photosensitizing drug in combination with visible light to kill cancer cells. PDT has an advantage over surgery or ionizing radiation because PDT can eliminate tumors without causing fibrosis or scarring. Disadvantages include the dual need for drug and light, and a generally lower efficacy for PDT versus surgery. This minireview describes basic principles of PDT, photosensitizers available, and aspects of tumor biology that may provide further opportunities for treatment optimization. An emerging biomodulatory approach, using methotrexate or Vitamin D in combination with aminolevulinate-based PDT, is described. Finally, current clinical uses of PDT for solid malignancies are reviewed. PMID:22842096

  15. Hypoxic cell turnover in different solid tumor lines

    SciTech Connect

    Ljungkvist, Anna S.E. . E-mail: a.ljungkvist@rther.umcn.nl; Bussink, Johan; Kaanders, Johannes H.A.M.; Rijken, Paulus F.J.W.; Begg, Adrian C.; Raleigh, James A.; Kogel, Albert J. van der

    2005-07-15

    Purpose: Most solid tumors contain hypoxic cells, and the amount of tumor hypoxia has been shown to have a negative impact on the outcome of radiotherapy. The efficacy of combined modality treatments depends both on the sequence and timing of the treatments. Hypoxic cell turnover in tumors may be important for optimal scheduling of combined modality treatments, especially when hypoxic cell targeting is involved. Methods and Materials: Previously we have shown that a double bioreductive hypoxic marker assay could be used to detect changes of tumor hypoxia in relation to the tumor vasculature after carbogen and hydralazine treatments. This assay was used in the current study to establish the turnover rate of hypoxic cells in three different tumor models. The first hypoxic marker, pimonidazole, was administered at variable times before tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. Hypoxic cell turnover was defined as loss of pimonidazole (first marker) relative to CCI-103F (second marker). Results: The half-life of hypoxic cell turnover was 17 h in the murine C38 colon carcinoma line, 23 h and 49 h in the human xenograft lines MEC82 and SCCNij3, respectively. Within 24 h, loss of pimonidazole-stained areas in C38 and MEC82 occurred concurrent with the appearance of pimonidazole positive cell debris in necrotic regions. In C38 and MEC82, most of the hypoxic cells had disappeared after 48 h, whereas in SCCNij3, viable cells that had been labeled with pimonidazole were still observed after 5 days. Conclusions: The present study demonstrates that the double hypoxia marker assay can be used to study changes in both the proportion of hypoxic tumor cells and their lifespan at the same time. The present study shows that large differences in hypoxic cell turnover rates may exist among tumor lines, with half-lives ranging from 17-49 h.

  16. Local iontophoretic administration of cytotoxic therapies to solid tumors

    PubMed Central

    Byrne, James D.; Jajja, Mohammad R. N.; O’Neill, Adrian T.; Bickford, Lissett R.; Keeler, Amanda W.; Hyder, Nabeel; Wagner, Kyle; Deal, Allison; Little, Ryan E.; Moffitt, Richard A.; Stack, Colleen; Nelson, Meredith; Brooks, Christopher R.; Lee, William; Luft, J. Chris; Napier, Mary E.; Darr, David; Anders, Carey K.; Stack, Richard; Tepper, Joel E.; Wang, Andrew Z.; Zamboni, William C.; Yeh, Jen Jen; DeSimone, Joseph M.

    2015-01-01

    Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents while mitigating their side effects, we have developed modalities for the localized iontophoretic delivery of cytotoxic agents. These iontophoretic devices were designed to be implanted proximal to the tumor with external control of power and drug flow. Three distinct orthotopic mouse models of cancer and a canine model were evaluated for device efficacy and toxicity. Orthotopic patient-derived pancreatic cancer xenografts treated biweekly with gemcitabine via the device for 7 weeks experienced a mean log2 fold change in tumor volume of −0.8 compared to a mean log2 fold change in tumor volume of 1.1 for intravenous (IV) gemcitabine, 3.0 for IV saline, and 2.6 for device saline groups. The weekly coadministration of systemic cisplatin therapy and transdermal device cisplatin therapy significantly increased tumor growth inhibition and doubled the survival in two aggressive orthotopic models of breast cancer. The addition of radiotherapy to this treatment further extended survival. Device delivery of gemcitabine in dogs resulted in more than 7-fold difference in local drug concentrations and 25-fold lower systemic drug levels than the IV treatment. Overall, these devices have potential paradigm shifting implications for the treatment of pancreatic, breast, and other solid tumors. PMID:25653220

  17. Local iontophoretic administration of cytotoxic therapies to solid tumors.

    PubMed

    Byrne, James D; Jajja, Mohammad R N; O'Neill, Adrian T; Bickford, Lissett R; Keeler, Amanda W; Hyder, Nabeel; Wagner, Kyle; Deal, Allison; Little, Ryan E; Moffitt, Richard A; Stack, Colleen; Nelson, Meredith; Brooks, Christopher R; Lee, William; Luft, J Chris; Napier, Mary E; Darr, David; Anders, Carey K; Stack, Richard; Tepper, Joel E; Wang, Andrew Z; Zamboni, William C; Yeh, Jen Jen; DeSimone, Joseph M

    2015-02-01

    Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents while mitigating their side effects, we have developed modalities for the localized iontophoretic delivery of cytotoxic agents. These iontophoretic devices were designed to be implanted proximal to the tumor with external control of power and drug flow. Three distinct orthotopic mouse models of cancer and a canine model were evaluated for device efficacy and toxicity. Orthotopic patient-derived pancreatic cancer xenografts treated biweekly with gemcitabine via the device for 7 weeks experienced a mean log2 fold change in tumor volume of -0.8 compared to a mean log2 fold change in tumor volume of 1.1 for intravenous (IV) gemcitabine, 3.0 for IV saline, and 2.6 for device saline groups. The weekly coadministration of systemic cisplatin therapy and transdermal device cisplatin therapy significantly increased tumor growth inhibition and doubled the survival in two aggressive orthotopic models of breast cancer. The addition of radiotherapy to this treatment further extended survival. Device delivery of gemcitabine in dogs resulted in more than 7-fold difference in local drug concentrations and 25-fold lower systemic drug levels than the IV treatment. Overall, these devices have potential paradigm shifting implications for the treatment of pancreatic, breast, and other solid tumors. PMID:25653220

  18. L-Asparaginase delivered by Salmonella typhimurium suppresses solid tumors

    PubMed Central

    Kim, Kwangsoo; Jeong, Jae Ho; Lim, Daejin; Hong, Yeongjin; Lim, Hyung-Ju; Kim, Geun-Joong; Shin, So-ra; Lee, Je-Jung; Yun, Misun; Harris, Robert A; Min, Jung-Joon; Choy, Hyon E

    2015-01-01

    Bacteria can be engineered to deliver anticancer proteins to tumors via a controlled expression system that maximizes the concentration of the therapeutic agent in the tumor. L-asparaginase (L-ASNase), which primarily converts asparagine to aspartate, is an anticancer protein used to treat acute lymphoblastic leukemia. In this study, Salmonellae were engineered to express L-ASNase selectively within tumor tissues using the inducible araBAD promoter system of Escherichia coli. Antitumor efficacy of the engineered bacteria was demonstrated in vivo in solid malignancies. This result demonstrates the merit of bacteria as cancer drug delivery vehicles to administer cancer-starving proteins such as L-ASNase to be effective selectively within the microenvironment of cancer tissue. PMID:27119104

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

    PubMed Central

    Namazi, Hamidreza; Kulish, Vladimir V.; Wong, Albert; Nazeri, Sina

    2016-01-01

    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. PMID:27376087

  20. Rationally Repurposing Ruxolitinib (Jakafi (®)) as a Solid Tumor Therapeutic.

    PubMed

    Tavallai, Mehrad; Booth, Laurence; Roberts, Jane L; Poklepovic, Andrew; Dent, Paul

    2016-01-01

    We determined whether the approved myelofibrosis drug ruxolitinib (Jakafi(®)), an inhibitor of Janus kinases 1/2 (JAK1 and JAK2), could be repurposed as an anti-cancer agent for solid tumors. Ruxolitinib synergistically interacted with dual ERBB1/2/4 inhibitors to kill breast as well as lung, ovarian and brain cancer cells. Knock down of JAK1/2 or of ERBB1/2/3/4 recapitulated on-target drug effects. The combination of (ruxolitinib + ERBB1/2/4 inhibitor) rapidly inactivated AKT, mTORC1, mTORC2, STAT3, and STAT5, and activated eIF2α. In parallel, the drug combination reduced expression of MCL-1, BCL-XL, HSP90, HSP70, and GRP78, and increased expression of Beclin1. Activated forms of STAT3, AKT, or mTOR prevented the drug-induced decline in BCL-XL, MCL-1, HSP90, and HSP70 levels. Over-expression of chaperones maintained AKT/mTOR activity in the presence of drugs and protected tumor cells from the drug combination. Expression of dominant negative eIF2α S51A prevented the increase in Beclin1 expression and protected tumor cells from the drug combination. Loss of mTOR activity was associated with increased ATG13 S318 phosphorylation and with autophagosome formation. Autophagosomes initially co-localized with mitochondria and subsequently with lysosomes. Knock down of Beclin1 suppressed: drug-induced mitophagy; the activation of the toxic BH3 domain proteins BAX and BAK; and tumor cell killing. Knock down of apoptosis-inducing factor (AIF) protected tumor cells from the drug combination, whereas blockade of caspase 9 signaling did not. The drug combination released AIF into the cytosol and increased nuclear AIF: eIF3A co-localization. A 4-day transient exposure of orthotopic tumors to (ruxolitinib + afatinib) profoundly reduced mammary tumor growth over the following 35 days. Re-grown tumors exhibited high levels of BAD S112 phosphorylation and activation of ERK1/2 and NFκB. Our data demonstrate that mitophagy is an essential component of (ruxolitinib

  1. Pediatric Cancers and Brain Tumors in Adolescents and Young Adults.

    PubMed

    McCabe, Martin G; Valteau-Couanet, Dominique

    2016-01-01

    Embryonal tumors classically occur in young children, some principally within the first year of life. Prospective national and international clinical trials during recent decades have brought about progressive improvements in survival, and associated biological studies have advanced our understanding of tumor biology, in some cases allowing biological tumor characteristics to be harnessed for therapeutic benefit. Embryonal tumors continue to occur, albeit less commonly, during childhood, adolescence and throughout adulthood. These tumors are less well understood, usually not managed according to standardized protocols and rarely included in clinical trials. Survival outcomes are generally poorer than their childhood equivalents. We present here a summary of the published literature on embryonal tumors that present ectopically during adolescence and adulthood. We show that for some tumors protocol-driven treatment, supported by accurate and complete diagnostics and staging, can result in equivalent outcomes to those seen during childhood. We make the case that clinical trial eligibility criteria should be disease-based rather than age-based, and support improvements in dialogue between children's and adults' cancer clinicians to improve outcomes for these rare tumors. PMID:27595358

  2. Drug delivery to solid tumors by elastin-like polypeptides

    PubMed Central

    McDaniel, Jonathan R.; Callahan, Daniel J.; Chilkoti, Ashutosh

    2010-01-01

    Thermally responsive elastin-like polypeptides (ELPs) are a promising class of recombinant biopolymers for the delivery of drugs and imaging agents to solid tumors via systemic or local administration. This article reviews four applications of ELPs to drug delivery, with each delivery mechanism designed to best exploit the relationship between the characteristic transition temperature (Tt) of the ELP and body temperature (Tb). First, when Tt >> Tb, small hydrophobic drugs can be conjugated to the C-terminus of the ELP to impart the amphiphilicity needed to mediate the self-assembly of nanoparticles. These systemically delivered ELP-drug nanoparticles preferentially localize to the tumor site via the EPR effect, resulting in reduced toxicity and enhanced treatment efficacy. The remaining three approaches take direct advantage of the thermal responsiveness of ELPs. In the second strategy, where Tb < Tt < 42 °C, an ELP-drug conjugate can be injected in conjunction with external application of mild hyperthermia to the tumor to induce ELP coacervation and an increase in concentration within the tumor vasculature. The third approach utilizes hydrophilic-hydrophobic ELP block copolymers that have been designed to assemble into nanoparticles in response to hyperthermai due to the independent thermal transition of the hydrophobic block, thus resulting in multivalent ligand display of a ligand for spatially enhanced vascular targeting. In the final strategy, ELPs with Tt < Tb are conjugated with radiotherapeutics, injtect intioa tumor where they undergo coacervation to form an injectable drug depot for intratumoral delivery. These injectable coacervate ELP-radionuclide depots display a long residence in the tumor and result in inhibition of tumor growth. PMID:20546809

  3. RO4929097 and Capecitabine in Treating Patients With Refractory Solid Tumors

    ClinicalTrials.gov

    2014-11-06

    Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Colon Cancer; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Rectal Cancer; Stage III Small Lymphocytic Lymphoma; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Breast Cancer; Stage IV Colon Cancer; 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 Rectal Cancer; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  4. Cross-talk among myeloid-derived suppressor cells, macrophages, and tumor cells impacts the inflammatory milieu of solid tumors

    PubMed Central

    Beury, Daniel W.; Parker, Katherine H.; Nyandjo, Maeva; Sinha, Pratima; Carter, Kayla A.; Ostrand-Rosenberg, Suzanne

    2014-01-01

    MDSC and macrophages are present in most solid tumors and are important drivers of immune suppression and inflammation. It is established that cross-talk between MDSC and macrophages impacts anti-tumor immunity; however, interactions between tumor cells and MDSC or macrophages are less well studied. To examine potential interactions between these cells, we studied the impact of MDSC, macrophages, and four murine tumor cell lines on each other, both in vitro and in vivo. We focused on IL-6, IL-10, IL-12, TNF-α, and NO, as these molecules are produced by macrophages, MDSC, and many tumor cells; are present in most solid tumors; and regulate inflammation. In vitro studies demonstrated that MDSC-produced IL-10 decreased macrophage IL-6 and TNF-α and increased NO. IL-6 indirectly regulated MDSC IL-10. Tumor cells increased MDSC IL-6 and vice versa. Tumor cells also increased macrophage IL-6 and NO and decreased macrophage TNF-α. Tumor cell-driven macrophage IL-6 was reduced by MDSC, and tumor cells and MDSC enhanced macrophage NO. In vivo analysis of solid tumors identified IL-6 and IL-10 as the dominant cytokines and demonstrated that these molecules were produced predominantly by stromal cells. These results suggest that inflammation within solid tumors is regulated by the ratio of tumor cells to MDSC and macrophages and that interactions of these cells have the potential to alter significantly the inflammatory milieu within the tumor microenvironment. PMID:25170116

  5. Targeting JAK kinase in solid tumors: emerging opportunities and challenges.

    PubMed

    Buchert, M; Burns, C J; Ernst, M

    2016-02-25

    Various human malignancies are characterized by excessive activation of the Janus family of cytoplasmic tyrosine kinases (JAK) and their associated transcription factors STAT3 and STAT5. In the majority of solid tumors, this occurs in response to increased abundance of inflammatory cytokines in the tumor microenvironment prominently produced by infiltrating innate immune cells. Many of these cytokines share common receptor subunits and belong to the interleukin (IL)-6/IL-11, IL-10/IL-22 and IL-12/IL-23 families. Therapeutic inhibition of the JAK/STAT3 pathway potentially offers considerable benefit owing to the capacity of JAK/STAT3 signaling to promote cancer hallmarks in the tumor and its environment, including proliferation, survival, angiogenesis, tumor metabolism while suppressing antitumor immunity. This is further emphasized by the current successful clinical applications of JAK-specific small molecule inhibitors for the treatment of inflammatory disorders and hematopoietic malignancies. Here we review current preclinical applications for JAK inhibitors for the treatment of solid cancers in mice, with a focus on the most common malignancies emanating from oncogenic transformation of the epithelial mucosa in the stomach and colon. Emerging data with small molecule JAK-specific adenosine triphosphate-binding analogs corroborate genetic findings and suggest that interference with the JAK/STAT3 pathway may suppress the growth of the most common forms of sporadic colon cancers that arise from mutations of the APC tumor suppressor gene. Likewise inhibition of cytokine-dependent activation of the JAK/STAT3 pathway may also afford orthogonal treatment opportunities for other oncogene-addicted cancer cells that have gained drug resistance. PMID:25982279

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

    PubMed

    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. PMID:25763737

  7. Developing vascular and hypoxia based theranostics in solid tumors

    NASA Astrophysics Data System (ADS)

    Koonce, Nathan A.

    Tissue hypoxia was recognized for its biological attenuating effects on ionizing radiation over a century ago and is a characteristic feature of many solid tumors. Clinical and experimental evidence indicates tumor hypoxia plays diverse and key roles in tumor progression, angiogenesis, and resistance to chemotherapy/radiotherapy. Hypoxia has known effects on progression and resistance to several standard treatment approaches and the significant history of study might suggest diagnostic imaging and therapeutic interventions would be routine in oncological practice. Curiously, this is not the case and the research results involved in this report will attempt to better understand and contribute to why this gap in knowledge exists and a rationale for harnessing the potential of detecting and targeting hypoxia. Despite the addition of oxygen and reversal of hypoxia being known as the best radiosensitizer, hypoxia remains unexploited in clinical cancer therapy. The studies reported herein detail development of a novel imaging technique to detect a subtype of tumor hypoxia, vascular hypoxia or hypoxemia, with a 17-fold increase (p<0.05) in uptake of pimonidazole targeted microbubbles observed compared to controls. This technique creates the potential to study the role of hypoxemia in progression and therapeutic response. Additionally, description of a nanoparticle-based therapy that targets tumor areas associated with tumor hypoxia and the tumor microenvironment in general is reported. TNF-loaded nanoparticles combined with radiotherapy resulted in a 5.25-fold growth delay that was found to be synergistic (p<0.05) and suggests clinical evaluation is warranted. An additional study to evaluate an approach to use thermal ablation of intratumoral hypoxia by an image-guided technique developed in our group is described along with a sequence dependence of radiation preceding ablation. A final study on the use of galectin-1 antagonist to significantly decrease (p<0.05) hypoxia

  8. Diagnosis of and therapy for solid tumors with radiolabeled antibodies and immune fragments

    SciTech Connect

    Carrasquillo, J.A.; Krohn, K.A.; Beaumier, P.; McGuffin, R.W.; Brown, J.P.; Hellstroem, K.E.; Hellstroem, I.; Larson, S.M.

    1984-01-01

    Antibodies which are directed against human tumor-associated antigens can potentially be used as carriers of radioactivity for in vivo diagnosis (radioimmunodetection) or treatment (radioimmunotherapy) of solid tumors, including colon, hepatoma, cholangiocarcinoma, and melanoma. Murine monoclonal antibodies (MOAB), produced by the hybridoma technique of Kohler and Milstein, are replacing conventional heterosera as sources of antibodies, because MOAB can be produced in large quantities as reproducible reagents with homogeneous binding properties. We have studied human melanoma using MOAB IgG and Fab fragments that recognize the human melanoma-associated antigens p97 and ''high-molecular-weight antigen''. Both antigens are found in the membrane of melanomas at much larger concentrations than in normal adult tissues. We have performed radioimmunodetection studies with whole immunoglobulin and have detected 88% of lesions greater than 1.5 cm. We have used Fab fragments for radioimmunotherapy and have found that large doses of radiolabeled antibodies (up to 342 mCi) can be repetitively given to patients without excessive end-organ toxicity. Two of three patients treated with high-dose radiolabeled antimelanoma Fab showed an effect from the treatment. Although both technical and biologic problems remain, the use of radiolabeled antibodies that are directed against tumor-associated antigens holds future promise as a new therapeutic approach to solid tumors that are resistant to conventional therapy.

  9. Life Satisfaction in Adult Survivors of Childhood Brain Tumors

    PubMed Central

    Crom, Deborah B.; Li, Zhenghong; Brinkman, Tara M.; Hudson, Melissa M.; Armstrong, Gregory T.; Neglia, Joseph; Ness, Kirsten K.

    2014-01-01

    Adult survivors of childhood brain tumors experience multiple, significant, life-long deficits as a consequence of their malignancy and therapy. Current survivorship literature documents the substantial impact such impairments have on survivors’ physical health and quality of life. Psychosocial reports detail educational, cognitive, and emotional limitations characterizing survivors as especially fragile, often incompetent, and unreliable in evaluating their circumstances. Anecdotal data suggests some survivors report life experiences similar to those of healthy controls. The aim of our investigation was to determine whether life satisfaction in adult survivors of childhood brain tumors differs from that of healthy controls and to identify potential predictors of life satisfaction in survivors. This cross-sectional study compared 78 brain tumor survivors with population–based matched controls. Chi-square tests, t-tests, and linear regression models were used to investigate patterns of life satisfaction and identify potential correlates. Results indicated life satisfaction of adult survivors of childhood brain tumors was similar to that of healthy controls. Survivors’ general health expectations emerged as the primary correlate of life satisfaction. Understanding life satisfaction as an important variable will optimize the design of strategies to enhance participation in follow-up care, reduce suffering, and optimize quality of life in this vulnerable population. PMID:25027187

  10. Upfront Stereotactic Radiosurgery for Pineal Parenchymal Tumors in Adults

    PubMed Central

    Park, Jong Hoon; Kim, Jeong Hoon; Kwon, Do Hoon; Kim, Chang Jin; Khang, Shin Kwang

    2015-01-01

    Objective Pineal parenchymal tumors (PPTs) in adults are rare, and knowledge regarding their optimal management and treatment outcome is limited. Herein, we present the clinical results of our series of PPTs other than pineoblastomas managed by stereotactic radiosurgery (SRS) at upfront setting. Methods Between 1997 and 2014, nine consecutive adult patients with the diagnosis of PPTs, either pineocytoma or pineal parenchymal tumor of intermediate differentiation, were treated with SRS. There were 6 men and 3 women. The median age was 39 years (range, 31-53 years). All of the patients presented with symptoms of hydrocephalus. Endoscopic third ventriculostomy and biopsy was done for initial management. After histologic diagnosis, patients were treated with Gamma Knife with the mean dose of 13.3 Gy (n=3) or fractionated Cyberknife with 32 Gy (n=6). Results After a mean follow-up of 78.6 months (range, 14-223 months), all patients were alive and all of their tumors were locally controlled except for one instance of cerebrospinal fluid seeding metastasis. On magnetic resonance images, tumor size decreased in all patients, resulting in complete response in 3 patients and partial response in 6. One patient had experienced temporary memory impairment after SRS, which improved spontaneously. Conclusion SRS is effective and safe for PPTs in adults and can be considered as a useful alternative to surgical resection at upfront setting. PMID:26587186

  11. Atypical teratoid/rhabdoid tumors in adult patients: CT and MR imaging features.

    PubMed

    Han, L; Qiu, Y; Xie, C; Zhang, J; Lv, X; Xiong, W; Wang, W; Zhang, X; Wu, P

    2011-01-01

    Primary AT/RT is a rare highly malignant tumor of the CNS, usually occurring in children younger than 5 years of age. The objective of this study was to characterize the CT and MR imaging findings in a series of 5 adult patients with pathologically proved AT/RT. All 5 AT/RTs were supratentorial. In 2 patients who underwent nonenhanced CT, the tumors appeared isoattenuated, and 1 of the 2 tumors contained calcifications. Solid portions of the tumors on MR imaging were isointense on T1-weighted, T2-weighted, and FLAIR images, and 1 case showed restricted diffusion on DWI. The tumors also demonstrated a bandlike rim of strong enhancement surrounding a central cystic area on contrast-enhanced T1-weighted imaging. One tumor was associated with destruction of the calvaria. Although AT/RTs can have nonspecific findings, the tumors in our series were large and isointense on T1-weighted, T2-weighted, and FLAIR images with central necrosis and prominent rim enhancement. PMID:21051520

  12. Eribulin Mesylate and Gemcitabine Hydrochloride in Treating Patients With Metastatic Solid Tumors or Solid Tumors That Cannot be Removed by Surgery

    ClinicalTrials.gov

    2016-04-05

    Adult Solid Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage III Ovarian Cancer; Stage III Uterine Corpus Cancer; Stage IV Ovarian Cancer; Stage IV Uterine Corpus Cancer

  13. Involvement of the ALL-1 gene in a solid tumor.

    PubMed Central

    Baffa, R; Negrini, M; Schichman, S A; Huebner, K; Croce, C M

    1995-01-01

    Translocations involving chromosome band 11q23, found in 5-10% of human acute leukemias, disrupt the ALL-1 gene. This gene is fused by reciprocal translocation with a variety of other genes in acute lymphoblastic and myelogenous leukemias, and it undergoes self-fusion in acute myeloid leukemias with normal karyotype or trisomy 11. Here we report an alteration of the ALL-1 gene in a gastric carcinoma cell line (Mgc80-3). Characterization of this rearrangement revealed a three-way complex translocation, involving chromosomes 1 and 11, resulting in a partial duplication of the ALL-1 gene. Sequencing of reverse transcription-PCR products and Northern blot analysis showed that only the partially duplicated ALL-1 gene was transcribed, producing an mRNA with exon 8 fused to exon 2. This report of ALL-1 gene rearrangement in a solid tumor suggests that ALL-1 plays a role in the pathogenesis of some solid malignancies. The absence of the normal transcript in this cell line, in association with the loss-of-heterozygosity studies on chromosome 11q23 seen in solid tumors, suggests that ALL-1 is involved in tumorigenesis by a loss-of-function mechanism. Images Fig. 1 Fig. 2 Fig. 3 PMID:7761425

  14. Pediatric solid tumors: Evaluation by gallium-67 SPECT studies

    SciTech Connect

    Rossleigh, M.A.; Murray, I.P.; Mackey, D.W.; Bargwanna, K.A.; Nayanar, V.V. )

    1990-02-01

    A retrospective review of 37 children with a variety of solid tumors who underwent 60 {sup 67}Ga single-photon emission computed tomographic (SPECT) studies was performed. These studies were correlated with clinical and radiological findings and, where possible, histopathologic confirmation. In all studies, SPECT gave better definition and better anatomic localization of disease sites than obtained with planar views. SPECT detected more lesions in the head and neck (planar 16, SPECT 19), chest (planar 39, SPECT 45), and abdomen (planar 22, SPECT 24). In six of 20 patients scanned following chemotherapy, SPECT was useful in demonstrating that tracer accumulation in a normally located and shaped thymus indicated uptake resulting from thymic regeneration rather than tumor recurrence. It is concluded that {sup 67}Ga SPECT studies are very useful in the pediatric population, where perhaps because of their small size, interpretation of standard planar views may be difficult.

  15. Tetraspanins: Spanning from solid tumors to hematologic malignancies.

    PubMed

    Yang, Ying-Gui; Sari, Ita Novita; Zia, Mohammad Farid; Lee, Sung Ryul; Song, Su Jung; Kwon, Hyog Young

    2016-05-01

    Tetraspanins (tetraspans or TM4SF) are a family of integral membrane proteins with four transmembrane helices, a small extracellular loop, and a large extracellular loop. Although tetraspanins are expressed in many types of cells, including immune cells, their biological roles are not fully defined. Nonetheless, recent studies have revealed the important roles of tetraspanins in solid tumors and hematologic malignancies, and expression of tetraspanins is associated with the malignancy of human tumors. Furthermore, genetic mouse models of tetraspanins highlight their contribution to tumorigenesis. In this review, we summarize the implication of tetraspanins in cancer with a special focus on tetraspanin 3 in myeloid leukemia. Our increasing knowledge of tetraspanins and the pathologies that alter their function will undoubtedly inform the rational design of novel cancer therapies. PMID:26930362

  16. Immune checkpoint inhibitor combinations in solid tumors: opportunities and challenges.

    PubMed

    Kyi, Chrisann; Postow, Michael A

    2016-06-01

    The emergence of immune 'checkpoint inhibitors' such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death receptor 1 (PD-1) has revolutionized treatment of solid tumors including melanoma, lung cancer, among many others. The goal of checkpoint inhibitor combination therapy is to improve clinical response and minimize toxicities. Rational design of checkpoint combinations considers immune-mediated mechanisms of antitumor activity: immunogenic cell death, antigen release and presentation, activation of T-cell responses, lymphocytic infiltration into tumors and depletion of immunosuppression. Potential synergistic combinations include checkpoint blockade with conventional (radiation, chemotherapy and targeted therapies) and newer immunotherapies (cancer vaccines, oncolytic viruses, among others). Reliable biomarkers are necessary to define patients who will achieve best clinical benefit with minimal toxicity in combination therapy. PMID:27349981

  17. Monoclonal antibodies and Fc fragments for treating solid tumors.

    PubMed

    Eisenbeis, Andrea M; Grau, Stefan J

    2012-01-01

    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. PMID:22291463

  18. Monoclonal antibodies and Fc fragments for treating solid tumors

    PubMed Central

    Eisenbeis, Andrea M; Grau, Stefan J

    2012-01-01

    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. PMID:22291463

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

    SciTech Connect

    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.

  20. Long-term theranostic hydrogel system for solid tumors.

    PubMed

    Kim, Jang Il; Lee, Beom Suk; Chun, Changju; Cho, Jung-Kyo; Kim, Sang-Yoon; Song, Soo-Chang

    2012-03-01

    The long-term theranostic hydrogel system for solid tumors was prepared via simple physical mixing, which consisted of three major parts: the thermosensitive/biodegradable poly(organophosphazene) hydrogel, PEGylated cobalt ferrite nanoparticles, and paclitaxel (PTX). The PEGylated cobalt ferrite nanoparticles showed extremely low cytotoxicity due to the surface modification using PEG chains. The long-term theranostic hydrogel system showed adequate properties to be used for long-term MR theragnosis. In particular, the theranostic hydrogel gradually degraded over 28 days, and the PTX was sustainedly released out from the theranostic hydrogel over the same period in vitro. Furthermore, the in vivo efficacy of long-term MR theragnosis using the theranostic hydrogel system was estimated successfully over 3 weeks by using high field (4.7 T) animal MRI and solid tumor-bearing mice. Based on our results, we expect that this system can supply multiple data regarding a) the progress of therapy and b) the treatment processes via one- or two-time i.t. administration for cases in which surgical approaches are difficult to apply. Meanwhile, cancer patients can be free from the pain of multiple surgical treatments and have the advantage of therapy through a simple i.t. administration. PMID:22189146

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

    ClinicalTrials.gov

    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

  2. Bevacizumab and Cediranib Maleate in Treating Patients With Metastatic or Unresectable Solid Tumor, Lymphoma, Intracranial Glioblastoma, Gliosarcoma or Anaplastic Astrocytoma

    ClinicalTrials.gov

    2014-02-14

    Childhood Large Cell Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Stage IV Childhood Small Noncleaved Cell 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 IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  3. PXD101 and 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-05-15

    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

  4. A Case of Adult Granulosa Cell Tumor of the Testis

    PubMed Central

    Tanner, Stephen B.; Morilla, Dan B.; Schaber, John D.

    2014-01-01

    Patient: Female, 22 Final Diagnosis: Testis granulosa cell tumor Symptoms: Pain in testicles • swelling of epididymides • tenderness of epididymiides Medication: — Clinical Procedure: — Specialty: Urology Objective: Rare disease Background: Adult granulosa cell tumors of the testis (AGCTT) are classified as sex cord-stromal tumors. Only 31 cases have been reported. Typical presentation includes a slowly enlarging, painless testicular mass. Associated findings are gynecomastia, decreased libido, and erectile dysfunction. Immunohistochemistry can be used to confirm the diagnosis. Case Rrport: A 22-year-old male presented with complaint of mild pain in both testicles. A testicular ultrasound revealed a 4.0×3.8×4.6 mm hypoechoic lesion within the left testicle. Serum tumor markers (STM) included lactate dehydrogenase (LDH) measuring 146 IU/L (98–192), serum alpha-1-fetoprotein (AFP), 2.89 ng/mL (0–9), and plasma beta human chorionic gonadotropin (Beta HCG) measuring less than 0.50 mIU/mL (<0.50–2.67). Computed tomography (CT) of the abdomen and pelvis with oral and intravenous contrast was normal. A radical orchiectomy was recommended but the patient refused. He agreed to surveillance with imaging and serum tumor markers (STM). The patient’s testicular ultrasound showed the mass to be stable in size and STMs remained negative. The patient agreed to an orchiectomy 9 months after his diagnosis. This case is the first reported with c-kit-positive immunohistochemistry. His post-operative course has been unremarkable. Conclusions: AGCTT is a rare tumor and information regarding its presentation, gross and microscopic morphology, and immunohistochemical characteristics is lacking. This report provides an update of the immunohistochemical findings and adds to the available data concerning this tumor. Based on the results of this case, future reports that include c-kit immunohistochemistry would be beneficial to evaluate its utility in diagnosing AGCTT. PMID

  5. Sorafenib in Treating Patients With Metastatic or Unresectable Solid Tumors, Multiple Myeloma, or Non-Hodgkin's Lymphoma With or Without Impaired Liver or Kidney Function

    ClinicalTrials.gov

    2013-01-04

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic 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 Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  6. Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors

    ClinicalTrials.gov

    2016-04-11

    Ewing's Sarcoma; Osteosarcoma; Astrocytoma; Atypical Teratoid/Rhabdoid Tumor; Ependymoma; Germ Cell Tumor; Glioma; Medulloblastoma; Rhabdoid Tumor; Retinoblastoma; Clear Cell Sarcoma; Renal Cell Carcinoma; Wilms Tumor; Hepatoblastoma; Neuroblastoma; Rhabdomyosarcoma

  7. Germ Cell Tumors in Adolescents and Young Adults.

    PubMed

    Calaminus, Gabriele; Joffe, Jonathan

    2016-01-01

    Germ cell tumors (GCTs) represent a group of biologically complex malignancies that affect patients at different sites within the body and at different ages. The varying nature of these tumors reflects their cell of origin which is the primordial germ cell, which normally gives rise to ovarian and testicular egg and sperm producing cells. These cells retain an ability to give rise to all types of human tissues, and this is illustrated by the different kinds of GCTs that occur. In adolescent and young adult (AYA) patients, GCTs predominantly present as testicular, ovarian or mediastinal primary GCTs, and represent some of the most complex therapeutic challenges within any AYA practice. The varying types of GCTs, defined by primary site and/or age at presentation, can look very similar microscopically. However, there is growing evidence that they may have different molecular characteristics, different biology and different requirements for curative treatments. Whilst in adult testicular GCTs there is evidence for an environmental cause during fetal development and a genetic component, these causative factors are much less well understood in other GCTs. GCTs are some of the most curable cancers in adults, but some patients exhibit resistance to standard treatments. Because of this, today's clinical research is directed at understanding how to best utilize toxic therapies and promote healthy survivorship. This chapter explores the biology, behavior and treatment of GCTs and discusses how the AYA group of GCTs may hold some of the keys to understanding fundamental unanswered questions of biological variance and curability in GCTs. PMID:27595361

  8. Solid tumors of the pancreas can put on a mask through cystic change

    PubMed Central

    2011-01-01

    Background Solid pancreatic tumors such as pancreatic ductal adenocarcinoma (PDAC), solid pseudopapillary tumor (SPT), and pancreatic endocrine tumor (PET) may occasionally manifest as cystic lesions. In this study, we have put together our accumulated experience with cystic manifestations of various solid tumors of the pancreas. Methods From 2000 to 2006, 376 patients with pancreatic solid tumor resections were reviewed. Ten (2.66%) of these tumors appeared on radiological imaging studies as cystic lesions. We performed a retrospective review of medical records and pathologic findings of these 10 cases. Results Of the ten cases in which solid tumors of the pancreas manifested as cystic lesions, six were PDAC with cystic degeneration, two were SPT undergone complete cystic change, one was cystic PET, and one was a cystic schwannoma. The mean tumor size of the cystic portion in PDAC was 7.3 cm, and three patients were diagnosed as 'pseudocyst' with or without cancer. Two SPT were found incidentally in young women and were diagnosed as other cystic neoplasms. One cystic endocrine tumor was preoperatively suspected as intraductal papillary mucinous neoplasm or mucinous cystic neoplasm. Conclusions Cystic changes of pancreas solid tumors are extremely rare. However, the possibility of cystic manifestation of pancreas solid tumors should be kept in mind. PMID:21771323

  9. Atypical Teratoid/Rhabdoid Tumors in Adults: A Case Report and Treatment-Focused Review

    PubMed Central

    Shonka, Nicole A.; Armstrong, Terri S.; Prabhu, Sujit S.; Childress, Amanda; Choi, Shauna; Langford, Lauren A.; Gilbert, Mark R.

    2011-01-01

    Atypical teratoid/rhabdoid tumor is predominantly a childhood tumor and has only been rarely reported in adults; therefore, treatment regimens are often extrapolated from the pediatric experience. Typically, children are treated with craniospinal radiation therapy which is often followed by systemic chemotherapy. Employing pediatric regimens to treat this tumor in adult patients poses a particular risk for myelosuppression, as the prescribed doses in pediatric protocols exceed those tolerated by adults, and conventional craniospinal radiation can be associated with prolonged myelotoxicity and a depletion of the bone marrow reserve in vertebrae of adults. Here we present a case of a woman with a pineal region atypical teratoid/rhabdoid tumor, an unusual adult cancer presenting in an atypical location. This is followed by a review of the disease in adult patients with an emphasis on treatment and suggestions to minimize myelotoxicity. Keywords Atypical rhabdoid tumor; AT/RT; Pineal tumor; Adult PMID:21811535

  10. Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven't Responded to Therapy

    ClinicalTrials.gov

    2012-03-14

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Leukemia; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  11. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-08-26

    ; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  12. Ultrasound mediated delivery of drugs and genes to solid tumors

    PubMed Central

    Frenkel, Victor

    2008-01-01

    It has long been shown that therapeutic ultrasound can be used effectively to ablate solid tumors, and a variety of cancers are presently being treated in the clinic using these types of ultrasound exposures. There is, however, an ever-increasing body of preclinical literature that demonstrates how ultrasound energy can also be used non-destructively for increasing the efficacy of drugs and genes for improving cancer treatment. In this review, a summary of the most important ultrasound mechanisms will be given with a detailed description of how each one can be employed for a variety of applications. This includes the manner by which acoustic energy deposition can be used to create changes in tissue permeability for enhancing the delivery of conventional agents, as well as for deploying and activating drugs and genes via specially tailored vehicles and formulations. PMID:18474406

  13. [Microflora of pharyngeal mucosa in children with solid tumors].

    PubMed

    Polishchuk, V B; Baturo, A P; Romanenko, E E; Kostinov, M P; Zaeva, G E; Mikhaĭlova, S N; Leonova, A Iu; Moiseenko, E I

    2008-01-01

    Microbiological study of pharyngeal mucosa in 43 children with solid tumors revealed that 77.2% of isolated microorganisms belonged to Gram-positive flora. It was shown that streptococci and Staphylococcus aureus were the main species. Species composition of streptococci included both pyogenic (S. pyogenes, S. agalactiae, S. dysgalactiae, S. equi) andviridans species (S. acidominimus, S. oralis and "S. milleri" group). Nocardioform actinomycetes, corynebacteria and other staphylococci were referred to additional microflora. Accidental microflora was represented by Neisseria spp., non-fermenting Gram-negative bacteria, enterobacteria and yeast-like fungi. Microbiologic study of pharyngeal mucosa biocenosis showed that monoculture was present only in 2.3% of cases; in other cases microorganisms formed both intra-genus and inter-species associations. 2-6-component associations were revealed with predominance of 3-4-component associations (37.2% and 32.6% respectively). Relationship of distribution of microorganisms belonging to main and additional microflora was revealed. PMID:19186552

  14. Gossypol, Paclitaxel, and Carboplatin in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2013-01-09

    ; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic 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 Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  15. Ultrasonic Enhancement of Drug Penetration in Solid Tumors

    PubMed Central

    Lai, Chun-Yen; Fite, Brett Z.; Ferrara, Katherine W.

    2013-01-01

    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. PMID:23967400

  16. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor

    PubMed Central

    Boissonnas, Alexandre; Fetler, Luc; Zeelenberg, Ingrid S.; Hugues, Stéphanie; Amigorena, Sebastian

    2007-01-01

    Although the immune system evolved to fight infections, it may also attack and destroy solid tumors. In most cases, tumor rejection is initiated by CD8+ cytotoxic T lymphocytes (CTLs), which infiltrate solid tumors, recognize tumor antigens, and kill tumor cells. We use a combination of two-photon intravital microscopy and immunofluorescence on ordered sequential sections to analyze the infiltration and destruction of solid tumors by CTLs. We show that in the periphery of a thymoma growing subcutaneously, activated CTLs migrate with high instantaneous velocities. The CTLs arrest in close contact to tumor cells expressing their cognate antigen. In regions where most tumor cells are dead, CTLs resume migration, sometimes following collagen fibers or blood vessels. CTLs migrating along blood vessels preferentially adopt an elongated morphology. CTLs also infiltrate tumors in depth, but only when the tumor cells express the cognate CTL antigen. In tumors that do not express the cognate antigen, CTL infiltration is restricted to peripheral regions, and lymphocytes neither stop moving nor kill tumor cells. Antigen expression by tumor cells therefore determines both CTL motility within the tumor and profound tumor infiltration. PMID:17261634

  17. Exploratory case-control study of brain tumors in adults

    SciTech Connect

    Burch, J.D.; Craib, K.J.; Choi, B.C.; Miller, A.B.; Risch, H.A.; Howe, G.R.

    1987-04-01

    An exploratory study of brain tumors in adults was carried out using 215 cases diagnosed in Southern Ontario between 1979 and 1982, with an individually matched, hospital control series. Significantly elevated risks were observed for reported use of spring water, drinking of wine, and consumption of pickled fish, together with a significant protective effect for the regular consumption of any of several types of fruit. While these factors are consistent with a role for N-nitroso compounds in the etiology of these tumors, for several other factors related to this hypothesis, no association was observed. Occupation in the rubber industry was associated with a significant relative risk of 9.0, though no other occupational associations were seen. Two previously unreported associations were with smoking nonfilter cigarettes with a significant trend and with the use of hair dyes or sprays. The data do not support an association between physical head trauma requiring medical attention and risk of brain tumors and indicate that exposure to ionizing radiation and vinyl chloride monomer does not contribute any appreciable fraction of attributable risk in the population studied. The findings warrant further detailed investigation in future epidemiologic studies.

  18. High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors

    ClinicalTrials.gov

    2016-08-17

    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

  19. Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer

    ClinicalTrials.gov

    2016-07-22

    Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

  20. APN401 in Treating Patients With Melanoma, Kidney Cancer, Pancreatic Cancer, or Other Solid Tumors That Are Metastatic or Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2016-06-07

    Recurrent Melanoma; Recurrent Pancreatic Cancer; Recurrent Renal Cell Cancer; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma; Stage IV Pancreatic Cancer; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  1. GTI-2040 and Docetaxel in Treating Patients With Recurrent, Metastatic, or Unresectable Locally Advanced Non-Small Cell Lung Cancer, Prostate Cancer, or Other Solid Tumors

    ClinicalTrials.gov

    2013-01-23

    Recurrent Non-small Cell Lung Cancer; Recurrent Prostate Cancer; Stage III Prostate Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  2. Solid cystic pseudopapillary tumor of pancreas with splenic metastasis: Case report and review of literature

    PubMed Central

    Yagmur, Yusuf; Yigit, Ebral; Gumus, Serdar; Babur, Mehmet; Can, Mehmet Ali

    2015-01-01

    Introduction Solid-cystic pseudopapillary tumor of the pancreas is rare and most commonly seen in young women. We present a young women with solid-cystic pseudopapillary tumor of the pancreas and discuss the literature. Presentation of case Thirty nine years old female patient with a mass about 12 cm in the pancreas with splenic invasion seen in our clinic. After having CT and PET-CT view, patient underwent surgery. Distal pancreatectomy with mass excision and splenectomy was performed. Microscopic examination result was solid cystic pseudopapillary tumor with spleen invasion. Discussion Solid-cystic pseudopapillary tumor of the pancreas has cystic solid pseudopapillary structures. Prognosis of tumor is better than other pancreatic tumor. Complete resection of tumor with splenic inclusion is surgical treatment. Conclusion In case of large slow growing pancreatic tumor with splenic metastasis, solid-cystic pseudopapillary tumor of the pancreas should be considered in the diagnosis. Complete surgical resection is associated with long-term survival even in the presence of metastatic disease. Close follow-up is necessary after surgery. PMID:26225837

  3. Hypoxia-directed and activated theranostic agent: Imaging and treatment of solid tumor.

    PubMed

    Kumar, Rajesh; Kim, Eun-Joong; Han, Jiyou; Lee, Hyunseung; Shin, Weon Sup; Kim, Hyun Min; Bhuniya, Sankarprasad; Kim, Jong Seung; Hong, Kwan Soo

    2016-10-01

    Hypoxia, a distinguished feature of various solid tumors, has been considered as a key marker for tumor progression. Inadequate vasculature and high interstitial pressures result in relatively poor drug delivery to these tumors. Herein, we developed an antitumor theranostic agent, 4, which is activated in hypoxic conditions and can be used for the diagnosis and treatment of solid tumors. Compound 4, bearing biotin, a tumor-targeting unit, and SN38, an anticancer drug, proved to be an effective theranostic agent for solid tumors. SN38 plays a dual role: as an anticancer drug for therapy and as a fluorophore for diagnosis, thus avoids an extra fluorophore and limits cytotoxicity. Compound 4, activated in the hypoxic environment, showed high therapeutic activity in A549 and HeLa cells and spheroids. In vivo imaging of solid tumors confirmed the tumor-specific localization, deep tissue penetration and activation of compound 4, as well as the production of a strong anticancer effect through the inhibition of tumor growth in a xenograft mouse model validating it as a promising strategy for the treatment of solid tumors. PMID:27449948

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

    PubMed

    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. PMID:1177472

  5. Development of cell-cycle checkpoint therapy for solid tumors.

    PubMed

    Tamura, Kenji

    2015-12-01

    Cellular proliferation is tightly controlled by several cell-cycle checkpoint proteins. In cancer, the genes encoding these proteins are often disrupted and cause unrestrained cancer growth. The proteins are over-expressed in many malignancies; thus, they are potential targets for anti-cancer therapies. These proteins include cyclin-dependent kinase, checkpoint kinase, WEE1 kinase, aurora kinase and polo-like kinase. Cyclin-dependent kinase inhibitors are the most advanced cell-cycle checkpoint therapeutics available. For instance, palbociclib (PD0332991) is a first-in-class, oral, highly selective inhibitor of CDK4/6 and, in combination with letrozole (Phase II; PALOMA-1) or with fulvestrant (Phase III; PALOMA-3), it has significantly prolonged progression-free survival, in patients with metastatic estrogen receptor-positive, HER2-negative breast cancer, in comparison with that observed in patients using letrozole, or fulvestrant alone, respectively. In this review, we provide an overview of the current compounds available for cell-cycle checkpoint protein-directed therapy for solid tumors. PMID:26486823

  6. Neoplastic Meningitis from Solid Tumors: New Diagnostic and Therapeutic Approaches

    PubMed Central

    Zustovich, Fable; Farina, Patrizia; Della Puppa, Alessandro; Manara, Renzo; Cecchin, Diego; Brunello, Antonella; Cappetta, Alessandro; Zagonel, Vittorina

    2011-01-01

    Neoplastic meningitis is a result of the spread of malignant cells to the leptomeninges and subarachnoid space and their dissemination within the cerebrospinal fluid. This event occurs in 4%–15% of all patients with solid tumors and represents an important prognostic factor for poor survival. Neoplastic meningitis should be diagnosed in the early stages of disease to prevent important neurological deficits and to provide the most appropriate treatment. Despite new diagnostic approaches developed in recent years, such as positron emission tomography–computed tomography and new biological markers, the combination of magnetic resonance imaging without and with gadolinium enhancement and cytology still has the greatest diagnostic sensitivity. Recently, no new randomized studies comparing intrathecal (i.t.) with systemic treatment have been performed, yet there have been a few small phase II studies and case reports about new molecularly targeted substances whose successful i.t. or systemic application has been reported. Trastuzumab, gefitinib, and sorafenib are examples of possible future treatments for neoplastic meningitis, in order to better individualize therapy thus allowing better outcomes. In this review, we analyze the most recent and interesting developments on diagnostic and therapeutic approaches. PMID:21795431

  7. NK Cells, Tumor Cell Transition, and Tumor Progression in Solid Malignancies: New Hints for NK-Based Immunotherapy?

    PubMed Central

    Huergo-Zapico, Leticia; Parodi, Monica; Pedrazzi, Marco; Mingari, Maria Cristina; Sparatore, Bianca; Gonzalez, Segundo; Olive, Daniel; Bottino, Cristina

    2016-01-01

    Several evidences suggest that NK cells can patrol the body and eliminate tumors in their initial phases but may hardly control established solid tumors. Multiple factors, including the transition of tumor cells towards a proinvasive/prometastatic phenotype, the immunosuppressive effect of the tumor microenvironment, and the tumor structure complexity, may account for limited NK cell efficacy. Several putative mechanisms of NK cell suppression have been defined in these last years; conversely, the cross talk between NK cells and tumor cells undergoing different transitional phases remains poorly explored. Nevertheless, recent in vitro studies and immunohistochemical analyses on tumor biopsies suggest that NK cells could not only kill tumor cells but also influence their evolution. Indeed, NK cells may induce tumor cells to change the expression of HLA-I, PD-L1, or NKG2D-L and modulate their susceptibility to the immune response. Moreover, NK cells may be preferentially located in the borders of tumor masses, where, indeed, tumor cells can undergo Epithelial-to-Mesenchymal Transition (EMT) acquiring prometastatic phenotype. Finally, the recently highlighted role of HMGB1 both in EMT and in amplifying the recruitment of NK cells provides further hints on a possible effect of NK cells on tumor progression and fosters new studies on this issue. PMID:27294158

  8. Bone marrow as a metastatic niche for disseminated tumor cells from solid tumors

    PubMed Central

    Shiozawa, Yusuke; Eber, Matthew R; Berry, Janice E; Taichman, Russell S

    2015-01-01

    Bone marrow is a heterogeneous organ containing diverse cell types, and it is a preferred metastatic site for several solid tumors such as breast and prostate cancer. Recently, it has been shown that bone metastatic cancer cells interact with the bone marrow microenvironment to survive and grow, and thus this microenvironment is referred to as the ‘metastatic niche'. Once cancer cells spread to distant organs such as bone, the prognosis for the patient is generally poor. There is an urgent need to establish a greater understanding of the mechanisms whereby the bone marrow niche influences bone metastasis. Here we discuss insights into the contribution of the bone marrow ‘metastatic niche' to progression of bone metastatic disease, with a particular focus on cells of hematopoietic and mesenchymal origin. PMID:26029360

  9. Structure of solid tumors and their vasculature: Implications for therapy with monoclonal antibodies

    SciTech Connect

    Dvorak, H.F.; Nagy, J.A.; Dvorak, A.M. )

    1991-03-01

    Delivery of monoclonal antibodies to solid tumors is a vexing problem that must be solved if these antibodies are to realize their promise in therapy. Such success as has been achieved with monoclonal antibodies is attributable to the local hyperpermeability of the tumor vasculature, a property that favors antibody extravasation at tumor sites and that is mediated by a tumor-secreted vascular permeability factor. However, leaky tumor blood vessels are generally some distance removed from target tumor cells, separated by stroma and by other tumor cells that together represent significant barriers to penetration by extravasated monoclonal antibodies. For this reason, alternative approaches may be attractive. These include the use of antibody-linked cytotoxins, which are able to kill tumor cells without immediate contact, and direction of antibodies against nontumor cell targets, for example, antigens unique to the tumor vascular endothelium or to tumor stroma. 50 refs.

