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Sample records for stage iii multiple

  1. Multiple stage railgun

    DOEpatents

    Hawke, Ronald S.; Scudder, Jonathan K.; Aaland, Kristian

    1982-01-01

    A multiple stage magnetic railgun accelerator (10) for accelerating a projectile (15) by movement of a plasma arc (13) along the rails (11,12). The railgun (10) is divided into a plurality of successive rail stages (10a-n) which are sequentially energized by separate energy sources (14a-n) as the projectile (15) moves through the bore (17) of the railgun (10). Propagation of energy from an energized rail stage back towards the breech end (29) of the railgun (10) can be prevented by connection of the energy sources (14a-n) to the rails (11,12) through isolation diodes (34a-n). Propagation of energy from an energized rail stage back towards the breech end of the railgun can also be prevented by dividing the rails (11,12) into electrically isolated rail sections (11a-n, 12a-n). In such case means (55a-n) are used to extinguish the arc at the end of each energized stage and a fuse (31) or laser device (61) is used to initiate a new plasma arc in the next energized rail stage.

  2. Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

    ClinicalTrials.gov

    2014-12-29

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  3. 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.

  4. Prognostic factors in stages II/III/IV and stages III/IV endometrioid and serous adenocarcinoma of the endometrium

    PubMed Central

    Mhawech-Fauceglia, P.; Herrmann, R.F.; Kesterson, J.; Izevbaye, I.; Lele, S.; Odunsi, K.

    2016-01-01

    Aims To explore and to compare the outcome of patients diagnosed with stage II/III/IV and stage III/IV endometrioid adenocarcinoma (EAC) with their serous carcinoma (USC) counterparts. Materials and methods A total of 107 patients (73 EAC and 34 USC) were evaluated. For statistical analysis, the following baseline variables were considered for their prognostic value: the patient’s age at presentation, the tumor size, the depth of myometrial invasion (MI), the lympho-vascular involvement (LVI) and the USC and the EAC subtypes (considered as binary variables). Disease free survival (DFS), death of disease (DOD) and overall survival (OS) were assessed using univariate and multiple Cox proportional hazards models. Results In univariate analysis, USC tends to recur more frequently than EAC (p = 0.004), a finding that disappeared in multivariate analysis. Furthermore, tumor histology had no significance in predicting the tumor outcomes. Among all of the prognostic factors and after adjusting for the aforementioned variables, MI ≥50% was the only independent factor in predicting DOD in stages II/III/IV (p = 0.009) and in stages III/IV (p = 0.004). MI was also an independent predictive factor for OS (p = 0.02) and early recurrences in stages III/IV. LVI was the only independent factor in predicting recurrences (p = 0.004) in stages II/III/IV but not in stages III/IV. Conclusion Based on our study, tumor histology was not a significant factor in predicting disease outcome in stages II/III/IV and II/IV. Despite our limited sample size, we believe that our findings provide meaningful insights into the clinical study of endometrial cancer patients which in turn warrants further investigation. PMID:20926229

  5. Multiple stage multiple filter hydrate store

    DOEpatents

    Bjorkman, Jr., Harry K.

    1983-05-31

    An improved hydrate store for a metal halogen battery system is disclosed which employs a multiple stage, multiple filter means or separating the halogen hydrate from the liquid used in forming the hydrate. The filter means is constructed in the form of three separate sections which combine to substantially cover the interior surface of the store container. Exit conduit means is provided in association with the filter means for transmitting liquid passing through the filter means to a hydrate former subsystem. The hydrate former subsystem combines the halogen gas generated during the charging of the battery system with the liquid to form the hydrate in association with the store. Relief valve means is interposed in the exit conduit means for controlling the operation of the separate sections of the filter means, such that the liquid flow through the exit conduit means from each of the separate sections is controlled in a predetermined sequence. The three separate sections of the filter means operate in three discrete stages to provide a substantially uniform liquid flow to the hydrate former subsystem during the charging of the battery system. The separation of the liquid from the hydrate causes an increase in the density of the hydrate by concentrating the hydrate along the filter means.

  6. Multiple stage multiple filter hydrate store

    DOEpatents

    Bjorkman, H.K. Jr.

    1983-05-31

    An improved hydrate store for a metal halogen battery system is disclosed which employs a multiple stage, multiple filter means for separating the halogen hydrate from the liquid used in forming the hydrate. The filter means is constructed in the form of three separate sections which combine to substantially cover the interior surface of the store container. Exit conduit means is provided in association with the filter means for transmitting liquid passing through the filter means to a hydrate former subsystem. The hydrate former subsystem combines the halogen gas generated during the charging of the battery system with the liquid to form the hydrate in association with the store. Relief valve means is interposed in the exit conduit means for controlling the operation of the separate sections of the filter means, such that the liquid flow through the exit conduit means from each of the separate sections is controlled in a predetermined sequence. The three separate sections of the filter means operate in three discrete stages to provide a substantially uniform liquid flow to the hydrate former subsystem during the charging of the battery system. The separation of the liquid from the hydrate causes an increase in the density of the hydrate by concentrating the hydrate along the filter means. 7 figs.

  7. Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer

    ClinicalTrials.gov

    2014-04-21

    Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx

  8. Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-02-09

    Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  9. Multiple stage miniature stepping motor

    DOEpatents

    Niven, William A.; Shikany, S. David; Shira, Michael L.

    1981-01-01

    A stepping motor comprising a plurality of stages which may be selectively activated to effect stepping movement of the motor, and which are mounted along a common rotor shaft to achieve considerable reduction in motor size and minimum diameter, whereby sequential activation of the stages results in successive rotor steps with direction being determined by the particular activating sequence followed.

  10. Oblimersen Sodium and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage I, Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2012-10-11

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  11. Multiple-stage integrating accelerometer

    DOEpatents

    Devaney, Howard F.

    1986-01-01

    An accelerometer assembly is provided for use in activating a switch in response to multiple acceleration pulses in series. The accelerometer includes a housing forming a chamber. An inertial mass or piston is slidably disposed in the chamber and spring biased toward a first or reset position. A damping system is also provided to damp piston movement in response to first and subsequent acceleration pulses. Additionally, a cam, including a Z-shaped slot, and cooperating follower pin slidably received therein are mounted to the piston and the housing. The middle or cross-over leg of the Z-shaped slot cooperates with the follower pin to block or limit piston movement and prevent switch activation in response to a lone acceleration pulse. The switch of the assembly is only activated after two or more separate acceleration pulses are sensed and the piston reaches the end of the chamber opposite the reset position.

  12. Multiple-stage integrating accelerometer

    DOEpatents

    Devaney, H.F.

    1984-06-27

    An accelerometer assembly is provided for use in activating a switch in response to multiple acceleration pulses in series. The accelerometer includes a housing forming a chamber. An inertial mass or piston is slidably disposed in the chamber and spring biased toward a first or reset position. A damping system is also provided to damp piston movement in response to first and subsequent acceleration pulses. Additionally, a cam, including a Z-shaped slot, and cooperating follower pin slidably received therein are mounted to the piston and the housing. The middle or cross-over leg of the Z-shaped slot cooperates with the follower pin to block or limit piston movement and prevent switch activation in response to a lone acceleration pulse. The switch of the assembly is only activated after two or more separate acceleration pulses are sensed and the piston reaches the end of the chamber opposite the reset position.

  13. VEGF Trap in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2015-02-02

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage III Melanoma; Stage IV Melanoma

  14. Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With Stage III or Stage IV Low-Grade Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-02-26

    Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Small Lymphocytic Lymphoma

  15. Psychosexual Intervention in Patients With Stage I-III Gynecologic or Breast Cancer

    ClinicalTrials.gov

    2016-05-02

    Ovarian Sarcoma; Ovarian Stromal Cancer; Stage I Uterine Sarcoma; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Endometrial Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Cervical Cancer; Stage IB Endometrial Carcinoma; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Ovarian Germ Cell Tumor; Stage IC Primary Peritoneal Cavity Cancer; Stage II Endometrial Carcinoma; Stage II Gestational Trophoblastic Tumor; Stage II Uterine Sarcoma; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Primary Peritoneal Cavity Cancer; Stage III Gestational Trophoblastic Tumor; Stage III Uterine Sarcoma; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Cervical Cancer; Stage IIIA Endometrial Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Cervical Cancer; Stage IIIB Endometrial Carcinoma; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Endometrial Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell

  16. Cetuximab and Radiation Therapy in Treating Patients With Stage III-IV Head and Neck Cancer

    ClinicalTrials.gov

    2016-03-11

    Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Tongue Cancer

  17. Lenalidomide and Rituximab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-07-28

    Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  18. Imatinib Mesylate in Treating Patients With Progressive, Refractory, or Recurrent Stage II or Stage III Testicular or Ovarian Cancer

    ClinicalTrials.gov

    2013-01-15

    Ovarian Dysgerminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage II Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage III Ovarian Germ Cell Tumor; Testicular Seminoma

  19. Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2016-09-08

    Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  20. Cisplatin, Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-11-02

    Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma

  1. Aldesleukin and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

    ClinicalTrials.gov

    2016-10-26

    Metastatic Melanoma; Stage III Mucosal Melanoma of the Head and Neck; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Stage IVA Mucosal Melanoma of the Head and Neck; Stage IVB Mucosal Melanoma of the Head and Neck; Stage IVC Mucosal Melanoma of the Head and Neck

  2. Cisplatin and Paclitaxel in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2014-12-29

    Chemotherapeutic Agent Toxicity; Endometrial Adenocarcinoma; Fallopian Tube Carcinoma; Gastrointestinal Complication; Malignant Ovarian Mixed Epithelial Tumor; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage II Ovarian Cancer; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  3. Analysis of Prognostic Factors and Patterns of Recurrence in Patients With Pathologic Stage III Endometrial Cancer

    SciTech Connect

    Patel, Samir; Portelance, Lorraine . E-mail: lorraine.portelance@muhc.mcgill.ca; Gilbert, Lucy; Tan, Leonard; Stanimir, Gerald; Duclos, Marie; Souhami, Luis

    2007-08-01

    Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) compared with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients.

  4. Erlotinib Hydrochloride and Radiation Therapy in Stage III-IV Squamous Cell Cancer of the Head and Neck

    ClinicalTrials.gov

    2012-10-30

    Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity

  5. Gefitinib and Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III or Stage IV Head and Neck Cancer

    ClinicalTrials.gov

    2013-01-24

    Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx

  6. Effect of Population III multiplicity on dark star formation

    NASA Astrophysics Data System (ADS)

    Stacy, Athena; Pawlik, Andreas H.; Bromm, Volker; Loeb, Abraham

    2012-03-01

    We numerically study the mutual interaction between dark matter (DM) and Population III (Pop III) stellar systems in order to explore the possibility of Pop III dark stars within this physical scenario. We perform a cosmological simulation, initialized at z˜ 100, which follows the evolution of gas and DM. We analyse the formation of the first minihalo at z˜ 20 and the subsequent collapse of the gas to densities of 1012 cm-3. We then use this simulation to initialize a set of smaller scale 'cut-out' simulations in which we further refine the DM to have spatial resolution similar to that of the gas. We test multiple DM density profiles, and we employ the sink particle method to represent the accreting star-forming region. We find that, for a range of DM configurations, the motion of the Pop III star-disc system serves to separate the positions of the protostars with respect to the DM density peak, such that there is insufficient DM to influence the formation and evolution of the protostars for more than ˜5000 years. In addition, the star-disc system causes gravitational scattering of the central DM to lower densities, further decreasing the influence of DM over time. Any DM-powered phase of Pop III stars will thus be very short-lived for the typical multiple system, and DM will not serve to significantly prolong the life of Pop III stars.

  7. Effect of Population III Multiplicity on Dark Star Formation

    NASA Technical Reports Server (NTRS)

    Stacy, Athena; Pawlik, Andreas H.; Bromm, Volker; Loeb, Abraham

    2012-01-01

    We numerically study the mutual interaction between dark matter (DM) and Population III (Pop III) stellar systems in order to explore the possibility of Pop III dark stars within this physical scenario. We perform a cosmological simulation, initialized at z approx. 100, which follows the evolution of gas and DM. We analyze the formation of the first mini halo at z approx. 20 and the subsequent collapse of the gas to densities of 10(exp 12)/cu cm. We then use this simulation to initialize a set of smaller-scale 'cut-out' simulations in which we further refine the DM to have spatial resolution similar to that of the gas. We test multiple DM density profiles, and we employ the sink particle method to represent the accreting star-forming region. We find that, for a range of DM configurations, the motion of the Pop III star-disk system serves to separate the positions of the protostars with respect to the DM density peak, such that there is insufficient DM to influence the formation and evolution of the protostars for more than approx. 5000 years. In addition, the star-disk system causes gravitational scattering of the central DM to lower densities, further decreasing the influence of DM over time. Any DM-powered phase of Pop III stars will thus be very short-lived for the typical multiple system, and DM will not serve to significantly prolong the life of Pop III stars.

  8. Cisplatin and Radiation Therapy With or Without Erlotinib Hydrochloride in Treating Patients With Stage III or Stage IV Head and Neck Cancer

    ClinicalTrials.gov

    2013-05-08

    Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx

  9. Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage III Ovarian Cancer

    ClinicalTrials.gov

    2016-03-17

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  10. Staging and prognostication of multiple myeloma

    PubMed Central

    Fonseca, Rafael; Monge, Jorge; Dimopoulos, Meletios A

    2014-01-01

    Multiple myeloma (MM) is a heterogeneous disease that, over the past 15 years, has seen an increased understanding of its biology and of novel therapeutic options. Distinctive subtypes of the disease have been described, each with different outcomes and clinic-pathological features. Even though a detailed classification of MM into at least seven or eight major subtypes is possible, a more practical clinical approach can classify the disease into high-risk and non-high-risk MM. Such classification has permitted a more personalized approach to the management of the disease. Additionally, risk stratification should be included in outcome discussions with patients, as survival differs significantly by high-risk status. Nowadays, test for risk stratification are widely available and can be routinely used in the clinic. A greater understanding of the genetic abnormalities underlying the biology of MM will allow for the development of novel targeted therapies and better prognostic markers of the disease. PMID:24483346

  11. Quantification of functional abilities in Rett syndrome: a comparison between stages III and IV

    PubMed Central

    Monteiro, Carlos BM; Savelsbergh, Geert JP; Smorenburg, Ana RP; Graciani, Zodja; Torriani-Pasin, Camila; de Abreu, Luiz Carlos; Valenti, Vitor E; Kok, Fernando

    2014-01-01

    We aimed to evaluate the functional abilities of persons with Rett syndrome (RTT) in stages III and IV. The group consisted of 60 females who had been diagnosed with RTT: 38 in stage III, mean age (years) of 9.14, with a standard deviation of 5.84 (minimum 2.2/maximum 26.4); and 22 in stage IV, mean age of 12.45, with a standard deviation of 6.17 (minimum 5.3/maximum 26.9). The evaluation was made using the Pediatric Evaluation of Disability Inventory, which has 197 items in the areas of self-care, mobility, and social function. The results showed that in the area of self-care, stage III and stage IV RTT persons had a level of 24.12 and 18.36 (P=0.002), respectively. In the area of mobility, stage III had 37.22 and stage IV had 14.64 (P<0.001), while in the area of social function, stage III had 17.72 and stage IV had 12.14 (P=0.016). In conclusion, although persons with stage III RTT have better functional abilities when compared with stage IV, the areas of mobility, self-care, and social function are quite affected, which shows a great functional dependency and need for help in basic activities of daily life. PMID:25061307

  12. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    ClinicalTrials.gov

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  13. CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer

    PubMed Central

    Dalerba, Piero; Sahoo, Debashis; Paik, Soonmyung; Guo, Xiangqian; Yothers, Greg; Song, Nan; Wilcox-Fogel, Nate; Forgó, Erna; Rajendran, Pradeep S.; Miranda, Stephen P.; Hisamori, Shigeo; Hutchison, Jacqueline; Kalisky, Tomer; Qian, Dalong; Wolmark, Norman; Fisher, George A.; van de Rijn, Matt; Clarke, Michael F.

    2016-01-01

    Background The identification of high-risk stage II colon cancers is key to the selection of patients who require adjuvant treatment after surgery. Microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice. Methods We used a new bioinformatics approach to search for biomarkers of colon epithelial differentiation across gene-expression arrays and then ranked candidate genes according to the availability of clinical-grade diagnostic assays. With the use of subgroup analysis involving independent and retrospective cohorts of patients with stage II or stage III colon cancer, the top candidate gene was tested for its association with disease-free survival and a benefit from adjuvant chemotherapy. Results The transcription factor CDX2 ranked first in our screening test. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P = 0.002). In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein–negative colon cancers than among the 276 (87.9%) with CDX2 protein–positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P = 0.003). In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. Among patients with stage II cancer, the difference in 5-year disease-free survival was significant both in the discovery data set (49% among 15 patients with CDX2-negative tumors vs. 87% among 191 patients with CDX2-positive tumors, P = 0.003) and in the validation data set (51% among 15 patients with CDX2

  14. 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

  15. 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.

  16. Radiotherapy Improves Survival in Unresected Stage I-III Bronchoalveolar Carcinoma

    SciTech Connect

    Urban, Damien; Mishra, Mark; Onn, Amir; Dicker, Adam P.; Symon, Zvi; Pfeffer, M. Raphael; Lawrence, Yaacov Richard

    2012-11-01

    Purpose: To test the hypothesis that radiotherapy (RT) improves the outcome of patients with unresected, nonmetastatic bronchoalveolar carcinoma (BAC) by performing a population-based analysis within the Surveillance, Epidemiology, and End Results (SEER) registry. Methods and Materials: Inclusion criteria were as follows: patients diagnosed with BAC, Stage I-III, between 2001 and 2007. Exclusion criteria included unknown stage, unknown primary treatment modality, Stage IV disease, and those diagnosed at autopsy. Demographic data, treatment details, and overall survival were retrieved from the SEER database. Survival was analyzed using the Kaplan-Meier method and log-rank test. Results: A total of 6933 patients with Stage I-III BAC were included in the analysis. The median age at diagnosis was 70 years (range, 10-101 years). The majority of patients were diagnosed with Stage I (74.4%); 968 patients (14%) did not undergo surgical resection. Unresected patients were more likely to be older (p < 0.0001), male (p = 0.001), black (p < 0.0001), and Stage III (p < 0.0001). Within the cohort of unresected patients, 300 (31%) were treated with RT. The estimated 2-year overall survival for patients with unresected, nonmetastatic BAC was 58%, 44%, and 27% in Stage I, II, and III, respectively. Factors associated with improved survival included female sex, earlier stage at diagnosis, and use of RT. Median survival in those not receiving RT vs. receiving RT was as follows: Stage I, 28 months vs. 33 months (n = 364, p = 0.06); Stage II, 18 months vs. not reached (n = 31, nonsignificant); Stage III, 10 months vs. 17 months (n = 517, p < 0.003). Conclusions: The use of RT is associated with improved prognosis in unresected Stage I-III BAC. Less than a third of patients who could have potentially benefited from RT received it, suggesting that the medical specialists involved in the care of these patients underappreciate the importance of RT.

  17. Theory of multiple-stage interband photovoltaic devices and ultimate performance limit comparison of multiple-stage and single-stage interband infrared detectors

    NASA Astrophysics Data System (ADS)

    Hinkey, Robert T.; Yang, Rui Q.

    2013-09-01

    A theoretical framework for studying signal and noise in multiple-stage interband infrared photovoltaic devices is presented. The theory flows from a general picture of electrons transitioning between thermalized reservoirs. Making the assumption of bulk-like absorbers, we show how the standard semiconductor transport and recombination equations can be extended to the case of multiple-stage devices. The electronic noise arising from thermal fluctuations in the transition rates between reservoirs is derived using the Shockley-Ramo and Wiener-Khinchin theorems. This provides a unified noise treatment accounting for both the Johnson and shot noise. Using a Green's function formalism, we derive consistent analytic expressions for the quantum efficiency and thermal noise in terms of the design parameters and macroscopic material properties of the absorber. The theory is then used to quantify the potential performance improvement from the use of multiple stages. We show that multiple-stage detectors can achieve higher sensitivities for applications requiring a fast temporal response. This is shown by deriving an expression for the optimal number of stages in terms of the absorption coefficient and absorber thicknesses for a multiple-stage detector with short absorbers. The multiple-stage architecture may also be useful for improving the sensitivity of high operating temperature detectors in situations where the quantum efficiency is limited by a short diffusion length. The potential sensitivity improvement offered by a multiple-stage architecture can be judged from the product of the absorption coefficient, α, and diffusion length, Ln, of the absorber material. For detector designs where the absorber lengths in each of the stages are equal, the multiple-stage architecture offers the potential for significant detectivity improvement when αLn ≤ 0.2. We also explore the potential of multiple-stage detectors with photocurrent-matched absorbers. In this architecture, the

  18. Multiple-Stage Screening of Youth Depression in Schools

    ERIC Educational Resources Information Center

    Morey, Melissa E.; Arora, Prerna; Stark, Kevin D.

    2015-01-01

    Schools present a unique environment in which to conduct universal screenings for youth depression. The present study examines the efficiency of a multiple-stage assessment procedure assessing youth depression in the schools by calculating hit rates and establishing diagnostic accuracy for the measures used. Girls (N = 3318) aged 8 to 13,…

  19. Bioimpedance Spectroscopy in Detecting Lower-Extremity Lymphedema in Patients With Stage I, Stage II, Stage III, or Stage IV Vulvar Cancer Undergoing Surgery and Lymphadenectomy

    ClinicalTrials.gov

    2016-02-09

    Lymphedema; Perioperative/Postoperative Complications; Stage IA Vulvar Cancer; Stage IB Vulvar Cancer; Stage II Vulvar Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVA Vulvar Cancer; Stage IVB Vulvar Cancer

  20. Entolimod in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer Receiving Cisplatin and Radiation Therapy

    ClinicalTrials.gov

    2013-12-10

    Mucositis; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; 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 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 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

  1. Navigated Early Survivorship Transition in Improving Survivorship Care Planning in Patients With Newly Diagnosed Stage I-III Breast, Lung, Prostate, or Colorectal Cancer and Their Caregivers

    ClinicalTrials.gov

    2015-12-17

    Cancer Survivor; Caregiver; Stage I Colon Cancer; Stage I Lung Cancer; Stage I Prostate Cancer; Stage I Rectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Lung Cancer; Stage IIA Breast Cancer; Stage IIA Colon Cancer; Stage IIA Prostate Cancer; Stage IIA Rectal Cancer; Stage IIB Breast Cancer; Stage IIB Colon Cancer; Stage IIB Prostate Cancer; Stage IIB Rectal Cancer; Stage III Lung Cancer; Stage III Prostate Cancer; Stage IIIA Breast Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Breast Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

  2. Walking Versus Jogging in Stages III and IV of the Bruce Treadmill Test.

    ERIC Educational Resources Information Center

    Cundiff, D.; Schwane, J.

    Observations during research involving the Bruce Treadmill Test (BTMT) indicating that Stage III for females and Stage IV for males represented speeds which are intermediate between comfortable walking and confortable jogging for many subjects, prompted this study to determine ways to obtain more consistent group results. Twenty-eight subjects…

  3. Proton Beam Therapy of Stage II and III Non-Small-Cell Lung Cancer

    SciTech Connect

    Nakayama, Hidetsugu; Satoh, Hiroaki; Sugahara, Shinji; Kurishima, Koichi; Tsuboi, Koji; Sakurai, Hideyuki; Ishikawa, Shigemi; Tokuuye, Koichi

    2011-11-15

    Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

  4. Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IV Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery

    ClinicalTrials.gov

    2016-10-04

    Head and Neck Squamous Cell Carcinoma; Laryngeal Squamous Cell Carcinoma, Spindle Cell Variant; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Laryngeal Verrucous Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oral Cavity Verrucous Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma

  5. Railway network design with multiple project stages and time sequencing

    NASA Astrophysics Data System (ADS)

    Kuby, Michael; Xu, Zhongyi; Xie, Xiaodong

    This paper presents a spatial decision support system for network design problems in which different kinds of projects can be built in stages over time. It was developed by the World Bank and China's Ministry of Railways to plan investment strategies for China's overburdened railway system. We first present a mixed-integer program for the single-period network design problem with project choices such as single or multiple tracks and/or electrification with economies of scale. Then, because such projects can be built all at once or in stages, we developed a heuristic backwards time sequencing procedure with a cost adjustment factor to solve the ``project staging'' problem. Other innovations include a preloading routine; coordinated modeling of arcs, paths, and corridors; and a custom-built GIS.

  6. Development of a Multiple-Stage Differential Mobility Analyzer (MDMA)

    SciTech Connect

    Chen, Da-Ren; Cheng, Mengdawn

    2007-01-01

    A new DMA column has been designed with the capability of simultaneously extracting monodisperse particles of different sizes in multiple stages. We call this design a multistage DMA, or MDMA. A prototype MDMA has been constructed and experimentally evaluated in this study. The new column enables the fast measurement of particles in a wide size range, while preserving the powerful particle classification function of a DMA. The prototype MDMA has three sampling stages, capable of classifying monodisperse particles of three different sizes simultaneously. The scanning voltage operation of a DMA can be applied to this new column. Each stage of MDMA column covers a fraction of the entire particle size range to be measured. The covered size fractions of two adjacent stages of the MDMA are designed somewhat overlapped. The arrangement leads to the reduction of scanning voltage range and thus the cycling time of the measurement. The modular sampling stage design of the MDMA allows the flexible configuration of desired particle classification lengths and variable number of stages in the MDMA. The design of our MDMA also permits operation at high sheath flow, enabling high-resolution particle size measurement and/or reduction of the lower sizing limit. Using the tandem DMA technique, the performance of the MDMA, i.e., sizing accuracy, resolution, and transmission efficiency, was evaluated at different ratios of aerosol and sheath flowrates. Two aerosol sampling schemes were investigated. One was to extract aerosol flows at an evenly partitioned flowrate at each stage, and the other was to extract aerosol at a rate the same as the polydisperse aerosol flowrate at each stage. We detail the prototype design of the MDMA and the evaluation result on the transfer functions of the MDMA at different particle sizes and operational conditions.

  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. A modified varying-stage adaptive phase II/III clinical trial design.

    PubMed

    Dong, Gaohong; Vandemeulebroecke, Marc

    2016-07-01

    Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Paclitaxel, Cisplatin, and Topotecan With or Without Filgrastim in Treating Patients With Newly Diagnosed Stage III or Stage IV Epithelial Ovarian Cancer

    ClinicalTrials.gov

    2013-01-23

    Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  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. Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

    ClinicalTrials.gov

    2016-11-01

    Advanced Pleural Malignant Mesothelioma; HLA-A*0201 Positive Cells Present; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pleural Malignant Mesothelioma; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pleural Mesothelioma

  12. Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer

    ClinicalTrials.gov

    2016-02-09

    Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer

  13. Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer

    ClinicalTrials.gov

    2016-05-02

    HER2-positive Breast Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor

  14. Time to Treatment in Patients With Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Wang Li; Correa, Candace R.; Hayman, James A.; Zhao Lujun; Cease, Kemp; Brenner, Dean; Arenberg, Doug; Curtis, Jeffery; Kalemkerian, Gregory P.; Kong, F.-M.

    2009-07-01

    Purpose: To determine whether time to treatment (TTT) has an effect on overall survival (OS) in patients with unresectable or medically inoperable Stage III non-small cell lung cancer (NSCLC) and whether patient or treatment factors are associated with TTT. Methods and Materials: Included in the study were 237 consecutive patients with Stage III NSCLC treated at University of Michigan Hospital (UM) or the Veterans Affairs Ann Arbor Healthcare System (VA). Patients were treated with either palliative or definitive radiotherapy and radiotherapy alone (n = 106) or either sequential (n = 69) or concurrent chemoradiation (n = 62). The primary endpoint was OS. Results: Median follow-up was 69 months, and median TTT was 57 days. On univariate analysis, the risk of death did not increase significantly with longer TTT (p = 0.093). However, subset analysis showed that there was a higher risk of death with longer TTT in patients who survived {>=} 5 years (p = 0.029). Younger age (p = 0.027), male sex (p = 0.013), lower Karnofsky Performance Score (KPS) (p = 0.002), and treatment at the VA (p = 0.001) were significantly associated with longer TTT. However, on multivariate analysis, only lower KPS remained significantly associated with longer TTT (p = 0.003). Conclusion: Time to treatment is significantly associated with OS in patients with Stage III NSCLC who lived longer than 5 years, although it is not a significant factor in Stage III patients as a whole. Lower KPS is associated with longer TTT.

  15. Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group

    PubMed Central

    Palumbo, Antonio; Avet-Loiseau, Hervé; Oliva, Stefania; Lokhorst, Henk M.; Goldschmidt, Hartmut; Rosinol, Laura; Richardson, Paul; Caltagirone, Simona; Lahuerta, Juan José; Facon, Thierry; Bringhen, Sara; Gay, Francesca; Attal, Michel; Passera, Roberto; Spencer, Andrew; Offidani, Massimo; Kumar, Shaji; Musto, Pellegrino; Lonial, Sagar; Petrucci, Maria T.; Orlowski, Robert Z.; Zamagni, Elena; Morgan, Gareth; Dimopoulos, Meletios A.; Durie, Brian G.M.; Anderson, Kenneth C.; Sonneveld, Pieter; San Miguel, Jésus; Cavo, Michele; Rajkumar, S. Vincent; Moreau, Philippe

    2015-01-01

    Purpose The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Patients and Methods Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)], and normal LDH level (less than the upper limit of normal range); R-ISS III (n = 295), including ISS stage III (serum β2-microglobulin level > 5.5 mg/L) and high-risk CA or high LDH level; and R-ISS II (n = 1,894), including all the other possible combinations. At a median follow-up of 46 months, the 5-year OS rate was 82% in the R-ISS I, 62% in the R-ISS II, and 40% in the R-ISS III groups; the 5-year PFS rates were 55%, 36%, and 24%, respectively. Conclusion The R-ISS is a simple and powerful prognostic staging system, and we recommend its use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival. PMID:26240224

  16. Titan III Mars Explorer Transfer Orbital Stage Delivery to the PHSF

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This NASA Kennedy Space Center video presents live footage of the delivery of the Titan III Mars Explorer Transfer Orbital Stage (TOS) to the Payload Hazardous Servicing Facility (PHSF). The TOS is a single-stage, solid propellant upper stage vehicle used to propel a spacecraft from low Earth orbit toward it's ultimate destination. The TOS is delivered to the PHSF where it is designed to accommodate a variety of NASA and NASA customer payloads and can be used as a payload processing facility (PPF) or a hazardous processing facility (HPF).

  17. Radiation Therapy With Cisplatin, Docetaxel, or Cetuximab After Surgery in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer

    ClinicalTrials.gov

    2016-03-14

    Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; 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 Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; 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 Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  18. Fosaprepitant Dimeglumine, Palonosetron Hydrochloride, and Dexamethasone in Preventing Nausea and Vomiting Caused by Cisplatin in Patients With Stage III or Stage IV Head and Neck Cancer Undergoing Chemotherapy and Radiation Therapy

    ClinicalTrials.gov

    2013-05-07

    Nausea and Vomiting; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx

  19. GALNT14 Genotype Predicts Postoperative Outcome of Stage III Colorectal Cancer With Oxaliplatin as Adjuvant Chemotherapy

    PubMed Central

    Lin, Wey-Ran; Chiang, Jy-Ming; Liang, Kung-Hao; Lim, Siew-Na; Lai, Ming-Wei; Tsou, Yung-Kuan; Hsieh, Tzu-Yun; Hsu, Chih-Kai; Yeh, Chau-Ting

    2016-01-01

    Abstract Adjuvant oxaliplatin-based chemotherapy is widely used for stage III colorectal cancer (CRC) after curative surgery. CRC is a molecularly heterogeneous disease, and our current knowledge of therapeutic response-related genetic factors remains limited. N-acetylgalactosaminyltransferase 14 (GALNT14)-rs9679162 genotype is a prognostic predictor for chemotherapy response in advanced hepatocellular carcinoma. Here, we investigated whether this genotype was related to the therapeutic outcome of stage III CRC. A cohort of 300 stage III CRC patients receiving curative resection followed by oxaliplatin-based chemotherapy was retrospectively recruited. GALNT14 genotypes and the clinicopathological factors were correlated with posttherapeutic prognosis. Of these patients, 18% patients had GALNT14-rs9679162 “TT” and 82% had the “GT” + “GG” genotypes. The analysis showed that the “TT” genotype was associated with unfavorable overall survival (OS, P = 0.009) but not with recurrence-free survival (RFS, P = 0.700). The subgroup analysis showed that the “TT” genotype was associated with unfavorable OS in the following subgroups: age ≤65 years, men, left side CRC, N2 stage, carcinoembryonic antigen >5 ng/mL, and mucinous histology (P = 0.012, 0.011, 0.009, 0.025, 0.013, and 0.007, respectively). Within the latter 2 subgroups, the “TT” genotype was the only independent predictor for OS. Finally, the “TT” genotype was associated with the T4 tumor stage (P = 0.017) and in patients with T4 tumors, the “TT” genotype was the only independent predictor for unfavorable RFS (P = 0.007). GALNT14 “TT” genotype was associated with unfavorable OS in stage III CRC patients receiving curative surgery and adjuvant oxaliplatin-based chemotherapy. PMID:27124048

  20. Impact of Neoadjuvant Radiation on Survival in Stage III Non-Small-Cell Lung Cancer

    SciTech Connect

    Koshy, Matthew; Goloubeva, Olga; Suntharalingam, Mohan

    2011-04-01

    Purpose: The role of surgery in Stage III non-small-cell lung cancer (NSCLC) is controversial. This study was undertaken to assess the impact of neoadjuvant radiation therapy for Stage III NSCLC. Methods and Materials: This was a retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included patients who were 18 years and older with NSCLC classified as Stage III and who underwent definitive therapy from 1988 to 2004. Patients were characterized by type of treatment received. Survival functions were estimated by the Kaplan-Meier method, and Cox regression model was used to analyze trends in overall (OS) and cause-specific survival (CSS). Results: A total of 48,131 patients were selected, with a median follow-up of 10 months (range, 0-203 months). By type of treatment, the 3-year OS was 10% with radiation therapy (RT), 37% with surgery (S), 34% with surgery and postoperative radiation (S-RT), and 45% with neoadjuvant radiation followed by surgery (Neo-RT) (p = 0.0001). Multivariable Cox model identified sex, race, laterality, T stage, N stage, and type of treatment as factors affecting survival. Estimated hazard ratios (HR) adjusted for other variables in regression model showed the types of treatment: S (HR, 1.3; 95% confidence interval [CI], 1.2-1.4), S-RT (HR, 1.2; 95% CI, 1.1-1.3), and RT (HR, 2.3; 95% CI, 2.15-2.53) were associated with significantly worse overall survival when compared with Neo-RT (p = 0.0001). Conclusion: This population based study demonstrates that patients with Stage III NSCLC receiving Neo-RT had significantly improved overall survival when compared with other treatment groups.

  1. Prognostic impact of mutation profiling in patients with stage II and III colon cancer

    PubMed Central

    Shen, Yinchen; Han, Xiaohong; Wang, Jianfei; Wang, Shuai; Yang, Hongying; Lu, Shih-Hsin; Shi, Yuankai

    2016-01-01

    Development of colorectal cancer (CRC) associates with accumulation of genetic mutations include the epidermal growth factor receptor (EGFR) signaling pathway. However, whether mutations in KRAS together with downstream factors BRAF, PIK3CA and NRAS impact prognosis is still unclear for stage II-III colon cancer. In the present study a total of 228 stage II-III colon cancer samples were retrospectively collected, KRAS (codons 12, 13 and 61), BRAF (exon 11 and exon 15), PIK3CA (exon 9 and exon 20) and NRAS (codons 12, 13 and 61) status was detected by Sanger sequencing, 37.89% (86/227) tumors harbored a KRAS mutation, 7.02% (16/228) harbored a BRAF mutation, 13.18% (29/220) harbored a PIK3CA mutation and 0.89% (2/224) harbored a NRAS mutation. NRAS mutations existed only in stage II colon cancer. Older groups harbored a higher KRAS and BRAF mutation (P < 0.05), PIK3CA (exon9) mutations appeared more common in worse differentiation tumors (P = 0.032). Moreover, PIK3CA (E545K) mutation was significantly associated with tumor recurrence (P = 0.031) and acted independently prognostic for poor OS (P = 0.044), while only in stage III colon cancer. KRAS, BRAF and NRAS mutations do not have major prognostic value in stage II and III colon cancer, subtypes of gene mutations should be further investigated for a better understanding in CRC. PMID:27074743

  2. Methylation of MGMT Is Associated with Poor Prognosis in Patients with Stage III Duodenal Adenocarcinoma

    PubMed Central

    Sharmab, Anup; Xie, Fei; Liu, Yanliang; Li, Kai; Wan, Weiwei; Baylin, Stephen B.; Wolfgang, Christopher L.; Ahuja, Nita

    2016-01-01

    Background O6-methylguanine-DNA methyltransferase (MGMT) methylation status has not been extensively investigated in duodenal adenocarcinoma (DA). The aim of this study was to evaluate the MGMT methylation status and examine its possible prognostic value in patients with stage III DA. Methods Demographics, tumor characteristics and survival were available for 64 patients with stage III DA. MGMT methylation was detected by using MethyLight. A Cox proportional hazard model was built to predict survival, adjusted for clinicopathological characteristics and tumor molecular features, including the CpG island methylator phenotype (CIMP), microsatellite instability (MSI), and KRAS mutations. Results MGMT methylation was detected in 17 of 64 (26.6%) patients, and was not correlated with sex, age, tumor differentiation, CIMP, MSI, or KRAS mutations. MGMT methylation was the only one factor associated with both overall survival (OS) and disease-free survival (DFS) on both univariate and multivariate analyses. In patients treated with surgery alone, MGMT-methylated group had worse OS and DFS when compared with MGMT-unmethylated group. However, in patients treated with chemotherapy/radiotherapy, outcomes became comparable between the two groups. Conclusions Our results demonstrate MGMT methylation is a reliable and independent prognostic factor in DAs. Methylation of MGMT is associated with poor prognosis in patients with stage III DAs. PMID:27643594

  3. The Benefit of Adjuvant Chemotherapy in Elderly Patients with Stage III Colorectal Cancer is Independent of Age and Comorbidity

    PubMed Central

    Wildes, Tanya M.; Kallogjeri, Dorina; Powers, Brian; Vlahiotis, Anna; Mutch, Matthew; Spitznagel, Edward L.; Tan, Benjamin; Piccirillo, Jay F.

    2010-01-01

    Objectives To determine the combined effect of age and comorbidity on receipt of chemotherapy and its impact on survival in elderly patients with stage III colorectal cancer (CRC). Materials and methods All patients over age 65 with Stage III CRC diagnosed 1996–2006 were identified from the Barnes-Jewish Hospital Oncology Data Services registry. An age/comorbidity staging system was created using the ACE-27 comorbidity index and data from both Stage II and III CRC. The staging system was then applied to patients with Stage III CRC. Odds of receiving chemotherapy were calculated, and survival analyses determined the impact of chemotherapy on overall survival in each age/comorbidity stage. Results 435 patients with Stage III CRC were evaluated [median age 75 years (range 65–99)]. Advancing age/comorbidity stage (Alpha, Beta, Gamma) was associated with decreasing odds of receiving chemotherapy for Stage III CRC [Odds Ratio 0.83 (95% CI, 0.51–1.35) for Beta and 0.14 (95% CI, 0.08–0.24) for Gamma, compared to Alpha]. Chemotherapy was associated with lower risk of death in each of the age/comorbidity stages, compared to those who underwent surgery only. The hazard ratio for death in patients who did not receive chemotherapy, relative to those who did, within each age/comorbidity stage was 1.8 [95%CI 1.06–3.06] for Alpha, 2.24 [95%CI 1.38–3.63] for Beta and 2.10 [95% CI 1.23–3.57] for Gamma. Conclusion While stage III CRC patients with increasing age and comorbidity are less likely to receive chemotherapy, receipt of chemotherapy is associated with a lower risk of death. PMID:21113435

  4. Erlotinib Hydrochloride in Treating Patients With Stage I-III Colorectal Cancer or Adenoma

    ClinicalTrials.gov

    2014-12-22

    Adenomatous Polyp; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage I Colon Cancer; Stage I Rectal Cancer; Stage IIA Colon Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

  5. Radiotherapy for Stage II and Stage III Breast Cancer Patients With Negative Lymph Nodes After Preoperative Chemotherapy and Mastectomy

    SciTech Connect

    Le Scodan, Romuald; Selz, Jessica; Stevens, Denise; Bollet, Marc A.; Lande, Brigitte de la; Daveau, Caroline; Lerebours, Florence; Labib, Alain; Bruant, Sarah

    2012-01-01

    Purpose: To evaluate the effect of postmastectomy radiotherapy (PMRT) in Stage II-III breast cancer patients with negative lymph nodes (pN0) after neoadjuvant chemotherapy (NAC). Patients and Materials: Of 1,054 breast cancer patients treated with NAC at our institution between 1990 and 2004, 134 had pN0 status after NAC and mastectomy. The demographic data, tumor characteristics, metastatic sites, and treatments were prospectively recorded. The effect of PMRT on locoregional recurrence-free survival and overall survival (OS) was evaluated by multivariate analysis, including known prognostic factors. Results: Of the 134 eligible patients, 78 (58.2%) received PMRT and 56 (41.8%) did not. At a median follow-up time of 91.4 months, the 5-year locoregional recurrence-free survival and OS rate was 96.2% and 88.3% with PMRT and 92.5% and 94.3% without PMRT, respectively (p = NS). The corresponding values at 10 years were 96.2% and 77.2% with PMRT and 86.8% and 87.7% without PMRT (p = NS). On multivariate analysis, PMRT had no effect on either locoregional recurrence-free survival (hazard ratio, 0.37; 95% confidence interval, 0.09-1.61; p = .18) or OS (hazard ratio, 2.06; 95% confidence interval, 0.71-6; p = .18). This remained true in the subgroups of patients with clinical Stage II or Stage III disease at diagnosis. A trend was seen toward poorer OS among patients who had not had a pathologic complete in-breast tumor response after NAC (hazard ratio, 6.65; 95% confidence interval, 0.82-54.12; p = .076). Conclusions: The results from the present retrospective study showed no increase in the risk of distant metastasis, locoregional recurrence, or death when PMRT was omitted in breast cancer patients with pN0 status after NAC and mastectomy. Whether the omission of PMRT is acceptable for these patients should be addressed prospectively.

  6. Epacadostat and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma

    ClinicalTrials.gov

    2016-10-31

    Mucosal Melanoma; Recurrent Melanoma; Recurrent Uveal Melanoma; Stage IIIA Skin Melanoma; Stage IIIA Uveal Melanoma; Stage IIIB Skin Melanoma; Stage IIIB Uveal Melanoma; Stage IIIC Skin Melanoma; Stage IIIC Uveal Melanoma; Stage IV Skin Melanoma; Stage IV Uveal Melanoma

  7. Progressive Staging of Pilot Studies to Improve Phase III Trials for Motor Interventions.

    PubMed

    Dobkin, Bruce H

    2009-01-01

    Based on the suboptimal research pathways that finally led to multicenter randomized clinical trials (MRCTs) of treadmill training with partial body weight support and of robotic assistive devices, strategically planned successive stages are proposed for pilot studies of novel rehabilitation interventions. Stage 1, consideration-of-concept studies, drawn from animal experiments, theories, and observations, delineate the experimental intervention in a small convenience sample of participants, so the results must be interpreted with caution. Stage 2, development-of-concept pilots, should optimize the components of the intervention, settle on most appropriate outcome measures, and examine dose-response effects. A well-designed study that reveals no efficacy should be published to counterweight the confirmation bias of positive trials. Stage 3, demonstration-of-concept pilots, can build out from what has been learned to test at least 15 participants in each arm, using random assignment and blinded outcome measures. A control group should receive an active practice intervention aimed at the same primary outcome. A third arm could receive a substantially larger dose of the experimental therapy or a combinational intervention. If only 1 site performed this trial, a different investigative group should aim to reproduce positive outcomes based on the optimal dose of motor training. Stage 3 studies ought to suggest an effect size of 0.4 or higher, so that approximately 50 participants in each arm will be the number required to test for efficacy in a stage 4, proof-of-concept MRCT. By developing a consensus around acceptable and necessary practices for each stage, similar to CONSORT recommendations for the publication of phase III clinical trials, better quality pilot studies may move quickly into better designed and more successful MRCTs of experimental interventions.

  8. Paclitaxel and Carboplatin Before Radiation Therapy With Paclitaxel in Treating HPV-Positive Patients With Stage III-IV Oropharynx, Hypopharynx, or Larynx Cancer

    ClinicalTrials.gov

    2016-09-07

    Human Papilloma Virus Infection; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Larynx

  9. Flexible design of two-stage adaptive procedures for phase III clinical trials.

    PubMed

    Koyama, Tatsuki

    2007-07-01

    The recent popularity of two-stage adaptive designs has fueled a number of proposals for their use in phase III clinical trials. Many of these designs assign certain restrictive functional forms to the design elements of stage 2, such as sample size, critical value and conditional power functions. We propose a more flexible method of design without imposing any particular functional forms on these design elements. Our methodology permits specification of a design based on either conditional or unconditional characteristics, and allows accommodation of sample size limit. Furthermore, we show how to compute the P value, confidence interval and a reasonable point estimate for any design that can be placed under the proposed framework. PMID:17307399

  10. Application of Thoracoscopic Hybrid Surgery in the Treatment of Stage III Tuberculous Empyema

    PubMed Central

    Cao, Sizhe; Zhu, Changsheng; Wei, Lin; Zhang, Huijun; Li, Qian

    2015-01-01

    Background: To investigate the efficacy and value of thoracoscopic hybrid surgery in the treatment of stage III chronic tuberculous empyema (CTE). Methods: 48 patients diagnosed as CTE with pleural thickening and encysted abscess cavity from were treated by hybrid operation (HO). Small incision operation was first used for resection of thickening pleural fibreboard and decortication of parietal pleura. Then, thoracoscopy was guided into chest to decorticate the visceral pleurali. Additional 25 patients with open operation of pleurectomy were set as control. Results: The average operation time of HO group was 70 ± 22 min compared to 130 ± 32 min of control. The amount of bleeding, hospitalization time and chest tube drainage of HO group (200 ± 55 ml, 18 ± 1.2 days, 3.5 ± 1.5 days) were significantly decreased compared to control (400 ± 45 ml, 28 ± 4.5 days, 6.5 ± 2.5 days). Post operation complications occurred in 5 (10.42%) and 3 (12%) cases for HO group and control, respectively. Conclusions: In stage III CTE, the small incision assisted thoracoscopic hybrid surgery help to remove thickening parietal pleura, promote the application of thoracoscopy, which has obvious advantages compared to traditional surgery. PMID:26278117

  11. 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.

  12. Carboplatin and Paclitaxel With or Without Bevacizumab Compared to Docetaxel, Carboplatin, and Paclitaxel in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Carcinoma (Cancer)

    ClinicalTrials.gov

    2013-03-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Stage II Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  13. Paclitaxel, Bevacizumab And Adjuvant Intraperitoneal Carboplatin in Treating Patients Who Had Initial Debulking Surgery for Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2014-06-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Stage II Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  14. [Cytological finding in the pre- and early stages of cervix carcinoma--a contribution to the evaluation of Papanicolau III].

    PubMed

    Bader, G; Büttner, H H; Neumann, H G; Rhode, E; Beust, M

    1977-01-01

    Cytologic findings and the histologic diagnosis are compared in 326 cervical cones. We have found following ratio of the groups Papanicolaou (Pap) III: Pap IV--in dysplasia 1: 1: 1, in "more dysplasia than carcinoma in situ (CIS)" 1:2:2. The Pap IV dominates in "pure" CIS and in cones with "more CIS than dysplasia". We take out of the Pap III ("with cytologic control") cases named "Pap III with necessity for histologic diagnosis". We have found in this subgroup of Pap III prestages or early stages of cervical carcinoma.

  15. High-Dose Conformal Radiotherapy for Patients With Stage III Non-Small-Cell Lung Carcinoma

    SciTech Connect

    Nakayama, Hidetsugu; Satoh, Hiroaki; Kurishima, Koichi; Ishikawa, Hiroichi; Tokuuye, Koichi

    2010-11-01

    Purpose: To determine the effectiveness of high-dose conformal radiotherapy to the involved field for patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Between May 1999 and April 2006, a total of 100 consecutive patients with inoperable Stage IIIA or IIIB NSCLC with a performance score of 0 to 2 and treatment by radical radiotherapy combined with chemotherapy were included. Up to August 2002, 33 patients underwent conventional radiotherapy of 56 Gy to 66 Gy using anteroposterior opposite ports to the primary tumor and elective lymph nodes (conventional group). After September 2002, the remaining 67 patients underwent high-dose radiotherapy of 66 Gy to 84 Gy to the involved volume with three-dimensional (3-D) conformal radiotherapy (conformal group). Results: The median survival was 13.2 months (95% confidence interval [CI], 7.5-18.5 months) in the conventional group and 17.3 months (95% CI, 10.7- 24.0 months) in the conformal group. The overall survival at 3 years were 9.1% (95% CI, -0.7-18.9%) in the conventional group and 31.0% (95% CI, 18.9-43.1%) in the conformal group; the conformal group had a significantly better overall survival (p < 0.05). The radiotherapy method (hazard ratio = 0.55, p < 0.05) and performance status (hazard ratio = 1.48, p < 0.05) were shown to be statistically significant independent prognostic factors. Conclusions: Based on the practical experience reported here, 3-D conformal radiotherapy allowed dose escalation without excessive toxicity, and may improve overall survival rates for patients with Stage III NSCLC.

  16. KRAS Mutation in Stage III Colon Cancer and Clinical Outcome Following Intergroup Trial CALGB 89803

    PubMed Central

    Ogino, Shuji; Meyerhardt, Jeffrey A.; Irahara, Natsumi; Niedzwiecki, Donna; Hollis, Donna; Saltz, Leonard B.; Mayer, Robert J.; Schaefer, Paul; Whittom, Renaud; Hantel, Alexander; Benson, Al B.; Goldberg, Richard M.; Bertagnolli, Monica M.; Fuchs, Charles S.

    2009-01-01

    Purpose Alterations in the RAS and RAF pathway relate to epigenetic and epigenomic aberrations, and are important in colorectal carcinogenesis. KRAS mutation in metastatic colorectal cancer predicts resistance to anti-EGFR targeted therapy (cetuximab or panitumumab). However, it remains uncertain whether KRAS mutation predicts prognosis or clinical outcome of colon cancer patients independent of anti-EGFR therapy. Methods We conducted a study of 508 cases identified among 1264 patients with stage III colon cancer who enrolled in a randomized adjuvant chemotherapy trial (5-fluorouracil, leucovorin with or without irinotecan) in 1999–2001 (CALGB 89803). KRAS mutations were detected in 178 tumors (35%) by Pyrosequencing. Kaplan-Meier and Cox proportional hazard models assessed the prognostic significance of KRAS mutation and adjusted for potential confounders including age, sex, tumor location, tumor/node stage, performance status, adjuvant chemotherapy arm and microsatellite instability (MSI) status. Results Compared to patients with KRAS-wild-type tumors, patients with KRAS-mutated tumors did not experience any difference in disease-free (DFS), recurrence-free (RFS), or overall survival (OS). Five-year DFS, RFS and OS (KRAS-mutated vs. KRAS-wild-type patients) were: 62% vs. 63% (log-rank p=0.89); 64% vs. 66% (p=0.84); and 75% vs. 73% (p=0.56), respectively. The effect of KRAS mutation on patient survival did not significantly differ according to clinical features, chemotherapy arm or MSI status, and the effect of adjuvant chemotherapy assignment on outcome did not differ according to KRAS status. Conclusions In this large trial of chemotherapy in stage III colon cancer patients, KRAS mutational status was not associated with any significant influence on disease-free or overall survival. PMID:19934290

  17. Reducing the Time From Diagnosis to Treatment of Patients With Stage II/III Rectal Cancer at a Large Public Hospital

    PubMed Central

    Leslie, Lori A.; Jacobs, Ryan W.; Millas, Stefanos; Surabhi, Venkateswar; Mok, Henry; Jhaveri, Pavan; Kott, Marylee M.; Jackson, Lymesia; Rieber, Alyssa; Bhadkamkar, Nishin A.

    2016-01-01

    Curative-intent therapy for stage II/III rectal cancer is necessarily complex. Current guidelines by the National Comprehensive Cancer Network recommend preoperative concurrent chemoradiation followed by resection and additional adjuvant chemotherapy. We used standard quality improvement methodology to implement a cost-effective intervention that reduced the time from diagnosis to treatment of patients with stage II/III rectal cancer by approximately 30% in a large public hospital in Houston, Texas. Implementation of the program resulted in a reduction in time from pathologic diagnosis to treatment of 29% overall, from 62 to 44 days. These gains were cost neutral and resulted from improvements in scheduling and coordination of care alone. Our results suggest that: (1) quality improvement methodology can be successfully applied to multidisciplinary cancer care, (2) effective interventions can be cost neutral, and (3) effective strategies can overcome complexities such as having multiple sites of care, high staff turnover, and resource limitations. PMID:26869658

  18. 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.

  19. Postoperative prophylactic hepatic arterial infusion chemotherapy for stage III colorectal cancer: a retrospective study

    PubMed Central

    Wang, Yao; Sun, Xin Rong; Feng, Wen Ming; Bao, Ying; Zheng, Yin Yuan

    2016-01-01

    Background Radical resection is the main treatment for colorectal cancer (CRC), but metastasis or recurrence is common in which liver metastasis accounted for 83% of the cases. Therefore, the prognosis of patients with advanced CRC may be improved if liver metastasis is prevented. This study aims to investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases of stage III CRC patients after curative resection. Methods Between 2002 and 2008, 287 stage III CRC patients who had undergone radical resection were included in this study. According to postoperative adjuvant chemotherapy modality, these patients were divided into two groups. Patients in the combined therapy group received two cycles of HAIC plus four cycles of systemic chemotherapy, while patients in the monotherapy group received six cycles of systemic chemotherapy alone. The HAIC regimen consisted of hepatic arterial infusion of oxaliplatin (OXA, 85 mg/m2) on day 1 and 5-fluorouracil (5-FU, 2,400 mg/m2) on days 2 and 3 followed by a vein infusion of folinic acid (FA, 200 mg/m2) as a 2-hour infusion on days 2 and 3. The systemic chemotherapy regimen consisted of a 2-hour infusion of OXA (85 mg/m2) on day 1 followed by FA (200 mg/m2) as a 2-hour infusion on days 2 and 3, and by 5-FU (2,400 mg/m2) as a 48-hour infusion. This was repeated every 4 weeks. All cases were followed up for 5 years or until death. The 5-year overall survival, disease-free survival, liver metastases-free survival, and the overall liver metastases rates were retrospectively compared. Results Significant differences were found in the 5-year overall survival (combined therapy, 70.71%; monotherapy, 57.14%; P=0.014), disease-free survival (combined therapy, 69.29%; monotherapy, 55.78%; P=0.021), and liver metastases-free survival rates (combined therapy, 70%; monotherapy, 56.46%; P=0.019). Conclusion Prophylactic adjuvant HAIC can prevent metachronous liver metastases and improve the prognosis of patients

  20. Automated VMAT treatment planning for stage III lung cancer: how does it compare with IMRT?

    PubMed Central

    Quan, Enzhuo M.; Chang, Joe Y.; Liao, Zhongxing; Xia, Tingyi; Yuan, Zhiyong; Liu, Hui; Li, Xiaoqiang; Wages, Cody A.; Mohan, Radhe; Zhang, Xiaodong

    2012-01-01

    Purpose To compare the quality of volumetric modulated arc therapy (VMAT) or intensity-modulated radiation therapy (IMRT) plans generated by an automated inverse planning system with that of dosimetrist-generated IMRT treatment plans for patients with stage III lung cancer. Methods and Materials Two groups of eight patients with stage III lung cancer were randomly selected. For group I, the dosimetrists spent their best effort in designing IMRT plans to compete with the automated inverse planning system (mdaccAutoPlan); for group II, the dosimetrists were not in competition and spent their regular effort. Five experienced radiation oncologists independently blind-reviewed and ranked the three plans for each patient, a rank of “1” being the best and “3” the worst. Dosimetric measures were also performed to quantitatively evaluate the three types of plans. Results Blind rankings from different oncologists were generally consistent. For group I, the auto-VMAT, auto-IMRT, and manual-IMRT plans received average ranks of 1.6, 2.13, and 2.18, respectively. The auto-VMAT plans in group I had 10% higher PTV conformality and 24% lower esophagus V70 than the manual-IMRT plans; they also resulted in over 20% higher complication-free tumor control probability (p+) than either type of IMRT plans. The auto- and manual-IMRT plans in this group yielded generally comparable dosimetric measures. For group II, the auto-VMAT, auto-IMRT, and manual-IMRT plans received average ranks of 1.55, 1.75, and 2.75, respectively. Compared to the manual-IMRT plans in this group, the auto-VMAT plans and the auto-IMRT plans showed, respectively, 17% and 14% higher PTV dose conformality, 8% and 17% lower mean lung dose, 17% and 26% lower mean heart dose, and 36% and 23% higher p+. Conclusions mdaccAutoPlan is capable of generating high-quality VMAT and IMRT treatment plans for stage III lung cancer. Manual-IMRT plans could achieve quality similar to auto-IMRT plans if best effort were spent

  1. Efficacy of one-stage surgical treatment and clinical features in patients with multiple pressure ulcers.

    PubMed

    Han, Hyun Ho; Choi, Eun Jeong; Choi, Jong Yun; Rhie, Jong Won

    2016-03-01

    Treating patients with multiple pressure ulcers is a very challenging task for physicians. However, there are very few reports on treatment protocols for multiple pressure ulcers and treatment outcomes. The authors have consistently treated multiple pressure ulcers in a one-stage operation rather than a staged operation. We evaluated multiple pressure ulcers patients who underwent a one-stage operation from 2007 to 2014. A comparison was made between 20 patients who underwent a one-stage operation on 44 foci and 68 patients with a single focus. Though the results, we could conclude that one-stage operation of multiple pressure ulcers was found to have a shorter recovery period and shorter hospitalization without a significant increase in complications.

  2. One-stage operation for rare multiple mirror intracranial aneurysms: a case report and literature review.

    PubMed

    Xu, Yan; Chen, Shu-da; Lei, Bin; Zhang, Wei-Hua; Wang, Wei-Yu

    2014-01-01

    Although intracranial multiple aneurysms are not uncommon, multiple mirror aneurysms are relatively rare. A few isolated cases have been described. However, to the best of our knowledge, 3 pairs of pure symmetrical mirror aneurysms in one patient have not been reported yet. We present a case of multiple mirror aneurysms involving the bilateral middle cerebral artery (MCA) bifurcations and posterior communicating arteries (P-com A) confirmation by one-stage operation. The possibility of one-stage treatment must be considered before surgery. Missed diagnosis and misdiagnosis must be avoided before one-stage operation for multiple mirror aneurysms.

  3. Omega-3 Fatty Acid in Treating Patients With Stage I-III Breast Cancer

    ClinicalTrials.gov

    2016-03-17

    Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Male Breast 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

  4. [First case described of isolated, complete and fluctuating cranial nerve III palsy heralding multiple myeloma].

    PubMed

    León-Ruiz, Moisés; Benito-León, Julián; Sierra-Hidalgo, Fernando; García-Soldevilla, Miguel Ángel; Izquierdo-Esteban, Laura; Tejeiro-Martínez, José; Cabrera-Valdivia, Francisco; García-Albea Ristol, Esteban

    2015-02-01

    Introduccion. El mieloma multiple es la neoplasia de celulas plasmaticas mas frecuente. Al ser incurable, el tratamiento persigue obtener el mayor tiempo de supervivencia libre de clinica. Constituye una causa extremadamente rara de afectacion de los nervios craneales y es producido habitualmente por un plasmocitoma intracraneal. Presentamos un caso de mieloma multiple, que asociaba un plasmocitoma intracraneal y que comenzo clinicamente con paralisis aislada, completa y fluctuante del III nervio craneal. Caso clinico. Mujer de 63 años que acudio a urgencias por presentar un cuadro clinico oscilante, consistente en diplopia binocular horizontal y, posteriormente, cefalea. La exploracion neurooftalmologica revelo una paralisis completa del III nervio craneal derecho. Se solicito una tomografia axial computarizada craneal urgente, que revelo multiples lesiones osteoliticas diploicas, asociando una de ellas componente de partes blandas en la hendidura esfenoidal derecha. La paciente fue ingresada, y se le diagnostico posteriormente un mieloma multiple IgA-kappa. Tras recibir induccion quimioterapica y ser sometida a un trasplante autologo de progenitores hematopoyeticos, alcanzo la remision completa. Conclusiones. El mieloma multiple es un trastorno raro de los nervios craneales, una causa muy infrecuente de paralisis aislada y completa del III nervio craneal y menos aun fluctuante, y no se ha encontrado ningun caso publicado con este inicio clinico. Tener en cuenta las posibles manifestaciones neurooftalmologicas del mieloma multiple puede contribuir a un diagnostico precoz y a una incidencia positiva sobre el curso de esta enfermedad.

  5. [Uterine cervix cancer. Clinical stage III. Combined radiotherapy and chemotherapy treatment].

    PubMed

    Ayala Hernández, J R; de la Huerta Sánchez, R; Morales Canfield, F; Fernández Orozco, A

    1991-07-01

    55 patients with stage III carcinoma of the uterine cervix were entered into a prospective randomized study to evaluate the possible radiation-potentiating properties of bleomycin. Group A received classical radiation treatment with telecobalt-therapy 50 Gy/25 fractions plus 32 Gy/4 fractions (Cathetron). The other two groups received 15 mg of bleomycin by continue infusion two time of week during 5 week, groups B before, and group C after, irradiation. The morbidity was minimal. The initial response was complete in 49 cases and partial in 6 cases. At 2 years there were 26 recurrences, 22 (88.8%), locoregional recurrences and 4 distant metastasis, 3 in the group of bleomycin treatment. The probability of actuarial survival was 62.1%, 30.1% and 35.6% respectively to groups A, B and C. Addition of bleomycin to radiotherapy failed to increase the recurrence-free survival.

  6. Predictive and Prognostic Analysis of PIK3CA Mutation in Stage III Colon Cancer Intergroup Trial

    PubMed Central

    Liao, Xiaoyun; Imamura, Yu; Yamauchi, Mai; McCleary, Nadine J.; Ng, Kimmie; Niedzwiecki, Donna; Saltz, Leonard B.; Mayer, Robert J.; Whittom, Renaud; Hantel, Alexander; Benson, Al B.; Mowat, Rex B.; Spiegelman, Donna; Goldberg, Richard M.; Bertagnolli, Monica M.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.

    2013-01-01

    Background Somatic mutations in PIK3CA (phosphatidylinositol-4,5-bisphosphonate 3-kinase [PI3K], catalytic subunit alpha gene) activate the PI3K-AKT signaling pathway and contribute to pathogenesis of various malignancies, including colorectal cancer. Methods We examined associations of PIK3CA oncogene mutation with relapse, survival, and treatment efficacy in 627 stage III colon carcinoma case subjects within a randomized adjuvant chemotherapy trial (5-fluorouracil and leucovorin [FU/LV] vs irinotecan [CPT11], fluorouracil and leucovorin [IFL]; Cancer and Leukemia Group B 89803 [Alliance]). We detected PIK3CA mutation in exons 9 and 20 by polymerase chain reaction and pyrosequencing. Cox proportional hazards model was used to assess prognostic and predictive role of PIK3CA mutation, adjusting for clinical features and status of routine standard molecular pathology features, including KRAS and BRAF mutations and microsatellite instability (mismatch repair deficiency). All statistical tests were two-sided. Results Compared with PIK3CA wild-type cases, overall status of PIK3CA mutation positivity or the presence of PIK3CA mutation in either exon 9 or 20 alone was not statistically significantly associated with recurrence-free, disease-free, or overall survival (log-rank P > .70; P > .40 in multivariable regression models). There was no statistically significant interaction between PIK3CA and KRAS (or BRAF) mutation status in survival analysis (P interaction > .18). PIK3CA mutation status did not appear to predict better or worse response to IFL therapy compared with FU/LV therapy (P interaction > .16). Conclusions Overall tumor PIK3CA mutation status is not associated with stage III colon cancer prognosis. PIK3CA mutation does not appear to serve as a predictive tumor molecular biomarker for response to irinotecan-based adjuvant chemotherapy. PMID:24231454

  7. Paclitaxel and Carboplatin With or Without Bevacizumab in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2015-12-21

    Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinofibroma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  8. A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

    SciTech Connect

    Oberije, Cary; De Ruysscher, Dirk; Houben, Ruud; Heuvel, Michel van de; Uyterlinde, Wilma; Deasy, Joseph O.; Belderbos, Jose; Dingemans, Anne-Marie C.; Rimner, Andreas; Din, Shaun; Lambin, Philippe

    2015-07-15

    Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.

  9. History of propulsion for SSTO and multiple stage vehicles

    NASA Astrophysics Data System (ADS)

    Martin, James A.

    1993-06-01

    Studies of advanced earth-to-orbit vehicles and the propulsion systems that might be used on them have continued since the Space Shuttle design was selected. This paper summarizes some of the history of those studies. Topics covered include dual-fuel propulsion, engines with both hydrocarbon and hydrogen fuels, two-stage vehicles with parallel burn, and the space transportation booster and main engine studies.

  10. Monoclonal gammopathy and smoldering multiple myeloma: diagnosis, staging, prognosis, management.

    PubMed

    Hillengass, Jens; Moehler, Thomas; Hundemer, Michael

    2011-01-01

    Monoclonal gammopathy of unknown significance (MGUS) as one of the most common premalignant disorders and smoldering multiple myeloma (sMM) are both caused by a proliferation of monoclonal plasma cells leading to a detectable serum monoclonal protein and/or excess of plasma cells in the bone marrow. Prerequisite for the diagnosis is that plasma cell disease does not cause clinical symptoms. Cytogenetic aberrations are detectable in the majority of patient in the clonally expanded plasma cells. MGUS consistently proceeds symptomatic MM. The lifetime risk of progression into symptomatic multiple myeloma lies between 15% and 59% for patients with MGUS or sMM. Prognostic parameters for development of symptomatic multiple myeloma from MGUS or sMM are concentration of monoclonal protein, bone marrow plasmocytosis, a non- IgG subtype and an abnormal free-light chain ratio. Detection of more than 1 focal lesion in whole body MRI, 95% or more of bone marrow plasma cells displaying an aberrant phenotype in flow cytometry and an evolving clinical course in two consecutive follow-up visits are additional prognostic parameters for sMM. Currently there is no accepted secondary prevention strategy available for sMM and MGUS progression. Future studies are required to combine increasing knowledge on risk factors and molecular pathogenesis with targeted agents to prevent progression. PMID:21509683

  11. [Is there alternative to FOLFOX adjuvant chemotherapy for stage III colorectal cancer patients?].

    PubMed

    Esch, Anouk; Coriat, Romain; Perkins, Géraldine; Brezault, Catherine; Chaussade, Stanislas

    2012-01-01

    Being the second cancer for men and the third cancer for women in France, colorectal cancer represents a serious public health issue. Its incidence has increased these last years and despite new therapeutics being developed, it still has a bad prognostic. Thanks in part to Hemoccult national mass screening program, its diagnosis is made possible at an earlier stage, which makes a surgical curative resection and the carrying out of adjuvant chemotherapy possible. For stage III colic cancer that has been surgically removed, adjuvant chemotherapy by FOLFOX 4 has to be offered. Nevertheless, because of its toxicities, the patient's high age, important comorbidities or post-surgical complications, this chemotherapy occasionally cannot be done. What are the colorectal cancer prognostic factors which would guide the chemotherapy? TNM classification, number of examined lymph nodes, MSI status, and presence or not of a perforation or a perinervous, lymphatic or venous invasion is recognized prognostic factors. Also, what are the alternatives of FOLFOX 4 regimen as colorectal cancer adjuvant treatment?

  12. Interim analysis of postoperative chemoradiotherapy with capecitabine and oxaliplatin versus capecitabine alone for pathological stage II and III rectal cancer: a randomized multicenter phase III trial

    PubMed Central

    Feng, Yan-Ru; Zhu, Yuan; Liu, Lu-Ying; Wang, Wei-Hu; Wang, Shu-Lian; Song, Yong-Wen; Wang, Xin; Tang, Yuan; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Zhang, Shi-Ping; Liu, Xin-Fan; Yu, Zi-Hao; Li, Ye-Xiong; Jin, Jing

    2016-01-01

    The aim of this study is to present an interim analysis of a phase III trial (NCT00714077) of postoperative concurrent capecitabine and radiotherapy with or without oxaliplatin for pathological stage II and III rectal cancer. Patients with pathologically confirmed stage II and III rectal cancer were randomized to either radiotherapy with concurrent capecitabine (Cap-RT group) or with capecitabine and oxaliplatin (Capox-RT group). The primary endpoint was 3-year disease-free survival rate (DFS). The 3-year DFS rate was 73.9% in the Capox-RT group and 71.6% in the Cap-RT group (HR 0.92, p = 0.647), respectively. No significant difference was observed in overall survival, cumulative incidence of local recurrence and distant metastasis between the two groups (p > 0.05). More grade 3–4 acute toxicity was observed in the Capox-RT group than in the Cap-RT group (38.1% vs. 29.2%, p = 0.041). Inclusion of oxaliplatin in the capecitabine-based postoperative regimen did not improve DFS but increased toxicities for pathological stage II and III rectal cancer in this interim analysis. PMID:27014909

  13. Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

    SciTech Connect

    Carmona, Ruben; Gulaya, Sachin; Murphy, James D.; Rose, Brent S.; Wu, John; Noticewala, Sonal; McHale, Michael T.; Yashar, Catheryn M.; Vaida, Florin; Mell, Loren K.

