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Sample records for chemotherapy improves survival

  1. Preoperative Chemotherapy, Radiation Improve Survival in Esophageal Cancer (Updated)

    Science.gov (United States)

    Patients with esophageal cancer who received chemotherapy and radiation before surgery survived, on average, nearly twice as long as patients treated with surgery alone, according to results of a randomized clinical trial published May 31, 2012, in NEJM.

  2. Improved survival with early adjuvant chemotherapy after colonic resection for stage III colonic cancer

    DEFF Research Database (Denmark)

    Klein, Mads; Azaquoun, Najah; Jensen, Benny Vittrup

    2015-01-01

    BACKGROUND AND OBJECTIVES: In stage III colonic cancer, time from surgery to start of adjuvant chemotherapy may influence survival. In this study, we evaluated the effect of timing of adjuvant therapy on survival. METHODS: Database study from the Danish Colorectal Cancer Group's national database....... RESULTS: The final population included 1,827 patients scheduled for adjuvant chemotherapy. Adjuvant therapy started within 4 and 8 weeks improved survival when compared to start later than 8 weeks (HR [95%CI]: 1.7 [1.1-2.6]; P = 0.024 and 1.4 [1.07-1.8]; P = 0.013, respectively), whereas...

  3. Increased tumour ADC value during chemotherapy predicts improved survival in unresectable pancreatic cancer

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    Nishiofuku, Hideyuki; Tanaka, Toshihiro; Kichikawa, Kimihiko [Nara Medical University, Department of Radiology and IVR Center, Kashihara-city, Nara (Japan); Marugami, Nagaaki [Nara Medical University, Department of Endoscopy and Ultrasound, Kashihara-city, Nara (Japan); Sho, Masayuki; Akahori, Takahiro; Nakajima, Yoshiyuki [Nara Medical University, Department of Surgery, Kashihara-city, Nara (Japan)

    2016-06-15

    To investigate whether changes to the apparent diffusion coefficient (ADC) of primary tumour in the early period after starting chemotherapy can predict progression-free survival (PFS) or overall survival (OS) in patients with unresectable pancreatic adenocarcinoma. Subjects comprised 43 patients with histologically confirmed unresectable pancreatic cancer treated with first-line chemotherapy. Minimum ADC values in primary tumour were measured using the selected area ADC (sADC), which excluded cystic and necrotic areas and vessels, and the whole tumour ADC (wADC), which included whole tumour components. Relative changes in ADC were calculated from baseline to 4 weeks after initiation of chemotherapy. Relationships between ADC and both PFS and OS were modelled by Cox proportional hazards regression. Median PFS and OS were 6.1 and 11.0 months, respectively. In multivariate analysis, sADC change was the strongest predictor of PFS (hazard ratio (HR), 4.5; 95 % confidence interval (CI), 1.7-11.9; p = 0.002). Multivariate Cox regression analysis for OS revealed sADC change and CRP as independent predictive markers, with sADC change as the strongest predictive biomarker (HR, 6.7; 95 % CI, 2.7-16.6; p = 0.001). Relative changes in sADC could provide a useful imaging biomarker to predict PFS and OS with chemotherapy for unresectable pancreatic adenocarcinoma. (orig.)

  4. Multimodality therapy including radiotherapy and chemotherapy improves event-free survival in stage C esthesioneuroblastoma

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    Eich, H.T.; Staar, S.; Mueller, R.P. [Dept. of Radiotherapy, Univ. of Cologne (Germany); Hero, B.; Berthold, F. [Dept. of Pediatric Oncology, Children' s Hospital, Univ. of Cologne (Germany); Micke, O. [Dept. of Radiotherapy, Univ. of Muenster (Germany); Seegenschmiedt, H. [Dept. of Radiotherapy, Alfried Krupp Hospital, Essen (Germany); Mattke, A. [Children' s Hospital, Olgaspital, Stuttgart (Germany)

    2003-04-01

    Background: To evaluate the efficacy of multimodality therapy in patients with esthesioneuroblastoma (ENB). Patients and Methods: From 01/1979 through 08/2001, 47 patients with ENB (20 men, 27 women, age 5-81 years), were registered from 18 oncologic centers. There were 14 tumors stage B and 33 stage C according to the Kadish classification. Initial treatment included surgery alone in seven patients, radiotherapy (RT) with or without chemotherapy (CTX) in twelve, surgery plus postoperative RT in 15, and multimodality therapy (surgery plus pre- or postoperative CTX plus postoperative RT) in 13. Results: The 5-year overall survival (OS) for the whole group was 64 {+-} 8% and the 5-year event-free survival (EFS) 50 {+-} 8%. Patients with multimodality treatment had a significantly better 5-year EFS (74 {+-} 13%) compared to the other patients (41 {+-} 9%; p = 0.05), while the 5-year OS was not significantly different between the treatment groups (p = 0.39). For patients with Kadish stage C, multimodality therapy (n = 11) resulted in superior 5-year EFS (72 {+-} 14% vs 17 {+-} 9%; p = 0.01). These patients tended to have an improved OS (69 {+-} 15% vs 47 {+-} 12%; p = 0.19) compared to the other treatment groups. None of the patients with multimodality treatment had a metastatic relapse. Conclusion: Multimodality treatment (surgery plus pre- or postoperative CTX plus postoperative RT) appears to be highly efficient in preventing local and systemic relapse in patients with advanced ENB. Timing and optimal agents of CTX need to be further evaluated. (orig.)

  5. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia

    DEFF Research Database (Denmark)

    Burnett, Alan K; Russell, Nigel H; Hills, Robert K

    2012-01-01

    PURPOSE There has been little survival improvement in older patients with acute myeloid leukemia (AML) in the last two decades. Improving induction treatment may improve the rate and quality of remission and consequently survival. In our previous trial, in younger patients, we showed improved sur...

  6. Effect of Neoadjuvant Chemotherapy on Improvement of Surgical Resectibility and Survival of Patients with Stage ⅢA Non Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    LIJian; YULichao; 等

    2002-01-01

    Ojbective To assess the effect of neoadjuvant chemotherapy on surgical resectibility and survival in patients with stage ⅢA non small cell lung cancer(NSCLC).Methods 42 patients with stage ⅢA NSCLC were randomized to receive either two cycles chemotherapy followed by surgery(neoadjuvant chemotherapy group)or surgery alone(surgery alone group).All patients received four cycles chemotherapy after surgery.Results The overall response to chemotherapy was 42.9%(38.1% partial response and 4.8% complete response).Toxicity of chemotherapy was minor and consisted mainly of gastroenterological side effects and myelosuppression.Patients treated with neoadjuvant chemotherapy had estimated surgical resection rate of 95.2%(n=20)and a complete resection rate in 52.4%(n=11) compared to 66.7%(n=14)and 28.6%(n=6)respectively,for patients with surgery alone(P<0.05).None of the patients died from the operation.The median survival was 24.6 months in the neoadjuvant chemotherapy group as compared to only 10.8 months in the surgery alone group(P<0.05).The 2-year survival rate was 57.1% in the chemotherapy group as compared to 28.6% in the surgery alone group(P<0.05).Conclusion Neoadjuvant chemotherapy improves the surgical resectibility and increases the median survival and 2-year survival rate of patients with stage ⅢA NSCLC.

  7. Modern induction chemotherapy before chemoradiation for bulky locally-advanced nonsmall cell lung cancer improves survival

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    Inaya Ahmed

    2016-01-01

    Conclusion: In patients with large tumors or bulky nodal NSCLC, carboplatin-based induction chemotherapy may be an important addition to definitive CCRT in the modern era. Our findings strongly support further investigation induction chemotherapy in this population.

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

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    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.

  9. Adding Chemotherapy to Radiation Improves Survival for Some Patients with Rare Brain Cancer

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    Long-term results from two clinical trials confirm that certain patients with anaplastic oligodendrogliomas live substantially longer if they are treated with a combination of chemotherapy and radiation therapy rather than radiatiation alone.

  10. Short-term Intensive Neoadjuvant Chemotherapy Improving 10-year Survival for Patients with Stage Ⅱ and Operable Stage Ⅲ Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    BinZhang; YueCai; QiZhang; ZiweiYing; ShulingJiang; HongXu; YongxueZheng; DaqingJiang

    2004-01-01

    OBJECTIVE To evaluate the 10-year curative effects of short-term intensive neoadjuvant chemotherapy for operable breast cancer. METHODS A total of 510 patients with stagell and operable stagelll breast cancer were divided into group A (preoperative neoadjuvant chemotherapy 251 cases) and group B (postoperative adjuvant chemotherapy 259 cases). The patients in group A received short-term and intensive neoadjuvant chemotherapy for 4 weeks followed by modified radical mastectomy two weeks after the chemotherapy. The postoperative adjuvant chemotherapy began within two weeks after surgery. The same chemotherapeutic regimen was used for both groups. RESULTS For stage Ⅲ in group A the 5-year overall survival rate (OS) and disease-free survival rate (DFS) were 59.2% and 54.9% respectively which were higher than those in group B (28.3% and 20.8% respectively, P<0.05). The 10-year OS and DFS were 78.1% and 73.5% respectively for stage Ⅱ in group A which were higher than those in group B (68.4% and 60.7%, P<0.05). The 10-year OS and DFS were 42.3% and 40.4% respectively forstage Ⅲ in group A which were higher than those in group B (20.4% and 18.4% respectively, P<0.05). CONCLUSION The results showed that intensive neoadjuvant chemotherapy can improve the 10-year survival for patients with stage Ⅱ and operablestage Ⅲ breast cancer.

  11. Addition of an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy improves survival in advanced malignancies.

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    Lasalvia-Prisco, Eduardo; Goldschmidt, Pablo; Galmarini, Felipe; Cucchi, Silvia; Vázquez, Jesús; Aghazarian, Martha; Lasalvia-Galante, Eduardo; Golomar, Wilson; Gordon, William

    2012-12-01

    Studies have shown that cancer requires two conditions for tumor progression: cancer cell proliferation and an environment permissive to and conditioned by malignancy. Chemotherapy aims to control the number and proliferation of cancer cells, but it does not effectively control the two best-known conditions of the tumor-permissive environment: neoangiogenesis and tolerogenic immunity. Many malignant diseases exhibit poor outcomes after treatment with chemotherapy. Therefore, we investigated the potential benefits of adding an induction regimen of antiangiogenesis and antitumor immunity to chemotherapy in poor outcome disease. In a prospective, randomized trial, we included patients with advanced, unresectable pancreatic adenocarcinomas, non-small cell lung cancer, or prostate cancer. Two groups of each primary condition were compared: group 1 (G1), n = 30, was treated with the standard chemotherapy and used as a control, and group 2 (G2), n = 30, was treated with chemotherapy plus an induction regimen of antiangiogenesis and antitumor immunity. This induction regimen included a low dose of metronomic cyclophosphamide, a high dose of Cox-2 inhibitor, granulocyte colony-stimulating factor, a sulfhydryl (SH) donor, and a hemoderivative that contained autologous tumor antigens released from patient tumors into the blood. After treatment, the G2 group demonstrated significantly longer survival, lower blood level of neoangiogenesis and immune-tolerance mediators, and higher blood levels of antiangiogenesis and antitumor immunity mediators compared with the G1 group. Toxicity and quality of life were not significantly different between the groups. In conclusion, in several advanced malignancies of different primary localizations, an increase in survival was observed by adding an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy.

  12. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

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    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  13. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival for patients with peritoneal carcinomatosis from colorectal cancer: a phase II study from a Chinese center.

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    Chao-Qun Huang

    Full Text Available Peritoneal carcinomatosis (PC is a difficult clinical challenge in colorectal cancer (CRC because conventional treatment modalities could not produce significant survival benefit, which highlights the acute need for new treatment strategies. Our previous case-control study demonstrated the potential survival advantage of cytoreductive surgery (CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC over CRS alone. This phase II study was to further investigate the efficacy and adverse events of CRS+HIPEC for Chinese patients with CRC PC.A total of 60 consecutive CRC PC patients underwent 63 procedures consisting of CRS+HIPEC and postoperative chemotherapy, all by a designated team focusing on this combined treatment modality. All the clinico-pathological information was systematically integrated into a prospective database. The primary end point was disease-specific overall survival (OS, and the secondary end points were perioperative safety profiles.By the most recent database update, the median follow-up was 29.9 (range 3.5-108.9 months. The peritoneal cancer index (PCI ≤20 was in 47.0% of patients, complete cytoreductive surgery (CC0-1 was performed in 53.0% of patients. The median OS was 16.0 (95% confidence interval [CI] 12.2-19.8 months, and the 1-, 2-, 3-, and 5-year survival rates were 70.5%, 34.2%, 22.0% and 22.0%, respectively. Mortality and grades 3 to 5 morbidity rates in postoperative 30 days were 0.0% and 30.2%, respectively. Univariate analysis identified 3 parameters with significant effects on OS: PCI ≤20, CC0-1 and adjuvant chemotherapy over 6 cycles. On multivariate analysis, however, only CC0-1 and adjuvant chemotherapy ≥6 cycles were found to be independent factors for OS benefit.CRS+HIPEC at a specialized treatment center could improve OS for selected CRC PC patients from China, with acceptable perioperative safety.

  14. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of gastric cancer with peritoneal carcinomatosis: evidence from an experimental study

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    Yonemura Yutaka

    2011-05-01

    Full Text Available Abstract Background Cytoreductive surgery (CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC has been considered as a promising treatment modality for gastric cancer with peritoneal carcinomatosis (PC. However, there have also been many debates regarding the efficacy and safety of this new approach. Results from experimental animal model study could help provide reliable information. This study was to investigate the safety and efficacy of CRS + HIPEC to treat gastric cancer with PC in a rabbit model. Methods VX2 tumor cells were injected into the gastric submucosa of 42 male New Zealand rabbits using a laparotomic implantation technique, to construct rabbit model of gastric cancer with PC. The rabbits were randomized into control group (n = 14, CRS alone group (n = 14 and CRS + HIPEC group (n = 14. The control group was observed for natural course of disease progression. Treatments were started on day 9 after tumor cells inoculation, including maximal removal of tumor nodules in CRS alone group, and maximal CRS plus heperthermic intraperitoneal chemoperfusion with docetaxel (10 mg/rabbit and carboplatin (40 mg/rabbit at 42.0 ± 0.5°C for 30 min in CRS + HIPEC group. The primary endpoint was overall survival (OS. The secondary endpoints were body weight, biochemistry, major organ functions and serious adverse events (SAE. Results Rabbit model of gastric cancer with PC was successfully established in all animals. The clinicopathological features of the model were similar to human gastric PC. The median OS was 24.0 d (95% confidence interval 21.8 - 26.2 d in the control group, 25.0 d (95% CI 21.3 - 28.7 d in CRS group, and 40.0 d (95% CI 34.6 - 45.4 d in CRS + HIPEC group (P = 0.00, log rank test. Compared with CRS only or control group, CRS + HIPEC could extend the OS by at least 15 d (60%. At the baseline, on the day of surgery and on day 8 after surgery, the peripheral blood cells counts, liver and kidney functions, and biochemistry

  15. Consolidation chemotherapy improves progression-free survival in stage III small-cell lung cancer following concurrent chemoradiotherapy: a retrospective study

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    Chen XR

    2016-09-01

    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. Keywords: stage III, small-cell lung cancer, consolidation chemotherapy, survival analysis, prognosis, toxicities 

  16. Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil: A p

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).METHODS: From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil.RESULTS: The mean course of chemotherapy was 14.4 (range, 9-21) mo. One patient showed complete response (CR) with disappearance of HCC and PVTT after treatment, and the two patients showed partialresponse (PR), response rate (CR + PR/All cases 30%).The median survival time after the therapy was 457.2 d. The one-year survival rate was 70%. Adverse reactions were tolerable.CONCLUSION: Although the prognosis of most patients with Stage IVA HCC by PVTT is poor, our combination chemotherapy may induces long-term survival and is an effective treatment and produced anti-tumor activity with tolerable adverse effects in patients for advanced Stage IVA HCC accompanied by PVTT.

  17. Combining Chemotherapy with Bevacizumab Improves Outcomes for Ovarian Cancer Patients

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    Results from two phase III randomized clinical trials suggest that, at least for some patients with ovarian cancer, adding the antiangiogenesis agent bevacizumab to chemotherapy increases the time to disease progression and may improve survival.

  18. Pre-treatment with oral hydroxyurea prior to intensive chemotherapy improves early survival of patients with high hyperleukocytosis in acute myeloid leukemia.

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    Mamez, Anne-Claire; Raffoux, Emmanuel; Chevret, Sylvie; Lemiale, Virginie; Boissel, Nicolas; Canet, Emmanuel; Schlemmer, Benoît; Dombret, Hervé; Azoulay, Elie; Lengliné, Etienne

    2016-10-01

    Acute myeloid leukemia with high white blood cell count (WBC) is a medical emergency. A reduction of tumor burden with hydroxyurea may prevent life-threatening complications induced by straight chemotherapy. To evaluate this strategy, we reviewed medical charts of adult patients admitted to our institution from 1997 to 2011 with non-promyelocytic AML and WBC over 50 G/L. One hundred and sixty patients were included with a median WBC of 120 G/L (range 50-450), 107 patients received hydroxyurea prior to chemotherapy, and 53 received emergency induction chemotherapy (CT). Hospital mortality was lower for patients treated with hydroxyurea (34% versus 19%, p = 0.047) even after adjusting for age (p < 0.01) and initial WBC count (p = 0.02). No evidence of any difference between treatment groups in terms of WBC decline kinetics and disease free survival (p = 0.87) was found. Oral hydroxyurea prior to chemotherapy seems a safe and efficient strategy to reduce early death of hyperleukocytic AML patients.

  19. Chemotherapy increases long-term survival in patients with adult medulloblastoma

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    Kocakaya, Selin; Beier, Christoph Patrick; Beier, Dagmar

    2016-01-01

    parts of treatment regimes; however, established prognostic factors and data clarifying the role of chemotherapy are missing. METHODS: We investigated 227 publications from 1969-2013, with 907 identifiable, individual patients being available for meta-analysis. Demographic data, risk stratification...... chemotherapy first-line survived significantly longer (mOS: 108 mo, 95% CI: 68.6-148.4) than patients treated with radiation alone (mOS: 57 mo, 95% CI: 39.6-74.4) or patients who received chemotherapy at tumor recurrence. This effect was not biased by tumor stage or decade of treatment. Importantly, (neo......)adjuvant chemotherapy also significantly increased the chance for long-term survival (>5 y) compared with radiotherapy alone or chemotherapy at tumor recurrence. CONCLUSIONS: This meta-analysis clarifies relevant prognostic factors and suggests that chemotherapy as part of first-line therapy improves overall survival...

  20. Population-based survival of patients with peritoneal carcinomatosis from colorectal origin in the era of increasing use of palliative chemotherapy.

    NARCIS (Netherlands)

    Klaver, Y.L.B.; Lemmens, V.E.; Creemers, G.J.; Rutten, H.J.; Nienhuijs, S.W.; Hingh, I.H.J.T. de

    2011-01-01

    BACKGROUND: Palliative chemotherapy improves survival in patients with metastasised colorectal cancer. However, there is a lack of data regarding the effectiveness of modern chemotherapy in patients with isolated peritoneal carcinomatosis (PC). PATIENTS AND METHODS: All patients with synchronous PC

  1. Salvage chemotherapy of gemcitabine, dexamethasone, and cisplatin (GDP) for patients with relapsed or refractory peripheral T-cell lymphomas: a consortium for improving survival of lymphoma (CISL) trial.

    Science.gov (United States)

    Park, Byeong-Bae; Kim, Won Seog; Suh, Cheolwon; Shin, Dong-Yeop; Kim, Jeong-A; Kim, Hoon-Gu; Lee, Won Sik

    2015-11-01

    There is no standard salvage chemotherapy for relapsed or refractory peripheral T-cell lymphomas (PTCLs). Gemcitabine combined with cisplatin has been known as an effective regimen for lymphoma treatment in the salvage setting. We investigated the efficacy and toxicity of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory PTCLs in search of a more effective and less toxic therapy. Patients with relapsed or refractory PTCLs with more than one previous regimen were eligible. Treatment consisted of gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4, and cisplatin 70 mg/m(2) i.v. on day 1, and then every 21 days. Patients could proceed to autologous stem cell transplantation (ASCT) after four cycles of GDP or receive up to six treatment cycles. Twenty-five eligible patients were evaluated for toxicity and response. The diagnoses of participants included 14 cases of PTCL-not otherwise specified (NOS) (56 %) and four cases of angioimmunoblastic T-cell lymphoma (16 %) among others. The median age of the patients was 59 years (range 20-75 years). After treatments with GDP, which delivered a median of four GDP cycles, there were 12 patients with complete responses (CR; 48 %) and six with partial responses (PR; 24 %). The overall response rate (RR) was 72 %. Four patients preceded to ASCT, and three patients finally achieved CR. The median progression free survival was 9.3 months (95 % confidence interval (CI); 4.1-14.6) with a median follow-up duration of 27.1 months. In a total of 86 cycles of GDP, grade 3 or 4 neutropenia and thrombocytopenia occurred in 16.3 and 12.8 % of cycles, respectively. Three patients (3.3 %) experienced febrile neutropenia. GDP is a highly effective and optimal salvage regimen for relapsed or refractory PTCLs and can be administered with acceptable toxicity.

  2. Eribulin Improves Survival of Women with Metastatic Breast Cancer

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    Treatment with eribulin (Halaven™) improved overall survival in women with metastatic breast cancer whose disease progressed despite multiple rounds of prior chemotherapy, according to the results of a phase III clinical trial called EMBRACE.

  3. High-risk bladder cancer: improving outcomes with perioperative chemotherapy

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    Daniel Y.C. Heng

    2011-12-01

    Full Text Available Despite treatment with radical cystectomy and pelvic lymph node dissection, muscle invasive bladder cancer has a relapse rate of 50%. Patients can develop regionally advanced or metastatic disease that ultimately leads to death. The addition of neoadjuvant or adjuvant chemotherapy to reduce the risk of relapse and death has been extensively studied over the past two decades. Two contemporary trials coupled with a recent meta-analysis evaluating neoadjuvant chemotherapy demonstrated a modest but real improvement in overall survival. This has made neoadjuvant chemotherapy a standard of care. Clinical trials evaluating adjuvant chemotherapy in patients with high-risk disease have been plagued with statistical flaws and have, therefore, been unable to define the survival impact of this approach. It is hoped that ongoing adjuvant trials that are powered to detect small but meaningful clinical differences will clarify the benefit of chemotherapy after cystectomy. Since there are theoretical advantages and disadvantages to each of these approaches, both are widely used in North America. The evidence behind each approach and potential future developments in this field will be described.

  4. Improving chemotherapy for patients with advanced non-small cell lung cancer

    DEFF Research Database (Denmark)

    von Plessen, Christian

    2011-01-01

    treatment option is palliative chemotherapy. Given the palliative intention of the chemotherapy, it is clinically highly relevant to establish the optimal treatment duration. While chemotherapy prolongs survival and improves quality of life (QoL), it also has side effects and only a minority of patients...... achieve an objective treatment response. Clinicians need guidance on treatment duration from controlled trials to balance these aspects. Improvements of the conditions under which chemotherapy is given can increase patient and staff satisfaction and increase system performance. This is especially relevant...... of care. Clinicians, health care administrators and the public need knowledge about the outcomes of palliative chemotherapy in unselected patient populations. The efficacy of palliative chemotherapy for advanced NSCLC has been amply documented in controlled clinical trials. Meanwhile, the elderly...

  5. The combination of FDG PET and dynamic contrast-enhanced MRI improves the prediction of disease-free survival in patients with advanced breast cancer after the first cycle of neoadjuvant chemotherapy

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    Lim, Ilhan; Kim, Byung II; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Nuclear Medicine, Korea Cancer Center Hospital, 75 Nowongil, Nowon Gu, Seoul (Korea, Republic of); Korea Institute of Radiological and Medical Sciences (KIRAMS), Molecular Imaging Research Center, Seoul (Korea, Republic of); Noh, Woo Chul; Kim, Hyun-Ah; Kim, Eun-Kyu [Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Surgery, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Park, Jihyun; Byun, Byung Hyun [Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Nuclear Medicine, Korea Cancer Center Hospital, 75 Nowongil, Nowon Gu, Seoul (Korea, Republic of); Park, Ji Ae; Kim, Kyeong Min [Korea Institute of Radiological and Medical Sciences (KIRAMS), Molecular Imaging Research Center, Seoul (Korea, Republic of); Park, Ko Woon [Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Radiology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Lee, Seung Sook [Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); You, Eun Young [Gachon University School of Medicine and Science, Department of Radiology, Gil Hospital, Incheon (Korea, Republic of)

    2014-10-15

    The aim of this study was to investigate the potential of FDG PET/CT and MRI in predicting disease-free survival (DFS) after neoadjuvant chemotherapy (NAC) and surgery in patients with advanced breast cancer. The analysis included 54 women with advanced breast cancer. All patients received three cycles of NAC, underwent curative surgery, and then received three cycles of additional chemotherapy. Before and after the first cycle of NAC, all patients underwent sequential PET/CT and MRI. All patients were analysed using a diverse range of parameters. including maximal standardized uptake value (SUV), percent change in SUV (ΔSUV), initial slope of the enhancement curve (MRslope), apparent diffusion coefficient (ADC), tumour size, change in MRslope (ΔMRslope), change in ADC (ΔADC), change in tumour size (Δsize) and other clinicopathological parameters. The relationships between covariates and DFS after surgery were analysed using the Kaplan-Meier method and the multivariate Cox proportional hazards model. Time-dependent receiver operating characteristic curves were used to determine the optimal cut-off values of imaging parameters for DFS. Of the 54 patients, 13 (24 %) experienced recurrence at a median follow-up of 38 months (range 25 - 45 months). Univariate and multivariate analyses showed that a lesser decline in SUV, a lesser decline in MRslope, a lesser increase in ADC, and ER negativity were significantly associated with a poorer DFS (P = 0.0006, ΔSUV threshold -41 %; P = 0.0016, ΔMRslope threshold -6 %; P = 0.011, ΔADC threshold 11 %; and P = 0.0086, ER status, respectively). Patients with a combination of ΔSUV >-41 % and ΔMRslope >-6 % showed a significantly higher recurrence rate (77.8 %) than the remaining of patients (13.3 %, P < 0.0001). Functional parameters of both FDG PET and MRI after the first cycle of NAC are useful for predicting DFS in patients with advanced breast cancer. This approach could lead to an improvement in patient care because

  6. Survival benefit of adding chemotherapy to intensity modulated radiation in patients with locoregionally advanced nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Xuemei Ji

    Full Text Available BACKGROUND: To evaluate the contribution of chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC treated by intensity modulated radiotherapy (IMRT and to identify the optimal combination treatment strategy. PATIENTS AND METHODS: Between 2006 and 2010, 276 patients with stage II-IVb NPC were treated by IMRT alone or IMRT plus chemotherapy. Cisplatin-based chemotherapy included neoadjuvant or concurrent, or neoadjuvant plus concurrent protocols. The IMRT alone and chemoradiotherapy groups were well-matched for prognostic factors, except N stage, with more advanced NPC in the chemoradiotherapy arm. RESULTS: With a mean follow-up of 33.8 months, the 3-year actuarial rates of overall survival (OS, metastasis-free survival (MFS, relapse-free survival (RFS, and disease-free survival (DFS were 90.3%, 84.2%, 80.3%, and 69.2% for all of the patients, respectively. Compared with the IMRT alone arm, patients treated by concurrent chemoradiotherapy had a significantly better DFS (HR = 2.64; 95% CI, 1.12-6.22; P = 0.03, patients with neoadjuvant-concurrent chemoradiotherapy had a significant improvement in RFS and DFS (HR = 4.03; 95% CI, 1.35-12.05; P = 0.01 and HR = 2.43; 95% CI, 1.09-5.44; P = 0.03, neoadjuvant chemoradiotherapy provided no significant benefit in OS, MFS, RFS, and DFS. Stage group and alcohol consumption were prognostic factors for OS and N stage was a significant predictor for DFS. CONCLUSIONS: Addition of concurrent or neoadjuvant-concurrent chemotherapy to IMRT is available to prolong RFS or DFS for locoregionally advanced NPC. Such work could be helpful to guide effective individualized therapy.