  10. Targeting and Treatment of Tumor Hypoxia by Newly Designed Prodrug Possessing High Permeability in Solid Tumors.

    PubMed

    Ikeda, Yutaka; Hisano, Hikaru; Nishikawa, Yuji; Nagasaki, Yukio

    2016-07-01

    Tumor hypoxia, which is associated with poor prognosis in cancer, is known to lead to resistance to radiotherapy and anticancer chemotherapy. Impaired drug penetration in hypoxic regions has been recognized as an essential barrier to drug development in solid tumors. Here, we propose novel hypoxia-activated prodrugs, which drastically improved the penetration property of commonly used anticancer drugs in the hypoxic region. In this design, conventional anticancer drugs were modified with 2-nitroimidazole derivatives. The most important point of this study was that the prodrug designed formed a 6-membered cyclic structure to allow liberation of the active drug in the hypoxic region. This design markedly increased the selectivity of the hypoxia-targeted prodrug, resulting in significant reduction of adverse effects in the normoxic region. In vitro studies confirmed the selective activation under hypoxic conditions. In vivo studies showed drastic reduction of adverse effects associated with conventional anticancer drugs and improvement of the survival rate of mice. Immunofluorescence analyses confirmed that the designed prodrug had a tendency to localize at the hypoxic region, in contrast to conventional anticancer drugs, which localize only at the normoxic region. PMID:27187083

  11. Metabolic reprogramming: a new relevant pathway in adult adrenocortical tumors

    PubMed Central

    Longatto-Filho, Adhemar; Faria, André M.; Fragoso, Maria C. B. V.; Lovisolo, Silvana M.; Lerário, Antonio M.; Almeida, Madson Q.

    2015-01-01

    Adrenocortical carcinomas (ACCs) are complex neoplasias that may present unexpected clinical behavior, being imperative to identify new biological markers that can predict patient prognosis and provide new therapeutic options. The main aim of the present study was to evaluate the prognostic value of metabolism-related key proteins in adrenocortical carcinoma. The immunohistochemical expression of MCT1, MCT2, MCT4, CD147, CD44, GLUT1 and CAIX was evaluated in a series of 154 adult patients with adrenocortical neoplasia and associated with patients' clinicopathological parameters. A significant increase in was found for membranous expression of MCT4, GLUT1 and CAIX in carcinomas, when compared to adenomas. Importantly MCT1, GLUT1 and CAIX expressions were significantly associated with poor prognostic variables, including high nuclear grade, high mitotic index, advanced tumor staging, presence of metastasis, as well as shorter overall and disease free survival. In opposition, MCT2 membranous expression was associated with favorable prognostic parameters. Importantly, cytoplasmic expression of CD147 was identified as an independent predictor of longer overall survival and cytoplasmic expression of CAIX as an independent predictor of longer disease-free survival. We provide evidence for a metabolic reprogramming in adrenocortical malignant tumors towards the hyperglycolytic and acid-resistant phenotype, which was associated with poor prognosis. PMID:26587828

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

    ClinicalTrials.gov

    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

  13. Succinate Dehydrogenase Deficiency in Pediatric and Adult Gastrointestinal Stromal Tumors

    PubMed Central

    Belinsky, Martin G.; Rink, Lori; von Mehren, Margaret

    2013-01-01

    Gastrointestinal stromal tumors (GISTs) in adults are generally driven by somatic gain-of-function mutations in KIT or PDGFRA, and biological therapies targeted to these receptor tyrosine kinases comprise part of the treatment regimen for metastatic and inoperable GISTs. A minority (10–15%) of GISTs in adults, along with ∼85% of pediatric GISTs, lacks oncogenic mutations in KIT and PDGFRA. Not surprisingly these wild type (WT) GISTs respond poorly to kinase inhibitor therapy. A subset of WT GISTs shares a set of distinguishing clinical and pathological features, and a flurry of recent reports has convincingly demonstrated shared molecular characteristics. These GISTs have a distinct transcriptional profile including over-expression of the insulin-like growth factor-1 receptor, and exhibit deficiency in the succinate dehydrogenase (SDH) enzyme complex. The latter is often but not always linked to bi-allelic inactivation of SDH subunit genes, particularly SDHA. This review will summarize the molecular, pathological, and clinical connections that link this group of SDH-deficient neoplasms, and offer a view toward understanding the underlying biology of the disease and the therapeutic challenges implicit to this biology. PMID:23730622

  14. Cisplatin Nephrotoxicity and Longitudinal Growth in Children With Solid Tumors

    PubMed Central

    Jiménez-Triana, Clímaco Andres; Castelán-Martínez, Osvaldo D.; Rivas-Ruiz, Rodolfo; Jiménez-Méndez, Ricardo; Medina, Aurora; Clark, Patricia; Rassekh, Rod; Castañeda-Hernández, Gilberto; Carleton, Bruce; Medeiros, Mara

    2015-01-01

    Abstract Cisplatin, a major antineoplastic drug used in the treatment of solid tumors, is a known nephrotoxin. This retrospective cohort study evaluated the prevalence and severity of cisplatin nephrotoxicity in 54 children and its impact on height and weight. We recorded the weight, height, serum creatinine, and electrolytes in each cisplatin cycle and after 12 months of treatment. Nephrotoxicity was graded as follows: normal renal function (Grade 0); asymptomatic electrolyte disorders, including an increase in serum creatinine, up to 1.5 times baseline value (Grade 1); need for electrolyte supplementation <3 months and/or increase in serum creatinine 1.5 to 1.9 times from baseline (Grade 2); increase in serum creatinine 2 to 2.9 times from baseline or need for electrolyte supplementation for more than 3 months after treatment completion (Grade 3); and increase in serum creatinine ≥3 times from baseline or renal replacement therapy (Grade 4). Nephrotoxicity was observed in 41 subjects (75.9%). Grade 1 nephrotoxicity was observed in 18 patients (33.3%), Grade 2 in 5 patients (9.2%), and Grade 3 in 18 patients (33.3%). None had Grade 4 nephrotoxicity. Nephrotoxicity patients were younger and received higher cisplatin dose, they also had impairment in longitudinal growth manifested as statistically significant worsening on the height Z Score at 12 months after treatment. We used a multiple logistic regression model using the delta of height Z Score (baseline-12 months) as dependent variable in order to adjust for the main confounder variables such as: germ cell tumor, cisplatin total dose, serum magnesium levels at 12 months, gender, and nephrotoxicity grade. Patients with nephrotoxicity Grade 1 where at higher risk of not growing (OR 5.1, 95% CI 1.07–24.3, P = 0.04). The cisplatin total dose had a significant negative relationship with magnesium levels at 12 months (Spearman r = −0.527, P = <0.001). PMID:26313789

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

    PubMed

    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. PMID:16307762

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

    NASA Astrophysics Data System (ADS)

    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.

  17. A Rare Case of Primary Anterior Mediastinal Yolk Sac Tumor in an Elderly Adult Male

    PubMed Central

    Nakhla, Sammy G.; Sundararajan, Srinath

    2016-01-01

    Mediastinal germ cell tumors are extragonadal germ cell tumors (EGGCTs) commonly seen in children and young adults. They are more common in men. Clinically they are classified as teratomas, seminomas, and nonseminomatous germ cell tumors. Primary mediastinal yolk sac neoplasm is an extremely rare tumor. We present here a very rare case of primary yolk sac tumor of the anterior mediastinum in a 73-year-old male. Mediastinal germ cell tumors have a worse prognosis than gonadal germ cell tumors. Chemotherapy followed by adjuvant surgery improves overall response in EGGCTs. However, comorbidities can render treatment with chemotherapy and surgery challenging in elderly patients. PMID:27144043

  18. Lenvatinib: Role in thyroid cancer and other solid tumors.

    PubMed

    Cabanillas, Maria E; Habra, Mouhammed Amir

    2016-01-01

    Despite recent breakthroughs in treatment of advanced thyroid cancers, prognoses remain poor. Treatment of advanced, progressive disease remains challenging, with limited treatment options. Small-molecule tyrosine kinase inhibitors, including vandetanib, cabozantinib, sorafenib, and lenvatinib, which are now FDA-approved for thyroid cancer, have shown clinical benefit in advanced thyroid cancer. Lenvatinib is approved for treatment of locally recurrent or metastatic, progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). It has been studied in phase II and III trials for treatment of advanced RAI-refractory DTC, and in a phase II trial for medullary thyroid cancer (MTC). Lenvatinib targets vascular endothelial growth factor receptors 1-3 (VEGFR1-3), fibroblast growth factor receptors 1-4 (FGFR-1-4), RET, c-kit, and platelet-derived growth factor receptor α (PDGFRα). Its antitumor activity may be due to antiangiogenic properties and direct antitumor effects. Lenvatinib has demonstrated antitumor activity in a variety of solid tumors, including MTC, in phase I and II clinical trials. In a phase II study in advanced RAI-refractory DTC, lenvatinib-treated patients achieved a 50% response rate (RR), with median progression-free survival (PFS) of 12.6 months. In a phase III trial in RAI-refractory DTC, median PFS in lenvatinib-treated patients was 18.3 months, with a 65% overall RR, versus 3.6 months in placebo-treated patients, with a 2% RR. Adverse events occurring in >50% of patients included hypertension, diarrhea, fatigue/asthenia, and decreased appetite. Lenvatinib is a promising new agent for treatment of patients with advanced thyroid cancer. PMID:26678514

  19. Immune Surveillance Against a Solid Tumor Fails because of Immunological Ignorance

    NASA Astrophysics Data System (ADS)

    Ochsenbein, Adrian F.; Klenerman, Paul; Karrer, Urs; Ludewig, Burkhard; Pericin, Marcus; Hengartner, Hans; Zinkernagel, Rolf M.

    1999-03-01

    Many peripheral solid tumors such as sarcomas and carcinomas express tumor-specific antigens that can serve as targets for immune effector T cells. Nevertheless, overall immune surveillance against such tumors seems relatively inefficient. We studied immune surveillance against a s.c. sarcoma expressing a characterized viral tumor antigen. Surprisingly, the tumor cells were capable of inducing a protective cytotoxic T cell response if transferred as a single-cell suspension. However, if they were transplanted as small tumor pieces, tumors readily grew. Tumor growth correlated strictly with (i) failure of tumor cells to reach the draining lymph nodes and (ii) absence of primed cytotoxic T cells. Cytotoxic T cells were not tolerant or deleted because a tumor antigen-specific cytotoxic T cell response was readily induced in lymphoid tissue by immunization with virus or with tumor cells even in the presence of large tumors. Established tumors were rejected by vaccine-induced effector T cells if effector T cells were maintained by prolonged or repetitive vaccination, but not by single-dose vaccination. Thus, in addition to several other tumor-promoting parameters, some antigenic peripheral sarcomas--and probably carcinomas--may grow not because they anergize or tolerize tumor-specific T cells, but because such tumors are immunologically dealt with as if they were in a so-called immunologically privileged site and are ignored for too long.

  20. Ineffective Vaccination Against Solid Tumors Can Be Enhanced by Hematopoetic Cell Transplantation

    PubMed Central

    Filatenkov, Alexander; Müller, Antonia M. S.; Tseng, William Wei-Lin; Dejbakhsh-Jones, Sussan; Winer, Daniel; Luong, Richard; Shizuru, Judith A.; Engleman, Edgar G.; Strober, Samuel

    2009-01-01

    Vaccination with tumor antigens has not been an effective treatment for solid tumors. The goal of the current study was to determine whether a combination of vaccination and hematopoetic cell transplantation (HCT) can effectively treat primary, disseminated or metastatic CT26 and MC38 murine colon tumors. Vaccination of tumor bearing mice with irradiated tumor cells and CpG adjuvant failed to alter progressive tumor growth. However, mice bearing primary, disseminated lung or metastatic liver tumors were uniformly cured after administration total body irradiation (TBI) followed by the transplantation of hematopoetic progenitor cells and T cells from syngeneic but not allogeneic vaccinated donors. Requirements for effective treatment of tumors included irradiation of hosts, vaccination of donors with both tumor cells and CpG, transfer of both CD4+ and CD8+ T cells along with progenitor cells, and ability of donor cells to produce IFN-γ. Irradiation markedly increased the infiltration of donor T cells into the tumors, and the combined irradiation and HCT altered the balance of tumor infiltrating cells to favor CD8+ effector memory T cells as compared to CD4+CD25+FoxP3+ Treg cells. The combination of vaccination and autologous hematopoetic cell transplantation was also effective in treating tumors. In conclusion, these findings show that otherwise ineffective vaccination to solid non-hematologic tumors can be dramatically enhanced by HCT. PMID:19890041

  1. Role of Constitutive Behavior and Tumor-Host Mechanical Interactions in the State of Stress and Growth of Solid Tumors

    PubMed Central

    Papageorgis, Panagiotis; Odysseos, Andreani D.; Stylianopoulos, Triantafyllos

    2014-01-01

    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. PMID:25111061

  2. Lenalidomide in Treating Young Patients With Relapsed or Refractory Solid Tumors or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2014-06-10

    Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Myelodysplastic Syndromes; Unspecified Childhood Solid Tumor, Protocol Specific

  3. Study of LOXO-101 in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE)

    ClinicalTrials.gov

    2016-08-19

    Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Sarcoma; Colorectal Neoplasms; Salivary Gland Neoplasms; Biliary Tract Neoplasms; Brain Neoplasm, Primary; Carcinoma, Ductal, Breast; Melanoma; Solid Tumors; Glioblastoma; Bile Duct Neoplasms; Astrocytoma; Head and Neck Squamous Cell Carcinoma; Pontine Glioma

  4. Cardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-09-07

    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 Neoplasms; Breast Diseases; Renal Neoplasm; Solid Tumors

  5. PD-L1 and Survival in Solid Tumors: A Meta-Analysis

    PubMed Central

    Li, Lijun; Chai, Ying; Huang, Jian

    2015-01-01

    Background Numerous agents targeting PD-L1/PD-1 check-point are in clinical development. However, the correlation between PD-L1expression and prognosis of solid tumor is still in controversial. Here, we elicit a systematic review and meta-analysis to investigate the potential value of PD-L1 in the prognostic prediction in human solid tumors. Methods Electronic databases were searched for studies evaluating the expression of PD-L1 and overall survival (OS) of patients with solid tumors. Odds ratios (ORs) from individual studies were calculated and pooled by using a random-effect model, and heterogeneity and publication bias analyses were also performed. Results A total of 3107 patients with solid tumor from 28 published studies were included in the meta-analysis. The median percentage of solid tumors with PD-L1 overexpression was 52.5%. PD-L1 overexpression was associated with worse OS at both 3 years (OR = 2.43, 95% confidence interval (CI) = 1.60 to 3.70, P < 0.0001) and 5 years (OR = 2.23, 95% CI = 1.40 to 3.55, P = 0.0008) of solid tumors. Among the tumor types, PD-L1 was associated with worse 3 year-OS of esophageal cancer, gastric cancer, hepatocellular carcinoma, and urothelial cancer, and 5 year-OS of esophageal cancer, gastric cancer and colorectal cancer. Conclusions These results suggest that expression of PD-L1 is associated with worse survival in solid tumors. However, the correlations between PD-L1 and prognosis are variant among different tumor types. More studies are needed to investigate the clinical value of PD-L1 expression in prognostic prediction and treatment option. PMID:26114883

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

    ClinicalTrials.gov

    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

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

    PubMed Central

    Guo, Yelei; Wang, Yao; Han, Weidong

    2016-01-01

    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. PMID:26998495

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

    ClinicalTrials.gov

    2016-02-15

    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

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

    ClinicalTrials.gov

    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

  10. Prognostic role of STAT3 in solid tumors: a systematic review and meta-analysis

    PubMed Central

    Zhao, Lufeng; Huang, Lijian; Shen, Gang; Huang, Jian; Chai, Ying

    2016-01-01

    Accumulated studies have provided controversial evidences of the association between signal transducer and activator of transcription proteins 3 (STAT3) expression and survival of human solid tumors. To address this inconsistency, we performed a meta-analysis with 63 studies identified from PubMed, Medline and EBSCO. We found STAT3 overexpression was significantly associated with worse 3-year overall survival (OS) (OR = 2.06, 95% CI = 1.57 to 2.71, P < 0.00001) and 5-year OS (OR = 2.00, 95% CI = 1.53 to 2.63, P < 0.00001) of human solid tumors. Similar results were observed when disease free survival (DFS) were analyzed. Subgroup analysis showed that elevated STAT3 expression was associated with poor prognosis of gastric cancer, lung cancer, gliomas, hepatic cancer, osteosarcoma, prostate cancer, pancreatic cancer but better prognosis of breast cancer. The correlation between STAT3 and survival of solid tumors was related to its phosphorylated state. High expression level of STAT3 was also associated with advanced tumor stage. In conclusion, elevated STAT3 expression is associated with poor survival in most solid tumors. STAT3 is a valuable biomarker for prognosis prediction and a promising therapeutic target in human solid tumors. PMID:26959884

  11. Lenalidomide enhances antibody-dependent cellular cytotoxicity of solid tumor cells in vitro: influence of host immune and tumor markers.

    PubMed

    Wu, Lei; Parton, Anastasia; Lu, Ling; Adams, Mary; Schafer, Peter; Bartlett, J Blake

    2011-01-01

    We evaluated the effect of combining lenalidomide with therapeutic antibodies on antibody-dependant cell-mediated cytotoxicity (ADCC) of solid tumor cells, and the requirement for expression of natural killer (NK) cell-activating receptors and their solid tumor surface ligands. Twenty-three human tumor cell lines (colon, breast, lung, head and neck, ovary, and bone sarcoma) were analyzed. NK effector cells were isolated from healthy donors, pre-treated with and without lenalidomide, and incubated with antibody-coated tumor cells to determine ADCC. In blocking experiments, NK cells were pre-incubated with anti-DNAM-1 or anti-NKG2D antibodies, and target colorectal cells were pre-incubated with anti-CD155 (PVR), anti-MIC-A/B, or anti-ULBP 3 antibodies. Differences between groups were assessed using unpaired and paired Student's t test and one-way ANOVA. Lenalidomide enhanced NK cell-mediated ADCC of trastuzumab- and cetuximab-coated tumor cells. Activity against colorectal cancer cells was dependent on target antigen expression, but independent of KRAS status and FcγRIIIa genotype. The extent of ADCC and its enhancement by lenalidomide correlated with NK cell expression of NKG2D and DNAM-1, and tumor cell expression of PVR and MIC-A. Blocking of NKG2D and, to a lesser extent, DNAM-1 inhibited ADCC. Anti-MIC-A/B monoclonal antibody blocked natural cytotoxicity, but not ADCC. Lenalidomide enhances the ability of IgG1-isotype antibodies to mediate ADCC of solid tumor cells, the extent of which is largely dependent on NKG2D-NKG2D ligand interactions, but appears to be independent of MIC-A/B. This provides a rationale for exploratory clinical studies and an assessment of potential biomarkers predictive of clinical benefit. PMID:20848094

  12. New Strategies for the Treatment of Solid Tumors with CAR-T Cells

    PubMed Central

    Zhang, Hao; Ye, Zhen-long; Yuan, Zhen-gang; Luo, Zheng-qiang; Jin, Hua-jun; qian, Qi-jun

    2016-01-01

    Recent years, we have witnessed significant progresses in both basic and clinical studies regarding novel therapeutic strategies with genetically engineered T cells. Modification with chimeric antigen receptors (CARs) endows T cells with tumor specific cytotoxicity and thus induce anti-tumor immunity against malignancies. However, targeting solid tumors is more challenging than targeting B-cell malignancies with CAR-T cells because of the histopathological structure features, specific antigens shortage and strong immunosuppressive environment of solid tumors. Meanwhile, the on-target/off-tumor toxicity caused by relative expression of target on normal tissues is another issue that should be reckoned. Optimization of the design of CAR vectors, exploration of new targets, addition of safe switches and combination with other treatments bring new vitality to the CAR-T cell based immunotherapy against solid tumors. In this review, we focus on the major obstacles limiting the application of CAR-T cell therapy toward solid tumors and summarize the measures to refine this new cancer therapeutic modality. PMID:27194949

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

    ClinicalTrials.gov

    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

  14. Physical performance limitations among adult survivors of childhood brain tumors

    PubMed Central

    Ness, Kirsten K.; Morris, E. Brannon; Nolan, Vikki G.; Howell, Carrie R.; Gilchrist, Laura S.; Stovall, Marilyn; Cox, Cheryl L.; Klosky, James L.; Gajjar, Amar; Neglia, Joseph P.

    2013-01-01

    Background Young adult survivors of childhood brain tumors (BT) may have late-effects that compromise physical performance and everyday task participation. Objective To evaluate muscle strength, fitness, physical performance, and task participation among adult survivors of childhood BT. Design/Method In-home evaluations and interviews were conducted for 156 participants (54% male). Results on measures of muscle strength, fitness, physical performance, and participation were compared between survivors and population-group members with chi-squared statistics and two-sample t-tests. Associations between late effects and physical performance, and physical performance and participation, were evaluated in regression models. Results BT survivors were a median age of 22 (18–58), and 14.7 (6.5–45.9) years from diagnosis. Survivors had lower estimates of grip strength (Female: 24.7±9.2 vs. 31.5±5.8, Male: 39.0±12.2 vs. 53.0±10.1 kilograms), knee extension strength (Female: 246.6±95.5 vs. 331.5±5.8, Male: 304.7±116.4 vs. 466.6±92.1 Newtons) and peak oxygen uptake (Female: 25.1±8.8 vs. 31.3±5.1, Male: 24.6±9.5 vs. 33.2±3.4 milliliters/kilogram/minute) than population-group members. Physical performance was lower among survivors and associated with not living independently (OR=5.0, 95% CI=2.0–12.2) and not attending college (OR=2.3, 95% CI 1.2–4.4). Conclusion Muscle strength and fitness values among BT survivors are similar to those among persons 60+ years, and are associated with physical performance limitations. Physical performance limitations are associated with poor outcomes in home and school environments. These data indicate an opportunity for interventions targeted at improving long-term physical function in this survivor population. PMID:20564409

  15. A novel tumor suppressor function of Kindlin-3 in solid cancer

    PubMed Central

    Menashi, Suzanne; Tost, Jorg; Podgorniak, Marie-Pierre; Sadoux, Aurelie; Daunay, Antoine; Teixeira, Luis; Soulier, Jean; Idbaih, Ahmed; Setterblad, Niclas; Fauvel, Françoise; Calvo, Fabien; Janin, Anne; Lebbé, Celeste; Mourah, Samia

    2014-01-01

    Kindlin-3 (FERMT-3) is known to be central in hemostasis and thrombosis control and its deficiency disrupts platelet aggregation and causes Leukocyte Adhesion Deficiency disease. Here we report that Kindlin-3 has a tumor suppressive role in solid cancer. Our present genetic and functional data show that Kindlin-3 is downregulated in several solid tumors by a mechanism involving gene hypermethylation and deletions. In vivo experiments demonstrated that Kindlin-3 knockdown in 2 tumor cell models (breast cancer and melanoma) markedly increases metastasis formation, in accord with the in vitro increase of tumor cell malignant properties. The metastatic phenotype was supported by a mechanism involving alteration in β3-integrin activation including decreased phosphorylation, interaction with talin and the internalization of its active form leading to less cell attachment and more migration/invasion. These data uncover a novel and unexpected tumor suppressor role of Kindin-3 which can influence integrins targeted therapies development. PMID:25344860

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

    ClinicalTrials.gov

    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

  17. Clinical actionability enhanced through deep targeted sequencing of solid tumors

    PubMed Central

    Chen, Ken; Meric-Bernstam, Funda; Zhao, Hao; Zhang, Qingxiu; Ezzeddine, Nader; Tang, Lin-ya; Qi, Yuan; Mao, Yong; Chen, Tenghui; Chong, Zechen; Zhou, Wanding; Zheng, Xiaofeng; Johnson, Amber; Aldape, Kenneth D.; Routbort, Mark J.; Luthra, Rajyalakshmi; Kopetz, Scott; Davies, Michael A.; de Groot, John; Moulder, Stacy; Vinod, Ravi; Farhangfar, Carol J.; Shaw, Kenna Mills; Mendelsohn, John; Mills, Gordon B.; Eterovic, Agda Karina

    2015-01-01

    Background Further advances of targeted cancer therapy require comprehensive in-depth profiling of somatic mutations that are present in subpopulations of tumor cells in a clinical tumor sample. However, it is unclear to what extent such intra-tumor heterogeneity is present and whether it may affect clinical decision making. To unravel this challenge, we established a deep targeted sequencing platform to identify potentially actionable DNA alterations in tumor samples. Methods We assayed 515 FFPE tumor samples and matched germline (475 patients) from 11 disease sites by capturing and sequencing all the exons in 201 cancer related genes. Mutations, indels and copy number data were reported. Results We obtained a 1000-fold average sequencing depth and identified 4794 non-synonymous mutations in the samples analyzed, which 15.2% were present at less than 10% allele frequency. Most of these low level mutations occurred at known oncogenic hotspots and are likely functional. Identifying low level mutations improved identification of mutations in actionable genes in 118 (24.84%) patients, among which 47 (9.8%) would otherwise be unactionable. In addition, acquiring ultra-high depth also ensured a low false discovery rate (less than 2.2%) from FFPE samples. Conclusion Our results were as accurate as a commercially available CLIA-compliant hotspot panel, but allowed the detection of a higher number of mutations in actionable genes. Our study revealed the critical importance of acquiring and utilizing high depth in profiling clinical tumor samples and presented a very useful platform for implementing routine sequencing in a cancer care institution. PMID:25626406

  18. Superior Performance of Aptamer in Tumor Penetration over Antibody: Implication of Aptamer-Based Theranostics in Solid Tumors

    PubMed Central

    Xiang, Dongxi; Zheng, Conglong; Zhou, Shu-Feng; Qiao, Shuxi; Tran, Phuong Ha-Lien; Pu, Chunwen; Li, Yong; Kong, Lingxue; Kouzani, Abbas Z.; Lin, Jia; Liu, Ke; Li, Lianhong; Shigdar, Sarah; Duan, Wei

    2015-01-01

    Insufficient penetration of therapeutic agents into tumor tissues results in inadequate drug distribution and lower intracellular concentration of drugs, leading to the increase of drug resistance and resultant failure of cancer treatment. Targeted drug delivery to solid tumors followed by complete drug penetration and durable retention will significantly improve clinical outcomes of cancer therapy. Monoclonal antibodies have been commonly used in clinic for cancer treatment, but their limitation of penetrating into tumor tissues still remains because of their large size. Aptamers, as “chemical antibodies”, are 15-20 times smaller than antibodies. To explore whether aptamers are superior to antibodies in terms of tumor penetration, we carried out the first comprehensive study to compare the performance of an EpCAM aptamer with an EpCAM antibody in theranostic applications. Penetration and retention were studied in in vitro three-dimensional tumorspheres, in vivo live animal imaging and mouse colorectal cancer xenograft model. We found that the EpCAM aptamer can not only effectively penetrate into the tumorsphere cores but can also be retained by tumor sphere cells for at least 24 h, while limited tumor penetration by EpCAM antibody was observed after 4 h incubation. As observed from in vivo live animal imaging, EpCAM aptamers displayed a maximum tumor uptake at around 10 min followed by a rapid clearance after 80 min, while the signal of peak uptake and disappearance of antibody appeared at 3 h and 6 h after intravenous injection, respectively. The signal of PEGylated EpCAM aptamers in xenograft tumors was sustained for 26 h, which was 4.3-fold longer than that of the EpCAM antibody. Consistently, there were 1.67-fold and 6.6-fold higher accumulation of PEGylated aptamer in xenograft tumors than that of antibody, at 3 h and 24 h after intravenous administration, respectively. In addition, the aptamer achieved at least a 4-time better tumor penetration in

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

    SciTech Connect

    Liu, Ying; Zhou, Mei; Luo, Dan; Wang, Lijun; Hong, Yuankai; Yang, Yepeng; Sha, Yinlin

    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. Pazopanib Hydrochloride in Treating Young Patients With Solid Tumors That Have Relapsed or Not Responded to Treatment

    ClinicalTrials.gov

    2013-09-27

    Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; 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; Metastatic Childhood Soft Tissue Sarcoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Visual Pathway Glioma; Unspecified Childhood Solid Tumor, Protocol Specific

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

    PubMed Central

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

    2015-01-01

    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. PMID:26212113

  2. BMP4/Thrombospondin-1 loop paracrinically inhibits tumor angiogenesis and suppresses the growth of solid tumors.

    PubMed

    Tsuchida, R; Osawa, T; Wang, F; Nishii, R; Das, B; Tsuchida, S; Muramatsu, M; Takahashi, T; Inoue, T; Wada, Y; Minami, T; Yuasa, Y; Shibuya, M

    2014-07-17

    Bone morphogenetic protein 4 (BMP4) has potential as an anticancer agent. Recent studies have suggested that BMP4 inhibits the survival of cancer stem cells (CSCs) of neural and colon cancers. Here, we showed that BMP4 paracrinically inhibited tumor angiogenesis via the induction of Thrombospondin-1 (TSP1), and consequently suppressed tumor growth in vivo. Although HeLa (human cervical cancer), HCI-H460-LNM35 (highly metastatic human lung cancer) and B16 (murine melanoma) cells did not respond to the BMP4 treatment in vitro, the growth of xeno- and allografts of these cells was suppressed via reductions in tumor angiogenesis after intraperitoneal treatment with BMP4. When we assessed the mRNA expression of major angiogenesis-related factors in grafted tumors, we found that the expression of TSP1 was significantly upregulated by BMP4 administration. We then confirmed that BMP4 was less effective in suppressing the tumor growth of TSP1-knockdown cancer cells. Furthermore, we found that BMP4 reduced vascular endothelial growth factor (VEGF) expression in vivo in a TSP1-dependent manner, which indicates that BMP4 interfered with the stabilization of tumor angiogenesis. In conclusion, the BMP4/TSP1 loop paracrinically suppressed tumor angiogenesis in the tumor microenvironment, which subsequently reduced the growth of tumors. BMP4 may become an antitumor agent and open a new field of antiangiogenic therapy. PMID:24013228

  3. Endothelial Jagged1 promotes solid tumor growth through both pro-angiogenic and angiocrine functions

    PubMed Central

    Pedrosa, Ana-Rita; Trindade, Alexandre; Carvalho, Catarina; Graça, José; Carvalho, Sandra; Peleteiro, Maria C.; Adams, Ralf H.; Duarte, António

    2015-01-01

    Angiogenesis is an essential process required for tumor growth and progression. The Notch signaling pathway has been identified as a key regulator of the neo-angiogenic process. Jagged-1 (Jag1) is a Notch ligand required for embryonic and retinal vascular development, which direct contribution to the regulation of tumor angiogenesis remains to be fully characterized. The current study addresses the role of endothelial Jagged1-mediated Notch signaling in the context of tumoral angiogenesis in two different mouse tumor models: subcutaneous Lewis Lung Carcinoma (LLC) tumor transplants and the autochthonous Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP). The role of endothelial Jagged1 in tumor growth and neo-angiogenesis was investigated with endothelial-specific Jag1 gain- and loss-of-function mouse mutants (eJag1OE and eJag1cKO). By modulating levels of endothelial Jag1, we observed that this ligand regulates tumor vessel density, branching, and perivascular maturation, thus affecting tumor vascular perfusion. The pro-angiogenic function is exerted by its ability to positively regulate levels of Vegfr-2 while negatively regulating Vegfr-1. Additionally, endothelial Jagged1 appears to exert an angiocrine function possibly by activating Notch3/Hey1 in tumor cells, promoting proliferation, survival and epithelial-to-mesenchymal transition (EMT), potentiating tumor development. These findings provide valuable mechanistic insights into the role of endothelial Jagged1 in promoting solid tumor development and support the notion that it may constitute a promising target for cancer therapy. PMID:26213336

  4. Endothelial Jagged1 promotes solid tumor growth through both pro-angiogenic and angiocrine functions.

    PubMed

    Pedrosa, Ana-Rita; Trindade, Alexandre; Carvalho, Catarina; Graça, José; Carvalho, Sandra; Peleteiro, Maria C; Adams, Ralf H; Duarte, António

    2015-09-15

    Angiogenesis is an essential process required for tumor growth and progression. The Notch signaling pathway has been identified as a key regulator of the neo-angiogenic process. Jagged-1 (Jag1) is a Notch ligand required for embryonic and retinal vascular development, which direct contribution to the regulation of tumor angiogenesis remains to be fully characterized. The current study addresses the role of endothelial Jagged1-mediated Notch signaling in the context of tumoral angiogenesis in two different mouse tumor models: subcutaneous Lewis Lung Carcinoma (LLC) tumor transplants and the autochthonous Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP). The role of endothelial Jagged1 in tumor growth and neo-angiogenesis was investigated with endothelial-specific Jag1 gain- and loss-of-function mouse mutants (eJag1OE and eJag1cKO). By modulating levels of endothelial Jag1, we observed that this ligand regulates tumor vessel density, branching, and perivascular maturation, thus affecting tumor vascular perfusion. The pro-angiogenic function is exerted by its ability to positively regulate levels of Vegfr-2 while negatively regulating Vegfr-1. Additionally, endothelial Jagged1 appears to exert an angiocrine function possibly by activating Notch3/Hey1 in tumor cells, promoting proliferation, survival and epithelial-to-mesenchymal transition (EMT), potentiating tumor development. These findings provide valuable mechanistic insights into the role of endothelial Jagged1 in promoting solid tumor development and support the notion that it may constitute a promising target for cancer therapy. PMID:26213336

  5. Remodeling of extracellular matrix due to solid stress accumulation during tumor growth.

    PubMed

    Pirentis, Athanassios P; Polydorou, Christiana; Papageorgis, Panagiotis; Voutouri, Chrysovalantis; Mpekris, Fotios; Stylianopoulos, Triantafyllos

    2015-01-01

    Solid stresses emerge as the expanding tumor displaces and deforms the surrounding normal tissue, and also as a result of intratumoral component interplay. Among other things, solid stresses are known to induce extensive extracellular matrix synthesis and reorganization. In this study, we developed a mathematical model of tumor growth that distinguishes the contribution to stress generation by collagenous and non-collagenous tumor structural components, and also investigates collagen fiber remodeling exclusively due to solid stress. To this end, we initially conducted in vivo experiments using an orthotopic mouse model for breast cancer to monitor primary tumor growth and derive the mechanical properties of the tumor. Subsequently, we fitted the mathematical model to experimental data to determine values of the model parameters. According to the model, intratumoral solid stress is compressive, whereas extratumoral stress in the tumor vicinity is compressive in the radial direction and tensile in the periphery. Furthermore, collagen fibers engaged in stress generation only in the peritumoral region, and not in the interior where they were slackened due to the compressive stress state. Peritumoral fibers were driven away from the radial direction, tended to realign tangent to the tumor-host interface, and were also significantly stretched by tensile circumferential stresses. By means of this remodeling, the model predicts that the tumor is enveloped by a progressively thickening capsule of collagen fibers. This prediction is consistent with long-standing observations of tumor encapsulation and histologic sections that we performed, and it further corroborates the expansive growth hypothesis for the capsule formation. PMID:26194953

  6. Favorable Alteration of Tumor Microenvironment by Immunomodulatory Cytokines for Efficient T-Cell Therapy in Solid Tumors

    PubMed Central

    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. PMID:26107883

  7. Clinical guidance on the perioperative use of targeted agents in solid tumor oncology.

    PubMed

    Mellor, James D; Cassumbhoy, Michelle; Jefford, Michael

    2011-06-01

    The use of targeted anti-cancer agents is increasing. It is common to utilize a multi-modal treatment approach towards solid tumors, often including surgical resection, and it has become apparent that some targeted agents can impair wound healing or cause an increased risk of perioperative complications. This article reviews targeted agents used in solid tumor oncology with an emphasis on clinically relevant details. Overall, the evidence of targeted agents causing surgical complications is limited. The greatest amount of evidence exists for bevacizumab causing perioperative complications, possibly due to its extended half-life. There are limited data for cetuximab, sorafenib and sunitinib and very little for other solid tumor targeted agents. Our findings suggest that there should be heightened pharmacovigilence around targeted agents with respect to perioperative complications and increased post-surgical support for patients to aid early detection of postoperative complications until definitive data become available. PMID:21585689

  8. Detection of BRAF mutations from solid tumors using Tumorplex™ technology

    PubMed Central

    Yo, Jacob; Hay, Katie S.L.; Vinayagamoorthy, Dilanthi; Maryanski, Danielle; Carter, Mark; Wiegel, Joseph; Vinayagamoorthy, Thuraiayah

    2015-01-01

    Allele specific multiplex sequencing (Tumorplex™) is a new molecular platform for the detection of single base mutation in tumor biopsies with high sensitivity for clinical testing. Tumorplex™ is a novel modification of Sanger sequencing technology that generates both mutant and wild type nucleotide sequences simultaneously in the same electropherogram. The molecular weight of the two sequencing primers are different such that the two sequences generated are separated, thus eliminating possible suppression of mutant signal by the more abundant wild type signal. Tumorplex™ platform technology was tested using BRAF mutation V600E. These studies were performed with cloned BRAF mutations and genomic DNA extracted from tumor cells carrying 50% mutant allele. The lower limit of detection for BRAF V600E was found to be 20 genome equivalents (GE) using genomic DNA extracted from mutation specific cell lines. Sensitivity of the assay was tested by challenging the mutant allele with wild type allele at 20 GE, and was able to detect BRAF mutant signal at a GE ration of 20:1 × 107 (mutant to wild-type). This level of sensitivity can detect low abundance of clonal mutations in tumor biopsies and eliminate the need for cell enrichment. • Tumorplex™ is a single tube assay that permits the recognition of mutant allele without suppression by wildtype signal. • Tumorplex™ provides a high level of sensitivity. • Tumorplex™ can be used with small sample size with mixed population of cells carrying heterogeneous gDNA. PMID:26258049

  9. High-intensity focused ultrasound for the treatment of solid tumor: Chinese clinical experience

    NASA Astrophysics Data System (ADS)

    Takeuchi, Akira; Zhang, Hong; Sun, Kun; Hasumura, Hiromi; Liu, Botao; Fu, Yurui; Yang, Zaocheng

    2006-05-01

    As a non-invasive modality, high-intensity focused ultrasound (HIFU) therapy has been received an interest for the treatment of solid tumor. There are some makers of HIFU for the equipment in China. The Sonic CZ901 is developed from the Mianyang stream that has a great advantage for guiding by color Doppler ultrasound imaging. For the research about possibility of this equipment, we evaluate the clinical usefulness to the solid tumor of HIFU treatment at Wujing general hospital in Beijing. We elucidate the result in 28 cases with benign and malignant tumor (Uterine myoma:16, Benign prostatic hypertrophy:5, Benign breast tumor:2, Breast cancer:1, Retroperitoneal tumor:1, Pheochromocytoma:1, Liver cancer: 2) . After 14˜90days, all cases show the reduction of tumor size (Max.3.2cm, Min.1.6cm, :Mean 2.2cm reduced), and the blood flow of tumor completely reduced in 7/23, partially reduced in16/23. Clinical symptoms disappeared in 7, clearly improved in 14, improved in 7. All treatments had no adverse event except for two cases of liver cancer. They felt an abdominal pain that controllable by medicine and it improved within 6hours. It is concluded that HIFU with guide by ultrasound imaging is very safe, painless and effective as the anti-tumor treatment.

  10. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors.

    PubMed

    Hedvat, Michael; Huszar, Dennis; Herrmann, Andreas; Gozgit, Joseph M; Schroeder, Anne; Sheehy, Adam; Buettner, Ralf; Proia, David; Kowolik, Claudia M; Xin, Hong; Armstrong, Brian; Bebernitz, Geraldine; Weng, Shaobu; Wang, Lin; Ye, Minwei; McEachern, Kristen; Chen, Huawei; Morosini, Deborah; Bell, Kirsten; Alimzhanov, Marat; Ioannidis, Stephanos; McCoon, Patricia; Cao, Zhu A; Yu, Hua; Jove, Richard; Zinda, Michael

    2009-12-01

    Persistent activation of Stat3 is oncogenic and is prevalent in a wide variety of human cancers. Chronic cytokine stimulation is associated with Stat3 activation in some tumors, implicating cytokine receptor-associated Jak family kinases. Using Jak2 inhibitors, we demonstrate a central role of Jaks in modulating basal and cytokine-induced Stat3 activation in human solid tumor cell lines. Inhibition of Jak2 activity is associated with abrogation of Stat3 nuclear translocation and tumorigenesis. The Jak2 inhibitor AZD1480 suppresses the growth of human solid tumor xenografts harboring persistent Stat3 activity. We demonstrate the essential role of Stat3 downstream of Jaks by inhibition of tumor growth using short hairpin RNA targeting Stat3. Our data support a key role of Jak kinase activity in Stat3-dependent tumorigenesis. PMID:19962667

  11. 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia

    ClinicalTrials.gov

    2013-06-03

    Acute Undifferentiated Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  12. Incidence of anemia, leukocytosis, and thrombocytosis in patients with solid tumors in China.

    PubMed

    Qiu, Miao-zhen; Xu, Rui-hua; Ruan, Dan-yun; Li, Zhuang-hua; Luo, Hui-yan; Teng, Kai-yuan; Wang, Zhi-qiang; Li, Yu-hong; Jiang, Wen-qi

    2010-12-01

    Despite the fact that malignancies are associated with hematological abnormalities, some clinical studies have been unable to detect such a relation. The aim of our study was to detect the prevalence of pretreatment hematologic abnormalities in patients with common solid tumors and to determine if such a profile could be used for prognostic evaluations. We identified all patients in Cancer Center of Sun Yat-sen University who were diagnosed as solid tumors (breast carcinoma, hepatocellular carcinoma, nasopharyngeal carcinoma, esophageal carcinoma, gastric cancer, cervical carcinoma, endometrial cancer, renal cell carcinoma, and non-small cell lung cancer) between January 2000 and August 2009. All subjects were investigated regarding levels of white blood cells, platelets, and hemoglobin concentration. We identified 3,180 patients with solid tumors and 285 patients with benign diseases for the final analysis. The percentages of leukocytosis, anemia, and thrombocytosis in patients with solid tumors ranged from 4.0% to 25.6%, 3.3% to 29.2%, and 2.1% to 9.7%, respectively. The multivariate Cox analysis revealed that anemia was an independent prognostic factor in patients with breast cancer (P = 0.006), hepatocellular carcinoma (P = 0.002), nasopharyngeal carcinoma (P = 0.008), and esophageal carcinoma (P = 0.001). Leukocytosis was an independent prognostic factor in patients with cervical cancer (P = 0.007). The incidence of hematological abnormalities in Chinese patients with solid tumors was relatively lower than that of the counterparts in the Western countries. A pretreatment anemia or leukocytosis can serve as a useful marker to predict outcome of patients in some of the solid tumors. PMID:20652781

  13. Wildtype adult stem cells, unlike tumor cells, are resistant to cellular damages in Drosophila.

    PubMed

    Ma, Meifang; Zhao, Hang; Zhao, Hanfei; Binari, Richard; Perrimon, Norbert; Li, Zhouhua

    2016-03-15

    Adult stem cells or residential progenitor cells are critical to maintain the structure and function of adult tissues (homeostasis) throughout the lifetime of an individual. Mis-regulation of stem cell proliferation and differentiation often leads to diseases including cancer, however, how wildtype adult stem cells and cancer cells respond to cellular damages remains unclear. We find that in the adult Drosophila midgut, intestinal stem cells (ISCs), unlike tumor intestinal cells, are resistant to various cellular damages. Tumor intestinal cells, unlike wildtype ISCs, are easily eliminated by apoptosis. Further, their proliferation is inhibited upon autophagy induction, and autophagy-mediated tumor inhibition is independent of caspase-dependent apoptosis. Interestingly, inhibition of tumorigenesis by autophagy is likely through the sequestration and degradation of mitochondria, as compromising mitochondria activity in these tumor models mimics the induction of autophagy and increasing the production of mitochondria alleviates the tumor-suppression capacity of autophagy. Together, these data demonstrate that wildtype adult stem cells and tumor cells show dramatic differences in sensitivity to cellular damages, thus providing potential therapeutic implications targeting tumorigenesis. PMID:26845534

  14. Use of Arsenic Trioxide as an Antivascular and Thermosensitizing Agent in Solid Tumors1

    PubMed Central

    Griffin, Robert J; Lee, Sang H; Rood, Kelly L; Stewart, Michael J; Lyons, John C; Lew, Young S; Park, Heonjoo; Song, Chang W

    2000-01-01

    Abstract 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 TNFα 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. PMID:11228548

  15. In-vivo imaging of nanoshell extravasation from solid tumor vasculature by photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Li, Meng-Lin; Schwartz, Jon A.; Wang, James; Stoica, George; Wang, Lihong V.

    2007-02-01

    In this study, high resolution reflection-mode (backward-mode) photoacoustic microscopy (PAM) is used to noninvasively image progressive extravasation and accumulation of nanoshells within a solid tumor in vivo. This study takes advantage of the strong near-infrared absorption of nanoshells, a novel type of optically tunable gold nanoparticles that tend to extravasate from leaky tumor vasculatures (i.e., passive targeting) via the "enhanced permeability and retention" effect due to their nanoscale size. Tumors were grown in immunocompetent BALB/c mice by subcutaneous inoculation of CT26.wt murine colon carcinoma cells. PEGylated nanoshells with a peak optical absorption at ~800 nm were intravenously administered. Pre-scans prior to nanoshell injection were taken using a 584-nm laser source to highlight blood content and an 800-nm laser source to mark the background limit for nanoshell accumulation. After injection, the three-dimensional nanoshell distribution inside the tumor was monitored by PAM for 7 hours. Experimental results show that nanoshell accumulation is heterogeneous in tumors: more concentrated within the tumor cortex and largely absent from the tumor core. This correlates with others' observation that drug delivery within tumor cores is ineffective because of both high interstitial pressure and tendency to necrosis of tumor cores. Since nanoshells have been recently applied to thermal therapy for subcutaneous tumors, we anticipate that PAM will be important to this therapeutic technique.

  16. Chemokines, costimulatory molecules and fusion proteins for the immunotherapy of solid tumors

    PubMed Central

    Lechner, Melissa G; Russell, Sarah M; Bass, Rikki S; Epstein, Alan L

    2011-01-01

    In this article, the role of chemokines and costimulatory molecules in the immunotherapy of experimental murine solid tumors and immunotherapy used in ongoing clinical trials are presented. Chemokine networks regulate physiologic cell migration that may be disrupted to inhibit antitumor immune responses or coopted to promote tumor growth and metastasis in cancer. Recent studies highlight the potential use of chemokines in cancer immunotherapy to improve innate and adaptive cell interactions and to recruit immune effector cells into the tumor microenvironment. Another critical component of antitumor immune responses is antigen priming and activation of effector cells. Reciprocal expression and binding of costimulatory molecules and their ligands by antigen-presenting cells and naive lymphocytes ensures robust expansion, activity and survival of tumor-specific effector cells in vivo. Immunotherapy approaches using agonist antibodies or fusion proteins of immunomodulatory molecules significantly inhibit tumor growth and boost cell-mediated immunity. To localize immune stimulation to the tumor site, a series of fusion proteins consisting of a tumor-targeting monoclonal antibody directed against tumor necrosis and chemokines or costimulatory molecules were generated and tested in tumor-bearing mice. While several of these reagents were initially shown to have therapeutic value, combination therapies with methods to delete suppressor cells had the greatest effect on tumor growth. In conclusion, a key conclusion that has emerged from these studies is that successful immunotherapy will require both advanced methods of immunostimulation and the removal of immunosuppression in the host. PMID:22053884

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

    PubMed Central

    Zhang, Xiaonan; de Milito, Angelo; Olofsson, Maria Hägg; Gullbo, Joachim; D’Arcy, Padraig; Linder, Stig

    2015-01-01

    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. PMID:26580606

  18. Albumin-bound paclitaxel in solid tumors: clinical development and future directions

    PubMed Central

    Kundranda, Madappa N; Niu, Jiaxin

    2015-01-01

    Albumin-bound paclitaxel (nab-paclitaxel) is a solvent-free formulation of paclitaxel that was initially developed more than a decade ago to overcome toxicities associated with the solvents used in the formulation of standard paclitaxel and to potentially improve efficacy. Nab-paclitaxel has demonstrated an advantage over solvent-based paclitaxel by being able to deliver a higher dose of paclitaxel to tumors and decrease the incidence of serious toxicities, including severe allergic reactions. To date, nab-paclitaxel has been indicated for the treatment of three solid tumors in the USA. It was first approved for the treatment of metastatic breast cancer in 2005, followed by locally advanced or metastatic non-small-cell lung cancer in 2012, and most recently for metastatic pancreatic cancer in 2013. Nab-paclitaxel is also under investigation for the treatment of a number of other solid tumors. This review highlights key clinical efficacy and safety outcomes of nab-paclitaxel in the solid tumors for which it is currently indicated, discusses ongoing trials that may provide new data for the expansion of nab-paclitaxel’s indications into other solid tumors, and provides a clinical perspective on the use of nab-paclitaxel in practice. PMID:26244011

  19. Pediatric Adrenocortical Tumors: What They Can Tell Us on Adrenal Development and Comparison with Adult Adrenal Tumors

    PubMed Central

    Lalli, Enzo; Figueiredo, Bonald C.

    2015-01-01

    Adrenocortical tumors (ACT) in children are very rare and are most frequently diagnosed in the context of the Li-Fraumeni syndrome, a multiple cancer syndrome linked to germline mutations of the tumor suppressor gene TP53 with loss of heterozygosity in the tumors. A peak of children ACT incidence is present in the states of southern Brazil, where they are linked to the high prevalence in the population of a specific TP53 mutation (R337H). Children ACT have specific features distinguishing them from adult tumors in their pathogenetic mechanisms, genomic profiles, and prognosis. Epidemiological and molecular evidence suggests that in most cases they are derived from the fetal adrenal. PMID:25741319

  20. Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias.