    2014-07-15

    Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.

  14. Evaluation of preoperative serum markers for individual patient prognosis in stage I-III rectal cancer.

    PubMed

    Giessen, Clemens; Nagel, Dorothea; Glas, Maria; Spelsberg, Fritz; Lau-Werner, Ulla; Modest, Dominik Paul; Michl, Marlies; Heinemann, Volker; Stieber, Petra; Schulz, Christoph

    2014-10-01

    Several independent serum biomarkers have been proposed as prognostic and/or predictive markers for colorectal cancer (CRC). To this date, carcinoembryonic antigen (CEA) remains the only recommended serological CRC biomarker. The present retrospective analysis investigates the prognostic value of several serum markers. A total of 256 patients with rectal cancer underwent surgery for curative intent in a university cancer center between January 1988 and June 2007. Preoperative serum was retrospectively analyzed for albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin, bilirubin, CA 125, cancer antigen 19-9, cancer antigen 72-4 (CA 72-4), CEA, CRP, CYFRA 21-1, ferritin, gamma-glutamyl transpeptidase, glutamate oxaloacetate transanunase, glutamate pyruvate transaminase, hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate-dehydrogenase, serum amyloid A (SAA), and 25-hydroxyvitamin D. Cancer-specific survival (CSS) and disease-free survival (DFS) were estimated. Median follow-up time was 8.4 years. Overall 3- and 5-year CSS was 88.6 and 78.9 %, respectively. DFS rates were 72.8 % (3 years) and 67.5 % (5 years). Univariate analysis of CSS indicated aP, CA 72-4, CEA, and SAA as prognostic factors, while aP, CEA, and SAA were also prognostic with regard to DFS. Multivariate analysis confirmed SAA together with T and N stage as prognostic factors. According to UICC stage, CEA and SAA add prognostic value in stages II and III with regard to DFS and CSS, respectively. The combined use of CEA and SAA is able to identify patients with favorable and poor prognosis. In addition to tumor baseline parameters, routine analysis of SAA together with CEA provided markedly improved prognostic value on CSS and DFS in resected rectal cancer. PMID:25027407

  15. The role of induction chemotherapy before radiation therapy in non-operative management of stage III NSCLC.

    PubMed

    Green, M R

    1994-11-01

    Radiation therapy alone has been 'standard' management of patients with Stage III non-small cell lung cancer for several decades. Palliative benefits are routinely achieved but significant survival benefits have not been documented. Patterns of failure in Stage III patients emphasize the need to pursue better treatment for both local macroscopic disease and distant micrometastatic sites. Improved control in both areas will be necessary to meaningfully enhance outcome for the universe of Stage III NSCLC patients. Several randomized trials show a significant survival benefit when cisplatin-containing induction chemotherapy is administered prior to locoregional treatment. In the favorable subset of Stage III patients selected for study by CALGB, the surviving fraction at 2-5 years post-therapy was > or = 2-fold larger in the chemoradiation group than in the cohort treated with radiation alone. The French trial documented a significant decrease in distant metastases rate among the chemotherapy treated patients. In all the trials where patterns of failure are discussed, local disease persistence is the overwhelming rule. Future trials must evaluate improved induction chemotherapy approaches. Stage III patients are an ethical population in which to test induction therapy with new drug combinations randomized against already 'active' regimens for comparative efficacy. End points would be initial response rates, patterns of failure, and overall survival. The feasibility of high-dose chemotherapy regimens with growth factor and hematopoietic support followed by aggressive radiation must be tested. If feasible, trials randomizing high dose versus conventional dose induction programs within the context of sequential multimodality therapy should follow. Intensified radiation approaches such as hyperfractionation or CHART should be paired with active concurrent chemotherapy following induction chemotherapy alone. Pursuit of these approaches over the next several years will

  16. The role of induction chemotherapy before radiation therapy in non-operative management of stage III NSCLC.

    PubMed

    Green, M R

    1994-11-01

    Radiation therapy alone has been 'standard' management of patients with Stage III non-small cell lung cancer for several decades. Palliative benefits are routinely achieved but significant survival benefits have not been documented. Patterns of failure in Stage III patients emphasize the need to pursue better treatment for both local macroscopic disease and distant micrometastatic sites. Improved control in both areas will be necessary to meaningfully enhance outcome for the universe of Stage III NSCLC patients. Several randomized trials show a significant survival benefit when cisplatin-containing induction chemotherapy is administered prior to locoregional treatment. In the favorable subset of Stage III patients selected for study by CALGB, the surviving fraction at 2-5 years post-therapy was > or = 2-fold larger in the chemoradiation group than in the cohort treated with radiation alone. The French trial documented a significant decrease in distant metastases rate among the chemotherapy treated patients. In all the trials where patterns of failure are discussed, local disease persistence is the overwhelming rule. Future trials must evaluate improved induction chemotherapy approaches. Stage III patients are an ethical population in which to test induction therapy with new drug combinations randomized against already 'active' regimens for comparative efficacy. End points would be initial response rates, patterns of failure, and overall survival. The feasibility of high-dose chemotherapy regimens with growth factor and hematopoietic support followed by aggressive radiation must be tested. If feasible, trials randomizing high dose versus conventional dose induction programs within the context of sequential multimodality therapy should follow. Intensified radiation approaches such as hyperfractionation or CHART should be paired with active concurrent chemotherapy following induction chemotherapy alone. Pursuit of these approaches over the next several years will

  17. Effectiveness of a thoracic multidisciplinary clinic in the treatment of stage III non-small-cell lung cancer

    PubMed Central

    Friedman, Eliot L; Kruklitis, Robert J; Patson, Brian J; Sopka, Dennis M; Weiss, Michael J

    2016-01-01

    Introduction The Institute of Medicine, the American Society of Clinical Oncology, and the European Society of Medical Oncology promote a multidisciplinary approach for the treatment of cancer. Stage III non-small-cell lung cancer (NSCLC) represents a heterogeneous group of diseases necessitating coordination of care among medical, radiation, and surgical oncology. The optimal care of stage III NSCLC underscores the need for a multidisciplinary approach. Methods From tumor registry data, we identified all cases of stage III NSCLC seen at Lehigh Valley Health Network between March 2010 and March 2013. The care received by patients when seen in the thoracic multidisciplinary clinic (MDC) was compared with the care received when not seen in the thoracic MDC. Results All patients seen in the MDC, compared to <50% of patients seen outside the MDC, were evaluated by more than one physician prior to beginning the treatment. Time to initiate treatment was shorter in MDC patients than in non-MDC patients. Patients seen in the MDC had a greater concordance with clinical pathways. A greater percentage of patients seen in the thoracic MDC had pathologic staging of their mediastinum. Patients seen in the MDC were more likely to receive all of their care at Lehigh Valley Health Network. Conclusion Multidisciplinary care is essential in the treatment of patients with stage III NSCLC. Greater utilization of MDCs for this complex group of patients will result in more efficient coordination of care, pretreatment evaluation, and therapy, which in turn should translate to improve patients’ outcomes. PMID:27358568

  18. High-Dose Recombinant Interferon Alfa-2B, Ipilimumab, or Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery

    ClinicalTrials.gov

    2016-11-03

    Metastatic Non-Cutaneous Melanoma; Non-Cutaneous Melanoma; Recurrent Melanoma of the Skin; Recurrent Non-Cutaneous Melanoma; Stage III Mucosal Melanoma of the Head and Neck; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Stage IVA Mucosal Melanoma of the Head and Neck; Stage IVB Mucosal Melanoma of the Head and Neck; Stage IVC Mucosal Melanoma of the Head and Neck

  19. Association of Family History with Cancer Recurrence and Survival Among Patients with Stage III Colon Cancer

    PubMed Central

    Chan, Jennifer A.; Meyerhardt, Jeffrey A.; Niedzwiecki, Donna; Hollis, Donna; Saltz, Leonard B.; Mayer, Robert J.; Thomas, James; Schaefer, Paul; Whittom, Renaud; Hantel, Alexander; Goldberg, Richard M.; Warren, Robert S.; Bertagnolli, Monica; Fuchs, Charles S.

    2011-01-01

    Context A family history of colorectal cancer in a first-degree relative increases the risk of developing colorectal cancer. However, the influence of family history on cancer recurrence and survival among patients with established disease remains uncertain. Objective To examine the association of family history of colorectal cancer with cancer recurrence and survival of patients with colon cancer. Design, Setting, and Participants Prospective observational study of 1,087 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial (CALGB 89803) between April 1999 and May 2001. Patients provided data on family history at baseline and were followed up until March 2007 for disease recurrence and death (median follow-up 5.6 years). In a subset of patients, we assessed microsatellite instability (MSI) and expression of the mismatch repair (MMR) proteins, MLH1 and MSH2, in tumor specimens. Main Outcome Measure Disease-free survival, recurrence-free survival, and overall survival according to the presence or absence of a family history of colorectal cancer. Results Among 1,087 eligible patients, 195 (17.9%) reported a family history of colorectal cancer in a first-degree relative. Cancer recurrence or death occurred in 57/195 patients (29%; 95% confidence interval [CI], 23%-36%) with a family history of colorectal cancer and 343/892 patients (38%; 95% CI, 35%-42%) without a family history. Compared to patients without a family history, the adjusted hazard ratios (HR) among those with ≥1 affected first-degree relatives were 0.72 (95% CI, 0.54-0.96) for disease-free survival (DFS), 0.74 (95% CI, 0.55-0.99) for recurrence-free survival (RFS), and 0.75 (95% CI, 0.54-1.05) for overall survival (OS). This reduction in risk of cancer recurrence or death associated with a family history became stronger with an increasing number of affected first-degree relatives. Compared to participants without a family history of colorectal cancer, those with 1

  20. On the interplay effects with proton scanning beams in stage III lung cancer

    SciTech Connect

    Li, Yupeng; Kardar, Laleh; Liao, Li; Lim, Gino; Li, Xiaoqiang; Li, Heng; Zhu, Ronald X.; Sahoo, Narayan; Gillin, Michael; Zhang, Xiaodong; Cao, Wenhua; Chang, Joe Y.; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D.

    2014-02-15

    Purpose: To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer. Methods: Eleven patients were sampled from 112 patients with stage III nonsmall cell lung cancer to well represent the distribution of 112 patients in terms of target size and motion. Clinical target volumes (CTVs) and planning target volumes (PTVs) were defined according to the authors' clinical protocol. Uniform and realistic breathing patterns were considered along with regular- and hypofractionation scenarios. The dose contributed by a spot was fully calculated on the computed tomography (CT) images corresponding to the respiratory phase that the spot is delivered, and then accumulated to the reference phase of the 4DCT to generate the dynamic dose that provides an estimation of what might be delivered under the influence of interplay effect. The dynamic dose distributions at different numbers of fractions were compared with the corresponding 4D composite dose which is the equally weighted average of the doses, respectively, computed on respiratory phases of a 4DCT image set. Results: Under regular fractionation, the average and maximum differences in CTV coverage between the 4D composite and dynamic doses after delivery of all 35 fractions were no more than 0.2% and 0.9%, respectively. The maximum differences between the two dose distributions for the maximum dose to the spinal cord, heart V40, esophagus V55, and lung V20 were 1.2 Gy, 0.1%, 0.8%, and 0.4%, respectively. Although relatively large differences in single fraction, correlated with small CTVs relative to motions, were observed, the authors' biological response calculations suggested that this interfractional dose variation may have limited biological impact. Assuming a hypofractionation scenario, the differences between the 4D composite and dynamic doses were well confined even for single fraction. Conclusions: Despite

  1. Trace elements and heavy metals in hair of stage III breast cancer patients.

    PubMed

    Benderli Cihan, Yasemin; Sözen, Selim; Oztürk Yıldırım, Sema

    2011-12-01

    This prospective study was designed to compare the hair levels of 36 elements in 52 patients with stage III breast cancer to those of an equal number of healthy individuals. Principal component and cluster analysis were used for source of identification and apportionment of heavy metals and trace elements in these two groups. A higher average level of iron was found in samples from patients while controls had higher levels of calcium. Both patients and controls had elevated levels of tin, magnesium, zinc, and sodium. Almost all element values in cancer patients showed higher dispersion and asymmetry than in healthy controls. Between the two groups, there were statistically significant differences in the concentrations of silver, arsenic, gold, boron, barium, beryllium, calcium, cadmium, cerium, cobalt, cesium, gadolinium, manganese, nickel, lead, antimony, scandium, selenium, and zinc (p < 0.05). Strong positive correlations were found between lead and gold (r = 0.785) in the cancer group and between palladium and cobalt (r = 0.945) in the healthy individuals. Our results show that there are distinct patterns of heavy metals and trace elements in the hair of breast cancer patients in comparison to healthy controls. These results could be of significance in the diagnosis of breast cancer. PMID:21660533

  2. Late Closure of a Stage III Idiopathic Macular Hole after Pars Plana Vitrectomy

    PubMed Central

    Afrashi, Filiz; Öztaş, Zafer; Nalçacı, Serhad

    2015-01-01

    A 57-year-old female presented to our hospital with decreased vision in her right eye. Detailed ocular examination was performed, and a macular hole was detected in the right eye. The presence of a full-thickness stage III macular hole was confirmed with optical coherence tomography (OCT) imaging. Pars plana vitrectomy followed by long-acting gas tamponade (C3F8) was performed as treatment. One month after surgery, clinical examination revealed a persistent macular hole, confirmed by an OCT scan. Although the patient was scheduled for reoperation, the surgery was postponed due to personal reasons of the patient. Surprisingly, after five months, a closure pattern with accompanying epiretinal membrane was observed in the macular hole area. The closure of the macular hole was completed without any further intervention 8 months post-surgery. In cases of unclosed macular hole after the first surgery, if a second surgery cannot be performed, follow-up with OCT recommended due to the possibility of spontaneous closure. However, spontaneous closure of a persistent macular hole following PPV is rare, so early diagnosis and surgical repair of unclosed macular holes must remain the primary goal. PMID:27800248

  3. Georgetown University Integrated Community Energy System (GU-ICES). Phase III, Stage I: feasibility analysis. Final report

    SciTech Connect

    Buck, Victor

    1980-10-01

    Candidate energy alternatives are analyzed in Phase III, Stage I, and the appendices are presented for the feasibility analysis. Information in eight appendices includes the following: detailed statement of work; PEPCO rate schedules; cogeneration schemes; added coal, limestone, and ash storage; hot and cold thermal storage; absorption refrigeration; high temperature heat pumps; and life cycle cost analysis. (MCW)

  4. 125I Seed Permanent Implantation as a Palliative Treatment for Stage III and IV Hypopharyngeal Carcinoma

    PubMed Central

    Li, Lei; Yang, Jie; Li, Xiaojiang; Wang, Xiaoli; Ren, Yanxin; Fei, Jimin; Xi, Yan; Sun, Ruimei; Ma, Jing

    2016-01-01

    Objectives. The aim of this study was to investigate the feasibility and safety of percutaneous 125I seed permanent implantation for advanced hypopharyngeal carcinoma from toxicity, tumor response, and short-term outcome. Methods. 125I seeds implant procedures were performed under computed tomography for 34 patients with advanced hypopharyngeal carcinoma. We observed the local control rate, overall survival, and acute or late toxicity rate. Results. In the 34 patients (stage III, n=6; stage IV, n=28), the sites of origin were pyriform sinus (n=29) and postcricoid area (n=5). All patients also received one to four cycles of chemotherapy after seed implantation. The post-plan showed that the actuarial D90 of 125I seeds ranged from 90 to 158 Gy (median, 127 Gy). The mean follow-up was 12.3 months (range, 3.4 to 43.2 months). The local control was 2.1–31.0 months with a median of 17.7 months (95% confidence interval [CI], 13.4 to 22.0 months). The 1-, 2-, and 3-year local controls were 65.3%, 28.6%, and 9.5% respectively. Twelve patients (35%) died of local recurrence, fourteen patients (41%) died of distant metastases, and three patients (9%) died of recurrence and metastases at the same time. Five patients (15%) still survived to follow-up. At the time of analysis, the median survival time was 12.5 months (95% CI, 9.5 to 15.4 months). The 1-, 2-, and 3-year overall survival rates were 55.2%, 20.3%, and 10.9%, respectively. Five patients (15%) experienced grade 3 toxic events and nine patients (26%) have experienced grade 2 toxic events. Conclusion. This review shows relatively low toxicity for interstitial 125I seed implantation in the patients with advanced stage hypopharyngeal cancer. The high local control results suggest that 125I seed brachytherapy implant as a salvage or palliative treatment for advanced hypopharyngeal carcinoma merit further investigation. PMID:27440132

  5. Preoperative serum markers for individual patient prognosis in stage I-III colon cancer.

    PubMed

    Giessen-Jung, Clemens; Nagel, Dorothea; Glas, Maria; Spelsberg, Fritz; Lau-Werner, Ulla; Modest, Dominik Paul; Schulz, Christoph; Heinemann, Volker; Di Gioia, Dorit; Stieber, Petra

    2015-09-01

    Carcinoembryonic antigen (CEA) remains the only recommended biomarker for follow-up care of colorectal cancer (CRC), but besides CEA, several other serological parameters have been proposed as prognostic markers for CRC. The present retrospective analysis investigates a comprehensive set of serum markers with regard to cancer-specific survival (CSS) and disease-free survival (DFS). A total of 472 patients with colon cancer underwent surgery for curative intent between January 1988 and June 2007. Preoperative serum was analyzed for the following parameters: albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin (βhCG), bilirubin, cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9), CA 72-4, CEA, C-reactive protein (CRP), cytokeratin-19 soluble fragment (CYFRA 21-1), ferritin, gamma-glutamyltransferase (γGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate dehydrogenase (LDH), serum amyloid A (SAA), and 25-hydroxyvitamin D. After a median follow-up period of 5.9 years, the overall 3- and 5-year CSS was 91.7 and 84.9 % and DFS rates were 82.7 % (3 years) and 77.6 % (5 years). Multivariate analyses confirmed preoperative CEA as an independent prognostic factor with regard to CSS and DFS. CA 19-9 and γGT also provided prognostic value for CSS and DFS, respectively. Younger age was negatively associated with DFS. According to UICC stage, CEA provided significant prognostic value with regard to CSS and DFS, while CA 19-9 was only prognostic for CSS. Combined analysis is able to identify patients with favorable prognosis. In addition to tumor baseline parameters, preoperative CEA could be confirmed as prognostic marker in colon cancer. CA 19-9 and γGT also provide additional prognostic value with regard to survival and recurrence in stage III and stage I disease, respectively. The combined use of CEA together with CA 19-9 and γGT improve

  6. 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.

  7. Motivational and Volitional Variables Associated with Stages of Change for Exercise in Multiple Sclerosis: A Multiple Discriminant Analysis

    ERIC Educational Resources Information Center

    Chiu, Chung-Yi; Fitzgerald, Sandra D.; Strand, David M.; Muller, Veronica; Brooks, Jessica; Chan, Fong

    2012-01-01

    The main objective of this study was to determine whether motivational and volitional variables identified in the health action process approach (HAPA) model can be used to successfully differentiate people with multiple sclerosis (MS) in different stages of change for exercise and physical activity. Ex-post-facto design using multiple…

  8. Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2015-12-22

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

  9. Combination Chemotherapy With or Without Rituximab in Treating Younger Patients With Stage III-IV Non-Hodgkin Lymphoma or B-Cell Acute Leukemia

    ClinicalTrials.gov

    2016-10-24

    Childhood B Acute Lymphoblastic Leukemia; Childhood Burkitt Leukemia; Childhood Diffuse Large Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma

  10. Neo-adjuvant Therapy With Anastrozole Plus Pazopanib in Stage II and III ER+ Breast Cancer

    ClinicalTrials.gov

    2016-05-24

    Estrogen Receptor-positive Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Male Breast Cancer; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer

  11. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC)

    PubMed Central

    Oki, E.; Murata, A.; Yoshida, K.; Maeda, K.; Ikejiri, K.; Munemoto, Y.; Sasaki, K.; Matsuda, C.; Kotake, M.; Suenaga, T.; Matsuda, H.; Emi, Y.; Kakeji, Y.; Baba, H.; Hamada, C.; Saji, S.; Maehara, Y.

    2016-01-01

    Backgrounds Preventing distant recurrence and achieving local control are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur–uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer. Patients and methods The ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20–80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500–600 mg/day on days 1–5, followed by 2 days rest) or S-1 (80–120 mg/day on days 1–28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events. Results In total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61.7% [95% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63–0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm. Conclusion One-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection. PMID:27056996

  12. Combined pulmonary and thoracic wall resection for stage III lung cancer.

    PubMed Central

    Shah, S. S.; Goldstraw, P.

    1995-01-01

    BACKGROUND--Carcinoma of the lung with thoracic wall involvement constitutes stage III disease. The management of patients with this condition is complicated. However, improvement in perioperative care coupled with advances in surgical technique have enabled a more aggressive approach to the problem to be adopted. METHODS--A retrospective review was carried out of 58 patients (40 men) of mean age 63 years who underwent thoracotomy for lung cancer with chest wall invasion between 1980 and 1993. RESULTS--Chest wall resection was performed in 55 patients (94.8%); in three patients the discovery of N2 disease at operation precluded resection. The TNM status was T3N0M0 in 38 patients, T3N1M0 in 13, and T3N2M0 in seven. Squamous cell carcinoma was the commonest cell type (26 patients). Reconstruction of the chest wall was performed in 29 patients (Marlex mesh in six, Marlex-methacrylate in 22, myocutaneous flap in one patient). The morbidity and mortality were 22.4% and 3.4% respectively. Follow up was complete in 51 patients. Nineteen (37.2%) survived > or = 5 years. The absolute five year survival for N0 and N1 disease was 44.7% and 38.4%, respectively. No patients with N2 disease survived five years. CONCLUSIONS--In patients with carcinoma of the lung and chest wall invasion, combined pulmonary and thoracic wall resection offers the prospect of cure with minimal morbidity and mortality. The prognosis of patients with coexistent N2 disease remains poor. PMID:7570416

  13. Intraperitoneal Paclitaxel, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Stage III-IV Endometrial Cancer

    ClinicalTrials.gov

    2016-10-26

    Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  14. Pair Box 8 (PAX8) protein expression in high grade, late stage (stages III and IV) ovarian serous carcinoma

    PubMed Central

    Mhawech-Fauceglia, Paulette; Wang, Dan; Samrao, Damanzoopinder; Godoy, Heidi; Ough, Faith; Liu, Song; Pejovic, Tanja; Lele, Shashikant

    2016-01-01

    Objectives Pair-Box 8 (PAX8) is a transcription factor which has been found to be overexpressed in ovarian serous carcinoma (OSC). Silencing PAX8 by using shRNA led to a drop in cell viability in ovarian cancer cell lines, suggesting its use as a targeted therapeutic agent. The prognostic value of PAX8 in OSC is still widely unknown. The aim of this study was to evaluate PAX8 as a prognostic biomarker in patients with advanced stage OSC. Methods PAX8 was evaluated using immunohistochemistry on a tissue microarray of 148 OSC and the expression was correlated to the following clinico-pathologic variables; age of diagnosis, tumor stage, optimal debulking, recurrence free survival (RFS) and overall survival (OS). Results We found that PAX8 was expressed in 61% of cases. There was no association between PAX8 and tumor stage, optimal debulking and disease recurrence. In addition, PAX8 failed to have a predictive value in disease outcome. Conclusion Despite showing that PAX8 protein is not a useful predictive marker in patients with high grade, advanced stage OSC, its overexpression in a large number of these cases makes the inhibition of PAX8 a very attractive targeted therapy. PMID:22705448

  15. Analysis of dynamic behavior of multiple-stage planetary gear train used in wind driven generator.

    PubMed

    Wang, Jungang; Wang, Yong; Huo, Zhipu

    2014-01-01

    A dynamic model of multiple-stage planetary gear train composed of a two-stage planetary gear train and a one-stage parallel axis gear is proposed to be used in wind driven generator to analyze the influence of revolution speed and mesh error on dynamic load sharing characteristic based on the lumped parameter theory. Dynamic equation of the model is solved using numerical method to analyze the uniform load distribution of the system. It is shown that the load sharing property of the system is significantly affected by mesh error and rotational speed; load sharing coefficient and change rate of internal and external meshing of the system are of obvious difference from each other. The study provides useful theoretical guideline for the design of the multiple-stage planetary gear train of wind driven generator.

  16. Intra-Arterial Infusion Chemotherapy Using Cisplatin With Radiotherapy for Stage III Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Kaneyasu, Yuko Nagai, Nobutaka; Nagata, Yasushi; Hashimoto, Yasutoshi; Yuki, Shintaro; Murakami, Yuji; Kenjo, Masahiro; Kakizawa, Hideaki; Toyota, Naoyuki; Fujiwara, Hisaya; Kudo, Yoshiki; Ito, Katsuhide

    2009-10-01

    Purpose: To examine the effectiveness of concomitant intra-arterial infusion chemotherapy (IAIC) using cisplatin (CDDP) with radiotherapy for Stage III squamous cell carcinoma of the cervix. Materials and Methods: We analyzed 29 cases of Stage III squamous cell carcinoma of the uterine cervix treated with radiotherapy and IAIC of CDDP from 1991 to 2006. External-beam therapy was given to the whole pelvis using four opposing parallel fields with an 18-MV linear accelerator unit. A central shield was used after 30-40 Gy with external whole-pelvic irradiation, and the total dose was 50 Gy. High-dose-rate brachytherapy was given with {sup 192}Ir microSelectron. The dose at Point A was 6 Gy per fraction, 2 fractions per week, and the total number of fractions was either 3 or 4. Two or three courses of IAIC were given concomitantly with CDDP 120 mg or carboplatin 300 mg. Results: We confirmed excellent medicine distribution directly by using computed tomographic angiography. The 5-year overall survival rate for Stage III patients was 62%, the cause-specific survival rate was 70%, and the local relapse-free survival rate was 89%. Local recurrence, distant metastasis, and occurrences of both were 7%, 38%, and 3%, respectively. The incidence of severe acute hematologic adverse reactions (Grade {>=}3) was 27% for all patients; however, all recovered without interruption of radiotherapy. Severe nonhematologic effects (Grade {>=}3) were 3%, including nausea and ileus. Only 1 patient's radiotherapy was interrupted for a period of 1 week because of ileus. Severe late complication rates (Grade {>=}3) for the bladder, rectum, and intestine were 3%, 3%, and 10%, respectively. Conclusion: A combination of IAIC and systemic chemotherapy should be considered to improve the prognosis of patients with Stage III squamous cell carcinoma of the cervix.

  17. Learning Multiple Band-Pass Filters for Sleep Stage Estimation: Towards Care Support for Aged Persons

    NASA Astrophysics Data System (ADS)

    Takadama, Keiki; Hirose, Kazuyuki; Matsushima, Hiroyasu; Hattori, Kiyohiko; Nakajima, Nobuo

    This paper proposes the sleep stage estimation method that can provide an accurate estimation for each person without connecting any devices to human's body. In particular, our method learns the appropriate multiple band-pass filters to extract the specific wave pattern of heartbeat, which is required to estimate the sleep stage. For an accurate estimation, this paper employs Learning Classifier System (LCS) as the data-mining techniques and extends it to estimate the sleep stage. Extensive experiments on five subjects in mixed health confirm the following implications: (1) the proposed method can provide more accurate sleep stage estimation than the conventional method, and (2) the sleep stage estimation calculated by the proposed method is robust regardless of the physical condition of the subject.

  18. An Application of Graphical Approach to Construct Multiple Testing Procedures in a Hypothetical Phase III Design

    PubMed Central

    Wang, Bushi; Ting, Naitee

    2014-01-01

    Many multiple testing procedures (MTP) have been developed in recent years. Among these new procedures, the graphical approach is flexible and easy to communicate with non-statisticians. A hypothetical Phase III clinical trial design is introduced in this manuscript to demonstrate how graphical approach can be applied in clinical product development. In this design, an active comparator is used. It is thought that this test drug under development could potentially be superior to this comparator. For comparison of efficacy, the primary endpoint is well established and widely accepted by regulatory agencies. However, an important secondary endpoint based on Phase II findings looks very promising. The target dose may have a good opportunity to deliver superiority to the comparator. Furthermore, a lower dose is included in case the target dose may demonstrate potential safety concerns. This Phase III study is designed as a non-inferiority trial with two doses, and two endpoints. This manuscript will illustrate how graphical approach is applied to this design in handling multiple testing issues. PMID:24432299

  19. Pharmacogenetic predictors of outcome in patients with stage II and III colon cancer treated with oxaliplatin and fluoropyrimidine-based adjuvant chemotherapy.

    PubMed

    Custodio, Ana; Moreno-Rubio, Juan; Aparicio, Jorge; Gallego-Plazas, Javier; Yaya, Ricardo; Maurel, Joan; Rodríguez-Salas, Nuria; Burgos, Emilio; Ramos, David; Calatrava, Ana; Andrada, Encarna; Díaz-López, Esther; Sánchez, Antonio; Madero, Rosario; Cejas, Paloma; Feliu, Jaime

    2014-09-01

    Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with colon cancer who are more likely to benefit from adjuvant chemotherapy. We investigated the effect of single-nucleotide polymorphisms (SNP) within genes involved in oxaliplatin and fluoropyrimidines metabolism, DNA repair mechanisms, drug transport, or angiogenesis pathways on outcome for patients with stage II and III colon cancer treated with adjuvant chemotherapy. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples of 202 patients with stage II and III colon cancer receiving oxaliplatin-based adjuvant chemotherapy from January 2004 to December 2009. Genotyping was performed for 67 SNPs in 32 genes using the MassARRAY (SEQUENOM) technology. Our results were validated in an independent cohort of 177 patients treated with the same chemotherapy regimens. The combination of the selectin E (SELE) rs3917412 G>A G/G and the methylentetrahydrofolate reductase (MTHFR) rs1801133 T/T genotypes was associated with a significantly increased risk for recurrence in both the training [RR = 4.103; 95% confidence interval (CI), 1.803-9.334; P = 0.001] and the validation cohorts (RR = 3.567; 95% CI, 1.253-10.151; P = 0.017) in the multiple regression analysis considering the stage, lymphovascular invasion, and bowel perforation as covariates. The combined analysis of these polymorphisms was also significantly associated with overall survival in both cohorts (RR = 3.388; 95% CI, 0.988-11.623; P = 0.052, and RR = 3.929; 95% CI, 1.144-13.485; P = 0.020, respectively). Our findings suggest that the SELE rs3917412 and MTHFR rs1801133 SNPs could serve as pharmacogenetic predictors of tumor recurrence in patients with early-stage colon cancer treated with oxaliplatin-based adjuvant chemotherapy, thus allowing personalized selection of treatment to optimize clinical outcomes.

  20. Multiple myeloma: new staging systems for diagnosis, prognosis and response evaluation.

    PubMed

    Rajkumar, S Vincent; Buadi, Francis

    2007-12-01

    Multiple myeloma must be distinguished from monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and several other closely related plasma-cell disorders. In recent years, new systems have emerged for diagnosis, staging, and risk stratification of myeloma. The criteria recommended are primarily derived from the International Myeloma Working Group, with certain updates and clarifications. The International Staging System (ISS) is the standard for staging of myeloma. However, for therapeutic purposes, a risk-stratification model is used to define high-risk patients who can benefit from novel therapeutic strategies. The International Myeloma Working Group uniform response criteria have been developed as the standard for response assessment in current and future clinical trials. The criteria incorporate the category 'very good partial response' (VGPR) which, given its importance in predicting outcome following therapy, should be reported in all trials; such reporting will also enable better comparisons between therapies. PMID:18070712

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

    ClinicalTrials.gov

    2013-01-04

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

  2. Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)

    ClinicalTrials.gov

    2014-11-17

    Recurrent Skin Cancer; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Squamous Cell Carcinoma of the Skin; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity

  3. The Frontier of Molecular Spintronics Based on Multiple-Decker Phthalocyaninato Tb(III) Single-Molecule Magnets.

    PubMed

    Katoh, Keiichi; Komeda, Tadahiro; Yamashita, Masahiro

    2016-04-01

    Ever since the first example of a double-decker complex (SnPc2) was discovered in 1936, MPc2 complexes with π systems and chemical and physical stabilities have been used as components in molecular electronic devices. More recently, in 2003, TbPc2 complexes were shown to be single-molecule magnets (SMMs), and researchers have utilized their quantum tunneling of the magnetization (QTM) and magnetic relaxation behavior in spintronic devices. Herein, recent developments in Ln(III)-Pc-based multiple-decker SMMs on surfaces for molecular spintronic devices are presented. In this account, we discuss how dinuclear Tb(III)-Pc multiple-decker complexes can be used to elucidate the relationship between magnetic dipole interactions and SMM properties, because these complexes contain two TbPc2 units in one molecule and their intramolecular Tb(III)-Tb(III) distances can be controlled by changing the number of stacks. Next, we focus on the switching of the Kondo signal of Tb(III)-Pc-based multiple-decker SMMs that are adsorbed onto surfaces, their characterization using STM and STS, and the relationship between the molecular structure, the electronic structure, and the Kondo resonance of Tb(III)-Pc multiple-decker complexes.

  4. A computer analysis of regenerator losses in a Stirling cryocooler with multiple expansion stages

    NASA Astrophysics Data System (ADS)

    Urieli, Israel; Tang, Kuo-Chiang

    An Ideal Adiabatic analysis of a Stirling cryocooler with multiple expansion stages has been presented previously. In this analysis the compression space and the various expansion spaces are adiabatic, the heat exchangers are isothermal and the regenerators are ideal. This paper is an extension of that analysis to evaluate the enthalpy losses associated with the interstage regenerators. The regenerator effectiveness is defined in terms of the total unidirectional heat flow from the regenerator matrix to the working gas. A new definition of regenerator figure-of-merit is proposed for the intermediate expansion stages based on a stage energy balance, and its evaluation and uses in design are discussed. The analysis of a typical three expansion stage cryocooler is presented.

  5. Monte Carlo analysis of the Titan III/Transfer Orbit Stage guidance system for the Mars Observer mission

    NASA Technical Reports Server (NTRS)

    Bell, Stephen C.; Ginsburg, Marc A.; Rao, Prabhakara P.

    1993-01-01

    An important part of space launch vehicle mission planning for a planetary mission is the integrated analysis of guidance and performance dispersions for both booster and upper stage vehicles. For the Mars Observer mission, an integrated trajectory analysis was used to maximize the scientific payload and to minimize injection errors by optimizing the energy management of both vehicles. This was accomplished by designing the Titan III booster vehicle to inject into a hyperbolic departure plane, and the Transfer Orbit Stage (TOS) to correct any booster dispersions. An integrated Monte Carlo analysis of the performance and guidance dispersions of both vehicles provided sensitivities, an evaluation of their guidance schemes and an injection error covariance matrix. The polynomial guidance schemes used for the Titan III variable flight azimuth computations and the TOS solid rocket motor ignition time and burn direction derivations accounted for a wide variation of launch times, performance dispersions, and target conditions. The Mars Observer spacecraft was launched on 25 September 1992 on the Titan III/TOS vehicle. The post flight analysis indicated that a near perfect park orbit injection was achieved, followed by a trans-Mars injection with less than 2sigma errors.

  6. Phage idiotype vaccination: first phase I/II clinical trial in patients with multiple myeloma

    PubMed Central

    2014-01-01

    Background Multiple myeloma is characterized by clonal expansion of B cells producing monoclonal immunoglobulins or fragments thereof, which can be detected in the serum and/or urine and are ideal target antigens for patient-specific immunotherapies. Methods Using phage particles as immunological carriers, we employed a novel chemically linked idiotype vaccine in a clinical phase I/II trial including 15 patients with advanced multiple myeloma. Vaccines composed of purified paraproteins linked to phage were manufactured successfully for each patient. Patients received six intradermal immunizations with phage idiotype vaccines in three different dose groups. Results Phage idiotype was well tolerated by all study participants. A subset of patients (80% in the middle dose group) displayed a clinical response indicated by decrease or stabilization of paraprotein levels. Patients exhibiting a clinical response to phage vaccines also raised idiotype-specific immunoglobulins. Induction of a cellular immune response was demonstrated by a cytotoxicity assay and delayed type hypersensitivity tests. Conclusion We present a simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible patient-specific therapy for patients with advanced multiple myeloma and produced promising anti-tumor activity in a subset of patients. PMID:24885819

  7. Dislocation Multiplication in the Early Stage of Deformation in Mo Single Crystals

    SciTech Connect

    Hsiung, L.; Lassila, D.H.

    2000-03-02

    Initial dislocation structure in annealed high-purity Mo single crystals and deformation substructure in a crystal subjected to 1% compression have been examined and studied using transmission electron microscopy (TEM) techniques in order to investigate dislocation multiplication mechanisms in the early stage of plastic deformation. The initial dislocation density is in a range of 10{sup 6} {approx} 10{sup 7} cm{sup -2}, and the dislocation structure is found to contain many grown-in superjogs along dislocation lines. The dislocation density increases to a range of 10{sup 8} {approx} 10{sup 9} cm{sup -2}, and the average jog height is also found to increase after compressing for a total strain of 1%. It is proposed that the preexisting jogged screw dislocations can act as (multiple) dislocation multiplication sources when deformed under quasi-static conditions. The jog height can increase by stress-induced jog coalescence, which takes place via the lateral migration (drift) of superjogs driven by unbalanced line-tension partials acting on link segments of unequal lengths. The coalescence of superjogs results in an increase of both link length and jog height. Applied shear stress begins to push each link segment to precede dislocation multiplication when link length and jog height are greater than critical lengths. This ''dynamic'' dislocation multiplication source is suggested to be crucial for the dislocation multiplication in the early stage of plastic deformation in Mo.

  8. Single-stage bilateral pulmonary resections by video-assisted thoracic surgery for multiple small nodules

    PubMed Central

    Yao, Feng; Yang, Haitang

    2016-01-01

    Background Surgical treatment is thought to be the most effective strategy for multiple small nodules. However, in general, one-stage bilateral resection is not recommended due to its highly invasive nature. Methods Clinical records of patients undergoing one-stage bilateral resections of multiple pulmonary nodules between January 2009 and September 2014 in a single institution were retrospectively reviewed. Results Simultaneous bilateral pulmonary resection by conventional video-assisted thoracic surgery (VATS) was undertaken in 29 patients. Ground glass opacity (GGO) accounted for 71.9% (46/64) of total lesions, including 26 pure GGO and 20 mixed GGO lesions. One case underwent bilateral lobectomy that was complicated by postoperative dyspnea. Lobar-sublobar (L/SL) resection and bilateral sublobar resection (SL-SL) were conducted in 16 and 12 cases, respectively, and most of these cases had uneventful postoperative courses. There was no significant difference with regard to postoperative complications (P=0.703), duration of use of chest drains (P=0.485), between one- and two-stage groups. Mean postoperative follow-up in cases of primary lung cancer was 31.4 (range, 10–51) months. There was neither recurrence nor deaths at final follow-up. Conclusions Single-stage bilateral surgery in selected cases with synchronous bilateral multiple nodules (SBMNs) is feasible and associated with satisfactory outcomes. PMID:27076942

  9. Perception of affective prosody in patients at an early stage of relapsing-remitting multiple sclerosis.

    PubMed

    Kraemer, Markus; Herold, Michele; Uekermann, Jennifer; Kis, Bernhard; Daum, Irene; Wiltfang, Jens; Berlit, Peter; Diehl, Rolf R; Abdel-Hamid, Mona

    2013-03-01

    Cognitive dysfunction is well known in patients suffering from multiple sclerosis (MS) and has been described for many years. Cognitive impairment, memory, and attention deficits seem to be features of advanced MS stages, whereas depression and emotional instability already occur in early stages of the disease. However, little is known about processing of affective prosody in patients in early stages of relapsing-remitting MS (RRMS). In this study, tests assessing attention, memory, and processing of affective prosody were administered to 25 adult patients with a diagnosis of RRMS at an early stage and to 25 healthy controls (HC). Early stages of the disease were defined as being diagnosed with RRMS in the last 2 years and having an Expanded Disability Status Scale (EDSS) of 2 or lower. Patients and HC were comparable in intelligence quotient (IQ), educational level, age, handedness, and gender. Patients with early stages of RRMS performed below the control group with respect to the subtests 'discrimination of affective prosody' and 'matching of affective prosody to facial expression' for the emotion 'angry' of the 'Tübingen Affect Battery'. These deficits were not related to executive performance. Our findings suggest that emotional prosody comprehension is deficient in young patients with early stages of RRMS. Deficits in discriminating affective prosody early in the disease may make misunderstandings and poor communication more likely. This might negatively influence interpersonal relationships and quality of life in patients with RRMS.

  10. Perception of affective prosody in patients at an early stage of relapsing-remitting multiple sclerosis.

    PubMed

    Kraemer, Markus; Herold, Michele; Uekermann, Jennifer; Kis, Bernhard; Daum, Irene; Wiltfang, Jens; Berlit, Peter; Diehl, Rolf R; Abdel-Hamid, Mona

    2013-03-01

    Cognitive dysfunction is well known in patients suffering from multiple sclerosis (MS) and has been described for many years. Cognitive impairment, memory, and attention deficits seem to be features of advanced MS stages, whereas depression and emotional instability already occur in early stages of the disease. However, little is known about processing of affective prosody in patients in early stages of relapsing-remitting MS (RRMS). In this study, tests assessing attention, memory, and processing of affective prosody were administered to 25 adult patients with a diagnosis of RRMS at an early stage and to 25 healthy controls (HC). Early stages of the disease were defined as being diagnosed with RRMS in the last 2 years and having an Expanded Disability Status Scale (EDSS) of 2 or lower. Patients and HC were comparable in intelligence quotient (IQ), educational level, age, handedness, and gender. Patients with early stages of RRMS performed below the control group with respect to the subtests 'discrimination of affective prosody' and 'matching of affective prosody to facial expression' for the emotion 'angry' of the 'Tübingen Affect Battery'. These deficits were not related to executive performance. Our findings suggest that emotional prosody comprehension is deficient in young patients with early stages of RRMS. Deficits in discriminating affective prosody early in the disease may make misunderstandings and poor communication more likely. This might negatively influence interpersonal relationships and quality of life in patients with RRMS. PMID:23126275

  11. A Phase I Study of Dasatinib with Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer

    PubMed Central

    Khurshid, Humera; Dipetrillo, Thomas; Ng, Thomas; Mantripragada, Kalyan; Birnbaum, Ariel; Berz, David; Radie-Keane, Kathy; Perez, Kimberly; Constantinou, Maria; Luppe, Denise; Schumacher, Andrew; Leonard, Kara; Safran, Howard

    2012-01-01

    Objectives: Src family kinases (SFKs) are expressed in non-small cell lung cancer (NSCLC) and may be involved in tumor growth and metastases. Inhibition of SFK may also enhance radiation. The purpose of this study was to evaluate if a maximum dose of 100 mg of dasatinib could be safely administered with concurrent chemoradiation and then continued as maintenance for patients with newly diagnosed stage III NSCLC. Methods: Patients with stage III locally advanced NSCLC received paclitaxel, 50 mg/m2/week, with carboplatin area under the curve (AUC) = 2, weekly for 7 weeks, and concurrent radiotherapy, 64.8 Gy. Three dose levels of dasatinib 50, 70, and 100 mg/day were planned. Results: 11 patients with locally advanced NSCLC were entered. At the 70 mg dose level 1 patient had grade 5 pneumonitis not responsive to therapy, and one patient had reversible grade 3 pneumonitis and grade 3 pericardial effusion. Due to these toxicities the Brown University Oncology Group Data Safety Monitoring Board terminated the study. Conclusion: Dasatinib could not be safely combined with concurrent chemoradiation for stage 3 lung cancer due to pneumonitis. PMID:22666662

  12. Molecular Phenotyping in Predicting Response in Patients With Stage IB-III Esophageal Cancer Receiving Combination Chemotherapy

    ClinicalTrials.gov

    2015-12-18

    Stage IB Esophageal Adenocarcinoma; Stage IIA Esophageal Adenocarcinoma; Stage IIB Esophageal Adenocarcinoma; Stage IIIA Esophageal Adenocarcinoma; Stage IIIB Esophageal Adenocarcinoma; Stage IIIC Esophageal Adenocarcinoma

  13. Multiple-stage correction of caudal duplication syndrome: a case report.

    PubMed

    Liu, Hao; Che, Xiangming; Wang, Shufeng; Chen, Gang

    2009-12-01

    Caudal duplication syndrome is a very rare congenital deformity. A 13-year-old boy was born with duplicated colon-rectum and anus, diphallus, hydronephrosis of left kidney with megaureter, double bladders and urethras, and vertebral abnormalities. Multiple-stage correction was performed to remove the duplicated colon and the mucosa of the duplicated rectum. A new colon was reconstructed. The left kidney and megaureter were excised. The septum in the bladders was removed to convert the double bladders into a single bladder. The double phalluses were fused into a single penis. After these staged procedures, the boy is now living a normal life. PMID:20006039

  14. Efficacy of Adjuvant 5-Fluorouracil Therapy for Patients with EMAST-Positive Stage II/III Colorectal Cancer

    PubMed Central

    Hamaya, Yasushi; Guarinos, Carla; Tseng-Rogenski, Stephanie S.; Iwaizumi, Moriya; Das, Ritabrata; Jover, Rodrigo; Castells, Antoni; Llor, Xavier; Andreu, Montserrat; Carethers, John M.

    2015-01-01

    Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST) is a genetic signature found in up to 60% of colorectal cancers (CRCs) that is caused by somatic dysfunction of the DNA mismatch repair (MMR) protein hMSH3. We have previously shown in vitro that recognition of 5-fluorouracil (5-FU) within DNA and subsequent cytotoxicity was most effective when both hMutSα (hMSH2-hMSH6 heterodimer) and hMutSβ (hMSH2-hMSH3 heterodimer) MMR complexes were present, compared to hMutSα > hMutSβ alone. We tested if patients with EMAST CRCs (hMutSβ defective) had diminished response to adjuvant 5-FU chemotherapy, paralleling in vitro findings. We analyzed 230 patients with stage II/III sporadic colorectal cancers for which we had 5-FU treatment and survival data. Archival DNA was analyzed for EMAST (>2 of 5 markers mutated among UT5037, D8S321, D9S242, D20S82, D20S85 tetranucleotide loci). Kaplan-Meier survival curves were generated and multivariate analysis was used to determine contribution to risk. We identified 102 (44%) EMAST cancers. Ninety-four patients (41%) received adjuvant 5-FU chemotherapy, and median follow-up for all patients was 51 months. Patients with EMAST CRCs demonstrated improved survival with adjuvant 5FU to the same extent as patients with non-EMAST CRCs (P<0.05). We observed no difference in survival between patients with stage II/III EMAST and non-EMAST cancers (P = 0.36). There is improved survival for stage II/III CRC patients after adjuvant 5-FU-based chemotherapy regardless of EMAST status. The loss of contribution of hMSH3 for 5-FU cytotoxicity may not adversely affect patient outcome, contrasting patients whose tumors completely lack DNA MMR function (MSI-H). PMID:25996601

  15. Dietary Glycemic Load and Cancer Recurrence and Survival in Patients with Stage III Colon Cancer: Findings From CALGB 89803

    PubMed Central

    2012-01-01

    Background The influence of glycemic load and related measures on survival among colon cancer patients remains largely unknown. Methods We conducted a prospective, observational study of 1011 stage III colon cancer patients reporting dietary intake during and 6 months after participation in an adjuvant chemotherapy trial. We examined the influence of glycemic load, glycemic index, fructose, and carbohydrate intakes on cancer recurrence and mortality using Cox proportional hazards regression; all tests of statistical significance were two-sided. Results Stage III colon cancer patients in the highest quintile of dietary glycemic load experienced an adjusted hazard ratio (HR) for disease-free survival of 1.79 (95% confidence interval [CI] = 1.29 to 2.48), compared with those in the lowest quintile (P trend across quintiles <.001). Increased glycemic load was associated with similar detriments in recurrence-free (P trend across quintiles <.001) and overall survival (P trend across quintiles <.001). These associations differed statistically significant by body mass index (BMI) (P interaction =.01). Whereas glycemic load was not associated with disease-free survival in patients with BMI < 25kg/m2, higher glycemic load was statistically significant associated with worse disease-free survival among overweight or obese participants (BMI ≥ 25kg/m2; HR = 2.26; 95% CI = 1.53 to 3.32; P trend across quintiles <.001). Increasing total carbohydrate intake was similarly associated with inferior disease-free, recurrence-free, and overall survival (P trend across quintiles <.001). Conclusion Higher dietary glycemic load and total carbohydrate intake were statistically significant associated with an increased risk of recurrence and mortality in stage III colon cancer patients. These findings support the role of energy balance factors in colon cancer progression and may offer potential opportunities to improve patient survival. PMID:23136358

  16. p27Kip1 in Stage III Colon Cancer: Implications for Outcome Following Adjuvant Chemotherapy in CALGB 89803

    PubMed Central

    Bertagnolli, Monica M.; Warren, Robert S.; Niedzwiecki, Donna; Mueller, Elke; Compton, Carolyn C.; Redston, Mark; Hall, Margaret; Hahn, Hejin P.; Jewell, Scott D.; Mayer, Robert J.; Goldberg, Richard M.; Saltz, Leonard B.; Loda, Massimo

    2010-01-01

    Background In retrospective studies, loss of p27Kip1 (p27), a cyclin dependent kinase inhibitor, has been associated with poor prognosis following colorectal cancer treatment. In a prospective study, we validated this relationship in patients enrolled on a trial of adjuvant chemotherapy for Stage III colon cancer. Methods Cancer and Leukemia Group B (CALGB) protocol 89803 randomized 1264 stage III colon cancer patients to receive weekly bolus fluorouracil/leucovorin (5FU/LV) or weekly bolus irinotecan, fluorouracil, and leucovorin (IFL). The primary endpoint was overall survival (OS); disease-free survival (DFS) was a secondary endpoint. Expression of p27 and DNA mismatch repair (MMR) proteins were determined by immunohistochemistry (IHC) in primary tumor and normal tissue from paraffin blocks. Data were analyzed using logrank test. Results Of 601 tumors analyzed, 207 (34.4%) demonstrated p27 loss, 377 (62.8%) retained p27, and 17 (2.8%) were indeterminate. Patients with p27 negative tumors showed reduced OS (5-year 66%; 95%CI 0.59-0.72 vs. 75%; 95%CI 0.70-0.79, logrank p=0.021). This relationship was not influenced by treatment arm. Combination of p27 status with MMR status, however, identified a small subset of patients that may benefit from IFL (n=36; 5-year DFS 81%; 95%CI 0.64-0.98 vs. 47%; 95%CI 0.21-0.72, logrank p=0.042; 5-year OS 81%; 95%CI 0.64-0.98 vs. 60%; 95%CI 0.35-0.85; logrank p=0.128). Conclusions Loss of p27 is associated with reduced survival in stage III colon cancer, but by itself does not indicate a significant difference in outcome between patients treated IFL or 5FU-LV. PMID:19276255

  17. Predictive and Prognostic Roles of BRAF Mutation in Stage III Colon Cancer: Results from Intergroup Trial CALGB 89803

    PubMed Central

    Ogino, Shuji; Shima, Kaori; Meyerhardt, Jeffrey A.; McCleary, Nadine J.; Ng, Kimmie; Hollis, Donna; Saltz, Leonard B.; Mayer, Robert J.; Schaefer, Paul; Whittom, Renaud; Hantel, Alexander; Benson, Al B.; Spiegelman, Donna; Goldberg, Richard M.; Bertagnolli, Monica M.; Fuchs, Charles S.

    2011-01-01

    Purpose Alterations in the RAS-RAF-MAP2K (MEK)-MAPK signaling pathway are major drivers in colon and rectal carcinogenesis. In colorectal cancer, BRAF mutation is associated with microsatellite instability (MSI), and typically predicts inferior prognosis. We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer. Methods We assessed status of BRAF c.1799T>A (p.V600E) mutation and MSI in 506 stage III colon cancer patients enrolled in a randomized adjuvant chemotherapy trial [5-fluorouracil and leucovorin (FU/LV) vs. irinotecan (CPT11), FU and LV (IFL); CALGB 89803]. Cox proportional hazards model was used to assess the prognostic role of BRAF mutation, adjusting for clinical features, adjuvant chemotherapy arm and MSI status. Results Compared to 431 BRAF-wild-type patients, 75 BRAF-mutated patients experienced significantly worse overall survival [OS; log-rank p=0.015; multivariate hazard ratio (HR)=1.66; 95% confidence interval (CI), 1.05-2.63]. By assessing combined status of BRAF and MSI, it appeared that BRAF-mutated MSS (microsatellite stable) tumor was an unfavorable subtype, while BRAF-wild-type MSI-high tumor was a favorable subtype, and BRAF-mutated MSI-high tumor and BRAF-wild-type MSS tumor were intermediate subtypes. Among patients with BRAF-mutated tumors, a non-significant trend toward improved OS was observed for IFL vs. FU/LV arm (multivariate HR=0.52; 95% CI, 0.25-1.10). Among patients with BRAF-wild-type cancer, IFL conferred no suggestion of benefit beyond FU/LV alone (multivariate HR=1.02; 95% CI, 0.72-1.46). Conclusions BRAF mutation is associated with inferior survival in stage III colon cancer. Additional studies are necessary to assess whether there is any predictive role of BRAF mutation for irinotecan-based therapy. PMID:22147942

  18. [Postoperative Adjuvant Chemotherapy for Stage III Colon Cancer--Drug Selection, Tolerability, and Safety in Clinical Practice].

    PubMed

    Okada, Kazutake; Sadahiro, Sotaro; Saito, Gota; Tanaka, Akira; Suzuki, Toshiyuki

    2016-05-01

    In the National Comprehensive Cancer Network (NCCN) guidelines, oxaliplatin (L-OHP)-based chemotherapeutic regimens, including 5-fluorouracil, Leucovorin (LV), and L-OHP (FOLFOX); capecitabine and L-OHP (CapeOX); and 5-fluorouracil, folinic acid, and L-OHP (FLOX) are designated as category 1 recommendations for postoperative adjuvant chemotherapy in Stage III colon cancer, followed by capecitabine and 5-fluorouracil plus LV as category 2A recommendations. We studied the selection of drugs for adjuvant chemotherapy and assessed the tolerability and safety of CapeOX and tegafur-uracil (UFT) plus LV (UFT/LV) in patients with Stage III colon cancer. The study group included 104 consecutive patients with Stage III colon cancer who underwent curative surgery. One patient changed hospitals immediately after surgery. Among the remaining 103 patients, 82 (80%) received adjuvant chemotherapy and 21 (20%) did not. CapeOX was administered to 32 patients (31%), UFT/LV to 49 patients (48%), and capecitabine to 1 patient (1%). In 59 patients, the treatment choice was determined according to the patient's preference; 32 patients (54%) selected CapeOX, 26 (44%) selected UFT/LV, and 1 (2%) selected no chemotherapy. The treatment completion rate was 80% for CapeOX and 84% for UFT/LV. Among patients who completed chemotherapy, dose reduction and drug withdrawal were not required in 22% of patients who received CapeOX and 80% of those who received UFT/LV. Neither CapeOX nor UFT/LV was associated with any serious adverse events. The tolerability and safety of CapeOX and UFT/LV were acceptable. However, CapeOX dose had to be carefully adjusted according to each patient's condition.

  19. A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Harris, Jeremy P.; Murphy, James D.; Hanlon, Alexandra L.; Le, Quynh-Thu; Loo, Billy W.; Diehn, Maximilian

    2014-03-15

    Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC from 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT.

  20. Mitigation of effects of extreme drought during stage III of peach fruit development by summer pruning and fruit thinning.

    PubMed

    Lopez, Gerardo; Mata, Mercè; Arbones, Amadeu; Solans, Josep R; Girona, Joan; Marsal, Jordi

    2006-04-01

    A water deficit during stage III of fruit growth was established with the aim of determining if it is possible to achieve an improvement in tree water status by summer pruning and fruit thinning. The experiment was set up as a randomized block split-plot design across trials (irrigation) where pruning was assigned to the main plot and fruit thinning to the sub-plots. The irrigation treatments were (1) standard full irrigation (FI), and (2) suppression of irrigation during stage III of fruit growth until leaves visibly withered (LWI); the pruning treatments were (1) experimental summer pruning (EP), and (2) standard summer pruning (CP); and three fruit thinning intensities were applied to facilitate analysis of the effects of the treatments in relation to fruit load. Changes in amount of light intercepted and in tree stem water potential (Psi stem) were evaluated. The EP treatment reduced the amount of light intercepted by the tree. In the FI treatment, there was a significant reduction in fruit growth measured as both water accumulation and dry mass accumulation. Under FI conditions, reductions in fruit load as a result of EP were not accompanied by a significant improvement in Psi stem. In the LWI treatment, EP produced a significant improvement of 0.17 MPa in Psi stem, but there was no improvement in fruit growth compared with CP trees. A reduction in fruit load from 350 (commercial load) to 150 per tree significantly improved Psi stem by 0.3 MPa at the end of stage III of fruit growth. These results indicate that improvements in water status in response to pruning may be insufficient to promote fruit growth if the pruned trees are unable to provide an adequate supply of assimilates to the developing fruits.

  1. ESCRT-III drives the final stages of CUPS maturation for unconventional protein secretion

    PubMed Central

    Curwin, Amy J; Brouwers, Nathalie; Alonso Y Adell, Manuel; Teis, David; Turacchio, Gabriele; Parashuraman, Seetharaman; Ronchi, Paolo; Malhotra, Vivek

    2016-01-01

    The unconventional secretory pathway exports proteins that bypass the endoplasmic reticulum. In Saccharomyces cerevisiae, conditions that trigger Acb1 secretion via this pathway generate a Grh1 containing compartment composed of vesicles and tubules surrounded by a cup-shaped membrane and collectively called CUPS. Here we report a quantitative assay for Acb1 secretion that reveals requirements for ESCRT-I, -II, and -III but, surprisingly, without the involvement of the Vps4 AAA-ATPase. The major ESCRT-III subunit Snf7 localizes transiently to CUPS and this was accelerated in vps4Δ cells, correlating with increased Acb1 secretion. Microscopic analysis suggests that, instead of forming intraluminal vesicles with the help of Vps4, ESCRT-III/Snf7 promotes direct engulfment of preexisting Grh1 containing vesicles and tubules into a saccule to generate a mature Acb1 containing compartment. This novel multivesicular / multilamellar compartment, we suggest represents the stable secretory form of CUPS that is competent for the release of Acb1 to cells exterior. DOI: http://dx.doi.org/10.7554/eLife.16299.001 PMID:27115345

  2. Randomized Phase III Trial of Concurrent Accelerated Radiation Plus Cisplatin With or Without Cetuximab for Stage III to IV Head and Neck Carcinoma: RTOG 0522

    PubMed Central

    Ang, K. Kian; Zhang, Qiang; Rosenthal, David I.; Nguyen-Tan, Phuc Felix; Sherman, Eric J.; Weber, Randal S.; Galvin, James M.; Bonner, James A.; Harris, Jonathan; El-Naggar, Adel K.; Gillison, Maura L.; Jordan, Richard C.; Konski, Andre A.; Thorstad, Wade L.; Trotti, Andy; Beitler, Jonathan J.; Garden, Adam S.; Spanos, William J.; Yom, Sue S.; Axelrod, Rita S.

    2014-01-01

    Purpose Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS). Patients and Methods Eligible patients with stage III or IV HNC were randomly assigned to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Acute and late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). Outcomes were correlated with patient and tumor features and markers. Results Of 891 analyzed patients, 630 were alive at analysis (median follow-up, 3.8 years). Cetuximab plus cisplatin-radiation, versus cisplatin-radiation alone, resulted in more frequent interruptions in radiation therapy (26.9% v 15.1%, respectively); similar cisplatin delivery (mean, 185.7 mg/m2 v 191.1 mg/m2, respectively); and more grade 3 to 4 radiation mucositis (43.2% v 33.3%, respectively), rash, fatigue, anorexia, and hypokalemia, but not more late toxicity. No differences were found between arms A and B in 30-day mortality (1.8% v 2.0%, respectively; P = .81), 3-year PFS (61.2% v 58.9%, respectively; P = .76), 3-year OS (72.9% v 75.8%, respectively; P = .32), locoregional failure (19.9% v 25.9%, respectively; P = .97), or distant metastasis (13.0% v 9.7%, respectively; P = .08). Patients with p16-positive oropharyngeal carcinoma (OPC), compared with patients with p16-negative OPC, had better 3-year probability of PFS (72.8% v 49.2%, respectively; P < .001) and OS (85.6% v 60.1%, respectively; P < .001), but tumor epidermal growth factor receptor (EGFR) expression did not distinguish outcome. Conclusion Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS

  3. Discovery of HDAC Inhibitors with Potent Activity Against Multiple Malaria Parasite Life Cycle Stages

    PubMed Central

    Hansen, Finn K.; Sumanadasa, Subathdrage D. M.; Stenzel, Katharina; Duffy, Sandra; Meister, Stephan; Marek, Linda; Schmetter, Rebekka; Kuna, Krystina; Hamacher, Alexandra; Mordmüller, Benjamin; Kassack, Matthias U.; Winzeler, Elizabeth A.; Avery, Vicky M.; Andrews, Katherine T.; Kurz, Thomas

    2015-01-01

    In this work we investigated the antiplasmodial activity of a series of HDAC inhibitors containing an alkoxyamide connecting-unit linker region. HDAC inhibitor 1a (LMK235), previously shown to be a novel and specific inhibitor of human HDAC4 and 5, was used as a starting point to rapidly construct a mini-library of HDAC inhibitors using a straightforward solid-phase supported synthesis. Several of these novel HDAC inhibitors were found to have potent in vitro activity against asexual stage P. falciparum malaria parasites. Representative compounds were shown to hyperacetylate P. falciparum histones and to inhibit deacetylase activity of recombinant PfHDAC1 and P. falciparum nuclear extracts. All compounds were also screened in vitro for activity against P. berghei exo-erythrocytic stages and selected compounds were further tested against late stage (IV and V) P. falciparum gametocytes. Of note, some compounds showed nanomolar activity against all three life cycle stages tested (asexual, exo-erythrocytic and gametocyte stages) and several compounds displayed significantly increased parasite selectivity compared to the reference HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). These data suggest that it may be possible to develop HDAC inhibitors that target multiple malaria parasite life cycle stages. PMID:24904967

  4. Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-01-07

    Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Breast Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Breast Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Breast Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Breast Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  5. Epoetin alfa improves survival after chemoradiation for Stage III esophageal cancer: Final results of a prospective observational study

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Tribius, Silke; Yekebas, Emre F.; Bahrehmand, Roia; Wildfang, Ingeborg; Kilic, Ergin; Muellerleile, Ulrich; Gross, Eberhard; Schild, Steven E.; Alberti, Winfried

    2006-06-01

    Purpose: This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC). Methods and Materials: Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT. Results: Both groups were balanced for age, sex, performance status, tumor length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09). Conclusions: The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.

  6. Prognostic value of BRAF and KRAS mutation status in stage II and III microsatellite instable colon cancers.

    PubMed

    de Cuba, E M V; Snaebjornsson, P; Heideman, D A M; van Grieken, N C T; Bosch, L J W; Fijneman, R J A; Belt, E; Bril, H; Stockmann, H B A C; Hooijberg, E; Punt, C J A; Koopman, M; Nagtegaal, I D; Coupé, V H M; Carvalho, B; Meijer, G A

    2016-03-01

    Microsatellite instability (MSI) has been associated with favourable survival in early stage colorectal cancer (CRC) compared to microsatellite stable (MSS) CRC. The BRAF V600E mutation has been associated with worse survival in MSS CRC. This mutation occurs in 40% of MSI CRC and it is unclear whether it confers worse survival in this setting. The prognostic value of KRAS mutations in both MSS and MSI CRC remains unclear. We examined the effect of BRAF and KRAS mutations on survival in stage II and III MSI colon cancer patients. BRAF exon 15 and KRAS exon 2-3 mutation status was assessed in 143 stage II (n = 85) and III (n = 58) MSI colon cancers by high resolution melting analysis and sequencing. The relation between mutation status and cancer-specific (CSS) and overall survival (OS) was analyzed using Kaplan-Meier and Cox regression analysis. BRAF V600E mutations were observed in 51% (n = 73) and KRAS mutations in 16% of cases (n = 23). Patients with double wild-type cancers (dWT; i.e., BRAF and KRAS wild-type) had a highly favourable survival with 5-year CSS of 93% (95% CI 84-100%), while patients with cancers harbouring mutations in either BRAF or KRAS, had 5-year CSS of 76% (95% CI 67-85%). In the subgroup of stage II patients with dWT cancers no cancer-specific deaths were observed. On multivariate analysis, mutation in either BRAF or KRAS vs. dWT remained significantly prognostic. Mutations in BRAF as well as KRAS should be analyzed when considering these genes as prognostic markers in MSI colon cancers.

  7. Removal of River-Stage Fluctuations from Well Response Using Multiple-Regression

    SciTech Connect

    Spane, Frank A.; Mackley, Rob D.

    2011-11-01

    Many contaminated unconfined aquifers are located in proximity to river systems. In groundwater studies, the physical presence of a river is commonly represented as a transient-head boundary that imposes hydrologic responses within the intersected unconfined aquifer. The periodic fluctuation of river-stage height at the boundary produces associated responses within the adjacent aquifer system, the magnitude of which is a function of the existing well, aquifer, boundary conditions, and river-stage fluctuation characteristics. The presence of well responses induced by the river stage can significantly limit characterization and monitoring of remedial activities within the stress-impacted area. This paper demonstrates the use of a time-domain, multiple-regression, convolution (superposition) method to develop well/aquifer river response function (RRF) relationships. Following RRF development, a multiple-regression deconvolution correction approach can be applied to remove river-stage effects from well water-level responses. Corrected well responses can then be analyzed to improve local aquifer characterization activities in support of optimizing remedial actions, assessing the area-of-influence of remediation activities, and determining mean groundwater flow and contaminant flux to the river system.

  8. Removal of river-stage fluctuations from well response using multiple regression.

    PubMed

    Spane, Frank A; Mackley, Rob D

    2011-01-01

    Many contaminated unconfined aquifers are located in proximity to river systems. In groundwater studies, the physical presence of a river is commonly represented as a transient-head boundary that imposes hydrologic responses within the intersected unconfined aquifer. The periodic fluctuation of river-stage height at the boundary produces associated responses within the adjacent aquifer system, the magnitude of which is a function of the existing well, aquifer, boundary conditions, and characteristics of river-stage fluctuations. The presence of well responses induced by the river stage can significantly limit characterization and monitoring of remedial activities within the stress-impacted area. This article demonstrates the use of a time-domain, multiple-regression, convolution (superposition) method to develop well/aquifer river response function (RRF) relationships. Following RRF development, a multiple-regression deconvolution correction approach can be applied to remove river-stage effects from well water-level responses. Corrected well responses can then be analyzed to improve local aquifer characterization activities in support of optimizing remedial actions, assessing the area-of-influence of remediation activities, and determining mean groundwater flow and contaminant flux to the river system.

  9. Dosimetric evaluation of a simple planning method for improving intensity-modulated radiotherapy for stage III lung cancer

    PubMed Central

    Lu, Jia-Yang; Lin, Zhu; Zheng, Jing; Lin, Pei-Xian; Cheung, Michael Lok-Man; Huang, Bao-Tian

    2016-01-01

    This study aimed to evaluate the dosimetric outcomes of a base-dose-plan-compensation (BDPC) planning method for improving intensity-modulated radiotherapy (IMRT) for stage III lung cancer. For each of the thirteen included patients, three types of planning methods were applied to obtain clinically acceptable plans: (1) the conventional optimization method (CO); (2) a split-target optimization method (STO), in which the optimization objectives were set higher dose for the target with lung density; (3) the BDPC method, which compensated for the optimization-convergence error by further optimization based on the CO plan. The CO, STO and BDPC methods were then compared regarding conformity index (CI), homogeneity index (HI) of the target, organs at risk (OARs) sparing and monitor units (MUs). The BDPC method provided better HI/CI by 54%/7% on average compared to the CO method and by 38%/3% compared to the STO method. The BDPC method also spared most of the OARs by up to 9%. The average MUs of the CO, STO and BDPC plans were 890, 937 and 1023, respectively. Our results indicated that the BDPC method can effectively improve the dose distribution in IMRT for stage III lung cancer, at the expense of more MUs. PMID:27009235

  10. Distribution of Resistant Esophageal Adenocarcinoma in the Resected Specimens of Clinical Stage III Patients After Chemoradiation: Its Clinical Implications

    PubMed Central

    Neishaboori, Nastaran; Wadhwa, Roopma; Nogueras-González, Graciela M.; Elimova, Elena; Shiozaki, Hironori; Sudo, Kazuki; Charalampakis, Nikolaos; Hiremath, Adarsh; Lee, Jeffrey H.; Bhutani, Manoop S.; Weston, Brian; Blum, Mariela A.; Rogers, Jane E.; Garris, Jeana L.; Rice, David C.; Komaki, Ritsuko; Swisher, Stephen G.; Skinner, Heath D.; Hofstetter, Wayne L.; Ajani, Jaffer A.

