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Sample records for advanced stage tumors

  1. Prospects in cancer immunotherapy: treating advanced stage disease or preventing tumor recurrence?

    PubMed

    Manjili, Masoud H; Payne, Kyle K

    2015-06-01

    Human vaccines against infectious agents are often effective in a prophylactic setting. However, they are usually not effective when used post-exposure. Rabies vaccine is one of the exceptions, which can be used post-exposure, but is effective only when used in combination with other treatments. Similar results have been obtained with cancer vaccines and immunotherapies. Cancer immunotherapies generally prolong patients' survival when they are used during advanced stage disease. The potential of immunotherapy to cure cancer could be revealed when it is applied in a prophylactic setting. This article provides a brief overview of cancer immunotherapeutics and suggests that immunotherapy can cure cancer if used at the right time against the right target; we suggest that targeting cancer during dormancy in order to prevent tumor recurrence as advanced stage disease is potentially curative.

  2. Primary Tumor Site as a Predictor of Treatment Outcome for Definitive Radiotherapy of Advanced-Stage Oral Cavity Cancers

    SciTech Connect

    Lin, Chien-Yu; Wang, Hung-Ming; Kang, Chung-Jan; Lee, Li-Yu; Huang, Shiang-Fu; Fan, Kang-Hsing; Chen, Eric Yen-Chao

    2010-11-15

    Purpose: To evaluate the outcome of definitive radiotherapy (RT) for oral cavity cancers and to assess prognostic factors. Methods and Materials: Definitive RT was performed on 115 patients with oral cavity cancers at Stages III, IVA, and IVB, with a distribution of 6%, 47%, and 47%, respectively. The median dose of RT was 72Gy (range, 62-76Gy). Cisplatin-based chemotherapy was administered to 95% of the patients. Eleven patients underwent salvage surgery after RT failure. Results: Eight-eight (76.5%) patients responded partially and 23 (20%) completely; of the patients who responded, 18% and 57%, respectively, experienced a durable effect of treatment. The 3-year overall survival, disease-specific survival, and progression-free survival were 22%, 27%, and 25%, respectively. The 3-year PFS rates based on the primary tumor sites were as follows: Group I (buccal, mouth floor, and gum) 51%, Group II (retromolar and hard palate) 18%, and Group III (tongue and lip) 6% (p < 0.0001). The 3-year progression-free survival was 41% for N0 patients and 19% for patients with N+ disease (p = 0.012). The T stage and RT technique did not affect survival. The patients who underwent salvage surgery demonstrated better 3-year overall survival and disease-specific survival (53% vs. 19%, p = 0.015 and 53% vs. 24%, p = 0.029, respectively). Subsite group, N+, and salvage surgery were the only significant prognostic factors for survival after multivariate analysis. Conclusion: The primary tumor site and neck stage are prognostic predictors in advanced-stage oral cancer patients who received radical RT. The primary tumor extension and RT technique did not influence survival.

  3. Stages of Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  4. Prospective assessment of the prognostic value of circulating tumor cells and their clusters in patients with advanced-stage breast cancer.

    PubMed

    Mu, Zhaomei; Wang, Chun; Ye, Zhong; Austin, Laura; Civan, Jesse; Hyslop, Terry; Palazzo, Juan P; Jaslow, Rebecca; Li, Bingshan; Myers, Ronald E; Jiang, Juntao; Xing, Jinliang; Yang, Hushan; Cristofanilli, Massimo

    2015-12-01

    The enumeration of circulating tumor cells (CTCs) provides important prognostic values in patients with metastatic breast cancer. Recent studies indicate that individual CTCs form clusters and these CTC-clusters play an important role in tumor metastasis. We aimed to assess whether quantification of CTC-clusters provides additional prognostic value over quantification of individual CTCs alone. In 115 prospectively enrolled advanced-stage (III and IV) breast cancer patients, CTCs and CTC-clusters were counted in 7.5 ml whole blood using the CellSearch system at baseline before first-line therapy. The individual and joint effects of CTC and CTC cluster counts on patients' progression-free survival (PFS) were analyzed using Cox proportional hazards modeling. Of the 115 patients, 36 (31.3 %) had elevated baseline CTCs (≥5 CTCs/7.5 ml) and 20 (17.4 %) had CTC-clusters (≥2 CTCs/7.5 ml). Patients with elevated CTCs and CTC-clusters both had worse PFS with a hazard ratio (HR) of 2.76 [95 % confidence interval (CI) 1.57-4.86, P log-rank = 0.0005] and 2.83 (1.48-5.39, P log-rank = 0.001), respectively. In joint analysis, compared with patients with <5 CTCs and without CTC-clusters, patients with elevated CTCs but without clusters, and patients with elevated CTCs and with clusters, had an increasing trend of progression risk, with an HR of 2.21 (1.02-4.78) and 3.32 (1.68-6.55), respectively (P log-rank = 0.0006, P trend = 0.0002). The additional prognostic value of CTC-clusters appeared to be more pronounced in patients with inflammatory breast cancer (IBC), the most aggressive form of breast cancer with the poorest survival. Baseline counts of both individual CTCs and CTC-clusters were associated with PFS in advanced-stage breast cancer patients. CTC-clusters might provide additional prognostic value compared with CTC enumeration alone, in patients with elevated CTCs.

  5. Stages of Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... symptoms of GI carcinoid tumors in the jejunum (middle part of the small intestine) and ileum (last part ... Treatment of GI carcinoid tumors in the jejunum (middle part of the small intestine) and ileum (last part ...

  6. Pancreatic endocrine tumors: recent advances.

    PubMed

    Jensen, R T

    1999-01-01

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

  7. TNM Staging of Pancreatic Neuroendocrine Tumors

    PubMed Central

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

    2015-01-01

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

  8. Photodynamic therapy of advanced malignant tumors

    NASA Astrophysics Data System (ADS)

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

    1993-03-01

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

  9. A Decade of Experience in Developing Preclinical Models of Advanced- or Early-Stage Spontaneous Metastasis to Study Antiangiogenic Drugs, Metronomic Chemotherapy, and the Tumor Microenvironment.

    PubMed

    Kerbel, Robert S

    2015-01-01

    The clinical circumstance of treating spontaneous metastatic disease, after resection of primary tumors, whether advanced/overt or microscopic in nature, is seldom modeled in mice and may be a major factor in explaining the frequent discordance between preclinical and clinical therapeutic outcomes where the trend is "overprediction" of positive results in preclinical mouse model studies. To evaluate this hypothesis, a research program was initiated a decade ago to develop multiple models of metastasis in mice, using variants of human tumor cell lines selected in vivo for enhanced spontaneous metastatic aggressiveness after surgical resection of established orthotopic primary tumors. These models have included breast, renal, and colorectal carcinomas; ovarian cancer (but without prior surgery); and malignant melanoma. They have been used primarily for experimental therapeutic investigations involving various antiangiogenic drugs alone or with chemotherapy, especially "metronomic" low-dose chemotherapy. The various translational studies undertaken have revealed a number of clinically relevant findings. These include the following: (i) the potential of metronomic chemotherapy, especially when combined with a vascular endothelial growth factor pathway targeting drug to successfully treat advanced metastatic disease; (ii) the development of relapsed spontaneous brain metastases in mice with melanoma or breast cancer whose systemic metastatic disease is successfully controlled for a period with a given therapy; (iii) foreshadowing the failure of adjuvant antiangiogenic drug-based phase III trials; (iv) recapitulating the failure of oral antiangiogenic tyrosine kinase inhibitors plus standard chemotherapy in contrast to the modest successes of antiangiogenic antibodies plus chemotherapy in metastatic breast cancer; and (v) revealing "vessel co-option" and absence of angiogenesis as a determinant of intrinsic resistance or minimal responsiveness to antiangiogenic therapy

  10. Advanced two-stage incinerator

    SciTech Connect

    Rehmat, A.; Khinkis, M.

    1991-01-01

    The Institute of Gas Technology (IGT) is developing an advanced incinerator that combines the fluidized-bed agglomeration/incineration and cyclonic combustion/incineration technologies that have been developed separately at IGT over many years. This combination results in a unique and extremely flexible incinerator for solid, sludge, liquid, and gaseous wastes. This system can operate over a wide range of conditions in the first stage, from low temperature (desorption) to high temperature (agglomeration), including gasification of high-Btu wastes. In the combined system, solid, liquid, and gaseous organic wastes would be easily and efficiently destroyed (>99.99% destruction and removal efficiency (DRE)), whereas solid inorganic contaminants would be contained within a glassy matrix, rendering them benign and suitable for disposal in an ordinary landfill. This technology is different from other existing technologies because of its agglomeration and encapsulation capability and its flexibility with respect to the types wastes it can handle. Both the fluidized-bed as well as the cyclonic incineration technologies have been fully developed and tested separately at pilot scales. 12 refs., 4 figs., 4 tabs.

  11. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    PubMed

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC.

  12. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    PubMed

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

  13. Imaging Tumor Hypoxia to Advance Radiation Oncology

    PubMed Central

    Lee, Chen-Ting; Boss, Mary-Keara

    2014-01-01

    Abstract Significance: Most solid tumors contain regions of low oxygenation or hypoxia. Tumor hypoxia has been associated with a poor clinical outcome and plays a critical role in tumor radioresistance. Recent Advances: Two main types of hypoxia exist in the tumor microenvironment: chronic and cycling hypoxia. Chronic hypoxia results from the limited diffusion distance of oxygen, and cycling hypoxia primarily results from the variation in microvessel red blood cell flux and temporary disturbances in perfusion. Chronic hypoxia may cause either tumor progression or regressive effects depending on the tumor model. However, there is a general trend toward the development of a more aggressive phenotype after cycling hypoxia. With advanced hypoxia imaging techniques, spatiotemporal characteristics of tumor hypoxia and the changes to the tumor microenvironment can be analyzed. Critical Issues: In this review, we focus on the biological and clinical consequences of chronic and cycling hypoxia on radiation treatment. We also discuss the advanced non-invasive imaging techniques that have been developed to detect and monitor tumor hypoxia in preclinical and clinical studies. Future Directions: A better understanding of the mechanisms of tumor hypoxia with non-invasive imaging will provide a basis for improved radiation therapeutic practices. Antioxid. Redox Signal. 21, 313–337. PMID:24329000

  14. Advances in understanding pituitary tumors

    PubMed Central

    Renner, Ulrich; Karl Stalla, Günter

    2014-01-01

    Pituitary tumors are common in the general population. Since neuroimaging techniques have improved, pituitary tumors are more often diagnosed incidentally. About 16.7% of the general population show changes in the pituitary gland. Predominantly, pituitary tumors are benign pituitary adenomas. Pituitary carcinomas or aggressive pituitary tumors are extremely rare. They might develop from benign adenomas. New genetic and epigenetic abnormalities help us to understand pituitary tumorigenesis and might lead to therapeutical targeting drugs in the future. Macroadenomas (>1 cm) can lead to visual field disturbances, compression of cranial nerves, hypopituitarism, and infiltration of the cavernous sinuses. The functional status of the pituitary tumor is important. About half to one third of all pituitary tumors are non-functioning pituitary adenomas. The other pituitary tumors show a specific pattern of hormone secretion. About 25% to 41% of all pituitary tumors are prolactinomas, acromegaly with production of growth hormone represents 10% to 15% of adenomas, Cushing's disease with production of adrenocorticotropic hormone accounts for 10%, and other hormonal characteristics are less common. Transsphenoidal resection and total adenomectomy are desirable. Radiosurgery has enriched the surgical treatment options. Surgical treatment is the intervention of choice except for prolactinomas, where pharmaceutical treatment is recommended. Pharmaceutical treatment consists of dopamine agonists such as cabergoline and somatostatin analogues that include octreotide and pasireotide; retinoic acid is of theoretical interest while peroxisome proliferator-activated receptor-gamma-ligands are not clinically useful. In acromegaly, pegvisomant is a further treatment option. Temozolomide should be considered in aggressive pituitary tumors. In general, pharmaceutical options developed recently have extended the repertoire of treatment possibilities of pituitary tumors. PMID:24592317

  15. Chemoradiation for Advanced Head and Neck Cancer: Potential for Improving Results to Match Those of Current Treatment Modalities for Early-Stage Tumors-Long-Term Results of Hyperfractionated Chemoradiation With Carbogen Breathing and Anemia Correction With Erythropoietin

    SciTech Connect

    Villar, Alfonso Martinez, Jose Carlos; Serdio, Jose Luis de

    2008-04-01

    Purpose: To attempt to improve results of chemoradiation for head and neck cancer. Methods and Materials: From March 1996 to April 2007, 98 patients with head and neck cancer (15 Stage III and 83 Stage IV) were treated with a twice-daily hyperfractionated schedule. Eleven patients presented with N0, 11 with N1, 13 with N2A, 17 with N2B, 24 with N2C, and 22 with N3. Each fraction of treatment consisted of 5 mg/m{sup 2} of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m{sup 2} of carboplatin plus 8050 cGy in 7 weeks. Anemia was corrected with erythropoietin. Results: Ninety-six patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Local toxicity remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Ninety-seven complete responses were achieved. After 11 years of follow-up (median, 81 months), actuarial locoregional control, cause-specific survival, overall survival, and nodal control rates at 5 and 10 years were, respectively, 83% and 83%, 68% and 68%, 57% and 55%, and 100% and 100%. Median follow-up of disease-free survivors was 80 months. No significant differences in survival were observed between the different subsites or between the pretreatment node status groups (N0 vs. N+, N0 vs. N1, N0 vs. N2A, N0 vs. N2B, N0 vs. N2C, and N0 vs. N3). Conclusions: Improving results of chemoradiation for advanced head and neck cancer up to the level obtained with current treatments for early-stage tumors is a potentially reachable goal.

  16. Tumor Stage Mycosis Fungoides in a Child.

    PubMed

    Dulmage, Brittany O'Neill; Villaseñor-Park, Jennifer; Ho, Jonhan; Geskin, Larisa J; Grandinetti, Lisa M

    2015-01-01

    Mycosis fungoides is uncommon in children and most often presents as stage IA/IB. We present a case of stage IIB mycosis fungoides in a 13-year-old boy and discuss diagnostic examination and treatment considerations.

  17. How Are Lung Carcinoid Tumors Staged?

    MedlinePlus

    ... from the abdomen (diaphragm), the membranes surrounding the space between the lungs (mediastinal pleura), or membranes of ... tumor of any size has grown into the space between the lungs (mediastinum), the heart, the large ...

  18. Staging Childhood Brain and Spinal Cord Tumors

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Childhood brain and spinal cord tumors ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. These are ...

  19. Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

    PubMed Central

    Kato, Hiroyuki; Yoshida, Hideo; Taniguch, Hiroyoshi; Nomura, Ryutaro; Sato, Kengo; Suzuki, Ichiro; Nakata, Ryo

    2015-01-01

    AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher’s exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral

  20. 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

  1. 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

  2. BRAF Mutation Is Rare in Advanced-Stage Low-Grade Ovarian Serous Carcinomas

    PubMed Central

    Wong, Kwong-Kwok; Tsang, Yvonne T.M.; Deavers, Michael T.; Mok, Samuel C.; Zu, Zhifei; Sun, Charlotte; Malpica, Anais; Wolf, Judith K.; Lu, Karen H.; Gershenson, David M.

    2010-01-01

    Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. PMID:20802181

  3. Treatment of advanced-stage Hodgkin lymphoma.

    PubMed

    Vassilakopoulos, Theodoros P; Johnson, Peter W M

    2016-07-01

    There is now good evidence that the escalated BEACOPP regimen (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) is more effective in controlling advanced-stage Hodgkin lymphoma (HL) than the widely used ABVD regimen (adriamycin, bleomycin, vinblastine, dacarbazine), but the extra efficacy comes at the expense of both short- and long-term toxicity, and there is debate as to whether overall survival is affected. Baseline prognostic factors have proven of limited utility for determining which patients require more intensive therapy and recent studies have sought to use interim fluoro-deoxyglucose positron emission tomography (FDG-PET) evaluation as a means to guide the modulation of treatment, both upwards and downwards in intensity. These suggest that if treatment starts with ABVD then patients remaining PET-positive after 2 months can be salvaged with escalated BEACOPP in around 65% of cases, but those becoming PET-negative may still experience recurrences in 15%-20%, an event that is more common in those with more advanced disease at presentation. There are early data to suggest that starting with escalated BEACOPP may reduce the rate of recurrence after a negative interim PET to less than 10%. This may be an attractive approach for those with very high-risk features at presentation, but risks overtreating many patients if applied nonselectively. New regimens incorporating antibody-drug conjugates may shift the balance of efficacy and toxicity once again, and further studies are underway to evaluate this. PMID:27496308

  4. Current and Future Lymphatic Imaging Modalities for Tumor Staging

    PubMed Central

    Gao, Kuo; Liu, Tiegang; Tariq, Imran; Sajjad, Ashif; Niu, Meiying; Liu, Guokai; Mehmood, Zahid; Tian, Guihua

    2014-01-01

    Tumor progression is supported by the lymphatic system which should be scanned efficiently for tumor staging as well as the enhanced therapeutic outcomes. Poor resolution and low sensitivity is a limitation of traditional lymphatic imaging modalities; thus new noninvasive approaches like nanocarriers, magnetic resonance imaging, positron-emission tomography, and quantum dots are advantageous. Some newer modalities, which are under development, and their potential uses will also be discussed in this review. PMID:24757671

  5. Targeting tumor vasculature through oncolytic virotherapy: recent advances

    PubMed Central

    Toro Bejarano, Marcela; Merchan, Jaime R

    2015-01-01

    The oncolytic virotherapy field has made significant advances in the last decade, with a rapidly increasing number of early- and late-stage clinical trials, some of them showing safety and promising therapeutic efficacy. Targeting tumor vasculature by oncolytic viruses (OVs) is an attractive strategy that offers several advantages over nontargeted viruses, including improved tumor viral entry, direct antivascular effects, and enhanced antitumor efficacy. Current understanding of the biological mechanisms of tumor neovascularization, novel vascular targets, and mechanisms of resistance has allowed the development of oncolytic viral vectors designed to target tumor neovessels. While some OVs (such as vaccinia and vesicular stomatitis virus) can intrinsically target tumor vasculature and induce vascular disruption, the majority of reported vascular-targeted viruses are the result of genetic manipulation of their viral genomes. Such strategies include transcriptional or transductional endothelial targeting, “armed” viruses able to downregulate angiogenic factors, or to express antiangiogenic molecules. The above strategies have shown preclinical safety and improved antitumor efficacy, either alone, or in combination with standard or targeted agents. This review focuses on the recent efforts toward the development of vascular-targeted OVs for cancer treatment and provides a translational/clinical perspective into the future development of new generation biological agents for human cancers. PMID:27512680

  6. Applications of a novel tumor-grading-metastasis staging system for pancreatic neuroendocrine tumors

    PubMed Central

    Yang, Min; Tan, Chun-Lu; Zhang, Yi; Ke, Neng-Wen; Zeng, Lin; Li, Ang; Zhang, Hao; Xiong, Jun-Jie; Guo, Zi-Heng; Tian, Bo-Le; Liu, Xu-Bao

    2016-01-01

    Abstract The ability to stratify patients with pancreatic neuroendocrine tumors (p-NETs) into prognostic groups has been hindered by the absence of a commonly accepted staging system. Both the 7th tumor-node-metastasis (TNM) staging guidelines by the American Joint Committee on Cancer (AJCC) and the 2010 grading classifications by the World Health Organization (WHO) were validated to be unsatisfactory. We aim to evaluate the feasibility of combining the latest AJCC and WHO criteria to devise a novel tumor-grading-metastasis (TGM) staging system. We also sought to examine the stage-specific survival rates and the prognostic value of this new TGM system for p-NETs. Data of 120 patients with surgical resection and histopathological diagnosis of p-NETs from January 2004 to February 2014 in our institution were retrospectively collected and analyzed. Based on the AJCC and WHO criteria, we replaced the stage N0 and N1 with stage Ga (NET G1 and NET G2) and Gb (NET G3 and MANEC) respectively, without changes of the definition of T or M stage. The present novel TGM staging system was grouped as follows: stage I was defined as T1–2, Ga, M0; stage II as T3, Ga, M0 or as T1–3, Gb, M0; stage III as T4, Ga–b, M0 and stage IV as any T, M1. The new TGM staging system successfully distributed 55, 42, 12, and 11 eligible patients in stage I to IV, respectively. Differences of survival compared stage I with III and IV for patients with p-NETs were both statistically significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001). Patients in stage I showed better a survival than those in stage II, whereas difference between stages III and IV was not notable (P = 0.001, P = 0.286, respectively). In multivariate models, when the TGM staging system was evaluated in place of the individual T, G, and M variables, this new criteria were proven to be an independent predictor of survival for surgically resected p-NETs (P < 0.05). Stratifying patients well

  7. A phase II study of axitinib in advanced neuroendocrine tumors

    PubMed Central

    Strosberg, J R; Cives, M; Hwang, J; Weber, T; Nickerson, M; Atreya, C E; Venook, A; Kelley, R K; Valone, T; Morse, B; Coppola, D; Bergsland, E K

    2016-01-01

    Neuroendocrine tumors (NETs) are highly vascular neoplasms overexpressing vascular endothelial growth factor (VEGF) as well as VEGF receptors (VEGFR). Axitinib is a potent, selective inhibitor of VEGFR-1, -2 and -3, currently approved for the treatment of advanced renal cell carcinoma. We performed an open-label, two-stage design, phase II trial of axitinib 5 mg twice daily in patients with progressive unresectable/metastatic low-to-intermediate grade carcinoid tumors. The primary end points were progression-free survival (PFS) and 12-month PFS rate. The secondary end points included time to treatment failure (TTF), overall survival (OS), overall radiographic response rate (ORR), biochemical response rate and safety. A total of 30 patients were enrolled and assessable for toxicity; 22 patients were assessable for response. After a median follow-up of 29 months, we observed a median PFS of 26.7 months (95% CI, 11.4–35.1), with a 12-month PFS rate of 74.5% (±10.2). The median OS was 45.3 months (95% CI, 24.4–45.3), and the median TTF was 9.6 months (95% CI, 5.5–12). The best radiographic response was partial response (PR) in 1/30 (3%) and stable disease (SD) in 21/30 patients (70%); 8/30 patients (27%) were unevaluable due to early withdrawal due to toxicity. Hypertension was the most common toxicity that developed in 27 patients (90%). Grade 3/4 hypertension was recorded in 19 patients (63%), leading to treatment discontinuation in six patients (20%). Although axitinib appears to have an inhibitory effect on tumor growth in patients with advanced, progressive carcinoid tumors, the high rate of grade 3/4 hypertension may represent a potential impediment to its use in unselected patients. PMID:27080472

  8. Tumor Marker Usage and Medical Care Costs Among Older Early-Stage Breast Cancer Survivors

    PubMed Central

    Ramsey, Scott D.; Henry, N. Lynn; Gralow, Julie R.; Mirick, Dana K.; Barlow, William; Etzioni, Ruth; Mummy, David; Thariani, Rahber; Veenstra, David L.

    2015-01-01

    Purpose Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors. Methods By using Surveillance, Epidemiology, and End Results-Medicare records for patients diagnosed with early-stage breast cancer between 2001 and 2007, tumor marker usage within 2 years after diagnosis was identified by billing codes. Logistic regression models were used to identify clinical and demographic factors associated with use of tumor markers. To determine impact on costs of care, we used multivariable regression, controlling for other factors known to influence total medical costs. Results We identified 39,650 eligible patients. Of these, 16,653 (42%) received at least one tumor marker assessment, averaging 5.7 tests over 2 years, with rates of use per person increasing over time. Factors significantly associated with use included age at diagnosis, diagnosis year, stage at diagnosis, race/ethnicity, geographic region, and urban/rural status. Rates of advanced imaging, but not biopsies, were significantly higher in the assessment group. Medical costs for patients who received at least one test were approximately 29% greater than costs for those who did not, adjusting for other factors. Conclusion Breast cancer tumor markers are frequently used among women with early-stage disease and are associated with an increase in both diagnostic procedures and total cost of care. A better understanding of factors driving the use of and the potential benefits and harms of surveillance-based tumor marker testing is needed. PMID:25332254

  9. Recent advances in systemic therapy for gastrointestinal neuroendocrine tumors.

    PubMed

    Pelley, R J; Bukowski, R M

    1999-01-01

    Neuroendocrine tumors of the gastrointestinal tract are rare tumors which can be classified as amine precursor uptake and decarboxylation tumors (APU-Domas). Although the majority of clinically apparent tumors are malignant, they are frequently slow growing. Despite this characteristic, they may generate disabling hormonal syndromes requiring aggressive treatment to achieve palliation. Recent advances in understanding the pathophysiology of these tumors has led to better medical therapy with chemotherapeutic agents, somatostatin analogues, and biologic therapies. This review will update the recent efforts in systemic therapies of the gastrointestinal neuroendocrine tumors.

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

    PubMed Central

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

    1997-01-01

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

  11. Neighborhood Composition and Cancer among Hispanics: Tumor Stage and Size at Time of Diagnosis

    PubMed Central

    Reyes-Ortiz, Carlos A.; Eschbach, Karl; Zhang, Dong D.; Goodwin, James S.

    2013-01-01

    Background We have previously reported that cancer incidence for lung, female breast, and colon and rectum for Hispanics decreases with increasing percentage of Hispanics at the census tract. In contrast, cervical cancer incidence increases with increasing percentage of Hispanics at the census tract. Methods In this study, we investigate the hypothesis that Hispanics living in census tracts with high percentages of Hispanics are diagnosed with more advanced cancer, with respect to tumor size and stage of diagnosis. Data from the Surveillance, Epidemiology, and End Results registry and the U.S. Census Bureau were used to estimate the odds of diagnosis at a “late” stage (II, III, IV) versus “early” stage (I) and breast cancer tumor size among Hispanics as a function of census tract percent Hispanic. Hispanic ethnicity in the Surveillance, Epidemiology, and End Results registry was identified by medical record review and Hispanic surname lists. The study also used income of Hispanics living in the census tract and controlled for age at diagnosis and gender. Results We found that Hispanics living in neighborhoods with higher density of Hispanic populations were more likely to be diagnosed with late-stage breast, cervical, or colorectal cancer, and to have a larger tumor size of breast cancer. Conclusions Our findings suggest that the benefits of lower cancer incidence in high tract percent Hispanics are partially offset by poorer access and reduced use of screening in conjunction with lower income, poorer health insurance coverage, and language barriers typical of these communities. PMID:18990733

  12. Surgical Approaches for Stage IVA Thymic Epithelial Tumors.

    PubMed

    Shapiro, Mark; Korst, Robert J

    2014-01-14

    Thymic epithelial tumors (TET) are rare mediastinal neoplasms that can metastasize to the pleural space (stage IVA). Complete surgical resection remains the backbone of therapy for patients with early stage TET, however, the role of surgery in the management of patients with stage IVA disease is not fully defined. Published reports in this regard are mainly small, retrospective, and uncontrolled, with unclear inclusion criteria. Surgical options to manage pleural disease include metastasectomy, extrapleural pneumonectomy, and metastasectomy/pleurectomy combined with heated intrapleural chemotherapy. The choice of the most appropriate surgical strategy needs to be individualized according to the quantity and location of disease, the patient's overall condition, as well as operator and institutional expertise. In the majority of cases, metastasectomy of pleural implants will be sufficient to achieve a complete resection. The available literature suggests that in selected patients with stage IVA TET, delivery of neoadjuvant chemotherapy followed by complete resection is a viable treatment option that can be associated with long-term survival.

  13. Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer Patients by Targeted Sequencing

    PubMed Central

    Chen, Ke-Zhong; Lou, Feng; Yang, Fan; Zhang, Jing-Bo; Ye, Hua; Chen, Wei; Guan, Tian; Zhao, Ming-Yu; Su, Xue-Xia; Shi, Rong; Jones, Lindsey; Huang, Xue F.; Chen, Si-Yi; Wang, Jun

    2016-01-01

    Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.4% and sensitivity and specificity of 53.8% and 47.3%, respectively. Cell-free (cfDNA) concentrations were found to be significantly associated with some clinical features, including tumor stage and subtype. Importantly, the presence of cfDNA had a higher positive predictive value than that of currently used protein tumor biomarkers. This study demonstrates the feasibility of identifying plasma ctDNA mutations in the earliest stage lung cancer patients via targeted sequencing, demonstrating a potential utility of targeted sequencing of ctDNA in the clinical management of NSCLC. PMID:27555497

  14. Advanced ultrasonic techniques for local tumor hyperthermia.

    PubMed

    Lele, P P

    1989-05-01

    Scanned, intensity-modulated, focused ultrasound (SIMFU) presently is the modality of choice for localized, controlled heating of deep as well as superficial tumors noninvasively. With the present SIMFU system, it was possible to heat 88 per cent of deep tumors up to 12 cm in depth and 15 cm in diameter, to 43 degrees C in 3 to 4 minutes. The infiltrative tumor margins could be heated to the desired therapeutic temperature. The temperature outside the treatment field fell off sharply. Excellent objective responses were obtained without local or systemic toxicity. Multiinstitutional clinical trials of local hyperthermia by this promising technique are clearly warranted.

  15. 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

  16. Ultrasound scanning of the pelvis and abdomen for staging of gynecological tumors: a review.

    PubMed

    Fischerova, D

    2011-09-01

    This Review documents examination techniques, sonographic features and clinical considerations in ultrasound assessment of gynecological tumors. The methodology of gynecological cancer staging, including assessment of local tumor extent, lymph nodes and distant metastases, is described. With increased technical quality, sonography has become an accurate staging method for early and advanced gynecological tumors. Other complementary imaging techniques, such as computed tomography and magnetic resonance imaging, can be used as an adjunct to ultrasound in specific cases, but are not essential to tumor staging if sonography is performed by a specialist in gynecological oncology. Ultrasound is established as the method of choice for evaluating local extent of endometrial cancer and is the most important imaging method for the differential diagnosis of benign and malignant ovarian tumors. Ultrasound can be used to detect early as well as locally advanced cancers that extend from the vagina, cervix or other locations to the paracolpium, parametria, rectum and sigmoid colon, urinary bladder and other adjacent organs or structures. In cases of ureteric involvement, ultrasound is also helpful in locating the site of obstruction. Furthermore, it is specific for the detection of extrapelvic tumor spread to the abdominal cavity in the form of parietal or visceral carcinomatosis, omental and/or mesenteric infiltration. Ultrasound can be used to assess changes in infiltrated lymph nodes, including demonstration of characteristic sonomorphologic and vascular patterns. Vascular patterns are particularly well visualized in peripheral nodes using high resolution linear array probes or in the pelvis using high-frequency probes. The presence of peripheral or mixed vascularity or displacement of vessels seems to be the sole criterion in the diagnosis of metastatic or lymphomatous nodes. In the investigation of distant metastases, if a normal visceral organ or characteristic diffuse or

  17. Advances take stage - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Regulatory advances in proteomics will be taking center stage at a Symposia scheduled to occur at the 2011 American Association for Clinical Chemistry (AACC) Annual Meeting. The symposium entitled "Enabling Translational Proteomics with NCI's Clinical Proteomic Technologies for Cancer" is scheduled for July 25, 2011 at AACC's annual Meeting.

  18. Adjuvant Ozonetherapy in Advanced Head and Neck Tumors: A Comparative Study

    PubMed Central

    2004-01-01

    Advanced head and neck (H&N) tumors have a poor prognosis, and this is worsened by the occurrence of hypoxia and ischemia in the tumors. Ozonetherapy has proved useful in the treatment of ischemic syndromes, and several studies have described a potential increase of oxygenation in tissues and tumors. The aim of this prospective study was to evaluate the clinical effect of ozonetherapy in patients with advanced H&N cancer in the course of their scheduled radiotherapy. Over a period of 3 years, 19 patients with advanced H&N tumors who were undergoing treatment in our department with non-standard fractionated radiotherapy plus oral tegafur. A group of 12 patients was additionally treated with intravenous chemotherapy before and/or during radiotherapy. In the other group of seven patients, systemic ozonetherapy was administered twice weekly during radiotherapy. The ozonetherapy group was older (64 versus 54 years old, P = 0.006), with a higher percentage of lymph node involvement (71% versus 8%, P = 0.019) and with a trend to more unfavorable tumor stage (57% versus 8% IVb + IVc stages, P = 0.073). However, there was no significant difference in overall survival between the chemotherapy (median 6 months) and ozonetherapy (8 months) groups. Although these results have to be viewed with caution because of the limited number of patients, they suggest that ozonetherapy could have had some positive effect during the treatment of our patients with advanced H&N tumors. The adjuvant administration of ozonetherapy during the chemo–radiotherapy for these tumors merits further research. PMID:15841266

  19. Differential protein mapping of ovarian serous adenocarcinomas: identification of potential markers for distinct tumor stage.

    PubMed

    Wang, Yanfei; Wu, Rong; Cho, Kathleen R; Thomas, Dafydd G; Gossner, Gabrielle; Liu, J Rebecca; Giordano, Thomas J; Shedden, Kerby A; Misek, David E; Lubman, David M

    2009-03-01

    Ovarian serous carcinomas (OSCs) comprise over half of all ovarian carcinomas and account for the majority of ovarian cancer-related deaths. We used a 2-dimensional liquid-based protein mapping strategy to characterize global protein expression patterns in 19 OSC tumor samples from 15 different patients to facilitate molecular classification of tumor stage. Protein expression profiles were produced, using pI-based separation in the first dimension and hydrophobicity-based separation in the second dimension, over a pH range of 4.0-7.0. Hierarchical clustering was applied to protein maps to indicate the tumor interrelationships. The 19 tumor samples could be classified into two different groups, one group associated with low stage (Stage 1) tumors and the other group associated with high stage (Stages 3/4) tumors. Proteins that were differentially expressed in different groups were selected for identification by LTQ-ESI-MS/MS. Fourteen of the selected proteins were overexpressed in the low stage tumors; 46 of the proteins were overexpressed in the high stage tumors. These proteins are known to play an important role in cellular functions such as glycolysis, protein biosynthesis, and cytoskeleton rearrangement and may serve as markers associated with different stages of OSCs. To further confirm the stage-dependent protein identifications, Lamin A/C and Vimentin expression in ovarian serous carcinomas was assessed by immunohistochemistry using ovarian tumor tissue microarrays for 66 samples.

  20. 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

  1. 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

  2. D-Dimer and Carcinoembryonic Antigen Levels: Useful Indicators for Predicting the Tumor Stage and Postoperative Survival.

    PubMed

    Tekeşin, Kemal; Bayrak, Savaş; Esatoğlu, Varol; Özdemir, Ebru; Özel, Leyla; Melih Kara, Veli

    2016-01-01

    The purpose of this prospective study is to determine the preoperative plasma D-dimer and serum Carcinoembryonic Antigen (CEA) levels of patients scheduled for curative surgical resection for colorectal cancer and to evaluate the significance of these levels on the prognosis and postoperative survival rate. One hundred sixty-five patients with colorectal cancer, who were scheduled to have elective resection between January 2008 and January 2011, were included in the study. A significant increase was observed in the D-dimer levels, particularly in poorly differentiated tumors. The distance covered by the tumor inside the walls of the colon and rectum (T-stage) was significant for both D-dimer and CEA levels. As the T-stage increased, there was also a significant increase in the D-dimer and CEA levels. A high significance and correlation level was detected between the TNM staging and both D-dimer and CEA. A significant relationship was found between the advanced tumor stage and short postoperative survival rate of patients with colorectal cancer. Therefore, the analysis of preoperative D-dimer and CEA levels can be useful in predicting the stage and differentiation of the tumor and the postoperative survival rate. PMID:27651789

  3. D-Dimer and Carcinoembryonic Antigen Levels: Useful Indicators for Predicting the Tumor Stage and Postoperative Survival

    PubMed Central

    Tekeşin, Kemal; Esatoğlu, Varol; Özdemir, Ebru; Özel, Leyla; Melih Kara, Veli

    2016-01-01

    The purpose of this prospective study is to determine the preoperative plasma D-dimer and serum Carcinoembryonic Antigen (CEA) levels of patients scheduled for curative surgical resection for colorectal cancer and to evaluate the significance of these levels on the prognosis and postoperative survival rate. One hundred sixty-five patients with colorectal cancer, who were scheduled to have elective resection between January 2008 and January 2011, were included in the study. A significant increase was observed in the D-dimer levels, particularly in poorly differentiated tumors. The distance covered by the tumor inside the walls of the colon and rectum (T-stage) was significant for both D-dimer and CEA levels. As the T-stage increased, there was also a significant increase in the D-dimer and CEA levels. A high significance and correlation level was detected between the TNM staging and both D-dimer and CEA. A significant relationship was found between the advanced tumor stage and short postoperative survival rate of patients with colorectal cancer. Therefore, the analysis of preoperative D-dimer and CEA levels can be useful in predicting the stage and differentiation of the tumor and the postoperative survival rate. PMID:27651789

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

    PubMed Central

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

    2013-01-01

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

  5. Advanced statistical methods for the definition of new staging models.

    PubMed

    Kates, Ronald; Schmitt, Manfred; Harbeck, Nadia

    2003-01-01

    Adequate staging procedures are the prerequisite for individualized therapy concepts in cancer, particularly in the adjuvant setting. Molecular staging markers tend to characterize specific, fundamental disease processes to a greater extent than conventional staging markers. At the biological level, the course of the disease will almost certainly involve interactions between multiple underlying processes. Since new therapeutic strategies tend to target specific processes as well, their impact will also involve interactions. Hence, assessment of the prognostic impact of new markers and their utilization for prediction of response to therapy will require increasingly sophisticated statistical tools that are capable of detecting and modeling complicated interactions. Because they are designed to model arbitrary interactions, neural networks offer a promising approach to improved staging. However, the typical clinical data environment poses severe challenges to high-performance survival modeling using neural nets, particularly the key problem of maintaining good generalization. Nonetheless, it turns out that by using newly developed methods to minimize unnecessary complexity in the neural network representation of disease course, it is possible to obtain models with high predictive performance. This performance has been validated on both simulated and real patient data sets. There are important applications for design of studies involving targeted therapy concepts and for identification of the improvement in decision support resulting from new staging markers. In this article, advantages of advanced statistical methods such as neural networks for definition of new staging models will be illustrated using breast cancer as an example.

  6. Advances in Personalized Targeted Treatment of Metastatic Melanoma and Non-Invasive Tumor Monitoring

    PubMed Central

    Klinac, Dragana; Gray, Elin S.; Millward, Michael; Ziman, Mel

    2013-01-01

    Despite extensive scientific progress in the melanoma field, treatment of advanced stage melanoma with chemotherapeutics and biotherapeutics has rarely provided response rates higher than 20%. In the past decade, targeted inhibitors have been developed for metastatic melanoma, leading to the advent of more personalized therapies of genetically characterized tumors. Here we review current melanoma treatments and emerging targeted molecular therapies. In particular we discuss the mutant BRAF inhibitors Vemurafenib and Dabrafenib, which markedly inhibit tumor growth and advance patients’ overall survival. However this response is almost inevitably followed by complete tumor relapse due to drug resistance hampering the encouraging initial responses. Several mechanisms of resistance within and outside the MAPK pathway have now been uncovered and have paved the way for clinical trials of combination therapies to try and overcome tumor relapse. It is apparent that personalized treatment management will be required in this new era of targeted treatment. Circulating tumor cells (CTCs) provide an easily accessible means of monitoring patient relapse and several new approaches are available for the molecular characterization of CTCs. Thus CTCs provide a monitoring tool to evaluate treatment efficacy and early detection of drug resistance in real time. We detail here how advances in the molecular analysis of CTCs may provide insight into new avenues of approaching therapeutic options that would benefit personalized melanoma management. PMID:23515890

  7. EFFICACY OF THE ENNEKING STAGING SYSTEM IN RELATION TO TREATING BENIGN BONE TUMORS AND TUMOR-LIKE BONE LESIONS

    PubMed Central

    Nogueira Drumond, José Marcos

    2015-01-01

    Objective: To evaluate the efficacy of the Enneking staging system for determining the prognosis, planning surgical treatment and indicating adjuvant therapy for benign bone tumors (BBT) and tumor-like bone lesions (TBL). Methods: A retrospective multicenter, descriptive, nonrandomized study was carried out on a representative sample comprising a large series of 165 patients with a total of 168 benign bone tumors and tumor-like bone lesions. The patient sample was typical, and matched the literature in all respects. All the patients were classified according to the Enneking staging system, and the initial staging of each lesion was correlated with its behavior after either conservative or surgical treatment, in order to determine the efficacy of the system. The treatment options and complications were described and analyzed. Results: The results from the treatment provided 95.2% agreement with the Enneking staging system, with a 95% confidence interval of between 90.8 and 97.9%. Of the 168 tumors treated, only eight (4.8%) could not be controlled in relation to the initial treatment indicated by the Enneking staging system. Tumors classified as active were the most prevalent, comprising 73.2% of the lesions. Tumor recurrence was significantly more frequent (p < 0.001) in the aggressive stage. All the patients staged as latent evolved to cure. The study suggested that surgery with wide margins, for aggressive lesions, could provide better lesion control, with a lower recurrence rate (p > 0.001). For latent and active lesions, the study demonstrated the efficacy of both expectant treatment and excision, with or without autogenous bone graft. Conclusion: The results confirm that the Enneking staging system was very efficient in determining the prognosis, enabling surgical planning and indicating adjuvant therapy for treatment of BBT and TBL. PMID:27019838

  8. Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

    PubMed Central

    2013-01-01

    Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

  9. Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages

    SciTech Connect

    Hoshiba, Takashi; Tanaka, Masaru

    2013-09-20

    Highlights: •Models mimicking ECM in tumor with different malignancy were prepared. •Cancer cell proliferation was suppressed on benign tumor ECM. •Benign tumor cell proliferation was suppressed on cancerous ECM. •Chemoresistance of cancer cell was enhanced on cancerous ECM. -- Abstract: Extracellular matrix (ECM) has been focused to understand tumor progression in addition to the genetic mutation of cancer cells. Here, we prepared “staged tumorigenesis-mimicking matrices” which mimic in vivo ECM in tumor tissue at each malignant stage to understand the roles of ECM in tumor progression. Breast tumor cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells, were cultured to form their own ECM beneath the cells and formed ECM was prepared as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF-10A cell proliferation was promoted on the matrices derived from MCF-10A cells. Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only matrices derived from MDA-MB-231 cells. Our results showed that the cells showed different behaviors on staged tumorigenesis-mimicking matrices according to the malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis-mimicking matrices might be a useful in vitro ECM models to investigate the roles of ECM in tumor progression.

  10. [Hormonal therapy of advanced or relapsed ovarian granulosa cell tumor].

    PubMed

    Sun, H; Bai, P

    2016-07-01

    Ovarian granulosa cell tumor is a rare gynecologic malignancy with hormonal activity. Surgical excision is the standard treatment for this disease. Most patients present excellent short term prognosis, however, late relapse often occurs, even after many years. Viable treatments of advanced or relapsed granulosa cell tumor are still limited, and the optimal therapy method has not been established. Compared with chemotherapy and radiotherapy, hormonal therapy is a well-tolerated treatment which can be administrated over a long period of time without serious side effects, and the combined application of hormones may achieve a better outcome. Therefore, hormonal therapy has been suggested as a potential treatment option for patients with advanced or relapsed granulosa cell tumor, and to extend the tumor-free interval and attenuate the disease progression. Future researches should be focused on the identification of the hormonal therapy which may provide the greatest clinical benefit, comparing and analyzing the effects of different combined therapeutic regimens of hormone drugs, and on the synthesis of drugs highly activating estrogen receptor β expressed in the granulosa cell tumor cells. PMID:27531259

  11. Advanced technologies for rocket single-stage-to-orbit vehicles

    NASA Astrophysics Data System (ADS)

    Wilhite, Alan W.; Bush, Lance B.; Cruz, Christopher I.; Lepsch, Roger A.; Morris, W. Douglas; Stanley, Douglas O.; Wurster, Kathryn E.

    1991-01-01

    A single-stage-to-orbit vertical takeoff/horizontal landing rocket vehicle was studied to determine the benefits of advanced technology. Advanced technologies that were included in the study were variable mixture ratio oxygen/hydrogen rocket engines and materials, structures, and subsystem technologies currently being developed in the National Aero-Space Plane Program. The application of advanced technology results in an 85 percent reduction in vehicle dry weight. With advanced materials, an external thermal protection system, like the Space Shuttle tiles, was not required. Compared to an all-airbreathing horizontal takeoff/horizontal landing vehicle using the same advanced technologies and mission requirements, the rocket vehicle is lighter in dry weight and has fewer subsystems. To increase reliability and safety, operational features were included in the rocket vehicle-robust subsystems, 5 percent additional margin, no slush hydrogen, fail-operational with an engine out, and a crew escape module. The resulting vehicle grew in dry weight and was still lower in dry weight than the airbreathing vehicle.

  12. Epigenetics in Brain Tumors: HDACs Take Center Stage

    PubMed Central

    Eyüpoglu, Ilker Y.; Savaskan, Nicolai E.

    2016-01-01

    Primary tumors of the brain account for 2 % of all cancers with malignant gliomas taking the lion’s share at 70 %. Malignant gliomas (high grade gliomas WHO° III and °IV) belong to one of the most threatening tumor entities known for their disappointingly short median survival time of just 14 months despite maximum therapy according to current gold standards. Malignant gliomas manifest various factors, through which they adapt and manipulate the tumor microenvironment to their advantage. Epigenetic mechanisms operate on the tumor microenvironment by de- and methylation processes and imbalances between the histone deacetylases (HDAC) and histone acetylases (HAT). Many compounds have been discovered modulating epigenetically controlled signals. Recent studies indicate that xCT (system xc-, SLC7a11) and CD44 (H-CAM, ECM-III, HUTCH-1) functions as a bridge between these epigenetic regulatory mechanisms and malignant glioma progression. The question that ensues is the extent to which therapeutic intervention on these signaling pathways would exert influence on the treatment of malignant gliomas as well as the extent to which manipulation of HDAC activity can sensitize tumor cells for chemotherapeutics through ‘epigenetic priming’. In light of considering the current stagnation in the development of therapeutic options, the need for new strategies in the treatment of gliomas has never been so pressing. In this context the possibility of pharmacological intervention on tumor-associated genes by epigenetic priming opens a novel path in the treatment of primary brain tumors. PMID:26521944

  13. The pursuit of a cholesteatoma by harvey cushing: staged approach to a complex skull base tumor.

    PubMed

    Malekpour, Mahdi; Cohen-Gadol, Aaron A

    2014-10-01

    Objective The evolution of neurosurgical techniques during Harvey Cushing's practice was immense. The authors illustrate this evolution using archived historical records from Harvey Cushing. Setting Historical patient records retained by the Cushing Center at Yale University Department of Neurosurgery. Design The authors present the case of one of Cushing's patients with a cholesteatoma. Results Cushing's surgical treatment of a cholesteatoma extending into the skull base is an example of his meticulous documentation and accelerated surgical techniques. Conclusions This case demonstrates how neurosurgical techniques advanced in the management of complex skull base tumors via a staged approach through the middle and posterior fossae at a time long before the development of modern skull base surgery. PMID:25276599

  14. The Pursuit of a Cholesteatoma by Harvey Cushing: Staged Approach to a Complex Skull Base Tumor

    PubMed Central

    Malekpour, Mahdi; Cohen-Gadol, Aaron A.

    2014-01-01

    Objective The evolution of neurosurgical techniques during Harvey Cushing's practice was immense. The authors illustrate this evolution using archived historical records from Harvey Cushing. Setting Historical patient records retained by the Cushing Center at Yale University Department of Neurosurgery. Design The authors present the case of one of Cushing's patients with a cholesteatoma. Results Cushing's surgical treatment of a cholesteatoma extending into the skull base is an example of his meticulous documentation and accelerated surgical techniques. Conclusions This case demonstrates how neurosurgical techniques advanced in the management of complex skull base tumors via a staged approach through the middle and posterior fossae at a time long before the development of modern skull base surgery. PMID:25276599

  15. Analysis of circulating tumor cells derived from advanced gastric cancer.

    PubMed

    Toyoshima, Kosei; Hayashi, Akira; Kashiwagi, Masahide; Hayashi, Naoko; Iwatsuki, Masaaki; Ishimoto, Takatsugu; Baba, Yoshifumi; Baba, Hideo; Ohta, Yoshikazu

    2015-08-15

    Studies in circulating tumor cells (CTCs) have proceeded to be accepted as prognostic markers in several types of cancers. But they are still limited because many are mainly from enumeration of CTCs. Here, we tried to evaluate the tumorigenicity of CTCs from advanced gastric cancer patients (n = 42). Peripheral blood mononuclear cells (PBMC) from the patients were separated into CD45 negative and positive fractions and both were subcutaneously injected into immunodeficient mice. Within 5 months nine tumor-like-structures from six patients but not from healthy volunteers were established. They were durable for passages and all had been confirmed human origin. Eight of the nine tumor-like-structures were from nonauthorized CTC containing cells expressing CD45 and B-cell markers. On the contrary, one of them was developed from CD45(-) PBMC fraction of a patient with bone marrow metastasis reflecting authorized CTCs. Histopathology showed common features with that of original gastric tumor. The cells isolated from the tumor-like-structure expressed EpCAM and CEA further supporting they were from the original tumor. Moreover the cells were CD44 positive to varying degree and a limiting dilution study showed that the CD44(+/high) fraction had tumorigenicity. The CD44 was dominantly in the form of CD44 variant 8-10. The CD44(+/high) cells had higher expression of the glutamate/cysteine transporter xCT compared with the CD44(-/low) cells. Our results showed the existence of tumor-initiating cells in blood of advanced gastric cancer patients and they could be a therapeutic target and prospective tool for further investigations.

  16. Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer.

    PubMed

    Panis, C; Victorino, V J; Herrera, A C S A; Freitas, L F; De Rossi, T; Campos, F C; Simão, A N Colado; Barbosa, D S; Pinge-Filho, P; Cecchini, R; Cecchini, A L

    2012-06-01

    Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1β, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure

  17. Advanced Low-Noise Research Fan Stage Design

    NASA Technical Reports Server (NTRS)

    Neubert, Robert; Bock, Larry; Malmborg, Eric; Owen-Peer, William

    1997-01-01

    This report describes the design of the Advanced Low-Noise Research Fan stage. The fan is a variable pitch design, which is designed at the cruise pitch condition. Relative to the cruise setting, the blade is closed at takeoff and opened for reverse thrust operation. The fan stage is a split flow design with fan exit guide vanes (FEGVs) and core stators. The fan stage design is combined with a nacelle and engine core duct to form a powered fan/nacelle subscale model. This model is intended for use in combined aerodynamic, acoustic, and structural testing in a wind tunnel. The fan has an outer diameter of 22 in. and a hub-to-tip of 0.426 in., which allows the use of existing NASA fan and cowl force balance and rig drive systems. The design parameters were selected to permit valid acoustic and aerodynamic comparisons with the Pratt & Whitney (P&W) 17- and 22-in. rigs previously tested under NASA contract. The fan stage design is described in detail. The results of the design axisymmetric and Navier-Stokes aerodynamic analysis are presented at the critical design conditions. The structural analysis of the fan rotor and attachment is included. The blade and attachment are predicted to have adequate low-cycle fatigue life and an acceptable operating range without resonant stress or flutter. The stage was acoustically designed with airfoil counts in the FEGV and core stator to minimize noise. A fan/FEGV tone analysis developed separately under NASA contract was used to determine the optimum airfoil counts. The fan stage was matched to the existing nacelle, designed under the previous P&W low-noise contract, to form a fan/nacelle model for wind tunnel testing. It is an axisymmetric nacelle for convenience in testing and analysis. Previous testing confirmed that the nacelle performed as required at various aircraft operating conditions.

  18. Advanced Imaging for Biopsy Guidance in Primary Brain Tumors

    PubMed Central

    Tsiouris, Apostolos J; Ramakrishna, Rohan

    2016-01-01

    Accurate glioma sampling is required for diagnosis and establishing eligibility for relevant clinical trials. MR-based perfusion and spectroscopy sequences supplement conventional MR in noninvasively predicting the areas of highest tumor grade for biopsy. We report the case of a patient with gliomatosis cerebri and multifocal patchy enhancement in whom the combination of advanced and conventional imaging attributes successfully guided a diagnostic biopsy. PMID:27014538

  19. Regorafenib in Treating Patients With Advanced or Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2015-08-29

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma

  20. Neuropsychological resiliency after treatment for advanced stage neuroblastoma.

    PubMed

    Carpentieri, S C; Diller, L R

    2005-06-01

    The purpose of this study was to describe the neuropsychological functioning of survivors of advanced stage neuroblastoma. In all, 16 survivors, diagnosed at a median of 2.8 years, who had received intensive chemotherapy and surgical treatments, were identified; 11 had received myeloablative consolidation therapy, eight with total body irradiation (TBI). All patients were evaluated with a neuropsychological assessment battery at a median age of 8.8 years. Analyses included comparison of the performances of the TBI group vs the no-TBI group; determination of whether the proportion of individuals with impaired or superior performance on each measure exceeded normative expectations; and performance indexes reflecting patterns of performance. Results indicate no significant deleterious impact of TBI and/or presence or absence of myeloablative therapy on neurocognitive and neurobehavioral functioning. For this cohort, resilience to neuropsychological vulnerability was observed, which included the emergence of a profile of full-scale IQ, verbal IQ, and mathematical achievement well above average expectations. We concluded that the results document a lack of neuropsychological morbidity among this cohort of survivors of advanced stage neuroblastoma, regardless of the inclusion of TBI. Moreover, a striking pattern of excellent neurocognitive functioning with intact neurobehavioral functioning was observed.

  1. Can advanced-stage ovarian cancer be cured?

    PubMed

    Narod, Steven

    2016-04-01

    Approximately 20% of women with advanced-stage ovarian cancer survive beyond 12 years after treatment and are effectively cured. Initial therapy for ovarian cancer comprises surgery and chemotherapy, and is given with the goal of eradicating as many cancer cells as possible. Indeed, the three phases of therapy are as follows: debulking surgery to remove as much of the cancer as possible, preferably to a state of no visible residual disease; chemotherapy to eradicate any microscopic disease that remains present after surgery; and second-line or maintenance therapy, which is given to delay disease progression among patients with tumour recurrence. If no cancer cells remain after initial therapy is completed, a cure is expected. By contrast, if residual cancer cells are present after initial treatment, then disease recurrence is likely. Thus, the probability of cure is contingent on the combination of surgery and chemotherapy effectively eliminating all cancer cells. In this Perspectives article, I present the case that the probability of achieving a cancer-free state is maximized through a combination of maximal debulking surgery and intraperitoneal chemotherapy. I discuss the evidence indicating that by taking this approach, cures could be achieved in up to 50% of women with advanced-stage ovarian cancer. PMID:26787282

  2. Lymph node staging in colorectal cancer: Old controversies and recent advances

    PubMed Central

    Resch, Annika; Langner, Cord

    2013-01-01

    Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor node metastasis (TNM) system is currently regarded as the strongest prognostic parameter for patients with colorectal cancer. For affected patients, the indication for adjuvant therapy is mainly guided by the presence of regional lymph node metastasis. In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen, several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node staging. These include changing definitions of lymph nodes, involved lymph nodes, and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be dissected. Methods to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone compression. Outcome prediction based on the lymph node ratio, defined as the number of positive lymph nodes divided by the total number of retrieved nodes, may be superior to the absolute numbers of involved nodes. Extracapsular invasion has been identified as additional prognostic factor. Adding step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological diagnosis. The clinical value of more recent technical advances, such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined. PMID:24379568

  3. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    ClinicalTrials.gov

    2016-07-10

    Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

  4. Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck

    ClinicalTrials.gov

    2016-08-10

    Squamous Cell Carcinoma of the Hypopharynx Stage III; Squamous Cell Carcinoma of the Hypopharynx Stage IV; Laryngeal Squamous Cell Carcinoma Stage III; Laryngeal Squamous Cell Carcinoma Stage IV; Oropharyngeal Squamous Cell Carcinoma Stage III; Oropharyngeal Squamous Cell Carcinoma Stage IV; Squamous Cell Carcinoma of the Oral Cavity Stage III; Squamous Cell Carcinoma of the Oral Cavity Stage IV; Locally Advanced Malignant Neoplasm

  5. 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.

  6. Endoscopic ultrasound for the characterization and staging of rectal cancer. Current state of the method. Technological advances and perspectives.

    PubMed

    Gersak, Mariana M; Badea, Radu; Graur, Florin; Hajja, Nadim Al; Furcea, Luminita; Dudea, Sorin M

    2015-06-01

    Endoscopic ultrasound is the most accurate type of examination for the assessment of rectal tumors. Over the years, the method has advanced from gray-scale examination to intravenous contrast media administration and to different types of elastography. The multimodal approach of tumors (transrectal, transvaginal) is adapted to each case. 3D ultrasound is useful for spatial representation and precise measurement of tumor formations, using CT/MR image reconstruction; color elastography is useful for tumor characterization and staging; endoscopic ultrasound using intravenous contrast agents can help study the amount of contrast agent targeted at the level of the tumor formations and contrast wash-in/wash-out time, based on the curves displayed on the device. The transvaginal approach often allows better visualization of the tumor than the transrectal approach. Performing the procedure with the rectal ampulla distended with contrast agent may be seen as an optimization of the examination methodology. All these aspects are additional methods for gray-scale endoscopic ultrasound, capable of increasing diagnostic accuracy. This paper aims at reviewing the progress of transrectal and transvaginal ultrasound, generically called endoscopic ultrasound, for rectal tumor diagnosis and staging, with emphasis on the current state of the method and its development trends.

  7. Advances in Medical Management of Early Stage and Advanced Breast Cancer: 2015.

    PubMed

    Witherby, Sabrina; Rizack, Tina; Sakr, Bachir J; Legare, Robert D; Sikov, William M

    2016-01-01

    Standard management of early stage and advanced breast cancer has been improved over the past few years by knowledge gained about the biology of the disease, results from a number of eagerly anticipated clinical trials and the development of novel agents that offer our patients options for improved outcomes or reduced toxicity or both. This review highlights recent major developments affecting the systemic therapy of breast cancer, broken down by clinically relevant patient subgroups and disease stage, and briefly discusses some of the ongoing controversies in the treatment of breast cancer and promising therapies on the horizon.

  8. Fast neutron irradiation for advanced tumors in the pelvis

    SciTech Connect

    Battermann, J.J.; Breur, K.

    1981-08-01

    Since the end of 1975, fast neutron irradiation has been used in the Antoni van Leeuwenhoek Hospital for the treatment of advanced tumors, which had no prospect of cure by other treatment modalities. Fifty-nine patients were irradiated in the pelvic area, 22 for inoperable bladder cancer, 25 for rectal and 12 for gynecological cancer. Treatments were given 5 times per week with a 14 MeV d + T neutron generator. Persisting complete tumor regression was achieved in 11 of 22 bladded patients, 14 of 25 rectum patients and 6 of 12 gynecological patients. Because of unfavorable beam characteristics, 15 of 59 (25%) treated patients had severe radiation-induced intestinal and skin complications.

  9. 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

  10. Tumor Heterogeneity of FIGO Stage III Carcinoma of the Uterine Cervix

    SciTech Connect

    Kim, Yong Bae; Lee, Ik Jae; Kim, Song Yih; Kim, Jun Won; Yoon, Hong In; Kim, Sang Wun; Kim, Sunghoon; Kim, Young Tae; Suh, Chang Ok; Kim, Gwi Eon

    2009-12-01

    Purpose: The purpose of this study was to analyze tumor heterogeneity based on tumor extent and suggest reappraisal of the system of the International Federation of Gynecology and Obstetrics (FIGO) for Stage III carcinoma of the uterine cervix from a radiotherapeutic viewpoint. Methods and Materials: Between 1986 and 2004, 407 patients with FIGO Stage III (FIGO Stage IIIa in 19 and IIIb in 388) were treated with external beam radiotherapy (RT) and high-dose rate brachytherapy. All patients were reviewed with respect to tumor extent. Patterns of failure and survival parameters were analyzed by use of the chi{sup 2} test and Kaplan-Meier method. Results: The complete response rate was 79.6%, and the 5-year overall survival rates for Stage IIIa and Stage IIIb carcinoma of the cervix were 82.1% and 54.8%, respectively. To determine which parameters of tumor extent had an influence on prognosis for Stage IIIb patients, pelvic wall (PW) extension and hydronephrosis (HD) retained significance on multivariate analysis. Stage IIIb patients were divided into three subgroups according to PW extension and HD: low risk (unilateral PW extension without HD), intermediate risk (HD without PW extension or bilateral PW extension without HD), and high risk (unilateral or bilateral PW extension with HD). The high-risk group had a remarkably low complete response rate, high locoregional failure rate, and low 5-year survival rate compared with the intermediate- and low-risk groups. Conclusions: FIGO Stage III carcinoma of the cervix covers considerably heterogeneous subgroups according to tumor extent. Before initiation of treatment, we suggest that physicians determine a tailored treatment policy based on tumor heterogeneity for each Stage III patient.

  11. Advanced bronchoscopic techniques in diagnosis and staging of lung cancer.

    PubMed

    Zaric, Bojan; Stojsic, Vladimir; Sarcev, Tatjana; Stojanovic, Goran; Carapic, Vladimir; Perin, Branislav; Zarogoulidis, Paul; Darwiche, Kaid; Tsakiridis, Kosmas; Karapantzos, Ilias; Kesisis, Georgios; Kougioumtzi, Ioanna; Katsikogiannis, Nikolaos; Machairiotis, Nikolaos; Stylianaki, Aikaterini; Foroulis, Christophoros N; Zarogoulidis, Konstantinos

    2013-09-01

    The role of advanced brochoscopic diagnostic techniques in detection and staging of lung cancer has steeply increased in recent years. Bronchoscopic imaging techniques became widely available and easy to use. Technical improvement led to merging in technologies making autofluorescence or narrow band imaging incorporated into one bronchoscope. New tools, such as autofluorescence imagining (AFI), narrow band imaging (NBI) or fuji intelligent chromo endoscopy (FICE), found their place in respiratory endoscopy suites. Development of endobronchial ultrasound (EBUS) improved minimally invasive mediastinal staging and diagnosis of peripheral lung lesions. Linear EBUS proven to be complementary to mediastinoscopy. This technique is now available in almost all high volume centers performing bronchoscopy. Radial EBUS with mini-probes and guiding sheaths provides accurate diagnosis of peripheral pulmonary lesions. Combining EBUS guided procedures with rapid on site cytology (ROSE) increases diagnostic yield even more. Electromagnetic navigation technology (EMN) is also widely used for diagnosis of peripheral lesions. Future development will certainly lead to new improvements in technology and creation of new sophisticated tools for research in respiratory endoscopy. Broncho-microscopy, alveoloscopy, optical coherence tomography are some of the new research techniques emerging for rapid technological development.

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

    PubMed

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

    1985-06-01

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

  13. The potential role of bevacizumab in early stages and locally advanced non-small cell lung cancer

    PubMed Central

    Schettino, Clorinda; Bareschino, Maria Anna; Rossi, Antonio; Maione, Paolo; Castaldo, Vincenzo; Mazzeo, Nicole; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Palazzolo, Giovanni; Ciardiello, Fortunato; Gridelli, Cesare

    2009-01-01

    Improving outcomes for early-stage non-small cell lung cancer (NSCLC) is a major research area considering that a significant percentage of such patients develop recurrent disease within 5 years of complete lung resection. Adjuvant chemotherapy prolongs survival, with an absolute improvement in 5-year overall survival of about 5% with drawbacks such as treatment toxicity. Approximately, one third of patients with newly diagnosed NSCLC have locally advanced disease not amenable for surgical resection – in this setting of patients concurrent chemoradiation is the standard of therapy. However, the treatment of locally advanced NSCLC is still controversial and clinical outcomes are disappointing, and so new approaches are required to improve the clinical benefit in this setting of patients. Vascular endothelial growth factor (VEGF) is a key angiogenic factor implicated in tumor blood vessels formation and permeability, and tumor VEGF overexpression in patients with early stage lung cancer has been associated with worse relapse free and overall survival. Several agents have been developed that inhibit VEGF or its receptor signalling system. Bevacizumab is the first recombinant humanized monoclonal antibody binding VEGF to demonstrate clinical benefit or rather a survival prolongation in combination with chemotherapy in the treatment of non-squamous advanced NSCLC patients. These positive results led to a large number of clinical trials to evaluate bevacizumab in combination with other targeted agents in advanced disease, and to define the role of this agent in early stage NSCLC such as the impact of bevacizumab integration in chemoradiotherapy strategy for locally advanced disease. PMID:21789109

  14. The potential role of bevacizumab in early stages and locally advanced non-small cell lung cancer.

    PubMed

    Schettino, Clorinda; Bareschino, Maria Anna; Rossi, Antonio; Maione, Paolo; Castaldo, Vincenzo; Mazzeo, Nicole; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Palazzolo, Giovanni; Ciardiello, Fortunato; Gridelli, Cesare

    2009-07-01

    Improving outcomes for early-stage non-small cell lung cancer (NSCLC) is a major research area considering that a significant percentage of such patients develop recurrent disease within 5 years of complete lung resection. Adjuvant chemotherapy prolongs survival, with an absolute improvement in 5-year overall survival of about 5% with drawbacks such as treatment toxicity. Approximately, one third of patients with newly diagnosed NSCLC have locally advanced disease not amenable for surgical resection - in this setting of patients concurrent chemoradiation is the standard of therapy. However, the treatment of locally advanced NSCLC is still controversial and clinical outcomes are disappointing, and so new approaches are required to improve the clinical benefit in this setting of patients. Vascular endothelial growth factor (VEGF) is a key angiogenic factor implicated in tumor blood vessels formation and permeability, and tumor VEGF overexpression in patients with early stage lung cancer has been associated with worse relapse free and overall survival. Several agents have been developed that inhibit VEGF or its receptor signalling system. Bevacizumab is the first recombinant humanized monoclonal antibody binding VEGF to demonstrate clinical benefit or rather a survival prolongation in combination with chemotherapy in the treatment of non-squamous advanced NSCLC patients. These positive results led to a large number of clinical trials to evaluate bevacizumab in combination with other targeted agents in advanced disease, and to define the role of this agent in early stage NSCLC such as the impact of bevacizumab integration in chemoradiotherapy strategy for locally advanced disease.

  15. Racial disparities in advanced stage colorectal cancer survival

    PubMed Central

    Wallace, Kristin; Hill, Elizabeth G.; Lewin, David N.; Williamson, Grace; Oppenheimer, Stephanie; Ford, Marvella E.; Wargovich, Michael J.; Berger, Franklin G.; Bolick, Susan W.; Thomas, Melanie B.; Alberg, Anthony J.

    2013-01-01

    Purpose African Americans (AA) have a higher incidence and lower survival from colorectal cancer (CRC) compared to European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry (SCCCR) is used to investigate the relationship between race and age on advanced stage CRC survival. Methods The study population was comprised of 3865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2673 (69%) EA and 1192 (31%) AA. Kaplan-Meier methods were used to generate median survival time and corresponding 95% confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards (CPH) regression models to generate Hazard Ratios (HR) and 95% CI. Results We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (< 50 years), AA race was associated with a 1.34 (95% CI 1.06-1.71) higher risk of death compared to EA. Among older patients, we observed a modest increase risk of death among AA men compared to EA (HR 1.16 (95% CI 1.01-1.32) but no difference by race among women (HR 0.94 (95% CI 0.82-1.08)). Moreover, we observed that the disparity in survival has worsened over the past 15 years. Conclusions Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those < 50 years old. PMID:23296454

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

    PubMed Central

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

    1995-01-01

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

  17. Locally Advanced Gastroesophageal Junction Tumor: A Treatment Dilemma

    PubMed Central

    Ashraf, Noman; Hoffe, Sarah

    2015-01-01

    Over the last several decades, the incidence of adenocarcinoma of the gastroesophageal junction (GEJ) has been increasing in developed countries. Although complete surgical resection remains the cornerstone of treatment for resectable disease, long-term outcomes are poor and recurrence rates are high with surgery alone in patients presenting with locally advanced disease. Multimodal therapy has been shown to improve survival; however, the optimal therapeutic approach remains controversial, and practices vary across the world. Preoperative chemoradiotherapy is generally used in the U.S., whereas perioperative chemotherapy without radiation is favored in most European countries. In this review, we discuss why the treatment of locally advanced GEJ tumors remains controversial, examine the evidence for various multimodal approaches, discuss their respective pros and cons, evaluate the role of radiation therapy, highlight some ongoing and planned clinical trials, and suggest areas that need further research. PMID:25561508

  18. Sporadic gastric carcinoid tumor successfully treated by two-stage laparoscopic surgery: A case report

    PubMed Central

    Kinoshita, Takahiro; Oshiro, Takashi; Urita, Tasuku; Yoshida, Yutaka; Ooshiro, Mitsuru; Okazumi, Shinichi; Katoh, Ryoji; Sasai, Daisuke; Hiruta, Nobuyuki

    2010-01-01

    We report a case of sporadic gastric carcinoid tumor successfully treated by two-stage laparoscopic surgery. A 38-year old asymptomatic woman was referred to our hospital for evaluation of a submucosal tumor of the stomach. Endoscopic examination showed a solitary submucosal tumor without ulceration or central depression on the posterior wall of the antrum and biopsy specimens were not sufficient to determine the diagnosis. Endoscopic ultrasound revealed a tumor nearly 2 cm in diameter arising from the muscle layer and a computed tomography scan showed the tumor enhanced in the arterial phase. Laparoscopic wedge resection was performed for definitive diagnosis. Pathologically, the tumor was shown to be gastric carcinoid infiltrating the muscle layer which indicated the probability of lymph node metastasis. Serum gastrin levels were normal. As a radical treatment, laparoscopy-assisted distal gastrectomy with regional lymphadenectomy was performed 3 wk after the initial surgery. Finally, pathological examination revealed no lymph node metastasis. PMID:21160902

  19. Staging of cervical cancer based on tumor heterogeneity characterized by texture features on 18F-FDG PET images

    NASA Astrophysics Data System (ADS)

    Mu, Wei; Chen, Zhe; Liang, Ying; Shen, Wei; Yang, Feng; Dai, Ruwei; Wu, Ning; Tian, Jie

    2015-07-01

    The aim of the study is to assess the staging value of the tumor heterogeneity characterized by texture features and other commonly used semi-quantitative indices extracted from 18F-FDG PET images of cervical cancer (CC) patients. Forty-two patients suffering CC at different stages were enrolled in this study. Firstly, we proposed a new tumor segmentation method by combining the intensity and gradient field information in a level set framework. Secondly, fifty-four 3D texture features were studied besides of SUVs (SUVmax, SUVmean, SUVpeak) and metabolic tumor volume (MTV). Through correlation analysis, receiver-operating-characteristic (ROC) curves analysis, some independent indices showed statistically significant differences between the early stage (ES, stages I and II) and the advanced stage (AS, stages III and IV). Then the tumors represented by those independent indices could be automatically classified into ES and AS, and the most discriminative feature could be chosen. Finally, the robustness of the optimal index with respect to sampling schemes and the quality of the PET images were validated. Using the proposed segmentation method, the dice similarity coefficient and Hausdorff distance were 91.78   ±   1.66% and 7.94   ±   1.99 mm, respectively. According to the correlation analysis, all the fifty-eight indices could be divided into 20 groups. Six independent indices were selected for their highest areas under the ROC curves (AUROC), and showed significant differences between ES and AS (P  <  0.05). Through automatic classification with the support vector machine (SVM) Classifier, run percentage (RP) was the most discriminative index with the higher accuracy (88.10%) and larger AUROC (0.88). The Pearson correlation of RP under different sampling schemes is 0.9991   ±   0.0011. RP is a highly stable feature and well correlated with tumor stage in CC, which suggests it could differentiate ES and AS with high

  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. KLF4 is downregulated but not mutated during human esophageal squamous cell carcinogenesis and has tumor stage-specific functions.