  7. SNRFCB: sub-network based random forest classifier for predicting chemotherapy benefit on survival for cancer treatment.

    Science.gov (United States)

    Shi, Mingguang; He, Jianmin

    2016-04-01

    Adjuvant chemotherapy (CTX) should be individualized to provide potential survival benefit and avoid potential harm to cancer patients. Our goal was to establish a computational approach for making personalized estimates of the survival benefit from adjuvant CTX. We developed Sub-Network based Random Forest classifier for predicting Chemotherapy Benefit (SNRFCB) based gene expression datasets of lung cancer. The SNRFCB approach was then validated in independent test cohorts for identifying chemotherapy responder cohorts and chemotherapy non-responder cohorts. SNRFCB involved the pre-selection of gene sub-network signatures based on the mutations and on protein-protein interaction data as well as the application of the random forest algorithm to gene expression datasets. Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer patients in the chemotherapy responder group (P = 0.008), but it was not beneficial to patients in the chemotherapy non-responder group (P = 0.657). Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer squamous cell carcinoma (SQCC) subtype patients in the chemotherapy responder cohorts (P = 0.024), but it was not beneficial to patients in the chemotherapy non-responder cohorts (P = 0.383). SNRFCB improved prediction performance as compared to the machine learning method, support vector machine (SVM). To test the general applicability of the predictive model, we further applied the SNRFCB approach to human breast cancer datasets and also observed superior performance. SNRFCB could provide recurrent probability for individual patients and identify which patients may benefit from adjuvant CTX in clinical trials.

  8. Removal of Endobronchial Malignant Mass by Cryotherapy Improved Performance Status to Receive Chemotherapy

    Directory of Open Access Journals (Sweden)

    Yueh-Fu Fang

    2014-01-01

    Full Text Available Although malignant endobronchial mass (MEM has poor prognosis, cryotherapy is reportedly a palliative treatment. Clinical data on postcryotherapy MEM patients in a university-affiliated hospital between 2007 and 2011 were evaluated. Survival curve with or without postcryotherapy chemotherapy and performance status (PS improvement of these subjects were analyzed using the Kaplan-Meier method. There were 59 patients (42 males, with median age of 64 years (range, 51–76, and median performance status of 2 (interquartile range [IQR], 2-3. Postcryotherapy complications included minor bleeding (n=12 and need for multiple procedures (n=10, while outcomes were relief of symptoms (n=51, improved PS (n=45, and ability to receive chemotherapy (n=40. The survival of patients with chemotherapy postcryotherapy was longer than that of patients without such chemotherapy (median, 534 versus 106 days; log-rank test, P=0.007; hazard ratio, 0.25; 95% confidence interval, 0.10–0.69. The survival of patients with PS improvement postcryotherapy was longer than that of patients without PS improvement (median, 406 versus 106 days; log-rank test, P=0.02; hazard ratio, 0.28; 95% confidence interval, 0.10–0.81. Cryotherapy is a feasible treatment for MEM. With better PS after cryotherapy, further chemotherapy becomes possible for patients to improve survival when MEM caused dyspnea and poor PS.

  9. Induction Chemotherapy Improved Long-term Outcomes of Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: A Propensity Matched Analysis of 5-year Survival Outcomes in the Era of Intensity-modulated Radiotherapy

    Science.gov (United States)

    Peng, Hao; Chen, Lei; Zhang, Jian; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Yuan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2017-01-01

    Background: The aim of this study is to evaluate the long-term therapeutic gain of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). Methods: Data on 957 patients with stage T1-2N2-3 or T3-4N1-3 NPC treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance influence of various covariates. Patient survival between IC and non-IC groups were compared. Results: For the 318 pairs selected from the original 957 patients by PSM, the median follow-up duration was 57.13 months (range, 1.27-78.1 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and locoregional relapse-free survival (LRRFS) rates for IC group vs. non-IC group were 87.2% vs. 80.8% (P = 0.023), 88.1% vs. 83.2% (P = 0.071), 80.7% vs. 71.4% (P = 0.011) and 92.1% vs. 86.7% (P = 0.081), respectively. Multivariate analysis identify IC as an independent prognostic factor for OS (HR, 0.595; 95% CI, 0.397-0.891; P = 0.012) and DFS (HR, 0.627; 95% CI, 0.451-0.872; P = 0.006). After excluding the patients not receiving concurrent chemotherapy, IC was found to be an independent prognostic factor for OS (HR, 0.566; 95% CI, 0.368-0.872; P = 0.01), DMFS (HR, 0.580; 95% CI, 0.367-0.916; P = 0.02) and DFS (HR, 0.633; 95% CI, 0.444-0.903; P = 0.012). Conclusions: IC is an effective treatment modality for patients with stage T1-2N2-3 and T3-4N1-3 NPC, and the incorporation of IC with standard CCRT could achieve the best therapeutic gain. PMID:28261337

  10. Percentage tumor necrosis following chemotherapy in neuroblastoma correlates with MYCN status but not survival.

    Science.gov (United States)

    Bomken, Simon; Davies, Beverley; Chong, Leeai; Cole, Michael; Wood, Katrina M; McDermott, Michael; Tweddle, Deborah A

    2011-03-01

    The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies, including high-risk metastatic diseases. In this retrospective pilot study, the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens. The authors reviewed all available histology of 31 high-risk neuroblastoma cases treated with COJEC (dose intensive etoposide and vincristine with either cyclophosphamide, cisplatin or carboplatin) or OPEC/OJEC (etoposide, vincristine and cyclophosphamide with alternating cisplatin [OPEC] or carboplatin [OJEC]) induction chemotherapy in 2 Children's Cancer & Leukaemia Group (CCLG) pediatric oncology centers. The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival. The median percentage of postchemotherapy tumor necrosis was 60%. MYCN status was available for 28 cases, of which 12 were amplified (43%). Survival in cases with ≥ 60% necrosis or ≥ 90% necrosis was not better than those with less necrosis, nor was percentage necrosis associated with survival using Cox regression. However, MYCN-amplified tumors showed a higher percentage of necrosis than non-MYCN-amplified tumors, 71.3% versus 37.2% (P = .006). This effect was not related to prechemotherapy necrosis and did not confer improved overall survival. Postchemotherapy tumor necrosis is higher in patients with MYCN amplification. In this study, postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment. However, these findings need to be confirmed in a larger prospective study of children with high-risk neuroblastoma.

  11. Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma: a prospective randomized phase 3 study

    NARCIS (Netherlands)

    C.M. Segeren (Christine); P.W. Wijermans (Pierre); S. Wittebol (Shulamit); J.W. Baars (Joke); W.E. Fibbe (Willem); P. Sonneveld (Pieter); B. van der Holt (Bronno); M.M. Steijaert; E. Vellenga (Edo); H.M. Lokhorst (Henk); D.H. Biesma (Douwe); A.J. Croockewit; G.E.G. Verhoef (Gregor); J.J. Cornelissen (Jan); M. van Marwijk Kooy (Marinus); R. Slater (Rosalyn); M.R. Schaafsma (Martijn); I. Buijt; M.H.J. van Oers (Marinus)

    2003-01-01

    textabstractWe compared the efficacy of intensified chemotherapy followed by myeloablative therapy and autologous stem cell rescue with intensified chemotherapy alone in patients newly diagnosed with multiple myeloma. There were 261 eligible patients younger than 66 years with stag

  12. Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer

    DEFF Research Database (Denmark)

    Als, Anne B; Dyrskjøt, Lars; von der Maase, Hans;

    2007-01-01

    in an independent material of 124 patients receiving cisplatin-containing therapy. RESULTS: Fifty-five differentially expressed genes correlated significantly to survival time. Two of the protein products (emmprin and survivin) were validated using immunohistochemistry. Multivariate analysis identified emmprin......PURPOSE: Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of response...... and survival. EXPERIMENTAL DESIGN: Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes with an expression highly correlated to survival time after chemotherapy was identified. Two genes were selected for validation by immunohistochemistry...

  13. Emmprin and Survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer

    DEFF Research Database (Denmark)

    Als, Anne Birgitte; Andersen, Lars Dyrskjøt; Maase, Hans von der;

    2007-01-01

    in an independent material of 124 patients receiving cisplatin-containing therapy. RESULTS: Fifty-five differentially expressed genes correlated significantly to survival time. Two of the protein products (emmprin and survivin) were validated using immunohistochemistry. Multivariate analysis identified emmprin......PURPOSE: Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of response...... and survival. EXPERIMENTAL DESIGN: Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes with an expression highly correlated to survival time after chemotherapy was identified. Two genes were selected for validation by immunohistochemistry...

  14. Prometheus' spirit: quality survival in advanced hepatocellular carcinoma after gemcitabine and cisplatin-based chemotherapy.

    Science.gov (United States)

    Doval, D C; Pande, S B; Sharma, J B; Pavithran, K; Jena, A; Vaid, A K

    2008-10-01

    In advanced virus-induced hepatocellular carcinoma (HCC) associated with cirrhosis, the average survival is four months. We report a 56-year-old man with a large-volume advanced HCC, in whom gemcitabine and cisplatin-based chemotherapy resulted in near-complete regression, and quality survival of 24 months.

  15. Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma.

    Science.gov (United States)

    Matsushita, K; Matsumoto, T; Ohtsubo, H; Fujiwara, H; Imamura, N; Hidaka, S; Kukita, T; Tei, C; Matsumoto, M; Arima, N

    1999-12-01

    Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.

  16. Lung Cancer Survival Improvement through Surgical Intervention in PUMCH Hospital

    Institute of Scientific and Technical Information of China (English)

    GUO Feng; ZHANG Zhiyong; CUI Yushang; LI Shanqing; LI Li; XU Xiaohui; GE Feng; GUO Huiqin; LI Zejian

    2006-01-01

    Objective: To investigate and evaluate improvement of lung cancer survival after surgical intervention in PUMC hospital during the last 15 years. Methods: From January 1989 to December 2003, 1574 lung cancer cases underwent surgical treatment and followed up. All cases in this series were divided into two groups according to time period: group A (1999-2003) and group B (1989-1998). The difference in the survival rate between groups A and B was compared. Results: The morbidity and mortality in group A was decreased significantly in comparison to group B (11.2% vs. 19.2%, 1.06% vs. 1.93%, respectively).However, the 3-year and 5-year survival rate was increased from 42.35% to 56.07%, and from 28.46% to38.99%, respectively. A significant improvement in survival was observed in patients with stage Ⅰ, Ⅱ and ⅢA, but not in those with stage ⅢB and Ⅳ. Also, patients with lobectomy had more satisfactory results than those receiving exploratory thoracotomy, limited resection, pneumonectomy and sleeve resection. Conclusion: Lobectomy plus systematic mediastinal lymph nodes dissection has become the standard mode for resectable lung cancer. Combination of complete resection along with lymph nodal dissection, and postoperative adjuvant chemotherapy based on platinum/3rd generation chemotherapy medicine, has preliminarily been justified, proving an important approach for effective improvement in long-term survival of non-small cell lung carcinoma.

  17. Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma : a prospective randomized phase 3 study

    NARCIS (Netherlands)

    Segeren, CM; Sonneveld, P; van der Holt, B; Vellenga, E; Croockewit, AJ; Verhoef, GEG; Cornelissen, JJ; van Oers, MHJ; Wijermans, PW; Fibbe, WE; Wittebol, S; Kooy, MV; Biesma, DH; Baars, JW; Slater, R; Steijaert, MMC; Buijt, [No Value; Lokhorst, HM; Schaafsma, M.R.

    2003-01-01

    We compared the efficacy of intensified chemotherapy followed by myeloablative therapy and autologous stem cell rescue with intensified chemotherapy alone in patients newly diagnosed with multiple myeloma. There were 261 eligible patients younger than 66 years with stage II/III multiple myeloma who

  18. Improving Survival in Decompensated Cirrhosis

    Directory of Open Access Journals (Sweden)

    Amar Nath Mukerji

    2012-01-01

    Full Text Available Mortality in cirrhosis is consequent of decompensation, only treatment being timely liver transplantation. Organ allocation is prioritized for the sickest patients based on Model for End Stage Liver Disease (MELD score. In order to improve survival in patients with high MELD score it is imperative to preserve them in suitable condition till transplantation. Here we examine means to prolong life in high MELD score patients till a suitable liver is available. We specially emphasize protection of airways by avoidance of sedatives, avoidance of Bilevel Positive Airway Pressure, elective intubation in grade III or higher encephalopathy, maintaining a low threshold for intubation with lesser grades of encephalopathy when undergoing upper endoscopy or colonoscopy as pre transplant evaluation or transferring patient to a transplant center. Consider post-pyloric tube feeding in encephalopathy to maintain muscle mass and minimize risk of aspiration. In non intubated and well controlled encephalopathy, frequent physical mobility by active and passive exercises are recommended. When renal replacement therapy is needed, night-time Continuous Veno-Venous Hemodialysis may be useful in keeping the daytime free for mobility. Sparing and judicious use of steroids needs to be borne in mind in treatment of ARDS and acute hepatitis from alcohol or autoimmune process.

  19. Effects of neoadjuvant chemotherapy on pathological parameters and survival in patients undergoing radical cystectomy for muscle-invasive bladder cancer

    OpenAIRE

    ÇAĞLAYAN, Alper; Akbulut, Ziya; Atmaca, Ali Fuat; Altinova,Serkan; KILIÇ, Metin; Balbay, Mevlana Derya

    2012-01-01

    Aim: To evaluate the effect of neoadjuvant chemotherapy on tumor pathology and patient survival in patients with muscle-invasive bladder cancer undergoing radical cystectomy. Neoadjuvant chemotherapy is believed to prevent micrometastasis and provide pathological downstaging. Materials and methods: Between June 2004 and March 2009, 74 patients with muscle-invasive bladder cancer were treated with radical cystectomy. Patients fit to receive chemotherapy were administered systemic chemotherapy...

  20. Does neoadjuvant chemotherapy impair long-term survival for ovarian cancer patients?

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten Lindberg; Ottesen, Bent Smedegaard; Kehlet, Henrik

    2014-01-01

    OBJECTIVE: In Denmark, the proportion of women with ovarian cancer treated with neoadjuvant chemotherapy (NACT) has increased, and the use of NACT varies among center hospitals. We aimed to evaluate the impact of first-line treatment on surgical outcome and median overall survival (MOS). METHODS...

  1. LONG-TERM SURVIVAL OF SMALL-CELL LUNG-CANCER PATIENTS AFTER CHEMOTHERAPY

    NARCIS (Netherlands)

    VANDERGAAST, A; POSTMUS, PE; BURGHOUTS, J; VANBOLHUIS, C; STAM, J; SPLINTER, TAW

    1993-01-01

    Eighty-one patients with small cell lung cancer (SCLC) with a survival Of more than 2 years start of chemotherapy were studied. Twenty-six of the 28 patients who died of relapsed SCLC had in relapsed before two years and of the 55 who had not then only two (4%) relapsed subsequently. It is stressed

  2. Adoptive T-cell therapy improves treatment of canine non–Hodgkin lymphoma post chemotherapy

    Science.gov (United States)

    O'Connor, Colleen M.; Sheppard, Sabina; Hartline, Cassie A.; Huls, Helen; Johnson, Mark; Palla, Shana L.; Maiti, Sourindra; Ma, Wencai; Davis, R. Eric; Craig, Suzanne; Lee, Dean A.; Champlin, Richard; Wilson, Heather; Cooper, Laurence J. N.

    2012-01-01

    Clinical observations reveal that an augmented pace of T-cell recovery after chemotherapy correlates with improved tumor-free survival, suggesting the add-back of T cells after chemotherapy may improve outcomes. To evaluate adoptive immunotherapy treatment for B-lineage non-Hodgkin lymphoma (NHL), we expanded T cells from client-owned canines diagnosed with NHL on artificial antigen presenting cells (aAPC) in the presence of human interleukin (IL)-2 and IL-21. Graded doses of autologous T cells were infused after CHOP chemotherapy and persisted for 49 days, homed to tumor, and significantly improved survival. Serum thymidine kinase changes predicted T-cell engraftment, while anti-tumor effects correlated with neutrophil-to-lymphocyte ratios and granzyme B expression in manufactured T cells. Therefore, chemotherapy can be used to modulate infused T-cell responses to enhance anti-tumor effects. The companion canine model has translational implications for human immunotherapy which can be readily exploited since clinical-grade canine and human T cells are propagated using identical approaches. PMID:22355761

  3. Significant survival benefit of adjuvant chemotherapy after concurrent chemoradiotherapy in locally advanced high-risk nasopharyngeal carcinoma

    Science.gov (United States)

    Liang, Zhong-Guo; Chen, Xiao-Qian; Lin, Guo-Xiang; Yu, Bin-Bin; Chen, Kai-Hua; Zhong, Qiu-Lu; Nong, Si-Kai; Li, Ling; Qu, Song; Su, Fang; Zhao, Wei; Li, Ye; Zhu, Xiao-Dong

    2017-01-01

    The present study aimed to define high-risk patients who may benefit from additional adjuvant chemotherapy (AC) after concurrent chemotherapy in combination with intensity-modulated radiotherapy among patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). A cohort of 511 NPC patients who received concomitant chemoradiotherapy (CCRT) with or without AC between January 2007 and December 2012 were retrospectively analysed. One hundred seventy-seven patients received CCRT alone, whereas 334 received CCRT + AC. The survival analysis showed that ages >45 years old, T3-T4 stages, N2-N3 disease and serum albumin levels ≤42 g/L were significant independent prognostic factors for overall survival (OS). Using these four risk factors, a prognostic model for OS was created as follows: (1) low-risk group: 0–1 risk factors; and (2) high-risk group: 2–4 risk factors. In the CCRT alone and CCRT + AC groups, significant differences in survival were found between the high- and low-risk groups. Patients in the high-risk group exhibited improved OS due to the addition of AC to CCRT, but no survival benefits were found in the low-risk group. In conclusion, high-risk patients may benefit from the addition of AC to CCRT regarding OS. PMID:28150694

  4. Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

    Directory of Open Access Journals (Sweden)

    Elva Jiménez-Hernández

    2015-01-01

    Full Text Available Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients, diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients, diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P=0.041. Overall survival for Group A (18, 90% was higher than that for Group B (60%. Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy.

  5. Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

    Science.gov (United States)

    Jiménez-Hernández, Elva; Dueñas-González, María Teresa; Arellano-Galindo, José; Medrano-Ortíz-De-Zárate, María Elena; Bekker-Méndez, Vilma Carolina; Berges-García, Adolfina; Solís-Labastida, Karina; Sánchez-Jara, Berenice; Tiznado-García, Héctor Manuel; Jaimes-Reyes, Ethel Zulie; García-Jiménez, Xochiketzalli; Espinoza-Hernández, Laura; Núñez-Villegas, Nora Nancy; Franco-Ornelas, Sergio; Pérez-Casillas, Ruy Xavier; Martínez Villegas, Octavio; Palomares, Teresa Marin; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy. PMID:25821830

  6. Role of comorbidity on survival after radiotherapy and chemotherapy for nonsurgically treated lung cancer

    DEFF Research Database (Denmark)

    Mellemgaard, Anders; Lüchtenborg, Margreet; Iachina, Maria

    2015-01-01

    , sex, lung function, and comorbidity were all associated with survival. Apart from excess mortality among patients with unspecified histological subtypes (hazard ratio), there was no clear difference between the specified subtypes. When adjusting for the other factors, particularly age, sex......, performance status, and stage proved to be robust while risk estimates for comorbidity were attenuated somewhat. When grouped by the three types of cancer treatment or no treatment, there was no influence of comorbidity on radiation therapy and modest influence on survival after chemotherapy...

  7. How much survival benefit is necessary for breast cancer patients to opt for adjuvant chemotherapy? Results from a Chilean survey

    Science.gov (United States)

    Acevedo, Francisco; Sanchez, Cesar; Jans, Jaime; Rivera, Solange; Camus, Mauricio; Besa, Pelayo

    2014-01-01

    Background: Breast cancer (BC) is the leading cause of cancer death in Chilean women. Adjuvant chemotherapy decreases recurrence and death from BC. The recommendation to indicate chemotherapy is complex. Adjuvant! Online is a valuable computational tool to predict survival benefit obtained with adjuvant systemic therapy. Previous studies in Caucasian patients with BC showed that they are willing to receive chemotherapy for a small benefit. No studies, to our knowledge, have been done in the Hispanic or Latino populations. Methods: We interviewed females with BC who had previously received adjuvant chemotherapy. Age, stage at presentation, time since last chemotherapy, type of chemotherapy, marital status, number of children, and level of education were recorded. We used the graphic representation from Adjuvant! Online to question each patient on how much survival benefit she required to accept chemotherapy. Results: There were 101 women surveyed. The average age was 55.9 (±10.2), 54.5% had involved lymph nodes, 59.4% were married, and 15.8% did not have parity; 62.3% of females accepted chemotherapy for an absolute survival benefit of 1% or less. In a multivariate analysis, younger (p = 0.02) and less-educated patients (p = 0.018) were associated with lower survival benefit required to opt for chemotherapy. Conclusion: In our study, the acceptance of chemotherapy by the Hispanic population requires minimal survival benefit and is in agreement with the Caucasian population reported elsewhere. To our knowledge, our report is the first study that evaluates the perception of Latino patients regarding the benefit of chemotherapy in early BC. PMID:24678346

  8. Astrocytes Upregulate Survival Genes in Tumor Cells and Induce Protection from Chemotherapy

    Directory of Open Access Journals (Sweden)

    Sun-Jin Kim

    2011-03-01

    Full Text Available In the United States, more than 40% of cancer patients develop brain metastasis. The median survival for untreated patients is 1 to 2 months, which may be extended to 6 months with conventional radiotherapy and chemotherapy. The growth and survival of metastasis depend on the interaction of tumor cells with host factors in the organ microenvironment. Brain metastases are surrounded and infiltrated by activated astrocytes and are highly resistant to chemotherapy. We report here that coculture of human breast cancer cells or lung cancer cells with murine astrocytes (but not murine fibroblasts led to the up-regulation of survival genes, including GSTA5, BCL2L1, and TWIST1, in the tumor cells. The degree of up-regulation directly correlated with increased resistance to all tested chemotherapeutic agents. We further show that the up-regulation of the survival genes and consequent resistance are dependent on the direct contact between the astrocytes and tumor cells through gap junctions and are therefore transient. Knocking down these genes with specific small interfering RNA rendered the tumor cells sensitive to chemotherapeutic agents. These data clearly demonstrate that host cells in the microenvironment influence the biologic behavior of tumor cells and reinforce the contention that the organ microenvironment must be taken into consideration during the design of therapy.

  9. Improved survival after rectal cancer in Denmark

    DEFF Research Database (Denmark)

    Bülow, S; Harling, H; Iversen, L H

    2010-01-01

    treated from 1994 to 2006. Method The study was based on the National Rectal Cancer Registry and the National Colorectal Cancer Database, supplemented with data from the Central Population Registry. The analysis included actuarial overall and relative survival. Results A total of 10 632 patients were......Objective In 1995, an analysis showed an inferior prognosis after rectal cancer in Denmark compared with the other Scandinavian countries. The Danish Colorectal Cancer Group (DCCG) was established with the aim of improving the prognosis, and in this study we present a survival analysis of patients...... operated on. The overall 5-year survival increased from 0.37 in 1994 to 0.51% in 2006; the improvement was greater in men (20% points) than in women (10% points), and greatest in stage III (20% points). The relative 5-year survival increased from 0.46 to 0.62, including an improvement of 23% points in men...

  10. Expression of p21WAF1 in Astler-Coller stage B2 colorectal cancer is associated with survival benefit from 5FU-based adjuvant chemotherapy.

    Science.gov (United States)

    Sulzyc-Bielicka, Violetta; Domagala, Pawel; Urasinska, Elzbieta; Bielicki, Dariusz; Safranow, Krzysztof; Domagala, Wenancjusz

    2011-04-01

    In several, but not all, previous studies, positive p21(WAF1) expression has been suggested as an indicator of a good prognosis in patients with stage III/IV colorectal cancer. However, it is not known whether the same is true for stage B2 patients. The purpose of this study is to assess the influence of p21(WAF1) expression in tumor cells on disease-free survival (DFS) and overall survival (OS) of Astler-Coller stage B2 and C patients with colorectal cancer who underwent 5-fluorouracil-based adjuvant chemotherapy. Nuclear p21(WAF1) was detected by immunohistochemistry in tissue microarrays from 275 colorectal cancers. The expression of p21(WAF1) was associated with DFS (p = 0.025) and OS (p = 0.008) in the subgroup of stage B2 patients that was treated with adjuvant chemotherapy. In multivariate analysis, it remained the only independent prognostic parameter in relation to DFS and OS (p = 0.035 and p = 0.02, respectively). In the subgroup of 72 stage B2 patients with positive p21(WAF1) expression but not in the subgroup of 61 stage B2 patients with negative p21(WAF1) expression, adjuvant chemotherapy was associated with better DFS (85% 5-year survival versus 65% without chemotherapy, p = 0.03) and OS (96% versus 82%, p = 0.014). In the combined stage B2 and C group of patients treated with adjuvant chemotherapy, positive p21(WAF1) expression was also associated with better DFS and OS (p = 0.03, p = 0.002, respectively). Expression of p21(WAF1) in colorectal tumor cells identifies a subgroup of Astler-Coller stage B2 patients who could benefit significantly from 5FU-based chemotherapy and may improve the selection of patients for adjuvant chemotherapy.

  11. Effect of inducing chemotherapy + chrono-chemotherapy + intensity-modulated radiation therapy on the survival and tumor malignancy in patients with nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hui Liu

    2016-01-01

    Objective:To analyze the effect of inducing chemotherapy + chrono-chemotherapy + intensity-modulated radiation therapy on the survival and tumor malignancy in patients with nasopharyngeal carcinoma.Methods: A total of 60 patients with locally advanced nasopharyngeal carcinoma were divided into observation group and control group according to different treatment, observation group received inducing chemotherapy + chrono-chemotherapy + intensity-modulated radiation therapy and control group received conventional treatment. Differences in the survival and tumor malignancy were compared between two groups.Results:miR-143 and miR-218 expression levels in nasopharyngeal carcinoma tissue of observation group after treatment were higher than those of control group, and miR-7 expression level was lower than that of control group; caspase-3, GRP-78 and Bax protein expression levels in tumor tissue of observation group after treatment were higher than those of control group, and Bcl-2 protein expression level was lower than that of control group;serum VEGF, -HBDH, CYFRA21-1 and PCⅢ levels of observation group after treatment were lower than those of control group.Conclusion:Inducing chemotherapy + chrono-chemotherapy + intensity-modulated radiation therapy can reduce the tumor malignancy and optimize the quality of life in patients with nasopharyngeal carcinoma.