    2015-01-01

    Background We have limited knowledge of the geographic distribution of resistant EAC in the resected specimen and its clinical importance can be enormous. Method We selected patients with baseline stage III EAC who had chemoradiation followed by surgery, and had residual EAC (resistant cases only). Outcomes were correlated with various endpoints (% of resistant EAC, anatomic distribution). Results 100 clinical stage III patients were studied. 90% had an R0 resection. 99% had either moderate or poorly differentiated EAC. 12% had >50% residual cancer, 31% had 11–50% residual cancer, 53% had 1–10% residual cancer, and 3% had positive nodes only. Each compartment was frequently involved: mucosa/submucosa=66%, muscularis propria=76%, serosa=62%, and all=35%. Lack of EAC (meaning response) was observed in mucosa/submucosa (34%), muscularis propria (24%), serosa (38%), and nodes (42%). Although the endoscopic biopsies prior to surgery had no EAC in 79% of patients, in the surgical specimen, however, resistant EAC was frequent (66%) in mucosa/submucosa. Conclusion Contrary to our belief that resistant EAC would be frequent in the nodes, our data show that its distribution is heterogeneous and unpredictable. Most importantly, the post-chemoradiation biopsies are misleading and a decision to delay/avoid surgery based on negative biopsies can be detrimental for the patients. PMID:25765719

  11. Pathologic changes of wound tissue in rats with stage III pressure ulcers treated by transplantation of human amniotic epithelial cells.

    PubMed

    Zheng, Xilan; Jiang, Zhixia; Zhou, Aiting; Yu, Limei; Quan, Mingtao; Cheng, Huagang

    2015-01-01

    This study aims to determine the impact of orthotopic transplantation of human amniotic epithelial cells (hAECs) on the pathologic changes of wound tissues in a self-prepared rat stage III pressure ulcer model. Ninety-six SD rats were randomly divided into the model group (group M), hAEC transplantation group (group H), traditional treatment group (group T), and the control group (group C), with 24 rats in each group. The wound healing time was observed in 6 rats from each group, and 6 rats of each group were selected for post-modeling on day(s) (D) 1, 3, and 7 for HE staining to compare the pathological changes. The healing time of group H was significantly shorter than the other three groups. Moreover, pathological observations revealed that group H exhibited significant proliferation of fibrous tissues and vessels in the dermal layer, and the appearance time and degree of skin appendages were significantly greater than that observed in the other three groups. Pathological observations showed that hAEC transplantation could significantly speed up the healing of stage III pressure ulcer.

  12. Dosimetric evaluation of a simple planning method for improving intensity-modulated radiotherapy for stage III lung cancer.

    PubMed

    Lu, Jia-Yang; Lin, Zhu; Zheng, Jing; Lin, Pei-Xian; Cheung, Michael Lok-Man; Huang, Bao-Tian

    2016-01-01

    This study aimed to evaluate the dosimetric outcomes of a base-dose-plan-compensation (BDPC) planning method for improving intensity-modulated radiotherapy (IMRT) for stage III lung cancer. For each of the thirteen included patients, three types of planning methods were applied to obtain clinically acceptable plans: (1) the conventional optimization method (CO); (2) a split-target optimization method (STO), in which the optimization objectives were set higher dose for the target with lung density; (3) the BDPC method, which compensated for the optimization-convergence error by further optimization based on the CO plan. The CO, STO and BDPC methods were then compared regarding conformity index (CI), homogeneity index (HI) of the target, organs at risk (OARs) sparing and monitor units (MUs). The BDPC method provided better HI/CI by 54%/7% on average compared to the CO method and by 38%/3% compared to the STO method. The BDPC method also spared most of the OARs by up to 9%. The average MUs of the CO, STO and BDPC plans were 890, 937 and 1023, respectively. Our results indicated that the BDPC method can effectively improve the dose distribution in IMRT for stage III lung cancer, at the expense of more MUs. PMID:27009235

  13. Improved five year survival after combined radiotherapy-chemotherapy for Stage I-II non-Hodgkin's lymphoma

    SciTech Connect

    Monfardini, S.; Banfi, A.; Bonadonna, G.; Rilke, F.; Milani, F.; Valagussa, P.; Lattuada, A.

    1980-02-01

    In order to improve the prognosis of patients with localized non-Hodgkin's lymphomas (NHL) who are treated with radiotherapy (RT), a prospective controlled study utilizing a combined modality approach was carried out in patients with pathologic Stage I-II NHL. After treatment with regional RT, patients in complete remission were randomized to receive either no further therapy or 6 cycles of cyclophosphamide, vincristine and prednisolone (CVP). At 5 years from completion of irradiation, the relapse-free survival was 46.3% after RT and 72.1% after RT plus CVP (P=0.005). The corresponding findings for the overall survival calculated from the beginning of irradiation were 55.8 and 82.8% respectively (P=0.03). The favorable effects of adjuvant chemotherapy on relapse-free survival were statistically significant only in the subgroup with diffuse histology. In patients who relapsed after RT alone, the salvage therapy failed to induce a high incidence of second durable remission. Adjuvant chemotherapy is indicated to improve the curve rate in pathologic stage I-II NHL with diffuse histology when regional RT is utilized.

  14. Dosimetric Feasibility of Dose Escalation Using SBRT Boost for Stage III Non-Small Cell Lung Cancer

    PubMed Central

    Hepel, Jaroslaw T.; Peter, Justin; Hiatt, Jessica R.; Patel, Salil; Osibanjo, Oluwademilade; Safran, Howard; Curran, Bruce; DiPetrillo, Thomas

    2012-01-01

    Purpose: Standard chemoradiation therapy for stage III non-small cell lung cancer (NSCLCa) results in suboptimal outcomes with a high rate of local failure and poor overall survival. We hypothesize that dose escalation using stereotactic body radiotherapy (SBRT) boost could improve upon these results. We present here a study evaluating the dosimetric feasibility of such an approach. Methods: Anonymized CT data sets from five randomly selected patients with stage III NSCLCa undergoing definitive chemoradiation therapy in our department with disease volumes appropriate for SBRT boost were selected. Three-dimensional conformal radiation therapy (3D-CRT) plans to 50.4 Gy in 28 fractions were generated follow by SBRT plans to two dose levels, 16 Gy in two fractions and 28 Gy in two fractions. SBRT plans and total composite (3D-CRT and SBRT) were optimized and evaluated for target coverage and dose to critical structures; lung, esophagus, cord, and heart. Results: All five plans met predetermined target coverage and normal tissue dose constraints. PTV V95 was equal to or greater than 95% in all cases. The cumulative lung V20 and V5 of the combined 3D-CRT and SBRT plans were less than or equal to 30 and 55%, respectively. The 5 cc esophageal dose was less than 12 Gy for all low and high dose SBRT plans. The cumulative dose to the esophagus was also acceptable with less than 10% of the esophagus receiving doses in excess of 50 Gy. The cumulative spinal cord dose was less than 33 Gy and heart V25 was less than 5%. Conclusion: The combination of chemoradiation to 50.4 Gy followed by SBRT boost to gross disease at the primary tumor and involved regional lymph nodes is feasible with respect to normal tissue dose constraints in this dosimetric pilot study. A phase I/II trial to evaluate the clinical safety and efficacy of this approach is being undertaken. PMID:23057009

  15. Genetic analysis of Upland cotton dynamic heterosis for boll number per plant at multiple developmental stages

    PubMed Central

    Shang, Lianguang; Wang, Yumei; Cai, Shihu; Ma, Lingling; Liu, Fang; Chen, Zhiwen; Su, Ying; Wang, Kunbo; Hua, Jinping

    2016-01-01

    Yield is an important breeding target. As important yield components, boll number per plant (BNP) shows dynamic character and strong heterosis in Upland cotton. However, the genetic basis underlying the dynamic heterosis is poorly understood. In this study, we conducted dynamic quantitative trait loci (QTL) analysis for BNP and heterosis at multiple developmental stages and environments using two recombinant inbred lines (RILs) and two corresponding backcross populations. By the single-locus analysis, 23 QTLs were identified at final maturity, while 99 QTLs were identified across other three developmental stages. A total of 48 conditional QTLs for BNP were identified for the adjacent stages. QTLs detected at later stage mainly existed in the partial dominance to dominance range and QTLs identified at early stage mostly showed effects with the dominance to overdominance range during plant development. By two-locus analysis, we observe that epistasis played an important role not only in the variation of the performance of the RIL population but also in the expression of heterosis in backcross population. Taken together, the present study reveals that the genetic basis of heterosis is dynamic and complicated, and it is involved in dynamic dominance effect, epistasis and QTL by environmental interactions. PMID:27748451

  16. Egg Size Effects across Multiple Life-History Stages in the Marine Annelid Hydroides diramphus

    PubMed Central

    Allen, Richard M.; Marshall, Dustin

    2014-01-01

    The optimal balance of reproductive effort between offspring size and number depends on the fitness of offspring size in a particular environment. The variable environments offspring experience, both among and within life-history stages, are likely to alter the offspring size/fitness relationship and favor different offspring sizes. Hence, the many environments experienced throughout complex life-histories present mothers with a significant challenge to optimally allocate their reproductive effort. In a marine annelid, we tested the relationship between egg size and performance across multiple life-history stages, including: fertilization, larval development, and post-metamorphosis survival and size in the field. We found evidence of conflicting effects of egg size on performance: larger eggs had higher fertilization under sperm-limited conditions, were slightly faster to develop pre-feeding, and were larger post-metamorphosis; however, smaller eggs had higher fertilization when sperm was abundant, and faster planktonic development; and egg size did not affect post-metamorphic survival. The results indicate that egg size effects are conflicting in H. diramphus depending on the environments within and among life-history stages. We suggest that offspring size in this species may be a compromise between the overall costs and benefits of egg sizes in each stage and that performance in any one stage is not maximized. PMID:25036850

  17. Investigation of X24C-2 10-Stage Axial-Flow Compressor. III - Surge Characteristics

    NASA Technical Reports Server (NTRS)

    Buckner, Howard A., Jr.; Downing, Richard M.

    1948-01-01

    Compressor operation at low air flows for a given speed is limited by unstable flow conditions, commonly called surge. An investigation of surge in centrifugal compressors (reference 1) showed that the pulsation of pressures and velocities occurred when the slope of the compressor characteristic curve was positive and that the magnitude and frequency, as well as the incidence of surge, depended on the capacity and resistance of the total system. Although the theory presented in reference 1 is applicable to axial-floe compressors, little experimental information is available on the surge characteristics of the individual stages of axial-flow compressors, or on the variation of the surge characteristics with operating conditions. During the investigation to determine the performance of the X24C-2 compressor (references 2 and 3), instrumentation was added to study the surge characteristics and to determine the effect of speed and inlet pressure on the frequency, amplitude, and phase relation of the pressure pulsations behind each stage.

  18. Prognostic indicators of laparotomy findings in clinical stage I-II supradiaphragmatic Hodgkin's disease.

    PubMed

    Leibenhaut, M H; Hoppe, R T; Efron, B; Halpern, J; Nelsen, T; Rosenberg, S A

    1989-01-01

    Between July 1968 and July 1986, 915 patients with clinical stage (CS) I and II Hodgkin's disease limited to sites above the diaphragm underwent laparotomy and splenectomy at Stanford University. Fifteen percent were CS I, of whom 76% had cervical/supraclavicular disease, 13% axillary disease, and 9% mediastinal presentations. CS I patients were more likely to be male, were significantly older, and were significantly less likely to have nodular sclerosis (NS) histology than CS II patients. Twenty percent of CS I patients and 30% of CS II patients were pathologically upstaged. No CS I patients were upstaged to pathological stage (PS) IV. Univariate and multivariate analyses of presenting clinical characteristics were performed to predict staging laparotomy findings. CS I women, CS I patients with mediastinal-only disease, and CS I men with either lymphocyte predominance or interfollicular histologies were at low risk for having disease below the diaphragm (5%) or requiring chemotherapy (0%). CS II women who were less than 27 years old and had only two or three sites of disease were also at low risk for upstaging (9%) or requiring chemotherapy (2%). Mixed cellularity histology and male gender were associated with increased risk for subdiaphragmatic disease and require laparotomy; the presence of systemic symptoms was not correlated with laparotomy findings. These results confirm the importance of performing staging laparotomy for the majority of patients who present with supradiaphragmatic Hodgkin's disease if treatment programs are based on the presence and extent of subdiaphragmatic disease. Selected subgroups are at low risk for subdiaphragmatic disease and might be spared laparotomy if they are treated with mantle, paraaortic, and splenic irradiation.

  19. Sleep stage classification by body movement index and respiratory interval indices using multiple radar sensors.

    PubMed

    Kagawa, Masayuki; Sasaki, Noriyuki; Suzumura, Kazuki; Matsui, Takemi

    2015-01-01

    Disturbed sleep has become more common in recent years. To increase the quality of sleep, undergoing sleep observation has gained interest as an attempt to resolve possible problems. In this paper, we evaluate a non-restrictive and non-contact method for classifying real-time sleep stages and report on its potential applications. The proposed system measures body movements and respiratory signals of a sleeping person using a multiple 24-GHz microwave radar placed beneath the mattress. We determined a body-movement index to identify wake and sleep periods, and fluctuation indices of respiratory intervals to identify sleep stages. For identifying wake and sleep periods, the rate agreement between the body-movement index and the reference result using the R&K method was 83.5 ± 6.3%. One-minute standard deviations, one of the fluctuation indices of respiratory intervals, had a high degree of contribution and showed a significant difference across the three sleep stages (REM, LIGHT, and DEEP; p <; 0.001). Although the degree that the 5-min fractal dimension contributed-another fluctuation index-was not as high as expected, its difference between REM and DEEP sleep was significant (p <; 0.05). We applied a linear discriminant function to classify wake or sleep periods and to estimate the three sleep stages. The accuracy was 79.3% for classification and 71.9% for estimation. This is a novel system for measuring body movements and body-surface movements that are induced by respiration and for measuring high sensitivity pulse waves using multiple radar signals. This method simplifies measurement of sleep stages and may be employed at nursing care facilities or by the general public to increase sleep quality.

  20. Sleep stage classification by body movement index and respiratory interval indices using multiple radar sensors.

    PubMed

    Kagawa, Masayuki; Sasaki, Noriyuki; Suzumura, Kazuki; Matsui, Takemi

    2015-01-01

    Disturbed sleep has become more common in recent years. To increase the quality of sleep, undergoing sleep observation has gained interest as an attempt to resolve possible problems. In this paper, we evaluate a non-restrictive and non-contact method for classifying real-time sleep stages and report on its potential applications. The proposed system measures body movements and respiratory signals of a sleeping person using a multiple 24-GHz microwave radar placed beneath the mattress. We determined a body-movement index to identify wake and sleep periods, and fluctuation indices of respiratory intervals to identify sleep stages. For identifying wake and sleep periods, the rate agreement between the body-movement index and the reference result using the R&K method was 83.5 ± 6.3%. One-minute standard deviations, one of the fluctuation indices of respiratory intervals, had a high degree of contribution and showed a significant difference across the three sleep stages (REM, LIGHT, and DEEP; p <; 0.001). Although the degree that the 5-min fractal dimension contributed-another fluctuation index-was not as high as expected, its difference between REM and DEEP sleep was significant (p <; 0.05). We applied a linear discriminant function to classify wake or sleep periods and to estimate the three sleep stages. The accuracy was 79.3% for classification and 71.9% for estimation. This is a novel system for measuring body movements and body-surface movements that are induced by respiration and for measuring high sensitivity pulse waves using multiple radar signals. This method simplifies measurement of sleep stages and may be employed at nursing care facilities or by the general public to increase sleep quality. PMID:26738053

  1. The role of postmastectomy radiotherapy in clinically node-positive, stage II-III breast cancer patients with pathological negative nodes after neoadjuvant chemotherapy: an analysis from the NCDB

    PubMed Central

    Jiang, Shuai; Jiang, Wen; Chen, Kai; Kim, Betty Y.S.; Liu, Qiang; Jacobs, Lisa K.

    2016-01-01

    Purpose The role of postmastectomy radiotherapy (PMRT) in clinically node-positive, stage II-III breast cancer patients with pathological negative nodes (ypN0) after neoadjuvant chemotherapy (NAC) remains controversial. Methods A total of 1560 clinically node-positive, stage II-III breast cancer patients treated with NAC and mastectomy who achieved ypN0 between 1998 and 2009 in the National Cancer Database were analyzed. The effects of PMRT on overall survival (OS) for the entire cohort and multiple subgroups were evaluated. Imputation and propensity score matching were used as sensitivity analyses to minimize biases. Results Of the entire 1560 eligible patients, 903 (57.9%) received PMRT and 657 (42.1%) didn’t. At a median follow-up of 56.0 months, no statistical difference was observed for OS between two groups by univariate and multivariate analyses (P = 0.120; HR 1.571, 95% CI 0.839-2.943). On subgroup analyses, PMRT significantly improved OS in patients with clinical stage IIIB/IIIC disease, T3/T4 tumor, or residual invasive breast cancer after NAC (P < 0.05). This improvement in OS remained significant after sensitivity analyses for the propensity score-matched patients. Conclusions This study demonstrated that PMRT showed a heterogeneous effect in clinically node-positive, stage II-III breast cancer patients with ypN0 following NAC. PMRT improved OS for patients with clinical stage IIIB/IIIC disease, T3/T4 tumor, or residual invasive breast tumor after NAC. In the absence of definitive conclusions from prospective studies, including the ongoing NSABP B-51 trial, our findings may help identify specific groups of women with clinically node-positive, stage II-III breast cancers who could benefit from PMRT after NAC. PMID:26709538

  2. Intravenous Chemotherapy or Oral Chemotherapy in Treating Patients With Previously Untreated Stage III-IV HIV-Associated Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-06-09

    AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma

  3. Comparison of toxicity and outcomes of concurrent radiotherapy with carboplatin/paclitaxel or cisplatin/etoposide in stage III non-small cell lung cancer.

    PubMed

    Liew, Mun Sem; Sia, Joseph; Starmans, Maud H W; Tafreshi, Ali; Harris, Sam; Feigen, Malcolm; White, Shane; Zimet, Allan; Lambin, Philippe; Boutros, Paul C; Mitchell, Paul; John, Thomas

    2013-12-01

    Concurrent chemoradiotherapy (CCRT) has become the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). The comparative merits of two widely used regimens: carboplatin/paclitaxel (PC) and cisplatin/etoposide (PE), each with concurrent radiotherapy, remain largely undefined. Records for consecutive patients with stage III NSCLC treated with PC or PE and ≥60 Gy chest radiotherapy between 2000 and 2011 were reviewed for outcomes and toxicity. Survival was estimated using the Kaplan-Meier method and Cox modeling with the Wald test. Comparison across groups was done using the student's t and chi-squared tests. Seventy-five (PC: 44, PE: 31) patients were analyzed. PC patients were older (median 71 vs. 63 years; P = 0.0006). Other characteristics were comparable between groups. With PE, there was significantly increased grade ≥3 neutropenia (39% vs. 14%, P = 0.024) and thrombocytopenia (10% vs. 0%, P = 0.039). Radiation pneumonitis was more common with PC (66% vs. 38%, P = 0.033). Five treatment-related deaths occurred (PC: 3 vs. PE: 2, P = 1.000). With a median follow-up of 51.6 months, there were no significant differences in relapse-free survival (median PC 12.0 vs. PE 11.5 months, P = 0.700) or overall survival (median PC 20.7 vs. PE 13.7 months; P = 0.989). In multivariate analyses, no factors predicted for improved survival for either regimen. PC was more likely to be used in elderly patients. Despite this, PC resulted in significantly less hematological toxicity but achieved similar survival outcomes as PE. PC is an acceptable CCRT regimen, especially in older patients with multiple comorbidities.

  4. Neurophysiological Evidence of Compensatory Brain Mechanisms in Early-Stage Multiple Sclerosis

    PubMed Central

    López-Góngora, Mariana; Escartín, Antonio; Martínez-Horta, Saul; Fernández-Bobadilla, Ramón; Querol, Luis; Romero, Sergio; Mañanas, Miquel Àngel; Riba, Jordi

    2015-01-01

    Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by white matter inflammation, demyelination and neurodegeneration. Although cognitive dysfunction is a common manifestation, it may go unnoticed in recently-diagnosed patients. Prior studies suggest MS patients develop compensatory mechanisms potentially involving enhanced performance monitoring. Here we assessed the performance monitoring system in early-stage MS patients using the error-related negativity (ERN), an event-related brain potential (ERP) observed following behavioral errors. Twenty-seven early-stage MS patients and 31 controls were neuropsychologically assessed. Electroencephalography recordings were obtained while participants performed: a) a stop task and b) an auditory oddball task. Behavior and ERP measures were assessed. No differences in performance were found between groups in most neuropsychological tests or in behavior or ERP components in the auditory oddball task. However, the amplitude of the ERN associated with stop errors in the stop task was significantly higher in patients. ERN amplitude correlated positively with scores on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and negatively with the time since last relapse. Patients showed higher neuronal recruitment in tasks involving performance monitoring. Results suggest the development of compensatory brain mechanisms in early-stage MS and reflect the sensitivity of the ERN to detect these changes. PMID:26322632

  5. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    SciTech Connect

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  6. Vitronectin and dermcidin serum levels predict the metastatic progression of AJCC I-II early-stage melanoma.

    PubMed

    Ortega-Martínez, Idoia; Gardeazabal, Jesús; Erramuzpe, Asier; Sanchez-Diez, Ana; Cortés, Jesús; García-Vázquez, María D; Pérez-Yarza, Gorka; Izu, Rosa; Luís Díaz-Ramón, Jose; de la Fuente, Ildefonso M; Asumendi, Aintzane; Boyano, María D

    2016-10-01

    Like many cancers, an early diagnosis of melanoma is fundamental to ensure a good prognosis, although an important proportion of stage I-II patients may still develop metastasis during follow-up. The aim of this work was to discover serum biomarkers in patients diagnosed with primary melanoma that identify those at a high risk of developing metastasis during the follow-up period. Proteomic and mass spectrophotometry analysis was performed on serum obtained from patients who developed metastasis during the first years after surgery for primary tumors and compared with that from patients who remained disease-free for more than 10 years after surgery. Five proteins were selected for validation as prognostic factors in 348 melanoma patients and 100 controls by ELISA: serum amyloid A and clusterin; immune system proteins; the cell adhesion molecules plakoglobin and vitronectin and the antimicrobial protein dermcidin. Compared to healthy controls, melanoma patients have high serum levels of these proteins at the moment of melanoma diagnosis, although the specific values were not related to the histopathological stage of the tumors. However, an analysis based on classification together with multivariate statistics showed that tumor stage, vitronectin and dermcidin levels were associated with the metastatic progression of patients with early-stage melanoma. Although melanoma patients have increased serum dermcidin levels, the REPTree classifier showed that levels of dermcidin <2.98 μg/ml predict metastasis in AJCC stage II patients. These data suggest that vitronectin and dermcidin are potent biomarkers of prognosis, which may help to improve the personalized medical care of melanoma patients and their survival. PMID:27216146

  7. Correlates of suicide and violence risk: III. A two-stage model of countervailing forces.

    PubMed

    Plutchik, R; van Praag, H M; Conte, H R

    1989-05-01

    Questionnaires and self-report scales were administered to 100 psychiatric inpatients. The scales measured such variables as depression, hopelessness, impulsivity, mental and life problems, family violence, personality characteristics, and dyscontrol tendencies. These were correlated with indices of suicide risk and violence risk. Most variables were found to correlate significantly with both suicide and violence risk. Partial correlation analyses revealed that 10 variables correlated significantly with suicide risk but not violence risk, while four variables correlated significantly with violence risk but not suicide risk. A two-stage model of countervailing forces, incorporating concepts from both psychoanalysis and ethology, is presented as a way of interpreting the results. PMID:2748772

  8. A new simple morphology-based risk score is prognostic in stage I/II colon cancers.

    PubMed

    Märkl, Bruno; Märkl, Maximilian; Schaller, Tina; Mayr, Patrick; Schenkirsch, Gerhard; Kriening, Bernadette; Anthuber, Matthias

    2016-07-01

    A portion of stage I/II colon cancers (10-20%) exhibit an adverse clinical course. The administration of adjuvant chemotherapy is recommended only in certain high-risk situations. However, these risk factors recently failed to predict benefit from adjuvant therapy. We composed a new morphology-based risk score that includes pT1/2 versus 3/4 stage, vascular or lymphovascular invasion, invasion type according to Jass, tumor budding and paucity (less than two) of lymph nodes larger than 5 mm. The occurrence of each of these factors accounts for one point in the score (Range 0-5). This score was evaluated in a retrospective study that included 301 cases. The overall survival differed significantly between the three groups with median survival times of 103, 90, and 48 months, respectively. Multivariable analysis revealed morphology-based risk-high risk and low risk-as the sole independent factors for the prediction of death. Morphology-based risk scoring was superior to microsatellite status and NCCN risk stratification. This method identifies a group of patients that comprises 18% of the stage II cases with an adverse clinical course. Further studies are necessary to confirm its prognostic value and the possible therapeutic consequences. PMID:27167601

  9. Subxiphoid and subcostal arch thoracoscopic extended thymectomy: a safe and feasible minimally invasive procedure for selective stage III thymomas

    PubMed Central

    Zhao, Jinbo; Wang, Juzheng; Zhao, Zhengwei; Han, Yong; Huang, Lijun; Li, Xiaofei

    2016-01-01

    Background Video-assisted thoracoscopic surgery (VATS) has been applied to resection of small and well-encapsulated thymomas. However, few data are available regarding to the application of VATS in stage III thymomas. Methods A novel subxiphoid and subcostal arch approach for thoracoscopic extended thymectomy was developed by us. From January 2014 to August 2015, 14 patients with stage III thymoma were treated by using this new technique in the Department of Thoracic Surgery, Tangdu hospital, Xi’an, China. These patients were retrospectively reviewed and analyzed. Results Among the 14 patients, 1 patient was converted to transsternal approach owning to invasion of the superior vena cava. The other 13 patients with thymomas invading the pericardium, lung tissues and left innominate vein (LIV), were successfully operated on by using this new technique. The average operation time was 120.0±32.7 min (80–170 min), the average volume of estimated blood loss was 51.5±44.8 min (10–150 mL) and the average postoperative hospital stay was 4.8±1.5 days (3-9 days). There was no perioperative death. Two patients suffered postoperative complications including one patient with atrial fibrillation (AF) and the other one with myasthenic crisis (MC). The postoperative pain score decreased dramatically from 3.8±1.0 [3–6] at 24 hours to 1.5±0.9 [0–6] at 48 hours, and finally to 0 at 3 months after surgery (P=0.000). The patients reported a higher cosmetic score of 92.6±2.7 [90–96]. There was no tumor recurrence and the five patients with myasthenia gravis had improvement and did not need any medication until follow-up. Conclusions Based on our limited experience, the subxiphoid and subcostal arch thoracoscopic extended thymectomy is safe and feasible for selective stage III thymoma, and might reduce the postoperative pain and provide satisfied cosmetic effect. PMID:27014472

  10. Sequential testing over multiple stages and performance analysis of data fusion

    NASA Astrophysics Data System (ADS)

    Thakur, Gaurav

    2013-05-01

    We describe a methodology for modeling the performance of decision-level data fusion between different sensor configurations, implemented as part of the JIEDDO Analytic Decision Engine (JADE). We first discuss a Bayesian network formulation of classical probabilistic data fusion, which allows elementary fusion structures to be stacked and analyzed efficiently. We then present an extension of the Wald sequential test for combining the outputs of the Bayesian network over time. We discuss an algorithm to compute its performance statistics and illustrate the approach on some examples. This variant of the sequential test involves multiple, distinct stages, where the evidence accumulated from each stage is carried over into the next one, and is motivated by a need to keep certain sensors in the network inactive unless triggered by other sensors.

  11. A novel multiple-stage antimalarial agent that inhibits protein synthesis

    NASA Astrophysics Data System (ADS)

    Baragaña, Beatriz; Hallyburton, Irene; Lee, Marcus C. S.; Norcross, Neil R.; Grimaldi, Raffaella; Otto, Thomas D.; Proto, William R.; Blagborough, Andrew M.; Meister, Stephan; Wirjanata, Grennady; Ruecker, Andrea; Upton, Leanna M.; Abraham, Tara S.; Almeida, Mariana J.; Pradhan, Anupam; Porzelle, Achim; Martínez, María Santos; Bolscher, Judith M.; Woodland, Andrew; Norval, Suzanne; Zuccotto, Fabio; Thomas, John; Simeons, Frederick; Stojanovski, Laste; Osuna-Cabello, Maria; Brock, Paddy M.; Churcher, Tom S.; Sala, Katarzyna A.; Zakutansky, Sara E.; Jiménez-Díaz, María Belén; Sanz, Laura Maria; Riley, Jennifer; Basak, Rajshekhar; Campbell, Michael; Avery, Vicky M.; Sauerwein, Robert W.; Dechering, Koen J.; Noviyanti, Rintis; Campo, Brice; Frearson, Julie A.; Angulo-Barturen, Iñigo; Ferrer-Bazaga, Santiago; Gamo, Francisco Javier; Wyatt, Paul G.; Leroy, Didier; Siegl, Peter; Delves, Michael J.; Kyle, Dennis E.; Wittlin, Sergio; Marfurt, Jutta; Price, Ric N.; Sinden, Robert E.; Winzeler, Elizabeth A.; Charman, Susan A.; Bebrevska, Lidiya; Gray, David W.; Campbell, Simon; Fairlamb, Alan H.; Willis, Paul A.; Rayner, Julian C.; Fidock, David A.; Read, Kevin D.; Gilbert, Ian H.

    2015-06-01

    There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.

  12. A novel multiple-stage antimalarial agent that inhibits protein synthesis.

    PubMed

    Baragaña, Beatriz; Hallyburton, Irene; Lee, Marcus C S; Norcross, Neil R; Grimaldi, Raffaella; Otto, Thomas D; Proto, William R; Blagborough, Andrew M; Meister, Stephan; Wirjanata, Grennady; Ruecker, Andrea; Upton, Leanna M; Abraham, Tara S; Almeida, Mariana J; Pradhan, Anupam; Porzelle, Achim; Martínez, María Santos; Bolscher, Judith M; Woodland, Andrew; Norval, Suzanne; Zuccotto, Fabio; Thomas, John; Simeons, Frederick; Stojanovski, Laste; Osuna-Cabello, Maria; Brock, Paddy M; Churcher, Tom S; Sala, Katarzyna A; Zakutansky, Sara E; Jiménez-Díaz, María Belén; Sanz, Laura Maria; Riley, Jennifer; Basak, Rajshekhar; Campbell, Michael; Avery, Vicky M; Sauerwein, Robert W; Dechering, Koen J; Noviyanti, Rintis; Campo, Brice; Frearson, Julie A; Angulo-Barturen, Iñigo; Ferrer-Bazaga, Santiago; Gamo, Francisco Javier; Wyatt, Paul G; Leroy, Didier; Siegl, Peter; Delves, Michael J; Kyle, Dennis E; Wittlin, Sergio; Marfurt, Jutta; Price, Ric N; Sinden, Robert E; Winzeler, Elizabeth A; Charman, Susan A; Bebrevska, Lidiya; Gray, David W; Campbell, Simon; Fairlamb, Alan H; Willis, Paul A; Rayner, Julian C; Fidock, David A; Read, Kevin D; Gilbert, Ian H

    2015-06-18

    There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.

  13. A novel multiple-stage antimalarial agent that inhibits protein synthesis

    PubMed Central

    Baragaña, Beatriz; Hallyburton, Irene; Lee, Marcus C. S.; Norcross, Neil R.; Grimaldi, Raffaella; Otto, Thomas D.; Proto, William R.; Blagborough, Andrew M.; Meister, Stephan; Wirjanata, Grennady; Ruecker, Andrea; Upton, Leanna M.; Abraham, Tara S.; Almeida, Mariana J.; Pradhan, Anupam; Porzelle, Achim; Martínez, María Santos; Bolscher, Judith M.; Woodland, Andrew; Norval, Suzanne; Zuccotto, Fabio; Thomas, John; Simeons, Frederick; Stojanovski, Laste; Osuna-Cabello, Maria; Brock, Paddy M.; Churcher, Tom S.; Sala, Katarzyna A.; Zakutansky, Sara E.; Jiménez-Díaz, María Belén; Sanz, Laura Maria; Riley, Jennifer; Basak, Rajshekhar; Campbell, Michael; Avery, Vicky M.; Sauerwein, Robert W; Dechering, Koen J.; Noviyanti, Rintis; Campo, Brice; Frearson, Julie A.; Angulo-Barturen, Iñigo; Ferrer-Bazaga, Santiago; Gamo, Francisco Javier; Wyatt, Paul G.; Leroy, Didier; Siegl, Peter; Delves, Michael J.; Kyle, Dennis E.; Wittlin, Sergio; Marfurt, Jutta; Price, Ric N.; Sinden, Robert E.; Winzeler, Elizabeth; Charman, Susan A.; Bebrevska, Lidiya; Gray, David W.; Campbell, Simon; Fairlamb, Alan H.; Willis, Paul; Rayner, Julian C.; Fidock, David A.; Read, Kevin D.; Gilbert, Ian H.

    2015-01-01

    Summary There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. We describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the parasite, with good pharmacokinetic properties, and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along mRNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery. PMID:26085270

  14. Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

    ClinicalTrials.gov

    2016-03-07

    Anxiety Disorder; Depression; Recurrent Breast 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

  15. Bevacizumab, Fluorouracil, Leucovorin Calcium, and Oxaliplatin Before Surgery in Treating Patients With Stage II-III Rectal Cancer

    ClinicalTrials.gov

    2015-10-24

    Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

  16. Interactive Gentle Yoga in Improving Quality of Life in Patients With Stage I-III Breast Cancer Undergoing Radiation Therapy

    ClinicalTrials.gov

    2015-02-03

    Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Fatigue; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  17. Heavy Metal Exposure in Predicting Peripheral Neuropathy in Patients With Stage I-III Breast Cancer Undergoing Chemotherapy

    ClinicalTrials.gov

    2015-05-01

    Male Breast Cancer; Neurotoxicity; Peripheral Neuropathy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  18. Strain preservation of experimental animals: vitrification of two-cell stage embryos for multiple mouse strains.

    PubMed

    Eto, Tomoo; Takahashi, Riichi; Kamisako, Tsutomu

    2015-04-01

    Strain preservation of experimental animals is crucial for experimental reproducibility. Maintaining complete animal strains, however, is costly and there is a risk for genetic mutations as well as complete loss due to disasters or illness. Therefore, the development of effective vitrification techniques for cryopreservation of multiple experimental animal strains is important. We examined whether a vitrification method using cryoprotectant solutions, P10 and PEPeS, is suitable for preservation of multiple inbred and outbred mouse strains. First, we investigated whether our vitrification method using cryoprotectant solutions was suitable for two-cell stage mouse embryos. In vitro development of embryos exposed to the cryoprotectant solutions was similar to that of fresh controls. Further, the survival rate of the vitrified embryos was extremely high (98.1%). Next, we collected and vitrified two-cell stage embryos of 14 mouse strains. The average number of embryos obtained from one female was 7.3-33.3. The survival rate of vitrified embryos ranged from 92.8% to 99.1%, with no significant differences among mouse strains. In vivo development did not differ significantly between fresh controls and vitrified embryos of each strain. For strain preservation using cryopreserved embryos, two offspring for inbred lines and one offspring for outbred lines must be produced from two-cell stage embryos collected from one female. The expected number of surviving fetuses obtained from embryos collected from one female of either the inbred or outbred strains ranged from 2.9 to 19.5. The findings of the present study indicated that this vitrification method is suitable for strain preservation of multiple mouse strains.

  19. 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

  20. Role of Postmastectomy Radiation After Neoadjuvant Chemotherapy in Stage II-III Breast Cancer

    SciTech Connect

    Fowble, Barbara L.; Einck, John P.; Kim, Danny N.; McCloskey, Susan; Mayadev, Jyoti; Yashar, Catheryn; Chen, Steven L.; Hwang, E. Shelley

    2012-06-01

    Purpose: To identify a cohort of women treated with neoadjuvant chemotherapy and mastectomy for whom postmastectomy radiation therapy (PMRT) may be omitted according to the projected risk of local-regional failure (LRF). Methods and Materials: Seven breast cancer physicians from University of California cancer centers created 14 hypothetical clinical case scenarios, identified, reviewed, and abstracted the available literature (MEDLINE and Cochrane databases), and formulated evidence tables with endpoints of LRF, disease-free survival, and overall survival. Using the American College of Radiology appropriateness criteria methodology, appropriateness ratings for postmastectomy radiation were assigned for each scenario. Finally, an overall summary risk assessment table was developed. Results: Of 24 sources identified, 23 were retrospective studies from single institutions. Consensus on the appropriateness rating, defined as 80% agreement in a category, was achieved for 86% of the cases. Distinct LRF risk categories emerged. Clinical stage II (T1-2N0-1) patients, aged >40 years, estrogen receptor-positive subtype, with pathologic complete response or 0-3 positive nodes without lymphovascular invasion or extracapsular extension, were identified as having {<=}10% risk of LRF without radiation. Limited data support stage IIIA patients with pathologic complete response as being low risk. Conclusions: In the absence of randomized trial results, existing data can be used to guide the use of PMRT in the neoadjuvant chemotherapy setting. Using available studies to inform appropriateness ratings for clinical scenarios, we found a high concordance of treatment recommendations for PMRT and were able to identify a cohort of women with a low risk of LRF without radiation. These low-risk patients will form the basis for future planned studies within University of California Athena Breast Health Network.

  1. Extensive hidradenitis suppurativa (HS) Hurly stage III disease treated with intravenous (IV) linezolid and meropenem with rapid remission.

    PubMed

    Scheinfeld, Noah

    2015-02-16

    A 57-year-old woman with Hurley Stage 3 hidradenitis suppurativa (HS) and multiple co-morbidities is presented. She had failed multiple antibiotic therapies and etanercept. She had end stage renal disease and was on dialysis. Her HS was put into remission with one month of daily IV treatment with 1.2 grams linezolid and 1 gram of meropenem, administered daily through her dialysis shunt. Unfortunately, her disease flared again two weeks after the cessation of the IV treatment. Nevertheless, more conventional therapy was then able to maintain her disease at a level that was significantly improved over baseline prior to the IV treatment. This case highlights above all a primary etiology of HS is stimulus of immune system's over-reaction in HS to the bacterial microbiome. If antibiotics are administered to a patient with stage 3 HS powerful enough to wipe out the bacterial biome, the immune system having no target retreats, permanent scarring in its wake and retreats to a certain but hardly permanent normalcy.

  2. Two-stage hierarchical group testing for multiple infections with application to the Infertility Prevention Project

    PubMed Central

    Tebbs, Joshua M.; McMahan, Christopher S.; Bilder, Christopher R.

    2015-01-01

    Summary Screening for sexually transmitted diseases has benefited greatly from the use of group testing (pooled testing) to lower costs. With the development of assays that detect multiple infections, screening practices now involve testing pools of individuals for multiple infections simultaneously. Building on the research for single infection group testing procedures, we examine the performance of group testing for multiple infections. Our work is motivated by chlamydia and gonorrhea testing for the Infertility Prevention Project (IPP), a national program in the United States. We consider a two-stage pooling algorithm currently used to perform testing for the IPP. We first derive the operating characteristics of this algorithm for classification purposes (e.g., expected number of tests, misclassification probabilities, etc.) and identify pool sizes that minimize the expected number of tests. We then develop an expectation-maximization algorithm to estimate probabilities of infection using both group and individual retest responses. Our research shows that group testing can offer large cost savings when classifying individuals for multiple infections and can provide prevalence estimates that are actually more efficient than those from individual testing. PMID:24117173

  3. Monolithic in-based III-V compound semiconductor focal plane array cell with single stage CCD output

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Inventor); Cunningham, Thomas J. (Inventor); Krabach, Timothy N. (Inventor); Staller, Craig O. (Inventor)

    1995-01-01

    A monolithic semiconductor imager includes an indium-based III-V compound semiconductor monolithic active layer of a first conductivity type, an array of plural focal plane cells on the active layer, each of the focal plane cells including a photogate over a top surface of the active layer, a readout circuit dedicated to the focal plane cell including plural transistors formed monolithically with the monolithic active layer and a single-stage charge coupled device formed monolithically with the active layer between the photogate and the readout circuit for transferring photo-generated charge accumulated beneath the photogate during an integration period to the readout circuit. The photogate includes thin epitaxial semiconductor layer of a second conductivity type overlying the active layer and an aperture electrode overlying a peripheral portion of the thin epitaxial semiconductor layer, the aperture electrode being connectable to a photogate bias voltage.

  4. Phase I-II clinical trial of Californium-252. Treatment of stage IB carcinoma of the cervix.

    PubMed

    Maruyama, Y; VanNagell, J R; Yoneda, J; Donaldson, E; Gallion, H; Rowley, K; Kryscio, R; Beach, J L

    1987-04-15

    Intracavitary Californium-252 combined with whole-pelvis photon radiotherapy was tested as the sole form of treatment for 22 patients with Stage IB carcinoma of the cervix. Californium-252 (Cf) is a fast neutron-emitting radioisotope currently being tested in trials of neutron brachytherapy (NT). The outcomes of the treated group of patients were traced for local tumor control, survival, patterns of failure, and complications. The Cf intracavitary therapy combined with whole-pelvis photon radiotherapy resulted in 95% 2-year and 91% 5-year actuarial survival. There were 9% Grade II-III complications by the Stockholm scale and 4% local failures. These results were obtained in an early clinical trial with a group of largely poor-risk patients with tumors of mean diameter of 4.3 cm.

  5. Monolithic in-based III-V compound semiconductor focal plane array cell with single stage CCD output

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Inventor); Cunningham, Thomas J. (Inventor); Krabach, Timothy N. (Inventor); Staller, Craig O. (Inventor)

    1994-01-01

    A monolithic semiconductor imager includes an indium-based III-V compound semiconductor monolithic active layer of a first conductivity type, an array of plural focal plane cells on the active layer, each of the focal plane cells including a photogate over a top surface of the active layer, a readout circuit dedicated to the focal plane cell including plural transistors formed monolithically with the monolithic active layer and a single-stage charge coupled device formed monolithically with the active layer between the photogate and the readout circuit for transferring photo-generated charge accumulated beneath the photogate during an integration period to the readout circuit. The photogate includes thin epitaxial semiconductor layer of a second conductivity type overlying the active layer and an aperture electrode overlying a peripheral portion of the thin epitaxial semiconductor layer, the aperture electrode being connectable to a photogate bias voltage.

  6. MGL ligand expression is correlated to BRAF mutation and associated with poor survival of stage III colon cancer patients

    PubMed Central

    Lenos, Kristiaan; Goos, Jeroen A.C.M.; Vuist, Ilona M.; den Uil, Sjoerd H.; Delis-van Diemen, Pien M.; Belt, Eric J.Th.; Stockmann, Hein B.A.C.; Bril, Herman; de Wit, Meike; Carvalho, Beatriz; Giblett, Susan; Pritchard, Catrin A.; Meijer, Gerrit A.; van Kooyk, Yvette; Fijneman, Remond J.A.; van Vliet, Sandra J.

    2015-01-01

    Colorectal cancer (CRC) is the third most prevalent cancer type worldwide with a mortality rate of approximately 50%. Elevated cell-surface expression of truncated carbohydrate structures such as Tn antigen (GalNAcα-Ser/Thr) is frequently observed during tumor progression. We have previously demonstrated that the C-type lectin macrophage galactose-type lectin (MGL), expressed by human antigen presenting cells, can distinguish healthy tissue from CRC through its specific recognition of Tn antigen. Both MGL binding and oncogenic BRAF mutations have been implicated in establishing an immunosuppressive microenvironment. Here we aimed to evaluate whether MGL ligand expression has prognostic value and whether this was correlated to BRAFV600E mutation status. Using a cohort of 386 colon cancer patients we demonstrate that high MGL binding to stage III tumors is associated with poor disease-free survival, independent of microsatellite instability or adjuvant chemotherapy. In vitro studies using CRC cell lines showed an association between MGL ligand expression and the presence of BRAFV600E. Administration of specific BRAFV600E inhibitors resulted in decreased expression of MGL-binding glycans. Moreover, a positive correlation between induction of BRAFV600E and MGL binding to epithelial cells of the gastrointestinal tract was found in vivo using an inducible BRAFV600E mouse model. We conclude that the BRAFV600E mutation induces MGL ligand expression, thereby providing a direct link between oncogenic transformation and aberrant expression of immunosuppressive glycans. The strong prognostic value of MGL ligands in stage III colon cancer patients, i.e. when tumor cells disseminate to lymph nodes, further supports the putative immune evasive role of MGL ligands in metastatic disease. PMID:26172302

  7. Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy

    SciTech Connect

    Pinkham, Mark B.; Foote, Matthew C.; Burmeister, Elizabeth; Thomas, Janine; Meakin, Janelle; Smithers, B. Mark; Burmeister, Bryan H.

    2013-07-15

    Purpose: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. Methods and Materials: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. Results: There were 121 patients who received adjuvant radiation therapy because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. Conclusions: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy.

  8. Overexpression of the S100A2 protein as a prognostic marker for patients with stage II and III colorectal cancer

    PubMed Central

    MASUDA, TAIKI; ISHIKAWA, TOSHIAKI; MOGUSHI, KAORU; OKAZAKI, SATOSHI; ISHIGURO, MEGUMI; IIDA, SATORU; MIZUSHIMA, HIROSHI; TANAKA, HIROSHI; UETAKE, HIROYUKI; SUGIHARA, KENICHI

    2016-01-01

    We aimed to identify a novel prognostic biomarker related to recurrence in stage II and III colorectal cancer (CRC) patients. Stage II and III CRC tissue mRNA expression was profiled using an Affymetrix Gene Chip, and copy number profiles of 125 patients were generated using an Affymetrix 250K Sty array. Genes showing both upregulated expression and copy number gains in cases involving recurrence were extracted as candidate biomarkers. The protein expression of the candidate gene was assessed using immunohistochemical staining of tissue from 161 patients. The relationship between protein expression and clinicopathological features was also examined. We identified 9 candidate genes related to recurrence of stage II and III CRC, whose mRNA expression was significantly higher in CRC than in normal tissue. Of these proteins, the S100 calcium-binding protein A2 (S100A2) has been observed in several human cancers. S100A2 protein overexpression in CRC cells was associated with significantly worse overall survival and relapse-free survival, indicating that S100A2 is an independent risk factor for stage II and III CRC recurrence. S100A2 overexpression in cancer cells could be a biomarker of poor prognosis in stage II and III CRC recurrence and a target for treatment of this disease. PMID:26783118

  9. The CYP19 RS4646 Polymorphism IS Related to the Prognosis of Stage I–II and Operable Stage III Breast Cancer

    PubMed Central

    Shao, Xiying; Guo, Yong; Xu, Xiaohong; Zheng, Yabing; Wang, Jiwen; Chen, Zhanhong; Huang, Jian; Huang, Ping; Cai, Jufen; Wang, Xiaojia

    2015-01-01

    Purpose Aromatase, encoded by the CYP19 gene, catalyzes the final step of the conversion of androgens to estrogens. Given the critical role of CYP19 in estrogen synthesis, the potential influence of CYP19 rs4646 polymorphism on breast cancer survival, deserves further study. Methods Genotyping for CYP19 rs4646 variants was performed on 406 Chinese women with stage I–II and operable stage III breast cancer. Associations were evaluated between CYP19 rs4646 genotypes and disease-free survival (DFS). Results In premenopausal patients, women who are homozygous for the minor allele (AA) have a longer DFS compared with those carrying the major allele (CC or AC) (87 months versus 48.7 months; Hazard ratio (HR) = 0.56, 95 % CI = 0.318-0.985, P = 0.041). These differences were further demonstrated by a multivariate analysis (HR = 0.456, 95 % CI = 0.249-0.836, P = 0.011). Conversely, the same variant (AA) was estimated to be associated with a poorer DFS in postmenopausal women (AA versus AC or CC: 13.7 months versus 56.3 months; HR = 2.758, 95 % CI = 1.432-5.313, P = 0.002). Furthermore, the differences were confirmed by the COX proportional hazards model (HR = 2.983, 95% CI =1.494-5.955, P = 0.002). Conclusions The present study indicates that CYP19 rs4646 polymorphism is related to DFS in early breast cancer and that the prognosis index of the homozygous for the minor allele (AA) may depend on menopause status. The findings are novel, if confirmed, rs4646 genotypes may provide useful information for routine management in breast cancer. PMID:25793413

  10. [Photodynamic therapy in combined treatment of stage III non-small cell lung carcinoma].

    PubMed

    Akopov, A L; Rusanov, A A; Molodtsova, V P; Chistiakov, I V; Kazakov, N V; Urtenova, M A; Rait, Makhmud; Papaian, G V

    2013-01-01

    The aim of the study was to evaluate the effectiveness of combined treatment of locally advanced lung cancer with the use of neoadjuvant chemotherapy and surgery with the use of pre- and intraoperative photodynamic therapy. 20 patients with IIIa (n=7) and IIIb (n=13) stage of non-small cell lung carcinoma were included. At the time of diagnosis the surgical treatment was decided to abstain because of the trachea invasion in 9 patients, wide mediastinal invasion in 2 patients and contralateral mediastinal lymph nodes metastases in 2 patients; pneumonectomy was not possible due to the poor respiratory function in 7 patients. Neoadjuvant therapy included 3 courses of chemotherapy and endobronchial photodynamic therapy. During the operation, along with the lung resection (pneumonectomy - 15, lobectomy - 5), photodynamic therapy of the resection margins were carried out. No adjuvant treatment was done. Preoperative treatment led to partial regress of the disease in all cases; the goal of surgery was the complete tumor removal. No complications of the photodynamic therapy were observed. 18 surgical interventions were radical and two non-complete microscopically (R1). Postoperative morbidity was 20%, one patient died due to massive gastrointestinal bleeding. The average follow-up period was 18 months: 19 patients were alive, of them 18 with no signs of the disease recurrence. The first experience of the combined use of neoadjuvant chemotherapy and surgery with pre- and intraoperative photodynamic therapy demonstrates safety and efficacy of the suggested treatment tactics. PMID:23612332

  11. A Novel Approach for Ganglioside Structural Analysis Based on Electrospray Multiple-Stage Mass Spectrometry

    PubMed Central

    Zamfir, Alina D.; Vukelić, Željka; Schneider, Andrea; Sisu, Eugen; Dinca, Nicolae; Ingendoh, Arnd

    2007-01-01

    A powerful method for detailed structural analysis based on electrospray ionization high-capacity ion-trap multiple-stage mass spectrometry (MS) is for the first time introduced in glycolipidomics. The method was optimized for accurate structural elucidation of human brain gangliosides and specifically applied to normal adult human hippocampus-associated structures. The multiple-stage MS experiments reported here allowed for a complete structural characterization of the oligosaccharide moiety of a GM1 ganglioside species. This was achieved by elucidating the sequence and identification of the GM1a structural isomer from the sialic acid attachment site at the neutral oligosaccharide chain. Moreover, the determination of the d18:1/18:0 sphingoid base/fatty acid composition of the ceramide moiety could be confirmed by this method. The novel protocol developed here proves high potential for rapid, reliable, and reproducible investigation of complex lipid-linked carbohydrates such as polysialylated gangliosides or species carrying some other groups that easily cleave off. PMID:17916791

  12. Multiple stages of learning in perceptual categorization: evidence and neurocomputational theory.

    PubMed

    Cantwell, George; Crossley, Matthew J; Ashby, F Gregory

    2015-12-01

    Virtually all current theories of category learning assume that humans learn new categories by gradually forming associations directly between stimuli and responses. In information-integration category-learning tasks, this purported process is thought to depend on procedural learning implemented via dopamine-dependent cortical-striatal synaptic plasticity. This article proposes a new, neurobiologically detailed model of procedural category learning that, unlike previous models, does not assume associations are made directly from stimulus to response. Rather, the traditional stimulus-response (S-R) models are replaced with a two-stage learning process. Multiple streams of evidence (behavioral, as well as anatomical and fMRI) are used as inspiration for the new model, which synthesizes evidence of multiple distinct cortical-striatal loops into a neurocomputational theory. An experiment is reported to test a priori predictions of the new model that: (1) recovery from a full reversal should be easier than learning new categories equated for difficulty, and (2) reversal learning in procedural tasks is mediated within the striatum via dopamine-dependent synaptic plasticity. The results confirm the predictions of the new two-stage model and are incompatible with existing S-R models.

  13. Multiple Xanthomonas euvesicatoria Type III Effectors Inhibit flg22-Triggered Immunity.

    PubMed

    Popov, Georgy; Fraiture, Malou; Brunner, Frederic; Sessa, Guido

    2016-08-01

    Xanthomonas euvesicatoria is the causal agent of bacterial spot disease in pepper and tomato. X. euvesicatoria bacteria interfere with plant cellular processes by injecting effector proteins into host cells through the type III secretion (T3S) system. About 35 T3S effectors have been identified in X. euvesicatoria 85-10, and a few of them were implicated in suppression of pattern-triggered immunity (PTI). We used an Arabidopsis thaliana pathogen-free protoplast-based assay to identify X. euvesicatoria 85-10 effectors that interfere with PTI signaling induced by the bacterial peptide flg22. Of 33 tested effectors, 17 inhibited activation of a PTI-inducible promoter. Among them, nine effectors also interfered with activation of an abscisic acid-inducible promoter. However, effectors that inhibited flg22-induced signaling did not affect phosphorylation of mitogen-activated protein (MAP) kinases acting downstream of flg22 perception. Further investigation of selected effectors revealed that XopAJ, XopE2, and XopF2 inhibited activation of a PTI-inducible promoter by the bacterial peptide elf18 in Arabidopsis protoplasts and by flg22 in tomato protoplasts. The effectors XopF2, XopE2, XopAP, XopAE, XopH, and XopAJ inhibited flg22-induced callose deposition in planta and enhanced disease symptoms caused by attenuated Pseudomonas syringae bacteria. Finally, selected effectors were found to localize to various plant subcellular compartments. These results indicate that X. euvesicatoria bacteria utilize multiple T3S effectors to suppress flg22-induced signaling acting downstream or in parallel to MAP kinase cascades and suggest they act through different molecular mechanisms. PMID:27529660

  14. Telomere Length in Predicting Toxicity in Older Patients With Stage III-IV Colorectal Cancer Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-03-01

    Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

  15. Two-Stage Path Planning Approach for Designing Multiple Spacecraft Reconfiguration Maneuvers

    NASA Technical Reports Server (NTRS)

    Aoude, Georges S.; How, Jonathan P.; Garcia, Ian M.

    2007-01-01

    The paper presents a two-stage approach for designing optimal reconfiguration maneuvers for multiple spacecraft. These maneuvers involve well-coordinated and highly-coupled motions of the entire fleet of spacecraft while satisfying an arbitrary number of constraints. This problem is particularly difficult because of the nonlinearity of the attitude dynamics, the non-convexity of some of the constraints, and the coupling between the positions and attitudes of all spacecraft. As a result, the trajectory design must be solved as a single 6N DOF problem instead of N separate 6 DOF problems. The first stage of the solution approach quickly provides a feasible initial solution by solving a simplified version without differential constraints using a bi-directional Rapidly-exploring Random Tree (RRT) planner. A transition algorithm then augments this guess with feasible dynamics that are propagated from the beginning to the end of the trajectory. The resulting output is a feasible initial guess to the complete optimal control problem that is discretized in the second stage using a Gauss pseudospectral method (GPM) and solved using an off-the-shelf nonlinear solver. This paper also places emphasis on the importance of the initialization step in pseudospectral methods in order to decrease their computation times and enable the solution of a more complex class of problems. Several examples are presented and discussed.

  16. Strong neutral spatial effects shape tree species distributions across life stages at multiple scales.

    PubMed

    Hu, Yue-Hua; Lan, Guo-Yu; Sha, Li-Qing; Cao, Min; Tang, Yong; Li, Yi-De; Xu, Da-Ping

    2012-01-01

    Traditionally, ecologists use lattice (regional summary) count data to simulate tree species distributions to explore species coexistence. However, no previous study has explicitly compared the difference between using lattice count and basal area data and analyzed species distributions at both individual species and community levels while simultaneously considering the combined scenarios of life stage and scale. In this study, we hypothesized that basal area data are more closely related to environmental variables than are count data because of strong environmental filtering effects. We also address the contribution of niche and the neutral (i.e., solely dependent on distance) factors to species distributions. Specifically, we separately modeled count data and basal area data while considering life stage and scale effects at the two levels with simultaneous autoregressive models and variation partitioning. A principal coordinates of neighbor matrix (PCNM) was used to model neutral spatial effects at the community level. The explained variations of species distribution data did not differ significantly between the two types of data at either the individual species level or the community level, indicating that the two types of data can be used nearly identically to model species distributions. Neutral spatial effects represented by spatial autoregressive parameters and the PCNM eigenfunctions drove species distributions on multiple scales, different life stages and individual species and community levels in this plot. We concluded that strong neutral spatial effects are the principal mechanisms underlying the species distributions and thus shape biodiversity spatial patterns. PMID:22666497

  17. Multi-PLL with two-stage fusion to mitigate ionospheric scintillation effects on GPS receivers

    NASA Astrophysics Data System (ADS)

    Xu, Rui; Liu, Zhizhao; Chen, Wu

    2015-07-01

    Ionospheric scintillation poses a great threat to the reliability and accuracy of Global Positioning System (GPS) in various applications. It can increase tracking errors of the phase-locked loop (PLL) in a GPS receiver and even cause the PLL loss of lock under severe scintillations. To mitigate the effect of scintillation on GPS receivers, especially to reduce the occurrence of loss of lock, a multi-PLL with two-stage fusion (i.e., tracking fusion and output fusion) is proposed in this paper. This algorithm integrates several parallel sub-PLLs with different loop parameters into one channel to track one GPS satellite's signal. Every sub-PLL has its own discriminator, loop filter, carrier numerical controlled oscillator, and a tracking fusion (i.e., the first stage fusion). The tracking fusion of each sub-PLL integrates the Doppler frequency measurements from all other sub-PLLs to detect the state of its own sub-PLL and feeds back reliable Doppler frequency measurements. Simultaneously, the tracking fusion outputs the Doppler frequency measurements to the second stage fusion (i.e., output fusion), which integrates the outputs from all tracking fusions to provide continuous and accurate Doppler frequency measurements for the following positioning/navigation estimator. Performances of the proposed algorithm are tested using real-world GPS data with different levels of scintillations and compared with results from single-PLLs. For three real-world scintillation cases (S4 = 0.26-1.1, σϕ = 0.05-1.49 rad, and average C/N0 = 41.2-45.7 dB Hz), the multi-PLL algorithm performs more robustly than the single-PLLs and is able to keep tracking in all scintillation cases.

  18. Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer

    ClinicalTrials.gov

    2016-10-04

    Estrogen Receptor Negative; HER2 Positive Breast Carcinoma; Progesterone Receptor Negative; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer

  19. Preoperative Lymphocyte-Monocyte Ratio Is a Predictor of Suboptimal Cytoreduction in Stage III-IV Epithelial Ovarian Cancer

    PubMed Central

    Eo, Wankyu; Kim, Hong-Bae; Lee, Yong Joo; Suh, Dong Soo; Kim, Ki Hyung; Kim, Heungyeol

    2016-01-01

    Objective: To determine whether the preoperative lymphocyte-monocyte ratio (LMR) is a predictor of suboptimal cytoreduction in advanced-stage epithelial ovarian cancer (EOC). Methods: Preoperative clinico-pathologic and hematologic parameters were reviewed in a total of 154 patients with EOC submitted to primary cytoreductive surgery. Patients were categorized into two different groups according to the results of cytoreductive surgery: optimal and suboptimal cytoreduction. Continuous variables were categorized into two groups using the best cutoff points selected on the receiver operating characteristic (ROC) curve for suboptimal cytoreduction. Results: Based on data collected from the 154 patients, 133 (86.4%) and 21 (13.6%) patients presented with stage III and IV disease, respectively. One hundred seventeen (76.0%) patients had serous adenocarcinoma, and 92 (59.7%) had histologic tumor grade 3. The optimal and suboptimal cytoreduction groups included 96 (62.3%) and 58 patients (37.7%), respectively. The best LMR cutoff point for suboptimal cytoreduction was 3.75. On multivariate logistic regression analysis, age, cancer antigen 125, white blood cell count, and LMR were found to be the strongest predictors for suboptimal cytoreduction (P=0.0037, 0.0249, 0.0062, and 0.0015, respectively). Conclusion: Preoperative LMR is an independent predictor of suboptimal cytoreduction. It provides additional prognostic information beyond the biological parameters of the tumor. PMID:27698915

  20. Concomitant 5-fluorouracil infusion and high-dose radiation for stage III non-small cell lung cancer

    SciTech Connect

    Lokich, J.; Chaffey, J.; Neptune, W. )

    1989-09-01

    Thirty patients with Stage III non-small cell lung cancer were entered on a trial to evaluate the feasibility of combined radiation and concomitant 5-fluorouracil infusion. Patients had received prior debulking surgery (nine), induction chemotherapy (16), or no therapy (five). Radiation employed standard fractionation (180-200 rad/day) administered to a median cumulative dose of 5500 rad (range, 4500-6200 rad). 5-Fluorouracil was infused 24 hours per day throughout the period of radiation at a dose of 300 mg/m2/day for a median of 42 days (range, 28-56 days). Radiation complications included pneumonitis three of 30 (10%) and esophagitis (27%). Chemotherapy complications included stomatitis, two of 27 (7%), and hand-foot syndrome, three of 30 (10%). Treatment interruptions were necessary in six of 30 (20%) and four of 30 required parenteral nutrition. At a median follow-up of 12 months 26/30 (87%) maintained local control and eight had distant metastases (three of whom presented with Stage IV disease). 5-Fluorouracil delivered continuously throughout standard fractionation radiation to high cumulative doses is feasible and practical. Comparative clinical trials of the various combined radiation and chemotherapy schedules employed are in order. One additional clinical observation was the identification of six of 30 (20%) with brain metastases at presentation or after 12 months, all of whom had adenocarcinoma histologic subtype.

  1. Preoperative Lymphocyte-Monocyte Ratio Is a Predictor of Suboptimal Cytoreduction in Stage III-IV Epithelial Ovarian Cancer

    PubMed Central

    Eo, Wankyu; Kim, Hong-Bae; Lee, Yong Joo; Suh, Dong Soo; Kim, Ki Hyung; Kim, Heungyeol

    2016-01-01

    Objective: To determine whether the preoperative lymphocyte-monocyte ratio (LMR) is a predictor of suboptimal cytoreduction in advanced-stage epithelial ovarian cancer (EOC). Methods: Preoperative clinico-pathologic and hematologic parameters were reviewed in a total of 154 patients with EOC submitted to primary cytoreductive surgery. Patients were categorized into two different groups according to the results of cytoreductive surgery: optimal and suboptimal cytoreduction. Continuous variables were categorized into two groups using the best cutoff points selected on the receiver operating characteristic (ROC) curve for suboptimal cytoreduction. Results: Based on data collected from the 154 patients, 133 (86.4%) and 21 (13.6%) patients presented with stage III and IV disease, respectively. One hundred seventeen (76.0%) patients had serous adenocarcinoma, and 92 (59.7%) had histologic tumor grade 3. The optimal and suboptimal cytoreduction groups included 96 (62.3%) and 58 patients (37.7%), respectively. The best LMR cutoff point for suboptimal cytoreduction was 3.75. On multivariate logistic regression analysis, age, cancer antigen 125, white blood cell count, and LMR were found to be the strongest predictors for suboptimal cytoreduction (P=0.0037, 0.0249, 0.0062, and 0.0015, respectively). Conclusion: Preoperative LMR is an independent predictor of suboptimal cytoreduction. It provides additional prognostic information beyond the biological parameters of the tumor.

  2. Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-10-27

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  3. Dynamics of an HIV Model with Multiple Infection Stages and Treatment with Different Drug Classes.

    PubMed

    Wang, Xia; Song, Xinyu; Tang, Sanyi; Rong, Libin

    2016-02-01

    Highly active antiretroviral therapy can effectively control HIV replication in infected individuals. Some clinical and modeling studies suggested that viral decay dynamics may depend on the inhibited stages of the viral replication cycle. In this paper, we develop a general mathematical model incorporating multiple infection stages and various drug classes that can interfere with specific stages of the viral life cycle. We derive the basic reproductive number and obtain the global stability results of steady states. Using several simple cases of the general model, we study the effect of various drug classes on the dynamics of HIV decay. When drugs are assumed to be 100% effective, drugs acting later in the viral life cycle lead to a faster or more rapid decay in viremia. This is consistent with some patient and experimental data, and also agrees with previous modeling results. When drugs are not 100% effective, the viral decay dynamics are more complicated. Without a second population of long-lived infected cells, the viral load decline can have two phases if drugs act at an intermediate stage of the viral replication cycle. The slopes of viral load decline depend on the drug effectiveness, the death rate of infected cells at different stages, and the transition rate of infected cells from one to the next stage. With a second population of long-lived infected cells, the viral load decline can have three distinct phases, consistent with the observation in patients receiving antiretroviral therapy containing the integrase inhibitor raltegravir. We also fit modeling prediction to patient data under efavirenz (a nonnucleoside reverse-transcriptase inhibitor) and raltegravir treatment. The first-phase viral load decline under raltegravir therapy is longer than that under efavirenz, resulting in a lower viral load at initiation of the second-phase decline in patients taking raltegravir. This explains why patients taking a raltegravir-based therapy were faster to achieve

  4. Dynamics of an HIV Model with Multiple Infection Stages and Treatment with Different Drug Classes.

    PubMed

    Wang, Xia; Song, Xinyu; Tang, Sanyi; Rong, Libin

    2016-02-01

    Highly active antiretroviral therapy can effectively control HIV replication in infected individuals. Some clinical and modeling studies suggested that viral decay dynamics may depend on the inhibited stages of the viral replication cycle. In this paper, we develop a general mathematical model incorporating multiple infection stages and various drug classes that can interfere with specific stages of the viral life cycle. We derive the basic reproductive number and obtain the global stability results of steady states. Using several simple cases of the general model, we study the effect of various drug classes on the dynamics of HIV decay. When drugs are assumed to be 100% effective, drugs acting later in the viral life cycle lead to a faster or more rapid decay in viremia. This is consistent with some patient and experimental data, and also agrees with previous modeling results. When drugs are not 100% effective, the viral decay dynamics are more complicated. Without a second population of long-lived infected cells, the viral load decline can have two phases if drugs act at an intermediate stage of the viral replication cycle. The slopes of viral load decline depend on the drug effectiveness, the death rate of infected cells at different stages, and the transition rate of infected cells from one to the next stage. With a second population of long-lived infected cells, the viral load decline can have three distinct phases, consistent with the observation in patients receiving antiretroviral therapy containing the integrase inhibitor raltegravir. We also fit modeling prediction to patient data under efavirenz (a nonnucleoside reverse-transcriptase inhibitor) and raltegravir treatment. The first-phase viral load decline under raltegravir therapy is longer than that under efavirenz, resulting in a lower viral load at initiation of the second-phase decline in patients taking raltegravir. This explains why patients taking a raltegravir-based therapy were faster to achieve

  5. Resolving Early Stages of Homogeneous Iron(III) Oxyhydroxide Formation from Iron(III) Nitrate Solutions at pH 3 Using Time-Resolved SAXS

    PubMed Central

    2015-01-01

    Small angle X-ray scattering (SAXS) measurements coupled to a stopped-flow device has permitted the observation of the kinetics of Fe(III) oxyhydroxide (FeOx) formation and transformation from around 1 s to 30 min after initiation under environmentally relevant conditions at pH 3. The Unified Model approach was used to determine the evolution of multiple key parameters (particle scattering mass, mean particle volume, particle concentration, particle dimensionality, and particle size) for two separate structural levels as a function of time, with the results obtained enabling clarification of the mechanisms underlying FeOx formation and transformation under these conditions. Colloidal primary particles (radius of gyration 2–10 nm) that were observable by SAXS formed within 1 s of stopping the flow and subsequently grew over several minutes, first by cluster–cluster addition and then by a monomer-addition mechanism. Aggregation of these primary particles via a secondary cluster–cluster addition mechanism simultaneously resulted in a distinct population of larger (25–40 nm radius of gyration) secondary particles. The primary particles evolved into compact spheroidal forms with fractally rough surfaces, while the secondary particles were relatively open mass fractal structures. Comparison of the observed rates of these processes with those predicted for Fe polymerization indicates that kinetics of primary particle formation were likely controlled initially by rates of exchange between water molecules coordinated with Fe and those in the bulk solution. These findings provide new insights into the mechanisms underlying FeOx formation and transformation, and the kinetics of these mechanisms, at pH 3. PMID:24601665

  6. Paclitaxel, Polyglutamate Paclitaxel, or Observation in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Peritoneal Cancer, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-03-17

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  7. Fulvestrant With or Without Lapatinib in Treating Postmenopausal Women With Stage III or Stage IV Breast Cancer That is Hormone Receptor-Positive

    ClinicalTrials.gov

    2016-08-29

    Estrogen Receptor Positive; HER2 Positive Breast Carcinoma; HER2/Neu Negative; Progesterone Receptor Positive; Recurrent Breast Carcinoma; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  8. Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2015-08-18

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  9. lLong-Term Outcomes after Proton Therapy, with Concurrent Chemotherapy, for Stage II-III Inoperable Non-Small Cell Lung Cancer

    PubMed Central

    Nguyen, Quynh-Nhu; Ly, Ngoc Bui; Komaki, Ritsuko; Levy, Lawrence B.; Gomez, Daniel R.; Chang, Joe Y.; Allen, Pamela K.; Mehran, Reza J.; Lu, Charles; Gillin, Michael; Liao, Zhongxing; Cox, James D.