    PubMed

    Pietra, Gabriella; Vitale, Chiara; Pende, Daniela; Bertaina, Alice; Moretta, Francesca; Falco, Michela; Vacca, Paola; Montaldo, Elisa; Cantoni, Claudia; Mingari, Maria Cristina; Moretta, Alessandro; Locatelli, Franco; Moretta, Lorenzo

    2016-04-01

    It is well established that natural killer (NK) cells play an important role in the immunity against cancer, while the involvement of other recently identified, NK-related innate lymphoid cells is still poorly defined. In the haploidentical hematopoietic stem cell transplantation for the therapy of high-risk leukemias, NK cells have been shown to exert a key role in killing leukemic blasts residual after conditioning. While the clinical results in the cure of leukemias are excellent, the exploitation of NK cells in the therapy of solid tumors is still limited and unsatisfactory. In solid tumors, NK cell function may be inhibited via different mechanisms, occurring primarily at the tumor site. The cellular interactions in the tumor microenvironment involve tumor cells, stromal cells and resident or recruited leukocytes and may favor tumor evasion from the host's defenses. In this context, a number of cytokines, growth factors and enzymes synthesized by tumor cells, stromal cells, suppressive/regulatory myeloid and lymphoid cells may substantially impair the function of different tumor-reactive effector cells, including NK cells. The identification and characterization of such mechanisms may offer clues for the development of new immunotherapeutic strategies to restore effective anti-tumor responses. In order to harness NK cell-based immunotherapies, several approaches have been proposed, including reinforcement of NK cell cytotoxicity by means of specific cytokines, antibodies or drugs. These new tools may improve NK cell function and/or increase tumor susceptibility to NK-mediated killing. Hence, the integration of NK-based immunotherapies with conventional anti-tumor therapies may increase chances of successful cancer treatment. PMID:26289090

  1. Pharmacokinetic strategies to improve drug penetration and entrapment within solid tumors.

    PubMed

    Al-Abd, Ahmed M; Aljehani, Zekra K; Gazzaz, Rana W; Fakhri, Sarah H; Jabbad, Aisha H; Alahdal, Abdulrahman M; Torchilin, Vladimir P

    2015-12-10

    Despite the discovery of a large number of anticancer agents, cancer still remains among the leading causes of death since the middle of the twentieth century. Solid tumors possess a high degree of genetic instability and emergence of treatment resistance. Tumor resistance has emerged for almost all approved anticancer drugs and will most probably emerge for newly discovered anticancer agents as well. The use of pharmacokinetic approaches to increase anticancer drug concentrations within the solid tumor compartment and prolong its entrapment might diminish the possibility of resistance emergence at the molecular pharmacodynamic level and might even reverse tumor resistance. Several novel treatment modalities such as metronomic therapy, angiogenesis inhibitors, vascular disrupting agents and tumor priming have been introduced to improve solid tumor treatment outcomes. In the current review we will discuss the pharmacokinetic aspect of these treatment modalities in addition to other older treatment modalities, such as extracellular matrix dissolving agents, extracellular matrix synthesis inhibitors, chemoembolization and cellular efflux pump inhibition. Many of these strategies showed variable degrees of success/failure; however, reallocating these modalities based on their influence on the intratumoral pharmacokinetics might improve their understanding and treatment outcomes. PMID:26342660

  2. High Intensity Focused Ultrasound induced Gene Activation in Solid Tumors

    NASA Astrophysics Data System (ADS)

    Liu, Yunbo; Kon, Takashi; Li, Chuanyuan; Zhong, Pei

    2006-05-01

    In this work, the feasibility of using high intensity focused ultrasound (HIFU) to activate trans-gene expression in a mouse tumor model was investigated. 4T1 cancer cells were implanted subcutaneously in the hind limbs of Balb/C mice and adenovirus luciferase gene vectors under the control of heat shock protein 70B promoter (Adeno-hsp70B-Luc) were injected intratumoraly for gene transfection. One day following the virus injection, the transfected tumors were heated to a peak temperature of 55, 65, 75, and 85°C, respectively, in 10s at multiple sites around the center of the tumor using a HIFU transducer operated at either 1.1-MHz (fundamental) or 3.3-MHz (3rd harmonic) frequency. Inducible luciferase gene expression was found to vary from 15-fold to 120-fold of the control group following 1.1-MHz HIFU exposure. The maximum gene activation was produced at a peak temperature of 65˜75°C one day following HIFU exposure and decayed gradually to baseline level within 7 days. The inducible gene activation produced by 3.3-MHz HIFU exposure (75°C-10s) was found to be comparable to that produced by hyperthermia (42°C-30min). Altogether, these results demonstrate the feasibility of using HIFU as a simple and versatile physical means to regulate trans-gene expression in vivo. This unique feature may be explored in the future for a synergistic combination of HIFU-induced thermal ablation with heat-induced gene therapy for improved cancer therapy.

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

    PubMed

    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. PMID:26851443

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

    NASA Astrophysics Data System (ADS)

    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

  5. Formation of solid tumors by a single multinucleated cancer cel

    PubMed Central

    Weihua, Zhang; Lin, Qingtang; Ramoth, Asa J.; Fan, Dominic; Fidler, Isaiah J.

    2011-01-01

    BACKGROUND Large multinucleated cells (MNC) commonly exist in tumorigenic cancer cell lines widely used in research, but their contributions to tumorigenesis are unknown. METHODS In this study, we characterized MNCs in the murine fibrosarcoma cell line UV-2237 in vitro and in vivo at a single cell level. RESULTS We observed that MNCs originated from a rare subpopulation of mononuclear cells; MNCs were positive for a senescent marker, β-galacosidase (SA-β-Gal); MNCs were responsible for the majority of clonogenic activity when cultured in hard agar; MNCs were more resistant to chemotherapeutic agents than were mononuclear cells; MNCs could undergo asymmetric division (producing mononuclear cells) and self-renewal in vitro and in vivo; and, most importantly a single MNC produced orthotopic subcutaneous tumors (composed mainly of mononuclear cells) that gave rise to spontaneous lung metastases in nude mice. CONCLUSIONS MNCs can be growth-arrested under stress, are highly resistant to chemotherapy, and can generate clonal orthotopic metastatic tumors PMID:21365635

  6. The oncolytic effects of reovirus in canine solid tumor cell lines

    PubMed Central

    IGASE, Masaya; HWANG, Chung Chew; COFFEY, Matt; OKUDA, Masaru; NOGUCHI, Shunsuke; MIZUNO, Takuya

    2015-01-01

    Oncolytic virotherapy is a new strategy for cancer treatment for humans and dogs. Reovirus has been proven to be a potent oncolytic virus in human medicine. Our laboratory has previously reported that canine mast cell tumor and canine lymphoma were susceptible to reovirus. In this study, canine solid tumor cell lines (mammary gland tumor, osteosarcoma and malignant melanoma) were tested to determine their susceptibility towards reovirus. We demonstrated that reovirus induces more than 50% cell death in three canine mammary gland tumors and one canine malignant melanoma cell line. The reovirus-induced cell death occurred via the activation of caspase 3. Ras activation has been shown to be one of the important mechanisms of reovirus-susceptibility in human cancers. However, Ras activation was not related to the reovirus-susceptibility in canine solid tumor cell lines, which was similar to reports in canine mast cell tumor and canine lymphoma. The results of this study highly suggest that canine mammary gland tumor and canine malignant melanoma are also potential candidates for reovirus therapy in veterinary oncology. PMID:25648933

  7. The oncolytic effects of reovirus in canine solid tumor cell lines.

    PubMed

    Igase, Masaya; Hwang, Chung Chew; Coffey, Matt; Okuda, Masaru; Noguchi, Shunsuke; Mizuno, Takuya

    2015-05-01

    Oncolytic virotherapy is a new strategy for cancer treatment for humans and dogs. Reovirus has been proven to be a potent oncolytic virus in human medicine. Our laboratory has previously reported that canine mast cell tumor and canine lymphoma were susceptible to reovirus. In this study, canine solid tumor cell lines (mammary gland tumor, osteosarcoma and malignant melanoma) were tested to determine their susceptibility towards reovirus. We demonstrated that reovirus induces more than 50% cell death in three canine mammary gland tumors and one canine malignant melanoma cell line. The reovirus-induced cell death occurred via the activation of caspase 3. Ras activation has been shown to be one of the important mechanisms of reovirus-susceptibility in human cancers. However, Ras activation was not related to the reovirus-susceptibility in canine solid tumor cell lines, which was similar to reports in canine mast cell tumor and canine lymphoma. The results of this study highly suggest that canine mammary gland tumor and canine malignant melanoma are also potential candidates for reovirus therapy in veterinary oncology. PMID:25648933

  8. SN-38-loaded nanofiber matrices for local control of pediatric solid tumors after subtotal resection surgery.

    PubMed

    Monterrubio, Carles; Pascual-Pasto, Guillem; Cano, Francisco; Vila-Ubach, Monica; Manzanares, Alejandro; Schaiquevich, Paula; Tornero, Jose A; Sosnik, Alejandro; Mora, Jaume; Carcaboso, Angel M

    2016-02-01

    In addition to surgery, local tumor control in pediatric oncology requires new treatments as an alternative to radiotherapy. SN-38 is an anticancer drug with proved activity against several pediatric solid tumors including neuroblastoma, rhabdomyosarcoma and Ewing sarcoma. Taking advantage of the extremely low aqueous solubility of SN-38, we have developed a novel drug delivery system (DDS) consisting of matrices made of poly(lactic acid) electrospun polymer nanofibers loaded with SN-38 microcrystals for local release in difficult-to-treat pediatric solid tumors. To model the clinical scenario, we conducted extensive preclinical experiments to characterize the biodistribution of the released SN-38 using microdialysis sampling in vivo. We observed that the drug achieves high concentrations in the virtual space of the surgical bed and penetrates a maximum distance of 2 mm within the tumor bulk. Subsequently, we developed a model of subtotal tumor resection in clinically relevant pediatric patient-derived xenografts and used such models to provide evidence of the activity of the SN-38 DDS to inhibit tumor regrowth. We propose that this novel DDS could represent a potential future strategy to avoid harmful radiation therapy as a primary tumor control together with surgery. PMID:26695118

  9. Evading anti-angiogenic therapy: resistance to anti-angiogenic therapy in solid tumors

    PubMed Central

    Dey, Nandini; De, Pradip; Brian, Leyland-Jones

    2015-01-01

    Vascular endothelial growth factor (VEGF) dependent tumor angiogenesis is an essential step for the initiation and promotion of tumor progression. The hypothesis that VEGF-driven tumor angiogenesis is necessary and sufficient for metastatic progression of the tumor, has been the major premise of the use of anti-VEGF therapy for decades. While the success of anti-VEGF therapy in solid tumors has led to the success of knowledge-based-therapies over the past several years, failures of this therapeutic approach due to the development of inherent/acquired resistance has led to the increased understanding of VEGF-independent angiogenesis. Today, tumor-angiogenesis is not a synonymous term to VEGF-dependent function. The extensive study of VEGF-independent angiogenesis has revealed several key factors responsible for this phenomenon including the role of myeloid cells, and the contribution of entirely new phenomenon like vascular mimicry. In this review, we will present the cellular and molecular factors related to the development of anti-angiogenic resistance following anti-VEGF therapy in different solid tumors. PMID:26692917

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

    PubMed Central

    Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

    2014-01-01

    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. PMID:25493378

  11. Evading anti-angiogenic therapy: resistance to anti-angiogenic therapy in solid tumors.

    PubMed

    Dey, Nandini; De, Pradip; Brian, Leyland-Jones

    2015-01-01

    Vascular endothelial growth factor (VEGF) dependent tumor angiogenesis is an essential step for the initiation and promotion of tumor progression. The hypothesis that VEGF-driven tumor angiogenesis is necessary and sufficient for metastatic progression of the tumor, has been the major premise of the use of anti-VEGF therapy for decades. While the success of anti-VEGF therapy in solid tumors has led to the success of knowledge-based-therapies over the past several years, failures of this therapeutic approach due to the development of inherent/acquired resistance has led to the increased understanding of VEGF-independent angiogenesis. Today, tumor-angiogenesis is not a synonymous term to VEGF-dependent function. The extensive study of VEGF-independent angiogenesis has revealed several key factors responsible for this phenomenon including the role of myeloid cells, and the contribution of entirely new phenomenon like vascular mimicry. In this review, we will present the cellular and molecular factors related to the development of anti-angiogenic resistance following anti-VEGF therapy in different solid tumors. PMID:26692917

  12. The combination of ISCOMATRIX adjuvant and TLR agonists induces regression of established solid tumors in vivo.

    PubMed

    Silva, Anabel; Mount, Adele; Krstevska, Karoline; Pejoski, David; Hardy, Matthew P; Owczarek, Catherine; Scotney, Pierre; Maraskovsky, Eugene; Baz Morelli, Adriana

    2015-03-01

    The development of therapeutic vaccines for treatment of established cancer has proven challenging. Cancer vaccines not only need to induce a robust tumor Ag-specific immune response but also need to overcome the tolerogenic and immunosuppressive microenvironments that exist within many solid cancers. ISCOMATRIX adjuvant (ISCOMATRIX) is able to induce both tumor Ag-specific cellular and Ab responses to protect mice against tumor challenge, but this is insufficient to result in regression of established solid tumors. In the current study, we have used B16-OVA melanoma, Panc-OVA pancreatic, and TRAMP-C1 prostate cancer mouse tumor models to test therapeutic efficacy of ISCOMATRIX vaccines combined with other immune modulators. The coadministration of an ISCOMATRIX vaccine with the TLR3 agonist, polyinosinic-polycytidylic acid, and TLR9 agonist, CpG, reduced tumor growth in all tumor models and the presence of ISCOMATRIX in the formulation was critical for the therapeutic efficacy of the vaccine. This vaccine combination induced a robust and multifunctional CD8(+) T cell response. Therapeutic protection required IFN-γ and CD8(+) T cells, whereas NK and CD4(+) T cells were found to be redundant. ISCOMATRIX vaccines combined with TLR3 and TLR9 agonists represent a promising cancer immunotherapy strategy. PMID:25646304

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

    PubMed

    Chauviere, Arnaud; Hatzikirou, Haralambos; Kevrekidis, Ioannis G; Lowengrub, John S; Cristini, Vittorio

    2012-03-01

    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. PMID:22489279

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

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

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

  15. Transient Mild Hyperthermia Induces E-selectin Mediated Localization of Mesoporous Silicon Vectors in Solid Tumors

    PubMed Central

    Kirui, Dickson K.; Mai, Juahua; Palange, Anna-Lisa; Qin, Guoting; van de Ven, Anne L.; Liu, Xuewu; Shen, Haifa; Ferrari, Mauro

    2014-01-01

    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/cm2) 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. PMID:24558362

  16. A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers

    ClinicalTrials.gov

    2016-04-05

    CD27 Expressing B-cell Malignancies, (for Example: Hodgkin's Lymphoma,; Chronic Lymphocytic Leukemia, Burkett's Lymphoma,; Mantle Cell Lymphoma, Primary Lymphoma of the Central Nervous System,; Marginal Zone B Cell Lymphoma);; Any T-cell Malignancy;; Solid Tumors (Metastatic Melanoma, Renal (Clear) Cell Carcinoma,; Hormone-refractory Prostate Adenocarcinoma, Ovarian Cancer; Colorectal Adenocarcinoma, Non-small Cell Lung Cancer)

  17. Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman

    PubMed Central

    Lestelle, Valentin; de Coster, Claire; Sarran, Anthony; Poizat, Flora; Delpero, Jean-Robert; Raoul, Jean-Luc

    2015-01-01

    We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare. PMID:26557078

  18. Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman.

    PubMed

    Lestelle, Valentin; de Coster, Claire; Sarran, Anthony; Poizat, Flora; Delpero, Jean-Robert; Raoul, Jean-Luc

    2015-01-01

    We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare. PMID:26557078

  19. Hydrodynamic Tail Vein Injection as a Simple Tool for Yielding Extended Transgene Expression in Solid Tumors.

    PubMed

    Takayama, Takuma; Ukawa, Masami; Kanazawa, Yuki; Ando, Hidenori; Shimizu, Taro; Ishida, Tatsuhiro

    2016-01-01

    Hydrodynamic tail vein injection was considered an in vivo transfection method that yields a higher level of gene expression mainly in the liver. This method has been applied to cancer gene therapy targeting both hepatic and non-hepatic cancers. However, intratumor transgene expression in non-hepatic tumors has not been well studied. In this study, we showed an extended transgene expression of β-galactosidase (LacZ), a nonsecretory protein, in a subcutaneously implanted murine solid tumor following the hydrodynamic injection of plasmid DNA (LacZ pDNA). Our result may indicate that the hydrodynamic injection method is a powerful tool that can be used to gain transgene expression not only in the liver but also in solid tumors. PMID:27582335

  20. Identification of recurrent regulated alternative splicing events across human solid tumors

    PubMed Central

    Danan-Gotthold, Miri; Golan-Gerstl, Regina; Eisenberg, Eli; Meir, Keren; Karni, Rotem; Levanon, Erez Y.

    2015-01-01

    Cancer is a complex disease that involves aberrant gene expression regulation. Discriminating the modified expression patterns driving tumor biology from the many that have no or little contribution is important for understanding cancer molecular basis. Recurrent deregulation patterns observed in multiple cancer types are enriched for such driver events. Here, we studied splicing alterations in hundreds of matched tumor and normal RNA-seq samples of eight solid cancer types. We found hundreds of cassette exons for which splicing was altered in multiple cancer types and identified a set of highly frequent altered splicing events. Specific splicing regulators, including RBFOX2, MBNL1/2 and QKI, appear to account for many splicing alteration events in multiple cancer types. Together, our results provide a first global analysis of regulated splicing alterations in cancer and identify common events with a potential causative role in solid tumor development. PMID:25908786

  1. Targeting cancer stem cells in solid tumors by vitamin D

    PubMed Central

    Jae Young, So; Nanjoo, Suh

    2014-01-01

    Cancer stem cells (CSCs) are a small subset of cells that may be responsible for initiation, progression and recurrence of tumors. Recent studies have demonstrated that CSCs are highly tumorigenic and resistant to conventional chemotherapies, making them a promising target for the development of preventive/therapeutic agents. A single or combination of various markers, such as CD44, EpCAM, CD49f, CD133, CXCR4, ALDH-1 and CD24, were utilized to isolate CSCs fromvarious types of human cancers. Notch, Hedgehog, Wnt, and TGF-β signalingregulate self-renewal and differentiation of normal stem cells andare aberrantly activated in CSCs. In addition, many studies have demonstrated that these stem cell-associated signaling pathways are required for the maintenance of CSCs in differentmalignancies, including breast, colorectal, prostate and pancreatic cancers. Accumulating evidence hasshowninhibitory effects of vitamin D and its analogs on the cancer stem cell signaling pathways, suggesting vitamin D as a potential preventive/therapeutic agent against CSCs.In this review, we summarize recent findings about the roles of Notch, Hedgehog, Wnt, and TGF-β signaling in CSCs as well as the effects of vitamin D on these stem cell signaling pathways. PMID:25460302

  2. Image-Guided Local Delivery Strategies Enhance Therapeutic Nanoparticle Uptake in Solid Tumors

    PubMed Central

    Mouli, Samdeep K.; Tyler, Patrick; McDevitt, Joseph L.; Eifler, Aaron C.; Guo, Yang; Nicolai, Jodi; Lewandowski, Robert .J.; Li, Weiguo; Procissi, Daniel; Ryu, Robert K.; Wang, Y. Andrew; Salem, Riad; Larson, Andrew C.; Omary, Reed A.

    2013-01-01

    Nanoparticles (NP) have emerged as a novel class of therapeutic agents that overcome many of the limitations of current cancer chemotherapeutics. However, a major challenge to many current NP platforms is unfavorable biodistribution, and limited tumor uptake, upon systemic delivery. Delivery, therefore, remains a critical barrier to widespread clinical adoption of NP therapeutics. To overcome these limitations, we have adapted the techniques of image-guided local drug delivery to develop nano-ablation and nano-embolization. Nano-ablation is a tumor ablative strategy that employs image-guided placement of electrodes into tumor tissue to electroporate tumor cells, resulting in rapid influx of NPs that is not dependent on cellular uptake machinery or stage of the cell cycle. Nano-embolization involves the image-guided delivery of NPs and embolic agents directly into the blood supply of tumors. We describe the design and testing of our innovative local delivery strategies using doxorubicin functionalized superparamagnetic iron oxide nanoparticles (DOX-SPIOs) in cell culture, and the N1S1 hepatoma and VX2 tumor models, imaged by high resolution 7T MRI. We demonstrate that local delivery techniques result in significantly increased intra-tumoral DOX-SPIO uptake, with limited off-target delivery in tumor bearing animal models. The techniques described are versatile enough to be extended to any NP platform, targeting any solid organ malignancy that can be accessed via imaging guidance. PMID:23952712

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

    PubMed Central

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

    2016-01-01

    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. PMID:26852805

  4. Innovative Delivery of siRNA to Solid Tumors by Super Carbonate Apatite

    PubMed Central

    Wu, Xin; Yamamoto, Hirofumi; Nakanishi, Hiroyuki; Yamamoto, Yuki; Inoue, Akira; Tei, Mitsuyoshi; Hirose, Hajime; Uemura, Mamoru; Nishimura, Junichi; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Hossain, Sharif; Akaike, Toshihiro; Matsuura, Nariaki; Doki, Yuichiro; Mori, Masaki

    2015-01-01

    RNA interference (RNAi) technology is currently being tested in clinical trials for a limited number of diseases. However, systemic delivery of small interfering RNA (siRNA) to solid tumors has not yet been achieved in clinics. Here, we introduce an in vivo pH-sensitive delivery system for siRNA using super carbonate apatite (sCA) nanoparticles, which is the smallest class of nanocarrier. These carriers consist simply of inorganic ions and accumulate specifically in tumors, yet they cause no serious adverse events in mice and monkeys. Intravenously administered sCA-siRNA abundantly accumulated in the cytoplasm of tumor cells at 4 h, indicating quick achievement of endosomal escape. sCA-survivin-siRNA induced apoptosis in HT29 tumors and significantly inhibited in vivo tumor growth of HCT116, to a greater extent than two other in vivo delivery reagents. With innovative in vivo delivery efficiency, sCA could be a useful nanoparticle for the therapy of solid tumors. PMID:25738937

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

    NASA Astrophysics Data System (ADS)

    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.

  6. The long-term side effects of radiation therapy for benign brain tumors in adults

    SciTech Connect

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R. )

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs.

  7. (99m)Tc-amitrole as a novel selective imaging probe for solid tumor: In silico and preclinical pharmacological study.

    PubMed

    Essa, B M; Sakr, T M; Khedr, Mohammed A; El-Essawy, F A; El-Mohty, A A

    2015-08-30

    Lactoperoxidase (LPO) inhibitors are very selective for solid tumor due to their high binding affinity to the LPO enzyme. A computational study was used to select top-ranked LPO inhibitor (alone and in complex with (99m)Tc) with high in silico affinity. The novel prepared (99m)Tc-amitrole complex demonstrated both in silico and in vivo high affinity toward solid tumors.(99m)Tc-amitrole was radio-synthesized with a high radiochemical yield (89.7±3.25). It showed in vitro stability for up to 6h. Its preclinical evaluation in solid tumor-bearing mice showed high retention and biological accumulation in solid tumor cells with a high Target/Non-Target (T/NT) ratio equal to 4.9 at 60min post-injection. The data described previously could recommend (99m)Tc-amitrole as potential targeting scintigraphic probe for solid tumor imaging. PMID:25956074

  8. Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction

    ClinicalTrials.gov

    2016-09-09

    Adult Mixed Glioma; Adult Pineal Gland Astrocytoma; Adult Solid Neoplasm; AIDS Related Immunoblastic Lymphoma; AIDS-Related Burkitt Lymphoma; AIDS-Related Diffuse Large Cell Lymphoma; AIDS-Related Diffuse Mixed Cell Lymphoma; AIDS-Related Diffuse Small Cleaved Cell Lymphoma; AIDS-Related Hodgkin Lymphoma; AIDS-Related Lymphoblastic Lymphoma; AIDS-Related Lymphoma; AIDS-Related Primary Central Nervous System Lymphoma; Glioma; Lymphoma; Recurrent Adult Brain Neoplasm; Recurrent Adult Soft Tissue Sarcoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Colorectal Carcinoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Melanoma; Recurrent Pancreatic Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Thyroid Gland Carcinoma; Refractory Chronic Lymphocytic Leukemia; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

  9. Desmoplastic small round cell tumor: A case report of a rare differential diagnosis of solid tumors of the pleura

    PubMed Central

    CAO, YUAN; CHEN, YING; YANG, LI; QIAN, ZI-HUA; HAN, SHU-GAO; LI, QING-HAI; YU, RI-SHENG

    2015-01-01

    Desmoplastic small round cell tumor (DSRCT) presents as a rare separate clinical pathological entity, and pleural DSRCT is very rare. Following review of the English literatures it was revealed that, to date, <15 cases of primary DSRCT of the pleura have been reported worldwide. Among these, there are few computed tomography (CT) findings of pleural DSRCT which have previously been described in detail. The present study reports a pathologically proven case of pleural DSRCT, with varying contrast CT findings in a 72-year-old female, which appeared as a large (12.0×10.0×6.5 cm), smooth, oval mass in the left lower thorax with slight-moderate uniform enhancement on contrast-enhanced CT. To the best of our knowledge, the present report is the first to describe the large solid-tumor pattern and the patient is the eldest reported case of pleural DSRCT. PMID:26722277

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

    PubMed

    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. PMID:26093178

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

    ClinicalTrials.gov

    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

  12. Multifrequency solid state YAG:Nd laser for diagnosis of malignant tumors

    NASA Astrophysics Data System (ADS)

    Lalayan, Asatur A.; Aidinian, Lusine E.; Galstian, Hayro M.

    1998-09-01

    The possibility of laser fluorescence diagnosis of malignant tumors with the aid of multifrequency (355, 440, 446, 532, 660, 670 nm) solid state YAG:Nd laser and the rise in accuracy of this method were discussed. Permitted for clinical employment sodium fluorescein has been used as human tumor-localizing dye. The fluorescence spectra of sodium fluorescein containing human normal tissue and breast, stomach, intestine, skin cancer during excitation with the third harmonics of YAG:Nd and with help of multichannel fiber-optic spectrofluorometer were studied. The contrast accumulation of the dye in tumors of different localization was investigated. The fluorescence spectra of chlorine e6, containing animal tissues at different excitation wavelength (355, 532 and 660 nm) were obtained. The pharmacokinetic behavior of chlorine e6, containing different organs and tumor tissues of rats, infected with Sarcoma-45 has been investigated.

  13. Improved tumor targeting and antitumor activity of camptothecin loaded solid lipid nanoparticles by preinjection of blank solid lipid nanoparticles.

    PubMed

    Jang, Dong-Jin; Moon, Cheol; Oh, Euichaul

    2016-05-01

    This study aimed to enhance the in vivo antitumor effects of camptothecin (CPT), a strong antitumor agent whose delivery is limited by poor aqueous solubility and instability of the active lactone form. CPT was loaded into sterically stabilized, solid lipid nanoparticles (CPT-SLNs) formulated for intravenous administration. The influence of preinjected blank SLNs on the tumor targeting, pharmacokinetics and antitumor activity of CPT-SLNs was investigated. The CPT-SLNs composed of trilaurin-based lipid matrix containing poloxamer188 and pegylated phospholipid as stabilizers were prepared by hot homogenization method and evaluated for in vitro characteristics and in vivo performance. The CPT-SLNs showed an in vitro long-term sustained release pattern and effectively protected the CPT lactone form from hydrolysis under physiological conditions. Notable tumor targeting and tumor growth inhibition were observed after intravenous administration of CPT-SLNs to mice with subcutaneous transplants of CT26 carcinoma cells. In pharmacokinetic studies in rats, CPT-SLNs markedly elevated plasma CPT level and prolonged blood circulation compared to free CPT. Nonetheless, high uptake of CPT-SLNs by reticuloendothelial system (RES)-rich tissues resulted in limited tumor targeting of CPT-SLNs and plasma CPT levels. Preinjection of blank SLNs before administration of CPT-SLNs to tumor-bearing mice substantially reduced the accumulation of CPT-SLNs in RES organs. This led to significantly enhanced tumor targeting, improved pharmacokinetic parameters and increased antitumor efficacy of CPT-SLNs. These results suggested that the in vivo antitumor effects of CPT-SLNs could be further enhanced by preinjection of blank SLNs. Therefore, CPT-SLNs with preinjected blank SLNs could be a potential approach for stable and effective CPT-based cancer therapy. PMID:27133053

  14. Discovery of structural alterations in solid tumor oligodendroglioma by single molecule analysis

    PubMed Central

    2013-01-01

    Background Solid tumors present a panoply of genomic alterations, from single base changes to the gain or loss of entire chromosomes. Although aberrations at the two extremes of this spectrum are readily defined, comprehensive discernment of the complex and disperse mutational spectrum of cancer genomes remains a significant challenge for current genome analysis platforms. In this context, high throughput, single molecule platforms like Optical Mapping offer a unique perspective. Results Using measurements from large ensembles of individual DNA molecules, we have discovered genomic structural alterations in the solid tumor oligodendroglioma. Over a thousand structural variants were identified in each tumor sample, without any prior hypotheses, and often in genomic regions deemed intractable by other technologies. These findings were then validated by comprehensive comparisons to variants reported in external and internal databases, and by selected experimental corroborations. Alterations range in size from under 5 kb to hundreds of kilobases, and comprise insertions, deletions, inversions and compound events. Candidate mutations were scored at sub-genic resolution and unambiguously reveal structural details at aberrant loci. Conclusions The Optical Mapping system provides a rich description of the complex genomes of solid tumors, including sequence level aberrations, structural alterations and copy number variants that power generation of functional hypotheses for oligodendroglioma genetics. PMID:23885787

  15. Distribution of porfiromycin in EMT6 solid tumors and normal tissues of BALB/c mice.

    PubMed

    Keyes, S R; Rockwell, S; Kennedy, K A; Sartorelli, A C

    1991-05-01

    The distribution of porfiromycin was studied in BALB/c mice bearing EMT6 mammary tumors. The levels of 3H in blood and most tissues peaked approximately 15 minutes after intraperitoneal injection of [3H]porfiromycin. The levels of radioactivity present in most of the tissues and in the tumors were similar at 4 hours and 24 hours after administration. Most of the normal tissues showed uniform, low grain densities when analyzed by autoradiography; the liver and the small intestine had the highest labeling densities. Only kidney, bladder, and tumor showed differential distributions of grains from [3H]porfiromycin. In the kidney, higher grain counts were found in cortex than in medullary regions; grains were uniformly distributed within each region. In the bladder, the highest labeling densities were found in regions near the lumen. Tumor regions that had some necrotic features or regions of necrosis that included some viable cells showed higher labeling intensities than healthy-looking tumor regions, probably because the abnormal microenvironments in these regions led to increased rates of activation of porfiromycin to electrophilic species. These findings show that porfiromycin can reach and be activated in tumor regions containing cells resistant to many chemotherapeutic agents and to x rays. The results also support the concept that agents such as porfiromycin can target cells in specific microenvironmental subpopulations of solid tumors. PMID:2023281

  16. Ultrasound-targeted microbubble destruction for chemotherapeutic drug delivery to solid tumors

    PubMed Central

    2013-01-01

    Ultrasound-targeted microbubble destruction (UTMD) is a promising technique for non-invasive, targeted drug delivery, and its applications in chemotherapeutic drug delivery to solid tumors have attracted growing interest. Ultrasound, which has been conventionally used for diagnostic imaging, has evolved as a promising tool for therapeutic applications mainly because of its ability to be focused deep inside the human body, providing a modality for targeted delivery. Although originally being introduced into clinics as ultrasound contrast agents, microbubbles (MBs) have been developed as a diagnostic and therapeutic agent that can both be tracked through non-invasive imaging and deliver therapeutic agents selectively at ultrasound-targeted locations. Whereas free drugs often possess harmful side effects, their encapsulation in MBs and subsequent local release at the targeted tissue by ultrasound triggering may help improve the margin of safety. In the past 10 years, the feasibility and safety of UTMD have been extensively tested using normal animal models. Most recently, a growing number of preclinical studies have been reported on the therapeutic benefits of UTMD in the delivery of chemotherapeutic drugs to various malignant tumors, such as brain, liver, eyelid, pancreas, and breast tumors. Increased drug concentration in tumors and reduced tumor sizes were achieved in those tumors treated with UTMD in combination with chemotherapeutic drugs, when compared to tumors treated with chemotherapy drugs alone. This review presents an overview of current preclinical applications of UTMD in chemotherapeutic drug delivery for the treatment of cancers along with a discussion of its future developments. PMID:25512858

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

    ClinicalTrials.gov

    2016-09-07

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

  18. Adult inflammatory myofibroblastic tumor of the trachea: case report and literature review.

    PubMed

    Oztuna, Funda; Pehlivanlar, Mehtap; Abul, Yasin; Tekinbas, Celal; Ozoran, Yavuz; Ozlu, Tevfik

    2013-07-01

    Inflammatory myofibroblastic tumor of the trachea is a rare benign tumor in adults. It is mostly seen before the age of 16. We describe a 20-year-old female patient who presented with stridor. She had a fixed obstruction on spirometry, and computed tomography and bronchoscopy confirmed tracheal thickening and stenosis below the vocal cords and bronchial wall thickening at the level of the carina. Bronchoscopic biopsy confirmed an inflammatory myofibroblastic tumor. She recovered after mechanical dilatation and resection via rigid bronchoscopy, followed by corticosteroid therapy. PMID:23258581

  19. Dissecting the PI3K Signaling Axis in Pediatric Solid Tumors: Novel Targets for Clinical Integration

    PubMed Central

    Loh, Amos H. P.; Brennan, Rachel C.; Lang, Walter H.; Hickey, Robert J.; Malkas, Linda H.; Sandoval, John A.

    2013-01-01

    Children with solid tumors represent a unique population. Recent improvements in pediatric solid tumor survival rates have been confined to low- and moderate-risk cancers, whereas minimal to no notable improvement in survival have been observed in high-risk and advanced-stage childhood tumors. Treatments for patients with advanced disease are rarely curative, and responses to therapy are often followed by relapse, which highlights the large unmet need for novel therapies. Recent advances in cancer treatment have focused on personalized therapy, whereby patients are treated with agents that best target the molecular drivers of their disease. Thus, a better understanding of the pathways that drive cancer or drug resistance is of critical importance. One such example is the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, which is activated in many solid cancer patients and represents a target for therapy. PI3K/Akt/mTOR pathway activation has also been observed in tumors resistant to agents targeting upstream receptor tyrosine kinases (RTKs). Agents that target this pathway have the potential to shut down survival pathways, and are being explored both in the setting of pathway-activating mutations and for their ability to restore sensitivity to upstream signaling targeted agents. Here, we examine the role of the PI3K/Akt/mTOR pathway in pediatric solid tumors, review the novel agents being explored to target this pathway, and explore the potential role of the inhibition of this pathway in the clinical development of these agents in children. PMID:23638435

  20. Primary intestinal mold infection in children with solid tumors: a case report in an adolescent with Ewing sarcoma, and literature review.

    PubMed

    Naselli, Aldo; Garaventa, Alberto; Buffa, Piero; Granata, Claudio; Bandettini, Roberto; Cangemi, Giuliana; Moscatelli, Andrea; Castagnola, Elio

    2016-09-01

    We report a case of primary intestinal infection due to filamentous fungi in an adolescent with Ewing sarcoma. The clinical picture was that of peritonitis secondary to intestinal perforation and the diagnosis was established only on histopathological bases. This condition is very rare, and only one case of primary intestinal mold infection in children with solid tumors has been reported in the literature, although more records can be found describing similar conditions in other cancer patient populations (i.e. adults with solid tumors or children with hematological malignancies or patients receiving hemopoietic stem cell transplant). Clinicians must be aware of this possibility since only an aggressive medical and surgical approach can improve patients' prognosis. PMID:27602424

  1. A cellular automata model for avascular solid tumor growth under the effect of therapy

    NASA Astrophysics Data System (ADS)

    Reis, E. A.; Santos, L. B. L.; Pinho, S. T. R.

    2009-04-01

    Tumor growth has long been a target of investigation within the context of mathematical and computer modeling. The objective of this study is to propose and analyze a two-dimensional stochastic cellular automata model to describe avascular solid tumor growth, taking into account both the competition between cancer cells and normal cells for nutrients and/or space and a time-dependent proliferation of cancer cells. Gompertzian growth, characteristic of some tumors, is described and some of the features of the time-spatial pattern of solid tumors, such as compact morphology with irregular borders, are captured. The parameter space is studied in order to analyze the occurrence of necrosis and the response to therapy. Our findings suggest that transitions exist between necrotic and non-necrotic phases (no-therapy cases), and between the states of cure and non-cure (therapy cases). To analyze cure, the control and order parameters are, respectively, the highest probability of cancer cell proliferation and the probability of the therapeutic effect on cancer cells. With respect to patterns, it is possible to observe the inner necrotic core and the effect of the therapy destroying the tumor from its outer borders inwards.

  2. Solid pseudopapillary tumor of the pancreas and concomitant urogenital malformations in a young woman

    PubMed Central

    2013-01-01

    Abstract Solid pseudopapillary tumor (SPT) of the pancreas is a rare pancreatic tumor with low malignant potential. It occurs characteristically more often in young women. SPT associated with extra- and pancreatic anomalies are occasionally reported. Here we report a case of pancreatic SPT with concomitant urogenital malformations including solitary kidney and uterus didelphys in a 25-year-old woman. The patient underwent central pancreatectomy, and SPT was confirmed with pathological results. Recurrence or metastasis was not found after 14 months of follow-up. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4264758678755142 PMID:23445554

  3. Solid pseudopapillary tumor of the pancreas and concomitant urogenital malformations in a young woman.

    PubMed

    Guan, Zhi-Wei; Sun, Lu; Wang, Yan-Qiu; Xu, Bai-Xuan

    2013-01-01

    Solid pseudopapillary tumor (SPT) of the pancreas is a rare pancreatic tumor with low malignant potential. It occurs characteristically more often in young women. SPT associated with extra- and pancreatic anomalies are occasionally reported. Here we report a case of pancreatic SPT with concomitant urogenital malformations including solitary kidney and uterus didelphys in a 25-year-old woman. The patient underwent central pancreatectomy, and SPT was confirmed with pathological results. Recurrence or metastasis was not found after 14 months of follow-up. PMID:23445554

  4. An Adult Gastric Duplication Cyst Mimicking a Gastrointestinal Stromal Tumor.

    PubMed

    Yoda, Takenori; Furihata, Makoto; Nagao, Sayaka; Wada, Tomonori

    2016-01-01

    We herein describe a rare case of a 24-year-old man who presented with severe epigastralgia after consuming a considerable amount of broiled meat. Computed tomography revealed a cystic lesion adjacent to the distal stomach, with high intensity on T2-weighted magnetic resonance imaging. Upper endoscopy showed a cystic mass measuring 6 cm in diameter, mimicking a submucosal tumor adjacent to the pyloric valve, with duodenum invagination, characteristic of ball valve syndrome. Endoscopic ultrasonography showed that the lesion was contiguous through the first to the third layer of the stomach. Therefore, we performed distal gastrectomy. Pathology showed that the lesion was a gastric duplication cyst without malignancy. PMID:27580540

  5. Pulsed focused ultrasound exposures enhance locally administered gene therapy in a murine solid tumor model

    PubMed Central

    Ziadloo, Ali; Xie, Jianwu; Frenkel, Victor

    2013-01-01

    Gene therapy by intratumoral injection is a promising approach for treating solid tumors. However, this approach has limited success due to insufficient distribution of gene vectors used for gene delivery. Previous studies have shown that pulsed-focused ultrasound (pFUS) can enhance both systemic and local delivery of therapeutic agents in solid tumors and other disease models. Here, murine squamous cell carcinoma flank tumors were treated with single intratumoral injection of naked tumor necrosis factor-alpha (TNF-α) plasmid, either with or without a preceding pFUS exposure. The exposures were given at 1 MHz, at a spatial average, temporal peak intensity of 2660 W cm–2, using 50 ms pulses, given at a pulse repetition frequency of 1 Hz. One hundred pulses were given at individual raster points, spaced evenly over the projected surface of the tumor at a distance of 2 mm. Exposures alone had no effect on tumor growth. Significant growth inhibition was observed with injection of TNF-α plasmid, and tumor growth was further inhibited with pFUS. Improved results with pFUS correlated with larger necrotic regions in histological sections and improved distribution and penetration of fluorescent surrogate nanoparticles. Electron microscopy demonstrated enlarged gaps between cells in exposed tissue, and remote acoustic palpation showed decreases in tissue stiffness after pFUS. Combined, these results suggest pFUS effects may be reducing barriers for tissue transport and additionally lowering interstitial fluid pressure to further improve delivery and distribution of injected plasmid for greater therapeutic effects. This suggests that pFUS could potentially be beneficial for improving local gene therapy treatment of human malignancies. PMID:23464051

  6. Treatment of solid tumors by interstitial release of recoiling short-lived alpha emitters

    NASA Astrophysics Data System (ADS)

    Arazi, L.; Cooks, T.; Schmidt, M.; Keisari, Y.; Kelson, I.

    2007-08-01

    A new method utilizing alpha particles to treat solid tumors is presented. Tumors are treated with interstitial radioactive sources which continually release short-lived alpha emitting atoms from their surface. The atoms disperse inside the tumor, delivering a high dose through their alpha decays. We implement this scheme using thin wire sources impregnated with 224Ra, which release by recoil 220Rn, 216Po and 212Pb atoms. This work aims to demonstrate the feasibility of our method by measuring the activity patterns of the released radionuclides in experimental tumors. Sources carrying 224Ra activities in the range 10-130 kBq were used in experiments on murine squamous cell carcinoma tumors. These included gamma spectroscopy of the dissected tumors and major organs, Fuji-plate autoradiography of histological tumor sections and tissue damage detection by Hematoxylin-Eosin staining. The measurements focused on 212Pb and 212Bi. The 220Rn/216Po distribution was treated theoretically using a simple diffusion model. A simplified scheme was used to convert measured 212Pb activities to absorbed dose estimates. Both physical and histological measurements confirmed the formation of a 5-7 mm diameter necrotic region receiving a therapeutic alpha-particle dose around the source. The necrotic regions shape closely corresponded to the measured activity patterns. 212Pb was found to leave the tumor through the blood at a rate which decreased with tumor mass. Our results suggest that the proposed method, termed DART (diffusing alpha-emitters radiation therapy), may potentially be useful for the treatment of human patients.

  7. Analgesic use and the risk of primary adult brain tumor.

    PubMed

    Egan, Kathleen M; Nabors, Louis B; Thompson, Zachary J; Rozmeski, Carrie M; Anic, Gabriella A; Olson, Jeffrey J; LaRocca, Renato V; Chowdhary, Sajeel A; Forsyth, Peter A; Thompson, Reid C

    2016-09-01

    Glioma and meningioma are uncommon tumors of the brain with few known risk factors. Regular use of aspirin has been linked to a lower risk of gastrointestinal and other cancers, though evidence for an association with brain tumors is mixed. We examined the association of aspirin and other analgesics with the risk of glioma and meningioma in a large US case-control study. Cases were persons recently diagnosed with glioma or meningioma and treated at medical centers in the southeastern US. Controls were persons sampled from the same communities as the cases combined with friends and other associates of the cases. Information on past use of analgesics (aspirin, other anti-inflammatory agents, and acetaminophen) was collected in structured interviews. Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for analgesic use adjusted for potential confounders. All associations were considered according to indication for use. A total of 1123 glioma cases, 310 meningioma cases and 1296 controls were included in the analysis. For indications other than headache, glioma cases were less likely than controls to report regular use of aspirin (OR 0.69; CI 0.56, 0.87), in a dose-dependent manner (P trend < 0.001). No significant associations were observed with other analgesics for glioma, or any class of pain reliever for meningioma. Results suggest that regular aspirin use may reduce incidence of glioma. PMID:26894804

  8. Adding chemo after radiation treatment improves survival for adults with a type of brain tumor

    Cancer.gov

    Adults with low-grade gliomas, a form of brain tumor, who received chemotherapy following completion of radiation therapy lived longer than patients who received radiation therapy alone, according to long-term follow-up results from a NIH-supported random

  9. Photodynamic Nanomedicine in the Treatment of Solid Tumors: Perspectives and Challenges

    PubMed Central

    Master, Alyssa; Livingston, Megan; Gupta, Anirban Sen

    2013-01-01

    Photodynamic therapy (PDT) is a promising treatment strategy where activation of photosensitizer drugs with specific wavelengths of light results in energy transfer cascades that ultimately yield cytotoxic reactive oxygen species which can render apoptotic and necrotic cell death. Without light the photosensitizer drugs are minimally toxic and the photoactivating light itself is non-ionizing. Therefore, harnessing this mechanism in tumors provides a safe and novel way to selectively eradicate tumor with reduced systemic toxicity and side effects on healthy tissues. For successful PDT of solid tumors, it is necessary to ensure tumor-selective delivery of the photosensitizers, as well as, the photoactivating light and to establish dosimetric correlation of light and drug parameters to PDT-induced tumor response. To this end, the nanomedicine approach provides a promising way towards enhanced control of photosensitizer biodistribution and tumor-selective delivery. In addition, refinement of nanoparticle designs can also allow incorporation of imaging agents, light delivery components and dosimetric components. This review aims at describing the current state-of-the-art regarding nanomedicine strategies in PDT, with a comprehensive narrative of the research that has been carried out in vitro and in vivo, with a discussion of the nanoformulation design aspects and a perspective on the promise and challenges of PDT regarding successful translation into clinical application. PMID:23474028

  10. Radiation induced oxidative stress: I. Studies in Ehrlich solid tumor in mice.

    PubMed

    Agrawal, A; Choudhary, D; Upreti, M; Rath, P C; Kale, R K

    2001-07-01

    Understanding the response of tumors to ionizing radiation might potentially lead to improvement in tumor control and patient morbidity. Since the antioxidant status is likely to be linked to radioresponse, its modulation needs to be examined. Therefore, Swiss albino male mice (7-8 weeks old) with Ehrlich solid tumors were irradiated with different doses of gamma rays (0-9 Gy) at a dose rate of 0.0153 Gy/s; and enzymes involved in antioxidant functions were determined in the tumors. Radiation effects in terms of oxidative damage, LDH, nitric oxide and DNA fragmentation were also examined. In tumors, the specific activity of SOD was increased with dose but declined 6 Gy onwards. GST, DTD and GSH showed an almost progressive increase. These enhanced activities might have resulted from the increased protein expression. This possibility was supported by the Western Blot analysis for GST protein. These changes might be closely linked to the radiation-induced oxidative stress as reflected by the enhanced levels of peroxidative damage, DNA fragmentation, LDH activity and nitric oxide levels. These findings may have relevance to radiation therapy of cancer as the elevated antioxidant status of irradiated tumors is likely to limit the effectiveness of radiation dose and adversely affect the therapeutic gain. PMID:11681724

  11. Photodynamic nanomedicine in the treatment of solid tumors: perspectives and challenges.

    PubMed

    Master, Alyssa; Livingston, Megan; Sen Gupta, Anirban

    2013-05-28

    Photodynamic therapy (PDT) is a promising treatment strategy where activation of photosensitizer drugs with specific wavelengths of light results in energy transfer cascades that ultimately yield cytotoxic reactive oxygen species which can render apoptotic and necrotic cell death. Without light the photosensitizer drugs are minimally toxic and the photoactivating light itself is non-ionizing. Therefore, harnessing this mechanism in tumors provides a safe and novel way to selectively eradicate tumor with reduced systemic toxicity and side effects on healthy tissues. For successful PDT of solid tumors, it is necessary to ensure tumor-selective delivery of the photosensitizers, as well as, the photoactivating light and to establish dosimetric correlation of light and drug parameters to PDT-induced tumor response. To this end, the nanomedicine approach provides a promising way towards enhanced control of photosensitizer biodistribution and tumor-selective delivery. In addition, refinement of nanoparticle designs can also allow incorporation of imaging agents, light delivery components and dosimetric components. This review aims at describing the current state-of-the-art regarding nanomedicine strategies in PDT, with a comprehensive narrative of the research that has been carried out in vitro and in vivo, with a discussion of the nanoformulation design aspects and a perspective on the promise and challenges of PDT regarding successful translation into clinical application. PMID:23474028

  12. Radiation Treatment for Ewing Family of Tumors in Adults: University of Florida Experience

    SciTech Connect

    Shi Wenyin; Indelicato, Daniel J.; Keole, Sameer R.; Morris, Christopher G.; Scarborough, Mark T.; Gibbs, Parker C.; Zlotecki, Robert A.

    2008-11-15

    Purpose: To review the clinical characteristics and outcomes of adult patients with Ewing family of tumors treated with radiation at University of Florida. Methods and Materials: Clinical features, treatment, and outcomes of 47 patients older than 18 years with Ewing family of tumors treated with combined radiation therapy and chemotherapy from 1970 to 2005 were retrospectively reviewed. Analysis was stratified by age older or younger than 30 years. Patients with metastatic disease at the time of diagnosis were excluded from the study. Results: The 29 men and 18 women had a median age of 24 years. Thirty-three patients were 18-30 years old and 14 patients were older than 30 years. Median follow-up of living patients was 8.2 years. The 5-year overall survival rate for all patients was 43% (p = 0.8523). The 5-year local control rate for all patients was 75% (p = 0.9326). The 5-year rate of freedom from distant metastasis for all patients was 45% (p = 0.5471). There were no significant differences in 5-year overall survival, local control, and freedom from distant metastasis rates; patterns of distant failure; or toxicity profiles between older adult patients and younger adult patients. Conclusions: We found that the natural history and treatment outcomes of the Ewing family of tumors were consistently similar in adults (young and old) and children. Thus, aggressive combined modality approaches should be considered for adult patients.