  12. A patient with unresectable advanced pancreatic cancer achieving long-term survival with Gemcitabine chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Yoshiki Okamoto; Takashi Maeba; Keitarou Kakinoki; Keiichi Okano; Kunihiko Izuishi; Hisao Wakabayashi; Hisashi Usuki; Yasuvuki Suzuki

    2008-01-01

    A 68-year-old female visited a local clinic with epigastralgia. A routine laboratory test revealed jaundice and liver dysfunction. She was referred to this hospital. Abdominal computed tomography (CT) and endoscopic retrograde cholangio-pancreatography (ERCP) revealed that the density of the entire pancreas had decreased, and showed dilatation of the common bile duct (CBD) and the main pancreatic duct (MPD). Pancreatic cancer was diagnosed by cytological examination analyzing the pancreatic juice obtained by ERCP. When jaundice had decreased the tumor was observed via laparotomy. No ascites, liver metastasis, or peritoneal dissemination was observed. The entire pancreas was a hard mass, and a needle biopsy was obtained from the head, body and tail of the pancreas. These biopsies diagnosed a poorly differentiated adenocarcinoma. Hepaticojejunostomy was thus performed, and postoperative progress was good. Chemotherapy with 1000 mg/body per week of gemcitabine was administered beginning 15 d postoperatively. However, the patient suffered relatively severe side effects, and it was necessary to change the dosing schedule of gemcitabine. Abdominal CT revealed a complete response (CR) after 3 treatments. Therefore, weekly chemotherapy was stopped and was changed to monthly administration. To date, for 4 years after chemotherapy, the tumor has not reappeared.Key werds: Gemcitabine; Long-term survival; Unresectable advanced pancreatic cancer

  13. Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

    OpenAIRE

    Fleischmann, Achim; Thalmann, George; Perren, Aurel; Seiler,Roland

    2014-01-01

    Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumor...

  14. Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas

    Directory of Open Access Journals (Sweden)

    Walsh Tom

    2009-07-01

    Full Text Available Abstract Background DNA repair genes critically regulate the cellular response to chemotherapy and epigenetic regulation of these genes may be influenced by chemotherapy exposure. Restoration of BRCA1 and BRCA2 mediates resistance to platinum chemotherapy in recurrent BRCA1 and BRCA2 mutated hereditary ovarian carcinomas. We evaluated BRCA1, BRCA2, and MLH1 protein expression in 115 sporadic primary ovarian carcinomas, of which 31 had paired recurrent neoplasms collected after chemotherapy. Additionally, we assessed whether promoter methylation of BRCA1, MLH1 or FANCF influenced response to chemotherapy or explained alterations in protein expression after chemotherapy exposure. Results Of 115 primary sporadic ovarian carcinomas, 39 (34% had low BRCA1 protein and 49 (42% had low BRCA2 expression. BRCA1 and BRCA2 protein expression were highly concordant (p Conclusion Low BRCA1 expression in primary sporadic ovarian carcinoma is associated with prolonged survival. Recurrent ovarian carcinomas commonly have increased BRCA1 and/or BRCA2 protein expression post chemotherapy exposure which could mediate resistance to platinum based therapies. However, alterations in expression of these proteins after chemotherapy are not commonly mediated by promoter methylation, and other regulatory mechanisms are likely to contribute to these alterations.

  15. Enhancing survival of mouse oocytes following chemotherapy or aging by targeting Bax and Rad51.

    Directory of Open Access Journals (Sweden)

    Loro L Kujjo

    Full Text Available BACKGROUND: Therapeutic approaches to preserve fertility in females undergoing cancer treatments are currently ineffective. This is partly due to limited knowledge of the molecular mechanisms that injured germ cells elicit to repair damage and survive or to abort repair and activate biochemical pathways leading to death. So far, we know that following spontaneously occurring or drug-induced DNA damage, the efficiency of DNA repair is a critical determinant of the cell's fate. The protein encoded by the Rad51 gene is one of several components recruited for homologous recombination-dependent DNA double-strand break repair in both somatic cells and germ cells. Recently, we showed that microinjection of recombinant Rad51 into AKR/J mouse oocytes decreased the extent of spontaneous DNA double-strand breaks, suppressed apoptosis, and restored the developmental competence in AKR/J embryos. Herein we characterized the nature of chemotherapy-induced lesions in oocytes, and the associated individual components of the DNA damage sensor and repair apparatus. For comparison, we also assessed parallel spontaneous changes in aging oocytes. METHODS: Data collected were derived from: analysis of apoptosis; immunodepletion; oocyte microinjections; immunocytochemistry; immunofluorescence; and CHIP-like assays. RESULTS: Our data show that: (i DNA damage in oocytes can be induced by both chemotherapy and spontaneously by the aging process; (ii oocytes possess the machinery and capability for repairing such DNA damage; (iii Rad51 is a critical player in the repair of both chemotherapy-induced and spontaneously-sustained DNA damage; and (iv in response to damage, oocytes exhibit an inverse functional relationship between presence of Bax and activity of Rad51. CONCLUSION/SIGNIFICANCE: Our results establish Rad51 and/or Bax as potential candidates that can be targeted for development of individualized chemotherapeutic interventions that are effective, but minimal in

  16. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Twu, Chih-Wen [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, Wen-Yi [Section of Basic Medicine, Department of Nursing, Hung Kuang University, Taichung, Taiwan (China); Chen, Chien-Chih [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Liang, Kai-Li; Jiang, Rong-San [Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wu, Ching-Te [Department of Radiation Oncology, Taichung Veterans General Hospital–Chiayi Branch, Chiayi, Taiwan (China); Shih, Yi-Ting [Department of Radiation Oncology, St. Martin De Porres Hospital, Chiayi, Taiwan (China); Lin, Po-Ju; Liu, Yi-Chun [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Lin, Jin-Ching, E-mail: jclin@vghtc.gov.tw [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine, China Medical University, Taichung, Taiwan (China)

    2014-05-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

  17. Texture analysis for survival prediction of pancreatic ductal adenocarcinoma patients with neoadjuvant chemotherapy

    Science.gov (United States)

    Chakraborty, Jayasree; Langdon-Embry, Liana; Escalon, Joanna G.; Allen, Peter J.; Lowery, Maeve A.; O'Reilly, Eileen M.; Do, Richard K. G.; Simpson, Amber L.

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The five-year survival rate for all stages is approximately 6%, and approximately 2% when presenting with distant disease.1 Only 10-20% of all patients present with resectable disease, but recurrence rates are high with only 5 to 15% remaining free of disease at 5 years. At this time, we are unable to distinguish between resectable PDAC patients with occult metastatic disease from those with potentially curable disease. Early classification of these tumor types may eventually lead to changes in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant treatments. Texture analysis is an emerging methodology in oncologic imaging for quantitatively assessing tumor heterogeneity that could potentially aid in the stratification of these patients. The present study derives several texture-based features from CT images of PDAC patients, acquired prior to neoadjuvant chemotherapy, and analyzes their performance, individually as well as in combination, as prognostic markers. A fuzzy minimum redundancy maximum relevance method with leave-one-image-out technique is included to select discriminating features from the set of extracted features. With a naive Bayes classifier, the proposed method predicts the 5-year overall survival of PDAC patients prior to neoadjuvant therapy and achieves the best results in terms of the area under the receiver operating characteristic curve of 0:858 and accuracy of 83:0% with four-fold cross-validation techniques.

  18. Impact of immunohistochemistry-based molecular subtype on chemosensitivity and survival in Hispanic breast cancer patients following neoadjuvant chemotherapy

    Science.gov (United States)

    Gómez, Rodolfo; Ossa, Carlos Andrés; Montoya, María Elvira; Echeverri, Carolina; Ángel, Gonzalo; Ascuntar, Johana; Borrero, Mauricio; Gil, Mónica; Herrera, Sabrina; Gutiérrez, Eduardo; Herazo, Fernando; Jiménez, Alejo; Madrid, Jorge; Reyes, Pedro Alejandro; Zuluaga, Lina; García, Héctor

    2015-01-01

    Background Neoadjuvant chemotherapy (NAC) is the standard treatment for patients with locally advanced breast cancer, showing improvement in disease-free survival (DFS) and overall survival (OS) rates in patients achieving pathological complete response (pCR). The relationship between immunohistochemistry-based molecular subtyping (IMS), chemo sensitivity and survival is currently a matter of interest. We explore this relationship in a Hispanic cohort of breast cancer patients treated with NAC. Methods A retrospective survival analysis was performed on Colombian females with breast cancer treated at Instituto de Cancerología-Clinica Las Américas between January 2009 and December 2011. Patients were classified according to immunohistochemistry-based subtyping into the following five groups: Luminal A, Luminal B, Luminal B/HER 2+, HER2-enriched, and triple-negative breast cancer. Demographic characteristics, recurrence pattern, and survival rate were reviewed by bivariate and multivariate analysis. Results A total of 328 patients fulfilled the study’s inclusion parameters and the distribution of subtypes were as follows: Luminal A: 73 (22.3%), Luminal B/HER2−: 110 (33.5%), Luminal B/HER2+: 75 (22.9%), HER2-enriched: 30 (9.1%), and triple-negative: 40 (12.2%). The median follow-up was 41 months (interquartile range: 31–52). Pathological response to NAC was as follows: complete pathological response (pCR) in 28 (8.5%) patients, partial 247 (75.3%); stable disease 47 (14.3%), and progression 6 (1.8%) patients. The presence of pCR had a significant DFS and OS in the entire group (p = 0.01) but subtypes had different DFS in Luminal B (p = 0.01) and triple negative (p = 0.02) and also OS in Luminal B (p = 0.01) and triple negative (p = 0.01). Conclusions pCR is associated with an improved overall survival and disease-free survival rates in this group of Hispanics patients. Advanced stages, Luminal B subtypes, triple-negative tumours and non-pCR showed lower DFS

  19. Impact of modern chemotherapy on the survival of women presenting with de novo metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Pal Sumanta K

    2012-09-01

    Full Text Available Abstract Background Data that directly associate utilization of novel systemic therapies with survival trends in metastatic breast cancer (MBC are limited. In the setting of de novo MBC, large registry analyses cite positive temporal trends in survival, but the extent to which advances in systemic therapy have contributed to these gains is not clear. Methods The City of Hope Cancer Registry was used to identify a consecutive series of patients with de novo MBC who received their first line of therapy between 1985 and 2004. Comprehensive clinicopathologic and treatment-related data were collected for each patient. Univariate analyses were conducted via Cox regression to identify factors associated with improved survival. Multivariate analysis was also conducted via Cox regression and the stepwise procedure was used to identify independent predictors of survival. Results A total of 324 patients with de novo MBC were identified. After application of exclusion criteria, including the sole presence of supraclavicular node metastasis, 274 patients were retained in the analysis. The treatment-related characteristics associated with improved survival included: use of endocrine therapy (hazard ratio [HR] 0.60, 95%CI 0.47-0.77; P Conclusions The overall survival of women with de novo metastatic breast cancer has improved over the past 20 years. However, the contribution of conventional cytotoxic agents to this improvement is minimal.

  20. Targeting Nuclear FGF Receptor to Improve Chemotherapy Response in Triple-Negative Breast Cancer

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-13-1-0404 TITLE: Targeting Nuclear FGF Receptor to Improve Chemotherapy Response in Triple-Negative Breast Cancer...4. TITLE AND SUBTITLE Targeting Nuclear FGF Receptor to Improve Chemotherapy response 5a. CONTRACT NUMBER Response in Triple-Negative Breast Cancer...patients post-chemotherapy treatment, validating our in vitro model. We determined that FGF receptor 1 (FGFR1) protein, but not FGF receptor 3 (FGFR3

  1. The Influence of Cyst Emptying, Lymph Node Resection and Chemotherapy on Survival in Stage IA and IC1 Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

    Rosendahl, Mikkel; Mosgaard, Berit Jul; Høgdall, Claus

    2016-01-01

    AIM: To determine if survival in stage I ovarian cancer is influenced by cyst emptying, lymph node resection and chemotherapy. PATIENTS AND METHODS: A survival analysis of 607 patients with ovarian cancer in stage IA, IA with cyst emptying (IAempty) and IC1 was performed. RESULTS......: There was no difference in five-year survival between IA (87%) and IC1 (87%) (p=0.899), between IA and IAempty (86%) (p=0.500) nor between IA+IAempty (87%) and IC1 without IAempty (84%) (p=0.527). Five-year survival rate (5YSR) was significantly higher after lymph node resection in stage IA (94% vs. 85%; p=0.01) and IA......+IC1 (93% vs. 85%; p=0.004). In multivariate analysis, lymph node resection improved prognosis significantly for all sub-stages, whereas stage and chemotherapy did not affect survival. CONCLUSION: In stage IA ovarian cancer, controlled cyst emptying without spill does not worsen prognosis. Lymph node...

  2. Clinical Factors Associated with Response or Survival after Chemotherapy in Patients with Waldenström Macroglobulinemia in Korea

    Directory of Open Access Journals (Sweden)

    Ho Sup Lee

    2014-01-01

    Full Text Available Waldenström’s macroglobulinemia (WM is a B-cell proliferative malignancy characterized by immunoglobulin M monoclonal gammopathy and bone marrow infiltration by lymphoplasmacytic cells. Clinical features and cytogenetics of WM in Asia including Republic of Korea remain unclear. Moreover, no study has reported treatment outcomes in patients with WM treated with novel agent combined with conventional chemotherapy. This study investigated clinical features and assessed treatment outcomes with novel agent and conventional chemotherapy in Republic of Korea. Data from all (n=71 patients with newly diagnosed WM at 17 hospitals who received chemotherapy between January 2005 and December 2012 were collected retrospectively. The median age of patients was 66 years (range: 37–92 years and male to female ratio was 5 : 1. Patients treated with novel agent combined chemotherapy displayed higher overall response rate (ORR compared to conventional chemotherapy alone (92.9% versus 52.6%, P=0.006. The 5-year overall survival rate was 62.6% (95% confidence interval: 34.73–111.07. Use of novel agents produced higher ORR but survival benefit was not apparent due to the small number of patients and short follow-up duration. Further studies are needed to confirm the efficacy of novel agents in patients with WM.

  3. Clinical factors associated with response or survival after chemotherapy in patients with Waldenström macroglobulinemia in Korea.

    Science.gov (United States)

    Lee, Ho Sup; Kim, Kihyun; Yoon, Dok Hyun; Kim, Jin Seok; Bang, Soo-Mee; Lee, Jeong-Ok; Eom, Hyeon Seok; Lee, Hyewon; Kim, Inho; Lee, Won Sik; Bae, Sung Hwa; Kim, Se Hyung; Lee, Mark Hong; Do, Young Rok; Lee, Jae Hoon; Hong, Junshik; Shin, Ho-Jin; Lee, Ji Hyun; Mun, Yeung-Chul; Min, Chang-Ki

    2014-01-01

    Waldenström's macroglobulinemia (WM) is a B-cell proliferative malignancy characterized by immunoglobulin M monoclonal gammopathy and bone marrow infiltration by lymphoplasmacytic cells. Clinical features and cytogenetics of WM in Asia including Republic of Korea remain unclear. Moreover, no study has reported treatment outcomes in patients with WM treated with novel agent combined with conventional chemotherapy. This study investigated clinical features and assessed treatment outcomes with novel agent and conventional chemotherapy in Republic of Korea. Data from all (n = 71) patients with newly diagnosed WM at 17 hospitals who received chemotherapy between January 2005 and December 2012 were collected retrospectively. The median age of patients was 66 years (range: 37-92 years) and male to female ratio was 5 : 1. Patients treated with novel agent combined chemotherapy displayed higher overall response rate (ORR) compared to conventional chemotherapy alone (92.9% versus 52.6%, P = 0.006). The 5-year overall survival rate was 62.6% (95% confidence interval: 34.73-111.07). Use of novel agents produced higher ORR but survival benefit was not apparent due to the small number of patients and short follow-up duration. Further studies are needed to confirm the efficacy of novel agents in patients with WM.

  4. Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

    Science.gov (United States)

    Fleischmann, Achim; Thalmann, George N; Perren, Aurel; Seiler, Roland

    2014-03-01

    Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumors and corresponding lymph nodes. The prognostic impact of these 2 TRGs, the highest (dominant) TRG per patient, and competing tumor features reflecting tumor regression (ypT/ypN stage, maximum diameter of the residual tumor) were determined. Tumor characteristics in initial transurethral resection of the bladder specimens were tested for response prediction. The frequency of TRGs 1, 2, and 3 in the primary tumors were n=16, n=19, and n=21; corresponding data from the lymph nodes were n=31, n=9, and n=16. Interobserver agreement in determination of the TRG was strong (κ=0.8). Univariately, all evaluated parameters were significantly (P ≤ 0.001) related to overall survival; however, the segregation of the Kaplan-Meier curves was best for the dominant TRG. In multivariate analysis, only dominant TRG predicted overall survival independently (P=0.035). In transurethral resection specimens of the chemotherapy-naive bladder cancer, the only tumor feature with significant (Ptumor regression, the dominant TRG was the only independent risk factor. A favorable chemotherapy response is associated with a high proliferation rate in the initial chemotherapy-naive bladder cancer. This feature might help personalize neoadjuvant chemotherapy.

  5. Long term (five-year survival following radical surgical treatment plus adjuvant chemotherapy (FAM in advanced gastric cancer: a controlled study

    Directory of Open Access Journals (Sweden)

    Bresciani Cláudio

    2000-01-01

    Full Text Available Several drugs and their associations are being used for adjuvant or complementary chemotherapy with the aim of improving results of gastric cancer treatment. The objective of this study was to verify the impact of these drugs on nutrition and on survival rate after radical treatment of 53 patients with gastric cancer in stage III of the TNM classification. A control group including 28 patients who had only undergone radical resection was compared to a group of 25 patients who underwent the same operative technique followed by adjuvant polychemotherapy with FAM (5-fluorouracil, Adriamycin, and mitomycin C. In this latter group, chemotherapy toxicity in relation to hepatic, renal, cardiologic, neurological, hematologic, gastrointestinal, and dermatological functions was also studied. There was no significant difference on admission between both groups in relation to gender, race, macroscopic tumoral type of tumor according to the Borrmann classification, location of the tumor in the stomach, length of the gastric resection, or response to cutaneous tests on delayed sensitivity. Chemotherapy was started on average, 2.3 months following surgical treatment. Clinical and laboratory follow-up of all patients continued for 5 years. The following conclusions were reached: 1 The nutritional status and incidence of gastrointestinal manifestation were similar in both groups; 2 There was no occurrence of cardiac, renal, neurological, or hepatic toxicity or death due to the chemotherapeutic method per se; 3 Dermatological alterations and hematological toxicity occurred exclusively in patients who underwent polychemotherapy; 4 There was no significant difference between the rate and site of tumoral recurrence, the disease-free interval, or the survival rate of both study groups; 5 Therefore, we concluded, after a 5-year follow-up, chemotherapy with the FAM regimen did not increase the survival rate.

  6. Effect of ABCB1 and ABCC3 polymorphisms on osteosarcoma survival after chemotherapy: a pharmacogenetic study.

    Directory of Open Access Journals (Sweden)

    Daniela Caronia

    Full Text Available BACKGROUND: Standard treatment for osteosarcoma patients consists of a combination of cisplatin, adriamycin, and methotrexate before surgical resection of the primary tumour, followed by postoperative chemotherapy including vincristine and cyclophosphamide. Unfortunately, many patients still relapse or suffer adverse events. We examined whether common germline polymorphisms in chemotherapeutic transporter and metabolic pathway genes of the drugs used in standard osteosarcoma treatment may predict treatment response. METHODOLOGY/PRINCIPAL FINDINGS: In this study we screened 102 osteosarcoma patients for 346 Single Nucleotide Polymorphisms (SNPs and 2 Copy Number Variants (CNVs in 24 genes involved in the metabolism or transport of cisplatin, adriamycin, methotrexate, vincristine, and cyclophosphamide. We studied the association of the genotypes with tumour response and overall survival. We found that four SNPs in two ATP-binding cassette genes were significantly associated with overall survival: rs4148416 in ABCC3 (per-allele HR = 8.14, 95%CI = 2.73-20.2, p-value = 5.1×10⁻⁵, and three SNPs in ABCB1, rs4148737 (per-allele HR = 3.66, 95%CI = 1.85-6.11, p-value = 6.9×10⁻⁵, rs1128503 and rs10276036 (r² = 1, per-allele HR = 0.24, 95%CI = 0.11-0.47 p-value = 7.9×10⁻⁵. Associations with these SNPs remained statistically significant after correction for multiple testing (all corrected p-values [permutation test] ≤ 0.03. CONCLUSIONS: Our findings suggest that these polymorphisms may affect osteosarcoma treatment efficacy. If these associations are independently validated, these variants could be used as genetic predictors of clinical outcome in the treatment of osteosarcoma, helping in the design of individualized therapy.

  7. {sup 18}F-FDG PET/CT predicts survival in patients with inflammatory breast cancer undergoing neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Carkaci, Selin [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); The Ohio State University, Department of Radiology, Columbus, OH (United States); Sherman, Christopher T.; Ozkan, Efe; Adrada, Beatriz E.; Yang, Wei T. [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Wei, Wei [The University of Texas MD Anderson Cancer Center, Department of Biostatistics, Houston, TX (United States); Rohren, Eric M. [The University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Mawlawi, Osama R. [The University of Texas MD Anderson Cancer Center, Department of Imaging Physics, Houston, TX (United States); Ueno, Naoto T. [The University of Texas MD Anderson Cancer Center, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Department of Breast Medical Oncology, Houston, TX (United States); Buchholz, Thomas A. [The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston, TX (United States)

    2013-12-15

    The objective of this study was to evaluate the role of {sup 18}F-FDG PET/CT in predicting overall survival in inflammatory breast cancer patients undergoing neoadjuvant chemotherapy. Included in this retrospective study were 53 patients with inflammatory breast cancer who had at least two PET/CT studies including a baseline study before the start of neoadjuvant chemotherapy. Univariate and multivariate analyses were performed to assess the effects on survival of the following factors: tumor maximum standardized uptake value (SUVmax) at baseline, preoperatively and at follow-up, decrease in tumor SUVmax, histological tumor type, grade, estrogen, progesterone, HER2/neu receptor status, and extent of disease at presentation including axillary nodal and distant metastases. By univariate analysis, survival was significantly associated with decrease in tumor SUVmax and tumor receptor status. Patients with decrease in tumor SUVmax had better survival (P = 0.02). Patients with a triple-negative tumor (P = 0.0006), a Her2/neu-negative tumor (P = 0.038) or an ER-negative tumor (P = 0.039) had worse survival. Multivariate analysis confirmed decrease in tumor SUVmax and triple-negative receptor status as significant predictors of survival. Every 10 % decrease in tumor SUVmax from baseline translated to a 15 % lower probability of death, and complete resolution of tumor FDG uptake translated to 80 % lower probability of death (P = 0.014). Patients with a triple-negative tumor had 4.11 times higher probability of death (P = 0.004). Decrease in tumor SUVmax is an independent predictor of survival in patients with inflammatory breast cancer undergoing neoadjuvant chemotherapy. Further investigation with prospective studies is warranted to clarify its role in assessing response and altering therapy. (orig.)

  8. Concurrent Radiotherapy and Gemcitabine for Unresectable Pancreatic Adenocarcinoma: Impact of Adjuvant Chemotherapy on Survival

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuhiko, E-mail: kogawa@med.u-ryukyu.ac.jp [Department of Radiology, University of the Ryukyus, Okinawa (Japan); Ito, Yoshinori [Department of Radiation Oncology, National Cancer Center, Tokyo (Japan); Hirokawa, Naoki [Department of Radiology, Sapporo Medical University, Sapporo (Japan); Shibuya, Keiko [Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto (Japan); Kokubo, Masaki [Department of Radiation Oncology, Institute of Biomedical Research and Innovation Hospital, Kobe (Japan); Ogo, Etsuyo [Department of Radiation Oncology, Kurume University, Kurume (Japan); Shibuya, Hitoshi [Department of Radiology, Tokyo Medical and Dental University, Tokyo (Japan); Saito, Tsutomu [Department of Radiation Oncology, Nihon University Itabashi Hospital, Tokyo (Japan); Onishi, Hiroshi [Department of Radiology, Yamanashi University, Yamanashi (Japan); Karasawa, Katsuyuki [Department of Radiation Oncology, Tokyo Metropolitan Komagome Hospital, Tokyo (Japan); Nemoto, Kenji [Department of Radiation Oncology, Yamagata University, Yamagata (Japan); Nishimura, Yasumasa [Department of Radiation Oncology, Kinki University School of Medicine, Osaka (Japan)

    2012-06-01

    Purpose: To retrospectively analyze results of concurrent chemoradiotherapy (CCRT) using gemcitabine (GEM) for unresectable pancreatic adenocarcinoma. Methods and Materials: Records of 108 patients treated with concurrent external beam radiotherapy (EBRT) and GEM were reviewed. The median dose of EBRT in all 108 patients was 50.4 Gy (range, 3.6-60.8 Gy), usually administered in conventional fractionations (1.8-2 Gy/day). During radiotherapy, most patients received GEM at a dosage of 250 to 350 mg/m{sup 2} intravenously weekly for approximately 6 weeks. After CCRT, 59 patients (54.6%) were treated with adjuvant chemotherapy (AC), mainly with GEM. The median follow-up for all 108 patients was 11.0 months (range, 0.4-37.9 months). Results: Initial responses after CCRT for 85 patients were partial response: 26 patients, no change: 51 patients and progressive disease: 8 patients. Local progression was observed in 35 patients (32.4%), and the 2-year local control (LC) rate in all patients was 41.9%. Patients treated with total doses of 50 Gy or more had significantly more favorable LC rates (2-year LC rate, 42.9%) than patients treated with total doses of less than 50 Gy (2-year LC rate, 29.6%). Regional lymph node recurrence was found in only 1 patient, and none of the 57 patients with clinical N0 disease had regional lymph node recurrence. The 2-year overall survival (OS) rate and the median survival time in all patients were 23.5% and 11.6 months, respectively. Patients treated with AC had significantly more favorable OS rates (2-year OS, 31.8%) than those treated without AC (2-year OS, 12.4%; p < 0.0001). On multivariate analysis, AC use and clinical T stage were significant prognostic factors for OS. Conclusions: CCRT using GEM yields a relatively favorable LC rate for unresectable pancreatic adenocarcinoma, and CCRT with AC conferred a survival benefit compared to CCRT without AC.