    PubMed

    Yang, Yizeng; Katz, Jonathan P

    2016-04-01

    The transcriptional regulator Krüppel-like factor 4 (KLF4) is decreased in human esophageal squamous cell cancer (ESCC), and Klf4 deletion in mice produces squamous cell dysplasia. Nonetheless the mechanisms of KLF4 downregulation in ESCC and the functions of KLF4 during ESCC development and progression are not well understood. Here, we sought to define the regulation of KLF4 and delineate the stage-specific effects of KLF4 in ESCC. We found that KLF4 expression was decreased in human ESCC and in 8 of 9 human ESCC cell lines. However, by genomic sequencing, we observed no KLF4 mutations or copy number changes in any of 52 human ESCC, suggesting other mechanisms for KLF4 silencing. In fact, KLF4 expression in human ESCC cell lines was increased by the DNA methylation inhibitor 5-azacytidine, suggesting an epigenetic mechanism for KLF4 silencing. Surprisingly, while KLF4 decreased in high-grade dysplasia and early stage tumors, KLF4 increased with advanced cancer stage, and KLF4 expression in ESCC was inversely correlated with survival. Interestingly, KLF4 promoted invasion of human ESCC cells, providing a functional link to the stage-specific expression of KLF4. Taken together, these findings suggest that KLF4 loss is necessary for esophageal tumorigenesis but that restored KLF4 expression in ESCC promotes tumor spread. Thus, the use of KLF4 as a diagnostic and therapeutic target in cancer requires careful consideration of context. PMID:26934576

  2. Bronchial involvement in advanced stage lymphangioleiomyomatosis: histopathologic and molecular analyses.

    PubMed

    Hayashi, Takuo; Kumasaka, Toshio; Mitani, Keiko; Okada, Yoshinori; Kondo, Takashi; Date, Hiroshi; Chen, Fengshi; Oto, Takahiro; Miyoshi, Shinichiro; Shiraishi, Takeshi; Iwasaki, Akinori; Hara, Kieko; Saito, Tsuyoshi; Ando, Katsutoshi; Kobayashi, Etsuko; Gunji-Niitsu, Yoko; Kunogi, Makiko; Takahashi, Kazuhisa; Yao, Takashi; Seyama, Kuniaki

    2016-04-01

    Lymphangioleiomyomatosis (LAM), a rare progressive disease that almost exclusively affects women, is characterized by pulmonary cysts and neoplastic proliferation of smooth muscle-like cells (LAM cells). Airflow obstruction is a physiologic consequence that is commonly observed in LAM and has been attributed to narrowing of peripheral airways. However, histopathologic examinations of the entire airway have been precluded by the limited availability of such specimens. Here, we used explanted lung tissues from 30 LAM patients for a thorough histologic analysis with a special emphasis on the bronchi. We found bronchial involvement by LAM cells and lymphatics in all patients examined. Furthermore, a moderate to severe degree of chronic inflammation (73%), goblet cell hyperplasia (97%), squamous cell metaplasia (83%) of the epithelium, and thickening of basal lamina (93%) were identified in the bronchi. Because LAM cells are transformed by the functional loss of the TSC genes leading to a hyperactivated mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, we confirmed the expression of phospho-p70S6K, phospho-S6, phospho-4E-BP1, and vascular endothelial growth factor (VEGF)-D in LAM cells from all of the patients examined. In contrast, no protein expression of hypoxia-inducible factor 1α, a downstream molecule indicative of mTORC1 activation and leading to VEGF production, was detected in any patient. Our study indicates that late-stage LAM patients commonly have bronchi involved by the proliferation of both LAM cells and lymphatics and that chronic inflammation complicated their disease. Furthermore, the up-regulation of hypoxia-inducible factor 1α, a common event in mTORC1-driven tumor cells, does not occur in LAM cells and plays no role in VEGF-D expression in LAM cells. PMID:26997436

  3. Recruitment of natural killer cells in advanced stages of endogenously arising B-cell lymphoma: implications for therapeutic cell transfer.

    PubMed

    Przewoznik, Margarethe; Hömberg, Nadine; Naujoks, Marcella; Pötzl, Johann; Münchmeier, Niklas; Brenner, Christoph D; Anz, David; Bourquin, Carole; Nelson, Peter J; Röcken, Martin; Mocikat, Ralph

    2012-04-01

    During inflammation and in transplantable tumor models, natural killer (NK) cells are recruited to pathologic tissues and activated to produce proinflammatory cytokines favoring adaptive immune responses of the T-helper type 1 (Th1) type. Interferon (IFN)-γ is needed to induce chemokines that attract NK cells in transplanted tumors. Nothing, however, is known on NK-cell migration in spontaneous tumors. As effective recruitment is a prerequisite for therapeutic NK-cell transfer, we investigated the cytokine milieu and the mechanisms that are instrumental for NK-cell accumulation in an endogenous tumor model. We make use of λ-myc transgenic mice that harbor the c-myc oncogene and develop spontaneous B-cell lymphoma. In contrast to lymphomas induced by tumor cell injection, virtually no IFN-γ produced by NK or by other cells was present in the tumor environment, particularly in advanced stages. Dendritic cells showed an impaired expression of interleukin-12, which is suggestive of deficient Th1 priming. The IFN-γ-dependent chemokines CXCL9 and CXCL10 were pivotal for NK-cell migration in the endogenous lymphoma model. Although IFN-γ was absent in late tumor stages, there was still expression of CXCL9 and CXCL10 with an ongoing influx of NK cells. The results demonstrate that transplantable tumor models do not reflect the situation as found in endogenously arising neoplasia, because in the latter, effective Th1 and cytotoxic T-lymphocyte responses are presumably not induced because of impaired IFN-γ production. The data also suggest that CXCL9 and CXCL10 production and NK-cell migration become independent of IFN-γ during tumor progression, and therefore support approaches of adoptive NK-cell transfer that hold promise for treatment of cancer. PMID:22421939

  4. Selecting the best strategy of treatment in newly diagnosed advanced-stage ovarian cancer patients.

    PubMed

    Minig, Lucas; Zorrero, Cristina; Iserte, Pablo Padilla; Poveda, Andres

    2015-12-26

    Although it is assumed that the combination of chemotherapy and radical surgery should be indicated in all newly diagnosed advanced-stage ovarian cancer patients, one of the main raised questions is how to select the best strategy of initial treatment in this group of patients, neoadjuvant chemotherapy followed by interval debulking surgery or primary debulking surgery followed by adjuvant chemotherapy. The selection criteria to offer one strategy over the other as well as a stepwise patient selection for initial treatment are described. Selecting the best strategy of treatment in newly diagnosed advanced stage ovarian cancer patients is a multifactorial and multidisciplinary decision. Several factors should be taken into consideration: (1) the disease factor, related to the extension and localization of the disease as well as tumor biology; (2) the patient factor, associated with patient age, poor performance status, and co-morbidities; and (3) institutional infrastructure factor, related to the lack of prolonged operative time, an appropriate surgical armamentarium, as well as well-equipped intensive care units with well-trained personnel.

  5. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    PubMed

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research. PMID:26925962

  6. Advances in Wilms Tumor Treatment and Biology: Progress Through International Collaboration

    PubMed Central

    Dome, Jeffrey S.; Graf, Norbert; Geller, James I.; Fernandez, Conrad V.; Mullen, Elizabeth A.; Spreafico, Filippo; Van den Heuvel-Eibrink, Marry; Pritchard-Jones, Kathy

    2015-01-01

    Clinical trials in Wilms tumor (WT) have resulted in overall survival rates of greater than 90%. This achievement is especially remarkable because improvements in disease-specific survival have occurred concurrently with a reduction of therapy for large patient subgroups. However, the outcomes for certain patient subgroups, including those with unfavorable histologic and molecular features, bilateral disease, and recurrent disease, remain well below the benchmark survival rate of 90%. Therapy for WT has been advanced in part by an increasingly complex risk-stratification system based on patient age; tumor stage, histology, and volume; response to chemotherapy; and loss of heterozygosity at chromosomes 1p and 16q. A consequence of this system has been the apportionment of patients into such small subgroups that only collaboration between large international WT study groups will support clinical trials that are sufficiently powered to answer challenging questions that move the field forward. This article gives an overview of the Children's Oncology Group and International Society of Pediatric Oncology approaches to WT and focuses on four subgroups (stage IV, initially inoperable, bilateral, and relapsed WT) for which international collaboration is pressing. In addition, biologic insights resulting from collaborative laboratory research are discussed. A coordinated expansion of international collaboration in both clinical trials and laboratory science will provide real opportunity to improve the treatment and outcomes for children with renal tumors on a global level. PMID:26304882

  7. C5b-9 Staining Correlates With Clinical and Tumor Stage in Gastric Adenocarcinoma

    PubMed Central

    Chen, Jian; Yang, Wei-jun; Sun, Hai-jian; Wu, Yu-zhang

    2016-01-01

    The complement system is a critical part of the immune response, acting in defense against viral infections, clearance of immune complexes, and maintenance of tissue homeostasis. Upregulated expression of the terminal complement complex, C5b-9, has been observed on various tumor cells, such as stomach carcinoma cells, and on cells in the necrotic regions of these tumors as well; however, whether and how C5b-9 is related to gastric cancer progression and severity remains unknown. In this study, human gastric adenocarcinoma (HGAC) tissues (n=47 cases) and patient-matched adjacent nontumoral parenchyma (n=20 cases) were evaluated by tissue microarray and immunohistochemistry. The HGAC tissues showed upregulated C5b-9 expression. Multinomial logistic regression and likelihood ratio testing showed that overexpression of C5b-9 in HGAC tissue was significantly correlated with clinical stage (P=0.007) and tumor stage (P=0.005), but not with tumor distant organ metastasis, lymphoid nodal status, sex, or age. Patients with late-stage gastric adenocarcinoma had a higher amount of tumor cells showing positive staining for C5b-9 than patients with early-stage disease. These results may help in diagnosis and assessment of disease severity of human gastric carcinoma. PMID:26186252

  8. The changing hope trajectory in patients with advanced-stage cancer: a nursing perspective.

    PubMed

    Sanders, Judith Brown; Seda, Julie S; Kardinal, Carl G

    2012-06-01

    As patients with advanced-stage cancer move from the initial diagnosis through treatment, remission, recurrence, and advanced-stage disease, the hope trajectory undergoes a dynamic transformation. By identifying the hope trajectory, nurses can help patients focus on obtainable hope objects while balancing the need to present a realistic prognosis. This, in turn, may help patients find meaning and purpose in advanced-stage cancer and facilitate realistic hope when faced with a life-threatening illness.

  9. Targeting mutant p53 protein and the tumor vasculature: an effective combination therapy for advanced breast tumors

    PubMed Central

    Liang, Yayun; Besch-Williford, Cynthia; Benakanakere, Indira; Thorpe, Philip E.

    2010-01-01

    Breast cancer progression depends upon the elaboration of a vasculature sufficient for the nourishment of the developing tumor. Breast tumor cells frequently contain a mutant form of p53 (mtp53), a protein which promotes their survival. The aim of this study was to determine whether combination therapy targeting mtp53 and anionic phospholipids (AP) on tumor blood vessels might be an effective therapeutic strategy for suppressing advanced breast cancer. We examined the therapeutic effects, singly, or in combination, of p53 reactivation and induction of massive apoptosis (PRIMA-1), which reactivates mtp53 and induces tumor cell apoptosis, and 2aG4, a monoclonal antibody that disrupts tumor vasculature by targeting AP on the surface of tumor endothelial cells and causes antibody-dependent destruction of tumor blood vessels, leading to ischemia and tumor cell death. Xenografts from two tumor cell lines containing mtp53, BT-474 and HCC-1428, were grown in nude mice to provide models of advanced breast tumors. After treatment with PRIMA-1 and/or 2aG4, regressing tumors were analyzed for vascular endothelial growth factor (VEGF) expression, blood vessel loss, and apoptotic markers. Individual drug treatment led to partial suppression of breast cancer progression. In contrast, combined treatment with PRIMA-1 and 2aG4 was extremely effective in suppressing tumor growth in both models and completely eradicated approximately 30% of tumors in the BT-474 model. Importantly, no toxic effects were observed in any treatment group. Mechanistic studies determined that PRIMA-1 reactivated mtp53 and also exposed AP on the surface of tumor cells as determined by enhanced 2aG4 binding. Combination treatment led to significant induction of tumor cell apoptosis, loss of VEGF expression, as well as destruction of tumor blood vessels. Furthermore, combination treatment severely disrupted tumor blood vessel perfusion in both tumor models. The observed in vitro PRIMA-1-induced exposure of

  10. Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors

    ClinicalTrials.gov

    2016-09-07

    Solid Neoplasm; Stage III Pancreatic Cancer; 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 Non-Small Cell Lung Cancer; Stage IVA Pancreatic Cancer; Stage IVB Pancreatic Cancer; Sarcoma; Colorectal Cancer; Head and Neck Cancer; Cancer of Unknown Primary; Bladder Cancer; Ovarian Cancer

  11. Low podoplanin expression in pretreatment biopsy material predicts poor prognosis in advanced-stage squamous cell carcinoma of the uterine cervix treated by primary radiation.

    PubMed

    Dumoff, Kimberly L; Chu, Christina S; Harris, Eleanor E; Holtz, David; Xu, Xiaowei; Zhang, Paul J; Acs, Geza

    2006-05-01

    Lymphatic invasion and nodal metastasis are predictors of poor outcome in cervix carcinoma. We have recently found that low podoplanin immunoreactivity in cervix carcinoma correlated with the presence of lymphatic invasion and nodal metastasis. In the current study, we examined whether podoplanin expression in pretreatment cervical biopsies can predict the presence lymphatic invasion, nodal metastasis, and outcome in advanced-stage tumors treated by nonsurgical means. Podoplanin expression was analyzed by immunohistochemistry in 48 cervical biopsies and corresponding hysterectomy specimens of early-stage invasive squamous cell carcinoma and in 74 pretreatment biopsies from advanced-stage tumors treated with primary radiation. We found a highly significant correlation between podoplanin expression obtained in biopsy and corresponding hysterectomy materials (r = 0.8962, P < 0.0001). Low podoplanin expression showed a significant correlation with lymphatic invasion (P < 0.0001) and nodal metastasis (P = 0.0058). Low podoplanin expression in pretreatment biopsy material showed a significant correlation with poor disease-free (P = 0.0009) and overall (P = 0.0002) survival in advanced-stage tumors. Our results suggest that in advanced-stage cervix carcinomas treated by radiation, when traditional prognostic indicators are not available and treatment decisions are based on biopsy material and clinical staging parameters, examination of podoplanin expression in pretreatment biopsy material may be a useful marker to predict lymphatic metastasis and patient outcome. Prospective studies involving larger numbers of patients are needed to further evaluate the clinical utility of examination of podoplanin expression in patients with cervix carcinoma.

  12. [A Case of HER2-Positive Stage IV Advanced Gastric Cancer Treated with Chemotherapy Combined with Trastuzumab].

    PubMed

    Takaya, Kai; Takahashi, Ryosuke; Honma, Satoru; Horii, Shinichiro; Takahashi, Hirokazu; Hagiwara, Motohisa; Chin, Masahiro; Hashizume, Eiji

    2016-09-01

    We report a case of human epidermal growth factor receptor(HER)2 positive stage IV advanced gastric cancer successfully treated with chemotherapy combined with trastuzumab. A 50-year-old man was diagnosed with type 3 gastric cancer complicated by liver and lymph node metastases. Owing to a HER2 immunohistochemistry tumor score of 3+, we initiated capecitabine plus CDDP plus trastuzumab chemotherapy. After 6 chemotherapy courses, computed tomography showed the liver metastasis had disappeared and the paraaortic lymph nodes had shrunk. We continued the capecitabine plus trastuzumab chemotherapy, which resulted in a progression free survival of 31 months. After 38 chemotherapy courses, the primary tumor progressed; therefore, the patient underwent surgery. Chemotherapy combined with trastuzumab can allow for resec- tion of the primary tumor. PMID:27628555

  13. Depth of invasion, tumor budding, and worst pattern of invasion: Prognostic indicators in early-stage oral tongue cancer

    PubMed Central

    Almangush, Alhadi; Bello, Ibrahim O; Keski–Säntti, Harri; Mäkinen, Laura K; Kauppila, Joonas H; Pukkila, Matti; Hagström, Jaana; Laranne, Jussi; Tommola, Satu; Nieminen, Outi; Soini, Ylermi; Kosma, Veli-Matti; Koivunen, Petri; Grénman, Reidar; Leivo, Ilmo; Salo, Tuula

    2014-01-01

    Background Oral (mobile) tongue squamous cell carcinoma (SCC) is characterized by a highly variable prognosis in early-stage disease (T1/T2 N0M0). The ability to classify early oral tongue SCCs into low-risk and high-risk categories would represent a major advancement in their management. Methods Depth of invasion, tumor budding, histologic risk-assessment score (HRS), and cancer-associated fibroblast (CAF) density were studied in 233 cases of T1/T2 N0M0 oral tongue SCC managed in 5 university hospitals in Finland. Results Tumor budding (≥5 clusters at the invasive front of the tumor) and depth of invasion (≥4 mm) were associated with poor prognosis in patients with early oral tongue SCC (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.17–3.55; HR, 2.55; 95% CI, 1.25–5.20, respectively) after multivariate analysis. The HRS and CAF density did not predict survival. However, high-risk worst pattern of invasion (WPOI), a component of HRS, was also an independent prognostic factor (HR, 4.47; 95% CI, 1.59–12.51). Conclusion Analyzing the depth of invasion, tumor budding, and/or WPOI in prognostication and treatment planning of T1/T2 N0M0 oral tongue SCC is recommended. PMID:23696499

  14. [Research advances of anti-tumor immune response induced by pulse electric field ablation].

    PubMed

    Cui, Guang-ying; Diao, Hong-yan

    2015-11-01

    As a novel tumor therapy, pulse electric field has shown a clinical perspective. This paper reviews the characteristics of tumor ablation by microsecond pulse and nanosecond pulse electric field, and the research advances of anti-tumor immune response induced by pulse electric field ablation. Recent researches indicate that the pulse electric field not only leads to a complete ablation of local tumor, but also stimulates a protective immune response, thereby inhibiting tumor recurrence and metastasis. These unique advantages will show an extensive clinical application in the future. However, the mechanism of anti-tumor immune response and the development of related tumor vaccine need further studies.

  15. HLA-G Expression and Role in Advanced-Stage Classical Hodgkin Lymphoma

    PubMed Central

    Caocci, G.; Greco, M.; Fanni, D.; Senes, G.; Littera, R.; Lai, S.; Risso, P.; Carcassi, C.; Faa, G.; La Nasa, G.

    2016-01-01

    Non-classical human leucocyte antigen (HLA)-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL), in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp) deletion-insertion (del-ins) polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy) patients with a 2-year progression-free survival rate (PFS) of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS) cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2. PMID:27349312

  16. Comparative analysis of BRAF, NRAS and c-KIT mutation status between tumor tissues and autologous tumor cell-lines of stage III/IV melanoma.

    PubMed

    Knol, Anne-Chantal; Pandolfino, Marie-Christine; Vallée, Audrey; Nguyen, Frédérique; Lella, Virginie; Khammari, Amir; Denis, Marc; Puaux, Anne-Laure; Dréno, Brigitte

    2015-01-01

    In the last decade, advances in molecular biology have provided evidence of the genotypic heterogeneity of melanoma. We analysed BRAF, NRAS and c-KIT alterations in tissue samples from 63 stage III/IV melanoma patients and autologous cell-lines, using either allele-specific or quantitative PCR. The expression of BRAF V600E protein was also investigated using an anti-BRAF antibody in the same tissue samples. 81% of FFPE samples and tumor cell-lines harboured a genetic alteration in either BRAF (54%) or NRAS (27%) oncogenes. There was a strong concordance (100%) between tissue samples and tumor cell-lines. The BRAF V600E mutant-specific antibody showed high sensitivity (96%) and specificity (100%) for detecting the presence of a BRAF V600E mutation. The correlation was of 98% between PCR and immunohistochemistry results for BRAF mutation. These results suggest that BRAF and NRAS mutation status of tumor cells is not affected by culture conditions.

  17. Transcriptome profile of the early stages of breast cancer tumoral spheroids

    PubMed Central

    Pacheco-Marín, Rosario; Melendez-Zajgla, Jorge; Castillo-Rojas, Gonzalo; Mandujano-Tinoco, Edna; Garcia-Venzor, Alfredo; Uribe-Carvajal, Salvador; Cabrera-Orefice, Alfredo; Gonzalez-Torres, Carolina; Gaytan-Cervantes, Javier; Mitre-Aguilar, Irma B.; Maldonado, Vilma

    2016-01-01

    Oxygen or nutrient deprivation of early stage tumoral spheroids can be used to reliably mimic the initial growth of primary and metastatic cancer cells. However, cancer cell growth during the initial stages has not been fully explored using a genome-wide approach. Thus, in the present study, we investigated the transcriptome of breast cancer cells during the initial stages of tumoral growth using RNAseq in a model of Multicellular Tumor Spheroids (MTS). Network analyses showed that a metastatic signature was enriched as several adhesion molecules were deregulated, including EPCAM, E-cadherin, integrins and syndecans, which were further supported by an increase in cell migration. Interestingly, we also found that the cancer cells at this stage of growth exhibited a paradoxical hyperactivation of oxidative mitochondrial metabolism. In addition, we found a large number of regulated (long non coding RNA) lncRNAs, several of which were co-regulated with neighboring genes. The regulatory role of some of these lncRNAs on mRNA expression was demonstrated with gain of function assays. This is the first report of an early-stage MTS transcriptome, which not only reveals a complex expression landscape, but points toward an important contribution of long non-coding RNAs in the final phenotype of three-dimensional cellular models. PMID:27021602

  18. [Research advance on clinical blood transfusion and tumor therapy].

    PubMed

    Jiang, Xue-Bing; Zhang, Li-Ping; Wang, Yan-Ju; Ma, Cong

    2010-08-01

    Clinical blood transfusion is one of the most important supportive therapy for patients with tumor. The blood transfusion has dual effects for patients with tumor. First, blood transfusion can rectify anemia and improve oxygen saturation, accelerate oxidation and necrosis for tumor cells; the second, blood transfusion can induce immunosuppression, tumor recurrence and postoperative infection for tumor patients. Filtering white blood cells (WBC) before blood transfusion can decrease the incidence of the adverse reactions. The rational perioperative autotransfusion for patients with tumors is focus to which the world medical sciences pay close attention. In this article, the support effect of blood transfusion for treatment of tumor patients, blood transfusion and immunosuppression, blood transfusion and postoperative infection and relapse of tumor patients, depleted leukocyte blood transfusion and autologous transfusion of tumor patients are reviewed.

  19. Immunohistochemical markers for tumor associated macrophages and survival in advanced classical Hodgkin’s lymphoma

    PubMed Central

    Sánchez-Espiridión, Beatriz; Martin-Moreno, Ana M.; Montalbán, Carlos; Medeiros, L. Jeffrey; Vega, Francisco; Younes, Anas; Piris, Miguel A.; Garcia, Juan F.

    2012-01-01

    A subset of patients with advanced classical Hodgkin’s lymphoma is refractory to standard therapies. Therefore, it is relevant to identify new biologically-based prognostic markers. Recently, tumor associated macrophages have been proposed as a factor that predicts survival, although contradictory results have also been reported. Here we analyzed four macrophage markers (CD68, CD163, LYZ, and STAT1) using immunohistochemistry and automated quantification, in two independent series of advanced classical Hodgkin’s lymphoma (n=266 and 103 patients, respectively). Our results did not confirm that specific macrophage immunohistochemical markers could be used as surrogates for gene expression profiling studies. Survival analyses did not show correlation between CD163, LYZ or STAT1 and either failure-free or disease-specific survival. There was an association between CD68 and disease-specific survival, but it was not consistent in both series. In conclusion, individual tumor associated macrophage markers cannot be used to predict outcome before technical standardization and prospective validation in independent series of patients with comparable stages and treatments. PMID:22315492

  20. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy

    PubMed Central

    Han, Dai Hoon; Joo, Dong Jin; Kim, Myoung Soo; Choi, Gi Hong; Choi, Jin Sub; Park, Young Nyun; Seong, Jinsil

    2016-01-01

    Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3–12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10–22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID:27401662

  1. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy.

    PubMed

    Han, Dai Hoon; Joo, Dong Jin; Kim, Myoung Soo; Choi, Gi Hong; Choi, Jin Sub; Park, Young Nyun; Seong, Jinsil; Han, Kwang Hyub; Kim, Soon Il

    2016-09-01

    Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID:27401662

  2. 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

  3. Towards Optimal Design of Cancer Nanomedicines: Multi-stage Nanoparticles for the Treatment of Solid Tumors.

    PubMed

    Stylianopoulos, Triantafyllos; Economides, Eva-Athena; Baish, James W; Fukumura, Dai; Jain, Rakesh K

    2015-09-01

    Conventional drug delivery systems for solid tumors are composed of a nano-carrier that releases its therapeutic load. These two-stage nanoparticles utilize the enhanced permeability and retention (EPR) effect to enable preferential delivery to tumor tissue. However, the size-dependency of the EPR, the limited penetration of nanoparticles into the tumor as well as the rapid binding of the particles or the released cytotoxic agents to cancer cells and stromal components inhibit the uniform distribution of the drug and the efficacy of the treatment. Here, we employ mathematical modeling to study the effect of particle size, drug release rate and binding affinity on the distribution and efficacy of nanoparticles to derive optimal design rules. Furthermore, we introduce a new multi-stage delivery system. The system consists of a 20-nm primary nanoparticle, which releases 5-nm secondary particles, which in turn release the chemotherapeutic drug. We found that tuning the drug release kinetics and binding affinities leads to improved delivery of the drug. Our results also indicate that multi-stage nanoparticles are superior over two-stage nano-carriers provided they have a faster drug release rate and for high binding affinity drugs. Furthermore, our results suggest that smaller nanoparticles achieve better treatment outcome.

  4. Is uniportal thoracoscopic surgery a feasible approach for advanced stages of non-small cell lung cancer?

    PubMed Central

    Fieira, Eva; Delgado, Maria; Mendez, Lucía; Fernandez, Ricardo; de la Torre, Mercedes

    2014-01-01

    Objectives Conventional video-assisted thoracoscopic (VATS) lobectomy for advanced lung cancer is a feasible and safe surgery in experienced centers. The aim of this study is to assess the feasibility of uniportal VATS approach in the treatment of advanced non-small cell lung cancer (NSCLC) and compare the perioperative outcomes and survival with those in early-stage tumors operated through the uniportal approach. Methods From June 2010 to December 2012, we performed 163 uniportal VATS major pulmonary resections. Only NSCLC cases were included in this study (130 cases). Patients were divided into two groups: (A) early stage and (B) advanced cases (>5 cm, T3 or T4, or tumors requiring neoadjuvant treatment). A descriptive and retrospective study was performed, comparing perioperative outcomes and survival obtained in both groups. A survival analysis was performed with Kaplan-Meier curves and the log-rank test was used to compare survival between patients with early and advanced stages. Results A total of 130 cases were included in the study: 87 (A) vs. 43 (B) patients (conversion rate 1.1 vs. 6.5%, P=0.119). Mean global age was 64.9 years and 73.8% were men. The patient demographic data was similar in both groups. Upper lobectomies (A, 52 vs. B, 21 patients) and anatomic segmentectomies (A, 4 vs. B, 0) were more frequent in group A while pneumonectomy was more frequent in B (A, 1 vs. B, 6 patients). Surgical time was longer (144.9±41.3 vs. 183.2±48.9, P<0.001), and median number of lymph nodes (14 vs. 16, P=0.004) were statistically higher in advanced cases. Median number of nodal stations (5 vs. 5, P=0.165), days of chest tube (2 vs. 2, P=0.098), HOS (3 vs. 3, P=0.072), and rate of complications (17.2% vs. 14%, P=0.075) were similar in both groups. One patient died on the 58th postoperative day. The 30-month survival rate was 90% for the early stage group and 74% for advanced cases Conclusions Uniportal VATS lobectomy for advanced cases of NSCLC is a safe and

  5. Efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung squamous cell carcinoma

    PubMed Central

    Pi, Guoliang; He, Hanping; Bi, Jianping; Li, Ying; Li, Yanping; Zhang, Yong; Wang, Mingwei; Han, Guang; Lin, Chi

    2016-01-01

    Abstract Introduction: Currently, the options are limited for the treatment of patients who have failed 2 lines of chemotherapy for advanced lung squamous cell carcinoma (SCC). Recently, nivolumab, a fully human IgG4 programmed death 1 immune checkpoint inhibitor antibody, was approved to treat patients with advanced stage, relapsed/refractory lung SCC. Although nivolumab has demonstrated antitumor activity with survival benefit in Caucasian patients, its efficacy in Asian patients is unknown. Case Report: In this report, we describe a Chinese patient with relapsed advanced stage lung SCC who had an excellent response to nivolumab after only 2 doses without any adverse effects. Immunohistochemical analysis indicated the tumor was stained positive for programmed death-ligand 1. Conclusion: To our knowledge, this is the first report of satisfactory efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung SCC. Further clinical trials in Asian countries are needed to test whether nivolumab immunotherapy is a safe and effective treatment for Asian patients with lung SCC. PMID:27749580

  6. Tumor response assessment in locally advanced colon cancer after neoadjuvant chemotherapy

    PubMed Central

    González, Ignacio; Baixauli, Jorge; Martínez, Patricia; Rodríguez, Javier; Pastor, Carlos; Ribelles, María Jesús; Sola, Jesús Javier; Hernández-Lizoain, José Luís

    2014-01-01

    Background Preoperative chemotherapy followed by radical surgery is a novel therapeutic approach for locally advanced colon cancer (LACC). Neoadjuvant strategies require highly accurate diagnostic tests for a proper selection of candidate patients, allowing a low risk of overtreatment. This paper assesses the radiological, metabolic and pathological findings induced by preoperative oxaliplatin and fluoropyrimidines-based chemotherapy in LACC. Methods Forty-four consecutive patients with a confirmed diagnosis of LACC who received neoadjuvant chemotherapy and colon surgery were included. All patients were staged at baseline and before surgery. Clinical diagnosis consisted of physical examination, endoscopy with biopsy and computed tomography (CT) scan. In selected cases, a positron emission tomography/CT (PET/CT) scan was also performed. Accuracy and correlations between CT scan findings and pathologic report was assayed for T stage, N stage and TN stage. This study is retrospective in design. Results After chemotherapy, a statistical significant tumor volume reduction of 62.5% was achieved by CT-scan (P<0.001; Wilcoxon test) and a 38.9% decrease of standard uptake value (SUVmax) was observed on PET/CT (P=0.004). No progressive disease was reported during neoadjuvant treatment. Accuracy for T and N classification was 62% and 87%, respectively. Accuracy for TN stage was 77%, with 13.6% and 9.1% of the patients being under or overstaged, respectively. Pathologic stage II and III disease was observed in 29/44 (65.9%) and 15/44 (34.1%) of the patients, respectively. Pathologic complete response was achieved in three patients. Conclusions Oxaliplatin/fluorpyrimidine neoadjuvant chemotherapy induces major tumour shrinkage at both the pathological and radiological levels. The CT scan shows a high accuracy and a low overstaged rate in LACC patients treated by means of a neoadjuvant approach. PMID:24772338

  7. Advanced two-stage incineration: Research and development

    SciTech Connect

    Rehmat, A.; Khinkis, M.

    1991-01-01

    IGT is currently developing a two-stage fluidized-bed/cyclonic agglomerating incineration system that is based on combining the fluidized-bed agglomeration/incineration and cyclonic combustion technologies, both of which have been developed individually at IGT over many years. This combination has resulted in a unique and extremely flexible incinerator for solid, liquid, and gaseous wastes. The system can operate over a wide range of conditions in the first stage, from low temperature (desorption) to high temperature (agglomeration), including gasification of high-Btu wastes. In the combined system, solid, liquid, and gaseous organic wastes are expected to be easily and efficiently destroyed (>99.99% destruction and removal efficiency (DRE)) while solid inorganic contaminants are expected to be contained within a glassy matrix, rendering them benign and suitable for disposal in an ordinary landfill. The development of the two-stage incinerator is a culmination of extensive research and development efforts on each stage of the incinerator. A variety of data obtained for both stages includes agglomeration of ash, incineration and reclamation of used blast grit and foundry sand, partial combustion of carbonaceous fuels, in-situ desulfurization, combustion of low-Btu gases, incineration of industrial wastewater, and incineration of carbon tetrachloride.

  8. Recent advances in diagnosis and therapy of neuroendocrine tumors of the gastrointestinal tract.

    PubMed

    Pelley, R J; Bukowski, R M

    1997-01-01

    Neuroendocrine tumors of the gastrointestinal tract are rare tumors that can be classified as APU-Domas (amine precursor uptake and decarboxylation). They can be subdivided into the carcinoid tumors of the gastrointestinal submucosa and the islet cell endocrine tumors of the pancreas. Although the majority of tumors that become clinically apparent are malignant, they are frequently slow growing. Despite this, neuroendocrine tumors may generate disabling hormonal syndromes requiring aggressive treatment to achieve palliation. Recent advances in understanding the pathophysiology of these tumors has led to better radiographic imaging and more accurate localization techniques. Medical therapies with somatostatin analogues, omeprazole, and locoregional tumor ablation have made a positive impact on curative and palliative therapy. This review updates the recent efforts made in the radiographic imaging and therapeutics of the gastrointestinal neuroendocrine tumors.

  9. Early-Stage Breast Cancer in the Octogenarian: Tumor Characteristics, Treatment Choices, and Clinical Outcomes

    PubMed Central

    Mamtani, Anita; Gonzalez, Julie J.; Neo, Dayna; Slanetz, Priscilla J.; Houlihan, Mary Jane; Herold, Christina I.; Recht, Abram; Hacker, Michele R.; Sharma, Ranjna

    2016-01-01

    Background Nodal staging with sentinel node biopsy (SLNB), post-lumpectomy radiotherapy (RT), and endocrine therapy (ET) for estrogen receptor-positive (ER+) tumors is valuable in the treatment of early-stage (stages 1 or 2) breast cancer but used less often for elderly women. Methods This retrospective study investigated women referred for surgical evaluation of biopsy-proven primary early-stage invasive breast cancer from January 2001 to December 2010. Clinicopathologic features, treatment course, and outcomes for women ages 80–89 years and 50–59 years were compared. Results The study identified 178 eligible women ages 80–89 years and 169 women ages 50–59 years. The elderly women more often had grade 1 or 2 disease (p = 0.003) and ER+ tumors (p = 0.007) and less frequently had undergone adjuvant therapies (all p ≤ 0.001). Lumpectomy was performed more commonly for the elderly (92 vs. 83 %, p = 0.02), and axillary surgery was less commonly performed (46 vs. 96 %; p < 0.001). Fewer elderly women had undergone post-lumpectomy RT (42 vs. 89 %; p < 0.001) and ET for ER+ tumors (72 vs. 95 %; p < 0.001). During the median follow-up period of 56 months for the 80- to 89-year old group and 98 months for the 50- to 59-year-old group, death from breast cancer was similar (4 vs. 5 %; p = 0.5). The two groups respectively experienced 7 versus 6 locoregional recurrences and 11 versus 13 distant recurrences. Conclusions The octogenarians had disease survivorship similar to that of the younger women despite less frequent use of adjuvant therapies, likely reflecting lower-risk disease features. Whether increased use of axillary surgery, post-lumpectomy RT, and/or ET for ER+ tumors would further improve outcomes is an important area for further study, but treatment should not be deferred solely on the basis of age. PMID:27364507

  10. Three-Staged Stereotactic Radiotherapy Without Whole Brain Irradiation for Large Metastatic Brain Tumors

    SciTech Connect

    Higuchi, Yoshinori Serizawa, Toru; Nagano, Osamu; Matsuda, Shinji; Ono, Junichi; Sato, Makoto; Iwadate, Yasuo; Saeki, Naokatsu

    2009-08-01

    Purpose: To evaluate the efficacy and toxicity of staged stereotactic radiotherapy with a 2-week interfraction interval for unresectable brain metastases more than 10 cm{sup 3} in volume. Patients and Methods: Subjects included 43 patients (24 men and 19 women), ranging in age from 41 to 84 years, who had large brain metastases (> 10 cc in volume). Primary tumors were in the colon in 14 patients, lung in 12, breast in 11, and other in 6. The peripheral dose was 10 Gy in three fractions. The interval between fractions was 2 weeks. The mean tumor volume before treatment was 17.6 {+-} 6.3 cm{sup 3} (mean {+-} SD). Mean follow-up interval was 7.8 months. The local tumor control rate, as well as overall, neurological, and qualitative survivals, were calculated using the Kaplan-Meier method. Results: At the time of the second and third fractions, mean tumor volumes were 14.3 {+-} 6.5 (18.8% reduction) and 10.6 {+-} 6.1 cm{sup 3} (39.8% reduction), respectively, showing significant reductions. The median overall survival period was 8.8 months. Neurological and qualitative survivals at 12 months were 81.8% and 76.2%, respectively. Local tumor control rates were 89.8% and 75.9% at 6 and 12 months, respectively. Tumor recurrence-free and symptomatic edema-free rates at 12 months were 80.7% and 84.4%, respectively. Conclusions: The 2-week interval allowed significant reduction of the treatment volume. Our results suggest staged stereotactic radiotherapy using our protocol to be a possible alternative for treating large brain metastases.

  11. 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

  12. Persistent Uroplakin Expression in Advanced Urothelial Carcinomas: Implications in Urothelial Tumor Progression and Clinical Outcome

    PubMed Central

    Huang, Hong-Ying; Shariat, Shahrokh F.; Sun, Tung-Tien; Lepor, Herbert; Shapiro, Ellen; Hsieh, Jer-Tsong; Ashfaq, Raheela; Lotan, Yair; Wu, Xue-Ru

    2007-01-01

    As the terminal differentiation products of human urothelium, uroplakins (UPs) would be expected to diminish during urothelial tumorigenesis. Surprisingly, recent studies found UPs to be retained even by well-advanced urothelial carcinomas, suggesting that the loss of UPs does not strictly parallel urothelial transformation. Little is known, however, about whether the status of UPs is associated with a particular pathological parameter, tumor’s biological behavior or patient outcome. Here we assessed UP expression by immunohistochemistry on tissue arrays from 285 patients with bladder urothelial carcinomas or non-tumor conditions. UPs were expressed in all 9 normal urothelial specimens, 63/74 (85%) patients with non-muscle-invasive urothelial carcinomas on transurethral resection, 104/202 (51.5%) patients who underwent radical cystectomy for advanced urothelial carcinomas, and 33/50 (66%) lymph node metastases. Normally associated with urothelial apical surface, UPs were localized aberrantly in tumors, including micro-luminal, basal-laminal, cytoplasmic or uniform patterns. In non-muscle-invasive diseases, there was no association between UP expression and disease recurrence, progression or mortality. In contrast, in invasive diseases, absent UP expression was significantly associated with advanced pathologic stage, lymph node metastases, disease recurrence and bladder cancer-specific mortality (p=0.042, p=0.035, p=0.023 and p=0.022, respectively) in univariate analyses. Furthermore, UP status was independent of key cell-cycle regulators, including p53, pRb, p27 and cyclin D1, thus excluding a functional link between these two groups of proteins. Our data demonstrate for the first time that persistent UP expression is associated with a favorable clinical outcome and that UPs may be used as adjunct markers for predicting the prognoses of patients with invasive and metastatic bladder carcinomas. Our results also suggest that UP-positive and –negative carcinomas

  13. Hypofractionated radiotheapy using helical tomotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis

    PubMed Central

    2013-01-01

    Background We want to evaluate the efficacy of helical tomotherapy (HT) for treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods We treated 35 patients for unresectable HCC combined with PVTT in whom other treatment modalities were not indicated. The tumor thrombi involved the main trunk of the portal vein in 18 patients (51.4%) and the first or second order branches in 17 patients (48.6%). A median dose of 50 Gy (range: 45–60 Gy) was delivered in 10 fractions. Capecitabine was given concomitantly at a dose of 600 mg/m2 twice daily during radiotherapy. Results The responses were evaluated via computed tomography. There was a complete response (CR) in 5 patients (14.3%), partial response (PR) in 10 patients (28.6%), stable disease (SD) in 18 patients (51.4%) and progressive disease (PD) in 2 patients (5.7%). The Child-Pugh classification (A vs B) and the Japan integrated staging (JIS) score (2 vs 3) were statistically significant parameters that predicted the response of PVTT (p = 0.010 and p = 0.026, respectively). The median survival, one and two year survival rate of all patients was 12.9 months, 51.4% and 22.2%, respectively. The patients with tumor thrombi in the main portal trunk showed statistically inferior overall survival than patients with tumor thrombi in the portal vein branches (9.8 versus 16.6 months, respectively, p = 0.036). The responders’ median survival was 13.9 months, double 6.9 months as the median survival of the non-responders. No radiation induced liver disease or treatment related mortality was not appeared. Conclusions Hypofractionated radiotherapy with HT was effective not only for tumor response but also for survival in the advanced HCC patients with PVTT. And stricter patient selection by Child-Pugh classification and JIS score may maximize the potential benefits of this treatment. PMID:23324259

  14. Factors related to advanced stage oral squamous cell carcinoma in southern Thailand.

    PubMed

    Kerdpon, D; Sriplung, H

    2001-04-01

    A critical factor that indicates a poor prognosis of oral squamous cell carcinoma (OSCC) is advanced stage disease. This study, therefore, aimed to identify the factors related to advanced stage (TNM staging III, IV) OSCC in Thailand. There were 161 patients with squamous cell carcinoma of the oral cavity and lip (ICD-9 140, 141, 143-5), included in the study. Sixty-two per cent of the patients presented with advanced stage disease. Information on demographic characteristics, risk habits, health-seeking behaviour prior to health care professional (HCP) consultation, tumour characteristics and patient and professional delay was obtained by questionnaire-based interview of the patients. These variables were included as initial variables in a logistic regression to calculate the odds ratio (OR) of advanced versus early stage OSCC. Having traditional herbal medication before HCP consultation significantly increased the risk of advanced stage OSCC (OR 5.77; 95% C.I. 1.25-26.62). Floor of mouth location of tumour was associated with a lower risk of advanced stage disease (OR 0.27; 95% C.I. 0.09-0.82) as was having an ulcer (OR 0.43, 95% C.I. 0.02-0.89). The findings indicate that having traditional herbal medication before HCP consultation increased the risk of advanced stage disease. The lower risk of advanced stage OSCC associated with ulcerative tumours and those on the floor of the mouth may be due to their being more readily detected by the patients. PMID:11287274

  15. Clofarabine in Adult Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2014-02-04

    Solid Tumors; Leukemia, Lymphocytic, Acute, Pediatric; Leukemia, Lymphocytic, Acute, Adult; Leukemia, Myelocytic, Acute, Pediatric; Leukemia, Myelocytic, Acute, Adult; Myelodysplastic Syndromes, Adult

  16. Comparison of Treatment Costs for Breast Cancer, by Tumor Stage and Type of Service

    PubMed Central

    Blumen, Helen; Fitch, Kathryn; Polkus, Vincent

    2016-01-01

    Background Diagnosis of breast cancer at early stages is associated with better clinical and survival outcomes. How the costs of care vary depending on the stage at which breast cancer was diagnosed has not been thoroughly examined. Objective To quantify the stage-dependent average per capita cost of breast cancer treatment for a commercially insured population of women with newly diagnosed breast cancer. Methods This retrospective analysis of claims data was based on a population selected from the Truven Healthcare MarketScan commercial claims database. The study comprised women aged 18 to 64 years with breast cancer who had ≥2 claims in 2010 that were ≥30 days apart and included an International Classification of Diseases, Ninth Revision diagnosis code for breast cancer (174.xx, 233.0) in any position of the claim. Two years of postdiagnosis claims data were analyzed by stage at diagnosis (ie, 0, I/II, III, and IV). Results In total, 8360 women met the criteria for study inclusion (stage 0, N = 2300; stage I/II, N = 4425; stage III, N = 1134; and stage IV, N = 501). The costs were higher for patients whose cancer was more advanced at diagnosis, for all cumulative 6-month periods (months 0–6, 0–12, 0–18, and 0–24). The average costs per patient allowed by the insurance company in the year after diagnosis were $60,637, $82,121, $129,387, and $134,682 for disease stage 0, I/II, III, and IV, respectively. The average costs allowed per patient in the 24 months after the index diagnosis were $71,909, $97,066, $159,442, and $182,655 for disease stage 0, I/II, III, and IV, respectively. The cost difference based on the stage at diagnosis was largely driven by the cost of chemotherapy and noncancer treatments. Conclusion Treating advanced- versus early-stage breast cancer is associated with significant increases in incremental costs. Knowledge of the relevant stage-specific cost data provides support for strengthening programs, such as breast cancer screening

  17. Interstitial radiation therapy for early-stage nasal vestibule cancer: A continuing quest for optimal tumor control and cosmesis

    SciTech Connect

    Levendag, Peter C. . E-mail: p.levendag@erasmusmc.nl; Nijdam, Wideke M.; Moolenburgh, Sanne E. van; Tan, Lisa; Noever, Inge R.T.T.; Rooy, Peter van; Mureau, Marc; Jansen, Peter P.; Munte, Kai; Hofer, Stefan O.P.

    2006-09-01

    Introduction: This article reports on the effectiveness, cosmetic outcome, and costs of interstitial high-dose-rate (HDR) brachytherapy for early-stage cancer of the nasal vestibule (NV) proper and/or columella high-dose-rate (HDR). Methods and Materials: Tumor control, survival, cosmetic outcome, functional results, and costs were established in 64 T1/T2N0 nasal vestibule cancers treated from 1991-2005 by fractionated interstitial radiation therapy (IRT) only. Total dose is 44 Gy: 2 fractions of 3 Gy per day, 6-hour interval, first and last fraction 4 Gy. Cosmesis is noted in the chart by the medical doctor during follow-up, by the patient (visual analog scale), and by a panel. Finally, full hospital costs are computed. Results: A local relapse-free survival rate of 92% at 5 years was obtained. Four local failures were observed; all four patients were salvaged. The neck was not treated electively; no neck recurrence in follow-up was seen. Excellent cosmetic and functional results were observed. With 10 days admission for full treatment, hospital costs amounted to Euro 5772 ($7044). Conclusion: Excellent tumor control, cosmesis, and function of nasal airway passage can be achieved when HDR-IRT for T1/T2N0 NV cancers is used. For the more advanced cancers (Wang classification: T3 tumor stage), we elect to treat by local excision followed by a reconstructive procedure. The costs, admission to hospital inclusive, for treatment by HDR-IRT amounts to Euro 5772 ($7044 US). This contrasts substantially with the full hospital costs when NV cancers are treated by plastic reconstructive surgery, being on average threefold as expensive.

  18. Testicular tumors: what radiologists need to know--differential diagnosis, staging, and management.

    PubMed

    Coursey Moreno, Courtney; Small, William C; Camacho, Juan C; Master, Viraj; Kokabi, Nima; Lewis, Melinda; Hartman, Matthew; Mittal, Pardeep K

    2015-01-01

    Cryptorchidism, family history, and infertility are risk factors for testicular cancer. Most testicular cancers occur in young men aged 18-35 years, and seminoma is the most common cell type. Testicular tumors are usually diagnosed at ultrasonography (US) and are staged at computed tomography (CT) or magnetic resonance (MR) imaging. At US, testicular tumors usually appear as a solid intratesticular mass. Because the differential diagnosis includes infarct and infection, correlation with patient history and symptoms is important. At staging CT or MR imaging, retroperitoneal lymph nodes are considered regional lymph nodes, and the greatest nodal diameter is used to distinguish among N1-N3 disease. The right testicular vein drains into the inferior vena cava, and the left testicular vein drains into the left renal vein. Because of venous and lymphatic drainage pathways, retroperitoneal lymph nodes are the initial landing station for testicular cancers. Enlarged lymph nodes in the supraclavicular region, chest, and pelvis are considered distant metastases. Testicular cancer is initially treated with orchiectomy. The patient may then undergo active surveillance, chemotherapy, radiation therapy, or retroperitoneal lymph node resection, depending primarily on the clinical stage. Radiologists play an important role in initial diagnosis, staging, and imaging surveillance of testicular malignancies.

  19. A Two-Stage Microfluidic Device for the Isolation and Capture of Circulating Tumor Cells

    NASA Astrophysics Data System (ADS)

    Cook, Andrew; Belsare, Sayali; Giorgio, Todd; Mu, Richard

    2014-11-01

    Analysis of circulating tumor cells (CTCs) can be critical for studying how tumors grow and metastasize, in addition to personalizing treatment for cancer patients. CTCs are rare events in blood, making it difficult to remove CTCs from the blood stream. Two microfluidic devices have been developed to separate CTCs from blood. The first is a double spiral device that focuses cells into streams, the positions of which are determined by cell diameter. The second device uses ligand-coated magnetic nanoparticles that selectively attach to CTCs. The nanoparticles then pull CTCs out of solution using a magnetic field. These two devices will be combined into a single 2-stage microfluidic device that will capture CTCs more efficiently than either device on its own. The first stage depletes the number of blood cells in the sample by size-based separation. The second stage will magnetically remove CTCs from solution for study and culturing. Thus far, size-based separation has been achieved. Research will also focus on understanding the equations that govern fluid dynamics and magnetic fields in order to determine how the manipulation of microfluidic parameters, such as dimensions and flow rate, will affect integration and optimization of the 2-stage device. NSF-CREST: Center for Physics and Chemistry of Materials. HRD-0420516; Department of Defense, Peer Reviewed Medical Research Program Award W81XWH-13-1-0397.

  20. HLA-G expression and role in advanced-stage classical Hodgkin lymphoma.

    PubMed

    Caocci, G; Greco, M; Fanni, D; Senes, G; Littera, R; Lai, S; Risso, P; Carcassi, C; Faa, G; La Nasa, G

    2016-01-01

    Non-classical human leucocyte antigen (HLA)-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL), in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp) deletion-insertion (del-ins) polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy) patients with a 2-year progression-free survival rate (PFS) of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS) cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2.These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2. PMID:27349312

  1. Recent Advances in Targeting Tumor Energy Metabolism with Tumor Acidosis as a Biomarker of Drug Efficacy

    PubMed Central

    Akhenblit, Paul J; Pagel, Mark D

    2016-01-01

    Cancer cells employ a deregulated cellular metabolism to leverage survival and growth advantages. The unique tumor energy metabolism presents itself as a promising target for chemotherapy. A pool of tumor energy metabolism targeting agents has been developed after several decades of efforts. This review will cover glucose and fatty acid metabolism, PI3K/AKT/mTOR, HIF-1 and glutamine pathways in tumor energy metabolism, and how they are being exploited for treatments and therapies by promising pre-clinical or clinical drugs being developed or investigated. Additionally, acidification of the tumor extracellular microenvironment is hypothesized to be the result of active tumor metabolism. This implies that tumor extracellular pH (pHe) can be a biomarker for assessing the efficacy of therapies that target tumor metabolism. Several translational molecular imaging methods (PET, MRI) for interrogating tumor acidification and its suppression are discussed as well. PMID:26962408

  2. Role of Adjuvant Radiotherapy for Stage II Thymoma After Complete Tumor Resection

    SciTech Connect

    Chen Yidong

    2010-12-01

    Purpose: To determine whether patients with Masaoka stage II thymoma benefit from adjuvant radiation therapy after complete tumor resection. Methods and Materials: A total of 107 patients with stage II thymoma who underwent complete resection of their tumors between September 1964 and October 2006 were retrospectively analyzed. Sixty-six patients were treated with adjuvant radiotherapy, and 41 patients received surgery alone. Results: Eight patients (7.5%) had a relapse of their disease, including two patients (4.5%) who had surgery alone, and 6 patients (9.5%) who had adjuvant radiation therapy. Disease-free survival rates at 5 and 10 years were 92.3% and 82.6%, respectively, for the surgery-plus-radiation group, and 97.6% and 93.1%, respectively, for the group that underwent surgery alone (p = 0.265). Disease-specific survival rates at 5 and 10 years were 96.4% and 89.3%, respectively, for the surgery-plus-radiation group and 97.5% and 97.5% for the surgery group (p = 0.973). On univariate analysis, patients with type B3 thymomas had the lowest disease-free survival rates among all subtypes (p = 0.001), and patients with large thymomas (>7 cm) had lower disease-specific survival rates than those with small tumors (<7 cm) (p = 0.017). On multivariate analysis, histological type (type B3) thymoma was a significant independent prognostic factor. Conclusions: Adjuvant radiotherapy after complete tumor resection for patients with stage II thymoma did not significantly reduce recurrence rates or improve survival rates. Histological type (type B3) thymoma was a significant independent prognostic factor. Further investigation should be carried out using a multicenter randomized or controlled study.

  3. Recent advances in lymphatic targeted drug delivery system for tumor metastasis

    PubMed Central

    Zhang, Xiao-Yu; Lu, Wei-Yue

    2014-01-01

    The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers. PMID:25610710

  4. Seventh tumor-node-metastasis staging of gastric cancer: Five-year follow-up.

    PubMed

    Rausei, Stefano; Ruspi, Laura; Galli, Federica; Pappalardo, Vincenzo; Di Rocco, Giuseppe; Martignoni, Francesco; Frattini, Francesco; Rovera, Francesca; Boni, Luigi; Dionigi, Gianlorenzo

    2016-09-14

    Seventh tumor-node-metastasis (TNM) classification for gastric cancer, published in 2010, introduced changes in all of its three parameters with the aim to increase its accuracy in prognostication. The aim of this review is to analyze the efficacy of these changes and their implication in clinical practice. We reviewed relevant Literature concerning staging systems in gastric cancer from 2010 up to March 2016. Adenocarcinoma of the esophago-gastric junction still remains a debated entity, due to its peculiar anatomical and histological situation: further improvement in its staging are required. Concerning distant metastases, positive peritoneal cytology has been adopted as a criterion to define metastatic disease: however, its search in clinical practice is still far from being routinely performed, as staging laparoscopy has not yet reached wide diffusion. Regarding definition of T and N: in the era of multimodal treatment these parameters should more influence both staging and surgery. The changes about T-staging suggested some modifications in clinical practice. Differently, many controversies on lymph node staging are still ongoing, with the proposal of alternative classification systems in order to minimize the extent of lymphadenectomy. The next TNM classification should take into account all of these aspects to improve its accuracy and the comparability of prognosis in patients from both Eastern and Western world. PMID:27678357

  5. Seventh tumor-node-metastasis staging of gastric cancer: Five-year follow-up

    PubMed Central

    Rausei, Stefano; Ruspi, Laura; Galli, Federica; Pappalardo, Vincenzo; Di Rocco, Giuseppe; Martignoni, Francesco; Frattini, Francesco; Rovera, Francesca; Boni, Luigi; Dionigi, Gianlorenzo

    2016-01-01

    Seventh tumor-node-metastasis (TNM) classification for gastric cancer, published in 2010, introduced changes in all of its three parameters with the aim to increase its accuracy in prognostication. The aim of this review is to analyze the efficacy of these changes and their implication in clinical practice. We reviewed relevant Literature concerning staging systems in gastric cancer from 2010 up to March 2016. Adenocarcinoma of the esophago-gastric junction still remains a debated entity, due to its peculiar anatomical and histological situation: further improvement in its staging are required. Concerning distant metastases, positive peritoneal cytology has been adopted as a criterion to define metastatic disease: however, its search in clinical practice is still far from being routinely performed, as staging laparoscopy has not yet reached wide diffusion. Regarding definition of T and N: in the era of multimodal treatment these parameters should more influence both staging and surgery. The changes about T-staging suggested some modifications in clinical practice. Differently, many controversies on lymph node staging are still ongoing, with the proposal of alternative classification systems in order to minimize the extent of lymphadenectomy. The next TNM classification should take into account all of these aspects to improve its accuracy and the comparability of prognosis in patients from both Eastern and Western world. PMID:27678357

  6. Seventh tumor-node-metastasis staging of gastric cancer: Five-year follow-up

    PubMed Central

    Rausei, Stefano; Ruspi, Laura; Galli, Federica; Pappalardo, Vincenzo; Di Rocco, Giuseppe; Martignoni, Francesco; Frattini, Francesco; Rovera, Francesca; Boni, Luigi; Dionigi, Gianlorenzo

    2016-01-01

    Seventh tumor-node-metastasis (TNM) classification for gastric cancer, published in 2010, introduced changes in all of its three parameters with the aim to increase its accuracy in prognostication. The aim of this review is to analyze the efficacy of these changes and their implication in clinical practice. We reviewed relevant Literature concerning staging systems in gastric cancer from 2010 up to March 2016. Adenocarcinoma of the esophago-gastric junction still remains a debated entity, due to its peculiar anatomical and histological situation: further improvement in its staging are required. Concerning distant metastases, positive peritoneal cytology has been adopted as a criterion to define metastatic disease: however, its search in clinical practice is still far from being routinely performed, as staging laparoscopy has not yet reached wide diffusion. Regarding definition of T and N: in the era of multimodal treatment these parameters should more influence both staging and surgery. The changes about T-staging suggested some modifications in clinical practice. Differently, many controversies on lymph node staging are still ongoing, with the proposal of alternative classification systems in order to minimize the extent of lymphadenectomy. The next TNM classification should take into account all of these aspects to improve its accuracy and the comparability of prognosis in patients from both Eastern and Western world.

  7. 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

  8. Integrative Genomic Characterization and a Genomic Staging System for Gastrointestinal Stromal Tumors

    PubMed Central

    Ylipää, Antti; Hunt, Kelly K.; Yang, Jilong; Lazar, Alexander J. F.; Torres, Keila E.; Lev, Dina Chelouche; Nykter, Matti; Pollock, Raphael E.; Trent, Jonathan; Zhang, Wei

    2010-01-01

    Gastrointestinal stromal tumors (GISTs) were historically grouped with leiomyosarcomas (LMSs) based on their morphological similarities, but recently they have been unequivocally established as a distinct type of sarcoma based on the molecular features and response to imatinib treatment. To gain further insight into the genomic differences between GISTs and LMSs, we mapped gene copy number aberrations (CNAs) in 42 GISTs and 30 LMSs and integrated them with gene expression profiles. Our studies revealed distinct patterns of CNAs between GISTs and LMSs. Losses in chromosomes 1p, 14q, 15q, and 22q were significantly more frequent in GISTs than in LMSs (P < 0.001), whereas losses in chromosomes 10 and 16 as well as gains in 1q, 14q, and 15q (P < 0.001) were more common in LMSs. By integrating CNAs with gene expression data and clinical information, we found several clinically relevant CNAs that were prognostic of survival in patients with GIST. Furthermore, GISTs were categorized into four groups according to an accumulating pattern of genetic alterations. Many key cellular pathways were differently expressed in the four groups and the patients had increasingly worse prognosis as the extent of genomic alterations increased. These findings lead us to propose a new tumor-progression genetic staging system termed Genomic Instability Stage (GIS) to complement the current prognostic predictive system based on tumor size, mitotic index (MI), and KIT mutation. PMID:20818650

  9. Quantification of microvascular cerebral blood flux and late-stage tumor compartmentalization in 9L gliosarcoma using flow enhanced MRI.

    PubMed

    Reynaud, Olivier; Geffroy, Françoise; Ciobanu, Luisa

    2013-06-01

    Measurements of tumor microvasculature are important to obtain an understanding of tumor angiogenesis and for the evaluation of therapies. In this work, we characterize the evolution of the microvascular flux at different stages of tumor growth in the 9L rat brain tumor model. The absolute quantification of cerebral blood flux is achieved with MRI at 7 T using the flow enhanced signal intensity (FENSI) method. FENSI flux maps were obtained between 5 and 14 days after glioma cell inoculation. Based on cerebral blood flux maps, we highlighted two main stages of tumor growth, below and above 3 mm, presenting distinct flux patterns and vascular properties. No significant difference emerged from the group analysis performed on the data collected at an early developmental stage (tumor size < 3 mm) when compared with healthy tissue. At a late developmental stage (tumor size > 3 mm), we observed a significant decrease in the cerebral blood flux inside the gliosarcoma (-33%, p < 0.01) and compartmentalization of the tumor (p < 0.05). FENSI flux maps delineated a low-flux tumor core (58 ± 17 μL/min/cm(2) ) and higher vascularized regions around the tumor periphery (85 ± 21 μL/min/cm(2) ). Histology was performed on 11 animals to finely probe the intratumor heterogeneity and microvessel density, and the results were compared with the information derived from FENSI flux maps. The hyper- and hypoperfused tumor regions revealed with FENSI at the late tumor developmental stage correlated well with the ratios of high and low blood vessel density (R(2) = 0.41) and fractional vascular surface (R(2) = 0.67) observed with fluorescence microscopy [cluster of differentiation 31 (CD31) staining].

  10. Immune checkpoint blockade reveals the stimulatory capacity of tumor-associated CD103(+) dendritic cells in late-stage ovarian cancer.

    PubMed

    Flies, Dallas B; Higuchi, Tomoe; Harris, Jaryse C; Jha, Vibha; Gimotty, Phyllis A; Adams, Sarah F

    2016-08-01

    Although immune infiltrates in ovarian cancer are associated with improved survival, the ovarian tumor environment has been characterized as immunosuppressive, due in part to functional shifts among dendritic cells with disease progression. We hypothesized that flux in dendritic cell subpopulations with cancer progression were responsible for observed differences in antitumor immune responses in early and late-stage disease. Here we identify three dendritic cell subsets with disparate functions in the ovarian tumor environment. CD11c+CD11b(-)CD103(+) dendritic cells are absent in the peritoneal cavity of healthy mice but comprise up to 40% of dendritic cells in tumor-bearing mice and retain T cell stimulatory capacity in advanced disease. Among CD11c+CD11b+ cells, Lair-1 expression distinguishes stimulatory and immunoregulatory DC subsets, which are also enriched in the tumor environment. Notably, PD-L1 is expressed by Lair-1(hi) immunoregulatory dendritic cells, and may contribute to local tumor antigen-specific T cell dysfunction. Using an adoptive transfer model, we find that PD-1 blockade enables tumor-associated CD103(+) dendritic cells to promote disease clearance. These data demonstrate that antitumor immune capacity is maintained among local dendritic cell subpopulations in the tumor environment with cancer progression. Similar dendritic cell subsets are present in malignant ascites from women with ovarian cancer, supporting the translational relevance of these results. PMID:27622059

  11. Effective hepatic artery chemoembolization for advanced hepatocellular carcinoma with multiple tumor thrombi and pulmonary metastases: A case report

    PubMed Central

    Huang, De-Jia; Li, Yan-Hao; Luo, Yao-Chang; Huang, Jun-Zhen; He, Hai-Yuan

    2016-01-01

    Advanced hepatocellular carcinoma (HCC) with tumor thrombi invading the portal vein and extending into the right atrium (RA) through the hepatic vein is regarded as a terminal-stage condition. Intracardiac tumor thrombus and treatment via liver resection has been reported in the current literature, but results from this therapeutic approach remain unsatisfactory. The present study describes a rare case of HCC with metastatic portal vein, middle hepatic vein, inferior vena cava (IVC) and RA tumor thrombi, and pulmonary metastases. A 29-year-old woman was admitted to The First Affiliated Hospital of Guangxi Traditional Chinese Medical University (Nanning, China) subsequent to experiencing right upper quadrant abdominal pain. Following diagnosis, based on computed tomography analysis and laboratory data, the patient underwent an initial transcatheter arterial chemoembolization (TACE) treatment using fluorouracil (5-FU), pirarubicin, mitomycin C, Lipiodol and sodium alginate microball (KMG). At 1 month post-treatment, serum α-fetoprotein levels remained at >1,000 ng/ml. Subsequently, the patient underwent a second TACE treatment. At 1 month after the second treatment, the abdominal pain had been alleviated and the serum α-fetoprotein levels were reduced to <20 ng/ml. Imaging analysis indicated a marked reduction in tumor burden in the liver and the hepatic vein and IVC tumor thrombi. Furthermore, the portal vein and RA tumor thrombi, and the pulmonary metastases had disappeared. At 40 months after the second TACE therapy, the patient remains alive without any signs of recurrence. The present case demonstrates that the administration of TACE, using 5-FU, pirarubicin, mitomycin C, Lipiodol and KMG, functions as an effective treatment in cases of unresectable advanced HCC presenting with pulmonary metastases and extensive tumor thrombi in the IVC, the RA and one branch of the portal vein. PMID:27602147

  12. Exprimental Results of the First Two Stages of an Advanced Transonic Core Compressor Under Isolated and Multi-Stage Conditions.

    NASA Technical Reports Server (NTRS)

    Prahst, Patricia S.; Kulkarni, Sameer; Sohn, Ki H.

    2015-01-01

    NASA's Environmentally Responsible Aviation (ERA) Program calls for investigation of the technology barriers associated with improved fuel efficiency for large gas turbine engines. Under ERA, the highly loaded core compressor technology program attempts to realize the fuel burn reduction goal by increasing overall pressure ratio of the compressor to increase thermal efficiency of the engine. Study engines with overall pressure ratio of 60 to 70 are now being investigated. This means that the high pressure compressor would have to almost double in pressure ratio while keeping a high level of efficiency. NASA and GE teamed to address this challenge by testing the first two stages of an advanced GE compressor designed to meet the requirements of a very high pressure ratio core compressor. Previous test experience of a compressor which included these front two stages indicated a performance deficit relative to design intent. Therefore, the current rig was designed to run in 1-stage and 2-stage configurations in two separate tests to assess whether the bow shock of the second rotor interacting with the upstream stage contributed to the unpredicted performance deficit, or if the culprit was due to interaction of rotor 1 and stator 1. Thus, the goal was to fully understand the stage 1 performance under isolated and multi-stage conditions, and additionally to provide a detailed aerodynamic data set for CFD validation. Full use was made of steady and unsteady measurement methods to understand fluid dynamics loss source mechanisms due to rotor shock interaction and endwall losses. This paper will present the description of the compressor test article and its measured performance and operability, for both the single stage and two stage configurations. We focus the paper on measurements at 97% corrected speed with design intent vane setting angles.

  13. The Critical Technologies and Applications on Advanced Upper Stage Vehicles

    NASA Astrophysics Data System (ADS)

    Qi, Feng; Wang, Guo-hui

    2016-07-01

    Upper Stage Vehicle(USV) is a kind of independent one-stop-into-space launching vehicles. In this article, different new-conception USVs are mentioned and out of them, on basis of the possibility in future application, laser propelling USV and nuclear-thermal propelling USV are selected and discussed in technical details, especially in critical technologies and recent relative technical improvements about new propelling methods within these two kinds. Furthermore, laser propelled USV and nuclear-thermal propelled USV both seem to have important roles to play in future space exploring projects. And several possible applications of the two kinds of USVs emphasized above are carried out at the end of this piece of article.