  13. Phase 1 Study of PLX7486 as Single Agent and With Gemcitabine Plus Nab-Paclitaxel in Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-06-07

    Solid Tumors; Untreated Pancreatic Adenocarcinoma; Pancreatic Cancer Non-resectable; Metastatic Pancreatic Adenocarcinoma; Tumors of Any Histology With Activating Trk (NTRK) Point or NTRK Fusion Mutations; Tenosynovial Giant Cell Tumor

  14. Detection and Identification of Hematologic Malignancies and Solid Tumors by an Electrochemical Technique

    PubMed Central

    Zhang, Bowen; Zhang, Xiaoping; Wang, Xuemei; Cheng, Jian; Chen, Baoan

    2016-01-01

    Purpose Develop and evaluate an electrochemical method to identify healthy individuals, malignant hematopathic patients and solid tumor patients by detecting the leukocytes in whole-blood. Methods A total of 114 individual blood samples obtained from our affiliated hospital in China (June 2015- August 2015) were divided into three groups: healthy individuals (n = 35), hematologic malignancies (n = 41) and solid tumors (n = 38). An electrochemical workstation system was used to measure differential pulse voltammetry due to the different electrochemical behaviors of leukocytes in blood samples. Then, one-way analysis of variance (ANOVA) was applied to analyze the scanning curves and to compare the peak potential and peak current. Results The scanning curve demonstrated the specific electrochemical behaviors of the blank potassium ferricyanide solution and that mixed with blood samples in different groups. Significant differences in mean peak potentials of mixture and shifts (ΔEp (mV)) were observed of the three groups (P< = 0.001). 106.00±9.00 and 3.14±7.48 for Group healthy individuals, 120.90±11.18 and 18.10±8.81 for Group hematologic malignancies, 136.84±11.53 and 32.89±10.50 for Group solid tumors, respectively. In contrast, there were no significant differences in the peak currents and shifts. Conclusions The newly developed method to apply the electrochemical workstation system to identify hematologic malignancies and solid tumors with good sensitivity and specificity might be effective, suggesting a potential utility in clinical application. PMID:27115355

  15. Induction of oncogene addiction shift to NF-{kappa}B by camptothecin in solid tumor cells

    SciTech Connect

    Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko; Nakashima, Makoto; Tsuruo, Takashi; Umezawa, Kazuo; Higashihara, Masaaki; Watanabe, Toshiki; Horie, Ryouichi

    2009-12-04

    The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-{kappa}B activity driven by I{kappa}B kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-{kappa}B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in this study present an example of the shift in signals that support the survival of solid tumor cells to NF-{kappa}B during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-{kappa}B inhibitors.

  16. Photodynamic therapy for treatment of solid tumors – potential and technical challenges

    PubMed Central

    Huang, Zheng; Xu, Heping; Meyers, Arlen D.; Musani, Ali I.; Wang, Luowei; Tagg, Randall; Barqawi, Al B.; Chen, Yang K.

    2008-01-01

    Photodynamic therapy (PDT) involves the administration of photosensitizer followed by local illumination with visible light of specific wavelength(s). In the presence of oxygen molecules, the light illumination of photosensitizer can lead to a series of photochemical reactions and consequently the generation of cytotoxic species. The quantity and location of PDT-induced cytotoxic species determine the nature and consequence of PDT. Much progress has been seen in both basic research and clinical application in recent years. Although the majority of approved PDT clinical protocols have primarily been used for the treatment of superficial lesions of both malignant and non-malignant diseases, interstitial PDT for the ablation of deep-seated solid tumors are now being investigated worldwide. The complexity of the geometry and non-homogeneity of solid tumor pose a great challenge on the implementation of minimally invasive interstitial PDT and the estimation of PDT dosimetry. This review will discuss the recent progress and technical challenges of various forms of interstitial PDT for the treatment of parenchymal and/or stromal tissues of solid tumors. PMID:18642969

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

    PubMed

    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. PMID:21933109

  18. Solid variant of orbital angioleiomyoma: An unusual tumor at an unusual site

    PubMed Central

    Nair, Akshay Gopinathan; Jain, Vandana; Gopinathan, Indumati; Murthy, Anuradha

    2016-01-01

    We describe the clinicopathological features of a solid variant of orbital angioleiomyoma. A review of clinical records, diagnostic, and radiographic studies combined with histopathological evaluation with standard histochemical staining and immunohistochemistry was conducted. A 22-year-old male patient presented with a mass in the region of the left lacrimal gland that was gradually increasing over the past 2 years. Radiological and clinical examinations showed no signs suspicious of a malignancy and fine needle aspiration cytology was inconclusive. Therefore, an excision biopsy was performed. On histopathological examination, the picture was consistent with a benign spindle cell tumor. Immunohistochemistry showed positivity for CD 34 and CD 31 (markers for vascular endothelium). The tumor also showed positivity for smooth muscle actin and Ki-67 proliferative index was low. Angioleiomyomas are rarely encountered in the orbit and has features seen in leiomyoma as well as some vascular tumor elements. In most cases, surgical excision is usually curative. PMID:27488159

  19. Solid variant of orbital angioleiomyoma: An unusual tumor at an unusual site.

    PubMed

    Nair, Akshay Gopinathan; Jain, Vandana; Gopinathan, Indumati; Murthy, Anuradha

    2016-06-01

    We describe the clinicopathological features of a solid variant of orbital angioleiomyoma. A review of clinical records, diagnostic, and radiographic studies combined with histopathological evaluation with standard histochemical staining and immunohistochemistry was conducted. A 22-year-old male patient presented with a mass in the region of the left lacrimal gland that was gradually increasing over the past 2 years. Radiological and clinical examinations showed no signs suspicious of a malignancy and fine needle aspiration cytology was inconclusive. Therefore, an excision biopsy was performed. On histopathological examination, the picture was consistent with a benign spindle cell tumor. Immunohistochemistry showed positivity for CD 34 and CD 31 (markers for vascular endothelium). The tumor also showed positivity for smooth muscle actin and Ki-67 proliferative index was low. Angioleiomyomas are rarely encountered in the orbit and has features seen in leiomyoma as well as some vascular tumor elements. In most cases, surgical excision is usually curative. PMID:27488159

  20. Diagnosis of Malignancy of Adult Mediastinal Tumors by Conventional and Transesophageal Echocardiography

    PubMed Central

    Zhou, Wei-Wei; Wang, Hong-Wei; Liu, Nan-Nan; Li, Jing-Jing; Yuan, Wei; Zhao, Rui; Xiang, Liang-Bi; Qi, Miao

    2015-01-01

    Background: Transesophageal echocardiography (TEE) is a well-established method for detecting and diagnosing heart tumors. In contrast, its role in assessing the presence, growth and evidence of malignant tumors originating from mediastinal sites remains unclear. The aim of this study was to compare the diagnostic impact of TEE and transthoracic echocardiography (TTE) for determining the localization, growth and malignancy of adult mediastinal tumors (MTs). Methods: In a prospective and investigator-blinded study, we evaluated 144 consecutive patients with MT lesions to assess the diagnostic impact of TEE and TTE for detecting the presence of tumors spreading both inside and outside of the heart and for determining infiltration and invasion using pathological examination results as a reference. Results: All tumor lesions were diagnosed and carefully evaluated by biopsy. Biopsy revealed malignant tumors in 79 patients and benign tumors in 65 patients. When compared to histological findings, TEE predicted malignancy from the presence of tumors spreading both inside and outside of the heart and from infiltration and invasion in 49/79 patients (62.0%). TTE predicted malignancy in only 8/79 patients (10.1%, P < 0.005). TEE visualized tumor lesions in 130 patients (90.3%) while the TTE visualized tumor lesions in 110 patients (76.4%) and was less effective at detecting MT lesions (P < 0.001). TTE and TEE could detect anterior MTs and adequately verified MTs (P > 0.05); TEE detected medium MTs better than TTE (P < 0.001). Conclusions: TEE is effective and superior to TTE for predicting the localization and growth of MTs as well as for accessing evidence of tumor malignancy. TTE and TEE were able to detect anterior MTs; TEE was able to detect medium MT better than TTE. PMID:25881598

  1. Local gene therapy of solid tumors with GM-CSF and B7-1 eradicates both treated and distal tumors.

    PubMed

    Collins, C G; Tangney, M; Larkin, J O; Casey, G; Whelan, M C; Cashman, J; Murphy, J; Soden, D; Vejda, S; McKenna, S; Kiely, B; Collins, J K; Barrett, J; Aarons, S; O'Sullivan, G C

    2006-12-01

    Gene therapy-induced expression of immunostimulatory molecules at tumor cell level may evoke antitumor immune mechanisms by recruiting and enhancing viability of antigen-processing cells and specific tumoricidal lymphocytes. The antitumor efficacy of a plasmid, coding for granulocyte-macrophage colony-stimulating factor (GM-CSF) and the B7-1 costimulatory immune molecule, delivered into growing solid tumors by electroporation was investigated. Murine fibrosarcomas (JBS) growing in Balb/C mice (tumor regression occurred in greater than 60% of treated animals. This response was systemic, durable and tumor specific, with all responding animals resistant to repeat tumor challenge. Using a liver metastatic model, effective cure of distal metastases was achieved following treatment of the primary subcutaneous tumor. This treatment strategy could be applicable in the clinical setting for effective elimination of both primary tumors and associated metastatic disease. PMID:16874363

  2. Rationally Repurposing Ruxolitinib (Jakafi®) as a Solid Tumor Therapeutic

    PubMed Central

    Tavallai, Mehrad; Booth, Laurence; Roberts, Jane L.; Poklepovic, Andrew; Dent, Paul

    2016-01-01

    We determined whether the approved myelofibrosis drug ruxolitinib (Jakafi®), an inhibitor of Janus kinases 1/2 (JAK1 and JAK2), could be repurposed as an anti-cancer agent for solid tumors. Ruxolitinib synergistically interacted with dual ERBB1/2/4 inhibitors to kill breast as well as lung, ovarian and brain cancer cells. Knock down of JAK1/2 or of ERBB1/2/3/4 recapitulated on-target drug effects. The combination of (ruxolitinib + ERBB1/2/4 inhibitor) rapidly inactivated AKT, mTORC1, mTORC2, STAT3, and STAT5, and activated eIF2α. In parallel, the drug combination reduced expression of MCL-1, BCL-XL, HSP90, HSP70, and GRP78, and increased expression of Beclin1. Activated forms of STAT3, AKT, or mTOR prevented the drug-induced decline in BCL-XL, MCL-1, HSP90, and HSP70 levels. Over-expression of chaperones maintained AKT/mTOR activity in the presence of drugs and protected tumor cells from the drug combination. Expression of dominant negative eIF2α S51A prevented the increase in Beclin1 expression and protected tumor cells from the drug combination. Loss of mTOR activity was associated with increased ATG13 S318 phosphorylation and with autophagosome formation. Autophagosomes initially co-localized with mitochondria and subsequently with lysosomes. Knock down of Beclin1 suppressed: drug-induced mitophagy; the activation of the toxic BH3 domain proteins BAX and BAK; and tumor cell killing. Knock down of apoptosis-inducing factor (AIF) protected tumor cells from the drug combination, whereas blockade of caspase 9 signaling did not. The drug combination released AIF into the cytosol and increased nuclear AIF: eIF3A co-localization. A 4-day transient exposure of orthotopic tumors to (ruxolitinib + afatinib) profoundly reduced mammary tumor growth over the following 35 days. Re-grown tumors exhibited high levels of BAD S112 phosphorylation and activation of ERK1/2 and NFκB. Our data demonstrate that mitophagy is an essential component of (ruxolitinib

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

    PubMed Central

    Xiao, Jian; Zou, Yong; Chen, Xi; Gao, Ying; Xie, Mingxuan; Lu, Xiaoxiao; Li, Wei; He, Bixiu; He, Shuya; You, Shaojin; Chen, Qiong

    2016-01-01

    Background 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. Methods 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. Results 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). Conclusion These results suggest that decreased LKB1 expression in patients with

  4. Neural Underpinnings of Working Memory in Adult Survivors of Childhood Brain Tumors.

    PubMed

    King, Tricia Z; Na, Sabrina; Mao, Hui

    2015-08-01

    Adult survivors of childhood brain tumors are at risk for cognitive performance deficits that require the core cognitive skill of working memory. Our goal was to examine the neural mechanisms underlying working memory performance in survivors. We studied the working memory of adult survivors of pediatric posterior fossa brain tumors using a letter n-back paradigm with varying cognitive workload (0-, 1-, 2-, and 3-back) and functional magnetic resonance imaging as well as neuropsychological measures. Survivors of childhood brain tumors evidenced lower working memory performance than demographically matched healthy controls. Whole-brain analyses revealed significantly greater blood-oxygen level dependent (BOLD) activation in the left superior / middle frontal gyri and left parietal lobe during working memory (2-back versus 0-back contrast) in survivors. Left frontal BOLD response negatively correlated with 2- and 3-back working memory performance, Auditory Consonant Trigrams (ACT), and Digit Span Backwards. In contrast, parietal lobe BOLD response negatively correlated with 0-back (vigilance task) and ACT. The results revealed that adult survivors of childhood posterior fossa brain tumors recruited additional cognitive control resources in the prefrontal lobe during increased working memory demands. This increased prefrontal activation is associated with lower working memory performance and is consistent with the allocation of latent resources theory. PMID:26234757

  5. Tumor-targeted delivery of paclitaxel using low density lipoprotein-mimetic solid lipid nanoparticles.

    PubMed

    Kim, Jin-Ho; Kim, Youngwook; Bae, Ki Hyun; Park, Tae Gwan; Lee, Jung Hee; Park, Keunchil

    2015-04-01

    Water-insoluble anticancer drugs, including paclitaxel, present severe clinical side effects when administered to patients, primarily associated with the toxicity of reagents used to solubilize the drugs. In efforts to develop alternative formulations of water-insoluble anticancer drugs suitable for intravenous administration, we developed biocompatible anticancer therapeutic solid lipid nanoparticles (SLNs), mimicking the structure and composition of natural particles, low-density lipoproteins (LDLs), for tumor-targeted delivery of paclitaxel. These therapeutic nanoparticles contained water-insoluble paclitaxel in the core with tumor-targeting ligand covalently conjugated on the polyethylene glycol (PEG)-modified surface (targeted PtSLNs). In preclinical human cancer xenograft mouse model studies, the paclitaxel-containing tumor-targeting SLNs exhibited pronounced in vivo stability and enhanced biocompatibility. Furthermore, these SLNs had superior antitumor activity to in-class nanoparticular therapeutics in clinical use (Taxol and Genexol-PM) and yielded long-term complete responses. The in vivo targeted antitumor activities of the SLN formulations in a mouse tumor model suggest that LDL-mimetic SLN formulations can be utilized as a biocompatible, tumor-targeting platform for the delivery of various anticancer therapeutics. PMID:25686010

  6. Filter Paper-based Nucleic Acid Storage in High-throughput Solid Tumor Genotyping.

    PubMed

    Stachler, Matthew; Jia, Yonghui; Sharaf, Nematullah; Wade, Jacqueline; Longtine, Janina; Garcia, Elizabeth; Sholl, Lynette M

    2015-01-01

    Molecular testing of tumors from formalin-fixed paraffin-embedded (FFPE) tissue blocks is central to clinical practice; however, it requires histology support and increases test turnaround time. Prospective fresh frozen tissue collection requires special handling, additional storage space, and may not be feasible for small specimens. Filter paper-based collection of tumor DNA reduces the need for histology support, requires little storage space, and preserves high-quality nucleic acid. We investigated the performance of tumor smears on filter paper in solid tumor genotyping, as compared with paired FFPE samples. Whatman FTA Micro Card (FTA preps) smears were prepared from 21 fresh tumor samples. A corresponding cytology smear was used to assess tumor cellularity and necrosis. DNA was isolated from FTA preps and FFPE core samples using automated methods and quantified using SYBR green dsDNA detection. Samples were genotyped for 471 mutations on a mass spectrophotometry-based platform (Sequenom). DNA concentrations from FTA preps and FFPE correlated for untreated carcinomas but not for mesenchymal tumors (Spearman σ=0.39 and σ=-0.1, respectively). Average DNA concentrations were lower from FTA preps as compared with FFPE, but DNA quality was higher with less fragmentation. Seventy-six percent of FTA preps and 86% of FFPE samples generated adequate DNA for genotyping. FTA preps tended to perform poorly for collection of DNA from pretreated carcinomas and mesenchymal neoplasms. Of the 16 paired DNA samples that were genotyped, 15 (94%) gave entirely concordant results. Filter paper-based sample preservation is a feasible alternative to FFPE for use in automated, high-throughput genotyping of carcinomas. PMID:25221956

  7. Leveraging Hypoxia-Activated Prodrugs to Prevent Drug Resistance in Solid Tumors.

    PubMed

    Lindsay, Danika; Garvey, Colleen M; Mumenthaler, Shannon M; Foo, Jasmine

    2016-08-01

    Experimental studies have shown that one key factor in driving the emergence of drug resistance in solid tumors is tumor hypoxia, which leads to the formation of localized environmental niches where drug-resistant cell populations can evolve and survive. Hypoxia-activated prodrugs (HAPs) are compounds designed to penetrate to hypoxic regions of a tumor and release cytotoxic or cytostatic agents; several of these HAPs are currently in clinical trial. However, preliminary results have not shown a survival benefit in several of these trials. We hypothesize that the efficacy of treatments involving these prodrugs depends heavily on identifying the correct treatment schedule, and that mathematical modeling can be used to help design potential therapeutic strategies combining HAPs with standard therapies to achieve long-term tumor control or eradication. We develop this framework in the specific context of EGFR-driven non-small cell lung cancer, which is commonly treated with the tyrosine kinase inhibitor erlotinib. We develop a stochastic mathematical model, parametrized using clinical and experimental data, to explore a spectrum of treatment regimens combining a HAP, evofosfamide, with erlotinib. We design combination toxicity constraint models and optimize treatment strategies over the space of tolerated schedules to identify specific combination schedules that lead to optimal tumor control. We find that (i) combining these therapies delays resistance longer than any monotherapy schedule with either evofosfamide or erlotinib alone, (ii) sequentially alternating single doses of each drug leads to minimal tumor burden and maximal reduction in probability of developing resistance, and (iii) strategies minimizing the length of time after an evofosfamide dose and before erlotinib confer further benefits in reduction of tumor burden. These results provide insights into how hypoxia-activated prodrugs may be used to enhance therapeutic effectiveness in the clinic. PMID

  8. Leveraging Hypoxia-Activated Prodrugs to Prevent Drug Resistance in Solid Tumors

    PubMed Central

    Lindsay, Danika; Garvey, Colleen M.; Mumenthaler, Shannon M.; Foo, Jasmine

    2016-01-01

    Experimental studies have shown that one key factor in driving the emergence of drug resistance in solid tumors is tumor hypoxia, which leads to the formation of localized environmental niches where drug-resistant cell populations can evolve and survive. Hypoxia-activated prodrugs (HAPs) are compounds designed to penetrate to hypoxic regions of a tumor and release cytotoxic or cytostatic agents; several of these HAPs are currently in clinical trial. However, preliminary results have not shown a survival benefit in several of these trials. We hypothesize that the efficacy of treatments involving these prodrugs depends heavily on identifying the correct treatment schedule, and that mathematical modeling can be used to help design potential therapeutic strategies combining HAPs with standard therapies to achieve long-term tumor control or eradication. We develop this framework in the specific context of EGFR-driven non-small cell lung cancer, which is commonly treated with the tyrosine kinase inhibitor erlotinib. We develop a stochastic mathematical model, parametrized using clinical and experimental data, to explore a spectrum of treatment regimens combining a HAP, evofosfamide, with erlotinib. We design combination toxicity constraint models and optimize treatment strategies over the space of tolerated schedules to identify specific combination schedules that lead to optimal tumor control. We find that (i) combining these therapies delays resistance longer than any monotherapy schedule with either evofosfamide or erlotinib alone, (ii) sequentially alternating single doses of each drug leads to minimal tumor burden and maximal reduction in probability of developing resistance, and (iii) strategies minimizing the length of time after an evofosfamide dose and before erlotinib confer further benefits in reduction of tumor burden. These results provide insights into how hypoxia-activated prodrugs may be used to enhance therapeutic effectiveness in the clinic. PMID

  9. Tumor-induced solid stress activates β-catenin signaling to drive malignant behavior in normal, tumor-adjacent cells

    PubMed Central

    Ou, Guanqing; Weaver, Valerie Marie

    2016-01-01

    Recent work by Fernández-Sánchez and coworkers examining the impact of applied pressure on the malignant phenotype of murine colon tissue in vivo revealed that mechanical perturbations can drive malignant behavior in genetically normal cells. Their findings build upon an existing understanding of how the mechanical cues experienced by cells within a tissue become progressively modified as the tissue transforms. Using magnetically stimulated ultra-magnetic liposomes to mimic tumor growth -induced solid stress, Fernández-Sánchez and coworkers were able to stimulate β-catenin to promote the cancerous behavior of both a normal and genetically modified colon epithelium. In this perspective, we discuss their findings in the context of what is currently known regarding the role of the mechanical landscape in cancer progression and β-catenin as a mechanotransducer. We review data that suggest that mechanically regulated activation of β-catenin fosters development of a malignant phenotype in tissue and predict that mechanical cues may contribute to tumor heterogeneity. PMID:26439949

  10. Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

    PubMed Central

    Dai, Wei; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Cheng, Yue; Zheng, Hong; Ngan, Roger Kai Cheong; Ng, Wai Tong; Lee, Anne Wing Mui; Yau, Chun Chung; Lee, Victor Ho Fu; Lung, Maria Li

    2015-01-01

    Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10−9), but was less obvious in other types of solid tumors except for prostate and Epstein–Barr virus (EBV)-positive gastric cancer (FDR<10−3). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection. PMID:25924914

  11. Auto Transplant for High Risk or Relapsed Solid or CNS Tumors

    ClinicalTrials.gov

    2016-08-15

    Ewing's Family Tumors; Renal Tumors; Hepatoblastoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Primary Malignant Brain Neoplasms; Retinoblastoma; Medulloblastoma; Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET); Atypical Teratoid/Rhabdoid Tumor (AT/RT); CNS Tumors; Germ Cell Tumors

  12. Pembrolizumab Combined With INCB039110 and/or Pembrolizumab Combined With INCB050465 in Advanced Solid Tumors

    ClinicalTrials.gov

    2016-07-08

    Advanced Solid Tumors; Endometrial Cancer; Melanoma; Microsatellite Unstable (MSI) Colorectal Cancer; MMR-deficient Tumors; Non-small Cell Lung Cancer; Renal Cell Carcinoma; Head and Neck Squamous Cell Carcinoma; Triple Negative Breast Cancer; Transitional Cell Carcinoma of the Genitourinary Tract; Pancreatic Ductal Adenocarcinoma

  13. Validation of Dynamic Contrast-Enhanced Ultrasound in Predicting Outcomes of Antiangiogenic Therapy for Solid Tumors

    PubMed Central

    Lassau, Nathalie; Bonastre, Julia; Kind, Michèle; Vilgrain, Valérie; Lacroix, Joëlle; Cuinet, Marie; Taieb, Sophie; Aziza, Richard; Sarran, Antony; Labbe-Devilliers, Catherine; Gallix, Benoit; Lucidarme, Olivier; Ptak, Yvette; Rocher, Laurence; Caquot, Louis-Michel; Chagnon, Sophie; Marion, Denis; Luciani, Alain; Feutray, Sylvaine; Uzan-Augui, Joëlle; Coiffier, Benedicte; Benastou, Baya; Koscielny, Serge

    2014-01-01

    Objectives Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. Materials and Methods This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. Results A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180€, which corresponds to $250 using the current exchange rate. Conclusions Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large

  14. Early Experience With Laparoscopic Approach for Solid Liver Tumors: Initial 16 Cases

    PubMed Central

    Descottes, Bernard; Lachachi, Fouzi; Sodji, Maxime; Valleix, Denis; Durand-Fontanier, Sylvaine; Pech, Bertrand; Laclause, de; Grousseau, Dominique

    2000-01-01

    Objective To evaluate the feasibility and outcome of laparoscopic hepatectomy in patients with solid liver tumors. Summary Background Data Although the laparoscopic approach has become popular in the surgical field, the value of laparoscopy in liver surgery is unknown. Methods Fifteen patients with solid liver tumors underwent 16 consecutive laparoscopic resections at the authors’ institution between 1994 and 1999. Indications were symptomatic hemangioma, focal nodular hyperplasia, liver cell adenoma, isolated metastasis from a colon cancer, and hepatocellular carcinoma. The laparoscopic procedure was performed using four to seven ports (four 10-mm, two 5-mm, and one 12-mm). Results One patient underwent a major hepatic resection (right lobectomy); the others underwent minor hepatic resections (left lateral segmentectomies, IVb subsegmentectomies, segmentectomy, and nonanatomical excisions). The laparoscopic procedure was uneventful in 15 patients; one patient required conversion to open laparotomy because of inadequate free surgical margins. Conclusion Laparoscopic surgery of the liver is feasible. The use of this new technical approach offers many advantages but requires extensive experience in hepatobiliary surgery and laparoscopic skills. The authors’ experience suggests that laparoscopic procedures should be reserved for benign tumors in selected cases. Its application must be verified by further studies. PMID:11066134

  15. Peripheral blood biomarkers of solid tumor angiogenesis in dogs: a polychromatic flow cytometry pilot study.

    PubMed

    Bentley, R Timothy; Mund, Julie A; Pollok, Karen E; Childress, Michael O; Case, Jamie

    2013-05-01

    A subset of peripheral blood hematopoietic stem and progenitor cells of bone marrow origin is elevated in humans with solid cancers before treatment and declines with therapy. This biomarker of angiogenesis is not specific to tumor type and has great potential in the objective assessment of treatment response in clinical trials. This pilot study was designed to develop a biomarker of neoangiogenesis in dogs for the diagnosis of cancer, the measurement of treatment response, and the provision of objective data in clinical trials. Polychromatic flow cytometry was used to quantify two subsets of circulating hematopoietic stem and progenitor cells in dogs with spontaneous solid tumors before (n = 8) and after (n = 3) treatment, and normal controls (n = 6). Pro-angiogenic peripheral blood cells of bone marrow origin were detected in all eight cases and the six normal controls; however, there was no statistically significant difference between the two groups. Interestingly, an apparent decline in pro-angiogenic cells was observed after treatment. Bone marrow derived hematopoietic cells appear to contribute to tumor angiogenesis in dogs, as has been previously reported in humans. While the methodology for pro-angiogenic cell quantification in a small number of dogs in the current study did not result in a significant difference from normal controls, an optimized canine polychromatic flow cytometry protocol holds great promise in the development of a canine cancer model and for the objective measurements of treatment response in clinical trials. PMID:23063489

  16. Managing teenage/young adult (TYA) brain tumors: a UK perspective.

    PubMed

    Alken, Scheryll P; D'Urso, Pietro; Saran, Frank H

    2015-01-01

    Tumors of the CNS are among the commonest malignancies occurring in teenage/young adult patients (i.e., those aged between 15 and 24 years). The treatment of this patient population is challenging. Adolescence and young adulthood are a turbulent period of life, with physical, emotional, social and cognitive changes. Best practice advocates their treatment in dedicated teenage/young adult units, with multidisciplinary team input and access to clinical trials. Treatment of CNS malignancies is dependent upon histological subtype and staging, with varying combinations of surgery, radiotherapy and chemotherapy used. Clinical trials directly targeted at this patient population are rare; treatments are based on pediatric protocols as studies have demonstrated improved outcomes in patients (with other malignancies) treated as such. Scope for improvement lies in minimizing patient risk of recurrence and long-term sequelae of treatment. Molecular characterization of tumors may provide further information. PMID:26118974

  17. [Gross tumor volume (GTV) and clinical target volume (CTV) in adult gliomas].

    PubMed

    Kantor, G; Loiseau, H; Vital, A; Mazeron, J J

    2001-10-01

    Glioblastoma multiform and astrocytoma are the most frequent primary cancer of the central nervous system of adult. Definitions of gross tumor volume (GTV) and clinical target volume (CTV) are based on the confrontation of clinical presentation (age, performance status, neurologic symptoms...), histological type and imaging aspects. For glioblastoma multiform, the GTV can be defined by the area of contrast enhancement observed on the CT scan or MRI. Definition of the CTV can be more difficult and have to take into account the risk of presence of isolated malignant cells in the oedema surrounding the tumor or in the adjacent brain structures. The classical concept of GTV plus a safety margin of 2 cm around is discussed with a CTV containing at least all the oedematous area and eventually adjacent brain structures (nuclei, corpus callosum or other long associative fibers...). For low grade astrocytoma, the definition of GTV can be difficult if the tumoral infiltration is diffuse without nodular visible tumor. CTV corresponds to at least T2 MRI hypersignal area when visible. For postoperative tumor, technical considerations are important for the detection of residual tumor. A safety margin around the resected area is designed according to the risk of presence of isolated cells or involvement of adjacent brain structures. PMID:11715309

  18. Multicenter study on adult growth hormone level in postoperative pituitary tumor patients.

    PubMed

    Cheng, Jing-min; Gu, Jian-wen; Kuang, Yong-qin; Ma, Yuan; Xia, Xun; Yang, Tao; Lu, Min; He, Wei-qi; Sun, Zhi-yong; Zhang, Yan-chao

    2015-03-01

    The objective of this study is to observe the adult growth hormone level in postoperative pituitary tumor patients of multi-centers, and explore the change of hypophyseal hormones in postoperative pituitary tumor patients. Sixty patients with pituitary tumor admitted during March, 2011-March, 2012 were selected. Postoperative hypophyseal hormone deficiency and the change of preoperative, intraoperative, and postoperative growth hormone levels were recorded. Growth hormone hypofunction was the most common hormonal hypofunction, which took up to 85.0 %. Adrenocortical hormone hypofunction was next to it and accounted for 58.33 %. GH + ACTH + TSH + Gn deficiency was the most common in postoperative hormone deficiency, which took up to 40.00 %, and GH + ACTH + TSH + Gn + AVP and GH deficiencies were next to it and accounted for 23.33 and 16.67 %, respectively. The hormone levels in patients after total pituitary tumor resection were significantly lower than those after partial pituitary tumor resection, and the difference was statistically significant; growth hormone and serum prolactin levels after surgery in two groups were decreased, and the difference was statistically significant. The incidence rate of growth hormone deficiency in postoperative pituitary tumor patients is high, which is usually complicated with deficiency of various hypophyseal hormones. In clinical, we should pay attention to the levels of the hypopnyseal hormones, and take timely measures to avoid postoperative complications. PMID:25403160

  19. Tumor Suppressor Inactivation in the Pathogenesis of Adult T-Cell Leukemia

    PubMed Central

    Nicot, Christophe

    2015-01-01

    Tumor suppressor functions are essential to control cellular proliferation, to activate the apoptosis or senescence pathway to eliminate unwanted cells, to link DNA damage signals to cell cycle arrest checkpoints, to activate appropriate DNA repair pathways, and to prevent the loss of adhesion to inhibit initiation of metastases. Therefore, tumor suppressor genes are indispensable to maintaining genetic and genomic integrity. Consequently, inactivation of tumor suppressors by somatic mutations or epigenetic mechanisms is frequently associated with tumor initiation and development. In contrast, reactivation of tumor suppressor functions can effectively reverse the transformed phenotype and lead to cell cycle arrest or death of cancerous cells and be used as a therapeutic strategy. Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoproliferative disease associated with infection of CD4 T cells by the Human T-cell Leukemia Virus Type 1 (HTLV-I). HTLV-I-associated T-cell transformation is the result of a multistep oncogenic process in which the virus initially induces chronic T-cell proliferation and alters cellular pathways resulting in the accumulation of genetic defects and the deregulated growth of virally infected cells. This review will focus on the current knowledge of the genetic and epigenetic mechanisms regulating the inactivation of tumor suppressors in the pathogenesis of HTLV-I. PMID:26170835

  20. Weekly Doses of Cilengitide and Paclitaxel in Treating Patients With Advanced Solid Tumors That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-03-14

    Adult Solid Neoplasm; Estrogen Receptor Negative; HER2/Neu Negative; Male Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  1. Veliparib in Combination With Carboplatin and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors

    ClinicalTrials.gov

    2015-05-22

    Adult Solid Neoplasm; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  2. Detection of human herpesvirus-6 in adult central nervous system tumors: predominance of early and late viral antigens in glial tumors.

    PubMed

    Crawford, John R; Santi, Maria Rita; Cornelison, Robbie; Sallinen, Satu-Leena; Haapasalo, Hannu; MacDonald, Tobey J

    2009-10-01

    The purpose is to determine the incidence of active and latent human herpesvirus-6 (HHV-6) infection in a large cohort of adult primary and recurrent CNS tumors. We screened a tissue microarray (TMA) containing more than 200 adult primary and recurrent CNS tumors with known clinical information for the presence of HHV-6 DNA by in situ hybridization (ISH) and protein by immunohistochemistry (IHC). One hundred six of 224 (47%) CNS tumors were positive for HHV-6 U57 Major Capsid Protein (MCP) gene by ISH compared to 0/25 non tumor control brain (P = 0.001). Fourteen of 30 (47%) tumors were HHV-6 MCP positive by nested PCR compared to 0/25 non-tumor brain controls (P = 0.001), revealing HHV-6 Variant A in 6 of 14 samples. HHV-6A/B early (p41) and late (gp116/64/54) antigens were detected by IHC in 66 of 277 (24%) (P = 0.003) and 84 of 282 (35%) (P = 0.002) tumors, respectively, suggesting active infection. HHV-6 p41 (P = 0.645) and gp116/64/54 (P = 0.198) antigen detection was independent of recurrent disease. Glial tumors were 3 times more positive by IHC compared to non glial tumors for both HHV-6 gp116/64/54 (P = 0.0002) and HHV-6 p41 (P = 0.004). Kaplan Meier survival analysis showed no effect of HHV-6 gp116/64/54 (P = 0.852) or HHV-6 p41 (P = 0.817) antigen detection on survival. HHV-6 early and late antigens are detected in adult primary and recurrent CNS tumors more frequently in glial tumors. We hypothesize that the glial-tropic features of HHV-6 may play an important modifying role in tumor biology that warrants further investigation. PMID:19424665

  3. Mitochondrially targeted wild-type p53 induces apoptosis in a solid human tumor xenograft model

    PubMed Central

    Palacios, Gustavo; Crawford, Howard C.; Vaseva, Angelina; Moll, Ute M.

    2013-01-01

    Classic but also novel roles of p53 are becoming increasingly well characterized. We previously showed that ex vivo retroviral transfer of mitochondrially targeted wild type p53 (mitop53) in the Eμ-myc mouse lymphoma model efficiently induces tumor cell killing in vivo. In an effort to further explore the therapeutic potential of mitop53 for its pro-apoptotic effect in solid tumors, we generated replication-deficient recombinant human Adenovirus type 5 vectors. We show here that adenoviral delivery of mitop53 by intratumoral injection into HCT116 human colon carcinoma xenograft tumors in nude mice is surprisingly effective, resulting in tumor cell death of comparable potency to conventional p53. These apoptotic effects in vivo were confirmed by Ad5-mitop53 mediated cell death of HCT116 cells in culture. Together, these data provide encouragement to further explore the potential for novel mitop53 proteins in cancer therapy to execute the shortest known circuitry of p53 death signaling. PMID:18719383

  4. Involvement of estrogen-related receptors in transcriptional response to hypoxia and growth of solid tumors.

    PubMed

    Ao, Ada; Wang, Heiman; Kamarajugadda, Sushama; Lu, Jianrong

    2008-06-01

    The development of intratumoral hypoxia is a universal hallmark of rapidly growing solid tumors. Adaptation to the hypoxic environment, which is critical for tumor cell survival and growth, is mediated primarily through a hypoxia-inducible factor (HIF)-dependent transcriptional program. HIF activates genes that facilitate crucial adaptive mechanisms including increased glucose uptake and glycolysis and tumor angiogenesis, making it an important therapeutic target. However, the HIF-dependent transcriptional mechanism remains incompletely understood, and targeting HIF is a difficult endeavor. Here, we show that the orphan nuclear receptor estrogen-related receptors (ERRs) physically interact with HIF and stimulate HIF-induced transcription. Importantly, ERRs appear to be essential for HIF's function. Transcriptional activation of hypoxic genes in cells cultured under hypoxia is largely blocked by suppression of ERRs through expression of a dominant negative form of ERR or treatment with a pharmacological ERR inhibitor, diethylstilbestrol. Systematic administration of diethylstilbestrol severely diminished growth and angiogenesis of tumor xenografts in vivo. Because nuclear receptors are outstanding targets for drug discovery, the findings not only may offer mechanistic insights into HIF-mediated transcription but also may open new avenues for targeting the HIF pathway for cancer therapy. PMID:18509053

  5. A rare case report of Solid Pseudopapillary Tumor of the pancreas with portal hypertension

    PubMed Central

    Reddy, Asha; Sanniyasi, Saravanan; George, Dilip Joseph; Narayanan, Cunnigaiper Dhanasekaran

    2016-01-01

    Introduction Solid Pseudopapillary Tumor of the pancreas (SPT) is a rare pancreatic tumor and represents 1–3% of all pancreatic tumors. It usually presents in young females with abdominal pain, nausea, vomiting and abdominal fullness. The first case report was documented in 1959 and since then multiple case reports have been documented on the various surgical approaches for SPT. However, there are not many reported cases where surgery has been performed on SPT with portal hypertension. Presentation of case In our case report, a 19 year old girl presented with a mass in the left side of the abdomen with associated dragging pain. Ultrasound Abdomen and CT (computed tomography) confirmed an SPT with portal hypertension, with the lesion involving the body and tail of pancreas. Discussion Although few reports are available on SPT with portal hypertension, ours is the first report on a benign SPT with sinistral portal hypertension treated with a distal pancreatectomy. The presence of portal hypertension made the excision of the tumor and delineation of the vessels very difficult. However, when great care is taken while handling the dilated vessels, dissection can be completed with minimal blood loss. Conclusion Meticulous surgical technique along with accurate identification of vasculature will aid in the resection. Although some SPTs behave aggressively, most of them are benign and patients with SPT have an excellent prognosis. PMID:27046101

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

    PubMed Central

    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

  7. Co-evolution of solid stress and interstitial fluid pressure in tumors during progression: Implications for vascular collapse

    PubMed Central

    Stylianopoulos, Triantafyllos; Martin, John D.; Snuderl, Matija; Mpekris, Fotios; Jain, Saloni R.; Jain, Rakesh K.

    2013-01-01

    The stress harbored by the solid phase of tumors is known as solid stress. Solid stress can be either applied externally by the surrounding normal tissue or induced by the tumor itself due to its growth. Fluid pressure is the isotropic stress exerted by the fluid phase. We recently demonstrated that growth-induced solid stress is on the order of 1.3–13.0 kPa (10–100 mmHg) - high enough to cause compression of fragile blood vessels resulting in poor perfusion and hypoxia. However, the evolution of growth-induced stress with tumor progression and its effect on cancer cell proliferation in vivo is not understood. To this end, we developed a mathematical model for tumor growth that takes into account all three types of stresses: growth-induced stress, externally applied stress and fluid pressure. First, we performed in vivo experiments and found that growth-induced stress is related to tumor volume through a bi-exponential relationship. Then, we incorporated this information into our mathematical model and showed that due to the evolution of growth-induced stress, total solid stress levels are higher in the tumor interior and lower in the periphery. Elevated compressive solid stress in the interior of the tumor is sufficient to cause the collapse of blood vessels and results in a lower growth rate of cancer cells compared to the periphery, independently from that caused by the lack of nutrients due to vessel collapse. Furthermore, solid stress in the periphery of the tumor causes blood vessels in the surrounding normal tissue to deform to elliptical shapes. We present histological sections of human cancers that demonstrate such vessel deformations. Finally, we found that fluid pressure increases with tumor growth due to increased vascular permeability and lymphatic impairment, and is governed by the microvascular pressure. Crucially, fluid pressure does not cause vessel compression of tumor vessels. Major Findings. Growth-induced solid stress is accumulated in

  8. Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity.

    PubMed

    Feng, Jin; Huang, Chao; Wren, Jonathan D; Wang, Dao-Wen; Yan, Jizhou; Zhang, Jiexin; Sun, Yujie; Han, Xiao; Zhang, Xin A

    2015-12-01

    Tetraspanin CD82 suppresses the progression and metastasis of a wide range of solid malignant tumors. However, its roles in tumorigenesis and hematopoietic malignancy remain unclear. Ubiquitously expressed CD82 restrains cell migration and cell invasion by modulating both cell-matrix and cell-cell adhesiveness and confining outside-in pro-motility signaling. This restraint at least contributes to, if not determines, the metastasis-suppressive activity and, also likely, the physiological functions of CD82. As a modulator of cell membrane heterogeneity, CD82 alters microdomains, trafficking, and topography of the membrane by changing the membrane molecular landscape. The functional activities of membrane molecules and the cytoskeletal interaction of the cell membrane are subsequently altered, followed by changes in cellular functions. Given its pathological and physiological importance, CD82 is a promising candidate for clinically predicting and blocking tumor progression and metastasis and also an emerging model protein for mechanistically understanding cell membrane organization and heterogeneity. PMID:26335499

  9. Magna-field irradiation and autologous marrow rescue in the treatment of pediatric solid tumors

    SciTech Connect

    Munoz, L.L.; Wharam, M.D.; Kaizer, H.; Leventhal, B.G.; Ruymann, R.

    1983-12-01

    Marrow ablative therapy has been given to pediatric patients with a variety of disseminated tumors. Eight patients with advanced neuroblastoma received autologous marrow reinfusion after intensive therapy. Three of eight are in continuous complete remission from 7 to 60 months. An additional four patients received allogeneic marrow transplantation and two remain in continuous complete response at 21 and 39 months. Intensive therapy and autologous marrow reinfusion have been applied to Ewing's sarcoma, but only preliminary results are available. Six patients with disseminated rhabdomyosarcoma and extra-osseous Ewing's sarcoma received conventional chemotherapy followed by sequential hemi-body irradiation. Four of six patients received autologous marrow rescue. Their median disease-free survival is 17 months. This preliminary experience demonstrates the feasibility of using marrow ablative therapy with autologous marrow transplantation in the treatment of pediatric solid tumors. Continuing Phase II studies are required to substantiate its efficacy.

  10. Giant primary ossified cavernous hemangioma of the skull in an adult: A rare calvarial tumor

    PubMed Central

    Tyagi, Devendra K; Balasubramaniam, Srikant; Sawant, Hemant V

    2011-01-01

    Primary intraosseous cavernous hemangiomas (PICHs) of the cranium are rare benign vascular tumors that account for about 0.2 % of all bone tumors and 10 % of benign skull tumors. They generally present as osteolytic lesions with honeycomb pattern of calcification. Completely ossified cavernous hemangioma of the calvarium in an adult has not been reported previously. A 28-year-old female presented to us with a large right parietal skull mass that had been present since the last 15 years. Total resection of the lesion was performed. Pathological examination was suggestive of cavernous hemangioma of the skull bone. Cavernous hemangioma should be considered as one of the differential diagnosis in any case of bony swelling of the calvarium so that adequate preoperative planning can be made to minimize blood loss and subsequent morbidity. PMID:21897684

  11. Profile of nintedanib in the treatment of solid tumors: the evidence to date

    PubMed Central

    Awasthi, Niranjan; Schwarz, Roderich E

    2015-01-01

    Angiogenesis is an essential process for tumor growth and metastasis, and remains a promising therapeutic target process in cancer treatment for several cancer types. Bevacizumab, a monoclonal antibody that targets vascular endothelial growth factor (VEGF), was the first antiangiogenic agent approved for cancer therapy. Novel antiangiogenic agents, such as sunitinib, sorafenib, pazopanib, or vandetanib that target additional proangiogenic signaling pathways beyond VEGF, have also been approved for the treatment of various malignant diseases. While most of these agents are approved in combination with cytotoxic chemotherapy for indications including metastatic colorectal cancer, non-small-cell lung cancer, breast cancer, renal cell carcinoma (RCC), and gastric cancer, some are used as approved monotherapy for advanced RCC, hepatocellular carcinoma and medullary thyroid cancer. Major challenges to the success of antiangiogenic therapy include associated toxicity risks, limitation of efficacy through the possible development of resistance and induction or promotion of metastatic progression. Nintedanib (formally known as BIBF 1120) is a triple angiokinase inhibitor of VEGF, fibroblast growth factor, platelet-derived growth factor signaling with lesser activity against RET, Flt-3, and Src. Through this unique targeting profile nintedanib has demonstrated significant antitumor activity in several tumor types in preclinical studies. Nintedanib has also shown promising clinical efficacy in combination with docetaxel and has been approved for treating patients with locally advanced and metastatic non-small-cell lung cancer in Europe. Nintedanib has also been found to be clinically promising in terms of efficacy and safety in several other solid tumors including ovarian cancer (Phase III), RCC (Phase II), and prostate cancer (Phase II). This review article provides a comprehensive summary of the preclinical and clinical efficacy of nintedanib in the treatment of solid

  12. Practical PERCIST: A Simplified Guide to PET Response Criteria in Solid Tumors 1.0.

    PubMed

    O, Joo Hyun; Lodge, Martin A; Wahl, Richard L

    2016-08-01

    Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST 1.0) describes in detail methods for controlling the quality of fluorine 18 fluorodeoxyglucose PET imaging conditions to ensure the comparability of PET images from different time points to allow quantitative expression of the changes in PET measurements and assessment of overall treatment response in PET studies. The steps for actual application of PERCIST are summarized. Several issues from PERCIST 1.0 that appear to require clarification, such as measurement of size and definition of unequivocal progression, also are addressed. (©) RSNA, 2016. PMID:26909647

  13. Effect of Fluid Friction on Interstitial Fluid Flow Coupled with Blood Flow through Solid Tumor Microvascular Network

    PubMed Central

    Sefidgar, Mostafa; Soltani, M.; Bazmara, Hossein

    2015-01-01

    A solid tumor is investigated as porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multiscale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. The mathematical method involves processes such as blood flow through vessels and solute and fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model predicts. PMID:25960764

  14. Liquid and Solid Meal Replacement Products Differentially Affect Postprandial Appetite and Food Intake in Older Adults

    PubMed Central

    Stull, April J.; Apolzan, John W.; Thalacker-Mercer, Anna E.; Iglay, Heidi B.; Campbell, Wayne W.

    2008-01-01

    Liquid and solid foods are documented to elicit differential appetitive and food intake responses. This study was designed to assess the influences of liquid vs solid meal replacement products on postprandial appetite ratings and subsequent food intake in healthy older adults. This study used a randomized and crossover design with two 1-day trials (1 week between trials), and 24 adults (12 men and 12 women) aged 50 to 80 years with body mass index (calculated as kg/m2) between 22 and 30 participated. After an overnight fast, the subjects consumed meal replacement products as either a beverage (liquid) or a bar (solid). The meal replacement products provided 25% of each subject's daily estimated energy needs with comparable macro-nutrient compositions. Subjects rated their appetite on a 100 mm quasilogarithmic visual analog scale before and 15, 30, 45, 60, 90, 120, and 150 minutes after consuming the meal replacement product. At minute 120, each subject consumed cooked oatmeal ad libitum to a “comfortable level of fullness.” Postprandial composite (area under the curve from minute 15 to minute 120) hunger was higher (P=0.04) for the liquid vs solid meal replacement products and desire to eat (P=0.15), preoccupation with thoughts of food (P=0.07), and fullness (P=0.25) did not differ for the liquid vs solid meal replacement products. On average, the subjects consumed 13.4% more oatmeal after the liquid vs solid (P=0.006) meal replacement product. These results indicate that meal replacement products in liquid and solid form do not elicit comparable appetitive and ingestive behavior responses and that meal replacement products in liquid form blunt the postprandial decline in hunger and increase subsequent food intake in older adults. PMID:18589034

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

    PubMed Central

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

    2016-01-01

    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. PMID:26755888

  16. Armed Oncolytic Virus Enhances Immune Functions of Chimeric Antigen Receptor-Modified T Cells in Solid Tumors

    PubMed Central

    Nishio, Nobuhiro; Diaconu, Iulia; Liu, Hao; Cerullo, Vincenzo; Caruana, Ignazio; Hoyos, Valentina; Bouchier-Hayes, Lisa; Savoldo, Barbara; Dotti, Gianpietro

    2014-01-01

    The clinical efficacy of chimeric antigen receptor (CAR)-redirected T cells remains marginal in solid tumors compared to leukemias. Failures have been attributed to insufficient T-cell migration and to the highly immunosuppressive milieu of solid tumors. To overcome these obstacles, we have combined CAR-T cells with an oncolytic virus (OV) armed with the chemokine RANTES and the cytokine IL-15, reasoning that the modified OV will have both a direct lytic effect on infected malignant cells and facilitate migration and survival of CAR-T cells. Using neuroblastoma (NB) as a tumor model we found that the adenovirus Ad5Δ24 exerted a potent, dose-dependent, cytotoxic effect on tumor cells, while CAR-T cells specific for the tumor antigen GD2 (GD2.CAR-T cells) were not damaged. When used in combination, Ad5Δ24 directly accelerated the caspase pathways in tumor cells exposed to CAR-T cells, while the intratumoral release of both RANTES and IL-15 attracted CAR-T cells and promoted their local survival, respectively, increasing the overall survival of tumor bearing mice. These preclinical data support the use of this innovative biological platform of immunotherapy for solid tumors. PMID:25060519

  17. Armed oncolytic virus enhances immune functions of chimeric antigen receptor-modified T cells in solid tumors.

    PubMed

    Nishio, Nobuhiro; Diaconu, Iulia; Liu, Hao; Cerullo, Vincenzo; Caruana, Ignazio; Hoyos, Valentina; Bouchier-Hayes, Lisa; Savoldo, Barbara; Dotti, Gianpietro

    2014-09-15

    The clinical efficacy of chimeric antigen receptor (CAR)-redirected T cells remains marginal in solid tumors compared with leukemias. Failures have been attributed to insufficient T-cell migration and to the highly immunosuppressive milieu of solid tumors. To overcome these obstacles, we have combined CAR-T cells with an oncolytic virus armed with the chemokine RANTES and the cytokine IL15, reasoning that the modified oncolytic virus will both have a direct lytic effect on infected malignant cells and facilitate migration and survival of CAR-T cells. Using neuroblastoma as a tumor model, we found that the adenovirus Ad5Δ24 exerted a potent, dose-dependent, cytotoxic effect on tumor cells, whereas CAR-T cells specific for the tumor antigen GD2 (GD2.CAR-T cells) were not damaged. When used in combination, Ad5Δ24 directly accelerated the caspase pathways in tumor cells exposed to CAR-T cells, whereas the intratumoral release of both RANTES and IL15 attracted CAR-T cells and promoted their local survival, respectively, increasing the overall survival of tumor-bearing mice. These preclinical data support the use of this innovative biologic platform of immunotherapy for solid tumors. Cancer Res; 74(18); 5195-205. ©2014 AACR. PMID:25060519

  18. Variant type of teratoma appearing as a primary solid dermoid tumor in the rectum: report of a case.

    PubMed

    Tabuchi, Y; Tsunemi, K; Matsuda, T

    1995-01-01

    We report herein the rare case of a 39-year-old woman found to have a primary solid dermoid tumor in the rectum. The patient presented after noticing a small amount of anal bleeding, and physical examination revealed a walnut-sized hard tumor, palpable in the anterior rectum, located about 9 cm from the anal verge. Morphologic examinations revealed a polypoid lesion with some hair surrounded by rectal mucosa, and four biopsy specimens from the lesion showed normal squamous epithelium. The tumor, which measured 2.5 x 2.1 x 1.3 cm, was removed by endoscopic polypectomy. Microscopically, the tumor was diagnosed as a solid dermoid tumor without a cyst, a variant type of mature teratoma or dermoid cyst. Since 1914, only 12 such cases, including ours, have been reported in Japan. The clinical features and diagnostic and therapeutic methods applied thereto are discussed. PMID:7749293

  19. Understanding and Targeting MET Signaling in Solid Tumors - Are We There Yet?

    PubMed Central

    Ariyawutyakorn, Witthawat; Saichaemchan, Siriwimon; Varella-Garcia, Marileila

    2016-01-01

    The MET signaling pathway plays an important role in normal physiology and its deregulation has proved critical for development of numerous solid tumors. Different technologies have been used to investigate the genomic and proteomic status of MET in cancer patients and its association with disease prognosis. Moreover, with the development of targeted therapeutic drugs, there is an urgent need to identify potential biomarkers for selection of patients who are more likely to derive benefit from these agents. Unfortunately, the variety of technical platforms and analysis criteria for diagnosis has brought confusion to the field and a lack of agreement in the evaluation of MET status as a prognostic or predictive marker for targeted therapy agents. We review the molecular mechanisms involved in the deregulation of the MET signaling pathway in solid tumors, the different technologies used for diagnosis, and the main factors that affect the outcome, emphasizing the urge for completing analytical and clinical validation of these tests. We also review the current clinical studies with MET targeted agents, which mostly focus on lung cancer. PMID:27076844

  20. Procalcitonin as diagnostic marker of infection in solid tumors patients with fever.

    PubMed

    Vincenzi, B; Fioroni, I; Pantano, F; Angeletti, S; Dicuonzo, G; Zoccoli, A; Santini, D; Tonini, G

    2016-01-01

    In oncologic patients fever is a non-specific clinical marker of different clinical settings. Procalcitonin (PCT) seems to be the most promising infection marker. We aimed to define the potential role of PCT as an earlier diagnostic marker in patients with fever and solid tumor. This retrospective study enrolled 431 patients. All of them performed hemoculture (HE) and basal PCT assessment (reference laboratory cut-off: ≤0.5 or >0.5 ng/dL) before starting antibiotic therapy. Gram positive (G+), negative (G-) or Fungi infection were detected. A statistically significant difference in PCT levels between patients with positive and negative HE was observed (P < 0.0001). Moreover comparing PCT values in patients with positive and negative HE, we obtain in the positive HE subpopulation an AUC of 0.7 and a cut-off of 1.52 ng/dL reached high sensitivity (61.6%) and specificity (70.1%). Using this last cut-off, instead of the normal reference value, we achieve a risk reduction to overestimate an infection status of 23.4%. We support the clinic usefulness of serum PCT dosage in febrile advanced solid tumor patients. A PCT cut-off of 1.52 ng/dL could be helpful in the management of the antibiotic therapy preventing delays of oncologic treatments. PMID:27312877

  1. Procalcitonin as diagnostic marker of infection in solid tumors patients with fever

    PubMed Central

    Vincenzi, B.; Fioroni, I.; Pantano, F.; Angeletti, S.; Dicuonzo, G.; Zoccoli, A.; Santini, D.; Tonini, G.