  9. Calpain-2 expression is associated with response to platinum based chemotherapy, progression-free and overall survival in ovarian cancer

    Science.gov (United States)

    Storr, Sarah J; Safuan, Sabreena; Woolston, Caroline M; Abdel-Fatah, Tarek; Deen, Suha; Chan, Stephen Y; Martin, Stewart G

    2012-01-01

    Ovarian cancer is routinely treated with surgery and platinum-based chemotherapy. Resistance is a major obstacle in the efficacy of this chemotherapy regimen and the ability to identify those patients at risk of developing resistance is of considerable clinical importance. The expression of calpain-1, calpain-2 and calpastatin were determined using standard immunohistochemistry on a tissue microarray of 154 primary ovarian carcinomas from patients subsequently treated with platinum-based adjuvant chemotherapy. High levels of calpain-2 expression was significantly associated with platinum resistant tumours (P = 0.031). Furthermore, high expression of calpain-2 was significantly associated with progression-free (P = 0.049) and overall survival (P = 0.006) in this cohort. The association between calpain-2 expression and overall survival remained significant in multivariate analysis accounting for tumour grade, stage, optimal debulking and platinum sensitivity (hazard ratio = 2.174; 95% confidence interval = 1.144–4.130; P = 0.018). The results suggest that determining calpain-2 expression in ovarian carcinomas may allow prognostic stratification of patients treated with surgery and platinum-based chemotherapy. The findings of this study warrant validation in a larger clinical cohort. PMID:22435971

  10. Prognostic model for predicting survival of patients with metastatic urothelial cancer treated with cisplatin-based chemotherapy.

    Science.gov (United States)

    Apolo, Andrea B; Ostrovnaya, Irina; Halabi, Susan; Iasonos, Alexia; Philips, George K; Rosenberg, Jonathan E; Riches, Jamie; Small, Eric J; Milowsky, Matthew I; Bajorin, Dean F

    2013-04-03

    A prognostic model that predicts overall survival (OS) for metastatic urothelial cancer (MetUC) patients treated with cisplatin-based chemotherapy was developed, validated, and compared with a commonly used Memorial Sloan-Kettering Cancer Center (MSKCC) risk-score model. Data from 7 protocols that enrolled 308 patients with MetUC were pooled. An external multi-institutional dataset was used to validate the model. The primary measurement of predictive discrimination was Harrell's c-index, computed with 95% confidence interval (CI). The final model included four pretreatment variables to predict OS: visceral metastases, albumin, performance status, and hemoglobin. The Harrell's c-index was 0.67 for the four-variable model and 0.64 for the MSKCC risk-score model, with a prediction improvement for OS (the U statistic and its standard deviation were used to calculate the two-sided P = .002). In the validation cohort, the c-indices for the four-variable and the MSKCC risk-score models were 0.63 (95% CI = 0.56 to 0.69) and 0.58 (95% CI = 0.52 to 0.65), respectively, with superiority of the four-variable model compared with the MSKCC risk-score model for OS (the U statistic and its standard deviation were used to calculate the two-sided P = .02).

  11. HE4 as a predictor of adjuvant chemotherapy resistance and survival in patients with epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Aarenstrup Karlsen, Mona; Høgdall, Claus; Nedergaard, Lotte

    2016-01-01

    The aim of this study was to investigate the value of serum human epididymis protein 4 (HE4) and HE4 tissue protein expression to predict tumor resistance to adjuvant chemotherapy, progression-free survival (PFS), and overall survival in patients with epithelial ovarian cancer (EOC). Consecutive...... inclusion of 198 patients diagnosed with EOC was conducted. Blood samples were collected prior to surgery and tissue samples during surgery. Patient data were registered prospectively in the Danish Gynecologic Cancer Database. The association between serum HE4 and HE4 tissue protein expression, resistance...... significantly (p tissue protein expression...

  12. Chemotherapy for children with medulloblastoma

    NARCIS (Netherlands)

    Michiels, E.M.; Schouten-van Meeteren, A.Y.; Doz, F.; Janssens, G.O.R.J.; Dalen, E.C. van

    2015-01-01

    BACKGROUND: Post-surgical radiotherapy (RT) in combination with chemotherapy is considered as standard of care for medulloblastoma in children. Chemotherapy has been introduced to improve survival and to reduce RT-induced adverse effects. Reduction of RT-induced adverse effects was achieved by delet

  13. Role of chemotherapy in stage llb nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xin-Bin Pan; Xiao-Dong Zhu

    2012-01-01

    The efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy on stage lib nasopharyngeal carcinoma(NPC) remains unclear.Conventional two-dimensional radiotherapy combined with concurrent chemotherapy can improve the overall survival,progression-free survival,recurrence-free survival,and distant metastasis-free survival of patients with stage lib NPC.Intensity-modulated radiotherapy without concurrent chemotherapy also provides good outcomes for patients with stage lib NPC.This article summarizes the features of stage lib NPC and reviews the role of chemotherapy in this subgroup of NPC.

  14. Prognostic significance of K-ras and TP53 mutations in the role of adjuvant chemotherapy on survival in patients with Dukes C colon cancer

    NARCIS (Netherlands)

    Bleeker, W A; Hayes, V M; Karrenbeld, A; Hofstra, R M; Verlind, E; Hermans, J; Poppema, S; Buys, C H; Plukker, J T

    2001-01-01

    PURPOSE: Mutations in K-ras and TP53 genes are common in colorectal cancer. They affect biologic behavior and might influence chemotherapy susceptibility in these tumors. We investigated whether the survival of patients with Dukes C colon cancer treated with adjuvant chemotherapy is influenced by K-

  15. Opioid growth factor improves clinical benefit and survival in patients with advanced pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Jill P Smith

    2010-03-01

    Full Text Available Jill P Smith1, Sandra I Bingaman1, David T Mauger2, Harold H Harvey1, Laurence M Demers3, Ian S Zagon41Departments of Medicine, 2Public Health Sciences, 3Pathology, and 4Neurosciences and Anatomy, Pennsylvania State University, College of Medicine, Hershey Medical Center, Hershey, PA, USABackground: Advanced pancreatic cancer carries the poorest prognosis of all gastrointestinal malignancies. Once the tumor has spread beyond the margins of the pancreas, chemotherapy is the major treatment modality offered to patients; however, chemotherapy does not significantly improve survival.Objective: Opioid growth factor (OGF; [Met5]-enkephalin is a natural peptide that has been shown to inhibit growth of pancreatic cancer in cell culture and in nude mice. The purpose of this study was to evaluate the effects of OGF biotherapy on subjects with advanced pancreatic cancer who failed chemotherapy.Methods: In a prospective phase II open-labeled clinical trial, 24 subjects who failed standard chemotherapy for advanced pancreatic cancer were treated weekly with OGF 250 μg/kg intravenously. Outcomes measured included clinical benefit, tumor response by radiographic imaging, quality of life, and survival.Results: Clinical benefit response was experienced by 53% of OGF-treated patients compared to historical controls of 23.8% and 4.8% for gemcitabine and 5-fluorouracil (5-FU, respectively. Of the subjects surviving more than eight weeks, 62% showed either a decrease or stabilization in tumor size by computed tomography. The median survival time for OGF-treated patients was three times that of untreated patients (65.5 versus 21 days, p < 0.001. No adverse effects on hematologic or chemistry parameters were noted, and quality of life surveys suggested improvement with OGF. Limitations: Measurements other than survival were not allowed in control patients, and clinical benefit comparisons were made to historical controls.Conclusion: OGF biotherapy improves the

  16. Quality of pathologic response and surgery correlate with survival for completely resected bladder cancer following neoadjuvant chemotherapy

    Science.gov (United States)

    Sonpavde, Guru; Goldman, Bryan H.; Speights, V.O.; Lerner, Seth P.; Wood, David P.; Vogelzang, Nicholas J.; Trump, Donald L.; Natale, Ronald B.; Grossman, H. Barton; Crawford, E. David

    2010-01-01

    BACKGROUND In a retrospective study of SWOG-S8710/INT-0080 (radical cystectomy [RC] alone vs 3 cycles of MVAC neoadjuvant chemotherapy [NC] before RC for bladder cancer), factors associated with improved overall survival (OS) included pathologic complete response (pCR) defined as P0, treatment with NC, completion of RC with negative margins and ≥10 pelvic lymph nodes (LNs) removed. METHODS We used stratified Cox regression to retrospectively study the association of quality of pathologic response post-RC with OS in the subset of S8710 patients that received NC and RC with negative margins. RESULTS Of 154 patients who received NC, 68 (44.2%) were improved OS. A combination of baseline clinical stage and post-RC pathologic stage may better predict OS. PMID:19517476

  17. Role of color Doppler indices in predicting disease-free survival of breast cancer patients during neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Gurpreet, E-mail: guraiims@gmail.co [Medical Physics Unit, IRCH, AIIMS, New Delhi 110029 (India); Kumar, Pratik [Medical Physics Unit, IRCH, AIIMS, New Delhi 110029 (India); Parshad, Rajinder [Department of Surgery, AIIMS, New Delhi 110029 (India); Seith, Ashu; Thulkar, Sanjay [Department of Radiology, AIIMS, New Delhi 110029 (India); Hosten, Norbert [Department of Radiology, University of Greifswald, Greifswald 17489 (Germany)

    2010-08-15

    The aim of our study was to evaluate whether blood flow in locally advanced and inflammatory breast cancer before and after neoadjuvant chemotherapy using color Doppler ultrasonography can be used to monitor the response to therapy and identify possible correlations between survival and various Doppler indices. Fifty patients with breast cancer underwent Doppler evaluation of the tumor with determination of Doppler indices such as pulsatility index (PI), resistive index (RI), and peak systolic velocity (PSV). RI and PI decreased in 27 (54%) and 20 (40%) patients, respectively, and increased in 23 (46%) and 30 (60%) patients, respectively. Thirty (60%) patients showed a decrease in PSV and 20 (40%) patients an increase. Patients with an intratumoral blood flow velocity increase after chemotherapy had a greater likelihood of local recurrence and metastasis compared with patients in whom flow velocity decreased after chemotherapy. The study also confirmed a greater correlation between Doppler PSV and clinical assessment. Tumor flow velocity measured by Doppler ultrasound can be used as an independent marker of disease-free survival in patients with breast cancer.

  18. Best Practices for Chemotherapy Administration in Pediatric Oncology: Quality and Safety Process Improvements (2015).

    Science.gov (United States)

    Looper, Karen; Winchester, Kari; Robinson, Deborah; Price, Andrea; Langley, Rachel; Martin, Gina; Jones, Sally; Holloway, Jodi; Rosenberg, Susanne; Flake, Susan

    2016-01-01

    The administration of chemotherapy to children with cancer is a high-risk process that must be performed in a safe and consistent manner with high reliability. Clinical trials play a major role in the treatment of children with cancer; conformance to chemotherapy protocol requirements and accurate documentation in the medical record are critical. Inconsistencies in the administration and documentation of chemotherapy were identified as opportunities for errors to occur. A major process improvement was initiated to establish best practices for nurses who administer chemotherapy to children. An interdisciplinary team was formed to evaluate the current process and to develop best practices based on current evidence, protocol requirements, available resources, and safety requirements. The process improvement focused on the establishment of standardized and safe administration techniques, exact administration times, and consistent electronic documentation that could easily be retrieved in medical record audits. Quality improvement tools including SBAR (Situation, Background, Assessment, Recommendation), process mapping, PDSA (Plan, Do. Study, Act) cycles, and quality metrics were used with this process improvement. The team established best practices in chemotherapy administration to children that have proven to be safe and reliable. Follow-up data have demonstrated that the project was highly successful and improved accuracy, patient and nurse safety, and effectiveness of chemotherapy administration.

  19. Changing incidence and improved survival of gliomas

    NARCIS (Netherlands)

    Ho, Vincent K. Y.; Reijneveld, Jaap C.; Enting, Roeline; Bienfait, Henri P.; Robe, Pierre; Baumert, Brigitta G.; Visser, Otto

    2014-01-01

    BACKGROUND: Tumours of the central nervous system (CNS) represent a relatively rare but serious health burden. This study provides insight into the incidence and survival patterns of gliomas in the Netherlands diagnosed in adult patients during the time period 1989-2010, with a focus on glioblastoma

  20. Prognostic value of DCE-MRI in breast cancer patients undergoing neoadjuvant chemotherapy: a comparison with traditional survival indicators

    Energy Technology Data Exchange (ETDEWEB)

    Pickles, Martin D.; Lowry, Martin; Turnbull, Lindsay W. [Hull York Medical School at University of Hull, Hull Royal Infirmary, Centre for Magnetic Resonance Investigations, Hull (United Kingdom); Manton, David J. [Hull and East Yorkshire Hospitals NHS Trust, Radiation Physics Department, Hull (United Kingdom)

    2015-04-01

    To determine associations between dynamic contrast-enhanced MR imaging (DCE-MRI) parameters and survival intervals in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC), surgery, and adjuvant therapies. Further, to compare the prognostic value of DCE-MRI parameters against traditional survival indicators. DCE-MRI and MR tumour volume measures were obtained prior to treatment and post 2nd NAC cycle. To demonstrate which parameters were associated with survival, Cox's proportional hazards models (CPHM) were employed. To avoid over-parameterisation, only those MR parameters with at least a borderline significant result were entered into the final CPHM. When considering disease-free survival positive axillary nodal status (hazard ratio [HR] 6.79), younger age (HR 3.37), negative oestrogen receptor status (HR 3.24), pre-treatment Maximum Enhancement Index (MaxEI) (HR 6.51), and percentage change in MaxEI (HR 1.02) represented the retained CPHM covariates. Similarly, positive axillary nodal status (HR 11.47), negative progesterone receptor status (HR 4.37) and percentage change in AUC{sub 90} (HR 1.01) represented the retained predictive variables for overall survival. Multivariate survival analysis has demonstrated that DCE-MRI parameters obtained prior to NAC and/or post 2nd cycle can provide independent prognostic information that can complement traditional prognostic indicators available prior to treatment. (orig.)

  1. Concurrent chemoradiotherapy improves survival outcome in muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Sang Jun; Kim, Jin Hee; Oh, Young Kee; Kim, Byung Hoon [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2015-12-15

    To evaluate survival rates and prognostic factors related to treatment outcomes after bladder preserving therapy including transurethral resection of bladder tumor, radiotherapy (RT) with or without concurrent chemotherapy in bladder cancer with a curative intent. We retrospectively studied 50 bladder cancer patients treated with bladder-preserving therapy at Keimyung University Dongsan Medical Center from January 1999 to December 2010. Age ranged from 46 to 89 years (median, 71.5 years). Bladder cancer was the American Joint Committee on Cancer (AJCC) stage II, III, and IV in 9, 27, and 14 patients, respectively. Thirty patients were treated with concurrent chemoradiotherapy (CCRT) and 20 patients with RT alone. Nine patients received chemotherapy prior to CCRT or RT alone. Radiation was delivered with a four-field box technique (median, 63 Gy; range, 48.6 to 70.2 Gy). The follow-up periods ranged from 2 to 169 months (median, 34 months). Thirty patients (60%) showed complete response and 13 (26%) a partial response. All patients could have their own bladder preserved. Five-year overall survival (OS) rate was 37.2%, and the 5-year disease-free survival (DFS) rate was 30.2%. In multivariate analysis, tumor grade and CCRT were statistically significant in OS. Tumor grade was a significant prognostic factor related to OS. CCRT is also considered to improve survival outcomes. Further multi-institutional studies are needed to elucidate the impact of RT in bladder cancer.

  2. Fighting Cancer Together: Development and Implementation of Shared Medical Appointments to Standardize and Improve Chemotherapy Education

    Science.gov (United States)

    Prescott, Lauren S.; Dickens, Andrea S.; Guerra, Sandra L.; Tanha, Jila M.; Phillips, Desiree G.; Patel, Katherine T.; Umberson, Katie M.; Lozano, Miguel A.; Lowe, Kathryn B.; Brown, Alaina J.; Taylor, Jolyn S.; Soliman, Pamela T.; Garcia, Elizabeth A.; Levenback, Charles F.; Bodurka, Diane C.

    2015-01-01

    Objective Shared medical appointments offer a novel approach to improve efficiency and quality of care consistent with the goals of the Institute of Medicine. Our objective was to develop and implement a shared medical appointment for gynecologic cancer patients initiating chemotherapy. Methods We first assessed the level of interest in shared medical appointments among our patients and providers through qualitative interviews. Both patients and providers identified pre-chemotherapy as an optimal area to pilot shared medical appointments. We subsequently created a multidisciplinary team comprised of physicians, advanced practice providers, nurses, pharmacists, administrators, health education specialists and members of the Quality Improvement Department to establish a Shared Medical Appointment and Readiness Teaching (SMART) program for all gynecologic oncology patients initiating chemotherapy with platinum- and/or taxane-based regimens. We developed a standardized chemotherapy education presentation and provided patients with a tool kit that consisted of chemotherapy drug education, a guide to managing side effects, advance directives, and center contact information. Results From May 9, 2014 to June 26, 2015, 144 patients participated in 51 SMART visits. The majority of patients had ovarian cancer and were treated with carboplatin/paclitaxel. Surveyed patients reported being highly satisfied with the group visit and would recommend shared medical appointments to other patients. Conclusions This model of care provides patient education within a framework of social support that empowers patients. Shared medical appointments for oncology patients initiating chemotherapy are both feasible and well accepted. PMID:26549108

  3. Abiraterone plus prednisone improves survival in metastatic castration-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Scott T Tagawa; Himisha Beltran

    2011-01-01

    In essentially just 1 year's time,we have seen science translated into exciting new therapeutic agents for men with metastatic castration-resistant prostate cancer (CRPC),1 most recently with the United States Food and Drug Administration (FDA) approval of abiraterone acetate in combination with prednisone.2 While prostate cancer has been known to be highly responsive to surgical or medical castration for well over half a century,3 what was once termed 'hormone refractory' prostate cancer inevitably developed,leading to cancerrelated death.Many consider the introduction of chemotherapy for CRPC initially for symptomatic benefit,then with improvements in survival,a substantial step forward.

  4. Chemotherapy for Melanoma.

    Science.gov (United States)

    Wilson, Melissa A; Schuchter, Lynn M

    2016-01-01

    Prior to the recent therapeutic advances, chemotherapy was the mainstay of treatment options for advanced-stage melanoma. A number of studies have investigated various chemotherapy combinations in order to expand on the clinical responses achieved with single-agent dacarbazine, but these have not demonstrated an improvement in overall survival. Similar objective responses were observed with the combination of carboplatin and paclitaxel as were seen with single-agent dacarbazine. The combination of chemotherapy and immunotherapy, known as biochemo-therapy, has shown high clinical responses; however, biochemo-therapy has not been shown to improve overall survival and resulted in increased toxicities. In contrast, palliation and long-term responses have been observed with localized treatment with isolated limb perfusion or infusion in limb-isolated disease. Although new, improved therapeutic options exist for first-line management of advanced-stage melanoma, chemotherapy may still be important in the palliative treatment of refractory, progressive, and relapsed melanoma. We review the various chemotherapy options available for use in the treatment and palliation of advanced-stage melanoma, discuss the important clinical trials supporting the treatment recommendations, and focus on the clinical circumstances in which treatment with chemotherapy is useful.

  5. Effectiveness of third-generation chemotherapy on the survival of patients with advanced non-small cell lung cancer in Norway

    DEFF Research Database (Denmark)

    von Plessen, C; Strand, T-E; Wentzel-Larsen, T;

    2008-01-01

    BACKGROUND: To investigate whether the introduction of modern third-generation chemotherapy was associated with survival benefits in a national population of patients with advanced non-small cell lung cancer (ANSCLC) and to explore geographical and temporary variations in the utilisation of chemo......BACKGROUND: To investigate whether the introduction of modern third-generation chemotherapy was associated with survival benefits in a national population of patients with advanced non-small cell lung cancer (ANSCLC) and to explore geographical and temporary variations in the utilisation...... of death (HR 0.84, 95% CI 0.73 to 0.98). County of residence predicted chemotherapy utilisation with odds ratios in the range 0.13 (95% CI 0.1 to 0.19) to 1.04 (95% CI 0.64 to 1.69), a county with traditionally high utilisation as reference. CONCLUSION: Utilisation of third-generation chemotherapy...

  6. A Case of Advanced Gastric Cancer with Poor Performance Status Which Improved by Chemotherapy

    Directory of Open Access Journals (Sweden)

    Kohei Shitara

    2010-07-01

    Full Text Available Introduction: The prognosis of advanced gastric cancer patients, especially those with poor performance status (PS, is generally dismally poor. Patients with PS 3–4 are usually ineligible for participation in clinical studies and are managed with only best supportive care. Case Report: A 63-year-old male with advanced gastric cancer was admitted to our hospital. His PS was markedly impaired (Eastern Cooperative Oncology Group PS 4, with dyspnea secondary to lymphangitis, pleuritis and pericarditis. He also had bilateral leg paralysis due to multiple bone metastases. He was treated with chemotherapy using 5-fluorouracil and leucovorin for 14 days with pericardial drainage followed by intrapericardial infusion of cisplatin. He was also treated with radiotherapy for bone metastasis. The patient required 5 l/min oxygen therapy at the start of chemotherapy, but his dyspnea was improved by day 14 and he no longer required supplemental oxygen therapy. His leg paralysis also improved with the radiation therapy. His PS was significantly improved with this multimodal treatment modality, and he was ultimately discharged with chemotherapy with oral fluoropyrimidine. Conclusion: This case suggests that multimodal therapy including chemotherapy may be beneficial in advanced gastric cancer patients even in the setting of poor PS. Further study might be required to confirm the benefit of chemotherapy in this patient population.

  7. THROMBOCYTOSIS AS PROGNOSTIC FACTOR FOR SURVIVAL IN PATIENTS WITH ADVANCED NON SMALL CELL LUNG CANCER TREATED WITH FIRST- LINE CHEMOTHERAPY.

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2014-12-01

    Full Text Available Objective: The aim of this study was to evaluate elevated platelet count as a prognostic factor for survival in patients with advanced (stage IIIB/ IV non- small cell lung cancer (NSCLC receiving first- line chemotherapy. Methods: From 2005 to 2009 three hundreds forty seven consecutive patients with stage IIIB or IV NSCLC, treated in Department of Medical Oncology, UMHAT "Dr Georgi Stranski" entered the study. The therapeutic regimens included intravenous administration of platinum- based doublets. Survival analysis was evaluated by Kaplan- Meier test. The influence of pretreatment thrombocytosis as prognostic factor for survival was analyzed using multivariate stepwise Cox regression analyses. Results: Elevated platelet counts were found in 78 patients. The overall survival for patients without elevated platelet counts was 9,6 months versus 6,9 months for these with thrombocytosis. In multivariate analysis as independent poor prognostic factors were identified: stage, performance status and elevated platelet counts. Conclusions: These results indicated that platelet counts as well as some clinical pathologic characteristics could be useful prognostic factors in patients with unresectable NSCLC.

  8. Novel Combination Chemotherapy for Localized Ewing Sarcoma

    Science.gov (United States)

    In this clinical trial, researchers will test whether the addition of the drug combination vincristine, topotecan, and cyclophosphamide to a standard chemotherapy regimen improves overall survival in patients with extracranial Ewing

  9. Twelve-year experience of radioembolization for colorectal hepatic metastases in 214 patients: survival by era and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lewandowski, Robert J.; Memon, Khairuddin; Hickey, Ryan; Gates, Vanessa L.; Atassi, Bassel; Vouche, Michael; Atassi, Rohi; Desai, Kush; Hohlastos, Elias; Sato, Kent; Habib, Ali [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Mulcahy, Mary F.; Kircher, Sheetal; Newman, Steven B.; Nimeiri, Halla; Benson, Al B. [Northwestern University, Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL (United States); Marshall, Karen; Williams, Melissa; Salzig, Krystina; Salem, Riad [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Northwestern University, Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL (United States)

    2014-10-15

    The aim of this study was to analyze the safety, treatment characteristics and survival outcomes of Yttrium-90 (Y90) radioembolization for unresectable colorectal carcinoma (CRC) liver metastases refractory to standard of care therapy. A total of 214 patients with CRC metastases were treated with Y90 radioembolization over 12 years. Toxicity was assessed using National Cancer Institute common terminology criteria. Overall survival was analyzed from date of diagnosis of primary cancer, hepatic metastases and from the first Y90. Uni/multivariate analyses were performed. Substratification by era of chemotherapeutics was performed. Most patients were male (60 %) and <65 years old (61 %). Of them, 98 % had been exposed to chemotherapy. Grade 3 lymphocyte, bilirubin, albumin, ALP and AST toxicities were observed in 39 %, 11 %, 10 %, 8 % and 4 % of patients, respectively. Grade 4 lymphocyte and ALP toxicities were observed in 5 % and 3 % of patients, respectively. Median overall survival was 43.0, 34.6, and 10.6 months from date of diagnosis of primary cancer, hepatic metastases and first Y90, respectively. Survival was significantly longer in patients: (1) who received ≤2 cytotoxic drugs (n = 104) than those who received 3 (n = 110) (15.2 vs. 7.5 months, p = 0.0001); and (2) who received no biologic agents (n = 52) compared with those that did (n = 162) (18.6 vs. 9.4 months, p = 0.0001). Multivariate analyses identified ≤2 cytotoxic agents, no exposure to biologics, ECOG 0, tumor burden <25 %, lack of extrahepatic disease and albumin >3 g/dL as independent predictors of survival. In this largest metastatic CRC series published to date, Y90 radioembolization was found to be safe; survival varied by prior therapy. Further studies are required to further refine the role of Y90 in metastatic CRC. (orig.)

  10. PD-L1 Expression and Survival among Patients with Advanced Non–Small Cell Lung Cancer Treated with Chemotherapy

    Directory of Open Access Journals (Sweden)

    Steffen Filskov Sorensen

    2016-02-01

    Full Text Available BACKGROUND: Recent clinical trial results have suggested that programmed cell death ligand 1 (PD-L1 expression measured by immunohistochemistry may predict response to anti–programmed cell death 1 (PD-1 therapy. Results on the association between PD-L1 expression and survival among patients with advanced non–small cell lung cancer (NSCLC treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD-L1 expression was measured using a prototype immunohistochemistry assay with the anti–PD-L1 22C3 antibody (Merck. PD-L1 strong positivity and weak positivity were defined to be traceable to the clinical trial version of the assay. RESULTS: Twenty-five percent of patients had PD-L1 strong-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9.8 months for the PD-L1 weak-positive group compared with the PD-L1–negative group (median OS, 7.5 months. No association was seen between PD-L1 expression and OS when PD-L1 expression levels were stratified by median or tertiles. CONCLUSIONS: In concordance with previous studies, we found PD-L1 measured by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy.