    2016-01-01

    Purpose We report long-term disease control, survival, and toxicity for patients with locally advanced non-small cell lung cancer prospectively treated with concurrent proton therapy and chemotherapy on a nonrandomized case-only obervational study. Methods All patients received passive-scatter proton therapy, planned with 4D-CT–based simulation; all received proton therapy concurrent with weekly chemotherapy. Endpoints were local and distant control, disease-free survival (DFS), and overall survival (OS). Results The 134 patients (21 stage II, 113 stage III; median age 69 years) had a median gross tumor volume (GTV) of 70 cm3 (range, 5-753 cm3); 77 patients (57%) received 74 Gy(RBE), and 57 (42% received 60–72 Gy(RBE) (range, 60-74.1 Gy(RBE)). At a median follow-up time of 4.7 years, median OS times were 40.4 months (stage II) and 30.4 months (stage III). Five-year DFS rates were 17.3% (stage II) and 18.0% (stage III). OS, DFS, and local and distant control rates at 5 years did not differ by disease stage. Age and GTV were related to OS and DFS. Toxicity was tolerable, with 1 grade 4 esophagitis and 16 grade 3 events (2 pneumonitis, 6 esophagitis, 8 dermatitis). Conclusion This report of outcomes after proton therapy for 134 patients indicated that this regimen produced excellent OS with tolerable toxicity. PMID:26028228

  10. 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

  11. Thymidine phosphorylase and hypoxia-inducible factor 1-α expression in clinical stage II/III rectal cancer: association with response to neoadjuvant chemoradiation therapy and prognosis.

    PubMed

    Lin, Shuhan; Lai, Hao; Qin, Yuzhou; Chen, Jiansi; Lin, Yuan

    2015-01-01

    The aim of this study was to determine whether pretreatment status of thymidine phosphorylase (TP), and hypoxia-inducible factor alpha (HIF-1α) could predict pathologic response to neoadjuvant chemoradiation therapy with oxaliplatin and capecitabine (XELOXART) and outcomes for clinical stage II/III rectal cancer patients. A total of 180 patients diagnosed with clinical stage II/III rectal cancer received XELOXART. The status of TP, and HIF-1α were determined in pretreatment biopsies by immunohistochemistry (IHC). Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. 5-year disease free survival (DFS) and 5-year overall survival (OS) were evaluated with the Kaplan-Meier method and were compared by the log-rank test. Over expression of TP and low expression of HIF-1α were associated with pathologic response to XELOXART and better outcomes (DFS and OS) in clinical stage II/III rectal cancer patients (P < 0.05). Our result suggested that pretreatment status of TP and HIF-1α were found to predict pathologic response and outcomes in clinical stage II/III rectal cancer received XELOXART. Additional well-designed, large sample, multicenter, prospective studies are needed to confirm the result of this study.

  12. Cryogenic Propulsion Stage (CPS) Configuration in Support of NASA's Multiple Design Reference Missions (DRMs)

    NASA Technical Reports Server (NTRS)

    Hanna, Stephen G.; Jones, David L.; Creech, Stephen D.; Lawrence, Thomas D.

    2012-01-01

    In support of the National Aeronautics and Space Administration's (NASA) Human Exploration and Operations Mission Directorate (HEOMD), the Space Launch System (SLS) is being designed for safe, affordable, and sustainable human and scientific exploration missions beyond Earth's or-bit (BEO). The SLS Team is tasked with developing a system capable of safely and repeatedly lofting a new fleet of spaceflight vehicles beyond Earth orbit. The Cryogenic Propulsion Stage (CPS) is a key enabler for evolving the SLS capability for BEO missions. This paper reports on the methodology and initial recommendations relative to the CPS, giving a brief retrospective of early studies on this promising propulsion hardware. This paper provides an overview of the requirements development and CPS configuration in support of NASA's multiple Design Reference Missions (DRMs).

  13. Electrospray ionization ion-trap multiple-stage mass spectrometry of Quillaja saponins.

    PubMed

    Bankefors, Johan; Broberg, Susanna; Nord, Lars I; Kenne, Lennart

    2011-07-01

    Fifteen identified C-18 fatty acyl-containing saponin structures from Quillaja saponaria Molina have been investigated by electrospray ionization ion-trap multiple-stage mass spectrometry (ESI-IT-MS(n)) in positive ion mode. Their MS(1)-MS(3) spectra were analyzed and ions corresponding to useful fragments, important for the structural identification of Quillaja saponins, were recognized. A few key fragments could describe the structural variations in the C-3 and the C-28 oligosaccharides of the Quillaja saponins. A flowchart involving a stepwise procedure based on key fragments from the MS(1)-MS(3) spectra of these saponins, together with key fragments from these saponins and 13 previously investigated saponins, was constructed for the identification of structural elements in Quillaja saponins. Peak intensity ratios in MS(3) spectra were found to be correlated to structural features of the investigated saponins and is therefore of value for the identification of regioisomers.

  14. Oligosaccharide sequences in Quillaja saponins by electrospray ionization ion trap multiple-stage mass spectrometry.

    PubMed

    Broberg, Susanna; Nord, Lars I; Kenne, Lennart

    2004-06-01

    Ten different samples with 13 previously identified saponin structures from Quillaja saponaria Molina were investigated by electrospray ionization ion trap multiple-stage mass spectrometry (ESI-ITMS(n)) in positive and negative ion modes. Both positive and negative ion mode MS(1)-MS(4) spectra were analyzed, showing that structural information on the two oligosaccharide parts in the saponin can be obtained from positive ion mode spectra whereas negative ion mode spectra mainly gave information on one of the oligosaccharide parts. Analysis of MS(1)-MS(4) spectra identified useful key fragment ions important for the structural elucidation of Quillaja saponins. A flowchart involving a stepwise procedure based on key fragments from MS(1)-MS(3) spectra was constructed for the identification of structural elements in the saponin. Peak intensity ratios in MS(3) spectra were found to be correlated with structural features of the investigated saponins and are therefore of value for the identification of terminal monosaccharide residues.

  15. Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma.

    PubMed

    Boland, A; Bagust, A; Hockenhull, J; Davis, H; Chu, P; Dickson, R

    2009-09-01

    This paper presents a summary of the evidence review group report into the clinical effectiveness and cost-effectiveness of rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma (NHL), in accordance with the licensed indication, based upon the evidence submission from Roche Products Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submitted clinical evidence included two randomised controlled trials [European Organisation for Research and Treatment of Cancer (EORTC) and German Low Grade Lymphoma Study Group - Fludarabine, Cyclophosphamide and Mitoxantrone and (GLSG-FCM)] comparing the clinical effects of chemotherapy with or without rituximab in the induction of remission at first or second relapse and the clinical benefits of rituximab maintenance therapy versus the NHS's current clinical practice of observation for follicular lymphoma (FL) patients. Both trials showed that in patients with relapsed FL the addition of rituximab to chemotherapy induction treatment increased overall response rates. Furthermore, rituximab maintenance therapy increased the median length of remission when compared with observation only. Safety data from the two trials showed that while the majority of patients reported some adverse events, the number of patients withdrawing from treatment in the EORTC trial was low, with rates not being reported for the GLSG-FCM trial. The most commonly reported adverse events were blood/bone marrow toxicity, skin rashes and allergies. The ERG reran the manufacturer's economic model after altering several of the assumptions and parameter values in order to recalculate the cost-utility ratios, quality-adjusted life-years (QALYs) and estimates of benefits. The manufacturer reported that maintenance therapy with rituximab was cost-effective compared with observation against commonly applied thresholds, with an incremental

  16. Prognostic Value and Reproducibility of Pretreatment CT Texture Features in Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Fried, David V.; Tucker, Susan L.; Zhou, Shouhao; Liao, Zhongxing; Mawlawi, Osama; Ibbott, Geoffrey; Court, Laurence E.

    2014-11-15

    Purpose: To determine whether pretreatment CT texture features can improve patient risk stratification beyond conventional prognostic factors (CPFs) in stage III non-small cell lung cancer (NSCLC). Methods and Materials: We retrospectively reviewed 91 cases with stage III NSCLC treated with definitive chemoradiation therapy. All patients underwent pretreatment diagnostic contrast enhanced computed tomography (CE-CT) followed by 4-dimensional CT (4D-CT) for treatment simulation. We used the average-CT and expiratory (T50-CT) images from the 4D-CT along with the CE-CT for texture extraction. Histogram, gradient, co-occurrence, gray tone difference, and filtration-based techniques were used for texture feature extraction. Penalized Cox regression implementing cross-validation was used for covariate selection and modeling. Models incorporating texture features from the 33 image types and CPFs were compared to those with models incorporating CPFs alone for overall survival (OS), local-regional control (LRC), and freedom from distant metastases (FFDM). Predictive Kaplan-Meier curves were generated using leave-one-out cross-validation. Patients were stratified based on whether their predicted outcome was above or below the median. Reproducibility of texture features was evaluated using test-retest scans from independent patients and quantified using concordance correlation coefficients (CCC). We compared models incorporating the reproducibility seen on test-retest scans to our original models and determined the classification reproducibility. Results: Models incorporating both texture features and CPFs demonstrated a significant improvement in risk stratification compared to models using CPFs alone for OS (P=.046), LRC (P=.01), and FFDM (P=.005). The average CCCs were 0.89, 0.91, and 0.67 for texture features extracted from the average-CT, T50-CT, and CE-CT, respectively. Incorporating reproducibility within our models yielded 80.4% (±3.7% SD), 78.3% (±4.0% SD), and 78

  17. Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery

    ClinicalTrials.gov

    2016-09-15

    Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  18. Veliparib and Atezolizumab Either Alone or in Combination in Treating Patients With Stage III-IV Triple Negative Breast Cancer

    ClinicalTrials.gov

    2016-09-12

    BRCA1 Gene Mutation; BRCA2 Gene Mutation; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  19. Metformin Hydrochloride and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-05-18

    Brenner Tumor; Malignant Ascites; Malignant Pleural Effusion; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cavity Cancer

  20. Space Shuttle guidance for multiple main engine failures during first stage

    NASA Technical Reports Server (NTRS)

    Sponaugle, Steven J.; Fernandes, Stanley T.

    1987-01-01

    This paper presents contingency abort guidance schemes recently developed for multiple Space Shuttle main engine failures during the first two minutes of flight (first stage). The ascent and entry guidance schemes greatly improve the possibility of the crew and/or the Orbiter surviving a first stage contingency abort. Both guidance schemes were required to meet certain structural and controllability constraints. In addition, the systems were designed with the flexibility to allow for seasonal variations in the atmosphere and wind. The ascent scheme guides the vehicle to a desirable, lofted state at solid rocket booster burnout while reducing the structural loads on the vehicle. After Orbiter separation from the solid rockets and the external tank, the entry scheme guides the Orbiter through one of two possible entries. If the proper altitude/range/velocity conditions have been met, a return-to-launch-site 'Split-S' maneuver may be attempted. Otherwise, a down-range abort to an equilibrium glide and subsequent crew bailout is performed.

  1. [Comparative estimation of results of remote and combined radiotherapy in patients with cancer of the cervix uteri of the III-IV stages of disease].

    PubMed

    Pereslegin, I A; Makarov, O V; Semko, V F; Frolova, E L

    2000-01-01

    The paper presents a procedure of teleradiotherapy in patients with stages III-IV cancer of the cervix uteri with significant concurrent pathology. Control patients with the similar disease stages underwent combined radiation therapy. If there are contraindications to combined radiation therapy, teleradiotherapy is possible and required as an independent treatment that prolongs and improves the patients' like quality irrespective of the extent of a tumorous process.

  2. Vasodilatation of multiple cerebral arteries in early stage of stroke-like episode with MELAS.

    PubMed

    Minobe, Shoko; Matsuda, Akiko; Mitsuhashi, Tetsuya; Ishikawa, Motonao; Nishimura, Yoshiko; Shibata, Koichi; Ito, Eiichi; Goto, Yu-ichi; Nakaoka, Takashi; Sakura, Hiroshi

    2015-02-01

    We describe a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), with multiple cerebral vasodilatations in a stroke-like episode visualised by using magnetic resonance angiography (MRA) and CT angiography (CTA). In the acute stroke-like episode stage, T2-weighted and fluid-attenuated inversion recovery MRI showed high-intensity areas in the left occipital area. In addition, MRA and CTA revealed prominent dilatation of the left posterior cerebral artery and temporal branches of the middle cerebral artery with focal hyperperfusions using CT perfusion (CTP) that corresponded to the MRI. After 10 days, with the development of aphasia, MRI indicated the lesions had spread to the temporal and parietal regions, and this distribution was not confined to major vascular territories. The patient's symptoms gradually improved, accompanied by the attenuation of MRI, CTA, and CTP findings. These characteristic features along with the MRI changes that spread beyond vascular boundaries and the multiple cerebral vasodilatations prior to the development of clinical symptoms are not fully explained by the mitochondrial angiopathy or cytopathy theories. These findings provide further evidence supporting neuronal hyperexcitability in stroke-like episodes of MELAS.

  3. Estimating the prevalence of multiple diseases from two-stage hierarchical pooling.

    PubMed

    Warasi, Md S; Tebbs, Joshua M; McMahan, Christopher S; Bilder, Christopher R

    2016-09-20

    Testing protocols in large-scale sexually transmitted disease screening applications often involve pooling biospecimens (e.g., blood, urine, and swabs) to lower costs and to increase the number of individuals who can be tested. With the recent development of assays that detect multiple diseases, it is now common to test biospecimen pools for multiple infections simultaneously. Recent work has developed an expectation-maximization algorithm to estimate the prevalence of two infections using a two-stage, Dorfman-type testing algorithm motivated by current screening practices for chlamydia and gonorrhea in the USA. In this article, we have the same goal but instead take a more flexible Bayesian approach. Doing so allows us to incorporate information about assay uncertainty during the testing process, which involves testing both pools and individuals, and also to update information as individuals are tested. Overall, our approach provides reliable inference for disease probabilities and accurately estimates assay sensitivity and specificity even when little or no information is provided in the prior distributions. We illustrate the performance of our estimation methods using simulation and by applying them to chlamydia and gonorrhea data collected in Nebraska. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27090057

  4. 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

  5. Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2016-06-28

    Adenocarcinoma of the Lung; Recurrent Non-small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  6. Cost-effectiveness of adjuvant chemotherapy with uracil–tegafur for curatively resected stage III rectal cancer

    PubMed Central

    Hisashige, A; Yoshida, S; Kodaira, S

    2008-01-01

    Recently, the National Surgical Adjuvant Study of Colorectal Cancer in Japan, a randomised controlled trial of oral uracil–tegafur (UFT) adjuvant therapy for stage III rectal cancer, showed remarkable survival gains, compared with surgery alone. To evaluate value for money of adjuvant UFT therapy, cost-effective analysis was carried out. Cost-effectiveness analysis of adjuvant UFT therapy was carried out from a payer's perspective, compared with surgery alone. Overall survival and relapse-free survival were estimated by Kaplan–Meier method, up to 5.6 years from randomisation. Costs were estimated from trial data during observation. Quality-adjusted life-years (QALYs) were calculated using utility score from literature. Beyond observation period, they were simulated by the Boag model combined with the competing risk model. For 5.6-year observation, 10-year follow-up and over lifetime, adjuvant UFT therapy gained 0.50, 0.96 and 2.28 QALYs, and reduced costs by $2457, $1771 and $1843 per person compared with surgery alone, respectively (3% discount rate for both effect and costs). Cost-effectiveness acceptability and net monetary benefit analyses showed the robustness of these results. Economic evaluation of adjuvant UFT therapy showed that this therapy is cost saving and can be considered as a cost-effective treatment universally accepted for wide use in Japan. PMID:18797469

  7. Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

    PubMed Central

    Lotem, Michal; Merims, Sharon; Frank, Stephen; Hamburger, Tamar; Nissan, Aviram; Kadouri, Luna; Cohen, Jonathan; Straussman, Ravid; Eisenberg, Galit; Frankenburg, Shoshana; Carmon, Einat; Alaiyan, Bilal; Shneibaum, Shlomo; Ozge Ayyildiz, Zeynep; Isbilen, Murat; Mert Senses, Kerem; Ron, Ilan; Steinberg, Hanna; Smith, Yoav; Shiloni, Eitan; Gure, Ali Osmay; Peretz, Tamar

    2016-01-01

    Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity. PMID:27294163

  8. [Results of open multicenter study of the safety of doxazosin in combination with indigal in men with stages I-II prostatic adenoma].

    PubMed

    Pavlov, V N; Komiakov, B K; Grigor'ev, M É; Sivkov, A V; Bliumberg, B I; Kazikhinoruv, A A; Izmaĭlov, A A; Boiarko, A V; Abzalilov, R A

    2013-01-01

    The article presents a method of conservative treatment of men with I-II stage prostatic adenoma using a combination of doxazosin and indigal, which has antioxidant, antiproliferative and anti-inflammatory properties, that allowed improving urodynamic parameters and reducing the progression prostate adenoma, minimizing the adverse effects of treatment.

  9. Validating NEXRAD MPE and Stage III precipitation products for uniform rainfall on the Upper Guadalupe River Basin of the Texas Hill Country

    NASA Astrophysics Data System (ADS)

    Wang, Xianwei; Xie, Hongjie; Sharif, Hatim; Zeitler, Jon

    2008-01-01

    SummaryThis study examines the performance of the Next Generation Weather Radar (NEXRAD) Multisensor Precipitation Estimator (MPE) and Stage III precipitation products, using a high-density rain gauge network located on the Upper Guadalupe River Basin of the Texas Hill Country. As point-area representativeness error of gauge rainfall is a major concern in assessment of radar rainfall estimation, this study develops a new method to automatically select uniform rainfall events based on coefficient of variation criterion of 3 by 3 radar cells. Only gauge observations of those uniform rainfall events are used as ground truth to evaluate radar rainfall estimation. This study proposes a new parameter probability of rain detection (POD) instead of the conditional probability of rain detection (CPOD) commonly used in previous studies to assess the capability that a radar or gauge detects rainfall. Results suggest that: (1) gauge observations of uniform rainfall better represent ground truth of a 4 × 4 km 2 radar cell than non-uniform rainfall; (2) the MPE has higher capability of rain detection than either gauge-only or Stage III; (3) the MPE has much higher linear correlation and lower mean relative difference with gauge measurements than the Stage III does; (4) the Stage III tends to overestimate precipitation (20%), but the MPE tends to underestimate (7%).

  10. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients.

    PubMed

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H T; Aarntzen, Erik H J G; Schreibelt, Gerty; Creemers, Jeroen H A; Punt, Cornelis J A; Figdor, Carl G; de Vries, I Jolanda M; Gerritsen, Winald R; Bol, Kalijn F

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8 T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  11. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients

    PubMed Central

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H.T.; Aarntzen, Erik H.J.G.; Schreibelt, Gerty; Creemers, Jeroen H.A.; Punt, Cornelis J.A.; Figdor, Carl G.; Gerritsen, Winald R.; Bol, Kalijn F.

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8+ T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  12. A phase 2, multicenter, open-label study of sepantronium bromide (YM155) plus docetaxel in patients with stage III (unresectable) or stage IV melanoma

    PubMed Central

    Kudchadkar, Ragini; Ernst, Scott; Chmielowski, Bartosz; Redman, Bruce G; Steinberg, Joyce; Keating, Anne; Jie, Fei; Chen, Caroline; Gonzalez, Rene; Weber, Jeffrey

    2015-01-01

    Survivin is a microtubule-associated protein believed to be involved in preserving cell viability and regulating tumor cell mitosis, and it is overexpressed in many primary tumor types, including melanoma. YM155 is a first-in-class survivin suppressant. The purpose of this Phase 2 study was to evaluate the 6-month progression-free survival (PFS) rate in patients with unresectable Stage III or IV melanoma receiving a combination of YM155 plus docetaxel. The study had two parts: Part 1 established the dose of docetaxel that was tolerable in combination with YM155, and Part 2 evaluated the tolerable docetaxel dose (75 mg/m2) in combination with YM155 (5 mg/m2 per day continuous infusion over 168 h every 3 weeks). The primary endpoint was 6-month PFS rate. Secondary endpoints were objective response rate (ORR), 1-year overall survival (OS) rate, time from first response to progression, clinical benefit rate (CBR), and safety. Sixty-four patients with metastatic melanoma were treated with docetaxel and YM155. Eight patients received an initial docetaxel dose of 100 mg/m2 and 56 patients received 75 mg/m2 of docetaxel. Six-month PFS rate per Independent Review Committee (IRC) was 34.8% (n = 64; 95% CI, 21.3–48.6%), and per Investigator was 31.3% (n = 64; 95% CI, 19.5–43.9%). The best ORR (complete response [CR] + partial response [PR]) per IRC was 12.5% (8/64). The stable disease (SD) rate was 51.6% (33/64), leading to a CBR (CR + PR + SD) of 64.1% (41/64). Estimated probability of 1-year survival was 56.3%. YM155 is a novel agent showing modest activity when combined with docetaxel for treating patients with melanoma. YM155 was generally well tolerated, but the predetermined primary efficacy endpoint (i.e., 6-month PFS rate ≥20%) was not achieved. PMID:25533314

  13. Paclitaxel and Carboplatin With or Without Metformin Hydrochloride in Treating Patients With Stage III, IV, or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-02-09

    Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  14. Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: part I: Management of stage III disease.

    PubMed

    Fox, Matthew C; Lao, Christopher D; Schwartz, Jennifer L; Frohm, Marcus L; Bichakjian, Christopher K; Johnson, Timothy M

    2013-01-01

    The incidence of melanoma has increased for decades, and while surgical treatment of early stage disease is often curative, metastatic disease continues to carry a significantly less promising outlook with high associated health burden and economic cost. An expanding number of dermatologists are playing a key role in coordinating the care of patients with melanoma, including in an increasingly important role among multidisciplinary melanoma clinics, many of which are anchored in dermatology departments. Advances in the understanding of the genetic and immunoregulatory aspects of melanoma development and progression have yielded a wave of novel therapeutics that has made significant impact on the approach to patients with metastatic disease. Frequently updated management guidelines and unfamiliarity with approved adjuvant treatment options, including interferon, clinical trials, or radiation therapy, can pose a challenge for dermatologists seeking to effectively coordinate the care of and establish proper expectations for patients with stage III disease. Moreover, greater awareness of treatment modalities for in-transit disease may allow dermatologists to play a more active role in the treatment of these patients and to expand their ability to explain and coordinate options, such as limb perfusion or infusion. Part I of this continuing medical education article will use clinical scenarios to outline the current management options for patients with stage III melanoma, including both adjuvant treatment options for resected stage III disease and primary treatment options for in-transit metastases. Part II of this series will address stage IV disease. PMID:23244383

  15. Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: part I: Management of stage III disease.

    PubMed

    Fox, Matthew C; Lao, Christopher D; Schwartz, Jennifer L; Frohm, Marcus L; Bichakjian, Christopher K; Johnson, Timothy M

    2013-01-01

    The incidence of melanoma has increased for decades, and while surgical treatment of early stage disease is often curative, metastatic disease continues to carry a significantly less promising outlook with high associated health burden and economic cost. An expanding number of dermatologists are playing a key role in coordinating the care of patients with melanoma, including in an increasingly important role among multidisciplinary melanoma clinics, many of which are anchored in dermatology departments. Advances in the understanding of the genetic and immunoregulatory aspects of melanoma development and progression have yielded a wave of novel therapeutics that has made significant impact on the approach to patients with metastatic disease. Frequently updated management guidelines and unfamiliarity with approved adjuvant treatment options, including interferon, clinical trials, or radiation therapy, can pose a challenge for dermatologists seeking to effectively coordinate the care of and establish proper expectations for patients with stage III disease. Moreover, greater awareness of treatment modalities for in-transit disease may allow dermatologists to play a more active role in the treatment of these patients and to expand their ability to explain and coordinate options, such as limb perfusion or infusion. Part I of this continuing medical education article will use clinical scenarios to outline the current management options for patients with stage III melanoma, including both adjuvant treatment options for resected stage III disease and primary treatment options for in-transit metastases. Part II of this series will address stage IV disease.

  16. Effect of {sup 18}F-FDG PET/CT Imaging in Patients With Clinical Stage II and III Breast Cancer

    SciTech Connect

    Groheux, David Moretti, Jean-Luc; Baillet, Georges; Espie, Marc; Giacchetti, Sylvie; Hindie, Elif; Hennequin, Christophe; Vilcoq, Jacques-Robert; Cuvier, Caroline; Toubert, Marie-Elisabeth; Filmont, Jean-Emmanuel; Sarandi, Farid; Misset, Jean-Louis

    2008-07-01

    Purpose: To investigate the potential effect of using {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial assessment of patients with clinical Stage II or III breast cancer. Methods and Materials: During 14 consecutive months, 39 patients (40 tumors) who presented with Stage II or III breast cancer on the basis of a routine extension assessment were prospectively included in this study. PET/CT was performed in addition to the initial assessment. Results: In 3 cases, PET/CT showed extra-axillary lymph node involvement that had not been demonstrated with conventional techniques. Two of these patients had hypermetabolic lymph nodes in the subpectoral and infraclavicular regions, and the third had a hypermetabolic internal mammary node. PET/CT showed distant uptake in 4 women. Of these 4 women, 1 had pleural involvement and 3 had bone metastasis. Overall, of the 39 women, the PET/CT results modified the initial stage in 7 (18%). The modified staging altered the treatment plan for 5 patients (13%). It led to radiotherapy in 4 patients (bone metastasis, pleural lesion, subpectoral lymph nodes, and internal mammary nodes) and excision of, and radiotherapy to, the infraclavicular lymph nodes in 1 patient. Conclusions: PET/CT can provide information on extra-axillary lymph node involvement and can uncover occult distant metastases in a significant percentage of patients. Therefore, initial PET/CT could enable better treatment planning for patients with Stage II and III breast cancer.

  17. Improved accuracy of acute graft-versus-host disease staging among multiple centers.

    PubMed

    Levine, John E; Hogan, William J; Harris, Andrew C; Litzow, Mark R; Efebera, Yvonne A; Devine, Steven M; Reshef, Ran; Ferrara, James L M

    2014-01-01

    The clinical staging of acute graft-versus-host disease (GVHD) varies significantly among bone marrow transplant (BMT) centers, but adherence to long-standing practices poses formidable barriers to standardization among centers. We have analyzed the sources of variability and developed a web-based remote data entry system that can be used by multiple centers simultaneously and that standardizes data collection in key areas. This user-friendly, intuitive interface resembles an online shopping site and eliminates error-prone entry of free text with drop-down menus and pop-up detailed guidance available at the point of data entry. Standardized documentation of symptoms and therapeutic response reduces errors in grade assignment and allows creation of confidence levels regarding the diagnosis. Early review and adjudication of borderline cases improves consistency of grading and further enhances consistency among centers. If this system achieves widespread use it may enhance the quality of data in multicenter trials to prevent and treat acute GVHD.

  18. Improved accuracy of acute graft-versus-host disease staging among multiple centers.

    PubMed

    Levine, John E; Hogan, William J; Harris, Andrew C; Litzow, Mark R; Efebera, Yvonne A; Devine, Steven M; Reshef, Ran; Ferrara, James L M

    2014-01-01

    The clinical staging of acute graft-versus-host disease (GVHD) varies significantly among bone marrow transplant (BMT) centers, but adherence to long-standing practices poses formidable barriers to standardization among centers. We have analyzed the sources of variability and developed a web-based remote data entry system that can be used by multiple centers simultaneously and that standardizes data collection in key areas. This user-friendly, intuitive interface resembles an online shopping site and eliminates error-prone entry of free text with drop-down menus and pop-up detailed guidance available at the point of data entry. Standardized documentation of symptoms and therapeutic response reduces errors in grade assignment and allows creation of confidence levels regarding the diagnosis. Early review and adjudication of borderline cases improves consistency of grading and further enhances consistency among centers. If this system achieves widespread use it may enhance the quality of data in multicenter trials to prevent and treat acute GVHD. PMID:25455279

  19. Distinct lncRNA transcriptional fingerprints characterize progressive stages of multiple myeloma

    PubMed Central

    Taiana, Elisa; Galletti, Serena; Manzoni, Martina; Todoerti, Katia; Musto, Pellegrino; Strozzi, Francesco; Neri, Antonino

    2016-01-01

    Although many efforts have recently contributed to improve our knowledge of molecular pathogenesis of multiple myeloma (MM), the role and significance of long non-coding RNAs (lncRNAs) in plasma cells (PC) malignancies remains virtually absent. To this aim, we developed a custom annotation pipeline of microarray data investigating lncRNA expression in PCs from 20 monoclonal gammopathies of undetermined significance, 33 smoldering MM, 170 MM, and 36 extra-medullary MMs/plasma cell leukemia patients, and 9 healthy donors. Our study identified 31 lncRNAs deregulated in tumor samples compared to normal controls; among these, the upregulation of MALAT1 appeared associated in MM patients with molecular pathways involving cell cycle regulation, p53-mediated DNA damage response, and mRNA maturation processes. Furthermore, we found 21 lncRNAs whose expression were progressively deregulated trough the more aggressive stages of PC dyscrasia, suggesting a possible role in the progression of the disease. Finally, in the context of molecular heterogeneity of MM, we identified a transcriptional fingerprint in hyperdiploid patients, characterized by the upregulation of lncRNAs/pseudogenes related to ribosomal protein genes, known to be upregulated in this molecular group. Overall, the data provides an important resource for future studies on the functions of lncRNAs in the pathology. PMID:26895470

  20. Distinct lncRNA transcriptional fingerprints characterize progressive stages of multiple myeloma.

    PubMed

    Ronchetti, Domenica; Agnelli, Luca; Taiana, Elisa; Galletti, Serena; Manzoni, Martina; Todoerti, Katia; Musto, Pellegrino; Strozzi, Francesco; Neri, Antonino

    2016-03-22

    Although many efforts have recently contributed to improve our knowledge of molecular pathogenesis of multiple myeloma (MM), the role and significance of long non-coding RNAs (lncRNAs) in plasma cells (PC) malignancies remains virtually absent. To this aim, we developed a custom annotation pipeline of microarray data investigating lncRNA expression in PCs from 20 monoclonal gammopathies of undetermined significance, 33 smoldering MM, 170 MM, and 36 extra-medullary MMs/plasma cell leukemia patients, and 9 healthy donors. Our study identified 31 lncRNAs deregulated in tumor samples compared to normal controls; among these, the upregulation of MALAT1 appeared associated in MM patients with molecular pathways involving cell cycle regulation, p53-mediated DNA damage response, and mRNA maturation processes. Furthermore, we found 21 lncRNAs whose expression were progressively deregulated trough the more aggressive stages of PC dyscrasia, suggesting a possible role in the progression of the disease. Finally, in the context of molecular heterogeneity of MM, we identified a transcriptional fingerprint in hyperdiploid patients, characterized by the upregulation of lncRNAs/pseudogenes related to ribosomal protein genes, known to be upregulated in this molecular group. Overall, the data provides an important resource for future studies on the functions of lncRNAs in the pathology. PMID:26895470

  1. Race and Insurance Differences in the Receipt of Adjuvant Chemotherapy Among Patients With Stage III Colon Cancer

    PubMed Central

    Murphy, Caitlin C.; Harlan, Linda C.; Warren, Joan L.; Geiger, Ann M.

    2015-01-01

    Purpose Although the incidence and mortality of colon cancer in the United States has declined over the past two decades, blacks have worse outcomes than whites. Variations in treatment may contribute to mortality differentials. Methods Patients diagnosed with stage III colon cancer were randomly sampled from the SEER program from the years 1990, 1991, 1995, 2000, 2005, and 2010. Patients were categorized as non-Hispanic white (n = 835) or black (n = 384). Treatment data were obtained from a review of the medical records, and these data were verified through contact with the original treating physicians. Log-binomial regression models were used to estimate the association between race and receipt of adjuvant chemotherapy. Effect modification by insurance was assessed with use of single referent models. Results Receipt of adjuvant chemotherapy among both white and black patients increased from the period encompassing the years 1990 and 1991 (white, 58%; black, 45%) to the year 2005 (white, 72%; black, 71%) and then decreased in the year 2010 (white, 66%; black, 57%). There were marked racial disparities in the time period of 1990 to 1991 and again in 2010, with black patients less likely to receive adjuvant chemotherapy as compared with white patients (risk ratio [RR], .82; 95% CI, .72 to .93). For black patients, receipt of adjuvant chemotherapy did not differ across insurance categories (RR for private insurance, .80; 95% CI, .69 to .93; RR for Medicare, .84; 95% CI, .69 to 1.02; and RR for Medicaid, .84; 95% CI, .69 to 1.02), although a larger proportion had Medicaid in all years of the study as compared with white patients. Conclusion The chemotherapy differential narrowed after the time period of 1990 to 1991, but our findings suggest that the disparity reemerged in 2010. Recent decreases in chemotherapy use may be due, in part, to the economic downturn and an increase in Medicaid coverage. PMID:26150445

  2. Pretreatment FDG-PET Metrics in Stage III Non–Small Cell Lung Cancer: ACRIN 6668/RTOG 0235

    PubMed Central

    Duan, Fenghai; Machtay, Mitchell; Gorelick, Jeremy J.; Snyder, Bradley S.; Alavi, Abass; Siegel, Barry A.; Johnson, Douglas W.; Bradley, Jeffrey D.; DeNittis, Albert; Werner-Wasik, Maria

    2015-01-01

    Background: ACRIN 6668/RTOG 0235 evaluated the prognostic value of positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) uptake before and after definitive, concurrent, platinum-based chemoradiotherapy for locally advanced non–small cell lung cancer (NSCLC). In this secondary analysis, we evaluate volumetric pretreatment PET measures as predictors of clinical outcomes. Methods: Patients with stage III NSCLC underwent FDG-PET prior to treatment. A commercially available gradient-based segmentation tool was used to contour all visible hypermetabolic lesions on each scan. For each patient, the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total glycolytic activity (TGA) for all contoured lesions were recorded. Cox proportional hazards regression models were used to evaluate clinical variables and PET metrics as predictors of overall survival (OS) and locoregional control (LRC). Time-dependent covariables were added to the models when necessary to address nonproportional hazards. All statistical tests were two-sided. Results: Complete data were available for 214 patients in the OS analysis and 189 subjects in the LRC analysis. In multivariable analysis incorporating clinical and imaging data available prior to treatment, MTV was an independent predictor of OS (HR = 1.04 per 10cm3 increase, 95% CI = 1.03 to 1.06, P < .001). High MTV was also associated with increased risk of locoregional failure at baseline (HR = 1.16 per 10cm3 increase, 95% CI = 1.08 to 1.23, P < .001) and at six months (HR = 1.05 per 10cm3 increase, 95% CI = 1.02 to 1.07, P < .001) but not at 12 months or later time points. Conclusion: Pretreatment MTV is a predictor of clinical outcomes for NSCLC patients treated with chemoradiotherapy. Quantitative PET measures may serve as stratification factors in clinical trials for this patient population and may help guide novel trial designs. PMID:25688115

  3. Multiple nucleic acid cleavage modes in divergent type III CRISPR systems

    PubMed Central

    Zhang, Jing; Graham, Shirley; Tello, Agnes; Liu, Huanting; White, Malcolm F.

    2016-01-01

    CRISPR-Cas is an RNA-guided adaptive immune system that protects bacteria and archaea from invading nucleic acids. Type III systems (Cmr, Csm) have been shown to cleave RNA targets in vitro and some are capable of transcription-dependent DNA targeting. The crenarchaeon Sulfolobus solfataricus has two divergent subtypes of the type III system (Sso-IIID and a Cmr7-containing variant of Sso-IIIB). Here, we report that both the Sso-IIID and Sso-IIIB complexes cleave cognate RNA targets with a ruler mechanism and 6 or 12 nt spacing that relates to the organization of the Cas7 backbone. This backbone-mediated cleavage activity thus appears universal for the type III systems. The Sso-IIIB complex is also known to possess a distinct ‘UA’ cleavage mode. The predominant activity observed in vitro depends on the relative molar concentration of protein and target RNA. The Sso-IIID complex can cleave plasmid DNA targets in vitro, generating linear DNA products with an activity that is dependent on both the cyclase and HD nuclease domains of the Cas10 subunit, suggesting a role for both nuclease active sites in the degradation of double-stranded DNA targets. PMID:26801642

  4. Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

    SciTech Connect

    Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia; Shi, Zheng; Liu, Yuan; Okwan-Duodu, Derrick; Flowers, Christopher R.; Khan, Mohammad K.

    2015-05-01

    Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy.

  5. AR-42 in Treating Patients With Advanced or Relapsed Multiple Myeloma, Chronic Lymphocytic Leukemia, or Lymphoma

    ClinicalTrials.gov

    2016-03-16

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic 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; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large

  6. The role of postoperative radiotherapy for stage I/II/III thymic tumor—results of the ChART retrospective database

    PubMed Central

    Liu, Qianwen; Gu, Zhitao; Yang, Fu; 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; Xiang, Jin; Liu, Yuan

    2016-01-01

    Background Postoperative radiotherapy (PORT) for thymic tumor is still controversial. The object of the study is to evaluate the role of PORT for stage I to III thymic tumors. Methods The Chinese Alliance for Research in Thymomas (ChART) was searched for patients with stage I to III thymic tumors who underwent surgical resection without neoajuvant therapy between 1994 and 2012. Univariate and multivariate survival analyses were performed. Cox proportional hazard model was used to determine the hazard ratio for death. Result From the ChART database, 1,546 stage I to III patients were identified. Among these patients, 649 (41.98%) received PORT. PORT was associated with gender, histological type (World Health Organization, WHO), thymectomy extent, resection status, Masaoka-Koga stage and adjuvant chemotherapy. The 5-year and 10-year overall survival (OS) rates and disease-free survival (DFS) rates for patients underwent surgery followed by PORT were 90% and 80%, 81% and 63%, comparing with 96% and 95%, 92% and 90% for patients underwent surgery alone (P=0.001, P<0.001) respectively. In univariate analysis, age, histological type (WHO), Masaoka-Koga stage, completeness of resection, and PORT were associated with OS. Multivariable analysis showed that histological type (WHO) (P=0.001), Masaoka-Koga stage (P=0.029) and completeness of resection (P=0.003) were independently prognostic factors of OS. In univariate analysis, gender, myasthenia gravis, histological subtype, Masaoka-Koga stage, surgical approach, PORT and completeness of resection were associated with DFS. Multivariate analysis showed that histological subtype (P<0.001), Masaoka-Koga stage (P=0.005) and completeness of resection (P=0.006) were independent prognostic factors for DFS. Subgroup analysis showed that patients with incomplete resection underwent PORT achieved better OS and DFS (P=0.010, 0.017, respectively). However, patients with complete resection underwent PORT had the worse OS and DFS (P<0

  7. The comorbidity of multiple personality disorder and DSM-III-R axis II disorders.

    PubMed

    Fink, D

    1991-09-01

    Our ability to differentiate MPD from DSM-III-R Axis I disorders has become increasingly refined. Differentiation of MPD from the Axis II personality disorders is an area of more recent clinical investigation. MPD can be found comorbidity with many other psychiatric conditions. It is found in association with each of the DSM-III-R personality disorders. At the present time, however, we lack research data that define the prevalence of the comorbidity of MPD with the personality disorders. Objective study of this area is complicated by the paucity of instruments available to assess personality dimensions in the presence of a DD. In addition, the currently available personality inventories tend to overdiagnose BPD in patients with a high level of distress and acuity of symptoms. The diagnosis of a personality disorder in a patient with MPD is made on the basis of the assessment of the "whole" human being. It is based on the presence of a pervasive and relatively inflexible pattern of behaviors that reflects the individual predominant mode of being. The diagnosis of a personality disorder is not made on the basis of personality traits contained within any single alternate personality or groups of personalities. The personality disorders defined by DSM-III-R are a heterogeneous group of conditions whose individual etiologies reflect a complex interplay of constitutional, genetic, environmental, interpersonal, and psychodynamic factors. The interplay is variable and diverse between these determinants of the personality disorders and the traumatic forces that result in the development of a DD. For the Cluster A personality disorders (schizoid, schizotypal, paranoid), there is evidence supporting a relationship with specific psychotic illnesses. The combination of dissociative pathology with these personality disorders commonly results in a greater impairment of reality testing than in either condition alone. The Cluster B personality disorders (histrionic, narcissistic

  8. Identification of novel metabolites from Aspergillus flavus by high resolution and multiple stage mass spectrometry.

    PubMed

    Malysheva, Svetlana V; Arroyo-Manzanares, Natalia; Cary, Jeffrey W; Ehrlich, Kenneth C; Vanden Bussche, Julie; Vanhaecke, Lynn; Bhatnagar, Deepak; Di Mavungu, José Diana; De Saeger, Sarah

    2014-01-01

    The filamentous fungus Aspergillus flavus is one of the most important species in the Aspergillus genus and is distributed worldwide as a prevalent aflatoxin-producing food and feed contaminant. A. flavus contains more than 55 gene clusters that are predicted to encode proteins involved in secondary metabolite production. One of these, cluster 27, contains a polyketide synthase (pks27) gene that encodes a protein that is highly homologous to the aflatoxin cluster PKS. Comparative metabolomics, using ultra-high performance liquid chromatography (UHPLC) coupled to high resolution Orbitrap mass spectrometry (MS) was used to detect metabolites differentially expressed in the A. flavus wild-type and ∆pks27 mutant strains. Metabolite profiling was aided by a statistical differential analysis of MS data using SIEVE software. This differential analysis combined with accurate mass data from the Orbitrap and ion trap multiple stage MS allowed four metabolites to be identified that were produced only by the wild-type culture. These included asparasone A (358 Da), an anthraquinone pigment, and related anthraquinones with masses of 316, 340 and 374 Da. These latter three compounds had similar fragmentation patterns to that of asparasone A. The 316 Da anthraquinone is particularly interesting because it is most likely formed by incorporation of seven malonyl-CoA units rather than the eight units required for the formation of asparasone A. The 340 and 374 Da metabolites are the dehydration and an oxy-derivative of asparasone A, respectively. Asparasone A was also identified in extracts from several other Aspergillus species. PMID:24405210

  9. Identification of novel metabolites from Aspergillus flavus by high resolution and multiple stage mass spectrometry.

    PubMed

    Malysheva, Svetlana V; Arroyo-Manzanares, Natalia; Cary, Jeffrey W; Ehrlich, Kenneth C; Vanden Bussche, Julie; Vanhaecke, Lynn; Bhatnagar, Deepak; Di Mavungu, José Diana; De Saeger, Sarah

    2014-01-01

    The filamentous fungus Aspergillus flavus is one of the most important species in the Aspergillus genus and is distributed worldwide as a prevalent aflatoxin-producing food and feed contaminant. A. flavus contains more than 55 gene clusters that are predicted to encode proteins involved in secondary metabolite production. One of these, cluster 27, contains a polyketide synthase (pks27) gene that encodes a protein that is highly homologous to the aflatoxin cluster PKS. Comparative metabolomics, using ultra-high performance liquid chromatography (UHPLC) coupled to high resolution Orbitrap mass spectrometry (MS) was used to detect metabolites differentially expressed in the A. flavus wild-type and ∆pks27 mutant strains. Metabolite profiling was aided by a statistical differential analysis of MS data using SIEVE software. This differential analysis combined with accurate mass data from the Orbitrap and ion trap multiple stage MS allowed four metabolites to be identified that were produced only by the wild-type culture. These included asparasone A (358 Da), an anthraquinone pigment, and related anthraquinones with masses of 316, 340 and 374 Da. These latter three compounds had similar fragmentation patterns to that of asparasone A. The 316 Da anthraquinone is particularly interesting because it is most likely formed by incorporation of seven malonyl-CoA units rather than the eight units required for the formation of asparasone A. The 340 and 374 Da metabolites are the dehydration and an oxy-derivative of asparasone A, respectively. Asparasone A was also identified in extracts from several other Aspergillus species.

  10. Use of CD-ROM-based tool for analyzing contouring variations in involved-field radiotherapy for Stage III NSCLC

    SciTech Connect

    Soernsen De Koste, John R. van . E-mail: j.vansornsendekoste@vumc.nl; Senan, Suresh; Underberg, Rene W.M.; Oei, Swie Swat; Elshove, Dionne; Slotman, Ben J.; Lagerwaard, Frank J.

    2005-10-01

    Background: Interclinician variability in defining target volumes is a problem in conformal radiotherapy. A CD-ROM-based contouring tool was used to conduct a dummy run in an international trial of involved-field chemoradiotherapy for Stage III non-small-cell lung cancer. Methods and Materials: The CT scan of an eligible patient was installed on an 'auto-run' CD-ROM incorporating a contouring program based on ImageJ for Windows, which runs on any personal computer equipped with a CD-ROM drive. This tool was initially piloted at four academic centers and was subsequently mailed, together with all relevant clinical, radiologic, and positron emission tomography findings, to all participating centers in the international trial. Clinicians were instructed to contour separate gross tumor volumes (GTVs) for the tumor and two enlarged nodes and a clinical target volume for the hilus. A reference 'consensus' target volume for each target was jointly generated by three other clinicians. Results: The data received from the four academic centers and 16 study participants were suitable for analysis. Data from one center was unsuitable for detailed analysis because the target volumes were contoured at 1.2-cm intervals. GTVs were available for a total of 21 tumors and 19 nodes, and 15 hilar clinical target volumes were available. The mean GTV of the primary tumor was 13.6 cm{sup 3} (SD, 5.2; median, 12.3; range, 8.3-26.9). The variation in the center of the mass relative to the mean center of the mass in the left-right, ventrodorsal, and craniocaudal axes was 1.5, 0.4, and 1.0 mm, respectively. The largest volume variation was observed for the right hilar clinical target volume (mean, 33.7 cm{sup 3}; SD, 31.2; median, 20.3; range, 4.8-109.9). Smaller variations were observed for the subcarinal node (mean, GTV, 1.9 cm{sup 3}; SD, 1.2; median, 1.7; range, 0.5-5.3), except caudally where the node was difficult to distinguish from the pericardium. The 'consensus' volumes for all

  11. Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-06-04

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  12. Semi-longitudinal Study of the Mcnamara Cephalometric Triangle in Class II and Class III Subjects Grouped by Cervical Vertebrae Maturation Stage.

    PubMed

    Arriola-Guillén, Luis E; Fitzcarrald, Fernando D; Flores-Mir, Carlos

    2015-12-01

    The aim was to compare the McNamara cephalometric triangle values in untreated normodivergent Class II and Class III malocclusion subjects of Latin American origin grouped by cervical vertebrae maturation stage to an untreated Class I malocclusion normodivergent control group. The study was conducted on a sample of 610 pretreatment lateral cephalograms (250 male, 360 female), examined and grouped according to their anteroposterior skeletal relationship (Class I, II or III), cervical vertebrae maturation stage (Pre Pubertal Peak P1 = CS1 and CS2, Pubertal Peak P2= CS3 and CS4, and Post Pubertal Peak P3 = CS5 and CS6) and sex. Co-A, Co-Gn and ENA-Me were measured in each lateral cephalogram. ANOVA and Tukey HSD post-hoc tests were performed to determine differences between the groups. The results showed that in males, the greatest maxillary and mandibular dimensional increases occurred during the P3 stage (CS5 to CS6), while in females, they occurred in the P2 stage (CS3 to CS4). The Co-A and Co-Gn showed significant differences between the malocclusion classes (p<0.05). The maxillary lengths in Class II subjects and the mandibular lengths in Class III subjects were already higher at the beginning of the period evaluated (P1). A worsening trend for the Class II and III malocclusions was identified during the period evaluated. Finally, changes in the McNamara cephalometric triangle values were markedly different in the three normodivergent skeletal malocclusion classes. In these Latin American subjects the pubertal growth spurt occurred at different times with respect to the Caucasian and Asian norms.

  13. Phase II Study of Chemoradiotherapy With 5-Fluorouracil and Cisplatin for Stage II-III Esophageal Squamous Cell Carcinoma: JCOG Trial (JCOG 9906)

    SciTech Connect

    Kato, Ken; Muro, Kei; Minashi, Keiko; Ohtsu, Atsushi; Ishikura, Satoshi; Boku, Narikazu; Takiuchi, Hiroya; Komatsu, Yoshito; Miyata, Yoshinori; Fukuda, Haruhiko

    2011-11-01

    Purpose: In this Phase II study, we evaluated the efficacy and toxicity of chemoradiotherapy (CRT) with cisplatin (CDDP) and 5-fluorouracil (5-FU) for Stage II-III esophageal squamous cell carcinoma (ESCC). Patients and Methods: Patients with clinical Stage II-III (T1N1M0 or T2-3N0-1M0) thoracic ESCC were enrolled between April 2000 and March 2002. Chemotherapy comprised two courses of protracted infusion of 5-FU (400 mg/m{sup 2}/day) on Days 1-5 and 8-12, and 2-h infusion of CDDP (40 mg/m{sup 2}) on Days 1 and 8; this regimen was repeated every 5 weeks. Concurrent radiotherapy involved 60-Gy irradiation (30 fractions) for 8 weeks with a 2-week break. Responders received two courses of 5-FU (800 mg/m{sup 2}/day) on Days 1-5 and CDDP (80 mg/m{sup 2}) on Day 1. Final analysis was conducted in March 2007. Survival and late toxicities were monitored for 5 years. Results: The characteristics of the 76 patients enrolled were as follows: median age, 61 years; male/female, 68/8; performance status 0/1, 59/17 patients; Stage IIA/IIB/III, 26/12/38 patients. Of the 74 eligible patients, 46 (62.2%) achieved complete response. Median survival time was 29 months, with 3- and 5-year survival rates of 44.7% and 36.8%, respectively. Acute toxicities included Grade 3/4 esophagitis (17%), nausea (17%), hyponatremia (16%), and infection without neutropenia (12%). Late toxicities comprised Grade 3/4 esophagitis (13%), pericardial (16%) and pleural (9%) effusion, and radiation pneumonitis (4%), causing 4 deaths. Conclusions: CRT is effective for Stage II-III ESCC with manageable acute toxicities and can provide a nonsurgical treatment option. However, further improvement is required for reduction in late toxicity.

  14. Chemoradiotherapy versus radiotherapy alone in elderly patients with stage III non-small cell lung cancer: A systematic review and meta-analysis.

    PubMed

    Dawe, David E; Christiansen, David; Swaminath, Anand; Ellis, Peter M; Rothney, Janet; Rabbani, Rasheda; Abou-Setta, Ahmed M; Zarychanski, Ryan; Mahmud, Salaheddin M

    2016-09-01

    In stage III non-small cell lung cancer (NSCLC), the standard of care in young patients is chemoradiotherapy, but this standard is not as clearly established for older patients. We aimed to determine the efficacy and harm associated with chemoradiotherapy versus radiotherapy alone in elderly (≥70 years), stage III NSCLC patients through a systematic review. We conducted a systematic search of MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science and conference proceedings. Two reviewers independently identified randomized trials (RCT) and extracted trial-level data. Risk of bias was assessed and meta-analysis was conducted looking at survival and safety outcomes. We included three trials and subgroup data from one systematic review. The three RCTs had high risk of bias due primarily to lack of blinding and the systematic review scored 4/11 using the AMSTAR tool. Overall survival (HR 0.66, 95% CI 0.53-0.82; I2 0%; 3 trials; 407 patients) and progression-free survival (HR 0.67, 95% CI 0.53-0.85; I2 0%; 2 trials; 327 patients) both favored chemoradiotherapy. Risk of treatment-related death and grade 3+ pneumonitis were not significantly different between groups. In conclusion, treatment of stage III NSCLC patients 70 years or older with chemotherapy and radiotherapy is associated with improved overall survival compared to radiotherapy alone. With the exception of increased hematological toxicity, CRT appears to be tolerable in fit elderly patients and represents a reasonable standard of clinical care. PMID:27565937

  15. Phase 3 Trial of Postoperative Chemotherapy Alone Versus Chemoradiation Therapy in Stage III-IV Gastric Cancer Treated With R0 Gastrectomy and D2 Lymph Node Dissection

    SciTech Connect

    Kim, Tae Hyun; Park, Sook Ryun; Ryu, Keun Won; Kim, Young-Woo; Bae, Jae-Moon; Lee, Jun Ho; Choi, Il Ju; Kim, Yeon-Joo; Kim, Dae Yong

    2012-12-01

    Purpose: To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. Methods and Materials: The chemotherapy arm received 5 cycles of fluorouracil and leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles of FL. Intent-to-treat analysis and per-protocol analyses were performed. Results: Between May 6, 2002 and June 29, 2006, a total of 90 patients were enrolled. Forty-four were randomly assigned to the chemotherapy arm and 46 to the chemoradiation therapy arm. Treatment was completed as planned by 93.2% of patients in the chemotherapy arm and 87.0% in the chemoradiation therapy arm. Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival (LRRFS) but not disease-free survival. In subgroup analysis for stage III, chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy (93.2% vs 66.8%, P=.014; 73.5% vs 54.6%, P=.056, respectively). Conclusions: Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection.

  16. Pretreatment Neutrophil to Lymphocyte Ratio Is Associated with Poor Survival in Patients with Stage I-III Non-Small Cell Lung Cancer

    PubMed Central

    Wang, Jun; Kalhor, Neda; Hu, Jianhua; Wang, Baocheng; Chu, Huili; Zhang, Bicheng; Guan, Yaping; Wu, Yun

    2016-01-01

    Background Neutrophil-to-lymphocyte ratio (NLR) has been shown to be a prognostic indicator in several types of cancer. We aimed to investigate the association between NLR and survival in surgery-treated non-small cell lung cancer (NSCLC) patients. Study Design This large retrospective study included 1,245 patients who underwent initial surgery for stage I–III NSCLC at The University of Texas MD Anderson Cancer Center between December 2002 and November 2010. We analyzed the relationship of NLR with clinicopathological variables, local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS) in patients with high or low NLR using Kaplan-Meier method. Hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the prognostic strength of NLR. Results There was a statistically significant association between the pretreatment NLR and histology type (P = 0.003) and tumor grade (P = 0.028). At a median follow-up time of 50.6 months, high NLR was associated with reduced DRFS (P = 0.011), OS (P < 0.0001) and DSS (P = 0.004); it was not associated with LRFS and RFS. Multivariable Cox analysis further revealed that NLR (P = 0.027), pathologic stage (P < 0.0001) and lymphovascular invasion (P < 0.0001) were strong independent predictors for DRFS. NLR was also an independent marker predicting poor OS (P = 0.002) and DSS (P = 0.017). Conclusion The pretreatment NLR can serve as a biomarker to predict distant recurrence and death in stage I–III NSCLC patients. Combination of NLR and pathologic stage can better predict the OS and DSS in stage I-II NSCLC patients. PMID:27695079

  17. Survival of patients with operable breast cancer (Stages I-III) at a Brazilian public hospital - a closer look into cause-specific mortality

    PubMed Central

    2013-01-01

    Background Breast cancer incidence is increasing. The survival rate varies and is longer in high-income countries. In Brazil, lower-income populations rely on the Unified Public Health System (Sistema Único de Saude, SUS) for breast cancer care. The goal of our study is to evaluate the survival of patients with operable breast cancer stages I-III at a Brazilian public hospital that treats mostly patients from the SUS. Methods A cohort study of patients who underwent surgery for breast cancer treatment at the Clinical Hospital of the Federal University of Minas Gerais from 2001 to 2008 was performed, with a population of 897 cases. Information on tumor pathology and staging, as well as patients’ age and type of health coverage (SUS or private system) was collected. A probabilistic record linkage was performed with the database of the Mortality Information System to identify patients who died by December 31th, 2011. The basic cause of death was retrieved, and breast cancer-specific survival rates were estimated with the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis of factors related to survival. Results A total of 282 deaths occurred during the study’s period, 228 of them due to breast cancer. Five-year breast cancer-specific survival rates were 95.5% for stage I, 85.1% for stage II and 62.1% for stage III disease. Patients from the SUS had higher stages at diagnosis (42% was in stage III, and from the private system only 17.6% was in this stage), and in the univariate but not multivariate analysis, being treated by the SUS was associated with shorter survival (hazard ratio, HR = 2.22, 95% CI 1.24-3.98). In the multivariate analysis, larger tumor size, higher histologic grade, higher number of positive nodes and age older than 70 years were associated with a shorter breast cancer-specific survival. Conclusions Five-year breast cancer survival was comparable to other Brazilian cohorts. Patients

  18. Multiple Stages of Weekend Field Trips To Expose Students to Nature: Emphasis on Discovery and Awareness.

    ERIC Educational Resources Information Center

    Krupa, James J.

    2002-01-01

    Describes the three stages of a field trip and reviews stage 1, weekend field trips, which focuses on an organism's morphology, behavior, and ecology. Presents activities on salamanders, small mammals, fish, birds, and bats. Explains the difficulties of weekend trips. (YDS)

  19. Multiple functional UV devices based on III-Nitride quantum wells for biological warfare agent detection

    NASA Astrophysics Data System (ADS)

    Wang, Qin; Savage, Susan; Persson, Sirpa; Noharet, Bertrand; Junique, Stéphane; Andersson, Jan Y.; Liuolia, Vytautas; Marcinkevicius, Saulius

    2009-02-01

    We have demonstrated surface normal detecting/filtering/emitting multiple functional ultraviolet (UV) optoelectronic devices based on InGaN/GaN, InGaN/AlGaN and AlxGa1-xN/AlyGa1-yN multiple quantum well (MQW) structures with operation wavelengths ranging from 270 nm to 450 nm. Utilizing MQW structure as device active layer offers a flexibility to tune its long cut-off wavelength in a wide UV range from solar-blind to visible by adjusting the well width, well composition and barrier height. Similarly, its short cut-off wavelength can be adjusted by using a GaN or AlGaN block layer on a sapphire substrate when the device is illuminated from its backside, which further provides an optical filtering effect. When a current injects into the device under forward bias the device acts as an UV light emitter, whereas the device performs as a typical photodetector under reverse biases. With applying an alternating external bias the device might be used as electroabsorption modulator due to quantum confined Stark effect. In present work fabricated devices have been characterized by transmission/absorption spectra, photoresponsivity, electroluminescence, and photoluminescence measurements under various forward and reverse biases. The piezoelectric effect, alloy broadening and Stokes shift between the emission and absorption spectra in different InGaN- and AlGaN-based QW structures have been investigated and compared. Possibilities of monolithic or hybrid integration using such multiple functional devices for biological warfare agents sensing application have also be discussed.

  20. Spectral Discrimination of the Invasive Plant Spartina alterniflora at Multiple Phenological Stages in a Saltmarsh Wetland

    PubMed Central

    Ouyang, Zu-Tao; Gao, Yu; Xie, Xiao; Guo, Hai-Qiang; Zhang, Ting-Ting; Zhao, Bin

    2013-01-01

    Spartina alterniflora has widely invaded the saltmarshes of the Yangtze River Estuary and brought negative effects to the ecosystem. Remote sensing technique has recently been used to monitor its distribution, but the similar morphology and canopy structure among S. alterniflora and its neighbor species make it difficult even with high-resolution images. Nevertheless, these species have divergence on phenological stages throughout the year, which cause distinguishing spectral characteristics among them and provide opportunities for discrimination. The field spectra of the S. alterniflora community as well as its major victims, native Phragmites australis and Scirpus mariqueter, were measured in 2009 and 2010 at multi-phenological stages in the Yangtze River Estuary, aiming to find the most appropriate periods for mapping S. alterniflora. Collected spectral data were analyzed separately for every stage firstly by re-sampling reflectance curves into continued 5-nm-wide hyper-spectral bands and then by re-sampling into broad multi-spectral bands – the same as the band ranges of the TM sensor, as well as calculating commonly used vegetation indices. The results showed that differences among saltmarsh communities’ spectral characteristics were affected by their phenological stages. The germination and early vegetative growth stage and the flowering stage were probably the best timings to identify S. alterniflora. Vegetation indices like NDVI, ANVI, VNVI, and RVI are likely to enhance spectral separability and also make it possible to discriminate S. alterniflora at its withering stage. PMID:23826265

  1. Performance of 15-Stage Experimental J71 Axial-Flow Compressor. III - Effects of Inlet-Guide-Vane Adjustment

    NASA Technical Reports Server (NTRS)

    Lucas, James G.; Filippi, Richard E.

    1955-01-01

    The stall-limit line at low speeds was improved somewhat by closing the inlet guide vanes 6 deg, while the design-speed maximum flow and pressure ratio were reduced. The first-stage characteristic curve was moved to lower values of both flog coefficient and equivalent pressure ratio. The second-stage pressure ratio was decreased slightly at high speeds, while the later stages were unaffected.

  2. Reducing bias in population and landscape genetic inferences: the effects of sampling related individuals and multiple life stages.

    PubMed

    Peterman, William; Brocato, Emily R; Semlitsch, Raymond D; Eggert, Lori S

    2016-01-01

    In population or landscape genetics studies, an unbiased sampling scheme is essential for generating accurate results, but logistics may lead to deviations from the sample design. Such deviations may come in the form of sampling multiple life stages. Presently, it is largely unknown what effect sampling different life stages can have on population or landscape genetic inference, or how mixing life stages can affect the parameters being measured. Additionally, the removal of siblings from a data set is considered best-practice, but direct comparisons of inferences made with and without siblings are limited. In this study, we sampled embryos, larvae, and adult Ambystoma maculatum from five ponds in Missouri, and analyzed them at 15 microsatellite loci. We calculated allelic richness, heterozygosity and effective population sizes for each life stage at each pond and tested for genetic differentiation (F ST and D C ) and isolation-by-distance (IBD) among ponds. We tested for differences in each of these measures between life stages, and in a pooled population of all life stages. All calculations were done with and without sibling pairs to assess the effect of sibling removal. We also assessed the effect of reducing the number of microsatellites used to make inference. No statistically significant differences were found among ponds or life stages for any of the population genetic measures, but patterns of IBD differed among life stages. There was significant IBD when using adult samples, but tests using embryos, larvae, or a combination of the three life stages were not significant. We found that increasing the ratio of larval or embryo samples in the analysis of genetic distance weakened the IBD relationship, and when using D C , the IBD was no longer significant when larvae and embryos exceeded 60% of the population sample. Further, power to detect an IBD relationship was reduced when fewer microsatellites were used in the analysis. PMID:26989639

  3. Reducing bias in population and landscape genetic inferences: the effects of sampling related individuals and multiple life stages

    PubMed Central

    Brocato, Emily R.; Semlitsch, Raymond D.; Eggert, Lori S.

    2016-01-01

    In population or landscape genetics studies, an unbiased sampling scheme is essential for generating accurate results, but logistics may lead to deviations from the sample design. Such deviations may come in the form of sampling multiple life stages. Presently, it is largely unknown what effect sampling different life stages can have on population or landscape genetic inference, or how mixing life stages can affect the parameters being measured. Additionally, the removal of siblings from a data set is considered best-practice, but direct comparisons of inferences made with and without siblings are limited. In this study, we sampled embryos, larvae, and adult Ambystoma maculatum from five ponds in Missouri, and analyzed them at 15 microsatellite loci. We calculated allelic richness, heterozygosity and effective population sizes for each life stage at each pond and tested for genetic differentiation (FST and DC) and isolation-by-distance (IBD) among ponds. We tested for differences in each of these measures between life stages, and in a pooled population of all life stages. All calculations were done with and without sibling pairs to assess the effect of sibling removal. We also assessed the effect of reducing the number of microsatellites used to make inference. No statistically significant differences were found among ponds or life stages for any of the population genetic measures, but patterns of IBD differed among life stages. There was significant IBD when using adult samples, but tests using embryos, larvae, or a combination of the three life stages were not significant. We found that increasing the ratio of larval or embryo samples in the analysis of genetic distance weakened the IBD relationship, and when using DC, the IBD was no longer significant when larvae and embryos exceeded 60% of the population sample. Further, power to detect an IBD relationship was reduced when fewer microsatellites were used in the analysis. PMID:26989639

  4. A Phase II Trial of R-CHOP Followed by Radioimmunotherapy for Early Stage (Stages I/II) Diffuse Large B-Cell Non-Hodgkin Lymphoma: ECOG3402

    PubMed Central

    Witzig, Thomas E.; Hong, Fangxin; Micallef, Ivana N.; Gascoyne, Randy D.; Dogan, Ahmet; Wagner, Henry; Kahl, Brad S.; Advani, Ranjana H.; Horning, Sandra J.

    2015-01-01

    Summary Patients with early stage diffuse large B-cell lymphoma (DLBCL) receive RCHOP alone or with involved field radiotherapy (IFRT). Anti-CD20 radioimmunotherapy (RIT) delivers radiation to microscopic sites outside of known disease. This phase II study aimed to achieve a functional CR rate of ≥75% to RCHOP and 90Yttrium-ibritumomab tiuxetan RIT. Patients with stages I/II DLBCL received 4–6 cycles of RCHOP followed by RIT (0.4 mCi/kg); patients with PET positive sites of disease after RCHOP/RIT received 30Gy IFRT. Of the 62 patients enrolled; 53 were eligible. 42% (22/53) had stage I/IE; 58% (31/53) stage II/IIE. After RCHOP, 79% (42/53) were in CR/CRu. Forty–eight patients proceeded to RIT and one patient in PR after RIT received IFRT and achieved a CR. The best response after RCHOP+RIT in all 53 patients was a functional CR rate of 89% (47/53; 95% CI:77–96%). With a median follow-up of 5.9 years, 7 (13%) patients have progressed and 4 (8%) have died (2 with DLBCL). At 5 years, 78% of patients remain in remission and 94% are alive. Chemoimmunotherapy and RIT is an active regimen for early stage DLBCL patients. Eighty-nine% of patients achieved functional CR without the requirement of IFRT. This regimen is worthy of further study for early stage DLBCL in a phase III trial. PMID:25974212

  5. Single-molecule magnetism in three related {Co(III)2Dy(III)2}-acetylacetonate complexes with multiple relaxation mechanisms.

    PubMed

    Langley, Stuart K; Chilton, Nicholas F; Moubaraki, Boujemaa; Murray, Keith S

    2013-06-17

    Three new heterometallic complexes with formulas of [Dy(III)2Co(III)2(OMe)2(teaH)2(acac)4(NO3)2] (1), [Dy(III)2Co(III)2(OH)2(teaH)2(acac)4(NO3)2]·4H2O (2), and [Dy(III)2Co(III)2(OMe)2(mdea)2(acac)4(NO3)2] (3) were characterized by single-crystal X-ray diffraction and by dc and ac magnetic susceptibility measurements. All three complexes have an identical "butterfly"-type metallic core that consists of two Dy(III) ions occupying the "body" position and two diamagnetic low-spin Co(III) ions occupying the outer "wing-tips". Each complex displays single-molecule magnet (SMM) behavior in zero applied magnetic field, with thermally activated anisotropy barriers of 27, 28, and 38 K above 7.5 K for 1-3, respectively, as well as observing a temperature-independent mechanism of relaxation below 5 K for 1 and 2 and at 3 K for 3, indicating fast quantum tunneling of magnetization (QTM). A second, faster thermally activated relaxation mechanism may also be active under a zero applied dc field as derived from the Cole-Cole data. Interestingly, these complexes demonstrate further relaxation modes that are strongly dependent upon the application of a static dc magnetic field. Dilution experiments that were performed on 1, in the {Y(III)2Co(III)2} diamagnetic analog, show that the slow magnetic relaxation is of a single-ion origin, but it was found that the neighboring ion also plays an important role in the overall relaxation dynamics.

  6. A multiplicity of factors contributes to selective RNA polymerase III occupancy of a subset of RNA polymerase III genes in mouse liver.

    PubMed

    Canella, Donatella; Bernasconi, David; Gilardi, Federica; LeMartelot, Gwendal; Migliavacca, Eugenia; Praz, Viviane; Cousin, Pascal; Delorenzi, Mauro; Hernandez, Nouria

    2012-04-01

    The genomic loci occupied by RNA polymerase (RNAP) III have been characterized in human culture cells by genome-wide chromatin immunoprecipitations, followed by deep sequencing (ChIP-seq). These studies have shown that only ∼40% of the annotated 622 human tRNA genes and pseudogenes are occupied by RNAP-III, and that these genes are often in open chromatin regions rich in active RNAP-II transcription units. We have used ChIP-seq to characterize RNAP-III-occupied loci in a differentiated tissue, the mouse liver. Our studies define the mouse liver RNAP-III-occupied loci including a conserved mammalian interspersed repeat (MIR) as a potential regulator of an RNAP-III subunit-encoding gene. They reveal that synteny relationships can be established between a number of human and mouse RNAP-III genes, and that the expression levels of these genes are significantly linked. They establish that variations within the A and B promoter boxes, as well as the strength of the terminator sequence, can strongly affect RNAP-III occupancy of tRNA genes. They reveal correlations with various genomic features that explain the observed variation of 81% of tRNA scores. In mouse liver, loci represented in the NCBI37/mm9 genome assembly that are clearly occupied by RNAP-III comprise 50 Rn5s (5S RNA) genes, 14 known non-tRNA RNAP-III genes, nine Rn4.5s (4.5S RNA) genes, and 29 SINEs. Moreover, out of the 433 annotated tRNA genes, half are occupied by RNAP-III. Transfer RNA gene expression levels reflect both an underlying genomic organization conserved in dividing human culture cells and resting mouse liver cells, and the particular promoter and terminator strengths of individual genes.