    2016-01-01

    In oncologic patients fever is a non-specific clinical marker of different clinical settings. Procalcitonin (PCT) seems to be the most promising infection marker. We aimed to define the potential role of PCT as an earlier diagnostic marker in patients with fever and solid tumor. This retrospective study enrolled 431 patients. All of them performed hemoculture (HE) and basal PCT assessment (reference laboratory cut-off: ≤0.5 or >0.5 ng/dL) before starting antibiotic therapy. Gram positive (G+), negative (G−) or Fungi infection were detected. A statistically significant difference in PCT levels between patients with positive and negative HE was observed (P < 0.0001). Moreover comparing PCT values in patients with positive and negative HE, we obtain in the positive HE subpopulation an AUC of 0.7 and a cut-off of 1.52 ng/dL reached high sensitivity (61.6%) and specificity (70.1%). Using this last cut-off, instead of the normal reference value, we achieve a risk reduction to overestimate an infection status of 23.4%. We support the clinic usefulness of serum PCT dosage in febrile advanced solid tumor patients. A PCT cut-off of 1.52 ng/dL could be helpful in the management of the antibiotic therapy preventing delays of oncologic treatments. PMID:27312877

  2. Engineering phosphopeptide-decorated magnetic nanoparticles as efficient photothermal agents for solid tumor therapy.

    PubMed

    Wu, Man; Guo, Qiaoyan; Xu, Feng; Liu, Shujun; Lu, Xuehong; Wang, Jing; Gao, Hongwen; Luo, Ping

    2016-08-15

    Due to the high therapeutic efficiency and minimum damage towards normal tissues, phototherapy has drawn a great deal of attention in recent decades. Herein, we reported the synthesis of novel phosphopeptide-decorated magnetic nanoparticles (peptide-Fe3O4 nanoparticles), and their usages in photothermal therapy against solid tumor. By using a classical coprecipitation method and a facile ligand exchange route, these peptide-Fe3O4 nanoparticles were prepared with inexpensive inhesion. Upon the irradiation of a near-infrared (NIR) light, these nanoagents exhibited great photothermal effect with high photo-stability. In vitro biocompatibility studies of these peptide-Fe3O4 nanoparticles indicated their low cytotoxicity, negligible hemolysis, and no effect on blood coagulation. As expected, 4T1 murine breast cancer cells could be effectively damaged by these light-mediated nanoagents. Significantly, animal experiments demonstrated that these nanoagents held great solid tumor ablation effect with the assistance of a NIR laser irradiation. Additional studies focused on the long-term toxicity of these nanoagents indicated their high bio-compatibility. Thus, these peptide-Fe3O4 nanoparticles could bring more opportunities to a new generation of photothermal agents in the field of biomedicine. PMID:27214146

  3. Expansion Cohorts in First-in-Human Solid Tumor Oncology Trials.

    PubMed

    Theoret, Marc R; Pai-Scherf, Lee H; Chuk, Meredith K; Prowell, Tatiana M; Balasubramaniam, Sanjeeve; Kim, Tamy; Kim, Geoffrey; Kluetz, Paul G; Keegan, Patricia; Pazdur, Richard

    2015-10-15

    In 1962, the passage of the Kefauver-Harris Amendment to the 1938 Food, Drug, and Cosmetic Act required that sponsors seeking approval of new drugs demonstrate the drug's efficacy, in addition to its safety, through a formal process that includes "adequate and well-controlled" clinical trials as the basis to support claims of effectiveness. As a result of this amendment, FDA formalized in regulation the definitions of various phases of clinical investigations (i.e., phase I, phase II, and phase III). The clinical drug development paradigm for anticancer drugs intended to support marketing approval has historically followed this "phased" approach with sequential, stand-alone trials, with an increasing number of patients exposed to an investigational drug with each trial in order to fulfill the objectives of that particular stage in development. Increasingly, it is the Office of Hematology and Oncology Products' experience that commercial sponsors of solid tumor oncology drug development programs are amending ongoing phase I trials to add expansion cohorts designed to evaluate study objectives typical of later-phase trials. For investigational anticancer drugs that demonstrate preliminary clinical evidence of substantial antitumor activity early in clinical testing, use of expansion cohorts as a component of the solid tumor oncology drug development pathway, with appropriate measures to mitigate the risks of this approach, may fit in well with the goals and concepts described by FDA's expedited programs for serious conditions. PMID:26473190

  4. Dual thermal ablation modality of solid tumors in a mouse model

    NASA Astrophysics Data System (ADS)

    Shafirstein, Gal; Barnes, Klressa; Hennings, Leah; Webber, Jessica; Moros, Eduardo G.; Przybyla, Beata; Griffin, Robert J.

    2011-03-01

    Purpose: Develop a new combination therapy consisting of cryoablation and conductive high-temperature ablation for enhanced thermal ablation of solid tumors. Methods: We have constructed an invasive probe that can be used for consecutive cryoablation and hightemperature ablation (C/HTA), with a single insertion. The C/HTA probe was tested, in Balb/c mice bearing solid 4T1 tumors, in comparison to cryoablation and high temperature ablation, only. Three days after ablation, the diameter of the ablated zone was evaluated with pathological examination. Results: The C/HTA device can be used to induce larger ablation zones, in comparison to high temperature or cryoablation alone, and at lower thermal doses and temperatures than either modality alone. Conclusions: The relatively high thermal conductivity of ice, in comparison to water and native tissue, enables rapid heating of the ice-ball that result in improved conductive high temperature ablation. The new dual thermal modality improves ablation outcomes at lower thermal doses in comparison to a single ablation modality.

  5. Interleukin-2 Plus Interferon Alfa in Treating Adults With Metastatic Cancer

    ClinicalTrials.gov

    2011-05-10

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous/Nonmalignant Condition; Unspecified Adult Solid Tumor, Protocol Specific

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

    PubMed Central

    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

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

    ClinicalTrials.gov

    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

  8. Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics

    PubMed Central

    Francaviglia, Ilaria; Dal Cin, Elena; Barbieri, Gianluca; Arrigoni, Gianluigi; Pecciarini, Lorenza; Doglioni, Claudio; Cangi, Maria Giulia

    2015-01-01

    Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance,we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies. PMID:26435479

  9. Neurocognitive Outcomes and School Performance in Solid Tumor Cancer Survivors Lacking Therapy to the Central Nervous System

    PubMed Central

    Mohrmann, Caroline; Henry, Jennifer; Hauff, Marnie; Hayashi, Robert J.

    2015-01-01

    School performance in patients who have received therapy for childhood cancers has been studied in depth. Risk factors have historically included cranial radiation, intrathecal chemotherapy, and high doses of chemotherapy, including methotrexate and cytarabine. Leukemia and brain tumor survivors who receive such therapy have been the primary focus of this area of investigation. Extracranial solid tumor cancer patients lacking such risk factors have historically been expected to have normal school performance. We examined the medical records of 58 young pediatric extracranial solid tumor patients who lacked CNS-directed therapy or other known risk factors for cognitive impairment to evaluate the incidence of reported difficulties or abnormalities in neuropsychological testing. Thirty-one percent of patients were found to have at least one reported difficulty or abnormality. Of note, 34% of patients with Wilms tumor possessed difficulties compared to 23% of patients with other extracranial solid tumors. Extracranial solid tumor cancer survivors without known risk factors for school performance difficulties appear to have a higher incidence of problems than expected. PMID:25867598

  10. Identification of Down's syndrome critical locus gene SIM2-s as a drug therapy target for solid tumors.

    PubMed

    DeYoung, Maurice Phil; Tress, Matthew; Narayanan, Ramaswamy

    2003-04-15

    We report here a cancer drug therapy use of a gene involved in Down's syndrome. Using bioinformatics approaches, we recently predicted Single Minded 2 gene (SIM2) from Down's syndrome critical region to be specific to certain solid tumors. Involvement of SIM2 in solid tumors has not previously been reported. Intrigued by a possible association between a Down's syndrome gene and solid tumors, we monitored SIM2 expression in solid tumors. Isoform-specific expression of SIM2 short-form (SIM2-s) was seen selectively in colon, prostate, and pancreatic carcinomas but not in breast, lung, or ovarian carcinomas nor in most normal tissues. In colon tumors, SIM2-s expression was seen in early stages. Antisense inhibition of SIM2-s expression in a colon cancer cell line caused inhibition of gene expression, growth inhibition, and apoptosis. The administration of the antisense, but not the control, oligonucleotides caused a pronounced inhibition of tumor growth in nude mice with no major toxicity. Our findings provide a strong rationale for the genes-to-drugs paradigm, establish SIM2-s as a molecular target for cancer therapeutics, and may further understanding of the cancer risk of Down's syndrome patients. PMID:12676991

  11. Role of p38 MAP Kinase Signal Transduction in Solid Tumors

    PubMed Central

    Pal, Mintu; Koul, Sweaty

    2013-01-01

    Mitogen-activated protein kinases (MAPKs) mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the main subgroups, the p38 MAP kinases, has been implicated in a wide range of complex biologic processes, such as cell proliferation, cell differentiation, cell death, cell migration, and invasion. Dysregulation of p38 MAPK levels in patients are associated with advanced stages and short survival in cancer patients (e.g., prostate, breast, bladder, liver, and lung cancer). p38 MAPK plays a dual role as a regulator of cell death, and it can either mediate cell survival or cell death depending not only on the type of stimulus but also in a cell type specific manner. In addition to modulating cell survival, an essential role of p38 MAPK in modulation of cell migration and invasion offers a distinct opportunity to target this pathway with respect to tumor metastasis. The specific function of p38 MAPK appears to depend not only on the cell type but also on the stimuli and/or the isoform that is activated. p38 MAPK signaling pathway is activated in response to diverse stimuli and mediates its function by components downstream of p38. Extrapolation of the knowledge gained from laboratory findings is essential to address the clinical significance of p38 MAPK signaling pathways. The goal of this review is to provide an overview on recent progress made in defining the functions of p38 MAPK pathways with respect to solid tumor biology and generate testable hypothesis with respect to the role of p38 MAPK as an attractive target for intervention of solid tumors. PMID:24349632

  12. Monocyte chemotactic protein-1 expression as a prognosic biomarker in patients with solid tumor: a meta analysis

    PubMed Central

    Wang, Hong; Zhang, Qiongwen; Kong, Hongyu; Zeng, Yunhui; Hao, Meiqin; Yu, Ting; Peng, Jing; Xu, Zhao; Chen, Jingquan; Shi, Huashan

    2014-01-01

    Purpose: A great deal of studies have been performed on the prognostic value of monocyte chemotactic protein-1 (MCP-1) in solid tumors in recent years. However, no consistent outcomes are reported. Therefore, the prognostic value of MCP-1 still remains controversial in patients with solid tumors. Here we aimed to evaluate the prognostic value of MCP-1 expression for patients with solid tumors. Methods: Comprehensive literature was selected from PUBMED and EMBASE and clinical studies which reported analysis of survival data about MCP-1 in solid tumors were included. Stata 11.0 was used for performing a meta-analysis on evaluating the relation between MCP-1 and clinical staging, overall survival (OS) and disease free survival (DFS). Results: Eleven studies with a total of 1324 patients with solid tumors were included into our meta-analysis. The result showed that high concentration of MCP-1 was related to a worse OS (HR = 1.95, 95% CI 1.32-2.88). The subgroup analysis on different location of tumors showed that high concentration of MCP-1 meant bad prognosis in patients with digestive cancer (HR = 2.66, 95% CI 1.44-4.91) and urogenital cancer (HR = 2.23, 95% CI 1.61-3.10), even head and neck cancer (HR = 1.99, 95% CI 0.95-4.18) other than respiratory cancer (HR = 1.10, 95% CI 0.39-3.11). Another subgroup analysed on different sites of cancer and indicated a poor prognosis on adenocarcinoma (HR = 2.10, 95% CI 1.63-2.69). Conclusions: Our findings suggest that MCP-1 can be regarded as a poor prognostic maker for solid tumors and may represent important new therapeutic targets. PMID:25120764

  13. Vorinostat in Combination With Paclitaxel and Carboplatin in Treating Patients With Metastatic or Recurrent Solid Tumors and HIV Infection

    ClinicalTrials.gov

    2016-08-03

    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

  14. Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors

    ClinicalTrials.gov

    2016-04-11

    Retinoblastoma; Clear Cell Sarcoma; Renal Cell Carcinoma; Rhabdoid Tumor; Wilms Tumor; Hepatoblastoma; Neuroblastoma; Germ Cell Tumors; Ewings Sarcoma; Non-rhabdomyosarcoma Soft Tissue Sarcoma; Osteosarcoma; Rhabdomyosarcoma

  15. Veliparib, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory Lymphoma, Multiple Myeloma, or Solid Tumors

    ClinicalTrials.gov

    2015-10-14

    Adult B Acute Lymphoblastic Leukemia; Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Adult Solid Neoplasm; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Plasma Cell Myeloma; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  16. Prognostic significance of interleukin-17 in solid tumors: a meta-analysis

    PubMed Central

    Zeng, Yunhui; Zhang, Qiongwen; Wang, Hong; Lu, Minxun; Kong, Hongyu; Zhang, Yingyi; Shi, Huashan

    2015-01-01

    Background: The prognostic significance of intratumoral and peripheral interleukin-17 (IL-17) in tumors has been studied worldwide during these years, providing un-uniformed conclusions. Methods: We conducted a meta-analysis of published literatures that evaluated the correlation between IL-17 and clinical staging, overall survival (OS) and/or disease free survival (DFS). Results: A total of 28 studies enrolling 2902 patients were included. For the overall population, a high expression of IL-17 was found significantly correlated with worse DFS (HR = 1.59, 95% CI: 1.24-2.03) in patients with solid tumors. For gastrointestinal tumors, patients with IL-17 high seemed to have worse OS (HR = 1.85, 95% CI: 1.24-2.75) and DFS (HR = 2.41, 95% CI: 1.98-2.92). Sub-group meta-analysis revealed that IL-17 indicated late clinical staging in non-small cell lung cancer (NSCLC) patients (HR = 2.33, 95% CI: 1.25-4.32), on the other hand, early clinical staging in patients with esophageal squamous carcinoma (HR = 0.63, 95% CI: 0.42-0.94). Negative impacts of IL-17 on OS were shown in patients with hepatocellular carcinoma (HCC) (HR = 1.87, 95% CI: 1.23-2.84) or NSCLC (HR = 1.55, 95% CI: 1.02-2.35). However, positive impacts on OS were provided in patients with esophageal squamous carcinoma (HR = 0.65, 95% CI: 0.50-0.84). Besides, a high expression of IL-17 predicted better DFS in ovarian cancer patients (HR = 0.33, 95% CI: 0.11-1.00). Conclusions: Our meta-analysis revealed that IL-17 might correlate with poor OS and DFS in gastrointestinal tumors. Specifically, IL-17 was a detrimental factor for HCC and NSCLC patients, whereas a beneficial factor for patients with esophageal squamous carcinoma and ovarian cancer. PMID:26379842

  17. A Platform for Rapid, Quantitative Assessment of Multiple Drug Combinations Simultaneously in Solid Tumors In Vivo

    PubMed Central

    Grenley, Marc O.; Casalini, Joseph R.; Tretyak, Ilona; Ditzler, Sally H.; Thirstrup, Derek J.; Frazier, Jason P.; Pierce, Daniel W.; Carleton, Michael; Klinghoffer, Richard A.

    2016-01-01

    While advances in high-throughput screening have resulted in increased ability to identify synergistic anti-cancer drug combinations, validation of drug synergy in the in vivo setting and prioritization of combinations for clinical development remain low-throughput and resource intensive. Furthermore, there is currently no viable method for prospectively assessing drug synergy directly in human patients in order to potentially tailor therapies. To address these issues we have employed the previously described CIVO platform and developed a quantitative approach for investigating multiple combination hypotheses simultaneously in single living tumors. This platform provides a rapid, quantitative and cost effective approach to compare and prioritize drug combinations based on evidence of synergistic tumor cell killing in the live tumor context. Using a gemcitabine resistant model of pancreatic cancer, we efficiently investigated nine rationally selected Abraxane-based combinations employing only 19 xenografted mice. Among the drugs tested, the BCL2/BCLxL inhibitor ABT-263 was identified as the one agent that synergized with Abraxane® to enhance acute induction of localized apoptosis in this model of human pancreatic cancer. Importantly, results obtained with CIVO accurately predicted the outcome of systemic dosing studies in the same model where superior tumor regression induced by the Abraxane/ABT-263 combination was observed compared to that induced by either single agent. This supports expanded use of CIVO as an in vivo platform for expedited in vivo drug combination validation and sets the stage for performing toxicity-sparing drug combination studies directly in cancer patients with solid malignancies. PMID:27359113

  18. Nonlinear simulations of solid tumor growth using a mixture model: invasion and branching

    PubMed Central

    Cristini, Vittorio; Li, Xiangrong; Lowengrub, John S.; Wise, Steven M.

    2011-01-01

    We develop a thermodynamically consistent mixture model for avascular solid tumor growth which takes into account the effects of cell-to-cell adhesion, and taxis inducing chemical and molecular species. The mixture model is well-posed and the governing equations are of Cahn–Hilliard type. When there are only two phases, our asymptotic analysis shows that earlier single-phase models may be recovered as limiting cases of a two-phase model. To solve the governing equations, we develop a numerical algorithm based on an adaptive Cartesian block-structured mesh refinement scheme. A centered-difference approximation is used for the space discretization so that the scheme is second order accurate in space. An implicit discretization in time is used which results in nonlinear equations at implicit time levels. We further employ a gradient stable discretization scheme so that the nonlinear equations are solvable for very large time steps. To solve those equations we use a nonlinear multilevel/multigrid method which is of an optimal order O (N) where N is the number of grid points. Spherically symmetric and fully two dimensional nonlinear numerical simulations are performed. We investigate tumor evolution in nutrient-rich and nutrient-poor tissues. A number of important results have been uncovered. For example, we demonstrate that the tumor may suffer from taxis-driven fingering instabilities which are most dramatic when cell proliferation is low, as predicted by linear stability theory. This is also observed in experiments. This work shows that taxis may play a role in tumor invasion and that when nutrient plays the role of a chemoattractant, the diffusional instability is exacerbated by nutrient gradients. Accordingly, we believe this model is capable of describing complex invasive patterns observed in experiments. PMID:18787827

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

    ClinicalTrials.gov

    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

  20. Dose-Dependent Incidence of Hepatic Tumors in Adult Mice following Perinatal Exposure to Bisphenol A

    PubMed Central

    Weinhouse, Caren; Anderson, Olivia S.; Bergin, Ingrid L.; Vandenbergh, David J.; Gyekis, Joseph P.; Dingman, Marc A.; Yang, Jingyun

    2014-01-01

    Background: Bisphenol A (BPA) is a high production volume chemical with hormone-like properties that has been implicated as a potential carcinogen. Early-life exposure has been linked to increased risk for precancerous lesions in mammary and prostate glands and the uterus, but no prior study has shown a significant association between BPA exposure and cancer development. Objective: We explored the effects of BPA exposure during gestation and lactation on adult incidence of hepatic tumors in mice. Methods: Isogenic mice were perinatally exposed to BPA through maternal diets containing one of four environmentally relevant doses of BPA (0, 50 ng, 50 μg, or 50 mg per kilogram of diet), and we followed approximately one male and one female per litter until they were 10 months of age. Animals were tested for known risk factors for hepatocellular carcinoma, including bacterial and viral infections. Results: We found dose-dependent incidence of hepatic tumors in 10-month-old BPA-exposed mice. Of the offspring examined, 23% presented with hepatic tumors or preneoplastic lesions. We observed a statistically significant dose–response relationship, with an odds ratio for neoplastic and preneoplastic lesions of 7.23 (95% CI: 3.23, 16.17) for mice exposed to 50 mg BPA/kg diet compared with unexposed controls. Observed early disease onset, absence of bacterial or viral infection, and lack of characteristic sexual dimorphism in tumor incidence support a nonclassical etiology. Conclusions: To our knowledge, this is the first report of a statistically significant association between BPA exposure and frank tumors in any organ. Our results link early-life exposure to BPA with the development of hepatic tumors in rodents, and have potential implications for human health and disease. Citation: Weinhouse C, Anderson OS, Bergin IL, Vandenbergh DJ, Gyekis JP, Dingman MA, Yang J, Dolinoy DC. 2014. Dose-dependent incidence of hepatic tumors in adult mice following perinatal exposure to

  1. Desmoid tumors in adults: the role of radiotherapy in their management

    SciTech Connect

    Bataini, J.P.; Belloir, C.; Mazabraud, A.; Pilleron, J.P.; Cartigny, A.; Jaulerry, C.; Ghossein, N.A.

    1988-06-01

    Twenty-six adult patients with the pathologic diagnosis of desmoid tumor were treated between 1964 and 1983 at the Institut Curie in Paris with megavoltage irradiation. Twenty of these patients (76 percent) had extraabdominal tumors. Definitive surgical resection was performed on nine patients (one received preoperative radiotherapy). At last follow-up 1 1/2 to 10 years after treatment, all of the patients had no evidence of disease. Seven of the nine had follow-up examinations from 5 to 10 years after treatment. Seven patients had postoperative radiotherapy with doses from 4,700 to 6,500 rads (47 to 65 Gy) for either microscopic (three patients) or gross (four patients) residual disease. All but one patient had no evidence of disease from 2 to 8 years after treatment. Nine patients had radiotherapy for recurrent inoperable tumors and six had no evidence of disease from 3 to 20 years after treatment. Recurrences developed in three patients; outside the treatment portal in one, and the other two had received less than 5,000 rads (50 Gy). Clinical regression of tumors after treatment was slow, with complete regression taking up to 2 years. Postoperative radiotherapy with doses of at least 5,000 to 6,000 rads (50 to 60 Gy) was effective in achieving local control of inoperable or incompletely resected tumors, thus the need for repeated resections was avoided. Computerized tomography has greatly improved the assessment of tumor extension and should be used routinely before either operation or radiotherapy to obtain adequate margins and minimize the chance of missing disease.

  2. Desmoplastic small round-cell tumor: an adult with previous exposure to agent orange.

    PubMed

    Baz, Walid; El-Soueidi, Raymond; Nakhl, Fadi; Aoun, Nelly; Chin, Nena; Dhar, Meeko

    2010-06-01

    Desmoplastic small round-cell tumor is an uncommon, highly aggressive tumor with a predilection for pediatric age groups and young adults. It is very unusual in the elderly population. Although Agent Orange has been associated with soft-tissue sarcoma, an association with desmoplastic small round-cell tumor has not been reported. A 52-year-old male presented with abdominal distention, dyspnea, and a 9 kg weight loss. Prior history was significant for hepatitis C and diabetes. He was a Vietnam veteran and he admitted being exposed to Agent Orange. On physical examination, the abdomen was distended and tense. Computed tomography scan of the chest, abdomen and pelvis demonstrated extensive mediastinal and retroperitoneal adenopathy, diffuse omental masses and extensive pleural, intra-abdominal and pelvic ascites. Omental core needle biopsy was consistent with desmoplastic small round-cell tumor based on morphology and immunohistochemistry. He responded poorly to chemotherapy with high-dose cyclophosphamide, doxorubicin and vincristine and died 5 months after presentation secondary to neutropenic sepsis despite G-CSF support and antibiotics. PMID:20382635

  3. Transcriptomic analysis of stage 1 versus advanced adult granulosa cell tumors

    PubMed Central

    Leung, Dilys; Gould, Jodee A.; Jobling, Tom; Fuller, Peter J.

    2016-01-01

    Ovarian granulosa cell tumors (GCT) are hormonally-active neoplasms characterized, in the adult-subtype, by a mutation in the FOXL2 gene (C134W). They exhibit an indolent course with an unexplained propensity for late recurrence; ∼80% of patients with aggressive, advanced stage tumors die from their disease; aside from surgery, therapeutic options are limited. To identify the molecular basis of advanced stage disease we have used whole transcriptome analysis of FOXL2 C134W mutation positive adult (a)GCT to identify genes that are differentially expressed between early (stage 1) and advanced (stage 3) aGCT. Transcriptome profiles for early (n = 6) and stage 3 (n = 6) aGCT, and for the aGCT-derived KGN, cell line identified 24 genes whose expression significantly differs between the early and stage 3 aGCT. Of these, 16 were more abundantly expressed in the stage 3 aGCT and 8 were higher in the stage 1 tumors. These changes were further examined for the genes which showed the greatest fold change: the cytokine CXCL14, microfibrillar-associated protein 5, insulin-like 3 and desmin. Gene Set Enrichment Analysis identified overexpression of genes on chromosome 7p15 which includes the homeobox A gene locus. The analysis therefore identifies a small number of genes with clearly discriminate patterns of expression arguing that the clinicopathological-derived distinction of the tumor stage is robust, whilst confirming the relative homogeneity of expression for many genes across the cohort and hence of aGCT. The expression profiles do however identify several overexpressed genes in both stage 1 and/or stage 3 aGCT which warrant further study as possible therapeutic targets. PMID:26893359

  4. Primary atypical teratoid/rhabdoid tumor of the spine in an adult patient

    PubMed Central

    Li, Luyuan; Patel, Mohit; Nguyen, Ha Son; Doan, Ninh; Sharma, Abhishiek; Maiman, Dennis

    2016-01-01

    Background: Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive neoplasm of the central nervous system that generally arises intracranially in patients under 2 years of age. Primary spinal AT/RT in an adult is rare. Case Description: A 23-year-old female presented with left lower extremity sciatica attributed to a magnetic resonance imaging (MRI)-documented intradural mass between L2 and L4. The lesion was biopsied (was unresectable) and treated with high-dose chemotherapy (methotrexate, vincristine, cyclophosphamide, etoposide, and cisplatin) with autologous hematopoietic stem cells rescue, followed by 2 months of radiation therapy (36 Gy to craniospinal axis, 20 Gy to lumbar region) with concurrent temozolomide; the latter was discontinued after 3 weeks due to myelosuppression. Tumor relapsed 1 year later at C7–T1 level. She was started on oral metronomic therapy, and bevacizumab was added 2 months later. Three months later, a cervical MRI showed progression of the tumor, along with new lesions in the thoracic/lumbar spine plus intracranial punctate nodular tumors. Following resection of the C7/T1 lesion, she was started on palliative alisertib; a month later, a cranial computed tomography showed progression of her disease with hydrocephalus. Treatment was discontinued, and she expired 12 months after initial diagnosis. Conclusion: Primary spinal AT/RT in the adult patient is rare. The pathology is associated with early recurrence and a poor prognosis. Although potential benefits of metronomic chemotherapy and alisertib have been reported, the patient in this study did not favorably respond to these modalities. PMID:27069744

  5. Dasatinib in Treating Patients With Solid Tumors or Lymphomas That Are Metastatic or Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2015-06-30

    Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia; Adult Hepatocellular Carcinoma; Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Adult Solid Neoplasm; Adult T Acute Lymphoblastic Leukemia; Advanced Adult Hepatocellular Carcinoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Localized Non-Resectable Adult Liver Carcinoma; Localized Resectable Adult Liver Carcinoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Progressive Hairy Cell Leukemia Initial Treatment; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Liver Carcinoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Small Lymphocytic Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult

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

    PubMed

    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. PMID:27061708

  7. Psychotherapy Interventions for Managing Anxiety and Depressive Symptoms in Adult Brain Tumor Patients: A Scoping Review

    PubMed Central

    Kangas, Maria

    2015-01-01

    Background Adult brain tumor (BT) patients and longer-term survivors are susceptible to experiencing emotional problems, including anxiety and/or depression disorders, which may further compromise their quality-of-life (QOL) and general well-being. The objective of this paper is to review psychological approaches for managing anxiety and depressive symptoms in adult BT patients. A review of psychological interventions comprising mixed samples of oncology patients, and which included BT patients is also evaluated. The review concludes with an overview of a recently developed transdiagnostic psychotherapy program, which was specifically designed to treat anxiety and/or depressive symptoms in adult BT patients. Methods Electronic databases (PsycINFO, Medline, Embase, and Cochrane) were searched to identify published studies investigating psychological interventions for managing anxiety and depressive symptoms in adult BT patients. Only four randomized controlled trials (RCTs) were identified. Results Only one of the RCTs tested a psychosocial intervention, which was specifically developed for primary BT patients, and which was found to improve QOL including existential well-being as well as reducing depressive symptoms. A second study tested a combined cognitive rehabilitation and problem-solving intervention, although was not found to significantly improve mood or QOL. The remaining two studies tested multidisciplinary psychosocial interventions in heterogeneous samples of cancer patients (included BT patients) with advanced stage disease. Maintenance of QOL was found in both studies, although no secondary gains were found for improvements in mood. Conclusion There is a notable paucity of psychological interventions for adult BT patients across the illness trajectory. Further research is required to strengthen the evidence base for psychological interventions in managing anxiety and depressive symptoms, and enhancing the QOL of distressed adults diagnosed with a BT

  8. Overview: Progression-Free Survival as an Endpoint in Clinical Trials with Solid Tumors

    PubMed Central

    Korn, Ronald L.; Crowley, John J.

    2013-01-01

    Progression-free survival (PFS) is increasingly used as an important and even a primary endpoint in randomized cancer clinical trials in the evaluation of patients with solid tumors, because of both practical and clinical considerations. Although in its simplest form PFS is the time from randomization to a pre-defined endpoint, there are many factors that can influence the exact moment of when disease progression is recorded. In this overview, we review the circumstances that can devalue the use of PFS as a primary endpoint, and attempt to provide a pathway for a future desired state when PFS will become not just a secondary alternative to overall survival but rather an endpoint of choice. PMID:23669420

  9. Solid Tumor-Targeting Theranostic Polymer Nanoparticle in Nuclear Medicinal Fields

    PubMed Central

    Makino, Akira; Kimura, Shunsaku

    2014-01-01

    Polymer nanoparticles can be prepared by self-assembling of amphiphilic polymers, and various types of molecular assemblies have been reported. In particular, in medicinal fields, utilization of these polymer nanoparticles as carriers for drug delivery system (DDS) has been actively tried, and some nanoparticulate drugs are currently under preclinical evaluations. A radionuclide is an unstable nucleus and decays with emission of radioactive rays, which can be utilized as a tracer in the diagnostic imaging systems of PET and SPECT and also in therapeutic purposes. Since polymer nanoparticles can encapsulate most of diagnostic and therapeutic agents with a proper design of amphiphilic polymers, they should be effective DDS carriers of radionuclides in the nuclear medicinal field. Indeed, nanoparticles have been recently attracting much attention as common platform carriers for diagnostic and therapeutic drugs and contribute to the development of nanotheranostics. In this paper, recent developments of solid tumor-targeting polymer nanoparticles in nuclear medicinal fields are reviewed. PMID:25379530

  10. Oxaliplatin, Ifosfamide and Etoposide in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2014-02-21

    Angioimmunoblastic T-cell Lymphoma; B-cell Childhood Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  11. Nanoparticle formulations of histone deacetylase inhibitors for effective chemoradiotherapy in solid tumors

    PubMed Central

    Wang, Edina C.; Min, Yuanzeng; Palm, Robert C.; Fiordalisi, James J.; Wagner, Kyle T.; Hyder, Nabeel; Cox, Adrienne D.; Caster, Joseph; Tian, Xi; Wang, Andrew Z.

    2015-01-01

    Histone deacetylase inhibitors (HDACIs) represent a class of promising agents that can improve radiotherapy in cancer treatment. However, the full therapeutic potential of HDACIs as radiosensitizers has been restricted by limited efficacy in solid malignancies. In this study, we report the development of nanoparticle (NP) formulations of HDACIs that overcome these limitations, illustrating their utility to improve the therapeutic ratio of the clinically established first generation HDACI vorinostat and a novel second generation HDACI quisinostat. We demonstrate that NP HDACIs are potent radiosensitizers in vitro and are more effective as radiosensitizers than small molecule HDACIs in vivo using mouse xenograft models of colorectal and prostate carcinomas. We found that NP HDACIs enhance the response of tumor cells to radiation through the prolongation of γ-H2AX foci. Our work illustrates an effective method for improving cancer radiotherapy treatment. PMID:25771011

  12. Solid tumor-targeting theranostic polymer nanoparticle in nuclear medicinal fields.

    PubMed

    Makino, Akira; Kimura, Shunsaku

    2014-01-01

    Polymer nanoparticles can be prepared by self-assembling of amphiphilic polymers, and various types of molecular assemblies have been reported. In particular, in medicinal fields, utilization of these polymer nanoparticles as carriers for drug delivery system (DDS) has been actively tried, and some nanoparticulate drugs are currently under preclinical evaluations. A radionuclide is an unstable nucleus and decays with emission of radioactive rays, which can be utilized as a tracer in the diagnostic imaging systems of PET and SPECT and also in therapeutic purposes. Since polymer nanoparticles can encapsulate most of diagnostic and therapeutic agents with a proper design of amphiphilic polymers, they should be effective DDS carriers of radionuclides in the nuclear medicinal field. Indeed, nanoparticles have been recently attracting much attention as common platform carriers for diagnostic and therapeutic drugs and contribute to the development of nanotheranostics. In this paper, recent developments of solid tumor-targeting polymer nanoparticles in nuclear medicinal fields are reviewed. PMID:25379530

  13. Prognostic factors and survival in late adolescent and adult patients with small round cell tumors.

    PubMed

    Eralp, Yeşim; Bavbek, Sevil; Başaran, Mert; Kaytan, Esra; Yaman, Fulya; Bilgiç, Bilge; Darendeliler, Emin; Onat, Haluk

    2002-08-01

    The primary objective of this study is to review the clinical characteristics of 25 patients in the adult and late adolescent age group, diagnosed and treated with small round cell tumors involving soft tissues (extraosseous Ewing sarcoma, rhabdo-myosarcoma, primitive neuroectodermal tumor, and undiffer-entiated small round cell tumors). Additionally, survival and prognostic factors influencing the outcome with multimodality treatment are evaluated. There were 19 males (76%) and 6 females (24%). The median age was 26 years (range: 15-56 years). In 9 patients (36%), the tumor was located at an extremity, whereas 16 patients (64%) had central localizations. Tumor size was larger than 10 cm in 7 patients (29.2%). Six patients (24%) had metastatic disease. Twelve patients (48%) received radiation and 16 patients (64%) underwent surgery. Among the resected tumors, 2 were resected with contaminated margins (12.5%), whereas 2 were radically resected and 12 (75%) were resected with wide margins. All patients were given a median of 4 cycles of multiagent chemotherapy (1-14 cycles). With preoperative chemotherapy, complete regression (CR) of the tumor was achieved in 6 patients (24%). In 4 patients (16%), a partial response was obtained. After the completion of multimodality treatment, 12 patients (48%) had a CR. Progression-free (PFS) and overall survival (OS) for the entire group was 25.0 +/- 10.8% at 1 year and 30.5 +/- 15.5% at 3 years, respectively. Nonmetastatic disease, wide and radical resection, and presence of CR to multimodality treatment were associated with a significantly longer PFS and OS by univariate analysis. By multivariate analysis, CR to multimodality treat-ment was the only independent predictive factor for a longer OS (p: 0.0036, relative risk [RR]: 23.6, 95% CI: 2.8; 198.7) and metastatic presentation was the only independent factor predic-tive for a shorter PFS (p: 0.017, RR. 15, 95% CI: 1.6; 141.2). Large-scale, multicenter studies are required for

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

    PubMed Central

    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 <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 high in patients with solid tumors receiving chemotherapy. The risk of anemia was greater in patients with distant metastasis. PMID:27186078

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

    ClinicalTrials.gov

    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

  16. Liposomal cytarabine for central nervous system embryonal tumors in children and young adults.

    PubMed

    Partap, Sonia; Murphy, Patricia A; Vogel, Hannes; Barnes, Patrick D; Edwards, Michael S B; Fisher, Paul G

    2011-07-01

    To assess the tolerability and efficacy of liposomal cytarabine (LC), an encapsulated, sustained-release, intrathecal (IT) formulation of cytosine arabinoside, in de novo and relapsed central nervous system (CNS) embryonal tumors in children and young adults. We studied retrospectively all patients less than age 30 at our institution treated consecutively with LC for medulloblastoma (MB), primitive neuroectodermal tumor (PNET), and atypical teratoid rhabdoid tumor (ATRT). Seventeen patients received LC (2 mg/kg up to 50 mg, every 2 weeks to monthly) at diagnosis of high-risk CNS embryonal tumor (2 PNET, 3 ATRT) or relapse of MB (12 MB; 9 had leptomeningeal metastases). Sixteen patients received concurrent systemic chemotherapy. A total of 108 doses were administered (IT 82, intraventricular 26) with a mean of six (range 1-16) treatments per patient. Only three administrations were associated with adverse effects of arachnoiditis or headache. None developed malignant cerebrospinal fluid (CSF) cytology while receiving LC. All the six evaluable patients with malignant CSF cytology and treated with at least two doses cleared their CSF (mean 3 doses, range 1-5). Median overall survival in relapse patients was 9.1 months. Five patients (4 de novo and 1 relapsed) remain alive in complete remission for a median 26.8 months from first LC. Liposomal cytarabine is an easily administered, well-tolerated, and active drug in patients with high-risk embryonal neoplasms. One-third of our cohort remains in remission from otherwise fatal diagnoses. Our findings warrant a phase II trial of LC in newly diagnosed or recurrent CNS embryonal tumors. PMID:20859651

  17. Safe and Immunocompatible Nanocarriers Cloaked in RBC Membranes for Drug Delivery to Treat Solid Tumors

    PubMed Central

    Luk, Brian T.; Fang, Ronnie H.; Hu, Che-Ming J.; Copp, Jonathan A.; Thamphiwatana, Soracha; Dehaini, Diana; Gao, Weiwei; Zhang, Kang; Li, Shulin; Zhang, Liangfang

    2016-01-01

    The therapeutic potential of nanoparticle-based drug carriers depends largely on their ability to evade the host immune system while delivering their cargo safely to the site of action. Of particular interest are simple strategies for the functionalization of nanoparticle surfaces that are both inherently safe and can also bestow immunoevasive properties, allowing for extended blood circulation times. Here, we evaluated a recently reported cell membrane-coated nanoparticle platform as a drug delivery vehicle for the treatment of a murine model of lymphoma. These biomimetic nanoparticles, consisting of a biodegradable polymeric material cloaked with natural red blood cell membrane, were shown to efficiently deliver a model chemotherapeutic, doxorubicin, to solid tumor sites for significantly increased tumor growth inhibition compared with conventional free drug treatment. Importantly, the nanoparticles also showed excellent immunocompatibility as well as an advantageous safety profile compared with the free drug, making them attractive for potential translation. This study demonstrates the promise of using a biomembrane-coating approach as the basis for the design of functional, safe, and immunocompatible nanocarriers for cancer drug delivery. PMID:27217833

  18. Profile of farletuzumab and its potential in the treatment of solid tumors

    PubMed Central

    Sato, Seiya; Itamochi, Hiroaki

    2016-01-01

    Folate receptor (FR) α expression in normal tissues is restricted to a subpopulation of epithelial cells. In contrast, FRα is overexpressed in epithelial ovarian cancer (EOC) and non-small-cell lung carcinoma. Therefore, FRα is considered a promising therapeutic target for EOC and non-small-cell lung carcinoma. Farletuzumab (MORAb-003) is a humanized monoclonal antibody of immunoglobulin G subtype 1 kappa, targeting human FRα. To date, Phase I/II clinical trials have clearly demonstrated the feasibility and safety of farletuzumab as a treatment option against solid tumors. However, in Phase III clinical trial that was conducted to verify the combined effect of paclitaxel–carboplatin combination therapy and farletuzumab for patients with recurrent EOC, improvement in progression-free survival was not statistically significant. This result might be owing to the fact that the eligibility criteria for these studies did not include FRα expression. The significance of FRα as a predictive/prognostic biomarker remains unclear. In addition, there is currently no established biomarker to predict the response and toxicities among patients receiving farletuzumab therapy. Furthermore, the primary mechanism of action of farletuzumab has not yet been identified. Therefore, further research to identify the mechanism of farletuzumab in tumor suppression is necessary to clarify the full potential of this chemotherapeutic agent. PMID:27022278

  19. A phase I study of ABT-510 plus bevacizumab in advanced solid tumors

    PubMed Central

    Uronis, Hope E; Cushman, Stephanie M; Bendell, Johanna C; Blobe, Gerard C; Morse, Michael A; Nixon, Andrew B; Dellinger, Andrew; Starr, Mark D; Li, Haiyan; Meadows, Kellen; Gockerman, Jon; Pang, Herbert; Hurwitz, Herbert I

    2013-01-01

    Targeting multiple regulators of tumor angiogenesis have the potential to improve treatment efficacy. Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor and ABT-510 is a synthetic analog of thrombospondin, an endogenous angiogenesis inhibitor. Dual inhibition may result in additional benefit. We evaluated the safety, tolerability, and efficacy of the combination of bevacizumab plus ABT-510 in patients with refractory solid tumors. We also explored the effects of these agents on plasma-based biomarkers and wound angiogenesis. Thirty-four evaluable subjects were enrolled and received study drug. Therapy was well tolerated; minimal treatment-related grade 3/4 toxicity was observed. One patient treated at dose level 1 had a partial response and five other patients treated at the recommended phase II dose had prolonged stable disease for more than 1 year. Biomarker evaluation revealed increased levels of D-dimer, von Willebrand factor, placental growth factor, and stromal-derived factor 1 in response to treatment with the combination of bevacizumab and ABT-510. Data suggest that continued evaluation of combination antiangiogenesis therapies may be clinically useful. PMID:23930208

  20. Safe and Immunocompatible Nanocarriers Cloaked in RBC Membranes for Drug Delivery to Treat Solid Tumors.

    PubMed

    Luk, Brian T; Fang, Ronnie H; Hu, Che-Ming J; Copp, Jonathan A; Thamphiwatana, Soracha; Dehaini, Diana; Gao, Weiwei; Zhang, Kang; Li, Shulin; Zhang, Liangfang

    2016-01-01

    The therapeutic potential of nanoparticle-based drug carriers depends largely on their ability to evade the host immune system while delivering their cargo safely to the site of action. Of particular interest are simple strategies for the functionalization of nanoparticle surfaces that are both inherently safe and can also bestow immunoevasive properties, allowing for extended blood circulation times. Here, we evaluated a recently reported cell membrane-coated nanoparticle platform as a drug delivery vehicle for the treatment of a murine model of lymphoma. These biomimetic nanoparticles, consisting of a biodegradable polymeric material cloaked with natural red blood cell membrane, were shown to efficiently deliver a model chemotherapeutic, doxorubicin, to solid tumor sites for significantly increased tumor growth inhibition compared with conventional free drug treatment. Importantly, the nanoparticles also showed excellent immunocompatibility as well as an advantageous safety profile compared with the free drug, making them attractive for potential translation. This study demonstrates the promise of using a biomembrane-coating approach as the basis for the design of functional, safe, and immunocompatible nanocarriers for cancer drug delivery. PMID:27217833

  1. Doxorubicin-transferrin conjugate triggers pro-oxidative disorders in solid tumor cells.

    PubMed

    Szwed, Marzena; Wrona, Dominika; Kania, Katarzyna D; Koceva-Chyla, Aneta; Marczak, Agnieszka

    2016-03-01

    The formation of reactive oxygen species (ROS) is a widely accepted mechanism of doxorubicin (DOX) toxicity toward cancer cells. However, little is known about the potential of new systems, designed for more efficient and targeted doxorubicin delivery (i.e. protein conjugates, polymeric micelles, liposomes, monoclonal antibodies), to induce oxidative stress (OS) in tumors and hematological malignancies. Therefore, the objective of our study was to determine the relation between the toxicity of doxorubicin-transferring (DOX-TRF) conjugate and its capability to generate oxidative/nitrosative stress in solid tumor cells. Our research proves that DOX-TRF conjugate displays higher cytotoxicity towards lung adenocarcinoma epithelial (A549) and hepatocellular carcinoma (HepG2) cell lines than the reference free drug (DOX) and induces more extensive OS, characterized by a significant decrease in the total cellular antioxidant capacity, glutathione level and amount of -SH groups and an increase in hydroperoxide content. The intracellular redox imbalance was accompanied by changes in the transcription of genes encoding key antioxidant enzymes engaged in the sustaining of cellular redox homeostasis: superoxide dismutase (SOD), catalase (CAT), glutathione transferase (GST) and glutathione peroxidase (GP). PMID:26607004

  2. Systemic irradiation for selected stage IV and recurrent pediatric solid tumors: method, toxicity, and preliminary results

    SciTech Connect

    Wharam, M.D.; Kaizer, H.; Leventhal, B.G.; Munoz, L.; Tutschka, P.J.; Santos, G.W.; Elfenbein, G.J.; Order, S.E.

    1980-02-01

    Eight patients with advanced pediatric solid tumors received either sequential upper and lower half-body irradiation (HBI) (7.5 rad/min to 500 rad total) or total body irradiation (TBI) (7.5 rad/min to 800 rad total) as part of two multimodality treatment regimens. All patients received combination chemotherapy; drugs were determined by the tumor type. The TBI regimen was selected for two patients who had progression of disease with conventional chemotherapy and for two patients with stage IV neuroblastoma. This intensive regimen consisted of bone marrow harvesting, followed by local radiation to gross disease, marrow-ablative chemotherapy, TBI, and re-infusion of the cryopreserved autologous marrow. Significant acute toxicity was followed by hematologic reconstitution in each patient within seven weeks. At this writing, two patients survived, one of whom is disease free two and one half years without maintenance chemotherapy. A less intensive, outpatient regimen was selected for four patients; three had a complete or good partial response to chemotherapy. The fourth patient had tumor-involved bone marrow not responsive to chemotherapy and was therefore ineligible for marrow cryopreservation and TBI. Each of these four patients received HBI after chemotherapy and local radiation to the primary and/or metastatic sites. Acute toxicity was limited to nausea and vomiting. Significant leukopenia and thrombocytopenia occurred in three patients. All four patients were alive 10 to 26 months post HBI. This pilot study demonstrates that chemotherapy can be integrated with local fractionated radiation, and systemic radiation given as HBI or TBI with acceptable toxicity; sufficient bone marrow stem cells can be harvested after conventional chemotherapy and then cryopreserved to permit hematologic reconstitution of the patient who receives marrow ablative therapy.

  3. Stress-mediated progression of solid tumors: effect of mechanical stress on tissue oxygenation, cancer cell proliferation, and drug delivery.

    PubMed

    Mpekris, Fotios; Angeli, Stelios; Pirentis, Athanassios P; Stylianopoulos, Triantafyllos

    2015-11-01

    Oxygen supply plays a central role in cancer cell proliferation. While vascular density increases at the early stages of carcinogenesis, mechanical solid stresses developed during growth compress tumor blood vessels and, thus, drastically reduce not only the supply of oxygen, but also the delivery of drugs at inner tumor regions. Among other effects, hypoxia and reduced drug delivery compromise the efficacy of radiation and chemo/nanotherapy, respectively. In the present study, we developed a mathematical model of tumor growth to investigate the interconnections among tumor oxygenation that supports cancer cell proliferation, the heterogeneous accumulation of mechanical stresses owing to tumor growth, the non-uniform compression of intratumoral blood vessels due to the mechanical stresses, and the insufficient delivery of oxygen and therapeutic agents because of vessel compression. We found that the high vascular density and increased cancer cell proliferation often observed in the periphery compared to the interior of a tumor can be attributed to heterogeneous solid stress accumulation. Highly vascularized peripheral regions are also associated with greater oxygenation compared with the compressed, less vascularized inner regions. We also modeled the delivery of drugs of two distinct sizes, namely chemotherapy and nanomedicine. Model predictions suggest that drug delivery is affected negatively by vessel compression independently of the size of the therapeutic agent. Finally, we demonstrated the applicability of our model to actual geometries, employing a breast tumor model derived from MR images. PMID:25968141

  4. Preclinical Validation of the Utility of BLZ-100 in Providing Fluorescence Contrast for Imaging Spontaneous Solid Tumors.