  14. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer

    PubMed Central

    Eruslanov, Evgeniy B.; Bhojnagarwala, Pratik S.; Quatromoni, Jon G.; Stephen, Tom Li; Ranganathan, Anjana; Deshpande, Charuhas; Akimova, Tatiana; Vachani, Anil; Litzky, Leslie; Hancock, Wayne W.; Conejo-Garcia, José R.; Feldman, Michael; Albelda, Steven M.; Singhal, Sunil

    2014-01-01

    Infiltrating inflammatory cells are highly prevalent within the tumor microenvironment and mediate many processes associated with tumor progression; however, the contribution of specific populations remains unclear. For example, the nature and function of tumor-associated neutrophils (TANs) in the cancer microenvironment is largely unknown. The goal of this study was to provide a phenotypic and functional characterization of TANs in surgically resected lung cancer patients. We found that TANs constituted 5%–25% of cells isolated from the digested human lung tumors. Compared with blood neutrophils, TANs displayed an activated phenotype (CD62LloCD54hi) with a distinct repertoire of chemokine receptors that included CCR5, CCR7, CXCR3, and CXCR4. TANs produced substantial quantities of the proinflammatory factors MCP-1, IL-8, MIP-1α, and IL-6, as well as the antiinflammatory IL-1R antagonist. Functionally, both TANs and neutrophils isolated from distant nonmalignant lung tissue were able to stimulate T cell proliferation and IFN-γ release. Cross-talk between TANs and activated T cells led to substantial upregulation of CD54, CD86, OX40L, and 4-1BBL costimulatory molecules on the neutrophil surface, which bolstered T cell proliferation in a positive-feedback loop. Together our results demonstrate that in the earliest stages of lung cancer, TANs are not immunosuppressive, but rather stimulate T cell responses. PMID:25384214

  15. Biopotential signals of breast cancer versus tumor types and proliferation stages.

    PubMed

    Hassan, Ahmed M; El-Shenawee, Magda

    2012-02-01

    Clinical studies have shown compelling data of elevated biopotential signals recorded noninvasively from the breasts of women with breast cancer. While these data are compelling and show a strong potential for use in the noninvasive early detection of breast cancer, there remains significant knowledge gaps which must be addressed before this technology can be routinely used for breast cancer detection. A diffusion-drift model is developed to study the spatial and temporal characteristics of the biopotential signals of breast tumors taking into account the morphology and cell division stages. The electric signals of the most common tumor types-papillary, compact, and comedo-are also considered. The largest biopotential signal is observed from the compact tumor, while the smallest signal is observed from the papillary type. The results also show an increase in the time duration of the generated biopotential signals when cancer cells start their transitions at different time instants. The spatial and temporal variations of the biopotential signals are correlated with the tumor pattern which can have important implications for breast cancer detection. PMID:22463250

  16. Biopotential signals of breast cancer versus tumor types and proliferation stages

    NASA Astrophysics Data System (ADS)

    Hassan, Ahmed M.; El-Shenawee, Magda

    2012-02-01

    Clinical studies have shown compelling data of elevated biopotential signals recorded noninvasively from the breasts of women with breast cancer. While these data are compelling and show a strong potential for use in the noninvasive early detection of breast cancer, there remains significant knowledge gaps which must be addressed before this technology can be routinely used for breast cancer detection. A diffusion-drift model is developed to study the spatial and temporal characteristics of the biopotential signals of breast tumors taking into account the morphology and cell division stages. The electric signals of the most common tumor types—papillary, compact, and comedo—are also considered. The largest biopotential signal is observed from the compact tumor, while the smallest signal is observed from the papillary type. The results also show an increase in the time duration of the generated biopotential signals when cancer cells start their transitions at different time instants. The spatial and temporal variations of the biopotential signals are correlated with the tumor pattern which can have important implications for breast cancer detection.

  17. Controversies in the management of stage 1 non-seminomatous germ cell tumors.

    PubMed

    Coleman, Sarah; Stephenson, Andrew

    2013-10-01

    Post-orchiectomy treatment for clinical stage 1 non-seminomatous germ cell tumors (NSGCT) remains highly debated. Cure rates for testicular germ cell tumors exceed 99 % in early stage disease despite the lack of consensus regarding post-orchiectomy treatment. The controversy relates to the challenge of identifying those patients with clinical stage 1 (CS 1) NSGCT who are most likely to benefit from adjuvant therapies. Established post-orchiectomy treatment options for CS 1 NSGCT include observation, adjuvant chemotherapy and retroperitoneal lymph node dissection. Effective salvage therapies allow for cure rates which approach 100 % for each of these options. The data suggest that low-risk CS 1 NSGCT can be treated with surveillance and consideration for all three options is necessary for high-risk patients. The data show that high-risk patients are those whose disease pathology demonstrates lymphovascular invasion. The decision regarding post-orchiectomy treatment should be based on a discussion with the patient and the specific expertise of the treating institution. PMID:23901036

  18. Advances in tumor diagnosis using OCT and Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Zakharov, V. P.; Bratchenko, I. A.; Kozlov, S. V.; Moryatov, A. A.; Kornilin, D. V.; Myakinin, O. O.; Artemyev, D. N.

    2014-05-01

    Complex investigation of malignant tumors was performed with combined optical coherence tomography (OCT) and Raman spectroscopy (RS) setup: 22 ex vivo lung tissue samples and 23 in vivo experiments with skin tumors. It was shown that combined RS-OCT unit may be used for precise tissue morphology visualization with simultaneous tumor type determination (BCC, malignant melanoma of skin tissues, adenocarcinoma and squamous cell carcinoma of lung). Fast RS phase method for skin and lung tumors identification was proposed. It is based on alteration of Raman spectral intensity in 1300-1340, 1440-1460 and 1640-1680 cm-1 bands for healthy and malignant tissue. Complex method could identify: malignant melanoma with 88.9% sensitivity and 87.8% specificity; adenocarcinoma with 100% sensitivity and 81.5% specificity; squamous cell carcinomas with 90.9% sensitivity and 77.8% specificity.

  19. Improving pancreatic cancer diagnosis using circulating tumor cells: prospects for staging and single-cell analysis

    PubMed Central

    Court, Colin M; Ankeny, Jacob S; Hou, Shuang; Tseng, Hsian-Rong; Tomlinson, James S

    2016-01-01

    Pancreatic cancer (PC) is the fourth most common cause of cancer-related death in the USA, primarily due to late presentation coupled with an aggressive biology. The lack of adequate biomarkers for diagnosis and staging confound clinical decision-making and delay potentially effective therapies. Circulating tumor cells (CTCs) are a promising new biomarker in PC. Preliminary studies have demonstrated their potential clinical utility, and newer CTC isolation platforms have the potential to provide clinicians access to tumor tissue in a reliable, real-time manner. Such a ‘liquid biopsy’ has been demonstrated in several cancers, and small studies have demonstrated its potential applications in PC. This article reviews the available literature on CTCs as a biomarker in PC and presents the latest innovations in CTC research as well as their potential applications in PC. PMID:26390158

  20. Prognosis and Clinicopathologic Features of Patients With Advanced Stage Isocitrate Dehydrogenase (IDH) Mutant and IDH Wild-Type Intrahepatic Cholangiocarcinoma

    PubMed Central

    Goyal, Lipika; Govindan, Aparna; Sheth, Rahul A.; Nardi, Valentina; Blaszkowsky, Lawrence S.; Faris, Jason E.; Clark, Jeffrey W.; Ryan, David P.; Kwak, Eunice L.; Allen, Jill N.; Murphy, Janet E.; Saha, Supriya K.; Hong, Theodore S.; Wo, Jennifer Y.; Ferrone, Cristina R.; Tanabe, Kenneth K.; Chong, Dawn Q.; Deshpande, Vikram; Borger, Darrell R.; Iafrate, A. John; Bardeesy, Nabeel; Zheng, Hui

    2015-01-01

    Background. Conflicting data exist regarding the prognostic impact of the isocitrate dehydrogenase (IDH) mutation in intrahepatic cholangiocarcinoma (ICC), and limited data exist in patients with advanced-stage disease. Similarly, the clinical phenotype of patients with advanced IDH mutant (IDHm) ICC has not been characterized. In this study, we report the correlation of IDH mutation status with prognosis and clinicopathologic features in patients with advanced ICC. Methods. Patients with histologically confirmed advanced ICC who underwent tumor mutational profiling as a routine part of their care between 2009 and 2014 were evaluated. Clinical and pathological data were collected by retrospective chart review for patients with IDHm versus IDH wild-type (IDHwt) ICC. Pretreatment tumor volume was calculated on computed tomography or magnetic resonance imaging. Results. Of the 104 patients with ICC who were evaluated, 30 (28.8%) had an IDH mutation (25.0% IDH1, 3.8% IDH2). The median overall survival did not differ significantly between IDHm and IDHwt patients (15.0 vs. 20.1 months, respectively; p = .17). The pretreatment serum carbohydrate antigen 19-9 (CA19-9) level in IDHm and IDHwt patients was 34.5 and 118.0 U/mL, respectively (p = .04). Age at diagnosis, sex, histologic grade, and pattern of metastasis did not differ significantly by IDH mutation status. Conclusion. The IDH mutation was not associated with prognosis in patients with advanced ICC. The clinical phenotypes of advanced IDHm and IDHwt ICC were similar, but patients with IDHm ICC had a lower median serum CA19-9 level at presentation. Implications for Practice: Previous studies assessing the prognostic impact of the isocitrate dehydrogenase (IDH) gene mutation in intrahepatic cholangiocarcinoma (ICC) mainly focused on patients with early-stage disease who have undergone resection. These studies offer conflicting results. The target population for clinical trials of IDH inhibitors is patients with

  1. Technological update of the video-endoscopic approach of the diagnosis and staging of tumors in children.

    PubMed

    Drăghici, Isabela Magdalena; Luca, Dragoş-Constantin; Popescu, Maria-Delia; Drăghici, Liviu

    2014-01-01

    The pediatric patient is often difficult to diagnose, especially since the surgical pathology is tumoral. Establishing the histopathological diagnosis of a tumor, staging of a disease and certifying the existence of rare pediatric affections are three of the motives for which the specialists frequently appeal to an exploratory laparoscopy, accompanied by biopsy procedures. The paper presents the laparoscopic biopsy experience of the team from the Department of Pediatric Surgery, "Maria Skłodowska Curie" Emergency Clinical Hospital for Children, Bucharest, Romania. From 2000 to 2013, 95 such procedures were performed (7.76% of a total of 1224 laparoscopic interventions). In many cases, the laparoscopy had an exclusive diagnostic purpose, of whose success has been primarily responsible the targeted biopsy. Current issues are discussed, centered on the most advanced technologies used in minimally invasive approach of pediatric malignancies, referring to the effect of minimizing the possible complications that can arise from this type of intervention. The authors concluded that laparoscopic technique is the method of choice in comparison to other ways of biopsy (classical surgery, ultrasound guidance, tomography, etc.), and it is characterized by a high diagnostic value.

  2. SU-E-J-269: Tracking of Tumor Regression for Stage III Lung Cancer Using CBCT

    SciTech Connect

    Kang, K; Biswas, T; Podder, T

    2015-06-15

    Purpose: This study is to evaluate the tumor regression over the course of EBRT treatment and to determine the difference of tumor reduction for stage III lung squamous cell cancer (SCC) and adenocarcinoma using CBCT. Methods: Twenty three stage III lung cancer patients treated in our clinic who had daily cone beam CT (CBCT) were selected for this study (16 adenocarcinoma and 7 SCC cases). Patients received prescription dose in the range of 50Gy–71.4Gy (mean =60.3Gy, median =50Gy) at 1.8Gy or 2Gy per fraction. Treatments spanned over a minimum of five weeks. Initial mean volume of the gross tumor volume (GTV) was 123cc (range = 14.7cc–353.3cc). For this study, we choose six sets of CBCTs at an interval of one week, starting from the first fraction of treatment. Daily CBCTs from treatment linac computer were transferred to MIM Software version 6.0. An experienced physician contoured the primary GTV on each slices of the CBCT for these patients. Results: A consistent regression of the GTVs was observed in all patients, except in one patient (adeno case) where GTV did not change. Weekly volumetric reduction was in the range of 11.2%–16.6%. Maximum reductions were noticed in the first two weeks of the treatment cycle; mean overall (for adeno+SCC) reductions were 16.6%, 14.2% in week-1 and week-2, respectively. Mean reduction over five weeks of treatment was 49.8% (range = 0.1%–75.5%). Higher reduction was observed in SCC patients as compare to adenocarcinoma cases (54.9% vs. 47.6%); however, the difference was not statistically significant (p-value > 0.05). Conclusion: Large regression of tumors over the course of EBRT for stage III lung cancer patients was observed. Both SCC and adenocarcinoma responded well; overall reduction for SCC cases was higher. A future study is warranted for determining the co-relation between tumor volume reduction and treatment outcome.

  3. Experimental Results of the First Two Stages of an Advanced Transonic Core Compressor Under Isolated and Multi-Stage Conditions

    NASA Technical Reports Server (NTRS)

    Prahst, Patricia S.; Kulkarni, Sameer; Sohn, Ki H.

    2015-01-01

    NASA's Environmentally Responsible Aviation (ERA) Program calls for investigation of the technology barriers associated with improved fuel efficiency of large gas turbine engines. Under ERA the task for a High Pressure Ratio Core Technology program calls for a higher overall pressure ratio of 60 to 70. This mean that the HPC would have to almost double in pressure ratio and keep its high level of efficiency. The challenge is how to match the corrected mass flow rate of the front two supersonic high reaction and high corrected tip speed stages with a total pressure ratio of 3.5. NASA and GE teamed to address this challenge by using the initial geometry of an advanced GE compressor design to meet the requirements of the first 2 stages of the very high pressure ratio core compressor. The rig was configured to run as a 2 stage machine, with Strut and IGV, Rotor 1 and Stator 1 run as independent tests which were then followed by adding the second stage. The goal is to fully understand the stage performances under isolated and multi-stage conditions and fully understand any differences and provide a detailed aerodynamic data set for CFD validation. Full use was made of steady and unsteady measurement methods to isolate fluid dynamics loss source mechanisms due to interaction and endwalls. The paper will present the description of the compressor test article, its predicted performance and operability, and the experimental results for both the single stage and two stage configurations. We focus the detailed measurements on 97 and 100 of design speed at 3 vane setting angles.

  4. Comparison of Survival Rates, Tumor Stages, and Localization in between Obese and Nonobese Patients with Gastric Cancer

    PubMed Central

    Dogan, Hakan; Oguz, Basak; Ocak Serin, Sibel; Okuturlar, Yildiz; Gunaldi, Meral; Erismis, Betul; Ozdemir, Bahar; Tural, Deniz; Hursitoglu, Mehmet; Harmankaya, Ozlem; Kumbasar, Abdulbaki

    2016-01-01

    Purpose. In this study we tried to determine the association between body-mass index (BMI), survival rate, and the stage of tumor at the time of diagnosis in patients with gastric cancer. Methods. A total of 270 gastric cancer patients' hospital records were retrospectively evaluated. Patients were grouped according to their BMI at the time of tumor diagnosis. Tumor stages at admission were compared according to their BMI values. Results. There were no differences in OS among BMI subgroups (p = 0.230). The percent of patients with stage III tumor was significantly higher in nonobese while the percent of stage IV tumor was surprisingly higher in obese patients (p was 0.011 and 0.004, resp.). Percent of patients who did not have any surgical intervention was significantly lower in overweight and obese patients than normal and/or underweight patients. Conclusions. At the time of diagnosis, obese patients had significantly higher percent of stage IV tumor than nonobese patients. Despite of that, there were no differences in survival rates among BMI subgroups. Our study results are consistent with “obesity paradox” in gastric cancer patients. We also did not find any relationship between BMI and localization of gastric tumor. PMID:27418926

  5. Primary Tumor Necrosis Predicts Distant Control in Locally Advanced Soft-Tissue Sarcomas After Preoperative Concurrent Chemoradiotherapy

    SciTech Connect

    MacDermed, Dhara M.; Miller, Luke L.; Peabody, Terrance D.; Simon, Michael A.; Luu, Hue H.; Haydon, Rex C.; Montag, Anthony G.; Undevia, Samir D.

    2010-03-15

    Purpose: Various neoadjuvant approaches have been evaluated for the treatment of locally advanced soft-tissue sarcomas. This retrospective study describes a uniquely modified version of the Eilber regimen developed at the University of Chicago. Methods and Materials: We treated 34 patients (28 Stage III and 6 Stage IV) with locally advanced soft-tissue sarcomas of an extremity between 1995 and 2008. All patients received preoperative therapy including ifosfamide (2.5 g/m2 per day for 5 days) with concurrent radiation (28 Gy in 3.5-Gy daily fractions), sandwiched between various chemotherapy regimens. Postoperatively, 47% received further adjuvant chemotherapy. Results: Most tumors (94%) were Grade 3, and all were T2b, with a median size of 10.3 cm. Wide excision was performed in 29 patients (85%), and 5 required amputation. Of the resected tumor specimens, 50% exhibited high (>=90%) treatment-induced necrosis and 11.8% had a complete pathologic response. Surgical margins were negative in all patients. The 5-year survival rate was 42.3% for all patients and 45.2% for Stage III patients. For limb-preservation patients, the 5-year local control rate was 89.0% and reoperation was required for wound complications in 17.2%. The 5-year freedom-from-distant metastasis rate was 53.4% (Stage IV patients excluded), and freedom from distant metastasis was superior if treatment-induced tumor necrosis was 90% or greater (84.6% vs. 19.9%, p = 0.02). Conclusions: This well-tolerated concurrent chemoradiotherapy approach yields excellent rates of limb preservation and local control. The resulting treatment-induced necrosis rates are predictive of subsequent metastatic risk, and this information may provide an opportunity to guide postoperative systemic therapies.

  6. Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies

    PubMed Central

    Bettegowda, Chetan; Sausen, Mark; Leary, Rebecca J.; Kinde, Isaac; Wang, Yuxuan; Agrawal, Nishant; Bartlett, Bjarne R.; Wang, Hao; Luber, Brandon; Alani, Rhoda M.; Antonarakis, Emmanuel S.; Azad, Nilofer S.; Bardelli, Alberto; Brem, Henry; Cameron, John L.; Lee, Clarence C.; Fecher, Leslie A.; Gallia, Gary L.; Gibbs, Peter; Le, Dung; Giuntoli, Robert L.; Goggins, Michael; Hogarty, Michael D.; Holdhoff, Matthias; Hong, Seung-Mo; Jiao, Yuchen; Juhl, Hartmut H.; Kim, Jenny J.; Siravegna, Giulia; Laheru, Daniel A.; Lauricella, Calogero; Lim, Michael; Lipson, Evan J.; Marie, Suely Kazue Nagahashi; Netto, George J.; Oliner, Kelly S.; Olivi, Alessandro; Olsson, Louise; Riggins, Gregory J.; Sartore-Bianchi, Andrea; Schmidt, Kerstin; Shih, le-Ming; Oba-Shinjo, Sueli Mieko; Siena, Salvatore; Theodorescu, Dan; Tie, Jeanne; Harkins, Timothy T.; Veronese, Silvio; Wang, Tian-Li; Weingart, Jon D.; Wolfgang, Christopher L.; Wood, Laura D.; Xing, Dongmei; Hruban, Ralph H.; Wu, Jian; Allen, Peter J.; Schmidt, C. Max; Choti, Michael A.; Velculescu, Victor E.; Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas; Diaz, Luis A.

    2014-01-01

    The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction–based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer. PMID:24553385

  7. Putative circulating markers of the early and advanced stages of breast cancer identified by high-resolution label-free proteomics.

    PubMed

    Panis, Carolina; Pizzatti, Luciana; Herrera, Ana Cristina; Cecchini, Rubens; Abdelhay, Eliana

    2013-03-01

    This study evaluated the plasmatic proteomic profile of breast cancer patients in the early (ED) and advanced (AD) stages, employing high-throughput proteomics. We identified 92 differentially expressed proteins in ED and 73 proteins in AD patients. Gelsolin, lumican, clusterin, SALL4 and PMS2, as well hTERT, TNF-α and GRHL3 were chosen for further investigation. ED presented augmented expression of GRHL3 and reduced circulating TNF-α with high expression of GRHL3 in tumors. AD displayed high TNF-α and a significant expression of PMS2 in tumors. These findings suggest processes enrolling stem cell division in ED, with TNF-α signaling and DNA mismatch repair in the advanced stage.

  8. Neuroimaging of pediatric brain tumors: from basic to advanced magnetic resonance imaging (MRI).

    PubMed

    Panigrahy, Ashok; Blüml, Stefan

    2009-11-01

    In this review, the basic magnetic resonance concepts used in the imaging approach of a pediatric brain tumor are described with respect to different factors including understanding the significance of the patient's age. Also discussed are other factors directly related to the magnetic resonance scan itself including evaluating the location of the tumor, determining if the lesion is extra-axial or intra-axial, and evaluating the contrast characteristics of the lesion. Of note, there are key imaging features of pediatric brain tumors, which can give information about the cellularity of the lesion, which can then be confirmed with advanced magnetic resonance imaging (MRI) techniques. The second part of this review will provide an overview of the major advanced MRI techniques used in pediatric imaging, particularly, magnetic resonance diffusion, magnetic resonance spectroscopy, and magnetic resonance perfusion. The last part of the review will provide more specific information about the use of advanced magnetic resonance techniques in the evaluation of pediatric brain tumors.

  9. Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis.

    PubMed

    Blakeley, Jaishri O; Plotkin, Scott R

    2016-05-01

    Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded byNF1) and merlin (encoded byNF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1andLZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations inNF1(ie, glioblastoma, breast cancer, melanoma),NF2(ie, meningioma, mesothelioma) andSMARCB1(ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations. PMID:26851632

  10. Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis.

    PubMed

    Blakeley, Jaishri O; Plotkin, Scott R

    2016-05-01

    Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded byNF1) and merlin (encoded byNF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1andLZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations inNF1(ie, glioblastoma, breast cancer, melanoma),NF2(ie, meningioma, mesothelioma) andSMARCB1(ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations.

  11. Gross Hematuria and Bladder Tumor in a Patient with Advanced Thyroid Papillary Carcinoma

    PubMed Central

    Matsuo, Yuki; Ikeoka, Toshiyuki; Oba, Kojiro; Miyata, Yasuyoshi; Sakai, Hideki; Abe, Kuniko; Kawakami, Atsushi

    2013-01-01

    We present a 73-year-old female with advanced thyroid papillary carcinoma who complained of gross hematuria. We found a bladder tumor and considered it the cause of her symptom. Cystoscopic findings of the tumor were unusual, with peri-tumor vessel formation. Pathological examination of the bladder tumor was consistent with metastasis of thyroid papillary carcinoma. Therefore, we identified thyroid carcinoma metastasis to the urinary bladder as the cause of hematuria in our patient. Thyroid carcinoma metastasis to the bladder is extremely rare, but it should be included among differential diagnoses for gross hematuria in patients with a clinical history of thyroid carcinoma. PMID:23762664

  12. Applications of a novel tumor-grading-metastasis staging system for pancreatic neuroendocrine tumors: An analysis of surgical patients from a Chinese institution.

    PubMed

    Yang, Min; Tan, Chun-Lu; Zhang, Yi; Ke, Neng-Wen; Zeng, Lin; Li, Ang; Zhang, Hao; Xiong, Jun-Jie; Guo, Zi-Heng; Tian, Bo-Le; Liu, Xu-Bao

    2016-07-01

    The ability to stratify patients with pancreatic neuroendocrine tumors (p-NETs) into prognostic groups has been hindered by the absence of a commonly accepted staging system. Both the 7th tumor-node-metastasis (TNM) staging guidelines by the American Joint Committee on Cancer (AJCC) and the 2010 grading classifications by the World Health Organization (WHO) were validated to be unsatisfactory.We aim to evaluate the feasibility of combining the latest AJCC and WHO criteria to devise a novel tumor-grading-metastasis (TGM) staging system. We also sought to examine the stage-specific survival rates and the prognostic value of this new TGM system for p-NETs.Data of 120 patients with surgical resection and histopathological diagnosis of p-NETs from January 2004 to February 2014 in our institution were retrospectively collected and analyzed. Based on the AJCC and WHO criteria, we replaced the stage N0 and N1 with stage Ga (NET G1 and NET G2) and Gb (NET G3 and MANEC) respectively, without changes of the definition of T or M stage. The present novel TGM staging system was grouped as follows: stage I was defined as T1-2, Ga, M0; stage II as T3, Ga, M0 or as T1-3, Gb, M0; stage III as T4, Ga-b, M0 and stage IV as any T, M1.The new TGM staging system successfully distributed 55, 42, 12, and 11 eligible patients in stage I to IV, respectively. Differences of survival compared stage I with III and IV for patients with p-NETs were both statistically significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001). Patients in stage I showed better a survival than those in stage II, whereas difference between stages III and IV was not notable (P = 0.001, P = 0.286, respectively). In multivariate models, when the TGM staging system was evaluated in place of the individual T, G, and M variables, this new criteria were proven to be an independent predictor of survival for surgically resected p-NETs (P < 0.05).Stratifying patients well, the current

  13. Applications of a novel tumor-grading-metastasis staging system for pancreatic neuroendocrine tumors: An analysis of surgical patients from a Chinese institution.

    PubMed

    Yang, Min; Tan, Chun-Lu; Zhang, Yi; Ke, Neng-Wen; Zeng, Lin; Li, Ang; Zhang, Hao; Xiong, Jun-Jie; Guo, Zi-Heng; Tian, Bo-Le; Liu, Xu-Bao

    2016-07-01

    The ability to stratify patients with pancreatic neuroendocrine tumors (p-NETs) into prognostic groups has been hindered by the absence of a commonly accepted staging system. Both the 7th tumor-node-metastasis (TNM) staging guidelines by the American Joint Committee on Cancer (AJCC) and the 2010 grading classifications by the World Health Organization (WHO) were validated to be unsatisfactory.We aim to evaluate the feasibility of combining the latest AJCC and WHO criteria to devise a novel tumor-grading-metastasis (TGM) staging system. We also sought to examine the stage-specific survival rates and the prognostic value of this new TGM system for p-NETs.Data of 120 patients with surgical resection and histopathological diagnosis of p-NETs from January 2004 to February 2014 in our institution were retrospectively collected and analyzed. Based on the AJCC and WHO criteria, we replaced the stage N0 and N1 with stage Ga (NET G1 and NET G2) and Gb (NET G3 and MANEC) respectively, without changes of the definition of T or M stage. The present novel TGM staging system was grouped as follows: stage I was defined as T1-2, Ga, M0; stage II as T3, Ga, M0 or as T1-3, Gb, M0; stage III as T4, Ga-b, M0 and stage IV as any T, M1.The new TGM staging system successfully distributed 55, 42, 12, and 11 eligible patients in stage I to IV, respectively. Differences of survival compared stage I with III and IV for patients with p-NETs were both statistically significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001). Patients in stage I showed better a survival than those in stage II, whereas difference between stages III and IV was not notable (P = 0.001, P = 0.286, respectively). In multivariate models, when the TGM staging system was evaluated in place of the individual T, G, and M variables, this new criteria were proven to be an independent predictor of survival for surgically resected p-NETs (P < 0.05).Stratifying patients well, the current

  14. [Survival after Sorafenib Treatment for Advanced Recurrent Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava].

    PubMed

    Matoba, Hideaki; Seta, Shinsuke

    2015-11-01

    A 72-year-old man with chronic viral hepatitis type B undergoing surgery for hepatocellular carcinoma was found to have a recurrent tumor in the left liver with peritoneal dissemination near the inferior vena cava(IVC)and tumor thrombus in the IVC. For this patient diagnosed with Barcelona clinic liver cancer (BCLC) classification stage C hepatocellular carcinoma, we initiated 800 mg/body sorafenib. Two weeks after the initiation of sorafenib, the patient experienced grade 3 hand-foot syndrome, after which, the dose of sorafenib was reduced to 400 mg/body. After 1 year, CT showed an enlarged tumor in the left liver and multiple metastases to the lung. However, no remarkable difference was observed in the peritoneal dissemination and the tumor thrombus. He has been receiving sorafenib for 19 months with a good quality of life. Sorafenib can be provided on an outpatient basis and it may facilitate long-term survival for patients with advanced recurrent hepatocellular carcinoma with IVC tumor thrombus. This clinical condition is very rare, and the standard treatment for it still has not been established.

  15. [Survival after Sorafenib Treatment for Advanced Recurrent Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava].

    PubMed

    Matoba, Hideaki; Seta, Shinsuke

    2015-11-01

    A 72-year-old man with chronic viral hepatitis type B undergoing surgery for hepatocellular carcinoma was found to have a recurrent tumor in the left liver with peritoneal dissemination near the inferior vena cava(IVC)and tumor thrombus in the IVC. For this patient diagnosed with Barcelona clinic liver cancer (BCLC) classification stage C hepatocellular carcinoma, we initiated 800 mg/body sorafenib. Two weeks after the initiation of sorafenib, the patient experienced grade 3 hand-foot syndrome, after which, the dose of sorafenib was reduced to 400 mg/body. After 1 year, CT showed an enlarged tumor in the left liver and multiple metastases to the lung. However, no remarkable difference was observed in the peritoneal dissemination and the tumor thrombus. He has been receiving sorafenib for 19 months with a good quality of life. Sorafenib can be provided on an outpatient basis and it may facilitate long-term survival for patients with advanced recurrent hepatocellular carcinoma with IVC tumor thrombus. This clinical condition is very rare, and the standard treatment for it still has not been established. PMID:26805098

  16. Small cell lung cancer: Circulating tumor cells of extended stage patients express a mesenchymal-epithelial transition phenotype.

    PubMed

    Hamilton, Gerhard; Hochmair, Maximilian; Rath, Barbara; Klameth, Lukas; Zeillinger, Robert

    2016-07-01

    Small cell lung cancer (SCLC) is distinguished by aggressive growth, early dissemination and a poor prognosis at advanced stage. The remarkably high count of circulating tumor cells (CTCs) of SCLC allowed for the establishment of permanent CTC cultures at our institution for the first time. CTCs are assumed to have characteristics of cancer stem cells (CSCs) and an epithelial-mesenchymal transition (EMT) phenotype, but extravasation of tumors at distal sites is marked by epithelial features. Two SCLC CTC cell lines, namely BHGc7 and BHGc10, as well as SCLC cell lines derived from primary tumors and metastases were analyzed for the expression of pluripotent stem cell markers and growth factors. Expression of E-cadherin and β-Catenin were determined by flow cytometry. Stem cell-associated markers SOX17, α-fetoprotein, OCT-3/4, KDR, Otx2, GATA-4, Nanog, HCG, TP63 and Goosecoid were not expressed in the 2 CTC lines. In contrast, high expression was found for HNF-3β/FOXA2, SOX2, PDX-1/IPF1 and E-cadherin. E-cadherin expression was restricted to the 2 CTCs and 2 cell lines derived from pleural effusion (SCLC26A) and bone metastases (NCI-H526), respectively. Thus, these SCLC CTCs established from extended disease SCLC patients lack expression of stem cell markers which suppress the epithelial phenotype. Instead they express high levels of E-cadherin consistent with a mesenchymal-epithelial transition (MET or EMrT) and form large tumorospheres possibly in response to the selection pressure of first-line chemotherapy. HNF-3β/FOXA2 and PDX-1/IPF1 expression seem to be related to growth factor dependence on insulin/IGF-1 receptors and IGF-binding proteins. PMID:26919626

  17. Wnt Pathway Activation Predicts Increased Risk of Tumor Recurrence in Patients with Stage I Non-Small Cell Lung Cancer

    PubMed Central

    Shapiro, Mark; Akiri, Gal; Chin, Cynthia; Wisnivesky, Juan P.; Beasley, Mary B.; Weiser, Todd S.; Swanson, Scott J.; Aaronson, Stuart A.

    2012-01-01

    Objective To determine the prevalence of Wnt pathway activation in patients with stage I NSCLC and its influence on lung cancer recurrence. Background Despite resection, the 5 year recurrence with localized stage I non-small cell lung cancer (NSCLC) is 18.4–24%. Aberrant Wnt signaling activation plays an important role in a wide variety of tumor types. However, there is not much known about the role Wnt pathway plays in patients with stage I lung cancer Methods Tumor and normal lung tissues from 55 patients following resection for stage I NSCLC were subjected to glutathione-S-transferase (GST) E-cadherin pull-down and immunoblot analysis to assess levels of uncomplexed β-catenin, a reliable measure of Wnt signaling activation. The β-catenin gene was also screened for oncogenic mutations in tumors with activated Wnt signaling. Cancer recurrence rates were correlated in a blinded manner in patients with Wnt pathway positive and negative tumors. Results Tumors in twenty patients (36.4%) scored as Wnt positive with only one exhibiting a β-catenin oncogenic mutation. Patients with Wnt positive tumors experienced a significantly higher rate of overall cancer recurrence than those with Wnt negative tumors (30.0% vs. 5.7%, p=0.02), with 25.0% exhibiting distal tumor recurrence compared to 2.9% in the Wnt negative group (p=0.02). Conclusions Wnt pathway activation was present in a substantial fraction of Stage I NSCLCs, which was rarely due to mutations. Moreover, Wnt pathway activation was associated with a significantly higher rate of tumor recurrence. These findings suggest that Wnt activation reflects a more aggressive tumor phenotype and identifies patients who may benefit from more aggressive therapy in addition to resection. PMID:23011390

  18. Cyclin D1 and Ki-67 expression correlates to tumor staging in tongue squamous cell carcinoma

    PubMed Central

    de Carli, Marina-Lara; Sperandio, Felipe-Fornias; Hanemann, João-Adolfo-Costa; Pereira, Alessandro-Antônio-Costa

    2015-01-01

    Background The immunohistochemical expression of Cyclin D1 and Ki-67 were analyzed in tongue squamous cell carcinomas (SCC), relating them to the clinical and morphological exhibition of these tumors. Material and Methods Twenty-nine patients fulfilled the inclusion criteria; clinical data included gender, age, ethnicity and use of licit drugs such as alcohol and tobacco. The TNM staging and histopathological differentiation grading was assessed for each case. In addition, T1 patients were gathered with T2 patients; and T3 patients were gathered with T4 patients to assemble two distinct groups: (T1/T2) and (T3/T4). Results The mean follow-up time was 24 months and 30% of the patients died as a consequence of the disease, while 23.3% lived with the disease and 46.7% lived lesion-free. T1 and T2 tumors showed statistically lesser Ki-67 and Cyclin D1 staining when compared to T3 and T4 tumors. Conclusions Ki-67 and Cyclin D1 pose as auxiliary tools when determining the progression of tongue SCC at the time of diagnosis. Key words:Carcinoma, squamous cell, cyclin D, immunohistochemistry, Ki-67 antigen, prognosis. PMID:26449430

  19. 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

  20. 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

  1. 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

  2. Time-to-Progression of NSCLC from Early to Advanced Stages: An Analysis of data from SEER Registry and a Single Institute

    PubMed Central

    Yuan, Ping; Cao, Jin Lin; Rustam, Azmat; Zhang, Chong; Yuan, Xiao Shuai; Bao, Fei Chao; Lv, Wang; Hu, Jian

    2016-01-01

    The average time required for cancers to progress through stages can be reflected in the average age of the patients diagnosed at each stage of disease. To estimate the time it takes for non-small-cell lung cancer (NSCLC) to progress through different tumor, node and metastasis (TNM) stages and sizes, we compared the mean adjusted age of 45904 NSCLC patients with different stages and tumor sizes from Surveillance, Epidemiology and End Results (SEER) cancer registry database and our institute. Multiple-linear-regression models for age were generated adjusting for various factors. Caucasian, African-American and Asian patients with stage IA cancers were on average 0.8, 1.0 and 1.38 adjusted years younger, respectively, than those with stage IIIB cancers (p < 0.001). And these with T1a cancers were on average 0.84, 0.92 and 1.21 adjusted years younger, respectively, than patients with T3 cancers (p < 0.001). Patients with tumors measuring larger than 8 cm in diameter were on average 0.85 adjusted years older than these with tumors smaller than 1 cm (p < 0.001), with Caucasian demonstrating the shortest age span (0.79 years, P < 0.001). In conclusion, the time-to-progression of NSCLC from early to advanced stages varied among ethnicities, Caucasian patients demonstrating a more rapid progression nature of tumor than their African-American and Asian counterparts. PMID:27346236

  3. 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

  4. Targeted labeling of an early-stage tumor spheroid in a chorioallantoic membrane model with upconversion nanoparticles

    NASA Astrophysics Data System (ADS)

    Liu, Kai; Holz, Jasmin A.; Ding, Yadan; Liu, Xiaomin; Zhang, Youlin; Tu, Langping; Kong, Xianggui; Priem, Bram; Nadort, Annemarie; Lambrechts, Saskia A. G.; Aalders, Maurice C. G.; Buma, Wybren Jan; Liu, Yichun; Zhang, Hong

    2015-01-01

    In vivo detection of cancer at an early-stage, i.e. smaller than 2 mm, is a challenge in biomedicine. In this work target labeling of an early-stage tumor spheroid (~500 μm) is realized for the first time in a chick embryo chorioallantoic membrane (CAM) model with monoclonal antibody functionalized upconversion nanoparticles (UCNPs-mAb).In vivo detection of cancer at an early-stage, i.e. smaller than 2 mm, is a challenge in biomedicine. In this work target labeling of an early-stage tumor spheroid (~500 μm) is realized for the first time in a chick embryo chorioallantoic membrane (CAM) model with monoclonal antibody functionalized upconversion nanoparticles (UCNPs-mAb). Electronic supplementary information (ESI) available: Details of experimental procedures for the sample preparation and characterization, Chick CAM model, 3-D multicellular tumor spheroids, UCNPs circulating in CAM. See DOI: 10.1039/c4nr05638h

  5. Studies on the mechanism of skin tumor promotion: evidence for several stages in promotion. [Mice

    SciTech Connect

    Slaga, T.J.; Fischer, S.M.; Nelson, K.; Gleason, G.L.

    1980-06-01

    The effects of nonpromoting and weakly promoting diterpenes on skin tumor promotion by 12-O-tetradecanoylphorbol 13-acetate (TPA) were investigated. When phorbol and phorbol 12,13-diacetate (both nonpromoting) were given simultaneously with TPA after 7,12-dimethylbenz(a)-anthracene (DMBA) initiation in female mice, they had no effect on TPA promotion. However, the nonpromoter 4-O-methyl-TPA and the weak promoter mezerein were found to inhibit TPA promotion in a dose-dependent manner when given simultaneously with TPA. Because mezerein was found to be an effective inhibitor of TPA promotion when given simultaneously and because it induces many biological responses similar to those to TPA, the capacity of mezerein to act as an incomplete promoter in a two-stage promotion protocol was also investigated. The results suggest that although mezerein by itself is a weak promotor and mimics TPA in many biochemical and morphological effects it is a potent second-stage promoter in a two-stage promotion regimen.

  6. Primary Tumor Volume Is an Important Predictor of Clinical Outcomes Among Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Treated With Definitive Chemoradiotherapy

    SciTech Connect

    Strongin, Anna; Yovino, Susannah; Taylor, Rodney; Wolf, Jeffrey; Cullen, Kevin; Zimrin, Ann; Strome, Scott; Regine, William; Suntharalingam, Mohan

    2012-04-01

    Purpose: The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy. Methods and Materials: A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis. Results: The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm{sup 3}, and patients with a tumor volume <35 cm{sup 3} had a significantly better prognosis than those with a tumor volume >35 cm{sup 3} at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume <35 cm{sup 3} had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p = < .001). On multivariate analysis, the primary tumor volume was the best predictor of recurrence (hazard ratio 4.7, 95% confidence interval 1.9-11.6; p = .001) and survival (hazard ratio 10.0, 95% confidence interval 2.9-35.1; p = < .001). In contrast, the T stage and N stage were not significant factors. Analysis of variance revealed that tumors with locoregional failure were on average 21.6 cm{sup 3} larger than tumors without locoregional failure (p = .028) and 27.1-cm{sup 3} larger than tumors that recurred as distant metastases (p = .020). Conclusion: The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer

  7. Clinicopathologic characteristics of patients with stage III/IV (M(0)) advanced gastric cancer, according to HER2 status assessed by immunohistochemistry and fluorescence in situ hybridization.

    PubMed

    Im, Seock-Ah; Kim, Jin Won; Kim, Jin-Soo; Kim, Min A; Jordan, Bruce; Pickl, Marlene; Han, Sae-Won; Oh, Do-Youn; Lee, Hyuk Joon; Kim, Tae-You; Kim, Woo Ho; Yang, Han-Kwang; Bang, Yung-Jue

    2011-06-01

    Despite recent advances in chemotherapy, the prognosis for patients with advanced gastric cancer (GC) or gastroesophageal junction cancer remains poor. Human epidermal growth factor receptor 2 (HER2) is a novel target for biologic therapy in metastatic GC. We analyzed the association between HER2 overexpression and the clinicopathologic characteristics of advanced GC. Formalin-fixed, paraffin-embedded tumor samples were collected from patients with stage III or to IV (M(0)) GC who subsequently underwent curative surgery followed by adjuvant chemotherapy with 5-fluorouracil and cisplatin. All the samples were analyzed for HER2 status by immunohistochemistry (IHC) and fluorescence in situ hybridization. Of 142 samples analyzed, 7.1% scored IHC 2+ and 8.6% scored IHC 3+, whereas 9.3% were HER2-amplified. Of HER2-amplified cases, 76.9% (10/13) scored IHC 3+, showing the correlation between HER2 amplification and overexpression (P=0.01). HER2 IHC 3+ cases were more common in the intestinal-type tumors compared with diffuse-type tumors (16.7% vs. 5.1%, respectively; P=0.049), and a nonsignificant trend was observed using fluorescence in situ hybridization (14.3% vs. 9.2%, respectively; P=0.399). HER2 gene amplification was more frequent in stage IV (M(0)) than stage III disease (15.4% vs. 4.0%, respectively; P=0.037). Interestingly, HER2-amplified disease was more common than nonamplified disease in patients with nodal stage 3 tumors (76.9% vs. 38.6%, respectively; P=0.009); a similar pattern was observed using IHC. HER2 overexpression correlated with nodal stage, and a lymph node ratio greater than 0.5 was more common in HER2-amplified tumors than HER2-nonamplified tumors (69.2% vs. 43.3%, respectively; P=0.086). These findings suggest that further investigations of adjuvant therapy with HER2-targeted therapy for advanced GC are warranted.

  8. Efficacy Comparison Between Total Laryngectomy and Nonsurgical Organ-Preservation Modalities in Treatment of Advanced Stage Laryngeal Cancer

    PubMed Central

    Fu, Xiaoyuan; Zhou, Qi; Zhang, Xianquan

    2016-01-01

    Abstract It remains unclear whether the efficacy of nonsurgical organ-preservation modalities (NOP) in the treatment of advanced-stage laryngeal cancer was noninferiority compared with that of total laryngectomy (TL). The objective of this study was to compare the curative effects between TL and NOP in the treatment of advanced-stage laryngeal cancer through a meta-analysis. Clinical studies were retrieved from the electronic databases of PubMed, Embase, Wanfang, and Chinese National Knowledge infrastructure. A meta-analysis was performed to investigate the differences in the curative efficacy of advanced-stage laryngeal cancer between TL and the nonsurgical method. Two reviewers screened all titles and abstracts, and independently assessed all articles. All identified studies were retrospective. Sixteen retrospective studies involving 8308 patients (4478 in the TL group and 3701 in the nonsurgical group) were included in this meta-analysis. The analysis results displayed the advantage of TL for 2-year and 5-year overall survival (OS)(OR 2.79, 95% CI 1.85–4.23 and OR 1.52, 95% CI 1.09–2.14) as well as in 5-year disease-specific survival (DSS)(OR 1.79, 95% CI 1.61–1.98), but no significant difference in 2-year DSS was detected between the 2 groups (OR = 2.09,95% CI0.69–6.40). Additionally, there were no significant differences between TL and NOP for 5-year local control (LC) either (OR = 1.75, 95% CI 0.87–3.53). When we carried out subgroup analyses, the advantage of TL was especially obvious in T4 subgroups, but not in T3 subgroups. This is the first study to compare the curative effects on advanced-stage laryngeal cancer using meta-analytic methodology. Although there was a trend in favor of TL for OS and DSS, there is no clear difference in oncologic outcome between TL and NOP. Therefore, other factors such as tumor T-stage and size, lymph node metastasis, and physical condition are also important indicators for treatment choice. PMID:27057837

  9. Peptide receptor radionuclide therapy for advanced neuroendocrine tumors.

    PubMed

    Bodei, Lisa; Cremonesi, Marta; Kidd, Mark; Grana, Chiara M; Severi, Stefano; Modlin, Irvin M; Paganelli, Giovanni

    2014-08-01

    Peptide receptor radionuclide therapy (PRRT) consists of the systemic administration of a synthetic peptide, labeled with a suitable β-emitting radionuclide, able to irradiate tumors and their metastases via internalization through a specific receptor (usually somatostatin S2), over-expressed on the cell membrane. After almost 2 decades of experience, PRRT, with either (90)Y-octreotide or (177)Lu-octreotate, has established itself to be an efficient and effective therapeutic modality. As a treatment, it is relatively safe up to the known thresholds of absorbed and bio-effective isotope dosages and the renal and hematological toxicity profiles are acceptable if adequate protective measures are undertaken.

  10. Endoscopic Tumor Length Should Be Reincluded in the Esophageal Cancer Staging System: Analyses of 662 Consecutive Patients.

    PubMed

    Valmasoni, Michele; Pierobon, Elisa Sefora; Ruol, Alberto; De Pasqual, Carlo Alberto; Zanchettin, Gianpietro; Moletta, Lucia; Salvador, Renato; Costantini, Mario; Merigliano, Stefano

    2016-01-01

    Esophageal cancer represents the 6th cause of cancer mortality in the World. New treatments led to outcome improvements, but patient selection and prognostic stratification is a critical aspect to gain maximum benefit from therapies. Today, patients are stratified into 9 prognostic groups, according to a staging system developed by the American Joint Committee on Cancer. Recently, trying to better select patients with curing possibilities several authors are reconsidering tumor length as a valuable prognostic parameter. Specifically, endoscopic tumor length can be easily measured with an esophageal endoscopy and, if its utility in esophageal cancer staging is demonstrated, it may represent a simple method to identify high risk patients and an easy-to-obtain variable in prognostic stratification. In this study we retrospectively analyzed 662 patients treated for esophageal cancer, stratified according to cancer histology and current staging system, to assess the possible role of endoscopic tumor length. We found a significant correlation between endoscopic tumor length, current staging parameters and 5-year survival, proving that endoscopic tumor length may be used as a simple risk stratification tool. Our results suggest a possible indication for preoperative therapy in early stage squamocellular carcinoma patients without lymph nodes involvement, who are currently treated with surgery alone. PMID:27088503

  11. Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy.

    PubMed

    Detappe, Alexandre; Kunjachan, Sijumon; Sancey, Lucie; Motto-Ros, Vincent; Biancur, Douglas; Drane, Pascal; Guieze, Romain; Makrigiorgos, G Mike; Tillement, Olivier; Langer, Robert; Berbeco, Ross

    2016-09-28

    Radiation therapy is a major treatment regimen for more than 50% of cancer patients. The collateral damage induced on healthy tissues during radiation and the minimal therapeutic effect on the organ-of-interest (target) is a major clinical concern. Ultra-small, renal clearable, silica based gadolinium chelated nanoparticles (SiGdNP) provide simultaneous MR contrast and radiation dose enhancement. The high atomic number of gadolinium provides a large photoelectric cross-section for increased photon interaction, even for high-energy clinical radiation beams. Imaging and therapy functionality of SiGdNP were tested in cynomolgus monkeys and pancreatic tumor-bearing mice models, respectively. A significant improvement in tumor cell damage (double strand DNA breaks), growth suppression, and overall survival under clinical radiation therapy conditions were observed in a human pancreatic xenograft model. For the first time, safe systemic administration and systematic renal clearance was demonstrated in both tested species. These findings strongly support the translational potential of SiGdNP for MR-guided radiation therapy in cancer treatment. PMID:27423325

  12. The tumor vessel targeting agent NGR-TNF controls the different stages of the tumorigenic process in transgenic mice by distinct mechanisms

    PubMed Central

    Porcellini, Simona; Asperti, Claudia; Valentinis, Barbara; Tiziano, Elena; Mangia, Patrizia; Bordignon, Claudio; Rizzardi, Gian-Paolo; Traversari, Catia

    2015-01-01

    NGR-TNF is a vascular targeting agent in advanced clinical development, coupling tumor necrosis factor-α (TNF) with the CNGRCG peptide, which targets a CD13 isoform specifically expressed by angiogenic vessels. Antitumor efficacy of NGR-TNF has been described in different transplantation tumor models. Nevertheless, the mechanism underlying its activity is not fully understood. In the wild type and in the immunodeficient (RAG−/−) RIP1-Tag2 models of multistage pancreatic carcinogenesis, we demonstrate that CD13 is highly expressed on endothelial cells of hyperplastic and angiogenic islets, whereas its expression is down regulated in tumors where it partially colocalize with pericytes. In vivo CNGRCG peptides coupled to fluorescent nanoparticles (quantum dots) bind to CD13 and colocalize with anti-CD31, in pancreatic islets. At early stage, low doses of NGR-murine (m)TNF have a direct cytotoxic effect inducing endothelial cell apoptosis, reducing vessel density and eventually inhibiting the development of angiogenic islets. At a later stage, NGR-mTNF is able to reduce tumor growth inducing vascular normalization, exclusively when treatment is carried out in the immunocompetent mice. Interestingly, NGR-mTNF-treated tumors from these mice are characterized by CD8+ T cell infiltration. At molecular level, overexpression of genes involved in vessels normalization was detected only in NGR-mTNF-treated tumors from immunocompetent mice. These findings identified a new mechanism of action of NGR-mTNF, providing support for the development of new therapeutic strategies combining chemotherapy or active/adoptive immunotherapies to low dose NGR-TNF treatment. PMID:26451306

  13. [Advance in Research of Angiotensin II and Its Receptor and Malignant Tumor].

    PubMed

    Sun, Lulu; Shi, Jian

    2016-09-20

    Angiotensin AngII, a linear small peptide,which is composed of eight amino acids, is the main effectors of renin-angiotensin systen (Renin-angiotensin system, RAS). AngII, a main biopolypeptide of the RAS, has important pathophysiologic in effects participating in cardiac hypertrophy, vascular cell proproliferation, inflammation and tissue remodeling through G-protein-coupled receptors. In recent years, Ang II can promote tumor cell proliferation, tumor vessel formation and inhibit the differentiation of the tumor cells. This suggests that inhibit the production of AngII or block its effect is expected to become a new measure for the treatment of malignant tumors. This article reviews the advances in research on the relationship between AngII and its receptor and malignant tumor in recent years. PMID:27666553

  14. Heterogeneity of Disease Classified as Stage III in Wilms Tumor: A Report From the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP)

    SciTech Connect

    Spreafico, Filippo; Gandola, Lorenza; Terenziani, Monica; Collini, Paola; Bianchi, Maurizio; Provenzi, Massimo; Indolfi, Paolo; Pession, Andrea; Nantron, Marilina; Di Cataldo, Andrea; Marchiano, Alfonso; Piva, Luigi

    2012-01-01

    Purpose: We analyzed whether the prognosis can differ among Wilms tumors (WT) labeled as Stage III according to currently adopted classification systems. Methods and Materials: Patients with nonanaplastic Stage III WT consecutively registered in two Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) trials (CNR-92, TW-2003) were the subjects in the present analysis. The steady mainstay of therapy was primary nephrectomy, followed by three-drug chemotherapy with vincristine, dactinomycin, doxorubicin, and abdominal radiotherapy (RT). Results: Ninety-nine WT patients met the criteria for classification as Stage III according to a revised version of the National Wilms Tumor Study-3 staging system (51 patients in CNR-92, 48 patients in TW-2003). Regional lymph nodes (LN) were not biopsied in 16 patients. After a median follow-up of 66 months, the 4-year disease-free survival (DFS) and overall survival (OS) rates were 85% {+-} 4% and 92% {+-} 3%, respectively, for the whole group. For 38 children with positive LN, the 4-year DFS rate was 73% {+-} 7%, as opposed to 98% {+-} 2% for the 45 children with Stage III WT according to the other criteria but with negative biopsied LN (p = 0.001). The subgroup with the worst prognosis consisted of children more than 2 years old with positive LN (DFS 67% {+-} 8%). A delay between surgery and RT > 30 days had an adverse impact on the abdominal tumor relapse rate. Conclusions: This study provides further evidence that Stage III tumors with LN metastases might be distinguished from WTs meeting the other criteria for classification as Stage III. The worse outcome of the former may warrant a prospective study on the effects of intensified therapy. A subclassification of Stage III tumors is discussed.

  15. Postoperative radiotherapy and tumor recurrence after complete resection of stage II/III thymic tumor: a meta-analysis of cohort studies

    PubMed Central

    Ma, Jietao; Sun, Xin; Huang, Letian; Xiong, Zhicheng; Yuan, Meng; Zhang, Shuling; Han, Cheng-Bo

    2016-01-01

    Background Whether postoperative radiotherapy (PORT) is effective for reducing the recurrence risk in patients who received complete resection of the stage II or III thymic tumors has not been determined. A meta-analysis was performed by combining the results of all available controlled trials. Methods PubMed, Cochrane’s Library, and the Embase databases were searched for studies which compared the recurrence data for patients with complete resection of the stage II or III thymic tumors assigned to an observing group, or a PORT group. A random effect model was applied to combine the results. Results Nineteen studies, all designed as retrospective cohort studies were included. These studies included 663 patients of PORT group and 617 patients of observing group. The recurrence rate for the patients in PORT group and observing group were 12.4% and 11.5%, respectively. Results of our study indicated that PORT has no significant influence on recurrent risk in patients with stage II or III thymic tumor after complete resection (odds ratio 1.02, 95% confidence interval 0.55–1.90, P=0.96). When stratified by stages, our meta-analyses did not indicate any significant effects of PORT on recurrent outcomes in either the stage II or the stage III patients. Moreover, subsequent analysis limited to studies only including patients with thymoma or thymic carcinoma also did not support the benefits of PORT on recurrent outcomes. Conclusion Although derived from retrospective cohort studies, current evidence did not support any benefit of PORT on recurrent risk in patients with complete resection of the stage II or III thymic tumors. PMID:27524907

  16. Advanced Stage Mucinous Adenocarcinoma of the Ovary is both Rare and Highly Lethal: A Gynecologic Oncology Group Study

    PubMed Central

    Zaino, Richard J.; Brady, Mark F.; Lele, Subodh M.; Michael, Helen; Greer, Benjamin; Bookman, Michael A.

    2010-01-01

    Background Primary mucinous adenocarcinomas of the ovary are uncommon and their biologic behavior uncertain. Retrospective studies suggest that many mucinous carcinomas diagnosed as primary to the ovary were actually metastatic from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes. Methods A phase III trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were re-classified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared with each other and with that of patients with serous carcinomas. Results Forty-four cases were classified as mucinous adenocarcinoma at review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high with unanimity of opinion in 30 of the 44 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, p<0.001). Conclusion Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary. PMID:20862744

  17. CT-Based Evaluation of Tumor Volume After Intra-Arterial Chemotherapy of Locally Advanced Carcinoma of the Oral Cavity: Comparison with Clinical Remission Rates

    SciTech Connect

    Rohde, Stefan Turowski, Bernd; Berkefeld, Joachim; Kovacs, Adorjan F.

    2007-02-15

    Purpose. To assess the volume of locally advanced tumors of the oral cavity and the oropharynx before and after intra-arterial (i.a.) chemotherapy by means of computed tomography and to compare these data with clinically determined treatment response of the same patient population. Methods. Eighty-eight patients with histologically proven, advanced carcinoma of the oral cavity and/or the oropharynx (local tumor stages T3/4) received neoadjuvant i.a. chemotherapy with cisplatin as part of a multimodal therapeutic regimen, comprising (1) local chemotherapy, (2) surgery, and (3) combined radio-chemotherapy. Three weeks after the intervention, residual disease was evaluated radiologically by measurement of the tumor volume and clinically by inspection and palpation of the primary tumor according to WHO criteria. Results. Comparison of treatment response according to radiological and clinical criteria respectively revealed complete remission in 5% vs. 8% (p < 0.05), partial remission in 30% vs. 31%, stable disease in 61% vs. 58%, and tumor progression in 5% vs. 2%. Conclusion. Radiological volumetry and clinical evaluation found comparable response rates after local chemotherapy. However, in patients with good response after local treatment, volumetric measurement with CT may help to distinguish between partial and complete remission. Thus, radiological tumor volumetry provides precise and differentiated information about tumor response and should be used as an additional tool in treatment monitoring after local chemotherapy.

  18. Thymectomy versus tumor resection for early-stage thymic malignancies: a Chinese Alliance for Research in Thymomas retrospective database analysis

    PubMed Central

    Gu, Zhitao; Fu, Jianhua; Shen, Yi; Wei, Yucheng; Tan, Lijie; Zhang, Peng; Han, Yongtao; Chen, Chun; Zhang, Renquan; Li, Yin; Chen, Keneng; Chen, Hezhong; Liu, Yongyu; Cui, Youbing; Wang, Yun; Pang, Liewen; Yu, Zhentao; Zhou, Xinming; Liu, Yangchun; Liu, Yuan

    2016-01-01

    Background To evaluate the surgical outcomes of tumor resection with or without total thymectomy for thymic epithelial tumors (TETs) using the Chinese Alliance for Research in Thymomas (ChART) retrospective database. Methods Patients without preoperative therapy, who underwent surgery for early-stage (Masaoka-Koga stage I and II) tumors, were enrolled for the study. They were divided into thymectomy and thymomectomy groups according to the resection extent of the thymus. Demographic and surgical outcomes were compared between the two patients groups. Results A total of 1,047 patients were enrolled, with 796 cases in the thymectomy group and 251 cases in the thymomectomy group. Improvement rate of myasthenia gravis (MG) was higher after thymectomy than after thymomectomy (91.6% vs. 50.0%, P<0.001). Ten-year overall survival was similar between the two groups (90.9% after thymectomy and 89.4% after thymomectomy, P=0.732). Overall, recurrence rate was 3.1% after thymectomy and 5.4% after thymomectomy, with no significant difference between the two groups (P=0.149). Stratified analysis revealed no significant difference in recurrence rates in Masaoka–Koga stage I tumors (3.2% vs. 1.4%, P=0.259). However in patients with Masaoka-Koga stage II tumors, recurrence was significantly less after thymectomy group than after thymomectomy (2.9% vs. 14.5%, P=0.001). Conclusions Thymectomy, instead of tumor resection alone, should still be recommended as the surgical standard for thymic malignancies, especially for stage II tumors and those with concomitant MG. PMID:27114835

  19. Dietary flavonoid intake, black tea consumption, and risk of overall and advanced stage prostate cancer.

    PubMed

    Geybels, Milan S; Verhage, Bas A J; Arts, Ilja C W; van Schooten, Frederik J; Goldbohm, R Alexandra; van den Brandt, Piet A

    2013-06-15

    Flavonoids are natural antioxidants found in various foods, and a major source is black tea. Some experimental evidence indicates that flavonoids could prevent prostate cancer. We investigated the associations between flavonoid intake, black tea consumption, and prostate cancer risk in the Netherlands Cohort study, which includes 58,279 men who provided detailed baseline information on several cancer risk factors. From 1986 to 2003, 3,362 prostate cancers were identified, including 1,164 advanced (stage III/IV) cancers. Cox proportional hazards regression using the case-cohort approach was used to estimate hazard ratios and 95% confidence intervals. Intake of total catechin, epicatechin, kaempferol, and myricetin and consumption of black tea were associated with a decreased risk of stage III/IV or stage IV prostate cancer. Hazard ratios of stage III/IV and stage IV prostate cancer for the highest versus the lowest category of black tea consumption (≥5 versus ≤1 cups/day) were 0.75 (95% confidence interval: 0.59, 0.97) and 0.67 (95% confidence interval: 0.50, 0.91), respectively. No associations were observed for overall and nonadvanced prostate cancer. In conclusion, dietary flavonoid intake and black tea consumption were associated with a decreased risk of advanced stage prostate cancer.

  20. 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

  1. Inhibitory effect of flavonoid derivatives on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

    PubMed

    Iwase, Y; Takemura, Y; Ju-ichi, M; Mukainaka, T; Ichiishi, E; Ito, C; Furukawa, H; Yano, M; Tokuda, H; Nishino, H

    2001-11-28

    To search for possible anti-tumor promoters, ten flavonoid derivatives (1-10) synthesized from morin and quercetin were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these compounds, pentaallyl ethers (9, 10) showed significant inhibitory effects on EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate. Further, quercetin pentaallyl ether (10) exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

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

    PubMed

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

    2013-05-01

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

  3. A transition in transcriptional activation by the glucocorticoid and retinoic acid receptors at the tumor stage of dermal fibrosarcoma development.

    PubMed Central

    Vivanco, M D; Johnson, R; Galante, P E; Hanahan, D; Yamamoto, K R

    1995-01-01

    In transgenic mice harboring the bovine papillomavirus genome, fibrosarcomas arise along an experimentally accessible pathway in which normal dermal fibroblasts progress through two pre-neoplastic stages, mild and aggressive fibromatosis, followed by a final transition to the tumor stage. We found that the glucocorticoid receptor (GR) displays only modest transcriptional regulatory activity in cells derived from the three non-tumor stages, whereas it is highly active in fibrosarcoma cells. Upon inoculation into mice, the aggressive fibromatosis cells progress to tumor cells that have high GR activity; thus, the increased transcriptional regulatory activity of GR correlates with the cellular transition to the tumor stage. The intracellular levels of GR, as well as its hormone-dependent nuclear translocation and specific DNA binding activities, are unaltered throughout the progression. Strikingly, the low GR activity observed in the pre-neoplastic stages cannot be overcome by exogenous GR introduced by co-transfection. Moreover, comparisons of primary embryo fibroblasts and their transformed derivatives revealed a similar pattern--modest GR activity, unresponsive to overexpressed GR protein, in the normal cells was strongly increased in the transformed cells. Likewise, the retinoic acid receptor (RAR) displayed similar differential activity in the fibrosarcoma pathway. Thus, the oncogenic transformation of fibroblasts, and likely other cell types, is accompanied by a striking increase in the activities of transcriptional regulators such as GR and RAR. We suggest that normal primary cells have a heretofore unrecognized capability to limit the magnitude of induction of gene expression. Images PMID:7774580

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

    PubMed

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

    2013-03-01

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

  5. Loss of heterozygosity on 10q and microsatellite instability in advanced stages of primary cutaneous T-cell lymphoma and possible association with homozygous deletion of PTEN.

    PubMed

    Scarisbrick, J J; Woolford, A J; Russell-Jones, R; Whittaker, S J

    2000-05-01

    Previous cytogenetic studies of primary cutaneous T-cell lymphoma (CTCL) were based on limited numbers of patients and seldom showed consistent nonrandom chromosomal abnormalities. In this study, 54 tumor DNA samples from patients with CTCL were analyzed for loss of heterozygosity on 10q. Allelic loss was identified in 10 samples, all of which were from the 44 patients with mycosis fungoides (10/44 patients; 23%). Of the patients with allelic loss, 3 were among the 29 patients with early-stage myosis fungoides (T(1) or T(2)) (3/29 patients; 10%), whereas the other 7 were among the 15 patients with advanced cutaneous disease (T(3) or T(4)) (7/15 patients; 47%). The overlapping region of deletion was between 10q23 and 10q24. In addition, microsatellite instability (MSI) was present in 13 of the 54 samples (24%), 12 from patients with mycosis fungoides and 1 from a patient with Sezary syndrome. There was also an association between MSI and disease progression in patients with mycosis fungoides, with 6 of 15 (40%) patients with MSI having advanced cutaneous disease and only 6 of 29 (21%) having early-stage disease. Samples with allelic loss on 10q were analyzed for abnormalities of the tumor suppressor gene PTEN (10q23.3). No tumor-specific mutations were detected, but homozygous deletion was found in 2 patients. Thus, we found loss of heterozygosity on 10q and MSI in advanced cutaneous stages of mycosis fungoides. These findings indicate that a tumor suppressor gene or genes in this region may be associated with disease progression. Furthermore, abnormalities of PTEN may be important in the pathogenesis of mycosis fungoides, but our data imply that this gene is rarely inactivated by small deletions or point mutations. (Blood. 2000;95:2937-2942)

  6. Advances in circulating tumor cells (ACTC): from basic research to clinical practice

    PubMed Central

    2013-01-01

    The first 'Advances in Circulating Tumor Cells (ACTC): from Basic Research to Clinical Practice' meeting was held in Athens, Greece, September 26–29, 2012 (abstracts, presentations and a more detailed meeting report are freely available online: http://www.actc2012.org). We summarize in this report most major findings presented and the main conclusions derived during the expert panel sessions. PMID:24314311

  7. Feasibility of sequential high-dose chemotherapy in advanced pediatric solid tumors.

    PubMed

    Kwon, Seung Yeon; Won, Sung Chul; Han, Jung Woo; Shin, Yoon Jung; Lyu, Chuhl Joo

    2010-02-01

    The purpose of this study was to evaluate the feasibility and tumor response of 3 cycles of sequential high-dose chemotherapy (HDCT) in advanced pediatric solid tumor patients. Medical records of 11 children who underwent 2 consequent courses of reduced conditioning HDCT followed by final HDCT with autologous HSC infusion were reviewed in a retrospective manner. Each median time to an absolute neutrophil count > 0.5 x 10(9)/L was 12, 13, and 12 days. Major toxic reactions were fever, infection, and vomiting. One patient experienced transplantation-related mortality. Nine patients showed complete and partial responses to the therapy at 6 months follow-up after final HDCT. Finally, 6 patients are alive without evidence of disease at median follow-up of 24 months. Even though it is a preliminary result, the authors think that this treatment could be a feasible treatment option for advanced pediatric solid tumor patients.

  8. Oligonucleotide array-CGH identifies genomic subgroups and prognostic markers for tumor stage mycosis fungoides.

    PubMed

    Salgado, Rocío; Servitje, Octavio; Gallardo, Fernando; Vermeer, Maarten H; Ortiz-Romero, Pablo L; Karpova, Maria B; Zipser, Marie C; Muniesa, Cristina; García-Muret, María P; Estrach, Teresa; Salido, Marta; Sánchez-Schmidt, Júlia; Herrera, Marta; Romagosa, Vicenç; Suela, Javier; Ferreira, Bibiana I; Cigudosa, Juan C; Barranco, Carlos; Serrano, Sergio; Dummer, Reinhard; Tensen, Cornelis P; Solé, Francesc; Pujol, Ramon M; Espinet, Blanca

    2010-04-01

    Mycosis fungoide (MF) patients who develop tumors or extracutaneous involvement usually have a poor prognosis with no curative therapy available so far. In the present European Organization for Research and Treatment of Cancer (EORTC) multicenter study, the genomic profile of 41 skin biopsies from tumor stage MF (MFt) was analyzed using a high-resolution oligo-array comparative genomic hybridization platform. Seventy-six percent of cases showed genomic aberrations. The most common imbalances were gains of 7q33.3q35 followed by 17q21.1, 8q24.21, 9q34qter, and 10p14 and losses of 9p21.3 followed by 9q31.2, 17p13.1, 13q14.11, 6q21.3, 10p11.22, 16q23.2, and 16q24.3. Three specific chromosomal regions, 9p21.3, 8q24.21, and 10q26qter, were defined as prognostic markers showing a significant correlation with overall survival (OS) (P=0.042, 0.017, and 0.022, respectively). Moreover, we have established two MFt genomic subgroups distinguishing a stable group (0-5 DNA aberrations) and an unstable group (>5 DNA aberrations), showing that the genomic unstable group had a shorter OS (P=0.05). We therefore conclude that specific chromosomal abnormalities, such as gains of 8q24.21 (MYC) and losses of 9p21.3 (CDKN2A, CDKN2B, and MTAP) and 10q26qter (MGMT and EBF3) may have an important role in prognosis. In addition, we describe the MFt genomic instability profile, which, to our knowledge, has not been reported earlier.

  9. Advanced (stage D) heart failure: a statement from the Heart Failure Society of America Guidelines Committee.

    PubMed

    Fang, James C; Ewald, Gregory A; Allen, Larry A; Butler, Javed; Westlake Canary, Cheryl A; Colvin-Adams, Monica; Dickinson, Michael G; Levy, Phillip; Stough, Wendy Gattis; Sweitzer, Nancy K; Teerlink, John R; Whellan, David J; Albert, Nancy M; Krishnamani, Rajan; Rich, Michael W; Walsh, Mary N; Bonnell, Mark R; Carson, Peter E; Chan, Michael C; Dries, Daniel L; Hernandez, Adrian F; Hershberger, Ray E; Katz, Stuart D; Moore, Stephanie; Rodgers, Jo E; Rogers, Joseph G; Vest, Amanda R; Givertz, Michael M

    2015-06-01

    We propose that stage D advanced heart failure be defined as the presence of progressive and/or persistent severe signs and symptoms of heart failure despite optimized medical, surgical, and device therapy. Importantly, the progressive decline should be primarily driven by the heart failure syndrome. Formally defining advanced heart failure and specifying when medical and device therapies have failed is challenging, but signs and symptoms, hemodynamics, exercise testing, biomarkers, and risk prediction models are useful in this process. Identification of patients in stage D is a clinically important task because treatments are inherently limited, morbidity is typically progressive, and survival is often short. Age, frailty, and psychosocial issues affect both outcomes and selection of therapy for stage D patients. Heart transplant and mechanical circulatory support devices are potential treatment options in select patients. In addition to considering indications, contraindications, clinical status, and comorbidities, treatment selection for stage D patients involves incorporating the patient's wishes for survival versus quality of life, and palliative and hospice care should be integrated into care plans. More research is needed to determine optimal strategies for patient selection and medical decision making, with the ultimate goal of improving clinical and patient centered outcomes in patients with stage D heart failure.

  10. Reusable launch vehicles, enabling technology for the development of advanced upper stages and payloads

    NASA Astrophysics Data System (ADS)

    Metzger, John D.

    1998-01-01

    In the near future there will be classes of upper stages and payloads that will require initial operation at a high-earth orbit to reduce the probability of an inadvertent reentry that could result in a detrimental impact on humans and the biosphere. A nuclear propulsion system, such as was being developed under the Space Nuclear Thermal Propulsion (SNTP) Program, is an example of such a potential payload. This paper uses the results of a reusable launch vehicle (RLV) study to demonstrate the potential importance of a Reusable Launch Vehicle (RLV) to test and implement an advanced upper stage (AUS) or payload in a safe orbit and in a cost effective and reliable manner. The RLV is a horizontal takeoff and horizontal landing (HTHL), two-stage-to-orbit (TSTO) vehicle. The results of the study shows that an HTHL is cost effective because it implements airplane-like operation, infrastructure, and flight operations. The first stage of the TSTO is powered by Rocket-Based-Combined-Cycle (RBCC) engines, the second stage is powered by a LOX/LH rocket engine. The TSTO is used since it most effectively utilizes the capability of the RBCC engine. The analysis uses the NASA code POST (Program to Optimize Simulated Trajectories) to determine trajectories and weight in high-earth orbit for AUS/advanced payloads. Cost and reliability of an RLV versus current generation expandable launch vehicles are presented.