  11. Second-line Chemotherapy and Its Survival Analysis of 181 Patients with
Extensive-stage Small Cell Lung Cancer in a Single Institute

    Directory of Open Access Journals (Sweden)

    Manjiao MA

    2013-11-01

    Full Text Available Background and objective Small cell lung cancer (SCLC is the most malignant neuroendocrine tumor and sensitive to chemotherapy and radiotherapy. However, most patients who receive first-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. Currently, the standard first-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen while the standard second-line chemotherapy regimen is open to debate. The aim of this study is to analysis the prognostic factors of second-line chemotherapy in extensive-stage SCLC and to compare the differences of objective response rate, side effects and survival among different second-line chemotherapy regimens. Methods 181 patients who were diagnosed as extensive-stage SCLC and received second-line chemotherapy were collected. χ2 test was used to analysis the differences of enumeration data and between different groups. Kaplan-Meier method was used to calculate the overall survival (OS and progression-free survival (PFS. Univariate analysis and Cox regression analysis were used to detect the prognostic factors. Objective response rate was evaluated by RECIST criteria and side effects were evaluated by WHO criteria. Results The patients who received second-line chemotherapy can be divided into 6 groups, namly group A (CE/EP regimen 27 cases, group B (regimens containing TPT 44 cases, group C (regimens containing CPT-11 33 cases, group D (regimens containing TAX/DXL 20 cases, group E (regimens containing IFO 28 cases and group F (other regimens 29 cases. The median OS in second-line chemotherapy as 7.0 months and was relevant with smoking history (P=0.004, ECOG PS (P<0.001, liver metastasis (P=0.019 and bone metastasis (P=0.028 independently. The median PFS in second-line chemotherapy as 3.0 months and was relevant with smoking history (P=0.034, ECOG PS (P=0.011 and bone metastasis (P=0.005. The response rate among six regimens was

  12. Improving the efficiency of a chemotherapy day unit: Applying a business approach to oncology

    NARCIS (Netherlands)

    Lent, van Wineke A.M.; Goedbloed, N.; Harten, van W.H.

    2009-01-01

    Aim: To improve the efficiency of a hospital-based chemotherapy day unit (CDU). - Methods: The CDU was benchmarked with two other CDUs to identify their attainable performance levels for efficiency, and causes for differences. Furthermore, an in-depth analysis using a business approach, called lean

  13. Circulating Tumor Cells in Metastatic Breast Cancer:Monitoring Response to Chemotherapy and Predicting Progression-Free Survival

    Institute of Scientific and Technical Information of China (English)

    Jian-ping Cheng; Ying Yan; Xiang-yi Wang; Yuan-li Lu; Yan-hua Yuan; Xiao-li Wang; Jun Jia; Jun Ren

    2010-01-01

    Objective:The purpose of this study is to explore RT-PCR method to set up the examination platform for detecting circulating tumor cells(CTC)in peripheral blood from metastatic breast cancer patients.The primary endpoint is to find out the correlation of existence of CTC with clinical responses and progression-free survival(PFS).Methods:The breast cancer cell line MCF-7 was serially diluted into the peripheral blood from 45 healthy donors to set up the sensitivity of RT-PCR assay.The expression of CK19 mRNA was amplified from both 49patients and 45 healthy donors respectively.The CK19 protein quantity from plasma was measured by competitive inhibition ELISA assay.Results:The sensitivity of RT-PCR could reach 1/106-107 white blood cells with specificity of 95.6%.The objective response rate(ORR)of patients with CK19 mRNA-negative undertaken one cycle chemotherapy was significantly higher than those with positive(P<0.0001).PFS among CK19 mRNA-negative patients was also increased,although there was no significance(P=0.098).The results of ELISA assay showed that CK19 protein was decreased significantly after one cycle chemotherapy,which gave rise to a little higher ORR(P=0.015)and increased PFS(P=0.016).Conclusion:Patients with unamplified CK19 mRNA after one cycle chemotherapy could achieve better radiographic evaluation and increased PFS,which was showed to be of consistency with the CK19 protein assay among the patients treated.

  14. Circulating Tumor Cells in Metastatic Breast Cancer: Monitoring Response to Chemotherapy and Predicting Progression-Free Survival

    Institute of Scientific and Technical Information of China (English)

    Jian-ping Cheng; Ying Yan; Xiang-yi Wang; Yuan-li Lu; Yan-hua Yuan; Xiao-li Wang; Jun Jia; Jun Ren

    2011-01-01

    Objective: The purpose of this study is to explore RT-PCR method to set up the examination platform for detecting circulating tumor cells(CTC) in peripheral blood from metastatic breast cancer patients.The primary endpoint is to find out the correlation of existence of CTC with clinical responses and progression-free survival (PFS).Methods: The breast cancer cell line MCF-7 was serially diluted into the peripheral blood from 45 healthy donors to set up the sensitivity of RT-PCR assay.The expression of CK19 mRNA was amplified from both 49 patients and 45 healthy donors respectively.The CK19 protein quantity from plasma was measured by competitive inhibition ELISA assay.Results: The sensitivity of RT-PCR could reach 1/106-107 white blood cells with specificity of 95.6%.The objective response rate(ORR) of patients with CK19 mRNA-negative undertaken one cycle chemotherapy was significantly higher than those with positive(P<0.0001).PFS among CK19 mRNA-negative patients was also increased,although there was no significance(P=0.098).The results of ELISA assay showed that CK19 protein was decreased significantly after one cycle chemotherapy,which gave rise to a little higher ORR(P=0.015) and increased PFS(P=0.016).Conclusion: Patients with unamplified CK19 mRNA after one cycle chemotherapy could achieve better radiographic evaluation and increased PFS,which was showed to be of consistency with the CK19 protein assay among the patients treated.

  15. Survival analysis of children with stage II testicular malignant germ cell tumors treated with surgery or surgery combined with adjuvant chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Su-Ying Lu; Xiao-Fei Sun; Zi-Jun Zhen; Zi-Ke Qin; Zhuo-Wei Liu; Jia Zhu; Juan Wang; Fei-Fei Sun

    2015-01-01

    For children with stage II testicular malignant germ cell tumors (MGCT), the survival is good with surgery and adjuvant chemotherapy. However, there is limited data on surgical results for cases in which there was no imaging or pathologic evidence of residual tumor, but in which serum tumor markers either increased or failed to normalize after an appropriate period of half-life time post-surgery. To determine the use of chemotherapy for children with stage II germ cel tumors, we analyzed the outcomes (relapse rate and overall survival) of patients who were treated at the Sun Yat-sen University Cancer Center between January 1990 and May 2013. Twenty-four pediatric patients with a median age of 20 months (range, 4 months to 17 years) were enrol ed in this study. In 20 cases (83.3%), the tumors had yolk sac histology. For definitive treatment, 21 patients underwent surgery alone, and 3 patients received surgery and adjuvant chemotherapy. No relapse was observed in the 3 patients who received adjuvant chemotherapy, whereas relapse occurred in 16 of the 21 patients (76.2%) treated with surgery alone. There were a total of 2 deaths. Treatment was stopped for 1 patient, who died 3 months later due to the tumor. The other patient achieved complete response after salvage treatment, but developed lung and pelvic metastases 7 months later and died of the tumor after stopping treatment. For children treated with surgery alone and surgery combined with adjuvant chemotherapy, the 3-year event-free survival rates were 23.8% and 100%, respectively (P=0.042), and the 3-year overal survival rates were 90.5%and 100%, respectively (P=0.588). These results suggest that adjuvant chemotherapy can help to reduce the recurrence rate and increase the survival rate for patients with stage II germ cel tumors.

  16. Use of biguanides to improve response to chemotherapy.

    Science.gov (United States)

    Sandulache, Vlad C; Yang, Liangpeng; Skinner, Heath D

    2014-01-01

    Metformin is a commonly utilized antidiabetic agent, which has been associated with improved clinical outcomes in cancer patients. The precise mechanism of action remains unclear, but preclinical evidence suggests that metformin can sensitize tumor cells to the effects to conventional chemotherapeutic agents and ionizing radiation (IR). In this chapter we discuss the general background of an approach to evaluate the effects of metformin on conventional chemotherapeutic agent toxicity in a preclinical model.

  17. Polymorphisms in the XRCC1 gene modify survival of bladder cancer patients treated with chemotherapy

    NARCIS (Netherlands)

    Sacerdote, C.; Guarrera, S.; Ricceri, F.; Pardini, B.; Polidoro, S.; Allione, A.; Critelli, R.; Russo, A.; Andrew, A.S.; Ye, Y.; Wu, X.; Kiemeney, L.A.L.M.; Bosio, A.; Casetta, G.; Cucchiarale, G.; Destefanis, P.; Gontero, P.; Rolle, L.; Zitella, A.; Fontana, D.; Vineis, P.; Matullo, G.

    2013-01-01

    Survival of bladder cancer patients depends on several factors including disease stage and grade at diagnosis, age, health status of the patient and the applied treatment. Several studies investigated the role of DNA repair genetic variants in cancer susceptibility, but only few studies investigated

  18. Association between different EGFR mutation status and survival in pemetrexed-based chemotherapy for advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    郏博

    2014-01-01

    Objective To explore the association between different epidermal growth factor receptor(EGFR)mutation status and survival in pemetrexed-based chemotherapy for advanced non-small-cell lung cancer(NSCLC).Methods A retrospective cohort study was performed to assess146 patients with advanced NSCLC at Cancer

  19. Current approaches to improve the anticancer chemotherapy with alkylating agents: state of the problem in world and Ukraine.

    Directory of Open Access Journals (Sweden)

    Iatsyshyna A. P.

    2012-01-01

    Full Text Available Alkylating agents are frequently used in many established anticancer chemotherapies. They alkylate the genomic DNA at various sites. Alkylation of the guanine at the O6-position is cytotoxic, it has the strongest mutagenic potential, as well as can cause the tumor development. Alkyl groups at the O6-position of guanine are removed by the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT. The effectiveness of alkylating chemotherapy is limited by MGMT in cancer cells and adverse toxic side effects in normal cells. Different approaches consisting in the modulation of the MGMT expression and activity are under development now to improve the cancer chemotherapy. They include two main directions, in particular, the increase in chemosensitivity of cancer cells to alkylating drugs and the protection of normal cells from the toxic side effects of chemotherapy. This review is focused on current attempts to improve the alkylating chemotherapy of malignant tumours worldwide and state of the issue in Ukraine

  20. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chun-Chieh [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China); Lai, Chyong-Huey [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Huang, Yi-Ting [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Chao, Angel; Chou, Hung-Hsueh [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Hong, Ji-Hong, E-mail: jihong@adm.cgmh.org.tw [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China)

    2012-11-15

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip Registered-Sign HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  1. Improved survival of children and adolescents with sickle cell disease.

    Science.gov (United States)

    Quinn, Charles T; Rogers, Zora R; McCavit, Timothy L; Buchanan, George R

    2010-04-29

    The survival of young children with sickle cell disease (SCD) has improved, but less is known about older children and adolescents. We studied the Dallas Newborn Cohort (DNC) to estimate contemporary 18-year survival for newborns with SCD and document changes in the causes and ages of death over time. We also explored whether improvements in the quality of medical care were temporally associated with survival. The DNC now includes 940 subjects with 8857 patient-years of follow-up. Most children with sickle cell anemia (93.9%) and nearly all children with milder forms of SCD (98.4%) now live to become adults. The incidence of death and the pattern of mortality changed over the duration of the cohort. Sepsis is no longer the leading cause of death. All the recent deaths in the cohort occurred in patients 18 years or older, most shortly after the transition to adult care. Quality of care in the DNC has improved over time, with significantly more timely initial visits and preventive interventions for young children. In summary, most children with SCD now survive the childhood years, but young adults who transition to adult medical care are at high risk for early death.

  2. Pilot study of "miracle fruit" to improve food palatability for patients receiving chemotherapy.

    Science.gov (United States)

    Wilken, Marlene K; Satiroff, Bernadette A

    2012-10-01

    Taste changes in patients undergoing chemotherapy are common and can be of long duration, are associated with poor nutrition, and can reduce quality of life. A pilot study of the fruit Synsepalum dulcificum-known as "miracle fruit"-as a novel supportive intervention was conducted with eight patients with cancer who were being treated with chemotherapy and reporting taste changes. Miraculin, a naturally occurring protein in miracle fruit, has the unusual ability to transduce a sweet signal in an acidic environment, profoundly changing food taste profiles for a short duration, masking unpleasant tastes, and increasing the palatability of certain foods. This pilot study was designed to determine whether consumption of the Miracle Fruit™ supplement would improve chemotherapy-associated taste changes, thereby improving the taste of food and ultimately leading to better nutrition. Four of the participants were given a two-week supply of the supplement and the other four were given a two-week supply of a placebo. After two weeks, the supplement group received a two-week supply of the placebo and the placebo group received a two-week supply of the supplement. Participants recorded food and drink intake in daily food dairies and rated taste changes with each food as better, worse, or no change. All study participants reported positive taste changes with the supplement.

  3. Chemotherapy for gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Javier Sastre; Jose Angel García-Saenz; Eduardo Díaz-Rubio

    2006-01-01

    Metastatic gastric cancer remains a non-curative disease.Palliative chemotherapy has been demonstrated to prolong survival without quality of life compromise. Many single-agents and combinations have been confirmed to be active in the treatment of metastatic disease. Objective response rates ranged from 10-30% for single-agent therapy and 30-60% for polychemotherapy. Results of phase Ⅱ and Ⅲ studies are reviewed in this paper as well as the potential efficacy of new drugs. For patients with localized disease, the role of adjuvant and neoadjuvant chemotherapy and radiation therapy is discussed.Most studies on adjuvant chemotherapy failed to demonstrate a survival advantage, and therefore, it is not considered as standard treatment in most centres. Adjuvant immunochemotherapy has been developed fundamentally in Korea and Japan. A meta-analysis of phase Ⅲ trials with OK-432 suggested that immunochemotherapy may improve survival of patients with curatively resected gastric cancer. Based on the results of US Intergroup 0116study, postoperative chemoradiation has been Accepted as standard care in patients with resected gastric cancer in North America. However, the results are somewhat confounded by the fact that patients underwent less than a recommended D1 lymph node dissection and the pattern of recurrence suggested a positive effect derived from local radiotherapy without any effect on micrometastatic disease.Neoadjuvant chemotherapy or chemoradiation therapy remains experimental, but several phase Ⅱstudies are showing promising results. Phase Ⅲ trials are needed.

  4. Peripherally administered orexin improves survival of mice with endotoxin shock

    Science.gov (United States)

    Ogawa, Yasuhiro; Irukayama-Tomobe, Yoko; Murakoshi, Nobuyuki; Kiyama, Maiko; Ishikawa, Yui; Hosokawa, Naoto; Tominaga, Hiromu; Uchida, Shuntaro; Kimura, Saki; Kanuka, Mika; Morita, Miho; Hamada, Michito; Takahashi, Satoru; Hayashi, Yu; Yanagisawa, Masashi

    2016-01-01

    Sepsis is a systemic inflammatory response to infection, accounting for the most common cause of death in intensive care units. Here, we report that peripheral administration of the hypothalamic neuropeptide orexin improves the survival of mice with lipopolysaccharide (LPS) induced endotoxin shock, a well-studied septic shock model. The effect is accompanied by a suppression of excessive cytokine production and an increase of catecholamines and corticosterone. We found that peripherally administered orexin penetrates the blood-brain barrier under endotoxin shock, and that central administration of orexin also suppresses the cytokine production and improves the survival, indicating orexin’s direct action in the central nervous system (CNS). Orexin helps restore body temperature and potentiates cardiovascular function in LPS-injected mice. Pleiotropic modulation of inflammatory response by orexin through the CNS may constitute a novel therapeutic approach for septic shock. DOI: http://dx.doi.org/10.7554/eLife.21055.001 PMID:28035899

  5. Assessment and monitoring of patients receiving chemotherapy for multiple myeloma: strategies to improve outcomes

    Directory of Open Access Journals (Sweden)

    Faiman B

    2016-05-01

    Full Text Available Beth Faiman, Jason Valent Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA Abstract: Improved understanding as to the biology of multiple myeloma (MM and the bone marrow microenvironment has led to the development of new drugs to treat MM. This explosion of new and highly effective drugs has led to dramatic advances in the management of MM and underscores the need for supportive care. Impressive and deep response rates to chemotherapy, monoclonal antibodies, and small molecule drugs provide hope of a cure or prolonged remission for the majority of individuals. For most patients, long-term, continuous therapy is often required to suppress the malignant plasma cell clone, thus requiring clinicians to become more astute in assessment, monitoring, and intervention of side effects as well as monitoring response to therapy. Appropriate diagnosis and monitoring strategies are essential to ensure that patients receive the appropriate chemotherapy and supportive therapy at relapse, and that side effects are appropriately managed to allow for continued therapy and adherence to the regimen. Multiple drugs with complex regimens are currently available with varying side effect profiles. Knowledge of the drugs used to treat MM and the common adverse events will allow for preventative strategies to mitigate adverse events and prompt intervention. The purpose of this paper is to review updates in the diagnosis and management of MM, and to provide strategies for assessment and monitoring of patients receiving chemotherapy for MM. Keywords: multiple myeloma, treatment, symptoms, assessment, monitoring, symptom management, targeted therapies

  6. Cyberknife Radiosurgery and Concurrent Intrathecal Chemotherapy for Leptomeningeal Metastases: Case Report of Prolonged Survival of a HER-2+ Breast Cancer Patient Status-Post Craniospinal Irradiation.

    Science.gov (United States)

    Lekovic, Gregory; Drazin, Doniel; Mak, Albert C; Schwartz, Marc S

    2016-01-07

    Leptomeningeal disease (LMD) from breast cancer is usually a rapidly fatal condition, with median overall survival reported to be 15 weeks. Conventional treatment for LMD includes craniospinal irradiation and intrathecal (IT) methotrexate. However, the role of stereotactic radiation for leptomeningeal disease remains poorly defined. This case report describes our experience using Cyberknife radiosurgery to treat a 49-year-old female with HER-2+ breast cancer and focal/nodular leptomeningeal metastases that were refractory to craniospinal irradiation and concurrent IT chemotherapy. This combined approach--i.e., craniospinal irradiation, IT chemotherapy, and Cyberknife Radiosurgery for local, recurrent metastases--resulted in survival of 46 months with controlled disease. Based on our experience with this patient, we believe further consideration of radiosurgery for LMD is warranted.

  7. Debulking treatment with CT-guided percutaneous radiofrequency ablation and hepatic artery infusion of floxuridine improves survival of patients with unresectable pulmonary and hepatic metastases of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Sheng Li; Ni He; Wang Li; Pei-Hong Wu

    2014-01-01

    The survival of most patients with both unresectable hepatic and pulmonary metastases of colorectal cancer is poor. In this retrospective study, we investigated the efficacy of computed tomography (CT)-guided radiofrequency ablation (RFA) and systemic chemotherapy plus hepatic artery infusion of floxuridine (HAI-FUDR). Sixty-one patients were selected from 1,136 patients with pulmonary and hepatic metastases from colorectal cancer. Patients were treated with RFA and systemic chemotherapy plus HAI-FUDR (ablation group, n=39) or systemic chemotherapy plus HAI-FUDR (FUDR group, n=22). Patients in the two groups were matched by sex, age, number of metastases, and calendar year of RFA or FUDR. Survival data were evaluated by using univariate and multivariate analyses. Clinical characteristics were comparable between the two groups. Al patients in the ablation group underwent RFA and chemotherapy. Median fol ow-up was 56.8 months. The 1-, 3-, and 5-year overall survival (OS) rates were 97%, 64%, and 37%, respectively, for the ablation group, and 82%, 32%, and 19%, respectively, for the FUDR group. The 1-, 3-, and 5-year survival rates after metastasis were 97%, 49%, and 26%for the ablation group, and 72%, 24%, and 24%for the FUDR group, respectively. The median OS times were 45 and 25 months for the ablation and FUDR groups, respectively. In the multivariate analysis, treatment al ocation was a favorable independent prognostic factor for OS (P = 0.001) and survival after metastasis (P = 0.009). These data suggest that the addition of RFA to systemic chemotherapy plus HAI-FUDR improves the survival of patients with both unresectable hepatic and pulmonary metastases from colorectal cancer.

  8. Improving the Safety of Oral Chemotherapy at an Academic Medical Center

    Science.gov (United States)

    Casella, Erica; Capozzi, Donna; McGettigan, Suzanne; Gangadhar, Tara C.; Schuchter, Lynn; Myers, Jennifer S.

    2016-01-01

    Purpose: Over the last decade, the use of oral chemotherapy (OC) for the treatment of cancer has dramatically increased. Despite their route of administration, OCs pose many of the same risks as intravenous agents. In this quality improvement project, we sought to examine our current process for the prescription of OC at the Abramson Cancer Center of the University of Pennsylvania and to improve on its safety. Methods: A multidisciplinary team that included oncologists, advanced-practice providers, and pharmacists was formed to analyze the current state of our OC practice. Using Lean Six Sigma quality improvement tools, we identified a lack of pharmacist review of the OC prescription as an area for improvement. To address these deficiencies, we used our electronic medical system to route OC orders placed by treating providers to an oncology-specific outpatient pharmacist at the Abramson Cancer Center for review. Results: Over 7 months, 63 orders for OC were placed for 45 individual patients. Of the 63 orders, all were reviewed by pharmacists, and, as a result, 22 interventions were made (35%). Types of interventions included dosage adjustment (one of 22), identification of an interacting drug (nine of 22), and recommendations for additional drug monitoring (12 of 22). Conclusion: OC poses many of the same risks as intravenous chemotherapy and should be prescribed and reviewed with the same oversight. At our institution, involvement of an oncology-trained pharmacist in the review of OC led to meaningful interventions in one third of the orders. PMID:26733627

  9. Additional Survival Benefit of Involved-Lesion Radiation Therapy After R-CHOP Chemotherapy in Limited Stage Diffuse Large B-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jeanny [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Il Han, E-mail: ihkim@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Kim, Byoung Hyuck [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Tae Min; Heo, Dae Seog [Department of Internal Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-05-01

    Purpose: The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. Methods and Materials: We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥7 cm); and 75.3% underwent ≥6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). Results: After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Conclusions: Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level.

  10. Comparing overall survival between first generation EGFR-TKIs and chemotherapy in lung cancer patients with Del19/L858R

    OpenAIRE

    Deng, Wei; Lei, Yuanyuan; Liu, Siyang; Yang, Jinji; Tu, Haiyan; Yan, Honghong; Wu, Yilong

    2016-01-01

    Objective Combined overall survival (OS) analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor (EGFR) exon 19 deletions (Del19) would benefit from first-line second generation EGFR tyrosine kinase inhibitors (TKIs) afatinib but not for those with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these t...

  11. Kaempferol and Chrysin Synergies to Improve Septic Mice Survival.

    Science.gov (United States)

    Harasstani, Omar A; Tham, Chau Ling; Israf, Daud A

    2017-01-06

    Previously, we reported the role of synergy between two flavonoids-namely, chrysin and kaempferol-in inhibiting the secretion of a few major proinflammatory mediators such as tumor necrosis factor-alpha (TNF-α), prostaglandin E₂ (PGE₂), and nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW 264.7 cells. The present study aims to evaluate the effects of this combination on a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Severe sepsis was induced in male ICR mice (n = 7) via the CLP procedure. The effects of chrysin and kaempferol combination treatment on septic mice were investigated using a 7-day survival study. The levels of key proinflammatory mediators and markers-such as aspartate aminotransferase (AST), TNF-α, and NO-in the sera samples of the septic mice were determined via ELISA and fluorescence determination at different time point intervals post-CLP challenge. Liver tissue samples from septic mice were harvested to measure myeloperoxidase (MPO) levels using a spectrophotometer. Moreover, intraperitoneal fluid (IPF) bacterial clearance and total leukocyte count were also assessed to detect any antibacterial effects exerted by chrysin and kaempferol, individually and in combination. Kaempferol treatment improved the survival rate of CLP-challenged mice by up to 16%. During this treatment, kaempferol expressed antibacterial, antiapoptotic and antioxidant activities through the attenuation of bacterial forming units, AST and NO levels, and increased polymorphonuclear leukocyte (PMN) count in the IPF. On the other hand, the chrysin treatment significantly reduced serum TNF-α levels. However, it failed to significantly improve the survival rate of the CLP-challenged mice. Subsequently, the kaempferol/chrysin combination treatment significantly improved the overall 7-day survival rate by 2-fold-up to 29%. Kaempferol and chrysin revealed some synergistic effects by acting individually upon multiple

  12. Combining gene signatures improves prediction of breast cancer survival.

    Directory of Open Access Journals (Sweden)

    Xi Zhao

    Full Text Available BACKGROUND: Several gene sets for prediction of breast cancer survival have been derived from whole-genome mRNA expression profiles. Here, we develop a statistical framework to explore whether combination of the information from such sets may improve prediction of recurrence and breast cancer specific death in early-stage breast cancers. Microarray data from two clinically similar cohorts of breast cancer patients are used as training (n = 123 and test set (n = 81, respectively. Gene sets from eleven previously published gene signatures are included in the study. PRINCIPAL FINDINGS: To investigate the relationship between breast cancer survival and gene expression on a particular gene set, a Cox proportional hazards model is applied using partial likelihood regression with an L2 penalty to avoid overfitting and using cross-validation to determine the penalty weight. The fitted models are applied to an independent test set to obtain a predicted risk for each individual and each gene set. Hierarchical clustering of the test individuals on the basis of the vector of predicted risks results in two clusters with distinct clinical characteristics in terms of the distribution of molecular subtypes, ER, PR status, TP53 mutation status and histological grade category, and associated with significantly different survival probabilities (recurrence: p = 0.005; breast cancer death: p = 0.014. Finally, principal components analysis of the gene signatures is used to derive combined predictors used to fit a new Cox model. This model classifies test individuals into two risk groups with distinct survival characteristics (recurrence: p = 0.003; breast cancer death: p = 0.001. The latter classifier outperforms all the individual gene signatures, as well as Cox models based on traditional clinical parameters and the Adjuvant! Online for survival prediction. CONCLUSION: Combining the predictive strength of multiple gene signatures improves

  13. Associations of polymorphisms in DNA repair genes and MDR1 gene with chemotherapy response and survival of non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Yan Du

    Full Text Available OBJECTIVES: We aimed to determine the associations of genetic polymorphisms of excision repair cross-complementation group 1 (ERCC1 rs11615, xeroderma pigmentosum group D (XPD/ERCC2 rs13181, X-ray repair cross complementing group 1 (XRCC1 rs25487, XRCC3 rs1799794, and breast cancer susceptibility gene 1 (BRCA1 rs1799966 from the DNA repair pathway and multiple drug resistance 1 (MDR1/ABCB1 rs1045642 with response to chemotherapy and survival of non-small cell lung cancer (NSCLC in a Chinese population. MATERIALS AND METHODS: A total of 352 NSCLC patients were enrolled to evaluate the associations of the six SNPs with response to chemotherapy and overall survival. Logistic regressions were applied to test the associations of genetic polymorphisms with response to chemotherapy in 161 advanced NSCLC patients. Overall survival was analyzed in 161 advanced and 156 early stage NSCLC patients using the Kaplan-Meier method with log-rank test, respectively. Multivariate Cox proportional hazards model was performed to determine the factors independently associated with NSCLC prognosis. RESULTS: BRCA1 rs1799966 minor allele C (TC+CC vs. TT, OR = 0.402, 95% CI = 0.204-0.794, p = 0.008 and MDR1/ABCB1 rs1045642 minor allele A (GA +AA vs. GG, OR = 0.478, 95% CI = 0.244-0.934, p = 0.030 were associated with a better response to chemotherapy in advanced NSCLC patients. Survival analyses indicated that BRCA1 rs1799966 TC+CC genotypes were associated with a decreased risk of death (HR = 0.617, 95% CI = 0.402-0.948, p = 0.028 in advanced NSCLC patients, and the association was still significant after the adjustment for covariates. Multivariate Cox regression analysis showed that ERCC1 rs11615 AA genotype (P = 0.020 and smoking (p = 0.037 were associated with increased risks of death in early stage NSCLC patients after surgery. CONCLUSIONS: Polymorphisms of genes in DNA repair pathway and MDR1 could contribute to chemotherapy response and survival of patients with

  14. Predictive factors for response and prognostic factors for long-term survival in consecutive, single institution patients with locally advanced and/or metastatic transitional cell carcinoma following cisplatin-based chemotherapy

    DEFF Research Database (Denmark)

    Jessen, Christian; Agerbaek, Mads; Von Der Maase, Hans

    2009-01-01

    PURPOSE: The study was undertaken to identify pre-treatment clinical and histopathological factors of importance for response and survival after cisplatin-based combination chemotherapy, in patients with locally advanced or metastatic transitional cell carcinoma of the urothelium. PATIENTS...