  7. Outcome Study of Cobalt Based Stereotactic Body Radiation Therapy for Patients with Inoperable Stage III Non-small Cell Lung Cancer.

    PubMed

    Wang, Yingjie; Lan, Fengming; Kang, Xiaoli; Shao, Yinjian; Li, Hongqi; Li, Ping; Wu, Weizhang; Wang, Jidong; Chang, Dongshu; Wang, Yong; Xia, Tingyi

    2015-10-01

    Aim of this paper is to retrospectively evaluate the efficacy and toxicity of specialized Body Cobalt based system (BCBS) treatment in the senior patients group (.65 years) with Stage III non-small cell lung carcinoma (NSCLC). A total of 49 patients (41 males and 8 females) with Stage III NSCLC according to UICC TNM classification (6(th) edition) were treated using OUR-QGD™ BCBS which was designed and manufactured in China. Post treatment evaluation with follow-up information was collected from April 2001 to December 2006 in our department. Median age of enrolled patients was 71 years old (65-85). Among those patients, 36 patients were pathologically identified with squamous cell carcinoma, and the other 13 patients were confirmed as adenocarcinoma. All patients were immobilized by vacuum based immobilization mold and then performed slow CT scan without any respiration gating devices. The daily radiation prescription dose was defined at 50% isodose line covering primary lesions and metastatic lymph nodes with doses from 2.5 to 6 Gy in 5 fractions per week according to the tumor stage and internally approved treatment protocols by the Institutional Review Board (IRB). Median daily dose and total delivery dose of 50% isodose line were 4 Gy and 41 Gy, respectively. In this study group, total of 3 patients received neoadjuvant cisplatin-based chemotherapy. Tumor response evaluated 12 weeks after radiation has demonstrated 13 complete responses (26.5%), 21 partial responses (42.9%). The overall survival (OS) rate of 1-year, 2-year and 3-year was 63.3%, 40.8% and 20.4%, respectively. The median and mean survival time was 22 and 24 months. All 49 patients tolerated the treatment well and have completed the planned therapy regiment. Body Cobalt based system treatment of those over 65 years old patients with Stage III NSCLC had reasonable and superior curative effect as well as local control, and at the same time without severe radiation side effects.

  8. Long-term results of high-dose-rate brachytherapy in the primary treatment of medically inoperable stage I-II endometrial carcinoma

    SciTech Connect

    Niazi, Tamim M.; Souhami, Luis . E-mail: luis.souhami@muhc.mcgill.ca; Portelance, Lorraine; Bahoric, Boris; Gilbert, Lucy; Stanimir, Gerald

    2005-11-15

    Purpose: Total-abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) is the gold-standard therapy for patients with endometrial carcinoma. However, patients with high operative risks are usually treated with radiation therapy (RT) alone. The goal of this study was to update our experience of high-dose-rate brachytherapy (HDRB), with or without external-beam irradiation (EBRT), for such patients. Methods and Materials: Between 1984 and 2003, 38 patients with Stage I and Stage II adenocarcinoma of the endometrium considered high operative risk received RT as the primary treatment. The median age was 74.1 years. Before 1996, the local extent of the disease was assessed by an examination under anesthesia (EUA) and by EUA and magnetic resonance imaging (MRI) thereafter. Eight patients (21%) were treated with combined HDRB and EBRT, and 30 patients (79%) were treated with with HDRB alone. The median HDRB dose was 23.9 Gy, typically delivered in 3 fractions in a weekly schedule. The median EBRT dose was 42 Gy. Results: At a median follow-up of 57.5 months for patients at risk, 11 patients (29%) have failed: 6 patients (16%) locally, 4 patients (10.5%) distantly, and 1 patient (3%) locally and distantly. Local failure was established by biopsy, and 4 patients were salvaged by TAHBSO. Higher stage and higher grade were both associated with increased failure rate. The 15-year disease-specific survival (DSS) was 78% for all stages, 90% for Stage I, and 42% for Stage II (p < 0.0001). The 15-year DSS was 91% for Grade I and 67% for Grade II and III combined (p = 0.0254). Patients with Stage I disease established by MRI (11 patients) and who received a total HDRB dose of 30 Gy had a DSS rate of 100% at 10 years. Four patients experienced late toxicities: 1 Grade II and 3 Grade III or IV. Conclusion: Medically inoperable Stage I endometrial carcinoma may be safely and effectively treated with HDRB as the primary therapy. In selected Stage I patients, our results are

  9. Transcriptome analysis of various flower and silique development stages indicates a set of class III peroxidase genes potentially involved in pod shattering in Arabidopsis thaliana

    PubMed Central

    2010-01-01

    Background Plant class III peroxidases exist as a large multigenic family involved in numerous functions suggesting a functional specialization of each gene. However, few genes have been linked with a specific function. Consequently total peroxidase activity is still used in numerous studies although its relevance is questionable. Transcriptome analysis seems to be a promising tool to overcome the difficulties associated with the study of this family. Nevertheless available microarrays are not completely reliable for this purpose. We therefore used a macroarray dedicated to the 73 class III peroxidase genes of A. thaliana to identify genes potentially involved in flower and fruit development. Results The observed increase of total peroxidase activity during development was actually correlated with the induction of only a few class III peroxidase genes which supports the existence of a functional specialization of these proteins. We identified peroxidase genes that are predominantly expressed in one development stage and are probable components of the complex gene networks involved in the reproductive phase. An attempt has been made to gain insight into plausible functions of these genes by collecting and analyzing the expression data of different studies in plants. Peroxidase activity was additionally observed in situ in the silique dehiscence zone known to be involved in pod shattering. Because treatment with a peroxidase inhibitor delayed pod shattering, we subsequently studied mutants of transcription factors (TF) controlling this mechanism. Three peroxidases genes -AtPrx13, AtPrx30 and AtPrx55- were altered by the TFs involved in pod shatter. Conclusions Our data illustrated the problems caused by linking only an increase in total peroxidase activity to any specific development stage or function. The activity or involvement of specific class III peroxidase genes needs to be assessed. Several genes identified in our study had not been linked to any particular

  10. Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial

    PubMed Central

    Boer, R H de; Smith, I E; Pastorino, U; O'Brien, M E R; Ramage, F; Ashley, S; Goldstraw, P

    1999-01-01

    Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m−2, vinblastine 6 mg m−2 and cisplatin 50 mg m−2 (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III–IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial. © 1999 Cancer Research Campaign PMID:10188899

  11. Highly efficient multiple-layer CdS quantum dot sensitized III-V solar cells.

    PubMed

    Lin, Chien-Chung; Han, Hau-Vei; Chen, Hsin-Chu; Chen, Kuo-Ju; Tsai, Yu-Lin; Lin, Wein-Yi; Kuo, Hao-Chung; Yu, Peichen

    2014-02-01

    In this review, the concept of utilization of solar spectrum in order to increase the solar cell efficiency is discussed. Among the three mechanisms, down-shifting effect is investigated in detail. Organic dye, rare-earth minerals and quantum dots are three most popular down-shift materials. While the enhancement of solar cell efficiency was not clearly observed in the past, the advances in quantum dot fabrication have brought strong response out of the hybrid platform of a quantum dot solar cell. A multiple layer structure, including PDMS as the isolation layer, is proposed and demonstrated. With the help of pulse spray system, precise control can be achieved and the optimized concentration can be found.

  12. Coherent nanocavity structures for enhancement in internal quantum efficiency of III-nitride multiple quantum wells

    SciTech Connect

    Kim, T.; Liu, B.; Smith, R.; Athanasiou, M.; Gong, Y.; Wang, T.

    2014-04-21

    A “coherent” nanocavity structure has been designed on two-dimensional well-ordered InGaN/GaN nanodisk arrays with an emission wavelength in the green spectral region, leading to a massive enhancement in resonance mode in the green spectra region. By means of a cost-effective nanosphere lithography technique, we have fabricated such a structure on an InGaN/GaN multiple quantum well epiwafer and have observed the “coherent” nanocavity effect, which leads to an enhanced spontaneous emission (SE) rate. The enhanced SE rate has been confirmed by time resolved photoluminescence measurements. Due to the coherent nanocavity effect, we have achieved a massive improvement in internal quantum efficiency with a factor of 88, compared with the as-grown sample, which could be significant to bridge the “green gap” in solid-state lighting.

  13. A new multiple-stage electrocoagulation process on anaerobic digestion effluent to simultaneously reclaim water and clean up biogas.

    PubMed

    Liu, Zhiguo; Stromberg, David; Liu, Xuming; Liao, Wei; Liu, Yan

    2015-03-21

    A new multiple-stage treatment process was developed via integrating electrocoagulation with biogas pumping to simultaneously reclaim anaerobic digestion effluent and clean up biogas. The 1st stage of electrocoagulation treatment under the preferred reaction condition led to removal efficiencies of 30%, 81%, 37% and >99.9% for total solids, chemical oxygen demand, total nitrogen and total phosphorus, respectively. Raw biogas was then used as a reactant and pumped into the effluent to simultaneously neutralize pH of the effluent and remove H2S in the biogas. The 2nd stage of electrocoagulation treatment on the neutralized effluent showed that under the selected reaction condition, additional 60% and 10% of turbidity and chemical oxygen demand were further removed. The study concluded a dual-purpose approach for the first time to synergistically combine biogas purification and water reclamation for anaerobic digestion system, which well addresses the downstream challenges of anaerobic digestion technology.

  14. A new multiple-stage electrocoagulation process on anaerobic digestion effluent to simultaneously reclaim water and clean up biogas.

    PubMed

    Liu, Zhiguo; Stromberg, David; Liu, Xuming; Liao, Wei; Liu, Yan

    2015-03-21

    A new multiple-stage treatment process was developed via integrating electrocoagulation with biogas pumping to simultaneously reclaim anaerobic digestion effluent and clean up biogas. The 1st stage of electrocoagulation treatment under the preferred reaction condition led to removal efficiencies of 30%, 81%, 37% and >99.9% for total solids, chemical oxygen demand, total nitrogen and total phosphorus, respectively. Raw biogas was then used as a reactant and pumped into the effluent to simultaneously neutralize pH of the effluent and remove H2S in the biogas. The 2nd stage of electrocoagulation treatment on the neutralized effluent showed that under the selected reaction condition, additional 60% and 10% of turbidity and chemical oxygen demand were further removed. The study concluded a dual-purpose approach for the first time to synergistically combine biogas purification and water reclamation for anaerobic digestion system, which well addresses the downstream challenges of anaerobic digestion technology. PMID:25540943

  15. Feasibility and efficacy of helical intensity-modulated radiotherapy for stage III non-small cell lung cancer in comparison with conventionally fractionated 3D-CRT

    PubMed Central

    He, Jian; Huang, Yan; Chen, Yixing; Shi, Shiming; Ye, Luxi; Hu, Yong; Zhang, Jianying

    2016-01-01

    Background The standard treatment for stage III non-small-cell lung cancer (NSCLC) is still 60 Gy in conventional fractions combined with concurrent chemotherapy; however, the resulting local controls are disappointing. The aim of this study was to compare and assess the feasibility and efficacy of hypofractionated chemoradiotherapy using helical tomotherapy (HT) with conventional fractionation as opposed to using three-dimensional conformal radiotherapy (3D-CRT) for stage III NSCLC. Methods Sixty-nine patients with stage III (AJCC 7th edition) NSCLC who underwent definitive radiation treatment at our institution between July 2011 and November 2013 were reviewed and analyzed retrospectively. A dose of 60 Gy in 20 fractions was delivered in the HT group (n=34), whereas 60 Gy in 30 fractions in the 3D-CRT group (n=35). Primary endpoints were toxicity, overall response rate, overall survival (OS) and progression-free survival (PFS). Results The median follow-up period was 26.4 months. V20 (P=0.005), V30 (P=0.001), V40 (P=0.004), mean lung dose (P=0.000) and max dose of spinal cord (P=0.005) were significantly lower in the HT group than in the 3D-CRT group. There was no significant difference in the incidences of acute radiation pneumonitis (RP) ≥ grade 2 between the two groups, whereas the incidences of acute radiation esophagitis ≥ grade 2 were significantly lower in the HT group than in the 3D-CRT group (P=0.027). Two-year overall response rate was significantly higher in the HT group than in the 3D-CRT group (P=0.015). One- and 2-year OS rates were significantly higher in the HT group (95.0% and 68.7%, respectively) than in the 3D-CRT group (85.5% and 47.6%, respectively; P=0.0236). One- and 2-year PFS rates were significantly higher in the HT group (57.8% and 26.3%, respectively) than in the 3D-CRT group (32.7% and 11.4%, respectively; P=0.0351). Univariate analysis indicated that performance status (PS), T stage and radiotherapy technique were significant

  16. Stage III and oestrogen receptor negativity are associated with poor prognosis after adjuvant high-dose therapy in high-risk breast cancer

    PubMed Central

    Hohaus, S; Funk, L; Martin, S; Schlenk, R F; Abdallah, A; Hahn, U; Egerer, G; Goldschmidt, H; Schneeweiß, A; Fersis, N; Kaul, S; Wallwiener, D; Bastert, G; Haas, R

    1999-01-01

    We report on the efficacy and toxicity of a sequential high-dose therapy with peripheral blood stem cell (PBSC) support in 85 patients with high-risk stage II/III breast cancer. There were 71 patients with more than nine tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7.5 g m−2) and epirubicin (120 mg m−2) was given, and PBSC were harvested during G-CSF-supported leucocyte recovery following the second cycle. The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide (total dose, 12 000 mg m−2), carboplatin (900 mg m−2) and epirubicin (180 mg m−2). Patients were autografted with a median number of 3.7 × 106 CD34+ cells kg−1 (range, 1.9–26.5 × 106) resulting in haematological reconstitution within approximately 2 weeks following high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-one patients relapsed between 3 and 30 months following the last cycle of high-dose therapy (median, 11 months). The probability of disease-free and overall survival at 4 years were 60% and 83%, respectively. According to a multivariate analysis, patients with stage II disease had a significantly better probability of disease-free survival (74%) in comparison to patients with stage III disease (36%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (70%) compared to patients with receptor-negative ones (40%). Bone marrow samples collected from 52 patients after high-dose therapy were examined to evaluate the prognostic relevance of isolated tumour cells. The proportion of patients presenting with tumour cell-positive samples did not change in comparison to that observed before high-dose therapy (65% vs 71%), but a decrease in the incidence and concentration of tumour cells was observed over time after high-dose therapy. This finding was true for patients with relapse

  17. Estimating service lives of organic vapor cartridges III: multiple vapors at all humidities.

    PubMed

    Wood, Gerry O; Snyder, Jay L

    2007-05-01

    A published model for estimating service lives of organic vapor (OV) air-purifying respirator cartridges has been extended to include multiple organic vapors at all humidities. Equilibria among the OVs are calculated using Ideal Adsorbed Solution Theory, whereas the effects of adsorbed water are considered as due to micropore volume exclusion. Solubilities of OVs in water must also be taken into account. Adsorption kinetics of components of mixtures are based on published correlations of the effects of covapors and water vapor. The dynamics of adsorption and competition are incorporated using expanding zones within the carbon bed, taking into account vapor and water displacements. Measurements of breakthrough curves for two ternary OV mixtures at high humidities have been done for a single cartridge type. The service life estimation model, implemented as a spreadsheet and a computer program, has been tested against these data as well as data for OV mixtures from literature sources. Good agreements were obtained between model predictions and experimental breakthrough times at dry conditions and humid conditions. PMID:17454504

  18. TOPoS. III. An ultra iron-poor multiple CEMP system

    NASA Astrophysics Data System (ADS)

    Caffau, E.; Bonifacio, P.; Spite, M.; Spite, F.; Monaco, L.; Sbordone, L.; François, P.; Gallagher, A. J.; Plez, B.; Zaggia, S.; Ludwig, H.-G.; Cayrel, R.; Koch, A.; Steffen, M.; Salvadori, S.; Klessen, R.; Glover, S.; Christlieb, N.

    2016-10-01

    Aims: One of the primary objectives of the TOPoS survey is to search for the most metal-poor stars. Our search has led to the discovery of one of the most iron-poor objects known, SDSS J092912.32+023817.0. This object is a multiple system, in which two components are clearly detected in the spectrum. Methods: We have analysed 16 high-resolution spectra obtained using the UVES spectrograph at the ESO 8.2 m VLT telescope to measure radial velocities and determine the chemical composition of the system. Results: Cross correlation of the spectra with a synthetic template yields a double-peaked cross-correlation function (CCF) for eight spectra, and in one case there is evidence for the presence of a third peak. Chemical analysis of the spectrum obtained by averaging all the spectra for which the CCF showed a single peak found that the iron abundance is [Fe/H] = -4.97. The system is also carbon enhanced with [C/Fe] = +3.91 (A(C) = 7.44). From the permitted oxygen triplet we determined an upper limit for oxygen of [O/Fe] < +3.52 such that C/O > 1.3. We are also able to provide more stringent upper limits on the Sr and Ba abundances ([Sr/Fe] < +0.70, and [Ba/Fe] < +1.46, respectively). Based on observations made with ESO Telescopes at the La Silla Paranal Observatory under programme ID 094.D-0488 and 096.D-0616.

  19. A Prospective Study of Comparing Multi-Gene Biomarker Chip and Serum Carcinoembryonic Antigen in the Postoperative Surveillance for Patients with Stage I-III Colorectal Cancer

    PubMed Central

    Chang, Yu-Tang; Huang, Ming-Yii; Yeh, Yung-Sung; Huang, Ching-Wen; Tsai, Hsiang-Lin; Cheng, Tian-Lu; Wang, Jaw-Yuan

    2016-01-01

    Background Circulating biomarkers can predict clinical outcomes in colorectal cancer patients. The aim of the study was to evaluate the feasibility of our multigene biomarker chip for detecting circulating tumor cells for postoperative surveillance of stage I–III colorectal cancer patients. Materials and Methods In total, 298 stage I–III colorectal cancer patients were analyzed after curative resection between June 2010 and October 2014. During each follow-up, a postoperative surveillance strategy, including ESMO Guidelines Working Group recommendations and the biochip, was used. Results After a 28.4-month median follow-up, 48 (16.1%) patients had postoperative relapse. Univariate analysis revealed that the postoperative relapse risk factors were rectal tumor, perineural invasion, elevated preoperative and postoperative serum carcinoembryonic antigen levels, and positive biochip results (all P < 0.05). Multivariate analyses revealed that postoperative relapse correlated significantly with elevated postoperative serum carcinoembryonic antigen levels (odds ratio = 4.136, P = 0.008) and positive biochip results (odds ratio = 66.878, P < 0.001). However, the sensitivity (P = 0.003), specificity (P = 0.003), positive (P = 0.002) and negative (P = 0.006) predictive values, and accuracy (P < 0.001) of the biochip for predicting postoperative relapse were significantly higher than those of elevated postoperative serum carcinoembryonic antigen levels. Moreover, the median lead time between positive biochip result and postoperative relapse detection was significantly earlier than that between elevated postoperative serum carcinoembryonic antigen level and postoperative relapse detection (10.7 vs. 2.8 months, P < 0.001). Furthermore, positive biochip results correlated strongly with lower disease-free survival and overall survival of colorectal cancer patients (both P < 0.001). Conclusion Compared with conventional serum carcinoembryonic antigen detection, our multigene

  20. Histology of the Oral Mucosa in Patients With BRONJ at III Stage: A Microscopic Study Proves the Unsuitability of Local Mucosal Flaps

    PubMed Central

    Lorenzo, Sara Di; Trapassi, Alberto; Corradino, Bartolo; Cordova, Adriana

    2013-01-01

    Background Bisphosphonate Osteonecrosis of the Jaw (BRONJ) is a newly recognized condition reported in patients treated with aminobisphosphonates (BF). BRONJ is defined as the presence of exposed necrotic alveolar bone that does not resolve over a period of 8 weeks in a patient taking bisphosphonates who has not had radiotherapy to the jaw. Treatment protocols have been outlined, but trials and outcomes of treatment and long-term follow-up data are not yet available. In 2004 an expert panel outlined recommendations for the management of bisphosphonate-associated osteonecrosis of the jaws. Through the histological study of the oral mucosa over the bone necrosis and around the osteonecrosis area in 8 patients affected by BRONJ at III stage, the authors highlight the inappropriateness of the local mucosal flaps to cover the losses of substance of the jaw, BF-related. Methods Mucosa tissue was taken from 8 patients, affected by BRONJ, III stage. The samples taken from the mucosa around and over the osteonecrosis area were fixed with formalin and an ematossilina-eosin dichromatic coloring was carried out. Results The samples of mucosa showed pathognomonic signs of cell suffering that prove that in these patients using local mucosa flaps is inappropriate. Conclusions The authors suggest that only a well vascularized flap as free flap must be used to cover the osteonecrosis area in patients with BRONJ stage III. Because of the structural instability of the mucosa in patients suffering of osteonecrosis Bf related the local flaps are prone to ulceration and to relapse. PMID:23390472

  1. Mutation Profiling and Microsatellite Instability in Stage II and III Colon Cancer: An Assessment of Their Prognostic and Oxaliplatin Predictive Value

    PubMed Central

    Gavin, Patrick G.; Colangelo, Linda H.; Fumagalli, Debora; Tanaka, Noriko; Remillard, Matthew Y.; Yothers, Greg; Kim, Chungyeul; Taniyama, Yusuke; Kim, Seung Il; Choi, Hyun Joo; Blackmon, Nicole L.; Lipchik, Corey; Petrelli, Nicholas J.; O'Connell, Michael J.; Wolmark, Norman; Paik, Soonmyung; Pogue-Geile, Kay L.

    2014-01-01

    Purpose The purpose of this study was to examine the prognostic and oxaliplatin predictive value of mismatch repair (MMR) status and common hot spot mutations, which we previously identified in stage II and III colon cancer. Experimental Design Mutations in BRAF, KRAS, NRAS, MET, and PIK3CA were profiled in 2,299 stage II and III colon tumors from National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials C-07 (n = 1,836) and C-08 (n = 463) with Type Plex chemistry and mass spectrometry. C-07 tested the worth of adding oxaliplatin to 5-fluorouracil plus leucovorin, and C-08 tested the worth of adding bevacizumab to FOLFOX. Cox proportional hazard models were used to assess prognostic or oxaliplatin predictive value of mutations for tumor recurrence, overall survival (OS), and survival after recurrence (SAR). Results BRAF mutations were associated with MMR-deficient tumors (P < 0.0001), poor OS [HR, 1.46; 95% confidence interval (CI), 1.20–1.79; P S: 0.0002], and poor SAR (HR, 2.31; 95% CI, 1.83–2.95; P < 0.0001). Mutations in KRAS, NRAS, MET, and PIK3CA were not associated with recurrence, OS, or SAR. MMR-deficient tumors were associated with an improved prognosis based on recurrence (HR, 0.48; 95% CI, 0.33–0.70; P < 0.0001). Mutations and MMR status were not predictive for oxaliplatin benefit. Conclusions This study shows that BRAF mutations profiled from stage II and III colon cancer tumors were associated with poor SAR and validates and explains, at least in part, previous observations associating it with poor OS. Profiling of all of these mutations is warranted for future clinical trials testing new targeted therapies that block relevant signaling pathways. Such clinical trials are under development at NSABP. PMID:23045248

  2. The Effect of Extrafascial Hysterectomy After Completion of External Beam Radiotherapy for Treatment of Locally Advanced Stages (IIB-III) of Cervical Cancer

    PubMed Central

    Sarraf, Zahra; Hamedi, Bahareh; Hooshmand, Soodabeh; Mosalaie, Ahmad; Robati, Minoo; Momtahan, Mozhdeh; Farhadi, Pouya

    2013-01-01

    Background: Worldwide, cervical cancer is one of the most challenging gynecologic cancers in treatment. Objectives: This study was designed with the aim of comparing patients treated with External Beam Radiotherapy (EBRT) and Interactivity Brachytherapy (ICBT) with EBRT and extrafascial hysterectomy in locally advanced stages of cervical cancer (IIB-III). Patients and Methods: The present study was designed as a case-control which was performed on the patients with cervical cancer in locally advanced stages (IIB-III) admitted to Namazi and Faghihi hospitals (university hospitals in Shiraz) between 2008-2011. 51 patients were included in two distinct groups: 25 patients were treated with EBRT and Interactivity Brachytherapy (group A). 26 patients were treated with EBRT and extrafascial hysterectomy group B. Results: In group A, the number of patients with FIGO stage IIb and III were 16 and 9, respectively, and 17 and 9 in group B. The median duration of follow-up was 24 months. There were no significant differences between two groups in metastasis and recurrence rate (P > 0.05). 5-years overall survival rate was 54.8% [95% CI: 39-70.9] in group A and in group B was 50.9% [95% CI: 41.5-60] and The LOG-rank test which controls the effect of treatment modalities on overall survival rate, did not show any significant difference between two groups (P = 0.407). Conclusion: The results of our study showed that the trend of treatment using EBRT along with intracavity brachytherapy may have the same outcome as the method of using EBRT and extrafascial hysterectomy. Overall, it seems that external beam radiation followed by extrafascial hysterectomy could be a proper substitute for brachytherapy. PMID:24693381

  3. Improved Survival in Patients With Stage III-IV Head and Neck Cancer Treated With Radiotherapy as Primary Local Treatment Modality

    SciTech Connect

    Rusthoven, Kyle E.; Raben, David; Chen Changhu

    2008-10-01

    Purpose: To evaluate the overall and cause-specific survival in patients with Stage III-IVb head and neck squamous cell carcinoma treated with radiotherapy (RT) as the primary local treatment modality. Methods and Materials: The survival of patients with American Joint Committee on Cancer Stage III-IVb head and neck squamous cell carcinoma treated with primary RT was queried using the Surveillance, Epidemiology and End Results database. The effect of the year of treatment on overall and cause-specific survival was analyzed as a categorical and continuous variable. The patterns of care for these patients were also evaluated. Results: Between 1988 and 2004, 6,759 patients were identified. Survival was significantly improved in patients treated more recently. When analyzed as a continuous variable, each year was associated with a 3% and 4.1% reduction in the relative risk of overall and cause-specific mortality, respectively (p < 0.0001). Patients treated after 1998 had a 7.6% and 6.1% absolute improvement in overall and cause-specific survival, respectively, compared with patients treated before 1998 (overall survival, hazard ratio, 0.81; cause-specific survival, hazard ratio, 0.77; p < 0.0001). This benefit in survival was limited to tumors of the oral cavity, oropharynx, and hypopharynx. The use of RT increased among patients treated more recently. This shift in patterns of care was most pronounced for tumors of the larynx and hypopharynx. Conclusions: The overall and cause-specific survival of patients with Stage III-IVb head and neck squamous cell carcinoma treated with primary RT has improved with time. The improvement is consistent with that observed in a large meta-analysis of randomized patients treated with concurrent chemoradiotherapy.

  4. Iii-V Compound Multiple Quantum Well Based Modulator and Switching Devices.

    NASA Astrophysics Data System (ADS)

    Hong, Songcheol

    A general formalism to study the absorption and photocurrent in multiple quantum well is provided with detailed consideration of quantum confined Stark shift, exciton binding energy, line broadening, tunneling, polarization, and strain effects. Results on variation of exciton size, binding energies and transition energies as a function electric field and well size have been presented. Inhomogeneous line broadening of exciton lines due to interface roughness, alloy disorder and well to well size fluctuation is calculated. The potential of material tailoring by introducing strain for specific optical response is discussed. Theoretical and experimental results on excitonic and band-to-band absorption spectra in strained multi-quantum well structures are shown. I also report on polarization dependent optical absorption for excitonic and interband transitions in lattice matched and strained multiquantum well structures in presence of transverse electric field. Photocurrent in a p-i(MQW)-n diode with monochromatic light is examined with respect to different temperatures and intensities. The negative resistance of I-V characteristic of the p-i-n diode is based on the quantum confined Stark effect of the heavy hole excitonic transition in a multiquantum well. This exciton based photocurrent characteristic allows efficient switching. A general purpose low power optical logic device using the controller-modulator concept bas been proposed and realized. The controller is a heterojunction phototransistor with multiquantum wells in the base-collector depletion region. This allows an amplified photocurrent controlled voltage feedback with low light intensity levels. Detailed analysis of the sensitivity of this device in various modes of operation is studied. Studies are also presented on the cascadability of the device as well as its integrating -thresholding properties. A multiquantum well heterojunction bipolar transistor (MHBT), which has N^+ -p^+-i(MQW)-N structure has been

  5. Functional FLT1 genetic variation is a prognostic factor for recurrence in stage I-III non-small cell lung cancer

    PubMed Central

    Glubb, Dylan M.; Paré-Brunet, Laia; Jantus-Lewintre, Eloisa; Jiang, Chen; Crona, Daniel; Etheridge, Amy S.; Mirza, Osman; Zhang, Wei; Seiser, Eric L.; Rzyman, Witold; Jassem, Jacek; Auman, Todd; Hirsch, Fred R.; Owzar, Kouros; Camps, Carlos; Dziadziuszko, Rafal; Innocenti, Federico

    2015-01-01

    Hypothesis We propose that single-nucleotide polymorphisms (SNPs) in genes of the VEGF-pathway of angiogenesis will associate with survival in non-small cell lung cancer (NSCLC) patients. Methods Fifty-three SNPs in VEGF-pathway genes were genotyped in 150 European stage I-III NSCLC patients and tested for associations with patient survival. Replication was performed in an independent cohort of 142 European stage I-III patients. Reporter gene assays were used to assess the effects of SNPs on transcriptional activity. Results In the initial cohort, five SNPs associated (q<0.05) with relapse-free survival (RFS). The minor alleles of intronic FLT1 SNPs, rs7996030 and rs9582036, associated with reduced RFS (HR=1.67 [95% CI, 1.22 to 2.29] and HR=1.51 [95% CI, 1.14 to 2.01], respectively) and reduced transcriptional activity. The minor alleles of intronic KRAS SNPs, rs12813551 and rs10505980, associated with increased RFS (HR=0.64 [0.46 to 0.87] and HR=0.64 [0.47 to 0.87], respectively) and the minor allelic variant of rs12813551 also reduced transcriptional activity. Lastly, the minor allele of the intronic KRAS SNP rs10842513 associated with reduced RFS (HR=1.65 [95% CI, 1.16 to 2.37]). Analysis of the functional variants suggests they are located in transcriptional enhancer elements. The negative effect of rs9582036 on RFS was confirmed in the replication cohort (HR=1.69 [0.99 to 2.89], p=0.028) and the association was significant in pooled analysis of both cohorts (HR=1.67 [1.21-2.30], p=0.0001). Conclusions The functional FLT1 variant rs9582036 is a prognostic determinant of recurrence in stage I-III NSCLC. Its predictive value should be tested in the adjuvant setting of stage I-III NSCLC. PMID:26134224

  6. The Impact of Extent and Location of Mediastinal Lymph Node Involvement on Survival in Stage III Non-Small Cell Lung Cancer Patients Treated With Definitive Radiotherapy

    SciTech Connect

    Fernandes, Annemarie T.; Mitra, Nandita; Xanthopoulos, Eric; Evans, Tracey; Stevenson, James; Langer, Corey; Kucharczuk, John C.; Lin, Lilie; Rengan, Ramesh

    2012-05-01

    Purpose: Several surgical series have identified subcarinal, contralateral, and multilevel nodal involvement as predictors of poor overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive resection. This retrospective study evaluates the impact of extent and location of mediastinal lymph node (LN) involvement on survival in patients with Stage III NSCLC treated with definitive radiotherapy. Methods and Materials: We analyzed 106 consecutive patients with T1-4 N2-3 Stage III NSCLC treated with definitive radiotherapy at University of Pennsylvania between January 2003 and February 2009. For this analysis, mediastinal LN stations were divided into four mutually exclusive groups: supraclavicular, ipsilateral mediastinum, contralateral mediastinum, and subcarinal. Patients' conditions were then analyzed according to the extent of involvement and location of mediastinal LN stations. Results: The majority (88%) of patients received sequential or concurrent chemotherapy. The median follow-up time for survivors was 32.6 months. By multivariable Cox modeling, chemotherapy use (hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63]) was associated with improved overall survival. Increasing primary tumor [18F]-fluoro-2-deoxy-glucose avidity (HR: 1.11 [CI: 1.06-1.19]), and subcarinal involvement (HR: 2.29 [CI: 1.11-4.73]) were significant negative predictors of overall survival. On univariate analysis, contralateral nodal involvement (HR: 0.70 [CI: 0.33-1.47]), supraclavicular nodal involvement (HR: 0.78 [CI: 0.38-1.67]), multilevel nodal involvement (HR: 0.97 [CI: 0.58-1.61]), and tumor size (HR: 1.04 [CI: 0.94-1.14]) did not predict for overall survival. Patients with subcarinal involvement also had lower rates of 2-year nodal control (51.2% vs. 74.9%, p = 0.047) and 2-year distant control (28.4% vs. 61.2%, p = 0.043). Conclusions: These data suggest that the factors that determine oncologic outcome in Stage III NSCLC

  7. Epacadostat Before Surgery in Treating Patients With Newly Diagnosed Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-03-09

    Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  8. Solar coronal temperature diagnostics using emission line from multiple stages of ionization of iron

    NASA Technical Reports Server (NTRS)

    Brosius, Jeffrey W.; Davila, Joseph M.; Thomas, Roger J.; Thompson, William T.

    1994-01-01

    We obtained spatially resolved extreme-ultraviolet (EUV) spectra of AR 6615 on 1991 May 7 with NASA/ Goddard Space Flight Center's Solar EUV Rocket Telescope and Spectrograph (SERTS). Included are emission lines from four different stages of ionization of iron: Fe(+15) lambda 335 A, Fe(+14) lambda 327 A, Fe(+13) lambda 334 A, and Fe(+12) lambda 348 A. Using intensity ratios from among these lines, we have calculated the active region coronal temperature along the Solar Extreme Ultraviolet Telescope and Spectrograph (SERTS) slit. Temperatures derived from line ratios which incorporate adjacent stages of ionization are most sensitive to measurement uncertainties and yield the largest scatter. Temperatures derived from line ratios which incorporate nonadjacent stages of ionization are less sensitive to measurement uncertainties and yield little scatter. The active region temperature derived from these latter ratios has an average value of 2.54 x 10(exp 6) K, with a standard deviation approximately 0.12 x 10(exp 6) K, and shows no significant variation with position along the slit.

  9. A Co-operative Training Scheme for Part-Time Teachers of Adults: A Pilot Course for Stage III Certification

    ERIC Educational Resources Information Center

    Bestwick, Dennis; Chadwick, Alan

    1977-01-01

    Describes the cooperative venture of a university in London, England and a local education agency (LEA) in which a pilot training program was established and offered to part-time teachers of adults seeking third stage certification (certification associated with an institution of higher education as opposed to certification through LEAs and…

  10. Proposal for therapeutic approach based on prognostic factors including morphometric and flow-cytometric features in stage III-IV ovarian cancer.

    PubMed

    Wils, J; van Geuns, H; Baak, J

    1988-05-01

    In 73 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage III and IV ovarian cancer the prognostic significance of morphometric and flow-cytometric features has been evaluated in comparison with more commonly used prognostic factors such as stage and tumor mass. Single features associated with prognosis were as follows: FIGO stage, bulky disease, mean and standard deviation of nuclear area, cellular DNA content, mitotic activity index, and volume percentage epithelium. Multivariate analysis showed that the most significant prognostic combination of features consisted of mean nuclear area, presence or absence of bulky disease, and FIGO stage (in sequence of decreasing importance; Mantel-Cox = 23.07, P less than 0.00001). On the basis of these factors patients with a poor prognosis can be identified. On the other hand two features were associated with an excellent prognosis namely a low mitotic index and a low-volume percentage epithelium. It is concluded that morphometric and flow-cytometric analysis in combination with clinical features can provide significant information to predict the prognosis of patients with advanced ovarian cancer treated with debulking surgery and platinum-based chemotherapy. On the basis of our data a tentative proposal for future therapeutic approaches is made.

  11. Pretreatment prognostic factors in patients with early-stage (I/II) non-small-cell lung cancer treated with hyperfractionated radiation therapy alone

    SciTech Connect

    Jeremic, Branislav . E-mail: b.jeremic@iaea.org; Milicic, Biljana; Dagovic, Aleksandar; Acimovic, Ljubisa; Milisavljevic, Slobodan

    2006-07-15

    Purpose: To investigate influence of various pretreatment prognostic factors in patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy alone. Patients and Methods: One hundred and sixteen patients were treated with tumor doses of 69.6 Gy, 1.2-Gy, twice-daily fractionation. There were 49 patients with Stage I and 67 patients with Stage II. Eighty patients had Karnofsky performance status (KPS) 90-100 and 95 patients had <5% weight loss. Peripheral tumors were observed in 57 patients. Squamous histology was observed in 70 patients and the majority of patients had concomitant disease (n = 72). Results: The median survival time for all patients was 29 months; 5-year survival was 29%. The median time to local progression and the distant metastasis were not achieved, whereas 5-year local progression-free and distant metastasis-free survivals were 50% and 72%, respectively. Multivariate analysis identified KPS, weight loss, location, histology, and the reason for not undergoing surgery as prognostic factors for survival. KPS, location, and histology influenced local progression-free survival, whereas only KPS and weight loss influenced distant metastasis-free survival. Conclusions: This retrospective analysis identified KPS and weight loss as the most important prognostic factors of outcome in patients with early-stage NSCLC treated with hyperfractionation radiation therapy.

  12. Total Gross Tumor Volume Is an Independent Prognostic Factor in Patients Treated With Selective Nodal Irradiation for Stage I to III Small Cell Lung Cancer

    SciTech Connect

    Reymen, Bart; Van Loon, Judith; Baardwijk, Angela van; Wanders, Rinus; Borger, Jacques; Dingemans, Anne-Marie C.; Bootsma, Gerben; Pitz, Cordula; Lunde, Ragnar; Geraedts, Wiel; Lambin, Philippe; De Ruysscher, Dirk

    2013-04-01

    Purpose: In non-small cell lung cancer, gross tumor volume (GTV) influences survival more than other risk factors. This could also apply to small cell lung cancer. Methods and Materials: Analysis of our prospective database with stage I to III SCLC patients referred for concurrent chemo radiation therapy. Standard treatment was 45 Gy in 1.5-Gy fractions twice daily concurrently with carboplatin-etoposide, followed by prophylactic cranial irradiation (PCI) in case of non-progression. Only fluorodeoxyglucose (FDG)-positron emission tomography (PET)-positive or pathologically proven nodal sites were included in the target volume. Total GTV consisted of post chemotherapy tumor volume and pre chemotherapy nodal volume. Survival was calculated from diagnosis (Kaplan-Meier ). Results: A total of 119 patients were included between May 2004 and June 2009. Median total GTV was 93 ± 152 cc (7.5-895 cc). Isolated elective nodal failure occurred in 2 patients (1.7%). Median follow-up was 38 months, median overall survival 20 months (95% confidence interval = 17.8-22.1 months), and 2-year survival 38.4%. In multivariate analysis, only total GTV (P=.026) and performance status (P=.016) significantly influenced survival. Conclusions: In this series of stage I to III small cell lung cancer patients treated with FDG-PET-based selective nodal irradiation total GTV is an independent risk factor for survival.

  13. Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II-III resectable disease.

    PubMed

    Sivendran, Shanthi; Chang, Rui; Pham, Lisa; Phelps, Robert G; Harcharik, Sara T; Hall, Lawrence D; Bernardo, Sebastian G; Moskalenko, Marina M; Sivendran, Meera; Fu, Yichun; de Moll, Ellen H; Pan, Michael; Moon, Jee Young; Arora, Sonali; Cohain, Ariella; DiFeo, Analisa; Ferringer, Tammie C; Tismenetsky, Mikhail; Tsui, Cindy L; Friedlander, Philip A; Parides, Michael K; Banchereau, Jacques; Chaussabel, Damien; Lebwohl, Mark G; Wolchok, Jedd D; Bhardwaj, Nina; Burakoff, Steven J; Oh, William K; Palucka, Karolina; Merad, Miriam; Schadt, Eric E; Saenger, Yvonne M

    2014-08-01

    Patients with resected stage II-III cutaneous melanomas remain at high risk for metastasis and death. Biomarker development has been limited by the challenge of isolating high-quality RNA for transcriptome-wide profiling from formalin-fixed and paraffin-embedded (FFPE) primary tumor specimens. Using NanoString technology, RNA from 40 stage II-III FFPE primary melanomas was analyzed and a 53-immune-gene panel predictive of non-progression (area under the curve (AUC)=0.920) was defined. The signature predicted disease-specific survival (DSS P<0.001) and recurrence-free survival (RFS P<0.001). CD2, the most differentially expressed gene in the training set, also predicted non-progression (P<0.001). Using publicly available microarray data from 46 primary human melanomas (GSE15605), a coexpression module enriched for the 53-gene panel was then identified using unbiased methods. A Bayesian network of signaling pathways based on this data identified driver genes. Finally, the proposed 53-gene panel was confirmed in an independent test population of 48 patients (AUC=0.787). The gene signature was an independent predictor of non-progression (P<0.001), RFS (P<0.001), and DSS (P=0.024) in the test population. The identified driver genes are potential therapeutic targets, and the 53-gene panel should be tested for clinical application using a larger data set annotated on the basis of prospectively gathered data.

  14. Dissection of Immune Gene Networks in Primary Melanoma Tumors Critical for Antitumor Surveillance of Patients with Stage II–III Resectable Disease

    PubMed Central

    Sivendran, Shanthi; Chang, Rui; Pham, Lisa; Phelps, Robert G.; Harcharik, Sara T.; Hall, Lawrence D.; Bernardo, Sebastian G.; Moskalenko, Marina M.; Sivendran, Meera; Fu, Yichun; de Moll, Ellen H.; Pan, Michael; Moon, Jee Young; Arora, Sonali; Cohain, Ariella; DiFeo, Analisa; Ferringer, Tammie C.; Tismenetsky, Mikhail; Tsui, Cindy L.; Friedlander, Philip A.; Parides, Michael K.; Banchereau, Jacques; Chaussabel, Damien; Lebwohl, Mark G.; Wolchok, Jedd D.; Bhardwaj, Nina; Burakoff, Steven J.; Oh, William K.; Palucka, Karolina; Merad, Miriam; Schadt, Eric E.; Saenger, Yvonne M.

    2014-01-01

    Patients with resected stage II–III cutaneous melanomas remain at high risk for metastasis and death. Biomarker development has been limited by the challenge of isolating high-quality RNA for transcriptome-wide profiling from formalin-fixed and paraffin-embedded (FFPE) primary tumor specimens. Using NanoString technology, RNA from 40 stage II–III FFPE primary melanomas was analyzed and a 53-immune-gene panel predictive of non-progression (area under the curve (AUC)=0.920) was defined. The signature predicted disease-specific survival (DSS P<0.001) and recurrence-free survival (RFS P<0.001). CD2, the most differentially expressed gene in the training set, also predicted non-progression (P<0.001). Using publicly available microarray data from 46 primary human melanomas (GSE15605), a coexpression module enriched for the 53-gene panel was then identified using unbiased methods. A Bayesian network of signaling pathways based on this data identified driver genes. Finally, the proposed 53-gene panel was confirmed in an independent test population of 48 patients (AUC=0.787). The gene signature was an independent predictor of non-progression (P<0.001), RFS (P<0.001), and DSS (P=0.024) in the test population. The identified driver genes are potential therapeutic targets, and the 53-gene panel should be tested for clinical application using a larger data set annotated on the basis of prospectively gathered data. PMID:24522433

  15. Activation status of human microglia is dependent on lesion formation stage and remyelination in multiple sclerosis.

    PubMed

    Peferoen, Laura A N; Vogel, Daphne Y S; Ummenthum, Kimberley; Breur, Marjolein; Heijnen, Priscilla D A M; Gerritsen, Wouter H; Peferoen-Baert, Regina M B; van der Valk, Paul; Dijkstra, Christine D; Amor, Sandra

    2015-01-01

    Similar to macrophages, microglia adopt diverse activation states and contribute to repair and tissue damage in multiple sclerosis. Using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, we show that in vitro M1-polarized (proinflammatory) human adult microglia express the distinctive markers CD74, CD40, CD86, and CCR7, whereas M2 (anti-inflammatory) microglia express mannose receptor and the anti-inflammatory cytokine CCL22. The expression of these markers was assessed in clusters of activated microglia in normal-appearing white matter (preactive lesions) and areas of remyelination, representing reparative multiple sclerosis lesions. We show that activated microglia in preactive and remyelinating lesions express CD74, CD40, CD86, and the M2 markers CCL22 and CD209, but not mannose receptor. To examine whether this intermediate microglia profile is static or dynamic and thus susceptible to changes in the microenvironment, we polarized microglia into M1 or M2 phenotype in vitro and then subsequently treated them with the opposing polarization regimen. These studies revealed that expression of CD40, CXCL10, and mannose receptor is dynamic and that microglia, like macrophages, can switch between M1 and M2 phenotypic profiles. Taken together, our data define the differential activation states of microglia during lesion development in multiple sclerosis-affected CNS tissues and underscore the plasticity of human adult microglia in vitro.

  16. Phylogenetic analysis with multiple markers indicates repeated loss of the adult medusa stage in Campanulariidae (Hydrozoa, Cnidaria).

    PubMed

    Govindarajan, Annette F; Boero, Ferdinando; Halanych, Kenneth M

    2006-03-01

    The Campanulariidae is a group of leptomedusan hydroids (Hydrozoa, Cnidaria) that exhibit a diverse array of life cycles ranging from species with a free medusa stage to those with a reduced or absent medusa stage. Perhaps the best-known member of the taxon is Obelia which is often used as a textbook model of hydrozoan life history. However, Obelia medusae have several unique features leading to a hypothesis that Obelia arose, in a saltational fashion, from an ancestor that lacked a medusa, possibly representing an example of a rare evolutionary reversal. To address the evolution of adult sexual stages in Campanulariidae, a molecular phylogenetic approach was employed using two nuclear (18S rDNA and calmodulin) and two mitochondrial (16S rDNA and cytochrome c oxidase subunit I) genes. Prior to the main analysis, we conducted a preliminary analysis of leptomedusan taxa which suggests that Campanulariidae as presently considered needs to be redefined. Campanulariid analyses are consistent with morphological understanding in that three major clades are recovered. However, several recognized genera are not monophyletic calling into question some "diagnostic" features. Furthermore, ancestral states were reconstructed using parsimony, and a sensitivity analysis was conducted to investigate possible evolutionary transitions in life-history stages. The results indicate that life-cycle transitions have occurred multiple times, and that Obelia might be derived from an ancestor with Clytia-like features.

  17. Attrition through Multiple Stages of Pre-Treatment and ART HIV Care in South Africa

    PubMed Central

    Fox, Matthew P.; Shearer, Kate; Maskew, Mhairi; Meyer-Rath, Gesine; Clouse, Kate; Sanne, Ian

    2014-01-01

    Introduction While momentum for increasing treatment thresholds is growing, if patients cannot be retained in HIV care from the time of testing positive through long-term adherence to antiretroviral therapy (ART), such strategies may fall short of expected gains. While estimates of retention on ART exist, few cohorts have data on retention from testing positive through long-term ART care. Methods We explored attrition (loss or death) at the Themba Lethu HIV clinic, Johannesburg, South Africa in 3 distinct cohorts enrolled at HIV testing, pre-ART initiation, and ART initiation. Results Between March 2010 and August 2012 we enrolled 380 patients testing HIV+, 206 initiating pre-ART care, and 185 initiating ART. Of the 380 patients enrolled at testing HIV-positive, 38.7% (95%CI: 33.9–43.7%) returned for eligibility staging within ≤3 months of testing. Of the 206 enrolled at pre-ART care, 84.5% (95%CI: 79.0–88.9%) were ART eligible at their first CD4 count. Of those, 87.9% (95%CI: 82.4–92.2%) initiated ART within 6 months. Among patients not ART eligible at their first CD4 count, 50.0% (95%CI: 33.1–66.9%) repeated their CD4 count within one year of the first ineligible CD4. Among the 185 patients in the ART cohort, 22 transferred out and were excluded from further analysis. Of the remaining 163, 81.0% (95%CI: 74.4–86.5%) were retained in care through two years on treatment. Conclusions Our findings from a well-resourced clinic demonstrate continual loss from all stages of HIV care and strategies to reduce attrition from all stages of care are urgently needed. PMID:25330087

  18. FLT PET in Measuring Treatment Response in Patients With Newly Diagnosed Estrogen Receptor-Positive, HER2-Negative Stage I-III Breast Cancer

    ClinicalTrials.gov

    2016-06-02

    Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  19. Multiple stage MS in analysis of plasma, serum, urine and in vitro samples relevant to clinical and forensic toxicology.

    PubMed

    Meyer, Golo M; Maurer, Hans H; Meyer, Markus R

    2016-01-01

    This paper reviews MS approaches applied to metabolism studies, structure elucidation and qualitative or quantitative screening of drugs (of abuse) and/or their metabolites. Applications in clinical and forensic toxicology were included using blood plasma or serum, urine, in vitro samples, liquids, solids or plant material. Techniques covered are liquid chromatography coupled to low-resolution and high-resolution multiple stage mass analyzers. Only PubMed listed studies published in English between January 2008 and January 2015 were considered. Approaches are discussed focusing on sample preparation and mass spectral settings. Comments on advantages and limitations of these techniques complete the review.

  20. Severe NDE1-mediated microcephaly results from neural progenitor cell cycle arrests at multiple specific stages.

    PubMed

    Doobin, David J; Kemal, Shahrnaz; Dantas, Tiago J; Vallee, Richard B

    2016-01-01

    Microcephaly is a cortical malformation disorder characterized by an abnormally small brain. Recent studies have revealed severe cases of microcephaly resulting from human mutations in the NDE1 gene, which is involved in the regulation of cytoplasmic dynein. Here using in utero electroporation of NDE1 short hairpin RNA (shRNA) in embryonic rat brains, we observe cell cycle arrest of proliferating neural progenitors at three distinct stages: during apical interkinetic nuclear migration, at the G2-to-M transition and in regulation of primary cilia at the G1-to-S transition. RNAi against the NDE1 paralogue NDEL1 has no such effects. However, NDEL1 overexpression can functionally compensate for NDE1, except at the G2-to-M transition, revealing a unique NDE1 role. In contrast, NDE1 and NDEL1 RNAi have comparable effects on postmitotic neuronal migration. These results reveal that the severity of NDE1-associated microcephaly results not from defects in mitosis, but rather the inability of neural progenitors to ever reach this stage. PMID:27553190

  1. Severe NDE1-mediated microcephaly results from neural progenitor cell cycle arrests at multiple specific stages

    PubMed Central

    Doobin, David J.; Kemal, Shahrnaz; Dantas, Tiago J.; Vallee, Richard B.

    2016-01-01

    Microcephaly is a cortical malformation disorder characterized by an abnormally small brain. Recent studies have revealed severe cases of microcephaly resulting from human mutations in the NDE1 gene, which is involved in the regulation of cytoplasmic dynein. Here using in utero electroporation of NDE1 short hairpin RNA (shRNA) in embryonic rat brains, we observe cell cycle arrest of proliferating neural progenitors at three distinct stages: during apical interkinetic nuclear migration, at the G2-to-M transition and in regulation of primary cilia at the G1-to-S transition. RNAi against the NDE1 paralogue NDEL1 has no such effects. However, NDEL1 overexpression can functionally compensate for NDE1, except at the G2-to-M transition, revealing a unique NDE1 role. In contrast, NDE1 and NDEL1 RNAi have comparable effects on postmitotic neuronal migration. These results reveal that the severity of NDE1-associated microcephaly results not from defects in mitosis, but rather the inability of neural progenitors to ever reach this stage. PMID:27553190

  2. Slow spinodal decomposition in binary liquid mixtures of polymers. III. Scaling analyses of later-stage unmixing

    NASA Astrophysics Data System (ADS)

    Izumitani, Tatsuo; Takenaka, Mikihito; Hashimoto, Takeji

    1990-03-01

    Later-stage unmixing process of a near critical mixture of polybutadiene (PB)/poly(styrene- r-butadiene)(SBR) were examined at real time t and in situ at several temperatures T by time-resolved light scattering method. The magnitude of scattering vector qm(t,T) at which the intensity becomes maximum and the maximum intensity Im(t,T) were analyzed in order to characterize the coarsening processes of the later-stage spinodal decomposition. The variations of Im and qm with t at different T's were found to fall onto master curves on the reduced plots, thus assuring the scaling postulate that the data obtained at different t and T for given mixtures are properly scaled with the temperature-dependent characteristic wave number qm(0,T) and characteristic time tc(T).

  3. Evolving force-free magnetic fields. III - States of nonequilibrium and the preflare stage. [in solar atmosphere

    NASA Technical Reports Server (NTRS)

    Low, B. C.

    1980-01-01

    The paper considers whether a neighboring magnetostatic equilibrium exists to allow a magnetic field initially in a force-free configuration to accommodate any imposed weak pressure. The following problem is treated. The foot points of the field are fixed and the plasma is frozen into the field lines under the approximation of infinite electrical conductivity. A weak pressure is introduced. It is determined infinitesimal plasma displacements exist to adjust the field lines to a new equilibrium without changing the field line connectivity. The analysis is carried out for the bipolar force-free fields forming one of two evolutionary sequences modeling the development of the preflare stage. It was found that for the force-free field corresponding to the quasi-static stage of evolution, the neighboring magnetostatic equilibrium always exists and the imposed gas pressure can be accommodated with a slight departure of the field from being exactly force free.

  4. The Impact of Skin-Sparing Mastectomy With Immediate Reconstruction in Patients With Stage III Breast Cancer Treated With Neoadjuvant Chemotherapy and Postmastectomy Radiation

    SciTech Connect

    Prabhu, Roshan; Godette, Karen; Carlson, Grant; Losken, Albert; Gabram, Sheryl; Fasola, Carolina; O'Regan, Ruth; Zelnak, Amelia; Torres, Mylin

    2012-03-15

    Purpose: The safety and efficacy of skin-sparing mastectomy (SSM) with immediate reconstruction (IR) in patients with locally advanced breast cancer are unclear. The purpose of this study is to compare the outcomes of women with noninflammatory Stage III SSM with IR vs. non-SSM-treated women who underwent neoadjuvant chemotherapy and adjuvant radiation therapy (XRT). Methods and Materials: Between October 1997 and March 2010, 100 consecutive patients (40 SSM with IR vs. 60 non-SSM) with Stage III breast cancer received anthracycline- and/or taxane-based neoadjuvant chemotherapy, mastectomy, and adjuvant XRT. Clinical stage (SSM with IR vs. for non-SSM) was IIIA (75% vs. 67%), IIIB (8% vs. 18%), and IIIC (8% vs. 8%). Tumors greater than 5 cm were found in 74% vs. 69%; 97% of patients in both groups were clinically node positive; and 8% vs. 18% had T4b disease. Results: The time from initial biopsy to XRT was prolonged for SSM-IR patients (274 vs. 254 days, p = 0.04), and there was a trend toward XRT delay of more than 8 weeks (52% vs. 31%, p = 0.07) after surgery. The rate of complications requiring surgical intervention was higher in the SSM-IR group (37.5% vs. 5%, p < 0.001). The 2-year actuarial locoregional control, breast cancer-specific survival, and overall survival rates for SSM with IR vs. non-SSM were 94.7% vs. 97.4%, 91.5% vs. 86.3%, and 87.4% vs. 84.8%, respectively (p = not significant). Conclusions: In our small study with limited follow-up, SSM with IR prolonged overall cancer treatment time and trended toward delaying XRT but did not impair oncologic outcomes. Complication rates were significantly higher in this group. Longer follow-up is needed.

  5. Comparison of NEXRAD Stage III and MPE precipitation products with constraints from high quality and density of raingauge networks in the Upper Guadalupe River Basin, Central Texas

    NASA Astrophysics Data System (ADS)

    Xie, H.; Wang, X.

    2006-05-01

    NEXRAD's Multisensor Precipitation Estimator (MPE) product replaced the Stage III product started in October 2003 at the West Gulf River Forecast Center (WGRFC) where includes most of the Texas and New Mexico. The MPE is an integrated product of rain gauge, NEXRAD, and satellite (GOES) precipitation estimates. The main objective of MPE is to reduce both areal-mean bias error and local bias error. The overall improved quality of MPE over Stage 3 is evident at the WGRFC. However, so far, there is no quantitative evaluation in a relative long period (one year or more) of a large area. In this study, high quality and density of 50 raingauge networks (6 minutes temporal resolution) in the Upper Guadalupe River Basin, Central Texas are used to evaluate both the Stage III (years 2001 and 2002) and MPE (year 2004) products. In this study, we propose two types of comparison (1) directly compare collocated radar cell and gauge of all rainfall events and (2) only compare collocated radar cell and gauge of homogeneous/uniform rainfall events. To find uniform rainfall events, 6-mintutes raingauge rainfall were used to calculate the correlation coefficient (CC) and coefficient of variation (CV) of a hour among one central gauge and its surrounding gauges (>= 4). For a particular rainfall hour, when CV is < 0.5 and CC is > 0.5, or CV is <0.1, the rainfall event of this hour is thus selected as a uniform or homogeneous rainfall event. Our preliminary results of CC from all rainfall events and homogeneous rainfall events for year 2004 (MPE) are 0.79 and 0.96, respectively. This indicates an overall good quality of MPE product in comparison with raingauge rainfall, especially for the homogeneous rainfall events. Work is in progress.

  6. Mastectomy With Immediate Expander-Implant Reconstruction, Adjuvant Chemotherapy, and Radiation for Stage II-III Breast Cancer: Treatment Intervals and Clinical Outcomes

    SciTech Connect

    Wright, Jean L.; Cordeiro, Peter G.; Ben-Porat, Leah; Van Zee, Kimberly J.; Hudis, Clifford; Beal, Kathryn; McCormick, Beryl

    2008-01-01

    Purpose: To determine intervals between surgery and adjuvant chemotherapy and radiation in patients treated with mastectomy with immediate expander-implant reconstruction, and to evaluate locoregional and distant control and overall survival in these patients. Methods and Materials: Between May 1996 and March 2004, 104 patients with Stage II-III breast cancer were routinely treated at our institution under the following algorithm: (1) definitive mastectomy with axillary lymph node dissection and immediate tissue expander placement, (2) tissue expansion during chemotherapy, (3) exchange of tissue expander for permanent implant, (4) radiation. Patient, disease, and treatment characteristics and clinical outcomes were retrospectively evaluated. Results: Median age was 45 years. Twenty-six percent of patients were Stage II and 74% Stage III. All received adjuvant chemotherapy. Estrogen receptor staining was positive in 77%, and 78% received hormone therapy. Radiation was delivered to the chest wall with daily 0.5-cm bolus and to the supraclavicular fossa. Median dose was 5040 cGy. Median interval from surgery to chemotherapy was 5 weeks, from completion of chemotherapy to exchange 4 weeks, and from exchange to radiation 4 weeks. Median interval from completion of chemotherapy to start of radiation was 8 weeks. Median follow-up was 64 months from date of mastectomy. The 5-year rate for locoregional disease control was 100%, for distant metastasis-free survival 90%, and for overall survival 96%. Conclusions: Mastectomy with immediate expander-implant reconstruction, adjuvant chemotherapy, and radiation results in a median interval of 8 weeks from completion of chemotherapy to initiation of radiation and seems to be associated with acceptable 5-year locoregional control, distant metastasis-free survival, and overall survival.

  7. Multiple congenital brachymetatarsia. A one-stage combined shortening and lengthening procedure without iliac bone graft.

    PubMed

    Kim, J S; Baek, G H; Chung, M S; Yoon, P W

    2004-09-01

    We performed nine metatarsal and three proximal phalangeal lengthenings in five patients with congenital brachymetatarsia of the first and one or two other metatarsal bones, by a one-stage combined shortening and lengthening procedure using intercalcary autogenous bone grafts from adjacent shortened metatarsal bones. Instead of the isolated lengthening of the first and the other metatarsal bones, we shortened the adjacent normal metatarsal and used the excised bone to lengthen the short toes, except for the great toe, to restore the normal parabola. One skin incision was used. All the operations were performed bilaterally and the patients were followed up for a mean period of 69.5 months (29 to 107). They all regained a nearly normal parabola and were satisfied with the cosmetic results. Our technique is straightforward and produces good cosmetic results. Satisfactory, bony union is achieved, morbidity is low, and no additional surgery is required for the removal of metal implants. PMID:15446529

  8. Multiple-stage decisions in a marine central-place forager

    PubMed Central

    Friedlaender, Ari S.; Johnston, David W.; Tyson, Reny B.; Kaltenberg, Amanda; Goldbogen, Jeremy A.; Stimpert, Alison K.; Curtice, Corrie; Hazen, Elliott L.; Halpin, Patrick N.; Read, Andrew J.; Nowacek, Douglas P.

    2016-01-01

    Air-breathing marine animals face a complex set of physical challenges associated with diving that affect the decisions of how to optimize feeding. Baleen whales (Mysticeti) have evolved bulk-filter feeding mechanisms to efficiently feed on dense prey patches. Baleen whales are central place foragers where oxygen at the surface represents the central place and depth acts as the distance to prey. Although hypothesized that baleen whales will target the densest prey patches anywhere in the water column, how depth and density interact to influence foraging behaviour is poorly understood. We used multi-sensor archival tags and active acoustics to quantify Antarctic humpback whale foraging behaviour relative to prey. Our analyses reveal multi-stage foraging decisions driven by both krill depth and density. During daylight hours when whales did not feed, krill were found in deep high-density patches. As krill migrated vertically into larger and less dense patches near the surface, whales began to forage. During foraging bouts, we found that feeding rates (number of feeding lunges per hour) were greatest when prey was shallowest, and feeding rates decreased with increasing dive depth. This strategy is consistent with previous models of how air-breathing diving animals optimize foraging efficiency. Thus, humpback whales forage mainly when prey is more broadly distributed and shallower, presumably to minimize diving and searching costs and to increase feeding rates overall and thus foraging efficiency. Using direct measurements of feeding behaviour from animal-borne tags and prey availability from echosounders, our study demonstrates a multi-stage foraging process in a central place forager that we suggest acts to optimize overall efficiency by maximizing net energy gain over time. These data reveal a previously unrecognized level of complexity in predator–prey interactions and underscores the need to simultaneously measure prey distribution in marine central place

  9. Multiple-stage decisions in a marine central-place forager

    NASA Astrophysics Data System (ADS)

    Friedlaender, Ari S.; Johnston, David W.; Tyson, Reny B.; Kaltenberg, Amanda; Goldbogen, Jeremy A.; Stimpert, Alison K.; Curtice, Corrie; Hazen, Elliott L.; Halpin, Patrick N.; Read, Andrew J.; Nowacek, Douglas P.

    2016-05-01

    Air-breathing marine animals face a complex set of physical challenges associated with diving that affect the decisions of how to optimize feeding. Baleen whales (Mysticeti) have evolved bulk-filter feeding mechanisms to efficiently feed on dense prey patches. Baleen whales are central place foragers where oxygen at the surface represents the central place and depth acts as the distance to prey. Although hypothesized that baleen whales will target the densest prey patches anywhere in the water column, how depth and density interact to influence foraging behaviour is poorly understood. We used multi-sensor archival tags and active acoustics to quantify Antarctic humpback whale foraging behaviour relative to prey. Our analyses reveal multi-stage foraging decisions driven by both krill depth and density. During daylight hours when whales did not feed, krill were found in deep high-density patches. As krill migrated vertically into larger and less dense patches near the surface, whales began to forage. During foraging bouts, we found that feeding rates (number of feeding lunges per hour) were greatest when prey was shallowest, and feeding rates decreased with increasing dive depth. This strategy is consistent with previous models of how air-breathing diving animals optimize foraging efficiency. Thus, humpback whales forage mainly when prey is more broadly distributed and shallower, presumably to minimize diving and searching costs and to increase feeding rates overall and thus foraging efficiency. Using direct measurements of feeding behaviour from animal-borne tags and prey availability from echosounders, our study demonstrates a multi-stage foraging process in a central place forager that we suggest acts to optimize overall efficiency by maximizing net energy gain over time. These data reveal a previously unrecognized level of complexity in predator-prey interactions and underscores the need to simultaneously measure prey distribution in marine central place forager

  10. Multiple-stage decisions in a marine central-place forager.

    PubMed

    Friedlaender, Ari S; Johnston, David W; Tyson, Reny B; Kaltenberg, Amanda; Goldbogen, Jeremy A; Stimpert, Alison K; Curtice, Corrie; Hazen, Elliott L; Halpin, Patrick N; Read, Andrew J; Nowacek, Douglas P

    2016-05-01

    Air-breathing marine animals face a complex set of physical challenges associated with diving that affect the decisions of how to optimize feeding. Baleen whales (Mysticeti) have evolved bulk-filter feeding mechanisms to efficiently feed on dense prey patches. Baleen whales are central place foragers where oxygen at the surface represents the central place and depth acts as the distance to prey. Although hypothesized that baleen whales will target the densest prey patches anywhere in the water column, how depth and density interact to influence foraging behaviour is poorly understood. We used multi-sensor archival tags and active acoustics to quantify Antarctic humpback whale foraging behaviour relative to prey. Our analyses reveal multi-stage foraging decisions driven by both krill depth and density. During daylight hours when whales did not feed, krill were found in deep high-density patches. As krill migrated vertically into larger and less dense patches near the surface, whales began to forage. During foraging bouts, we found that feeding rates (number of feeding lunges per hour) were greatest when prey was shallowest, and feeding rates decreased with increasing dive depth. This strategy is consistent with previous models of how air-breathing diving animals optimize foraging efficiency. Thus, humpback whales forage mainly when prey is more broadly distributed and shallower, presumably to minimize diving and searching costs and to increase feeding rates overall and thus foraging efficiency. Using direct measurements of feeding behaviour from animal-borne tags and prey availability from echosounders, our study demonstrates a multi-stage foraging process in a central place forager that we suggest acts to optimize overall efficiency by maximizing net energy gain over time. These data reveal a previously unrecognized level of complexity in predator-prey interactions and underscores the need to simultaneously measure prey distribution in marine central place forager

  11. 5-aza-2'-deoxycytidine impairs mouse spermatogenesis at multiple stages through different usage of DNA methyltransferases.

    PubMed

    Song, Ning; Endo, Daisuke; Song, Bin; Shibata, Yasuaki; Koji, Takehiko

    2016-06-15

    Mammalian spermatogenesis is a progressive process comprising spermatogonial proliferation, spermatocytic meiosis, and later spermiogenesis, which is considered to be under the regulation of epigenetic parameters. To gain insights into the significance of DNA methylation in early spermatogenesis, 5-azadC was used as a molecular biological tool to mimic the level of DNA methylation in vivo. Since the drug is incorporated into DNA during the S-phase, spermatogonia and spermatocytes would be affected primarily in mouse spermatogenesis. Adult male ICR mice were intraperitoneally injected with 5-azadC at a dose of 0.25mg/kg/day for 10 consecutive days, allowing us to examine its maximum effect on the kinetics of spermatogonia and spermatocytes. In this short-term protocol, 5-azadC induced significant histological abnormalities, such as a marked increase in apoptosis of spermatogonia and spermatocytes, followed by severe loss of spermatids, while after termination of 5-azadC treatment, normal histology was restored in the testis within 35days. Quantification of the methylation level of CCGG sites as well as whole DNA showed spermatogonial hypomethylation, which correlated with increased apoptosis of spermatogonia. Interestingly, the hypomethylated cells were simultaneously positive for tri-methylated histone H3 at K4. On the other hand, no changes in methylation level were found in spermatocytes, but PCNA staining clearly showed disordered accumulation of S-phase spermatocytes, which increased their apoptosis in stage XII. In addition, different immunohistochemical staining pattern was found for DNA methyltransferases (DNMTs); DNMT1was expressed in the majority of all germ cells, but DNMT3a and b were only expressed in spermatogonia. Our results indicate that 5-azadC caused DNA hypomethylation in spermatogonia, but induced prolongation of S-phase in spermatocytes, resulting in the induction of apoptosis in both cases. Thus, 5-azadC affects spermatogenesis at more than

  12. Multiple-stage deformation along the southern flank of the North Chukchi High, Chukchi Sea, Alaska

    SciTech Connect

    Johnson, P.P. )

    1990-05-01

    Structural and stratigraphic relations along the southern edge of the North Chukchi high provide insights into the timing and mechanics of Late Cretaceous and Cenozoic tectonic events in the northern Chukchi Sea. In this area, the easternmost strand of the north-trending Hanna wrench fault zone is deflected to the northeast and terminates in a series of reverse faults along the southern edge of the high. Areas east of the Hanna fault zone were characterized by tectonic stability during this period of time. Within the fault zone, east-west-trending box folds and reverse faults accompanied uplift of the North Chukchi high and erosion of the entire Ellesmerian sequence along its southern margin. Stratigraphic and structural relations indicate that this compressional deformation began during the Early Cretaceous (Albian ) but ceased prior to the Late( ) Cretaceous. During the early Cenozoic( ), the northern part of the Hanna fault zone was reactivated as an extensional systems which controlled the development of a local basin. Some faults which showed an early history of reverse displacement were reactivated as normal faults during this late-stage tectonic event. This data is consistent with a model for Early Cretaceous impingement of adjacent blocks at a constrained corner near the North Chukchi high during the rift opening of the North Chukchi basin. The compressional deformation ceased prior to the Cenozoic when the opposing blocks in the constrained corner finally escaped past each other. Continued rifting and subsidence of the North Chukchi basin resulted in late-stage extensional overprinting of earlier compressional structures.