  11. Reusable launch vehicles, enabling technology for the development of advanced upper stages and payloads

    SciTech Connect

    Metzger, John D.

    1998-01-15

    In the near future there will be classes of upper stages and payloads that will require initial operation at a high-earth orbit to reduce the probability of an inadvertent reentry that could result in a detrimental impact on humans and the biosphere. A nuclear propulsion system, such as was being developed under the Space Nuclear Thermal Propulsion (SNTP) Program, is an example of such a potential payload. This paper uses the results of a reusable launch vehicle (RLV) study to demonstrate the potential importance of a Reusable Launch Vehicle (RLV) to test and implement an advanced upper stage (AUS) or payload in a safe orbit and in a cost effective and reliable manner. The RLV is a horizontal takeoff and horizontal landing (HTHL), two-stage-to-orbit (TSTO) vehicle. The results of the study shows that an HTHL is cost effective because it implements airplane-like operation, infrastructure, and flight operations. The first stage of the TSTO is powered by Rocket-Based-Combined-Cycle (RBCC) engines, the second stage is powered by a LOX/LH rocket engine. The TSTO is used since it most effectively utilizes the capability of the RBCC engine. The analysis uses the NASA code POST (Program to Optimize Simulated Trajectories) to determine trajectories and weight in high-earth orbit for AUS/advanced payloads. Cost and reliability of an RLV versus current generation expandable launch vehicles are presented.

  12. Advances of wogonin, an extract from Scutellaria baicalensis, for the treatment of multiple tumors.

    PubMed

    Wu, Xue; Zhang, Haijun; Salmani, Jumah Masoud Mohammad; Fu, Rong; Chen, Baoan

    2016-01-01

    As the major bioactive compound of Scutellaria baicalensis that has been approved to be effective as an anti-inflammatory and antiviral inhibitor in cardiovascular diseases, wogonin (WG) showed potent and promising antitumor effects both in vitro and in vivo. It has been proved that WG has the ability to inhibit the growth of tumor cells, induce apoptosis, and suppress angiogenesis. The molecular mechanisms involve reactive oxygen species, Ca(2+), NF-κB, tumor necrosis factor-related apoptosis-inducing ligand, and tumor necrosis factor-alpha. Furthermore, the synergistic effect of WG with 5-fluorouracil, etoposide, and adriamycin to enhance chemotherapy and reverse drug resistance has also been confirmed. In this review, we summarize the advances in recent years on the antitumor effect of WG on multiple tumors; in addition, we also present information regarding the synergistic and chemosensitizing effects of WG with other drugs to illustrate its potential use in the clinic. PMID:27274287

  13. The Influence of Frontal Lobe Tumors and Surgical Treatment on Advanced Cognitive Functions.

    PubMed

    Fang, Shengyu; Wang, Yinyan; Jiang, Tao

    2016-07-01

    Brain cognitive functions affect patient quality of life. The frontal lobe plays a crucial role in advanced cognitive functions, including executive function, meta-cognition, decision-making, memory, emotion, and language. Therefore, frontal tumors can lead to serious cognitive impairments. Currently, neurosurgical treatment is the primary method to treat brain tumors; however, the effects of the surgical treatments are difficult to predict or control. The treatment may both resolve the effects of the tumor to improve cognitive function or cause permanent disabilities resulting from damage to healthy functional brain tissue. Previous studies have focused on the influence of frontal lesions and surgical treatments on patient cognitive function. Here, we review cognitive impairment caused by frontal lobe brain tumors. PMID:27072331

  14. Advances of wogonin, an extract from Scutellaria baicalensis, for the treatment of multiple tumors

    PubMed Central

    Wu, Xue; Zhang, Haijun; Salmani, Jumah Masoud Mohammad; Fu, Rong; Chen, Baoan

    2016-01-01

    As the major bioactive compound of Scutellaria baicalensis that has been approved to be effective as an anti-inflammatory and antiviral inhibitor in cardiovascular diseases, wogonin (WG) showed potent and promising antitumor effects both in vitro and in vivo. It has been proved that WG has the ability to inhibit the growth of tumor cells, induce apoptosis, and suppress angiogenesis. The molecular mechanisms involve reactive oxygen species, Ca2+, NF-κB, tumor necrosis factor-related apoptosis-inducing ligand, and tumor necrosis factor-alpha. Furthermore, the synergistic effect of WG with 5-fluorouracil, etoposide, and adriamycin to enhance chemotherapy and reverse drug resistance has also been confirmed. In this review, we summarize the advances in recent years on the antitumor effect of WG on multiple tumors; in addition, we also present information regarding the synergistic and chemosensitizing effects of WG with other drugs to illustrate its potential use in the clinic. PMID:27274287

  15. Detection and characterization of chemical-induced abnormal tissue and rat tumors at different stages using fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Jassemnejad, Baha; Crull, Jason; Knobbe, Edward T.; Nordquist, Robert E.

    1996-04-01

    Fluorescence spectroscopy of diseased tissues, including chemical-induced rat liver, kidney and testis lesions, as well as murine mammary tumor, was studied. The rat liver, kidney and testis tissues were excited by radiation of 350 and 366 nm, which appeared to provide the optimal differentiation between normal and lesion tissues; the tumor tissues were excited by both 350 nm and 775 nm wavelengths. In comparison with normal liver tissue, at (lambda) ex equals 366 nm, the fluorescent spectrum of liver lesion showed a clear red shift around the emission peak of 470 nm, the major native fluorescent peak of organized tissue. When excited by 350 nm wavelength, all the chemically induced lesion tissues (liver, kidney and testis) appeared to cause a significant reduction of emission intensity at the 470 nm peak. While the 775 nm excitation did not reveal any significant difference among tumor, muscle and skin tissues, the 350 nm excitation did provide some interesting features among the tumor tissues at different stages. Compared with muscle tissue, the viable tumor showed an overall reduction of emission intensity around 470 nm. In addition, the viable tumor tissue showed a secondary emission peak at 390 nm with necrotic tumor tissue having a reduced intensity. The histology of both viable and necrotic tumor tissue was examined and appeared to correlate with the results of the fluorescent spectroscopy observation.

  16. The Influence of Social Norms on Advancement Through Bystander Stages for Preventing Interpersonal Violence.

    PubMed

    Deitch-Stackhouse, Jacqueline; Kenneavy, Kristin; Thayer, Richard; Berkowitz, Alan; Mascari, Janine

    2015-10-01

    This research evaluates the impact of social norms on the advancement through the bystander stages toward prosocial (active) intervention in interpersonal violence (IPV): emotional abuse, physical violence, controlling behavior, sexual violence, and stalking. The influence of social norms on bystander behavior across stages and types of violence varies. Accurate social norms perceptions are associated with routine intervention, although social norms misperceptions are not always a strong deterrent to intervention. Interpretation of a violent situation as problematic predicts increased willingness to intervene. Implications for the development of social norms antiviolence campaigns and strategies for reducing barriers to prosocial intervention are discussed. PMID:26175519

  17. Therapy of metastatic pancreatic neuroendocrine tumors (pNETs): recent insights and advances

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato

    2013-01-01

    Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years. PMID:22886480

  18. Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

    SciTech Connect

    Yeo, Seung-Gu; Kim, Dae Yong; Park, Ji Won; Oh, Jae Hwan; Kim, Sun Young; Chang, Hee Jin; Kim, Tae Hyun; Kim, Byung Chang; Sohn, Dae Kyung; Kim, Min Ju

    2012-02-01

    Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and Materials: In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume - post-CRT tumor volume) Multiplication-Sign 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS). Results: The median TVRR was 70.2% (mean, 64.7% {+-} 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.

  19. Treatment of locally advanced, high-grade, malignant tumors of major salivary glands

    SciTech Connect

    Reddy, S.P.; Marks, J.E.

    1988-04-01

    A retrospective review of 45 patients with Stage III and IV malignant tumors of the major salivary glands was undertaken to determine tumor control and patient survival after treatment with surgery and conventional ionizing-radiation therapy. Eight of the 23 patients received early postoperative radiotherapy after initial surgical resection, with a local control rate of 75%. Twelve of 23 patients had surgery as definitive treatment and the tumor recurred locally in all; seven of these 12 patients were subsequently salvaged by further surgery plus postoperative radiotherapy or by radiotherapy alone, with 58% ultimate local control. The remaining three patients had unresectable tumors at diagnosis and received radiation alone, with a local tumor control rate of 33%. Patients were also analyzed according to the extent of surgical resection prior to radiation therapy and according to radiation dose. Eighty-eight percent of completely resected, 50% of partially resected, and 44% of unresected tumors were locally controlled for an overall local control rate of 61%. The 5-year survival rate was significantly higher for patients with local tumor control than for patients who failed locally (31% vs. 0%).

  20. Outcome of Primary Tumor in Patients With Synchronous Stage IV Colorectal Cancer Receiving Combination Chemotherapy Without Surgery As Initial Treatment

    PubMed Central

    Poultsides, George A.; Servais, Elliot L.; Saltz, Leonard B.; Patil, Sujata; Kemeny, Nancy E.; Guillem, Jose G.; Weiser, Martin; Temple, Larissa K.F.; Wong, W. Douglas; Paty, Phillip B.

    2009-01-01

    Purpose The purpose of this study was to describe the frequency of interventions necessary to palliate the intact primary tumor in patients who present with synchronous, stage IV colorectal cancer (CRC) and who receive up-front modern combination chemotherapy without prophylactic surgery. Patients and Methods By using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin; bolus fluorouracil, leucovorin, and irinotecan; or fluorouracil, leucovorin, and irinotecan) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded. Results Of 233 patients, 217 (93%) never required surgical palliation of their primary tumor. Sixteen patients (7%) required emergent surgery for primary tumor obstruction or perforation, 10 patients (4%) required nonoperative intervention (ie, stent or radiotherapy), and 213 (89%) never required any direct symptomatic management for their intact primary tumor. Of those 213 patients, 47 patients (20%) ultimately underwent elective colon resection at the time of metastasectomy, and eight patients (3%) underwent this resection during laparotomy for hepatic artery infusion pump placement. Use of bevacizumab, location of the primary tumor in the rectum, and metastatic disease burden were not associated with increased intervention rate. Conclusion Most patients with synchronous, stage IV CRC who receive up-front modern combination chemotherapy never require palliative surgery for their intact primary tumor. These data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary

  1. The Tumor-Log Odds of Positive Lymph Nodes-Metastasis Staging System, a Promising New Staging System for Gastric Cancer after D2 Resection in China

    PubMed Central

    Wang, Zhi-qiang; Ren, Chao; Wang, De-shen; Zhang, Dong-sheng; Luo, Hui-yan; Li, Yu-hong; Xu, Rui-hua

    2012-01-01

    Background In this study, we established a hypothetical tumor-lodds-metastasis (TLM) and tumor-ratio-metastasis (TRM) staging system. Moreover, we compared them with the 7th edition of American Joint Committee on Cancer tumor-nodes-metastasis (AJCC TNM) staging system in gastric cancer patients after D2 resection. Methods A total of 1000 gastric carcinoma patients receiving treatment in our center were selected for the analysis. Finally, 730 patients who received D2 resection were retrospectively studied. Patients were staged using the TLM, TRM and the 7th edition AJCC TNM system. Survival analysis was performed with a Cox regression model. We used two parameters to compare the TNM, TRM and TLM staging system, the −2log likelihood and the hazard ratio. Results The cut points of lymph node ratio (LNR) were set as 0, 0–0.3, 0.3–0.6, 0.6–1.0. And for the log odds of positive lymph nodes (LODDS), the cut points were established as≤−0.5, −0.5-0, 0-0.5, >0.5. There were significant differences in survival among patients in different LODDS classifications for each pN or LNR groups. When stratified by the LODDS classifications, the prognosis was highly homologous between those in the according pN or LNR classifications. Multivariate analysis showed that TLM staging system was better than the TRM or TNM system for the prognostic evaluation. Conclusions The TLM system was superior to the TRM or TNM system for prognostic assessment of gastric adenocarcinoma patients after D2 resection. PMID:22348125

  2. Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Osti, Mattia Falchetto; Agolli, Linda; Valeriani, Maurizio; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Enrici, Riccardo Maurizi

    2013-03-01

    Purpose: Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Methods and Materials: Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. Results: The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Conclusions: Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized

  3. Romidepsin in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2013-06-03

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Regional Gastrointestinal Carcinoid Tumor; Somatostatinoma

  4. The added value of circulating tumor cells examination in ovarian cancer staging.

    PubMed

    Kolostova, Katarina; Matkowski, Rafał; Jędryka, Marcin; Soter, Katarzyna; Cegan, Martin; Pinkas, Michael; Jakabova, Anna; Pavlasek, Jiri; Spicka, Jan; Bobek, Vladimir

    2015-01-01

    Delayed diagnosis of ovarian cancer (OC) is usually a cause of its high mortality. OC counts for one of the most aggressive gynecological malignancies. Noninvasive biomarkers may be used to help with diagnostic and treatment decisions in OC management. The incidence and clinical significance of occult OC cells (circulating tumor cells-CTCs) in the peripheral blood of patients with newly diagnosed or nondiagnosed OC at the time of surgical intervention were examined in our study. The objective of the study was to isolate and cultivate CTCs in OC patients (mainly stage IIIB-C) by a recently introduced size-based separation method (MetaCell(®)). CTCs were successfully isolated in patients with OC capturing cells with proliferation potential. The cells were enriched in good fitness, which enabled the short term in vitro culture of the CTCs. The CTCs may be used for further downstream applications (e.g. gene expression analysis) even if in the majority of the in vitro CTC cultures no confluence was reached. The CTCs were detected in 77 out of 118 patients (65.2%). CTC positivity was given to the relationship with different disease stage parameters with special focus on CA125 marker levels. The results show that the information on CTC presence may provide new and independent prognosis staging information to the patient description. Several interesting relationships of CA125, age and ascites presence are reported. As shown in our patient sample, patients with ascites tend to have higher CA125 levels, even if the CTCs were not found in the peripheral blood. It suggests that hematogenous dissemination is fully represented by the CTCs while lymphogenic dissemination is represented by elevated CA125. In this context, easy access to CTCs provided by the method applied in our study, both at the time of diagnosis and relapse, may become an increasingly valuable tool in future. This methodology may provide an opportunity for more personalized medicine where treatment for OC may

  5. The experience of living with advanced-stage cancer: a thematic synthesis of the literature.

    PubMed

    García-Rueda, N; Carvajal Valcárcel, A; Saracíbar-Razquin, M; Arantzamendi Solabarrieta, M

    2016-07-01

    The aim of the study was to understand the experience of people living with advanced-stage cancer through literature. The search included The Cochrane Library, PubMed, PsycInfo, CINAHL and Cuiden. Thirteen studies were included. A qualitative meta-synthesis was conducted. One thread emerged from the thematic synthesis: the desire to live as normally as possible, despite being aware of the proximity of death. Three themes also emerged: "a process that is unique" with its four sub-themes; "support network" and "health context," each of them having two sub-themes. This study concludes that living with advanced-stage cancer is a unique and complex process which has both positive and negative aspects. The review provides a comprehensive view of the experience, which considers the importance of the support network and the health context in which the person lives. In this study, "normalcy" is the adjustment to the new reality and living as closely as possible to the way one lived before the disease, while developing a new relationship with being finite and death. A better understanding of the experience of living with advanced-stage cancer will help health professionals to identify the needs of the patients in order to plan individual, high-quality care. PMID:27297131

  6. Physical activity in patients with advanced-stage cancer: a systematic review of the literature.

    PubMed

    Albrecht, Tara A; Taylor, Ann Gill

    2012-06-01

    The importance of physical activity for chronic disease prevention and management has become generally well accepted. The number of research interventions and publications examining the benefits of physical activity for patients with cancer has been rising steadily. However, much of that research has focused on the impact of physical activity either prior to or early in the cancer diagnosis, treatment, and survivorship process. Research focusing on the effects of physical activity, specifically for patients with advanced-stage cancer and poorer prognostic outcomes, has been addressed only recently. The purpose of this article is to examine the state of the science for physical activity in the advanced-stage disease subset of the cancer population. Exercise in a variety of intensities and forms, including yoga, walking, biking, and swimming, has many health benefits for people, including those diagnosed with cancer. Research has shown that, for people with cancer (including advanced-stage cancer), exercise can decrease anxiety, stress, and depression while improving levels of pain, fatigue, shortness of breath, constipation, and insomnia. People diagnosed with cancer should discuss with their oncologist safe, easy ways they can incorporate exercise into their daily lives. PMID:22641322

  7. Preoperative Kidney Tumor Embolization as Procedure for Therapy of Advanced Kidney Cancer

    PubMed Central

    Jaganjac, Suad; Schefe, L.; Avdagić, Edin; Spahović, Hajrudin; Hiros, Mustafa

    2014-01-01

    ABSTRACT Introduction: Preoperative kidney tumor embolization is standard procedure for therapy in advanced kidney cancer. Preoperative embolization has a goal to reduce intraoperative bleeding and also to shorten the time of surgery. Materials and methods: We retrospectively observed 50 patients between 2000-2011, in which the preoperative embolization was performed. Mean age of patients was 64 years. All patients with preoperative embolization were compared with the group of 51 patients from Urology Sarajevo, who underwent nephrectomy without preoperative embolization. Results: Symptoms that are dominating among patients were haematuria and pain. Analysis of mean size of tumors based on CT evaluation showed statistically significance in between the biggest size of tumors in group from Hamburg (9.11±3cm) and the smallest size of tumors in Sarajevo group (4.94±1.6cm) p=0.0001. Reason for this is difference in selection of patients for treatment in Hamburg from Sarajevo. Conclusion Kidney as functional finishing organ is extremely suitable for transcatheter therapeutic procedures. The gold standard in the treatment of advanced and metastatic tumor is the nephrectomy. As preparation for nephrectomy in metastatic cancer total capillary embolization is performed. After embolization, surgery is shorter, procedure can be done 24-48 hours after embolization or delayed nephrectomy done 2-3 weeks after the intervention. PMID:25568577

  8. Early identification of non-responding locally advanced breast tumors receiving neoadjuvant chemotherapy

    NASA Astrophysics Data System (ADS)

    Van de Giessen, Martijn; Schaafsma, Boudewijn E.; Charehbili, Ayoub; Smit, Vincent T. H. B. M.; Kroep, Judith R.; Lelieveldt, Boudewijn P. F.; Liefers, Gerrit-Jan; Chan, Alan; Löwik, Clemens W. G. M.; Dijkstra, Jouke; van de Velde, Cornelis J. H.; Wasser, Martin N. J. M.; Vahrmeijer, Alexander L.

    2015-02-01

    Diffuse optical spectroscopy (DOS) may be advantageous for monitoring tumor response during chemotherapy treatment, particularly in the early treatment stages. In this paper we perform a second analysis on the data of a clinical trial with 25 breast cancer patients that received neoadjuvant chemotherapy. Patients were monitored using delayed contrast enhanced MRI and additionally with diffuse optical spectroscopy at baseline, after 1 cycle of chemotherapy, halfway therapy and before surgery. In this analysis hemoglobin content between tumor tissue and healthy tissue of the same breast is compared on all four monitoring time points. Furthermore, the predictive power of the tumor-healthy tissue difference of HbO2 for non-responder prediction is assessed. The difference in HbO2 content between tumor and healthy tissue was statistically significantly higher in responding tumors than in non-responding tumors at baseline (10.88 vs -0.57 μM, P=0.014) and after one cycle of chemotherapy (6.45 vs -1.31 μM, P=0.048). Before surgery this difference had diminished. In the data of this study, classification on the HbO2 difference between tumor and healthy tissue was able to predict tumor (non-)response at baseline and after 1 cycle with an area-under-curve of 0.95 and 0.88, respectively. While this result suggests that tumor response can be predicted before chemotherapy onset, one should be very careful with interpreting these results. A larger patient population is needed to confirm this finding.

  9. Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients

    PubMed Central

    Boudewijns, Steve; Bol, Kalijn F.; Schreibelt, Gerty; Westdorp, Harm; Textor, Johannes C.; van Rossum, Michelle M.; Scharenborg, Nicole M.; de Boer, Annemiek J.; van de Rakt, Mandy W. M. M.; Pots, Jeanne M.; van Oorschot, Tom G. M.; Duiveman-de Boer, Tjitske; Olde Nordkamp, Michel A.; van Meeteren, Wilmy S. E. C.; van der Graaf, Winette T. A.; Bonenkamp, Johannes J.; de Wilt, Johannes H. W.; Aarntzen, Erik H. J. G.; Punt, Cornelis J. A.; Gerritsen, Winald R.; Figdor, Carl G.; de Vries, I. Jolanda M.

    2016-01-01

    ABSTRACT Purpose: To determine the effectiveness of adjuvant dendritic cell (DC) vaccination to induce tumor-specific immunological responses in stage III melanoma patients. Experimental design: Retrospective analysis of stage III melanoma patients, vaccinated with autologous monocyte-derived DC loaded with tumor-associated antigens (TAA) gp100 and tyrosinase after radical lymph node dissection. Skin-test infiltrating lymphocytes (SKILs) obtained from delayed-type hypersensitivity skin-test biopsies were analyzed for the presence of TAA-specific CD8+ T cells by tetrameric MHC-peptide complexes and by functional TAA-specific T cell assays, defined by peptide-recognition (T2 cells) and/or tumor-recognition (BLM and/or MEL624) with specific production of Th1 cytokines and no Th2 cytokines. Results: Ninety-seven patients were analyzed: 21 with stage IIIA, 34 with stage IIIB, and 42 had stage IIIC disease. Tetramer-positive CD8+ T cells were present in 68 patients (70%), and 24 of them showed a response against all 3 epitopes tested (gp100:154–162, gp100:280–288, and tyrosinase:369–377) at any point during vaccinations. A functional T cell response was found in 62 patients (64%). Rates of peptide-recognition of gp100:154–162, gp100:280–288, and tyrosinase:369–377 were 40%, 29%, and 45%, respectively. Median recurrence-free survival and distant metastasis-free survival of the whole study population were 23.0 mo and 36.8 mo, respectively. Conclusions: DC vaccination induces a functional TAA-specific T cell response in the majority of stage III melanoma patients, indicating it is more effective in stage III than in stage IV melanoma patients. Furthermore, performing multiple cycles of vaccinations enhances the chance of a broader immune response. PMID:27622047

  10. Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients

    PubMed Central

    Boudewijns, Steve; Bol, Kalijn F.; Schreibelt, Gerty; Westdorp, Harm; Textor, Johannes C.; van Rossum, Michelle M.; Scharenborg, Nicole M.; de Boer, Annemiek J.; van de Rakt, Mandy W. M. M.; Pots, Jeanne M.; van Oorschot, Tom G. M.; Duiveman-de Boer, Tjitske; Olde Nordkamp, Michel A.; van Meeteren, Wilmy S. E. C.; van der Graaf, Winette T. A.; Bonenkamp, Johannes J.; de Wilt, Johannes H. W.; Aarntzen, Erik H. J. G.; Punt, Cornelis J. A.; Gerritsen, Winald R.; Figdor, Carl G.; de Vries, I. Jolanda M.

    2016-01-01

    ABSTRACT Purpose: To determine the effectiveness of adjuvant dendritic cell (DC) vaccination to induce tumor-specific immunological responses in stage III melanoma patients. Experimental design: Retrospective analysis of stage III melanoma patients, vaccinated with autologous monocyte-derived DC loaded with tumor-associated antigens (TAA) gp100 and tyrosinase after radical lymph node dissection. Skin-test infiltrating lymphocytes (SKILs) obtained from delayed-type hypersensitivity skin-test biopsies were analyzed for the presence of TAA-specific CD8+ T cells by tetrameric MHC-peptide complexes and by functional TAA-specific T cell assays, defined by peptide-recognition (T2 cells) and/or tumor-recognition (BLM and/or MEL624) with specific production of Th1 cytokines and no Th2 cytokines. Results: Ninety-seven patients were analyzed: 21 with stage IIIA, 34 with stage IIIB, and 42 had stage IIIC disease. Tetramer-positive CD8+ T cells were present in 68 patients (70%), and 24 of them showed a response against all 3 epitopes tested (gp100:154–162, gp100:280–288, and tyrosinase:369–377) at any point during vaccinations. A functional T cell response was found in 62 patients (64%). Rates of peptide-recognition of gp100:154–162, gp100:280–288, and tyrosinase:369–377 were 40%, 29%, and 45%, respectively. Median recurrence-free survival and distant metastasis-free survival of the whole study population were 23.0 mo and 36.8 mo, respectively. Conclusions: DC vaccination induces a functional TAA-specific T cell response in the majority of stage III melanoma patients, indicating it is more effective in stage III than in stage IV melanoma patients. Furthermore, performing multiple cycles of vaccinations enhances the chance of a broader immune response.

  11. Treatment of Children with Advanced-Stage Lymphoblastic Lymphoma with Pegaspargase

    PubMed Central

    Yu-tong, Zhang; Li-hua, FENG; Xiao-dan, Zhong; Li-zhe, Wang; Jian, Chang

    2014-01-01

    Objective: To evaluate the feasibility of Pegaspargase instead of L-asparaginase to treat children with advanced-stage lymphoblastic lymphoma (LBL) on the Berlin-Frankfurt-Munster (BFM)-95 protocol. Methods: Fifty-four newly diagnosed patients with stage III or IV LBL and without any treatment were enrolled in this study. Pegaspargase took place of L-asparaginase in BFM-95. The complications and treatment responses of patients treated on the BFM-95 protocol and modified BFM-95 protocol were then evaluated respectively. Findings : For LBL patients treated with BFM-95 protocol or modified BFM-95 protocol, the complete response, event-free survival, overall survival were similar. Stage 4 myelosuppression was the most common complication in both groups. Besides that, among 31 patients receiving modified BFM-95 protocol, coagulation defects were the most common complication. In contrast, anaphylactic reaction was the most common complication in the other 23 patients receiving BFM-95 protocol. Conclusion: Modified BFM-95 protocol is available to children with advanced-stage LBL with an equal outcome and enhances its compliance and decreases the incidence of anaphylactic reaction, compared to BFM-95 protocol. Coagulation defects are the major complication and tolerable in modified one. PMID:25793049

  12. Significantly greater expression of ER, PR, and ECAD in advanced-stage low-grade ovarian serous carcinoma as revealed by immunohistochemical analysis.

    PubMed

    Wong, Kwong-Kwok; Lu, Karen H; Malpica, Anais; Bodurka, Diane C; Shvartsman, Hyun S; Schmandt, Rosemarie E; Thornton, Angela D; Deavers, Michael T; Silva, Elvio G; Gershenson, David M

    2007-10-01

    A 2-tier system that classifies ovarian serous carcinoma (OSC) as low grade or high grade is gaining acceptance. Women with low-grade OSC generally have higher 5-year survival rates than do women with high-grade OSC. We examined the expression of various markers to further understand the molecular differences between low-grade and high-grade OSCs: the potential therapeutic targets or prognostic markers Her-2/neu, estrogen receptor, and progesterone receptor (PR); the metastasis-associated markers cyclin D1 (BCL1), E-cadherin, matrix metalloproteinase (MMP) 2, and MMP-9; and the cell proliferation-associated markers BCL1, Ki-67 antigen (Ki-67), and p53. For this immunohistochemical analysis, we used paraffin-embedded specimens from 47 patients with advanced-stage low-grade OSC and from 49 patients with advanced-stage high-grade OSC. Our results showed that low-grade tumors expressed significantly higher levels of estrogen receptor, PR, and E-cadherin than did high-grade tumors, suggesting the involvement of gonadal steroid hormones, especially in the pathogenesis of low-grade OSC; the PR positivity was also observed in the stromal component of these low-grade tumors. On the other hand, high-grade tumors trended toward increased expression of MMP-9, BCL1, p53, and Ki-67, and robust MMP-9 positivity was observed in the stromal component of these high-grade tumors. These differences may lead to the development of different therapeutic strategies for women with either the low-grade or the high-grade form of OSC.

  13. SU-E-QI-20: A Review of Advanced PET and CT Image Features for the Evaluation of Tumor Response

    SciTech Connect

    Lu, W

    2014-06-15

    Purpose: To review the literature in using quantitative PET and CT image features for the evaluation of tumor response. Methods: We reviewed and summarized more than fifty papers that use advanced, quantitative PET/CT image features for the evaluation of tumor response. We also discussed future works on extracting disease-specific features, combining multiple and complementary features in response modeling, delineating tumor in multimodality images, and exploring biological explanations of these advanced features. Results: Advanced PET image features considering spatial information, such as tumor volume, tumor shape, total glycolytic volume, histogram distance, and texture features (characterizing spatial distribution of FDG uptake) have been found more informative than the traditional SUVmax for the prediction of tumor response. Advanced CT features, including volumetric, attenuation, morphologic, structure, and texture descriptors, have also been found advantage over the traditional RECIST and WHO criteria in certain tumor types. Conclusions: Advanced, quantitative FDG PET/CT image features have been shown promising for the evaluation of tumor response. With the emerging multi-modality imaging performed at multiple time points for each patient, it becomes more important to analyze the serial images quantitatively, select and combine both complementary and contradictory information from various sources, for accurate and personalized evaluation of tumor response to therapy.

  14. Ares First Stage "Systemology" - Combining Advanced Systems Engineering and Planning Tools to Assure Mission Success

    NASA Technical Reports Server (NTRS)

    Seiler, James; Brasfield, Fred; Cannon, Scott

    2008-01-01

    Ares is an integral part of NASA s Constellation architecture that will provide crew and cargo access to the International Space Station as well as low earth orbit support for lunar missions. Ares replaces the Space Shuttle in the post 2010 time frame. Ares I is an in-line, two-stage rocket topped by the Orion Crew Exploration Vehicle, its service module, and a launch abort system. The Ares I first stage is a single, five-segment reusable solid rocket booster derived from the Space Shuttle Program's reusable solid rocket motor. The Ares second or upper stage is propelled by a J-2X main engine fueled with liquid oxygen and liquid hydrogen. This paper describes the advanced systems engineering and planning tools being utilized for the design, test, and qualification of the Ares I first stage element. Included are descriptions of the current first stage design, the milestone schedule requirements, and the marriage of systems engineering, detailed planning efforts, and roadmapping employed to achieve these goals.

  15. The Significance of Tumoral ERCC1 Status in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiation Therapy: A Multicenter Clinicopathologic Analysis

    SciTech Connect

    Doll, Corinne M.; Aquino-Parsons, Christina; Pintilie, Melania; Petrillo, Stephanie K.; Milosevic, Michael; Craighead, Peter S.; Clarke, Blaise; Lees-Miller, Susan P.; Fyles, Anthony W.; Magliocco, Anthony M.

    2013-03-01

    Purpose: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. Methods and Materials: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. Results: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). Conclusions: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on

  16. Immunohistochemical analyses at the late stage of tumor promotion by oxfendazole in a rat hepatocarcinogenesis model.

    PubMed

    Dewa, Yasuaki; Nishimura, Jihei; Jin, Meilan; Kawai, Masaomi; Saegusa, Yukie; Kenmochi, Sayaka; Shimamoto, Keisuke; Harada, Tomoaki; Shibutani, Makoto; Mitsumori, Kunitoshi

    2011-02-01

    The present study was performed to characterize immunohistochemically the expression levels of molecules related to not only xenobiotic and antioxidant functions but also cell proliferation and apoptosis in neoplastic lesions induced by the benzimidazole anthelmintic, oxfendazole (OX), at the late stage of its tumor promotion in a rat hepatocarcinogenesis model. Male F344 rats were initiated with an intraperitoneal injection of 200 mg/kg N-diethylnitrosamine, and 2 weeks later they were fed a diet containing 0% (basal diet) or 0.05% OX for 26 weeks. All animals were subjected to a two-thirds partial hepatectomy at week 3 and killed at week 28. Histopathologically, OX increased the incidence and multiplicity of altered foci (4.0- and 3.6-fold, respectively) and hepatocellular adenomas (HCAs) (3.0- and 5.5-fold, respectively). OX treatment induced 5.2- and 5.6-fold increases in the number of proliferating cell nuclear antigen (PCNA)-positive cells and single-stranded DNA (ssDNA)-positive cells in HCAs compared with the surrounding tissue, respectively. Staining for the cell cycle regulators P21 and C/EBPα and the AhR-regulated CYP1A1 molecules decreased but increased reactivity of the Nrf2-regulated, detoxifing/antioxidant molecules aldo-keto reductase 7 (AKR7) and glutathione peroxidase 2 (GPX2) were also seen in HCAs compared with the surrounding hepatocytes. These results suggest that dysregulation of cell proliferation and apoptosis and escape from oxidative stress elicited by OX treatment play an important role in OX-induced hepatocarcinogenesis in rats.

  17. Recent advances in surgical planning & navigation for tumor biopsy and resection.

    PubMed

    Wang, Defeng; Ma, Diya; Wong, Matthew Lun; Wáng, Yì Xiáng J

    2015-10-01

    This paper highlights recent advancements in imaging technologies for surgical planning and navigation in tumor biopsy and resection which need high-precision in detection and characterization of lesion margin in preoperative planning and intraoperative navigation. Multimodality image-guided surgery platforms brought great benefits in surgical planning and operation accuracy via registration of various data sets with information on morphology [X-ray, magnetic resonance (MR), computed tomography (CT)], function connectivity [functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), rest-status fMRI], or molecular activity [positron emission tomography (PET)]. These image-guided platforms provide a correspondence between the pre-operative surgical planning and intra-operative procedure. We envisage that the combination of advanced multimodal imaging, three-dimensional (3D) printing, and cloud computing will play increasingly important roles in planning and navigation of surgery for tumor biopsy and resection in the coming years. PMID:26682133

  18. Fiber-optic technologies for advanced thermo-therapy applied ex vivo to liver tumors

    NASA Astrophysics Data System (ADS)

    Tosi, D.; Perrone, G.; Vallan, A.; Braglia, A.; Liu, Y.; Macchi, E. G.; Braschi, G.; Gallati, M.; Cigada, A.; Poeggel, S.; Duraibabu, D. B.; Leen, G.; Lewis, E.

    2015-07-01

    Thermal ablation, using radiofrequency, microwave, and laser sources, is a common treatment for hepatic tumors. Sensors allow monitoring, at the point of treatment, the evolution of thermal ablation procedures. We present optical fiber sensors that allow advanced capabilities for recording the biophysical phenomena occurring in the tissue in real time. Distributed or quasi-distributed thermal sensors allow recording temperature with spatial resolution ranging from 0.1 mm to 5 mm. In addition, a thermally insensitive pressure sensor allows recording pressure rise, supporting advanced treatment of encapsulated tumors. Our investigation is focused on two case studies: (1) radiofrequency ablation of hepatic tissue, performed on a phantom with a stem-shaped applicator; (2) laser ablation of a liver phantom, performed with a fiber laser. The main measurement results are discussed, comparing the technologies used for the investigation, and drawing the potential for using optical fiber sensors for "smart"-ablation.

  19. Results of fast neutron teletherapy for locally advanced head and neck tumors

    SciTech Connect

    Battermann, J.J.; Breur, K.

    1981-08-01

    An analysis is given of the results of fast neutron therapy for locally advanced tumors of the head and neck region. All patients were treated five times per week with a 14 MeV d + T neutron beam and received dosages of about 19 Gy/sub nadvanced tumors were treated in this pilot study, the survival time is rather short for most patients. Only 8 patients are alive at the time of writing. The results of treatment for inoperable malignancies of the major salivary glands are very promising, as initial complete regression was achieved in over 90% (12/13).

  20. Recent advances in surgical planning & navigation for tumor biopsy and resection

    PubMed Central

    Ma, Diya; Wong, Matthew Lun; Wáng, Yì Xiáng J.

    2015-01-01

    This paper highlights recent advancements in imaging technologies for surgical planning and navigation in tumor biopsy and resection which need high-precision in detection and characterization of lesion margin in preoperative planning and intraoperative navigation. Multimodality image-guided surgery platforms brought great benefits in surgical planning and operation accuracy via registration of various data sets with information on morphology [X-ray, magnetic resonance (MR), computed tomography (CT)], function connectivity [functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), rest-status fMRI], or molecular activity [positron emission tomography (PET)]. These image-guided platforms provide a correspondence between the pre-operative surgical planning and intra-operative procedure. We envisage that the combination of advanced multimodal imaging, three-dimensional (3D) printing, and cloud computing will play increasingly important roles in planning and navigation of surgery for tumor biopsy and resection in the coming years. PMID:26682133

  1. Evaluation of overall tumor cellularity after neoadjuvant chemotherapy in patient with locally advanced hypopharyngeal cancer.

    PubMed

    Chitose, Shun-ichi; Chijiwa, Hideki; Maeda, Akiteru; Umeno, Hirohito; Nakashima, Tadashi; Kiyokawa, Kensuke; Hayabuchi, Naofumi; Fujita, Hiromasa

    2012-11-01

    The aim of this study is to clarify the prognostic value of the pathological overall tumor cellularity after neoadjuvant chemotherapy for locally advanced hypopharyngeal cancer. In consecutive series of 45 operable patients with locally advanced hypopharyngeal cancer, neoadjuvant chemotherapy by cisplatin and 5-fluorouracil was administered. Pathological image analysis was performed in 30 patients using the large cross-section specimen after total resection to evaluate the overall tumor cellularity. The chemotherapeutic responses were classified according to the pathological grading scale by dividing into four categories; more than 70% overall tumor cellularity in Grade 1, between an estimated 10 and 70% in Grade 2, less than 10% in Grade 3, and no identifiable malignant tumor cells in Grade 4. The pathological grades were taken into account for analysis of the survival. In 30 available patients, 40% had Grade 1 pathological response, 30% had Grade 2, and 30% had Grade 3. There was no Grade 4 patient. The overall 5-year survival rate for these 30 patients was 53.33%. The survival rate (61.66%) for patients with Grade 2 and 3 responses was significantly higher than that (27.78%) for patients with Grade 1 response (p = 0.009). Cox regression analysis revealed that the increasing pathological grade was an independent predictor of a better survival in patients undergoing neoadjuvant chemotherapy. We have shown that the prognosis of patients with locally advanced hypopharyngeal cancer, who had been treated by neoadjuvant chemotherapy followed by total resection, can be predicted by evaluation of pathological overall tumor cellularity from the large section specimen.

  2. Two-stage, low noise advanced technology fan. 5: Acoustic final report

    NASA Technical Reports Server (NTRS)

    Sofrin, T. G.; Riloff, N., Jr.

    1975-01-01

    The NASA Q2S(quiet two-stage) fan is a 0.836m (32.9 in.) diameter model of the STF 433 engine fan, selected in a 1972 study for an Advanced Technology Transport (ATT) airplane. Noise-control features include: low tip speed, moderate stage pressure rise, large blade-vane spacings, no inlet guide vanes, and optimum blade and vane numbers. Tests were run on the baseline Q2S fan with standard inlet and discharge ducts. Further tests were made of a translating centerbody sonic inlet device and treated discharge ducts. Results were scaled to JT8D and JT3D engine fan size for comparison with current two-stage fans, and were also scaled to STF 433 fan size to compare calculated ATT flyover noise with FAR 36 limits. Baseline Q2S results scaled to JT8D and JT3D engine fan sizes showed substantial noise reductions. Calculated unsuppressed baseline ATT flyovers averaged about 2.5 EPNdB below FAR 36 limits. Using measured sonic inlet results, scaled baseline Q2S fan results, and calculated attenuations for a 1975 technology duct liner, projected flyover noise calculations for the ATT averaged about FAR 36 limits minus 10 EPNdB. Advances in suppression technology required to meet the 1985 goal of FAR 36 limits minus 20 EPNdB are discussed.

  3. Gene Expression in Wilms’ Tumor Mimics the Earliest Committed Stage in the Metanephric Mesenchymal-Epithelial Transition

    PubMed Central

    Li, Chi-Ming; Guo, Meirong; Borczuk, Alain; Powell, Charles A.; Wei, Michelle; Thaker, Harshwardhan M.; Friedman, Richard; Klein, Ulf; Tycko, Benjamin

    2002-01-01

    Wilms’ tumor (WT) has been considered a prototype for arrested cellular differentiation in cancer, but previous studies have relied on selected markers. We have now performed an unbiased survey of gene expression in WTs using oligonucleotide microarrays. Statistical criteria identified 357 genes as differentially expressed between WTs and fetal kidneys. This set contained 124 matches to genes on a microarray used by Stuart and colleagues (Stuart RO, Bush KT, Nigam SK: Changes in global gene expression patterns during development and maturation of the rat kidney. Proc Natl Acad Sci USA 2001, 98:5649–5654) to establish genes with stage-specific expression in the developing rat kidney. Mapping between the two data sets showed that WTs systematically overexpressed genes corresponding to the earliest stage of metanephric development, and underexpressed genes corresponding to later stages. Automated clustering identified a smaller group of 27 genes that were highly expressed in WTs compared to fetal kidney and heterologous tumor and normal tissues. This signature set was enriched in genes encoding transcription factors. Four of these, PAX2, EYA1, HBF2, and HOXA11, are essential for cell survival and proliferation in early metanephric development, whereas others, including SIX1, MOX1, and SALL2, are predicted to act at this stage. SIX1 and SALL2 proteins were expressed in the condensing mesenchyme in normal human fetal kidneys, but were absent (SIX1) or reduced (SALL2) in cells at other developmental stages. These data imply that the blastema in WTs has progressed to the committed stage in the mesenchymal-epithelial transition, where it is partially arrested in differentiation. The WT-signature set also contained the Wnt receptor FZD7, the tumor antigen PRAME, the imprinted gene NNAT and the metastasis-associated transcription factor E1AF. PMID:12057921

  4. Ongoing advances in quantitative PpIX fluorescence guided intracranial tumor resection (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Olson, Jonathan D.; Kanick, Stephen C.; Bravo, Jaime J.; Roberts, David W.; Paulsen, Keith D.

    2016-03-01

    Aminolevulinc-acid induced protoporphyrin IX (ALA-PpIX) is being investigated as a biomarker to guide neurosurgical resection of brain tumors. ALA-PpIX fluorescence can be observed visually in the surgical field; however, raw fluorescence emissions can be distorted by factors other than the fluorophore concentration. Specifically, fluorescence emissions are mixed with autofluorescence and attenuated by background absorption and scattering properties of the tissue. Recent work at Dartmouth has developed advanced fluorescence detection approaches that return quantitative assessments of PpIX concentration, which are independent of background optical properties. The quantitative fluorescence imaging (qFI) approach has increased sensitivity to residual disease within the resection cavity at the end of surgery that was not visible to the naked eye through the operating microscope. This presentation outlines clinical observations made during an ongoing investigation of ALA-PpIX based guidance of tumor resection. PpIX fluorescence measurements made in a wide-field hyperspectral imaging approach are co-registered with point-assessment using a fiber optic probe. Data show variations in the measured PpIX accumulation among different clinical tumor grades (i.e. high grade glioma, low grade glioma), types (i.e. primary tumors. metastases) and normal structures of interest (e.g. normal cortex, hippocampus). These results highlight the contrast enhancement and underscore the potential clinical benefit offered from quantitative measurements of PpIX concentration during resection of intracranial tumors.

  5. Primary Tumor Resection Is Associated with Improved Survival in Stage IV Colorectal Cancer: An Instrumental Variable Analysis

    PubMed Central

    Xu, Hong; Xia, Zuguang; Jia, Xiaoyan; Chen, Kai; Li, Dapeng; Dai, Yun; Tao, Min; Mao, Yixiang

    2015-01-01

    Primary tumor resection (PTR) is recommended for patients with unresectable stage IV colorectal cancer (CRC) who present with symptoms related to their primary tumor. However, the survival benefit of PTR for asymptomatic patients is controversial. We investigated the change in PTR rates and the contribution of PTR to survival in patients with unresectable stage IV CRC over the past two decades in the United States. Clinicopathological factors and long-term survival were compared for 44 514 patients diagnosed with unresectable stage IV CRC from January 1, 1988, through December 31, 2010, who had or had not undergone PTR. Multivariable Cox regression and the instrumental variable method were used to identify independent factors for survival. Of the 44 514 patients with unresectable stage IV CRC, 27 931 (62.7%) had undergone PTR. The annual rate of PTR decreased from 74.4% to 50.2% diagnosed in 1988 and 2010, and the median overall survival increased for both PTR and non-PTR patients. Instrumental variable analyses revealed that PTR was associated with better overall, cancer-specific, and other-cause survival of patients with unresectable stage IV CRC. PMID:26563729

  6. A Two Stage Solution Procedure for Production Planning System with Advance Demand Information

    NASA Astrophysics Data System (ADS)

    Ueno, Nobuyuki; Kadomoto, Kiyotaka; Hasuike, Takashi; Okuhara, Koji

    We model for ‘Naiji System’ which is a unique corporation technique between a manufacturer and suppliers in Japan. We propose a two stage solution procedure for a production planning problem with advance demand information, which is called ‘Naiji’. Under demand uncertainty, this model is formulated as a nonlinear stochastic programming problem which minimizes the sum of production cost and inventory holding cost subject to a probabilistic constraint and some linear production constraints. By the convexity and the special structure of correlation matrix in the problem where inventory for different periods is not independent, we propose a solution procedure with two stages which are named Mass Customization Production Planning & Management System (MCPS) and Variable Mesh Neighborhood Search (VMNS) based on meta-heuristics. It is shown that the proposed solution procedure is available to get a near optimal solution efficiently and practical for making a good master production schedule in the suppliers.

  7. Stomach Cancer: Interconnection between the Redox State, Activity of MMP-2, MMP-9 and Stage of Tumor Growth.

    PubMed

    Burlaka, Anatoly P; Ganusevich, Irina I; Gafurov, Marat R; Lukin, Sergey M; Sidorik, Evgeny P

    2016-04-01

    High levels of reactive oxygen (ROS) and nitrogen (RNS) species can lead to the destruction of extracellular matrix facilitating tumor progression. ROS can activate matrix metalloproteinases (MMP), damage DNA and RNA. Therefore, the levels of MMP, ROS and RNS can serve as additional prognostic markers and for the estimation of the effectiveness of tumor therapy. Concerning gastric cancer, the prognostic role of MMP, its connection with the cancer staging remains controversial and correlations between the activity of MMP with the ROS and RNS levels are insufficiently confirmed. Superoxide generation rates, nitric oxide (NO) levels, concentrations of active forms of matrix metalloproteinases MMP-2 and MMP-9 in tumor and adjacent tissues of patients with stomach cancer at different disease stages were measured by electron spin resonance (ESR) including spin-trapping and polyacrylamide gel zymography. It is shown that the activity of MMP-2 and MMP-9 in tumor tissue correlate with the superoxide radicals generation rate and NO levels (r = 0.48÷0.67, p < 0.05). The activity of MMP-2 and MMP-9 in tumor tissues and superoxide radical generation rates correlate positively with the stage of regional dissemination (r = 0.45 and 0.37, correspondingly, p < 0.05), but MMP-2 and MMP-9 activity inversely depends on distant metastatic degree of stomach cancer (r = 0.58; p < 0.05). Additionally, the feasibility of ESR to locally determine oxidative stress is demonstrated. PMID:26905073

  8. Stomach Cancer: Interconnection between the Redox State, Activity of MMP-2, MMP-9 and Stage of Tumor Growth.

    PubMed

    Burlaka, Anatoly P; Ganusevich, Irina I; Gafurov, Marat R; Lukin, Sergey M; Sidorik, Evgeny P

    2016-04-01

    High levels of reactive oxygen (ROS) and nitrogen (RNS) species can lead to the destruction of extracellular matrix facilitating tumor progression. ROS can activate matrix metalloproteinases (MMP), damage DNA and RNA. Therefore, the levels of MMP, ROS and RNS can serve as additional prognostic markers and for the estimation of the effectiveness of tumor therapy. Concerning gastric cancer, the prognostic role of MMP, its connection with the cancer staging remains controversial and correlations between the activity of MMP with the ROS and RNS levels are insufficiently confirmed. Superoxide generation rates, nitric oxide (NO) levels, concentrations of active forms of matrix metalloproteinases MMP-2 and MMP-9 in tumor and adjacent tissues of patients with stomach cancer at different disease stages were measured by electron spin resonance (ESR) including spin-trapping and polyacrylamide gel zymography. It is shown that the activity of MMP-2 and MMP-9 in tumor tissue correlate with the superoxide radicals generation rate and NO levels (r = 0.48÷0.67, p < 0.05). The activity of MMP-2 and MMP-9 in tumor tissues and superoxide radical generation rates correlate positively with the stage of regional dissemination (r = 0.45 and 0.37, correspondingly, p < 0.05), but MMP-2 and MMP-9 activity inversely depends on distant metastatic degree of stomach cancer (r = 0.58; p < 0.05). Additionally, the feasibility of ESR to locally determine oxidative stress is demonstrated.

  9. Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

    PubMed Central

    Wang, Xue; Chen, Meng; Wu, Jing; Xu, Jian-Hua; Qian, Pu-Dong; Guo, Wen-Jie; Jiang, Xue-Song; Zhu, Huan-Feng; Gu, Jia-Jia; Wu, Jian-Feng; Zhang, Ye-wei; He, Xia

    2015-01-01

    Background N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). Patients and Methods Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. Results With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. Conclusion IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute

  10. A modified duodenal neuroendocrine tumor staging schema better defines the risk of lymph node metastasis and disease-free survival.

    PubMed

    Kachare, Swapnil D; Liner, Kendall R; Vohra, Nasreen A; Zervos, Emmanuel E; Fitzgerald, Timothy L

    2014-08-01

    Duodenal neuroendocrine tumors are rare but increasing in incidence and optimal management is hindered by lack of duodenum-specific staging. Duodenal carcinoids were identified in the Surveillance, Epidemiology and End Results tumor registry. Depth of invasion was defined as limited to lamina propria (LP), invading muscularis propria (MP), through muscularis propria (TMP), and through serosa (S). Nine hundred forty-nine patients were identified with majorities being male (57%), white (70%), and node-negative (87%). Tumor size (cm) was less than 1, 47 per cent; 1 to 2, 35 per cent; and greater than 2, 8 per cent with 76 per cent LP. Lymph node (LN) involvement was associated with age, depth of invasion (LP 4%, MP 28%, TMP 54%, and S 57%) and size (less than 1 cm, 3%; 1 to 2 cm, 13%; and greater than 2 cm, 40%). Using the current T staging, LN involvement was: T1 (LP) 2 per cent, T2 (MP or greater than 1 cm) 13 per cent, T3 (TMP) 54 per cent, and T4 (S) 57 per cent. We reclassified current T1 to T1a and current T2 stage to T1b (1 to 2 cm and LP) and T2 (MP or greater than 2 cm). LN metastasis for T1b tumors was 4.7 per cent compared with 20.8 per cent for T2. The resulting TNM classification better defines 5-year disease-specific survival. Our modified staging schema identifies a low-risk group (T1a and T1b) that may be considered for local therapy.

  11. Influence of Pulmonary Nodules on Chest Computed Tomography and Risk of Recurrence in Stage IV Wilms Tumor

    SciTech Connect

    Kirkland, Robert S.; Nanda, Ronica H.; Alazraki, Adina; Esiashvili, Natia

    2015-06-01

    Purpose: Chest computed tomography (CT) is currently accepted as the main modality for initial disease staging and response assessment in Wilms tumor (WT). However, there is great variability in the number and size of lung metastases at the time of diagnosis and after induction chemotherapy. There is a lack of clinical evidence as to how this variability in tumor burden affects choice of therapy and disease outcome. This study sought to evaluate a previously proposed lung metastases risk stratification system based on CT findings and clinical outcomes in stage IV WT patients. Methods and Materials: Thirty-five pediatric patients with a diagnosis of stage IV WT with evaluable pre- and postdiagnosis CT scans between 1997 and 2012 were included in the analysis. Patients were divided into low-, intermediate-, and high-risk categories based on the size and number of pulmonary metastases before and after 6 weeks of chemotherapy. Association of the lung risk groups with lung recurrence-free survival and overall survival at each time point was analyzed with relevant covariates. Results: Risk group distribution both at diagnosis and after induction chemotherapy was not influenced by tumor histology. Initial risk grouping suggested an association with disease-free survival at 5 years (P=.074); however, the most significant correlation was with postinduction chemotherapy disease status (P=.027). In patients with an intermediate or high burden of disease after 6 weeks of chemotherapy, despite receiving whole-lung and boost irradiation, survival outcomes were poorer. Conclusions: Pulmonary tumor burden in stage IV WT on chest CT can predict disease outcome. Patients with intermediate- or low-risk disease, especially after induction therapy, have a higher risk for recurrence. After prospective validation, this method may become a valuable tool in adaptation of therapy to improve outcome.

  12. Preliminary oncological results of endosopic laser surgery in advanced head and neck tumors

    NASA Astrophysics Data System (ADS)

    Baker-Schreyer, Antonio; Sadick, Haneen; Juncker, Cathrine; Bergler, Wolfgang; Hoermann, Karl

    1998-01-01

    Lasersurgery has established itself in the treatment of minor tumors (T1 - T2) of the upper aerodigestive tract. However, advanced carcinomas of the head and neck (T3 - T4) are generally treated with conventional surgical procedures which include pharyngolaryngectomy. The purpose of this study was to evaluate the oncological outcome of endoscopic lasersurgery in advanced head and neck tumors and to compare the results with conventional surgical procedures. Between January 1994 to December 1996, 86 patients with advanced squamous cell carcinomas of the larynx and hypopharynx underwent endoscopic lasersurgery instead of pharyngolaryngectomy as a curative measure. Besides the recurrence and survival rate, the necessity of tracheostomy, postoperative complications and the mean duration of hospitalization were documented. The results showed that the recurrence and survival rate were similar or even better after conventional pharyngolaryngectomy, whereas the patients' postoperative rehabilitation was better after lasersurgery. In this contribution the indication for lasersurgical intervention or pharyngolaryngectomy in advanced carcinomas of the head and neck is discussed.

  13. Prospective Study of FLT PET for Early Interim Response Assessment in Advanced Stage B-cell Lymphoma

    PubMed Central

    Schöder, Heiko; Zelenetz, Andrew D.; Hamlin, Paul; Gavane, Somali; Horwitz, Steven; Matasar, Matthew; Moskowitz, Alison; Noy, Ariela; Palomba, Lia; Portlock, Carol; Straus, David; Grewal, Ravinder; Migliacci, Jocelyn C.; Larson, Steven M.; Moskowitz, Craig H.

    2016-01-01

    Purpose Current clinical and imaging tools remain suboptimal for early assessment of prognosis and treatment response in aggressive lymphomas. Positron emission tomography (PET) with 18F-fluorothymidine (FLT) can be used to measure tumor cell proliferation and treatment response. In a prospective study in patients with advanced stage B-cell lymphoma we investigated the prognostic and predictive value of FLT PET in comparison to standard imaging with FDG PET and clinical outcome. Patients and Methods 65 patients were treated with an induction/consolidation regimen consisting of four cycles of R-CHOP-14 followed by 3 cycles of ICE. FLT PET was performed at baseline and at interim (iPET) after 1–2 cycles of therapy. FDG PET was performed at baseline, after cycle 4, and at the end of therapy. The relationship between PET findings, progression free survival (PFS) and overall survival (OS) was investigated. Results With a median follow-up of 51 months, PFS and OS were 71% and 86% respectively. FLT iPET, analyzed visually, using a 5-point score, or semi-quantitatively, using SUV and ΔSUV, predicted both PFS and OS (p<0.01 for all parameters). Residual FLT SUVmax on iPET was associated with an inferior PFS (HR: 1.26, p=0.001) and OS (HR: 1.27, p=0.002). Using FDG PET, findings in the end of treatment scan were better predictors of PFS and OS than findings on interim scan. Baseline PET imaging parameters, including SUV, proliferative or metabolic tumor volume, did not correlate with outcome. Conclusion FLT PET after 1–2 cycles of chemotherapy predicts PFS and OS, and a negative FLT iPET may potentially help design risk-adapted therapies in patients with aggressive lymphomas. In contrast, the positive predictive value of FLT iPET remains too low to justify changes in patient management. PMID:26719374

  14. Treatment of liver cancer of middle and advanced stages using ultrasound-guided percutaneous ethanol injection combined with radiofrequency ablation: A clinical analysis

    PubMed Central

    SUN, XUE; LI, RU; ZHANG, BOTAO; YANG, YUEJIE; CUI, ZHIFEI

    2016-01-01

    Liver cancer is a malignancy of the digestive system and has a high morbidity and mortality rate. Local intervention has become a viable option in identifying liver treatment. The aim of the present study was to analyze the clinical effects of treating liver cancer in middle and advanced stages using ultrasound-guided percutaneous ethanol injection (PEI) in tumors combined with radiofrequency ablation (RFA). A total of 100 patients with stage III–IV liver cancers were selected to participate in the study. Patients were divided into groups. In group A, treatment was initiated with PEI and after 1–2 weeks RFA was applied while in group B treatment was initiated with RFA and after 1–2 weeks PEI was applied. Patients in group C received PEI and RFA simultaneously. The clinical effects in the 3 groups were compared after 6-month follow ups. The volume of tumor ablation necrosis in group A was significantly greater than that in the groups B and C, while the size was significantly smaller compared to groups B and C after ablation. For group A, the complete ablation rate was significantly higher than that in groups B and C, and the differences were statistically significant (P<0.05). Liver damage indices, including raising levels of glutamic-pyruvic transaminase and total bilirubin, were significantly decreased in group A (P<0.05). The survival rate in group A was also significantly higher than in groups B and C (P<0.05). In conclusion, for patients with liver cancer in middle and advanced stages, the treatment method using PEI followed by RFA was more beneficial in terms of improving the tumor ablation rate, alleviating liver damages and increasing survival rates. PMID:26998128

  15. Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

    NASA Astrophysics Data System (ADS)

    Wendel, Marco; Bazhenova, Lyudmila; Boshuizen, Rogier; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H.; Marrinucci, Dena; Sandhu, Ajay; Perricone, Anthony; Thistlethwaite, Patricia; Bethel, Kelly; Nieva, Jorge; van den Heuvel, Michel; Kuhn, Peter

    2012-02-01

    Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL-1 (range 0-515.6) and a mean of 44.7 (±95.2) HD-CTCs mL-1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in

  16. Once-Weekly, High-Dose Stereotactic Body Radiotherapy for Lung Cancer: 6-Year Analysis of 60 Early-Stage, 42 Locally Advanced, and 7 Metastatic Lung Cancers

    SciTech Connect

    Salazar, Omar M. Sandhu, Taljit S.; Lattin, Paul B.; Chang, Jung H.; Lee, Choon K.; Groshko, Gayle A.; Lattin, Cheryl J.

    2008-11-01

    Purpose: To explore once-weekly stereotactic body radiotherapy (SBRT) in nonoperable patients with localized, locally advanced, or metastatic lung cancer. Methods and Materials: A total of 102 primary (89 untreated plus 13 recurrent) and 7 metastatic tumors were studied. The median follow-up was 38 months, the average patient age was 75 years. Of the 109 tumors studied, 60 were Stage I (45 IA and 15 IB), 9 were Stage II, 30 were Stage III, 3 were Stage IV, and 7 were metastases. SBRT only was given in 73% (40 Gy in four fractions to the planning target volume to a total dose of 53 Gy to the isocenter for a biologically effective dose of 120 Gy{sub 10}). SBRT was given as a boost in 27% (22.5 Gy in three fractions once weekly for a dose of 32 Gy at the isocenter) after 45 Gy in 25 fractions to the primary plus the mediastinum. The total biologically effective dose was 120 Gy{sub 10}. Respiration gating was used in 46%. Results: The overall response rate was 75%; 33% had a complete response. The overall response rate was 89% for Stage IA patients (40% had a complete response). The local control rate was 82%; it was 100% and 93% for Stage IA and IB patients, respectively. The failure rate was 37%, with 17% within the planning target volume. No Grade 3-4 acute toxicities developed in any patient; 12% and 7% of patients developed Grade 1 and 2 toxicities, respectively. Late toxicity, all Grade 2, developed in 3% of patients. The 5-year cause-specific survival rate for Stage I was 70% and was 74% and 64% for Stage IA and IB patients, respectively. The 3-year Stage III cause-specific survival rate was 30%. The patients with metastatic lung cancer had a 57% response rate, a 27% complete response rate, an 86% local control rate, a median survival time of 19 months, and 23% 3-year survival rate. Conclusions: SBRT is noninvasive, convenient, fast, and economically attractive; it achieves results similar to surgery for early or metastatic lung cancer patients who are older

  17. Efficacy of in vivo 31Phosphorus Magnetic Resonance Spectroscopy in Differentiation and Staging of Adult Human Brain Tumors.

    PubMed

    Bulakbasi, N; Kocaoglu, M; Sanal, H T; Tayfun, C

    2007-12-31

    The aim of this study was to evaluate the efficacy of (31)P magnetic resonance spectroscopy ((31)P-MRS) in the differentiation and staging of brain tumors. Fifteen volunteers and 44 patients with brain tumors (14 meningiomas, 13 low- and 17 high-grade gliomas) were prospectively evaluated by (31)P-MRS. The pH (r=0.493, p<0.001), [Mg(+2)] (r=0.850, p<0.001) PME/α-ATP (r=0.776, p<0.001), PDE/α-ATP (r=-0.569, p<0.001) and (PCr+β-ATP)/Pi ratios were well correlated with tumor differentiation. High-grade gliomas had significantly higher pH (r=0.912, p<0.001) and [Mg(+2)] (r=0.855, p<0.001) and PME/α-ATP (r=0.894, p<0.001) ratio, and lower PCr/α-ATP (r=-0.959, p<0.001), Pi/α-ATP (r=-0.788, p<0.001) and PDE/α-ATP ratios (r=-0.968, p<0.001) than those of low-grade gliomas. Changes in (31)P-MRS parameters by the degree of malignancy are good indicators of increased anaerobic metabolism and hypoxia of tumoral tissue to compensate intratumoral energy deficiency. (31)P-MRS parameters are very useful for grading and differentiation of brain tumors. PMID:24299999

  18. Reproducibility of Digital PCR Assays for Circulating Tumor DNA Analysis in Advanced Breast Cancer

    PubMed Central

    Hrebien, Sarah; O’Leary, Ben; Beaney, Matthew; Schiavon, Gaia; Fribbens, Charlotte; Bhambra, Amarjit; Johnson, Richard; Turner, Nicholas

    2016-01-01

    Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48–72 hours after collection. Plasma DNA was analysed with multiplex digital PCR (mdPCR) assays for hotspot mutations in PIK3CA, ESR1 and ERBB2, and for AKT1 E17K. There was 94.8% (91/96) agreement in mutation calling between immediate and delayed processed tubes, kappa 0.88 95% CI 0.77–0.98). Discordance in mutation calling resulted from low allele frequency and likely stochastic effects. In concordant samples there was high correlation in mutant copies per ml plasma (r2 = 0.98; p<0.0001). There was elevation of total cell free plasma DNA concentrations in 10.3% of delayed processed tubes, although overall quantification of total cell free plasma DNA had similar prognostic effects in immediate (HR 3.6) and delayed (HR 3.0) tubes. There was moderate agreement in changes in allele fraction between sequential samples in quantitative mutation tracking (r = 0.84, p = 0.0002). Delayed processing of samples using preservative tubes allows for centralized ctDNA digital PCR mutation screening in advanced breast cancer. The potential of preservative tubes in quantitative mutation tracking requires further research. PMID:27760227

  19. Autologous peripheral blood stem cell transplantation in tumor-stage mycosis fungoides: predictors of disease-free survival.

    PubMed

    Russell-Jones, R; Child, F; Olavarria, E; Whittaker, S; Spittle, M; Apperley, J

    2001-09-01

    Nine patients with mycosis fungoides (age range 27-67) underwent autologous peripheral blood stem cell transplantation (PBSCT). All patients had tumor-stage disease, and four had lymph node involvement. Eight patients exhibited a peripheral blood T cell clone using PCR/SSCP analysis of the TCR gamma gene, six prior to harvest and two at the time of harvest. Mobilization of CD34+ stem cells was achieved with etoposide and G-CSF. Harvested cells were positively selected for CD34. After negative selection for CD4 and CD8, only two samples became PCR negative. Conditioning prior to reinfusion of stem cells was achieved with various combinations of total skin electron beam (TSEB), total body irradiation (TBI), and chemotherapy, depending upon the patient's prior exposure to radiotherapy. One patient failed to engraft and died of candidal septicemia 15 days posttransplant. The other eight patients achieved complete remission, but this was short-lived in four (median disease-free survival [DFS] = 2 months) and prolonged in three (median DFS 11 months). Those with a short DFS were distinguished by rapid tumor onset prior to transplant but not by stage at transplant. Loss of a detectable T cell clone after manipulation of the harvest did not discriminate between the two groups, but rapid relapsers had been subjected to a greater degree of T cell depletion, possibly indicating a compromised cytotoxic response post-PBSCT. The median survival of the cohort is four years from tumor onset, 15 months from PBSCT, and 27 months from the date a peripheral blood clone was first detected in the presence of tumor-stage disease. Rapid relapse was associated with poor overall survival. Our data demonstrate the value of PBSCT for inducing remission in tumor-stage mycosis fungoides. Reinfusion of neoplastic cells could be avoided by harvesting stem cells at an earlier stage in the disease process, preferably before a T cell clone is detectable in the peripheral blood. Alternatively T cell

  20. 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

  1. [Value of computer tomography in staging urological tumors before radical surgery].

    PubMed

    Romics, I; Will, C; Beutler, W; Bach, D

    1991-12-15

    The authors investigated by conventional CT 66 urological tumorous patients before radical operations, and compared with the findings of the histological investigations of the lymph nodes removed by the lymphadenectomy. The coincidence between the two investigations were 80%.

  2. END STAGE RENAL DISEASE IN PATIENTS WITH WILMS TUMOR: RESULTS FROM THE NATIONAL WILMS TUMOR STUDY GROUP AND THE U.S. RENAL DATA SYSTEM

    PubMed Central

    Breslow, Norman E.; Grigoriev, Yevgeny A.; Peterson, Susan M.; Collins, Allan J.; Ritchey, Michael L.; Green, Daniel M.

    2006-01-01

    Purpose: To accurately assess the full spectrum of end stage renal disease (ESRD) in Wilms tumor survivors by combining the unique resources of the National Wilms Tumor Study Group (NWTSG) and the U.S. Renal Data System (USRDS), and to confirm preliminary reports of an increased incidence of ESRD in those with the Wilms tumor-aniridia (WAGR) syndrome. Material and Methods: ESRD was ascertained for 5,910 patients enrolled on NWTSG studies during 1969-1994 both by record linkage to USRDS and by direct follow-up. Cumulative ESRD incidence was estimated accounting for inter-current mortality. Results: Ten of 115 cases of ESRD (9%) were ascertained by NWTSG alone, 13 (11%) by USRDS alone and 92 (80%) by both. Cumulative incidence of ESRD at 20 years from diagnosis of unilateral Wilms tumor (WT) was 74% for 17 patients with Deny-Drash syndrome (DDS), 36% for 37 patients with WAGR syndrome, 7% for 125 male patients with hypospadias or cryptorchism (GU anomalies) and 0.6% for 5,347 patients with none of these conditions. The incidence for bilateral Wilms tumor was 50% for DDS (n=6), 90% for WAGR (n=10), 25% for GU anomaly (n=25) and 12% for other patients (n=409). ESRD for patients with WAGR syndrome or GU anomalies tended to occur relatively late, often during or after adolescence. Conclusions: The risk of ESRD is remarkably low for the majority of WT patients. Those with WAGR syndrome or associated GU anomalies, however, are at higher risk and should be screened indefinitely to facilitate prospective management of impaired renal function. PMID:16217371

  3. Restoration of tumor equilibrium after immunotherapy for advanced melanoma: three illustrative cases.

    PubMed

    Wilgenhof, Sofie; Pierret, Lauranne; Corthals, Jurgen; Van Nuffel, An M T; Heirman, Carlo; Roelandt, Truus; De Coninck, Arlette; Verfaillie, Guy; Vandenbroucke, Frederik; Van Riet, Ivan; Bonehill, Aude; Thielemans, Kris; Neyns, Bart

    2011-04-01

    Metastatic melanoma runs a predictable detrimental course in the vast majority of patients. New modalities of immunotherapy, such as melanoma antigen-specific therapeutic vaccination and cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor blockade by monoclonal antibodies (mAbs), have been associated with atypical kinetics of tumor response that differ from those observed during cytotoxic treatment. Recently, new tumor response criteria have been proposed based on the tumor response characteristics observed in clinical studies with ipilimumab (the so-called 'immune-related response criteria'). We report three illustrative cases of the American Joint Committee on Cancer stage IV-M1c melanoma patients who experienced atypical kinetics of tumor response to the treatment with the CTLA-4-blocking mAb, ipilimumab (case 1), or an autologous dendritic cell vaccine in combination with interferon α-2b (cases 2 and 3). These cases show that atypical response patterns not only relate to the outcome of CTLA-4-blocking mAb therapy but also to the treatment with therapeutic vaccines and interferon α-2b.