    PubMed

    Fidel, Janean; Kennedy, Katie C; Dernell, William S; Hansen, Stacey; Wiss, Valorie; Stroud, Mark R; Molho, Joshua I; Knoblaugh, Sue E; Meganck, Jeffrey; Olson, James M; Rice, Brad; Parrish-Novak, Julia

    2015-10-15

    There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint agent BLZ-100 is a peptide-fluorophore conjugate that can specifically bind solid tumors and fluoresce in the near-infrared range, minimizing light scatter and signal attenuation. In this study, we provide a preclinical proof of concept for use of this imaging contrast agent as administered before surgery to dogs with a variety of naturally occurring spontaneous tumors. Imaging was performed on excised tissues as well as intraoperatively in a subset of cases. Actionable contrast was achieved between tumor tissue and surrounding normal tissues in adenocarcinomas, squamous cell carcinomas, mast cell tumors, and soft tissue sarcomas. Subcutaneous soft tissue sarcomas were labeled with the highest fluorescence intensity and greatest tumor-to-background signal ratio. Our results establish a foundation that rationalizes clinical studies in humans with soft tissue sarcoma, an indication with a notably high unmet need. PMID:26471914

  5. Stress-mediated progression of solid tumors: effect of mechanical stress on tissue oxygenation, cancer cell proliferation and drug delivery

    PubMed Central

    Mpekris, Fotios; Angeli, Stelios; Pirentis, Athanassios P.; Stylianopoulos, Triantafyllos

    2015-01-01

    Oxygen supply plays a central role in cancer cell proliferation. While vascular density increases at the early stages of carcinogenesis, mechanical solid stresses developed during growth compress tumor blood vessels and, thus, drastically reduce the supply of oxygen, but also the delivery of drugs at inner tumor regions. Among other effects, hypoxia and reduced drug delivery compromise the efficacy of radiation and chemo/nano therapy, respectively. In the present study, we developed a mathematical model of tumor growth to investigate the interconnections among tumor oxygenation that supports cancer cell proliferation, the heterogeneous accumulation of mechanical stresses owing to tumor growth, the non-uniform compression of intratumoral blood vessels due to the mechanical stresses, and the insufficient delivery of oxygen and therapeutic agents because of vessel compression. We found that the high vascular density and increased cancer cell proliferation often observed in the periphery compared to the interior of a tumor can be attributed to heterogeneous solid stress accumulation. Highly vascularized peripheral regions are also associated with greater oxygenation compared with the compressed, less vascularized inner regions. We also modeled the delivery of drugs of two distinct sizes, namely chemotherapy and nanomedicine. Model predictions suggest that drug delivery is affected negatively by vessel compression independently of the size of the therapeutic agent. Finally, we demonstrated the applicability of our model to actual geometries, employing a breast tumor model derived from MR images. PMID:25968141

  6. Self-reported electrical appliance use and risk of adult brain tumors.

    PubMed

    Kleinerman, Ruth A; Linet, Martha S; Hatch, Elizabeth E; Tarone, Robert E; Black, Peter M; Selker, Robert G; Shapiro, William R; Fine, Howard A; Inskip, Peter D

    2005-01-15

    Electrical appliances produce the highest intensity exposures to residential extremely low frequency electromagnetic fields. The authors investigated whether appliances may be associated with adult brain tumors in a hospital-based case-control study at three centers in the United States from 1994 to 1998. A total of 410 glioma, 178 meningioma, and 90 acoustic neuroma cases and 686 controls responded to a self-administered questionnaire about 14 electrical appliances. There was little evidence of association between brain tumors and curling iron, heating pad, vibrating massager, electric blanket, heated water bed, sound system, computer, television, humidifier, microwave oven, and electric stove. Ever use of hair dryers was associated with glioma (odds ratio = 1.7, 95% confidence interval: 1.1, 2.5), but there was no evidence of increasing risk with increasing amount of use. In men, meningioma was associated with electric shaver use (odds ratio = 10.9, 95% confidence interval: 2.3, 50), and odds ratios increased with cumulative minutes of use, although they were based on only two nonexposed cases. Recall bias for appliances used regularly near the head or chance may provide an alternative explanation for the observed associations. Overall, results indicate that extremely low frequency electromagnetic fields from commonly used household appliances are unlikely to increase the risk of brain tumors. PMID:15632263

  7. Immunogenicity of murine solid tumor models as a defining feature of in vivo behavior and response to immunotherapy.

    PubMed

    Lechner, Melissa G; Karimi, Saman S; Barry-Holson, Keegan; Angell, Trevor E; Murphy, Katherine A; Church, Connor H; Ohlfest, John R; Hu, Peisheng; Epstein, Alan L

    2013-01-01

    Immune profiling has been widely used to probe mechanisms of immune escape in cancer and identify novel targets for therapy. Two emerging uses of immune signatures are to identify likely responders to immunotherapy regimens among individuals with cancer and to understand the variable responses seen among subjects with cancer in immunotherapy trials. Here, the immune profiles of 6 murine solid tumor models (CT26, 4T1, MAD109, RENCA, LLC, and B16) were correlated to tumor regression and survival in response to 2 immunotherapy regimens. Comprehensive profiles for each model were generated using quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry, and flow cytometry techniques, as well as functional studies of suppressor cell populations (regulatory T cells and myeloid-derived suppressor cells), to analyze intratumoral and draining lymphoid tissues. Tumors were stratified as highly or poorly immunogenic, with highly immunogenic tumors showing a significantly greater presence of T-cell costimulatory molecules and immune suppression in the tumor microenvironment. An absence of tumor-infiltrating cytotoxic T lymphocytes and mature dendritic cells was seen across all models. Delayed tumor growth and increased survival with suppressor cell inhibition and tumor-targeted chemokine+/-dendritic cells vaccine immunotherapy were associated with high tumor immunogenicity in these models. Tumor MHC class I expression correlated with the overall tumor immunogenicity level and was a singular marker to predict immunotherapy response with these regimens. By using experimental tumor models as surrogates for human cancers, these studies demonstrate how select features of an immune profile may be utilized to identify patients most likely to respond to immunotherapy regimens. PMID:24145359

  8. Ceftriaxone as a single agent in empirical therapy of unexplained fever in granulocytopenic children with solid tumors.

    PubMed

    Bartolozzi, S; Clerico, A; Properzi, E; Minori, A; Castello, M A

    1997-06-01

    The optimal management of fever in granulocytopenic cancer patients remains controversial. Antibiotic monotherapy is increasingly an option for the initial empiric treatment of febrile granulocytopenic patients with solid tumors. Available data show that response to empiric therapy is often more related to disease classification (solid tumors vs. acute leukemia) than to the regimen used. In this study we based empiric monotherapy on the underlying disease (solid tumors) in treating 33 episodes of fever in 26 granulocytopenic children with cancer. We investigated the potential effectiveness of single daily doses of ceftriaxone administered empirically in febrile granulocytopenic children with solid tumors. Fever was treated successfully with ceftriaxone monotherapy in 91% (30/33) of febrile episodes. None of the patients died as a result of primary infection. These results suggest that empirical monotherapy with once-daily ceftriaxone is safe and effective. In addition, when compared with other extended-spectrum cephalosporins such as ceftazidime, once-daily administration of ceftriaxone reduces cost and patient inconvenience, allowing convenient parenteral therapy even on an outpatient basis. PMID:9210007

  9. Oncolytic virus expressing RANTES and IL-15 enhances function of CAR-modified T cells in solid tumors

    PubMed Central

    Nishio, Nobuhiro; Dotti, Gianpietro

    2015-01-01

    We improved the migration and survival of chimeric antigen receptor (CAR)-modified T cells in solid tumors by combining CAR-T cells with an armed oncolytic virus. Local delivery of the chemokine RANTES and the cytokine IL-15 by the oncolytic virus enhanced the trafficking and persistence of the CAR-T cells, resulting in improved antitumor effects. PMID:25949885

  10. Phase Ib, Dose Escalation Study of Oral LDE225 in Combination With BKM120 in Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-02-18

    Dose Escalation; Safety; Preliminary Efficacy; Advanced Solid Tumors; Metastatic Breast Cancer; Advanced Pancreatic Adenocarcinoma; Metastatic Colorectal Cancer; Recurrent Glioblastoma Multiforme; Gastric Cancer; Gastroesophageal Junction Cancer; Triple Negative Metastatic Breast Cancer; Hormone Receptor Positive (ER+/PR+, and Her2-) Metastatic Breast Cancer

  11. Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas

    ClinicalTrials.gov

    2016-08-30

    Childhood Solid Neoplasm; Metastatic Melanoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Hodgkin Lymphoma; Recurrent Melanoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Rhabdomyosarcoma; Refractory Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  12. Imatinib Mesylate in Treating Patients With Relapsed or Refractory Solid Tumors of Childhood

    ClinicalTrials.gov

    2015-04-14

    Childhood Desmoplastic Small Round Cell Tumor; Childhood Synovial Sarcoma; Gastrointestinal Stromal Tumor; Lung Metastases; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

  13. Violacein induces p44/42 mitogen-activated protein kinase-mediated solid tumor cell death and inhibits tumor cell migration

    PubMed Central

    MEHTA, TORAL; VERCRUYSSE, KOEN; JOHNSON, TERRANCE; EJIOFOR, ANTHONY OKECHUKWU; MYLES, ELBERT; QUICK, QUINCY ANTOINE

    2015-01-01

    Microbial secondary metabolites have emerged as alternative novel drugs for the treatment of human cancers. Violacein, a purple pigment produced by Chromobacterium violaceum, was investigated in the present study for its anti-tumor properties in tumor cell lines. Clinically applicable concentrations of violacein were demonstrated to inhibit the proliferative capacity of tumor cell lines according to a crystal violet proliferation assay. The underlying mechanism was the promotion of apoptotic cell death, as indicated by poly(ADP ribose) polymerase cleavage and p44/42 mitogen-activated protein kinase signaling determined by western blot analysis. Collectively, this provided mechanistic evidence that violacein elicits extracellular-signal regulated kinase-induced apoptosis via the intrinsic pathway. The anti-malignant properties of violacein in the present study were further demonstrated by its inhibitory effects on brain tumor cell migration, specifically glioblastomas, one of the most invasive and therapeutically resistant neoplasms in the clinic. Additionally, solid tumors examined in the present study displayed differential cellular responses and sensitivities to violacein as observed by morphologically induced cellular changes that contributed to its anti-migratory properties. In conclusion, violacein is a novel natural product with the potential to kill several types of human tumor cell lines, as well as prevent disease recurrence by antagonizing cellular processes that contribute to metastatic invasion. PMID:25816226

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

    NASA Astrophysics Data System (ADS)

    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

  15. Comparison of nanoparticle penetration into solid tumors and sites of inflammation: studies using targeted and nontargeted liposomes

    PubMed Central

    Poh, Scott; Chelvam, Venkatesh; Low, Philip S

    2015-01-01

    Aim: The vast majority of nanomedicine research is focused on the use of nanoparticles for the diagnosis and treatment of cancer. However, the dense extracellular matrix of solid tumors restricts nanoparticle penetration, raising the question of whether the best applications of nanomedicines lie in oncology. Materials & methods: In this study, the uptake of folate-conjugated liposomes was compared between folate receptor-expressing tumors and folate receptor+ inflammatory lesions within the same mouse. Results: We demonstrate here that both folate-targeted and nontargeted liposomes accumulate more readily at sites of inflammation than in solid tumors. Conclusion: These data suggest that nanosized imaging and therapeutic agents may be better suited for the treatment and diagnosis of inflammatory/autoimmune diseases than cancer. PMID:25996118

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

    ClinicalTrials.gov

    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

  17. Preclinical Evaluation of Laromustine for use in Combination with Radiation Therapy in the Treatment of Solid Tumors

    PubMed Central

    Rockwell, Sara; Liu, Yanfeng; Seow, Helen A.; Ishiguro, Kimiko; Baumann, Raymond P.; Penketh, Philip G.; Shyam, Krishnamurthy; Akintujoye, Oluwatoyin M.; Glazer, Peter M.; Sartorelli, Alan C.

    2013-01-01

    Purpose These studies explored questions related to the potential use of Laromustine in the treatment of solid tumors and in combination with radiotherapy. Materials and Methods These studies used mouse EMT6 cells [both parental and transfected with genes for O6-alkylguanine transferase (AGT)], repair-deficient human Fanconi Anemia C and Chinese hamster VC8 (BRCA2−/ −) cells and corresponding control cells, and EMT6 tumors in mice assayed using cell survival and tumor growth assays. Results Hypoxia during Laromustine treatment did not protect EMT6 cells or human fibroblasts from this agent. Rapidly proliferating EMT6 cells were more sensitive than quiescent cultures. EMT6 cells expressing mouse or human AGT, which removes O6 -alkyl groups from DNA guanine, thereby protecting against G-C crosslink formation, increased resistance to Laromustine. Crosslink-repair-deficient Fanconi Anemia C and VC8 cells were hypersensitive to Laromustine, confirming the importance of crosslinks as lethal lesions. In vitro, Laromustine and radiation produced additive toxicities to EMT6 cells. Studies using tumor cell survival and tumor growth assays showed effects of regimens combining Laromustine and radiation that were compatible with additive or subadditive interactions. Conclusions The effects of Laromustine on solid tumors and with radiation are complex and are influenced by microenvironmental and proliferative heterogeneity within these malignancies. PMID:22111842

  18. Cancer incidence in atomic bomb survivors. Part II: Solid tumors, 1958-1987.

    PubMed

    Thompson, D E; Mabuchi, K; Ron, E; Soda, M; Tokunaga, M; Ochikubo, S; Sugimoto, S; Ikeda, T; Terasaki, M; Izumi, S

    1994-02-01

    This report presents, for the first time, comprehensive data on the incidence of solid cancer and risk estimates for A-bomb survivors in the extended Life Span Study (LSS-E85) cohort. Among 79,972 individuals, 8613 first primary solid cancers were diagnosed between 1958 and 1987. As part of the standard registration process of the Hiroshima and Nagasaki tumor registries, cancer cases occurring among members of the LSS-E85 cohort were identified using a computer linkage system supplemented by manual searches. Special efforts were made to ensure complete case ascertainment, data quality and data consistency in the two cities. For all sites combined, 75% of the cancers were verified histologically, 6% were diagnosed by direct observation, 8% were based on a clinical diagnosis, and 12.6% were ascertained by death certificate only. A standard set of analyses was carried out for each of the organs and organ systems considered. Depending on the cancer site, Dosimetry System 1986 (DS86) organ or kerma doses were used for computing risk estimates. Analyses were based on a general excess relative risk model (the background rate times one plus the excess relative risk). Analyses carried out for each site involved fitting the background model with no dose effect, a linear dose-response model with no effect modifiers, a linear-quadratic dose-response model with no effect modifiers, and a series of linear dose-response models that included each of the covariates (sex, age at exposure, time since exposure, attained age and city) individually as effect modifiers. Because the tumor registries ascertain cancers in the registry catchment areas only, an adjustment was made for the effects of migration. In agreement with prior LSS findings, a statistically significant excess risk for all solid cancers was demonstrated [excess relative risk at 1 Sv (ERR1Sv) = 0.63; excess absolute risk (EAR) per 10(4) person-year sievert (PY Sv) = 29.7]. For cancers of the stomach (ERR1SV = 0.32), colon

  19. Mammary gland tumors in captive African hedgehogs.

    PubMed

    Raymond, J T; Gerner, M

    2000-04-01

    From December 1995 to July 1999, eight mammary gland tumors were diagnosed in eight adult captive female African hedgehogs (Atelerix albiventris). The tumors presented as single or multiple subcutaneous masses along the cranial or caudal abdomen that varied in size for each hedgehog. Histologically, seven of eight (88%) mammary gland tumors were malignant. Tumors were classified as solid (4 cases), tubular (2 cases), and papillary (2 cases). Seven tumors had infiltrated into the surrounding stroma and three tumors had histologic evidence of neoplastic vascular invasion. Three hedgehogs had concurrent neoplasms. These are believed to be the first reported cases of mammary gland tumors in African hedgehogs. PMID:10813628

  20. Molecular cytogenetic analysis of formalin-fixed, paraffin-embedded solid tumors by comparative genomic hybridization after universal DNA-amplification.

    PubMed

    Speicher, M R; du Manoir, S; Schröck, E; Holtgreve-Grez, H; Schoell, B; Lengauer, C; Cremer, T; Ried, T

    1993-11-01

    We present a technique which allows the detection and chromosomal localization of DNA sequence copy number changes in solid tumor genomes from frozen sections and paraffin embedded, formalin fixed specimens. Based on comparative genomic hybridization and on universal DNA amplification procedures this technique is possible even if only a few tumor cells are available. We demonstrate the feasibility of this method to visualize complete and partial chromosome gains and losses and gene amplifications in archived solid tumor samples. PMID:8281155

  1. Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer

    ClinicalTrials.gov

    2016-02-05

    Adult Solid Neoplasm; Hormone-Resistant Prostate Cancer; Recurrent Melanoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma

  2. The Effect of Mushroom Beta-Glucans from Solid Culture of Ganoderma lucidum on Inhibition of the Primary Tumor Metastasis

    PubMed Central

    Hung, Ming-Hsin; Chen, Sherwin; Wang, William; Lu, Chung-Lun

    2014-01-01

    This study evaluates the effect of mushroom beta-glucans (MBGS) derived from solid culture of Ganoderma lucidum on tumor inhibition by examining size of the primary tumor and rate of metastasis in Lewis lung carcinoma (LLC) bearing mice (C57BL/6), given oral administration of MBGS with radiation therapy. A previous result showed that MBGS enhances NK cell-mediated cytotoxicity in mice without LLC bearing in advance. Furthermore, applications of MBGS in conjunction with radiation therapy were effective in controlling tumor growth, and rate of metastasis, life threatening, and can potentially serve as a protective factor for wounds and hair loss that resulted from the overgrowth of primary tumor in LLC bearing mice. PMID:24799937

  3. Interactions of BMS-181174 and radiation: studies with EMT6 cells in vitro and in solid tumors.

    PubMed

    Rockwell, S; Kelley, M

    1996-04-01

    N-7[2-(4-nitrophenyldithio)-ethyl] mitomycin C, (BMS-181174; previously designated as BMY25067) is a mitomycin C analog now in initial clinical trials. The experiments described in this report were performed to assess whether BMS-181174, like mitomycin C and porfiromycin, was selectively toxic to the hypoxic cells in solid tumors and might therefore prove valuable in combination with radiotherapy. In contrast to mitomycin C and porfiromycin, BMS-181174 was more toxic to aerobic EMT6 cells in vitro than to cells made acutely hypoxic. In vitro, BMS-181174 and radiation produced cytotoxicity compatible with either additive or slightly supra-additive cytotoxicity. In vivo, BMS-181174 was effective in killing cells in solid EMT6 tumors. The effects of regimens combining BMS-181174 and radiation in vivo were complex. Combinations of low doses of BMS-181174 plus a large dose of radiation were very effective in killing cells in solid tumors. However, the survival curve plateaued at high doses of BMS-181174, providing evidence for a subpopulation of tumor cells which were resistant to both BMS-181174 and radiation; this was hypothesized to be a hypoxic cell population. PMID:8735495

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

    PubMed

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

    2016-02-21

    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. PMID:26840759

  5. Tissue Distribution and Efficacy of Gold Nanorods Coupled with Laser Induced Photoplasmonic Therapy in Ehrlich Carcinoma Solid Tumor Model

    PubMed Central

    El-Sayed, Mostafa A.; Shabaka, Ali A.; El-Shabrawy, Osama A.; Yassin, Nemat A.; Mahmoud, Sawsan S.; El-Shenawy, Siham M.; Al-Ashqar, Emad; Eisa, Wael H.; Farag, Niveen M.; El-Shaer, Marwa A.; Salah, Nabila; Al-Abd, Ahmed M.

    2013-01-01

    Gold nanorods (GNR) within tumor microregions are characterized by their ability to absorb near IR light and emit heat in what is called photoplasmonic effect. Yet, the efficacy of nanoparticles is limited due to intratumoral tissue distribution reasons. In addition, distribution of GNRs to normal tissue might result in non specific toxicity. In the current study, we are assessing the intratumoral and tissue distribution of PEGylated GNRs on the top of its antitumor characteristics when given intravenously or intratumoral to solid tumor bearing mice and coupled with laser photoplasmonic sessions. PEGylated GNRs with a longitudinal size of less than 100 nm were prepared with aspect ratio of 4.6 showing strong surface plasmon absorption at wavelength 800 nm. Pharmacokinetics of GNR after single I.V. administration (0.1 mg/kg) showed very short systemic circulating time (less than 3 h). On the other hand, tissue distribution of I.V. GNR (0.1 mg/kg) to normal animals showed preferential deposition in spleen tissue. Repeated administration of I.V. GNR resulted in preferential accumulation in both liver and spleen tissues. In addition, I.V. administration of GNR to Ehrlich carcinoma tumor bearing mice resulted in similar tissue distribution; tumor accumulation and anti-tumor effect compared to intratumoral administration. In conclusion, the concentration of GNR achieved within tumors microregions after I.V. administration was comparable to I.T. administration and sufficient to elicit tumoral growth arrest when coupled with laser-aided photoplasmonic treatment. PMID:24098446

  6. The treatment of solid tumors by alpha emitters released from 224Ra-loaded sources—internal dosimetry analysis

    NASA Astrophysics Data System (ADS)

    Arazi, L.; Cooks, T.; Schmidt, M.; Keisari, Y.; Kelson, I.

    2010-02-01

    Diffusing alpha-emitters radiation therapy (DART) is a proposed new form of brachytherapy, allowing the treatment of solid tumors by alpha particles. DART utilizes implantable sources carrying small activities of radium-224, which continually release into the tumor radon-220, polonium-216 and lead-212 atoms, while radium-224 itself remains fixed to the source. The released atoms disperse inside the tumor by diffusive and convective processes, creating, through their alpha emissions, a high-dose region measuring several mm in diameter about each source. The efficacy of DART has been demonstrated in preclinical studies on mice-borne squamous cell carcinoma and lung tumors and the method is now being developed toward clinical trials. This work studies DART safety with respect to the dose delivered to distant organs as a result of lead-212 leakage from the tumor through the blood, relying on a biokinetic calculation coupled to internal dose assessments. It is found that the dose-limiting organs are the kidneys and red bone marrow. Assuming a typical source spacing of ~5 mm and a typical radium-224 activity density of 0.4-0.8 MBq g-1 of tumor tissue, it is predicted that tumors weighing up to several hundred grams may be treated without reaching the tolerance dose in any organ.

  7. Atypical Teratoid/Rhabdoid Tumor (AT/RT) Arising From the Acoustic Nerve in a Young Adult

    PubMed Central

    Wang, Xingfu; Liu, Xueyong; Lin, Zhixiong; Chen, Yupeng; Wang, Pengcheng; Zhang, Sheng

    2015-01-01

    Abstract Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, highly malignant central nervous system tumors that predominantly occur in young children. A 22-year-old woman presented with a 4-year history of relapsing tinnitus and gradual hearing loss. Neuroimaging revealed an enhanced intrinsic left internal auditory canal mass. The patient underwent radiotherapy treatment. Three years later, the tumor size continued to increase, as observed by imaging, and ultimately evolved into the left cerebellopontine angle. As a consequence, a total tumor resection was performed, and a pathological diagnosis of AT/RT was made. Aggressive radiotherapy and chemotherapy treatment continued; however, the tumor recurred within 11 months after the total tumor resection. The patient died within 4 months of the second operation. Histopathologically, the tumor contained characteristic rhabdoid cells with areas that resembled a classical primitive neuroectodermal tumor. Immunostaining showed loss of INI1 protein expression in tumor cells, and fluorescence in situ hybridization showed a hemizygous deletion of the hSNF5/INI1 gene region on 22q11.2. This is the first report of an AT/RT that arised from the acoustic nerve in a young adult. Despite manifold diagnostic and therapeutic advances, the prognosis of patients with AT/RT remains poor. PMID:25634176

  8. Biomodulation of capecitabine by paclitaxel and carboplatin in advanced solid tumors and adenocarcinoma of unknown primary.

    PubMed

    Mikhail, Sameh; Lustberg, Maryam B; Ruppert, Amy S; Mortazavi, Amir; Monk, Paul; Kleiber, Barbara; Villalona-Calero, Miguel; Bekaii-Saab, Tanios

    2015-11-01

    Paclitaxel and carboplatin upregulate thymidine phosphorylase and thus may provide synergistic antitumor activity in combination with capecitabine (CTX). We, therefore, performed a phase I/II study of CTX. In the phase I study, patients with advanced solid tumors received carboplatin on day 1, paclitaxel on days 1, 8, 15 and capecitabine orally twice a day on days 8-21, every 4 weeks. Phase II patients with advanced adenocarcinoma of unknown primary (ACUP) were treated at the maximal tolerable dose. The phase I study enrolled 29 patients evaluable for dose limiting toxicity. The recommended phase II dose was capecitabine 750 mg/m(2) bid, paclitaxel 60 mg/m(2)/week and carboplatin AUC of 6. There were 9 confirmed responses, 5 partial responses and disease stabilization >3 months in 14 patients. The phase II study was prematurely terminated at 25 patients due to cessation of funding. The objective response rate was 32 % (95 % CI 0.15-0.54), the median progression-free survival 5.5 months (95 % CI 2.8-10.8 months) and the median overall survival 10.8 months (95 % CI 6.0-32.0 months). CTX demonstrated acceptable tolerability and antitumor activity. At the recommended dose level in patients with ACUP, this regimen showed encouraging preliminary activity. PMID:26416564

  9. MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia

    ClinicalTrials.gov

    2014-04-28

    Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  10. Risk Factors for Febrile Neutropenia in Children With Solid Tumors Treated With Cisplatin-based Chemotherapy.

    PubMed

    Castelán-Martínez, Osvaldo D; Rodríguez-Islas, Felipe; Vargas-Neri, Jessica L; Palomo-Colli, Miguel A; López-Aguilar, Enrique; Clark, Patricia; Castañeda-Hernández, Gilberto; Rivas-Ruiz, Rodolfo

    2016-04-01

    Febrile neutropenia (FN) is a common and potentially fatal adverse drug reaction of cisplatin-based chemotherapy (CDDPBC) in pediatric patients. Hence, the aim of this study was to determine the incidence and independent risk factors for FN in pediatric patients with solid tumors treated with CDPPBC. Cohort integration was performed in the first cycle of chemotherapy with CDDPBC and patients were followed up to 6 months after the last cycle. FN was defined according to the Common Terminology Criteria for Adverse Events. Relative risks were calculated with confidence intervals at 95% (95% CI) to determine FN risk factors. Multiple logistic regression was performed to identify independent risk factors. One hundred and thirty-nine pediatric patients (median age 7.4 y, range 0.08 to 17 y) were included in the study. FN incidence was 62.5%. Independent risk factors for FN were chemotherapy regimens including anthracyclines (odds ratio [OR]=19.44 [95% CI, 5.40-70.02), hypomagnesaemia (OR=8.20 [95% CI, 1.81-37.14]), and radiotherapy (OR=6.67 [95% CI, 1.24-35.94]). It is therefore concluded that anthracyclines-containing regimens, hypomagnesaemia, and radiotherapy are independent risk factors for FN in patients receiving CDDPBC. PMID:26907640

  11. Prevention of Nausea and Vomiting in Patients Undergoing Oral Anticancer Therapies for Solid Tumors

    PubMed Central

    Costa, Ana Lúcia; Abreu, Catarina; Pacheco, Teresa Raquel; Macedo, Daniela; Sousa, Ana Rita; Pulido, Catarina; Quintela, António; Costa, Luís

    2015-01-01

    Chemotherapy-induced nausea and vomiting (CINV) is still a common and debilitating side effect despite recent advances in its prevention and treatment. The intrinsic emetogenicity of chemotherapy agents allowed grouping into four risk groups (high, moderate, low, and minimal risk of emetogenicity). The prevention of acute and delayed CINV for intravenous agents and one day regimens is well studied, although, there are few data about management of CINV induced by oral cytotoxic agents and targeted therapies, usually administered in extended regimens of daily oral use. Until now treatment of nausea and vomiting caused by oral antineoplastic agents remains largely empirical. The level of evidence of prophylactic antiemetics recommended for these agents is low. There are differences in the classification of emetogenic potential of oral antineoplastic agents between the international guidelines and different recommendations for prophylactic antiemetic regimens. Herein we review the evidence for antiemetic regimens for the most used oral antineoplastic agents for solid tumors and propose antiemetic regimens for high to moderate risk and low to minimal risk of emetogenicity. PMID:26421283

  12. Novel agents and new combination treatments on phase I studies on solid tumors and pancreatic cancer.

    PubMed

    Strimpakos, Alexios S; Syrigos, Kostas N; Saif, Muhammad W

    2012-07-01

    Pancreatic cancer is a relatively rare malignancy with a very aggressive natural course, not restrained by the existing current treatments. At the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, the results of few phase I clinical studies on solid tumors and pancreatic cancer were presented. In particular, in the field of immunotherapy, a pilot phase I study tested for first time a carcinoembryonic antigen (CEA)-based vaccine (Abstract #2561) on patients with pancreatic adenocarcinoma and another one the optimal dose and efficacy of trabedersen, an inhibitor of tissue growth factor-beta 2 (TGF-β2) aiming to enhance antitumor immune responses (Abstract #4034). Other phase I studies explored the pharmacokinetic and pharmacodynamic properties of an oral gemcitabine pro-drug (LY2334737; Abstract #2554), or of the combination of gemcitabine with sirolimus (Abstract #3096) or the combination of gemcitabine with an inhibitor of mitogen-activated protein kinase (MAPK), extracellular signal-regulated protein kinase (ERK) (MEK 1/2; Abstract #4034). PMID:22797386

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

    PubMed Central

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

    2016-01-01

    Abstract 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. PMID:27223488

  14. Dimers of Melampomagnolide B Exhibit Potent Anticancer Activity against Hematological and Solid Tumor Cells.

    PubMed

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

    2015-11-25

    Novel carbamate (7a-7h) and carbonate (7i, 7j, and 8) dimers of melampomagnolide B have been synthesized by reaction of the melampomagnolide-B-triazole carbamate synthon 6 with various terminal diamino- and dihydroxyalkanes. Dimeric carbamate products 7b, 7c, and 7f exhibited potent growth inhibition (GI50 = 0.16-0.99 μM) against the majority of cell lines in the NCI panel of 60 human hematological and solid tumor cell lines. Compound 7f and 8 exhibited anticancer activity that was 300-fold and 1 × 10(6)-fold more cytotoxic than DMAPT, respectively, at a concentration of 10 μM against rat 9L-SF gliosarcoma cells. Compounds 7a-7j and 8 were also screened against M9-ENL1 and acute myelogenous leukemia (AML) primary cell lines and exhibited 2- to 10-fold more potent antileukemic activity against M9-ENL1 cells (EC50 = 0.57-2.90 μM) when compared to parthenolide (EC50 = 6.0) and showed potent antileukemic activity against five primary AML cell lines (EC50 = 0.76-7.3 μM). PMID:26540463

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

    PubMed

    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. PMID:27223488

  16. Sella Turcica Atypical Teratoid/Rhabdoid Tumor Complicated with Lung Metastasis in an Adult Female

    PubMed Central

    Moretti, Costanzo; Lupoi, Domenico; Spasaro, Francesca; Chioma, Laura; Di Giacinto, Paola; Colicchia, Martina; Frajoli, Mario; Mocini, Renzo; Ulisse, Salvatore; Antonelli, Manila; Giangaspero, Felice; Gnessi, Lucio

    2013-01-01

    Here we present the case of a 60-year-old woman with a rare sellar region atypical teratoid/rhabdoid tumor (AT/RT), complicated by lung metastasis and treated with neurosurgery, radiotherapy, and chemotherapy. The patient had recurrent headache associated with left cavernous sinus syndrome after a previous endonasal transsphenoidal resection for a presumptive pituitary macroadenoma. Pituitary magnetic resonance imaging showed a tumor regrowth in the original location with a haemorrhagic component involving the left cavernous sinus. A near complete transsphenoidal resection of the sellar mass was performed followed by 3 months of stereotactic radiotherapy. Because of a worsening of the general clinical conditions, respiratory failure, and asthenia, the patient underwent a contrast enhanced computer tomography of the whole body which showed the presence of lung metastasis. The histopathological diagnosis on samples from pituitary and lung tissues was AT/RT. The patient survived 30 months after diagnosis regardless chemotherapy. In the adult, the AT/RT should be considered as a possible rare, aggressive, and malignant neoplasm localized in the sella turcica. PMID:24324353

  17. Molecularly Defined Adult Granulosa Cell Tumor of the Ovary: The Clinical Phenotype.

    PubMed

    McConechy, Melissa K; Färkkilä, Anniina; Horlings, Hugo M; Talhouk, Aline; Unkila-Kallio, Leila; van Meurs, Hannah S; Yang, Winnie; Rozenberg, Nirit; Andersson, Noora; Zaby, Katharina; Bryk, Saara; Bützow, Ralf; Halfwerk, Johannes B G; Hooijer, Gerrit K J; van de Vijver, Marc J; Buist, Marrije R; Kenter, Gemma G; Brucker, Sara Y; Krämer, Bernhard; Staebler, Annette; Bleeker, Maaike C G; Heikinheimo, Markku; Kommoss, Stefan; Blake Gilks, C; Anttonen, Mikko; Huntsman, David G

    2016-11-01

    The histopathologic features of adult granulosa cell tumors (AGCTs) are relatively nonspecific, resulting in misdiagnosis of other cancers as AGCT, a problem that has not been well characterized. FOXL2 mutation testing was used to stratify 336 AGCTs from three European centers into three categories: 1) FOXL2 mutant molecularly defined AGCT (MD-AGCT) (n = 256 of 336), 2) FOXL2 wild-type AGCT (n = 17 of 336), 3) misdiagnosed other tumor types (n = 63 of 336). All statistical tests were two-sided. The overall and disease-specific survival of the misdiagnosed cases was lower than in the MD-AGCTs (P < .001). The misdiagnosed cases accounted for 71.9% of disease-specific deaths within five years. In the population-based cohort, overall survival of MD-AGCT patients was not different from age-matched, population-based controls. Even though 35.2% of all the MD-AGCT patients in our study experienced a relapse, AGCT is usually an indolent disease. The historical, premolecular data underpinning our clinical understanding of AGCT was likely skewed by inclusion of misdiagnosed cases, and future management strategies should reflect the potential for surgical cure and long survival even after relapse. PMID:27297428

  18. Competence in Caregivers of Adolescent and Young Adult Childhood Brain Tumor Survivors

    PubMed Central

    Deatrick, Janet A.; Hobbie, Wendy; Ogle, Sue; Fisher, Michael J.; Barakat, Lamia; Hardie, Thomas; Reilly, Maureen; Li, Yimei; Ginsberg, Jill P.

    2015-01-01

    Objective Caregivers of adolescents and young adults (AYA) with complex medical conditions, including brain tumor survivors, have protracted and often complex roles, yet a gap exists in understanding their perceived competence. The aim of this study is to test a hypothesized model based on the theoretical and empirical literature: better caregiver health, better survivor health, and better family functioning contribute directly to fewer caregiving demands, which in turn contribute to greater caregiver competence. Method Telephone interviews using structured self-report questionnaires were conducted in this cross-sectional study with a sample of 186 caregivers (mothers) of childhood brain tumor survivors aged 14–40 years old who live with at least one parent. Structural equation modeling (SEM) was used to test the hypothesized model. Results The final SEM model suggests that survivor health and family functioning directly predict caregiver competence. Caregiver health indirectly predicts caregiver competence through caregiver demands and then family functioning. Family income directly predicts family functioning. The model showed adequate fit (CFI = 0.905, TFI = 0.880, and RMSEA = 0.081). Overall, the model accounted for 45% of variance in caregiver competence. Conclusions For this sample of caregivers of AYA with medically complex conditions, family functioning and the health of survivors are both important to how they evaluate their skills as caregivers. The results of this study underscore the crucial role of care models that focus on optimizing the health of the survivor, caregiver, and family, along with supporting a family centered approach to their care. PMID:23957900

  19. Validation of a Hypoxia-Inducible Factor-1α Specimen Collection Procedure and Quantitative ELISA in Solid Tumor Tissues

    PubMed Central

    Park, Sook Ryun; Kinders, Robert J.; Khin, Sonny; Hollingshead, Melinda; Antony, Smitha; Parchment, Ralph E.; Tomaszewski, Joseph E.; Kummar, Shivaani; Doroshow, James H.

    2016-01-01

    Hypoxia-inducible factor-1 alpha (HIF-1α) is an important marker of hypoxia in human tumors and has been implicated in tumor progression. Drugs targeting HIF-1α are being developed, but the ability to measure drug-induced changes in HIF-1α is limited by the lability of the protein in normoxia. Our goal was to devise methods for specimen collection and processing that preserve HIF-1α in solid tumor tissues and to develop and validate a two-site chemiluminescent quantitative ELISA for HIF-1α. We tested various strategies for HIF-1α stabilization in solid tumors including nitrogen gas-purged lysis buffer, addition of proteasome inhibitors, or the prolyl hydroxylase inhibitor 2-hydroxyglutarate, and bead homogenization. Degassing and addition of 2-hydroxyglutarate to the collection buffer significantly increased HIF-1α recovery, while bead-homogenization in sealed tubes improved HIF-1α recovery and reduced sample variability. Validation of the ELISA demonstrated intra- and inter-assay variability of less than 15% and accuracy of 99.8% ± 8.3% as assessed by spike recovery. Inter-laboratory reproducibility was also demonstrated (R2 = 0.999). Careful sample handling techniques allow us to quantitatively detect HIF-1α in samples as small as 2.5 µg of total protein extract, and this method is currently being applied to analyze tumor biopsy specimens in early-phase clinical trials. PMID:24799347

  20. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    ClinicalTrials.gov

    2015-07-27

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

  1. A phase I/pilot study of radiofrequency ablation for the treatment of recurrent pediatric solid tumors

    PubMed Central

    Hoffer, Fredric A.; Daw, Najat C.; Xiong, Xiaoping; Anghelescu, Doralina; Krasin, Matthew; Yan, Xiaowei; Davidoff, Andrew M.; Furman, Wayne L.; Rodriguez-Galindo, Carlos; Spunt, Sheri L.

    2010-01-01

    Background This prospective study was designed to be the first to evaluate the toxicity of radiofrequency ablation (RFA) in patients with recurrent pediatric solid tumors. Methods From 2003 through 2008, we conducted a phase I/pilot study of RFA for recurrent pediatric solid tumors. A multidisciplinary cancer management team selected appropriate candidates for the study. Imaging-guided RFA was performed percutaneously. Repeat RFA was performed for recurrences when appropriate. Toxicity and imaging response was assessed at 1 and 3 months prospectively. Accrual stopped in 2006 and data collection stopped in 2008. Results Sixteen patients (age 4 – 33 years, median 15 years) and 56 tumor sites were treated in 37 RFA sessions including 38 pulmonary, 11 musculoskeletal, and 7 hepatic lesions (82 lesion-treatments). Post-procedural pain was moderate (median 5 on a scale from 1 to 10) and lasted a median of 9 days. Prolonged hospitalization (beyond 1 day) occurred 17 times (range 2–25 days, median 3 days). Hypoxia supported by supplemental oxygen occurred in 8 of 16 patients and resolved within one month after each RFA. No patient had tumor lysis syndrome but myoglobinuria/hemoglobinuria occurred in 6 of 16 patients all without renal damage. Serious complications from pulmonary RFA included two diaphragmatic hernias. Twenty-four of 82 (29%) lesions imaged remained ablated at the end of the study. Conclusion The toxicity from RFA of recurrent pediatric solid tumors is real but limited and RFA may offer a local tumor control alternative in carefully selected cases. PMID:19180637

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

    PubMed

    Soltani, M; Chen, P

    2013-01-01

    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. PMID:23840579

  3. YAP Regulates Cell Proliferation, Migration, and Steroidogenesis in Adult Granulosa Cell Tumors

    PubMed Central

    Fu, David; Lv, Xiangmin; Hua, Guohua; He, Chunbo; Dong, Jixin; Lele, Subodh M.; Li, David Wan-Cheng; Zhai, Qiongli; Davis, John S.; Wang, Cheng

    2014-01-01

    The Hippo signaling pathway has been implicated as a conserved regulator of organ size in both Drosophila and mammals. Yes associated protein (YAP), the central component of the Hippo signaling cascade, functions as an oncogene in several malignancies. Ovarian granulosa cell tumors (GCT) are characterized by enlargement of ovary, excess production of estrogen, high frequency of recurrence and potential of malignancy and metastasis. Whether the Hippo pathway plays a role in the pathogenesis of GCT is unknown. This study was conducted to examine the expression of YAP in human adult GCTs and to determine the role of YAP in the proliferation and steroidogenesis of GCT cells. Compared with age-matched normal human ovaries, GCT tissues exhibited higher levels of YAP expression. YAP protein was predominantly expressed in the nucleus of tumor cells, whereas the non-tumor ovarian stromal cells expressed very low levels of YAP. YAP was also expressed in cultured primary human granulosa cells and in KGN and COV434 GCT cell lines. siRNA-mediated knockdown of YAP in KGN cells resulted in a significant reduction in cell proliferation (P<0.001). Conversely, overexpression of wild-type YAP or a constitutively active YAP mutant resulted in a significant increase in KGN cell proliferation and migration. Moreover, YAP knockdown reduced FSH-induced aromatase (CYP19A1) protein expression and estrogen production in KGN cells. These results demonstrate that YAP plays an important role in regulating GCT cell proliferation, migration and steroidogenesis. Targeting the Hippo/YAP pathway may provide a novel therapeutic approach for GCT. PMID:24389730

  4. Dimers of melampomagnolide B exhibit potent anticancer activity against hematological and solid tumor cells

    PubMed Central

    Janganati, Venumadhav; Ponder, Jessica; Jordan, Craig T.; Borrelli, Michael J.; Penthala, Narsimha Reddy; Crooks, Peter A.

    2016-01-01

    A series of novel carbamate and carbonate dimers of melampomagnolide B (MMB) have been synthesized by reaction of the MMB-triazole carbamate synthon 6 with various terminal diamino and dihydroxy alkanes. The resulting dimeric products 7b, 7c and 7f were selected and evaluated for anticancer activity against a panel of 60 human hematological and solid tumor cell lines. The most active compounds, 7b, 7c and 7f, exhibited GI50 values in the range 250-780 nM against the majority of leukemia cell lines in the tumor cell panel. Specifically, compounds 7b and 7f exhibited potent growth inhibition against non-small cell lung cancer cell lines NCI-H522 (GI50 = 160 nM) and HOP-92 (GI50 = 170 nM), respectively. Also, compound 7f also potently inhibited the growth of melanoma cell lines LOX IMVI, MALME-3M, and UACC-62 (GI50 values = 170, 190 and 190 nM, respectively); breast cancer cell line MDA-MB-468 (GI50 = 190 nM); colon cancer cell line HCT-116 (GI50 = 190 nM); and renal cancer cell line RXF 393 (GI50 = 160 nM). Compound 7f and the simple dicarbonate dimer of MMB (8) showed anticancer activity 300-fold and 1 × 106-fold, respectively, more cytotoxic than 7f and DMAPT at a concentration of 10 μM against rat 9L-SF gliosarcoma cells. The dimeric compounds 7a-7j & 8 were also screened for antileukemic activity against M9-ENL1 acute myelogenous leukemia (AML) cells and primary AML cell specimens. These compounds exhibited two to twelve-fold more potent antileukemic activity (EC50 = 0.5-2.9 μM) against the M9-ENL1 cell line when compared to parthenolide (EC50 = 6.0 μM). The dimeric analogues were also active against the primary AML cell specimens in the nanomolar to lower micromolar range and exhibited two to ten-fold more potent antileukemic activity (EC50 = 0.86-4.2 μM) when compared to parthenolide (EC50 = 2.5-16 μM). Thus, dimer 7f exhibited promising anticancer activity against a variety of both hematological and solid human tumor cell lines, while dimer 8 was

  5. Clinical Outcomes of Patients with Rare and Heavily Pretreated Solid Tumors Treated according to the Results of Tumor Molecular Profiling

    PubMed Central

    Hayden, Ingrid

    2016-01-01

    Patients with heavily pretreated advanced cancer or with rare tumors are difficult to treat. Molecular profiling (MP) of tumors to identify biomarkers that predict potential outcomes with individual therapies is an emerging strategy to guide treatment decisions. Patients with rare tumors for which standard-of-care therapy was unavailable or more common tumors for which standard-of-care options had been exhausted underwent MP at a single Australian center. Data regarding treating physicians' choice of therapy, MP results and recommendations, and patient outcomes were collected. Seven patients had received prior standard first-line therapy (PST), 16 had rare tumors, and 31 had been heavily pretreated (HPT; ≥2 prior lines). Most treatments suggested by MP (541/594; 91.1%) were common chemotherapy drugs available in generic formulations. MP-guided therapy recommendations differed from physician's recommendations in 48 patients (88.9%). MP-guided therapy produced clinical benefit (improved QOL and/or performance status, symptoms, bodyweight, or RECIST) in 19/31 (61.3%), 11/16 (68.8%), and 3/7 (42.9%) patients with HPTs, rare tumors, and PSTs, respectively, and had a PFS ratio ≥1.3 in 22/37 evaluable patients (59.5%; 95% confidence interval 44–76%). The null hypothesis that ≤15% of these patients would have a PFS ratio ≥1.3 was rejected (one-sided p < 0.0001). In conclusion, using MP to guide therapy selection is feasible in clinical practice and may improve patient outcomes. PMID:27525268

  6. Clinical Outcomes of Patients with Rare and Heavily Pretreated Solid Tumors Treated according to the Results of Tumor Molecular Profiling.

    PubMed

    Dean, Andrew; Byrne, Aisling; Marinova, Mira; Hayden, Ingrid

    2016-01-01

    Patients with heavily pretreated advanced cancer or with rare tumors are difficult to treat. Molecular profiling (MP) of tumors to identify biomarkers that predict potential outcomes with individual therapies is an emerging strategy to guide treatment decisions. Patients with rare tumors for which standard-of-care therapy was unavailable or more common tumors for which standard-of-care options had been exhausted underwent MP at a single Australian center. Data regarding treating physicians' choice of therapy, MP results and recommendations, and patient outcomes were collected. Seven patients had received prior standard first-line therapy (PST), 16 had rare tumors, and 31 had been heavily pretreated (HPT; ≥2 prior lines). Most treatments suggested by MP (541/594; 91.1%) were common chemotherapy drugs available in generic formulations. MP-guided therapy recommendations differed from physician's recommendations in 48 patients (88.9%). MP-guided therapy produced clinical benefit (improved QOL and/or performance status, symptoms, bodyweight, or RECIST) in 19/31 (61.3%), 11/16 (68.8%), and 3/7 (42.9%) patients with HPTs, rare tumors, and PSTs, respectively, and had a PFS ratio ≥1.3 in 22/37 evaluable patients (59.5%; 95% confidence interval 44-76%). The null hypothesis that ≤15% of these patients would have a PFS ratio ≥1.3 was rejected (one-sided p < 0.0001). In conclusion, using MP to guide therapy selection is feasible in clinical practice and may improve patient outcomes. PMID:27525268

  7. Oxaliplatin in Treating Young Patients With Recurrent Solid Tumors That Have Not Responded to Previous Treatment

    ClinicalTrials.gov

    2013-06-04

    Childhood Central Nervous System Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Hepatoblastoma; Childhood Hepatocellular Carcinoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Recurrent Adrenocortical Carcinoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Colon Cancer; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Nasopharyngeal Cancer; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer

  8. Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CD1 Mice

    EPA Science Inventory

    Developmental exposure to inorganic arsenic is carcinogenic in humans and mice, and adult offspring of mice exposed to inorganic arsenic can develop tumors of the lung, liver, adrenal, uterus, and ovary. It has been suggested that methylarsonous acid (MMA3+), a product of the bi...

  9. Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CDl Mice.

    EPA Science Inventory

    Inorganic arsenic exposure is carcinogenic in humans and rodents. When pregnant mice are exposed to inorganic arsenic in the drinking water their offspring, when adults, develop tumors and proliferative lesions at several sites, such as lung, liver, adrenal, uterus, ovary and ovi...