  13. 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.

  14. A Phase I/II Radiation Dose Escalation Study With Concurrent Chemotherapy for Patients With Inoperable Stages I to III Non-Small-Cell Lung Cancer: Phase I Results of RTOG 0117

    SciTech Connect

    Bradley, Jeffrey D.; Moughan, Jennifer; Graham, Mary V.; Byhardt, Roger; Govindan, Ramaswamy; Fowler, Jack; Purdy, James A.; Michalski, Jeff M.; Gore, Elizabeth; Choy, Hak

    2010-06-01

    Purpose: In preparation for a Phase III comparison of high-dose versus standard-dose radiation therapy, this Phase I/II study was initiated to establish the maximum tolerated dose of radiation therapy in the setting of concurrent chemotherapy, using three-dimensional conformal radiation therapy for non-small-cell lung cancer. Methods and Materials: Eligibility included patients with histologically proven, unresectable Stages I to III non-small-cell lung cancer. Concurrent chemotherapy consisted of paclitaxel, 50 mg/m{sup 2}, and carboplatin, AUC of 2, given weekly. The radiation dose was to be sequentially intensified by increasing the daily fraction size, starting from 75.25 Gy/35 fractions. Results: The Phase I portion of this study accrued 17 patients from 10 institutions and was closed in January 2004. After the initial 8 patients were accrued to cohort 1, the trial closed temporarily on September 26, 2002, due to reported toxicity. Two acute treatment-related dose-limiting toxicities (DLTs) were reported at the time: a case of grade 5 and grade 3 radiation pneumonitis. The protocol, therefore, was revised to de-escalate the radiation therapy dose (74 Gy/37 fractions). Patients in cohort 1 continued to develop toxicity, with 6/8 (75%) patients eventually developing grade >=3 events. Cohort 2 accrued 9 patients. There was one DLT, a grade 3 esophagitis, in cohort 2 in the first 5 patients (1/5 patients) and no DLTs for the next 2 patients (0/2 patients). Conclusions: The maximum tolerated dose was determined to be 74 Gy/37 fractions (2.0 Gy per fraction) using three-dimensional conformal radiation therapy with concurrent paclitaxel and carboplatin therapy. This dose level in the Phase II portion has been well tolerated, with low rates of acute and late lung toxicities.

  15. Phase I/II trial of whole-abdominal plus pelvic irradiation for Astler-Coller stage beta 2, C colorectal cancer

    SciTech Connect

    Patanaphan, V.; Salazar, O.M.; Slawson, R.G.; Sewchand, W.

    1988-02-01

    From 1982 to 1986, after radical surgery (S) for carcinoma of the rectum and rectosigmoid colon, 25 consecutive patients were entered into a Phase I/II study exploring adjuvant radiation (RT). The latter was given with a single fraction of whole abdomen (mid-body) irradiation (MBI), followed by conventional whole pelvis irradiation (WPI). The minimum follow-up time was 12 months, and the maximum was 44 months. There was escalation of the single MBI dose: 5 Gy in 11 patients, 6 Gy in two patients, and 8 Gy in 10 patients. The 2-year survival rate has been 100 and 45% for Stages B2 and C patients. Only 1/7 Astler-Coller Stage B2 patients failed; this failure was in the lungs. Seven of 15 patients with Stage C failed: one locally, three in the liver, and three in the lungs. Single MBI doses greater than 5 Gy have yielded a high incidence of intestinal obstruction when combined with routine WPI. Consequently, this combination requires both some modification and careful attention if used in future trials exploring new treatment approaches for colorectal cancer.

  16. Myeloma (multiple)

    PubMed Central

    2006-01-01

    Introduction Multiple myeloma is the most common primary cancer of the bones in adults, representing about 1% of all cancers diagnosed in the US in 2004, and 14% of all haematological malignancies. In the UK, multiple myeloma accounts for 1% of all new cases of cancer diagnosed each year. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment in people with asymptomatic early stage multiple myeloma (stage I)? What are the effects of first-line treatments in people with advanced stage multiple myeloma (stages II and III)? What are the effect of salvage treatments, or supportive therapy, in people with advanced stage multiple myeloma (stages II and III)? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2004 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: allogenic transplant (non-myeloablative), autologous stem cell transplant (early or late transplantation, double or single, purging of), bisphosphonates, bone marrow stem cells, bortezomib, chemotherapy (combination, conventional dose, intermediate dose plus stem cell rescue, high-dose plus stem cell rescue), combination chemotherapy plus corticosteroids, deferred treatment (in stage I disease), early chemotherapy plus corticosteroids (in stage I disease), epoetin alpha, first-line treatments, infection prophylaxis, interferon, maintenance therapy (in advanced multiple myeloma), melphalan (normal dose

  17. Effective multiple stages continuous acetone-butanol-ethanol fermentation by immobilized bioreactors: Making full use of fresh corn stalk.

    PubMed

    Chang, Zhen; Cai, Di; Wang, Yong; Chen, Changjing; Fu, Chaohui; Wang, Guoqing; Qin, Peiyong; Wang, Zheng; Tan, Tianwei

    2016-04-01

    In order to make full use of the fresh corn stalk, the sugar containing juice was used as the sole substrate for acetone-butanol-ethanol production without any nutrients supplement, and the bagasse after squeezing the juice was used as the immobilized carrier. A total 21.34g/L of ABE was produced in batch cells immobilization system with ABE yield of 0.35g/g. A continuous fermentation containing three stages with immobilized cells was conducted and the effect of dilution rate on fermentation was investigated. As a result, the productivity and ABE solvents concentration reached 0.80g/Lh and 19.93g/L, respectively, when the dilution rate in each stage was 0.12/h (corresponding to a dilution rate of 0.04/h in the whole system). And the long-term operation indicated the continuous multiple stages ABE fermentation process had good stability and showed the great potential in future industrial applications.

  18. A case of a patient with stage III familial hidradenitis suppurativa treated with 3 courses of infliximab and died of metastatic squamous cell carcinoma.

    PubMed

    Scheinfeld, Noah

    2014-03-01

    Although rare, severe hidradenitis suppurativa (HS) of the anal, perianal, gluteal, thigh, and groin regions can evolve into squamous cell carcinoma (SCC). This usually does not occur until the HS has been present for more than 20 years. Malignant degeneration of HS in the axilla has not been reported. SCC has developed in dissecting cellulitis, acne conglobata, and pilonidal cysts (other members of the follicular tetrad). Whereas the male to female ratio of HS is 1:3, SCC in HS has a male to female ration of 5:1. The reasons behind malignant degeneration in HS are complex and might differ from the malignant degeneration causing Marjolin ulcers. It likely involves the presence of human papilloma virus (HPV) in affected areas (a rarity in the axilla), and impaired defensins, which combat HPV, in the skin of Hurley Stage III HS. In familial HS, the odds of developing SCC are likely greater because of independent loss-of-function mutations in the γ-secretase multiprotein complex, which regulates the Notch signaling pathway. Compromise of the Notch signaling pathway can undermine immune function and increase the risk of neoplastic development. Coincident SCC with use of tumor necrosis factor α blockers has been reported. I report a patient with long standing Hurley Stage III, familial HS, wwho developed metastatic SCC after 3 courses of infliximab and expired 11 months after the infliximab was started. A 47-year-old male presented with progressive HS since early adulthood. His stage III hidradenitis suppurativa (HS) involved his groin, legs buttocks, and perineal areas. Interestingly, his HS was familial; one daughter also suffered from HS. A pilonidal cyst had been excised in the past. He suffered from hypertension for which he took ramipril, 2.5 mg per day. He did not admit to smoking. He had undergone numerous surgeries and courses of clindamycin with rifampin and clindamycin with minocycline. He used pregablin among other stronger medications for pain control. He

  19. Hhex is Required at Multiple Stages of Adult Hematopoietic Stem and Progenitor Cell Differentiation

    PubMed Central

    Goodings, Charnise; Smith, Elizabeth; Mathias, Elizabeth; Elliott, Natalina; Cleveland, Susan M.; Tripathi, Rati M.; Layer, Justin H.; Chen, Xi; Guo, Yan; Shyr, Yu; Hamid, Rizwan; Du, Yang; Davé, Utpal P.

    2015-01-01

    Hhex encodes a homeodomain transcription factor that is widely expressed in hematopoietic stem and progenitor cell populations. Its enforced expression induces T-cell leukemia and we have implicated it as an important oncogene in early T-cell precursor leukemias where it is immediately downstream of an LMO2-associated protein complex. Conventional Hhex knockouts cause embryonic lethality precluding analysis of adult hematopoiesis. Thus, we induced highly efficient conditional knockout (cKO) using vav-Cre transgenic mice. Hhex cKO mice were viable and born at normal litter sizes. At steady state, we observed a defect in B-cell development that we localized to the earliest B-cell precursor, the pro-B-cell stage. Most remarkably, bone marrow transplantation using Hhex cKO donor cells revealed a more profound defect in all hematopoietic lineages. In contrast, sublethal irradiation resulted in normal myeloid cell repopulation of the bone marrow but markedly impaired repopulation of T- and B-cell compartments. We noted that Hhex cKO stem and progenitor cell populations were skewed in their distribution and showed enhanced proliferation compared to WT cells. Our results implicate Hhex in the maintenance of LT-HSCs and in lineage allocation from multipotent progenitors especially in stress hematopoiesis. PMID:25968920

  20. Hhex is Required at Multiple Stages of Adult Hematopoietic Stem and Progenitor Cell Differentiation.

    PubMed

    Goodings, Charnise; Smith, Elizabeth; Mathias, Elizabeth; Elliott, Natalina; Cleveland, Susan M; Tripathi, Rati M; Layer, Justin H; Chen, Xi; Guo, Yan; Shyr, Yu; Hamid, Rizwan; Du, Yang; Davé, Utpal P

    2015-08-01

    Hhex encodes a homeodomain transcription factor that is widely expressed in hematopoietic stem and progenitor cell populations. Its enforced expression induces T-cell leukemia and we have implicated it as an important oncogene in early T-cell precursor leukemias where it is immediately downstream of an LMO2-associated protein complex. Conventional Hhex knockouts cause embryonic lethality precluding analysis of adult hematopoiesis. Thus, we induced highly efficient conditional knockout (cKO) using vav-Cre transgenic mice. Hhex cKO mice were viable and born at normal litter sizes. At steady state, we observed a defect in B-cell development that we localized to the earliest B-cell precursor, the pro-B-cell stage. Most remarkably, bone marrow transplantation using Hhex cKO donor cells revealed a more profound defect in all hematopoietic lineages. In contrast, sublethal irradiation resulted in normal myeloid cell repopulation of the bone marrow but markedly impaired repopulation of T- and B-cell compartments. We noted that Hhex cKO stem and progenitor cell populations were skewed in their distribution and showed enhanced proliferation compared to WT cells. Our results implicate Hhex in the maintenance of LT-HSCs and in lineage allocation from multipotent progenitors especially in stress hematopoiesis.

  1. A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

    PubMed Central

    Rothman, Nathaniel; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Malats, Nuria; Wu, Xifeng; Figueroa, Jonine; Real, Francisco X; Van Den Berg, David; Matullo, Giuseppe; Baris, Dalsu; Thun, Michael; Kiemeney, Lambertus A; Vineis, Paolo; De Vivo, Immaculata; Albanes, Demetrius; Purdue, Mark P; Rafnar, Thorunn; Hildebrandt, Michelle A T; Kiltie, Anne E; Cussenot, Olivier; Golka, Klaus; Kumar, Rajiv; Taylor, Jack A; Mayordomo, Jose I; Jacobs, Kevin B; Kogevinas, Manolis; Hutchinson, Amy; Wang, Zhaoming; Fu, Yi-Ping; Prokunina-Olsson, Ludmila; Burdette, Laurie; Yeager, Meredith; Wheeler, William; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Johnson, Alison; Schwenn, Molly; Karagas, Margaret R; Schned, Alan; Andriole, Gerald; Grubb, Robert; Black, Amanda; Jacobs, Eric J; Diver, W Ryan; Gapstur, Susan M; Weinstein, Stephanie J; Virtamo, Jarmo; Cortessis, Victoria K; Gago-Dominguez, Manuela; Pike, Malcolm C; Stern, Mariana C; Yuan, Jian-Min; Hunter, David; McGrath, Monica; Dinney, Colin P; Czerniak, Bogdan; Chen, Meng; Yang, Hushan; Vermeulen, Sita H; Aben, Katja K; Witjes, J Alfred; Makkinje, Remco R; Sulem, Patrick; Besenbacher, Soren; Stefansson, Kari; Riboli, Elio; Brennan, Paul; Panico, Salvatore; Navarro, Carmen; Allen, Naomi E; Bueno-de-Mesquita, H Bas; Trichopoulos, Dimitrios; Caporaso, Neil; Landi, Maria Teresa; Canzian, Federico; Ljungberg, Borje; Tjonneland, Anne; Clavel-Chapelon, Francoise; Bishop, David T; Teo, Mark T W; Knowles, Margaret A; Guarrera, Simonetta; Polidoro, Silvia; Ricceri, Fulvio; Sacerdote, Carlotta; Allione, Alessandra; Cancel-Tassin, Geraldine; Selinski, Silvia; Hengstler, Jan G; Dietrich, Holger; Fletcher, Tony; Rudnai, Peter; Gurzau, Eugen; Koppova, Kvetoslava; Bolick, Sophia C E; Godfrey, Ashley; Xu, Zongli; Sanz-Velez, José I; García-Prats, María D; Sanchez, Manuel; Valdivia, Gabriel; Porru, Stefano; Benhamou, Simone; Hoover, Robert N; Fraumeni, Joseph F; Silverman, Debra T; Chanock, Stephen J

    2010-01-01

    We conducted a multi-stage, genome-wide association study (GWAS) of bladder cancer with a primary scan of 589,299 single nucleotide polymorphisms (SNPs) in 3,532 cases and 5,120 controls of European descent (5 studies) followed by a replication strategy, which included 8,381 cases and 48,275 controls (16 studies). In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1; rs1014971, (P=8×10−12) maps to a non-genic region of chromosome 22q13.1; rs8102137 (P=2×10−11) on 19q12 maps to CCNE1; and rs11892031 (P=1×10−7) maps to the UGT1A cluster on 2q37.1. We confirmed four previous GWAS associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P=4×10−11) and a tag SNP for NAT2 acetylation status (P=4×10−11), as well as demonstrated smoking interactions with both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into mechanisms of carcinogenesis. PMID:20972438

  2. Multiple life stage sensitivity of a deposit-feeding polychaete to chemical toxicants in sediment

    SciTech Connect

    Rice, C.A.; Sibley, T.; Ylitalo, G.M.; Casillas, E.

    1995-12-31

    By focusing on acute toxicity in species with habitat and food preferences often quite different from the environments of primary interest; that is, the depositional, fine-grained, organically enriched benthos, standard methods of testing sediment toxicity using single species have important problems of relevance in terms of test endpoints and target species. This study addresses these issues by building a set of baseline toxicity data that emphasizes critical life stage sensitivity over a wide range of toxicant concentrations in long-term sediment exposures for an animal with a model life history. The opportunistic, deposit-feeding polychaete Armandia brevis was exposed to sediments supplemented with fluoranthene, cadmium, copper, lead, and mercury, alone and in a model mixture, for 60 days. Mortality and emergence from sediment were recorded daily, and growth and maturity were measured at 20, 40, and 60d. To measure recruitment, cultured larvae were presented with the same sediments and allowed to settle and complete metamorphosis. Differential endpoint sensitivity, and differential chemical toxicity were evaluated. In addition, sediment and tissue concentrations of organic toxicants were used to link toxic responses to body burdens, and to consider the role of benthic infauna as contaminant vectors in the marine environment.

  3. Design and evaluation of multiple level data staging for Blue Gene systems.

    SciTech Connect

    Isaila, F.; Blas, J. G.; Carretero, J.; Latham, R.; Ross, R.

    2011-06-01

    Parallel applications currently suffer from a significant imbalance between computational power and available I/O bandwidth. Additionally, the hierarchical organization of current Petascale systems contributes to an increase of the I/O subsystem latency. In these hierarchies, file access involves pipelining data through several networks with incremental latencies and higher probability of congestion. Future Exascale systems are likely to share this trait. This paper presents a scalable parallel I/O software system designed to transparently hide the latency of file system accesses to applications on these platforms. Our solution takes advantage of the hierarchy of networks involved in file accesses, to maximize the degree of overlap between computation, file I/O-related communication, and file system access. We describe and evaluate a two-level hierarchy for Blue Gene systems consisting of client-side and I/O node-side caching. Our file cache management modules coordinate the data staging between application and storage through the Blue Gene networks. The experimental results demonstrate that our architecture achieves significant performance improvements through a high degree of overlap between computation, communication, and file I/O.

  4. Circulating plasma cells in multiple myeloma: characterization and correlation with disease stage.

    PubMed

    Rawstron, A C; Owen, R G; Davies, F E; Johnson, R J; Jones, R A; Richards, S J; Evans, P A; Child, J A; Smith, G M; Jack, A S; Morgan, G J

    1997-04-01

    The aim of this study was to develop a flow cytometric test to quantitate low levels of circulating myeloma plasma cells, and to determine the relationship of these cells with disease stage. Cells were characterized using five-parameter flow cytometric analysis with a panel of antibodies, and results were evaluated by comparison with fluorescent consensus-primer IgH-PCR. Bone marrow myeloma plasma cells, defined by high CD38 and Syndecan-1 expression, did not express CD10, 23, 30, 34 or 45RO, and demonstrated weak expression of CD37 and CD45. 65% of patients had CD19- 56+ plasma cells, 30% CD19- 56(low), and 5% CD19+ 56+, and these two antigens discriminated myeloma from normal plasma cells, which were all CD19+ 56(low). Peripheral blood myeloma plasma cells had the same composite phenotype, but expressed significantly lower levels of CD56 and Syndecan-1, and were detected in 75% (38/51) of patients at presentation, 92% (11/12) of patients in relapse, and 40% (4/10) of stem cell harvests. Circulating plasma cells were not detectable in patients in CR (n = 9) or normals (n = 10), at a sensitivity of up to 1 in 10,000 cells. There was good correlation between the flow cytometric test and IgH-PCR results: myeloma plasma cells were detectable by flow cytometry in all PCR positive samples, and samples with no detectable myeloma plasma cells were PCR negative. Absolute numbers decreased in patients responding to treatment, remained elevated in patients with refractory disease, and increased in patients undergoing relapse. We conclude that flow cytometry can provide an effective aternative to IgH-PCR that will allow quantitative assessment of low levels of residual disease.

  5. 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.

  6. Prognostic Impact of Erythropoietin Expression and Erythropoietin Receptor Expression on Locoregional Control and Survival of Patients Irradiated for Stage II/III Non-Small-Cell Lung Cancer

    SciTech Connect

    Rades, Dirk; Setter, Cornelia; Dahl, Olav; Schild, Steven E.; Noack, Frank

    2011-06-01

    Purpose: Prognostic factors can guide the physician in selecting the optimal treatment for an individual patient. This study investigates the prognostic value of erythropoietin (EPO) and EPO receptor (EPO-R) expression of tumor cells for locoregional control and survival in non-small-cell lung cancer (NSCLC) patients. Methods and Materials: Fourteen factors were investigated in 62 patients irradiated for stage II/III NSCLC, as follows: age, gender, Karnofsky performance score (KPS), histology, grading, TNM/American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, pack years (average number of packages of cigarettes smoked per day multiplied by the number of years smoked), smoking during radiotherapy, hemoglobin levels during radiotherapy, EPO expression, and EPO-R expression. Additionally, patients with tumors expressing both EPO and EPO-R were compared to those expressing either EPO or EPO-R and to those expressing neither EPO nor EPO-R. Results: On univariate analysis, improved locoregional control was associated with AJCC stage II cancer (p < 0.048), surgery (p < 0.042), no smoking during radiotherapy (p = 0.024), and no EPO expression (p = 0.001). A trend was observed for a KPS of >70 (p = 0.08), an N stage of 0 to 1 (p = 0.07), and no EPO-R expression (p = 0.10). On multivariate analysis, AJCC stage II and no EPO expression remained significant. No smoking during radiotherapy was almost significant. On univariate analysis, improved survival was associated with N stage 0 to 1 (p = 0.009), surgery (p = 0.039), hemoglobin levels of {>=}12 g/d (p = 0.016), and no EPO expression (p = 0.001). On multivariate analysis, N stage 0 to 1 and no EPO expression maintained significance. Hemoglobin levels of {>=}12 g/d were almost significant. On subgroup analyses, patients with tumors expressing both EPO and EPO-R had worse outcomes than those expressing either EPO or EPO-R and those expressing neither EPO nor RPO-R. Conclusions: EPO expression of tumor cells

  7. Industrial Application of an Improved Multiple Injection and Multiple Staging Combustion Technology in a 600 MWe Supercritical Down-Fired Boiler.

    PubMed

    Song, Minhang; Zeng, Lingyan; Chen, Zhichao; Li, Zhengqi; Zhu, Qunyi; Kuang, Min

    2016-02-01

    To solve the water wall overheating in lower furnace, and further reduce NOx emissions and carbon in fly ash, continuous improvement of the previously proposed multiple injection and multiple staging combustion (MIMSC) technology lies on three aspects: (1) along the furnace arch breadth, changing the previously centralized 12 burner groups into a more uniform pattern with 24 burners; (2) increasing the mass ratio of pulverized coal in fuel-rich flow to that in fuel-lean flow from 6:4 to 9:1; (3) reducing the arch-air momentum by 23% and increasing the tertiary-air momentum by 24%. Industrial-size measurements (i.e., adjusting overfire air (OFA) damper opening of 20-70%) uncovered that, compared with the prior MIMSC technology, the ignition distance of fuel-rich coal/air flow shortened by around 1 m. The gas temperature in the lower furnace was symmetric and higher, the flame kernel moved upward and therefore made the temperature in near-wall region of furnace hopper decrease by about 400 °C, the water wall overheating disappeared completely. Under the optimal OFA damper opening (i.e, 55%), NOx emissions and carbon in fly ash attained levels of 589 mg/m(3) at 6% O2 and 6.18%, respectively, achieving NOx and carbon in fly ash significant reduction by 33% and 37%, respectively. PMID:26752460

  8. Improving combustion characteristics and NO(x) emissions of a down-fired 350 MW(e) utility boiler with multiple injection and multiple staging.

    PubMed

    Kuang, Min; Li, Zhengqi; Xu, Shantian; Zhu, Qunyi

    2011-04-15

    Within a Mitsui Babcock Energy Limited down-fired pulverized-coal 350 MW(e) utility boiler, in situ experiments were performed, with measurements taken of gas temperatures in the burner and near the right-wall regions, and of gas concentrations (O(2) and NO) from the near-wall region. Large combustion differences between zones near the front and rear walls and particularly high NO(x) emissions were found in the boiler. With focus on minimizing these problems, a new technology based on multiple-injection and multiple-staging has been developed. Combustion improvements and NO(x) reductions were validated by investigating three aspects. First, numerical simulations of the pulverized-coal combustion process and NO(x) emissions were compared in both the original and new technologies. Good agreement was found between simulations and in situ measurements with the original technology. Second, with the new technology, gas temperature and concentration distributions were found to be symmetric near the front and rear walls. A relatively low-temperature and high-oxygen-concentration zone formed in the near-wall region that helps mitigate slagging in the lower furnace. Third, NO(x) emissions were found to have decreased by as much as 50%, yielding a slight decrease in the levels of unburnt carbon in the fly ash.

  9. Industrial Application of an Improved Multiple Injection and Multiple Staging Combustion Technology in a 600 MWe Supercritical Down-Fired Boiler.

    PubMed

    Song, Minhang; Zeng, Lingyan; Chen, Zhichao; Li, Zhengqi; Zhu, Qunyi; Kuang, Min

    2016-02-01

    To solve the water wall overheating in lower furnace, and further reduce NOx emissions and carbon in fly ash, continuous improvement of the previously proposed multiple injection and multiple staging combustion (MIMSC) technology lies on three aspects: (1) along the furnace arch breadth, changing the previously centralized 12 burner groups into a more uniform pattern with 24 burners; (2) increasing the mass ratio of pulverized coal in fuel-rich flow to that in fuel-lean flow from 6:4 to 9:1; (3) reducing the arch-air momentum by 23% and increasing the tertiary-air momentum by 24%. Industrial-size measurements (i.e., adjusting overfire air (OFA) damper opening of 20-70%) uncovered that, compared with the prior MIMSC technology, the ignition distance of fuel-rich coal/air flow shortened by around 1 m. The gas temperature in the lower furnace was symmetric and higher, the flame kernel moved upward and therefore made the temperature in near-wall region of furnace hopper decrease by about 400 °C, the water wall overheating disappeared completely. Under the optimal OFA damper opening (i.e, 55%), NOx emissions and carbon in fly ash attained levels of 589 mg/m(3) at 6% O2 and 6.18%, respectively, achieving NOx and carbon in fly ash significant reduction by 33% and 37%, respectively.

  10. Removal of multiple electron acceptors by pilot-scale, two-stage membrane biofilm reactors.

    PubMed

    Zhao, He-Ping; Ontiveros-Valencia, Aura; Tang, Youneng; Kim, Bi-O; Vanginkel, Steven; Friese, David; Overstreet, Ryan; Smith, Jennifer; Evans, Patrick; Krajmalnik-Brown, Rosa; Rittmann, Bruce

    2014-05-01

    We studied the performance of a pilot-scale membrane biofilm reactor (MBfR) treating groundwater containing four electron acceptors: nitrate (NO3(-)), perchlorate (ClO4(-)), sulfate (SO4(2-)), and oxygen (O2). The treatment goal was to remove ClO4(-) from ∼200 μg/L to less than 6 μg/L. The pilot system was operated as two MBfRs in series, and the positions of the lead and lag MBfRs were switched regularly. The lead MBfR removed at least 99% of the O2 and 63-88% of NO3(-), depending on loading conditions. The lag MBfR was where most of the ClO4(-) reduction occurred, and the effluent ClO4(-) concentration was driven to as low as 4 μg/L, with most concentrations ≤10 μg/L. However, SO4(2-) reduction occurred in the lag MBfR when its NO3(-) + O2 flux was smaller than ∼0.18 g H2/m(2)-d, and this was accompanied by a lower ClO4(-) flux. We were able to suppress SO4(2-) reduction by lowering the H2 pressure and increasing the NO3(-) + O2 flux. We also monitored the microbial community using the quantitative polymerase chain reaction targeting characteristic reductase genes. Due to regular position switching, the lead and lag MBfRs had similar microbial communities. Denitrifying bacteria dominated the biofilm when the NO3(-) + O2 fluxes were highest, but sulfate-reducing bacteria became more important when SO4(2-) reduction was enhanced in the lag MBfR due to low NO3(-) + O2 flux. The practical two-stage strategy to achieve complete ClO4(-) and NO3(-) reduction while suppressing SO4(2-) reduction involved controlling the NO3(-) + O2 surface loading between 0.18 and 0.34 g H2/m(2)-d and using a low H2 pressure in the lag MBfR.

  11. Two-Stage Mucogingival Surgery with Free Gingival Autograft and Biomend Membrane and Coronally Advanced Flap in Treatment of Class III Millers Recession.

    PubMed

    Rath, Avita; Varma, Smrithi; Paul, Renny

    2016-01-01

    Introduction. Gingival recession is an apical shift of the gingival margin with exposure of the root surface. This migration of the marginal tissue leads to esthetic concerns, dentin hypersensitivity, root caries, and cervical wear. It is, paradoxically, a common finding in patients with a high standard of oral hygiene, as well as in periodontally untreated populations with poor oral hygiene. Changing the topography of the marginal soft tissue in order to facilitate plaque control is a common indication for root coverage procedures and forms a major aspect of periodontal plastic surgeries. The regeneration of a new connective tissue attachment to denuded root surface is by allowing the selective coronal regrowth of periodontal ligament cells while excluding the gingival tissues from the root during wound healing by means of a barrier membrane. Case Presentation. This case reports a two-stage surgical technique for treatment of Miller's class III defect using free gingival autograft and type I absorbable collagen membrane (BioMend®, Zimmer Dental, USA)(§). Conclusions. The 6-month follow-up of the case showed a significant increase in attached gingiva suggesting it as a predictable alternative in the treatment of Millers class III defects. PMID:27525131

  12. Two-Stage Mucogingival Surgery with Free Gingival Autograft and Biomend Membrane and Coronally Advanced Flap in Treatment of Class III Millers Recession

    PubMed Central

    Paul, Renny

    2016-01-01

    Introduction. Gingival recession is an apical shift of the gingival margin with exposure of the root surface. This migration of the marginal tissue leads to esthetic concerns, dentin hypersensitivity, root caries, and cervical wear. It is, paradoxically, a common finding in patients with a high standard of oral hygiene, as well as in periodontally untreated populations with poor oral hygiene. Changing the topography of the marginal soft tissue in order to facilitate plaque control is a common indication for root coverage procedures and forms a major aspect of periodontal plastic surgeries. The regeneration of a new connective tissue attachment to denuded root surface is by allowing the selective coronal regrowth of periodontal ligament cells while excluding the gingival tissues from the root during wound healing by means of a barrier membrane. Case Presentation. This case reports a two-stage surgical technique for treatment of Miller's class III defect using free gingival autograft and type I absorbable collagen membrane (BioMend®, Zimmer Dental, USA)§. Conclusions. The 6-month follow-up of the case showed a significant increase in attached gingiva suggesting it as a predictable alternative in the treatment of Millers class III defects. PMID:27525131

  13. Thyroid Function in Women after Multimodal Treatment for Breast Cancer Stage II/III: Comparison With Controls From a Population Sample

    SciTech Connect

    Reinertsen, Kristin Valborg; Cvancarova, Milada; Wist, Erik; Bjoro, Trine; Dahl, Alv A.; Danielsen, Turi; Fossa, Sophie D.

    2009-11-01

    Purpose: A possible association between thyroid diseases (TD) and breast cancer (BC) has been debated. We examined prevalence and development of TD in women after multimodal treatment for Stage II/III BC compared with women from a general population. Secondarily, we explored the impact of two different radiotherapy (RT) techniques (standardized field arrangements vs. computed tomography [CT]-based dose planning) on TD in BC patients examined 35-120 months after primary BC treatment. Methods and Materials: A total of 403 BC patients completed a questionnaire about TD and had blood samples taken for analyses of thyroid function. All had undergone postoperative RT with or without (2%) adjuvant systemic treatment. The results in the BC patients were compared with a cancer-free, age-matched control group from a general population (CGr). Results: There was higher prevalence of self-reported hypothyroidism in the BC patients as compared with the CGr (18% vs. 6%, p < 0.001). The raised prevalence was predominantly due to a substantial increase in the development of hypothyroidism after BC diagnosis, whereas the prevalence of hypothyroidism before BC diagnosis was similar to that observed in the CGr. Patients treated with CT-based RT showed a trend for increased post-BC development of hypothyroidism as compared with those treated with standardized field arrangements (p = 0.08). Conclusions: Hypothyroidism is significantly increased in women after multimodal treatment for Stage II/III BC. Radiation to the thyroid gland may be a contributing factor. BC patients should be routinely screened for hypothyroidism.

  14. Predictors of Long-Term Quality of Life for Survivors of Stage II/III Rectal Cancer in the Cancer Care Outcomes Research and Surveillance Consortium

    PubMed Central

    Charlton, Mary E.; Stitzenberg, Karyn B.; Lin, Chi; Schlichting, Jennifer A.; Halfdanarson, Thorvardur R.; Juarez, Grelda Yazmin; Pendergast, Jane F.; Chrischilles, Elizabeth A.; Wallace, Robert B.

    2015-01-01

    Purpose: Many patients do not receive guideline-recommended neoadjuvant chemoradiotherapy for resectable rectal cancer. Little is known regarding long-term quality of life (QOL) associated with various treatment approaches. Our objective was to determine patient characteristics and subsequent QOL associated with treatment approach. Methods: Our study was a geographically diverse population- and health system–based cohort study that included adults age 21 years or older with newly diagnosed stage II/III rectal cancer who were recruited from 2003 to 2005. Eligible patients were contacted 1 to 4 months after diagnosis and asked to participate in a telephone survey and to consent to medical record review, with separate follow-up QOL surveys conducted 1 and 7 years after diagnosis. Results: Two hundred thirty-nine patients with stage II/III rectal cancer were included in this analysis. Younger age (< 65 v ≥ 65 years: odds ratio, 2.49; 95% CI, 1.33 to 4.65) was significantly associated with increased odds of receiving neoadjuvant or adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy group had significantly worse mean EuroQol-5D (range, 0 to 1) and Short Form-12 physical health component scores (standardized mean, 50) at 1-year follow-up than the neoadjuvant chemoradiotherapy group (0.75 v 0.85; P = .002; 37.2 v 43.3; P = .01, respectively) and the group that received only one or neither form of treatment (0.75 v 0.85; P = .02; 37.2 v 45.1; P = .008, respectively). Conclusion: Neoadjuvant treatment may result in better QOL and functional status 1 year after diagnosis. Further evaluation of patient and provider reasons for not pursuing neoadjuvant therapy is necessary to determine how and where to target process improvement and/or education efforts to ensure that patients have access to recommended treatment options. PMID:26080831

  15. Genetic variants within obesity-related genes are associated with tumor recurrence in patients with stages II/III colon cancer

    PubMed Central

    Sebio, Ana; Gerger, Armin; Matsusaka, Satoshi; Yang, Dongyun; Zhang, Wu; Stremitzer, Stefan; Stintizing, Sebastian; Sunakawa, Yu; Yamauchi, Shinichi; Ning, Yan; Fujimoto, Yoshiya; Ueno, Masashi; Lenz, Heinz-Josef

    2014-01-01

    Objective Obesity is an established risk factor for colorectal cancer (CRC) incidence and it is also linked to CRC recurrence and survival. Polymorphisms located in obesity-related genes are associated with increased risk of developing several cancer types including colorectal cancer. We evaluated whether SNPs in obesity-related genes may predict tumor recurrence in colon cancer patients. Methods Genotypes were obtained from germline DNA from 207 patients with stage II or III colon cancer at the Norris Comprehensive Cancer Center. Nine polymorphisms in eight obesity-related genes (PPAR, LEP, NFKB, CD36, DRG1, NGAL, REGIA and DSCR1) were evaluated. The primary endpoint of the study was 3-year recurrence rate. Positive associations were also tested in an independent Japanese cohort of 350 stage III CRC patients. Results In univariate analysis, for PPAR rs1801282, patients with a CC genotype had significantly lower recurrence probability (29± 4% standard error, SE) compared to patients with a CG genotype (48% ± 8% SE), HR: 1.77; 95%CI, 1.01-3.10; p=0.040. For DSCR1 rs6517239, patients with an AA genotype had higher recurrence probability than patients carrying at least one allele G (37% ± 4% SE vs 15% ± 6% SE), HR: 0.51, 95% CI, 0.27-0.94; p=0.027. This association was stronger in the patients bearing a left-sided tumor (HR: 0.34; 95%CI, 0.13-0.88; p=0.018). In the Japanese cohort no associations were found. Conclusion This hypothesis generating study suggests a potential influence of polymorphisms within obesity-related genes in the recurrence probability of colon cancer. These interesting results should be further evaluated. PMID:25379721

  16. Multivitamin Use Is Not Associated With Cancer Recurrence or Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803

    PubMed Central

    Ng, Kimmie; Meyerhardt, Jeffrey A.; Chan, Jennifer A.; Niedzwiecki, Donna; Hollis, Donna R.; Saltz, Leonard B.; Mayer, Robert J.; Benson, Al B.; Schaefer, Paul L.; Whittom, Renaud; Hantel, Alexander; Goldberg, Richard M.; Fuchs, Charles S.

    2010-01-01

    Purpose Multivitamin use is widespread in the United States, especially among patients with cancer. However, the influence of multivitamin supplementation on cancer recurrence and death after a curative resection of colon cancer is unknown. Patients and Methods We conducted a prospective, observational study of 1,038 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial. Patients reported on multivitamin use during and 6 months after adjuvant chemotherapy. Patients were observed until March 2009 for disease recurrence and death. To minimize bias by occult recurrence, we excluded patients who recurred or died within 90 days of their multivitamin assessment. Results Among 1,038 patients, 518 (49.9%) reported multivitamin use during adjuvant chemotherapy. Compared with nonusers, the multivariate hazard ratio (HR) for disease-free survival was 0.94 (95% CI, 0.77 to 1.15) for patients who used multivitamins. Similarly, multivitamin use during adjuvant chemotherapy was not significantly associated with recurrence-free survival (multivariate HR, 0.93; 95% CI, 0.75 to 1.15) or overall survival (multivariate HR 0.92; 95% CI, 0.74 to 1.16). Multivitamin use reported 6 months after completion of adjuvant chemotherapy was also not associated with improved patient outcome, and consistent use both during and following adjuvant therapy conferred no benefit. Neither an increasing number of tablets nor increasing duration of use before cancer diagnosis was associated with cancer recurrence or mortality. Multivitamin use also did not improve the rates of grade 3 and higher GI toxicity. Conclusion Multivitamin use during and after adjuvant chemotherapy was not significantly associated with improved outcomes in patients with stage III colon cancer. PMID:20805450

  17. The Effects of Comorbidity and Age on RTOG Study Enrollment in Stage III Non-Small Cell Lung Cancer Patients Who Are Eligible for RTOG Studies

    SciTech Connect

    Firat, Selim; Byhardt, Roger W.; Gore, Elizabeth

    2010-12-01

    Purpose: To determine the influence of measured comorbidity in Radiation Therapy Oncology Group (RTOG) combined modality therapy (CMT) study enrollment in Stage III non-small cell lung cancer (NSCLC). Methods and Materials: One hundred and seventy-one patients with a Karnofsky Performance Score {>=}70 and clinical Stage III NSCLC were analyzed retrospectively for comorbidity, RTOG study eligibility, and enrollment at initial consultation. Effect of comorbidity scores (Cumulative Illness Rating Scale) were tested on patient selection for CMT, RTOG enrollment, and overall survival. Results: Comorbidity (Grade 4; p < 0.005) and use of radiation only (p {<=} 0.001) were associated with inferior survival independent of other factors. Patient selection for CMT was affected by age ({>=}70, p < 0.001), comorbidity (severity index [SI]> 2, p = 0.001), and weight loss (>5%, p = 0.001). Thirty-three patients (19%) were enrolled in a CMT RTOG study (Group 1). Forty-nine patients (29%) were eligible but not enrolled (Group 2), and 57 (33%) were ineligible (Group 3). The most common ineligibility reasons were weight loss (67%) and comorbidity in the exclusion criteria of the RTOG studies (63%). Group 1 patients were the youngest (p = 0.02), with the lowest comorbidity scores (p < 0.001) and SI (p < 0.001) compared with Groups 2 and 3. Group 3 patients were the oldest with the most unfavorable comorbidity profile. Comorbidity scores (SI >2; p = 0.006) and age ({>=}70; p = 0.05) were independent factors influencing RTOG study enrollment in patients meeting study eligibility requirements (Groups 1 and 2). Conclusions: Comorbidity scales could be useful in stratification of patients in advanced lung cancer trials and interpretation of results particularly regarding the elderly population.

  18. Assessment and classification of early-stage multiple sclerosis with inertial sensors: comparison against clinical measures of disease state.

    PubMed

    Greene, Barry R; Rutledge, Stephanie; McGurgan, Iain; McGuigan, Christopher; OConnell, Karen; Caulfield, Brian; Tubridy, Niall

    2015-07-01

    A cross-sectional study on patients with early-stage multiple sclerosis (MS) was conducted to examine the reliability of manual and automatic mobility measures derived from shank-mounted inertial sensors during the Timed Up and Go (TUG) test, compared to control subjects. Furthermore, we aimed to determine if disease status [as measured by the Multiple Sclerosis Impact Scale (MSIS-20) and the Expanded Disability Status Score (EDSS)] can be explained by measurements obtained using inertial sensors. We also aimed to determine if patients with early-stage MS could be automatically distinguished from healthy controls subjects, using inertial parameters recorded during the TUG test. The mobility of 38 patients (aged 25-65 years, 14 M, 24 F), diagnosed with relapsing-remitting MS and 33 healthy controls (14 M, 19 F, age 50-65), was assessed using the TUG test, while patients wore inertial sensors on each shank. Reliability analysis showed that 36 of 53 mobility parameters obtained during the TUG showed excellent intrasession reliability, while nine of 53 showed moderate reliability. This compared favorably with the reliability of the mobility parameters in healthy controls. Exploratory regression models of the EDSS and MSIS-20 scales were derived, using mobility parameters and an elastic net procedure in order to determine which mobility parameters influence disease state. A cross-validated elastic net regularized regression model for MSIS-20 yielded a mean square error (MSE) of 1.1 with 10 degrees of freedom (DoF). Similarly, an elastic net regularized regression model for EDSS yielded a cross-validated MSE of 1.3 with 10 DoF. Classification results show that the mobility parameters of participants with early-stage MS could be distinguished from controls with 96.90% accuracy. Results suggest that mobility parameters derived from MS patients while completing the TUG test are reliable, are associated with disease state in MS, and may have utility in screening for early-stage

  19. Bevacizumab and Intravenous or Intraperitoneal Chemotherapy in Treating Patients With Stage II-III Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-07-05

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  20. Test-retest reliability of UPDRS-III, dyskinesia scales, and timed motor tests in patients with advanced Parkinson's disease: an argument against multiple baseline assessments.

    PubMed

    Metman, Leo Verhagen; Myre, Brian; Verwey, Niek; Hassin-Baer, Sharon; Arzbaecher, Jean; Sierens, Diane; Bakay, Roy

    2004-09-01

    The primary objective of this study was to assess the intra-rater reliability of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III) in patients with advanced Parkinson's disease (PD). The secondary objective was to assess the intra-rater reliability of standard timed motor tests and dyskinesia scales to determine the necessity of multiple baseline core evaluations before surgery for PD. We carried out two standardized preoperative core evaluations of patients with advanced PD scheduled to undergo deep brain stimulation. Patients were examined in the defined off and on conditions by the same rater. UPDRS-III, timed tests, and dyskinesia scores from the two evaluations were compared using Wilcoxon Signed Ranks tests and intraclass correlation coefficients (ICC). Differences in UPDRS-III scores for the two visits were clinically and statistically nonsignificant, and the ICC was 0.9. Similarly, there were no significant differences in timed motor tests or dyskinesia scores, with a median ICC of 0.8. The results indicate that previous findings of high test-retest reliability of UPDRS-III in early untreated PD patients can now be extended to those with advanced disease complicated by motor fluctuations. In addition, test-retest reliability of dyskinesia scales and timed motor tests was high. Taken together, these findings challenge the need for multiple baseline assessments as currently stipulated in core assessment protocols for surgical intervention in PD. PMID:15372601

  1. Analysis of mRNA decay and rRNA processing in Escherichia coli multiple mutants carrying a deletion in RNase III.

    PubMed Central

    Babitzke, P; Granger, L; Olszewski, J; Kushner, S R

    1993-01-01

    RNase III is an endonuclease involved in processing both rRNA and certain mRNAs. To help determine whether RNase III (rnc) is required for general mRNA turnover in Escherichia coli, we have created a deletion-insertion mutation (delta rnc-38) in the structural gene. In addition, a series of multiple mutant strains containing deficiencies in RNase II (rnb-500), polynucleotide phosphorylase (pnp-7 or pnp-200), RNase E (rne-1 or rne-3071), and RNase III (delta rnc-38) were constructed. The delta rnc-38 single mutant was viable and led to the accumulation of 30S rRNA precursors, as has been previously observed with the rnc-105 allele (P. Gegenheimer, N. Watson, and D. Apirion, J. Biol. Chem. 252:3064-3073, 1977). In the multiple mutant strains, the presence of the delta rnc-38 allele resulted in the more rapid decay of pulse-labeled RNA but did not suppress conditional lethality, suggesting that the lethality associated with altered mRNA turnover may be due to the stabilization of specific mRNAs. In addition, these results indicate that RNase III is probably not required for general mRNA decay. Of particular interest was the observation that the delta rnc-38 rne-1 double mutant did not accumulate 30S rRNA precursors at 30 degrees C, while the delta rnc-38 rne-3071 double mutant did. Possible explanations of these results are discussed. Images PMID:8416898

  2. Influence of branch autonomy on fruit, scaffold, trunk and root growth during stage III of peach fruit development.

    PubMed

    Marsal, Jordi; Basile, Boris; Solari, Luis; DeJong, Theodore M

    2003-04-01

    We studied the influence of branch autonomy on the growth of reproductive and vegetative organs by establishing different patterns of fruit distribution within and between large branch units (scaffolds) in mature peach trees (Prunus persica (L.) Batsch cv. 'Elegant Lady'). Different patterns of fruit distribution were established by defruiting either whole scaffolds (uneven fruit distribution between scaffolds; US) or several selected hangers (small fruiting branches) per tree (uneven fruit distribution between hangers; UH). The effects of these patterns were compared with the effects of an even fruit distribution treatment (EVEN) in which fruits were thinned to achieve maximum uniformity of fruit distribution within the canopy. The desired fruit loads were obtained by differentially thinning the remaining bearing parts. On a tree basis, the response of mean fruit mass to fruit load was strongly affected by fruit distribution. The steepest mean fruit mass to fruit load relationship was found in US trees, whereas the relationship in UH trees was intermediate between the US and EVEN trees. On a scaffold basis, differences in fruit size between EVEN and US trees with similar fruit loads, though statistically significant, were relatively small, indicating that scaffolds were almost totally autonomous with respect to dry matter partitioning to fruit during the final stage of peach fruit growth. Hangers also appeared to exhibit significant autonomy with respect to the distribution of dry matter during the final phase of fruit growth. Branch autonomy was evident in scaffold growth: defruited scaffolds in the US treatment grew more than fruited scaffolds, and fruit distribution treatments had little impact on scaffold cross-sectional area on a tree basis. On the other hand, as observed for fruit growth, branch autonomy did not appear to be complete because the fruited scaffolds grew more in US trees than in EVEN trees under heavy cropping conditions. However, the effect of

  3. Doxorubicin, vinblastine, and gemcitabine (CALGB 50203) for stage I/II nonbulky Hodgkin lymphoma: pretreatment prognostic factors and interim PET

    PubMed Central

    Johnson, Jeffrey L.; LaCasce, Ann S.; Bartlett, Nancy L.; Kostakoglu, Lale; Hsi, Eric D.; Schöder, Heiko; Hall, Nathan C.; Jung, Sin-Ho; Canellos, George P.; Schwartz, Lawrence H.; Takvorian, Ronald W.; Juweid, Malik E.; Cheson, Bruce D.

    2011-01-01

    To reduce doxorubicin, bleomycin, vinblastine and dacarbazine toxicity, the Cancer and Leukemia Group B conducted a phase 2 trial of doxorubicin, vinblastine, and gemcitabine for newly diagnosed, nonbulky stages I and II Hodgkin lymphoma. Ninety-nine assessable patients received 6 cycles of doxorubicin 25 mg/m2, vinblastine 6 mg/m2, and gemcitabine 800 mg/m2 (1000 mg/m2 in first 6) on days 1 and 15 every 28 days. Computed tomography (CT) and positron emission tomography (PET) were performed before and after 2 and 6 cycles. Complete remission (CR)/CR unconfirmed was achieved in 72 of 99 patients (72.7%) and partial remission in 24 of 99 patients (24.2%). The CR rate was 81% when using PET criteria. Two patients have died of Hodgkin lymphoma progression. Median follow-up for nonprogressing patients is 3.3 years. The progression-free survival (PFS) at 3 years was 77% (95% confidence interval, 68%-84%). The relapse rate was less than 10% for patients with favorable prognostic factors. The 2-year PFS for cycle 2 PET-negative and -positive patients was 88% and 54%, respectively (P = .0009), compared with 89% and 27% for cycle 6 PET-negative and -positive patients (P = .0001). Although the CR rate and PFS were lower than anticipated, patients with favorable prognostic features had a low rate of relapse. Cycle 2 PET and cycle 6 PET were predictive of PFS. This clinical trial is registered at www.clinicaltrials.gov as #NCT00086801. PMID:21355087

  4. Children With ADHD Show Impairments in Multiple Stages of Information Processing in a Stroop Task: An ERP Study.

    PubMed

    Kóbor, Andrea; Takács, Ádám; Bryce, Donna; Szűcs, Dénes; Honbolygó, Ferenc; Nagy, Péter; Csépe, Valéria

    2015-01-01

    This study investigated the role of impaired inhibitory control as a factor underlying attention deficit hyperactivity disorder (ADHD). Children with ADHD and typically developing children completed an animal Stroop task while electroencephalogram (EEG) was recorded. The lateralized readiness potential and event-related brain potentials associated with perceptual and conflict processing were analyzed. Children with ADHD were slower to give correct responses irrespective of congruency, and slower to prepare correct responses in the incongruent condition. This delay could result from enhanced effort allocation at earlier processing stages, indicated by differences in P1, N1, and conflict sustained potential. Results suggest multiple deficits in information processing rather than a specific response inhibition impairment. PMID:26421914

  5. Multiple stages of hydrothermal REE remobilization recorded in fluorapatite in the Paleoproterozoic Yinachang Fe-Cu-(REE) deposit, Southwest China

    NASA Astrophysics Data System (ADS)

    Li, Xiaochun; Zhou, Mei-Fu

    2015-10-01

    The Yinachang deposit in the Kangdian region, Southwest China, contains large amounts of Fe, Cu and REE, and formed at ˜1700 Ma. In this deposit, there are three stages of alteration and mineralization, including pre-ore Na-(Fe) alteration, Fe-(REE) mineralization, and Cu-(REE) mineralization. In the Fe-(REE) mineralization stage, REE-rich fluorapatite, with total REE concentrations ranging from 10,700 to 34,000 ppm, formed together with magnetite. In the following Cu-(REE) mineralization stage, large amounts of REE, especially LREE, were leached out of the REE-rich fluorapatite due to the interaction between fluorapatite and Cl-, F-, CO2-, and Ca-rich, but REE-unsaturated fluids. The leaching of REE was associated with the removal of Si, Na, Th, U, Pb, and Ba, and modification of the oxygen isotope signature in the fluorapatite. During a ˜840 Ma tectonothermal event, REE-rich fluorapatite underwent the second interaction with oxidized, F-, CO2-, and possibly Cl-rich, but Na- and Ca-deficient fluids. Due to fluid-fluorapatite interaction, REE were removed from the fluorapatite, but were immediately reincorporated into new phases within the fluorapatite. Thus, the altered fluorapatite contains abundant REE mineral inclusions, including bastnäsite-(Ce), monazite-(Ce), and minor xenotime-(Y). A very small portion of the LREE were transported out of the fluorapatite, and formed bastnäsite-(Ce) and monazite-(Ce) grains in the vicinity of the altered fluorapatite. In addition to the metasomatism of fluorapatite, allanite and "primary" synchysite-(Ce) from the Cu-(REE) mineralization stage were also altered with variable replacement of allanite by an assemblage of synchysite-(Ce) + chlorite ± bastnäsite-(Ce) and "primary" synchysite-(Ce) by bastnäsite-(Ce). These styles of alteration were possibly synchronous with the second alteration phase of the fluorapatite. This study demonstrates that REE can be mobilized during multiple stages of hydrothermal activities and

  6. Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III Non–Small-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score Matched Analysis

    SciTech Connect

    Rodrigues, George; Oberije, Cary; Senan, Suresh; Tsujino, Kayoko; Wiersma, Terry; Moreno-Jimenez, Marta; Kim, Tae Hyun; Marks, Lawrence B.; Rengan, Ramesh; De Petris, Luigi; Ramella, Sara; DeRuyck, Kim; De Dios, Núria Rodriguez; Warner, Andrew; Bradley, Jeffrey D.; Palma, David A.

    2015-01-01

    Purpose: The clinical benefits and risks of dose escalation (DE) for stage III non–small-cell lung cancer (NSCLC) remain uncertain despite the results from Radiation Therapy Oncology Group (RTOG) protocol 0617. There is significant heterogeneity of practice, with many clinicians prescribing intermediate dose levels between the 0617 study arms of 60 and 74 Gy. This study investigated whether this strategy is associated with any survival benefits/risks by analyzing a large multi-institutional database. Methods and Materials: An individual patient database of stage III NSCLC patients treated with radical intent concurrent chemoradiation therapy was created (13 institutions, n=1274 patients). Patients were divided into 2 groups based on tumor Biological Effective Dose at 10 Gy (BED 10): those receiving standard dose (SD; n=552), consisting of 72Gy ≤ BED 10 ≤ 76.8 Gy (eg 60-64 Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy < BED 10 < 100.8 Gy (eg >64 Gy/32 fr and <74 Gy/37 fr), with lower-dose patients (n=225) excluded from consideration. Patients were then matched using propensity scores, leading to 2 matched groups of 196 patients. Outcomes were compared using various statistics including interquartile range (IQR), Kaplan-Meier curves, and adjusted Cox regression analysis. Results: Matched groups were found to be balanced except for N stage (more N3 disease in SD), median treatment year (SD in 2003; ID in 2007), platinum and taxane chemotherapy (SD in 28%; ID in 39%), and median follow-up (SD were 89 months; ID were 40 months). Median dose fractionation was 60 Gy/30 fr in SD (BED 10 IQR: 72.0-75.5 Gy) and 66 Gy/33 fr (BED 10 IQR: 78.6-79.2 Gy) in ID. Survival curves for SD and ID matched cohorts were statistically similar (P=.27); however, a nonstatistically significant trend toward better survival for ID was observed after 15 months (median survival SD: 19.3 months; ID: 21.0

  7. Carboplatin and Paclitaxel With or Without Atezolizumab Before Surgery in Treating Patients With Newly Diagnosed, Stage II-III Triple-Negative Breast Cancer

    ClinicalTrials.gov

    2016-09-12

    Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  8. Doxorubicin Hydrochloride, Cisplatin, and Paclitaxel or Carboplatin and Paclitaxel in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-10-26

    Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  9. Akt Inhibitor MK-2206 and Anastrozole With or Without Goserelin Acetate in Treating Patients With Stage II-III Breast Cancer

    ClinicalTrials.gov

    2016-09-12

    Estrogen Receptor Positive; HER2/Neu Negative; Recurrent Breast Carcinoma; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  10. Prognostic significance of full-length estrogen receptor beta expression in stage I-III triple negative breast cancer

    PubMed Central

    Shanle, Erin K; Onitilo, Adedayo A; Huang, Wei; Kim, KyungMann; Zang, Chong; Engel, Jessica M; Xu, Wei; Wisinski, Kari B

    2015-01-01

    Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype for which there is a need to identify new therapeutic targets. Full-length estrogen receptor beta (ERβ1) may be a possible target given its antiproliferative effects on breast cancer cells. The prognostic significance of ERβ in breast cancer subtypes has remained elusive, and disparate results observed across previously published reports might be due to the detection of multiple ERβ isoforms, the lack of specific antibodies and the use of different cutoffs to define ERβpositivity. The objective of this retrospective study was to determine the association between ERβ1 expression and disease-free and overall survival, as well as Ki67 expression, in non-metastatic TNBC. Immunohistochemical protocols were optimized using xenograft tissues obtained from a breast cancer cell line with inducible ERβ1 expression. ERβ1 localization and expression were assessed in two cohorts of TNBC using the VECTRATM platform. There was a close relationship between nuclear and cytoplasmic ERβ1 expression. ERβ1 was expressed in a subset of TNBCs, but its expression was significantly associated with Ki67 in only one of the cohorts. There was no significant association between ERβ1 expression and disease-free and overall survival in either cohort. Although these results suggest that ERβ1 expression alone may not be informative in TNBCs, this study provides a new strategy for optimizing and objectively measuring ERβ1 expression in tissues, which may provide a standard for ERβ1 immunohistochemistry in future large-scale clinical studies aimed at better understanding the role of ERβ1 in breast cancer. PMID:26328009

  11. Extended culture up to the blastocyst stage: a strategy to avoid multiple pregnancies in assisted reproductive technologies.

    PubMed

    Sepúlveda, Soledad J; Portella, Jimmy R; Noriega, Luis P; Escudero, Ernesto L; Noriega, Luis H

    2011-01-01

    The aim of this study was to review the experience and outcomes of assisted reproduction cycles with embryos grown up to day 5 of development, comparing different parameters according to the ages of the patients. We retrospectively studied 1,874 assisted reproduction cycles where embryo culture was extended up to the fifth or sixth day of development. All IVF and ICSI cycles were included, comparing, according to patient age, the following rates: blastocyst formation, pregnancy, implantation and abortion. As control, we analyzed cycles with donated oocytes from young donors (OD). The number of embryos reaching the blastocyst stage is similar in all groups of patients. Only the OD group was different in terms of blastocyst formation, pregnancy and implantation rates. Patients over 39 years of age had an abortion rate of 59.1 %, which is significantly higher than the other groups. Extended embryo culture up to the blastocyst stage can be implemented in programs of assisted reproduction in order to increase the pregnancy rate. The potential of blastocyst implantation is high, allowing us to transfer fewer embryos and reduce the probability of multiple pregnancies.

  12. CT for Assessment of Thrombosis and Pulmonary Embolism in Multiple Stages of Single-Ventricle Palliation: Challenges and Suggested Protocols.

    PubMed

    Ghadimi Mahani, Maryam; Agarwal, Prachi P; Rigsby, Cynthia K; Lu, Jimmy C; Fazeli Dehkordy, Soudabeh; Wright, Robyn A; Dorfman, Adam L; Krishnamurthy, Rajesh

    2016-01-01

    The total cavopulmonary connection (TCPC), or Fontan procedure, diverts systemic venous blood directly into the pulmonary arteries and is the palliative surgery of choice for patients with a wide variety of congenital heart diseases with single-ventricle physiologic characteristics. Pulmonary embolism and thrombosis are known complications and are among the major causes of morbidity and mortality in patients after TCPC. Magnetic resonance (MR) imaging is usually performed for postoperative evaluation of patients after single-ventricle repair; however, screening for thrombosis or embolism with MR imaging is not always feasible because of the emergent nature of the clinical presentation or because of artifacts from metallic devices or coils. Computed tomographic (CT) angiography is an effective method for diagnosing pulmonary embolism in children. However, because of altered hemodynamics after single-ventricle palliation, there are unique challenges in achieving optimal opacification of the pulmonary arteries and Fontan circuit that can result in nondiagnostic CT angiographic studies or erroneous image interpretation. Radiologists should be familiar with the multiple stages of single-ventricle palliation, understand the technique for performing pulmonary CT angiography at each stage, and recognize common pitfalls in obtaining and interpreting pulmonary CT angiographic images in patients who have undergone single-ventricle repair. Online supplemental material is available for this article. (©)RSNA, 2016. PMID:27618316

  13. Randomised controlled trial evaluating the efficacy of wrap therapy for wound healing acceleration in patients with NPUAP stage II and III pressure ulcer

    PubMed Central

    Mizuhara, Akihiro; Oonishi, Sandai; Takeuchi, Kensuke; Suzuki, Masatsune; Akiyama, Kazuhiro; Kobayashi, Kazuyo; Matsunaga, Kayoko

    2012-01-01

    Objectives To evaluate if ‘wrap therapy’ using food wraps, which is widely used in Japanese clinical sites, is not inferior when compared to guideline adhesion treatments. Design Multicentre, prospective, randomised, open, blinded endpoint clinical trial. Setting 15 hospitals in Japan. Patients 66 older patients with new National Pressure Ulcer Advisory Panel stage II or III pressure ulcers. Interventions Of these 66 patients, 31 were divided into the conventional treatment guidelines group and 35 into the wrap therapy group. Main outcome measures The primary end point was the period until the pressure ulcers were cured. The secondary end point was a comparison of the speed of change in the Pressure Ulcer Scale for Healing score. Results 64 of the 66 patients were analysed. The estimated mean period until healing was 57.5 days (95% CI 45.2 to 69.8) in the control group as opposed to 59.8 days (95% CI 49.7 to 69.9) in the wrap therapy group. By the extent of pressure ulcer infiltration, the mean period until healing was 16.0 days (95% CI 8.1 to 23.9) in the control group as opposed to 18.8 days (95% CI 10.3 to 27.2) in the wrap therapy group with National Pressure Ulcer Advisory Panel stage II ulcers, and 71.8 days (95% CI 61.4 to 82.3) as opposed to 63.2 days (95% CI 53.0 to 73.4), respectively, with stage III ulcers. There is no statistical significance in difference in Pressure Ulcer Scale for Healing scores. Conclusions It might be possible to consider wrap therapy as an alternative choice in primary care settings as a simple and inexpensive dressing care. Clinical Trial registration UMIN Clinical Trials Registry UMIN000002658. Summary protocol is available on https://upload.umin.ac.jp/cgi-bin/ctr/ctr.cgi?function=brows&action=brows&type=detail&recptno=R000003235&admin=0&language=J PMID:22223842

  14. Is kidney function affecting the management of myocardial infarction? A retrospective cohort study in patients with normal kidney function, chronic kidney disease stage III-V, and ESRD.

    PubMed

    Saad, Marc; Karam, Boutros; Faddoul, Geovani; Douaihy, Youssef El; Yacoub, Harout; Baydoun, Hassan; Boumitri, Christine; Barakat, Iskandar; Saifan, Chadi; El-Charabaty, Elie; Sayegh, Suzanne El

    2016-01-01

    Patients with chronic kidney disease (CKD) are three times more likely to have myocardial infarction (MI) and suffer from increased morbidity and higher mortality. Traditional and unique risk factors are prevalent and constitute challenges for the standard of care. However, CKD patients have been largely excluded from clinical trials and little evidence is available to guide evidence-based treatment of coronary artery disease in patients with CKD. Our objective was to assess whether a difference exists in the management of MI (ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction) among patients with normal kidney function, CKD stage III-V, and end-stage renal disease (ESRD) patients. We conducted a retrospective cohort study on patients admitted to Staten Island University Hospital for the diagnosis of MI between January 2005 and December 2012. Patients were assigned to one of three groups according to their kidney function: Data collected on the medical management and the use of statins, platelet inhibitors, beta-blockers, and angiotensin converting enzyme inhibitors/angiotensin receptor blockers were compared among the three cohorts, as well as medical interventions including: catheterization and coronary artery bypass graft (CABG) when indicated. Chi-square test was used to compare the proportions between nominal variables. Binary logistic analysis was used in order to determine associations between treatment modalities and comorbidities, and to account for possible confounding factors. Three hundred and thirty-four patients (mean age 67.2±13.9 years) were included. In terms of management, medical treatment was not different among the three groups. However, cardiac catheterization was performed less in ESRD when compared with no CKD and CKD stage III-V (45.6% vs 74% and 93.9%) (P<0.001). CABG was performed in comparable proportions in the three groups and CABG was not associated with the degree of CKD (P=0.078) in binary

  15. Granisetron, Aprepitant, and Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Stage II, III, or IV Ovarian Cancer

    ClinicalTrials.gov

    2016-03-16

    Malignant Ovarian Mixed Epithelial Tumor; Nausea and Vomiting; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  16. Postsurgical Relapse in Class III Patients Treated With Two-Jaw Surgery: Conventional Three-Stage Method Versus Surgery-First Approach.

    PubMed

    Park, Heon-Mook; Yang, Il-Hyung; Choi, Jin-Young; Lee, Jong-Ho; Kim, Myung-Jin; Baek, Seung-Hak

    2015-11-01

    The aim of this study was to investigate the pattern, amount, and distribution of postsurgical relapse in skeletal Class III patients treated with two-jaw surgery (TJS) using conventional three-stage method (CTM) and surgery-first approach (SFA). A total of 38 patients who underwent the nonextraction approach and TJS (LeFort I posterior impaction and mandibular setback) were divided into CTM and SFA groups (all n = 19/group). Lateral cephalograms were taken before treatment (T0), at 1 month before surgery (T1), immediately after surgery (T2), and at debonding (T3) for CTM patients and at T0, T2, and T3 stages for SFA patients. Cephalometric measurements and statistical analyses were performed. There were no significant differences in the cephalometric variables at all stages except maxillary incisor inclination (U1-UOP) and overbite at T0 between 2 groups. They also did not exhibit significant differences in the amounts of surgical movement except for advancement of the maxilla. The mandible in both groups was rotated slightly clockwise by surgery and counterclockwise during T2-T3 without a significant difference. Distribution of cases with "high relapse" (>30%) and "low relapse" (<30%) of the mandible differed for 2 groups (P < 0.05). SFA group had more "high relapse" cases than CTM group (57.9% versus 26.3%). Postsurgical relapse of the mandible had a positive relationship with the amount of mandibular setback in SFA group (P < 0.01) and clockwise rotation of the proximal segment of the mandible in both groups (P < 0.05 and P < 0.01). The results suggest that SFA might be an effective alternative to CTM if the cause of "high relapse" including amounts of mandibular setback and clockwise rotation of the proximal segment of the mandible during surgery can be controlled.

  17. Pancreatic Cancer Stage 3

    MedlinePlus

    ... historical Searches are case-insensitive Pancreatic Cancer Stage 3 Add to My Pictures View /Download : Small: 720x576 ... Large: 3000x2400 View Download Title: Pancreatic Cancer Stage 3 Description: Stage III pancreatic cancer; drawing shows cancer ...

  18. Bortezomib and Filgrastim in Promoting Stem Cell Mobilization in Patients With Non-Hodgkin Lymphoma or Multiple Myeloma Undergoing Stem Cell Transplant

    ClinicalTrials.gov

    2016-04-19

    Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage I Small Lymphocytic Lymphoma; Stage II Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Untreated Hairy Cell Leukemia; Waldenström Macroglobulinemia

  19. Ruxolitinib Phosphate, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-03-21

    Fallopian Tube Carcinosarcoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Neoplasm; High Grade Ovarian Serous Adenocarcinoma; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  20. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development.

    PubMed

    Nissim, Sahar; Weeks, Olivia; Talbot, Jared C; Hedgepeth, John W; Wucherpfennig, Julia; Schatzman-Bone, Stephanie; Swinburne, Ian; Cortes, Mauricio; Alexa, Kristen; Megason, Sean; North, Trista E; Amacher, Sharon L; Goessling, Wolfram

    2016-10-01

    The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic vs. pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease.

  1. Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer

    SciTech Connect

    Burstein, Harold J. . E-mail: hburstein@partners.org; Bellon, Jennifer R.; Galper, Sharon; Lu, H.-M.; Kuter, Irene; Wong, Julia; Gelman, Rebecca; Bunnell, Craig A.; Parker, Leroy M.; Garber, Judy E.; Winer, Eric P.; Harris, Jay R.; Powell, Simon N.

    2006-02-01

    Purpose: To evaluate the safety and feasibility of concurrent radiation therapy and paclitaxel-based adjuvant chemotherapy, given either weekly or every 3 weeks, after adjuvant doxorubicin and cyclophosphamide (AC). Methods and Materials: After definitive breast surgery and AC chemotherapy, 40 patients with operable Stage II or III breast cancer received protocol-based treatment with concurrent paclitaxel and radiation therapy. Paclitaxel was evaluated on 2 schedules, with treatment given either weekly x 12 weeks (60 mg/m{sup 2}), or every 3 weeks x 4 cycles (135-175 mg/m{sup 2}). Radiation fields and schedules were determined by the patient's surgery and pathology. The tolerability of concurrent therapy was evaluated in cohorts of 8 patients as a phase I study. Results: Weekly paclitaxel treatment at 60 mg/m{sup 2} per week with concurrent radiation led to dose-limiting toxicity in 4 of 16 patients (25%), including 3 who developed pneumonitis (either Grade 2 [1 patient] or Grade 3 [2 patients]) requiring steroids. Efforts to eliminate this toxicity in combination with weekly paclitaxel through treatment scheduling and CT-based radiotherapy simulation were not successful. By contrast, dose-limiting toxicity was not encountered among patients receiving concurrent radiation with paclitaxel given every 3 weeks at 135-175 mg/m{sup 2}. However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion. Excessive radiation dermatitis was not observed with either paclitaxel schedule. Conclusions: Concurrent treatment with weekly paclitaxel and radiation therapy is not feasible after adjuvant AC chemotherapy for early-stage breast cancer. Concurrent treatment using a less frequent paclitaxel dosing schedule may be possible, but caution is warranted in light of the apparent possibility of pulmonary injury.

  2. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    SciTech Connect

    Olszewski, Adam J. Desai, Amrita

    2014-03-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas.