  4. Impact of underweight after treatment on prognosis of advanced-stage ovarian cancer.

    PubMed

    Kim, Se Ik; Kim, Hee Seung; Kim, Tae Hun; Suh, Dong Hoon; Kim, Kidong; No, Jae Hong; Chung, Hyun Hoon; Kim, Yong Beom; Song, Yong Sang

    2014-01-01

    This study aimed to investigate the impact of underweight status on the prognosis of advanced-stage ovarian cancer. A total of 360 patients with stage III-IV epithelial ovarian cancer were enrolled and divided into three groups by body mass indexes (BMIs): underweight (BMI < 18.5 kg/m(2)); normal weight to overweight (18.5 kg/m(2) BMI < 27.5 kg/m(2)); obesity (BMI ≥ 27.5 kg/m(2)). Progression-free survival (PFS), overall survival (OS), CA-125, and neutrophil to lymphocyte ratio (NLR) as a marker reflecting host inflammation and immunity were compared among the three groups according to the three treatment times: at diagnosis; after surgery; and after treatment. Only underweight status after treatment was associated with poor OS in comparison with normal weight to overweight or obesity (mean value, 44.9 versus 78.8 or 67.4 months; P = 0.05); it was also an unfavorable factor for OS (adjusted HR, 2.29; 95% CI, 1.08-4.85). Furthermore, NLR was higher in patients with underweight than in those with obesity after treatment (median value, 2.15 versus 1.47; P = 0.03), in spite of no difference in CA-125 among the three groups at the three treatment times. In conclusion, underweight status after treatment may be a poor prognostic factor in patients with advanced-stage ovarian cancer, which accompanies increased host inflammation and decreased immunity.

  5. Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

    ClinicalTrials.gov

    2016-01-13

    Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  6. The Management of Advanced Germ Cell Tumors in 2016: The Memorial Sloan Kettering Approach.

    PubMed

    Funt, Samuel A; Feldman, Darren R; Bosl, George J

    2016-07-01

    The high cure rate of patients with advanced germ cell tumors is the result of effective cisplatin-based chemotherapy; both previously untreated and relapsing patients can be cured. Risk stratification is particularly important in previously untreated patients. While retrospective salvage therapy analyses suggest that a number of clinical factors are associated with outcome, the appropriate selection of patients for, and the sequencing of, conventional- and high-dose regimens are subjects of debate because of the introduction of paclitaxel and different approaches to the administration of high-dose chemotherapy. This therapeutic landscape has been molded in part by our current understanding of treatment-associated toxicity. In this paper, we review the use of serum tumor markers in risk assignment and response evaluation; the treatment of previously untreated and relapsing patients; the role of surgical resection of residual disease, including retroperitoneal node dissection; and the importance of clinical trials for addressing unanswered questions and testing new therapies. Management controversies and possible future treatment enhancements that incorporate serum tumor marker decline and tumor genomics will also be discussed. PMID:27422113

  7. Advanced malignant solitary fibrous tumor in pelvis responding to radiation therapy.

    PubMed

    Kawamura, Shinobu; Nakamura, Takafumi; Oya, Takeshi; Ishizawa, Shin; Sakai, Yuta; Tanaka, Tomonori; Saito, Shigeru; Fukuoka, Junya

    2007-04-01

    Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm that is benign in most cases. Although SFT was first recognized to arise only in the pleura, recent reports indicate that SFT can involve a wide range of anatomical sites. To date, 17 cases of pelvic SFT have been reported. Herein is reported a case of a 74-year-old woman with a giant malignant SFT in the pelvis. Along with massive invasion to adjacent organs and multiple lung metastases detected on radiography, biopsy from the tumor through the vaginal wall showed malignant looking spindle-cell neoplasm with increased cellularity, areas of necrosis, and high mitotic activity (5/10 high-power fields). Immunohistochemically, the tumor cells were diffusely and strongly positive for CD34, CD99, and bcl-2. Based on pathological features and clinical presentation, diagnosis of malignant SFT was made. The patient received systemic and the intra-arterial chemotherapy followed by whole pelvic radiation therapy (50 Gy). Initial chemotherapies failed to control the tumor. Afterwards, improvement was observed radiologically and pathologically in the 12 months' follow up after the radiation therapy. This is the first report related to therapeutic remarks on advanced malignant SFT.

  8. Molecular targeted therapies in advanced gastric cancer: does tumor histology matter?

    PubMed Central

    Wong, Hilda

    2013-01-01

    It is increasingly recognized that gastric cancer is a heterogeneous disease which may be divided into subgroups based on histological, anatomical, epidemiological and molecular classifications. Distinct molecular drivers and tumor biology, and thus different treatment targets and predictive biomarkers, may be implicated in each subtype. However, there is little evidence in the literature regarding the correlation among these different classifications, and particularly the molecular aberrations present in each subtype. In this review, we approach advanced gastric cancer (AGC) by presenting aberrant molecular pathways and their potential therapeutic targets in gastric cancer according to histological and anatomical classification, dividing gastric cancer into proximal nondiffuse, distal nondiffuse and diffuse disease. Several pathways are involved predominantly, although not exclusively, in different subtypes. This may help to explain the disappointing results of many published AGC trials in which study populations were heterogeneous regardless of clinicopathological characteristics of the primary tumor. Histological and anatomical classification may provide insights into tumor biology and facilitate selection of an enriched patient population for targeted agents in future studies and in the clinic. However, some molecular pathways implicated in gastric cancer have not been studied in correlation with histological or anatomical subtypes. Further studies are necessary to confirm the suggestion that such classification may predict tumor biology and facilitate selection of an enriched patient population for targeted agents in future studies and in the clinic. PMID:23320047

  9. Management of inferior vena cava tumor thrombus in locally advanced renal cell carcinoma

    PubMed Central

    Psutka, Sarah P.

    2015-01-01

    The diagnosis of renal cell carcinoma is accompanied by intravascular tumor thrombus in up to 10% of cases, of which nearly one-third of patients also have concurrent metastatic disease. Surgical resection in the form of radical nephrectomy and caval thrombectomy represents the only option to obtain local control of the disease and is associated with durable oncologic control in approximately half of these patients. The objective of this clinical review is to outline the preoperative evaluation for, and operative management of patients with locally advanced renal cell carcinoma with venous tumor thrombi involving the inferior vena cava. Cornerstones of the management of these complex patients include obtaining high-quality imaging to characterize the renal mass and tumor thrombus preoperatively, with further intraoperative real-time evaluation using transesophageal echocardiography, careful surgical planning, and a multidisciplinary approach. Operative management of patients with high-level caval thrombi should be undertaken in high-volume centers by surgical teams with capacity for bypass and invasive intraoperative monitoring. In patients with metastatic disease at presentation, cytoreductive nephrectomy and tumor thrombectomy may be safely performed with simultaneous metastasectomy if possible. In the absence of level one evidence, neoadjuvant targeted therapy should continue to be viewed as experimental and should be employed under the auspices of a clinical trial. However, in patients with significant risk factors for postoperative complications and mortality, and especially in those with metastatic disease, consultation with medical oncology and frontline targeted therapy may be considered. PMID:26445601

  10. Two-stage, low noise advanced technology fan. Volume 2: Aerodynamic data

    NASA Technical Reports Server (NTRS)

    Harley, K. G.; Odegard, P. A.

    1975-01-01

    Aerodynamic data from static tests of a two-stage advanced technology fan designed to minimize noise are presented. Fan design conditions include delivery of 209.1kg/sec/sq m (42.85 lbm/sec/sq ft) specific corrected flow at an overall pressure ratio of 1.9 and an adiabatic efficiency of 85.3 percent. The 0.836m (2.74ft) diameter first stage rotor has a hub/tip ratio of 0.4 and 365.8m/sec (1200ft/sec) design tip speed. In addition to the moderate tip speed and pressure rise per stage, other noise control design features involve widely spaced blade rows and proper selection of blade-vane ratios. Aerodynamic data are presented for tests with unifrom and with hub and tip radially distorted inlet flow. Aerodynamic data are also presented for tests of this fan with acoustic treatments, including acoustically treated casing walls, a flowpath exit acoustic ring, and a translating centerbody sonic inlet device. A complete tabulation of the overall performance data, the blade element data, and the power spectral density information relating to turbulence levels generated by the sonic inlet obtained during these tests is included. For vol. 1, see N74-33789.

  11. Correlating planned radiation dose to the cochlea with primary site and tumor stage in patients with head and neck cancer treated with intensity-modulated radiation therapy

    SciTech Connect

    Zhang, Jeanette; Qureshi, Muhammad M.; Kovalchuk, Nataliya; Truong, Minh Tam

    2014-04-01

    The aim of the study was to determine tumor characteristics that predict higher planned radiation (RT) dose to the cochlea in patients with head and neck cancer (HNC) treated with intensity-modulated radiotherapy (IMRT). From 2004 to 2012, 99 patients with HNC underwent definitive IMRT to a median dose of 69.96 Gy in 33 fractions, with the right and left cochlea-vestibular apparatus contoured for IMRT optimization as avoidance structures. If disease involvement was adjacent to the cochlea, preference was given to tumor coverage by prescription dose. Descriptive statistics were calculated for dose-volume histogram planning data, and mean planning dose to the cochlea (from left or right cochlea, receiving the greater amount of RT dose) was correlated to primary site and tumor stage. Mean (standard deviation) cochlear volume was 1.0 (0.60) cm{sup 3} with maximum and mean planned doses of 31.9 (17.5) Gy and 22.1 (13.7) Gy, respectively. Mean planned dose (Gy) to cochlea by tumor site was as follows: oral cavity (18.6, 14.4), oropharynx (21.7, 9.1), nasopharynx (36.3, 10.4), hypopharynx (14.9, 7.1), larynx (2.1, 0.62), others including the parotid gland, temporal bone, and paranasal sinus (33.6, 24.0), and unknown primary (25.6, 6.7). Average mean planned dose (Gy) to the cochlea in T0-T2 and T3-T4 disease was 22.0 and 29.2 Gy, respectively (p = 0.019). By site, a significant difference was noted for nasopharynx and others (31.6 and 50.7, p = 0.012) but not for oropharynx, oral cavity, and hypopharynx. Advanced T category predicted for higher mean cochlear dose, particularly for nasopharyngeal, parotid gland, temporal bone, and paranasal sinus HNC sites.

  12. Primary Tumor Resection and Survival in Patients with Stage IV Gastric Cancer

    PubMed Central

    Mutlu, Hasan; Karaağaç, Mustafa; Eryilmaz, Melek Karakurt; Gündüz, Şeyda; Artaç, Mehmet

    2016-01-01

    Purpose The aim of this study was to determine whether surgical resection of the primary tumor contributes to survival in patients with metastatic gastric cancer. Materials and Methods A total of 288 patients with metastatic gastric cancer from the Akdeniz University, Antalya Training and Research Hospital, and the Meram University of Konya database were retrospectively analyzed. The effect of primary tumor resection on survival of patients with metastatic gastric cancer was investigated using the log-rank test. Kaplan-Meier survival estimates were calculated. Multivariate analysis was performed using Cox proportional hazards regression modeling. Results The median overall survival was 12.0 months (95% confidence intewrval [CI], 10.4~13.6 months) and 7.8 months (95% CI, 5.5~10.0 months) for patients with and without primary tumor resection, respectively (P<0.001). The median progression-free survival was 8.3 months (95% CI, 7.1~9.5 months) and 6.2 months (95% CI, 5.8~6.7 months) for patients with and without primary tumor resection, respectively (P=0.002). Conclusions Non-curative gastrectomy in patients with metastatic gastric cancer might increase their survival rate regardless of the occurrence of life-threatening tumor-related complications. PMID:27433392

  13. Telomere length of tumor tissues and survival in patients with early stage non-small cell lung cancer.

    PubMed

    Jeon, Hyo-Sung; Choi, Yi Young; Choi, Jin Eun; Lee, Won Kee; Lee, Eungbae; Yoo, Seung Soo; Lee, Shin Yup; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Park, Jae Yong

    2014-04-01

    Telomere shortening leads to genomic instability that drives oncogenesis through the activation of telomerase and the generation of other mutations necessary for tumor progression. This study was conducted to determine the impact of telomere shortening on the survival of patients with early stage non-small cell lung cancer (NSCLC). Relative telomere length in tumor tissues was measured by quantitative polymerase chain reaction in 164 patients with surgically resected NSCLC. The association between telomere length and overall survival (OS) and disease-free survival (DFS) was analyzed. When the patients were categorized into quartiles based on telomere length, those patients with the 1st quartile (shortest) of telomere length had a significantly worse OS and DFS compared to patients with the 2nd to the 4th quartiles of telomere length (adjusted hazard ratio for OS = 2.67, 95% confidence interval = 1.50-4.75, P = 0.001; and adjusted hazard ratio for DFS = 1.92, 95% confidence interval = 1.17-3.14, P = 0.01). An association between telomere length and survival outcome was more pronounced in squamous cell carcinomas than adenocarcinomas (P-value of test for homogeneity for OS and DFS = 0.05 and 0.02, respectively). Telomere length of tumor tissues is an independent prognostic factor in patients with surgically resected early stage NSCLC.

  14. Transcatheter Arterial Chemoembolization for Advanced Hepatocellular Carcinoma with Inferior Vena Cava and Right Atrial Tumors

    SciTech Connect

    Chern, M. C. Chuang, V. P. Cheng, T. Lin, Z. H. Lin, Y. M.

    2008-07-15

    Advanced hepatocelluar carcinoma (HCC) with invasion of venous systems usually indicates not only a poor prognosis but also a contraindication for transcatheter arterial chemoembolization (TACE). This study evaluated the feasibility of TACE for advanced HCC with inferior vena cava (IVC) and right atrium (RA) tumors and, also, to search for the ideal embolization particle size. Twenty-six patients who had HCC invasion into the IVC included five patients with coexistent RA tumors that were treated with TACE. The chemoembolization method was cisplatin, doxorubicin, and mitomycin C mixed with Lipiodol and Ivalon. The selection of Ivalon particles was divided into two groups based on their size: (A) >180 {mu}m, N = 9; and (B) 47-180 {mu}m, N = 17. The overall response rate was 53.8% (14/26). Based on the response to TACE, the median survival period of the entire group was 4.2 months (range, 1.5 to 76.7 months). The median survival period of the 14 responders was 13.5 months (1.5-76.7 months), and that of the 12 nonresponders, 3.3 months (2.1 to 24.3 months) (p < 0.002). Comparing the two Ivalon particle sizes, the response rate was 12.5% (1/9 patients) for group A and 76.5% for group B (13/17 patients) (p < 0.02). No serious complication was observed post-chemoembolization. In conclusion, TACE is a safe and effective treatment for advanced HCC with IVC and RA tumors, and small Ivalon particles (47-180 {mu}m) are superior to large ones (>180 {mu}m).

  15. Lymphadenectomy in locally advanced cervical cancer study (LiLACS): Phase III clinical trial comparing surgical with radiologic staging in patients with stages IB2-IVA cervical cancer.

    PubMed

    Frumovitz, Michael; Querleu, Denis; Gil-Moreno, Antonio; Morice, Philippe; Jhingran, Anuja; Munsell, Mark F; Macapinlac, Homer A; Leblanc, Eric; Martinez, Alejandra; Ramirez, Pedro T

    2014-01-01

    Radiation treatment planning for women with locally advanced cervical cancer (stages IB2-IVA) is often based on positron emission tomography (PET). PET, however, has poor sensitivity in detecting metastases in aortocaval nodes. We have initiated a study with the objective of determining whether pre-therapeutic laparoscopic surgical staging followed by tailored chemoradiation improves survival as compared with PET/computed tomography (CT) radiologic staging alone followed by chemoradiation. This international, multicenter phase III trial will enroll 600 women with stages IB2-IVA cervical cancer and PET/CT findings showing fluorodeoxyglucose-avid pelvic nodes and fluorodeoxyglucose-negative para-aortic nodes. Eligible patients will be randomized to undergo either pelvic radiotherapy with chemotherapy (standard-of-care arm) or surgical staging via a minimally invasive extraperitoneal approach followed by tailored radiotherapy with chemotherapy (experimental arm). The primary end point is overall survival. Secondary end points are disease-free survival, short- and long-term morbidity with pre-therapeutic surgical staging, and determination of anatomic locations of metastatic para-aortic nodes in relationship to the inferior mesenteric artery. We believe this study will show that tailored chemoradiation after pre-therapeutic surgical staging improves survival as compared with chemoradiation based on PET/CT in women with stages IB2-IVA cervical cancer.

  16. Increased Levels of Plasma Epstein Barr Virus DNA Identify a Poor-Risk Subset of Patients With Advanced Stage Cutaneous T-Cell Lymphoma

    PubMed Central

    Haverkos, Bradley M.; Gru, Alejandro A.; Geyer, Susan M.; Bingman, Anissa K.; Hemminger, Jessica A.; Mishra, Anjali; Wong, Henry K.; Pancholi, Preeti; Freud, Aharon G.; Caligiuri, Michael A.; Baiocchi, Robert A.; Porcu, Pierluigi

    2016-01-01

    Discovering prognostic factors that simultaneously describe tumor characteristics and improve risk stratification is a priority in cutaneous T-cell lymphoma (CTCL). More than a third of advanced stage CTCL patients in this cohort had detectable cell free plasma Epstein–Barr virus (EBV)-DNA (pEBVd) using quantitative real-time polymerase chain reaction. An increased level of pEBVd was highly concordant with EBV (ie, Epstein–Barr virus RNAs) in tumor tissue and was associated with inferior survival. Introduction Outcomes in advanced stage (AS) cutaneous T-cell lymphomas (CTCL) are poor but with great variability. Epstein–Barr virus (EBV) is associated with a subset of non-Hodgkin lymphomas. Frequency of plasma EBV-DNA (pEBVd) detection, concordance with EBV RNA (EBER) in tumor tissue, codetection of plasma cytomegalovirus DNA (pCMVd), and prognostic effect in AS CTCL are unknown. Patients and Methods Patients (n = 46; 2006–2013) with AS CTCL (≥IIB) were retrospectively studied. pEBVd and pCMVd were longitudinally measured using quantitative real-time polymerase chain reaction. EBER in situ hybridization (ISH) was performed on tumor samples. Survival from time of diagnosis (ToD) and time of progression to AS was assessed. Results Plasma EBV-DNA and pCMVd were detected in 37% (17 of 46) and 17% (8 of 46) of AS CTCL patients, respectively. pCMVd detection was significantly more frequent in pEBVd-positive (pEBVd+) than pEBVd− patients (35% vs. 7%; P = .038). Tumor tissue for EBER-ISH was available in 14 of 17 pEBVd+ and 22 of 29 pEBVd− patients; 12 of 14 (85.7%) pEBVd+ patients were EBER+ versus 0 of 22 pEBVd− patients. Frequency of large cell transformation (LCT) tended to be greater in pEBVd+ patients, but was not significant (10 of 14 pEBVd+ vs. 10 of 23 pEBVd−; P = .17). No notable differences in rates of increased levels of serum lactate dehydrogenase (LDH) were observed (17 of 17 pEBVd+ vs. 27 of 29 pEBVd−). pEBVd detection was associated with

  17. 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

  18. Molecular analysis of tumor-promoting CD8+ T cells in two-stage cutaneous chemical carcinogenesis.

    PubMed

    Kwong, Bernice Y; Roberts, Scott J; Silberzahn, Tobias; Filler, Renata B; Neustadter, Jason H; Galan, Anjela; Reddy, Swapna; Lin, William M; Ellis, Peter D; Langford, Cordelia F; Hayday, Adrian C; Girardi, Michael

    2010-06-01

    T-pro are tumor-infiltrating TCRalphabeta(+)CD8(+) cells of reduced cytotoxic potential that promote experimental two-stage chemical cutaneous carcinogenesis. Toward understanding their mechanism of action, this study uses whole-genome expression analysis to compare T-pro with systemic CD8(+) T cells from multiple groups of tumor-bearing mice. T-pro show an overt T helper 17-like profile (high retinoic acid-related orphan receptor-(ROR)gammat, IL-17A, IL-17F; low T-bet and eomesodermin), regulatory potential (high FoxP3, IL-10, Tim-3), and transcripts encoding epithelial growth factors (amphiregulin, Gro-1, Gro-2). Tricolor flow cytometry subsequently confirmed the presence of TCRbeta(+) CD8(+) IL-17(+) T cells among tumor-infiltrating lymphocytes (TILs). Moreover, a time-course analysis of independent TIL isolates from papillomas versus carcinomas exposed a clear association of the "T-pro phenotype" with malignant progression. This molecular characterization of T-pro builds a foundation for elucidating the contributions of inflammation to cutaneous carcinogenesis, and may provide useful biomarkers for cancer immunotherapy in which the widely advocated use of tumor-specific CD8(+) cytolytic T cells should perhaps accommodate the cells' potential corruption toward the T-pro phenotype. The data are also likely germane to psoriasis, in which the epidermis may be infiltrated by CD8(+) IL-17-producing T cells.

  19. The Shh receptor Boc promotes progression of early medulloblastoma to advanced tumors.

    PubMed

    Mille, Frédéric; Tamayo-Orrego, Lukas; Lévesque, Martin; Remke, Marc; Korshunov, Andrey; Cardin, Julie; Bouchard, Nicolas; Izzi, Luisa; Kool, Marcel; Northcott, Paul A; Taylor, Michael D; Pfister, Stefan M; Charron, Frédéric

    2014-10-13

    During cerebellar development, Sonic hedgehog (Shh) signaling drives the proliferation of granule cell precursors (GCPs). Aberrant activation of Shh signaling causes overproliferation of GCPs, leading to medulloblastoma. Although the Shh-binding protein Boc associates with the Shh receptor Ptch1 to mediate Shh signaling, whether Boc plays a role in medulloblastoma is unknown. Here, we show that BOC is upregulated in medulloblastomas and induces GCP proliferation. Conversely, Boc inactivation reduces proliferation and progression of early medulloblastomas to advanced tumors. Mechanistically, we find that Boc, through elevated Shh signaling, promotes high levels of DNA damage, an effect mediated by CyclinD1. High DNA damage in the presence of Boc increases the incidence of Ptch1 loss of heterozygosity, an important event in the progression from early to advanced medulloblastoma. Together, our results indicate that DNA damage promoted by Boc leads to the demise of its own coreceptor, Ptch1, and consequently medulloblastoma progression. PMID:25263791

  20. Exposure to ACEI/ARB and β-Blockers Is Associated with Improved Survival and Decreased Tumor Progression and Hospitalizations in Patients with Advanced Colon Cancer1

    PubMed Central

    Engineer, Diana R; Burney, Basil O; Hayes, Teresa G; Garcia, Jose M

    2013-01-01

    BACKGROUND: Advanced colon cancer is associated with weight loss and decreased survival. Studies suggest that angiotensin and β-adrenergic blockade decrease colon cancer progression and ameliorate weight loss. This study aims to determine whether exposure to β-adrenoceptor blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) is associated with decreased mortality, tumor progression, number of hospitalizations, or weight loss in colorectal cancer. METHODS: Retrospective chart review included patients with advanced colorectal cancer. Survival, stage, hospitalization, cancer progression, cancer treatment, and body weight history were collected. RESULTS: Two hundred sixty-two of 425 new stage III to IV colorectal cancer cases reviewed met the study criteria. Those exposed to ACEI/ARB, BB, or both were more likely to have diabetes, hypertension, and stage III colorectal cancer. Adjusting for age, presence of hypertension and diabetes, and stage, ACEI/ARB + BB exposure was associated with decreased mortality compared to unexposed individuals [hazard ratio (HR) = 0.5, confidence interval (CI) = 0.29–0.85; Cox regression, P = .01]. Fewer total and cancer-related hospitalizations and decreased cancer progression in the ACEI/ARB + BB group versus the unexposed group (HR = 0.59, CI = 0.36–0.99, P = .047) were seen. Exposure did not affect weight changes; furthermore, body weight changes from both prediagnosis and at diagnosis to 6, 12, 18, and 24 months postdiagnosis predicted survival. CONCLUSIONS: We have observed an association between exposure to a combination of ACEI/ARB + BB and increased survival, decreased hospitalizations, and decreased tumor progression in advanced colorectal cancer. Future studies will be needed to replicate these results and generalize them to broader populations. Determination of causality will require a randomized controlled trial. PMID:24151534

  1. Exome sequencing identifies early gastric carcinoma as an early stage of advanced gastric cancer.

    PubMed

    Kang, Guhyun; Hwang, Woo Cheol; Do, In-Gu; Wang, Kai; Kang, So Young; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Kang, Won Ki; Jang, Jiryeon; Choi, Min-Gew; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung; Kim, Min Ji; Kim, Seonwoo; Park, Cheol Keun; Kim, Kyoung-Mee

    2013-01-01

    Gastric carcinoma is one of the major causes of cancer-related mortality worldwide. Early detection and treatment leads to an excellent prognosis in patients with early gastric cancer (EGC), whereas the prognosis of patients with advanced gastric cancer (AGC) remains poor. It is unclear whether EGCs and AGCs are distinct entities or whether EGCs are the beginning stages of AGCs. We performed whole exome sequencing of four samples from patients with EGC and compared the results with those from AGCs. In both EGCs and AGCs, a total of 268 genes were commonly mutated and independent mutations were additionally found in EGCs (516 genes) and AGCs (3104 genes). A higher frequency of C>G transitions was observed in intestinal-type compared to diffuse-type carcinomas (P = 0.010). The DYRK3, GPR116, MCM10, PCDH17, PCDHB1, RDH5 and UNC5C genes are recurrently mutated in EGCs and may be involved in early carcinogenesis.

  2. Photoacoustic microscopy of arteriovenous shunts and blood diffusion in early-stage tumors

    NASA Astrophysics Data System (ADS)

    Yeh, Chenghung; Liang, Jinyang; Zhou, Yong; Hu, Song; Sohn, Rebecca E.; Arbeit, Jeffrey M.; Wang, Lihong V.

    2016-02-01

    Angiogenesis in a tumor region creates arteriovenous (AV) shunts that cause an abnormal venous blood oxygen saturation (sO2) distribution. Here, we applied optical-resolution photoacoustic microscopy to study the AV shunting in vivo. First, we built a phantom to image sO2 distribution in a vessel containing converged flows from two upstream blood vessels with different sO2 values. The phantom experiment showed that the blood from the two upstream vessels maintained a clear sO2 boundary for hundreds of seconds, which is consistent with our theoretical analysis using a diffusion model. Next, we xenotransplanted O-786 tumor cells in mouse ears and observed abnormal sO2 distribution in the downstream vein from the AV shunts in vivo. Finally, we identified the tumor location by tracing the sO2 distribution. Our study suggests that abnormal sO2 distribution induced by the AV shunts in the vessel network may be used as a new functional benchmark for early tumor detection.

  3. Hyperandrogenism produced by ovarian tumors in women at different life stages.

    PubMed

    Fux-Otta, Carolina; Szafryk de Mereshian, Paula; López de Corominas, Mónica; Fuster, Margarita; López, Carlos R

    2014-01-01

    Objetivo: evaluar las diferentes manifestaciones del hiperandrogenismo tumoral de origen ovárico en distintos grupos etarios. Diseño: reporte de casos.Lugar de trabajo: centros académicos.Pacientes: son reportadas tres pacientes con exceso de andrógenos. Resultados: describimos una paciente de 10 años con hiperandrogenemia y signos de masculinización secundarios a un tumor de células de Leydig; otra paciente, en edad fértil, con un tumor carcinoide de ovario asociado a hiperplasia estromal que se manifestó con signos de masa abdominal y de virilización. El tercer caso una mujer, en etapa postmenopáusica con alopecia severa, tenía un tumor de células esteroideas, raro en este grupo etario. onclusión: la evaluación de una mujer con signos y síntomas de virilización debe incluir una detallada historia clínica, examen físico y apropiados dosajes hormonales, especialmente si existe dificultad en establecer su origen cuando los estudios imagenológicos son normales.

  4. Single stage, low noise, advanced technology fan. Volume 5: Fan acoustics. Section 1: Results and analysis

    NASA Technical Reports Server (NTRS)

    Jutras, R. R.

    1976-01-01

    The acoustic tests and data analysis for a 0.508-scale fan vehicle of a 111,300 newton (25,000 pound) thrust, full-size engine, which would have application on an advanced transport aircraft, is described. The single-stage advanced technology fan was designed to a pressure ratio of 1.8 at a tip speed of 503 m/sec (1,650 ft/sec) to achieve the desired pressure ratio in a single-stage fan with low radius ratio (0.38), and to maintain adequate stall margin. The fan has 44 tip-shrouded rotor blades and 90 outlet guide vanes. The two basic approaches taken in the acoustic design were: (1) minimization of noise at the source, and (2) suppression of the generated noise in the inlet and bypass exhaust duct. Suppression of the generated noise was accomplished in the inlet through use of the hybrid concept (wall acoustic treatment plus airflow acceleration suppression) and in the exhaust duct with extensive acoustic treatment including a splitter. The goal of the design was attainment of twenty effective perceived noise decibels (20 EPNdB) below current Federal Air Regulation noise standards for a full-scale fan at the takeoff, cutback, and approach conditions. The suppression goal of FAR 36-20 was not reached, but improvements in the technology of both front and aft fan-noise suppression were realized. The suppressed fan noise was shown to be consistent with the proposed federal regulation on aircraft noise.

  5. Generation of tumor immunity by bone marrow-derived dendritic cells correlates with dendritic cell maturation stage.

    PubMed

    Labeur, M S; Roters, B; Pers, B; Mehling, A; Luger, T A; Schwarz, T; Grabbe, S

    1999-01-01

    Bone marrow-derived dendritic cells (BmDC) are potent APC and can promote antitumor immunity in mice when pulsed with tumor Ag. This study aimed to define the culture conditions and maturation stages of BmDC that enable them to optimally function as APC in vivo. BmDC cultured under various conditions (granulocyte-macrophage CSF (GM-CSF) or GM-CSF plus IL-4 alone or in combination with Flt3 ligand, TNF-alpha, LPS, or CD40 ligand (CD40L)) were analyzed morphologically, phenotypically, and functionally and were tested for their ability to promote prophylactic and/or therapeutic antitumor immunity. Each of the culture conditions generated typical BmDC. Whereas cells cultured in GM-CSF alone were functionally immature, cells incubated with CD40L or LPS were mature BmDC, as evident by morphology, capacity to internalize Ag, migration into regional lymph nodes, IL-12 secretion, and alloantigen or peptide Ag presentation in vitro. The remaining cultures exhibited intermediate dendritic cell maturation. The in vivo Ag-presenting capacity of BmDC was compared with respect to induction of both protective tumor immunity and immunotherapy of established tumors, using the poorly immunogenic squamous cell carcinoma, KLN205. In correspondence to their maturation stage, BmDC cultured in the presence of CD40L exhibited the most potent immunostimulatory effects. In general, although not entirely, the capacity of BmDC to induce an antitumor immune response in vivo correlated to their degree of maturation. The present data support the clinical use of mature, rather than immature, tumor Ag-pulsed dendritic cells as cancer vaccines and identifies CD40L as a potent stimulus to enhance their in vivo Ag-presenting capacity.

  6. The receptor for advanced glycation end products influences the expression of its S100 protein ligands in melanoma tumors.

    PubMed

    Meghnani, Varsha; Wagh, Anil; Indurthi, Venkata S K; Koladia, Mohit; Vetter, Stefan W; Law, Benedict; Leclerc, Estelle

    2014-12-01

    Recent studies have suggested that the receptor for advanced glycation end products (RAGE) participates in melanoma progression by promoting tumor growth. However, the mechanisms of RAGE activation in melanoma tumors are not clearly understood. To get deeper insights into these mechanisms, we transfected a melanoma cell line, which was established from a human melanoma primary tumor, with RAGE, and studied the effect of RAGE overexpression on cell proliferation and migration in vitro. We observed that overexpression of RAGE in these cells not only resulted in significantly increased migration rates compared to control cells, but also in decreased proliferation rates (Meghnani et al., 2014). In the present study, we compared the growth of xenograft tumors established from RAGE overexpressing WM115 cells, to that of control cells. We observed that when implanted in mice, RAGE overexpressing cells generated tumors faster than control cells. Analysis of protein tumor extracts showed increased levels of the RAGE ligands S100B, S100A2, S100A4, S100A6 and S100A10 in RAGE overexpressing tumors compared to control tumors. We show that the tumor growth was significantly reduced when the mice were treated with anti-RAGE antibodies, suggesting that RAGE, and probably several S100 proteins, were involved in tumor growth. We further demonstrate that the anti-RAGE antibody treatment significantly enhanced the efficacy of the alkylating drug dacarbazine in reducing the growth rate of RAGE overexpressing tumors. PMID:25310905

  7. Immunomodulation by MYB is associated with tumor relapse in patients with early stage colorectal cancer.

    PubMed

    Millen, Rosemary; Malaterre, Jordane; Cross, Ryan S; Carpinteri, Sandra; Desai, Jayesh; Tran, Ben; Darcy, Phillip; Gibbs, Peter; Sieber, Oliver; Zeps, Nikolajs; Waring, Paul; Fox, Stephen; Pereira, Lloyd; Ramsay, Robert G

    2016-07-01

    The presence of tumor immune infiltrating cells (TILs), particularly CD8(+) T-cells, is a robust predictor of outcome in patients with colorectal cancer (CRC). We revisited TIL abundance specifically in patients with microsatellite stable (MSS) CRC without evidence of lymph node or metastatic spread. Examination of the density of CD8(+) T-cells in primary tumors in the context of other pro-oncogenic markers was performed to investigate potential regulators of TILs. Two independent cohorts of patients with MSS T2-4N0M0 CRC, enriched for cases with atypical relapse, were investigated. We quantified CD8(+) and CD45RO(+) -TILs, inflammatory markers, NFkBp65, pStat3, Cyclo-oxygenase-2 (COX2) and GRP78 as well as transcription factors (TF), β-catenin and MYB. High CD8(+) TILs correlated with a better relapse-free survival in both cohorts (p = 0.002) with MYB and its target gene, GRP78 being higher in the relapse group (p = 0.001); no difference in pSTAT3 and p65 was observed. A mouse CRC (CT26) model was employed to evaluate the effect of MYB on GRP78 expression as well as T-cell infiltration. MYB over-expressing in CT26 cells increased GRP78 expression and the analysis of tumor-draining lymph nodes adjacent to tumors showed reduced T-cell activation. Furthermore, MYB over-expression reduced the efficacy of anti-PD-1 to modulate CT26 tumor growth. This high MYB and GRP78 show a reciprocal relationship with CD8(+) TILs which may be useful refining the prediction of patient outcome. These data reveal a new immunomodulatory function for MYB suggesting a basis for further development of anti-GRP78 and/or anti-MYB therapies. PMID:27622014

  8. Immunomodulation by MYB is associated with tumor relapse in patients with early stage colorectal cancer

    PubMed Central

    Millen, Rosemary; Malaterre, Jordane; Cross, Ryan S.; Carpinteri, Sandra; Desai, Jayesh; Tran, Ben; Darcy, Phillip; Gibbs, Peter; Sieber, Oliver; Zeps, Nikolajs; Waring, Paul; Fox, Stephen; Pereira, Lloyd; Ramsay, Robert G.

    2016-01-01

    ABSTRACT The presence of tumor immune infiltrating cells (TILs), particularly CD8+ T-cells, is a robust predictor of outcome in patients with colorectal cancer (CRC). We revisited TIL abundance specifically in patients with microsatellite stable (MSS) CRC without evidence of lymph node or metastatic spread. Examination of the density of CD8+ T-cells in primary tumors in the context of other pro-oncogenic markers was performed to investigate potential regulators of TILs. Two independent cohorts of patients with MSS T2-4N0M0 CRC, enriched for cases with atypical relapse, were investigated. We quantified CD8+ and CD45RO+ -TILs, inflammatory markers, NFkBp65, pStat3, Cyclo-oxygenase-2 (COX2) and GRP78 as well as transcription factors (TF), β-catenin and MYB. High CD8+ TILs correlated with a better relapse-free survival in both cohorts (p = 0.002) with MYB and its target gene, GRP78 being higher in the relapse group (p = 0.001); no difference in pSTAT3 and p65 was observed. A mouse CRC (CT26) model was employed to evaluate the effect of MYB on GRP78 expression as well as T-cell infiltration. MYB over-expressing in CT26 cells increased GRP78 expression and the analysis of tumor-draining lymph nodes adjacent to tumors showed reduced T-cell activation. Furthermore, MYB over-expression reduced the efficacy of anti-PD-1 to modulate CT26 tumor growth. This high MYB and GRP78 show a reciprocal relationship with CD8+ TILs which may be useful refining the prediction of patient outcome. These data reveal a new immunomodulatory function for MYB suggesting a basis for further development of anti-GRP78 and/or anti-MYB therapies. PMID:27622014

  9. Immunomodulation by MYB is associated with tumor relapse in patients with early stage colorectal cancer

    PubMed Central

    Millen, Rosemary; Malaterre, Jordane; Cross, Ryan S.; Carpinteri, Sandra; Desai, Jayesh; Tran, Ben; Darcy, Phillip; Gibbs, Peter; Sieber, Oliver; Zeps, Nikolajs; Waring, Paul; Fox, Stephen; Pereira, Lloyd; Ramsay, Robert G.

    2016-01-01

    ABSTRACT The presence of tumor immune infiltrating cells (TILs), particularly CD8+ T-cells, is a robust predictor of outcome in patients with colorectal cancer (CRC). We revisited TIL abundance specifically in patients with microsatellite stable (MSS) CRC without evidence of lymph node or metastatic spread. Examination of the density of CD8+ T-cells in primary tumors in the context of other pro-oncogenic markers was performed to investigate potential regulators of TILs. Two independent cohorts of patients with MSS T2-4N0M0 CRC, enriched for cases with atypical relapse, were investigated. We quantified CD8+ and CD45RO+ -TILs, inflammatory markers, NFkBp65, pStat3, Cyclo-oxygenase-2 (COX2) and GRP78 as well as transcription factors (TF), β-catenin and MYB. High CD8+ TILs correlated with a better relapse-free survival in both cohorts (p = 0.002) with MYB and its target gene, GRP78 being higher in the relapse group (p = 0.001); no difference in pSTAT3 and p65 was observed. A mouse CRC (CT26) model was employed to evaluate the effect of MYB on GRP78 expression as well as T-cell infiltration. MYB over-expressing in CT26 cells increased GRP78 expression and the analysis of tumor-draining lymph nodes adjacent to tumors showed reduced T-cell activation. Furthermore, MYB over-expression reduced the efficacy of anti-PD-1 to modulate CT26 tumor growth. This high MYB and GRP78 show a reciprocal relationship with CD8+ TILs which may be useful refining the prediction of patient outcome. These data reveal a new immunomodulatory function for MYB suggesting a basis for further development of anti-GRP78 and/or anti-MYB therapies.

  10. Dual-Fuel Propulsion in Single-Stage Advanced Manned Launch System Vehicle

    NASA Technical Reports Server (NTRS)

    Lepsch, Roger A., Jr.; Stanley, Douglas O.; Unal, Resit

    1995-01-01

    As part of the United States Advanced Manned Launch System study to determine a follow-on, or complement, to the Space Shuttle, a reusable single-stage-to-orbit concept utilizing dual-fuel rocket propulsion has been examined. Several dual-fuel propulsion concepts were investigated. These include: a separate-engine concept combining Russian RD-170 kerosene-fueled engines with space shuttle main engine-derivative engines: the kerosene- and hydrogen-fueled Russian RD-701 engine; and a dual-fuel, dual-expander engine. Analysis to determine vehicle weight and size characteristics was performed using conceptual-level design techniques. A response-surface methodology for multidisciplinary design was utilized to optimize the dual-fuel vehicles with respect to several important propulsion-system and vehicle design parameters, in order to achieve minimum empty weight. The tools and methods employed in the analysis process are also summarized. In comparison with a reference hydrogen- fueled single-stage vehicle, results showed that the dual-fuel vehicles were from 10 to 30% lower in empty weight for the same payload capability, with the dual-expander engine types showing the greatest potential.

  11. Single stage, low noise, advanced technology fan. Volume 1: Aerodynamic design

    NASA Technical Reports Server (NTRS)

    Sullivan, T. J.; Younghans, J. L.; Little, D. R.

    1976-01-01

    The aerodynamic design for a half-scale fan vehicle, which would have application on an advanced transport aircraft, is described. The single stage advanced technology fan was designed to a pressure ratio of 1.8 at a tip speed of 503 m/sec 11,650 ft/sec). The fan and booster components are designed in a scale model flow size convenient for testing with existing facility and vehicle hardware. The design corrected flow per unit annulus area at the fan face is 215 kg/sec sq m (44.0 lb m/sec sq ft) with a hub-tip ratio of 0.38 at the leading edge of the fan rotor. This results in an inlet corrected airflow of 117.9 kg/sec (259.9 lb m/sec) for the selected rotor tip diameter if 90.37 cm (35.58 in.). The variable geometry inlet is designed utilizing a combination of high throat Mach number and acoustic treatment in the inlet diffuser for noise suppression (hybrid inlet). A variable fan exhaust nozzle was assumed in conjunction with the variable inlet throat area to limit the required area change of the inlet throat at approach and hence limit the overall diffusion and inlet length. The fan exit duct design was primarily influenced by acoustic requirements, including length of suppressor wall treatment; length, thickness and position on a duct splitter for additional suppressor treatment; and duct surface Mach numbers.

  12. Non-functional neuroendocrine tumors of the pancreas: Advances in diagnosis and management

    PubMed Central

    Cloyd, Jordan M; Poultsides, George A

    2015-01-01

    Nonfunctional neuroendocrine tumors of the pancreas (NF-PNETs) are a heterogeneous group of neoplasms. Although rare, the incidence of NF-PNETs is increasing significantly. The classification of PNETs has evolved over the past decades and is now based on a proliferation grading system. While most NF-PNETs are slow growing, tumors with more aggressive biology may become incurable once they progress to unresectable metastatic disease. Tumors of higher grade can be suspected preoperatively based on the presence of calcifications, hypoenhancement on arterial phase computed tomography, positron emission technology avidity and lack of octreotide scan uptake. Surgery is the only curative treatment and is recommended for most patients for whom complete resection is possible. Liver-directed therapies (thermal ablation, transarterial embolization) can be useful in controlling unresectable hepatic metastatic disease. In the presence of unresectable progressive disease, somatostatin analogues, everolimus and sunitinib can prolong progression-free survival. This article provides a comprehensive review of NF-PNETs with special emphasis on recent advances in diagnosis and management. PMID:26327759

  13. pH-Responsive Core-Shell Structured Nanoparticles for Triple-Stage Targeted Delivery of Doxorubicin to Tumors.

    PubMed

    Han, Lu; Tang, Cui; Yin, Chunhua

    2016-09-14

    The application of cytotoxic chemotherapeutics in cancer therapy has been largely restricted by their lack of selectivity. Despite the existence of numerous targeted delivery systems, it is practically challenging to develop one single system to simultaneously cover tumor-targeted delivery of chemotherapeutics at the tissue, cellular, and subcellular levels. To solve this problem, pH-responsive core-shell structured nanoparticles (CSNPs) were self-assembled in this study to provide triple-stage targeted delivery of doxorubicin (DOX) from the injection site to the nuclei of cancer cells. Amino-functionalized mesoporous silica nanoparticles (MSN) were doubly modified with TAT peptide and acid-cleavable polyethylene glycol (PEG) as the DOX-loaded cationic core. The anionic shell was constituted by galactose-modified poly(allylamine hydrochloride)-citraconic anhydride, a hepato-carcinoma-targeting polymer with charge-reversible property. In vitro results showed that PEG effectively reduced protein adsorption and phagocytic capture of CSNPs in the circulating blood (pH 7.4), thus facilitating passive accumulation in tumors (tissue level). Following PEG detachment via acidic hydrolysis in tumor microenvironment (pH 6.5), the exposed galactose ligands endowed CSNPs with active internalization into hepato-carcinoma cells (cellular level). Afterward, the acidity in endosomes and lysosomes (pH 5.0) triggered the conversion of anionic shell into positive charges, leading to core-shell disassembly and subsequent TAT-mediated delivery of DOX to the nuclei (subcellular level). Importantly, the efficiencies of each targeting moiety were nicely preserved when combining together in CSNPs. As a result, improved tumorous distribution and potent therapeutic efficacy of CSNPs were noted in tumor-bearing mice at a relatively low dose. CSNPs therefore provide an efficient and nontoxic platform for the targeted delivery of antitumor drugs. PMID:27558413

  14. pH-Responsive Core-Shell Structured Nanoparticles for Triple-Stage Targeted Delivery of Doxorubicin to Tumors.

    PubMed

    Han, Lu; Tang, Cui; Yin, Chunhua

    2016-09-14

    The application of cytotoxic chemotherapeutics in cancer therapy has been largely restricted by their lack of selectivity. Despite the existence of numerous targeted delivery systems, it is practically challenging to develop one single system to simultaneously cover tumor-targeted delivery of chemotherapeutics at the tissue, cellular, and subcellular levels. To solve this problem, pH-responsive core-shell structured nanoparticles (CSNPs) were self-assembled in this study to provide triple-stage targeted delivery of doxorubicin (DOX) from the injection site to the nuclei of cancer cells. Amino-functionalized mesoporous silica nanoparticles (MSN) were doubly modified with TAT peptide and acid-cleavable polyethylene glycol (PEG) as the DOX-loaded cationic core. The anionic shell was constituted by galactose-modified poly(allylamine hydrochloride)-citraconic anhydride, a hepato-carcinoma-targeting polymer with charge-reversible property. In vitro results showed that PEG effectively reduced protein adsorption and phagocytic capture of CSNPs in the circulating blood (pH 7.4), thus facilitating passive accumulation in tumors (tissue level). Following PEG detachment via acidic hydrolysis in tumor microenvironment (pH 6.5), the exposed galactose ligands endowed CSNPs with active internalization into hepato-carcinoma cells (cellular level). Afterward, the acidity in endosomes and lysosomes (pH 5.0) triggered the conversion of anionic shell into positive charges, leading to core-shell disassembly and subsequent TAT-mediated delivery of DOX to the nuclei (subcellular level). Importantly, the efficiencies of each targeting moiety were nicely preserved when combining together in CSNPs. As a result, improved tumorous distribution and potent therapeutic efficacy of CSNPs were noted in tumor-bearing mice at a relatively low dose. CSNPs therefore provide an efficient and nontoxic platform for the targeted delivery of antitumor drugs.

  15. Biomarkers in Tissue Samples From Patients With High-Risk Wilms Tumor

    ClinicalTrials.gov

    2016-05-17

    Clear Cell Sarcoma of the Kidney; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Rhabdoid Tumor of the Kidney; Stage I Wilms Tumor; Stage II Wilms Tumor; Stage III Wilms Tumor; Stage IV Wilms Tumor; Stage V Wilms Tumor

  16. Associating liver partition with portal vein ligation and staged hepatectomy (ALPPS) for the treatment of liver tumors in children.

    PubMed

    Wiederkehr, Julio Cesar; Avilla, Sylvio Gilberto; Mattos, Elisângela; Coelho, Izabel Meister; Ledesma, Jorge Alberto; Conceição, Alexandra Fernandes; Wiederkehr, Henrique Aguiar; Wiederkehr, Barbara Aguiar

    2015-07-01

    Resection is the only curative treatment option for primary and secondary malignant tumors of the liver. Although curative resection is associated with long-term survival rates, it can only be performed in 10% of patients with primary tumors and 25% of patients with liver metastases. Liver insufficiency is one of the most serious postoperative complications of patients undergoing extensive liver resections. When total liver resection is necessary liver transplant is mandatory, with the burden of long-term immunosuppression and its complications. Among several different strategies to increase the resectability of liver tumors, portal vein occlusion (embolization or ligature), bilateral tumor resection in two stages, and resection combined with loco regional therapy are the most popular. A new strategy for patients with marginally resectable liver tumors previously considered to be unresectable was formally reported by Baumgart et al. in 2011, originally developed by Hans Schlitt in 2007. This technique consists of a two-staged hepatectomy with initial portal vein ligation and in situ splitting of the liver parenchyma, and it is known as ALPPS (associating liver partition with portal vein ligation for staged hepatectomy). The aim of this study is to present the first series of pediatric patients with marginally resectable liver tumors previously considered to be unresectable treated with two-stage hepatectomy with initial portal vein ligation and in situ splitting of the liver parenchyma. Two patients were diagnosed with hepatoblastoma, and one each with rhabdomyosarcoma, hepatocellular carcinoma, and nodular focal hyperplasia. ALPPS technique was considered whenever the future liver remnant (FLR) was 40% or less of the total liver volume (TLV) determined by CT or MRI scans. The ratio of FLR to TLV before the first procedure ranged from 0.15 to 0.38, with a mean±sd of 0.253±0.07. In all patients, a rapid growth of the FLR was observed. Estimates of the FRL volume

  17. Phase I clinical study with multiple peptide vaccines in combination with tetanus toxoid and GM-CSF in advanced-stage HLA-A*0201-positive melanoma patients.

    PubMed

    Bins, Adriaan; Mallo, Henk; Sein, Johan; van den Bogaard, Colette; Nooijen, Willem; Vyth-Dreese, Florry; Nuijen, Bastiaan; de Gast, Gijsbert C; Haanen, John B A G

    2007-01-01

    Successful induction of functional tumor-specific T cells by peptide vaccination in animal models has resulted in many clinical trials to test this approach in advanced-stage melanoma patients. In this phase I clinical trial, 11 end-stage melanoma patients were vaccinated intradermally with 3 peptides: MART-1(26-35) E27L (ELAGIGILTV), tyrosinase(368-376) N375Q (YMDGTMSQV), and gp100(209-217) T210M (IMQVPFSV), admixed with tetanus toxoid and granulocyte-monocyte colony stimulating factor. The peptide vaccine was well tolerated at all tested doses, and led to grade 1-2 toxicity only. Although all patients did show a rise in antitetanus IgG titers, in only 3 patients peptide-specific CD8 T-cells were induced. In 2 cases, the response was directed against MART-1(26-35) and consisted of 0.2% and 3.3% of the CD8 population; however, in both instances these cells did not produce interferon-gamma on stimulation with the unmodified peptide. The third patient mounted a small (0.1%) response against gp100. In a fourth patient, a nonfunctional tyrosinase-specific response (0.6%) was found that was present before vaccination, but was not affected in size nor in function by the vaccine. None of the 11 patients responded clinically according to response evaluation criteria in solid tumors criteria. Although this study is a small scale phase I clinical trial, the efficacy that was observed was disappointingly low. In accordance with previously published peptide vaccination studies, these results add to the increasing evidence that peptide vaccination in itself is not potent enough as an effective melanoma immunotherapy in advanced-stage patients.

  18. 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

  19. Trousseau’s syndrome in a patient with advanced stage gastric cancer

    PubMed Central

    Chien, Tai-Long; Rau, Kung-Ming; Chung, Wen-Jung; Tai, Wei-Chen; Wang, Shih-Ho; Chiu, Yi-Chun; Wu, Keng-Liang; Chou, Yeh-Pin; Wu, Chia-Che; Chen, Yen-Hao; Chuah, Seng-Kee

    2015-01-01

    Patients with cancer are at high risk for thrombotic events, which are known collectively as Trousseau’s syndrome. Herein, we report a 66-year-old male patient who was diagnosed with terminal stage gastric cancer and liver metastasis and who had an initial clinical presentation of upper gastrointestinal bleeding. Acute ischemia of the left lower leg that resulted in gangrenous changes occurred during admission. Subsequent angiography of the left lower limb was then performed. This procedure revealed arterial thrombosis of the left common iliac artery with extension to the external iliac artery, the left common iliac artery, the posterior tibial artery, and the peroneal artery, which were occluded by thrombi. Aspiration of the thrombi demonstrated that these were not tumor thrombi. The interesting aspect of our case was that the disease it presented as arterial thrombotic events, which may correlate with gastric adenocarcinoma. In summary, we suggested that the unexplained thrombotic events might be one of the initial presentations of occult malignancy and that thromboprophylaxis should always be considered. PMID:26379411

  20. Targeting receptor for advanced glycation end products (RAGE) expression induces apoptosis and inhibits prostate tumor growth

    SciTech Connect

    Elangovan, Indira; Thirugnanam, Sivasakthivel; Chen, Aoshuang; Zheng, Guoxing; Bosland, Maarten C.; Kajdacsy-Balla, Andre; Gnanasekar, Munirathinam

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer Targeting RAGE by RNAi induces apoptosis in prostate cancer cells. Black-Right-Pointing-Pointer Silencing RAGE expression abrogates rHMGB1 mediated cell proliferation. Black-Right-Pointing-Pointer Down regulation of RAGE by RNAi inhibits PSA secretion of prostate cancer cells. Black-Right-Pointing-Pointer Knock down of RAGE abrogates prostate tumor growth in vivo. Black-Right-Pointing-Pointer Disruption of RAGE expression in prostate tumor activates death receptors. -- Abstract: Expression of receptor for advanced glycation end products (RAGE) plays a key role in the progression of prostate cancer. However, the therapeutic potential of targeting RAGE expression in prostate cancer is not yet evaluated. Therefore in this study, we have investigated the effects of silencing the expression of RAGE by RNAi approach both in vitro and in vivo. The results of this study showed that down regulation of RAGE expression by RNAi inhibited the cell proliferation of androgen-dependent (LNCaP) and androgen-independent (DU-145) prostate cancer cells. Furthermore, targeting RAGE expression resulted in apoptotic elimination of these prostate cancer cells by activation of caspase-8 and caspase-3 death signaling. Of note, the levels of prostate specific antigen (PSA) were also reduced in LNCaP cells transfected with RAGE RNAi constructs. Importantly, the RAGE RNAi constructs when administered in nude mice bearing prostate tumors, inhibited the tumor growth by targeting the expression of RAGE, and its physiological ligand, HMGB1 and by up regulating death receptors DR4 and DR5 expression. Collectively, the results of this study for the first time show that targeting RAGE by RNAi may be a promising alternative therapeutic strategy for treating prostate cancer.

  1. [The pathomorphology of complicated colorectal cancer and the stages in the development of the tumor process].

    PubMed

    Iarŭmov, N; Popkhristova, E; Viiachki, I; Terziev, I; Gachev, N

    1999-01-01

    A comprehensive pathomorphological assessment is done in 385 patients presenting complicated colorectal carcinoma, covering the period 1990 through 1995. The patients are distributed in 4 groups according to stage, with those in stage III being the most numerous--141 cases. The growth pattern of the neoplasm is as follows: exophytic growth--110 cases, ulcerous growth--57, cup-like growth--13, and endophytic growth--205 cases. On establishing metastatic lymph nodes within I and II lymph collectors, prophylactic postoperative chemo- and immunotherapy are undertaken. In case of lymph nodes present in III lymph collector, the operation is taken to be relatively radical, and for that reason chemo- and immunotherapy assume a therapeutic character.

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

    PubMed

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

    2011-08-01

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

  3. Coexistence of malignant phyllodes tumor and her2-positive locally advanced breast cancer in distinct breasts: A case report

    PubMed Central

    Sato, Tomoi; Muto, Ichiro; Sakai, Takeshi

    2016-01-01

    Introduction Phyllodes tumor of the breast is a rare biphasic neoplasm, accounting for less than 1% of all breast tumors. Coexistence of phyllodes tumor and breast cancer in distinct breasts is extremely rare. Case presentation A 47-year-old Japanese woman presented with bilateral breast lumps. A HER2-positive, unresectable invasive carcinoma in the right breast and fibroadenoma in the left were diagnosed via core needle biopsy. During chemotherapy with anti-HER2 therapy, the breast cancer shrank quickly, while the left breast lump suddenly enlarged. Under a diagnosis of malignant neoplasm of the breast, left mastectomy was performed. Malignant phyllodes tumor was diagnosed by postoperative histological examination and recurred in multiple areas as early as 2 months after surgery. Discussion Only 10 cases of coexisting phyllodes tumor and breast cancer in distinct breasts have been reported in the English literature. Phyllodes tumor associated with breast cancer in distinct breasts tends to be malignant. This is the first case of phyllodes tumor rapidly enlarging during anti-HER2 chemotherapy for locally advanced HER2-positive breast cancer. Conclusion Even during effective treatment of advanced or recurrent breast cancer, attention should also be paid to the contralateral breast for the possible association of a second malignancy such as phyllodes tumor. PMID:26773878

  4. Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors

    ClinicalTrials.gov

    2016-10-05

    Recurrent Colorectal Carcinoma; Recurrent Lung Carcinoma; Recurrent Pancreatic Carcinoma; Solid Neoplasm; Stage III Lung Cancer; Stage III Pancreatic Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Colorectal Cancer; Stage IV Lung Cancer; Stage IV Pancreatic Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

  5. Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-10-19

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  6. TNM staging of pancreatic neuroendocrine tumors: an observational analysis and comparison by both AJCC and ENETS systems from 1 single institution.

    PubMed

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

    2015-03-01

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

  7. Clinical decision support systems for brain tumor characterization using advanced magnetic resonance imaging techniques.

    PubMed

    Tsolaki, Evangelia; Kousi, Evanthia; Svolos, Patricia; Kapsalaki, Efthychia; Theodorou, Kyriaki; Kappas, Constastine; Tsougos, Ioannis

    2014-04-28

    In recent years, advanced magnetic resonance imaging (MRI) techniques, such as magnetic resonance spectroscopy, diffusion weighted imaging, diffusion tensor imaging and perfusion weighted imaging have been used in order to resolve demanding diagnostic problems such as brain tumor characterization and grading, as these techniques offer a more detailed and non-invasive evaluation of the area under study. In the last decade a great effort has been made to import and utilize intelligent systems in the so-called clinical decision support systems (CDSS) for automatic processing, classification, evaluation and representation of MRI data in order for advanced MRI techniques to become a part of the clinical routine, since the amount of data from the aforementioned techniques has gradually increased. Hence, the purpose of the current review article is two-fold. The first is to review and evaluate the progress that has been made towards the utilization of CDSS based on data from advanced MRI techniques. The second is to analyze and propose the future work that has to be done, based on the existing problems and challenges, especially taking into account the new imaging techniques and parameters that can be introduced into intelligent systems to significantly improve their diagnostic specificity and clinical application.

  8. Two-stage model of radon-induced malignant lung tumors in rats: effects of cell killing

    NASA Technical Reports Server (NTRS)

    Luebeck, E. G.; Curtis, S. B.; Cross, F. T.; Moolgavkar, S. H.

    1996-01-01

    A two-stage stochastic model of carcinogenesis is used to analyze lung tumor incidence in 3750 rats exposed to varying regimens of radon carried on a constant-concentration uranium ore dust aerosol. New to this analysis is the parameterization of the model such that cell killing by the alpha particles could be included. The model contains parameters characterizing the rate of the first mutation, the net proliferation rate of initiated cells, the ratio of the rates of cell loss (cell killing plus differentiation) and cell division, and the lag time between the appearance of the first malignant cell and the tumor. Data analysis was by standard maximum likelihood estimation techniques. Results indicate that the rate of the first mutation is dependent on radon and consistent with in vitro rates measured experimentally, and that the rate of the second mutation is not dependent on radon. An initial sharp rise in the net proliferation rate of initiated cell was found with increasing exposure rate (denoted model I), which leads to an unrealistically high cell-killing coefficient. A second model (model II) was studied, in which the initial rise was attributed to promotion via a step function, implying that it is due not to radon but to the uranium ore dust. This model resulted in values for the cell-killing coefficient consistent with those found for in vitro cells. An "inverse dose-rate" effect is seen, i.e. an increase in the lifetime probability of tumor with a decrease in exposure rate. This is attributed in large part to promotion of intermediate lesions. Since model II is preferable on biological grounds (it yields a plausible cell-killing coefficient), such as uranium ore dust. This analysis presents evidence that a two-stage model describes the data adequately and generates hypotheses regarding the mechanism of radon-induced carcinogenesis.

  9. Leser-Trélat Sign in Tumor-Stage Mycosis Fungoides.

    PubMed

    Rowe, Brandon; Shevchenko, Alina; Yosipovitch, Gil

    2016-01-01

    A 71-year-old man presented with numerous pruritic seborrheic keratoses, with an eruptive onset over the course of 3 months. At presentation, he was also found to have hypopigmented tumors diffusely scattered throughout his body that were found to be mycosis fungoides on histologic examination. A theory regarding the pathophysiology of the development of eruptive seborrheic keratoses in the presence of mycosis fungoides is briefly discussed and 10 previous case reports of the Leser-Trélat sign in the setting of mycosis fungoides are reviewed.

  10. A block matching-based registration algorithm for localization of locally advanced lung tumors

    SciTech Connect

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2014-04-15

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm{sup 3}), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0

  11. A block matching-based registration algorithm for localization of locally advanced lung tumors

    PubMed Central

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2014-01-01

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm3), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%; p < 0.001). Left

  12. Expression patterns of the immunomodulatory enzyme arginase 1 in blood, lymph nodes and tumor tissue of early-stage breast cancer patients.

    PubMed

    de Boniface, Jana; Mao, Yumeng; Schmidt-Mende, Jan; Kiessling, Rolf; Poschke, Isabel

    2012-11-01

    Arginase 1 (ARG1) is an important enzyme in amino acid metabolism that also exerts immunoregulatory function. High ARG1 expression, which is associated with cell cycle arrest and functional unresponsiveness in T cells, has been observed after trauma, infections and in cancer patients. We studied ARG1 expression in early-stage breast cancer patients (stage 1, n = 20; stage 2, n = 23) by multi-parametric flow cytometry and immunohistochemistry. Despite a low tumor burden, ARG1 expression was significantly increased in blood-derived myeloid cells of breast cancer patients compared with healthy controls. The ARG1(hi) myeloid population in the blood of cancer patients contained a high frequency of CD14(+) cells and was, therefore, distinct from the granulocytic ARG1(+) population observed in control individuals. Expression of ARG1 in patient blood cells correlated with tumor grade and was significantly reduced after surgical tumor removal. ARG1(+) myeloid cells could also be detected in tumors and tumor-draining lymph nodes, where ARG1 expression levels exceeded those measured in the blood. We conclude that even patients with early-stage breast cancer exhibit tumor-related changes of ARG1 expression. The level of ARG1-mediated immunomodulation at this early stage remains to be determined. However, high ARG1 expression is likely to interfere with antitumor T-cell responses and immunotherapeutic interventions, making ARG1 or its downstream effector interesting therapeutic targets.

  13. Oxidized low-density lipoprotein is associated with advanced-stage prostate cancer.

    PubMed

    Wan, Fangning; Qin, Xiaojian; Zhang, Guiming; Lu, Xiaolin; Zhu, Yao; Zhang, Hailiang; Dai, Bo; Shi, Guohai; Ye, Dingwei

    2015-05-01

    Clinical and epidemiological data suggest coronary artery disease shares etiology with prostate cancer (PCa). The aim of this work was to assess the effects of several serum markers reported in cardiovascular disease on PCa. Serum markers (oxidized low-density lipoprotein [ox-LDL], apolipoprotein [apo] B100, and apoB48) in peripheral blood samples from 50 patients from Fudan University Shanghai Cancer Center (FUSCC) with localized or lymph node metastatic PCa were investigated in this study. Twenty-five samples from normal individuals were set as controls. We first conducted enzyme-linked immunosorbent assay analysis to select candidate markers that were significantly different between these patients and controls. Then, the clinical relevance between OLR1 (the ox-LDL receptor) expression and PCa was analyzed in The Cancer Genome Atlas (TCGA) cohort. We also investigated the function of ox-LDL in PCa cell lines in vitro. Phosphorylation protein chips were used to analyze cell signaling pathways in ox-LDL-treated PC-3 cells. The ox-LDL level was found to be significantly correlated with N stage of prostate cancer. OLR1 expression was correlated with lymph node metastasis in the TCGA cohort. In vitro, ox-LDL stimulated the proliferation, migration, and invasion of LNCaP and PC-3 in a dose-dependent manner. The results of phosphoprotein microarray illustrated that ox-LDL could influence multiple signaling pathways of PC-3. Activation of proliferation promoting signaling pathways (including β-catenin, cMyc, NF-κB, STAT1, STAT3) as well as apoptosis-associating signaling pathways (including p27, caspase-3) demonstrated that ox-LDL had complicated effects on prostate cancer. Increased serum ox-LDL level and OLR1 expression may indicate advanced-stage PCa and lymph node metastasis. Moreover, ox-LDL could stimulate PCa proliferation, migration, and invasion in vitro.

  14. Results of two different surgical techniques in the treatment of advanced-stage Freiberg's disease

    PubMed Central

    Özkul, Emin; Gem, Mehmet; Alemdar, Celil; Arslan, Hüseyin; Boğatekin, Ferit; Kişin, Bülent

    2016-01-01

    Background: Freiberg's disease is an osteochondrosis most commonly seen in adolescent women and characterized by pain, swelling and motion restriction in the second metatarsal. The early stages of this disease can be managed with semirigid orthoses, metatarsal bars and short leg walking cast. Number of operative methods are suggested which can be used depending on the pathophysiology of the disease, including abnormal biomechanics, joint congruence and degenerative process. We evaluated the outcomes of the patients with Freiberg's disease who were treated with dorsal closing-wedge osteotomy and resection of the metatarsal head. Patients and Methods: 16 patients (11 female, 5 male) with a mean age of 24.5 (range 13–49 years) years who underwent dorsal closing wedge osteotomy or resection of the metatarsal head were included in this retrospective study. Second metatarsal was affected in 13 and third metatarsal in three patients. According to the Smillie's classification system, ten patients had type IV osteonecrosis and six patients had type V. The results of the patients were evaluated using the lesser metatarsophalangeal-interphalangeal (LMPI) scale. Results: According to the LMPI scale, the postoperative scores for the osteotomy and excision groups were 86 (range 64–100) and 72.6 (range 60–85), respectively. In the osteotomy group, mean passive flexion restriction was 18° (range 0°–35°) and mean passive extension restriction was 12° (range 0°–25°). Mean metatarsal shortening was 2.2 mm (range 2–4 mm) in the osteotomy group as opposed to 9.8 mm (range 7–14 mm) in the excision group. Significant pain relief was obtained in both groups following the surgery. Conclusions: The decision of performing osteotomy or resection arthroplasty in the patients with advanced-stage Freiberg's disease should be based on the joint injury and the patients should be informed about the cosmetic problems like shortening which may arise from resection. PMID:26955180

  15. Study of Kidney Tumors in Younger Patients

    ClinicalTrials.gov

    2016-05-17

    Clear Cell Sarcoma of the Kidney; Congenital Mesoblastic Nephroma; Diffuse Hyperplastic Perilobar Nephroblastomatosis; Rhabdoid Tumor of the Kidney; Stage I Renal Cell Cancer; Stage I Wilms Tumor; Stage II Renal Cell Cancer; Stage II Wilms Tumor; Stage III Renal Cell Cancer; Stage III Wilms Tumor; Stage IV Renal Cell Cancer; Stage IV Wilms Tumor; Stage V Wilms Tumor

  16. The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancer

    PubMed Central

    Škof, Erik; Merlo, Sebastjan; Pilko, Gasper

    2016-01-01

    Abstract Background Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. Methods We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005–2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. Results Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. Conclusions Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery. PMID:27679552

  17. The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancer

    PubMed Central

    Škof, Erik; Merlo, Sebastjan; Pilko, Gasper

    2016-01-01

    Abstract Background Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. Methods We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005–2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. Results Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. Conclusions Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery.

  18. TP53 mutation at early stage of colorectal cancer progression from two types of laterally spreading tumors.

    PubMed

    Sakai, Eiji; Fukuyo, Masaki; Matsusaka, Keisuke; Ohata, Ken; Doi, Noriteru; Takane, Kiyoko; Matsuhashi, Nobuyuki; Fukushima, Junichi; Nakajima, Atsushi; Kaneda, Atsushi

    2016-06-01

    Although most sporadic colorectal cancers (CRC) are thought to develop from protruded adenomas through the adenoma-carcinoma sequence, some CRC develop through flat lesions, so-called laterally spreading tumors (LST). We previously analyzed epigenetic aberrations in LST and found that LST are clearly classified into two molecular subtypes: intermediate-methylation with KRAS mutation and low-methylation with absence of oncogene mutation. Intermediate-methylation LST were mostly granular type LST (LST-G) and low-methylation LST were mostly non-granular LST (LST-NG). In the present study, we conducted a targeted exon sequencing study including 38 candidate CRC driver genes to gain insight into how these genes modulate the development of LST. We identified a mean of 11.5 suspected nonpolymorphic variants per sample, including indels and non-synonymous mutations, although there was no significant difference in the frequency of total mutations between LST-G and LST-NG. Genes associated with RTK/RAS signaling pathway were mutated more frequently in LST-G than LST-NG (P = 0.004), especially KRAS mutation occurring at 70% (30/43) of LST-G but 26% (13/50) of LST-NG (P < 0.0001). Both LST showed high frequency of APC mutation, even at adenoma stage, suggesting its involvement in the initiation stage of LST, as it is involved at early stage of colorectal carcinogenesis via adenoma-carcinoma sequence. TP53 mutation was never observed in adenomas, but was specifically detected in cancer samples. TP53 mutation occurred during development of intramucosal cancer in LST-NG, but during development of cancer with submucosal invasion in LST-G. It is suggested that TP53 mutation occurs in the early stages of cancer development from adenoma in both LST-G and LST-NG, but is involved at an earlier stage in LST-NG. PMID:26991699

  19. SU-E-J-87: Ventilation Weighting Effect On Mean Doses of Both Side Lungs for Patients with Advanced Stage Lung Cancer

    SciTech Connect

    Qu, H; Xia, P; Yu, N

    2015-06-15

    Purpose: To study ventilation weighting effect on radiation doses to both side lungs for patients with advanced stage lung cancer. Methods: Fourteen patients with advanced stage lung cancer were included in this retrospective study. Proprietary software was developed to calculate the lung ventilation map based on 4DCT images acquired for radiation therapy. Two phases of inhale (0%) and exhale (50%) were used for the lung ventilation calculations. For each patient, the CT images were resampled to the same dose calculation resolution of 3mmx3mmx3mm. The ventilation distribution was then normalized by the mean value of the ventilation. The ventilation weighted dose was calculated by applying linearly weighted ventilation to the dose of each pixel. The lung contours were automatically delineated from patient CT image with lung window, excluding the tumor and high density tissues. For contralateral and ipsilateral lungs, the mean lung doses from the original plan and ventilation weighted mean lung doses were compared using two tail t-Test. Results: The average of mean dose was 6.1 ±3.8Gy for the contralateral lungs, and 26.2 ± 14.0Gy for the ipsilateral lungs. The average of ventilation weighted dose was 6.3± 3.8Gy for the contralateral lungs and 24.6 ± 13.1Gy for the ipsilateral lungs. The statistics analysis shows the significance of the mean dose increase (p<0.015) for the contralateral lungs and decrease (p<0.005) for the ipsilateral lungs. Conclusion: Ventilation weighted doses were greater than the un-weighted doses for contralateral lungs and smaller for ipsilateral lungs. This Result may be helpful to understand the radiation dosimetric effect on the lung function and provide planning guidance for patients with advance stage lung cancer.