  10. Impact of Treatment Site in Adolescents and Young Adults With Central Nervous System Tumors

    PubMed Central

    Wolfson, Julie; Sun, Can-Lan; Kang, Tongjun; Wyatt, Laura; D’Appuzzo, Massimo

    2014-01-01

    Background Adolescents and young adults (AYAs; aged 15–39 years) have inferior survival in comparison with younger (aged 0–14 years) cancer patients. Impact of care at specialized centers such as National Cancer Institute–designated Comprehensive Cancer Centers (NCICCC) for AYAs of all ages or the Children’s Oncology Group (COG) for AYAs aged 15 to 21 years with central nervous system (CNS) tumors remains unstudied. Methods We constructed a cohort of 560 children and 784 AYAs with CNS tumors reported to the Los Angeles cancer registry from 1998 to 2008. Cox and logistic regression models were used, with two-sided P values from Wald χ2 tests. Results In Cox regression analysis restricted to World Health Organization (WHO) grade II tumors, patients of all ages saw worse outcome if not treated at NCICCC/COG sites (non-NCICCC/COG vs NCICCC/COG: hazard ratio [HR] =1.73; 95% confidence interval [CI] = 1.09 to 2.72). Furthermore, the worse outcome for AYAs compared with children (HR = 1.90; 95% CI = 1.21 to 2.98; P = .005) was abrogated (HR = 1.35; 95% CI = 0.79 to 2.29; P = .27) by care at NCICCC/COGs. Those less likely to receive care at NCICCC/COG sites included young AYAs (aged 15–21 years vs children: odds ratio [OR] = 0.23; 95% CI = 0.11 to 0.48; P < .001) and older AYAs (aged 22–39 years) with low socioeconomic status (OR = 0.39; 95% CI = 0.17 to 0.89; P = .02), public/no insurance (OR = 0.30; 95% CI = 0.12 to 0.71; P < .01), and distance to care greater than 5 miles (OR = 0.29; 95% CI = 0.15 to 0.57; P < .001). Conclusions Population-based data reveal that care at NCICCC/COG sites mitigates inferior outcome in AYAs with WHO grade II CNS tumors compared with children. Compared with children, AYAs are less likely to receive care at NCICCC/COGs. Insurance, socioeconomic status, and distance serve as barriers to care at NCICCCs for older AYAs. PMID:25178694

  11. Positron Emission Tomography Using Fluorine F 18 EF5 to Find Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Newly Diagnosed Brain Tumors

    ClinicalTrials.gov

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Meningeal Melanocytoma

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

    ClinicalTrials.gov

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

    ClinicalTrials.gov

    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

  14. Phase I study of XL281 (BMS-908662), a potent oral RAF kinase inhibitor, in patients with advanced solid tumors.

    PubMed

    Dickson, Mark A; Gordon, Michael S; Edelman, Gerald; Bendell, Johanna C; Kudchadkar, Ragini R; LoRusso, Patricia M; Johnston, Stuart H; Clary, Douglas O; Schwartz, Gary K

    2015-04-01

    Background XL281 is a potent and selective inhibitor of wild-type and mutant RAF kinases with anti-tumor activity in multiple xenograft models. Mutations in KRAS or BRAF can activate the RAF/MEK/ERK pathway in human tumors and may confer sensitivity to RAF kinase inhibitors. Methods We performed a phase I study of XL281 in patients with advanced solid tumors. Patients were enrolled in successive cohorts of XL281 orally once daily in 28-day cycles. Twice daily dosing, different formulations, and the effect of food and famotidine were also studied. At the MTD expanded cohorts with defined mutations were treated. Results In total, 160 patients were treated. The MTD on the QD schedule was 150 mg. The most common toxicities were diarrhea, nausea, and fatigue. Plasma Cmax and AUC increased with dose. Famotidine resulted in lower AUC while food had no effect. Two patients had partial responses by RECIST: One with papillary thyroid cancer with NRAS mutation and one with uveal melanoma. Another nine patients had tumor decrease of >10% but did not meet RECIST criteria for PR. Matched tumors pairs from 33 patients showed evidence of RAF inhibition with significant decreases in pERK, pMEK and pAKT. Conclusions XL281 was generally well tolerated and the MTD was established at 150 mg/day. Partial responses and clinical benefit were observed in several patients. Tumor biopsies demonstrated effective target inhibition. PMID:25476894

  15. Characterization of small spheres derived from various solid tumor cell lines: are they suitable targets for T cells?

    PubMed

    Busse, Antonia; Letsch, Anne; Fusi, Alberto; Nonnenmacher, Anika; Stather, David; Ochsenreither, Sebastian; Regenbrecht, Christian R A; Keilholz, Ulrich

    2013-08-01

    T cell based immunotherapy has been investigated in a variety of malignancies and analyses have been mostly founded on in vitro data with tumor cell monolayers. However, three-dimensional (3D) culture models might mimic more closely the 'in vivo' conditions than 2D monolayers. Therefore, we analyzed the expression of tumor-associated antigens (TAA) and of molecules involved in antigen processing and presentation (APM) in tumor spheres, which served as an in vitro model for micrometastasis which might be enriched in tumor propagating cancer stem cells. For enrichment of sphere cells 12 human solid tumor cell lines were cultured in serum-free medium. Expression of a variety of TAA and APM were analyzed by RT-PCR and/or flow cytometry and compared to expression in corresponding adherent bulk cells grown in regular growth medium. Compared to adherent cells, spheres showed equal or higher mRNA expression levels of LMP2, LMP7 and MECL-1, of TAP1 and TAP2 transporters and, surprisingly, also of TAA including differentiation antigens. However, downregulation or loss of HLA-I and HLA-II molecules in spheres was observed in 8 of 10 and 1 of 2 cell lines, respectively, and was unresponsive to stimulation with IFN-γ. Although tumor spheres express TAA and molecules of intracellular antigen processing, they are defective in antigen presentation due to downregulation of HLA surface expression which may lead to immune evasion. PMID:23519726

  16. A New Biological Feature of Natural Killer Cells: The Recognition of Solid Tumor-Derived Cancer Stem Cells

    PubMed Central

    Tallerico, Rossana; Garofalo, Cinzia; Carbone, Ennio

    2016-01-01

    Natural killer (NK) cells are classified as a member of the innate lymphoid cells (ILCs) group 1. ILCs have been recently identified and grouped on the basis of their phenotypical and functional characteristics. They are effectors of innate immunity and are involved in secondary lymphoid organ generation and tissue remodeling. NK cells are powerful cytotoxic lymphocytes able to recognize and eliminate tumor- and virus-infected cells by limiting their spread and tissue damage. The recognition of tumor cells is mediated by both activating and inhibitory receptors. While in hematological malignancies the role played by NK cells is widely known, their role in recognizing solid tumors remains unclear. Recently, tumor cell populations have been divided into two compartments: cancer-initiating cells (CICs) or cancer stem cells (CSCs) and senescent tumor cells. Here, CSC will be used. CSCs are a small subset of malignant cells with stem-like properties that are involved in tumor maintenance and recurrence due to their ability to survive to traditional therapies; they are, moreover, poorly recognized by T lymphocytes. Recent data showed that NK cells recognize in vitro cancer-initiating cells derived from colon cancer, glioblastoma, and melanoma. However, more in vivo studies are urgently required to fully understand whether these new antitumor NK cells with cytotoxic capability may be considered in the design of new immunotherapeutic interventions. PMID:27242786

  17. Differences in attitudes and beliefs toward end-of-life care between hematologic and solid tumor oncology specialists

    PubMed Central

    Hui, D.; Bansal, S.; Park, M.; Reddy, A.; Cortes, J.; Fossella, F.; Bruera, E.

    2015-01-01

    Background Patients with hematologic malignancies often receive aggressive care at the end-of-life. To better understand the end-of-life decision-making process among oncology specialists, we compared the cancer treatment recommendations, and attitudes and beliefs toward palliative care between hematologic and solid tumor specialists. Patients and methods We randomly surveyed 120 hematologic and 120 solid tumor oncology specialists at our institution. Respondents completed a survey examining various aspects of end-of-life care, including palliative systemic therapy using standardized case vignettes and palliative care proficiency. Results Of 240 clinicians, 182 (76%) clinicians responded. Compared with solid tumor specialists, hematologic specialists were more likely to favor prescribing systemic therapy with moderate toxicity and no survival benefit for patients with Eastern Cooperative Oncology Group (ECOG) performance status 4 and an expected survival of 1 month (median preference 4 versus 1, in which 1 = strong against treatment and 7 = strongly recommend treatment, P < 0.0001). This decision was highly polarized. Hematologic specialists felt less comfortable discussing death and dying (72% versus 88%, P = 0.007) and hospice referrals (81% versus 93%, P = 0.02), and were more likely to feel a sense of failure with disease progression (46% versus 31%, P = 0.04). On multivariate analysis, hematologic specialty [odds ratio (OR) 2.77, P = 0.002] and comfort level with prescribing treatment to ECOG 4 patients (OR 3.79, P = 0.02) were associated with the decision to treat in the last month of life. Conclusions We found significant differences in attitudes and beliefs toward end-of-life care between hematologic and solid tumor specialists, and identified opportunities to standardize end-of-life care. PMID:26041765

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

    PubMed Central

    Soltani, M.; Chen, P.

    2013-01-01

    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. PMID:23840579

  19. Phase I study of olaratumab in Japanese patients with advanced solid tumors.

    PubMed

    Doi, Toshihiko; Ma, Yan; Dontabhaktuni, Aruna; Nippgen, Cornelia; Nippgen, Johannes; Ohtsu, Atsushi

    2014-07-01

    Olaratumab (IMC-3G3) is a fully human IgG1 monoclonal antibody that selectively binds the external domain of human platelet-derived growth factor receptor-α with high affinity and blocks ligand binding. This was a single-center, dose-escalation, phase I trial of olaratumab in Japanese patients with advanced/refractory solid malignancies. Three to six patients were enrolled into each of three cohorts: Patients received i.v. olaratumab: 10 mg/kg on days 1 and 8 every 3 weeks (cohort 1); 20 mg/kg every 2 weeks (cohort 2); and 15 mg/kg on days 1 and 8 every 3 weeks (cohort 3). Doses were escalated from cohort 1 through cohort 3. The primary objective was to establish the safety and pharmacokinetic profile of olaratumab. Sixteen patients were treated across three cohorts. There were no dose-limiting toxicities, so the maximum tolerated dose was not reached. The most common olaratumab-related treatment-emergent adverse events (TEAEs) were proteinuria (25.0%) and elevated aspartate transaminase (12.5%). One patient (cohort 2) had two olaratumab-related Grade 3 TEAEs (increased aspartate aminotransferase and tumor hemorrhage); otherwise, olaratumab-related TEAEs were Grade 1/2. Seven patients (43.8%) had a best response of stable disease. Based on the pharmacokinetic concentration profile of olaratumab, the trough concentrations following single and multiple doses at 15 mg/kg on days 1 and 8 every 3 weeks (cohort 3) and multiple doses at 20 mg/kg every 2 weeks (cohort 2) were above the 155 μg/mL target. Thus, these two doses could represent an acceptable schedule for future trials in Japanese patients. Olaratumab had an acceptable safety profile and was well tolerated. PMID:24816152

  20. Hemorheological changes in solid tumor patients after treatment with recombinant erythropoetin.

    PubMed

    Muravyov, A V; Cheporov, S V; Kislov, N V; Volkova, E L

    2009-01-01

    The subject of this study was the effect of erythropoetin (Epoetin) treatment of anemic patients (n=30) with solid tumors on parameters of hemorheological profile. Both prior to and following Epoetin treatment (10,000 units subcutaneously thrice weekly) for four weeks hemorheological measurements included plasma and red blood cell (RBC) suspension viscosity; high and low shear whole blood viscosity; hematocrit (Hct), hemoglobin, RBC aggregation (RBCA) and deformation. It was found that the patients had reduced Hb up to 92.96+/-2.99 g/l, and the Hct - 28.2%. These parameters were significant increased after four weeks of Epoetin treatment: Hb by 28% (p<0.01) and Hct by 31% (p<0.01). In macrorheological part of the profile, both the high shear blood viscosity, and the low one were increased by 23 and 27% (p<0.05), respectively. These changes were mainly associated with the Hct rise. As for microrheological part of profile after Epoetin treatment, RBCA was decreased by 25% (p<0.05). While the red cell rigidity index (Tk) was lowered only slightly (by 8%). RBC incubation with Epoetin (10.0 I.E./ml) was accompanied by 10% decrease of Tk. It is important to note that before Epoetin treatment incubation with it led to decrease of RBCA by 30% (p<0.05), whereas after four week of the treatment period a 27% (p<0.05) rise of aggregation was found in majority of patients. Thus these results suggest that Epoetin is an effective, safe and convenient therapy for the management of anaemia in patients with cancer. And this drug has a moderate positive hemorheological effect on RBC and on the microrheological properties in particular. These data suggested that Epoetin has an effect on the membrane properties regulating RBC aggregation and deformation and affects by the signal transduction system, including Ca2+-dependant signaling pathway and tyrosine kinase and phosphotase activity change. PMID:19136741

  1. Capturing Treatment Decision Making Among Patients With Solid Tumors and Their Caregivers

    PubMed Central

    Jones, Randy A.; Steeves, Richard; Ropka, Mary E.; Hollen, Patricia

    2013-01-01

    Purpose/Objectives To examine the feasibility and acceptability of using a decision aid with an interactive decision-making process in patients with solid tumors and their caregivers during cancer-related treatment. Research Approach A phenomenologic approach was used to analyze qualitative data, with a focus on the meaning of participants’ lived experiences. Interviews were conducted by telephone or in person. Setting Outpatient clinics at two regional cancer centers. Participants 160 total individuals; 80 patients with newly diagnosed breast (n = 22), advanced-stage prostate (n = 19), or advanced-stage lung (n = 39) cancer, and their caregivers (n = 80). Methodologic Approach Twenty-seven of the 80 pairs engaged in audio recorded interviews that were conducted using a semistructured interview guide. Continuous text immersion revealed themes. Validity of qualitative analysis was achieved by member checking. Findings Significant findings included three themes: (a) the decision aid helped patients and caregivers understand treatment decisions better, (b) the decision aid helped patients and caregivers to be more involved in treatment decisions, and (c) frequent contact with the study nurse was valuable. Conclusions Decision making was more complex than participants expected. The decision aid helped patients and caregivers make satisfying treatment decisions and become integral in a shared treatment decision-making process. Interpretation Decision aids can help patients and their caregivers make difficult treatment decisions affecting quantity and quality of life during cancer treatment. The findings provide valuable information for healthcare providers helping patients and their caregivers make treatment decisions through a shared, informed, decision-making process. Knowledge Translation Decision aids can be helpful with treatment choices. Caregivers’ understanding about treatment is just as important in the decision-making process as the patients

  2. Phase 1 Study of VEGF Trap (Aflibercept) Administered Subcutaneously to Patients with Advanced Solid Tumors

    PubMed Central

    Tew, William P.; Gordon, Michael; Murren, John; Dupont, Jakob; Pezzulli, Sandra; Aghajanian, Carol; Sabbatini, Paul; Mendelson, David; Schwartz, Lawrence; Gettinger, Scott; Psyrri, Amanda; Cedarbaum, Jesse M.; Spriggs, David R.

    2014-01-01

    Purpose To determine the maximum tolerated dose (MTD) or maximal administered dose (MAD) and pharmacokinetic and safety profiles of subcutaneously administered VEGF Trap (aflibercept), a novel anti-angiogenic agent. Experimental Design In this open-label, dose-escalation study, patients with advanced solid tumors were treated with subcutaneous doses of aflibercept at seven dose levels. Patients received a single dose of aflibercept and then underwent safety and pharmacokinetic assessments over the next 4 weeks. Patients then received weekly or bi-weekly treatment over the subsequent 6 weeks. Patients tolerating and benefiting could continue on aflibercept at the same dose and schedule until progression of disease. Results Thirty-eight patients received at least one dose of aflibercept. MTD was not reached. Due to solubility/dosing limits with the subcutaneous formulation, 1600mcg/kg/week was the MAD. The most common toxicities were proteinuria (37%), fatigue (32%), injection site reactions (18%), nausea (17%), myalgia and anorexia (16% each), hypertension (13%), and voice hoarseness (11%). Drug-related grade 3–4 toxicity was uncommon (7%) and reversible: dehydration, cerebral ischemia, proteinuria, hypertension, leukopenia, and pulmonary embolism. We identified dose-proportional increases in plasma concentrations of aflibercept bound to VEGF with a t1/2 of 18 days. No anti-aflibercept antibodies were detected. Stable disease was maintained for at least 10 weeks in 18 patients (47%), and 2 patients maintained on study for more than 1 year. Conclusion Subcutaneous aflibercept was well-tolerated and had manageable side effects. Its favorable pharmacokinetic profile and potential antitumor activity warrants further evaluation. PMID:20028764

  3. Glycoengineered mesenchymal stem cells as an enabling platform for two-step targeting of solid tumors.

    PubMed

    Layek, Buddhadev; Sadhukha, Tanmoy; Prabha, Swayam

    2016-05-01

    Current tumor targeted drug and diagnostic delivery systems suffer from a lack of selectivity for tumor cells. Here, we propose a two-step tumor targeting strategy based on mesenchymal stem cells (MSCs), which actively traffic to tumors. We developed glycoengineering protocols to induce expression of non-natural azide groups on the surface of MSCs without affecting their viability or tumor homing properties. Glycoengineered MSCs demonstrated active tumor homing in subcutaneous and orthotopic lung and ovarian tumor models. Subsequent systemic administration of dibenzyl cyclooctyne (DBCO)-labeled fluorophores or nanoparticles to MSC pretreated mice resulted in enhanced tumor accumulation of these agents through bio-orthogonal copper-free click chemistry. Further, administration of glycoengineered MSCs along with paclitaxel-loaded DBCO-functionalized nanoparticles resulted in significant (p < 0.05) inhibition of tumor growth and improved survival (p < 0.0001) in an orthotopic metastatic ovarian tumor model. These results provide evidence for the potential of MSC-based two-step targeting strategy to improve the tumor specificity of diagnostic agents and drugs, and thus potentially improve the treatment outcomes for patients diagnosed with cancer. PMID:26946263

  4. A Phase I Dose Finding Study of 5-Azacytidine in Combination with Sodium Phenylbutyrate in Patients with Refractory Solid Tumors

    PubMed Central

    Lin, Jianqing; Gilbert, Jill; Rudek, Michelle A.; Zwiebel, James A.; Gore, Steve; Jiemjit, Anchalee; Zhao, Ming; Baker, Sharyn D.; Ambinder, Richard F.; Herman, James G.; Donehower, Ross C.; Carducci, Michael A.

    2010-01-01

    Purpose This was a phase I trial to determine the minimal effective dose and optimal dose schedule of 5-AC in combination with sodium phenylbutyrate in patients with refractory solid tumors. The pharmacokinetics, pharmacodynamics, and antineoplastic effects were also studied. Experimental design Three dosing regimens were studied in 27 patients with advanced solid tumors and toxicity was recorded. The pharmacokinetics of the combination of drugs was evaluated. Repeat tumor biopsies and peripheral blood mononuclear cells (PBMC) were analyzed to evaluate epigenetic changes in response to therapy. Epstein Barr Virus (EBV) titers were evaluated as a surrogate measure for gene re-expression of epigenetic modulation in PBMC. Results The three dose regimens of 5-AC and PB were generally well tolerated and safe. A total of 48 cycles was administrated to 27 patients. The most common toxicities were bone marrow suppression related neutropenia and anemia, which were minor. The clinical response rate was disappointing for the combination of agents. One patient demonstrated stable disease for 5 months while 26 patients demonstrated progressive disease as best tumor response. The administration of PB and 5-AC did not appear to alter the pharmacokinetics of either drug. Although there were individual cases of targeted DNMT activity and histone H3/4 acetylation changes from paired biopsy or PBMC, no conclusive statement can be made based on these limited correlative studies. Conclusion The combination of 5-AC and PB across three dose schedules was generally well tolerated and safe, yet lacked any real evidence for clinical benefit. PMID:19789320

  5. Investigation of Particle Accumulation, Chemosensitivity and Thermosensitivity for Effective Solid Tumor Therapy Using Thermosensitive Liposomes and Hyperthermia

    PubMed Central

    Lokerse, Wouter J.M.; Bolkestein, Michiel; ten Hagen, Timo L.M.; de Jong, Marion; Eggermont, Alexander M.M.; Grüll, Holger; Koning, Gerben A.

    2016-01-01

    Doxorubicin (Dox) loaded thermosensitive liposomes (TSLs) have shown promising results for hyperthermia-induced local drug delivery to solid tumors. Typically, the tumor is heated to hyperthermic temperatures (41-42 °C), which induced intravascular drug release from TSLs within the tumor tissue leading to high local drug concentrations (1-step delivery protocol). Next to providing a trigger for drug release, hyperthermia (HT) has been shown to be cytotoxic to tumor tissue, to enhance chemosensitivity and to increase particle extravasation from the vasculature into the tumor interstitial space. The latter can be exploited for a 2-step delivery protocol, where HT is applied prior to i.v. TSL injection to enhance tumor uptake, and after 4 hours waiting time for a second time to induce drug release. In this study, we compare the 1- and 2-step delivery protocols and investigate which factors are of importance for a therapeutic response. In murine B16 melanoma and BFS-1 sarcoma cell lines, HT induced an enhanced Dox uptake in 2D and 3D models, resulting in enhanced chemosensitivity. In vivo, therapeutic efficacy studies were performed for both tumor models, showing a therapeutic response for only the 1-step delivery protocol. SPECT/CT imaging allowed quantification of the liposomal accumulation in both tumor models at physiological temperatures and after a HT treatment. A simple two compartment model was used to derive respective rates for liposomal uptake, washout and retention, showing that the B16 model has a twofold higher liposomal uptake compared to the BFS-1 tumor. HT increases uptake and retention of liposomes in both tumors models by the same factor of 1.66 maintaining the absolute differences between the two models. Histology showed that HT induced apoptosis, blood vessel integrity and interstitial structures are important factors for TSL accumulation in the investigated tumor types. However, modeling data indicated that the intraliposomal Dox fraction did not

  6. Potentiation of mitomycin C and porfiromycin antitumor activity in solid tumor models by recombinant human interleukin 1 alpha.

    PubMed

    Braunschweiger, P G; Jones, S A; Johnson, C S; Furmanski, P

    1991-10-15

    The time- and dose-dependent effects of recombinant human interleukin 1 alpha (IL-1 alpha) on the antitumor activity of mitomycin C (MMC) and porfiromycin (PORF) were studied in RIF-1 and Panc02 solid tumor model systems. IL-1 alpha produced dose-dependent sensitization of clonogenic RIF-1 tumor cells to MMC in vivo. IL-1 alpha chemosensitization was highly schedule dependent, and the most efficacious schedules produced dose-modifying factors of 3.6 and 5.1 for MMC and PORF, respectively. More than additive clonogenic cell kill after IL-1 alpha-chemotherapy combinations reflected increased cellular sensitivity to MMC and PORF. The combinations also produced marked decreases in the yield of viable tumor cells, suggesting that the bioreductive drugs may have also potentiated the microvascular injury and ischemia produced by IL-1 alpha. Dexamethasone inhibited and ketoconazole, an inhibitor of corticosterone biosynthesis, enhanced IL-1 alpha-mediated chemosensitization in these models. IL-1 alpha mediated chemosensitization to MMC, and PORF was also demonstrated by tumor growth inhibition in the RIF-1 model and increased survival of mice in the spontaneously metastasizing Panc02 system. Chemosensitization of bone marrow spleen colony-forming units was not seen. IL-1 alpha (1000 units/ml) had no effect on MMC and PORF cytotoxicity in RIF-1 and PORF cell lines in vitro. The results indicate that the tumor-specific IL-1 alpha-induced pathophysiologies can sensitize solid tumors to agents which are preferentially activated, retained, and cytotoxic to cells under hypoxic conditions. Our results suggest that strategies combining bioreductively activated hypoxic cell cytotoxins and biological agents might offer efficacious alternatives or adjuvants to conventional combination approaches. PMID:1913664

  7. Angiography and embolisation for solid abdominal organ injury in adults - a current perspective

    PubMed Central

    2010-01-01

    Over the past twenty years there has been a shift towards non-operative management (NOM) for haemodynamically stable patients with abdominal trauma. Embolisation can achieve haemostasis and salvage organs without the morbidity of surgery, and the development and refinement of embolisation techniques has widened the indications for NOM in the management of solid organ injury. Advances in computed tomography (CT) technology allow faster scanning times with improved image quality. These improvements mean that whilst surgery is still usually recommended for patients with penetrating injuries, multiple bleeding sites or haemodynamic instability, the indications for NOM are expanding. We present a current perspective on angiography and embolisation in adults with blunt and penetrating abdominal trauma with illustrative examples from our practice including technical advice. PMID:20584325

  8. Fatty acid synthase overexpression in adult testicular germ cell tumors: potential role in the progression of non-seminomatous germ cell tumors.

    PubMed

    Miyai, Kosuke; Iwaya, Keiichi; Asano, Tomohiko; Tamai, Seiichi; Matsubara, Osamu; Tsuda, Hitoshi

    2014-02-01

    Overexpression of fatty acid synthase (FASN), which is a key enzyme responsible for the endogenous synthesis of fatty acids, and its association with multistep progression have been demonstrated in various human malignant tumors. We aimed to clarify the potential role of FASN overexpression in the development and progression of adult testicular germ cell tumors (TGCTs). From the primary sites of a cohort of 113 TGCT cases, we obtained 221 histological components: 53 intratubular germ cell neoplasias, unclassified (IGCNUs), 84 seminomas, 32 embryonal carcinomas, seven choriocarcinomas, 21 yolk sac tumors, and 24 teratomas. Samples were analyzed for overexpression of FASN by immunohistochemistry. Intensities of immunoreactivity and the fraction of positive cells were classified into each four categories (intensity, 0 to 3; fraction, 0-10 % = 1, 11-50 % = 2, 51-80 % = 3, and >80 % = 4). The overall score was determined by multiplication of both scores and overall scores greater than 6 were considered FASN overexpression. On a component basis, FASN overexpression was detected in 8 % of seminomas but not in IGCNUs (0 %) and was detected frequently in non-seminomatous germ cell tumors (NSGCTs) (88 % of embryonal carcinomas, all choriocarcinomas, 81 % of yolk sac tumors, and 54 % of teratomas). There were no cases of a mixed tumor (i.e., a tumor with multiple histological components) that overexpressed FASN in seminoma components but not in co-existing NSGCT components, suggesting sequential progression. Our immunohistochemical data suggest that FASN overexpression occurs as a late event during the progression from IGCNUs/seminomas to NSGCTs. PMID:24337182

  9. Initial Solid Tumor Testing (Stage 1) of AZD1480, an Inhibitor of Janus Kinases 1 and 2 by the Pediatric Preclinical Testing Program

    PubMed Central

    Houghton, Peter J.; Kurmasheva, Raushan T.; Lyalin, Dmitry; Maris, John M.; Kolb, E. Anders; Gorlick, Richard; Reynolds, C. Patrick; Kang, Min H.; Keir, Stephen T.; Wu, Jianrong; Smith, Malcolm A.

    2014-01-01

    Background AZD1480 is an ATP competitive inhibitor of Janus kinases 1 and 2 (JAK1, 2) that has been shown to inhibit the growth of solid tumor models. This agent was selected for testing the putative role of JAK/STAT signaling in the standard PPTP solid tumor models. Procedures AZD1480 was tested against the PPTP in vitro cell line panel at concentrations from 1.0 nM to 10 M and against the PPTP in vivo solid tumor xenograft panels at (60 mg/kg once daily (SID) × 5) for 3 consecutive weeks. Additional studies evaluated 5 to 20 mg/kg BID × 5 with SID dosing at 7–30 mg/kg at weekends for 3 consecutive weeks. Results In vitro the median relative IC50 (rIC50) for the PPTP cell lines was 1.5 µM, with a range from 0.3 µM to 5.9 µM. The two cell lines with rIC50 values of 0.3 µM both had ALK activating genomic alterations. AZD1480 demonstrated statistically significant differences (p<0.05) in EFS distribution compared to control in 89% of the solid tumor xenografts. AZD1480 induced intermediate (EFS T/C > 2) or high-level growth inhibition in 15 of 30 (50%) solid tumor xenografts. Tumor regressions were observed in 3 of 6 Wilms tumor models at doses that induced inhibition of Stat3(Y705) phosphorylation. Conclusions AZD1480 demonstrated significant tumor growth inhibition against most PPTP solid tumor xenografts, similar to that observed for antiangiogenic agents tested by the PPTP. Tumor regressing activity was noted for Wilms tumor xenografts. PMID:25131802

  10. Preferential action of arsenic trioxide in solid-tumor microenvironment enhances radiation therapy

    SciTech Connect

    Griffin, Robert J. . E-mail: griff007@umn.edu; Williams, Brent W.; Park, Heon Joo; Song, Chang W.

    2005-04-01

    Purpose: To investigate the effect of arsenic trioxide, Trisenox (TNX), on primary cultures of endothelial cells and tumor tissue under varying pH and pO{sub 2} environments and the effects of combined TNX and radiation therapy on experimental tumors. Methods and Materials: Human dermal microvascular endothelial cells were cultured in vitro and exposed to TNX under various combinations of aerobic, hypoxic, neutral, or acidic conditions, and levels of activated JNK MAP kinase were assessed by Western blotting. FSaII fibrosarcoma cells grown in the hind limb of female C3H mice were used to study the effect of TNX on tumor blood perfusion and oxygenation. The tumor-growth delay after a single or fractionated irradiation with or without TNX treatment was assessed. Results: A single intraperitoneal injection of 8 mg/kg TNX reduced the blood perfusion in FSaII tumors by 53% at 2 hours after injection. To increase the oxygenation of the tumor vasculature during TNX treatment, some animals were allowed to breathe carbogen (95% O{sub 2}/5% CO{sub 2}). Carbogen breathing alone for 2 hours reduced tumor perfusion by 33%. When carbogen breathing was begun immediately after TNX injection, no further reduction occurred in tumor blood perfusion at 2 hours after injection. In vitro, TNX exposure increased activity JNK MAP kinase preferentially in endothelial cells cultured in an acidic or hypoxic environment. In vivo, the median oxygenation in FSaII tumors measured at 3 or 5 days after TNX injection was found to be significantly elevated compared with control tumors. Subsequently, radiation-induced tumor-growth delay was synergistically increased when radiation and TNX injection were fractionated at 3-day or 5-day intervals. Conclusions: Trisenox has novel vascular-damaging properties, preferentially against endothelium in regions of low pH or pO{sub 2}, which leads to tumor cell death and enhancement of the response of tumors to radiotherapy.

  11. High-efficiency immunomagnetic isolation of solid tissue-originated integrin-expressing adult stem cells.

    PubMed

    Palmon, Aaron; David, Ran; Neumann, Yoav; Stiubea-Cohen, Raluca; Krief, Guy; Aframian, Doron J

    2012-02-01

    Isolation of highly pure specific cell types is crucial for successful adult stem cell-based therapy. As the number of such cells in adult tissue is low, an extremely efficient method is needed for their isolation. Here, we describe cell-separation methodologies based on magnetic-affinity cell sorting (MACS) MicroBeads with monoclonal antibodies against specific membrane proteins conjugated to superparamagnetic particles. Cells labeled with MACS MicroBeads are retained in a magnetic field within a MACS column placed in a MACS separator, allowing fast and efficient separation. Both positively labeled and non-labeled fractions can be used directly for downstream applications as the separated cell fractions remain viable with no functional impairment. As immunomagnetic separation depends on the interaction between a cell's membrane and the magnetically labeled antibody, separation of specific cells originating from solid tissues is more complex and demands a cell-dissociating pretreatment. In this paper, we detail the use of immunomagnetic separation for the purpose of regenerating damaged salivary gland (SG) function in animal and human models of irradiated head and neck cancer. Each year 500,000 new cases of head and neck cancer occur worldwide. Most of these patients lose SG function following irradiation therapy. SGs contain integrin α6β1-expressing epithelial stem cells. We hypothesized that these cells can be isolated, multiplied in culture and auto-implanted into the irradiated SGs to regenerate damaged SG function. PMID:22019721

  12. The antioxidant response induced by Lonicera caerulaea berry extracts in animals bearing experimental solid tumors.

    PubMed

    Gruia, Maria Iuliana; Oprea, Eliza; Gruia, Ion; Negoita, Valentina; Farcasanu, Ileana Cornelia

    2008-01-01

    Lonicera caerulea is a species of bush native to the Kamchatka Peninsula (Russian Far East) whose berries have been extensively studied due to their potential high antioxidant activity. The aim of our work was to investigate the in vivo effects of the antioxidant action of Lonicera caerulea berry extracts on the dynamics of experimentally-induced tumors. Our data showed that aqueous Lonicera caerulaea extracts reduced the tumor volume when administered continuously during the tumor growth and development stages, but augmented the tumor growth when the administration of extracts started three weeks before tumor grafting. Prolonged administration of Lonicera caerulaea berry extracts induced the antioxidant defense mechanism in the tumor tissues, while surprisingly amplifying the peripheral oxidative stress. PMID:18560338

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

    PubMed

    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. PMID:9661892

  14. Development and validation of the JAX Cancer Treatment Profile™ for detection of clinically actionable mutations in solid tumors

    PubMed Central

    Ananda, Guruprasad; Mockus, Susan; Lundquist, Micaela; Spotlow, Vanessa; Simons, Al; Mitchell, Talia; Stafford, Grace; Philip, Vivek; Stearns, Timothy; Srivastava, Anuj; Barter, Mary; Rowe, Lucy; Malcolm, Joan; Bult, Carol; Karuturi, Radha Krishna Murthy; Rasmussen, Karen; Hinerfeld, Douglas

    2015-01-01

    Background The continued development of targeted therapeutics for cancer treatment has required the concomitant development of more expansive methods for the molecular profiling of the patient’s tumor. We describe the validation of the JAX Cancer Treatment Profile™ (JAX-CTP™), a next generation sequencing (NGS)-based molecular diagnostic assay that detects actionable mutations in solid tumors to inform the selection of targeted therapeutics for cancer treatment. Methods NGS libraries are generated from DNA extracted from formalin fixed paraffin embedded tumors. Using hybrid capture, the genes of interest are enriched and sequenced on the Illumina HiSeq 2500 or MiSeq sequencers followed by variant detection and functional and clinical annotation for the generation of a clinical report. Results The JAX-CTP™ detects actionable variants, in the form of single nucleotide variations and small insertions and deletions (≤50bp) in 190 genes in specimens with a neoplastic cell content of ≥10%. The JAX-CTP™ is also validated for the detection of clinically actionable gene amplifications. Conclusions There is a lack of consensus in the molecular diagnostics field on the best method for the validation of NGS-based assays in oncology, thus the importance of communicating methods, as contained in this report. The growing number of targeted therapeutics and the complexity of the tumor genome necessitates continued development and refinement of advanced assays for tumor profiling to enable precision cancer treatment. PMID:25562415

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

    PubMed Central

    Swat, Maciej H.; Thomas, Gilberto L.; Shirinifard, Abbas; Clendenon, Sherry G.; Glazier, James A.

    2015-01-01

    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. PMID:26083246

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

    PubMed

    Swat, Maciej H; Thomas, Gilberto L; Shirinifard, Abbas; Clendenon, Sherry G; Glazier, James A

    2015-01-01

    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. PMID:26083246

  17. Cancer: An Oxidative Crosstalk between Solid Tumor Cells and Cancer Associated Fibroblasts

    PubMed Central

    Arcucci, Alessandro; Ruocco, Maria Rosaria; Granato, Giuseppina; Sacco, Anna Maria

    2016-01-01

    Redox balance is associated with the regulation of several cell signalling pathways and functions. In fact, under physiological conditions, cells maintain a balance between oxidant and antioxidant systems, and reactive oxygen species (ROS) can act as second messengers to regulate cell proliferation, cell death, and other physiological processes. Cancer tissues usually contain higher levels of ROS than normal tissues, and this ROS overproduction is associated with tumor development. Neoplastic tissues are very heterogeneous systems, composed of tumor cells and microenvironment that has a critical role in tumor progression. Cancer associated fibroblasts (CAFs) represent the main cell type of tumor microenvironment, and they contribute to tumor growth by undergoing an irreversible activation process. It is known that ROS can be transferred from cancer cells to fibroblasts. In particular, ROS affect the behaviour of CAFs by promoting the conversion of fibroblasts to myofibroblasts that support tumor progression and dissemination. Furthermore, the wrecking of redox homeostasis in cancer cells and tumor microenvironment induces a metabolic reprogramming in tumor cells and cancer associated fibroblasts, giving advantage to cancer growth. This review describes the role of ROS in tumor growth, by focusing on CAFs activation and metabolic interactions between cancer cells and stromal fibroblasts. PMID:27595103

  18. Cancer: An Oxidative Crosstalk between Solid Tumor Cells and Cancer Associated Fibroblasts.

    PubMed

    Arcucci, Alessandro; Ruocco, Maria Rosaria; Granato, Giuseppina; Sacco, Anna Maria; Montagnani, Stefania

    2016-01-01

    Redox balance is associated with the regulation of several cell signalling pathways and functions. In fact, under physiological conditions, cells maintain a balance between oxidant and antioxidant systems, and reactive oxygen species (ROS) can act as second messengers to regulate cell proliferation, cell death, and other physiological processes. Cancer tissues usually contain higher levels of ROS than normal tissues, and this ROS overproduction is associated with tumor development. Neoplastic tissues are very heterogeneous systems, composed of tumor cells and microenvironment that has a critical role in tumor progression. Cancer associated fibroblasts (CAFs) represent the main cell type of tumor microenvironment, and they contribute to tumor growth by undergoing an irreversible activation process. It is known that ROS can be transferred from cancer cells to fibroblasts. In particular, ROS affect the behaviour of CAFs by promoting the conversion of fibroblasts to myofibroblasts that support tumor progression and dissemination. Furthermore, the wrecking of redox homeostasis in cancer cells and tumor microenvironment induces a metabolic reprogramming in tumor cells and cancer associated fibroblasts, giving advantage to cancer growth. This review describes the role of ROS in tumor growth, by focusing on CAFs activation and metabolic interactions between cancer cells and stromal fibroblasts. PMID:27595103

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

    ClinicalTrials.gov

    2014-06-03

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

  20. Spatial Measurements of Perfusion, Interstitial Fluid Pressure and Liposomes Accumulation in Solid Tumors.

    PubMed

    Stapleton, Shawn; Mirmilshteyn, Daniel; Zheng, Jinzi; Allen, Christine; Jaffray, David A

    2016-01-01

    The heterogeneous intra-tumoral accumulation of liposomes is a critical determinant of their efficacy. Both the chaotic tumor microcirculation and elevated IFP are linked to the heterogeneous intra-tumoral distribution of nanotechnology-based drug delivery systems such as liposomes. In the present study, the relationship between tumor microcirculation, elevated IFP, and accumulation of nanoparticles was investigated through in vivo experimentation. This was accomplished by evaluation of the tumor microcirculation using dynamic contrast enhanced computed tomography (DCE-CT) and measurement of tumor IFP using a novel image-guided robotic needle placement system connected to the micro-CT scanner. The intra-tumoral accumulation of liposomes was determined by CT image-based assessment of a nanoparticle liposomal formulation that stably encapsulate the contrast agent iohexol (CT-liposomes). CT imaging allowed for co-localization of the spatial distribution of tumor hemodynamics, IFP and CT-liposome accumulation in an individual subcutaneous xenograft mouse model of breast cancer. Measurements led to the discovery that perfusion and plasma volume fraction are strong mediators of the intra-tumoral distribution of liposomes. Furthermore, the results suggest that IFP plays an indirect role in mediating liposome distribution through modulating blood flow. PMID:27583578

  1. Tumor

    MedlinePlus

    ... be removed because of their location or harmful effect on the surrounding normal brain tissue. If a tumor is cancer , possible treatments may include: Chemotherapy Radiation Surgery Targeted cancer therapy Biologic therapy Other treatment options

  2. T lymphocytes redirected against the chondroitin sulfate proteoglycan-4 control the growth of multiple solid tumors both in vitro and in vivo

    PubMed Central

    Geldres, Claudia; Savoldo, Barbara; Hoyos, Valentina; Caruana, Ignazio; Zhang, Ming; Yvon, Eric; Vecchio, Michele Del; Creighton, Chad J; Ittmann, Michael; Ferrone, Soldano; Dotti, Gianpietro

    2014-01-01

    Purpose Because of its high expression on various types of tumors and its restricted distribution in normal tissues, chondroitin sulfate proteoglycan-4 (CSPG4) represents an attractive target for the antibody-based therapy of several solid tumors. We tested whether T cells transduced with a CSPG4-specific chimeric antigen receptor (CAR) inhibited the growth of CSPG4-expressing tumor cells both in vitro and in vivo. Experimental Design We first independently validated by immunohistochemistry (IHC) the expression of CSPG4 in an extensive panel of tumor arrays and normal tissues as well as queried public gene expression profiling datasets of human tumors. We constructed a second generation CSPG4-specific CAR also encoding the CD28 costimulatory endodomain (CAR.CSPG4). We then evaluated human T lymphocytes expressing this CAR for their ex vivo and in vivo anti-tumor activity against a broad panel of solid tumors. Results IHC showed that CSPG4 is highly expressed in melanoma, breast cancer, head and neck squamous cell carcinoma (HNSCC) and mesothelioma. In addition, in silico analysis of microarray expression data identified other important potential tumors expressing this target, including glioblastoma, clear cell renal carcinoma and sarcomas. T lymphocytes genetically modified with a CSPG4-CAR controlled tumor growth in vitro and in vivo in NSG mice engrafted with human melanoma, HNSCC and breast carcinoma cell lines. Conclusions CAR.CSPG4-redirected T cells should provide an effective treatment modality for a variety of solid tumors. PMID:24334762

  3. Pyruvate kinase M2 overexpression and poor prognosis in solid tumors of digestive system: evidence from 16 cohort studies

    PubMed Central

    Wu, Jiayuan; Hu, Liren; Chen, Manyu; Cao, Wenjun; Chen, Haicong; He, Taiping

    2016-01-01

    Purpose The expression of pyruvate kinase M2 (PKM2) has been linked to tumor formation and invasion. Specifically, the relationship between high PKM2 expression and prognosis has been evaluated in solid tumors of digestive system. However, the prognostic value of PKM2 remains controversial. Methods A literature search of PubMed, Embase, and Cochrane databases was conducted until October 2015. The end point focused on overall survival (OS). The pooled hazard ratio (HR) or odds ratio and the 95% confidence intervals were calculated to correlate PKM2 overexpression with OS and clinicopathological characteristics by employing fixed- or random-effects models, depending on the heterogeneity of the included studies. Results We identified 18 cohorts in 16 studies involving 2,812 patients for this meta-analysis. Overall, the combined HR for OS in all tumor types was 1.74 (1.44–2.11; P<0.001). When stratified by tumor type, the influence of PKM2 expression on poor prognosis was also found in gastric cancer (HR =1.54 [1.08–2.21], P=0.018), esophageal squamous cell carcinoma (HR =1.71 [1.38–2.12], P<0.001), hepatocellular cancer (HR =1.92 [1.52–2.42], P<0.001), biliary cancer (HR =2.11 [1.50–2.95], P<0.001), and oral cancer (HR =3.49 [1.97–6.18], P<0.001), but not in pancreatic ductal adenocarcinoma (HR =1.03 [0.28–3.76], P=0.968). Furthermore, PKM2 overexpression had a negative effect on the late clinical stage of all tumor types except for pancreatic ductal adenocarcinoma. The high density of PKM2 overexpression was significantly associated with some clinical characteristics in different cancer types, such as tumor stage, modal metastasis, and tumor size. Conclusion Our findings revealed significant association of PKM2 overexpression with OS and certain clinicopathological features in solid tumors of digestive system, thereby suggesting that PKM2 might be an indicator of poor prognosis in digestive system cancers. PMID:27478385

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

    PubMed

    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. PMID:27000274

  5. Efficacy of combined antiangiogenic and vascular disrupting agents in treatment of solid tumors

    SciTech Connect

    Siemann, Dietmar W. . E-mail: siemadw@ufl.edu; Shi Wenyin

    2004-11-15

    Purpose: To evaluate the antitumor efficacy of a vascular targeting strategy that combines an agent that disrupts established tumor blood vessels (ZD6126) with one that interferes with new vessel formation (ZD6474) in models of human renal cell carcinoma (Caki-1) and Kaposi's sarcoma (KSY-1). Methods and materials: Caki-1 and KSY-1 xenograft-bearing nude mice were treated with ZD6126 and ZD6474 either as single agents or in combination when the tumors reached a size of {approx}200 mm{sup 3}. ZD6126 therapy consisted of three doses of 100 mg/kg administered 1, 3, and 5 days after the tumor reached the starting size. ZD6474 was administered daily (25 mg/kg) on Days 1-5. In the combination studies, ZD6474 treatment began immediately after the first dose of ZD6126. The tumor response to treatment was evaluated using a regrowth delay endpoint. Results: Significant tumor growth delays were observed in both tumor models with either agent with the treatment regimen used. In the Caki-1 and KSY-1 models, respectively, ZD6126 treatment resulted in a tumor growth delay of 23 and 26 days and ZD6474 produced a tumor growth delay of 24.5 and 14.5 days. When ZD6126 and ZD6474 were combined, the tumor growth delays increased to 55 (Caki-1) and 86 (KSY-1) days. In the KSY-1 model, the combination therapy also resulted in 3 of 8 long-term tumor-free survivors. Conclusion: These results indicate that statistically significant antitumor efficacy can be achieved using a treatment strategy that combines a therapy that targets the established tumor blood vessels with one that interferes with the process of angiogenesis.

  6. The impact of ranitidine on monocyte responses in the context of solid tumors.

    PubMed

    Vila-Leahey, Ava; Rogers, Dakota; Marshall, Jean S

    2016-03-01

    Monocytes and myeloid derived suppressor cells (MDSC) have been implicated on the regulation of tumor growth. Histamine is also important for regulating MDSC responses. Oral administration of the H2 receptor antagonist ranitidine can inhibit breast tumor growth and metastasis. In the current study, we examined the impact of oral ranitidine treatment, at a clinically relevant dose, on multiple murine tumor models. The impact of ranitidine on monocyte responses and the role of CCR2 in ranitidine-induced tumor growth inhibition were also investigated. Oral ranitidine treatment did not reduce tumor growth in the B16-F10 melanoma, LLC1 lung cancer and EL4 thymoma models. However, it consistently reduced E0771 primary tumor growth and metastasis in the 4T1 model. Ranitidine had no impact on E0771 tumor growth in mice deficient in CCR2, where monocyte recruitment to tumors was limited. Analysis of splenic monocytes also revealed an elevated ratio of H2 versus H1 expression from tumor-bearing compared with naïve mice. More detailed examination of the role of ranitidine on monocyte development demonstrated a decrease in monocyte progenitor cells following ranitidine treatment. Taken together, these results reveal that H2 signaling may be a novel target to alter the monocyte population in breast tumor models, and that targeting H2 on monocytes via oral ranitidine treatment impacts effective tumor immunity. Ranitidine is widely used for control of gastrointestinal disorders. The potential role of ranitidine as an adjunct to immunotherapies for breast cancer and the potential impact of H2 antagonists on breast cancer outcomes should be considered. PMID:26863636

  7. The impact of ranitidine on monocyte responses in the context of solid tumors

    PubMed Central

    Vila-Leahey, Ava; Rogers, Dakota; Marshall, Jean S.

    2016-01-01

    Monocytes and myeloid derived suppressor cells (MDSC) have been implicated on the regulation of tumor growth. Histamine is also important for regulating MDSC responses. Oral administration of the H2 receptor antagonist ranitidine can inhibit breast tumor growth and metastasis. In the current study, we examined the impact of oral ranitidine treatment, at a clinically relevant dose, on multiple murine tumor models. The impact of ranitidine on monocyte responses and the role of CCR2 in ranitidine-induced tumor growth inhibition were also investigated. Oral ranitidine treatment did not reduce tumor growth in the B16-F10 melanoma, LLC1 lung cancer and EL4 thymoma models. However, it consistently reduced E0771 primary tumor growth and metastasis in the 4T1 model. Ranitidine had no impact on E0771 tumor growth in mice deficient in CCR2, where monocyte recruitment to tumors was limited. Analysis of splenic monocytes also revealed an elevated ratio of H2 versus H1 expression from tumor-bearing compared with naïve mice. More detailed examination of the role of ranitidine on monocyte development demonstrated a decrease in monocyte progenitor cells following ranitidine treatment. Taken together, these results reveal that H2 signaling may be a novel target to alter the monocyte population in breast tumor models, and that targeting H2 on monocytes via oral ranitidine treatment impacts effective tumor immunity. Ranitidine is widely used for control of gastrointestinal disorders. The potential role of ranitidine as an adjunct to immunotherapies for breast cancer and the potential impact of H2 antagonists on breast cancer outcomes should be considered. PMID:26863636

  8. The combined effect of electroporation and borocaptate in boron neutron capture therapy for murine solid tumors.

    PubMed

    Ono, K; Kinashi, Y; Suzuki, M; Takagaki, M; Masunaga, S I

    2000-08-01

    10 B-Enriched borocaptate (BSH) was administered intraperitoneally to SCCVII tumor-bearing C3H / He mice. Electroporation (EP) was conducted by using a tweezers-type electrode. The (10) B contents in tumors were measured by prompt gamma-ray spectrometry. The colony formation assay was applied to investigate the antitumor effects of boron neutron capture therapy (BNCT) and thereby to estimate the intratumor localization of BSH. The (10) B concentrations in tumors decreased with time following BSH administration, falling to 5.4(0. 1) ppm at 3 h, whereas EP treatment (3 repetitions) 15 min after BSH injection delayed the clearance of BSH from tumors, and the (10) B level remained at 19.4(0.9) ppm at 3 h. The effect of BNCT increased with the (10) B concentration in tumors, and the combination with EP showed a remarkably large cell killing effect even at 3 h after BSH injection. The effect of BNCT, i.e., slope coefficient of the cell survival curve of tumors, without EP was proportional to tumor (10) B level (r = 0.982), and that of BSH-BNCT combined with EP lay close to the same correlation line. However, tumors subjected to EP after BSH injection did not show high radiosensitivity when irradiated after conversion to a single cell suspension by enzymatic digestion. This indicates that the increase of the BNCT effect by EP was a consequence of enclosure of BSH in the interstitial space of tumor tissue and not within tumor cells. This is different from a previous in vitro study. The combination of EP and BNCT may be clinically useful, if a procedure to limit EP to the tumor region becomes available or if an alternative similar method is employed. PMID:10965028

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

    PubMed Central

    Ghaghada, Ketan B.; Sato, Amy F.; Starosolski, Zbigniew A.; Berg, John; Vail, David M.