  15. Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Boda-Heggemann, J.; Schneider, V. [Heidelberg Univ., Universitaetsmedizin Mannheim (Germany). Dept. of Radiation Oncology; Weiss, C. [Heidelberg Univ., Universitaetsmedizin Mannheim (Germany). Dept. of Biomathematics and Medical Statistics] [and others

    2013-05-15

    Purpose: In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. Patients and methods: Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Results: Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed. Conclusion: After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity. (orig.)

  16. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy

    DEFF Research Database (Denmark)

    Bellmunt, J; Fougeray, R; Rosenberg, J E;

    2013-01-01

    To compare long-term, updated overall survival (OS) of patients with advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine plus best supportive care (BSC) or BSC alone, after failure of platinum-based chemotherapy.......To compare long-term, updated overall survival (OS) of patients with advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine plus best supportive care (BSC) or BSC alone, after failure of platinum-based chemotherapy....

  17. TP53 hotspot mutations are predictive of survival in primary central nervous system lymphoma patients treated with combination chemotherapy.

    Science.gov (United States)

    Munch-Petersen, Helga D; Asmar, Fazila; Dimopoulos, Konstantinos; Areškevičiūtė, Aušrinė; Brown, Peter; Girkov, Mia Seremet; Pedersen, Anja; Sjö, Lene D; Heegaard, Steffen; Broholm, Helle; Kristensen, Lasse S; Ralfkiaer, Elisabeth; Grønbæk, Kirsten

    2016-04-22

    Primary central nervous system lymphoma (PCNSL) is an aggressive variant of diffuse large B-cell lymphoma (DLBCL) confined to the CNS. TP53 mutations (MUT-TP53) were investigated in the context of MIR34A/B/C- and DAPK promoter methylation status, and associated with clinical outcomes in PCNSL patients. In a total of 107 PCNSL patients clinical data were recorded, histopathology reassessed, and genetic and epigenetic aberrations of the p53-miR34-DAPK network studied. TP53 mutational status (exon 5-8), with structural classification of single nucleotide variations according to the IARC-TP53-Database, methylation status of MIR34A/B/C and DAPK, and p53-protein expression were assessed. The 57/107 (53.2 %) patients that were treated with combination chemotherapy +/- rituximab (CCT-treated) had a significantly better median overall survival (OS) (31.3 months) than patients treated with other regimens (high-dose methotrexate/whole brain radiation therapy, 6.0 months, or no therapy, 0.83 months), P TP53 mutations were identified in 32/86 (37.2 %), among which 12 patients had hotspot/direct DNA contact mutations. CCT-treated patients with PCNSL harboring a hotspot/direct DNA contact MUT-TP53 (n = 9) had a significantly worse OS and progression free survival (PFS) compared to patients with non-hotspot/non-direct DNA contact MUT-TP53 or wild-type TP53 (median PFS 4.6 versus 18.2 or 45.7 months), P = 0.041 and P = 0.00076, respectively. Multivariate Cox regression analysis confirmed that hotspot/direct DNA contact MUT-TP53 was predictive of poor outcome in CCT-treated PCNSL patients, P = 0.012 and P = 0.008; HR: 1.86 and 1.95, for OS and PFS, respectively. MIR34A, MIR34B/C, and DAPK promoter methylation were detected in 53/93 (57.0 %), 80/84 (95.2 %), and 70/75 (93.3 %) of the PCNSL patients with no influence on survival. Combined MUT-TP53 and MIR34A methylation was associated with poor PFS (median 6.4 versus 38.0 months), P = 0.0070. This

  18. Abiraterone in metastatic prostate cancer without previous chemotherapy

    NARCIS (Netherlands)

    Ryan, C.J.; Smith, M.R.; Bono, J. De; Molina, A.; Logothetis, C.J.; Souza, P. de; Fizazi, K.; Mainwaring, P.; Piulats, J.M.; Ng, S.; Carles, J.; Mulders, P.F.A.; Basch, E.; Small, E.J.; Saad, F.; Schrijvers, D.; Poppel, H. van; Mukherjee, S.D.; Suttmann, H.; Gerritsen, W.R.; Flaig, T.W.; George, D.J.; Yu, E.Y.; Efstathiou, E.; Pantuck, A.; Winquist, E.; Higano, C.S.; Taplin, M.E.; Park, Y.; Kheoh, T.; Griffin, T.; Scher, H.I.; Rathkopf, D.E.

    2013-01-01

    BACKGROUND: Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. METHODS: In this double-blind study, we

  19. Obese non-Hodgkin lymphoma patients tolerate full uncapped doses of chemotherapy with no increase in toxicity, and a similar survival to that seen in nonobese patients.

    Science.gov (United States)

    Chan, Henry; Jackson, Sharon; McLay, Jessica; Knox, Angela; Lee, Jae; Wang, Sarah; Issa, Samar

    2016-11-01

    The aim of this study is to compare the risk of treatment-related toxicities and long-term survival between obese and nonobese patients with non-Hodgkin lymphoma when treated with full uncapped doses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. A total of 133 patients and 733 cycles of chemotherapy were analyzed. Obese patients did not experience an increased risk of acute treatment-related toxicities (adjusted odds ratio 0.825, p = 0.197), or delayed toxicities (adjusted odds ratio 0.819, p = 0.779). In the subgroup of diffuse large B-cell lymphoma patients (n = 109), treatment response rate was similar between the two body mass index (BMI) groups, and obese patients tended to have superior overall and progression-free survivals, albeit not statistically significant. Full uncapped doses of R-CHOP chemotherapy administered to obese patients with non-Hodgkin lymphoma (NHL) are safe, well tolerated, and do not lead to inferior treatment response or long-term outcomes.

  20. PREDICTORS OF OVERALL SURVIVAL IN PATIENTS WITH RECURRENT NON-SEMINOMATOUS GERMINAL TESTICULAR TUMORS ON CURRENT SECOND-LINE CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2010-01-01

    Full Text Available Objective: to define predictors that influence longevity in patients with recurrent non-seminomatous germinal testicular tumors (NGTT on standard second-line chemotherapy (CT including cisplatin and iphosphamide. Statistical analysis was performed using the statistical packages Graph Pad Prism 4.00 for Windows and SPSS 15.0 for Windows. Subjects and methods. Case history data were analyzed in 693 patients with disseminated NGTT who had received current CT and followed up at the Department of Clinical Pharmacology and CT, N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences. The median follow-up was 32 (range 3-215 months. The disease progressed in 181 (26% patients. Detailed information was available on the nature of second-line CT in only 138 patients. Half (71 (51.7% of the 138 patients had second-line CT including iphosphamide. Uni- and multivariate analyses were made to identify predictors that influence longevity in patients with recurrent NGTT on standard secondline CT including cisplatin and iphosphamide. Results. Five-year overall survival (OS was 32% (95% confidence interval 25-41%. The multivariate analysis showed the morphological pattern of a primary tumor (a yolk sac tumor component, a pre-induction CT lactate dehydrogenase (LDH level of ?d1.5 units of the upper normal range, progression during induction CT, and a pre-second-line CT LDH level of ?d 1000 U/l to be negative predictors. According to the number of negative factors, the patients were classified into 3 groups: 1 good prognosis [n = 10 (14% of the 71 patients], 100% 3-year OS; 2 intermediate prognosis (one negative factor [n = 33 (46.5% of the 71 patients], 50.2% 3-year OS; 3 poor prognosis (?d 2 negative factors, 6.7% 3-year OS. Conclusion. Standard iphosphamide-containing therapy enables all patients to be treated in the good prognosis group of those with recurrent NGTT. That fails to achieve such striking results in the intermediate and

  1. Cytochrome P450 Bioconjugate as a Nanovehicle for Improved Chemotherapy Treatment.

    Science.gov (United States)

    Quester, Katrin; Juarez-Moreno, Karla; Secundino, Isamel; Roseinstein, Yvonne; Alejo, Karla P; Huerta-Saquero, Alejandro; Vazquez-Duhalt, Rafael

    2016-11-28

    Cancer is still a growing public health problem, especially breast cancer that is one of the most important cancers in women. Chemotherapy, even though a successful treatment, is accompanied by severe side effects. Moreover, most of the drugs used for chemotherapy are administered as prodrugs and need to be transformed to the active form by cytochromes P450 (CYPs). In addition, increasing numbers of cancer tissues show lower CYP activity than the surrounding healthy tissues in which prodrugs are preferentially activated causing cytotoxicity. Here, the design of a functionalized cytochrome P450 bioconjugate is reported as nanovehicle for the enzyme direct delivery to the tumor tissue in order to improve the local drug activation. MCF-7 breast cancer cells are treated with CYP-polyethylene glycol bioconjugate functionalized folic acid, where it activates the prodrug tamoxifen and significantly reduces the dose of tamoxifen needed to kill the tumor cells. The CYP bioconjugate covered with polyethylene glycol shows no immunogenic activity. The advantages of increasing the site-specific CYP activity in tumor tissues are discussed.

  2. A meta-analysis of neoadjuvant chemotherapy plus radiation in the treatment of locally advanced nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Xun He

    2015-01-01

    Conclusion: Neoadjuvant chemotherapy followed by radiation can decrease the risk of recurrence and metastasis but not improve the 5 years overall survival and 5 years disease free survival compared to radiotherapy alone in the patients with locally advanced nasopharyngeal carcinoma.

  3. Split Course Hyperfractionated Accelerated Radio-Chemotherapy (SCHARC for patients with advanced head and neck cancer: Influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Sprague Lisa D

    2006-12-01

    Full Text Available Abstract Background The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. Methods From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %, one third with tongue and floor of mouth tumors (29 % and one fifth (19 % suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1–5: 20 mg/m2/d DDP + 750–1000 mg/m2/d 5FU (cont. infusion. This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69–70.5 Gy. All patients assigned to this scheme were included in the survival evaluation. Results Forty patients (63 % received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d and the median follow up was 1.9 years (678 d, respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 % had acute grade 2–3 mucositis, and 33 patients (58 % suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient 10.5 g/dl and for patients who completed the protocol. Conclusion The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led to long-term disease control and survival in about 50 % of the patients with significant but acceptable toxicity. Most patients

  4. Receipt of maintenance therapy is most predictive of survival in older acute lymphoblastic leukemia patients treated with intensive induction chemotherapy regimens.

    Science.gov (United States)

    Landsburg, Daniel J; Stadtmauer, Edward; Loren, Alison; Goldstein, Steven; Frey, Noelle; Nasta, Sunita D; Porter, David L; Tsai, Donald E; Perl, Alexander E; Hexner, Elizabeth O; Luger, Selina

    2013-08-01

    While the prognosis for older adults diagnosed with acute lymphoblastic leukemia (ALL) is frequently poor, long-term survival can be achieved in patients treated with curative intent. We reviewed the outcomes of 37 patients age ≥60 treated at our institution with either DVP- or hyperCVAD-based chemotherapy regimens from 2003-2011. In this patient population, a complete response rate of 92%, relapse rate of 56% and median overall survival of 18.1 months was experienced. Univariate analysis revealed that receipt of maintenance therapy vs. no maintenance therapy was associated with a statistically-significant impact on overall survival (p = 0.001, HR 0.15 for death), while disease-related characteristics including high-risk white blood cell count at diagnosis and Philadelphia chromosome status as well as treatment-related factors including chemotherapy regimen or completion of intensive therapy were not. Many patients were unable to initiate or remain on maintenance therapy due to toxicities including infections and cytopenias. Our analysis reveals the benefit of prolonged therapy in the treatment of older adults with ALL as well as the high incidence of treatment-related toxicity experienced by these patients.

  5. Prognostic evaluation of PET/CT in residual post-chemotherapy masses in patients with diffuse large B-cell lymphoma and its impact on survival

    OpenAIRE

    Dina M. ABO-Sheisha; Omnia Abdel Fattah

    2014-01-01

    Aim of the work: To evaluate the prognostic value and accuracy of PET/CT in DLBCL patients with post-treatment CT-residual masses with concern in overall (OAS) and progression-free survival (PFS). Materials and methods: We retrospectively studied 62 patients with DLBCL who had CT documented residual masses (CRu) after completion of chemotherapy. Results: Forty-four patients with negative PET scan were free of relapse while 4 out of 18 patients with positive scan showed CR, the other 14 ...

  6. Efficacy and safety of goserelin combined with adjuvant chemotherapy in premenopausal women with breast cancer

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2015-12-01

    Full Text Available This study aims to evaluate the efficacy and safety of goserelin combined with chemotherapy for premenopausal women with breast cancer. Literatures were extracted from databases including Excerpta Medica Database, Springer, Pubmed, China National Knowledge Infrastructure and Chinese Biological Medicine from their inception up to May 2014. The main efficacy measures were 5 years overall survival (OS, 10 years OS, 5 years disease free survival and 5 years progress free survival. Ten randomized comparison clinical trials were eligible in this study. The result showed that goserelin combined with chemotherapy group can improve the survival rate and decrease the incidence of arthralgia in postmenopausal breast cancer patients, respectively, compared to the control group. However, they can increase the occurrence of vomiting during the chemotherapy process. Compared with the simple chemotherapy, goserelin combined with chemotherapy can provide benefits for premenopausal women with breast cancer on improving the survival rate and reducing arthralgia.

  7. Survival is associated with complete response on MRI after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer

    NARCIS (Netherlands)

    Loo, Claudette E; Rigter, Lisanne S; Pengel, Kenneth E; Wesseling, Jelle; Rodenhuis, Sjoerd; Peeters, Marie-Jeanne T F D Vrancken; Sikorska, Karolina; Gilhuijs, Kenneth G A

    2016-01-01

    BACKGROUND: Pathological complete remission (pCR) of estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer is rarely achieved after neoadjuvant chemotherapy (NAC). In addition, the prognostic value of pCR for this breast cancer subtype is limited. We

  8. Prolonged Survival in a Case of Chemotherapy-Sensitive Gastric Cancer That Produced Alpha-Fetoprotein and Protein Induced by Vitamin K Antagonist-II

    Directory of Open Access Journals (Sweden)

    Naotaka Ogasawara

    2015-04-01

    Full Text Available The number of reported cases of alpha-fetoprotein (AFP-producing gastric cancer has gradually increased, with a reported prevalence of 1.3-1.5% of all gastric cancer cases. However, reports of gastric cancer accompanied by elevated serum levels of both AFP and protein induced by vitamin K antagonist-II (PIVKA-II are rare. The prognosis of AFP- and PIVKA-II-producing gastric cancer has been reported to be very poor because the tumor cells were considered to have a high malignant potential and the cancer progressed rapidly. We described a case of gastric cancer producing AFP and PIVKA-II in which chemotherapy was effective and resulted in prolonged survival, and these two tumor markers were useful for monitoring the treatment response. Routine health screening using upper abdominal ultrasonography revealed hepatic tumors in an apparently healthy 65-year-old man. Whole-body computed tomography (CT revealed multiple hepatic tumors, and an esophagogastroduodenoscopy (EGD revealed a Bormann type 3 tumor in the lower stomach. A biopsy specimen confirmed that the tumor was immunohistochemically positive for AFP, PIVKA-II, and human epidermal growth factor receptor 2. After chemotherapy, the gastric tumor appeared as a small elevated lesion on EGD, and CT revealed a remarkable reduction in the size of the metastatic liver tumors. The patient is still alive, 35 months after the initial chemotherapy.

  9. Prediction of neoadjuvant radiation chemotherapy response and survival using pretreatment [{sup 18}F]FDG PET/CT scans in locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Ji-In; Ha, Seunggyun; Kim, Sang Eun [Seoul National University Bundang Hospital, Department of Nuclear Medicine, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Kang, Sung-Bum; Oh, Heung-Kwon [Seoul National University Bundang Hospital, Department of Surgery, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Lee, Keun-Wook [Seoul National University Bundang Hospital, Department of Internal Medicine, Seongnam (Korea, Republic of); Lee, Hye-Seung [Seoul National University Bundang Hospital, Department of Pathology, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Kim, Jae-Sung [Seoul National University Bundang Hospital, Department of Radiation Oncology, Seongnam (Korea, Republic of); Lee, Ho-Young [Seoul National University Bundang Hospital, Department of Nuclear Medicine, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of)

    2016-03-15

    The aim of this study was to investigate metabolic and textural parameters from pretreatment [{sup 18}F]FDG PET/CT scans for the prediction of neoadjuvant radiation chemotherapy response and 3-year disease-free survival (DFS) in patients with locally advanced rectal cancer (LARC). We performed a retrospective review of 74 patients diagnosed with LARC who were initially examined with [{sup 18}F]FDG PET/CT, and who underwent neoadjuvant radiation chemotherapy followed by complete resection. The standardized uptake value (mean, peak, and maximum), metabolic volume (MV), and total lesion glycolysis of rectal cancer lesions were calculated using the isocontour method with various thresholds. Using three-dimensional textural analysis, about 50 textural features were calculated for PET images. Response to neoadjuvant radiation chemotherapy, as assessed by histological tumour regression grading (TRG) after surgery and 3-year DFS, was evaluated using univariate/multivariate binary logistic regression and univariate/multivariate Cox regression analyses. MVs calculated using the thresholds mean standardized uptake value of the liver + two standard deviations (SDs), and mean standard uptake of the liver + three SDs were significantly associated with TRG. Textural parameters from histogram-based and co-occurrence analysis were significantly associated with TRG. However, multivariate analysis revealed that none of these parameters had any significance. On the other hand, MV calculated using various thresholds was significantly associated with 3-year DFS, and MV calculated using a higher threshold tended to be more strongly associated with 3-year DFS. In addition, textural parameters including kurtosis of the absolute gradient (GrKurtosis) were significantly associated with 3-year DFS. Multivariate analysis revealed that GrKurtosis could be a prognostic factor for 3-year DFS. Metabolic and textural parameters from initial [{sup 18}F]FDG PET/CT scans could be indexes to assess

  10. Prolonged survival of a woman with lung cancer diagnosed and treated with chemotherapy during pregnancy. Review of cases reported.

    Science.gov (United States)

    Garrido, M; Clavero, J; Huete, A; Sánchez, C; Solar, A; Alvarez, M; Orellana, E

    2008-05-01

    Lung cancer is the most common cause of cancer death in women in the US, diagnosis during pregnancy is rare and has been reported 34 times. We report a case of a 34-year-old woman with stage III locally advanced lung cancer diagnosed during the 27th week of pregnancy. Chest X-ray and thorax MRI revealed a 9cmx7cm mass in the upper right lung lobe. CT guided FNA biopsy indicated adenocarcinoma. Neoadjuvant chemotherapy was administered with vinorelvine (Navelbine) and cisplatin for three cycles with partial response. At 39 weeks, she delivered a healthy baby. Right upper lobectomy with complete lymphadenectomy was performed 3 weeks later. Final pathology was reported as an adenocarcinoma of 7.5cmx6.2cm with involvement of 16/30 lymph nodes. She received three additional cycles of chemotherapy and radiotherapy. Follow-up with CT scan after 11 months did not show recurrence.

  11. Optimizing initial chemotherapy for metastatic pancreatic cancer.

    Science.gov (United States)

    Mantripragada, Kalyan C; Safran, Howard

    2016-05-01

    The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients.

  12. Expression of CDKN1C in the bone marrow of patients with myelodysplastic syndrome and secondary acute myeloid leukemia is associated with poor survival after conventional chemotherapy.

    Science.gov (United States)

    Radujkovic, Aleksandar; Dietrich, Sascha; Andrulis, Mindaugas; Benner, Axel; Longerich, Thomas; Pellagatti, Andrea; Nanda, Kriti; Giese, Thomas; Germing, Ulrich; Baldus, Stefan; Boultwood, Jacqueline; Ho, Anthony D; Dreger, Peter; Luft, Thomas

    2016-09-15

    We tested the hypothesis that proliferative activity of hematopoietic stem cells has impact on survival in newly diagnosed patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML). RNA expression profiles of CD34(+) cells were analyzed in 125 MDS patients and compared to healthy controls. Prognostic impact on overall survival (OS) of mRNA proliferation signatures established for solid tumor cells was analyzed retrospectively. For validation on the protein level, immunofluorescence and immunohistochemistry analyses in bone marrow (BM) biopsies were performed, and an independent cohort of 223 MDS and secondary AML patients was investigated. Lower proliferative activity correlated with the expression of cyclin-dependent kinase inhibitor 1C (CDKN1C) and with shorter OS (p < 0.001). In multivariable analysis, higher CDKN1C expression was associated with worse OS (p = 0.02). On the BM level, a total of 84 (38%) patients showed CDKN1C protein expression before start of treatment. Patient, disease and treatment characteristics did not differ between CDKN1C-positive and -negative patients. Positive CDKN1C BM status was associated with shorter OS in multivariable analysis (HR 1.54, p = 0.04). There was an interaction between CDKN1C BM status and subsequent treatment with negative impact on OS being most pronounced in patients receiving conventional cytotoxic chemotherapy (n = 83, 2-year OS 30% versus 58%, p = 0.002). In conclusion, low-proliferative phenotype and CDKN1C expression were associated with shorter OS. CDKN1C protein expression in the BM of newly diagnosed, treatment-naïve MDS and secondary AML patients was identified as a prognostic factor for poor survival in patients treated with antiproliferative chemotherapy.

  13. Improving survival among Brazilian children with perinatally-acquired AIDS

    Directory of Open Access Journals (Sweden)

    Luiza Harunari Matida

    2004-12-01

    Full Text Available Brazil was the first developing country to provide free, universal access to antiretroviral treatment for AIDS patients. The Brazilian experience thus provides the first evidence regarding the impact of such treatment on the survival of perinatally acquired AIDS cases in the developing world. MATERIAL AND METHODS: This retrospective cohort study used medical record reviews to examine characteristics and trends in the survival of a representative sample of 914 perinatally acquired AIDS cases in 10 Brazilian cities diagnosed between 1983 and 1998. RESULTS: Survival time increased steadily and substantially. Whereas half of the children died within 20 months of diagnosis at the beginning of the epidemic, 75% of children diagnosed in 1997 and 1998 were still alive after four years of follow-up. CONCLUSIONS: Advances in management and treatment have made a great difference in the survival of Brazilian children with AIDS. These results argue strongly for making such treatment available to children in the entire developing world.

  14. Improvement of quality of life and survival using self-expandable metal stent placement for severe malignant stenosis of the gastric body: a case report

    Directory of Open Access Journals (Sweden)

    Kumagai Hozumi

    2012-09-01

    Full Text Available Abstract Introduction Advanced gastric carcinoma often decreases quality of life because of upper gastrointestinal tract stenosis. Self-expandable metal stents have been thought to be an effective, minimally invasive treatment for stenosis. However, the effectiveness of self-expandable metal stent placement for carcinomatous stenosis of the gastric body and antrum has not been clarified, and there have been few reports of such cases. Case presentation A 74-year-old Japanese woman developed stenosis of the gastric body and antrum caused by advanced gastric cancer during first-line chemotherapy. She developed weight loss and poor nutrition due to inadequate intake. Self-expandable metal stent placement for stenosis of the gastric body and antrum ameliorated her symptoms rapidly and improved her general condition and quality of life. Eight days after self-expandable metal stent placement, second-line chemotherapy could be administered safely. Oral intake and nutritional status were maintained for 117 days after self-expandable metal stent placement, and she died of gastric cancer 176 days after self-expandable metal stent placement and initiation of second-line chemotherapy. Conclusions Self-expandable metal stent placement for carcinomatous stenosis in the gastric body and antrum could be an effective therapeutic strategy for patients with inadequate oral uptake. It may provide rapid improvement of the patient’s general condition and oral intake with minimal complications, comparatively long-term symptom relief, and a survival benefit by allowing second-line chemotherapy.

  15. Prophylactic cranial irradiation could improve overall survival in patients with extensive small cell lung cancer. A retrospective study

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yi [Tsinghua University, Medical Center Tsinghua University, Beijing (China); Li, Jinyu; Hu, Yi; Lin, Zhi; Jiao, Shunchang [Chinese PLA General Hospital, Department of Medical Oncology, Beijing (China); Zhang, Yibao [Peking University Cancer Hospital and Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiotherapy, Beijing (China); Zhao, Zhifei [Chinese PLA General Hospital, Department of Radiation Oncology, Beijing (China)

    2016-12-15

    To evaluate the effect of prophylactic cranial irradiation (PCI) on overall survival (OS) in patients with extensive small cell lung cancer (ESCLC). Between April 2005 and May 2014, 204 patients with ESCLC who had any response (according to RECIST 1.1) to initial chemotherapy were reviewed. All patients had undergone appropriate imaging tests to exclude brain metastases before initial chemotherapy. PCI was performed on 45 patients (22.1 %) and the remaining patients (77.9 %) received no such treatment (control group). Primary endpoint was OS. The incidence of brain metastases, brain metastases-free survival (BMFS), and adverse effects were also evaluated. Survival data of the 204 patients were analyzed statistically. PCI significantly prolonged median OS from 12.6 to 16.5 months as compared to the control group (hazard ratio, HR, 0.63; 95 % confidence interval, CI, 0.41 to 0.96; p = 0.033). PCI significantly lowered the risk of brain metastases (HR 0.48; 95 % CI 0.30 to 0.76; p = 0.001). The 1-year incidence of brain metastases was 17.1 and 55.9 % in the PCI and control group, respectively. PCI significantly correlated with the increased median BMFS (p = 0.002). Additionally, multivariate analyses demonstrated that PCI was a favorable independent predictor of OS, BMFS, and the incidence of brain metastases. Acute and chronic adverse effects were generally low grade and well tolerated in patients receiving PCI. PCI after any response to initial chemotherapy significantly improved OS of ESCLC patients analyzed in this study. (orig.) [German] Beurteilung des Effekts der prophylaktischen kranialen Bestrahlung (PCI) auf das Gesamtueberleben (OS) bei Patienten mit ausgedehntem kleinzelligem Lungenkarzinom (ESCLC). Zwischen April 2005 und Mai 2014 wurden 204 Patienten mit ESCLC nach Ansprechen auf eine initiale Chemotherapie (gemaess RECIST 1.1) untersucht. Vor der Chemotherapie wurden bei allen Patienten Untersuchungen mit entsprechenden Bildgebungsverfahren

  16. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Science.gov (United States)

    2010-07-01

    ...-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... rates—Surviving children. (a) General. The provisions of this section apply to children of a deceased veteran not in the custody of a surviving spouse who has basic eligibility to receive improved...