  20. Experimental and theoretical advances in functional understanding of flavonoids as anti-tumor agents.

    PubMed

    Babu, Bandarugattu V; Konduru, Naveen K; Nakanishi, Waro; Hayashi, Satoko; Ahmed, Naseem; Mitrasinovic, Petar M

    2013-02-01

    The potential of flavonoids to act as anti-tumor agents has been recognized but not fully understood because flavonoids are acting at several stages in cancer progression with distinct structure-function relationships. A whole family of structurally different flavonoids is herein described by reviewing some critical aspects of their pro-oxidant behavior in vitro/vivo and in cell systems by which they may work as antioxidants. Different classes of flavonoids (chalcones, flavones, isoflavones, flavanols, flavanones and anthocyanins) are synthetically mimicked using natural product structure-antioxidant activity relationships that are relevant for their enhanced function against cancer as well as severe inflammation conditions under which an increased oxidative stress is often implicated. In the context of the common mechanisms of flavonoid action, clinical data on benefits of flavonoids in fighting against cancer are discussed. A structural basis needed to improve antioxidant activity of these agents is elaborated in more detail.

  1. Priming of tumor-specific T cells in the draining lymph nodes after immunization with interleukin 2-secreting tumor cells: three consecutive stages may be required for successful tumor vaccination.

    PubMed Central

    Maass, G; Schmidt, W; Berger, M; Schilcher, F; Koszik, F; Schneeberger, A; Stingl, G; Birnstiel, M L; Schweighoffer, T

    1995-01-01

    Although both CD4+ and CD8+ T cells are clearly required to generate long-lasting anti-tumor immunity induced by s.c. vaccination with interleukin 2 (IL-2)-transfected, irradiated M-3 clone murine melanoma cells, some controversy continues about the site and mode of T-cell activation in this system. Macrophages, granulocytes, and natural killer cells infiltrate the vaccination site early after injection into either syngeneic euthymic DBA/2 mice or athymic nude mice and eliminate the inoculum within 48 hr. We could not find T cells at the vaccination site, which argues against the concept that T-cell priming by the IL-2-secreting cancer cells occurs directly at that location. However, reverse transcription-PCR revealed transcripts indicative of T-cell activation and expansion in the draining lymph nodes of mice immunized with the IL-2-secreting vaccine but not in mice vaccinated with untransfected, irradiated M-3 cells. We therefore propose that the antigen-presenting cells, which invade the vaccination site, process tumor-derived antigens and, subsequently, initiate priming of tumor-specific T lymphocytes in lymphoid organs. These findings suggest a three-stage process for the generation of effector T cells after vaccination with IL-2-secreting tumor cells: (i) tumor-antigen uptake and processing at the site of injection by antigen-presenting cells, (ii) migration of antigen-presenting cells into the regional draining lymph nodes, where T-cell priming occurs, and (iii) circulation of activated T cells that either perform or initiate effector mechanisms leading to tumor cell destruction. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:7777545

  2. Efficacy Comparison Between Total Laryngectomy and Nonsurgical Organ-Preservation Modalities in Treatment of Advanced Stage Laryngeal Cancer: A Meta-Analysis.

    PubMed

    Fu, Xiaoyuan; Zhou, Qi; Zhang, Xianquan

    2016-04-01

    It remains unclear whether the efficacy of nonsurgical organ-preservation modalities (NOP) in the treatment of advanced-stage laryngeal cancer was noninferiority compared with that of total laryngectomy (TL). The objective of this study was to compare the curative effects between TL and NOP in the treatment of advanced-stage laryngeal cancer through a meta-analysis.Clinical studies were retrieved from the electronic databases of PubMed, Embase, Wanfang, and Chinese National Knowledge infrastructure. A meta-analysis was performed to investigate the differences in the curative efficacy of advanced-stage laryngeal cancer between TL and the nonsurgical method. Two reviewers screened all titles and abstracts, and independently assessed all articles. All identified studies were retrospective.Sixteen retrospective studies involving 8308 patients (4478 in the TL group and 3701 in the nonsurgical group) were included in this meta-analysis. The analysis results displayed the advantage of TL for 2-year and 5-year overall survival (OS)(OR 2.79, 95% CI 1.85-4.23 and OR 1.52, 95% CI 1.09-2.14) as well as in 5-year disease-specific survival (DSS)(OR 1.79, 95% CI 1.61-1.98), but no significant difference in 2-year DSS was detected between the 2 groups (OR = 2.09,95% CI0.69-6.40). Additionally, there were no significant differences between TL and NOP for 5-year local control (LC) either (OR = 1.75, 95% CI 0.87-3.53). When we carried out subgroup analyses, the advantage of TL was especially obvious in T4 subgroups, but not in T3 subgroups.This is the first study to compare the curative effects on advanced-stage laryngeal cancer using meta-analytic methodology. Although there was a trend in favor of TL for OS and DSS, there is no clear difference in oncologic outcome between TL and NOP. Therefore, other factors such as tumor T-stage and size, lymph node metastasis, and physical condition are also important indicators for treatment choice. PMID:27057837

  3. Relative value of physical examination, mammography, and breast sonography in evaluating the size of the primary tumor and regional lymph node metastases in women receiving neoadjuvant chemotherapy for locally advanced breast carcinoma.

    PubMed

    Herrada, J; Iyer, R B; Atkinson, E N; Sneige, N; Buzdar, A U; Hortobagyi, G N

    1997-09-01

    The purpose of this study was to correlate physical examination and sonographic and mammographic measurements of breast tumors and regional lymph nodes with pathological findings and to evaluate the effect of neoadjuvant chemotherapy on clinical Tumor-Node-Metastasis stage by noninvasive methods. This was a retrospective analysis of 100 patients with locally advanced breast cancer registered and treated in prospective trials of neoadjuvant chemotherapy. All patients received four cycles of a doxorubicin-containing regimen and had noninvasive evaluation of the primary tumor and regional lymph nodes before and after neoadjuvant chemotherapy by physical examination, sonography, and mammography and underwent breast surgery and axillary dissection within 5 weeks after completion of neoadjuvant chemotherapy. The correlations between clinical and pathological measurements were determined by Spearman rank correlation analysis. A proportional odds model was used to examine predictive values. Eighty-three patients had both a clinically detectable primary tumor and lymph node metastases. Sixty-four patients had a decrease in Tumor-Node-Metastasis stage after chemotherapy. For 54% of patients, there was concordance in clinical response between the primary tumor and lymph node compartment; for the rest, results were discordant. Physical examination correlated best with pathological findings in the measurement of the primary tumor (P = 0.0003), whereas sonography was the most accurate predictor of size for axillary lymph nodes (P = 0.0005). The combination of physical examination and mammography worked best for assessment of the primary tumor (P = 0.003), whereas combining physical examination with sonography gave optimal evaluation of regional lymph nodes (P = 0.0001). In conclusion, physical examination is the best noninvasive predictor of the real size of locally advanced primary breast cancer, whereas sonography correlates better with the real dimensions of axillary lymph

  4. Intraoperative radiation therapy as adjuvant treatment in locally advanced stage tumours involving the middle ear: a hypothesis-generating retrospective study.

    PubMed

    Cristalli, G; Mercante, G; Marucci, L; Soriani, A; Telera, S; Spriano, G

    2016-04-01

    The objective of this study was to evaluate the safety, effectiveness and functional outcomes of intraoperative radiotherapy (IORT) followed by intensity-modulated radiation therapy (IMRT) in locally advanced stage tumours involving the middle ear. Data on 13 consecutive patients treated for malignant tumor of external auditory canal involving the middle ear were retrospectively reviewed. Median follow-up was 33 months (range 6-133). Five (38%) patients were stage III and 8 (62%) were Stage IV according to the University of Pittsburgh staging system. Lateral temporal bone resection (LTBR) was performed in all cases. LTBR was associated with parotidectomy in 5 (38%) cases, and with neck dissection and parotidectomy in 6 (46%) cases. No patients had gross residual tumour. Surgical treatment was followed by IORT (12 Gy) and IMRT (50 Gy). Adjuvant chemotherapy was used in 4 (30%) cases. Preoperative and postoperative audiometric tests were performed to assess hearing loss. 5-year local-control (LC), 5-year distant-metastasis (DM), 5-year disease-free-survival (DFS) and 5-year overall-survival (OS) were calculated with Kaplan-Meyer method. Significant changes in bone conduction were reported after treatment. Partial flap necrosis was the only early complication observed in three (23%) cases, while meningeal fistula was seen in one (7.6%) case as a late complication. The 5-year LC-rate was 68%. The 5-year DM-rate was 90%. The 5-year DFS-rate was 61%. The 5-year OS-rate was 69%. IORT followed by IMRT for the treatment of advanced external auditory canal and middle ear tumours seems to be safe. No intraoperative death was reported. IORT may reduce the postoperative irradiation of remnant tissue obtaining the same full dose on the tumour bed. No complications of the residual external ear were observed. Detriment of neurosensory hearing may be expected. Future studies are required to confirm the benefit of this procedure in the ear.

  5. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.

    PubMed

    Tie, Jeanne; Wang, Yuxuan; Tomasetti, Cristian; Li, Lu; Springer, Simeon; Kinde, Isaac; Silliman, Natalie; Tacey, Mark; Wong, Hui-Li; Christie, Michael; Kosmider, Suzanne; Skinner, Iain; Wong, Rachel; Steel, Malcolm; Tran, Ben; Desai, Jayesh; Jones, Ian; Haydon, Andrew; Hayes, Theresa; Price, Tim J; Strausberg, Robert L; Diaz, Luis A; Papadopoulos, Nickolas; Kinzler, Kenneth W; Vogelstein, Bert; Gibbs, Peter

    2016-07-01

    Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing-based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence.

  6. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.

    PubMed

    Tie, Jeanne; Wang, Yuxuan; Tomasetti, Cristian; Li, Lu; Springer, Simeon; Kinde, Isaac; Silliman, Natalie; Tacey, Mark; Wong, Hui-Li; Christie, Michael; Kosmider, Suzanne; Skinner, Iain; Wong, Rachel; Steel, Malcolm; Tran, Ben; Desai, Jayesh; Jones, Ian; Haydon, Andrew; Hayes, Theresa; Price, Tim J; Strausberg, Robert L; Diaz, Luis A; Papadopoulos, Nickolas; Kinzler, Kenneth W; Vogelstein, Bert; Gibbs, Peter

    2016-07-01

    Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing-based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence. PMID:27384348

  7. Advanced Imaging and Receipt of Guideline Concordant Care in Women with Early Stage Breast Cancer

    PubMed Central

    Buist, Diana S. M.; Gold, Laura S.; Zeliadt, Steven; Hunter Merrill, Rachel; Etzioni, Ruth; Ramsey, Scott D.; Sullivan, Sean D.; Kessler, Larry

    2016-01-01

    Objective. It is unknown whether advanced imaging (AI) is associated with higher quality breast cancer (BC) care. Materials and Methods. Claims and Surveillance Epidemiology and End Results data were linked for women diagnosed with incident stage I-III BC between 2002 and 2008 in western Washington State. We examined receipt of preoperative breast magnetic resonance imaging (MRI) or AI (defined as computed tomography [CT]/positron emission tomography [PET]/PET/CT) versus mammogram and/or ultrasound (M-US) alone and receipt of guideline concordant care (GCC) using multivariable logistic regression. Results. Of 5247 women, 67% received M-US, 23% MRI, 8% CT, and 3% PET/PET-CT. In 2002, 5% received MRI and 5% AI compared to 45% and 12%, respectively, in 2008. 79% received GCC, but GCC declined over time and was associated with younger age, urban residence, less comorbidity, shorter time from diagnosis to surgery, and earlier year of diagnosis. Breast MRI was associated with GCC for lumpectomy plus radiation therapy (RT) (OR 1.55, 95% CI 1.08–2.26, and p = 0.02) and AI was associated with GCC for adjuvant chemotherapy for estrogen-receptor positive (ER+) BC (OR 1.74, 95% CI 1.17–2.59, and p = 0.01). Conclusion. GCC was associated with prior receipt of breast MRI and AI for lumpectomy plus RT and adjuvant chemotherapy for ER+ BC, respectively. PMID:27525122

  8. Advanced Imaging and Receipt of Guideline Concordant Care in Women with Early Stage Breast Cancer.

    PubMed

    Loggers, Elizabeth Trice; Buist, Diana S M; Gold, Laura S; Zeliadt, Steven; Hunter Merrill, Rachel; Etzioni, Ruth; Ramsey, Scott D; Sullivan, Sean D; Kessler, Larry

    2016-01-01

    Objective. It is unknown whether advanced imaging (AI) is associated with higher quality breast cancer (BC) care. Materials and Methods. Claims and Surveillance Epidemiology and End Results data were linked for women diagnosed with incident stage I-III BC between 2002 and 2008 in western Washington State. We examined receipt of preoperative breast magnetic resonance imaging (MRI) or AI (defined as computed tomography [CT]/positron emission tomography [PET]/PET/CT) versus mammogram and/or ultrasound (M-US) alone and receipt of guideline concordant care (GCC) using multivariable logistic regression. Results. Of 5247 women, 67% received M-US, 23% MRI, 8% CT, and 3% PET/PET-CT. In 2002, 5% received MRI and 5% AI compared to 45% and 12%, respectively, in 2008. 79% received GCC, but GCC declined over time and was associated with younger age, urban residence, less comorbidity, shorter time from diagnosis to surgery, and earlier year of diagnosis. Breast MRI was associated with GCC for lumpectomy plus radiation therapy (RT) (OR 1.55, 95% CI 1.08-2.26, and p = 0.02) and AI was associated with GCC for adjuvant chemotherapy for estrogen-receptor positive (ER+) BC (OR 1.74, 95% CI 1.17-2.59, and p = 0.01). Conclusion. GCC was associated with prior receipt of breast MRI and AI for lumpectomy plus RT and adjuvant chemotherapy for ER+ BC, respectively. PMID:27525122

  9. A Positive Prospective Trial of Antibiotic Therapy in Advanced Stage, Non-Bulky Indolent Lymphoma

    PubMed Central

    Portlock, Carol S; Hamlin, Paul A; Gerecitano, John F; Noy, Ariela; Palomba, Maria Lia; Walkley, Janelle; Corcoran, Stacie; Migliacci, Jocelyn; Schoder, Heiko; Papanicolaou, Genovefa; Markowitz, Arnold J

    2016-01-01

    Background We have prospectively studied a three month course of clarithromycin (substituted by Prevpac®, lansoprazole/ amoxicillin/ clarithromycin, in the first two wks when stool H pylori+) for non-bulky, advanced stage indolent lymphoma. These patients are often candidates for expectant monitoring and it is during this period that a window of opportunity may exist to identify and treat associated infections. Methods All previously untreated patients with a new diagnosis of indolent lymphoma (FL and non-FL) meeting GELF criteria were treated with 12 weeks of clarithromycin. There were 32 evaluable patients, 4 of whom had stool H pylori. Results At one month post-antibiotic therapy, we have observed lymphoma responses in 7 of 32 patients (21.9%). Two additional patients had objective response during followup (28.1% overall response). The median treatment free survival for antibiotic responders is 69.9 months and for non-responders, 30.6 months (p = 0.019). Conclusion Three response patterns have been noted, perhaps suggestive of an immune-mediated response -- prompt PET negative; flair with delayed PET negative response; and gradual continuous improvement. This prospective study appears promising, may be a step toward developing a lymphoma prevention strategy by reducing “antigen drive,” and deserves further clinical/biological study. http://clinicaltrials.gov/show/NCT00461084 PMID:26798624

  10. Cost-utility analysis of imatinib mesilate for the treatment of advanced stage chronic myeloid leukaemia.

    PubMed

    Gordois, A; Scuffham, P; Warren, E; Ward, S

    2003-08-18

    Imatinib mesilate (Glivec), Novartis Pharmaceuticals) is a novel therapy for the treatment of chronic myeloid leukaemia (CML). We evaluated the cost-effectiveness of imatinib (600 mg daily) when used for the treatment of patients in advanced stages of CML (accelerated phase and blast crisis) against conventional therapies of combination chemotherapy (DAT) and palliative care in hospital or at home. A Markov model simulated the transitions of hypothetical patient cohorts and outcomes were modelled for 5 years from the start of treatment. Costs were estimated from the perspective of the UK National Health Service. Over 5 years, a patient in accelerated phase will, on average, accrue an additional 2.09 QALYs with imatinib compared to conventional therapies, while patients in blast crisis will accrue an additional 0.58 quality-adjusted life-years (QALYs) with imatinib compared to conventional therapies. The costs per additional QALY gained from treatment with imatinib compared with conventional therapies were pound 29344 (accelerated phase) and pound 42239 (blast crisis). The results were particularly sensitive to the price of imatinib, improvements in quality of life, and the duration of haematological responses. We conclude that treatment of CML with imatinib confers considerably greater survival and quality of life than conventional treatments but at a cost. PMID:12915870

  11. Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients

    NASA Astrophysics Data System (ADS)

    Ruiz, Carmen; Li, Julia; Luttgen, Madelyn S.; Kolatkar, Anand; Kendall, Jude T.; Flores, Edna; Topp, Zheng; Samlowski, Wolfram E.; McClay, Edward; Bethel, Kelly; Ferrone, Soldano; Hicks, James; Kuhn, Peter

    2015-02-01

    Purpose. Circulating melanoma cells (CMCs) constitute a potentially important representation of time-resolved tumor biology in patients. To date, genomic characterization of CMCs has been limited due to the lack of a robust methodology capable of identifying them in a format suitable for downstream characterization. Here, we have developed a methodology to detect intact CMCs that enables phenotypic, morphometric and genomic analysis at the single cell level. Experimental design. Blood samples from 40 metastatic melanoma patients and 10 normal blood donors were prospectively collected. A panel of 7 chondroitin sulfate proteoglycan 4 (CSPG4)-specific monoclonal antibodies (mAbs) was used to immunocytochemically label CMCs. Detection was performed by automated digital fluorescence microscopy and multi-parametric computational analysis. Individual CMCs were captured by micromanipulation for whole genome amplification and copy number variation (CNV) analysis. Results. Based on CSPG4 expression and nuclear size, 1-250 CMCs were detected in 22 (55%) of 40 metastatic melanoma patients (0.5-371.5 CMCs ml-1). Morphometric analysis revealed that CMCs have a broad spectrum of morphologies and sizes but exhibit a relatively homogeneous nuclear size that was on average 1.5-fold larger than that of surrounding PBMCs. CNV analysis of single CMCs identified deletions of CDKN2A and PTEN, and amplification(s) of TERT, BRAF, KRAS and MDM2. Furthermore, novel chromosomal amplifications in chr12, 17 and 19 were also found. Conclusions. Our findings show that CSPG4 expressing CMCs can be found in the majority of advanced melanoma patients. High content analysis of this cell population may contribute to the design of effective personalized therapies in patients with melanoma.

  12. Limited Genomic Heterogeneity of Circulating Melanoma Cells in Advanced Stage Patients

    PubMed Central

    Ruiz, Carmen; Li, Julia; Luttgen, Madelyn S.; Kolatkar, Anand; Kendall, Jude T.; Flores, Edna; Topp, Zheng; Samlowski, Wolfram E.; McClay, Ed; Bethel, Kelly; Ferrone, Soldano; Hicks, James; Kuhn, Peter

    2015-01-01

    Purpose Circulating melanoma cells (CMCs) constitute a potentially important representation of time-resolved tumor biology in patients. To date, genomic characterization of CMCs has been limited due to the lack of a robust methodology capable of identifying them in a format suitable for downstream characterization. Here, we have developed a methodology to detect intact CMCs that enables phenotypic, morphometric and genomic analysis at the single cell level. Experimental design Blood samples from 40 metastatic melanoma patients and 10 normal blood donors (NBD) were prospectively collected. A panel of 7 chondroitin sulfate proteoglycan 4 (CSPG4)-specific monoclonal antibodies (mAb) was used to immunocytochemically label CMCs. Detection was performed by automated digital fluorescence microscopy and multi-parametric computational analysis. Individual CMCs were captured by micromanipulation for whole genome amplification (WGA) and copy number variation (CNV) analysis. Results Based on CSPG4 expression and nuclear size, 1 to 250 CMCs were detected in 22 (55%) of 40 metastatic melanoma patients (0.5 to 371.5 CMCs/ml). Morphometric analysis revealed that CMCs have a broad spectrum of morphologies and sizes but exhibit a relatively homogeneous nuclear size that was on average 1.5-fold larger than that of surrounding PBMCs. CNV analysis of single CMCs identified deletions of CDKN2A and PTEN, and amplification(s) of TERT, BRAF, KRAS and MDM2. Furthermore, novel chromosomal amplifications in chr12, 17 and 19 were also found. Conclusions Our findings show that CSPG4 expressing CMCs can be found in the majority of advanced melanoma patients. High content analysis of this population may contribute to develop effective therapeutic strategies. PMID:25574741

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

    PubMed Central

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

    2014-01-01

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

  14. CA125-related tumor cell kinetics variables after chemotherapy in advanced ovarian cancer: a systematic review.

    PubMed

    Colloca, G; Venturino, A; Governato, I

    2016-08-01

    Various kinetic parameters, based on a minimum of two time points, have been built with CA125 determinations. The aim of this study is to review studies about the clinical application of CA125-related tumor cell kinetics variables in patients with advanced ovarian cancer (AOC) receiving chemotherapy. A literature search for studies about CA125-related variables in patients with AOC was undertaken on three databases, by predefined search criteria, and a selection of studies was performed. Sixty-two studies were selected. CA125-related variables were summarized in three groups: response-related, time-to-event, and other CA125-related tumor cell kinetics variables. Even though CA125 changes and half-life after chemotherapy were the most studied, other variables and two models have been well defined, and often showed an interesting power to predict survival. These kinetics variables are related to the CA125 regression curve, pre- and post-chemotherapy kinetics, or are variables inferred from a population model of CA125 kinetics.

  15. Tumor

    MedlinePlus

    ... plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by viruses are: Cervical cancer (human papillomavirus) Hepatocellular carcinoma (hepatitis B and hepatitis C ...

  16. Can Locoregional Treatment of the Primary Tumor Improve Outcomes for Women With Stage IV Breast Cancer at Diagnosis?

    SciTech Connect

    Nguyen, David H.A.; Truong, Pauline T.; Alexander, Cheryl; Walter, Caroline V.; Hayashi, Emily; Christie, Jennifer; Lesperance, Mary

    2012-09-01

    Purpose: To examine the effect of locoregional treatment (LRT) of the primary tumor on survival in patients with Stage IV breast cancer at diagnosis. Methods and Materials: The study cohort comprised 733 women referred to the British Columbia Cancer Agency between 1996 and 2005 with newly diagnosed clinical or pathologic M1 breast cancer. Tumor and treatment characteristics, overall survival (OS), and locoregional progression-free survival were compared between patients treated with (n = 378) and without (n = 355) LRT of the primary disease. Multivariable analysis was performed with Cox regression modeling. Results: The median follow-up time was 1.9 years. LRT consisted of surgery alone in 67% of patients, radiotherapy alone in 22%, and both in 11%. LRT was used more commonly in women with age <50 years, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, Stage T1-2 tumors, N0-1 disease, limited M1 burden, and asymptomatic M1 disease (all p < 0.05). Systemic therapy was used in 92% of patients who underwent LRT and 85% of patients who did not. In patients treated with LRT compared with those without LRT, the 5-year OS rates were 21% vs. 14% (p < 0.001), and the rates of locoregional progression-free survival were 72% vs. 46% (p < 0.001). Among 378 patients treated with LRT, the rates of 5-year OS were higher in patients with age <50, ECOG performance status 0-1, estrogen receptor-positive disease, clear surgical margins, single subsite, bone-only metastasis, and one to four metastatic lesions (all p < 0.003). On multivariable analysis, LRT was associated with improved OS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.94, p = 0.009). Conclusion: Locoregional treatment of the primary disease is associated with improved survival in some women with Stage IV breast cancer at diagnosis. Among those treated with LRT, the most favorable rates of survival were observed in subsets with young age, good performance status, estrogen receptor-positive disease

  17. Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer.

    PubMed

    Singhal, Sunil; Bhojnagarwala, Pratik S; O'Brien, Shaun; Moon, Edmund K; Garfall, Alfred L; Rao, Abhishek S; Quatromoni, Jon G; Stephen, Tom Li; Litzky, Leslie; Deshpande, Charuhas; Feldman, Michael D; Hancock, Wayne W; Conejo-Garcia, Jose R; Albelda, Steven M; Eruslanov, Evgeniy B

    2016-07-11

    Based on studies in mouse tumor models, granulocytes appear to play a tumor-promoting role. However, there are limited data about the phenotype and function of tumor-associated neutrophils (TANs) in humans. Here, we identify a subset of TANs that exhibited characteristics of both neutrophils and antigen-presenting cells (APCs) in early-stage human lung cancer. These APC-like "hybrid neutrophils," which originate from CD11b(+)CD15(hi)CD10(-)CD16(low) immature progenitors, are able to cross-present antigens, as well as trigger and augment anti-tumor T cell responses. Interferon-γ and granulocyte-macrophage colony-stimulating factor are requisite factors in the tumor that, working through the Ikaros transcription factor, synergistically exert their APC-promoting effects on the progenitors. Overall, these data demonstrate the existence of a specialized TAN subset with anti-tumor capabilities in human cancer.

  18. Proton Therapy for Thoracoabdominal Tumors

    NASA Astrophysics Data System (ADS)

    Sakurai, Hideyuki; Okumura, Toshiyuki; Sugahara, Shinji; Nakayama, Hidetsugu; Tokuuye, Koichi

    In advanced-stage disease of certain thoracoabdominal tumors, proton therapy (PT) with concurrent chemotherapy may be an option to reduce side effects. Several technological developments, including a respiratory gating system and implantation of fiducial markers for image guided radiation therapy (IGRT), are necessary for the treatment in thoracoabdominal tumors. In this chapter, the role of PT for tumors of the lung, the esophagus, and liver are discussed.

  19. EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-01-15

    Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage

  20. 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.

  1. Electrochemotherapy in combination with chemoradiotherapy in the treatment of oral carcinomas in advanced stages of disease: efficacy, safety, and clinical outcomes in a small number of selected cases

    PubMed Central

    Domanico, Rossana; Trapasso, Serena; Santoro, Mariaquila; Pingitore, Domenico; Allegra, Eugenia

    2015-01-01

    Introduction Electrochemotherapy (ECT) is a new therapeutic method that is used in oncology as palliative treatment in patients with recurrent head and neck tumors and who are not candidates for standard therapeutic options. The aim of our study was to evaluate the cytoreductive effect of ECT in patients subjected to chemoradiotherapy for squamous cell carcinoma of the oral cavity. The primary endpoint of the study was to verify tumor debulking after ECT treatment as neoadjuvant, before conventional chemoradiotherapy. The secondary endpoint was to assess the safety and tolerability of ECT treatment. Materials and methods This experimental study was conducted at the Division of Otolaryngology, University of Catanzaro, Italy. From February 2013 to February 2014, four patients were enrolled, two males and two females, with a mean age of 56 years (range: 47–65 years), and with squamous cell carcinoma of the oral cavity in advanced stages of disease (T3–T4). All patients, with their informed consent, received ECT treatment in accordance with the Standard Operating Procedures defined in the European Standard Operating Procedures on Electrochemotherapy (ESOPE) study, followed by conventional chemoradiotherapy. Their response to ECT treatment was assessed after 30 days. For each patient, the following parameters were evaluated with the appropriate forms: local tumor control, control of pain (analgesia postsurgery scale [APS]), and quality of life (Short Form [36] Health Survey [SF-36]; v1). Results Three of four patients (75%) showed a partial response, whereas in one patient (25%), the disease remained stable. The treatment was well-tolerated by all patients, according to the APS and SF-36 results. Conclusion Although the study was conducted on a small number of cases, data from this study show that ECT represents a safe and effective treatment in terms of tumor cytoreduction and locoregional control of the disease. It also allows good control of postoperative pain

  2. A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors

    ClinicalTrials.gov

    2016-09-30

    Estrogen Receptor Negative; HER2/Neu Negative; Metastatic Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Small Cell Lung Carcinoma; Stage III Pancreatic Cancer; Stage IIIA Breast Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Small Cell Lung Carcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Small Cell Lung Carcinoma; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Small Cell Lung Carcinoma; Stage IVA Pancreatic Cancer; Stage IVB Pancreatic Cancer; Triple-Negative Breast Carcinoma

  3. Elevation in Peripheral Blood Circulating Tumor Cell Number Correlates with Macroscopic Progression in UICC Stage IV Colorectal Cancer Patients

    PubMed Central

    Molnar, Bela; Floro, Lajos; Sipos, Ferenc; Toth, Bernadett; Sreter, Lydia; Tulassay, Zsolt

    2008-01-01

    Aims: Cytokeratin(CK) based real-time RT-PCR assays (QRT-PCR) are now available for peripheral blood circulating tumor cell (CTC) evaluations in colorectal cancer(CRC) patients. Results are non-existent for the application of these techniques to the determination of progression and therapy response in Dukes stage D CRC patients. Patients and methods: Each month 30 ml peripheral blood of 30 Dukes D patients (17 with progression) were drawn. CEA, CA19-9, CA72-A and TPA-M determinations were made. CK20, thymidilate synthase(TS) QRT-PCR was performed, as well. Buffy coat was used for immunmagnetic cancer cell isolation and CTC counting. Correlation between elevated CTC and macroscopic progression within 3 months was determined by Chi2 test. Results: Microscopic CTC single cell, doublet, cluster number were found in correlation with CK20 QRT-PCR results (p < 0.01). There was a significant increase in microscopic CTC number, CK20 and decrease in TS QRT-PCR levels (p < 0.05) in the peripheral blood of the non-responder as compared to responder patients. Elevation of the CTC was in significant correlation with macroscopic progression of the disease in 3 months (p < 0.01). Conclusions: CTC number reflects the chemotherapeutic sensitivity of CRC patients. Elevation of circulating tumor cell number in peripheral blood is in correlation with macroscopic progression. PMID:18334735

  4. Mucoepidermoid tumors of the lung.

    PubMed

    Yousem, S A; Hochholzer, L

    1987-09-15

    Mucoepidermoid tumors of lung (MET) are rare tumors derived from the minor salivary gland tissue of the proximal tracheobronchial tree. The authors studied 58 cases of MET confined to the lung and used criteria derived from similar tumors of the salivary glands to separate them into low-grade and high-grade variants. The overwhelming majority of low-grade tumors behaved in a benign fashion, whereas 23% of high-grade tumors resulted in patient death. Prognostic factors which appeared to predict future aggressive behavior included high-grade classification, advanced stage at presentation, and perhaps lymph node metastases.

  5. Melanoma susceptibility as a complex trait: genetic variation controls all stages of tumor progression.

    PubMed

    Ferguson, B; Ram, R; Handoko, H Y; Mukhopadhyay, P; Muller, H K; Soyer, H P; Morahan, G; Walker, G J

    2015-05-28

    Susceptibility to most common cancers is likely to involve interaction between multiple low risk genetic variants. Although there has been great progress in identifying such variants, their effect on phenotype and the mechanisms by which they contribute to disease remain largely unknown. We have developed a mouse melanoma model harboring two mutant oncogenes implicated in human melanoma, CDK4(R24C) and NRAS(Q61K). In these mice, tumors arise from benign precursor lesions that are a recognized strong risk factor for this neoplasm in humans. To define molecular events involved in the pathway to melanoma, we have for the first time applied the Collaborative Cross (CC) to cancer research. The CC is a powerful resource designed to expedite discovery of genes for complex traits. We characterized melanoma genesis in more than 50 CC strains and observed tremendous variation in all traits, including nevus and melanoma age of onset and multiplicity, anatomical site predilection, time for conversion of nevi to melanoma and metastases. Intriguingly, neonatal ultraviolet radiation exposure exacerbated nevus and melanoma formation in most, but not all CC strain backgrounds, suggesting that genetic variation within the CC will help explain individual sensitivity to sun exposure, the major environmental skin carcinogen. As genetic variation brings about dramatic phenotypic diversity in a single mouse model, melanoma-related endophenotype comparisons provide us with information about mechanisms of carcinogenesis, such as whether melanoma incidence is dependent upon the density of pre-existing nevus cells. Mouse models have been used to examine the functional role of gene mutations in tumorigenesis. This work represents their next phase of development to study how biological variation greatly influences lesion onset and aggressiveness even in the setting of known somatic driver mutations.

  6. Melanoma susceptibility as a complex trait: genetic variation controls all stages of tumor progression.

    PubMed

    Ferguson, B; Ram, R; Handoko, H Y; Mukhopadhyay, P; Muller, H K; Soyer, H P; Morahan, G; Walker, G J

    2015-05-28

    Susceptibility to most common cancers is likely to involve interaction between multiple low risk genetic variants. Although there has been great progress in identifying such variants, their effect on phenotype and the mechanisms by which they contribute to disease remain largely unknown. We have developed a mouse melanoma model harboring two mutant oncogenes implicated in human melanoma, CDK4(R24C) and NRAS(Q61K). In these mice, tumors arise from benign precursor lesions that are a recognized strong risk factor for this neoplasm in humans. To define molecular events involved in the pathway to melanoma, we have for the first time applied the Collaborative Cross (CC) to cancer research. The CC is a powerful resource designed to expedite discovery of genes for complex traits. We characterized melanoma genesis in more than 50 CC strains and observed tremendous variation in all traits, including nevus and melanoma age of onset and multiplicity, anatomical site predilection, time for conversion of nevi to melanoma and metastases. Intriguingly, neonatal ultraviolet radiation exposure exacerbated nevus and melanoma formation in most, but not all CC strain backgrounds, suggesting that genetic variation within the CC will help explain individual sensitivity to sun exposure, the major environmental skin carcinogen. As genetic variation brings about dramatic phenotypic diversity in a single mouse model, melanoma-related endophenotype comparisons provide us with information about mechanisms of carcinogenesis, such as whether melanoma incidence is dependent upon the density of pre-existing nevus cells. Mouse models have been used to examine the functional role of gene mutations in tumorigenesis. This work represents their next phase of development to study how biological variation greatly influences lesion onset and aggressiveness even in the setting of known somatic driver mutations. PMID:25088201

  7. Effects of amifostine in a patient with an advanced-stage myelodysplastic syndrome.

    PubMed

    Yilmaz, A; Kaufmann, C C; Binder, C; Wörmann, B; Haase, D

    2001-01-01

    We report on a 63-year-old man with myelodysplastic syndrome at the stage of a refractory anemia with an excess of blasts in transformation (MDS-RAEB-T), first diagnosed in December 1996. After a period of stability, with no need for transfusions, the MDS progressed into acute myeloid leukemia (AML) in August 1998 with the emergence of a cytogenetic abnormality (11q-). Two courses of chemotherapy were given, resulting in prolonged pancytopenia; however, no clearance of bone marrow (BM) blasts was achieved. At that time, severe infections and daily epistaxis occurred. Frequent transfusions of packed red blood cells (RBC) and platelets (2-3/week) were necessary. After 2 months of persisting severe pancytopenia, we started a therapy with amifostine: 4 x 250 mg intravenously (i.v.) weekly for 1 month, followed by a maintenance therapy with 500 mg once weekly. After 2 weeks of amifostine therapy, hematopoiesis began to improve. In the subsequent 2 months, the patient became completely independent of the platelet transfusions; the transfusion frequency of RBC was permanently reduced (2 RBC transfusions/month) and a significant decrease of BM blasts was achieved. After 30 weeks of amifostine therapy, the morphology of the MDS switched to a chronic myelomonocytic leukemia (CMML)-like appearance, with continuously increasing leukocytes, so that we discontinued amifostine therapy for 1 month to exclude a possible side effect of amifostine. At that time, leukocytes further increased to 74,000/microl; thus, we decided to perform a cytoreductive chemotherapy (hydroxycarbamide) and continued weekly amifostine infusions. During 1 year of amifostine therapy, the patient had a good quality of life, with no need for hospitalization and a complete cytogenetic remission. We conclude that, in this case, amifostine had two effects: a significant improvement of impaired hematopoiesis and a slowing down of disease progression. Thus, amifostine might be a therapeutic option in older

  8. Tumor size and T stage correlate independently with recurrence and progression in high-risk non-muscle-invasive bladder cancer patients treated with adjuvant BCG.

    PubMed

    Zachos, Ioannis; Tzortzis, Vasileios; Mitrakas, Lampros; Samarinas, Michael; Karatzas, Anastasios; Gravas, Stavros; Vandoros, Gerasimos P; Melekos, Michael D; Papavassiliou, Athanasios G

    2014-05-01

    We conducted a retrospective study to determine the prognostic significance of age, gender, associated carcinoma in situ, stage, number of tumors, and tumor size for patients with high-risk non-muscle-invasive bladder tumors treated with bacillus Calmette-Guérin (BCG). Data were evaluated on 144 high-risk patients with non-muscle-invasive bladder cancer treated with BCG immunotherapy after the initial treatment with transurethral resection. According to their response to BCG, patients were divided into groups, and the differences in factors, associated with recurrence and progression, were evaluated. Patients were categorized into two groups: group A, complete responders without recurrence and without progression, and group B, patients with recurrence and with progression. Furthermore, group B was divided into two subgroups: group B1, patients with recurrence, and group B2, patients with progression. Univariate analysis of group B showed that only tumor size of >3 cm diameter (hazard ratio (HR) 11.99; 95% confidence interval (CI) range 5.69-25.3; p < 0.001) is associated with recurrence. After multivariate analysis, the same factor appeared to be prognostic for recurrence as well. In addition, group B2 was statistically correlated with group B1. Univariate analysis proved that tumor stage (Ta or T1) is the unique factor associated with progression (HR 6.4; 95% CI 1.29-31.9; p = 0.02). Tumor stage seems to be associated with disease's progression after the multivariate analysis too. Tumor size and stage may serve as prognostic factors, because of its independent correlation with recurrence and progression for patients with high-risk non-muscle-invasive bladder tumors treated with BCG.

  9. Ku Protein Levels, Localization and Association to Replication Origins in Different Stages of Breast Tumor Progression

    PubMed Central

    Abdelbaqi, Khalil; Di Paola, Domenic; Rampakakis, Emmanouil; Zannis-Hadjopoulos, Maria

    2013-01-01

    Human origins of DNA replication are specific sequences within the genome whereby DNA replication is initiated. A select group of proteins, known as the pre-replication (pre-RC) complex, in whose formation the Ku protein (Ku70/Ku86) was shown to play a role, bind to replication origins to initiate DNA replication. In this study, we have examined the involvement of Ku in breast tumorigenesis and tumor progression and found that the Ku protein expression levels in human breast metastatic (MCF10AC1a) cells were higher in the chromatin fraction compared to hyperplastic (MCF10AT) and normal (MCF10A) human breast cells, but remained constant in both the nuclear and cytoplasmic fractions. In contrast, in human intestinal cells, the Ku expression level was relatively constant for all cell fractions. Nascent DNA abundance and chromatin association of Ku70/86 revealed that the c-myc origin activity in MCF10AC1a is 2.5 to 5-fold higher than in MCF10AT and MCF10A, respectively, and Ku was bound to the c-myc origin more abundantly in MCF10AC1a, by approximately 1.5 to 4.2-fold higher than in MCF10AT and MCF10A, respectively. In contrast, similar nascent DNA abundance and chromatin association was found for all cell lines for the lamin B2 origin, associated with the constitutively active housekeeping lamin B2 gene. Electrophoretic mobility shift assays (EMSAs) performed on the nuclear extracts (NEs) of the three cell types revealed the presence of protein-DNA replication complexes on both the c-myc and lamin B2 origins, but an increase in binding activity was observed from normal, to transformed, to cancer cells for the c-myc origin, whereas no such difference was seen for the lamin B2 origin. Overall, the results suggest that increased Ku chromatin association, beyond wild type levels, alters cellular processes, which have been implicated in tumorigenesis. PMID:23781282

  10. Ku protein levels, localization and association to replication origins in different stages of breast tumor progression.

    PubMed

    Abdelbaqi, Khalil; Di Paola, Domenic; Rampakakis, Emmanouil; Zannis-Hadjopoulos, Maria

    2013-01-01

    Human origins of DNA replication are specific sequences within the genome whereby DNA replication is initiated. A select group of proteins, known as the pre-replication (pre-RC) complex, in whose formation the Ku protein (Ku70/Ku86) was shown to play a role, bind to replication origins to initiate DNA replication. In this study, we have examined the involvement of Ku in breast tumorigenesis and tumor progression and found that the Ku protein expression levels in human breast metastatic (MCF10AC1a) cells were higher in the chromatin fraction compared to hyperplastic (MCF10AT) and normal (MCF10A) human breast cells, but remained constant in both the nuclear and cytoplasmic fractions. In contrast, in human intestinal cells, the Ku expression level was relatively constant for all cell fractions. Nascent DNA abundance and chromatin association of Ku70/86 revealed that the c-myc origin activity in MCF10AC1a is 2.5 to 5-fold higher than in MCF10AT and MCF10A, respectively, and Ku was bound to the c-myc origin more abundantly in MCF10AC1a, by approximately 1.5 to 4.2-fold higher than in MCF10AT and MCF10A, respectively. In contrast, similar nascent DNA abundance and chromatin association was found for all cell lines for the lamin B2 origin, associated with the constitutively active housekeeping lamin B2 gene. Electrophoretic mobility shift assays (EMSAs) performed on the nuclear extracts (NEs) of the three cell types revealed the presence of protein-DNA replication complexes on both the c-myc and lamin B2 origins, but an increase in binding activity was observed from normal, to transformed, to cancer cells for the c-myc origin, whereas no such difference was seen for the lamin B2 origin. Overall, the results suggest that increased Ku chromatin association, beyond wild type levels, alters cellular processes, which have been implicated in tumorigenesis.

  11. Human Leukocyte Antigen G Polymorphism and Expression Are Associated with an Increased Risk of Non-Small-Cell Lung Cancer and Advanced Disease Stage

    PubMed Central

    Ben Amor, Amira; Beauchemin, Karine; Faucher, Marie-Claude; Hamzaoui, Agnes; Hamzaoui, Kamel; Roger, Michel

    2016-01-01

    Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression may enable tumor cells to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G allelic variants and serum soluble HLA-G (sHLA-G) levels on risk of non-small-cell lung cancer (NSCLC). We analyzed 191 Caucasian adults with NSCLC and 191 healthy subjects recruited between January 2009 and March 2014 in Ariana (Tunisia). Serum sHLA-G levels were measured by immunoassay and HLA-G alleles were determined using a direct DNA sequencing procedures. The heterozygous genotypes of HLA-G 010101 and -G 010401 were associated with increased risks of both NSCLC and advanced disease stages. In contrast, the heterozygous genotypes of HLA-G 0105N and -G 0106 were associated with decreased risks of NSCC and clinical disease stage IV, respectively. Serum sHLA-G levels were significantly higher in patients with NSCLC and particularly in those with advanced disease stages compared to healthy subjects. The area under the receiver-operating characteristic (ROC) curves was 0.82 for controls vs patients. Given 100% specificity, the highest sensitivity achieved to detect NSCLC was 52.8% at a cutoff value of 24.9 U/ml. Patients with the sHLA-G above median level (≥ 50 U/ml) had a significantly shorter survival time. This study demonstrates that HLA-G allelic variants are independent risk factors for NSCLC. Serum sHLA-G levels in NSCLC patients could be useful biomarkers for the diagnostic and prognosis of NSCLC. PMID:27517300

  12. Human Leukocyte Antigen G Polymorphism and Expression Are Associated with an Increased Risk of Non-Small-Cell Lung Cancer and Advanced Disease Stage.

    PubMed

    Ben Amor, Amira; Beauchemin, Karine; Faucher, Marie-Claude; Hamzaoui, Agnes; Hamzaoui, Kamel; Roger, Michel

    2016-01-01

    Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression may enable tumor cells to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G allelic variants and serum soluble HLA-G (sHLA-G) levels on risk of non-small-cell lung cancer (NSCLC). We analyzed 191 Caucasian adults with NSCLC and 191 healthy subjects recruited between January 2009 and March 2014 in Ariana (Tunisia). Serum sHLA-G levels were measured by immunoassay and HLA-G alleles were determined using a direct DNA sequencing procedures. The heterozygous genotypes of HLA-G 010101 and -G 010401 were associated with increased risks of both NSCLC and advanced disease stages. In contrast, the heterozygous genotypes of HLA-G 0105N and -G 0106 were associated with decreased risks of NSCC and clinical disease stage IV, respectively. Serum sHLA-G levels were significantly higher in patients with NSCLC and particularly in those with advanced disease stages compared to healthy subjects. The area under the receiver-operating characteristic (ROC) curves was 0.82 for controls vs patients. Given 100% specificity, the highest sensitivity achieved to detect NSCLC was 52.8% at a cutoff value of 24.9 U/ml. Patients with the sHLA-G above median level (≥ 50 U/ml) had a significantly shorter survival time. This study demonstrates that HLA-G allelic variants are independent risk factors for NSCLC. Serum sHLA-G levels in NSCLC patients could be useful biomarkers for the diagnostic and prognosis of NSCLC.

  13. Loss of Expression of Reprimo, a p53-induced Cell Cycle Arrest Gene, Correlates with Invasive Stage of Tumor Progression and p73 Expression in Gastric Cancer

    PubMed Central

    Saavedra, Kathleen; Valbuena, José; Olivares, Wilda; Marchant, María José; Rodríguez, Andrés; Torres-Estay, Verónica; Carrasco-Avino, Gonzalo; Guzmán, Leda; Aguayo, Francisco; Roa, Juan Carlos; Corvalán, Alejandro H.

    2015-01-01

    Reprimo (RPRM), a downstream effector of p53-induced cell cycle arrest at G2/M, has been proposed as a putative tumor suppressor gene (TSG) and as a potential biomarker for non-invasive detection of gastric cancer (GC). The aim of this study was to evaluate the epigenetic silencing of RPRM gene by promoter methylation and its tumor suppressor function in GC cell lines. Furthermore, clinical significance of RPRM protein product and its association with p53/p73 tumor suppressor protein family was explored. Epigenetic silencing of RPRM gene by promoter methylation was evaluated in four GC cell lines. Protein expression of RPRM was evaluated in 20 tumor and non-tumor matched cases. The clinical significance of RPRM association with p53/p73 tumor suppressor protein family was assessed in 114 GC cases. Tumor suppressor function was examined through functional assays. RPRM gene expression was negatively correlated with promoter methylation (Spearman rank r = -1; p = 0.042). RPRM overexpression inhibited colony formation and anchorage-independent growth. In clinical samples, RPRM gene protein expression was detected in 75% (15/20) of non-tumor adjacent mucosa, but only in 25% (5/20) of gastric tumor tissues (p = 0.001). Clinicopathological correlations of loss of RPRM expression were significantly associated with invasive stage of GC (stage I to II-IV, p = 0.02) and a positive association between RPRM and p73 gene protein product expression was found (p<0.0001 and kappa value = 0.363). In conclusion, epigenetic silencing of RPRM gene by promoter methylation is associated with loss of RPRM expression. Functional assays suggest that RPRM behaves as a TSG. Loss of expression of RPRM gene protein product is associated with the invasive stage of GC. Positive association between RPRM and p73 expression suggest that other members of the p53 gene family may participate in the regulation of RPRM expression. PMID:25954972

  14. [Incidence and Risk Assessment of Tumor Lysis Syndrome in Patients with Advanced Germ Cell Cancer].

    PubMed

    Kurobe, Masahiro; Kawai, Koji; Tanaka, Ken; Ichioka, Daishi; Yoshino, Takayuki; Kandori, Shuya; Kawahara, Takashi; Waku, Natsui; Takaoka, Ei-Ichirou; Kojima, Takahiro; Joraku, Akira; Suetomi, Takahiro; Miyazaki, Jun; Nishiyama, Hiroyuki

    2016-05-01

    Tumor lysis syndrome (TLS) is a major oncological emergency. TLS is common in patients with hematological malignancies, but it can occur across a spectrum of cancer types. Germ cell tumors (GCT) have rapid cancer cell turnover and often present with bulky metastasis. The international TLS expert consensus panel has recommended guidelines for a medical decision tree to assign low, intermediate and high risk to patients with cancer at risk for TLS. GCT is classified as intermediate risk for TLS, and the patients who have other TLS risks factors are classified to be at high risk for TLS. In this study, we retrospectively analyzed 67 patients with metastatic GCT who were treated with induction chemotherapy at Tsukuba University Hospital between 2000 and 2013. Thirty-one, 15 and 21 patients were classified with good-, intermediate- and poor-prognosis disease, respectively, according to the International Germ Cell Cancer Collaborative Group criteria. Twelve patients (18%) were classified to be at high risk for TLS, and two patients were treated with allopurinol or rasburicase as prophylaxes for TLS. They did not show progression to laboratory TLS (L-TLS). In the remaining 10 TLS high-risk patients, three (30%) patients developed L-TLS after chemotherapy and started receiving oral allopurinol. As a result, no patients developed clinical TLS (C-TLS). In this study, 30% of TLS-high risk patients developed L-TLS without prophylactic treatment. Therefore, it is important to conduct TLS-risk stratification and consider prophylaxis such as rasburicase for advanced GCT patients at induction chemotherapy. PMID:27320114

  15. Prognostic value of aberrant promoter hypermethylation of tumor-related genes in early-stage head and neck cancer

    PubMed Central

    Misawa, Kiyoshi; Mochizuki, Daiki; Imai, Atsushi; Endo, Shiori; Mima, Masato; Misawa, Yuki; Kanazawa, Takeharu; Carey, Thomas E.; Mineta, Hiroyuki

    2016-01-01

    Staging and pathological grading are useful, but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Accordingly, molecular biomarkers that predict the risk of recurrence are necessary to improve clinical outcomes. The methylation statuses of the promoters of 11 tumor-related genes (p16, RASSF1A, E-cadherin, H-cadherin, MGMT, DAPK, DCC, COL1A2, TAC1, SST, and GALR1) were analyzed in 133 HNSCC cases using quantitative methylation-specific PCR. We detected frequent methylation of p16 (44%), RASSF1A (18%), E-cadherin (53%), H-cadherin (35%), MGMT (35%), DAPK (53%), DCC (42%), COL1A2 (44%), TAC1 (61%), SST (64%), and GALR1 (44%) in HNSCC. Disease-free survival was lower in patients with 6–11 methylated genes than in those with 0–5 methylated genes (log-rank test, P = 0.001). In a multivariate Cox proportional hazards analysis, the methylation of E-cadherin, COL1A2, TAC1, and GALR1 was associated with poor survival, with hazard ratios of 4.474 (95% CI, 1.241–16.124). In a joint analysis of these four genes, patients with 2–4 methylated genes had a significantly lower survival rate than those with 0–1 methylated genes in early-stage HNSCC. Importantly, the methylation of some genes was closely related to poor prognosis in early-stage HNSCC, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. PMID:27027429

  16. Prognostic value of aberrant promoter hypermethylation of tumor-related genes in early-stage head and neck cancer.

    PubMed

    Misawa, Kiyoshi; Mochizuki, Daiki; Imai, Atsushi; Endo, Shiori; Mima, Masato; Misawa, Yuki; Kanazawa, Takeharu; Carey, Thomas E; Mineta, Hiroyuki

    2016-05-01

    Staging and pathological grading are useful, but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Accordingly, molecular biomarkers that predict the risk of recurrence are necessary to improve clinical outcomes. The methylation statuses of the promoters of 11 tumor-related genes (p16, RASSF1A, E-cadherin, H-cadherin, MGMT, DAPK, DCC, COL1A2, TAC1, SST, and GALR1) were analyzed in 133 HNSCC cases using quantitative methylation-specific PCR. We detected frequent methylation of p16 (44%), RASSF1A (18%), E-cadherin (53%), H-cadherin (35%), MGMT (35%), DAPK (53%), DCC (42%), COL1A2 (44%), TAC1 (61%), SST (64%), and GALR1 (44%) in HNSCC. Disease-free survival was lower in patients with 6-11 methylated genes than in those with 0-5 methylated genes (log-rank test, P = 0.001). In a multivariate Cox proportional hazards analysis, the methylation of E-cadherin, COL1A2, TAC1, and GALR1 was associated with poor survival, with hazard ratios of 4.474 (95% CI, 1.241-16.124). In a joint analysis of these four genes, patients with 2-4 methylated genes had a significantly lower survival rate than those with 0-1 methylated genes in early-stage HNSCC. Importantly, the methylation of some genes was closely related to poor prognosis in early-stage HNSCC, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. PMID:27027429

  17. Use of extended curettage with osteotomy and fenestration followed by reconstruction with conservation of muscle insertion in the treatment of Enneking stage II locally aggressive bone tumor of the proximal extremities: resection and treatment of bone tumors

    PubMed Central

    2013-01-01

    Background The purpose of this study was to investigate the clinical efficacy of extended resection with osteotomy, fenestration and conservation of muscle (tendon) insertion in the treatment of bone tumors. Methods A total of 15 patients with locally aggressive bone tumors (Enneking stage II) in the adjacent muscle (tendon) insertion of the proximal extremity were enrolled in the present study (mean age of 29 years). Extended curettage of lesions with osteotomy, fenestration and/or conservation of muscle (tendon) insertion and internal fixation with a bone graft or bone cement was performed at stage I. Postsurgical brace protection was used for 4 to 12 weeks and the patients were periodically followed-up by X-ray and functional assessment. Recurrence, postsurgical Enneking score and outcome rating were assessed. Results Treated cases included 15 patients aged 29 ±7.75 years (range, 18 to 42) with a male to female ratio of 8:7. Six had a femoral tumor and nine had a humeral tumor. These tumors comprised three chondroblastomas, five giant-cell tumors and seven aneurysmal bone cysts. Follow-up for 48 ±12.95 months (range, 25 to 72) revealed that 13 of 15 (87%) patients exhibited no recurrence. Local recurrence was observed in a patient with an aneurysmal bone cyst (nine months) and one with a giant-cell tumor (12 months). Mean Enneking scores were 27 ±4.07 (range, 18 to 29). Except for the patient with the recurrent giant-cell tumor, all patients reported good (13%, 2 out of 15) or very good (80%, 12 out of 15) outcomes. Very good outcomes were reported in 92% of patients (12 out of 13) without recurrence. Conclusions The procedures used in this study achieved high clinical efficacy, complete lesion removal, reduced recurrence and good restoration of joint function in patients with primary locally aggressive Enneking stage II bone tumors of the proximal extremities. PMID:23497479

  18. Advanced Launch Vehicle Upper Stages Using Liquid Propulsion and Metallized Propellants

    NASA Technical Reports Server (NTRS)

    Palaszewski, Bryan A.

    1990-01-01

    Metallized propellants are liquid propellants with a metal additive suspended in a gelled fuel or oxidizer. Typically, aluminum (Al) particles are the metal additive. These propellants provide increase in the density and/or the specific impulse of the propulsion system. Using metallized propellant for volume-and mass-constrained upper stages can deliver modest increases in performance for low earth orbit to geosynchronous earth orbit (LEO-GEO) and other earth orbital transfer missions. Metallized propellants, however, can enable very fast planetary missions with a single-stage upper stage system. Trade studies comparing metallized propellant stage performance with non-metallized upper stages and the Inertial Upper Stage (IUS) are presented. These upper stages are both one- and two-stage vehicles that provide the added energy to send payloads to altitudes and onto trajectories that are unattainable with only the launch vehicle. The stage designs are controlled by the volume and the mass constraints of the Space Transportation System (STS) and Space Transportation System-Cargo (STS-C) launch vehicles. The influences of the density and specific impulse increases enabled by metallized propellants are examined for a variety of different stage and propellant combinations.

  19. Advanced launch vehicle upper stages using liquid propulsion and metallized propellants

    NASA Technical Reports Server (NTRS)

    Palaszewski, B. A.

    1990-01-01

    Metallized propellants are liquid propellants with a metal additive suspended in a gelled fuel or oxidizer. Typically, aluminum particles are the metal additives. These propellants provide increase in the density and/or the specific impulse of the propulsion system. Using metallized propellants for volume- and mass-constrained upper stages can deliver modest increases in performance for Low Earth Orbit to Geosynchronous Earth Orbit and other Earth orbital transfer missions. Metallized propellants, however, can enable very fast planetary missions with a single-stage upper stage system. Trade studies comparing metallized propellant stage performance with non-metallized upper stages and the Inertial Upper Stage are presented. These upper stages are both one- and two-stage vehicles that provide the added energy to send payloads to altitudes and onto trajectories that are unattainable with only the launch vehicle. The stage designs are controlled by the volume and the mass constraints of the Space Transportation System and Space Transportation System-Cargo launch vehicles. The influences of the density and specific impulse increases enabled by metallized propellants are examined for a variety of different stage and propellant combinations.

  20. Population-based Estimate of the Prevalence of HER-2 Positive Breast Cancer Tumors for Early Stage Patients in the US

    PubMed Central

    Cronin, Kathleen A.; Harlan, Linda C.; Dodd, Kevin W.; Abrams, Jeffrey S.; Ballard-Barbash, Rachel

    2010-01-01

    The goal of this study was to estimate prevalence of HER-2 positive tumors in a population-based sample of 1026 women diagnosed in 2005 with early stage breast cancer. We modeled the relationship between patient and tumor characteristics and HER-2. HER-2 positive estimates were 19% for women aged ≤49 years and 15% aged ≥50 years. HER-2 varied by tumor grade and size in women aged ≤49 years but was not significant in multivariate analysis. Tumor grade and race were associated with HER-2 for women aged ≥50 years after controlling for other variables. HER-2 varies by age and by race and tumor in older women. PMID:20690807

  1. Contrary melanoma-associated antigen-A expression at the tumor front and center: A comparative analysis of stage I and IV head and neck squamous cell carcinoma

    PubMed Central

    Hartmann, Stefan; Brisam, Muna; Rauthe, Stephan; Driemel, Oliver; Brands, Roman C.; Rosenwald, Andreas; Kübler, Alexander C.; Müller-Richter, Urs D. A.

    2016-01-01

    There is a growing body of evidence indicating that several melanoma-associated antigen-A (MAGE-A) subgroups contribute to the malignancy of head and neck cancer. The present study retrospectively analyzed the expression of all known MAGE-A subgroups in the tumor front and center of 38 head and neck cancer patients (Union for International Cancer Control stage I or IV) by immunohistochemistry. MAGE-A1, -A6, -A8, -A9 and -A11 were expressed at significantly higher levels at the tumor front of stage IV specimens compared with the tumor front of stage I specimens. In stage I cancer, the tumor center and front ratio (C/F ratio) for each subgroup was >1.0. In stage IV cancer, the C/F ratio was <1.0 in 9/11 subgroups. The most significant change in the expression pattern was observed for MAGE-A11. These results indicated that there is a marked alteration and shift to the invasive front of almost all MAGE-A subgroups, but particularly MAGE-A11, during the progression of head and neck squamous cell carcinoma. PMID:27703530

  2. Pediatric Cerebellar Tumors: Emerging Imaging Techniques and Advances in Understanding of Genetic Features.

    PubMed

    Choudhri, Asim F; Siddiqui, Adeel; Klimo, Paul

    2016-08-01

    Cerebellar tumors are the most common group of solid tumors in children. MR imaging provides an important role in characterization of these lesions, surgical planning, and postsurgical surveillance. Preoperative imaging can help predict the histologic subtype of tumors, which can provide guidance for surgical planning. Beyond histology, pediatric brain tumors are undergoing new classification schemes based on genetic features. Intraoperative MR imaging has emerged as an important tool in the surgical management of pediatric brain tumors. Effective understanding of the imaging features of pediatric cerebellar tumors can benefit communication with neurosurgeons and neuro-oncologists and can improve patient management.

  3. Pediatric Cerebellar Tumors: Emerging Imaging Techniques and Advances in Understanding of Genetic Features.

    PubMed

    Choudhri, Asim F; Siddiqui, Adeel; Klimo, Paul

    2016-08-01

    Cerebellar tumors are the most common group of solid tumors in children. MR imaging provides an important role in characterization of these lesions, surgical planning, and postsurgical surveillance. Preoperative imaging can help predict the histologic subtype of tumors, which can provide guidance for surgical planning. Beyond histology, pediatric brain tumors are undergoing new classification schemes based on genetic features. Intraoperative MR imaging has emerged as an important tool in the surgical management of pediatric brain tumors. Effective understanding of the imaging features of pediatric cerebellar tumors can benefit communication with neurosurgeons and neuro-oncologists and can improve patient management. PMID:27423803

  4. The Impact of Tumor Size on Outcomes After Stereotactic Body Radiation Therapy for Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Allibhai, Zishan; Taremi, Mojgan; Bezjak, Andrea; Brade, Anthony; Hope, Andrew J.; Sun, Alexander; Cho, B.C. John

    2013-12-01

    Purpose: Stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC) offers excellent control rates. Most published series deal mainly with small (usually <4 cm), peripheral, solitary tumors. Larger tumors are associated with poorer outcomes (ie, lower control rates, higher toxicity) when treated with conventional RT. It is unclear whether SBRT is sufficiently potent to control these larger tumors. We therefore evaluated and examined the influence of tumor size on treatment outcomes after SBRT. Methods and Materials: Between October 2004 and October 2010, 185 medically inoperable patients with early (T1-T2N0M0) NSCLC were treated on a prospective research ethics board-approved single-institution protocol. Prescription doses were risk-adapted based on tumor size and location. Follow-up included prospective assessment of toxicity (as per Common Terminology Criteria for Adverse Events, version 3.0) and serial computed tomography scans. Patterns of failure, toxicity, and survival outcomes were calculated using Kaplan-Meier method, and the significance of tumor size (diameter, volume) with respect to patient, treatment, and tumor factors was tested. Results: Median follow-up was 15.2 months. Tumor size was not associated with local failure but was associated with regional failure (P=.011) and distant failure (P=.021). Poorer overall survival (P=.001), disease-free survival (P=.001), and cause-specific survival (P=.005) were also significantly associated with tumor size (with tumor volume more significant than diameter). Gross tumor volume and planning target volume were significantly associated with grade 2 or worse radiation pneumonitis. However, overall rates of grade ≥3 pneumonitis were low and not significantly affected by tumor or target size. Conclusions: Currently employed stereotactic body radiation therapy dose regimens can provide safe effective local therapy even for larger solitary NSCLC tumors (up to 5.7 cm

  5. Real-world study of everolimus in advanced progressive neuroendocrine tumors.

    PubMed

    Panzuto, Francesco; Rinzivillo, Maria; Fazio, Nicola; de Braud, Filippo; Luppi, Gabriele; Zatelli, Maria Chiara; Lugli, Francesca; Tomassetti, Paola; Riccardi, Ferdinando; Nuzzo, Carmen; Brizzi, Maria Pia; Faggiano, Antongiulio; Zaniboni, Alberto; Nobili, Elisabetta; Pastorelli, Davide; Cascinu, Stefano; Merlano, Marco; Chiara, Silvana; Antonuzzo, Lorenzo; Funaioli, Chiara; Spada, Francesca; Pusceddu, Sara; Fontana, Annalisa; Ambrosio, Maria Rosaria; Cassano, Alessandra; Campana, Davide; Cartenì, Giacomo; Appetecchia, Marialuisa; Berruti, Alfredo; Colao, Annamaria; Falconi, Massimo; Delle Fave, Gianfranco

    2014-09-01

    Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3-4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold increased risk for severe toxicity was observed, with grade 3-4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS, and OS were reported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs.

  6. Real-world study of everolimus in advanced progressive neuroendocrine tumors.

    PubMed

    Panzuto, Francesco; Rinzivillo, Maria; Fazio, Nicola; de Braud, Filippo; Luppi, Gabriele; Zatelli, Maria Chiara; Lugli, Francesca; Tomassetti, Paola; Riccardi, Ferdinando; Nuzzo, Carmen; Brizzi, Maria Pia; Faggiano, Antongiulio; Zaniboni, Alberto; Nobili, Elisabetta; Pastorelli, Davide; Cascinu, Stefano; Merlano, Marco; Chiara, Silvana; Antonuzzo, Lorenzo; Funaioli, Chiara; Spada, Francesca; Pusceddu, Sara; Fontana, Annalisa; Ambrosio, Maria Rosaria; Cassano, Alessandra; Campana, Davide; Cartenì, Giacomo; Appetecchia, Marialuisa; Berruti, Alfredo; Colao, Annamaria; Falconi, Massimo; Delle Fave, Gianfranco

    2014-09-01

    Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3-4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold increased risk for severe toxicity was observed, with grade 3-4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS, and OS were reported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs. PMID:25117065

  7. Cancer Progression and Tumor Growth Kinetics

    NASA Astrophysics Data System (ADS)

    Blagoev, Krastan; Kalpathy-Cramer, Jayashree; Wilkerson, Julia; Sprinkhuizen, Sara; Song, Yi-Qiao; Bates, Susan; Rosen, Bruce; Fojo, Tito

    2013-03-01

    We present and analyze tumor growth data from prostate and brain cancer. Scaling the data from different patients shows that early stage prostate tumors show non-exponential growth while advanced prostate and brain tumors enter a stage of exponential growth. The scaling analysis points to the existence of cancer stem cells and/or massive apoptosis in early stage prostate cancer and that late stage cancer growth is not dominated by cancer stem cells. Statistical models of these two growth modes are discussed. Work supported by the National Science Foundation and the National Institutes of Health

  8. Comparison of diagnostic performance of CT and MRI for abdominal staging of pediatric renal tumors: a report from the Children's Oncology Group

    PubMed Central

    Servaes, Sabah; Naranjo, Arlene; Geller, James I.; Ehrlich, Peter F.; Gow, Kenneth W.; Perlman, Elizabeth J.; Dome, Jeffrey S.; Gratias, Eric; Mullen, Elizabeth A.

    2015-01-01

    Background CT and MRI are both used for abdominal staging of pediatric renal tumors. The diagnostic performance of the two modalities for local and regional staging of renal tumors has not been systematically evaluated. Objective To compare the diagnostic performance of CT and MRI for local staging of pediatric renal tumors. Materials and methods The study population was derived from the AREN03B2 study of the Children's Oncology Group. Baseline abdominal imaging performed with both CT and MRI within 30 days of nephrectomy was available for retrospective review in 82 renal tumor cases. Each case was evaluated for capsular penetration, lymph node metastasis, tumor thrombus, preoperative tumor rupture, and synchronous contralateral lesions. The surgical and pathological findings at central review were the reference standard. Results The sensitivity of CT and MRI for detecting capsular penetration was 68.6% and 62.9%, respectively (P=0.73), while specificity was 86.5% and 83.8% (P=1.0). The sensitivity of CT and MRI for detecting lymph node metastasis was 76.5% and 52.9% (P=0.22), and specificity was 90.4% and 92.3% (P=1.0). Synchronous contralateral lesions were identified by CT in 4/9 cases and by MRI in 7/9 cases. Conclusion CT and MRI have similar diagnostic performance for detection of lymph node metastasis and capsular penetration. MR detected more contralateral synchronous lesions; however these were present in a very small number of cases. Either modality can be used for initial loco–regional staging of pediatric renal tumors. PMID:25135711

  9. Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

    PubMed

    Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

    2015-03-01

    Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

  10. Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management and controversies

    PubMed Central

    Jensen, Robert T.; Berna, Marc J.; Bingham, David B; Norton, Jeffrey A.

    2008-01-01

    Pancreatic endocrine tumors (PETs) can occur in as part of four inherited disorders including: Multiple Endocrine Neoplasia type 1 (MEN1), von Hippel-Lindau disease (VHL), neurofibromatosis 1(NF-1) [von Recklinghausen’s disease] and the tuberous sclerosis complex (TSC). The relative frequency with which patients with these disorders develop PETs is MEN1>VHL>NF-1>TSC. Over the last few years there have been major advances in the understanding of the genetics and molecular pathogenesis of these disorders as well in the localization, medical and surgical treatment of the PETs in these patients. The study of the PETs in these disorders has not only provided insights into the possible pathogenesis of sporadic PETs, but have also presented a number of unique management and treatment issues, some of which are applicable to patients with sporadic PETs. Therefore the study of PETs in these uncommon disorders has provided valuable insights that in many cases are applicable to the general group of patients with sporadic PETs. In this article these areas are briefly reviewed as well as the current state of knowledge of the PETs in these disorders and the controversies that exist in their management are briefly summarized and discussed. PMID:18798544

  11. Three-Dimensional Ground Glass Opacity Ratio in CT Images Can Predict Tumor Invasiveness of Stage IA Lung Cancer

    PubMed Central

    Yu, Woo Sik; Hong, Sae Rom; Lee, Jin Gu; Lee, Jae Seok; Jung, Hee Suk; Kim, Dae Joon; Chung, Kyung Young

    2016-01-01

    Purpose We investigated the relationship between various parameters, including volumetric parameters, and tumor invasiveness according to the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification. Materials and Methods We retrospectively reviewed 99 patients with completely resected stage IA lung adenocarcinoma. The correlation between several parameters [one-dimensional ground glass opacity (1D GGO) ratio, two-dimensional (2D) GGO ratio, three-dimensional (3D) GGO ratio, 1D solid size, 2D solid size, and 3D solid size] and tumor invasiveness according to IASLC/ATS/ERS classification was investigated using receiver operating characteristic (ROC) analysis. Adenocarcinoma in situ and minimally invasive adenocarcinoma were referred to as noninvasive adenocarcinoma. Results The areas under the curve (AUC) to predict invasive adenocarcinoma for the 1D, 2D, and 3D GGO ratios were 0.962, 0.967, and 0.971, respectively. The optimal cut-off values for the 1D, 2D, and 3D GGO ratios were 38%, 62%, and 74%, respectively. The AUC values for 1D, 2D, and 3D solid sizes to predict invasive adenocarcinoma were 0.933, 0.944, and 0.903, respectively. The optimal cut-off values for 1D, 2D, and 3D solid sizes were 1.2 cm, 1.5 cm2, and 0.7 cm3, respectively. The difference in the ROC curves for 3D GGO ratio and 3D solid size was significant (p=0.01). Conclusion Computed tomography image-related parameters based on GGO were well correlated with and predictive of invasiveness according to IASLC/ATS/ERS classification. 3D GGO ratio was more strongly correlated with pathologic invasiveness than 3D solid size. PMID:27401643

  12. EF5 in Measuring Tumor Hypoxia in Patients With Stage I-III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2015-04-10

    Stage IA Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  13. Method and apparatus for advanced staged combustion utilizing forced internal recirculation

    DOEpatents

    Rabovitser, Iosif K.; Knight, Richard A.; Cygan, David F.; Nester, Serguei; Abbasi, Hamid A.