  3. Fibroblast Growth Factor 2-A Predictor of Outcome for Patients Irradiated for Stage II-III Non-Small-Cell Lung Cancer

    SciTech Connect

    Rades, Dirk; Setter, Cornelia; Dahl, Olav; Schild, Steven E.; Noack, Frank

    2012-01-01

    Purpose: The prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients with non-small-cell lung cancer (NSCLC) is unclear. The present study investigated the effect of tumor cell expression of FGF-2 on the outcome of 60 patients irradiated for Stage II-III NSCLC. Methods and Materials: The effect of FGF-2 expression and 13 additional factors on locoregional control (LRC), metastasis-free survival (MFS), and overall survival (OS) were retrospectively evaluated. These additional factors included age, gender, Karnofsky performance status, histologic type, histologic grade, T and N category, American Joint Committee on Cancer stage, surgery, chemotherapy, pack-years, smoking during radiotherapy, and hemoglobin during radiotherapy. Locoregional failure was identified by endoscopy or computed tomography. Univariate analyses were performed with the Kaplan-Meier method and the Wilcoxon test and multivariate analyses with the Cox proportional hazard model. Results: On univariate analysis, improved LRC was associated with surgery (p = .017), greater hemoglobin levels (p = .036), and FGF-2 negativity (p <.001). On multivariate analysis of LRC, surgery (relative risk [RR], 2.44; p = .037), and FGF-2 expression (RR, 5.06; p <.001) maintained significance. On univariate analysis, improved MFS was associated with squamous cell carcinoma (p = .020), greater hemoglobin levels (p = .007), and FGF-2 negativity (p = .001). On multivariate analysis of MFS, the hemoglobin levels (RR, 2.65; p = .019) and FGF-2 expression (RR, 3.05; p = .004) were significant. On univariate analysis, improved OS was associated with a lower N category (p = .048), greater hemoglobin levels (p <.001), and FGF-2 negativity (p <.001). On multivariate analysis of OS, greater hemoglobin levels (RR, 4.62; p = .002) and FGF-2 expression (RR, 3.25; p = .002) maintained significance. Conclusions: Tumor cell expression of FGF-2 appeared to be an independent negative predictor

  4. The Drosophila Transcription Factor Dimmed Affects Neuronal Growth and Differentiation in Multiple Ways Depending on Neuron Type and Developmental Stage

    PubMed Central

    Liu, Yiting; Luo, Jiangnan; Nässel, Dick R.

    2016-01-01

    Growth of postmitotic neurons occurs during different stages of development, including metamorphosis, and may also be part of neuronal plasticity and regeneration. Recently we showed that growth of post-mitotic neuroendocrine cells expressing the basic helix loop helix (bHLH) transcription factor Dimmed (Dimm) in Drosophila could be regulated by insulin/IGF signaling and the insulin receptor (dInR). Dimm is also known to confer a secretory phenotype to neuroendocrine cells and can be part of a combinatorial code specifying terminal differentiation in peptidergic neurons. To further understand the mechanisms of Dimm function we ectopically expressed Dimm or Dimm together with dInR in a wide range of Dimm positive and Dimm negative peptidergic neurons, sensory neurons, interneurons, motor neurons, and gut endocrine cells. We provide further evidence that dInR mediated cell growth occurs in a Dimm dependent manner and that one source of insulin-like peptide (DILP) for dInR mediated cell growth in the CNS is DILP6 from glial cells. Expressing both Dimm and dInR in Dimm negative neurons induced growth of cell bodies, whereas dInR alone did not. We also found that Dimm alone can regulate cell growth depending on specific cell type. This may be explained by the finding that the dInR is a direct target of Dimm. Conditional gene targeting experiments showed that Dimm alone could affect cell growth in certain neuron types during metamorphosis or in the adult stage. Another important finding was that ectopic Dimm inhibits apoptosis of several types of neurons normally destined for programmed cell death (PCD). Taken together our results suggest that Dimm plays multiple transcriptional roles at different developmental stages in a cell type-specific manner. In some cell types ectopic Dimm may act together with resident combinatorial code transcription factors and affect terminal differentiation, as well as act in transcriptional networks that participate in long term maintenance

  5. 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.

  6. Neoadjuvant Chemoradiotherapy vesus Chemotherapy alone Followed by Surgery for Resectable Stage III Non-Small-Cell Lung Cancer: a Meta-Analysis

    PubMed Central

    Guo, Shan xian; Jian, Yan; Chen, Ying lan; Cai, Yun; Zhang, Qing yuan; Tou, Fang fang

    2016-01-01

    Neoadjuvant Chemotherapy has been used for the stage III of non-small cell lung cancer (NSCLC) and has shown good clinical effects. However, the survival benefits of radiation therapy added in induction regimens remains controversial. We therefore conducted a meta-analysis of the published clinical trials to quantitatively evaluate the benefit of preoperative chemoradiotherapy. After searching the database of Pubmed, CNKI, EMBASE, ESMO, The Cochrane Library databases, The American Society of Clinical Oncology and Clinical Trials.gov. Trials were selected for meta-analysis if they provided an independent assessment of neoadjuvant chemoradiation and neoadjuvant chemotherapy, odds ratio(OR) for tumor downstaging, mediastinal lymph nodes pathological complete response and local control, hazard ratios (HRs) for 5-year survival and progression-free survival were pooled by the stata software version 12.0. Twelve studies involving 2,724 patients were identified, tumor downstaging (p = 0.01), mediastinal lymph nodes pathological complete responses (p = 0.028) and local control (P = 0.002) were achieved, when compared with neoadjuvant chemotherapy. The meta-analysis demonstrated neither 5-year survival nor progression-free-survival benefit in survival from adding radiation. In conclusion, the addition of radiotherapy into chemotherapy was not superior to neoadjuvant chemotherapy. The higher quality of trials need be investigated combining with the histopathological type and genotyping of lung cancer by clinicians. PMID:27677242

  7. Gefitinib in Combination With Irradiation With or Without Cisplatin in Patients With Inoperable Stage III Non-Small Cell Lung Cancer: A Phase I Trial

    SciTech Connect

    Rothschild, Sacha; Bucher, Stephan E.; Bernier, Jacques; Aebersold, Daniel M.; Zouhair, Aberrahim; Ries, Gerhard; Lombrieser, Norbert; Lippuner, Thomas; Luetolf, Urs M.; Glanzmann, Christoph; Ciernik, I. Frank

    2011-05-01

    Purpose: To establish the feasibility and tolerability of gefitinib (ZD1839, Iressa) with radiation (RT) or concurrent chemoradiation (CRT) with cisplatin (CDDP) in patients with advanced non-small cell lung cancer (NSCLC). Patients and Methods: In this multicenter Phase I study, 5 patients with unresectable NSCLC received 250 mg gefitinib daily starting 1 week before RT at a dose of 63 Gy (Step 1). After a first safety analysis, 9 patients were treated daily with 250 mg gefitinib plus CRT in the form of RT and weekly CDDP 35 mg/m{sup 2} (Step 2). Gefitinib was maintained for up to 2 years until disease progression or toxicity. Results: Fourteen patients were assessed in the two steps. In Step 1 (five patients were administered only gefitinib and RT), no lung toxicities were seen, and there was no dose-limiting toxicity (DLT). Adverse events were skin and subcutaneous tissue reactions, limited to Grade 1-2. In Step 2, two of nine patients (22.2%) had DLT. One patient suffered from dyspnea and dehydration associated with neutropenic pneumonia, and another showed elevated liver enzymes. In both steps combined, 5 of 14 patients (35.7%) experienced one or more treatment interruptions. Conclusions: Gefitinib (250 mg daily) in combination with RT and CDDP in patients with Stage III NSCLC is feasible, but CDDP likely enhances toxicity. The impact of gefitinib on survival and disease control as a first-line treatment in combination with RT remains to be determined.

  8. Expression of Ribonucleotide Reductase Subunit-2 and Thymidylate Synthase Correlates with Poor Prognosis in Patients with Resected Stages I–III Non-Small Cell Lung Cancer

    PubMed Central

    Grossi, Francesco; Dal Bello, Maria Giovanna; Salvi, Sandra; Puzone, Roberto; Pfeffer, Ulrich; Fontana, Vincenzo; Alama, Angela; Rijavec, Erika; Barletta, Giulia; Genova, Carlo; Sini, Claudio; Ratto, Giovanni Battista; Taviani, Mario; Truini, Mauro; Merlo, Domenico Franco

    2015-01-01

    Biomarkers can help to identify patients with early-stages or locally advanced non-small cell lung cancer (NSCLC) who have high risk of relapse and poor prognosis. To correlate the expression of seven biomarkers involved in DNA synthesis and repair and in cell division with clinical outcome, we consecutively collected 82 tumour tissues from radically resected NSCLC patients. The following biomarkers were investigated using IHC and qRT-PCR: excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2), subunit p53R2, thymidylate synthase (TS), and class III beta-tubulin (TUBB3). Gene expression levels were also validated in an available NSCLC microarray dataset. Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS). Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours. For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. The NSCLC microarray dataset showed RRM2 and TS as biomarkers significantly associated with OS. This study suggests that high expression levels of RRM2 and TS might be negative prognostic factors for resected NSCLC patients. PMID:26663950

  9. A single-institution retrospective analysis of outcomes for stage I-II primary mediastinal large B-cell lymphoma treated with immunochemotherapy with or without radiotherapy.

    PubMed

    Binkley, Michael S; Hiniker, Susan M; Wu, Sharon; Natkunam, Yasodha; Mittra, Erik S; Advani, Ranjana H; Hoppe, Richard T

    2016-01-01

    As the optimal treatment for primary mediastinal large B-cell lymphoma (PMBCL) remains undefined, we evaluated outcomes of patients treated with standard and dose-intense rituximab-chemotherapy (R-CT) with and without radiotherapy (RT). We retrospectively identified 28 patients with stage I-II PMBCL in our lymphoma database, re-reviewed pathology slides and scored interim or post-chemotherapy PET/CTs using the Deauville scale. Fourteen patients received RT (36-45 Gy) preceded by either six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or 12 weeks of rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin (R-VACOP-B) with median follow-up of 94 months. Fourteen patients received 4-8 cycles of dose-adjusted etoposide, vincristine, doxorubicin, cyclophosphamide and rituximab (DA-EPOCH-R) with median follow-up of 38 months; one of these received RT (36 Gy) due to post-chemotherapy PET/CT Deauville score 4. Following R-CT and RT or DA-EPOCH-R, 5-year and 3-year FFP and OS were both 100%. Both R-CHOP/R-VACOP-B with RT and DA-EPOCH-R demonstrate excellent outcomes. PMID:26159046

  10. In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

    PubMed Central

    Neves, Bruno J.; Braga, Rodolpho C.; Bezerra, José C. B.; Cravo, Pedro V. L.; Andrade, Carolina H.

    2015-01-01

    Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes. PMID:25569258

  11. In silico repositioning-chemogenomics strategy identifies new drugs with potential activity against multiple life stages of Schistosoma mansoni.

    PubMed

    Neves, Bruno J; Braga, Rodolpho C; Bezerra, José C B; Cravo, Pedro V L; Andrade, Carolina H

    2015-01-01

    Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes.

  12. A phase III randomized trial of postoperative pelvic irradiation in stage IB cervical carcinoma with poor prognostic features: Follow-up of a gynecologic oncology group study

    SciTech Connect

    Rotman, Marvin . E-mail: mrotman@downstate.edu; Sedlis, Alexander; Piedmonte, Marion R.; Bundy, Brian; Lentz, Samuel S.; Muderspach, Laila I.; Zaino, Richard J.

    2006-05-01

    Purpose: To investigate, in a phase III randomized trial, whether postoperative external-beam irradiation to the standard pelvic field improves the recurrence-free interval and overall survival (OS) in women with Stage IB cervical cancers with negative lymph nodes and certain poor prognostic features treated by radical hysterectomy and pelvic lymphadenectomy. Methods and Materials: Eligible patients had Stage IB cervical cancer with negative lymph nodes but with 2 or more of the following features: more than one third (deep) stromal invasion, capillary lymphatic space involvement, and tumor diameter of 4 cm or more. The study group included 277 patients: 137 randomized to pelvic irradiation (RT) and 140 randomized to observation (OBS). The planned pelvic dose was from 46 Gy in 23 fractions to 50.4 Gy in 28 fractions. Results: Of the 67 recurrences, 24 were in the RT arm and 43 were in the OBS arm. The RT arm showed a statistically significant (46%) reduction in risk of recurrence (hazard ratio [HR] = 0.54, 90% confidence interval [CI] = 0.35 to 0.81, p = 0.007) and a statistically significant reduction in risk of progression or death (HR = 0.58, 90% CI = 0.40 to 0.85, p = 0.009). With RT, 8.8% of patients (3 of 34) with adenosquamous or adenocarcinoma tumors recurred vs. 44.0% (11 of 25) in OBS. Fewer recurrences were seen with RT in patients with adenocarcinoma or adenosquamous histologies relative to others (HR for RT by histology interaction = 0.23, 90% CI = 0.07 to 0.74, p = 0.019). After an extensive follow-up period, 67 deaths have occurred: 27 RT patients and 40 OBS patients. The improvement in overall survival (HR = 0.70, 90% CI = 0.45 to 1.05, p = 0.074) with RT did not reach statistical significance. Conclusions: Pelvic radiotherapy after radical surgery significantly reduces the risk of recurrence and prolongs progression-free survival in women with Stage IB cervical cancer. RT appears to be particularly beneficial for patients with adenocarcinoma or

  13. Conservative surgery and radiotherapy for stage I/II breast cancer using lung density correction: 10-year and 15-year results

    SciTech Connect

    Pierce, Lori J. . E-mail: ljpierce@umich.edu; Griffith, Kent A.; Hayman, James A.; Douglas, Kathye R.; Lichter, Allen S.

    2005-04-01

    Purpose: Radiotherapy (RT) planning for breast cancer using lung density correction improves dose homogeneity. Its use obviates the need for a medial wedge, thus reducing scatter to the opposite breast. Although lung density correction is used at many centers in planning for early-stage breast cancer, long-term results of local control and survival have not been reported. Since 1984, we have used lung density correction for dose calculations at the University of Michigan. We now present our 10-year and 15-year results. Methods and Materials: The records of 867 patients with Stage I/II breast cancer treated with breast-conserving surgery and RT with or without systemic therapy were reviewed. Tangential fields delivering 45-50 Gy to the whole breast calculated using lung density correction were used. A boost was added in 96.8% of patients for a total median dose of 61.8 Gy. Results: With a median follow-up of 6.6 years (range, 0.2-18.9 years), 5-, 10-, and 15-year actuarial rates of in-breast tumor recurrence as only first failure were 2.2%, 3.6%, and 5.4%, respectively. With surgical salvage, the 15-year cumulative rate of local control was 99.7%. Factors that significantly predicted for increased rate of local recurrence in multivariate analysis were age {<=} 35 years, hazard ratio 4.8 (95% confidence interval [CI], 1.6-13.9) p = 0.004; negative progesterone receptor status, hazard ratio 6.8 (95% CI, 2.3-20.3) p = < 0.001; negative estrogen receptor status, hazard ratio 4.0 (95% CI, 1.5-11.1) p = 0.007; and lack of adjuvant tamoxifen therapy, hazard ratio 7.7 (95% CI, 1.7-33.3) p = 0.008. Relapse-free survival rates at 5, 10, and 15 years were 84.6%, 70.8%, and 55.9%, respectively; breast cancer-specific survival rates were 94.4%, 90.5%, and 86.9%, respectively; and corresponding estimates for overall survival were 89.7%, 75.7%, and 61.3%. Conclusions: Use of lung density correction was associated with high rates of local control, relapse-free survival, breast

  14. Pegylated Liposomal Doxorubicin Hydrochloride and Carboplatin Followed by Surgery and Paclitaxel in Treating Patients With Triple Negative Stage II-III Breast Cancer

    ClinicalTrials.gov

    2016-10-12

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  15. Paclitaxel and Cyclophosphamide With or Without Trastuzumab Before Surgery in Treating Patients With Previously Untreated Stage I-III Breast Cancer

    ClinicalTrials.gov

    2012-12-12

    Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  16. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development.

    PubMed

    Nissim, Sahar; Weeks, Olivia; Talbot, Jared C; Hedgepeth, John W; Wucherpfennig, Julia; Schatzman-Bone, Stephanie; Swinburne, Ian; Cortes, Mauricio; Alexa, Kristen; Megason, Sean; North, Trista E; Amacher, Sharon L; Goessling, Wolfram

    2016-10-01

    The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic vs. pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease. PMID:27474396

  17. YKL-40 in Serum Samples From Patients With Newly Diagnosed Stage III-IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer Receiving Chemotherapy

    ClinicalTrials.gov

    2016-02-19

    Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Mixed Epithelial Tumor; Malignant Ovarian Mucinous Tumor; Malignant Ovarian Neoplasm; Malignant Ovarian Serous Tumor; Malignant Ovarian Transitional Cell Tumor; Ovarian Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  18. Exome capture sequencing of adenoma reveals genetic alterations in multiple cellular pathways at the early stage of colorectal tumorigenesis.

    PubMed

    Zhou, Donger; Yang, Liu; Zheng, Liangtao; Ge, Weiting; Li, Dan; Zhang, Yong; Hu, Xueda; Gao, Zhibo; Xu, Jinghong; Huang, Yanqin; Hu, Hanguang; Zhang, Hang; Zhang, Hao; Liu, Mingming; Yang, Huanming; Zheng, Lei; Zheng, Shu

    2013-01-01

    Most of colorectal adenocarcinomas are believed to arise from adenomas, which are premalignant lesions. Sequencing the whole exome of the adenoma will help identifying molecular biomarkers that can predict the occurrence of adenocarcinoma more precisely and help understanding the molecular pathways underlying the initial stage of colorectal tumorigenesis. We performed the exome capture sequencing of the normal mucosa, adenoma and adenocarcinoma tissues from the same patient and sequenced the identified mutations in additional 73 adenomas and 288 adenocarcinomas. Somatic single nucleotide variations (SNVs) were identified in both the adenoma and adenocarcinoma by comparing with the normal control from the same patient. We identified 12 nonsynonymous somatic SNVs in the adenoma and 42 nonsynonymous somatic SNVs in the adenocarcinoma. Most of these mutations including OR6X1, SLC15A3, KRTHB4, RBFOX1, LAMA3, CDH20, BIRC6, NMBR, GLCCI1, EFR3A, and FTHL17 were newly reported in colorectal adenomas. Functional annotation of these mutated genes showed that multiple cellular pathways including Wnt, cell adhesion and ubiquitin mediated proteolysis pathways were altered genetically in the adenoma and that the genetic alterations in the same pathways persist in the adenocarcinoma. CDH20 and LAMA3 were mutated in the adenoma while NRXN3 and COL4A6 were mutated in the adenocarcinoma from the same patient, suggesting for the first time that genetic alterations in the cell adhesion pathway occur as early as in the adenoma. Thus, the comparison of genomic mutations between adenoma and adenocarcinoma provides us a new insight into the molecular events governing the early step of colorectal tumorigenesis. PMID:23301059

  19. Spatial patterns of density at multiple life stages in protected and fished conditions: An example from a Mediterranean coastal fish

    NASA Astrophysics Data System (ADS)

    Di Franco, A.; Di Lorenzo, M.; Guidetti, P.

    2013-02-01

    Settlement and recruitment are well known to have critical influences on the demography of most marine fishes. Few studies have compared processes like larval supply, settlement and recruitment of fishes between protected (i.e. in marine protected areas, MPAs) and unprotected conditions and little information is available about the potential influence of early life history traits (e.g. pelagic larval duration, PLD) on these processes. In the present study, using the white sea bream Diplodus sargus sargus as a model species in the south-western Adriatic Sea, we investigated: 1) potential differences in the densities of adults, settlers, recruits and 1-YOs (one year old specimens) within an MPA and in unprotected areas, at multiple spatial scales; 2) the existence of local relationships between densities of adults (i.e. spawners), settlers, recruits and 1-YOs; and 3) the possible relationships between PLD and density of settlers. Both in 2009 and 2010 the density of settlers was higher at sites down-current to the MPA and showed a significant variability at the scale of sites (kms). Density of recruits only revealed variability among sites (both in 2009 and 2010), while density of 1-YOs was variable at the scale of sites and was higher in protected condition in 2011, but not in 2010. No significant relationships were found between the densities of adults, settlers, recruits and 1-YOs at the site scale, nor between PLD and the density of settlers. Results suggest a possible decoupling in space between the sequential life history stages of fish (from settlers to 1-YOs) due to dispersal (through sea currents or active fish movements). Further study may help better understand the actual contribution of MPAs to larval supply and recruitment in both MPAs and adjacent sites.

  20. Structure analysis of triterpene saponins in Polygala tenuifolia by electrospray ionization ion trap multiple-stage mass spectrometry.

    PubMed

    Liu, Jiangyun; Yang, Xuedong; He, Jiuming; Xia, Min; Xu, Lizhen; Yang, Shilin

    2007-07-01

    Eighteen different triterpene saponins isolated from Polygala tenuifolia were investigated by electrospray ionization ion trap multiple-stage mass spectrometry (ESI-ITMS(n)) in positive and negative ion modes. MS(1)-MS(3)/MS(4) spectra of the both modes were analyzed, and they all gave fragments in line and shared common fragmentation patterns. Key fragments from MS(n) spectra of both the modes and their proposed fragmentation pathways were constructed with examples illustrated for the formation of characteristic fragments in the saponins. Two special fragmentation patterns were proposed: (1) the formation of fragments by cleavage of CH(2)O from Delta(12)-14alpha-CH(2)OH of the oleanene-type saponin aglycone in both positive and negative MS(n) (n > or = 2) modes; (2) the occurrence of fragments by cleavage of CO(2) and 3-glucose as the characteristic structure feature of 23-COOH at the oleanene-type saponin aglycones coupled with 3-Glc substitutes in the negative MS(n) (n > or = 2) modes. Peak intensities in MS(n) spectra were also correlated with structural features and fragmentation preferences of the investigated saponins, which are discussed in detail. In general, fragments formed predominantly by cleavages of glycosidic bonds in the positive mode, while selective cleavages of acyl bonds preceded that of glycosidic bonds in negative MS(n) (n > or = 2) mode, both of which could well be applied to the structural analysis of these saponins. Interpretation of MS(n) spectra presented here provided diagnostic key fragment ions important for the structural elucidation of saponins in P.tenuifolia.

  1. Phase 2 Study of Docetaxel, Cisplatin, and Concurrent Radiation for Technically Resectable Stage III-IV Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Inohara, Hidenori; Takenaka, Yukinori; Yoshii, Tadashi; Nakahara, Susumu; Yamamoto, Yoshifumi; Tomiyama, Yoichiro; Seo, Yuji; Isohashi, Fumiaki; Suzuki, Osamu; Yoshioka, Yasuo; Sumida, Iori; Ogawa, Kazuhiko

    2015-04-01

    Purpose: We investigated the efficacy and safety of weekly low-dose docetaxel and cisplatin therapy concurrent with conventionally fractionated radiation in patients with technically resectable stage III-IV squamous cell carcinoma of the head and neck. Methods and Materials: Between March 2004 and October 2011, we enrolled 117 patients, of whom 116 were analyzable (43 had oropharyngeal cancer, 54 had hypopharyngeal cancer, and 19 had laryngeal cancer), and 85 (73%) had stage IV disease. Radiation consisted of 66 Gy in 33 fractions. Docetaxel, 10 mg/m{sup 2}, followed by cisplatin, 20 mg/m{sup 2}, administered on the same day were given once a week for 6 cycles. The primary endpoint was overall complete response (CR) rate after chemoradiation therapy. Human papillomavirus (HPV) DNA in oropharyngeal cancer was examined by PCR. Results: Of 116 patients, 82 (71%) completed treatment per protocol; 102 (88%) received the full radiation therapy dose; and 90 (78%) and 12 (10%) patients received 6 and 5 chemotherapy cycles, respectively. Overall CR rate was 71%. After median follow-up of 50.9 months (range: 15.6-113.9 months for surviving patients), 2-year and 4-year overall survival rates were 82% and 68%, respectively. Cumulative 2-year and 4-year local failure rates were 27% and 28%, respectively, whereas distant metastasis rates were 15% and 22%, respectively. HPV status in oropharyngeal cancer was not associated with treatment efficacy. Acute toxicity included grade 3 and 4 in-field mucositis in 73% and 5% of patients, respectively, whereas myelosuppression and renal injury were minimal. No patients died of toxicity. Feeding tube dependence in 8% and tracheostomy in 1% of patients were evident at 2 years postchemoradiation therapy in patients who survived without local treatment failure. Conclusions: Local control and survival with this regimen were satisfactory. Although acute toxicity, such as mucositis, was common, late toxicity, such as laryngoesophageal

  2. [A case of multiple liver metastases from colon cancer treated with complete resection via two-stage hepatectomy after regeneration of the liver].

    PubMed

    Sugishita, Toshiya; Ganno, Hideaki; Hataji, Kenichiro; Ami, Katunori; Nagahama, Takeo; Fukuda, Akira; Ando, Masayuki; Arai, Kuniyoshi

    2015-01-01

    A 55-year-old woman underwent low anterior resection for sigmoid colon cancer with multiple bilobar metastases. She then received 23 courses of Leucovorin, fluorouracil, and oxaliplatin (mFOLFOX) plus bevacizumab and 13 courses of Leucovorin, fluorouracil, and irinotecan (FOLFIRI) plus bevacizumab as down staging chemotherapy. A two-stage hepatectomy was planned to avoid the risk of hepatic failure due to radial resection of bilobar metastases. Therefore, a right lobectomy was performed, and curative resection was achieved 54 days after the first hepatectomy. Two-stage hepatectomy as well as a combination of induction chemotherapy and portal vein embolization may have contributed to the improved prognosis of the initially unresectable multiple bilobar liver metastases.

  3. Associations between serum CA724 and HER2 overexpression among stage II–III resectable gastric cancer patients: an observational study

    PubMed Central

    Chen, Xin-Zu; Liu, Jian-Ping; He, Du; Liu, Yang; Liu, Kai; Chen, Xiao-Long; Mo, Xian-Ming; Zhou, Zong-Guang; Hu, Jian-Kun

    2016-01-01

    Objectives Associations between serum tumor biomarkers and human epidermal growth factor receptor 2 (HER2) overexpression among locally advanced gastric cancer patients were yet to be determined and therefore warranted investigation. Results A total of 318 patients were analyzed. The odds ratios of CA724 were 4.79 (95% CI 1.55–14.79) and 6.29 (1.40–28.19) in comparing the HER2 (2+/3+) and HER2 (3+) with the negative group, respectively (p < 0.05). A combination of the four biomarkers yielded slightly but not significantly greater areas under the curve (AUC = 0.83; 0.71–0.94) than that of serum CA724 alone (0.80; 0.68–0.91); however, an index generated from the combination had better diagnostic performance with 85.7% sensitivity, 80.4% specificity and 97.8% negative predictive value to predict the strong overexpression of HER2 (3+). CA199, CEA or CA125 alone was not associated with HER2 overexpression. Leave-one-out cross-validation found a consistent association between serum CA724 and HER2 (2+/3+) overexpression. Methods Patients undergoing radical gastrectomy from 8/2012 to 12/2013 and with pathological stage II–III gastric cancer were retrospectively analyzed. HER2 expression of the surgical samples was estimated using immunohistochemistry; serum CA724, CA199, CEA and CA125 were preoperatively tested. Internal validation was performed using the leave-one-out approach. Conclusions Serum CA724 is significantly associated with the overexpression of HER2 among locally advanced gastric cancer patients. The combination of CA724, CA199, CEA and CA125 is better than serum CA724 alone in predicting HER2 overexpression. External validation and further investigation of the biological mechanisms of these associations are required. PMID:27027339

  4. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    SciTech Connect

    Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; Ende, Piet van den; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.

    2012-02-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  5. Expression of Folate Pathway Genes in Stage III Colorectal Cancer Correlates with Recurrence Status Following Adjuvant Bolus 5-FU-Based Chemotherapy.

    PubMed

    Odin, Elisabeth; Sondén, Arvid; Gustavsson, Bengt; Carlsson, Göran; Wettergren, Yvonne

    2015-01-01

    Colorectal cancer is commonly treated with 5-fluorouracil and 5-formyltetrahydrofolate (leucovorin). Metabolic action of leucovorin requires several enzymatic steps that are dependent on expression of corresponding coding genes. To identify folate pathway genes with possible impact on leucovorin metabolism, a retrospective study was performed on 193 patients with stage III colorectal cancer. Relative expression of 22 genes putatively involved in leucovorin transport, polyglutamation and metabolism was determined in tumor and mucosa samples using quantitative real-time polymerase chain reaction. After surgery, patients received adjuvant 5-fluorouracil-based bolus chemotherapy with leucovorin during six months, and were followed for 3 to 5 years. Cox regression analysis showed that high tumoral expression of the genes SLC46A1/PCFT (proton-coupled folate transporter) and SLC19A1/RFC-1 (reduced folate carrier 1) correlated significantly (p < 0.001 and p < 0.01, respectively) with a decreased risk of recurrent disease, measured as disease-free survival (DFS). These two genes are involved in the transport of folates into the cells and each functions optimally at a different pH. We conclude that SLC46A1/PCFT and SLC19A1/RFC-1 are associated with DFS of patients with colorectal cancer and hypothesize that poor response to 5-fluorouracil plus leucovorin therapy in some patients may be linked to low expression of these genes. Such patients might need a more intensified therapeutic approach than those with high gene expression. Future prospective studies will determine if the expression of any of these genes can be used to predict response to leucovorin. PMID:26193446

  6. Phase I Study of Oxaliplatin in Combination With Capecitabine and Radiotherapy as Postoperative Treatment for Stage II and III Rectal Cancer

    SciTech Connect

    Jin Jing

    2008-11-01

    Purpose: A Phase I study was conducted to determine the maximal tolerated dose and the dose-limiting toxicity (DLT) of oxaliplatin (OXA) combined with capecitabine and radiotherapy as adjuvant treatment in patients with operable rectal cancer. Patients and Methods: A total of 21 patients with Stage II or III rectal adenocarcinoma after curative surgery were treated with radiotherapy to a total dose of 50 Gy in 5 weeks. OXA was administered at a dosage of 40 (n = 6), 50 (n = 3),60 (n = 3), 70 (n = 3), or 80 mg/m{sup 2} (n = 6) once a week for 2 weeks (first cycle) followed by a second cycle after a 7-day break. Capecitabine at a fixed dose of 1,300 mg/m{sup 2}/d was administered orally at the same schedule as for OXA. DLT was defined as Grade 3 or 4 hematologic and nonhematologic toxicity. Results: Grade 1-3 leukopenia, diarrhea, and nausea/vomiting were the most common toxic side effects, and most were Grade 1-2. A DLT was first observed in 1 of 3 patients at 40 mg/m{sup 2} (Grade 3 diarrhea) but was not observed in the next 3 patients at the same level or in patients who received a dose level of 50-70 mg/m{sup 2}. At 80 mg/m{sup 2}, DLT occurred in 3 of 6 patients (1 Grade 4 leukopenia and 2 Grade 3 diarrhea). Conclusions: OXA combined with a fixed dose of capecitabine at 625 mg/m{sup 2} twice daily by mouth plus radiotherapy in the adjuvant setting was tolerable and clinically feasible. The maximal tolerated dose of OXA in this setting was 80 mg/m{sup 2}, comparable to the maximal tolerated dose of OXA in the neoadjuvant setting.

  7. 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 necrosis factor receptor superfamily that is expressed in digestive system neoplasms. The expression of DcR3 is regulated by the mitogen-activated protein kinase (MAPK)/MAPK kinase/extracellular signal-regulated kinase (ERK) signaling pathway. Reverse transcription-polymerase chain reaction was performed to detect the expression of TIPE, ERK and DcR3 in the pathological and tumor-adjacent normal gastric tissues of 30 patients that demonstrated stage III gastric adenocarcinoma. The expression and distribution of the TIPE protein was examined using immunohistochemistry, and the clinical significance and expression levels of DcR3 and ERK1/2 were evaluated. The expression of TIPE, ERK1/2 and DcR3 in the tumor tissues of GC was significantly increased compared with paracarcinoma tissues (P<0.05). In addition, TIPE expression positively correlated with DcR3 and ERK1 levels (r=0.538 and r=0.462, respectively; P<0.05). There was no statistical difference between tumor tissues from patients with varying age, gender, differentiation or lymph node metastasis (P>0.05). TIPE may be vital in the progression of GC. TIPE may be associated with the expression of DcR3 and ERK1/2, which may be involved in the cell apoptosis of GC. The present study elucidates the potential function of TIPE as a novel marker and therapeutic target for GC. PMID:26998086

  8. Feasibility of radiotherapy after high-dose dense chemotherapy with epirubicin, preceded by dexrazoxane, and paclitaxel for patients with high-risk Stage II-III breast cancer

    SciTech Connect

    De Giorgi, Ugo . E-mail: ugo_degiorgi@yahoo.com; Giannini, Massimo; Frassineti, Luca; Kopf, Barbara; Palazzi, Silvia; Giovannini, Noemi; Zumaglini, Federica; Rosti, Giovanni; Emiliani, Ermanno; Marangolo, Maurizio

    2006-07-15

    Purpose: To verify the feasibility of, and quantify the risk of, pneumonitis from locoregional radiotherapy (RT) after high-dose dense chemotherapy with epirubicin and paclitaxel with peripheral blood progenitor cell support in patients with high-risk Stage II-III breast cancer. Methods and Materials: Treatment consisted of a mobilizing course of epirubicin 150 mg/m{sup 2}, preceded by dexrazoxane (Day 1), paclitaxel 175 mg/m{sup 2} (Day 2), and filgrastim; followed by three courses of epirubicin 150 mg/m{sup 2}, preceded by dexrazoxane (Day 1), paclitaxel 400 mg/m{sup 2} (Day 2), and peripheral blood progenitor cell support and filgrastim, every 16-19 days. After chemotherapy, patients were treated with locoregional RT, which included the whole breast or the chest wall, axilla, and supraclavicular area. Results: Overall, 64 of 69 patients were evaluable. The interval between the end of chemotherapy and the initiation of RT was at least 1.5-2 months (mean 2). No treatment-related death was reported. After a median follow-up of 27 months from RT (range 5-77 months), neither clinically relevant radiation pneumonitis nor congestive heart failure had been reported. Minor and transitory lung and cardiac toxicities were observed. Conclusion: Sequential high doses of epirubicin, preceded by dexrazoxane, and paclitaxel did not adversely affect the tolerability of locoregional RT in breast cancer patients. The risk of pneumonitis was not affected by the use of sequential paclitaxel with an interval of at least 1.5-2 months between the end of chemotherapy and the initiation of RT. Long-term follow-up is needed to define the risk of cardiotoxicity in these patients.

  9. Oral nutritional supplements containing (n-3) polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment.

    PubMed

    van der Meij, Barbara S; Langius, Jacqueline A E; Smit, Egbert F; Spreeuwenberg, Marieke D; von Blomberg, B Mary E; Heijboer, Annemieke C; Paul, Marinus A; van Leeuwen, Paul A M

    2010-10-01

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), (n-3) fatty acids from fish oil, have immune-modulating effects and may improve nutritional status in cancer. The objective of this study was to investigate the effects of an oral nutritional supplement containing (n-3) fatty acids on nutritional status and inflammatory markers in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. In a double-blind experiment, 40 patients with stage III NSCLC were randomly assigned to receive 2 cans/d of a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids (2.0 g EPA + 0.9 g DHA/d) or an isocaloric control supplement. EPA in plasma phospholipids, energy intake, resting energy expenditure (REE), body weight, fat free mass (FFM), mid-upper arm circumference (MUAC), and inflammatory markers were assessed. Effects of intervention were analyzed by generalized estimating equations and expressed as regression coefficients (B). The intervention group (I) had a better weight maintenance than the control (C) group after 2 and 4 wk (B = 1.3 and 1.7 kg, respectively; P < 0.05), a better FFM maintenance after 3 and 5 wk (B = 1.5 and 1.9 kg, respectively; P < 0.05), a reduced REE (B = -16.7% of predicted; P = 0.01) after 3 wk, and a trend for a greater MUAC (B = 9.1; P = 0.06) and lower interleukin-6 production (B = -27.9; P = 0.08) after 5 wk. After 4 wk, the I group had a higher energy and protein intake than the C group (B = 2456 kJ/24 h, P = 0.03 and B = 25.0 g, P = 0.01, respectively). In conclusion, a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids beneficially affects nutritional status during multimodality treatment in patients with NSCLC.

  10. Survival Outcomes and Patterns of Recurrence in Patients with Stage III or IV Oropharyngeal Cancer Treated with Primary Surgery or Radiotherapy

    PubMed Central

    Banerjee, Robyn; Warkentin, Heather; Ghosh, Sunita; Scrimger, Rufus; Jha, Naresh; Parliament, Matthew

    2016-01-01

    Purpose To compare and contrast the patterns of failure in patients with locally advanced squamous cell oropharyngeal cancers undergoing curative-intent treatment with primary surgery or radiotherapy +/- chemotherapy. Methods and materials Two hundred and thirty-three patients with stage III or IV oropharyngeal squamous cell carcinoma who underwent curative-intent treatment from 2006-2012, were reviewed. The median length of follow-up for patients still alive at the time of analysis was 4.4 years. Data was collected retrospectively from a chart review. Results One hundred and thirty-nine patients underwent primary surgery +/- adjuvant therapy, and 94 patients underwent primary radiotherapy +/- chemotherapy (CRT). Demographics were similar between the two groups, except primary radiotherapy patients had a higher age-adjusted Charleston co-morbidity score (CCI). Twenty-nine patients from the surgery group recurred; 15 failed distantly only, seven failed locoregionally, and seven failed both distantly and locoregionally. Twelve patients recurred who underwent chemoradiotherapy; ten distantly alone, and two locoregionally. One patient who underwent radiotherapy (RT) alone failed distantly. Two and five-year recurrence-free survival rates for patients undergoing primary RT were 86.6% and 84.9% respectively. Two and five-year recurrence-free survival rates for primary surgery was 80.9% and 76.3% respectively (p=0.21). There was no significant difference in either treatment when they were stratified by p16 status or smoking status. Conclusions Our analysis does not show any difference in outcomes for patients treated with primary surgery or radiotherapy. Although the primary pattern of failure in both groups was distant metastatic disease, some local failures may be preventable with careful delineation of target volumes, especially near the base of skull region. PMID:27610285

  11. Does immunohistochemistry affect response to therapy and survival of inoperable non-small cell lung carcinoma patients? A survey of 145 stage III-IV consecutive cases.

    PubMed

    Pelosi, Giuseppe; Haspinger, Eva Regina; Bimbatti, Manuela; Leone, Giorgia; Paolini, Biagio; Fabbri, Alessandra; Tamborini, Elena; Perrone, Federica; Testi, Adele; Garassino, Marina; Maisonneuve, Patrick; de Braud, Filippo; Pilotti, Silvana; Pastorino, Ugo

    2014-04-01

    Whether non-small cell lung carcinoma (NSCLC) unveiled by immunohistochemistry (IHC) has the same clinical outcome as those typed by morphology is still matter of debate. A total of 145 stage III-IV, consecutive inoperable NSCLC patients treated by chemotherapy (133 cases) or EGFR tyrosine kinase inhibitor (12 cases) and including 100 biopsies, 11 surgical specimens, and 34 cytological samples had originally accounted for 120 adenocarcinomas (ADs), 19 squamous cell carcinomas (SQCs), and 6 adenosquamous carcinomas (ADSQCs) by integrating morphology and thyroid transcription factor-1 (TTF1)/p40 IHC. Thirty-two NSCLC-not otherwise specified (NSCLC-NOS) cases were identified by morphology revision of the original diagnoses, which showed solid growth pattern (P < .001), 22 ADs, 5 SQCs, and 5 ADSQCs by IHC profiling (P < .001), and 10 gene-altered tumors (3 EGFR, 5 KRAS, and 2 ALK). While no significant relationships were observed between response to therapy and original, morphology or IHC diagnoses, driver mutations and tumor differentiation by TTF1 expression, AD run better progression-free survival (PFS) or overall survival (OS) than other tumor types by morphology (P = .010 and P = .047) and IHC (P = .033 and P = .046), respectively. Furthermore, patients with NSCLC-NOS confirmed as AD by IHC tended to have poorer OS (P = .179) and PFS (P = .193) similar to that of ADSQC and SQC (P = .702 and P = .540, respectively). A category of less differentiated AD with poorer prognosis on therapy could be identified by IHC, while there were no differences for SQC or ADSQC. The terminology of "NSCLC-NOS, favor by IHC" is appropriate to alert clinicians toward more aggressive tumors. PMID:24326823

  12. Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study

    PubMed Central

    Haslett, Kate; Franks, Kevin; Harden, Susan; Hatton, Matthew; McDonald, Fiona; Ashcroft, Linda; Falk, Sally; Groom, Nicki; Harris, Catherine; McCloskey, Paula; Whitehurst, Philip; Bayman, Neil

    2016-01-01

    Introduction The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of ‘isotoxic’ radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable. Methods and analysis Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years. Ethics and dissemination The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West—Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally. Trial registration number NCT01836692; Pre-results. PMID:27084277

  13. Impact of KRAS mutation on response and outcome of patients with stage III non-squamous non-small cell lung cancer

    PubMed Central

    Yagishita, Shigehiro; Horinouchi, Hidehito; Sunami, Kuniko S; Kanda, Shintaro; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru; Sumi, Minako; Shiraishi, Kouya; Kohno, Takashi; Furuta, Koh; Tsuta, Koji; Tamura, Tomohide; Ohe, Yuichiro

    2015-01-01

    The frequency and clinical profile of patients with stage III non-small cell lung cancer harboring KRAS mutations have not yet been well documented. Here, we analyzed hotspot KRAS mutations using high-resolution melting analyses in tumor specimens from patients who received chemoradiotherapy between January 2001 and December 2010 at the National Cancer Center Hospital. The associations between the presence of KRAS mutations and the response rate, relapse-free survival, first relapse sites, survival post-progression and overall survival were investigated. A total of 274 non-squamous non-small cell lung cancer patients received chemoradiotherapy at our hospital. After excluding 121 patients for whom tumor specimens were not available and 34 patients with EGFR mutations, the remaining 119 patients were included in the analysis. KRAS mutations were found at a frequency of 13%. Patients with KRAS mutations had a shorter median relapse-free survival (6.1 vs 10.9 months) and a lower response rate (63% vs 81%). As for the first relapse site, patients with KRAS mutations had fewer local relapses (8% vs 23%) and more brain metastases (46% vs 12%). After disease progression, patients with KRAS mutations had a significantly shorter median survival post-progression (2.5 vs 7.3 months, P = 0.028) and median overall survival (15.1 vs 29.1 months, P = 0.022). Our results suggested that KRAS mutation could be associated with a reduced efficacy of chemoradiotherapy and a shortened survival time. PMID:26177347

  14. Robust and efficient amide-based nonheme manganese(III) hydrocarbon oxidation catalysts: substrate and solvent effects on involvement and partition of multiple active oxidants.

    PubMed

    Song, Young Joo; Lee, Sun Hwa; Park, Hyun Min; Kim, Soo Hyun; Goo, Hyo Geun; Eom, Geun Hee; Lee, Ju Hoon; Lah, Myoung Soo; Kim, Youngmee; Kim, Sung-Jin; Lee, Ju Eun; Lee, Hong-In; Kim, Cheal

    2011-06-20

    Two new mononuclear nonheme manganese(III) complexes of tetradentate ligands containing two deprotonated amide moieties, [Mn(bpc)Cl(H(2)O)] (1) and [Mn(Me(2)bpb)Cl(H(2)O)]⋅CH(3)OH (2), were prepared and characterized. Complex 2 has also been characterized by X-ray crystallography. Magnetic measurements revealed that the complexes are high spin (S = 5/2) Mn(III) species with typical magnetic moments of 4.76 and 4.95 μ(B), respectively. These nonheme Mn(III) complexes efficiently catalyzed olefin epoxidation and alcohol oxidation upon treatment with MCPBA under mild experimental conditions. Olefin epoxidation by these catalysts is proposed to involve the multiple active oxidants Mn(V)=O, Mn(IV)=O, and Mn(III)-OO(O)CR. Evidence for this approach was derived from reactivity and Hammett studies, KIE (k(H)/k(D)) values, H(2)(18)O-exchange experiments, and the use of peroxyphenylacetic acid as a mechanistic probe. In addition, it has been proposed that the participation of Mn(V)=O, Mn(IV)=O, and Mn(III)-OOR could be controlled by changing the substrate concentration, and that partitioning between heterolysis and homolysis of the O-O bond of a Mn-acylperoxo intermediate (Mn-OOC(O)R) might be significantly affected by the nature of solvent, and that the O-O bond of the Mn-OOC(O)R might proceed predominantly by heterolytic cleavage in protic solvent. Therefore, a discrete Mn(V)=O intermediate appeared to be the dominant reactive species in protic solvents. Furthermore, we have observed close similarities between these nonheme Mn(III) complex systems and Mn(saloph) catalysts previously reported, suggesting that this simultaneous operation of the three active oxidants might prevail in all the manganese-catalyzed olefin epoxidations, including Mn(salen), Mn(nonheme), and even Mn(porphyrin) complexes. This mechanism provides the greatest congruity with related oxidation reactions by using certain Mn complexes as catalysts.

  15. Overall evaluation of combustion and NO(x) emissions for a down-fired 600 MW(e) supercritical boiler with multiple injection and multiple staging.

    PubMed

    Kuang, Min; Li, Zhengqi; Liu, Chunlong; Zhu, Qunyi

    2013-05-01

    To achieve significant reductions in NOx emissions and to eliminate strongly asymmetric combustion found in down-fired boilers, a deep-air-staging combustion technology was trialed in a down-fired 600 MWe supercritical utility boiler. By performing industrial-sized measurements taken of gas temperatures and species concentrations in the near wing-wall region, carbon in fly ash and NOx emissions at various settings, effects of overfire air (OFA) and staged-air damper openings on combustion characteristics, and NOx emissions within the furnace were experimentally determined. With increasing the OFA damper opening, both fluctuations in NOx emissions and carbon in fly ash were initially slightly over OFA damper openings of 0-40% but then lengthened dramatically in openings of 40-70% (i.e., NOx emissions reduced sharply accompanied by an apparent increase in carbon in fly ash). Decreasing the staged-air declination angle clearly increased the combustible loss but slightly influenced NOx emissions. In comparison with OFA, the staged-air influence on combustion and NOx emissions was clearly weaker. Only at a high OFA damper opening of 50%, the staged-air effect was relatively clear, i.e., enlarging the staged-air damper opening decreased carbon in fly ash and slightly raised NOx emissions. By sharply opening the OFA damper to deepen the air-staging conditions, although NOx emissions could finally reduce to 503 mg/m(3) at 6% O2 (i.e., an ultralow NOx level for down-fired furnaces), carbon in fly ash jumped sharply to 15.10%. For economical and environment-friendly boiler operations, an optimal damper opening combination (i.e., 60%, 50%, and 50% for secondary air, staged-air, and OFA damper openings, respectively) was recommended for the furnace, at which carbon in fly ash and NOx emissions attained levels of about 10% and 850 mg/m(3) at 6% O2, respectively.

  16. A DNA nanomachine based on rolling circle amplification-bridged two-stage exonuclease III-assisted recycling strategy for label-free multi-amplified biosensing of nucleic acid.

    PubMed

    Xue, Qingwang; Lv, Yanqin; Cui, Hui; Gu, Xiaohong; Zhang, Shuqiu; Liu, Jifeng

    2015-01-26

    An autonomous DNA nanomachine based on rolling circle amplification (RCA)-bridged two-stage exonuclease III (Exo III)-induced recycling amplification (Exo III-RCA-Exo III) was developed for label-free and highly sensitive homogeneous multi-amplified detection of DNA combined with sensitive fluorescence detection technique. According to the configuration, the analysis of DNA is accomplished by recognizing the target to a unlabeled molecular beacon (UMB) that integrates target-binding and signal transducer within one multifunctional design, followed by the target-binding of UMB in duplex DNA removed stepwise by Exo III accompanied by the releasing of target DNA for the successive hybridization and cleavage process and autonomous generation of the primer that initiate RCA process with a rational designed padlock DNA. The RCA products containing thousands of repeated catalytic sequences catalytically hybridize with a hairpin reporter probe that includes a "caged" inactive G-quadruplex sequence (HGP) and were then detected by Exo III-assisted recycling amplification, liberating the active G-quadruplex and generating remarkable ZnPPIX/G-quadruplex fluorescence signals with the help of zinc(II)-protoporphyrin IX (ZnPPIX). The proposed strategy showed a wide dynamic range over 7 orders of magnitude with a low limit of detection of 0.51 aM. In addition, this designed protocol can discriminate mismatched DNA from perfectly matched target DNA, and holds a great potential for early diagnosis in gene-related diseases.

  17. FIGO Stage III Metastatic Gestational Choriocarcinoma Developed From an Antecedent Partial Hydatidiform Molar Pregnancy Bearing a Numerical Chromosomal Aberration 68, XX: A Case Report and Literature Review.

    PubMed

    Ma, Naili; Litkouhi, Babak; Mannion, Ciaran M

    2016-03-01

    A 36-yr-old, gravida 5 para 4 woman presented with uterine bleeding and was discovered to have a 3.7-cm uterine mass with multiple, bilateral, lung metastases. Six months earlier, the patient was diagnosed with a partial hydatidiform mole that demonstrated a rare chromosomal karyotype 68, XX[12]. The patient's serum β-human chorionic gonadotropin was elevated from baseline to 12,039 mIU/mL before the treatment. A total hysterectomy was performed and revealed a markedly hemorrhagic, extensively necrotic choriocarcinoma. The tumor mass invaded to a depth of 1/3 of the uterine wall thickness. Cytogenetic analysis of the choriocarcinoma revealed the same 68, XX karyotype, as observed in the antecedent partial hydatidiform mole. A clinical diagnosis of advanced stage invasive choriocarcinoma was rendered, with a risk factor score of 5. Following the development of chemoresistance to a single-agent (methotrexate) regimen, the patient subsequently received 5 cycles of chemotherapy (EMA-CO), without any major complication. She is currently >5 yr posttreatment and is asymptomatic. Her most recent imaging studies, including scans of chest and brain, show no evidence of disease, and her serum β-human chorionic gonadotropin level has remained consistently below detectable levels.

  18. Development and evaluation of a novel contamination device that targets multiple life-stages of Aedes aegypti

    PubMed Central

    2014-01-01

    Background The increasing global threat of Dengue demands new and easily applicable vector control methods. Ovitraps provide a low-tech and inexpensive means to combat Dengue vectors. Here we describe the development and optimization process of a novel contamination device that targets multiple life-stages of the Aedes aegypti mosquito. Special focus is directed to the diverse array of control agents deployed in this trap, covering adulticidal, larvicidal and autodissemination impacts. Methods Different trap prototypes and their parts are described, including a floater to contaminate alighting gravid mosquitoes. The attractiveness of the trap, different odor lures and floater design were studied using fluorescent powder adhering to mosquito legs and via choice tests. We demonstrate the mosquitocidal impacts of the control agents: a combination of the larvicide pyriproxyfen and the adulticidal fungus Beauveria bassiana. The impact of pyriproxyfen was determined in free-flight dissemination experiments. The effect on larval development inside the trap and in surrounding breeding sites was measured, as well as survival impacts on recaptured adults. Results The developmental process resulted in a design that consists of a black 3 Liter water-filled container with a ring-shaped floater supporting vertically placed gauze dusted with the control agents. On average, 90% of the mosquitoes in the fluorescence experiments made contact with the gauze on the floater. Studies on attractants indicated that a yeast-containing tablet was the most attractive odor lure. Furthermore, the fungus Beauveria bassiana was able to significantly increase mortality of the free-flying adults compared to controls. Dissemination of pyriproxyfen led to >90% larval mortality in alternative breeding sites and 100% larval mortality in the trap itself, against a control mortality of around 5%. Conclusion This ovitrap is a promising new tool in the battle against Dengue. It has proven to be attractive

  19. Aqueous extract of some indigenous medicinal plants inhibits glycation at multiple stages and protects erythrocytes from oxidative damage-an in vitro study.

    PubMed

    Tupe, Rashmi S; Sankhe, Neena M; Shaikh, Shamim A; Phatak, Devyani V; Parikh, Juhi U; Khaire, Amrita A; Kemse, Nisha G

    2015-04-01

    Azadirachta indica, Emblica officinalis, Syzygium cumini and Terminalia bellirica are common in Indian system of traditional medicine for the prevention of diabetes and its complications. The aim of the present study was to comprehensively and comparatively investigate the antiglycation potential of these plant extracts at multiple stages and their possible protective effect against glycated albumin mediated toxicity to erythrocytes. Antiglycation activities of these plant extracts was measured by co-incubation of plant extract with bovine serum albumin-fructose glycation model. The multistage glycation markers- fructosamines (early stage), protein carbonyls (intermediate stage) and AGEs (late stage) are investigated along with measurement of thiols and β aggregation of albumin using amyloid-specific dyes-Congo red and Th T. Protection of erythrocytes from glycated albumin induced toxicity by these plant extracts was assessed by measuring erythrocytes hemolysis, lipid peroxidation, reduced glutathione and intracellular antioxidant capacity. Total phenolics, reducing power and antioxidant activities of the plant extracts were also measured. In vitro glycation assays showed that plant extracts exerted site specific inhibitory effects at multiple stages, with T. bellirica showing maximum attenuation. In erythrocytes, along with the retardation of glycated albumin induced hemolysis and lipid-peroxidation, T. bellirica considerably maintained cellular antioxidant potential. Significant positive correlations were observed between erythrocyte protection parameters with total phenolics. These plant extracts especially T. bellirica prevents glycation induced albumin modifications and subsequent toxicity to erythrocytes which might offer additional protection against diabetic vascular complications. PMID:25829572

  20. Hierarchical Cluster Analysis of Three-Dimensional Reconstructions of Unbiased Sampled Microglia Shows not Continuous Morphological Changes from Stage 1 to 2 after Multiple Dengue Infections in Callithrix penicillata

    PubMed Central

    Diniz, Daniel G.; Silva, Geane O.; Naves, Thaís B.; Fernandes, Taiany N.; Araújo, Sanderson C.; Diniz, José A. P.; de Farias, Luis H. S.; Sosthenes, Marcia C. K.; Diniz, Cristovam G.; Anthony, Daniel C.; da Costa Vasconcelos, Pedro F.; Picanço Diniz, Cristovam W.

    2016-01-01

    It is known that microglial morphology and function are related, but few studies have explored the subtleties of microglial morphological changes in response to specific pathogens. In the present report we quantitated microglia morphological changes in a monkey model of dengue disease with virus CNS invasion. To mimic multiple infections that usually occur in endemic areas, where higher dengue infection incidence and abundant mosquito vectors carrying different serotypes coexist, subjects received once a week subcutaneous injections of DENV3 (genotype III)-infected culture supernatant followed 24 h later by an injection of anti-DENV2 antibody. Control animals received either weekly anti-DENV2 antibodies, or no injections. Brain sections were immunolabeled for DENV3 antigens and IBA-1. Random and systematic microglial samples were taken from the polymorphic layer of dentate gyrus for 3-D reconstructions, where we found intense immunostaining for TNFα and DENV3 virus antigens. We submitted all bi- or multimodal morphological parameters of microglia to hierarchical cluster analysis and found two major morphological phenotypes designated types I and II. Compared to type I (stage 1), type II microglia were more complex; displaying higher number of nodes, processes and trees and larger surface area and volumes (stage 2). Type II microglia were found only in infected monkeys, whereas type I microglia was found in both control and infected subjects. Hierarchical cluster analysis of morphological parameters of 3-D reconstructions of random and systematic selected samples in control and ADE dengue infected monkeys suggests that microglia morphological changes from stage 1 to stage 2 may not be continuous. PMID:27047345

  1. Hierarchical Cluster Analysis of Three-Dimensional Reconstructions of Unbiased Sampled Microglia Shows not Continuous Morphological Changes from Stage 1 to 2 after Multiple Dengue Infections in Callithrix penicillata.

    PubMed

    Diniz, Daniel G; Silva, Geane O; Naves, Thaís B; Fernandes, Taiany N; Araújo, Sanderson C; Diniz, José A P; de Farias, Luis H S; Sosthenes, Marcia C K; Diniz, Cristovam G; Anthony, Daniel C; da Costa Vasconcelos, Pedro F; Picanço Diniz, Cristovam W

    2016-01-01

    It is known that microglial morphology and function are related, but few studies have explored the subtleties of microglial morphological changes in response to specific pathogens. In the present report we quantitated microglia morphological changes in a monkey model of dengue disease with virus CNS invasion. To mimic multiple infections that usually occur in endemic areas, where higher dengue infection incidence and abundant mosquito vectors carrying different serotypes coexist, subjects received once a week subcutaneous injections of DENV3 (genotype III)-infected culture supernatant followed 24 h later by an injection of anti-DENV2 antibody. Control animals received either weekly anti-DENV2 antibodies, or no injections. Brain sections were immunolabeled for DENV3 antigens and IBA-1. Random and systematic microglial samples were taken from the polymorphic layer of dentate gyrus for 3-D reconstructions, where we found intense immunostaining for TNFα and DENV3 virus antigens. We submitted all bi- or multimodal morphological parameters of microglia to hierarchical cluster analysis and found two major morphological phenotypes designated types I and II. Compared to type I (stage 1), type II microglia were more complex; displaying higher number of nodes, processes and trees and larger surface area and volumes (stage 2). Type II microglia were found only in infected monkeys, whereas type I microglia was found in both control and infected subjects. Hierarchical cluster analysis of morphological parameters of 3-D reconstructions of random and systematic selected samples in control and ADE dengue infected monkeys suggests that microglia morphological changes from stage 1 to stage 2 may not be continuous. PMID:27047345

  2. Microsatellite Instability Predicts Improved Response to Adjuvant Therapy With Irinotecan, Fluorouracil, and Leucovorin in Stage III Colon Cancer: Cancer and Leukemia Group B Protocol 89803

    PubMed Central

    Bertagnolli, Monica M.; Niedzwiecki, Donna; Compton, Carolyn C.; Hahn, Hejin P.; Hall, Margaret; Damas, Beatrice; Jewell, Scott D.; Mayer, Robert J.; Goldberg, Richard M.; Saltz, Leonard B.; Warren, Robert S.; Redston, Mark

    2009-01-01

    Purpose Colon cancers exhibiting DNA mismatch repair (MMR) defects demonstrate distinct clinical and pathologic features, including better prognosis and reduced response to fluorouracil (FU) –based chemotherapy. This prospective study investigated adjuvant chemotherapy containing FU and irinotecan in patients with MMR deficient (MMR-D) colon cancers. Patients and Methods Cancer and Leukemia Group B 89803 randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly bolus FU/leucovorin (LV) or weekly bolus irinotecan, FU, and LV (IFL). The primary end point was overall survival; disease-free survival (DFS) was a secondary end point. Tumor expression of the MMR proteins, MLH1 and MSH2, was determined by immunohistochemistry (IHC). DNA microsatellite instability was also assessed using a panel of mono- and dinucleotide markers. Tumors with MMR defects were those demonstrating loss of MMR protein expression (MMR-D) and/or microsatellite instability high (MSI-H) genotype. Results Of 723 tumor cases examined by genotyping and IHC, 96 (13.3%) were MMR-D/MSI-H. Genotyping results were consistent with IHC in 702 cases (97.1%). IFL-treated patients with MMR-D/MSI-H tumors showed improved 5-year DFS as compared with those with mismatch repair intact tumors (0.76; 95% CI, 0.64 to 0.88 v 0.59; 95% CI, 0.53 to 0.64; P = .03). This relationship was not observed among patients treated with FU/LV. A trend toward longer DFS was observed in IFL-treated patients with MMR-D/MSI-H tumors as compared with those receiving FU/LV (0.57; 95% CI, 0.42 to 0.71 v 0.76; 95% CI, 0.64 to 0.88; P = .07; hazard ratio interaction between tumor status and treatment, 0.51; likelihood ratio P = .117). Conclusion Loss of tumor MMR function may predict improved outcome in patients treated with the IFL regimen as compared with those receiving FU/LV. PMID:19273709

  3. HLA-G 3’UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment

    PubMed Central

    Garziera, Marica; Bidoli, Ettore; Cecchin, Erika; Mini, Enrico; Nobili, Stefania; Lonardi, Sara; Buonadonna, Angela; Errante, Domenico; Pella, Nicoletta; D’Andrea, Mario; De Marchi, Francesco; De Paoli, Antonino; Zanusso, Chiara; De Mattia, Elena; Tassi, Renato; Toffoli, Giuseppe

    2015-01-01

    An important hallmark of CRC is the evasion of immune surveillance. HLA-G is a negative regulator of host’s immune response. Overexpression of HLA-G protein in primary tumour CRC tissues has already been associated to worse prognosis; however a definition of the role of immunogenetic host background is still lacking. Germline polymorphisms in the 3’UTR region of HLA-G influence the magnitude of the protein by modulating HLA-G mRNA stability. Soluble HLA-G has been associated to 3’UTR +2960 Ins/Ins and +3035 C/T (lower levels) and +3187 G/G (high levels) genotypes. HLA-G 3’UTR SNPs have never been explored in CRC outcome. The purpose of this study was to investigate if common HLA-G 3’UTR polymorphisms have an impact on DFS and OS of 253 stage II-III CRC patients, after primary surgery and ADJ-CT based on FL. The 3’UTR was sequenced and SNPs were analyzed for their association with survival by Kaplan-Meier and multivariate Cox models; results underwent internal validation using a resampling method (bootstrap analysis). In a multivariate analysis, we estimated an association with improved DFS in Ins allele (Ins/Del +Ins/Ins) carriers (HR 0.60, 95% CI 0.38–0.93, P = 0.023) and in patients with +3035 C/T genotype (HR 0.51, 95% CI 0.26–0.99, P = 0.045). The +3187 G/G mutated carriers (G/G vs A/A+A/G) were associated to a worst prognosis in both DFS (HR 2.46, 95% CI 1.19–5.05, P = 0.015) and OS (HR 2.71, 95% CI 1.16–6.63, P = 0.022). Our study shows a prognostic and independent role of 3 HLA-G 3’UTR SNPs, +2960 14-bp INDEL, +3035 C>T, and +3187 A>G. PMID:26633805

  4. Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-10-19

    Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Lung Adenocarcinoma; Malignant Pericardial Effusion; Malignant Pleural Effusion; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  5. Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2016-05-26

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  6. Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-10-14

    Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Lung Adenocarcinoma, Mixed Subtype; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  7. Temporal uncertainty analysis of human errors based on interrelationships among multiple factors: a case of Minuteman III missile accident.

    PubMed

    Rong, Hao; Tian, Jin; Zhao, Tingdi

    2016-01-01

    In traditional approaches of human reliability assessment (HRA), the definition of the error producing conditions (EPCs) and the supporting guidance are such that some of the conditions (especially organizational or managerial conditions) can hardly be included, and thus the analysis is burdened with incomprehensiveness without reflecting the temporal trend of human reliability. A method based on system dynamics (SD), which highlights interrelationships among technical and organizational aspects that may contribute to human errors, is presented to facilitate quantitatively estimating the human error probability (HEP) and its related variables changing over time in a long period. Taking the Minuteman III missile accident in 2008 as a case, the proposed HRA method is applied to assess HEP during missile operations over 50 years by analyzing the interactions among the variables involved in human-related risks; also the critical factors are determined in terms of impact that the variables have on risks in different time periods. It is indicated that both technical and organizational aspects should be focused on to minimize human errors in a long run. PMID:26360211

  8. Temporal uncertainty analysis of human errors based on interrelationships among multiple factors: a case of Minuteman III missile accident.

    PubMed

    Rong, Hao; Tian, Jin; Zhao, Tingdi

    2016-01-01

    In traditional approaches of human reliability assessment (HRA), the definition of the error producing conditions (EPCs) and the supporting guidance are such that some of the conditions (especially organizational or managerial conditions) can hardly be included, and thus the analysis is burdened with incomprehensiveness without reflecting the temporal trend of human reliability. A method based on system dynamics (SD), which highlights interrelationships among technical and organizational aspects that may contribute to human errors, is presented to facilitate quantitatively estimating the human error probability (HEP) and its related variables changing over time in a long period. Taking the Minuteman III missile accident in 2008 as a case, the proposed HRA method is applied to assess HEP during missile operations over 50 years by analyzing the interactions among the variables involved in human-related risks; also the critical factors are determined in terms of impact that the variables have on risks in different time periods. It is indicated that both technical and organizational aspects should be focused on to minimize human errors in a long run.

  9. Molecular spintronics based on single-molecule magnets composed of multiple-decker phthalocyaninato terbium(III) complex.

    PubMed

    Katoh, Keiichi; Isshiki, Hironari; Komeda, Tadahiro; Yamashita, Masahiro

    2012-06-01

    Unlike electronics, which is based on the freedom of the charge of an electron whose memory is volatile, spintronics is based on the freedom of the charge, spin, and orbital of an electron whose memory is non-volatile. Although in most GMR, TMR, and CMR systems, bulk or classical magnets that are composed of transition metals are used, this Focus Review considers the growing use of single-molecule magnets (SMMs) that are composed of multinuclear metal complexes and nanosized magnets, which exhibit slow magnetic-relaxation processes and quantum tunneling. Molecular spintronics, which combines spintronics and molecular electronics, is an emerging field of research. Using molecules is advantageous because their electronic and magnetic properties can be manipulated under specific conditions. Herein, recent developments in [LnPc]-based multiple-decker SMMs on surfaces for molecular spintronic devices are presented. First, we discuss the strategies for preparing single-molecular-memory devices by using SMMs. Next, we focus on the switching of the Kondo signal of [LnPc]-based multiple-decker SMMs that are adsorbed onto surfaces, their characterization by using STM and STS, and the relationship between the molecular structure, the electronic structure, and the Kondo resonance of [TbPc(2)]. Finally, the field-effect-transistor (FET) properties of surface-adsorbed [LnPc(2)] and [Ln(2)Pc(3)] cast films are reported, which is the first step towards controlling SMMs through their spins for applications in single-molecular memory and spintronics devices.

  10. A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

    SciTech Connect

    Knisely, Jonathan P.S. Berkey, Brian; Chakravarti, Arnab; Yung, Al W.K.; Curran, Walter J.; Robins, H. Ian; Movsas, Benjamin; Brachman, David G.; Henderson, Randall H.; Mehta, Minesh P.

    2008-05-01

    Purpose: To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. Patients and Methods: Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. Results: Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. Conclusion: Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects.

  11. Concurrent Chemoradiotherapy Followed by Consolidation Chemotherapy With Bi-Weekly Docetaxel and Carboplatin for Stage III Unresectable, Non-Small-Cell Lung Cancer: Clinical Application of a Protocol Used in a Previous Phase II Study

    SciTech Connect

    Saitoh, Jun-Ichi; Saito, Yoshihiro; Kazumoto, Tomoko; Kudo, Shigehiro; Yoshida, Daisaku; Ichikawa, Akihiro; Sakai, Hiroshi; Kurimoto, Futoshi; Kato, Shingo; Shibuya, Kei

    2012-04-01

    Purpose: To assess the clinical applicability of a protocol evaluated in a previously reported phase II study of concurrent chemoradiotherapy followed by consolidation chemotherapy with bi-weekly docetaxel and carboplatin in patients with stage III, unresectable, non-small-cell lung cancer (NSCLC). Methods and Materials: Between January 2000 and March 2006, 116 previously untreated patients with histologically proven, stage III NSCLC were treated with concurrent chemoradiotherapy. Radiation therapy was administered in 2-Gy daily fractions to a total dose of 60 Gy in combination with docetaxel, 30 mg/m{sup 2}, and carboplatin at an area under the curve value of 3 every 2 weeks during and after radiation therapy. Results: The median survival time for the entire group was 25.5 months. The actuarial 2-year and 5-year overall survival rates were 53% and 31%, respectively. The 3-year cause-specific survival rate was 60% in patients with stage IIIA disease, whereas it was 35% in patients with stage IIIB disease (p = 0.007). The actuarial 2-year and 5-year local control rates were 62% and 55%, respectively. Acute hematologic toxicities of Grade {>=}3 severity were observed in 20.7% of patients, while radiation pneumonitis and esophagitis of Grade {>=}3 severity were observed in 2.6% and 1.7% of patients, respectively. Conclusions: The feasibility of the protocol used in the previous phase II study was reconfirmed in this series, and excellent treatment results were achieved.

  12. Radiotherapy for Early-Stage Hodgkin's Lymphoma: A 21st Century Perspective and Review of Multiple Randomized Clinical Trials

    SciTech Connect

    Bar Ad, Voichita Paltiel, Ora; Glatstein, Eli

    2008-12-01

    The treatment of Hodgkin's lymphoma has improved dramatically over the past decades. Over the last half century, Hodgkin's lymphoma has become one of the most curable cancers of adulthood. More than 90% of the patients with localized stages of the disease can be cured with modern treatment strategies. Long-term toxicities are now the major concern for survivors of early-stage disease. Contemporary therapeutic approaches for Hodgkin's lymphoma attempt to preserve the high cure rate achieved, while reducing treatment-related acute and late toxicities. The aim of this review is to re-examine the historical and the current role of radiotherapy for early-stage Hodgkin's lymphoma, given the latest evidence of an increasing role of chemotherapy for the treatment of this malignancy. The literature search was performed in PubMed Plus. Studies on children were excluded.

  13. Broad-spectrum Antibiotic Plus Metronidazole May Not Prevent the Deterioration of Necrotizing Enterocolitis From Stage II to III in Full-term and Near-term Infants: A Propensity Score-matched Cohort Study.