  17. An Epigenomic Approach to Improving Response to Neoadjuvant Cisplatin Chemotherapy in Bladder Cancer.

    Science.gov (United States)

    Xylinas, Evanguelos; Hassler, Melanie R; Zhuang, Dazhong; Krzywinski, Martin; Erdem, Zeynep; Robinson, Brian D; Elemento, Olivier; Clozel, Thomas; Shariat, Shahrokh F

    2016-09-02

    Bladder cancer is among the five most common cancers diagnosed in the Western world and causes significant mortality and morbidity rates in affected patients. Therapeutic options to treat the disease in advanced muscle-invasive bladder cancer (MIBC) include cystectomy and chemotherapy. Neoadjuvant cisplatin-based combination chemotherapy is effective in MIBC; however, it has not been widely adopted by the community. One reason is that many patients do not respond to neoadjuvant chemotherapy, and no biomarker currently exists to identify these patients. It is also not clear whether a strategy to sensitize chemoresistant patients may exist. We sought to identify cisplatin-resistance patterns in preclinical models of bladder cancer, and test whether treatment with the epigenetic modifier decitabine is able to sensitize cisplatin-resistant bladder cancer cell lines. Using a screening approach in cisplatin-resistant bladder cancer cell lines, we identified dysregulated genes by RNA sequencing (RNAseq) and DNA methylation assays. DNA methylation analysis of tumors from 18 patients receiving cisplatin-based chemotherapy was used to confirm in vitro results. Cisplatin-resistant bladder cancer cells were treated with decitabine to investigate epigenetic sensitization of resistant cell lines. Our results show that HOXA9 promoter methylation status is associated with response to cisplatin-based chemotherapy in bladder cancer cell lines and in metastatic bladder cancer. Bladder cancer cells resistant to cisplatin chemotherapy can be sensitized to cisplatin by the DNA methylation inhibitor decitabine. Our data suggest that HOXA9 promoter methylation could serve as potential predictive biomarker and decitabine might sensitize resistant tumors in patients receiving cisplatin-based chemotherapy.

  18. An Epigenomic Approach to Improving Response to Neoadjuvant Cisplatin Chemotherapy in Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Evanguelos Xylinas

    2016-09-01

    Full Text Available Bladder cancer is among the five most common cancers diagnosed in the Western world and causes significant mortality and morbidity rates in affected patients. Therapeutic options to treat the disease in advanced muscle-invasive bladder cancer (MIBC include cystectomy and chemotherapy. Neoadjuvant cisplatin-based combination chemotherapy is effective in MIBC; however, it has not been widely adopted by the community. One reason is that many patients do not respond to neoadjuvant chemotherapy, and no biomarker currently exists to identify these patients. It is also not clear whether a strategy to sensitize chemoresistant patients may exist. We sought to identify cisplatin-resistance patterns in preclinical models of bladder cancer, and test whether treatment with the epigenetic modifier decitabine is able to sensitize cisplatin-resistant bladder cancer cell lines. Using a screening approach in cisplatin-resistant bladder cancer cell lines, we identified dysregulated genes by RNA sequencing (RNAseq and DNA methylation assays. DNA methylation analysis of tumors from 18 patients receiving cisplatin-based chemotherapy was used to confirm in vitro results. Cisplatin-resistant bladder cancer cells were treated with decitabine to investigate epigenetic sensitization of resistant cell lines. Our results show that HOXA9 promoter methylation status is associated with response to cisplatin-based chemotherapy in bladder cancer cell lines and in metastatic bladder cancer. Bladder cancer cells resistant to cisplatin chemotherapy can be sensitized to cisplatin by the DNA methylation inhibitor decitabine. Our data suggest that HOXA9 promoter methylation could serve as potential predictive biomarker and decitabine might sensitize resistant tumors in patients receiving cisplatin-based chemotherapy.

  19. Influence of comorbidity on survival, toxicity and health-related quality of life in patients with advanced non-small-cell lung cancer receiving platinum-doublet chemotherapy

    DEFF Research Database (Denmark)

    Grønberg, Bjørn H; Sundstrøm, Stein; Kaasa, Stein;

    2010-01-01

    AIM OF THE STUDY: To investigate whether patients with severe comorbidity receiving platinum-based chemotherapy for advanced non-small-cell lung cancer (NSCLC) have a shorter overall survival, experience more toxicity or more deterioration of health-related quality of life (HRQoL) than other....... Comorbidity was assessed from hospital medical records using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Toxicity was graded using the CTCAE v3.0 and the patients reported HRQoL on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30...... neutropenic fevers (12% versus 5%; p=.012) and deaths from neutropenic infections (3% versus 0%; p=.027). They had more thrombocytopenia (46% versus 36%; p=.03), but not more thrombocytopenic bleedings (3% versus 4%; p=.65). In general, the patients with severe comorbidity reported poorer HRQoL...

  20. Recent improvement in survival of breast cancer patients in Saarland, Germany.

    Science.gov (United States)

    Brenner, H; Stegmaier, C; Ziegler, H

    1998-09-01

    A new method for more timely monitoring of cancer patient survival was employed to assess progress in 5-year survival of breast cancer patients in Saarland, Germany, between 1980-84 and 1990-94. Five-year relative survival gradually increased from 68.8% to 73.5%. Improvements were most pronounced among age groups 50-59 and 60-69. The latter had the highest 5-year relative survival (77.1%) in 1990-94.

  1. XRCC3 Thr241Met is associated with response to platinum-based chemotherapy but not survival in advanced non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Mantang Qiu

    Full Text Available BACKGROUND: A lot of studies have investigated the correlation between x-ray repair cross-complementing group 3 (XRCC3 Thr241Met polymorphism and clinical outcomes in non-small cell cancer (NSCLC, while the conclusion is still conflicting. MATERIALS AND METHODS: We conducted this meta-analysis to evaluate the predictive value of XRCC3 Thr241Met polymorphism on response and overall survival of patients with NSCLC. Pooled odds ratios (ORs and hazard ratios (HRs and corresponding 95% confidence intervals (95% CIs were used to estimate the association strength. RESULTS: A total of 14 eligible studies with 2828 patients were identified according to our inclusion criteria. Meta-analysis results showed that carriers of the variant 241Met allele were significantly associated with good response, compared with those harboring the wild 241Thr allele (Met vs. Thr, OR = 1.453, 95% CI: 1.116-1.892, Pheterogeneity = 0.968 and ThrMet+MetMet vs. ThrThr, OR = 1.476, 95% CI: 1.087-2.004, Pheterogeneity = 0.696. This significant association was observed in Caucasian population but not in Asian population. On the other hand, there was no significant association of XRCC3 Thr241Met polymorphism with survival (ThrMet+MetMet vs. ThrThr, HR = 1.082, 95% CI: 0.929-1.261, Pheterogeneity = 0.564, and there was no difference between Asian and Caucasian population. CONCLUSIONS: These findings suggest a predictive role of XRCC3 Thr241Met polymorphism on response to platinum-based chemotherapy in patients with advanced NSCLC. Additionally, we first report that the XRCC3 Thr241Met polymorphism is associated with response to platinum-based chemotherapy and highlights the prognostic value of the XRCC3 Thr241Met polymorphism.

  2. Better pathologic complete response and relapse-free survival after carboplatin plus paclitaxel compared with epirubicin plus paclitaxel as neoadjuvant chemotherapy for locally advanced triple-negative breast cancer: a randomized phase 2 trial

    Science.gov (United States)

    Yin, Yi; Mo, Hongnan; Zhang, Bailin; Wang, Xiang; Li, Qing; Yuan, Peng; Wang, Jiayu; Zheng, Shan; Cai, Ruigang; Ma, Fei; Fan, Yin

    2016-01-01

    Background: No standard chemotherapy is used as neoadjuvant therapy in triple negative breast cancer (TNBC). This study has compared carboplatin plus paclitaxel with commonly used epirubicin plus paclitaxel as neoadjuvant chemotherapy (NAC) in TNBC. Results: 91 patients with a median age of 47 years (PC 47 patients, EP 44 patients) were enrolled. 65% of the patients were premenopausal. While the objective response rate was similar in the PC and EP arm (89.4% vs. 79.5%, P = 0.195), the pCR rate in the PC arm was significantly higher (38.6% vs. 14.0%, P = 0.014). The median follow-up time was 55.0 months. 5-year RFS were 77.6% and 56.2%, significantly higher in the PC arm, P = 0.043. No significant difference in OS was observed between the two arms (P = 0.350). Adverse events were similar, except for more thrombocytopenia in the PC arm (P = 0.001). Methods: Patients with stage II/III TNBC were randomized to receive either paclitaxel (175 mg/m2, day1) plus carboplatin (Area Under the Curve = 5, day2) (PC) or epirubicin (75mg/m2, day1) plus paclitaxel (175 mg/m2, day2) (EP) as NAC every three weeks for 4-6 cycles. The primary endpoint was rate of pathologic complete response (pCR).The secondary endpoints included relapse-free survival (RFS), overall survival (OS) and safety. Conclusions:This study suggested that the addition of carboplatin to paclitaxel was superior to the regimen of epirubicin plus paclitaxel as NAC for TNBC in terms of improving pCR rate and RFS. Further phase 3 study has already started. PMID:27447966

  3. Long-Term Survival and Improved Quality of Life following Multiple Repeat Gamma Knife Radiosurgeries for Recurrent Glioblastoma Multiforme: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Erik W. Larson

    2013-01-01

    Full Text Available The management of glioblastoma multiforme (GBM is in most cases complex and must be specifically tailored to the needs of the patient with the goals of extended survival and improved quality of life. Despite advancements in therapy, treatment outcomes remain almost universally poor. Salvage treatment options for the recurrence of the disease is an area of intense study. The following case highlights the utility of Gamma Knife Radiosurgery (GKRS as a salvage treatment. In this clinical situation, three sequential GKRS treatments led to prolonged survival (beyond four years after diagnosis and improved quality of life in a patient who was unable to receive further chemotherapy regimens and was unwilling to undergo further aggressive resection. To date, there have been few reports of three or more sequential GKRS treatment sessions utilized as salvage therapy for recurrent GBM in patients who can no longer tolerate chemotherapy. This report provides evidence that aggressive local treatment with GKRS at the time of recurrence may be appropriate, depending on a patient’s individual clinical situation, and can lead to prolonged survival and improved quality of life.

  4. UPEC biomimickry at the urothelial barrier: lectin-functionalized PLGA microparticles for improved intravesical chemotherapy.

    Science.gov (United States)

    Neutsch, Lukas; Wambacher, Michael; Wirth, Eva-Maria; Spijker, Sylvia; Kählig, Hanspeter; Wirth, Michael; Gabor, Franz

    2013-06-25

    The urgent demand for more potent treatment schedules in bladder cancer (BCa) therapy calls for a refinement of the intravesical administration modalities. However, progress on drug delivery systems tailored to the penetration-hostile urothelial barrier lags behind the advancements in comparable fields. This study reports on a multimodal, carrier-based delivery concept that combines biorecognitive targeting with modified release strategies for improved intravesical chemotherapy. The plant lectin wheat germ agglutinin (WGA) was immobilized on poly(lactide-co-glycolide) (PLGA) microparticles (MP) to induce stable cytoadhesion via cellular carbohydrate chains, similar to the specific attachment mechanism utilized by uropathogenic bacteria. A panel of DNA-selective chemotherapeutics with established track record in uro-oncology was screened for physicochemical compatibility with the polymeric carrier formulation. Critical limitations in encapsulation efficiency were found for mitomycin C (MMC), doxorubicin (DOX), and gemcitabine hydrochloride (GEM), despite multiparametric optimization of the preparation conditions. In contrast, the amphiphilic 4-(N)-stearoyl prodrug of gemcitabine (GEM-C18) exhibited excellent processability with PLGA. In vitro bioassays on 5637 human BCa cells showed that the enhanced cytoadhesion of WGA-GEM-C18-PGLA-MP traces back to the specific lectin/carbohydrate interaction, and is not easily disrupted by adverse environmental factors. Owing to several synergistic effects, the combined prodrug/targeting approach resulted in strong cytostatic response even when adjusting the exposure scheme to the confined temporal conditions of instillative treatment. Our results highlight the importance of fine-tuning both pharmacokinetic and pharmacologic parameters to gain adequate impact on urothelial cancer cells, and assign promising potential to glycan-targeted delivery concepts for the intravesical route.

  5. Pretreatment anti-Müllerian hormone predicts for loss of ovarian function after chemotherapy for early breast cancer

    DEFF Research Database (Denmark)

    Anderson, Richard A; Rosendahl, Mikkel; Kelsey, Thomas W

    2013-01-01

    Improving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea.......Improving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea....

  6. Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment

    Directory of Open Access Journals (Sweden)

    Bonanno L

    2016-06-01

    Full Text Available Laura Bonanno,1 Giulia Zago,1 Giuseppe Marulli,2 Paola Del Bianco,3 Marco Schiavon,2 Giulia Pasello,1 Valentina Polo,1,4 Fabio Canova,1 Fabrizio Tonetto,5 Lucio Loreggian,5 Federico Rea,2 PierFranco Conte,1,4 Adolfo Favaretto1 1Medical Oncology Unit 2, Veneto Institute of Oncology IOV-IRCCS, 2Thoracic Surgery Department, University of Padova, 3Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV-IRCCS, 4Department of Surgery, Oncology and Gastroenterology, University of Padova, 5Radiotherapy Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy Objectives: If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs. No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods: We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1, paclitaxel (200 mg/m2, d1, and gemcitabine (1,000 mg/m2 d1, 8 for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS and overall survival (OS were correlated to response, surgery, and clinical features. Results: In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system. A total of 36 (62% patients achieved partial response (PR, and six (10% progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62% cases. After chemotherapy, 37 (64% patients underwent surgery

  7. Normal carcinoembryonic antigen indicates benefit from perioperative chemotherapy to gastric carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Shi Chen; Ying-Bo Chen; Yuan-Fang Li; Xing-Yu Feng; Zhi-Wei Zhou; Xiu-Hong Yuan; Chao-Nan Qian

    2012-01-01

    AIM:To evaluate pretreatment serum carcinoembryonic antigen (CEA) as a predictor of survival for patients with locally advanced gastric cancer receiving perioperative chemotherapy.METHODS:We retrospectively studied a cohort of 228gastric cancer patients who underwent D2 gastrectomy combined with chemotherapy at the Sun Yat-sen University Cancer Center between January 2005 and December 2009.Among them,168 patients received 6-12 cycles of oxaliplatin-based adjuvant (post-operative) chemotherapy,while 60 received perioperative chemotherapy (2 cycles of FOLFOX6 or XELOX before surgery and 4-10 cycles after surgery).Serum CEA was measured using an enzyme immunoassay.The followup lasted until December 2010.RESULTS:In the group that had elevated serum CEA,the difference in survival time between patients receiving perioperative chemotherapy and those receiving adjuvant chemotherapy had no statistical significance (P >0.05).However,in the group that had normal serum CEA,patients receiving perioperative chemotherapy had a longer survival time.In multivariate analysis,T staging and lymph node metastatic rate were independent prognostic factors for the patients.Perioperative chemotherapy improved the overall survival of patients who had a normal pretreatment CEA level (P =0.070).CONCLUSION:Normal pretreatment serum CEA is a predictor of survival for patients receiving perioperative chemotherapy.

  8. Use of Aspirin postdiagnosis improves survival for colon cancer patients

    Science.gov (United States)

    Bastiaannet, E; Sampieri, K; Dekkers, O M; de Craen, A J M; van Herk-Sukel, M P P; Lemmens, V; van den Broek, C B M; Coebergh, J W; Herings, R M C; van de Velde, C J H; Fodde, R; Liefers, G J

    2012-01-01

    Background: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based study was to assess the therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment used after the diagnosis of colorectal cancer patients. Methods: Data concerning prescriptions were obtained from PHARMO record linkage systems and all patients diagnosed with colorectal cancer (1998–2007) were selected from the Eindhoven Cancer Registry (population-based cancer registry). Aspirin/NSAID use was classified as none, prediagnosis and postdiagnosis and only postdiagnosis. Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of the colorectal cancer to the date of first use of aspirin or NSAIDs and user from first use to the end of follow-up. Poisson regression was performed with user status as time-varying exposure. Results: In total, 1176 (26%) patients were non-users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were only postdiagnosis users (total n=4481). Compared with non-users, a survival gain was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95% confidence interval (CI) 0.63–0.95; P=0.015). Stratified for colon and rectal, the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50–0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61 (95%CI 0.46–0.81; P=0.001). In rectal cancer, aspirin use was not associated with survival (adjusted RR 1.10 (95%CI 0.79–1.54; P=0.6). The NSAIDs use was associated with decreased survival (adjusted RR 1.93 (95%CI 1.70–2.20; P<0.001). Conclusion: Aspirin use initiated or continued after diagnosis of colon cancer is associated with a lower risk of overall mortality. These findings strongly support initiation of

  9. Change in volume parameters induced by neoadjuvant chemotherapy provide accurate prediction of overall survival after resection in patients with oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tamandl, Dietmar; Fueger, Barbara; Kinsperger, Patrick; Haug, Alexander; Ba-Ssalamah, Ahmed [Medical University of Vienna, Department of Biomedical Imaging and Image-Guided Therapy, Comprehensive Cancer Center GET-Unit, Vienna (Austria); Gore, Richard M. [University of Chicago Pritzker School of Medicine, Department of Radiology, Chicago, IL (United States); Hejna, Michael [Medical University of Vienna, Department of Internal Medicine, Division of Medical Oncology, Comprehensive Cancer Center GET-Unit, Vienna (Austria); Paireder, Matthias; Schoppmann, Sebastian F. [Medical University of Vienna, Department of Surgery, Upper-GI-Service, Comprehensive Cancer Center GET-Unit, Vienna (Austria)

    2016-02-15

    To assess the prognostic value of volumetric parameters measured with CT and PET/CT in patients with neoadjuvant chemotherapy (NACT) and resection for oesophageal cancer (EC). Patients with locally advanced EC, who were treated with NACT and resection, were retrospectively analysed. Data from CT volumetry and {sup 18} F-FDG PET/CT (maximum standardized uptake [SUVmax], metabolic tumour volume [MTV], and total lesion glycolysis [TLG]) were recorded before and after NACT. The impact of volumetric parameter changes induced by NACT (MTV{sub RATIO}, TLG{sub RATIO}, etc.) on overall survival (OS) was assessed using a Cox proportional hazards model. Eighty-four patients were assessed using CT volumetry; of those, 50 also had PET/CT before and after NACT. Low post-treatment CT volume and thickness, MTV, TLG, and SUVmax were all associated with longer OS (p < 0.05), as were CTthickness{sub RATIO}, MTV{sub RATIO}, TLG{sub RATIO}, and SUVmax{sub RATIO} (p < 0.05). In the multivariate analysis, only MTV{sub RATIO} (Hazard ratio, HR 2.52 [95 % Confidence interval, CI 1.33-4.78], p = 0.005), TLG{sub RATIO} (HR 3.89 [95%CI 1.46-10.34], p = 0.006), and surgical margin status (p < 0.05), were independent predictors of OS. MTV{sub RATIO} and TLG{sub RATIO} are independent prognostic factors for survival in patients after NACT and resection for EC. (orig.)

  10. ASSOCIATION BETWEEN RADIOTHERAPY VS NO RADIOTHERAPY BASED ON EARLY RESPONSE TO VAMP CHEMOTHERAPY AND SURVIVAL AMONG CHILDREN WITH FAVORABLE RISK HODGKIN LYMPHOMA

    Science.gov (United States)

    Metzger, Monika L.; Weinstein, Howard J.; Hudson, Melissa M.; Billett, Amy L.; Larsen, Eric C.; Friedmann, Alison; Howard, Scott C.; Donaldson, Sarah S.; Krasin, Matthew J.; Kun, Larry E.; Marcus, Karen J.; Yock, Torunn I.; Tarbell, Nancy; Billups, Catherine A.; Wu, Jianrong; Link, Michael P.

    2012-01-01

    Context Maintaining excellent cure rates in pediatric Hodgkin lymphoma while minimizing toxicity. Objective To evaluate the efficacy of 4 cycles of vinblastine, Adriamycin, methotrexate, and prednisone (VAMP) in patients with favorable risk Hodgkin lymphoma who achieve a complete response after 2 cycles and do not receive radiotherapy. Design, Setting, and Patients Multi-institutional, unblinded, non-randomized single group phase II clinical trial to assess the need for radiotherapy based on early response to chemotherapy. Eighty-eight eligible patients with Hodgkin lymphoma stage I and II (< 3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) enrolled between March 3, 2000 through December 9, 2008. Data frozen March 12, 2012. Interventions Patients who achieved a complete response (n=47) after 2 cycles received no radiotherapy, and those with less than complete response (n=41) were given 25.5 Gy involved field radiotherapy. Main Outcome Measures 2-year event-free survival was the primary outcome measure. A 2-year event-free survival of greater than 90% was desired, and 80% was considered to be unacceptably low. Results Two-year event-free survival was 90.8% (95% CI, 84.7% – 96.9%); for patients who did not require radiotherapy it was 89.4% (95% CI, 80.8% – 98%), compared with 92.5% (95% CI, 84.5% – 100%) for those who did (P=0.61). Most common acute side effects were neuropathic pain (2% of patients), nausea/vomiting (3% of patients), neutropenia (32% of cycles), and febrile neutropenia (2% of patients). Nine patients (10%) were hospitalized 11 times (3% of cycles) for febrile neutropenia or non-neutropenic infection. Long term side effects after radiotherapy were asymptomatic compensated hypothyroidism in 9 patients (10%), osteonecrosis and moderate osteopenia in 2 patients each, subclinical pulmonary dysfunction in 12 patients (26%) and asymptomatic left ventricular dysfunction in 4 patients (5%). No second malignant neoplasms were

  11. RH-01THE SIGNIFICANCE OF ACUTE INPATIENT REHABILITATION FOR GLIOMA PATIENTS: IMPROVING THE PHYSICAL FUNCTION, QUALITY OF LIFE AND SURVIVAL

    Science.gov (United States)

    Beverly Fu, D.; Bota, Daniela A.

    2014-01-01

    OBJECTIVE: To assess the effects of inpatient acute rehabilitation on overall function, quality of life and overall survival for glioma patients. DESIGN: A retrospective study of glioma patients treated at UCI Neuro-Oncology Program. PARTICIPANTS: We have identified 12 patients with glioma diagnosis who underwent inpatient acute rehabilitation program using our IRB approved neuro-oncology database. OUTCOME ASSESSMENT TOOLS: Functional status based upon Karnofsky performance scale (KPS), quality of life as assessed by Functional Assessment of Cancer Therapy Brain (FACT-Br) and overall survival. RESULTS: We identified on our study 3 patients with glioblastoma, 7 patients with anaplastic gliomas, and 2 patients with low grade gliomas. All of them had radiation and chemotherapy, except 2 patients with low grade gliomas who had radiation treatment only. The age range is from 26 to 77 and the mean age is 49-year-old. All the patients who underwent the acute inpatient rehabilitation program at our institution, not only improved their KPS scale significantly, but also enhanced their social and emotional well-being. The median KPS improvement is 30 points from a 3-6 weeks stay. Functional Assessment of Cancer Therapy Brain (FACT-Br) is obtained from 4 patients at this time (further information will be presented at SNO conference). The mean FACT-Br TOI is 60.8, and the total FACT0Br Score is 119.6. Survival data are still collected. CONCLUSIONS: The patients who underwent acute inpatient rehabilitation program, showed significant improvements in their functional status and quality of life. The observation from this pilot study warrants further research and demonstrates the acute inpatient rehabilitation may be beneficial to glioma patients with good physical functions and tolerance for 3 hours a day of physical, occupation and speech therapies.

  12. Improving village poultry’s survival rate through community-based poultry health management

    DEFF Research Database (Denmark)

    Sodjinou, Epiphane; Henningsen, Arne; Koudande, Olorounto D.

    that governments and development agencies can improve village poultry survival rates by investing in the dissemination of information regarding best husbandry management practices through approaches that rely on the community such as CBM because CBM groups serve as channels for the dissemination of village poultry...... of technologies – poultry vaccination, construction of henhouses, and improved feed – disseminated through the CBM also significantly improves the survival rate. The access to markets for inputs and veterinary services is also important in improving the survival rate of poultry. Finally, the study suggests...

  13. Improving village poultry's survival rate through community-based poultry health management

    DEFF Research Database (Denmark)

    Sodjinou, Epiphane; Henningsen, Arne; Koudande, Olorounto Delphin

    2012-01-01

    that governments and development agencies can improve village poultry survival rates by investing in the dissemination of information regarding best husbandry management practices through approaches that rely on the community such as CBM because CBM groups serve as channels for the dissemination of village poultry...... of technologies—poultry vaccination, construction of henhouses, and improved feed—disseminated through the CBM also significantly improves the survival rate. The access to markets for inputs and veterinary services is also important in improving the survival rate of poultry. Finally, the study suggests...

  14. Cancer pathways are associated with improved long-term survival

    DEFF Research Database (Denmark)

    Jensen, Kenneth Højsgaard; Maina, Pierre Jean-Claude

    2015-01-01

    INTRODUCTION: The impact of cancer patient pathways (CPP) on long-term outcome after surgery for colorectal cancer has not been documented. This study aimed to investigate the effect of CPP on survival in patients who underwent surgery for colorectal cancer. METHODS: This was a retrospective cohort...... study performed in a single centre on prospectively collected data from a national database, the Danish Colorectal Cancer Group. In total, we reviewed 309 consecutive patients (145 females) with a median age of 70 years (range: 30-92 years), who underwent surgery for colorectal cancer between 2007...

  15. Improved survival in HIV-infected persons: consequences and perspectives

    DEFF Research Database (Denmark)

    Lohse, Nicolai; Hansen, Ann-Brit Eg; Gerstoft, Jan

    2007-01-01

    . Further, they may expect to be treated equally with other members of society with respect to access to mortgage, health insurance and life insurance. As the infected population ages, more patients will contract age-related diseases, and the disease burden on some individuals may even come to be dominated......, with lifestyle factors potentially playing a pronounced role. Consequently, an effort to further increase survival must target risk factors for both HIV-related and -unrelated mortality. The continuation of the positive trend may be achieved by increased HIV testing, earlier initiation of antiretroviral therapy...