    2003-12-16

    A method and apparatus for combustion of a fuel in which a first-stage fuel and a first-stage oxidant are introduced into a combustion chamber and ignited, forming a primary combustion zone. At least about 5% of the total heat output produced by combustion of the first-stage fuel and the first-stage oxidant is removed from the primary combustion zone, forming cooled first-stage combustion products. A portion of the cooled first-stage combustion products from a downstream region of the primary combustion zone is recirculated to an upstream region of primary combustion zone. A second-stage fuel is introduced into the combustion chamber downstream of the primary combustion zone and ignited, forming a secondary combustion zone. At least about 5% of the heat from the secondary combustion zone is removed. In accordance with one embodiment, a third-stage oxidant is introduced into the combustion chamber downstream of the secondary combustion zone, forming a tertiary combustion zone.

  14. Downregulation of Six MicroRNAs Is Associated with Advanced Stage, Lymph Node Metastasis and Poor Prognosis in Small Cell Carcinoma of the Cervix

    PubMed Central

    Huang, Long; Lin, Jia-Xin; Yu, Yan-Hong; Zhang, Mei-Yin; Wang, Hui-Yun; Zheng, Min

    2012-01-01

    Background Small cell carcinoma of the cervix (SCCC) is very rare, and due to the long time period required to recruit sufficient numbers of patients, there is a paucity of information regarding the prognostic factors associated with survival. MicroRNAs (miRNAs) have been used as cancer-related biomarkers in a variety of tumor types, and the objective of this study was to determine whether microRNA expression profiles can predict clinical outcome in SCCC. Methodology/Principal Findings Forty-four patients with SCCC who underwent radical hysterectomy between January 2000 and October 2009 were enrolled. Using the GeneCopoeia All-in-One™ Customized Human qPCR Primer Array, the expression profiles of 30 miRNAs associated with tumor metastasis was obtained from the formalin-fixed paraffin embedded samples of all 44 patients. Seven miRNAs, has-let-7c, has-miR-10b, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly down-regulated in advanced stage SCCCpatients (FIGO IB2-IV) compared to early stage SCCC patients (FIGOIB1). Among, downregulation of six miRNAs, has-let-7c, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly associated with lymph node metastasis and reduced survival in SCCC. Kaplan–Meier survival analyses revealed that SCCC patients with low expression of has-miR-100 (P = 0.019) and has-miR-125b (P = 0.020) projected a significant tendency towards poorer prognosis. Conclusions/Significance This study demonstrates that downregulation of 7 miRNA associated with advanced stage, 6 miRNAs with metastasis and 2 with poor prognosis in SCCC. Functional analysis of these miRNAs may enhance our understanding of SCCC, as altered expression of specific miRNAs may regulate the metastatic pathway and provide novel targets for therapy. PMID:22438992

  15. Impact of Pretreatment Tumor Growth Rate on Outcome of Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy

    SciTech Connect

    Atallah, Soha; Cho, B.C. John; Allibhai, Zishan; Taremi, Mojgan; Giuliani, Meredith; Le, Lisa W.; Brade, Anthony; Sun, Alexander; Bezjak, Andrea; Hope, Andrew J.

    2014-07-01

    Purpose: To determine the influence of pretreatment tumor growth rate on outcomes in patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Methods and Materials: A review was conducted on 160 patients with T1-T2N0M0 NSCLC treated with SBRT at single institution. The patient's demographic and clinical data, time interval (t) between diagnostic and planning computed tomography (CT), vital status, disease status, and cause of death were extracted from a prospectively kept database. Differences in gross tumor volume between diagnostic CT (GTV1) and planning CT (GTV2) were recorded, and growth rate was calculated by use of specific growth rate (SGR). Kaplan-Meier curves were constructed for overall survival (OS). Differences between groups were compared with a log-rank test. Multivariate analyses were performed by use of the Cox proportional hazard model with SGR and other relevant clinical factors. Cumulative incidence was calculated for local, regional, and distant failures by use of the competing risk approach and was compared with Gray's test. Results: The median time interval between diagnostic and planning CT was 82 days. The patients were divided into 2 groups, and the median SGR was used as a cut-off. The median survival times were 38.6 and 27.7 months for the low and high SGR groups, respectively (P=.03). Eastern Cooperative Oncology Group performance status (P=.01), sex (P=.04), SGR (P=.03), and GTV2 (P=.002) were predictive for OS in multivariable Cox regression analysis and, except sex, were similarly predictive for failure-free survival (FFS). The 3-year cumulative incidences of regional failure were 19.2% and 6.0% for the high and low SGR groups, respectively (P=.047). Conclusion: High SGR was correlated with both poorer OS and FFS in patients with early-stage NSCLC treated with SBRT. If validated, this measurement may be useful in identifying patients most likely to benefit from adjuvant

  16. Two-Stage Phase I Dose-Escalation Study of Intratumoral Reovirus Type 3 Dearing and Palliative Radiotherapy in Patients with Advanced Cancers

    PubMed Central

    Harrington, Kevin J.; Karapanagiotou, Eleni M.; Roulstone, Victoria; Twigger, Katie R.; White, Christine L.; Vidal, Laura; Beirne, Debbie; Prestwich, Robin; Newbold, Kate; Ahmed, Merina; Thway, Khin; Nutting, Christopher M.; Coffey, Matt; Harris, Dean; Vile, Richard G.; Pandha, Hardev S.; DeBono, Johann S.; Melcher, Alan A.

    2013-01-01

    Purpose To determine the safety and feasibility of combining intratumoral reovirus and radiotherapy in patients with advanced cancer and to assess viral biodistribution, reoviral replication in tumors, and antiviral immune responses. Experimental Design Patients with measurable disease amenable to palliative radiotherapy were enrolled. In the first stage, patients received radiotherapy (20 Gy in five fractions) plus two intratumoral injections of RT3D at doses between 1 × 108 and 1 × 1010 TCID50. In the second stage, the radiotherapy dose was increased (36 Gy in 12 fractions) and patients received two, four, or six doses of RT3D at 1 × 1010 TCID50. End points were safety, viral replication, immunogenicity, and antitumoral activity. Results Twenty-three patients with various solid tumors were treated. Dose-limiting toxicity was not seen. The most common toxicities were grade 2 (or lower) pyrexia, influenza-like symptoms, vomiting, asymptomatic lymphopenia, and neutropenia. There was no exacerbation of the acute radiation reaction. Reverse transcription-PCR (RT-PCR) studies of blood, urine, stool, and sputum were negative for viral shedding. In the low-dose (20 Gy in five fractions) radiation group, two of seven evaluable patients had a partial response and five had stable disease. In the high-dose (36 Gy in 12 fractions) radiation group, five of seven evaluable patients had partial response and two stable disease. Conclusions The combination of intratumoral RT3D and radiotherapy was well tolerated. The favorable toxicity profile and lack of vector shedding means that this combination should be evaluated in newly diagnosed patients receiving radiotherapy with curative intent. PMID:20484020

  17. Somatic DNA Hypomethylation in H. pylori-Associated High-Risk Gastritis and Gastric Cancer: Enhanced Somatic Hypomethylation Associates with Advanced Stage Cancer

    PubMed Central

    Leodolter, Andreas; Alonso, Sergio; González, Beatriz; Ebert, Matthias P; Vieth, Michael; Röcken, Christoph; Wex, Thomas; Peitz, Ullrich; Malfertheiner, Peter; Perucho, Manuel

    2015-01-01

    Objectives: Helicobacter pylori-related high-risk gastritis (HRG) is a severe risk factor for gastric cancer (GC). The link between HRG and long-term risk for GC may involve genetic and epigenetic alterations underlying a field defect, i.e. a region of the mucosa prone to cancer development. Global DNA hypomethylation is a pervasive alteration in GC that associates with chromosomal instability and poor prognosis. The aim of this study was to determine the chronology of this alteration along the progression of HRG to GC, to test the hypothesis that it occurs early in the chronology of this pathway and plays a mechanistic role in the long-term cancer risk. Methods: We comparatively measured the genomic methylation level in gastric biopsies from 94 GC patients and 16 of their cancer-free relatives, 38 HRG patients, and 17 GERD patients, using a quantitative enzymatic method. Results: GC biopsies were hypomethylated compared to their matching non-tumor mucosa (P=9.4 × 10−12), irrespective of the tumor location or patients' country of origin. Genome-wide hypomethylation was also found in gastric mucosa of GC (P=1.5 × 10−5) and HRG (P=0.004) patients compared with healthy donors and GC relatives, regardless of the biopsy location within the stomach or previous H. pylori eradication therapy. An enhanced hypomethylation, distinguished by a bi-slope distribution of the differences in methylation between tumor and normal tissues, associated with a more invasive (P=0.005) and advanced stage (P=0.017) type of GC. Conclusions: Universal DNA demethylation in normal gastric mucosa in GC patients appears sporadic rather than familial. Genomic hypomethylation in HRG possibly contributes to a field defect for cancerization that is not reversed by bacterial eradication. Enhanced somatic hypomethylation may stratify GC for prognostic purposes. PMID:25928808

  18. Initial Evaluation of Treatment-Related Pneumonitis in Advanced-Stage Non-Small-Cell Lung Cancer Patients Treated With Concurrent Chemotherapy and Intensity-Modulated Radiotherapy

    SciTech Connect

    Yom, Sue S.; Liao Zhongxing . E-mail: zliao@mdanderson.org; Liu, H. Helen; Tucker, Susan L.; Hu, C.-S.; Wei Xiong; Wang Xuanming; Wang Shulian; Mohan, Radhe; Cox, James D.; Komaki, Ritsuko

    2007-05-01

    Purpose: To investigate the rate of high-grade treatment-related pneumonitis (TRP) in patients with advanced non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). Methods and Materials: From August 2002 to August 2005, 151 NSCLC patients were treated with IMRT. We excluded patients who did not receive concurrent chemotherapy or who had early-stage cancers, a history of major lung surgery, prior chest RT, a dose <50 Gy, or IMRT combined with three-dimensional conformal RT (3D-CRT). Toxicities were graded by Common Terminology Criteria for Adverse Events version 3.0. Grade {>=}3 TRP for 68 eligible IMRT patients was compared with TRP among 222 similar patients treated with 3D-CRT. Results: The median follow-up durations for the IMRT and 3D-CRT patients were 8 months (range, 0-27 months) and 9 months (range, 0-56 months), respectively. The median IMRT and 3D-CRT doses were 63 Gy. The median gross tumor volume was 194 mL (range, 21-911 mL) for IMRT, compared with 142 mL (range, 1.5-1,186 mL) for 3D-CRT (p = 0.002). Despite the IMRT group's larger gross tumor volume, the rate of Grade {>=}3 TRP at 12 months was 8% (95% confidence interval 4%-19%), compared with 32% (95% confidence interval 26%-40%) for 3D-CRT (p = 0.002). Conclusions: In advanced NSCLC patients treated with chemoradiation, IMRT resulted in significantly lower levels of Grade {>=}3 TRP compared with 3D-CRT. Clinical, dosimetric, and patient selection factors that may have influenced rates of TRP require continuing investigation. A randomized trial comparing IMRT with 3D-CRT has been initiated.

  19. Optimal tumor shrinkage predicts long-term outcome in advanced nonsmall cell lung cancer (NSCLC) treated with target therapy

    PubMed Central

    He, Xiaobo; Zhang, Yang; Ma, Yuxiang; Zhou, Ting; Zhang, Jianwei; Hong, Shaodong; Sheng, Jin; Zhang, Zhonghan; Yang, Yunpeng; Huang, Yan; Zhang, Li; Zhao, Hongyun

    2016-01-01

    Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as standard therapies for advanced nonsmall cell lung cancer (NSCLC) patients with EGFR mutation positive. Because these targeted therapies could cause tumor necrosis and shrinkage, the purpose of the study is to search for a value of optimal tumor shrinkage as an appropriate indicator of outcome for advanced NSCLC. A total of 88 NSCLC enrollees of 3 clinical trials (IRESSA registration clinical trial, TRUST study and ZD6474 study), who received Gefitinib (250 mg, QD), Erlotinib (150 mg, QD), and ZD6474 (100 mg, QD), respectively, during December 2003 and October 2007, were retrospectively analyzed. The response evaluation criteria in solid tumors (RECIST) were used to identify responders, who had complete response (CR) or partial responses (PR) and nonresponders who had stable disease (SD) or progressive disease (PD). Receiver operating characteristics (ROC) analysis was used to find the optimal tumor shrinkage as an indicator for tumor therapeutic outcome. Univariate and multivariate Cox regression analyses were performed to compare the progression-free survival (PFS) and overall survival (OS) between responders and nonresponders stratified based on radiologic criteria. Among the 88 NSCLC patients, 26 were responders and 62 were nonresponders based on RECIST 1.0. ROC indicated that 8.32% tumor diameter shrinkage in the sum of the longest tumor diameter (SLD) was the cutoff point of tumor shrinkage outcomes, resulting in 46 responders (≤8.32%) and 42 nonresponders (≥8.32%). Univariate and multivariate Cox regression analyses indicated that (1) the responders (≤8.32%) and nonresponders (≥ −8.32%) were significantly different in median PFS (13.40 vs 1.17 months, P < 0.001) and OS (19.80 vs 7.90 months, P < 0.001) and (2) –8.32% in SLD could be used as the optimal threshold for PFS (hazard ratio [HR], 8.11, 95% CI, 3.75 to 17.51, P < 0.001) and OS

  20. Optimization of two-stage production/inventory systems under order base stock policy with advance demand information

    NASA Astrophysics Data System (ADS)

    Nakade, Koichi; Yokozawa, Shiori

    2016-08-01

    It is important to share demand information among the members in supply chains. In recent years, production and inventory systems with advance demand information (ADI) have been discussed, where advance demand information means the information of demand which the decision maker obtains before the corresponding actual demand arrives. Appropriate production and inventory control using demand information leads to the decrease of inventory and backlog costs. For a single stage system, the optimal base stock and release lead time have been discussed in the literature. In practical production systems the manufacturing system has multiple processes. The multiple stage production and inventory system with ADI, however, has been analyzed by simulation or assuming exponential processing time. That is, their theoretical analysis and optimization of release lead time and base stock level have little been obtained because of its difficulty. In this paper, theoretical analysis of a two-stage production inventory system with advance demand information is developed, where the processing time is assumed deterministic and identical; demand arrival process is Poisson, and an order base stock policy is adopted. Using the analytical results, optimal release lead time and optimal base stock levels for minimizing the average cost on the holding and backlog costs are explicitly derived.

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

    ClinicalTrials.gov

    2016-09-09

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

  2. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification.

    PubMed

    Travis, William D; Brambilla, Elisabeth; Nicholson, Andrew G; Yatabe, Yasushi; Austin, John H M; Beasley, Mary Beth; Chirieac, Lucian R; Dacic, Sanja; Duhig, Edwina; Flieder, Douglas B; Geisinger, Kim; Hirsch, Fred R; Ishikawa, Yuichi; Kerr, Keith M; Noguchi, Masayuki; Pelosi, Giuseppe; Powell, Charles A; Tsao, Ming Sound; Wistuba, Ignacio

    2015-09-01

    The 2015 World Health Organization (WHO) Classification of Tumors of the Lung, Pleura, Thymus and Heart has just been published with numerous important changes from the 2004 WHO classification. The most significant changes in this edition involve (1) use of immunohistochemistry throughout the classification, (2) a new emphasis on genetic studies, in particular, integration of molecular testing to help personalize treatment strategies for advanced lung cancer patients, (3) a new classification for small biopsies and cytology similar to that proposed in the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (4) a completely different approach to lung adenocarcinoma as proposed by the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (5) restricting the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation with reclassification of the remaining former large cell carcinoma subtypes into different categories, (6) reclassifying squamous cell carcinomas into keratinizing, nonkeratinizing, and basaloid subtypes with the nonkeratinizing tumors requiring immunohistochemistry proof of squamous differentiation, (7) grouping of neuroendocrine tumors together in one category, (8) adding NUT carcinoma, (9) changing the term sclerosing hemangioma to sclerosing pneumocytoma, (10) changing the name hamartoma to "pulmonary hamartoma," (11) creating a group of PEComatous tumors that include (a) lymphangioleiomyomatosis, (b) PEComa, benign (with clear cell tumor as a variant) and PMID:26291008

  3. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer.

    PubMed

    Eberhardt, W E E; De Ruysscher, D; Weder, W; Le Péchoux, C; De Leyn, P; Hoffmann, H; Westeel, V; Stahel, R; Felip, E; Peters, S

    2015-08-01

    To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.

  4. Malignant extrarenal rhabdoid tumor of the spine: staging and evaluation of response to therapy with F-18 FDG PET/CT.

    PubMed

    Makis, William; Ciarallo, Anthony; Hickeson, Marc

    2011-07-01

    Malignant extrarenal rhabdoid tumor (ERRT) is a very rare type of soft-tissue sarcoma with a reported incidence of 0.3% of all soft-tissue sarcomas. Only 7 cases of spinal malignant ERRT have been reported in the literature, and to our knowledge, F-18 FDG PET/CT imaging for staging and evaluation of response to therapy for these tumors has not been previously described. This is a case of an 8-month-old boy with malignant ERRT of the spine, who was staged with F-18 FDG PET/CT, and had his tumor burden assessed with PET/CT after chemotherapy, which altered the subsequent chemotherapy regimen. PMID:21637073

  5. Malignant extrarenal rhabdoid tumor of the spine: staging and evaluation of response to therapy with F-18 FDG PET/CT.

    PubMed

    Makis, William; Ciarallo, Anthony; Hickeson, Marc

    2011-07-01

    Malignant extrarenal rhabdoid tumor (ERRT) is a very rare type of soft-tissue sarcoma with a reported incidence of 0.3% of all soft-tissue sarcomas. Only 7 cases of spinal malignant ERRT have been reported in the literature, and to our knowledge, F-18 FDG PET/CT imaging for staging and evaluation of response to therapy for these tumors has not been previously described. This is a case of an 8-month-old boy with malignant ERRT of the spine, who was staged with F-18 FDG PET/CT, and had his tumor burden assessed with PET/CT after chemotherapy, which altered the subsequent chemotherapy regimen.

  6. Novel actions of next-generation taxanes benefit advanced stages of prostate cancer

    PubMed Central

    de Leeuw, Renée; Berman-Booty, Lisa D; Schiewer, Matthew J; Ciment, Stephen J; Den, Robert B; Dicker, Adam P; Kelly, William K; Trabulsi, Edouard J; Lallas, Costas D; Gomella, Leonard G; Knudsen, Karen E

    2014-01-01

    Purpose To improve the outcomes of patients with castrate resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individual specific treatments for patients with CRPC. The current studies compared the novel taxane, cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond. Experimental design Cabazitaxel (CBTX) and docetaxel (DCTX) were compared via in vitro modeling to determine molecular mechanism, biochemical and cell biological impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro, and in xenograft tumors for cabazitaxel response. Results The data herein show that i. CBTX exerts stronger cytostatic and cytotoxic response compared to DCTX, especially in CRPC; ii. CBTX induces aberrant mitosis, leading to pyknotic and multinucleated cells; iii. taxanes do not act through the androgen receptor (AR); iv. Gene expression profiling reveals distinct molecular actions for CBTX v. tumors that have progressed to castration resistance via loss of RB show enhanced sensitivity to CBTX. Conclusions CBTX not only induces improved cytostatic and cytotoxic effects, but also impacts distinct molecular pathways, compared to DCTX, which could underlie its efficacy after DCTX treatment has failed in CRPC patients. Finally, RB is identified as the first potential biomarker that could define the therapeutic response to taxanes in metastatic CRPC. This would suggest that loss of RB function induces sensitization taxanes, which could benefit up to 50% of CRPC cases. PMID:25691773

  7. Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

    ClinicalTrials.gov

    2016-10-26

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  8. Stages of Wilms Tumor

    MedlinePlus

    ... waist. Tiny tubules in the kidneys filter and clean the blood . They take out waste products and ... bacteria . Ultrasound exam : A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues ...

  9. Association between vascular-poor area of primary tumors and epidermal growth factor receptor gene status in advanced lung adenocarcinoma.

    PubMed

    Togashi, Yosuke; Masago, Katsuhiro; Kubo, Takeshi; Fujimoto, Daichi; Sakamori, Yuichi; Nagai, Hiroki; Kim, Young Hak; Togashi, Kaori; Mishima, Michiaki

    2012-12-01

    Mutation of the epidermal growth factor receptor gene (EGFR mutation) is a very important marker in the treatment for non-small cell lung cancer. Since signaling from this receptor induces tumor-associated angiogenesis, we hypothesized that lung cancers with EGFR mutations tend to develop locally with increased angiogenesis. Thus, the association between vascular-poor area of primary tumors and EGFR status was retrospectively investigated in advanced lung adenocarcinomas. To assess vascular-poor area, contrast-enhanced computed tomography scans taken before initial treatment for lung cancer were analyzed, together with primary tumor location (peripheral or central) and size. We analyzed 178 patients with advanced lung adenocarcinoma. EGFR mutations were detected in 95 of the 178 patients (53.4 %). EGFR mutation was found to be significantly related to women (P = 0.0070), never-smokers (P < 0.0001), and tumors without vascular-poor area (P < 0.0001). Based on a multivariate analysis, presence of EGFR mutations was independently associated with never-smokers (P = 0.0046), lack of vascular-poor area (P = 0.0001), and tumor size >30 mm (P = 0.0080). EGFR mutations were found in 41 of 51 never-smokers without vascular-poor area (80.4 %), 19 of 36 never-smokers with vascular-poor area (52.8 %), 19 of 37 current or former-smokers without vascular-poor area (51.4 %), and 16 of 54 current or former-smokers with vascular-poor area (29.6 %). This study showed an association between vascular-poor area of primary tumors and EGFR status. As a consequence, evaluation using a combination of smoking status and vascular-poor area allows us to predict presence of EGFR mutations at a high frequency.

  10. Staging Early Esophageal Cancer.

    PubMed

    Old, O J; Isabelle, M; Barr, H

    2016-01-01

    Staging esophageal cancer provides a standardized measure of the extent of disease that can be used to inform decisions about therapy and guide prognosis. For esophageal cancer, the treatment pathways vary greatly depending on stage of disease, and accurate staging is therefore crucial in ensuring the optimal therapy for each patient. For early esophageal cancer (T1 lesions), endoscopic resection can be curative and simultaneously gives accurate staging of depth of invasion. For tumors invading the submucosa or more advanced disease, comprehensive investigation is required to accurately stage the tumor and assess suitability for curative resection. A combined imaging approach of computed tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS) offers complementary diagnostic information and gives the greatest chance of accurate staging. Staging laparoscopy can identify peritoneal disease and small superficial liver lesions that could be missed on CT or PET, and alters management in up to 20 % of patients. Optical diagnostic techniques offer the prospect of further extending the possibilities of endoscopic staging in real time. Optical coherence tomography can image superficial lesions and could provide information on depth of invasion for these lesions. Real-time lymph node analysis using optical diagnostics such as Raman spectroscopy could be used to support immediate endoscopic therapy without waiting for results of cytology or further investigations. PMID:27573772

  11. Tumor budding score based on 10 high-power fields is a promising basis for a standardized prognostic scoring system in stage II colorectal cancer.

    PubMed

    Horcic, Milo; Koelzer, Viktor H; Karamitopoulou, Eva; Terracciano, Luigi; Puppa, Giacomo; Zlobec, Inti; Lugli, Alessandro

    2013-05-01

    Tumor budding is recognized by the World Health Organization as an additional prognostic factor in colorectal cancer but remains unreported in diagnostic work due to the absence of a standardized scoring method. This study aims to assess the most prognostic and reproducible scoring systems for tumor budding in colorectal cancer. Tumor budding on pancytokeratin-stained whole tissue sections from 105 well-characterized stage II patients was scored by 3 observers using 7 methods: Hase, Nakamura, Ueno, Wang (conventional and rapid method), densest high-power field, and 10 densest high-power fields. The predictive value for clinicopathologic features, the prognostic significance, and interobserver variability of each scoring method was analyzed. Pancytokeratin staining allowed accurate evaluation of tumor buds. Interobserver agreement for 3 observers was excellent for densest high-power field (intraclass correlation coefficient, 0.83) and 10 densest high-power fields (intraclass correlation coefficient, 0.91). Agreement was moderate to substantial for the conventional Wang method (κ = 0.46-0.62) and moderate for the rapid method (κ = 0.46-0.58). For Nakamura, moderate agreement (κ = 0.41-0.52) was reached, whereas concordance was fair to moderate for Ueno (κ = 0.39-0.56) and Hase (κ = 0.29-0.51). The Hase, Ueno, densest high-power field, and 10 densest high-power field methods identified a significant association of tumor budding with tumor border configuration. In multivariate analysis, only tumor budding as evaluated in densest high-power field and 10 densest high-power fields had significant prognostic effects on patient survival (P < .01), with high prognostic accuracy over the full 10-year follow-up. Scoring tumor buds in 10 densest high-power fields is a promising method to identify stage II patients at high risk for recurrence in daily diagnostics; it is highly reproducible, accounts for heterogeneity, and has a strong predictive value for adverse outcome

  12. Delayed type hypersensitivity response to recall antigens does not accurately reflect immune competence in advanced stage breast cancer patients.

    PubMed

    Schiffman, Kathy; Rinn, Kristine; Disis, Mary L

    2002-07-01

    The development of delayed-type hypersensitivity (DTH) response to recall antigens has long been utilized as a measure of immune competence. It is assumed that because patients with advanced stage cancers exhibit multiple immune system defects they may not be responsive to immunization. We pre-selected patients with advanced HER-2/neu (HER2) overexpressing breast and ovarian cancers for enrolment into a phase I trial designed to evaluate the immunogenicity of a HER2 peptide vaccine based on the patient's immune competence as assessed by DTH skin testing to common recall antigens (Multitest CMI, Institut Merieux, Lyon, France). At the time of a positive DTH response to tetanus toxoid (tt) peripheral blood was obtained to measure T cell responses to tt. Of 53 patients evaluated, 38 (72%) were not anergic. Among the 15 (28%) who were, seven patients with advanced stage breast cancer were re-tested a median of 26 days (range 12-150 days) after receiving a tt bopster vaccination. Five of the seven had positive DTH responses when re-challenged with tt and six had peripheral blood tetanus specific T cell response with stimulation index >2.0. Thus, the majority of patients studied with advanced stage breast or ovarian cancer were able to mount a DTH response to common recall antigens. Moreover, a negative response by DTH testing to a battery of common recall antigens was not a reflection of the breast cancer patient's ability to mount a cell-mediated immune response to a vaccinated antigen, tt.

  13. Single high dose intraoperative electrons for advanced stage pancreatic cancer: Phase I pilot study

    SciTech Connect

    Goldson, A.L.; Ashaveri, E.; Espinoza, M.C.

    1981-07-01

    Phase I toxicity studies with intraoperative radiotherapy proved to be a feasible adjunct to surgery for unresectable malignancies of the pancreas at Howard University Hospital. There have been minimal side effects or complications related to the combination of limited surgical decompression and intraoperative radiotherapy alone. The toxic effects of intraoperative radiotherapy on normal tissues is being assessed on a dose volume basis. Doses of 2000 to 2500 rad in a single exposure to include the pancreas, regional nodes and duodenum are acceptable if the total treatment volume is less than or equal to 100 cm. The tumoricidal effects on the cancer are demonstratable when one reviews the pathological specimens that illustrate massive tumor necrosis and fibros replacement, but in all cases reviewed, viable cancer was noted. Intraoperative radiotherapy, therefore, represents a significant boost dose for resectable, partially resectable or non-resectable tumors when added to conventional external beam irradiation and/or chemotherapy. Preliminary clinical data and minimal toxicity justifies further investigation.

  14. Neoadjuvant chemotherapy in early-stage and locally advanced small bulk squamous cell carcinoma of the oral cavity and oropharynx.

    PubMed

    Tichler, T; Ramon, Y; Rath, P; Hendler, S; Brenner, H J

    1988-01-01

    Thirty patients with Stages I, II and III squamous cell carcinoma of the oral cavity and oropharynx (6, 12 and 12 patients, respectively) were entered into a combined modality protocol using preoperative chemotherapy, followed by resection with or without radical neck dissection and radiotherapy. None of the patients received prior treatment and all had good performance status. Primary sites included alveolar ridge (in nine patients), buccal mucosa (in eight), tongue (in six), floor of mouth (in five), and hard palate and tonsillar fossa in one each. Chemotherapy was given as a neoadjuvant debulking procedure using two courses of the Price-Hill regimen (5FU, methotrexate with citrovorum rescue, vincristine, bleomycin, and hydrocortisone) followed in 10 to 14 days by local resection for Stage I-II patients and radical neck dissection plus radiotherapy for Stage III patients. Response to chemotherapy alone was observed in 70% (21 of 30), with 17% (5 of 30) complete responders. Responses were seen in 100% of Stage I, 75% of Stage II, and 50% of Stage III patients. Age greater than 80 years was a poor prognostic indicator. Both men and women responded equally well. Of the 25 patients not entering CR with chemotherapy, a further 75% (11 of 15) did so after local resection and 50% (5 of 10) after local resection, radical neck dissection, and radiotherapy. Overall salvage rate post chemotherapy was 64% (16 of 25). All five patients in CR with chemotherapy alone are alive at a median follow-up time of greater than or equal to 43 months; full survival data are discussed. Toxicity was minimal and did not affect change in treatment course in any patient. These results show that further investigations on the use of neoadjuvant chemotherapy in early-stage and locally advanced squamous cell carcinoma of the oral cavity and oropharynx are indicated.

  15. Advance in diagnosis of female genital tract tumor with laser fluorescence

    NASA Astrophysics Data System (ADS)

    Ding, Ai-Hua; Tseng, Quen; Lian, Shao-Hui

    1998-11-01

    In order to improve the diagnostic accuracy of malignant tumors with laser fluorescence, in 1996, our group successfully created the computerized laser fluorescence spectrograph type II with more reliable images shown overshadowing the naked eye method before 74 cases of female genital tract diseases had been examined by the LFS II resulting in 10 positive cases which were also proven pathologically as malignant tumors, without nay false negative, 3 cases presented suspicious positive but all were proven pathologically as non-tumors lesions, the false positive rate was 4 percent. Our work showed that the method of LFS II can provide a more rapid and accurate diagnosis for the clinical malignant tumors.

  16. Could S6K1 immunopositivity be used to distinguish early and advanced stages of endometrioid endometrial adenocarcinoma?

    PubMed Central

    Gün, İsmet; Özdamar, Özkan; Küçükodacı, Zafer; Muhçu, Murat; Demirel, Dilaver

    2016-01-01

    Objective To assess whether the immunopositivity of S6K1, a crucial effector of the mTOR signaling pathway, varies between early-stage low-grade and advanced-stage high-grade endometrial endometrioid adenocarcinoma (EEA) as well as to discuss its prognostic significance. Material and Methods A total of 22 normal endometrial tissue samples (Control group) and 41 EEA specimens (Study group) were enrolled in the study, and all the samples underwent immunohistochemical staining for S6 kinase alpha (S6K1). The study group was further evaluated in two subgroups; stage 1A, grade 1 (Group 1) and stage ≥1A, grade 2 or 3 (Group 2). Group 2 patients were considered as a poor prognosis for EEA. The samples were examined by two independent pathologists. Statistical analyses were performed using the Student’s t-test for continuous variables, the Chi-square test for categorical variables, and one-way analysis of variance for the comparison of multiple variables. Results The immunopositivity rate for all the included EEA patients was 56.1%, whereas none of the 22 normal endometrial tissue samples revealed immunoreactivity for S6K1. The immunopositivity rates were significantly different between Groups 1 and 2 [38.1% (8/21) and 75.0% (15/20), respectively, p=0.039]. When S6K1 positivity was used as a criterion of poor prognosis in EEA, the sensitivity, specificity, positive predictive value, and negative predictive value were calculated to be 62%, 75%, 72%, and 65%, respectively (OR: 4.9 and 95% CI: 1.3–18.7). Conclusion S6K1 was positive in the majority of EEAs and malignancies at an advanced stage. Higher grade disease had a significantly higher rate of S6K1 positivity. S6K1 immunopositivity appears to be a promising method to predict poor prognosis in EEA.

  17. Could S6K1 immunopositivity be used to distinguish early and advanced stages of endometrioid endometrial adenocarcinoma?

    PubMed Central

    Gün, İsmet; Özdamar, Özkan; Küçükodacı, Zafer; Muhçu, Murat; Demirel, Dilaver

    2016-01-01

    Objective To assess whether the immunopositivity of S6K1, a crucial effector of the mTOR signaling pathway, varies between early-stage low-grade and advanced-stage high-grade endometrial endometrioid adenocarcinoma (EEA) as well as to discuss its prognostic significance. Material and Methods A total of 22 normal endometrial tissue samples (Control group) and 41 EEA specimens (Study group) were enrolled in the study, and all the samples underwent immunohistochemical staining for S6 kinase alpha (S6K1). The study group was further evaluated in two subgroups; stage 1A, grade 1 (Group 1) and stage ≥1A, grade 2 or 3 (Group 2). Group 2 patients were considered as a poor prognosis for EEA. The samples were examined by two independent pathologists. Statistical analyses were performed using the Student’s t-test for continuous variables, the Chi-square test for categorical variables, and one-way analysis of variance for the comparison of multiple variables. Results The immunopositivity rate for all the included EEA patients was 56.1%, whereas none of the 22 normal endometrial tissue samples revealed immunoreactivity for S6K1. The immunopositivity rates were significantly different between Groups 1 and 2 [38.1% (8/21) and 75.0% (15/20), respectively, p=0.039]. When S6K1 positivity was used as a criterion of poor prognosis in EEA, the sensitivity, specificity, positive predictive value, and negative predictive value were calculated to be 62%, 75%, 72%, and 65%, respectively (OR: 4.9 and 95% CI: 1.3–18.7). Conclusion S6K1 was positive in the majority of EEAs and malignancies at an advanced stage. Higher grade disease had a significantly higher rate of S6K1 positivity. S6K1 immunopositivity appears to be a promising method to predict poor prognosis in EEA. PMID:27651726

  18. Modeling of an advanced concept of a double stage Hall effect thruster

    SciTech Connect

    Garrigues, L.; Boniface, C.; Hagelaar, G. J. M.; Boeuf, J. P.

    2008-11-15

    We present a study of the principle and operation of a two-stage Hall effect thruster, the SPT-MAG, using a two-dimensional quasineutral hybrid model coupled with a Monte Carlo simulation of electron transport. The purpose of the two-stage design is the separation of ion production and acceleration in two separate chambers, the ionization stage and the acceleration stage, with separate control of acceleration voltage and total ionization. The originality of the SPT-MAG lies in the magnetic field configuration in the ionization chamber. Electrons are confined by this magnetic field while ions are supposed to be trapped in the electric potential well supposedly resulting from the magnetic configuration, and guided toward the acceleration stage. The acceleration stage is similar to the channel of a conventional Hall effect thruster. The purpose of this paper is to clarify the physics of the SPT-MAG and to understand the formation of the positive ion trap in the ionization chamber. Using a hybrid model and a Monte Carlo simulation we show that under typical operating conditions most of the ionization in the chamber is due to high energy electrons accelerated in the channel and entering the chamber rather than to electrons accelerated by the voltage applied in the ionization chamber. We also raise the question of the possible role of an additional emissive cathode inside the ionization chamber. The model predicts that an electric potential well guiding the ions to the channel entrance forms in the chamber only if the intermediate electrode inside the chamber is an emissive cathode (which is not the case in recent configurations used for this thruster)

  19. Contemporary surgical management of advanced end stage emphysema: an evidence based review.

    PubMed

    Sachithanandan, Anand; Badmanaban, Balaji

    2012-06-01

    Emphysema is a progressive unrelenting component of chronic obstructive pulmonary disease and a major source of mortality and morbidity globally. The prevalence of moderate to severe emphysema is approximately 5% in Malaysia and likely to increase in the future. Hence advanced emphysema will emerge as a leading cause of hospital admission and a major consumer of healthcare resources in this country in the future. Patients with advanced disease have a poor quality of life and reduced survival. Medical therapy has been largely ineffective for many patients however certain subgroups have disease amenable to surgical palliation. Effective surgical therapies include lung volume reduction surgery, lung transplantation and bullectomy. This article is a comprehensive evidence based review of the literature evaluating the rationale, efficacy, safety and limitations of surgery for advanced emphysema highlighting the importance of meticulous patient selection and local factors relevant to Malaysia.

  20. Survival Analyses for Patients With Surgically Resected Pancreatic Neuroendocrine Tumors by World Health Organization 2010 Grading Classifications and American Joint Committee on Cancer 2010 Staging Systems.

    PubMed

    Yang, Min; Ke, Neng-wen; Zeng, Lin; Zhang, Yi; Tan, Chun-lu; Zhang, Hao; Mai, Gang; Tian, Bo-le; Liu, Xu-bao

    2015-12-01

    In 2010, World Health Organization (WHO) reclassified pancreatic neuroendocrine tumors (p-NETs) into 4 main groups: neuroendocrine tumor G1 (NET G1), neuroendocrine tumor G2 (NET G2), neuroendocrine carcinoma G3 (NEC G3), mixed adeno and neuroendocrine carcinoma (MANEC). Clinical value of these newly updated WHO grading criteria has not been rigorously validated. The authors aimed to evaluate the clinical consistency of the new 2010 grading classifications by WHO and the 2010 tumor-node metastasis staging systems by American Joint Committee on Cancer (AJCC) on survivals for patients with surgically resected p-NETs. Moreover, the authors would validate the prognostic value of both criteria for p-NETs.The authors retrospectively collected the clinicopathologic data of 120 eligible patients who were all surgically treated and histopathologically diagnosed as p-NETs from January 2004 to February 2014 in our single institution. The new WHO criteria were assigned to 4 stratified groups with a respective distribution of 62, 35, 17, and 6 patients. Patients with NET G1 or NET G2 obtained a statistically better survival compared with those with NEC G3 or MANEC (P < 0.001). Survivals of NET G1 was also better than those of NET G2 (P = 0.023), whereas difference of survivals between NEC G3 and MANEC present no obvious significance (P = 0.071). The AJCC 2010 staging systems were respectively defined in 61, 36, 12, and 11 patients for each stage. Differences of survivals of stage I with stage III and IV were significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001); whereas comparisons of stage I with stage II and stage III with IV were not statistically significant (P = 0.129, P = 0.286; respectively). Together with radical resection, these 2 systems were both significant in univariate and multivariate analysis (P < 0.05).The newly updated WHO 2010 grading classifications and the AJCC 2010 staging systems could consistently reflect the clinical outcome

  1. Survival Analyses for Patients With Surgically Resected Pancreatic Neuroendocrine Tumors by World Health Organization 2010 Grading Classifications and American Joint Committee on Cancer 2010 Staging Systems

    PubMed Central

    Yang, Min; Ke, Neng-wen; Zeng, Lin; Zhang, Yi; Tan, Chun-lu; Zhang, Hao; Mai, Gang; Tian, Bo-le; Liu, Xu-bao

    2015-01-01

    Abstract In 2010, World Health Organization (WHO) reclassified pancreatic neuroendocrine tumors (p-NETs) into 4 main groups: neuroendocrine tumor G1 (NET G1), neuroendocrine tumor G2 (NET G2), neuroendocrine carcinoma G3 (NEC G3), mixed adeno and neuroendocrine carcinoma (MANEC). Clinical value of these newly updated WHO grading criteria has not been rigorously validated. The authors aimed to evaluate the clinical consistency of the new 2010 grading classifications by WHO and the 2010 tumor-node metastasis staging systems by American Joint Committee on Cancer (AJCC) on survivals for patients with surgically resected p-NETs. Moreover, the authors would validate the prognostic value of both criteria for p-NETs. The authors retrospectively collected the clinicopathologic data of 120 eligible patients who were all surgically treated and histopathologically diagnosed as p-NETs from January 2004 to February 2014 in our single institution. The new WHO criteria were assigned to 4 stratified groups with a respective distribution of 62, 35, 17, and 6 patients. Patients with NET G1 or NET G2 obtained a statistically better survival compared with those with NEC G3 or MANEC (P < 0.001). Survivals of NET G1 was also better than those of NET G2 (P = 0.023), whereas difference of survivals between NEC G3 and MANEC present no obvious significance (P = 0.071). The AJCC 2010 staging systems were respectively defined in 61, 36, 12, and 11 patients for each stage. Differences of survivals of stage I with stage III and IV were significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001); whereas comparisons of stage I with stage II and stage III with IV were not statistically significant (P = 0.129, P = 0.286; respectively). Together with radical resection, these 2 systems were both significant in univariate and multivariate analysis (P < 0.05). The newly updated WHO 2010 grading classifications and the AJCC 2010 staging systems could

  2. Survival Analyses for Patients With Surgically Resected Pancreatic Neuroendocrine Tumors by World Health Organization 2010 Grading Classifications and American Joint Committee on Cancer 2010 Staging Systems.

    PubMed

    Yang, Min; Ke, Neng-wen; Zeng, Lin; Zhang, Yi; Tan, Chun-lu; Zhang, Hao; Mai, Gang; Tian, Bo-le; Liu, Xu-bao

    2015-12-01

    In 2010, World Health Organization (WHO) reclassified pancreatic neuroendocrine tumors (p-NETs) into 4 main groups: neuroendocrine tumor G1 (NET G1), neuroendocrine tumor G2 (NET G2), neuroendocrine carcinoma G3 (NEC G3), mixed adeno and neuroendocrine carcinoma (MANEC). Clinical value of these newly updated WHO grading criteria has not been rigorously validated. The authors aimed to evaluate the clinical consistency of the new 2010 grading classifications by WHO and the 2010 tumor-node metastasis staging systems by American Joint Committee on Cancer (AJCC) on survivals for patients with surgically resected p-NETs. Moreover, the authors would validate the prognostic value of both criteria for p-NETs.The authors retrospectively collected the clinicopathologic data of 120 eligible patients who were all surgically treated and histopathologically diagnosed as p-NETs from January 2004 to February 2014 in our single institution. The new WHO criteria were assigned to 4 stratified groups with a respective distribution of 62, 35, 17, and 6 patients. Patients with NET G1 or NET G2 obtained a statistically better survival compared with those with NEC G3 or MANEC (P < 0.001). Survivals of NET G1 was also better than those of NET G2 (P = 0.023), whereas difference of survivals between NEC G3 and MANEC present no obvious significance (P = 0.071). The AJCC 2010 staging systems were respectively defined in 61, 36, 12, and 11 patients for each stage. Differences of survivals of stage I with stage III and IV were significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001); whereas comparisons of stage I with stage II and stage III with IV were not statistically significant (P = 0.129, P = 0.286; respectively). Together with radical resection, these 2 systems were both significant in univariate and multivariate analysis (P < 0.05).The newly updated WHO 2010 grading classifications and the AJCC 2010 staging systems could consistently reflect the clinical outcome

  3. Correlation between ultrasound reflection intensity and tumor ablation ratio of late-stage pancreatic carcinoma in HIFU therapy: dynamic observation on ultrasound reflection intensity.

    PubMed

    Ge, Hui-Yu; Miao, Li-Ying; Wang, Jin-Rui; Xiong, Liu-Lin; Yan, Fang; Zheng, Cui-Shan; Jia, Jian-Wen; Cui, Li-Gang; Chen, Wen

    2013-01-01

    The minimally invasive high-intensity focused ultrasound (HIFU) therapy is thermal ablation treatment for late-stage pancreatic carcinoma with widely recognized safety and effectiveness, but there are currently no instant assessment methods for its ablation effect. It is vital to find a real-time high-sensitive assessment method. This research aims to dynamically observe the variation rules of ultrasound reflection intensity, analyze the correlation between ultrasound reflection intensity and tumor ablation ratio, and find out the value of ultrasound reflection intensity in prognosis of HIFU ablation effect. HIFU intermittent therapies were retrospectively analyzed for 31 subjects with late-stage pancreatic carcinoma from March 2007 to December 2009 in the study. The variation rules of the ultrasound reflection intensity during HIFU therapy were summarized and the correlation between ultrasound reflection intensity and tumor ablation ratio was analyzed based on the tumor ablation ratio indicated by CT scanning. The conclusion is that variation of ultrasound reflection intensity can be used for initial assessment of tumor ablation in HIFU therapy and early prognosis of overall HIFU ablation, providing important clinical basis for improving safety and effectiveness of HIFU therapy. Ultrasound can work as a real-time imaging instrument for observation of HIFU ablation effect in treating late-stage pancreatic carcinoma.

  4. A population-based study of prognosis in advanced stage follicular lymphoma managed by watch and wait.

    PubMed

    El-Galaly, Tarec Christoffer; Bilgrau, Anders E; de Nully Brown, Peter; Mylam, Karen J; Ahmad, Syed A; Pedersen, Lars M; Gang, Anne O; Bentzen, Hans H; Juul, Maja B; Bergmann, Olav J; Pedersen, Robert S; Nielsen, Berit J; Johnsen, Hans E; Dybkaer, Karen; Bøgsted, Martin; Hutchings, Martin

    2015-05-01

    Watch and wait (WAW) is a common approach for asymptomatic, advanced stage follicular lymphoma (FL), but single-agent rituximab is an alternative for these patients. In this nationwide study we describe the outcome of patients selected for WAW. A cohort of 286 out of 849 (34%) stage III-IVA FL patients seen between 2000 and 2011, were managed expectantly and included. The 5-year progression-free survival (PFS) was 35% [95% confidence interval (CI) 29-42]. The 10-year overall survival (OS) was 65% (95%CI 54-78), and the cumulative risk of dying from lymphoma within 10 years of diagnosis was 13% (95%CI 7-20). Elevated lactate dehydrogenase and > four nodal regions involved were associated with a higher risk of lymphoma treatment and death from lymphoma. The WAW patients and a matched background population had similar OS during the first 50 months after diagnosis (P = 0·7), but WAW patients had increased risk of death after 50 months (P < 0·001). The estimated loss of residual life after 10 years was 6·8 months. The 10-year cumulative risk of histological transformation was 22% (95%CI 15-29) and the 3-year OS after transformation was 71% (95%CI 58-87%). In conclusion, advanced stage FL managed by WAW had a favourable outcome and abandoning this strategy could lead to overtreatment in some patients.

  5. A heartrending burden of gynaecological cancers in advance stage at nuclear institute of medicine and radiotherapy Jamshoro Sindh

    PubMed Central

    Bibi, Seema; Ashfaque, Sanober; Laghari, Naeem Ahmed

    2016-01-01

    Objectives: In Pakistan gynaecological cancers are among the leading causes of women’s morbidity and mortality posing huge financial burden on families, communities and state. Due to lack of national cancer registry exact facts and figures are unknown therefore this study was planned to find out prevalence, age, site and stage of presentation of gynaecological cancers at Nuclear Institute of Medicine and Radiotherapy (NIMRA), Jamshoro. Methods: A retrospective, cross sectional study was conducted from 1st January 2011 to 31st December 2011 at NIMRA Jamshoro. All cases of genital tract cancers were evaluated, required data was entered on predesigned performa and results were analyzed manually. Results: Out of 2401 total registered cancer cases, 231 (9.6%) patients were suffering from gynaecological cancer making it third most common cancer. Ovary was commonest site followed by cervix and uterus. More than 60% cases presented in advanced stage, mostly during 4th and 5th decade of life. Conclusion: Gynecological cancer was among top three cancers at one of the busiest public sector cancer institute in Sindh province and significant number presented in advance stage making treatment difficult and expensive. There is urgent need for development and implementation of an effective health policy regarding cancer prevention and treatment. PMID:27022358

  6. “EXHALE”: exercise as a strategy for rehabilitation in advanced stage lung cancer patients: a randomized clinical trial comparing the effects of 12 weeks supervised exercise intervention versus usual care for advanced stage lung cancer patients

    PubMed Central

    2013-01-01

    Background Lung cancer is the leading cause of cancer death in North America and Western Europe. Patients with lung cancer in general have reduced physical capacity, functional capacity, poor quality of life and increased levels of anxiety and depression. Intervention studies indicate that physical training can address these issues. However, there is a lack of decisive evidence regarding the effect of physical exercise in patients with advanced lung cancer. The aim of this study is to evaluate the effects of a twelve weeks, twice weekly program consisting of: supervised, structured training in a group of advanced lung cancer patients (cardiovascular and strength training, relaxation). Methods/Design A randomized controlled trial will test the effects of the exercise intervention in 216 patients with advanced lung cancer (non-small cell lung cancer (NSCLC) stage IIIb - IV and small cell lung cancer (SCLC) extensive disease (ED)). Primary outcome is maximal oxygen uptake (VO2peak). Secondary outcomes are muscle strength (1RM), functional capacity (6MWD), lung capacity (Fev1) and patient reported outcome (including anxiety, depression (HADS) and quality of life (HRQOL)). Discussion The present randomized controlled study will provide data on the effectiveness of a supervised exercise intervention in patients receiving systemic therapy for advanced lung cancer. It is hoped that the intervention can improve physical capacity and functional level, during rehabilitation of cancer patients with complex symptom burden and help them to maintain independent function for as long as possible. Trial registration http://ClinicalTrials.gov, NCT01881906 PMID:24124893

  7. Outcomes of Patients With Revised Stage I Clear Cell Sarcoma of Kidney Treated in National Wilms Tumor Studies 1-5

    SciTech Connect

    Kalapurakal, John A.; Perlman, Elizabeth J.; Seibel, Nita L.; Ritchey, Michael; Dome, Jeffrey S.; Grundy, Paul E.

    2013-02-01

    Purpose: To report the clinical outcomes of children with revised stage I clear cell sarcoma of the kidney (CCSK) using the National Wilms Tumor Study Group (NWTS)-5 staging criteria after multimodality treatment on NWTS 1-5 protocols. Methods and Materials: All CCSK patients enrolled in the National Wilms Tumor Study Group protocols had their pathology slides reviewed, and only those determined to have revised stage I tumors according to the NWTS-5 staging criteria were included in the present analysis. All patients were treated with multimodality therapy according to the NWTS 1-5 protocols. Results: A total of 53 children were identified as having stage I CCSK. All patients underwent primary surgery with radical nephrectomy. The chemotherapy regimens used were as follows: regimen A, C, F, or EE in 4 children (8%); regimen DD or DD4A in 33 children (62%); regimen J in 4 children (8%); and regimen I in 12 children (22%). Forty-six patients (87%) received flank radiation therapy (RT). Seven children (13%) did not receive flank RT. The median delay between surgery and the initiation of RT was 9 days (range, 3-61). The median RT dose was 10.8 Gy (range, 10-36). The flank RT doses were as follows: 10.5 or 10.8 Gy in 25 patients (47%), 11-19.9 Gy in 2 patients (4%), 20-29.9 Gy in 9 patients (17%), and 30-40 Gy in 10 patients (19%). The median follow-up for the entire group was 17 years (range, 2-36). The relapse-free and cancer-specific survival rate was 100% at the last follow-up examination. Conclusions: The present results have demonstrated that children with revised stage I CCSK using the NWTS-5 staging criteria have excellent survival rates despite the use of varying RT doses and chemotherapy regimens in the NWTS 1-5 protocols.

  8. Comparison of weight changes following unilateral and staged bilateral STN DBS for advanced PD

    PubMed Central

    Lee, Eric M; Kurundkar, Ashish; Cutter, Gary R; Huang, He; Guthrie, Barton L; Watts, Ray L; Walker, Harrison C

    2011-01-01

    Unilateral and bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease (PD) result in weight gain in the initial postoperative months, but little is known about the changes in weight following unilateral and staged bilateral STN DBS over longer time intervals. A case–control comparison evaluated weight changes over 2 years in 43 consecutive unilateral STN DBS patients, among whom 25 elected to undergo staged bilateral STN DBS, and 21 age-matched and disease severity matched PD controls without DBS. Regression analyses incorporating age, gender, and baseline weight in case or control were conducted to assess weight changes 2 years after the initial unilateral surgery. Unilateral STN DBS and staged bilateral STN DBS patients gained 3.9 ± 2.0 kg and 5.6 ± 2.1 kg versus their preoperative baseline weight (P < 0.001, respectively) while PD controls without DBS lost 0.8 ± 1.1 kg. Although bilateral STN DBS patients gained 1.7 kg more than unilateral STN DBS patients at 2 years, this difference was not statistically significant (P = 0.885). Although there was a trend toward greater weight gain in staged bilateral STN DBS patients versus unilateral patients, we found no evidence for an equivalent or synergistic increase in body weight following placement of the second DBS electrode. PMID:22398977

  9. Prognostic significance of polymerase chain reaction detected human papillomavirus of tumors and lymph nodes in surgically treated stage IB cervical cancer.

    PubMed

    Burnett, A F; Barnes, W A; Johnson, J C; Grendys, E; Willett, G D; Barter, J F; Doniger, J

    1992-12-01

    This study describes the prognostic role of polymerase chain reaction detected human papillomavirus (HPV) in Stage IB cervical cancer patients treated with radical hysterectomy and pelvic and paraaortic node dissection. All tumors were confined to the cervix and all margins and nodes were disease free. Twenty-one patients were analyzed: 6 patients recurred within 20 months of initial therapy, while 15 had no evidence of disease with a minimum follow-up of 36 months. Polymerase chain reaction (PCR) was performed on paraffin-block tissue of the hysterectomy specimen cervical tumor and lymph nodes. Oligonucleotide probes for HPV types 6, 11, 16, 18, 31, 33, and 35 were used with consensus primers for uncharacterized HPV types created from an L1 constant region. Control tissues were run with each tumor sample to assure against contamination. HPV type confirmation was performed using diagnostic restriction sites. HPV was detected in all cervical tumors. Recurring tumors were infected with multiple types of HPV in all 6 tumors versus only 5 of 15 nonrecurring tumors being multiply infected (P = 0.023). No tumor had HPV 6 or 11, and the incidence of HPV 16, 31, 33, and 35 was not significantly different for recurrent versus nonrecurrent groups. HPV 18 was found in 5 of 6 recurring cancers versus 1 of 15 nonrecurring tumors (P = 0.0029). PCR typing of the histologically negative nodes that had been obtained at radical hysterectomy was done in all 6 recurring patients and in 6 nonrecurring patients. The recurrent patients had a significantly higher incidence of lymph nodes positive for HPV DNA (71%) than the nonrecurring patients (35%) (P = 0.0047). These observations suggest that HPV 18 cervical cancer patients, those with infections of multiple types, and those with HPV DNA in histologically negative lymph nodes may be at increased risk for recurrence.

  10. Prognostic significance of polymerase chain reaction detected human papillomavirus of tumors and lymph nodes in surgically treated stage IB cervical cancer.

    PubMed

    Burnett, A F; Barnes, W A; Johnson, J C; Grendys, E; Willett, G D; Barter, J F; Doniger, J

    1992-12-01

    This study describes the prognostic role of polymerase chain reaction detected human papillomavirus (HPV) in Stage IB cervical cancer patients treated with radical hysterectomy and pelvic and paraaortic node dissection. All tumors were confined to the cervix and all margins and nodes were disease free. Twenty-one patients were analyzed: 6 patients recurred within 20 months of initial therapy, while 15 had no evidence of disease with a minimum follow-up of 36 months. Polymerase chain reaction (PCR) was performed on paraffin-block tissue of the hysterectomy specimen cervical tumor and lymph nodes. Oligonucleotide probes for HPV types 6, 11, 16, 18, 31, 33, and 35 were used with consensus primers for uncharacterized HPV types created from an L1 constant region. Control tissues were run with each tumor sample to assure against contamination. HPV type confirmation was performed using diagnostic restriction sites. HPV was detected in all cervical tumors. Recurring tumors were infected with multiple types of HPV in all 6 tumors versus only 5 of 15 nonrecurring tumors being multiply infected (P = 0.023). No tumor had HPV 6 or 11, and the incidence of HPV 16, 31, 33, and 35 was not significantly different for recurrent versus nonrecurrent groups. HPV 18 was found in 5 of 6 recurring cancers versus 1 of 15 nonrecurring tumors (P = 0.0029). PCR typing of the histologically negative nodes that had been obtained at radical hysterectomy was done in all 6 recurring patients and in 6 nonrecurring patients. The recurrent patients had a significantly higher incidence of lymph nodes positive for HPV DNA (71%) than the nonrecurring patients (35%) (P = 0.0047). These observations suggest that HPV 18 cervical cancer patients, those with infections of multiple types, and those with HPV DNA in histologically negative lymph nodes may be at increased risk for recurrence. PMID:1335431

  11. Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Cisplatin and Pemetrexed

    ClinicalTrials.gov

    2016-09-09

    Advanced Peritoneal Malignant Mesothelioma; Advanced Pleural Malignant Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Solid Neoplasm; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pleural Mesothelioma; Thymoma

  12. 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.

  13. Two stage low noise advanced technology fan. 1: Aerodynamic, structural, and acoustic design

    NASA Technical Reports Server (NTRS)

    Messenger, H. E.; Ruschak, J. T.; Sofrin, T. G.

    1974-01-01

    A two-stage fan was designed to reduce noise 20 db below current requirements. The first-stage rotor has a design tip speed of 365.8 m/sec and a hub/tip ratio of 0.4. The fan was designed to deliver a pressure ratio of 1.9 with an adiabatic efficiency of 85.3 percent at a specific inlet corrected flow of 209.2kg/sec/sq m. Noise reduction devices include acoustically treated casing walls, a flowpath exit acoustic splitter, a translating centerbody sonic inlet device, widely spaced blade rows, and the proper ratio of blades and vanes. Multiple-circular-arc rotor airfoils, resettable stators, split outer casings, and capability to go to close blade-row spacing are also included.

  14. Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats.

    PubMed

    Kensara, Osama Adnan; El-Shemi, Adel Galal; Mohamed, Amr Mohamed; Refaat, Bassem; Idris, Shakir; Ahmad, Jawwad

    2016-01-01

    Colorectal cancer (CRC) is one of the most prevalent cancers and has a high mortality rate. Insensitivity and the limited therapeutic efficacy of its standard chemotherapeutic drug, 5-fluorouracil (5-FU), represents an important challenge in CRC treatment. The robust antitumor properties of thymoquinone (TQ), the main bioactive constituent of Nigella sativa, have recently been demonstrated on different cancers. We investigated whether TQ could potentiate the chemopreventive effect of 5-FU to eradicate the early stages of CRC and elucidated its underlying mechanisms. An intermediate-term (15 weeks) model of colorectal tumorigenesis was induced in male Wistar rats by azoxymethane (AOM), and the animals were randomly and equally divided into five groups: control, AOM, AOM/5-FU, AOM/TQ, and AOM/5-FU/TQ. TQ (35 mg/kg/d; 3 d/wk) was given during the seventh and 15th weeks post-AOM injection, while 5-FU was given during the ninth and tenth weeks (12 mg/kg/d for 4 days; then 6 mg/kg every other day for another four doses). At week 15, the resected colons were subjected to macroscopic, histopathological, molecular, and immunohistochemical examinations. Interestingly, 5-FU/TQ combination therapy resulted in a more significant reduction on AOM-induced colorectal tumors and large aberrant crypts foci than treatment with the individual drugs. Mechanistically, 5-FU and TQ remarkably cooperated to repress the expression of procancerous Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF, and TBRAS and upregulate the expression of anti-tumorigenesis DKK-1, CDNK-1A, TGF-β1, TGF-βRII, Smad4, and GPx. Overall, our findings present the first report describing the in vivo enhancement effect of combined TQ and 5-FU against early stages of CRC; however, further studies are required to determine the value of this combination therapy in an advanced long-term model of CRC and also to realize its clinical potential. PMID:27468227

  15. Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats

    PubMed Central

    Kensara, Osama Adnan; El-Shemi, Adel Galal; Mohamed, Amr Mohamed; Refaat, Bassem; Idris, Shakir; Ahmad, Jawwad

    2016-01-01

    Colorectal cancer (CRC) is one of the most prevalent cancers and has a high mortality rate. Insensitivity and the limited therapeutic efficacy of its standard chemotherapeutic drug, 5-fluorouracil (5-FU), represents an important challenge in CRC treatment. The robust antitumor properties of thymoquinone (TQ), the main bioactive constituent of Nigella sativa, have recently been demonstrated on different cancers. We investigated whether TQ could potentiate the chemopreventive effect of 5-FU to eradicate the early stages of CRC and elucidated its underlying mechanisms. An intermediate-term (15 weeks) model of colorectal tumorigenesis was induced in male Wistar rats by azoxymethane (AOM), and the animals were randomly and equally divided into five groups: control, AOM, AOM/5-FU, AOM/TQ, and AOM/5-FU/TQ. TQ (35 mg/kg/d; 3 d/wk) was given during the seventh and 15th weeks post-AOM injection, while 5-FU was given during the ninth and tenth weeks (12 mg/kg/d for 4 days; then 6 mg/kg every other day for another four doses). At week 15, the resected colons were subjected to macroscopic, histopathological, molecular, and immunohistochemical examinations. Interestingly, 5-FU/TQ combination therapy resulted in a more significant reduction on AOM-induced colorectal tumors and large aberrant crypts foci than treatment with the individual drugs. Mechanistically, 5-FU and TQ remarkably cooperated to repress the expression of procancerous Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF, and TBRAS and upregulate the expression of anti-tumorigenesis DKK-1, CDNK-1A, TGF-β1, TGF-βRII, Smad4, and GPx. Overall, our findings present the first report describing the in vivo enhancement effect of combined TQ and 5-FU against early stages of CRC; however, further studies are required to determine the value of this combination therapy in an advanced long-term model of CRC and also to realize its clinical potential. PMID:27468227

  16. Advancements in Estimating Crop Growth Stages Using RADARSAT-2 and Terrasar-X Polarimetric Data

    NASA Astrophysics Data System (ADS)

    Lampropoulos, G.; Li, Y.; Liu, T.

    2015-04-01

    This paper uses RADARSAT-2 quad Polarimetric Synthetic Aperture Radar (PolSAR) and TerraSAR-X dual polarimetric SAR data to monitor agriculture crop growth stages. Two RADARSAT-2 Fine Quad Wide (FQW) beam modes FQ2W and FQ10W, each with 5 sets of data and 13 sets of Stripmap TerraSAR-X data were used in the study. Both RADARSAT-2 POLSAR data and TerraSARX data were acquired in summer 2012 outside Winnipeg, Manitoba, Canada. The study was carried out to two crop types: canola and wheat, each contains 5 regions of interest from ground truth crop classification map in the image scene. Polarimetric features such as differential reflectivity bands ratio, entropy, anisotropy, alpha angle, lambda, scattering diversity and polarization index were evaluated for two crop types. The results from both RADARSAT-2 and TerraSAR-X data were compared and they demonstrated clear relationships between crop growth stages and polarimetric parameters. It is observed that entropy, lambda and differential reflectivity from both data have similar responses to crop growth stages in their common coverage period. The results were also validated using ground truth information.

  17. A dose-finding and pharmacodynamic study of bortezomib in combination with weekly paclitaxel in patients with advanced solid tumors

    PubMed Central

    Bekaii-Saab, Tanios; Schaaf, Larry J.; Lesinski, Gregory B.; Lucas, David M.; Young, Donn C.; Ruppert, Amy S.; Byrd, John C.; Culler, Kristy; Wilkins, Diedre; Wright, John J.; Grever, Michael R.; Shapiro, Charles L.

    2012-01-01

    Purpose A phase I study to determine the maximum tolerated dose (MTD) of bortezomib (B) when combined with weekly paclitaxel in patients with advanced solid tumors. Patients and methods Eligible patients received escalating doses of intravenous (IV) bortezomib (0.6–2 mg/m2) on days 2 and 9 and IV paclitaxel at 100 mg/m2 on days 1 and 8 of a 21-day cycle. Dose escalation was based on two end-points: not exceeding 80% 20S-proteasome inhibition (20-S PI) and the development of dose-limiting toxicity defined as grade 3 or greater non-hematologic or grade 4 hematologic toxicities. Results Forty-five patients with advanced solid tumors and a median of 3 prior chemotherapy regimens (range 0– 9), received 318 doses (median 5, range 1–34) of bortezomib and paclitaxel. Dose-related inhibition of 20-S PI was observed with a maximum inhibition of 70–80% at the MTD of 1.8 mg/m2 of bortezomib. At the MTD (N = 9) the following toxicities were observed: grade 4 neutropenia without fever (n = 2) and cerebrovascular ischemia (n = 1); grade 3 neutropenia (n = 3), diarrhea (n = 2), nausea (n = 1), and fatigue (n = 1); grade 2 fatigue (n = 5), diarrhea (n = 4), and dyspnea (n = 2). There was one partial response in a patient with an eccrine porocarcinoma. Stabilization of disease was observed in 7 (16%) patients, 3 of whom had advanced pancreatic cancer. Conclusion Sequential paclitaxel and bortezomib in previously treated patients with advanced solid tumors resulted in acceptable toxicity and no evidence of interaction. The recommended phase II dose of bortezomib in combination with weekly paclitaxel was 1.8 mg/m2. PMID:19774377

  18. Technology requirements for advanced earth-orbital transportation systems: Summary report. [single stage to orbit vehicles

    NASA Technical Reports Server (NTRS)

    Haefeli, R. C.; Littler, E. G.; Hurley, J. B.; Winter, M. G.

    1977-01-01

    Areas of advanced technology that are either critical or offer significant benefits to the development of future Earth-orbit transportation systems were identified. Technology assessment was based on the application of these technologies to fully reusable, single-state-to-orbit (SSTO) vehicle concepts with horizontal landing capability. Study guidelines included mission requirements similar to space shuttle, an operational capability beginning in 1995, and main propulsion to be advanced hydrogen-fueled rocket engines. The technical and economic feasibility of this class of SSTO concepts were evaluated as well as the comparative features of three operational take-off modes, which were vertical boost, horizontal sled launch, and horizontal take-off with subsequent inflight fueling. Projections of both normal and accelerated technology growth were made. Figures of merit were derived to provide relative rankings of technology areas. The influence of selected accelerated areas on vehicle design and program costs was analyzed by developing near-optimum point designs.

  19. Feasibility and Timing of Cytoreduction Surgery in Advanced (Metastatic or Recurrent) Gastrointestinal Stromal Tumors During the Era of Imatinib

    PubMed Central

    Chang, Shih-Chun; Liao, Chien-Hung; Wang, Shang-Yu; Tsai, Chun-Yi; Chiang, Kun-Chun; Cheng, Chi-Tung; Yeh, Ta-Sen; Chen, Yen-Yang; MA, Ming-Chun; Liu, Chien-Ting; Yeh, Chun-Nan

    2015-01-01

    Abstract The prognosis of advanced gastrointestinal stromal tumors (GISTs) was dramatically improved in the era of imatinib. Cytoreduction surgery was advocated as an additional treatment for advanced GISTs, especially when patients having poor response to imatinib or developing resistance to it. However, the efficacy and benefit of cytoreduction were still controversial. Likewise, the sequence between cytoreduction surgery and imatinib still need evaluation. In this study, we tried to assess the feasibility and efficiency of cytoreduction in advanced GISTs. Furthermore, we analyzed the impact of timing of the cytoreduction surgery on the prognosis of advanced GISTs. We conducted a prospective collecting retrospective review of patients with advanced GISTs (metastatic, unresectable, and recurrent GISTs) treated in Chang Gung memorial hospital (CGMH) since 2001 to 2013. We analyzed the impact of cytoreduction surgery to response to imatinib, progression-free survival (PFS), and overall survival (OS) in patients with advanced GISTs. Moreover, by the timing of cytoreduction to imatinib, we divided the surgical patients who had surgery before imatinib use into early group and those who had surgery after imatinib into late. We compared the clinical response to imatinib, PFS and OS between early and late cytoreduction surgical groups. Totally, 182 patients were enrolled into this study. Seventy-six patients underwent cytoreduction surgery. The demographic characteristics and tumor presentation were similar between surgical and non-surgical groups. The surgical group showed better complete response rate (P < 0.001) and partial response rate (P = 0.008) than non-surgical group. The 1-year, 3-year, and 5-year PFS were significantly superior in surgical group (P = 0.003). The 1-year, 3-year, and 5-year OS were superior in surgical group, but without statistical significance (P = 0.088). Dividing by cytoreduction surgical timing, the demographic

  20. Therapy of advanced-stage mature B-cell lymphoma and leukemia in children and adolescents with rituximab and reduced intensity induction chemotherapy (B-NHL 2004M protocol): the results of a multicenter study.