    PubMed

    Luo, Li-Juan; Li, Xin; Yang, Kai-Di; Lu, Jiang-Yi; Li, Lu-Quan

    2015-10-01

    Necrotizing enterocolitis (NEC) is the most common and frequently dangerous neonatal gastrointestinal disease. Studies have shown broad-spectrum antibiotics plus anaerobic antimicrobial therapy did not prevent the deterioration of NEC among very low birth preterm infants. However, few studies about this therapy which focused on full-term and near-term infant with NEC has been reported. The aim of this study was to evaluate the effect of broad-spectrum antibiotic plus metronidazole in preventing the deterioration of NEC from stage II to III in full-term and near-term infants.A retrospective cohort study based on the propensity score (PS) 1:1 matching was performed among the full-term and near-term infants with NEC (Bell stage ≥II). All infants who received broad-spectrum antibiotics were divided into 2 groups: group with metronidazole treatment (metronidazole was used ≥4 days continuously, 15 mg/kg/day) and group without metronidazole treatment. The depraved rates of stage II NEC between the 2 groups were compared. Meanwhile, the risk factors associated with the deterioration of stage II NEC were analyzed by case-control study in the PS-matched cases.A total of 229 infants met the inclusion criteria. Before PS-matching, we found the deterioration of NEC rate in the group with metronidazole treatment was higher than that in the group without metronidazole treatment (18.1% [28/155] vs 8.1% [6/74]; P = 0.048). After PS-matching, 73 pairs were matched, and the depraved rate of NEC in the group with metronidazole treatment was not lower than that in the group without metronidazole treatment (15.1% vs 8.2%; P = 0.2). Binary logistic regression analysis showed that sepsis after NEC (odds ratio [OR] 3.748, 95% confidence interval [CI] 1.171-11.998, P = 0.03), the need to use transfusion of blood products after diagnosis of NEC (OR 8.003, 95% CI 2.365-27.087, P = 0.00), and the need of longer time for nasogastric suction were risk factors for stage II NEC progressing to

  14. Validation of Kepler's Multiple Planet Candidates. III. Light Curve Analysis and Announcement of Hundreds of New Multi-planet Systems

    NASA Astrophysics Data System (ADS)

    Rowe, Jason F.; Bryson, Stephen T.; Marcy, Geoffrey W.; Lissauer, Jack J.; Jontof-Hutter, Daniel; Mullally, Fergal; Gilliland, Ronald L.; Issacson, Howard; Ford, Eric; Howell, Steve B.; Borucki, William J.; Haas, Michael; Huber, Daniel; Steffen, Jason H.; Thompson, Susan E.; Quintana, Elisa; Barclay, Thomas; Still, Martin; Fortney, Jonathan; Gautier, T. N., III; Hunter, Roger; Caldwell, Douglas A.; Ciardi, David R.; Devore, Edna; Cochran, William; Jenkins, Jon; Agol, Eric; Carter, Joshua A.; Geary, John

    2014-03-01

    The Kepler mission has discovered more than 2500 exoplanet candidates in the first two years of spacecraft data, with approximately 40% of those in candidate multi-planet systems. The high rate of multiplicity combined with the low rate of identified false positives indicates that the multiplanet systems contain very few false positive signals due to other systems not gravitationally bound to the target star. False positives in the multi-planet systems are identified and removed, leaving behind a residual population of candidate multi-planet transiting systems expected to have a false positive rate less than 1%. We present a sample of 340 planetary systems that contain 851 planets that are validated to substantially better than the 99% confidence level; the vast majority of these have not been previously verified as planets. We expect ~two unidentified false positives making our sample of planet very reliable. We present fundamental planetary properties of our sample based on a comprehensive analysis of Kepler light curves, ground-based spectroscopy, and high-resolution imaging. Since we do not require spectroscopy or high-resolution imaging for validation, some of our derived parameters for a planetary system may be systematically incorrect due to dilution from light due to additional stars in the photometric aperture. Nonetheless, our result nearly doubles the number verified exoplanets.

  15. Validation of Kepler's multiple planet candidates. III. Light curve analysis and announcement of hundreds of new multi-planet systems

    SciTech Connect

    Rowe, Jason F.; Bryson, Stephen T.; Lissauer, Jack J.; Jontof-Hutter, Daniel; Mullally, Fergal; Howell, Steve B.; Borucki, William J.; Haas, Michael; Huber, Daniel; Thompson, Susan E.; Quintana, Elisa; Barclay, Thomas; Still, Martin; Marcy, Geoffrey W.; Issacson, Howard; Gilliland, Ronald L.; Ford, Eric; Steffen, Jason H.; Gautier, T. N. III; and others

    2014-03-20

    The Kepler mission has discovered more than 2500 exoplanet candidates in the first two years of spacecraft data, with approximately 40% of those in candidate multi-planet systems. The high rate of multiplicity combined with the low rate of identified false positives indicates that the multiplanet systems contain very few false positive signals due to other systems not gravitationally bound to the target star. False positives in the multi-planet systems are identified and removed, leaving behind a residual population of candidate multi-planet transiting systems expected to have a false positive rate less than 1%. We present a sample of 340 planetary systems that contain 851 planets that are validated to substantially better than the 99% confidence level; the vast majority of these have not been previously verified as planets. We expect ∼two unidentified false positives making our sample of planet very reliable. We present fundamental planetary properties of our sample based on a comprehensive analysis of Kepler light curves, ground-based spectroscopy, and high-resolution imaging. Since we do not require spectroscopy or high-resolution imaging for validation, some of our derived parameters for a planetary system may be systematically incorrect due to dilution from light due to additional stars in the photometric aperture. Nonetheless, our result nearly doubles the number verified exoplanets.

  16. A hydrodynamical study of multiple-shell planetary nebulae. III. Expansion properties and internal kinematics: Theory versus observation

    NASA Astrophysics Data System (ADS)

    Schönberner, D.; Jacob, R.; Lehmann, H.; Hildebrandt, G.; Steffen, M.; Zwanzig, A.; Sandin, C.; Corradi, R. L. M.

    We present the result of a study on the expansion properties and internal kinematics of round/elliptical planetary nebulae of the Milky Way disk, the halo, and of the globular cluster M 15. The purpose of this study is to considerably enlarge the small sample of nebulae with precisely determined expansion properties (Schönberner et al. \\cite{SJSPCA.05}). To this aim, we selected a representative sample of objects with different evolutionary stages and metallicities and conducted high-resolution échelle spectroscopy. In most cases we succeeded in detecting the weak signals from the outer nebular shell which are attached to the main line emission from the bright nebular rim. Next to the measurement of the motion of the rim gas by decomposition of the main line components into Gaussians, we were able to measure separately, for most objects for the first time, the gas velocity immediately behind the leading shock of the shell, i.e. the post-shock velocity. We more than doubled the number of objects for which the velocities of both rim and shell are known and confirm that the overall expansion of planetary nebulae is accelerating with time. There are, however, differences between the expansion behaviour of the shell and the rim: The post-shock velocity is starting at values as low as around 20 km s-1 for the youngest nebulae, just above the AGB wind velocity of ˜ 10-15 km s-1, and is reaching values of about 40 km s-1 for the nebulae around hotter central stars. Contrarily, the rim matter is at first decelerated below the typical AGB-wind velocity and remains at about 5-10 km s-1 for a while until finally a typical flow velocity of up to 30 km s-1 is reached. This observed distinct velocity evolution of both rim and shell is explained by radiation-hydrodynamics simulations, at least qualitatively: It is due to the ever changing stellar radiation field and wind-wind interaction together with the varying density profile ahead of the leading shock during the progress

  17. Development of a straightness measurement and compensation system with multiple right-angle reflectors and a lead zirconate titanate-based compensation stage

    SciTech Connect

    Liu, Chien-Hung; Chen, Jui-Hung; Teng, Yun-Feng

    2009-11-15

    This paper presents a real-time straightness measurement and compensation system with an optical straightness measurement system and a single-axis flexure-hinge type lead zirconate titanate (PZT)-based compensation stage. The optical straightness measurement system consists of a He-Ne laser, a quadrant photodiode detector, and five right-angle reflectors. Multiple laser beam reflections between the right-angle reflectors increase the sensitivity of the straightness measurement by a factor of 6. The right-angle reflectors can be moved by the flexure-hinge type PZT-based compensation stage that is actuated by a PZT actuator to ensure that the laser beam is always projected onto the center of the quadrant detector. These two systems are integrated and fixed on a scanning stage. The resolution of the straightness measurement system is 0.1 {mu}m. Using the real-time straightness compensation system, the straightness error of the scanning stage is fed back to the control system. The compensated straightness error of the scanning stage system was reduced from 6.5 {mu}m to less than 1 {mu}m.

  18. The influence of baseline characteristics and disease stage on health-related quality of life in multiple myeloma: findings from six randomized controlled trials.

    PubMed

    Robinson, Don; Esseltine, Dixie-Lee; Regnault, Antoine; Meunier, Juliette; Liu, Kevin; van de Velde, Helgi

    2016-08-01

    This descriptive, cross-sectional analysis evaluated the impact of baseline characteristics on health-related quality of life (HR-QoL) at different stages of multiple myeloma (MM). The bortezomib clinical-trial programme evaluated HR-QoL early and consistently, producing a large multi-study dataset. Baseline data, captured using the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire (QLQ-C30), were pooled from six bortezomib randomized trials conducted in different disease-stage categories: 'New' (previously untreated; n = 753), 'Early' (1-3 prior therapies; n = 1569) and 'Late' (≥4 prior therapies; n = 239) disease. Mean EORTC global health scores were similar across the three stages. Unexpectedly, emotional, physical and role functioning were higher in the later stages, indicating better perceived health. Symptom scores, including pain, were largely similar or lower in the later versus earlier stages, signifying a lower symptom burden/better symptom control with more advanced disease. Notable variation in HR-QoL was observed by age and clinical parameters within and across stages. Multivariate modelling indicated that opioid use and performance status were key factors driving overall HR-QoL across stages. Using an age-restricted analysis, transplant eligibility had little impact on HR-QoL in New disease patients. Thus, changes in HR-QoL over the treatment course of MM are complex and impacted by baseline factors. A prospective observational international inception cohort study that captures key clinical, HR-QoL and demographic characteristics, along with safety and supportive care information, is needed. PMID:27265837

  19. Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-06-17

    Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Non-Small Cell Lung Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  20. Regional Office Procedures. Stage I Final Report for the Study of Program Management Procedures in the Campus-Based and Basic Grant Programs. (Volume III).

    ERIC Educational Resources Information Center

    Puma, Michael J.

    Volume III of a study of program management procedures in the campus-based and Basic Educational Opportunity Grant (BEOG) programs provides a description of procedures employed within the U.S. Office of Education regional offices to administer the Basic Grant and campus-based student financial assistance programs. The objective of the report is to…

  1. Tuning a single ligand system to stabilize multiple spin states of manganese: a first example of a hydrazone-based manganese(III) spin-crossover complex.

    PubMed

    Shongwe, Musa S; Al-Barhi, Kaltham S; Mikuriya, Masahiro; Adams, Harry; Morris, Michael J; Bill, Eckhard; Molloy, Kieran C

    2014-07-28

    A series of bis-chelate pseudo-octahedral mononuclear coordination complexes of manganese with the chromophore [MnN4 O2 ](n+) (n=0, 1) have been generated in all three principal oxidation states of this transition-metal center under ambient conditions by utilizing a readily tunable, versatile phenolic pyridylhydrazone ligand system (i.e., H2 (3,5-R(1) ,R(2) )-L; L=ligand). Strategic combinations of the nature and position of a variety of substituent groups afforded selective, spontaneous stabilization of multiple spin states of the manganese center, which, upon close crystallographic scrutiny, appears to be in part due to the occurrence or absence of hydrogen-bonding interactions that involve the phenolate/phenolic oxygen atom. The divalent complexes are isolable in two forms, namely, molecular [Mn(II) {H(3,5-R(1) ,R(2) )-L}2 ] and ionic [Mn(II) {H2 (3,5-R(1) ,R(2) )-L}{H(3,5-R(1) ,R(2) )-L}]ClO4 , with the latter complex converting easily into the former complex on deprotonation. Accessibility of the higher-valent states is achievable only when the phenolate oxygen atom is sterically hindered from participation in hydrogen bonding. The [Mn(III) {H(3,5-tBu2 )-L}2 ]ClO4 complex is the first example of a hydrazone-based Mn(III) complex to exhibit spin crossover. Formation of the tetravalent complexes [Mn(IV) {(3,5-R(1) ,R(2) )-L}2 ] (R(1) =tBu, R(2) =H; R(1) =R(2) =tBu) necessitates base-assisted abstraction of the hydrazinic proton.

  2. Parametric and exergetic analysis of a two-stage transcritical combined organic Rankine cycle used for multiple grades waste heat recovery of diesel engine

    NASA Astrophysics Data System (ADS)

    Tian, H.; Zhang, J.; Xu, X. F.; Shu, G. Q.; Wei, H. Q.

    2013-12-01

    Diesel engine has multiple grades of waste heat with different ratios of combustion heat, exhaust is 400 °C with the ratio of 21% and coolant is 90 °C with 19%. Few previous publications investigate the recovery of multiple grades waste heat together. In this paper, a two-stage transcritical combined organic rankine cycle (CORC) is presented and analyzed. In the combined system, the high and low temperature stages transcritical cycle recover the high grades waste heat, and medium to low grades waste heat respectively, and being combined efficiently. Meanwhile, the suitable working fluids for high stage are chosen and analyzed. The cycle parameters, including thermal efficiency (ηth), net power output (Pnet), energy efficiency (ηexg) and global thermal efficiency of DE-CORC(ηglo) have also been analyzed and optimized. The results indicate that this combined system could recover all the waste heat with a high recovery ratio (above 90%) and obtain a maximum power output of 37kW for a DE of 243kW. The global thermal efficiency of DE-CORC can get a max value of 46.2% compared with 40% for single DE. The results also indicate that all the energy conversion process have a high exergy efficiency.

  3. Dual modality optical coherence and whole-body photoacoustic tomography imaging of chick embryos in multiple development stages

    PubMed Central

    Liu, Mengyang; Maurer, Barbara; Hermann, Boris; Zabihian, Behrooz; Sandrian, Michelle G.; Unterhuber, Angelika; Baumann, Bernhard; Zhang, Edward Z.; Beard, Paul C.; Weninger, Wolfgang J.; Drexler, Wolfgang

    2014-01-01

    Chick embryos are an important animal model for biomedical studies. The visualization of chick embryos, however, is limited mostly to postmortem sectional imaging methods. In this work, we present a dual modality optical imaging system that combines swept-source optical coherence tomography and whole-body photoacoustic tomography, and apply it to image chick embryos at three different development stages. The explanted chick embryos were imaged in toto with complementary contrast from both optical scattering and optical absorption. The results serve as a prelude to the use of the dual modality system in longitudinal whole-body monitoring of chick embryos in ovo. PMID:25401028

  4. Multiple periodic solutions of a delayed predator–prey model with non-monotonic functional response and stage structure

    PubMed Central

    Liu, Yingyuan; Zhang, Xiaolan; Zhou, Tiejun

    2014-01-01

    The paper studies a periodic and delayed predator–prey system with non-monotonic functional responses and stage structure. In the system, both the predator and prey are divided into immature individuals and mature individuals by two fixed ages. It is assumed that the immature predators cannot attack preys, and the case of the mature predators attacking the immature preys is also ignored. Based on Mawhin's coincidence degree, sufficient conditions are obtained for the existence of two positive periodic solutions of the system. An example is presented to illustrate the feasibility of the main results. PMID:24963983

  5. Radiotherapy With 8-MHz Radiofrequency-Capacitive Regional Hyperthermia for Stage III Non-Small-Cell Lung Cancer: The Radiofrequency-Output Power Correlates With the Intraesophageal Temperature and Clinical Outcomes

    SciTech Connect

    Ohguri, Takayuki Imada, Hajime; Yahara, Katsuya; Morioka, Tomoaki; Nakano, Keita; Terashima, Hiromi; Korogi, Yukunori

    2009-01-01

    Purpose: To assess the efficacy of radiotherapy (RT) combined with regional hyperthermia (HT) guided by radiofrequency (RF)-output power and intraesophageal temperature and evaluate the potential contribution of HT to clinical outcomes in patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Thirty-five patients with Stage III NSCLC treated with RT plus regional HT were retrospectively analyzed. Twenty-two of the 35 patients underwent intraesophageal temperature measurements. Patients with subcutaneous fat of 2.5 cm or greater, older age, or other serious complications did not undergo this therapy. The 8-MHz RF-capacitive heating device was applied, and in all patients, both the upper and lower electrodes were 30 cm in diameter, placed on opposite sides of the whole thoracic region, and treatment posture was the prone position. The HT was applied within 15 minutes after RT once or twice a week. Results: All thermal parameters, minimum, maximum, and mean of the four intraesophageal temperature measurements at the end of each session and the proportion of the time during which at least one of the four intraesophageal measurements was 41{sup o}C or higher in the total period of each session of HT, of the intraesophageal temperature significantly correlated with median RF-output power. Median RF-output power ({>=}1,200 W) was a statistically significant prognostic factor for overall, local recurrence-free, and distant metastasis-free survival. Conclusions: The RT combined with regional HT using a higher RF-output power could contribute to better clinical outcomes in patients with Stage III NSCLC. The RF-output power thus may be used as a promising parameter to assess the treatment of deep regional HT if deep heating using this device is performed with the same size electrodes and in the same body posture.

  6. A comparison of volumetric modulated arc therapy and sliding-window intensity-modulated radiotherapy in the treatment of Stage I-II nasal natural killer/T-cell lymphoma.

    PubMed

    Liu, Xianfeng; Yang, Yong; Jin, Fu; He, Yanan; Zhong, Mingsong; Luo, Huanli; Qiu, Da; Li, Chao; Yang, Han; He, Guanglei; Wang, Ying

    2016-01-01

    This article is aimed to compare the dosimetric differences between volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) for Stage I-II nasal natural killer/T-cell lymphoma (NNKTL). Ten patients with Stage I-II NNKTL treated with IMRT were replanned with VMAT (2 arcs). The prescribed dose of the planning target volume (PTV) was 50Gy in 25 fractions. The VMAT plans with the Anisotropic Analytical Algorithm (Version 8.6.15) were based on an Eclipse treatment planning system; the monitor units (MUs) and treatment time (T) were scored to measure the expected treatment efficiency. All the 10 patients under the study were subject to comparisons regarding the quality of target coverage, the efficiency of delivery, and the exposure of normal adjacent organs at risk (OARs). The study shows that VMAT was associated with a better conformal index (CI) and homogeneity index (HI) (both p < 0.05) but slightly higher dose to OARs than IMRT. The MUs with VMAT (650.80 ± 24.59) were fewer than with IMRT (1300.10 ± 57.12) (relative reduction of 49.94%, p = 0.00) when using 2-Gy dose fractions. The treatment time with VMAT (3.20 ± 0.02 minutes) was shorter than with IMRT (7.38 ± 0.18 minutes) (relative reduction of 56.64%, p = 0.00). We found that VMAT and IMRT both provide satisfactory target dosimetric coverage and OARs sparing clinically. Likely to deliver a bit higher dose to OARs, VMAT in comparison with IMRT, is still a better choice for treatment of patients with Stage I-II NNKTL, thanks to better dose distribution, fewer MUs, and shorter delivery time. PMID:26428072

  7. Microsatellite Instability and Loss of Heterozygosity at Chromosomal Location 18q: Prospective Evaluation of Biomarkers for Stages II and III Colon Cancer—A Study of CALGB 9581 and 89803

    PubMed Central

    Bertagnolli, Monica M.; Redston, Mark; Compton, Carolyn C.; Niedzwiecki, Donna; Mayer, Robert J.; Goldberg, Richard M.; Colacchio, Thomas A.; Saltz, Leonard B.; Warren, Robert S.

    2011-01-01

    Purpose Colorectal cancer (CRC) develops as a result of a series of accumulated genomic changes that produce oncogene activation and tumor suppressor gene loss. These characteristics may classify CRC into subsets of distinct clinical behaviors. Patients and Methods We studied two of these genomic defects—mismatch repair deficiency (MMR-D) and loss of heterozygosity at chromosomal location 18q (18qLOH)—in patients enrolled onto two phase III cooperative group trials for treatment of potentially curable colon cancer. These trials included prospective secondary analyses to determine the relationship between these markers and treatment outcome. A total of 1,852 patients were tested for MMR status and 955 (excluding patients with MMR-D tumors) for 18qLOH. Results Compared with stage III, more stage II tumors were MMR-D (21.3% v 14.4%; P < .001) and were intact at 18q (24.2% v 15.1%; P = .001). For the combined cohort, patients with MMR-D tumors had better 5-year disease-free survival (DFS; 0.76 v 0.67; P < .001) and overall survival (OS; 0.81 v 0.78; P = .029) than those with MMR intact (MMR-I) tumors. Among patients with MMR-I tumors, the status of 18q did not affect outcome, with 5-year values for patients with 18q intact versus 18qLOH tumors of 0.74 versus 0.65 (P = .18) for DFS and 0.81 versus 0.77 (P = .18) for OS. Conclusion We conclude that MMR-D tumor status, but not the presence of 18qLOH, has prognostic value for stages II and III colon cancer. PMID:21747089

  8. Chemically mediated interactions between macroalgae Dictyota spp. and multiple life-history stages of the coral Porites astreoides

    USGS Publications Warehouse

    Paul, V.J.; Kuffner, I.B.; Walters, L.J.; Ritson-Williams, R.; Beach, K.S.; Becerro, M.A.

    2011-01-01

    Competition between corals and macroalgae is often assumed to occur on reefs, especially those that have undergone shifts from coral to algal dominance; however, data examining these competitive interactions, especially during the early life-history stages of corals, are scarce. We conducted a series of field and outdoor seawater-table experiments to test the hypothesis that allelopathy (chemical inhibition) mediates interactions between 2 common brown macroalgae, Dictyota pulchella and D. pinnatifida, and the coral Porites astreoides at different life-history stages of the coral. D. pinnatifida significantly reduced larval survival and larval recruitment. The extracts of both D. pinnatifida and D. pulchella significantly reduced larval survival, and the extract of D. pulchella also negatively influenced larval recruitment. There was no measurable effect of the crude extracts from Dictyota spp. on the photophysiology of adult corals. Our results provide evidence that these Dictyota species chemically compete with P. astreoides by negatively affecting larval settlement and recruitment as well as the survival of larvae and new recruits. Macroalgae may perpetuate their dominance on degraded reefs by chemically inhibiting the process of coral recruitment. ?? 2011 Inter-Research.

  9. Chemically-mediated interactions between macroalgae Dictyota spp. and multiple life-history stages of the coral Porites astreoides

    USGS Publications Warehouse

    Paul, Valerie J.; Kuffner, Ilsa B.; Walters, Linda J.; Ritson-Williams, Raphael; Beach, Kevin S.; Becerro, Mikel A.

    2011-01-01

    Competition between corals and macroalgae is often assumed to occur on reefs, especially those that have undergone shifts from coral to algal dominance; however, data examining these competitive interactions, especially during the early life-history stages of corals, are scarce. We conducted a series of field and outdoor seawater-table experiments to test the hypothesis that allelopathy (chemical inhibition) mediates interactions between 2 common brown macroalgae, Dictyota pulchella and D. pinnatifida, and the coral Porites astreoides at different life-history stages of the coral. D. pinnatifida significantly reduced larval survival and larval recruitment. The extracts of both D. pinnatifida and D. pulchella significantly reduced larval survival, and the extract of D. pulchella also negatively influenced larval recruitment. There was no measurable effect of the crude extracts from Dictyota spp. on the photophysiology of adult corals. Our results provide evidence that these Dictyota species chemically compete with P. astreoides by negatively affecting larval settlement and recruitment as well as the survival of larvae and new recruits. Macroalgae may perpetuate their dominance on degraded reefs by chemically inhibiting the process of coral recruitment.

  10. Guide to using Multiple Regression in Excel (MRCX v.1.1) for Removal of River Stage Effects from Well Water Levels

    SciTech Connect

    Mackley, Rob D.; Spane, Frank A.; Pulsipher, Trenton C.; Allwardt, Craig H.

    2010-09-01

    A software tool was created in Fiscal Year 2010 (FY11) that enables multiple-regression correction of well water levels for river-stage effects. This task was conducted as part of the Remediation Science and Technology project of CH2MHILL Plateau Remediation Company (CHPRC). This document contains an overview of the correction methodology and a user’s manual for Multiple Regression in Excel (MRCX) v.1.1. It also contains a step-by-step tutorial that shows users how to use MRCX to correct river effects in two different wells. This report is accompanied by an enclosed CD that contains the MRCX installer application and files used in the tutorial exercises.

  11. A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle

    PubMed Central

    Chockalingam, Karuppiah; Simeon, Rudo L.; Rice, Charles M.; Chen, Zhilei

    2010-01-01

    The hepatitis C virus (HCV) life cycle involves multiple steps, but most current drug candidates target only viral replication. The inability to systematically discover inhibitors targeting multiple steps of the HCV life cycle has hampered antiviral development. We present a simple screen for HCV antivirals based on the alleviation of HCV-mediated cytopathic effect in an engineered cell line—n4mBid. This approach obviates the need for a secondary screen to avoid cytotoxic false-positive hits. Application of our screen to 1280 compounds, many in clinical trials or approved for therapeutic use, yielded >200 hits. Of the 55 leading hits, 47 inhibited one or more aspects of the HCV life cycle by >40%. Six compounds blocked HCV entry to levels similar to an antibody (JS-81) targeting the HCV entry receptor CD81. Seven hits inhibited HCV replication and/or infectious virus production by >100-fold, with one (quinidine) inhibiting infectious virus production by 450-fold relative to HCV replication levels. This approach is simple and inexpensive and should enable the rapid discovery of new classes of HCV life cycle inhibitors. PMID:20142494

  12. The Role of Postmastectomy Radiation Therapy After Neoadjuvant Chemotherapy in Clinical Stage II-III Breast Cancer Patients With pN0: A Multicenter, Retrospective Study (KROG 12-05)

    SciTech Connect

    Shim, Su Jung; Park, Won; Huh, Seung Jae; Choi, Doo Ho; Shin, Kyung Hwan; Lee, Nam Kwon; Suh, Chang-Ok; Keum, Ki Chang; Kim, Yong Bae; Ahn, Seung Do; Kim, Su Ssan; Ha, Sung W.; Chie, Eui Kyu; Kim, Kyubo; Shin, Hyun Soo; Kim, Jin Hee; Lee, Hyung-Sik

    2014-01-01

    Purpose: The purpose of this study was to investigate the role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) in clinical stage II-III breast cancer patients with pN0. Methods and Materials: We retrospectively identified 417 clinical stage II-III breast cancer patients who achieved an ypN0 at surgery after receiving NAC between 1998 and 2009. Of these, 151 patients underwent mastectomy after NAC. The effect of PMRT on disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and overall survival (OS) was evaluated by multivariate analysis including known prognostic factors using the Kaplan-Meier method and compared using the log–rank test and Cox proportional regression analysis. Results: Of the 151 patients who underwent mastectomy, 105 (69.5%) received PMRT and 46 patients (30.5%) did not. At a median follow-up of 59 months, 5 patients (3.3%) developed LRR (8 sites of recurrence) and 14 patients (9.3%) developed distant metastasis. The 5-year DFS, LRRFS, and OS rates were 91.2, 98.1, and 93.3% with PMRT and 83.0%, 92.3%, and 89.9% without PMRT, respectively (all P values not significant). By univariate analysis, only age (≤40 vs >40 years) was significantly associated with decreased DFS (P=.027). By multivariate analysis, age (≤40 vs >40 years) and pathologic T stage (0-is vs 1 vs 2-4) were significant prognostic factors affecting DFS (hazard ratio [HR] 0.353, 95% confidence interval [CI] 0.135-0.928, P=.035; HR 2.223, 95% CI 1.074-4.604, P=.031, respectively). PMRT showed no correlation with a difference in DFS, LRRFS, or OS by multivariate analysis. Conclusions: PMRT might not be necessary for pN0 patients after NAC, regardless of clinical stage. Prospective randomized clinical trial data are needed to assess whether PMRT can be safely omitted in pN0 patients after NAC and mastectomy for clinical stage II-III breast cancer.

  13. Hypofractionated High-Dose Proton Beam Therapy for Stage I Non-Small-Cell Lung Cancer: Preliminary Results of A Phase I/II Clinical Study

    SciTech Connect

    Hata, Masaharu . E-mail: mhata@syd.odn.ne.jp; Tokuuye, Koichi; Kagei, Kenji; Sugahara, Shinji; Nakayama, Hidetsugu; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Mizumoto, Masashi; Ohara, Kiyoshi; Akine, Yasuyuki

    2007-07-01

    Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade {>=}3 was observed. Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC.

  14. Improved survival rate in children with stage III and IV B cell non-Hodgkin's lymphoma and leukemia using multi-agent chemotherapy: results of a study of 114 children from the French Pediatric Oncology Society.

    PubMed

    Patte, C; Philip, T; Rodary, C; Bernard, A; Zucker, J M; Bernard, J L; Robert, A; Rialland, X; Benz-Lemoine, E; Demeocq, F

    1986-08-01

    Children with B cell non-Hodgkin's lymphoma who have not relapsed 1 year after diagnosis and treatment are generally cured. We report here the results of treatment in 114 children who all had a minimum follow-up of 20 months. The protocol LMB 0281 from the French Pediatric Oncology Society was used. This nine-drug intensive-pulsed chemotherapy was based on high-dose cyclophosphamide, high-dose methotrexate (HD MTX), and cytosine arabinoside (ara-C) in continuous infusion. CNS prophylaxis was with chemotherapy only. No local irradiation was performed. No debulking surgery was recommended. There were 72 patients with stage III lymphoma and 42 patients with stage IV lymphoma or B cell acute lymphocytic leukemia (B-ALL). Among those 42 patients, seven had CNS involvement alone, 21 had bone marrow alone, and 14 had both; 26 had greater than 25% blast cells in bone marrow, 14 of whom had blast cells in blood. The primary site of involvement was the abdomen in 90 patients, the Waldeyer Ring in nine, and various sites in eight; seven patients presented without tumor. Seventy-seven patients are alive with a median follow-up of 2 years and 8 months. Seven patients died due to initial treatment failure, 11 died from toxicity, and 19 died after relapse. Among the 93 patients without initial CNS involvement, only one isolated relapse in CNS occurred. Survival and disease-free survival rates reached 67% and 64%, respectively, for all patients, 75% and 73% for stage III patients and 54% and 48% for stage IV and B-ALL patients. Bone marrow involvement was not an adverse prognostic factor. Contrary initial CNS involvement indicated a bad prognosis with a disease-free survival rate of 19% compared with 76% without CNS disease. This study showed that CNS prophylaxis and local control of the primary tumor can be achieved by intensive chemotherapy alone, without radiotherapy or debulking surgery. PMID:3525767

  15. An inexact fuzzy-chance-constrained two-stage mixed-integer linear programming approach for flood diversion planning under multiple uncertainties

    NASA Astrophysics Data System (ADS)

    Guo, P.; Huang, G. H.; Li, Y. P.

    2010-01-01

    In this study, an inexact fuzzy-chance-constrained two-stage mixed-integer linear programming (IFCTIP) approach is developed for flood diversion planning under multiple uncertainties. A concept of the distribution with fuzzy boundary interval probability is defined to address multiple uncertainties expressed as integration of intervals, fuzzy sets and probability distributions. IFCTIP integrates the inexact programming, two-stage stochastic programming, integer programming and fuzzy-stochastic programming within a general optimization framework. IFCTIP incorporates the pre-regulated water-diversion policies directly into its optimization process to analyze various policy scenarios; each scenario has different economic penalty when the promised targets are violated. More importantly, it can facilitate dynamic programming for decisions of capacity-expansion planning under fuzzy-stochastic conditions. IFCTIP is applied to a flood management system. Solutions from IFCTIP provide desired flood diversion plans with a minimized system cost and a maximized safety level. The results indicate that reasonable solutions are generated for objective function values and decision variables, thus a number of decision alternatives can be generated under different levels of flood flows.

  16. Multiple Off-Ice Performance Variables Predict On-Ice Skating Performance in Male and Female Division III Ice Hockey Players.

    PubMed

    Janot, Jeffrey M; Beltz, Nicholas M; Dalleck, Lance D

    2015-09-01

    The purpose of this study was to determine if off-ice performance variables could predict on-ice skating performance in Division III collegiate hockey players. Both men (n = 15) and women (n = 11) hockey players (age = 20.5 ± 1.4 years) participated in the study. The skating tests were agility cornering S-turn, 6.10 m acceleration, 44.80 m speed, modified repeat skate, and 15.20 m full speed. Off-ice variables assessed were years of playing experience, height, weight and percent body fat and off-ice performance variables included vertical jump (VJ), 40-yd dash (36.58m), 1-RM squat, pro-agility, Wingate peak power and peak power percentage drop (% drop), and 1.5 mile (2.4km) run. Results indicated that 40-yd dash (36.58m), VJ, 1.5 mile (2.4km) run, and % drop were significant predictors of skating performance for repeat skate (slowest, fastest, and average time) and 44.80 m speed time, respectively. Four predictive equations were derived from multiple regression analyses: 1) slowest repeat skate time = 2.362 + (1.68 x 40-yd dash time) + (0.005 x 1.5 mile run), 2) fastest repeat skate time = 9.762 - (0.089 x VJ) - (0.998 x 40-yd dash time), 3) average repeat skate time = 7.770 + (1.041 x 40-yd dash time) - (0.63 x VJ) + (0.003 x 1.5 mile time), and 4) 47.85 m speed test = 7.707 - (0.050 x VJ) - (0.01 x % drop). It was concluded that selected off-ice tests could be used to predict on-ice performance regarding speed and recovery ability in Division III male and female hockey players. Key pointsThe 40-yd dash (36.58m) and vertical jump tests are significant predictors of on-ice skating performance specific to speed.In addition to 40-yd dash and vertical jump, the 1.5 mile (2.4km) run for time and percent power drop from the Wingate anaerobic power test were also significant predictors of skating performance that incorporates the aspect of recovery from skating activity.Due to the specificity of selected off-ice variables as predictors of on-ice performance, coaches can

  17. Multiple Off-Ice Performance Variables Predict On-Ice Skating Performance in Male and Female Division III Ice Hockey Players

    PubMed Central

    Janot, Jeffrey M.; Beltz, Nicholas M.; Dalleck, Lance D.

    2015-01-01

    The purpose of this study was to determine if off-ice performance variables could predict on-ice skating performance in Division III collegiate hockey players. Both men (n = 15) and women (n = 11) hockey players (age = 20.5 ± 1.4 years) participated in the study. The skating tests were agility cornering S-turn, 6.10 m acceleration, 44.80 m speed, modified repeat skate, and 15.20 m full speed. Off-ice variables assessed were years of playing experience, height, weight and percent body fat and off-ice performance variables included vertical jump (VJ), 40-yd dash (36.58m), 1-RM squat, pro-agility, Wingate peak power and peak power percentage drop (% drop), and 1.5 mile (2.4km) run. Results indicated that 40-yd dash (36.58m), VJ, 1.5 mile (2.4km) run, and % drop were significant predictors of skating performance for repeat skate (slowest, fastest, and average time) and 44.80 m speed time, respectively. Four predictive equations were derived from multiple regression analyses: 1) slowest repeat skate time = 2.362 + (1.68 x 40-yd dash time) + (0.005 x 1.5 mile run), 2) fastest repeat skate time = 9.762 - (0.089 x VJ) - (0.998 x 40-yd dash time), 3) average repeat skate time = 7.770 + (1.041 x 40-yd dash time) - (0.63 x VJ) + (0.003 x 1.5 mile time), and 4) 47.85 m speed test = 7.707 - (0.050 x VJ) - (0.01 x % drop). It was concluded that selected off-ice tests could be used to predict on-ice performance regarding speed and recovery ability in Division III male and female hockey players. Key points The 40-yd dash (36.58m) and vertical jump tests are significant predictors of on-ice skating performance specific to speed. In addition to 40-yd dash and vertical jump, the 1.5 mile (2.4km) run for time and percent power drop from the Wingate anaerobic power test were also significant predictors of skating performance that incorporates the aspect of recovery from skating activity. Due to the specificity of selected off-ice variables as predictors of on-ice performance, coaches

  18. Electron microscopic observation of the early stages of Cryptosporidium parvum asexual multiplication and development in in vitro axenic culture.

    PubMed

    Aldeyarbi, Hebatalla M; Karanis, Panagiotis

    2016-02-01

    The stages of Cryptosporidium parvum asexual exogenous development were investigated at high ultra-structural resolution in cell-free culture using transmission electron microscopy (TEM). Early C. parvum trophozoites were ovoid in shape, 1.07 × 1.47 μm(2) in size, and contained a large nucleus and adjacent Golgi complex. Dividing and mature meronts containing four to eight developing merozoites, 2.34 × 2.7 μm(2) in size, were observed within the first 24h of cultivation. An obvious peculiarity was found within the merozoite pellicle, as it was composed of the outer plasma membrane with underlying middle and inner membrane complexes. Further novel findings were vacuolization of the meront's residuum and extension of its outer pellicle, as parasitophorous vacuole-like membranes were also evident. The asexual reproduction of C. parvum was consistent with the developmental pattern of both eimerian coccidia and Arthrogregarinida (formerly Neogregarinida). The unique cell-free development of C. parvum described here, along with the establishment of meronts and merozoite formation, is the first such evidence obtained from in vitro cell-free culture at the ultrastructural level. PMID:26587578

  19. Electron microscopic observation of the early stages of Cryptosporidium parvum asexual multiplication and development in in vitro axenic culture.

    PubMed

    Aldeyarbi, Hebatalla M; Karanis, Panagiotis

    2016-02-01

    The stages of Cryptosporidium parvum asexual exogenous development were investigated at high ultra-structural resolution in cell-free culture using transmission electron microscopy (TEM). Early C. parvum trophozoites were ovoid in shape, 1.07 × 1.47 μm(2) in size, and contained a large nucleus and adjacent Golgi complex. Dividing and mature meronts containing four to eight developing merozoites, 2.34 × 2.7 μm(2) in size, were observed within the first 24h of cultivation. An obvious peculiarity was found within the merozoite pellicle, as it was composed of the outer plasma membrane with underlying middle and inner membrane complexes. Further novel findings were vacuolization of the meront's residuum and extension of its outer pellicle, as parasitophorous vacuole-like membranes were also evident. The asexual reproduction of C. parvum was consistent with the developmental pattern of both eimerian coccidia and Arthrogregarinida (formerly Neogregarinida). The unique cell-free development of C. parvum described here, along with the establishment of meronts and merozoite formation, is the first such evidence obtained from in vitro cell-free culture at the ultrastructural level.

  20. Impact of Body Mass Index and Weight Change After Treatment on Cancer Recurrence and Survival in Patients With Stage III Colon Cancer: Findings From Cancer and Leukemia Group B 89803

    PubMed Central

    Meyerhardt, Jeffrey A.; Niedzwiecki, Donna; Hollis, Donna; Saltz, Leonard B.; Mayer, Robert J.; Nelson, Heidi; Whittom, Renaud; Hantel, Alexander; Thomas, James; Fuchs, Charles S.

    2008-01-01

    Purpose Obesity is a risk factor for the development of colon cancer. However, the influence of body mass index (BMI) on the outcome of patients with established colon cancer remains uncertain. Moreover, the impact of change in body habitus after diagnosis has not been studied. Patients and Methods We conducted a prospective, observational study of 1,053 patients who had stage III colon cancer and who were enrolled on a randomized trial of adjuvant chemotherapy. Patients reported on height and weight during and 6 months after adjuvant chemotherapy. Patients were observed for cancer recurrence or death. Results In this cohort of patients with stage III cancer, 35% of patients were overweight (BMI, 25 to 29.9 kg/m2), and 34% were obese (BMI ≥ 30 kg/m2). Increased BMI was not significantly associated with a higher risk of colon cancer recurrence or death (P trend = .54). Compared with normal-weight patients (BMI, 21 to 24.9 kg/m2), the multivariate hazard ratio for disease-free survival was 1.00 (95% CI, 0.72 to 1.40) for patients with class I obesity (BMI, 30 to 34.9 kg/m2) and 1.24 (95% CI, 0.84 to 1.83) for those with class II to III obesity (BMI ≥ 35 kg/m2) after analysis was adjusted for tumor-related prognostic factors, physical activity, tobacco history, performance status, age, and sex. Similarly, after analysis was controlled for BMI, weight change (either loss or gain) during the time period between ongoing adjuvant therapy and 6 months after completion of therapy did not significantly impact on cancer recurrence and/or mortality. Conclusion Neither BMI nor weight change was significantly associated with an increased risk of cancer recurrence and death in patients with colon cancer. PMID:18757324

  1. Characterization of phthiocerol and phthiodiolone dimycocerosate esters of M. tuberculosis by multiple-stage linear ion-trap MS.

    PubMed

    Flentie, Kelly N; Stallings, Christina L; Turk, John; Minnaard, Adriaan J; Hsu, Fong-Fu

    2016-01-01

    Both phthiocerol/phthiodiolone dimycocerosate (PDIM) and phenolic glycolipids are abundant virulent lipids in the cell wall of various pathogenic mycobacteria, which can synthesize a wide range of complex high-molecular-mass lipids. In this article, we describe linear ion-trap MS(n) mass spectrometric approach for structural study of PDIMs, which were desorbed as the [M + Li](+) and [M + NH(4)](+) ions by ESI. We also applied charge-switch strategy to convert the mycocerosic acid substituents to their N-(4-aminomethylphenyl) pyridinium (AMPP) derivatives and analyzed them as M (+) ions, following alkaline hydrolysis of the PDIM to release mycocerosic acids. The structural information from MS(n) on the [M + Li](+) and [M + NH(4)](+) molecular species and on the M (+) ions of the mycocerosic acid-AMPP derivative affords realization of the complex structures of PDIMs in Mycobacterium tuberculosis biofilm, differentiation of phthiocerol and phthiodiolone lipid families and complete structure identification, including the phthiocerol and phthiodiolone backbones, and the mycocerosic acid substituents, including the locations of their multiple methyl side chains, can be achieved.

  2. Susceptibility of Brassica species to cauliflower mosaic virus infection is related to a specific stage in the virus multiplication cycle.

    PubMed

    Saunders, K; Lucy, A P; Covey, S N

    1990-08-01

    The relative susceptibilities and symptom responses of different Brassica species to infection by cauliflower mosaic virus (CaMV) have been compared and related to molecular events of the virus multiplication cycle. Variants of B. rapa (genome descriptor aa) were highly susceptible to infection by CaMV strain Cabb B-JI and contained relatively large amounts of virus; B. oleracea (cc) variants showed low susceptibility and contained small amounts of virus. B. nigra (bb) and allotetraploid species. B. juncea (aabb), B. napus (aacc) and B. carinata (bbcc), showed moderate responses to CaMV. CaMV unencapsidated DNA forms were isolated from different Brassica plants and examined by two-dimensional gel electrophoresis and blot hybridization. Viral RNA was estimated by dot blot analysis. These analyses showed differences in accumulation of key viral replication cycle intermediates within the broad range of host plants studied. The most susceptible species contained relatively small amounts of supercoiled (SC) DNA, a component of the CaMV mini-chromosome, but abundant viral transcripts and reverse transcription replication products. Tolerant plant hosts contained high levels of SC DNA but low levels of viral transcripts and reverse transcription DNA products. Allotetraploids contained SC DNA, RNA transcripts and replication product levels which were generally intermediate between those of their respective progenitor species. Evidence is presented that accumulation of CaMV SC DNA in the less susceptible host species is probably not due to autonomous DNA replication or tissue-specific expression. We conclude that a major component of the susceptibility of Brassica plants (and probably all CaMV host species) to CaMV infection is the level of viral minichromosome expression, influenced directly by the host genotype.

  3. Pain and Psychological Outcomes After Rehabilitative Treatment for a Woman With Chronic Pelvic Pain With Stage III Cervical Cancer: A Case Report

    PubMed Central

    Alappattu, Meryl J.

    2016-01-01

    Background Chronic pelvic pain and sexual dysfunction are adverse effects of treatment of cervical cancer. Surgery and radiation therapies may result in soft tissue pain and dysfunction, including spasms and trigger points of the pelvic floor muscles that result in pain. In addition to physical restrictions, negative mood associated with pain is believed to intensify and prolong the pain experience. Study Design The purpose of this case report was to describe outcomes of pelvic physical therapy in a 58-year-old woman with chronic pelvic pain after medical treatments for cervical cancer. Case Description The patient reported dyspareunia, hip pain, and lower abdominal, pelvic pain, and fatigue with activities lasting greater than 30 minutes. Interventions included pelvic floor massage, dilator use, and patient education. Symptoms were assessed at baseline and completion of physical therapy, using the Female Sexual Function Index, Fear of Pain Questionnaire–III, Pain Catastrophizing Scale, and Numerical Pain Rating Scale. Outcomes The Female Sexual Function Index score decreased from 7.8 to 2.8, the Fear of Pain Questionnaire– III score decreased from 85 to 73, the Pain Catastrophizing Scale score decreased from 18 to 8, and lower abdominal and pelvic pain decreased from 4 of 10 to 0 of 10, while bilateral hip pain remained at 4 of 10. In addition, she exhibited increased tolerance to mechanical pressure, evidenced by progression in size of a vaginal dilator. Discussion These results suggest that pelvic physical therapy may be useful in treating chronic pelvic pain after cervical cancer treatments and may also help decrease the magnitude of negative mood aspects such as pain-related fear and catastrophizing. PMID:27134605

  4. Effect of cumulative bortezomib dose on survival in multiple myeloma patients receiving bortezomib-melphalan-prednisone in the phase III VISTA study.

    PubMed

    Mateos, María Victoria; Richardson, Paul G; Dimopoulos, Meletios A; Palumbo, Antonio; Anderson, Kenneth C; Shi, Hongliang; Elliott, Jennifer; Dow, Edward; van de Velde, Helgi; Niculescu, Liviu; San Miguel, Jesús F

    2015-04-01

    This analysis, using data from the bortezomib-melphalan-prednisone (VMP) arm of the Phase III VISTA study, investigated whether increased cumulative bortezomib dose could improve overall survival (OS) in transplant-ineligible patients with previously untreated multiple myeloma. Median cumulative bortezomib dose received by the 340 patients was 39 mg/m(2); this was selected as the cut-off for defining the dose groups to be compared for OS. Patient characteristics were well balanced between dose groups except for age. OS was significantly longer in the higher (≥39 mg/m(2)) versus lower (<39 mg/m(2)) cumulative bortezomib dose group (median 66.3 vs. 46.2 months; hazard ratio (HR) 0.533, P < 0.0001; age-adjusted HR 0.561, P = 0.0002). To overcome confounding effects of early discontinuations/deaths, which were more common in the lower cumulative dose group (27 vs. 4% of patients discontinued due to adverse events (AEs) in the lower and higher cumulative dose groups, respectively), a landmark analysis was conducted at 180 days, eliminating patients who died or discontinued before this time from the analysis. OS from this landmark remained significantly longer in the higher dose group (median 60.4 vs. 50.3 months; HR 0.709, P = 0.0372). Thus, higher cumulative bortezomib dose, reflecting prolonged treatment duration and/or dose intensity, appears associated with improved OS. Approaches to achieve higher cumulative doses could include subcutaneous bortezomib administration, dose/schedule modifications, continuing therapy in responding patients, and proactive AE management.

  5. Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

    PubMed Central

    Weisel, Katja C.; Dimopoulos, Meletios A.; Moreau, Philippe; Lacy, Martha Q.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrian; Chen, Christine; Cavo, Michele; Garderet, Laurent; Ivanova, Valentina; Martinez-Lopez, Joaquin; Knop, Stefan; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Miguel, Jesus San

    2016-01-01

    Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. PMID:27081177

  6. A Phase II Study of Synchronous Three-Dimensional Conformal Boost to the Gross Tumor Volume for Patients With Unresectable Stage III Non-Small-Cell Lung Cancer: Results of Korean Radiation Oncology Group 0301 Study

    SciTech Connect

    Cho, Kwan Ho Ahn, Sung Ja; Pyo, Hong Ryull; Kim, Kyu-Sik; Kim, Young-Chul; Moon, Sung Ho; Han, Ji-Youn; Kim, Heung Tae; Koom, Woong Sub; Lee, Jin Soo

    2009-08-01

    Purpose: We evaluated the efficacy of synchronous three-dimensional (3D) conformal boost to the gross tumor volume (GTV) in concurrent chemoradiotherapy for patients with locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Eligibility included unresectable Stage III NSCLC with no pleural effusion, no supraclavicular nodal metastases, and Eastern Cooperative Oncology Group performance score of 0-1. Forty-nine patients with pathologically proven NSCLC were enrolled. Eighteen patients had Stage IIIA and 31 had Stage IIIB. By using 3D conformal radiotherapy (RT) techniques, a dose of 1.8 Gy was delivered to the planning target volume with a synchronous boost of 0.6 Gy to the GTV, with a total dose of 60 Gy to the GTV and 45 Gy to the planning target volume in 25 fractions during 5 weeks. All patients received weekly chemotherapy consisting of paclitaxel and carboplatin during RT. Results: With a median follow-up of 36.8 months (range, 29.0-45.5 months) for surviving patients, median survival was 28.1 months. One-, 2- and 3-year overall survival rates were 77%, 56.4%, and 43.8%, respectively. Corresponding local progression-free survival rates were 71.2%, 53.7%, and 53.7%. Compliance was 90% for RT and 88% for chemotherapy. Acute esophagitis of Grade 2 or higher occurred in 29 patients. Two patients with T4 lesions died of massive bleeding and hemoptysis during treatment (Grade 5). Overall late toxicity was acceptable. Conclusions: Based on the favorable outcome with acceptable toxicity, the acceleration scheme using 3D conformal GTV boost in this trial is warranted to compare with conventional fractionation in a Phase III trial.

  7. Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population-based series and a randomized phase III study on adjuvant chemotherapy.

    PubMed

    Boye, Kjetil; Jacob, Havjin; Frikstad, Kari-Anne M; Nesland, Jahn M; Maelandsmo, Gunhild M; Dahl, Olav; Nesbakken, Arild; Flatmark, Kjersti

    2016-08-01

    Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis-promoting protein S100A4 predicts poor outcome in colorectal cancer, but whether it could be used to guide clinical decision making remains to be resolved. S100A4 expression was analyzed by immunohistochemistry in primary colorectal carcinomas from a consecutively collected, population-representative cohort and a randomized phase III study on adjuvant 5-fluorouracil/levamisole. Sensitivity to treatment with 5-fluorouracil in S100A4 knockdown cells was investigated using 2D and 3D cell culture assays. Strong nuclear expression of S100A4 was detected in 19% and 23% of the tumors in the two study cohorts, respectively. In both cohorts, nuclear immunoreactivity was associated with reduced relapse-free (P < 0.001 and P = 0.010) and overall survival (P = 0.046 and P = 0.006) in univariate analysis. In multivariate analysis, nuclear S100A4 was a predictor of poor relapse-free survival in the consecutive series (P = 0.002; HR 1.9), but not in the randomized study. Sensitivity to treatment with 5-fluorouracil was not affected by S100A4 expression in in vitro cell culture assays, and there was no indication from subgroup analyses in the randomized study that S100A4 expression was associated with increased benefit of adjuvant treatment with 5-fluorouracil/levamisole. The present study confirms that nuclear S100A4 expression is a negative prognostic biomarker in colorectal cancer, but the clinical utility in selection of patients for adjuvant fluoropyrimidine-based chemotherapy is limited. PMID:27273130

  8. Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in stage III-IVb nasopharyngeal carcinoma patients with Epstein-Barr virus DNA ≥4000 copies/ml: a matched study

    PubMed Central

    Chen, Qiu-Yan; Zhang, Lu; Liu, Li-Ting; Guo, Ling; Mo, Hao-Yuan; Luo, Dong-Hua; Huang, Pei-Yu; Xiang, Yan-Qun; Sun, Rui; Chen, Ming-Yuan; Wang, Lin; Lv, Xing; Zhao, Chong; Guo, Xiang; Cao, Ka-Jia; Qian, Chao-Nan; Zeng, Mu-Shen; Bei, Jin-Xin; Hong, Ming-Huang; Shao, Jian-Yong; Sun, Ying; Ma, Jun; Mai, Hai-Qiang

    2016-01-01

    Background The effects of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in high-risk (stage III-IVb with EBV DNA≥4000 copies/ml) nasopharyngeal carcinoma (NPC) patients are unclear. Methods A total of 325 high-risk NPC patients treated with IC+CCRT or CCRT alone who were treated with intensity-modulated radiation therapy (IMRT) between March 2007 and March 2013 were included. For each patient in the IC+CCRT group, a matched pair in the CCRT group was matching for: gender, age, T stage, N stage, clinical stage and WHO (World Health Organization) type. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS). Results There were no significant differences in OS, PFS, DMFS, and LRFS between the IC+CCRT (148 patients) and CCRT (177 patients) groups. After matching, 103 paired patients were analyzed, and there were no differences between the IC+CCRT and CCRT groups regarding clinical outcomes. Based on the subgroup analysis of 156 very-high-risk patients (stage N2-3 with EBV DNA ≥4000 copies/ml), the 5-year OS of the IC+CCRT and CCRT groups was 84.3% and 67.5% (P =0.033), respectively. Based on our multivariate analysis, the treatment group was significantly associated with OS (P=0.034; HR0.451, 95%CI 0.216-0.941). Conclusions IC+CCRT did not improve the clinical outcomes of high-risk NPC patients compared to CCRT alone. However, in very-high-risk patients, IC+CCRT treatment led to increased OS compared to patients received CCRT treatment alone. PMID:27105538

  9. Consolidation chemotherapy improves progression-free survival in stage III small-cell lung cancer following concurrent chemoradiotherapy: a retrospective study

    PubMed Central

    Chen, Xin-Ru; Liang, Jian-Zhong; Ma, Shu-Xiang; Fang, Wen-Feng; Zhou, Ning-Ning; Liao, Hai; Li, De-Lan; Chen, Li-Kun

    2016-01-01

    Background Concurrent chemoradiotherapy (CCRT) is the standard treatment for limited-stage small-cell lung cancer (LD-SCLC). However, the efficacy of consolidation chemotherapy (CCT) in LD-SCLC remains controversial despite several studies that were performed in the early years of CCT use. The aim of this study was to reevaluate the effectiveness and toxicities associated with CCT. Methods This retrospective analysis evaluated 177 patients with stage IIIA and IIIB small-cell lung cancer (SCLC) who underwent CCRT from January 2001 to December 2013 at Sun Yat-Sen University Cancer Center (SYSUCC). Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier methods. Univariate and multivariate analyses were performed to analyze patient prognosis factors. Results Among the 177 patients, 72 (41%) received CCT and 105 (59%) did not receive CCT. PFS was significantly better for patients in the CCT group compared to that for patients in the non-CCT group (median PFS: 17.0 vs 12.9 months, respectively, P=0.031), whereas the differences in OS were not statistically significant (median OS: 31.6 vs 24.8 months, respectively, P=0.118). The 3- and 5-year OS rates were 33.3% and 20.8% for patients in the CCT group and 27.6% and 6.7% for patients in the non-CCT group, respectively. Multivariate analysis revealed that having a pretreatment carcinoembryonic antigen level <5 ng/mL (P=0.035), having undergone prophylactic cranial irradiation (P<0.001), and having received CCT (P=0.002) could serve as favorable independent prognostic factors for PFS. Multivariate analysis for OS also showed that having undergone PCI (P<0.001) and having received CCT (P=0.006) were independent significant prognostic factors. Conclusion CCT can improve PFS for patients with stage IIIA and IIIB SCLC following CCRT without significantly increasing treatment-related toxicities. PMID:27703372

  10. Multiple stages of carbonation and brecciation in a peridotite from the ultra-slow spreading Gakkel Ridge

    NASA Astrophysics Data System (ADS)

    Von Der Handt, A.; Menzel, M.; Oencue, A.; Danilewsky, A. N.; Hellebrand, E.; Kluegel, A.; Snow, J. E.

    2013-12-01

    Carbonate breccias and carbonate veins have been described from fossil and modern day ocean floor peridotites. Their fabric can vary from fractured serpentinite to clast-supported in-situ breccia to matrix-supported breccia. It has been shown that hydrothermal flow is partly responsible for carbonation of seafloor lithologies as well as fluids from serpentinization reactions and low-temperature precipitation from seawater. Therefore, the study of carbonated peridotites can provide important information on fluid flow and fluid-rock interaction at the sea floor and give implications for the global carbon cycle as well as carbon sequestration. We carried out a detailed petrographic, geochemical and microstructural study of a peridotite breccia that contains texturally and compositionally complex carbonate veins. The sample was dredged in the Sparsely Magmatic Zone of the ultraslow-spreading Gakkel Ridge where a magmatic cover is missing and only mantle rocks are exposed for more than 100 km in the axial valley. The sample, a harzburgitic mylonite, is brecciated in places with angular to sub-angular clasts cemented by carbonates. Narrow (0.1- 5 mm) carbonate veins crosscut the sample and make-up around 20% of the sample. A prominent up to 12 mm wide carbonate vein records the interplay of brecciation and carbonate-forming reactions. Mg-calcite (9 mol% Mg) and aragonite occur in the proportion 30:70 in the central vein while thin crosscutting veins consist dominantly of Mg-calcite. Multiple generations of carbonates can be discerned in the central vein, alternating between Mg-calcite and aragonite. The earliest carbonate generation consists of fibrous overgrowths on serpentine veins suggesting an early link between carbonation and serpentinization reactions. Furthermore, bend aragonite needles indicate syntectonic growth. The next generation consists of spherulitic aragonites that are in places brecciated and cemented by a Mg-calcite matrix. Notably, the following

  11. The Number of Positive Pelvic Lymph Nodes and Multiple Groups of Pelvic Lymph Node Metastasis Influence Prognosis in Stage IA–IIB Cervical Squamous Cell Carcinoma

    PubMed Central

    Liu, Yu; Zhao, Li-Jun; Li, Ming-Zhu; Li, Ming-Xia; Wang, Jian-Liu; Wei, Li-Hui

    2015-01-01

    Background: Pelvic lymph node metastasis (LNM) is an important prognostic factor in cervical cancer. Cervical squamous cell carcinoma accounts for approximately 75–80% of all cervical cancers. Analyses of the effects of the number of positive lymph nodes (LNs), unilateral versus bilateral pelvic LNM and a single group versus multiple groups of pelvic LNM on survival and recurrence of cervical squamous cell carcinoma are still lacking. The study aimed to analyze the effects of the number of positive pelvic LNs and a single group versus multiple groups of pelvic LNM on survival and recurrence. Methods: We performed a retrospective review of 296 patients diagnosed with Stage IA–IIB cervical squamous cell carcinoma who received extensive/sub-extensive hysterectomy with pelvic lymphadenectomy/pelvic LN sampling at Peking University People's Hospital from November 2004 to July 2013. Ten clinicopathological variables were evaluated as risk factors for pelvic LNM: Age at diagnosis, gravidity, clinical stage, histological grade, tumor diameter, lymph-vascular space involvement (LVSI), depth of cervical stromal invasion, uterine invasion, parametrial invasion, and neoadjuvant chemotherapy. Results: The incidence of pelvic LNM was 20.27% (60/296 cases). Pelvic LNM (P = 0.00) was significantly correlated with recurrence. Pelvic LNM (P = 0.00), the number of positive pelvic LNs (P = 0.04) and a single group versus multiple groups of pelvic LNM (P = 0.03) had a significant influence on survival. Multivariate analysis revealed that LVSI (P = 0.00), depth of cervical stromal invasion (P = 0.00) and parametrial invasion (P = 0.03) were independently associated with pelvic LNM. Conclusions: Patients with pelvic LNM had a higher recurrence rate and poor survival outcomes. Furthermore, more than 2 positive pelvic LNs and multiple groups of pelvic LNM appeared to identify patients with worse survival outcomes in node-positive IA-IIB cervical squamous cell carcinoma. LVSI

  12. Two or Three Year Disease Free Survival (DFS) as a Primary Endpoint in Stage III Adjuvant Colon Cancer Trials with fluoropyrimidines with or without Oxaliplatin or Irinotecan: Data from 12,676 patients from MOSAIC, X-ACT, PETACC-3, C-06, C-07, and C89803

    PubMed Central

    Sargent, D; Shi, Q; Yothers, G; Van Cutsem, E; Cassidy, J; Saltz, L; Wolmark, N; Bot, B; Grothey, A; Buyse, M; de Gramont, A

    2011-01-01

    Summary Background The ACCENT group previously established disease-free survival (DFS) with 2 or 3 years median follow-up to predict 5 year overall survival (5yr OS) in stage II and III colon cancer. ACCENT further proposed (1) a stronger association between DFS and OS in stage III than II, and (2) 6 or 7 years necessary to demonstrate DFS/OS surrogacy in recent trials. The relationship between endpoints in trials with oral fluoropyrimidines, oxaliplatin, and irinotecan is unknown. Methods Associations between the treatment effect hazard ratios (HRs) on 2 and 3yr DFS, and 5 and 6yr OS were examined in 6 phase III trials not included in prior analyses from 1997-2002. Individual data for 12,676 patients were analyzed; two trials each tested oxaliplatin, irinotecan, and oral treatment vs 5-FU/LV. Findings Overall association between 2/3 yr DFS and 5/6 yr OS HRs was modest to poor (simple R2 measures: 0.58 to 0.76, model-based R2: 0.17 to 0.49). In stage III patients, the association increased (model-based R2≥0.79). Observed treatment effects on 2 yr DFS accurately 5/6 yr OS effects overall and in stage III patients. Interpretation In recent trials of cytotoxic chemotherapy, 2 or 3yr DFS HRs are highly predictive of 5 and 6yr OS HRs in stage III but not stage II patients. In all patients the DFS/OS association is stronger for 6yr OS, thus at least 6 year follow-up is recommended to assess OS benefit. These data support DFS as the primary endpoint for stage III colon cancer trials testing cytotoxic agents. Funding Funded by NCI Grant CA-25224 to the Mayo Clinic to support the North Central Cancer Treatment Group. PMID:21257306

  13. Structural Distinction of Diacyl-, Alkylacyl, and Alk-1-Enylacyl Glycerophosphocholines as [M - 15]- Ions by Multiple-Stage Linear Ion-Trap Mass Spectrometry with Electrospray Ionization

    NASA Astrophysics Data System (ADS)

    Hsu, Fong-Fu; Lodhi, Irfan J.; Turk, John; Semenkovich, Clay F.

    2014-08-01

    We describe a linear ion-trap (LIT) multiple-stage (MSn) mass spectrometric approach towards differentiation of alkylacyl, alk-1-enylacyl- and diacyl-glycerophoscholines (PCs) as the [M - 15]- ions desorbed by electrospray ionization (ESI) in the negative-ion mode. The MS4 mass spectra of the [M - 15 - R2'CH = CO]- ions originated from the three PC subfamilies are readily distinguishable, resulting in unambiguous distinction of the lipid classes. This method is applied to two alkyl ether rich PC mixtures isolated from murine bone marrow neutrophils and kidney, respectively, to explore its utility in the characterization of complex PC mixture of biological origin, resulting in the realization of the detailed structures of the PC species, including various classes and many minor isobaric isomers.

  14. Overall and blade-element performance of a transonic compressor stage with multiple-circular-arc blades at tip speed of 419 meters per second

    NASA Technical Reports Server (NTRS)

    Kovich, G.; Reid, L.

    1973-01-01

    A 50-centimeter-diameter axial-flow transonic compressor stage with multiple-circular-arc blades was designed and tested to study the effects of blade shape on efficiency and stall margin. At design speed, peak efficiency of 0.80 occurred at an equivalent weight flow of 29.0 kilograms per second. Measured total pressure ratio and total temperature ratio at peak efficiency were 1.69 and 1.20, respectively. The stall margin at design speed and an equivalent weight flow of 29.0 kilograms per second was 9 percent. The measured stall margin at design weight flow and speed was 15 percent. A comparison of rotor performance made with and without the stator showed a decrease in pressure ratio, peak efficiency, and maximum weight flow with the addition of the stator.

  15. The general theory of multistage geminate reactions of isolated pairs of reactants. III. Two-stage reversible dissociation in geminate reaction A + A↔C↔B + B

    NASA Astrophysics Data System (ADS)

    Kipriyanov, Alexey A.; Kipriyanov, Alexander A.; Doktorov, Alexander B.

    2016-04-01

    Specific two-stage reversible reaction A + A↔C↔B + B of the decay of species C reactants by two independent transition channels is considered on the basis of the general theory of multistage reactions of isolated pairs of reactants. It is assumed that at the initial instant of time, the reacting system contains only reactants C. The employed general approach has made it possible to consider, in the general case, the inhomogeneous initial distribution of reactants, and avoid application of model concepts of a reaction system structure (i.e., of the structure of reactants and their molecular mobility). Slowing of multistage reaction kinetics as compared to the kinetics of elementary stages is established and physically interpreted. To test approximations (point approximation) used to develop a universal kinetic law, a widely employed specific model of spherical particles with isotropic reactivity diffusing in solution is applied. With this particular model as an example, ultimate kinetics of chemical conversion of reactants is investigated. The question concerning the depths of chemical transformation at which long-term asymptotes are reached is studied.

  16. How does community context influence coalitions in the formation stage? a multiple case study based on the Community Coalition Action Theory

    PubMed Central

    2010-01-01

    Background Community coalitions are rooted in complex and dynamic community systems. Despite recognition that environmental factors affect coalition behavior, few studies have examined how community context impacts coalition formation. Using the Community Coalition Action theory as an organizing framework, the current study employs multiple case study methodology to examine how five domains of community context affect coalitions in the formation stage of coalition development. Domains are history of collaboration, geography, community demographics and economic conditions, community politics and history, and community norms and values. Methods Data were from 8 sites that participated in an evaluation of a healthy cities and communities initiative in California. Twenty-three focus groups were conducted with coalition members, and 76 semi-structured interviews were conducted with local coordinators and coalition leaders. Cross-site analyses were conducted to identify the ways contextual domains influenced selection of the lead agency, coalition membership, staffing and leadership, and coalition processes and structures. Results History of collaboration influenced all four coalition factors examined, from lead agency selection to coalition structure. Geography influenced coalition formation largely through membership and staffing, whereas the demographic and economic makeup of the community had an impact on coalition membership, staffing, and infrastructure for coalition processes. The influence of community politics, history, norms and values was most noticeable on coalition membership. Conclusions Findings contribute to an ecologic and theory-based understanding of the range of ways community context influences coalitions in their formative stage. PMID:20178633

  17. Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent

    ClinicalTrials.gov

    2016-02-15

    Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Serous Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  18. Performance of Single-Stage Turbine of Mark 25 Torpedo Power Plant with Two Special Nozzles. III; Efficiency with Standard Rotor Blades

    NASA Technical Reports Server (NTRS)

    Schum, Harold J.; Whitney, Warren J.

    1949-01-01

    A Mark 25 torpedo power plant modified to operate as a single-stage turbine was investigated to determine the performance with two nozzle designs and a standard first-stage rotor having 0.40-inch blades with a 17O met-air angle. Both nozzles had smaller port cross-sectional areas than those nozzles of similar design, which were previously investigated. The performance of the two nozzles was compared on the basis of blade, rotor, and brake efficiencies as a function of blade-jet speed ratio for pressure ratios of 8, 15 (design), and 20. At pressure ratios of 15 and 20, the blade efficiency obtained with the nozzle having circular passages (K) was higher than that obtained with the nozzle having rectangular passages (J). At a pressure ratio of 8, the efficiencies obtained with the two nozzles were comparable for blade-jet speed ratios of less than 0.260. For blade-jet speed ratios exceeding this value, nozzle K yielded slightly higher efficiencies. The maximum blade efficiency of 0.569 was obtained with nozzle K at a pressure ratio of 8 and a blade-jet speed ratio of 0.295. At design speed and pressure ratio, nozzle K yielded a maximum blade efficiency of 0.534, an increase of 0.031 over that obtained with nozzle J. When the blade efficiencies of the two nozzles were compared with those of four other nozzles previously investigated, the maximum difference for the six nozzles with this rotor was 0.050. From, this comparison, no specific effect of nozzles size or shape on over-all performance was discernible.

  19. Mining Missing Membrane Proteins by High-pH Reverse Phase StageTip Fractionation and Multiple Reaction Monitoring Mass Spectrometry

    PubMed Central

    Kitata, Reta Birhanu; Dimayacyac-Esleta, Baby Rorielyn T.; Choong, Wai-Kok; Tsai, Chia-Feng; Lin, Tai-Du; Tsou, Chih-Chiang; Weng, Shao-Hsing; Chen, Yi-Ju; Yang, Pan-Chyr; Arco, Susan D.; Nesvizhskii, Alexey I.; Sung, Ting-Yi; Chen, Yu-Ju

    2016-01-01

    Despite significant efforts in the past decade towards complete mapping of the human proteome, 3564 proteins (neXtProt, 09-2014) are still “missing proteins”. Over one-third of these missing proteins are annotated as membrane proteins, owing to their relatively challenging accessibility with standard shotgun proteomics. Using non-small cell lung cancer (NSCLC) as a model study, we aim to mine missing proteins from