    2016-01-01

    Objectives 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. Materials and Methods 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. Results Liposomal-I resulted in significant (p < 0.05) enhancement and uniform opacification of the vascular compartment. Non-renal, reticulo-endothelial systemic clearance of the contrast agent was demonstrated. Liposomal-I enabled visualization of primary and metastatic liver tumors. Sub-cm sized liver lesions grossly appeared as hypo-enhanced compared to the surrounding normal parenchyma with improved lesion conspicuity in the post-24 hour scan. Large liver tumors (> 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. Conclusions The long circulating liposomal-iodine contrast agent enabled prolonged visualization of small

  10. Characterization of Solid Tumors Induced by Polycyclic Aromatic Hydrocarbons in Mice

    PubMed Central

    Wang, Qiulan; Xue, Yongjie

    2015-01-01

    Background To assess the effects of single polycyclic aromatic hydrocarbons (PAHs) on solid tumor initiation, and investigate their roles in immune response regulation. Material/Methods Mice (100) were randomly divided into 5 groups (n=20) to be intraperitoneally injected with 10 daily doses of DMSO (control), anthracene (50 mg/kg), benzo-(a)-pyrene (10 mg/kg), benzo-(a)-pyrene (20 mg/kg), and benzo-[G, H, I])-perylene (5 mg/kg), respectively. Three months later, serum IL-2 and IL-6 levels were assessed by ELISA; liver, kidney, stomach and lung tissues were subjected to histopathological examinations. Results Liver cancer incidences after benzo-[G, H, I]-perylene, benzo-(a)-pyrene (10 mg/kg), benzo-(a)-pyrene (20 mg/kg), and anthracene were 21.1, 26.3, 35.3, and 27.8%, respectively; 21.1, 0, 41.2, and 0% showed stomach cancer, respectively; 0, 0, 11.8 and 0% displayed kidney cancer, respectively. The occurrences of precancerous liver lesions for benzo-[G, H, I]-perylene, benzo-(a)-pyrene (10 mg/kg), benzo-(a)-pyrene (20 mg/kg) and anthracene groups, respectively, were 68.4, 73.7, 64.7, and 55.6%; 78.9, 68.4, 29.4, and 27.8% showed precancerous stomach lesions, while 42.1, 47.4, 58.8, and 33.3% had precancerous kidney lesions; respectively. No obvious lung lesions were found in any group. Serum IL-2 and IL-6 levels in treatment groups were significantly lower compared with control values (P<0.01). Conclusions PAHs induce cancer and precancerous lesions in the liver, stomach, and kidney. Benzo (a) pyrene initiates gastric cancer in a dose-dependent manner, but does not induce precancerous lung lesions. Lower IL-2 and IL-6 levels in treatment groups compared with controls suggest that PAHs cause overt immune inhibition. PMID:25913077

  11. Phase I Pharmacokinetic and Pharmacodynamic Study of Pazopanib in Children With Soft Tissue Sarcoma and Other Refractory Solid Tumors: A Children's Oncology Group Phase I Consortium Report

    PubMed Central

    Glade Bender, Julia L.; Lee, Alice; Reid, Joel M.; Baruchel, Sylvain; Roberts, Timothy; Voss, Stephan D.; Wu, Bing; Ahern, Charlotte H.; Ingle, Ashish M.; Harris, Pamela; Weigel, Brenda J.; Blaney, Susan M.

    2013-01-01

    Purpose Pazopanib, an oral multikinase angiogenesis inhibitor, prolongs progression-free survival in adults with soft tissue sarcoma (STS). A phase I pharmacokinetic and pharmacodynamic study of two formulations of pazopanib was performed in children with STS or other refractory solid tumors. Patients and Methods Pazopanib (tablet formulation) was administered once daily in 28-day cycles at four dose levels (275 to 600 mg/m2) using the rolling-six design. Dose determination for a powder suspension was initiated at 50% of the maximum-tolerated dose (MTD) for the intact tablet. Ten patients with STS underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scanning at baseline and 15 ± 2 days after initiation of pazopanib at the tablet MTD. Results Fifty-three patients were enrolled; 51 were eligible (26 males; median age, 12.9 years; range, 3.8 to 23.9 years). Hematologic and nonhematologic toxicities were generally mild, with dose-limiting lipase, amylase, and ALT elevation, proteinuria, and hypertension. One patient with occult brain metastasis had grade 4 intracranial hemorrhage. The MTD was 450 mg/m2 for tablet and 160 mg/m2 for suspension. Steady-state trough concentrations were reached by day 15 and did not seem to be dose dependent. One patient each with hepatoblastoma or desmoplastic small round cell tumor achieved a partial response; eight patients had stable disease for ≥ six cycles, seven of whom had sarcoma. All patients with evaluable DCE-MRI (n = 8) experienced decreases in tumor blood volume and permeability (P < .01). Placental growth factor increased, whereas endoglin and soluble vascular endothelial growth factor receptor-2 decreased (P < .01; n = 41). Conclusion Pazopanib is well tolerated in children, with evidence of antiangiogenic effect and potential clinical benefit in pediatric sarcoma. PMID:23857966

  12. Therapy of solid tumors using probiotic Symbioflor-2 – restraints and potential

    PubMed Central

    Kocijancic, Dino; Felgner, Sebastian; Frahm, Michael; Komoll, Ronja-Melinda; Iljazovic, Aida; Pawar, Vinay; Rohde, Manfred; Heise, Ulrike; Zimmermann, Kurt; Gunzer, Florian; Hammer, Juliane; Crull, Katja; Leschner, Sara; Weiss, Siegfried

    2016-01-01

    To date, virulent bacteria remain the basis of most bacteria mediated cancer therapies. For clinical application attenuation is required. However, this might result in a drastically lowered therapeutic capacity. Herein we argue that the E. coli probiotic Symbioflor-2, with a history of safe application may constitute a viable tumor therapeutic candidate. We demonstrate that Symbioflor-2 displays a highly specific tumor targeting ability as determined in murine CT26 and RenCa tumor models. The excellent specificity was ascribed to reduced levels of adverse colonization. A high safety standard was demonstrated in WT and Rag1−/− mice. Thus, Symbioflor-2 may represent an ideal tumor targeting delivery system for therapeutic molecules. Moreover, Symbioflor-2 was capable of inducing CT26 tumor clearance as result of an adjuvant effect on tumor specific CD8+ T cells analogous to the Salmonella variant SL7207. However, lower therapeutic efficacy against RenCa tumors suggested a generally reduced therapeutic potency for probiotics. Interestingly, concurrent depletion of Gr-1+ or Ly6G+ cells installed therapeutic efficacy equal to SL7207, thus highlighting the role of innate effector cells in restraining the anti-tumor effects of Symbioflor-2. Collectively, our findings argue for a strategy of safe strain application and a more sustainable use of bacteria as a delivery system for therapeutic molecules. PMID:26981777

  13. Therapy of solid tumors using probiotic Symbioflor-2: restraints and potential.

    PubMed

    Kocijancic, Dino; Felgner, Sebastian; Frahm, Michael; Komoll, Ronja-Melinda; Iljazovic, Aida; Pawar, Vinay; Rohde, Manfred; Heise, Ulrike; Zimmermann, Kurt; Gunzer, Florian; Hammer, Juliane; Crull, Katja; Leschner, Sara; Weiss, Siegfried

    2016-04-19

    To date, virulent bacteria remain the basis of most bacteria mediated cancer therapies. For clinical application attenuation is required. However, this might result in a drastically lowered therapeutic capacity. Herein we argue that the E. coli probiotic Symbioflor-2, with a history of safe application may constitute a viable tumor therapeutic candidate. We demonstrate that Symbioflor-2 displays a highly specific tumor targeting ability as determined in murine CT26 and RenCa tumor models. The excellent specificity was ascribed to reduced levels of adverse colonization. A high safety standard was demonstrated in WT and Rag1-/- mice. Thus, Symbioflor-2 may represent an ideal tumor targeting delivery system for therapeutic molecules. Moreover, Symbioflor-2 was capable of inducing CT26 tumor clearance as result of an adjuvant effect on tumor specific CD8+ T cells analogous to the Salmonella variant SL7207. However, lower therapeutic efficacy against RenCa tumors suggested a generally reduced therapeutic potency for probiotics. Interestingly, concurrent depletion of Gr-1+ or Ly6G+ cells installed therapeutic efficacy equal to SL7207, thus highlighting the role of innate effector cells in restraining the anti-tumor effects of Symbioflor-2. Collectively, our findings argue for a strategy of safe strain application and a more sustainable use of bacteria as a delivery system for therapeutic molecules. PMID:26981777

  14. Evaluation of uptake and distribution of gold nanoparticles in solid tumors

    NASA Astrophysics Data System (ADS)

    England, Christopheri G.; Gobin, André M.; Frieboes, Hermann B.

    2015-11-01

    Although nanotherapeutics offer a targeted and potentially less toxic alternative to systemic chemotherapy in cancer treatment, nanotherapeutic transport is typically hindered by abnormal characteristics of tumor tissue. Once nanoparticles targeted to tumor cells arrive in the circulation of tumor vasculature, they must extravasate from irregular vessels and diffuse through the tissue to ideally reach all malignant cells in cytotoxic concentrations. The enhanced permeability and retention effect can be leveraged to promote extravasation of appropriately sized particles from tumor vasculature; however, therapeutic success remains elusive partly due to inadequate intra-tumoral transport promoting heterogeneous nanoparticle uptake and distribution. Irregular tumor vasculature not only hinders particle transport but also sustains hypoxic tissue kregions with quiescent cells, which may be unaffected by cycle-dependent chemotherapeutics released from nanoparticles and thus regrow tumor tissue following nanotherapy. Furthermore, a large proportion of systemically injected nanoparticles may become sequestered by the reticulo-endothelial system, resulting in overall diminished efficacy. We review recent work evaluating the uptake and distribution of gold nanoparticles in pre-clinical tumor models, with the goal to help improve nanotherapy outcomes. We also examine the potential role of novel layered gold nanoparticles designed to address some of these critical issues, assessing their uptake and transport in cancerous tissue.

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

    ClinicalTrials.gov

    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

  16. Growth of tumor-infiltrating lymphocytes from human solid cancers: summary of a 5-year experience.

    PubMed

    Yannelli, J R; Hyatt, C; McConnell, S; Hines, K; Jacknin, L; Parker, L; Sanders, M; Rosenberg, S A

    1996-02-01

    Between 1989 and 1993, 255 tumor biopsies representing 4 tumor histologies (melanoma, breast cancer, colon cancer and renal cell cancer) were received by the Surgery Branch of the National Cancer Institute. Tumor-infiltrating lymphocytes (TIL) were grown from single-cell suspensions of tumor biopsies over the course of 30-45 days. The TIL were grown in medium containing IL-2. To obtain numbers suitable for therapy (>10(11)), TIL were expanded using a large-scale system of cell culture and harvesting. While the largest number of biopsies was obtained from melanoma patients, TIL were successfully grown from 160 of 255 tumor biopsies representing all 4 histologies. Under the culture conditions employed, several characteristics of TIL expansion were observed. The cell surface phenotype of TIL which grew out from the tumor biopsies was generally a mix of CD3+/CD4+ or CD3+/CD8+ lymphocytes. Only TIL from melanoma biopsies were found to be consistently cytolytic and, in many cases, lysed autologous tumor cells preferentially. Interestingly, TIL derived from extra-nodal sites of metastatic melanoma biopsies (subcutaneous, lung, bowel; 36 of 67, 54%) were more likely to have these cytolytic characteristics than TIL derived from tumor-involved lymph node biopsies (7 of 39, 18%). The present study summarizes 5 years of laboratory effort and validates the technologies developed for the large-scale growth and harvesting of TIL. In addition, it summarizes the laboratory effort supporting previously published clinical reports on TIL from our group. PMID:8621219

  17. Interstitial Laser Irradiation of Solid Tumors in Laser Assisted Cancer Immunotherapy

    NASA Astrophysics Data System (ADS)

    Evans, Lindsay; Bandyopadhyay, Pradip

    2006-03-01

    Laser Assisted Cancer Immunotherapy (LACI) is an experimental therapeutic approach in cancer treatment. Current experiments in our laboratory begin with growing superficial tumors 5 to 7 mm in diameter in BALB/C mice using the CRL-2539 cell line. Tumor sizes were measured with a vernier caliper prior to injection of light absorbing dye (Indocyanine Green, ICG) and immunoadjuvant (Glycated Chitosan, GC). These measurements were continued during the post-therapy period. After injection with the ICG and GC, the mice underwent interstitial irradiation of the tumor with a diode laser operating at 804 nm. Microthermocouples were inserted into the tumor and the laser power was varied in order to monitor the temperature and keep it within in the desired range. Tumors were irradiated at 55^o C, 65^oC, and 75^oC to find out at which temperature the maximum amount of tumor necrosis and strong immune response could be elicited. The growth of the tumors after the LACI treatment will be plotted to show the affect of the therapy at different temperatures. The data suggest that the growth rate of the tumors is slowed down considerably using this approach. * This work is supported by a grant from The National Institutes of Health.

  18. DETECTION OF HUMAN LUNG EPITHELIA CELL GROWTH FACTORS PRODUCED BY A LUNG CARCINOMA CELL LINE: USE IN CULTURE OF PRIMARY SOLID LUNG TUMORS

    EPA Science Inventory

    Serum-free medium conditioned for 72 h by a human undifferentiated adenocarcinoma of lung, Cal u 6, stimulated the colony formation of normal human bronchial epithelial cells, newly cultured cells from human solid lung tumors, and established human lung tumor cell lines, includin...

  19. The Mediating Role of Visuospatial Planning Skills on Adaptive Function Among Young-Adult Survivors of Childhood Brain Tumor.

    PubMed

    King, Tricia Z; Smith, Kristen M; Ivanisevic, Mirjana

    2015-08-01

    The Boston Qualitative Scoring System (BQSS) was used as a method to examine executive skills on the Rey-Osterrieth complex figure (ROCF). Young-adult survivors of childhood brain tumor (N = 31) and a demographically-matched comparison group (N = 33) completed the ROCF copy version and Grooved Pegboard, and informants were administered the Scales of Independent Behavior-Revised (SIB-R) and Behavior Rating Inventory of Executive Function (BRIEF). Survivors had significantly lower BQSS planning and SIB-R community living skills and greater perseveration. Mediation analyses found that BQSS planning skills mediate the relationship between group and community living skills. Convergent findings of the BRIEF Planning, and discriminant findings with the BQSS Fragmentation, BRIEF Emotional Control, and Grooved Pegboard support the planning construct as the specific mediator in this model. Together, these findings highlight the role of planning skills in adaptive functions of young-adult survivors of childhood brain tumor. PMID:26055499

  20. The EGFR-HER2 module: a stem cell approach to understanding a prime target and driver of solid tumors

    PubMed Central

    Schneider, Marlon R.; Yarden, Yosef

    2015-01-01

    The epidermal growth factor receptor (EGFR) and a co-receptor denoted HER2/ERBB2, are frequently overexpressed or mutated in solid tumors, such as carcinomas and gliomas. In line with driver roles, cancer drugs intercepting EGFR or HER2 currently outnumber therapies targeting other hubs of signal transduction. To explain the roles for EGFR and HER2 as prime drivers and targets, we take lessons from invertebrates and refer to homeostatic regulation of several mammalian tissues. The model we infer ascribes to the EGFR-HER2 module pivotal functions in rapid clonal expansion of progenitors called transient amplifying cells (TACs). Accordingly, TACs of tumors suffer from replication stress, hence accumulate mutations. In addition, several lines of evidence propose that in response to EGF and related mitogens, TACs might undergo de-differentiation into tissue stem cells, which might enable entry of oncogenic mutations into the stem cell compartment. According to this view, antibodies or kinase inhibitors targeting EGFR-HER2 effectively retard some solid tumors because they arrest mutation-enriched TACs and possibly inhibit their dedifferentiation. Deeper understanding of the EGFR-HER2 module and relations between cancer stem cells and TACs will enhance our ability to control a broad spectrum of human malignancies. PMID:26434585

  1. Golgi phosphoprotein3 overexpression is associated with poor survival in patients with solid tumors: a meta-analysis

    PubMed Central

    Jiang, Yaqi; Su, Yuqi; Zhao, Yang; Pan, Changqie; Chen, Li

    2015-01-01

    Golgi phosphoprotein3 (GOLPH3) is known as an oncoprotein and may be a prognostic biomarker in various tumors. Here we performed a meta-analysis on the association of GOLPH3 expression and survival in solid tumors. All eligible studies were identified in Embase, PubMed and Web of Science Databases up to November 2014. Data about overall survival (OS), and disease-free survival (DFS) were extracted and pooled hazard ratios (HRs) of GOLPH3 for survival were calculated by using a random-effect model. Heterogeneity and publication bias were also assessed. A total of 15 eligible studies which comprised of 2529 cases were included in this global analysis: 14 were dealing with overall survival (OS) and 6 were with disease-free survival (DFS). We found that GOLPH3 overexpression was associated with shorter OS (HR 2.487, 95% CI 1.897-3.258, P < 0.001) and DFS (HR 1.911, 95% CI 1.245-2.932, P = 0.003) in general carcinomas. Importantly, subgroup analysis suggested that overexpression of GOLPH3 correlated with shorter OS in urogenital system cancers (HR 4.258, 95% CI 1.81-4.91, P < 0.001). Moreover, publication bias was not significant (P > 0.05). In conclusion, the present meta-analysis showed that overexpression of GOLPH3 predicts poor prognosis in solid tumors. PMID:26617771

  2. The EGFR-HER2 module: a stem cell approach to understanding a prime target and driver of solid tumors.

    PubMed

    Schneider, M R; Yarden, Y

    2016-06-01

    The epidermal growth factor receptor (EGFR) and a coreceptor denoted HER2/ERBB2 are frequently overexpressed or mutated in solid tumors, such as carcinomas and gliomas. In line with driver roles, cancer drugs intercepting EGFR or HER2 currently outnumber therapies targeting other hubs of signal transduction. To explain the roles for EGFR and HER2 as prime drivers and targets, we take lessons from invertebrates and refer to homeostatic regulation of several mammalian tissues. The model we infer ascribes to the EGFR-HER2 module pivotal functions in rapid clonal expansion of progenitors called transient amplifying cells (TACs). Accordingly, TACs of tumors suffer from replication stress, and hence accumulate mutations. In addition, several lines of evidence propose that in response to EGF and related mitogens, TACs might undergo dedifferentiation into tissue stem cells, which might enable entry of oncogenic mutations into the stem cell compartment. According to this view, antibodies or kinase inhibitors targeting EGFR-HER2 effectively retard some solid tumors because they arrest mutation-enriched TACs and possibly inhibit their dedifferentiation. Deeper understanding of the EGFR-HER2 module and relations between cancer stem cells and TACs will enhance our ability to control a broad spectrum of human malignancies. PMID:26434585

  3. Pancreatoblastoma in an adult.

    PubMed

    Zhang, Di; Tang, Na; Liu, Yang; Wang, En-Hua

    2015-01-01

    Pancreatoblastoma is a malignant pancreatic tumor that rarely occurs in adults. We report a case of an adult female with pancreatoblastoma. A mass was detected in the pancreatic head using computed tomography and ultrasonography. The clinical diagnosis was a solid-pseudopapillary neoplasm of the pancreas. However, after the operation, the final diagnosis was pancreatoblastoma, which showed two lines of differentiation: Acinar differentiation and squamoid corpuscles. The patient is currently in good condition. PMID:25673604

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

    ClinicalTrials.gov

    2016-05-23

    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

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

    ClinicalTrials.gov

    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

  6. Systematic Review of Interventions to Improve the Provision of Information for Adults with Primary Brain Tumors and Their Caregivers

    PubMed Central

    Langbecker, Danette; Janda, Monika

    2014-01-01

    Background: Adults with primary brain tumors and their caregivers have significant information needs. This review assessed the effect of interventions to improve information provision for adult primary brain tumor patients and/or their caregivers. Methods: We included randomized or non-randomized trials testing educational interventions that had outcomes of information provision, knowledge, understanding, recall, or satisfaction with the intervention, for adults diagnosed with primary brain tumors and/or their family or caregivers. PubMed, MEDLINE, EMBASE, and Cochrane Reviews databases were searched for studies published between 1980 and June 2014. Results: Two randomized controlled, 1 non-randomized controlled, and 10 single group pre–post trials enrolled more than 411 participants. Five group, four practice/process change, and four individual interventions assessed satisfaction (12 studies), knowledge (4 studies), and information provision (2 studies). Nine studies reported high rates of satisfaction. Three studies showed statistically significant improvements over time in knowledge and two showed greater information was provided to intervention than control group participants, although statistical testing was not performed. Discussion: The trials assessed intermediate outcomes such as satisfaction, and only 4/13 reported on knowledge improvements. Few trials had a randomized controlled design and risk of bias was either evident or could not be assessed in most domains. PMID:25667919

  7. Effects of hyperthermia and calcium channel blocker co-therapy on mice injected with Meth A solid of Meth A ascites tumors

    SciTech Connect

    Prince, R.N.

    1986-01-01

    A study was made to determine the effectiveness of treating tumor-injected mice with verapamil, a calcium antagonist, and hyperthermia. The co-treatment reduced the incidence of tumors in animals injected with Meth A solid cells. It was shown that the decrease in tumors corresponded to increases in natural killer (NK) cell activity measured in a /sup 51/Cr release assay, in the amount of anti-Meth A antibody measured in an immunofluorescence assay, and a decrease in the amount of intra-tumor cyclic AMP measured by radioimmunoassay in co-treated compared to untreated sarcoma-injected animals. A role of the immune system for mediating the prevention of sarcoma growth was indicated by Winn assays. Splenocytes sensitized in vivo against Meth A solid cells for 14 days exhibited an enhanced cytotoxic activity against syngeneic target cells compared to untreated tumor-sensitized splenocytes following heat-drug co-treatment. It was established that the stimulation of cytotoxic T cells against a histocompatibility antigen (H-2/sup d/) present on Meth A sarcoma cells resulted in tumor cell lysis. Animals bearing established Meth A solid sarcomas did not manifest tumor regressions following the administration of co-treatment alone or the adoptive transfer of co-treated tumor-sensitized splenocytes. The growth of Meth A ascites and Meth A ascites-derived solid sarcomas, unlike Meth A solid cell tumors, were not prevented in Winn assays. Additionally, the lifespan of animals injected with Meth A ascites cells was reduced by 50% compared to animals injected with Meth A solid sarcoma cells.

  8. Attenuated and Protease-Profile Modified Sendai Virus Vectors as a New Tool for Virotherapy of Solid Tumors

    PubMed Central

    Zimmermann, Martina; Armeanu-Ebinger, Sorin; Bossow, Sascha; Lampe, Johanna; Smirnow, Irina; Schenk, Andrea; Lange, Sebastian; Weiss, Thomas S.; Neubert, Wolfgang; Lauer, Ulrich M.; Bitzer, Michael

    2014-01-01

    Multiple types of oncolytic viruses are currently under investigation in clinical trials. To optimize therapeutic outcomes it is believed that the plethora of different tumor types will require a diversity of different virus types. Sendai virus (SeV), a murine parainfluenza virus, displays a broad host range, enters cells within minutes and already has been applied safely as a gene transfer vector in gene therapy patients. However, SeV spreading naturally is abrogated in human cells due to a lack of virus activating proteases. To enable oncolytic applications of SeV we here engineered a set of novel recombinant vectors by a two-step approach: (i) introduction of an ubiquitously recognized cleavage-motive into SeV fusion protein now enabling continuous spreading in human tissues, and (ii) profound attenuation of these rSeV by the knockout of viral immune modulating accessory proteins. When employing human hepatoma cell lines, newly generated SeV variants now reached high titers and induced a profound tumor cell lysis. In contrast, virus release from untransformed human fibroblasts or primary human hepatocytes was found to be reduced by about three log steps in a time course experiment which enables the cumulation of kinetic differences of the distinct phases of viral replication such as primary target cell infection, target cell replication, and progeny virus particle release. In a hepatoma xenograft animal model we found a tumor-specific spreading of our novel recombinant SeV vectors without evidence of biodistribution into non-malignant tissues. In conclusion, we successfully developed novel tumor-selective oncolytic rSeV vectors, constituting a new tool for virotherapy of solid tumors being ready for further preclinical and clinical development to address distinct tumor types. PMID:24598703

  9. Attenuated and protease-profile modified sendai virus vectors as a new tool for virotherapy of solid tumors.

    PubMed

    Zimmermann, Martina; Armeanu-Ebinger, Sorin; Bossow, Sascha; Lampe, Johanna; Smirnow, Irina; Schenk, Andrea; Lange, Sebastian; Weiss, Thomas S; Neubert, Wolfgang; Lauer, Ulrich M; Bitzer, Michael

    2014-01-01

    Multiple types of oncolytic viruses are currently under investigation in clinical trials. To optimize therapeutic outcomes it is believed that the plethora of different tumor types will require a diversity of different virus types. Sendai virus (SeV), a murine parainfluenza virus, displays a broad host range, enters cells within minutes and already has been applied safely as a gene transfer vector in gene therapy patients. However, SeV spreading naturally is abrogated in human cells due to a lack of virus activating proteases. To enable oncolytic applications of SeV we here engineered a set of novel recombinant vectors by a two-step approach: (i) introduction of an ubiquitously recognized cleavage-motive into SeV fusion protein now enabling continuous spreading in human tissues, and (ii) profound attenuation of these rSeV by the knockout of viral immune modulating accessory proteins. When employing human hepatoma cell lines, newly generated SeV variants now reached high titers and induced a profound tumor cell lysis. In contrast, virus release from untransformed human fibroblasts or primary human hepatocytes was found to be reduced by about three log steps in a time course experiment which enables the cumulation of kinetic differences of the distinct phases of viral replication such as primary target cell infection, target cell replication, and progeny virus particle release. In a hepatoma xenograft animal model we found a tumor-specific spreading of our novel recombinant SeV vectors without evidence of biodistribution into non-malignant tissues. In conclusion, we successfully developed novel tumor-selective oncolytic rSeV vectors, constituting a new tool for virotherapy of solid tumors being ready for further preclinical and clinical development to address distinct tumor types. PMID:24598703

  10. A facile preparation method of a PFC-containing nano-sized emulsion for theranostics of solid tumors.

    PubMed

    Shiraishi, Kouichi; Endoh, Reiko; Furuhata, Hiroshi; Nishihara, Masamichi; Suzuki, Ryo; Maruyama, Kazuo; Oda, Yusuke; Jo, Jun-ichiro; Tabata, Yasuhiko; Yamamoto, Jun; Yokoyama, Masayuki

    2011-12-15

    Theranostics means a therapy conducted in a diagnosis-guided manner. For theranostics of solid tumors by means of ultrasound, we designed a nano-sized emulsion containing perfluoropentane (PFC5). This emulsion can be delivered into tumor tissues through the tumor vasculatures owing to its nano-size, and the emulsion is transformed into a micron-sized bubble upon sonication through phase transition of PFC5. The micron-sized bubbles can more efficiently absorb ultrasonic energy for better diagnostic images and can exhibit more efficient ultrasound-driven therapeutic effects than nano-sized bubbles. For more efficient tumor delivery, smaller size is preferable, yet the preparation of a smaller emulsion is technically more difficult. In this paper, we used a bath-type sonicator to successfully obtain small PFC5-containing emulsions in a diameter of ca. 200nm. Additionally, we prepared these small emulsions at 40°C, which is above the boiling temperature of PFC5. Accordingly, we succeeded in obtaining very small nano-emulsions for theranostics through a very facile method. PMID:22023827

  11. More than a Decade of Tyrosine Kinase Inhibitors in the Treatment of Solid Tumors: What We Have Learned and What the Future Holds

    PubMed Central

    Vergoulidou, Maria

    2015-01-01

    The use of tyrosine kinase inhibitors (TKIs) in the treatment of solid tumors is the expected standard of care for many types of tumors. Since the description of signal transduction pathways, followed by the development of small molecules designed to inhibit those pathways, there has been significant improvement not only in progression-free survival and overall survival but also in aiming toward chemotherapy-free treatment of solid tumors to maximize quality of life. This article reviews available TKIs and discusses toxicity, dosing, and resistance. PMID:26483606

  12. Flow cytometric monitoring of hormone receptor expression in human solid tumors

    NASA Astrophysics Data System (ADS)

    Krishan, Awtar

    2002-05-01

    Hormone receptor expression in human breast and prostate tumors is of diagnostic and therapeutic importance. With the availability of anti-estrogen, androgen and progesterone antibodies, immunohistochemistry has become a standard tool for determination of receptor expression in human tumor biopsies. However, this method is dependent on examination of a small number of cells under a microscope and the data obtained in most cases is not quantitative. As most of the commercially used anti-hormone antibodies have nuclear specificity, we have developed methods for isolation and antigen unmasking of nuclei from formalin fixed/paraffin embedded archival human tumors. After immunostaining with the antibodies and propidium iodide (for DNA content and cell cycle analysis), nuclei are analyzed by multiparametric laser flow cytometry for hormone receptor expression, DNA content, aneuploidy and cell cycle determination. These multiparametric methods are especially important for retrospective studies seeking to correlate hormone receptor expression with clinical response to anti-hormonal therapy of human breast and prostate tumors.

  13. Molecular mechanisms of lymphatic metastasis in solid tumors of the gastrointestinal tract

    PubMed Central

    Langheinrich, Melanie C; Schellerer, Vera; Perrakis, Aristotelis; Lohmüller, Clemens; Schildberg, Claus; Naschberger, Elisabeth; Stürzl, Michael; Hohenberger, Werner; Croner, Roland S

    2012-01-01

    Tumor cell dissemination from the primary tumor site to distant organs is one of the characteristic properties of malignant tumors and represents a crucial step in the progression of disease. Although the pattern of spread may vary in different types of carcinomas, dissemination via the lymphatic system represents a common event in metastasis. The extent of lymph node metastasis is one of the major determinants for the prognosis of patients with gastrointestinal carcinomas and guides the therapeutically management. During the last decades, significant attention has been given to the molecular mechanisms that control lymphatic metastasis. The process of lymphangiogenesis has come into the focus. Lymphangiogenesis, the formation of newly lymphatics, comprises a series of complex cellular events and is controlled by a balance between pro- and anti-lymphangiogenic signals. This article will briefly describe the lymphatic system and then provide an overview of the molecular players involved in tumor lymphangiogenesis. PMID:22977656

  14. Phthalocyanine Labels for Near-Infrared Fluorescence Imaging of Solid Tumors.

    PubMed

    Lobo, Ana C S; Silva, Alexandre D; Tomé, Vanessa A; Pinto, Sara M A; Silva, Elsa F F; Calvete, Mário J F; Gomes, Célia M F; Pereira, Mariette M; Arnaut, Luis G

    2016-05-26

    Diamagnetic metal complexes of phthalocyanines with n-butoxyl groups in all the α-benzo positions of the macrocycle skeleton, MPc(OBu)8, have strong near-infrared absorptions and intense fluorescences that are Stokes shifted by more than 15 nm. Interestingly, the silicon complex 6 is also remarkably photostable and nontoxic. The use of 6 in the fluorescence imaging of BALB/c mice bearing a 4T1-luc2 tumor in the mammary fat pad unambiguously revealed the presence of the tumor when it was only 1 mm in diameter and was not visible with the naked eye. Compound 6 has an intrinsic ability to accumulate in the tumor, adequate spectroscopic properties, and excellent stability to function as a NIR fluorescent label in the early detection of tumors. PMID:27070884

  15. Atypical teratoid/rhabdoid tumor in sellar turcica in an adult: A case report and review of the literature

    PubMed Central

    Shitara, Satoshi; Akiyama, Yoshinori

    2014-01-01

    Background: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare central nervous system tumor composed of primitive rhabdoid cells that may differentiate along neuroectodermal, mesenchymal and epithelial lineages. AT/RT in adults is rare but not completely exceptional. It generally arises from the posterior fossa of infants, but the broad majority of the reported AT/RT in adults manifested supratentorially with the exception of four cases that arose in the cerebellum and two that arose in the spinal cord. Case Description: A 44-year-old female complained of visual disturbance. We performed craniotomies twice and removed partially for each time, but any malignant cells were not found in the specimens. Finally, we determined histological diagnosis from the extended lesion. She died of respiratory failure 17 months after the initial treatment. Conclusion: AT/RT should be considered in the differential diagnosis of a sellar lesion in adult patients. However AT/RT is rare in adults, the appropriate immunohistochemical evaluation should be performed to diagnose this rare entity. PMID:24949218

  16. A Stem Cell-Like Chromatin Pattern May Predispose Tumor Suppressor Genes to DNA Hypermethylation and Silencing in Adult Cancers

    PubMed Central

    Ohm, Joyce E.; McGarvey, Kelly M.; Yu, Xiaobing; Cheng, Linzhao; Schuebel, Kornel E.; Cope, Leslie; Mohammad, Helai P.; Chen, Wei; Daniel, Vincent C.; Yu, Wayne; Berman, David M.; Jenuwein, Thomas; Pruitt, Kevin; Sharkis, Saul J.; Watkins, D. Neil; Herman, James G.; Baylin, Stephen B.

    2009-01-01

    Adult cancers may derive from stem or early progenitor cells1,2. Epigenetic modulation of gene expression is essential for normal function of these early cells, but is highly abnormal in cancers, which often exhibit aberrant promoter CpG island hypermethylation and transcriptional silencing of tumor suppressor genes and pro-differentiation factors3-5. We find that, for such genes, both normal and malignant embryonic cells generally lack the gene DNA hypermethylation found in adult cancers. In embryonic stem (ES) cells, these genes are held in a “transcription ready” state mediated by a “bivalent” promoter chromatin pattern consisting of the repressive polycomb group (PcG) H3K27me mark plus the active mark, H3K4me. However, embryonic carcinoma (EC) cells add two key repressive marks, H3K9me2 and H3K9me3, both associated with DNA hypermethylated genes in adult cancers6-8. We hypothesize that cell chromatin patterns and transient silencing of these important growth regulatory genes in stem or progenitor cells of origin for cancer may leave these genes vulnerable to aberrant DNA hypermethylation and heritable gene silencing in adult tumors. PMID:17211412

  17. International retrospective study of over 1000 adults with anaplastic oligodendroglial tumors

    PubMed Central

    Lassman, Andrew B.; Iwamoto, Fabio M.; Cloughesy, Timothy F.; Aldape, Kenneth D.; Rivera, Andreana L.; Eichler, April F.; Louis, David N.; Paleologos, Nina A.; Fisher, Barbara J.; Ashby, Lynn S.; Cairncross, J. Gregory; Roldán, Gloria B.; Wen, Patrick Y.; Ligon, Keith L.; Schiff, David; Robins, H. Ian; Rocque, Brandon G.; Chamberlain, Marc C.; Mason, Warren P.; Weaver, Susan A.; Green, Richard M.; Kamar, Francois G.; Abrey, Lauren E.; DeAngelis, Lisa M.; Jhanwar, Suresh C.; Rosenblum, Marc K.; Panageas, Katherine S.

    2011-01-01

    Treatment for newly diagnosed anaplastic oligodendroglial tumors is controversial. Radiotherapy (RT) alone and in combination with chemotherapy (CT) are the most well studied strategies. However, CT alone is often advocated, especially in cases with 1p19q codeletion. We retrospectively identified 1013 adults diagnosed from 1981–2007 treated initially with RT alone (n = 200), CT + RT (n = 528), CT alone (n = 201), or other strategies (n = 84). Median overall survival (OS) was 6.3 years and time to progression (TTP) was 3.1 years. 1p19q codeletion correlated with longer OS and TTP than no 1p or 19q deletion. In codeleted cases, median TTP was longer following CT + RT (7.2 y) than following CT (3.9 y, P = .003) or RT (2.5 y, P < .001) alone but without improved OS; median TTP was longer following treatment with PCV alone than temozolomide alone (7.6 vs. 3.3 y, P = .019). In cases with no deletion, median TTP was longer following CT + RT (3.1 y) than CT (0.9 y, P = .0124) or RT (1.1 y, P < .0001) alone; OS also favored CT + RT (median 5.0 y) over CT (2.2 y, P = .02) or RT (1.9 y, P < .0001) alone. In codeleted cases, CT alone did not appear to shorten OS in comparison with CT + RT, and PCV appeared to offer longer disease control than temozolomide but without a clear survival advantage. Combined CT + RT led to longer disease control and survival than did CT or RT alone in cases with no 1p19q deletion. Ongoing trials will address these issues prospectively. PMID:21636710

  18. Variation in Insurance Status by Patient Demographics and Tumor Site Among Nonelderly Adult Patients With Cancer

    PubMed Central

    Grant, Stephen R.; Walker, Gary V.; Guadagnolo, B. Ashleigh; Koshy, Matthew; Allen, Pamela K.; Mahmood, Usama

    2016-01-01

    BACKGROUND In the United States, an estimated 48 million individuals live without health insurance. The purpose of the current study was to explore the variation in insurance status by patient demographics and tumor site among nonelderly adult patients with cancer. METHODS A total of 688,794 patients aged 18 to 64 years who were diagnosed with one of the top 25 incident cancers (representing 95% of all cancer diagnoses) between 2007 and 2010 in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patient characteristics included age, race, sex, marital status, and rural or urban residence. County-level demographics included percent poverty level. Insurance status was defined as having non-Medicaid insurance, Medicaid coverage, or no insurance. RESULTS On multivariate logistic regression analyses, younger age, male sex, nonwhite race, being unmarried, residence in counties with higher levels of poverty, and rural residence were associated with being uninsured versus having non-Medicaid insurance (all P <.001). The highest rates of non-Medicaid insurance were noted among patients with prostate cancer (92.3%), melanoma of the skin (92.5%), and thyroid cancer (89.5%), whereas the lowest rates of non-Medicaid insurance were observed among patients with cervical cancer (64.2%), liver cancer (67.9%), and stomach cancer (70.9%) (P <.001). Among uninsured individuals, the most prevalent cancers were lung cancer (14.9%), colorectal cancer (12.1%), and breast cancer (10.2%) (P <.001). Lung cancer caused the majority of cancer mortality in all insurance groups. CONCLUSIONS Rates of insurance coverage vary greatly by demographics and by cancer type. The expansion of health insurance coverage would be expected to disproportionally benefit certain demographic populations and cancer types. PMID:25917222

  19. Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy

    PubMed Central

    2010-01-01

    Background Electrochemotherapy treats tumors by combining specific chemotherapeutic drugs with an intracellular target and electric pulses, which increases drug uptake into the tumor cells. Electrochemotherapy has been successfully used for treatment of easily accessible superficial tumor nodules. In this paper, we present the first case of deep-seated tumor electrochemotherapy based on numerical treatment planning. Methods The aim of our study was to treat a melanoma metastasis in the thigh of a patient. Treatment planning for electrode positioning and electrical pulse parameters was performed for two different electrode configurations: one with four and another with five long needle electrodes. During the procedure, the four electrode treatment plan was adopted and the patient was treated accordingly by electrochemotherapy with bleomycin. The response to treatment was clinically and radiographically evaluated. Due to a partial response of the treated tumor, the metastasis was surgically removed after 2 months and pathological analysis was performed. Results A partial response of the tumor to electrochemotherapy was obtained. Histologically, the metastasis showed partial necrosis due to electrochemotherapy, estimated to represent 40-50% of the tumor. Based on the data obtained, we re-evaluated the electrical treatment parameters in order to correlate the treatment plan with the clinical response. Electrode positions in the numerical model were updated according to the actual positions during treatment. We compared the maximum value of the measured electric current with the current predicted by the model and good agreement was obtained. Finally, tumor coverage with an electric field above the reversible threshold was recalculated and determined to be approximately 94%. Therefore, according to the calculations, a small volume of tumor cells remained viable after electrochemotherapy, and these were sufficient for tumor regrowth. Conclusions In this, the first

  20. Blood outgrowth endothelial cell-based systemic delivery of antiangiogenic gene therapy for solid tumors

    PubMed Central

    Bodempudi, Vidya; Ohlfest, John R.; Terai, Kaoru; Zamora, Edward A.; Vogel, Rachel Isaksson; Gupta, Kalpna; Hebbel, Robert P.; Dudek, Arkadiusz Z.

    2016-01-01

    Endothelial cells and endothelial cell precursors encoding a therapeutic gene have induced antitumor responses in preclinical models. Culture of peripheral blood provides a rich supply of autologous, highly proliferative endothelial cells, also referred to as blood outgrowth endothelial cells (BOECs). The aim of this study was to evaluate a novel antiangiogenic strategy using BOECs expressing fms-like tyrosine kinase-1 (sFlt1) and/or angiostatin-endostatin (AE) fusion protein. Conditioned medium from BOECs expressing sFlt1 or AE suppressed in vitro growth of pulmonary vein endothelial cells by 70% compared to conditioned medium from non-transduced BOEC controls. RT-PCR analysis indicated that systemically administered BOECs proliferated in tumor tissue relative to other organs in C3TAG mice with spontaneous mammary tumors. Tumor volume was reduced by half in C3TAG mice and in mice bearing established lung or pancreatic tumors in response to treatment with sFlt1-BOECs, AE-BOECs or their combination. Studies of tumor vascular density confirmed that angiogenic inhibition contributed to slowed tumor growth. In an orthotopic model of glioma, the median survival of mice treated with sFlt1-BOECs was double that of mice receiving no BOEC treatment (p=0.0130). These results indicate that further research is warranted to develop BOECs for clinical application. PMID:20725100

  1. An Adaptive Multigrid Algorithm for Simulating Solid Tumor Growth Using Mixture Models

    PubMed Central

    Wise, S.M.; Lowengrub, J.S.; Cristini, V.

    2010-01-01

    In this paper we give the details of the numerical solution of a three-dimensional multispecies diffuse interface model of tumor growth, which was derived in (Wise et al., J. Theor. Biol. 253 (2008)) and used to study the development of glioma in (Frieboes et al., NeuroImage 37 (2007) and tumor invasion in (Bearer et al., Cancer Research, 69 (2009)) and (Frieboes et al., J. Theor. Biol. 264 (2010)). The model has a thermodynamic basis, is related to recently developed mixture models, and is capable of providing a detailed description of tumor progression. It utilizes a diffuse interface approach, whereby sharp tumor boundaries are replaced by narrow transition layers that arise due to differential adhesive forces among the cell-species. The model consists of fourth-order nonlinear advection-reaction-diffusion equations (of Cahn-Hilliard-type) for the cell-species coupled with reaction-diffusion equations for the substrate components. Numerical solution of the model is challenging because the equations are coupled, highly nonlinear, and numerically stiff. In this paper we describe a fully adaptive, nonlinear multigrid/finite difference method for efficiently solving the equations. We demonstrate the convergence of the algorithm and we present simulations of tumor growth in 2D and 3D that demonstrate the capabilities of the algorithm in accurately and efficiently simulating the progression of tumors with complex morphologies. PMID:21076663

  2. An Adaptive Multigrid Algorithm for Simulating Solid Tumor Growth Using Mixture Models.

    PubMed

    Wise, S M; Lowengrub, J S; Cristini, V

    2011-01-01

    In this paper we give the details of the numerical solution of a three-dimensional multispecies diffuse interface model of tumor growth, which was derived in (Wise et al., J. Theor. Biol. 253 (2008)) and used to study the development of glioma in (Frieboes et al., NeuroImage 37 (2007) and tumor invasion in (Bearer et al., Cancer Research, 69 (2009)) and (Frieboes et al., J. Theor. Biol. 264 (2010)). The model has a thermodynamic basis, is related to recently developed mixture models, and is capable of providing a detailed description of tumor progression. It utilizes a diffuse interface approach, whereby sharp tumor boundaries are replaced by narrow transition layers that arise due to differential adhesive forces among the cell-species. The model consists of fourth-order nonlinear advection-reaction-diffusion equations (of Cahn-Hilliard-type) for the cell-species coupled with reaction-diffusion equations for the substrate components. Numerical solution of the model is challenging because the equations are coupled, highly nonlinear, and numerically stiff. In this paper we describe a fully adaptive, nonlinear multigrid/finite difference method for efficiently solving the equations. We demonstrate the convergence of the algorithm and we present simulations of tumor growth in 2D and 3D that demonstrate the capabilities of the algorithm in accurately and efficiently simulating the progression of tumors with complex morphologies. PMID:21076663

  3. Ultrasonic rf-based imaging for the purposes of characterizing the microstructure of solid tumors

    NASA Astrophysics Data System (ADS)

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

    2002-04-01

    Eight retired breeder rats were acquired that had developed spontaneous mammary tumors. Tumors were diagnosed microscopically as mammary gland fibroadenomas. Two-dimensional gray-scale B-mode images of the tumors in the rats were constructed from backscattered echoes using an 8 MHz (90% bandwidth) single element ultrasonic transducer. From the gray-scale B-mode images, regions-of-interest (ROIs) were selected in the tumors and surrounding tissues. The power spectra of backscattered RF echoes gated from the ROIs were used to estimate the average scatterer diameters and concentrations. A unique estimation scheme was used to obtain the average scatterer diameters and concentrations. The average scatterer diameter was related to the slope of the best-fit line to the reduced measured power spectrum versus the frequency squared. The scatterer concentration was determined from the intercept of the best-fit line. The reduced measured power spectrum is the measured power spectrum minus 40 log of the frequency. Parametric B-mode images were constructed by converting ROI boxes into colored pixels. The color of the pixels was related to the estimated scatterer properties. The images showed a distinct difference between the tumor and surrounding healthy tissues. Scatterer sizes inside the tumor were on average 30% larger than scatterer sizes in surrounding normal tissues.

  4. Comprehensive Screening of Gene Copy Number Aberrations in Formalin-Fixed, Paraffin-Embedded Solid Tumors Using Molecular Inversion Probe-Based Single-Nucleotide Polymorphism Array.

    PubMed

    Singh, Rajesh R; Mehrotra, Meenakshi; Chen, Hui; Almohammedsalim, Alaa A; Sahin, Ayesagul; Bosamra, Alex; Patel, Keyur P; Routbort, Mark J; Lu, Xinyan; Ronald, Abraham; Mishra, Bal Mukund; Virani, Shumaila; Medeiros, L Jeffrey; Luthra, Rajyalakshmi

    2016-09-01

    Gene copy number aberrations (CNAs) represent a major class of cancer-related genomic alterations that drive solid tumors. Comprehensive and sensitive detection of CNAs is challenging because of often low quality and quantity of DNA isolated from the formalin-fixed, paraffin-embedded (FFPE) solid tumor samples. Here, in a clinical molecular diagnostic laboratory, we tested the utility and validated a molecular inversion probe-based (MIP) array to routinely screen for CNAs in solid tumors. Using low-input FFPE DNA, the array detects genome-wide CNAs with a special focus on 900 cancer-related genes. A cohort of 76 solid tumors of various types and tumor cellularity (20% to 100%), and four cancer cell lines were used. These harbored CNAs in clinically important genes (ERBB2, EGFR, FGFR1, KRAS, MYC) as detected by orthogonal techniques like next-generation sequencing or fluorescence in situ hybridization. Results of the MIP array were concordant with results from orthogonal techniques, and also provided additional information regarding the allelic nature of the CNAs. Limit-of-detection and assay reproducibility studies showed a high degree of sensitivity and reproducibility of detection, respectively. FFPE compatibility, ability to detect CNAs with high sensitivity, accuracy, and provide valuable information such as loss of heterozygosity along with relatively short turnaround times makes the MIP array a desirable clinical platform for routine screening of solid tumors in a clinical laboratory. PMID:27392636

  5. Hyaluronic acid based self-assembling nanosystems for CD44 target mediated siRNA delivery to solid tumors

    PubMed Central

    Ganesh, Shanthi; Iyer, Arun K.; Morrissey, David V.; Amiji, Mansoor M.

    2013-01-01

    Anticancer therapeutics employing RNA interference mechanism holds promising potentials for sequence-specific silencing of target genes. However targeted delivery of siRNAs to tumor tissues and cells and more importantly, their intracellular release at sites of interest still remains a major challenge that needs to be addressed before this technique could become a clinically viable option. In the current study, we have engineered and screened a series of CD44 targeting hyaluronic acid (HA) based self-assembling nanosystems for targeted siRNA delivery. The HA polymer was functionalized with lipids of varying carbon chain lengths/nitrogen content, as well as polyamines for assessing siRNA encapsulation. From the screens, several HA-derivatives were identified that could stably encapsulate/complex siRNAs and form self-assembled nanosystems, as determined by gel retardation assays and dynamic light scattering. Many HA derivatives could transfect siRNAs into cancer cells overexpressing CD44 receptors. Interestingly, blocking the CD44 receptors on the cells using free excess soluble HA prior to incubation of cy3-labeled-siRNA loaded HA nano-assemblies resulted in >90% inhibition of the receptor mediated uptake, confirming target specificity. In addition, SSB/PLK1 siRNA encapsulated in HA-PEI/PEG nanosystems demonstrated dose dependent and target specific gene knockdown in both sensitive and resistant A549 lung cancer cells overexpressing CD44 receptors. More importantly, these siRNA encapsulated nanosystems demonstrated tumor selective uptake and target specific gene knock down in vivo in solid tumors as well as in metastatic tumors. The HA based nanosystems thus portend to be promising siRNA delivery vectors for systemic targeting of CD44 overexpressing cancers including tumor initiating (stem-) cells and metastatic lesions. PMID:23410679

  6. TORC1/2 Inhibitor MLN0128 and Bevacizumab in Treating Patients With Recurrent Glioblastoma or Advanced Solid Tumors

    ClinicalTrials.gov

    2016-06-17

    Adult Glioblastoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Solid Neoplasm; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  7. Increase in Testicular Germ Cell Tumor Incidence among Hispanic Adolescents and Young Adults in the United States

    PubMed Central

    Chien, Franklin L.; Schwartz, Stephen M.; Johnson, Rebecca H.

    2014-01-01

    Background While rising incidence rates of testicular germ cell tumors have been well documented in white men, relatively little is known about rates in men of Hispanic origin. In the current study, we compared germ cell tumor trends between men of Hispanic and non-Hispanic origin as a function of age at diagnosis. Methods We analyzed testicular germ cell tumor incidence trends in white men by Hispanic ethnicity in two datasets of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program, spanning 1992 to 2010 and 2000 to 2010, and sampling 15% and 28% of the United States population, respectively. Rates were age-adjusted to the year 2000 United States standard population. Results Between 1992 and 2010, the annual incidence of testicular germ cell tumors in 15- to 39-year-old Hispanic whites increased 58% from 7.18 cases per 100,000 in 1992 to 11.34 cases per 100,000 by 2010 (p < 1×10−9). Their incidence rates increased in metropolitan areas for both seminoma and non-seminoma subtypes and for all stages at diagnosis. In the same 19-year interval, incidence among non-Hispanic white young adults increased 7%, from 12.41 to 13.22 per 100,000. During the 2000 to 2010 interval, no significant trends were observed in incidence among non-Hispanic whites. Conclusion There has been a recent substantial increase in testicular germ cell tumor incidence among Hispanic adolescents and young adults in the United States. Similar trends were not observed in non-Hispanic whites. PMID:25044313

  8. Identification of Sleeping Beauty Transposon Insertions in Solid Tumors using Linker-mediated PCR

    PubMed Central

    Janik, Callie L.; Starr, Timothy K.

    2013-01-01

    Genomic, proteomic, transcriptomic, and epigenomic analyses of human tumors indicate that there are thousands of anomalies within each cancer genome compared to matched normal tissue. Based on these analyses it is evident that there are many undiscovered genetic drivers of cancer1. Unfortunately these drivers are hidden within a much larger number of passenger anomalies in the genome that do not directly contribute to tumor formation. Another aspect of the cancer genome is that there is considerable genetic heterogeneity within similar tumor types. Each tumor can harbor different mutations that provide a selective advantage for tumor formation2. Performing an unbiased forward genetic screen in mice provides the tools to generate tumors and analyze their genetic composition, while reducing the background of passenger mutations. The Sleeping Beauty (SB) transposon system is one such method3. The SB system utilizes mobile vectors (transposons) that can be inserted throughout the genome by the transposase enzyme. Mutations are limited to a specific cell type through the use of a conditional transposase allele that is activated by Cre Recombinase. Many mouse lines exist that express Cre Recombinase in specific tissues. By crossing o