    PubMed

    Samochatova, Elena V; Maschan, Alexey A; Shelikhova, Larisa N; Myakova, Natalia V; Belogurova, Margarita B; Khlebnikova, Olga P; Shamardina, Anastasia V; Ryskal, Olga V; Roumiantseva, Julia V; Konovalov, Dmitriy M; Dubrovina, Maria E; Rumyantsev, Alexander G

    2014-07-01

    Pediatric mature B-cell non-Hodgkin lymphomas (B-NHLs) are highly aggressive malignant tumors that are curable with chemotherapy (ChT). High-dose methotrexate (MTX) is considered indispensable for successful treatment, but this therapy frequently induces severe mucositis and infectious complications, especially in induction, which can cause treatment failure. A prospective multicenter trial of combined immunochemotherapy for advanced-stage B-NHL with rituximab and the modified NHL-BFM-90 protocol was conducted. The major differences from the original protocol were a decrease in the dose of MTX from 5000 to 1000 mg/m/24 h in the first 2 ChT blocks and the addition of rituximab at 375 mg/m to each of the first 4 blocks of ChT. Eighty-three newly diagnosed patients with a median age of 8.84 years with Burkitt lymphoma/leukemia and diffuse large B-cell lymphomas stage III to IV were included. Four patients died during induction ChT due to tumor lysis syndrome and infection. Two additional patients died subsequently due to tumor resistance. Complete remission was achieved in 77 (92.8%) patients; 2 patients relapsed at 1 and 3 months, and 2 developed secondary malignancies at 1 and 6.5 years, respectively, after the completion of therapy. The overall survival probability was 82%±8% with a median follow-up of 65.2 months. Combined therapy with rituximab and intensive ChT with a reduced MTX dose of 1 g/m in the 2 induction courses was feasible and produced high cure rates in patients with pediatric advanced-stage mature B-NHL. PMID:23823112

  1. 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

  2. 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

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

    ClinicalTrials.gov

    2016-09-16

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

  4. Biologic Determinants of Tumor Recurrence in Stage II Colon Cancer: Validation Study of the 12-Gene Recurrence Score in Cancer and Leukemia Group B (CALGB) 9581

    PubMed Central

    Venook, Alan P.; Niedzwiecki, Donna; Lopatin, Margarita; Ye, Xing; Lee, Mark; Friedman, Paula N.; Frankel, Wendy; Clark-Langone, Kim; Millward, Carl; Shak, Steven; Goldberg, Richard M.; Mahmoud, Najjia N.; Warren, Robert S.; Schilsky, Richard L.; Bertagnolli, Monica M.

    2013-01-01

    Purpose A greater understanding of the biology of tumor recurrence should improve adjuvant treatment decision making. We conducted a validation study of the 12-gene recurrence score (RS), a quantitative assay integrating stromal response and cell cycle gene expression, in tumor specimens from patients enrolled onto Cancer and Leukemia Group B (CALGB) 9581. Patients and Methods CALGB 9581 randomly assigned 1,713 patients with stage II colon cancer to treatment with edrecolomab or observation and found no survival difference. The analysis reported here included all patients with available tissue and recurrence (n = 162) and a random (approximately 1:3) selection of nonrecurring patients. RS was assessed in 690 formalin-fixed paraffin-embedded tumor samples with quantitative reverse transcriptase polymerase chain reaction by using prespecified genes and a previously validated algorithm. Association of RS and recurrence was analyzed by weighted Cox proportional hazards regression. Results Continuous RS was significantly associated with risk of recurrence (P = .013) as was mismatch repair (MMR) gene deficiency (P = .044). In multivariate analyses, RS was the strongest predictor of recurrence (P = .004), independent of T stage, MMR, number of nodes examined, grade, and lymphovascular invasion. In T3 MMR-intact (MMR-I) patients, prespecified low and high RS groups had average 5-year recurrence risks of 13% (95% CI, 10% to 16%) and 21% (95% CI, 16% to 26%), respectively. Conclusion The 12-gene RS predicts recurrence in stage II colon cancer in CALGB 9581. This is consistent with the importance of stromal response and cell cycle gene expression in colon tumor recurrence. RS appears to be most discerning for patients with T3 MMR-I tumors, although markers such as grade and lymphovascular invasion did not add value in this subset of patients. PMID:23530100

  5. Evaluation of the circulating levels of IL-12 and IL-33 in patients with breast cancer: influences of the tumor stages and cytokine gene polymorphisms

    PubMed Central

    Jafarzadeh, Abdollah; Minaee, Kayhan; Farsinejad, Ali-Reza; Nemati, Maryam; Khosravimashizi, Arezu; Daneshvar, Hamid; Mohammadi, Mohammad Mehdi; Sheikhi, Abdolkarim; Ghaderi, Abbas

    2015-01-01

    Objective(s): IL-12 as an anti-tumor cytokine and IL-33 a novel identified cytokine with both pro- or anti-tumor activities, play important roles in response against tumor cells. Our aim was to evaluate the IL-12 and IL-33 levels and single nucleotide polymorphisms (SNP) in their genes in patients with breast cancer. Materials and Methods: Blood samples were collected from 100 patients with breast cancer, and 100 healthy women were controls. The serum IL-12 and IL-33 levels were measured by ELISA. The SNP rs3212227 (in IL-12 gene) and rs1929992 (in IL-33 gene) were determined using PCR-RFLP. Results: The IL-12 levels similarly expressed in patients and controls. IL-12 levels in patients at stage I were significantly lower than in the healthy group (P<0.05). IL-33 levels and the IL-33/IL-12 ratio were significantly higher in patients than the control group (P<0.001). The IL-33 levels and IL-33/IL-12 ratio in stage IV patients were significantly higher than other stages and controls (P<0.0001 and P<0.001, respectively). There were no significant differences in the frequencies of genotypes in rs3212227 and rs1929992 between patients and the control group. No significant differences were observed between subjects with various genotypes at rs3212227 and rs1929992 with respect to related cytokine levels. Conclusion: These results indicate that the diminished IL-12 production may contribute to the tumor establishment. The higher IL-33 levels and IL-33/IL-12 ratio in patients also indicate an imbalance in Th1/Th2 responses that may contribute to tumor development. Thus, correcting the imbalance of Th1/Th2 could be an important strategy for cancer immunotherapy. PMID:26877848

  6. A first-in-human phase I study to evaluate the MEK1/2 inhibitor, cobimetinib, administered daily in patients with advanced solid tumors.

    PubMed

    Rosen, Lee S; LoRusso, Patricia; Ma, Wen Wee; Goldman, Jonathan W; Weise, Amy; Colevas, A Dimitrios; Adjei, Alex; Yazji, Salim; Shen, Angela; Johnston, Stuart; Hsieh, Hsin-Ju; Chan, Iris T; Sikic, Branimir I

    2016-10-01

    Objective Cobimetinib, a MEK1/2 inhibitor, was administered to patients with advanced solid tumors to assess safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity. Methods For dose-escalation, a 3 + 3 design was used. Oral cobimetinib was administered once daily on a 21-day on/7-day off (21/7) or a 14-day on/14-day off (14/14) schedule. Serial plasma samples were collected for pharmacokinetic (PK) analysis on Day 1 and at steady state. In expansion stages, patients with RAS or RAF mutant tumors were treated at the maximum tolerated dose (MTD) of the 21/7 or 14/14 schedule. Results Ninety-seven patients received cobimetinib. In the 21/7 dose escalation, 36 patients enrolled in 8 cohorts (0.05 mg/kg-80 mg). Dose-limiting toxicities (DLTs) were Grade 4 hepatic encephalopathy, Grade 3 diarrhea, and Grade 3 rash. In the 14/14 dose escalation, 20 patients enrolled in 4 cohorts (60-125 mg). DLTs were Grade 3 rash and Grade 3 blurred vision associated with presence of reversible subretinal fluid. The MTD was 60 mg on 21/7 schedule and 100 mg on 14/14 schedule. Cobimetinib PK showed dose-proportional increases in exposure. The most frequent adverse events attributed to cobimetinib were diarrhea, rash, fatigue, edema, nausea, and vomiting. In patients treated at the 60-mg (21/7) or 100-mg (14/14) dose, one unconfirmed complete response and 6 confirmed partial responses were observed. All responses occurred in melanoma patients; 6 harbored the BRAF(V600E) mutation. Conclusions Cobimetinib is generally well tolerated and durable responses were observed in BRAF(V600E) mutant melanoma patients. Evaluation of cobimetinib in combination with other therapies is ongoing. PMID:27424159

  7. Monitoring of Circulating Tumor Cells and Their Expression of EGFR/Phospho-EGFR During Combined Radiotherapy Regimens in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Tinhofer, Ingeborg; Hristozova, Tsvetana; Stromberger, Carmen; KeilhoIz, Ulrich; Budach, Volker

    2012-08-01

    Purpose: The numbers of circulating tumor cells (CTCs) and their expression/activation of epidermal growth factor receptor (EGFR) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck (SCCHN) were determined. Methods and Materials: Peripheral blood samples from SCCHN patients with locally advanced stage IVA/B disease who were treated with concurrent radiochemotherapy or induction chemotherapy followed by bioradiation with cetuximab were included in this study. Using flow cytometry, the absolute number of CTCs per defined blood volume as well as their expression of EGFR and its phosphorylated form (pEGFR) during the course of treatment were assessed. Results: Before treatment, we detected {>=}1 CTC per 3.75 mL blood in 9 of 31 patients (29%). Basal expression of EGFR was detected in 100% and pEGFR in 55% of the CTC+ cases. The frequency of CTC detection was not influenced by induction chemotherapy. However, the number of CTC+ samples significantly increased after radiotherapy. This radiation-induced increase in CTC numbers was less pronounced when radiotherapy was combined with cetuximab compared to its combination with cisplatin/5-fluorouracil. The former treatment regimen was also more effective in reducing pEGFR expression in CTCs. Conclusions: Definitive radiotherapy regimens of locally advanced SCCHN can increase the number of CTCs and might thus contribute to a systemic spread of tumor cells. Further studies are needed to evaluate the predictive value of the radiation-induced increase in CTC numbers and the persistent activation of the EGFR signalling pathway in individual CTC+ cases.

  8. Tumor heterogeneity and resistance to EGFR-targeted therapy in advanced nonsmall cell lung cancer: challenges and perspectives

    PubMed Central

    Cheng, Xinghua; Chen, Haiquan

    2014-01-01

    Lung cancer, mostly nonsmall cell lung cancer, continues to be the leading cause of cancer-related death worldwide. With the development of tyrosine kinase inhibitors that selectively target lung cancer-related epidermal growth factor receptor mutations, management of advanced nonsmall cell lung cancer has been greatly transformed. Improvements in progression-free survival and life quality of the patients were observed in numerous clinical studies. However, overall survival is not prolonged because of later-acquired drug resistance. Recent studies reveal a heterogeneous subclonal architecture of lung cancer, so it is speculated that the tumor may rapidly adapt to environmental changes via a Darwinian selection mechanism. In this review, we aim to provide an overview of both spatial and temporal tumor heterogeneity as potential mechanisms underlying epidermal growth factor receptor tyrosine kinase inhibitor resistance in nonsmall cell lung cancer and summarize the possible origins of tumor heterogeneity covering theories of cancer stem cells and clonal evolution, as well as genomic instability and epigenetic aberrations in lung cancer. Moreover, investigational measures that overcome heterogeneity-associated drug resistance and new assays to improve tumor assessment are also discussed. PMID:25285017

  9. An unusual presentation of tumor lysis syndrome in a patient with advanced gastric adenocarcinoma: case report and literature review.

    PubMed

    Vodopivec, Danica Maria; Rubio, Jose Enrique; Fornoni, Alessia; Lenz, Oliver

    2012-01-01

    Tumor lysis syndrome (TLS) is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia in patients with a malignancy. When these laboratory abnormalities develop rapidly, clinical complications such as cardiac arrhythmias, acute renal failure, seizures, or death may occur. TLS is caused by rapid release of intracellular contents by dying tumor cells, a condition that is expected to be common in hematologic malignancies. However, TLS rarely occurs with solid tumors, and here we present the second chemotherapy-induced TLS in a patient with advanced gastric adenocarcinoma to be reported in the literature. We also provide information regarding the total cases of TLS in solid tumors reported from 1977 to present day. Our methodology involved identifying key articles from existing reviews of the literature and then using search terms from these citations in MEDLINE to find additional publications. We relied on a literature review published in 2003 by Baeksgaard et al., where they gathered all total 45 cases reported from 1977 to 2003. Then, we looked for new reported cases from 2004 to present day. All reports (case reports, brief reports, letters to editor, correspondence, reviews, journals, and short communications) identified through these searches were reviewed and included.

  10. Two-Stage Axial Compressor Rig Designed To Develop and Validate Advanced Aerodynamic Technologies

    NASA Technical Reports Server (NTRS)

    Larosiliere, Louis M.

    2003-01-01

    Future aeropropulsion gas turbine engines must be affordable in addition to being energy efficient and environmentally benign. Progress in aerodynamic design capability is required not only to maximize the specific thrust of next-generation engines without sacrificing fuel consumption, but also to reduce parts count by increasing the aerodynamic loading of the compression system. To meet future compressor requirements, the NASA Glenn Research Center is investigating advanced aerodynamic design concepts that will lead to more compact, higher efficiency, and wider operability configurations than are currently in operation.

  11. The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer.

    PubMed

    Travis, William D; Asamura, Hisao; Bankier, Alexander A; Beasley, Mary Beth; Detterbeck, Frank; Flieder, Douglas B; Goo, Jin Mo; MacMahon, Heber; Naidich, David; Nicholson, Andrew G; Powell, Charles A; Prokop, Mathias; Rami-Porta, Ramón; Rusch, Valerie; van Schil, Paul; Yatabe, Yasushi

    2016-08-01

    This article proposes codes for the primary tumor categories of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and a uniform way to measure tumor size in part-solid tumors for the eighth edition of the tumor, node, and metastasis classification of lung cancer. In 2011, new entities of AIS, MIA, and lepidic predominant adenocarcinoma were defined, and they were later incorporated into the 2015 World Health Organization classification of lung cancer. To fit these entities into the T component of the staging system, the Tis category is proposed for AIS, with Tis (AIS) specified if it is to be distinguished from squamous cell carcinoma in situ (SCIS), which is to be designated Tis (SCIS). We also propose that MIA be classified as T1mi. Furthermore, the use of the invasive size for T descriptor size follows a recommendation made in three editions of the Union for International Cancer Control tumor, node, and metastasis supplement since 2003. For tumor size, the greatest dimension should be reported both clinically and pathologically. In nonmucinous lung adenocarcinomas, the computed tomography (CT) findings of ground glass versus solid opacities tend to correspond respectively to lepidic versus invasive patterns seen pathologically. However, this correlation is not absolute; so when CT features suggest nonmucinous AIS, MIA, and lepidic predominant adenocarcinoma, the suspected diagnosis and clinical staging should be regarded as a preliminary assessment that is subject to revision after pathologic evaluation of resected specimens. The ability to predict invasive versus noninvasive size on the basis of solid versus ground glass components is not applicable to mucinous AIS, MIA, or invasive mucinous adenocarcinomas because they generally show solid nodules or consolidation on CT.

  12. [Diagnosis and treatment of depression in the advanced stage of cancer].

    PubMed

    Ronson, A

    2002-10-01

    The diagnosis of depression in patients with advanced cancer is a particularly complex task. The lack of diagnostic tools specifically developed for this patient population, the difficulty of interpreting neurovegetative symptoms of depression--which can result from the neoplastic disease--and the "normal and understandable" nature of many symptoms or signs of psychological distress are among the main obstacles to a clear-cut diagnosis of depression. Things go even more complex when it comes about to discuss whether one should treat patients displaying psychological distress that does not meet established criteria for the diagnosis of a depressive illness. When the indication to treat is finally acknowledged, the choice of the optimal antidepressant will depend upon a series of parameters including survival expectancy, tolerance profile and drug interactions. Though we currently lack prospective data about the efficacy and safety of antidepressants in depressed patients with advanced cancer, extrapolation of data available from other patient populations with severe medical conditions and clinical experience allow to draw guidelines aimed at helping healthcare professionals faced with those problems to improve the quality of life of their patients. These elements are presented and discussed in this paper in the light of the recent developments resulting from the growing interest of the medical community to the care to patients with terminal illness. PMID:12474322

  13. Collecting Tumor Samples From Patients With Gynecological Tumors

    ClinicalTrials.gov

    2016-10-26

    Borderline Ovarian Clear Cell Tumor; Borderline Ovarian Serous Tumor; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Ovarian Germ Cell Tumor; Endometrioid Stromal Sarcoma; Gestational Trophoblastic Tumor; Malignant Mesothelioma; Malignant Ovarian Epithelial Tumor; Melanoma; Neoplasm of Uncertain Malignant Potential; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Paget Disease of the Vulva; Recurrent Cervical Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vaginal Carcinoma; Recurrent Vulvar Carcinoma; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Cervical Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell

  14. 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

  15. Association Between the Cytogenetic Profile of Tumor Cells and Response to Preoperative Radiochemotherapy in Locally Advanced Rectal Cancer

    PubMed Central

    González-González, María; Garcia, Jacinto; Alcazar, José A.; Gutiérrez, María L.; Gónzalez, Luis M.; Bengoechea, Oscar; Abad, María M.; Santos-Briz, Angel; Blanco, Oscar; Martín, Manuela; Rodríguez, Ana; Fuentes, Manuel; Muñoz-Bellvis, Luis; Orfao, Alberto; Sayagues, Jose M.

    2014-01-01

    Abstract Neoadjuvant radiochemotherapy to locally advanced rectal carcinoma patients has proven efficient in a high percentage of cases. Despite this, some patients show nonresponse or even disease progression. Recent studies suggest that different genetic alterations may be associated with sensitivity versus resistance of rectal cancer tumor cells to neoadjuvant therapy. We investigated the relationship between intratumoral pathways of clonal evolution as assessed by interphase fluorescence in situ hybridization (51 different probes) and response to neoadjuvant radiochemotherapy, evaluated by Dworak criteria in 45 rectal cancer tumors before (n = 45) and after (n = 31) treatment. Losses of chromosomes 1p (44%), 8p (53%), 17p (47%), and 18q (38%) and gains of 1q (49%) and 13q (75%) as well as amplification of 8q (38%) and 20q (47%) chromosomal regions were those specific alterations found at higher frequencies. Significant association (P < 0.05) was found between alteration of 1p, 1q, 11p, 12p, and 17p chromosomal regions and degree of response to neoadjuvant therapy. A clear association was observed between cytogenetic profile of the ancestral tumor cell clone and response to radiochemotherapy; cases presenting with del(17p) showed a poor response to neoadjuvant treatment (P = 0.03), whereas presence of del(1p) was more frequently observed in responder patients (P = 0.0002). Moreover, a significantly higher number of copies of chromosomes 8q (P = 0.004), 13q (P = 0.003), and 20q (P = 0.002) were found after therapy versus paired pretreatment rectal cancer samples. Our results point out the existence of an association between tumor cytogenetics and response to neoadjuvant therapy in locally advanced rectal cancer. Further studies in larger series of patients are necessary to confirm our results. PMID:25474426

  16. Non-albuminuric renal disease among subjects with advanced stages of chronic kidney failure related to type 2 diabetes mellitus.

    PubMed

    Boronat, Mauro; García-Cantón, César; Quevedo, Virginia; Lorenzo, Dionisio L; López-Ríos, Laura; Batista, Fátima; Riaño, Marta; Saavedra, Pedro; Checa, María D

    2014-03-01

    Urinary albumin excretion has been consistently found to be normal in a significant number of subjects with early stages of diabetic kidney disease. This study was aimed to estimate the prevalence and characteristics of non-albuminuric chronic kidney disease associated with type 2 diabetes mellitus among subjects who reach advanced stages of renal failure. Study population was composed of incident patients with advanced chronic kidney disease (glomerular filtration rate <30 mL/min) related to type 2 diabetes in a tertiary hospital from Gran Canaria (Spain) during a period of 2 years. Subjects were classified as normoalbuminuric (urinary albumin-to-creatine ratio [UACR] <30 mg/g), microalbuminuric (UACR ≥30 and <300 mg/g), or proteinuric (UACR ≥300 mg/g). Of 78 eligible patients, 21.8% had normoalbuminuria, 20.5% had microalbuminuria, and 57.7% had proteinuria. Individuals with normoalbuminuria were mostly women and had a lower prevalence of smoking and polyneuropathy than subjects with microalbuminuria or proteinuria. They also presented greater measures of body mass index and waist circumference, higher values of total and LDL cholesterol, and lower values of HbA1c and serum creatinine than subjects with microalbuminuria or proteinuria. Multivariate analysis demonstrated that female sex (positively) and HbA1c and polyneuropathy (negatively) were independently associated with absence of albuminuria. In conclusion, around 20% of subjects with diabetes-related advanced chronic kidney disease, characteristically women, have normal urinary albumin excretion. HbA1c and polyneuropathy are inversely related to this non-albuminuric form of nephropathy.

  17. Sulfur removal in advanced two-stage fluidized-bed combustion. [Quarterly] technical report, December 1, 1993--February 28, 1994

    SciTech Connect

    Abbasian, J.; Hill, A.H.; Wangerow, J.R.; Rue, D.M.

    1994-06-01

    The objective of this study is to obtain data on the rates of reaction between, hydrogen sulfide (H{sub 2}S) and uncalcined calcium-based sorbents under operating conditions relevant to first stage (carbonizer) of Advanced Two-Stage Pressurized Fluidized-Bed Combustors (PFBC). In these systems the CO{sub 2} partial pressure in the first stage generally exceeds the equilibrium value for calcium carbonate decomposition. Therefore, removal of sulfur compounds takes place through the reaction between H{sub 2}S and calcium carbonate. To achieve this objective the rates of reaction between hydrogen sulfide and uncalcined calcium-based sorbents will be determined by conducting tests in pressurized thermogravimetric analyzer (TGA) and high-pressure/high-temperature fluidized-bed reactor (HPTR) units. The effects of sorbent type, sorbent particle size, reactor temperature and pressure, and CO{sub 2} and H{sub 2}S partial pressures on the sulfidation reaction rate will be determined. During this quarter, the high-pressure thermogravimetric analyzer (HPTGA) unit was installed and the shakedown process was completed. Several tests were conducted in the HPTGA unit to establish the operating procedure and the repeatability of the experimental results. Sulfidation by conducting the baseline sulfidation tests. The results are currently being analyzed.

  18. Sulfur removal in advanced two-staged pressurized fluidized-bed combustion; [Quarterly] report, September 1--November 1993

    SciTech Connect

    Abbasian, J.; Hill, A.H.; Wangerow, J.R.; Rue, D.M.

    1994-03-01

    The objective of this study is to obtain data on the rates of reaction between hydrogen sulfide (H{sub 2}S) and uncalcined calcium-based sorbents under operating conditions relevant to first stage (carbonizer) of Advanced Two-Stage Pressurized Fluidized-Bed Combustors (PFBC). In these systems the CO{sub 2} partial pressure in the first stage generally exceeds the equilibrium value for calcium carbonate decomposition. Therefore, removal of sulfur compounds takes place through the reaction between H{sub 2}S and calcium carbonate. To achieve this objective, the rates of reaction between hydrogen sulfide and uncalcined calcium-based sorbents will be determined by conducting tests in pressurized thermogravimetric analyzer (TGA) and high-pressure/high-temperature fluidized-bed reactor (HPTR) units. The effects of sorbent type, sorbent particle size, reactor temperature and pressure, and CO{sub 2} and H{sub 2}S partial pressures on the sulfidation reaction rate will be determined. A pressurized TGA unit has been purchased by IGT for use in this project.

  19. Design and development of an advanced two-stage centrifugal compressor

    SciTech Connect

    Palmer, D.L.; Waterman, W.F.

    1995-04-01

    Small turboshaft engines require high-pressure-ratio, high-efficiency compressors to provide low engine fuel consumption. This paper describes the aeromechanical design and development of a 3.3 kg/s (7.3 lb/sec), 14:1 pressure ratio two-stage centrifugal compressor, which is used in the T800-LHT-800 helicopter engine. The design employs highly nonradial, splitter bladed impellers with swept leading edges and compact vaned diffusers to achieve high performance in a small and robust configuration. The development effort quantified the effects of impeller diffusion and passive inducer shroud bleed on surge margin as well as the effects of impeller loading on tip clearance sensitivity and the impact of sand erosion and shroud roughness on performance. The developed compressor exceeded its performance objectives with a minimum of 23% surge margin without variable geometry. The compressor provides a high-performance, rugged, low-cost configuration ideally suited for helicopter applications.

  20. Phase 1 results from a study of romidepsin in combination with gemcitabine in patients with advanced solid tumors.

    PubMed

    Jones, Suzanne F; Infante, Jeffrey R; Spigel, David R; Peacock, Nancy W; Thompson, Dana S; Greco, F Anthony; McCulloch, William; Burris, Howard A

    2012-07-01

    Romidepsin is a potent histone deacetylase inhibitor; preclinical studies showed potential synergy with the nucleoside analog gemcitabine. This phase 1 trial was conducted to determine the maximum tolerated dose for two schedules of romidepsin plus gemcitabine in patients with advanced solid tumors in which gemcitabine had previously demonstrated clinical activity. The recommended phase 2 dose was 12 mg/m(2) romidepsin plus 800 mg/m(2) gemcitabine on days 1 and 15 every 28 days. Results suggest additive hematologic toxicities of romidepsin plus gemcitabine, but the level of antitumor activity observed warrants more formal trials of this combination to further assess safety and efficacy.

  1. In vivo proton-electron double-resonance imaging of extracellular tumor pH using an advanced nitroxide probe.

    PubMed

    Samouilov, Alexandre; Efimova, Olga V; Bobko, Andrey A; Sun, Ziqi; Petryakov, Sergey; Eubank, Timothy D; Trofimov, Dmitrii G; Kirilyuk, Igor A; Grigor'ev, Igor A; Takahashi, Wataru; Zweier, Jay L; Khramtsov, Valery V

    2014-01-21

    A variable radio frequency proton-electron double-resonance imaging (VRF PEDRI) approach for pH mapping of aqueous samples has been recently developed (Efimova et al. J. Magn. Reson. 2011, 209, 227-232). A pH map is extracted from two PEDRI acquisitions performed at electron paramagnetic resonance (EPR) frequencies of protonated and unprotonated forms of a pH-sensitive probe. To translate VRF PEDRI to an in vivo setting, an advanced pH probe was synthesized. Probe deuteration resulted in a narrow spectral line of 1.2 G compared to a nondeuterated analogue line width of 2.1 G allowing for an increase of Overhauser enhancements and reduction in rf power deposition. Binding of the probe to the cell-impermeable tripeptide, glutathione (GSH), allows for targeting to extracellular tissue space for monitoring extracellular tumor acidosis, a prognostic factor in tumor pathophysiology. The probe demonstrated pH sensitivity in the 5.8-7.8 range, optimum for measurement of acidic extracellular tumor pH (pH(e)). In vivo VRF PEDRI was performed on Met-1 tumor-bearing mice. Compared to normal mammary glands with a neutral mean pH(e) (7.1 ± 0.1), we observed broader pH distribution with acidic mean pH(e) (6.8 ± 0.1) in tumor tissue. In summary, VRF PEDRI in combination with a newly developed pH probe provides an analytical approach for spatially resolved noninvasive pHe monitoring, in vivo.

  2. In vivo proton-electron double-resonance imaging of extracellular tumor pH using an advanced nitroxide probe.

    PubMed

    Samouilov, Alexandre; Efimova, Olga V; Bobko, Andrey A; Sun, Ziqi; Petryakov, Sergey; Eubank, Timothy D; Trofimov, Dmitrii G; Kirilyuk, Igor A; Grigor'ev, Igor A; Takahashi, Wataru; Zweier, Jay L; Khramtsov, Valery V

    2014-01-21

    A variable radio frequency proton-electron double-resonance imaging (VRF PEDRI) approach for pH mapping of aqueous samples has been recently developed (Efimova et al. J. Magn. Reson. 2011, 209, 227-232). A pH map is extracted from two PEDRI acquisitions performed at electron paramagnetic resonance (EPR) frequencies of protonated and unprotonated forms of a pH-sensitive probe. To translate VRF PEDRI to an in vivo setting, an advanced pH probe was synthesized. Probe deuteration resulted in a narrow spectral line of 1.2 G compared to a nondeuterated analogue line width of 2.1 G allowing for an increase of Overhauser enhancements and reduction in rf power deposition. Binding of the probe to the cell-impermeable tripeptide, glutathione (GSH), allows for targeting to extracellular tissue space for monitoring extracellular tumor acidosis, a prognostic factor in tumor pathophysiology. The probe demonstrated pH sensitivity in the 5.8-7.8 range, optimum for measurement of acidic extracellular tumor pH (pH(e)). In vivo VRF PEDRI was performed on Met-1 tumor-bearing mice. Compared to normal mammary glands with a neutral mean pH(e) (7.1 ± 0.1), we observed broader pH distribution with acidic mean pH(e) (6.8 ± 0.1) in tumor tissue. In summary, VRF PEDRI in combination with a newly developed pH probe provides an analytical approach for spatially resolved noninvasive pHe monitoring, in vivo. PMID:24372284

  3. Survival analysis of patients with advanced-stage nasopharyngeal carcinoma according to the Epstein-Barr virus status

    PubMed Central

    Peng, Hao; Chen, Lei; Zhang, Yuan; Guo, Rui; Li, Wen-Fei; Mao, Yan-Ping; Tan, Ling-Long; Sun, Ying; Zhang, Fan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Ma, Jun

    2016-01-01

    Purpose The main aim of this study is to analyze the prognostic differences in nasopharyngeal carcinoma (NPC) patients who are positive and negative for Epstein-Barr virus (EBV). Results Of the 1106 patients, 248 (22.4%) had undetectable pre-treatment plasma EBV DNA levels. The total distant metastasis rate for EBV-negative group vs. EBV-positive group were 3.6% (9/248) vs. 15.0% (128/858) (P < 0.001). The estimated 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) for EBV-negative group vs. EBV-positive group were 88.9% vs. 76.9% (P < 0.001), 93.6% vs. 85.9% (P = 0.001), 96.7% vs. 84.8% (P < 0.001) and 94.1% vs. 90.0% (P = 0.1), respectively. Multivariate analysis revealed that the EBV status was an independent prognostic factor for DFS (HR, 1.813; 95% CI, 1.219-2.695; P = 0.003), OS (HR, 1.828; 95% CI, 1.075-3.107; P = 0.026) and DMFS (HR, 3.678; 95% CI, 1.859-7.277; P <0.001), and overall stage still remained the most important prognostic factor in patients with stage III-IVB NPC. Methods and Materials Data on 1106 patients with non-metastatic, histologically proven advanced-stage (III-IVB) NPC who underwent intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Patient survival between different EBV status groups were compared. Conclusions EBV status was an independent prognostic factor for patients with stage III–IVB NPC. Neoadjuvant chemotherapy (NCT) plus concurrent chemoradiotherapy (CCRT) should be better treatment regimen for EBV-positive patients since distant metastasis was the main failure pattern, and CCRT may be enough for EBV-negative patients. PMID:27008701

  4. A window of opportunity study of potential tumor and soluble biomarkers of response to preoperative erlotinib in early stage non-small cell lung cancer

    PubMed Central

    Sacher, Adrian G.; Le, Lisa W.; Lara-Guerra, Humberto; Waddell, Thomas K.; Sakashita, Shingo; Chen, Zhuo; Kim, Lucia; Zhang, Tong; Kamel-Reid, Suzanne; Salvarrey, Alexandra; Darling, Gail; Yasufuku, Kazuhiro; Keshavjee, Shaf; de Perrot, Marc; Shepherd, Frances A.; Liu, Geoffrey; Tsao, Ming Sound; Leighl, Natasha B.

    2016-01-01

    Background: Erlotinib is highly active in EGFR mutant NSCLC, but may benefit some with wild-type tumors. We examined pre-operative erlotinib in early stage NSCLC to assess response and correlation with potential biomarkers. Results: Twenty-five patients were enrolled; 22 received erlotinib treatment and were evaluable (median follow-up 4.4 years). Histology was predominantly adenocarcinoma although 31% had squamous carcinoma. PET response was observed in 2 patients (9%), both with squamous carcinoma. Most (20/22) had stable disease (RECIST), with frequent minor radiographic regression and histologic findings of fibrosis/necrosis including in squamous histology. Only two had EGFR mutations identified, one with minor radiographic response and the other stable disease after 4 weeks of EGFR TKI. High pre-treatment serum levels of TGF-α correlated with primary resistance to erlotinib (p = 0.02), whereas high post-treatment soluble EGFR levels correlated with response (p = 0.03). EGFR, PTEN, cMET and AXL expression did not correlate with tumor response. Methods: Clinical stage IA–IIB NSCLC patients received erlotinib 150 mg daily for 4 weeks followed by resection. Tumor response was assessed using CT, PET and pathological response. Tumor genotype was established using Sequenom Mass ARRAY; EGFR, PTEN, cMET and AXL expression was assessed by immunohistochemistry, circulating markers of EGFR activation (TGF-α, amphiregulin, epiregulin, EGFR ECD) by ELISA and EGFR, MET copy number by FISH. Conclusions: Erlotinib appears to demonstrate activity in EGFR wild-type tumors including squamous carcinoma. Further research is needed to characterize those wild-type patients that may benefit from EGFR TKI and predictive biomarkers including TGF-α, EGFR copy and others. PMID:27028852

  5. Intact PTEN Expression by Immunohistochemistry is Associated With Decreased Survival in Advanced Stage Ovarian/Primary Peritoneal High-grade Serous Carcinoma.

    PubMed

    Bakkar, Rania M; Xie, Su-Su; Urbauer, Diana L; Djordjevic, Bojana; Vu, Kim; Broaddus, Russell R

    2015-11-01

    Ovarian high-grade serous carcinoma is an aggressive malignancy with poor prognosis. Optimal surgical debulking and tumor sensitivity to platinum-based chemotherapy are 2 well-established prognostics for this tumor type. Molecular markers that identify more clinically aggressive tumors would potentially allow for the development of individualized treatment options. PTEN is a key negative regulator of the PI3K signaling pathway. Loss of PTEN expression in endometrial carcinoma is associated with endometrioid histology; women with endometrioid tumors have a better prognosis than those with nonendometrioid tumors. The prognostic and predictive value for PTEN has not been effectively explored in ovarian/peritoneal high-grade serous carcinoma. PTEN immunohistochemistry was assessed in 126 women with Stage III, high-grade serous carcinoma of the ovary/peritoneum treated with surgery and then a platinum-based regimen. Compared with PTEN-negative or PTEN-reduced tumors, positive PTEN immunohistochemistry, detected in 58% of tumors, was associated with decreased pS6 and increased PTEN mRNA levels. Positive PTEN expression was independent of surgical debulking status or platinum sensitivity. PTEN-positive tumors were associated with significantly decreased recurrence-free survival. Importantly, the devised PTEN immunohistochemistry scoring system was reproducible among pathologists.

  6. [Clinical study of retroperitoneal lymph node dissection for patients with advanced germ cell tumors].

    PubMed

    Okamura, K; Yuba, H; Nishimura, T; Mizutani, K; Takashi, M; Gotoh, M; Ono, Y; Ohshima, S

    1999-02-01

    We performed retroperitoneal lymph node dissection (RPLND) on 14 patients (IIA: 1, IIB: 4, IIIA: 3, IIIB2: 2, IIIC: 4) with testicular and one with retroperitoneal germ cell tumor at the Nagoya University Hospital between 1986 and 1997. According to the international germ cell consensus classification, 4 patients were classified as "good-prognosis", three as "intermediate-prognosis" and eight as "poor-prognosis". RPLND was performed on 12 patients with the tumor marker levels normalized preoperatively and on three without the marker normalization. The mean surgical time was 510 (195-1, 125) minutes and the mean bleeding volume was 3,806 (100-12,598) g. The surgical time and bleeding volume were correlated with the size of the tumor in the body axis. Intraoperative complications occurred in 5 (33%) out of 15 patients: injury of renal artery (2), renal vein (1), ureter (1) and common iliac artery (2). Postoperative complications occurred in 2 patients: ileus (2) and lower extremity edema resulting from resection of the inferior vena cava (1) and would dehiscence (1). Of the 8 patients whose completely resected retroperitoneal tumors were necrosis/fibrosis or teratoma (psCR), 6 achieved survival with no evidence of disease (NED). Among 4 patients, whose tumor was not completely resected but pathologically diagnosed as necrosis/fibrosis or teratoma (pCR), NED without recurrence was achieved in 2 and also in one with resection of relapsed teratoma 2.5 years after RPLND. All three patients with cancer tissues pathologically retained in the resected tumors (sCR or psIR), consequently died of the disease. In six patients with relapse, the initial sign was elevation of the tumor marker levels, which was noted more than 30 days postoperatively in 2 patients with psCR and 7 to 15 days in 4 patients without psCR. We believe that RPLND is needed to examine the pathology and to predict the prognosis of the poor-risk patients with NSGCT. Careful dissection of vessels is needed to

  7. Potential Prognostic Impact of Baseline CEA Level and Surgery of Primary Tumor Among Patients with Synchronous Stage IV Colorectal Cancer: A Large Population Based Study.

    PubMed

    Dawood, Shaheenah; Sirohi, Bhawna; Shrikhande, Shailesh V; Toh, Han-Chong; Eng, Cathy

    2015-09-01

    Prognostic role of surgical resection of the primary tumor and baseline CEA among patients with synchronous stage IV colorectal cancer (CRC) remains an area of debate. The objective of this study was to determine the prognostic value of baseline CEA and surgical resection of the primary among patients with synchronous stage IV CRC in the era of modern chemotherapy and biologic therapy. The Surveillance, Epidemiology and End Results Registry was searched to identify patients with synchronous stage IV CRC diagnosed between 2004 and 2009. Colorectal-cancer-specific survival (CCS) was estimated using the Kaplan-Meier product limit method. Cox models were fitted to assess the multivariable relationship of various patient and tumor characteristics and CCS. Three hundred thirty-three thousand, three hundred ninety nine patients were identified in the SEER registry. Median CCS among patients with their primary tumor removed was 21 M vs. 7 M (primary intact) respectively (p < 0.001). Median CCS among patients who had an elevated vs. non-elevated baseline CEA level was 14 M vs. 24 M respectively (p < 0.0001). By multivariable analysis, patients with an elevated baseline CEA had a 56 % increased risk of death from CRC compared to those with a non-elevated CEA level (HR = 1.56, 95%CI 1.47-1.65, p < 0.0001). Similarly patients who underwent surgical resection of the primary tumor had a 33 % decreased risk of death from CRC compared to those who did not (HR = 0.61, 95%CI 0.54-0.69, p < 0.0001). In our review of this large population SEER based study, an elevated baseline CEA level and surgical resection of the primary tumor among patients with synchronous stage IV CRC appeared to impact survival outcomes. Prospective validation of these results in a surgically unresectable patient population will be required.

  8. Understanding the Racial and Ethnic Differences in Cost and Mortality Among Advanced Stage Prostate Cancer Patients (STROBE).

    PubMed

    Chhatre, Sumedha; Bruce Malkowicz, Stanley; Sanford Schwartz, J; Jayadevappa, Ravishankar

    2015-08-01

    The aims of the study were to understand the racial/ethnic differences in cost of care and mortality in Medicare elderly with advanced stage prostate cancer.This retrospective, observational study used SEER-Medicare data. Cohort consisted of 10,509 men aged 66 or older and diagnosed with advanced-stage prostate cancer between 2001and 2004. The cohort was followed retrospectively up to 2009. Racial/ethnic variation in cost was analyzed using 2 part-models and quantile regression. Step-wise GLM log-link and Cox regression was used to study the association between race/ethnicity and cost and mortality. Propensity score approach was used to minimize selection bias.Pattern of cost and mortality varies between racial/ethnic groups. Compared with other racial/ethnic groups, non-Hispanic white patients had higher unadjusted costs in treatment and follow-up phases. Quintile regression results indicated that in treatment phase, Hispanics had higher costs in the 95th quantile and non-Hispanic blacks had lower cost in the 95th quantile, compared with non-Hispanic white men. In terminal phase non-Hispanic blacks and Hispanics had higher cost. After controlling for treatment, all-cause and prostate cancer-specific mortality was not significant for non-Hispanic black men, compared with non-Hispanic white men. However, for Asians, mortality remained significantly lower compared with non-Hispanic white men.In conclusion, relationship between race/ethnicity, cost of care, and mortality is intricate. For non-Hispanic black men, disparity in mortality can be attributed to treatment differences. To reduce racial/ethnic disparities in prostate cancer care and outcomes, tailored policies to address underuse, overuse, and misuse of treatment and health services are necessary. PMID:26266389

  9. The Modern Role of Radiation Therapy in Treating Advanced-Stage Retinoblastoma: Long-Term Outcomes and Racial Differences

    SciTech Connect

    Orman, Amber; Koru-Sengul, Tulay; Miao, Feng; Markoe, Arnold; Panoff, Joseph E.

    2014-12-01

    Purpose/Objective(s): To evaluate the effects of various patient characteristics and radiation therapy treatment variables on outcomes in advanced-stage retinoblastoma. Methods and Materials: This was a retrospective review of 41 eyes of 30 patients treated with external beam radiation therapy between June 1, 1992, and March 31, 2012, with a median follow-up time of 133 months (11 years). Outcome measures included overall survival, progression-free survival, local control, eye preservation rate, and toxicity. Results: Over 90% of the eyes were stage V. Definitive external beam radiation therapy (EBRT) was delivered in 43.9% of eyes, adjuvant EBRT in 22% of eyes, and second-line/salvage EBRT in 34.1% of eyes. A relative lens sparing (RLS) technique was used in 68.3% of eyes and modified lens sparing (MLS) in 24.4% of eyes. Three eyes were treated with other techniques. Doses ≥45 Gy were used in 68.3% of eyes. Chemotherapy was a component of treatment in 53.7% of eyes. The 10-year overall survival was 87.7%, progression-free survival was 80.5%, and local control was 87.8%. White patients had significantly better overall survival than did African-American patients in univariate analysis (hazard ratio 0.09; 95% confidence interval 0.01-0.84; P=.035). Toxicity was seen in 68.3% of eyes, including 24.3% with isolated acute dermatitis. Conclusions: External beam radiation therapy continues to be an effective treatment modality for advanced retinoblastoma, achieving excellent long-term local control and survival with low rates of treatment-related toxicity and secondary malignancy.

  10. Stage IV Wilms Tumor Treated by Korean Medicine, Hyperthermia and Thymosin-α1: A Case Report

    PubMed Central

    Lee, Donghyun; Kim, Sung Su; Seong, Shin; Cho, Wonjun; Yu, Hyejin

    2016-01-01

    Introduction Wilms tumor is one of general solid cancers that occur in children, which carries a death rate of 7–8 in a million. The cure rate of Wilms tumor in the recent 30 years has dramatically been improved, but a proper remedy is still not prepared enough in terms of application in tumor therapy upon recurrence after radiotherapy, surgery and chemotherapy. We present an integrative medical remedy – hyperthermia and thymosin-α1 treatment focused on herbal remedy – since there have been cases in which this remedy contributed to remission in the liver-transferred part in the 4th phase of Wilms tumor and stable maintenance of metastatic lung lesion. Case Presentation Our patient, a female Korean mongoloid outpatient, was treated from October 25, 2014, to July 22, 2015. The herbal remedy consisted of 8 ml inhalation of Soram nebulizer solution q.d., Soramdan S 8 g p.o., Hangamdan S 1 g p.o., t.i.d., Cheongjangtang 10–30 ml, and Spiam HC 8 g p.o. The integrative medical therapy was done with hyperthermia therapy (oncothermia) and 1.6 mg of thymosin-α1 treatment (Zadaxin) i.m. According to the CT result on July 15th, 2015, the liver metastasis was not seen anymore, while the lung metastasis was maintained stably without tumor progress. Conclusions Accompanying integrative medical therapy with herbal remedy in the treatment of Wilms tumor showing progress patterns after surgery and chemotherapy can be meaningful as a new remedy. PMID:27293398

  11. Extended Intervals after Neoadjuvant Therapy in Locally Advanced Rectal Cancer: The Key to Improved Tumor Response and Potential Organ Preservation

    PubMed Central

    Probst, Christian P; Becerra, Adan Z; Aquina, Christopher T; Tejani, Mohamedtaki A; Wexner, Steven D; Garcia-Aguilar, Julio; Remzi, Feza H; Dietz, David W; Monson, John RT; Fleming, Fergal J

    2016-01-01

    Background Many rectal cancer patients experience tumor downstaging and some are found to achieve a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT). Previous data suggest that there is an association between the time interval from nCRT completion to surgery and tumor response rates, including pCR. However, these studies have been primarily from single institutions with small sample sizes. The aim of this study was to examine the relationship between a longer interval after nCRT and pCR in a nationally representative cohort of rectal cancer patients. Study Design Clinical stage II–III rectal cancer patients undergoing nCRT with a documented surgical resection were selected from the 2006 – 2011 National Cancer Data Base. Multivariable logistic regression analysis was used to assess the association between nCRT-surgery interval time (<6 weeks, 6–8 weeks, >8 weeks) and the odds of pCR. The relationship between nCRT-surgery interval, surgical morbidity, and tumor downstaging was also examined. Results Overall, 17,255 patients met the inclusion criteria. A nCRT-surgery interval time >8 weeks was associated with higher odds of pCR (OR=1.12, 95%CI=1.01–1.25) and tumor downstaging (OR=1.11, 95%CI =1.02–1.25). The longer time delay was also associated with lower odds of 30-day readmission (OR=0.82, 95%CI: 0.70–0.92). Conclusions A nCRT-surgery interval time >8 weeks results in increased odds of pCR with no evidence of associated increased surgical complications compared to 6–8 weeks. This data supports the implementation of a lengthened interval after nCRT to optimize the chances of pCR and perhaps add to the possibility of ultimate organ preservation (non-operative management). PMID:26206642

  12. Sulfur removal in advanced two stage pressurized fluidized bed combustion. Technical report, March 1--May 31, 1995

    SciTech Connect

    Abbasian, J.

    1995-12-31

    The objective of this study is to obtain data on the rates and the extent of sulfation reactions involving partially sulfided calcium-based sorbents, and oxygen as well as sulfur dioxide, at operating conditions closely simulating those prevailing in the second stage (combustor) of Advanced Two-Stage Pressurized Fluidized-Bed Combustors. In these systems the CO{sub 2} partial pressure generally exceeds the equilibrium value for calcium carbonate decomposition. Therefore, calcium sulfate is produced through the reactions between SO{sub 2} and calcium carbonate as well as the reaction between calcium sulfide and oxygen. To achieve this objective, the rates of reaction involving SO{sub 2} and oxygen, calcium sulfide and calcium carbonate will be determined by conducting tests in a pressurized thermogravimetric analyzer unit. The sulfate tests conducted during this quarter, focused on the determination of the rate of sulfation reaction involving partially sulfided half-calcined dolomite and oxygen. The test parameters included CO{sub 2} and O{sub 2} concentrations, reaction temperature and pressure, as well as the sorbent particle size. The results obtained during this quarter suggest that the rate of sulfation reaction involving partially sulfided half-calcined dolomite and oxygen is very fast at temperatures above 850 C which rapidly increases with increasing temperature, achieving more than 85% conversion in less than a few minutes. The reaction appears to continue to completion, however, above 85% conversion, the rate of reaction appears to be low, requiring long residence time to reach complete conversion.

  13. Sulfur removal in advanced two stage pressurized fluidized bed combustion. Technical report, December 1, 1994--February 28, 1995

    SciTech Connect

    Abbasian, J.

    1996-03-01

    The objective of this study is to obtain data on the rates and the extent of sulfation reactions involving partially sulfided calcium-based sorbents, and oxygen as well as sulfur dioxide, at operating conditions closely simulating those prevailing in the second stage (combustor) of Advanced Two-Stage Pressurized Fluidized-Bed Combustors (PFBC). In these systems the CO{sub 2} partial pressure generally exceeds the equilibrium value for calcium carbonate decomposition. Therefore, calcium sulfate is produced through the reactions between SO{sub 2} and calcium carbonate as well as the reaction between calcium sulfide and oxygen. To achieve this objective, the rates of reaction involving SO{sub 2} and oxygen (gaseous reactant); and calcium sulfide and calcium carbonate (solid reactants), will be determined by conducting tests in a pressurized thermogravimetric analyzer (HPTGA) unit. The effects of sorbent type, sorbent particle size, reactor temperature and pressure; and O{sub 2} as well as SO{sub 2} partial pressures on the sulfation reactions rate will be determined. During this quarter, samples of the selected limestone and dolomite, sulfided in the fluidized-bed reactor during last quarter, were analyzed. The extent of sulfidation in these samples was in the range of 20 to 50%, which represent carbonizer discharge material at different operating conditions. The high pressure thermogravimetric analyzer (BPTGA) unit has been modified and a new pressure control system was installed to eliminate pressure fluctuation during the sulfation tests.

  14. Sulfur removal in advanced two stage pressurized fluidized bed combustion. Technical report, September 1--November 30, 1994

    SciTech Connect

    Abbasian, J.; Hill, A.; Wangerow, J.R.

    1994-12-31

    The objective of this study is to obtain data on the rates and the extent of sulfation reactions involving partially sulfided calcium-based sorbents, and oxygen as well as sulfur dioxide, at operating conditions closely simulating those prevailing in the second stage (combustor) of Advanced Two-Stage Pressurized Fluidized-Bed Combustors (PFBC). In these systems the CO{sub 2} partial pressure generally exceeds the equilibrium value for calcium carbonate decomposition. Therefore, calcium sulfate is produced through the reactions between SO{sub 2} and calcium carbonate as well as the reaction between calcium sulfide and oxygen. To achieve this objective, the rates of reaction involving SO{sub 2} and oxygen (gaseous reactant); and calcium sulfide and calcium carbonate (solid reactants), will be determined by conducting tests in a pressurized thermogravimetric analyzer (HPTGA) unit. The effects of sorbent type, sorbent particle size, reactor temperature and pressure; and O{sub 2} as well as SO{sub 2} partial pressures on the sulfation reactions rate will be determined. During this quarter, samples of the selected limestone and dolomite were sulfided in the fluidized-bed reactor. These tests were conducted in both calcining and non-calcining operating conditions to produce partially-sulfided sorbents containing calcium oxide and calcium carbonate, respectively. These samples which represent the carbonizer discharge material, will be used as the feed material in the sulfation tests to be conducted in the HPTGA unit during the next quarter.

  15. The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

    NASA Astrophysics Data System (ADS)

    (Jay Chen, Zhe; Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

    2011-08-01

    Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than

  16. Advances in SPECT for Optimizing the Liver Tumors Radioembolization Using Yttrium-90 Microspheres

    PubMed Central

    Roshan, Hoda Rezaei; Azarm, Ahmadreza; Mahmoudian, Babak; Islamian, Jalil Pirayesh

    2015-01-01

    Radioembolization (RE) with Yttrium-90 (90Y) microspheres is an effective treatment for unresectable liver tumors. The activity of the microspheres to be administered should be calculated based on the type of microspheres. Technetium-99m macroaggregated albumin (99mTc-MAA) single photon emission computed tomography/computed tomography (SPECT/CT) is a reliable assessment before RE to ensure the safe delivery of microspheres into the target. 90Y bremsstrahlung SPECT imaging as a posttherapeutic assessment approach enables the reliable determination of absorbed dose, which is indispensable for the verification of treatment efficacy. This article intends to provide a review of the methods of optimizing 90Y bremsstrahlung SPECT imaging to improve the treatment efficacy of liver tumor RE using 90Y microspheres. PMID:26097416

  17. Results of Two-Stage Light-Gas Gun Development Efforts and Hypervelocity Impact Tests of Advanced Thermal Protection Materials

    NASA Technical Reports Server (NTRS)

    Cornelison, C. J.; Watts, Eric T.

    1998-01-01

    Gun development efforts to increase the launching capabilities of the NASA Ames 0.5-inch two-stage light-gas gun have been investigated. A gun performance simulation code was used to guide initial parametric variations and hardware modifications, in order to increase the projectile impact velocity capability to 8 km/s, while maintaining acceptable levels of gun barrel erosion and gun component stresses. Concurrent with this facility development effort, a hypervelocity impact testing series in support of the X-33/RLV program was performed in collaboration with Rockwell International. Specifically, advanced thermal protection system materials were impacted with aluminum spheres to simulate impacts with on-orbit space debris. Materials tested included AETB-8, AETB-12, AETB-20, and SIRCA-25 tiles, tailorable advanced blanket insulation (TABI), and high temperature AFRSI (HTA). The ballistic limit for several Thermal Protection System (TPS) configurations was investigated to determine particle sizes which cause threshold TPS/structure penetration. Crater depth in tiles was measured as a function of impact particle size. The relationship between coating type and crater morphology was also explored. Data obtained during this test series was used to perform a preliminary analysis of the risks to a typical orbital vehicle from the meteoroid and space debris environment.

  18. Sulfur removal in advanced two stage pressurized fluidized bed combustion. Technical report, 1 March--31 May 1994

    SciTech Connect

    Abbasian, J.; Chowdiah, P.; Hill, A.H.; Rue, D.M.

    1994-09-01

    The objective of this study is to obtain data on the rates of reaction between hydrogen sulfide (H{sub 2}S) and uncalcined calcium-based sorbents under operating conditions relevant to first stage (carbonizer) of Advanced Two-Stage Pressurized Fluidized-Bed Combustors (PFBC). In these systems the CO{sub 2} partial pressure in the first stage generally exceeds the equilibrium value for calcium carbonate decomposition. Therefore, removal of sulfur compounds takes place through the reaction between H{sub 2}S and calcium carbonate. To achieve this objective, the rates of reaction between hydrogen sulfide and uncalcined calcium-based sorbents will be determined by conducting tests in pressurized thermogravimetric analyzer (TGA) and high-pressure/high-temperature fluidized-bed reactor (HPTR) units. The effects of sorbent type, sorbent particle size, reactor temperature and pressure, and CO{sub 2} and H{sub 2}S partial pressures on the sulfidation reaction rate will be determined. During this quarter a series of sulfidation tests were conducted in the high-pressure/high-temperature fluidized-bed reactor (HPTR) units. The effects of sorbent type, sorbent particle size, reactor temperature and pressure, and CO{sub 2} and H{sub 2}S partial pressures on the sulfidation reaction rate will be determined. During this quarter a series of sulfidation tests were conducted in the high-pressure high-temperature thermogravimetric analyzer (HPTGA unit) using limestone and dolomite. The results suggest that half-calcined dolomite is much more reactive than uncalcined limestone. Also, temperature in the range of 800 to 950 C did not significantly affect the sulfidation reaction rates for both limestone and dolomite.

  19. Advances in the biology of bone metastasis: how the skeleton affects tumor behavior.

    PubMed

    Sterling, Julie A; Edwards, James R; Martin, T John; Mundy, Gregory R

    2011-01-01

    It is increasingly evident that the microenvironment of bone can influence the cancer phenotype in many ways that favor growth in bone. The ability of cancer cells to adhere to bone matrix and to promote osteoclast formation are key requirements for the establishment and growth of bone metastases. Several cytokine products of breast cancers (e.g. PTHrP, IL-11, IL-8) have been shown to act upon host cells of the bone microenvironment to promote osteoclast formation, allowing for excessive bone resorption. The increased release of matrix-derived growth factors, especially TGF-β, acts back upon the tumor to facilitate further tumor expansion and enhance cytokine production, and also upon osteoblasts to suppress bone formation. This provides a self-perpetuating cycle of bone loss and tumor growth within the skeleton. Other contributing factors favoring tumor metastasis and colonization in bone include the unique structure and stiffness of skeletal tissue, along with the diverse cellular composition of the marrow environment (e.g. bone cells, stromal fibroblasts, immune cells), any of which can contribute to the phenotypic changes that can take place in metastatic deposits that favor their survival. Additionally, it is also apparent that breast cancer cells begin to express different bone specific proteins as well as proteins important for normal breast development and lactation that allow them to grow in bone and stimulate bone destruction. Taken together, these continually emerging areas of study suggest new potential pathways important in the pathogenesis of bone metastasis and potential areas for targeting therapeutics.

  20. Atypical teratoid/rhabdoid tumors-current concepts, advances in biology, and potential future therapies.

    PubMed

    Frühwald, Michael C; Biegel, Jaclyn A; Bourdeaut, Franck; Roberts, Charles W M; Chi, Susan N

    2016-06-01

    Atypical teratoid/rhabdoid tumor (AT/RT) is the most common malignant CNS tumor of children below 6 months of age. The majority of AT/RTs demonstrate genomic alterations in SMARCB1 (INI1, SNF5, BAF47) or, to a lesser extent, SMARCA4 (BRG1) of the SWItch/sucrose nonfermentable chromatin remodeling complex. Recent transcription and methylation profiling studies suggest the existence of molecular subgroups. Thus, at the root of these seemingly enigmatic tumors lies a network of factors related to epigenetic regulation, which is not yet completely understood. While conventional-type chemotherapy may have significant survival benefit for certain patients, it remains to be determined which patients will eventually prove resistant to chemotherapy and thus need novel therapeutic strategies. Elucidation of the molecular consequences of a disturbed epigenome has led to the identification of a series of transduction cascades, which may be targeted for therapy. Among these are the pathways of cyclin D1/cyclin-dependent kinases 4 and 6, Hedgehog/GLI1, Wnt/ß-catenin, enhancer of zeste homolog 2, and aurora kinase A, among others. Compounds specifically targeting these pathways or agents that alter the epigenetic state of the cell are currently being evaluated in preclinical settings and in experimental clinical trials for AT/RT. PMID:26755072

  1. Results of d+T fast neutron irradiation on advanced tumors of bladder and rectum

    SciTech Connect

    Battermann, J.J.

    1982-12-01

    From November, 1975 to November, 1981, around 400 patients were irradiated with 14 MeV d+T fast neutrons at the Antoni van Leeuwenhoek Hospital in Amsterdam. Special interest was focused on inoperable tumors of bladder and rectum. During the pilot phase of the study 47 patients were treated, mostly via two parallel opposed ports with dosages that ranged from 18 to more than 22 Gy. Although persistent local control was achieved in 23 patients (48%), 14 patients (29%) died of severe complications. By the introduction of a six field technique, the fatal complication rate could be reduced significantly. Since May 1978 patients were randomized in a three arm trial, using two dose levels on the neutron site. The preliminary results of a group of 91 patients show a similar survival in the three treatment arms with a somewhat better local control rate for high dose neutrons. An attempt was made to estimate RBE values for tumor control and normal tissue reactions by comparing the data for neutron irradiation with the data obtained with photons on a similar group of patients. From the values derived it must be concluded that the gain for neutron irradiation on these tumors in the pelvis will be negligible.

  2. Results of d+T fast neutron irradiation on advanced tumors of bladder and rectum

    SciTech Connect

    Battermann, J.J.

    1982-12-01

    From November, 1975 to November, 1981, around 400 patients were irradiated with 14 MeV d+T fast neutrons at the Antoni van Leeuwenhoek Hospital in Amsterdam. Special interest was focused on inoperable tumors of bladder and rectum. During the pilot phase of the study 47 patients were treated, mostly via two parallel opposed ports with dosages that ranged from 18 to more than 22 Gy. Although persistent local control was achieved in 23 patients (48%), 14 patients (29%) died of severe complications. By the introduction of a six field technique, the fatal complication rate could be reduced significantly. Since May 1978 patients were randomized in a three arm trial, using two dose levels on the neutron site. The preliminary results of a group of 91 patients show a similar survival in the three treatment arms with a somewhat better local control rate for high dose neutrons. An attempt was made to estimate RBE values for tumor control and normal tissue reaction by comparing the data for neutron irradiation with the data obtained with photons on a similar group of patients. From the values derived it must be concluded that the gain for neutron irradiation on these tumors in the pelvis will be negligible.

  3. Inhibitory effect of α-lipoic acid on thioacetamide-induced tumor promotion through suppression of inflammatory cell responses in a two-stage hepatocarcinogenesis model in rats.

    PubMed

    Fujii, Yuta; Segawa, Risa; Kimura, Masayuki; Wang, Liyun; Ishii, Yuji; Yamamoto, Ryuichi; Morita, Reiko; Mitsumori, Kunitoshi; Shibutani, Makoto

    2013-09-25

    To investigate the protective effect of α-lipoic acid (a-LA) on the hepatocarcinogenic process promoted by thioacetamide (TAA), we used a two-stage liver carcinogenesis model in N-diethylnitrosamine (DEN)-initiated and TAA-promoted rats. We examined the modifying effect of co-administered a-LA on the liver tissue environment surrounding preneoplastic hepatocellular lesions, with particular focus on hepatic macrophages and the mechanism behind the decrease in apoptosis of cells surrounding preneoplastic hepatocellular lesions during the early stages of hepatocellular tumor promotion. TAA increased the number and area of glutathione S-transferase placental form (GST-P)(+) liver cell foci and the numbers of proliferating and apoptotic cells in the liver. Co-administration with a-LA suppressed these effects. TAA also increased the numbers of ED2(+), cyclooxygenase-2(+), and heme oxygenase-1(+) hepatic macrophages as well as the number of CD3(+) lymphocytes. These effects were also suppressed by a-LA. Transcript levels of some inflammation-related genes were upregulated by TAA and downregulated by a-LA in real-time RT-PCR analysis. Outside the GST-P(+) foci, a-LA reduced the numbers of apoptotic cells, active caspase-8(+) cells and death receptor (DR)-5(+) cells. These results suggest that hepatic macrophages producing proinflammatory factors may be activated in TAA-induced tumor promotion. a-LA may suppress tumor-promoting activity by suppressing the activation of these macrophages and the subsequent inflammatory responses. Furthermore, a-LA may suppress tumor-promoting activity by suppressing the DR5-mediated extrinsic pathway of apoptosis and the subsequent regeneration of liver cells outside GST-P(+) foci.

  4. Inferring Positions of Tumor and Nodes in Stage III Lung Cancer From Multiple Anatomical Surrogates Using Four-Dimensional Computed Tomography

    SciTech Connect

    Malinowski, Kathleen T.; Pantarotto, Jason R.; Senan, Suresh

    2010-08-01

    Purpose: To investigate the feasibility of modeling Stage III lung cancer tumor and node positions from anatomical surrogates. Methods and Materials: To localize their centroids, the primary tumor and lymph nodes from 16 Stage III lung cancer patients were contoured in 10 equal-phase planning four-dimensional (4D) computed tomography (CT) image sets. The centroids of anatomical respiratory surrogates (carina, xyphoid, nipples, mid-sternum) in each image set were also localized. The correlations between target and surrogate positions were determined, and ordinary least-squares (OLS) and partial least-squares (PLS) regression models based on a subset of respiratory phases (three to eight randomly selected) were created to predict the target positions in the remaining images. The three-phase image sets that provided the best predictive information were used to create models based on either the carina alone or all surrogates. Results: The surrogate most correlated with target motion varied widely. Depending on the number of phases used to build the models, mean OLS and PLS errors were 1.0 to 1.4 mm and 0.8 to 1.0 mm, respectively. Models trained on the 0%, 40%, and 80% respiration phases had mean ({+-} standard deviation) PLS errors of 0.8 {+-} 0.5 mm and 1.1 {+-} 1.1 mm for models based on all surrogates and carina alone, respectively. For target coordinates with motion >5 mm, the mean three-phase PLS error based on all surrogates was 1.1 mm. Conclusions: Our results establish the feasibility of inferring primary tumor and nodal motion from anatomical surrogates in 4D CT scans of Stage III lung cancer. Using inferential modeling to decrease the processing time of 4D CT scans may facilitate incorporation of patient-specific treatment margins.

  5. Esophageal cancer: anatomic particularities, staging, and imaging techniques.

    PubMed

    Encinas de la Iglesia, J; Corral de la Calle, M A; Fernández Pérez, G C; Ruano Pérez, R; Álvarez Delgado, A

    2016-01-01

    Cancer of the esophagus is a tumor with aggressive behavior that is usually diagnosed in advanced stages. The absence of serosa allows it to spread quickly to neighboring mediastinal structures, and an extensive lymphatic drainage network facilitates tumor spread even in early stages. The current TNM classification, harmonized with the classification for gastric cancer, provides new definitions for the anatomic classification, adds non-anatomic characteristics of the tumor, and includes tumors of the gastroesophageal junction. Combining endoscopic ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging provides greater accuracy in determining the initial clinical stage, and these imaging techniques play an essential role in the selection, planning, and evaluation of treatment. In this article, we review some particularities that explain the behavior of this tumor and we describe the current TNM staging system; furthermore, we discuss the different imaging tests available for its evaluation and include a diagnostic algorithm.

  6. Esophageal cancer: anatomic particularities, staging, and imaging techniques.

    PubMed

    Encinas de la Iglesia, J; Corral de la Calle, M A; Fernández Pérez, G C; Ruano Pérez, R; Álvarez Delgado, A

    2016-01-01

    Cancer of the esophagus is a tumor with aggressive behavior that is usually diagnosed in advanced stages. The absence of serosa allows it to spread quickly to neighboring mediastinal structures, and an extensive lymphatic drainage network facilitates tumor spread even in early stages. The current TNM classification, harmonized with the classification for gastric cancer, provides new definitions for the anatomic classification, adds non-anatomic characteristics of the tumor, and includes tumors of the gastroesophageal junction. Combining endoscopic ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging provides greater accuracy in determining the initial clinical stage, and these imaging techniques play an essential role in the selection, planning, and evaluation of treatment. In this article, we review some particularities that explain the behavior of this tumor and we describe the current TNM staging system; furthermore, we discuss the different imaging tests available for its evaluation and include a diagnostic algorithm. PMID:27469407

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

    PubMed

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

    2014-04-01

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

  8. Three-dimensional conformal radiotherapy for locally advanced (Stage II and worse) head-and-neck cancer: Dosimetric and clinical evaluation

    SciTech Connect

    Portaluri, Maurizio . E-mail: portaluri@hotmail.com; Fucilli, Fulvio I.M.; Castagna, Roberta; Bambace, Santa; Pili, Giorgio; Tramacere, Francesco; Russo, Donatella; Francavilla, Maria Carmen

    2006-11-15

    Purpose: To evaluate the dosimetric parameters of three-dimensional conformal radiotherapy (3D-CRT) in locally advanced head-and-neck tumors (Stage II and above) and the effects on xerostomia. Methods and Materials: A total of 49 patients with histologically proven squamous cell cancer of the head and neck were consecutively treated with 3D-CRT using a one-point setup technique; 17 had larynx cancer, 12 oropharynx, 12 oral cavity, and 6 nasopharynx cancer; 2 had other sites of cancer. Of the 49 patients, 41 received postoperative RT and 8 definitive treatment. Also, 13 were treated with cisplatin-based chemotherapy before and during RT; in 6 cases, 5-fluorouracil was added. The follow-up time was 484-567 days (median, 530 days). Results: One-point setup can deliver 96% of the prescribed dose to the isocenter, to the whole planning target volume, including all node levels of the neck and without overdosages. The mean dose to the primary planning target volume was 49.54 {+-} 4.82 Gy (51.53 {+-} 5.47 Gy for larynx cases). The average dose to the contralateral parotid gland was approximately 38 Gy (30 Gy for larynx cases). The maximal dose to the spinal cord was 46 Gy. A Grade 0 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer xerostomia score corresponded to a mean dose of 30 Gy to one parotid gland. A lower xerostomia score with a lower mean parotid dose and longer follow-up seemed to give rise to a sort of functional recovery phenomenon. Conclusion: Three dimensional-CRT in head-and-neck cancers permits good coverage of the planning target volume with about 10-11 segments and one isocenter. With a mean dose of approximately 30 Gy to the contralateral parotid, we observed no or mild xerostomia.

  9. Growth-inhibiting effect of tumor necrosis factor on human umbilical vein endothelial cells is enhanced with advancing age in vitro

    SciTech Connect

    Shimada, Y.; Kaji, K.; Ito, H.; Noda, K.; Matsuo, M. )

    1990-01-01

    We have examined the effects of in vitro aging on the growth capacity of human umbilical vein endothelial cells (HUVECs) under the influence of tumor necrosis factor (TNF) with or without interferon-gamma (IFN-gamma). The growth and colony-forming abilities of control cells were impaired with advancing age in vitro, especially at later stages (more than 70-80% of life span completed). It was found that treatment with TNF inhibited growth and colony-forming efficiency at any in vitro age. The effects of TNF were shown to increase with increasing in vitro age, as reflected by a more pronounced increase in doubling times, a decrease in saturation density, and a reduction in colony-forming efficiency. However, the characteristics of TNF receptors, including the dissociation constant, and the number of TNF-binding sites per cell-surface area remained rather constant. The effect of TNF was augmented by IFN-gamma at a dose that alone affected growth and colony formation only slightly. The augmentation by IFN-gamma was also found to depend on in vitro age; the synergy with TNF in the deterioration of colony-forming ability was observed only in aged cells. These results suggest that the intrinsic responsiveness of HUVECs to growth-inhibiting factors, as well as to growth-stimulating factors, changes during aging in vitro.

  10. Brain Tumor Symptoms

    MedlinePlus

    ... Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning About Us Our Founders Board of Directors Staff ... Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning Donate to the ABTA Help advance the understanding ...

  11. Expression of tumor necrosis factor-α-induced protein 8 in stage III gastric cancer and the correlation with DcR3 and ERK1/2

    PubMed Central

    HU, RUYI; LIU, WENMING; QIU, XINGFENG; LIN, ZHENGHE; XIE, YAN; HONG, XINGYA; PAERHATI, REYILA; QI, ZHONGQUAN; ZHUANG, GUOHONG; LIU, ZHONGCHEN

    2016-01-01

    Tumor necrosis factor (TNF)-α-induced protein 8 (TIPE) is a recently identified protein that is considered to be associated with various malignancies, including esophageal, breast and pancreatic cancer; however, the importance of TIPE in gastric cancer (GC) remains unknown. Decoy receptor 3 (DcR3) is a member of the tumor