  16. Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis

    Science.gov (United States)

    Bajic, Juliana E; Eden, Georgina L; Lampton, Lorrinne S; Cheah, Ker Y; Lymn, Kerry A; Pei, Jinxin V; Yool, Andrea J; Howarth, Gordon S

    2016-01-01

    AIM To investigate the effects of orally gavaged aqueous rhubarb extract (RE) on 5-fluorouracil (5-FU)-induced intestinal mucositis in rats. METHODS Female Dark Agouti rats (n = 8/group) were gavaged daily (1 mL) with water, high-dose RE (HDR; 200 mg/kg) or low-dose RE (LDR; 20mg/kg) for eight days. Intestinal mucositis was induced (day 5) with 5-FU (150 mg/kg) via intraperitoneal injection. Intestinal tissue samples were collected for myeloperoxidase (MPO) activity and histological examination. Xenopus oocytes expressing aquaporin 4 water channels were prepared to examine the effect of aqueous RE on cell volume, indicating a potential mechanism responsible for modulating net fluid absorption and secretion in the gastrointestinal tract. Statistical significance was assumed at P < 0.05 by one-way ANOVA. RESULTS Bodyweight was significantly reduced in rats administered 5-FU compared to healthy controls (P < 0.01). Rats administered 5-FU significantly increased intestinal MPO levels (≥ 307%; P < 0.001), compared to healthy controls. However, LDR attenuated this effect in 5-FU treated rats, significantly decreasing ileal MPO activity (by 45%; P < 0.05), as compared to 5-FU controls. 5-FU significantly reduced intestinal mucosal thickness (by ≥ 29% P < 0.001) as compared to healthy controls. LDR significantly increased ileal mucosal thickness in 5-FU treated rats (19%; P < 0.05) relative to 5-FU controls. In xenopus oocytes expressing AQP4 water channels, RE selectively blocked water influx into the cell, induced by a decrease in external osmotic pressure. As water efflux was unaltered by the presence of extracellular RE, the directional flow of water across the epithelial barrier, in the presence of extracellular RE, indicated that RE may alleviate water loss across the epithelial barrier and promote intestinal health in chemotherapy-induced intestinal mucositis. CONCLUSION In summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal

  17. Why chemotherapy can fail?

    Science.gov (United States)

    Król, M; Pawłowski, K M; Majchrzak, K; Szyszko, K; Motyl, T

    2010-01-01

    There are many reasons that lead to failure of cancer chemotherapy. Cancer has the ability to become resistant to many different types of drugs. Increased efflux of drug, enhanced repair/increased tolerance to DNA damage, high antiapoptotic potential, decreased permeability and enzymatic deactivation allow cancer cell survive the chemotherapy. Treatment can lead to the death of most tumor cells (drug-sensitive), but some of them (drug-resistant) survive and grow again. These tumor cells may arise from stem cells. There are many studies describing human experiments with multidrug resistance, especially in breast cancer. Unfortunately, studies of canine or feline ABC super family members are not as extensive as in human or mice and they are limited to several papers describing PGP in mammary cancer, cutaneous mast cell tumors and lymphoma. Multidrug resistance is one of the most significant problems in oncology today. The involvement of many different, not fully recognized, mechanisms in multidrug resistance of cancer cells makes the development of effective methods of therapy very difficult. Understanding the mechanisms of drug resistance in cancer cells may improve the results of treatment. This review article provides a synopsis of all aspects that refer to cancer cell resistance to antitumor drugs.

  18. The impact of both platinum-based chemotherapy and EGFR-TKIs on overall survival of patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jian-Wei Zhang; Wen-Feng Fang; Yu-Xiang Ma; Li Zhang; Yuan-Yuan Zhao; Ying Guo; Cong Xue; Zhi-Huang Hu; Yan Huang; Hong-Yun Zhao; Jing Zhang; Xuan Wu

    2014-01-01

    Both platinum-based doublet chemotherapy (PBC) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival (OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials-involving 11,456 adult patients in 32 arms-were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian (predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs (r = 0.797,P < 0.001). The correlation was obvious in the trials in Asian populations (r = 0.936,P < 0.001) but was not statisticaly significant in the trials in predominantly Caucasian populations (r = 0.116,P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy.

  19. Breast conserving treatment of breast carcinoma T2 ({<=} 4 cm) and T3 by neoadjuvant chemotherapy, quadrantectomy, high dose rate brachytherapy as a boost, external beam radiotherapy and adjuvant chemotherapy: local control and overall survival analysis; Tratamento conservador do cancer de mama T2 ({<=} 4 cm) e T3 por quimioterapia neoadjuvante, quadrantectomia, braquiterapia com alta taxa de dose como reforco de dose, teleterapia complementar e quimioterapia adjuvante: analise de controle local e sobrevida global

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Celia Regina; Miziara Filho, Miguel Abrao; Fogaroli, Ricardo Cesar; Baraldi, Helena Espindola; Pellizzon, Antonio Cassio Assis; Pelosi, Edilson Lopes [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Radioterapia], e-mail: celiarsoares@terra.com.br; Fristachi, Carlos Elias [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Onco-Ginecologia e Mastologia; Paes, Roberto Pinto [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil)

    2008-12-15

    Objective: to assess the treatment of breast cancer T2 ({<=} 4 cm) and T3 through neoadjuvant chemotherapy, quadrantectomy and high dose rate brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering local control and overall survival. Material and method: this clinical prospective descriptive study was based on the evaluation of 88 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIb and IIIa, responsive to the neoadjuvant chemotherapy, treated from June/1995 to December/2006. Median follow-up was 58 months. Using clinical methods the tumor was evaluated before and after three or four cycles of chemotherapy based on anthracyclines. Overall survival and local control were assessed according to Kaplan-Meier methodology. Results: Local control and overall survival in five years were 90% and 73.5%, respectively. Conclusion: local control and overall survival were comparable to other forms of treatment. (author)

  20. Reductions in Anaemia and Fatigue are Associated with Improvements in Productivity in Cancer Patients Receiving Chemotherapy

    OpenAIRE

    2005-01-01

    Objective: Cancer-related anaemia is associated with fatigue that adversely affects patients' everyday functioning and wellbeing. We explore the impact of fatigue on patient productivity and caregiver burden. Methods: The analyses are based on data from a randomised, open-label, active-controlled, dose-finding trial of darbepoetin alfa among solid-tumour cancer patients with anaemia, who are receiving chemotherapy. Fatigue is assessed with the Functional Assessment of Cancer Therapy (FACT)-Fa...

  1. Understanding Chemotherapy

    Science.gov (United States)

    N ational C ancer I nstitute Understanding Chemotherapy What is chemotherapy? Chemotherapy is a cancer treatment that uses drugs to destroy cancer cells. It is also called “chemo.” Today, there are ...

  2. Improved Survival with the Patients with Variceal Bleed

    OpenAIRE

    Praveen Sharma; Sarin, Shiv K.

    2011-01-01

    Variceal hemorrhage is a major cause of death in patients with cirrhosis. Over the past two decades new treatment modalities have been introduced in the management of acute variceal bleeding (AVB) and several recent studies have suggested that the outcome of patients with cirrhosis and AVB has improved. Improved supportive measures, combination therapy which include early use of portal pressure reducing drugs with low rates of adverse effects (somatostatin, octerotide or terlipressin) and end...

  3. Failure to Adhere to Protocol Specified Radiation Therapy Guidelines Was Associated With Decreased Survival in RTOG 9704-A Phase III Trial of Adjuvant Chemotherapy and Chemoradiotherapy for Patients With Resected Adenocarcinoma of the Pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Abrams, Ross A., E-mail: Ross_a_abrams@rush.edu [Rush University Medical Center, Chicago, IL (United States); Winter, Kathryn A. [Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA (United States); Regine, William F. [University of Maryland, Baltimore, MD (United States); Safran, Howard [Brown University, Providence, RI (United States); Hoffman, John P. [Fox Chase Cancer Center, Philadelphia, PA (United States); Lustig, Robert [Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA (United States); Konski, Andre A. [Wayne State Medical Center, Detroit, MI (United States); Benson, Al B. [Northwestern University, Chicago, IL (United States); Macdonald, John S. [St. Vincent' s Cancer Care Center, New York, NY (United States); Rich, Tyvin A. [University of Virginia, Charlottesville, VA (United States); Willett, Christopher G. [Duke University, Durham, NC (United States)

    2012-02-01

    Purpose: In Radiation Therapy Oncology Group 9704, as previously published, patients with resected pancreatic adenocarcinoma received continuous infusion 5-FU and concurrent radiotherapy (5FU-RT). 5FU-RT treatment was preceded and followed by randomly assigned chemotherapy, either 5-FU or gemcitabine. This analysis explored whether failure to adhere to specified RT guidelines influenced survival and/or toxicity. Methods and Materials: RT requirements were protocol specified. Adherence was scored as per protocol (PP) or less than per protocol (survival (MS) for PP vs. improved MS (p = 0.016, p = 0.043, respectively). For all tumor locations, PP score was associated with decreased risk of failure (p = 0.016) and, for gemcitabine patients, a trend toward reduced Grade 4/5 nonhematologic toxicity (p = 0.065). Conclusions: This is the first Phase III, multicenter, adjuvant protocol for pancreatic adenocarcinoma to evaluate the impact of adherence to specified RT protocol guidelines on protocol outcomes. Failure to adhere to specified RT guidelines was associated with reduced survival and, for patients receiving gemcitabine, trend toward increased nonhematologic toxicity.

  4. Failure to Adhere to Protocol Specified Radiation Therapy Guidelines Was Associated With Decreased Survival in RTOG 9704 - A Phase III Trial of Adjuvant Chemotherapy and Chemoradiotherapy for Patients with Resected Adenocarcinoma of the Pancreas

    Science.gov (United States)

    Abrams, Ross A.; Winter, Kathryn A.; Regine, William F.; Safran, Howard; Hoffman, John P.; Lustig, Robert; Konski, Andre A.; Benson, Al B.; Macdonald, John S.; Rich, Tyvin A.; Willett, Christopher G.

    2011-01-01

    Purpose In RTOG 9704, as previously published, patients with resected pancreatic adenocarcinoma received continuous infusion 5-FU and concurrent radiotherapy (5FU-RT). 5FU-RT treatment was preceded and followed by randomly assigned chemotherapy, either 5-FU or gemcitabine. This analysis explored whether failure to adhere to specified RT guidelines influenced survival and/or toxicity. Methods and Materials RT requirements were protocol specified. Adherence was scored as per protocol (PP) or less than per protocol (survival (MS) for PP vs. improved MS (p=0.016, p=0.043, respectively). For all tumor locations PP score was associated with decreased risk of failure (p=0.016) and, for gemcitabine patients, a trend toward reduced grade 4/5 non-hematologic toxicity (p=0.065). Conclusions This is the first phase III, multi-center, adjuvant protocol for pancreatic adenocarcinoma to evaluate the impact of adherence to specified RT protocol guidelines on protocol outcomes. Failure to adhere to specified RT guidelines was associated with reduced survival and, for patients receiving gemcitabine, trend toward increased non-hematologic toxicity. PMID:21277694

  5. Pomalidomide Plus Low-Dose Dexamethasone Improves Survival for Patients with Multiple Myeloma

    Science.gov (United States)

    ... Health Professional Plasma Cell Neoplasms Treatment Research Pomalidomide plus Low-Dose Dexamethasone Improves Survival for Patients with ... pomalidomide, bortezomib, and low-dose dexamethasone with bortezomib plus low-dose dexamethasone in patients with previously treated ...

  6. Improving the Survivability of a Stochastic Communication Network

    Science.gov (United States)

    1988-12-01

    algorithm is called a labelling algorithm, and it has been the basis for other researchers, such as Edmonds and Karp [15], for developing a more...15. Edmonds, J. and R. M. Karp . "Theoretical Improvements in Logorithmic Effi- ciency for Network Flow Problems," Jour. A CM, 19: 248-264 (April, 1972...Conference Proceedings, 41: 49-54 (1972). 19. Hillier, Frederick S. and Gerald J. Lievernan. Introduction to Opt rafio., R(- search (Fourth Edition). Oakland

  7. Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy

    Directory of Open Access Journals (Sweden)

    Mathieu D. Saint-Pierre

    2015-01-01

    Full Text Available Introduction. Malignant pleural mesothelioma (MPM is associated with a poor prognosis. Palliative platinum-based chemotherapy may help to improve symptoms and prolong life. Since 2004, the platinum is commonly partnered with a folate antimetabolite. We performed a review investigating if survival had significantly changed before and after the arrival of folate antimetabolites in clinical practice. Methods. All MPM patients from January 1991 to June 2012 were identified. Data collected included age, gender, asbestos exposure, presenting signs/symptoms, performance status, histology, stage, bloodwork, treatment modalities including chemotherapy, and date of death or last follow-up. The primary endpoint was overall survival. Cox models were applied to determine variables associated with survival. Results. There were 245 patients identified. Median overall survival for all patients was 9.4 months. After multivariate analysis, performance status, stage, histology, leucocytosis, and thrombophilia remained independently associated with survival. Among all patients who received chemotherapy, there was no difference in overall survival between the periods before and after folate antimetabolite approval: 14.2 versus 13.2 months (P=0.35. Specifically receiving combined platinum-based/folate antimetabolite chemotherapy did not improve overall survival compared to all other chemotherapy regimens: 14.1 versus 13.6 months (P=0.97. Conclusions. In this review, we did not observe an incremental improvement in overall survival after folate antimetabolites became available.

  8. Improved survival with the patients with variceal bleed.

    Science.gov (United States)

    Sharma, Praveen; Sarin, Shiv K

    2011-01-01

    Variceal hemorrhage is a major cause of death in patients with cirrhosis. Over the past two decades new treatment modalities have been introduced in the management of acute variceal bleeding (AVB) and several recent studies have suggested that the outcome of patients with cirrhosis and AVB has improved. Improved supportive measures, combination therapy which include early use of portal pressure reducing drugs with low rates of adverse effects (somatostatin, octerotide or terlipressin) and endoscopic variceal ligation has become the first line treatment in the management of AVB. Short-term antibiotic prophylaxis, early use of lactulose for prevention of hepatic encephalopathy, application of early transjugular intrahepatic portasystemic shunts (TIPS), fully covered self-expandable metallic stent in patients for AVB may be useful in those cases where balloon tamponade is considered. Early and wide availability of liver transplantation has changed the armamentarium of the clinician for patients with AVB. High hepatic venous pressure gradient (HVPG) >20 mmHg in AVB has become a useful predictor of outcomes and more aggressive therapies with early TIPS based on HVPG measurement may be the treatment of choice to reduce mortality further.

  9. Improved Survival with the Patients with Variceal Bleed

    Directory of Open Access Journals (Sweden)

    Praveen Sharma

    2011-01-01

    Full Text Available Variceal hemorrhage is a major cause of death in patients with cirrhosis. Over the past two decades new treatment modalities have been introduced in the management of acute variceal bleeding (AVB and several recent studies have suggested that the outcome of patients with cirrhosis and AVB has improved. Improved supportive measures, combination therapy which include early use of portal pressure reducing drugs with low rates of adverse effects (somatostatin, octerotide or terlipressin and endoscopic variceal ligation has become the first line treatment in the management of AVB. Short-term antibiotic prophylaxis, early use of lactulose for prevention of hepatic encephalopathy, application of early transjugular intrahepatic portasystemic shunts (TIPS, fully covered self-expandable metallic stent in patients for AVB may be useful in those cases where balloon tamponade is considered. Early and wide availability of liver transplantation has changed the armamentarium of the clinician for patients with AVB. High hepatic venous pressure gradient (HVPG >20 mmHg in AVB has become a useful predictor of outcomes and more aggressive therapies with early TIPS based on HVPG measurement may be the treatment of choice to reduce mortality further.

  10. A single center experience: post-transplantation adjuvant chemotherapy impacts the prognosis of hepatocellular carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Wu Junyi; Sun Hongcheng; Han Zhongbo; Peng Zhihai

    2014-01-01

    Background The aim of this research was to investigate the impact of post-transplantation adjuvant chemotherapy in the prevention of tumor recurrence and metastasis for hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation.Methods A total of 117 patients with HCC exceeding the Milan criteria who had undergone orthotopic liver transplantation (OLT) from August 2002 to February 2009 were enrolled and retrospectively analyzed.The patients were divided into four groups according to chemotherapy regimens and the impact of different chemotherapy regimens on survival,disease-free survival,and adverse effects were compared.Results One year survival rates for the gemicitabine,conventional chemotherapy,oxaliplatin plus capecitabine and the best supportive care (BSC) group were 87.5%,84.2%,81.6%,and 67.5%.The 3-year survival rates were 48.1%,25.9%,31.6%,and 33.7%,respectively for the four groups.One year disease free survival rates for the four groups were 69.8%,47.4%,53.8%,and 45.7% respectively.And 3-year disease free survival rates were 43.2%,23.7%,23.6%,and 25.1% for the four groups.Stratification analysis showed that the gemcitabine regimen and conventional chemotherapy could significantly improve the survival rate and disease free survival rate for HCC patients who had major vascular invasion and/or microvascular invasion after liver transplantation compared with BSC group.Conclusions For HCC patients beyond Milan criteria,especially who had vascular invasion and/or micorvascular invasion,post-transplantation adjuvant chemotherapy can significantly improve survival.Gemcitabine is a proper regimen for postoperative adjuvant chemotherapy.Conventional chemotherapy can also benefit patients,but the adverse effects are not satisfactory.

  11. Role of TIPS in Improving Survival of Patients with Decompensated Liver Disease

    Directory of Open Access Journals (Sweden)

    Sundeep J. Punamiya

    2011-01-01

    Full Text Available Liver cirrhosis is associated with higher morbidity and reduced survival with appearance of portal hypertension and resultant decompensation. Portal decompression plays a key role in improving survival in these patients. Transjugular intrahepatic portosystemic shunts are known to be efficacious in reducing portal venous pressure and control of complications such as variceal bleeding and ascites. However, they have been associated with significant problems such as poor shunt durability, increased encephalopathy, and unchanged survival when compared with conservative treatment options. The last decade has seen a significant improvement in these complications, with introduction of covered stents, better selection of patients, and clearer understanding of procedural end-points. Use of TIPS early in the period of decompensation also appears promising in further improvement of survival of cirrhotic patients.

  12. Long-term survival after a favorable response to anti-EGFR antibody plus chemotherapy to treat bone marrow metastasis: a case report of KRAS-wildtype rectal cancer

    Science.gov (United States)

    Nakamura, Sho; Fukui, Tadahisa; Suzuki, Shuhei; Takeda, Hiroyuki; Watanabe, Kaname; Yoshioka, Takashi

    2017-01-01

    Bone marrow metastasis is a rare consequence of colorectal cancer that results in a poor prognosis; few reports describe a favorable response to doublet chemotherapy combined with targeted therapy, which is currently the standard treatment. We experienced a case where anti-epidermal growth factor receptor (EGFR) antibody produced a marked anti-tumor response to bone marrow metastasis that led to long-term survival. A 51-year-old man was diagnosed with a primary KRAS-wildtype rectal cancer with multiple metastases, including the bone marrow. Disease control was achieved for 10.8 months following chemotherapy with a modified FOLFOX6 regimen combined with an anti-EGFR antibody. He died of cancer 22.7 and 16.6 months after disease onset and first-line chemotherapy, respectively. This case shows that early tumor shrinkage and deepness of response to the anti-EGFR antibody were observed even in a patient with bone marrow metastasis. Anti-EGFR antibody therapy should therefore be considered even when a patient’s medical condition appears to be poor owing to bone marrow metastasis. Moreover, tumors that are likely to be sensitive to chemotherapy, such as RAS-wildtype colorectal cancers, can be considered for anti-EGFR antibody therapy even if the patient is considered unfit for chemotherapy.

  13. [Improvement of child survival in Mexico: the diagonal approach].

    Science.gov (United States)

    Sepúlveda, Jaime; Bustreo, Flavia; Tapia, Roberto; Rivera, Juan; Lozano, Rafael; Olaiz, Gustavo; Partida, Virgilio; García-García, Ma de Lourdes; Valdespino, José Luis

    2007-01-01

    Public health interventions aimed at children in Mexico have placed the country among the seven countries on track to achieve the goal of child mortality reduction by 2015. We analysed census data, mortality registries, the nominal registry of children, national nutrition surveys, and explored temporal association and biological plausibility to explain the reduction of child, infant, and neonatal mortality rates. During the past 25 years, child mortality rates declined from 64 to 23 per 1000 livebirths. A dramatic decline in diarrhoea mortality rates was recorded. Polio, diphtheria, and measles were eliminated. Nutritional status of children improved significantly for wasting, stunting, and underweight. A selection of highly cost-effective interventions bridging clinics and homes, what we called the diagonal approach, were central to this progress. Although a causal link to the reduction of child mortality was not possible to establish, we saw evidence of temporal association and biological plausibility to the high level of coverage of public health interventions, as well as significant association to the investments in women education, social protection, water, and sanitation. Leadership and continuity of public health policies, along with investments on institutions and human resources strengthening, were also among the reasons for these achievements.

  14. Improvement of child survival in Mexico: the diagonal approach.

    Science.gov (United States)

    Sepúlveda, Jaime; Bustreo, Flavia; Tapia, Roberto; Rivera, Juan; Lozano, Rafael; Oláiz, Gustavo; Partida, Virgilio; García-García, Lourdes; Valdespino, José Luis

    2006-12-01

    Public health interventions aimed at children in Mexico have placed the country among the seven countries on track to achieve the goal of child mortality reduction by 2015. We analysed census data, mortality registries, the nominal registry of children, national nutrition surveys, and explored temporal association and biological plausibility to explain the reduction of child, infant, and neonatal mortality rates. During the past 25 years, child mortality rates declined from 64 to 23 per 1000 livebirths. A dramatic decline in diarrhoea mortality rates was recorded. Polio, diphtheria, and measles were eliminated. Nutritional status of children improved significantly for wasting, stunting, and underweight. A selection of highly cost-effective interventions bridging clinics and homes, what we called the diagonal approach, were central to this progress. Although a causal link to the reduction of child mortality was not possible to establish, we saw evidence of temporal association and biological plausibility to the high level of coverage of public health interventions, as well as significant association to the investments in women education, social protection, water, and sanitation. Leadership and continuity of public health policies, along with investments on institutions and human resources strengthening, were also among the reasons for these achievements.

  15. Improved survival using oxygen free radical scavengers in the presence of ischemic bowel anastomosis.

    Science.gov (United States)

    Bergren, C T; Bodzin, J H; Cortez, J A

    1988-06-01

    A rat model was developed to determine the efficacy of oxygen free radical scavenger compounds in improving small bowel anastomotic healing in ischemia. 50 Sprague-Dawley rats underwent laparotomy and were divided into groups: I. sham operation; II. ischemia produced by ligation of mesenteric vessels along 3-5 cm of bowel; III. bowel transection and anastomosis; IV. ligation of vessels with bowel transection and anastomosis; V. ligation of vessels, bowel transection and IV administration of superoxide dismutase (SOD) (5000 U/kg) prior to anastomosis. All surviving animals were sacrificed after 2 weeks. Anastomotic tensile strength and histology were evaluated. Percent survival and the average length of survival for all groups is seen in the table below. (table: see text) A significant decrease in survival was present with the anastomotic group and the ischemic anastomotic group when compared with controls. An improved survival similar to ischemia alone was present in SOD group. No significant difference was noted between SOD and control groups. The results of this study indicate an improved survival rate and length of survival similar to controls in animals undergoing ischemic and penetrating injury to the bowel with the use of oxygen free radical scavenger compounds prior to anastomosis.

  16. Ginseng and Anticancer Drug Combination to Improve Cancer Chemotherapy: A Critical Review

    Directory of Open Access Journals (Sweden)

    Shihong Chen

    2014-01-01

    Full Text Available Ginseng, a well-known herb, is often used in combination with anticancer drugs to enhance chemotherapy. Its wide usage as well as many documentations are often cited to support its clinical benefit of such combination therapy. However the literature based on objective evidence to make such recommendation is still lacking. The present review critically evaluated relevant studies reported in English and Chinese literature on such combination. Based on our review, we found good evidence from in vitro and in vivo animal studies showing enhanced antitumor effect when ginseng is used in combination with some anticancer drugs. However, there is insufficient clinical evidence of such benefit as very few clinical studies are available. Future research should focus on clinically relevant studies of such combination to validate the utility of ginseng in cancer.

  17. A novel human-derived antibody against NY-ESO-1 improves the efficacy of chemotherapy.

    Science.gov (United States)

    Gupta, Anurag; Nuber, Natko; Esslinger, Christoph; Wittenbrink, Mareike; Treder, Martin; Landshammer, Alexandro; Noguchi, Takuro; Kelly, Marcus; Gnjatic, Sacha; Ritter, Erika; von Boehmer, Lotta; Nishikawa, Hiroyoshi; Shiku, Hiroshi; Old, Lloyd; Ritter, Gerd; Knuth, Alexander; van den Broek, Maries

    2013-01-01

    We investigated whether antibodies against intracellular tumor-associated antigens support tumor-specific immunity when administered together with a treatment that destroys the tumor. We propose that released antigens form immune complexes with the antibodies, which are then efficiently taken up by dendritic cells. We cloned the first human monoclonal antibodies against the Cancer/Testis (CT) antigen, NY-ESO-1. We tested whether the monoclonal anti-NY-ESO-1 antibody (12D7) facilitates cross-presentation of a NY-ESO-1-derived epitope by dendritic cells to human CD8+ T cells, and whether this results in the maturation of dendritic cells in vitro. We investigated the efficacy of 12D7 in combination with chemotherapy using BALB/c mice bearing syngeneic CT26 tumors that express intracellular NY-ESO-1. Human dendritic cells that were incubated with NY-ESO-1:12D7 immune complexes efficiently stimulated NY-ESO-1(157-165)/HLA-A2-specific human CD8+ T cells to produce interferon-γ, whereas NY-ESO-1 alone did not. Furthermore, the incubation of dendritic cells with NY-ESO-1:12D7 immune complexes resulted in the maturation of dendritic cells. Treatment of BALB/c mice that bear CT26/NY-ESO-1 tumors with 5-fluorouracil (5-FU) plus 12D7 was significantly more effective than chemotherapy alone. We propose systemic injection of monoclonal antibodies (mAbs) against tumor-associated antigens plus a treatment that promotes the local release of those antigens resulting in immune complex formation as a novel therapeutic modality for cancer.

  18. Effective treatment of depression improves post-myocardial infarction survival

    Institute of Scientific and Technical Information of China (English)

    Soudabeh; Khojasteh; Banankhah; Erika; Friedmann; Sue; Thomas

    2015-01-01

    effective treatment of depression reduced mortality in depressed post-MI patients.It is important to monitor the effectiveness of depression treatment and change treatments if necessary to reduce depression and improve cardiac outcomes in depressed post-MI patients.

  19. Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Wei, Xiong [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Blumenschein, George R. [Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tang, Ximing [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lee, J. Jack [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wistuba, Ignacio I. [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Diane D. [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hong, Waun Ki [Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-06-01

    Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of

  20. A Prospective Randomized Study of Adjuvant Chemotherapy in Completely Resected Stage Ⅲ-N2 Non Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To evaluate the effect of postoperative adjuvant chemotherapy on survival after complete resection of stage Ⅲ-N2 non-small-cell lung cancer. Methods: From Jan. 1999 to Dec. 2003, one-hundred and fifty patients, who were diagnosed as stage Ⅲ-N2 non-small cell lung cancer after operation, were randomly devided into chemotherapy group and control group. The former received four cycles of chemotherapy with NVB (25 mg/m2,D1, D5)/paclitaxel (175 mg/m2, DI) and Carboplatin (AUC=5, D1). Results: In chemotherapy group, 75.8% (68/79) of patients had finished the 4 cycles of chemotherapy and no one died of toxic effects of chemotherapy.Twenty-five percent of the patients had grade 3-4 neutropenia and 2% had febrile neutropenia. The median survival for the entire 150 patients was 879 d, with 1-year survival rate of 81%, 2-year survival rate of 59% and 3-year survival rate of 43%. There was no significant difference in median survival between chemotherapy and control group (897 d vs 821 d, P=0.0527), but there was significant difference in the 1-year and 2-year overall survival (94.71%, 76.28% vs 512 d, P=0.122), but there was significant difference in the 2-year survival rate between two groups with brain metastases (66.7% vs 37.6% P<0.05). The median survival after brain metastasis appeared was 190 days. Conclusion: Postoperative adjuvant chemotherapy does not significantly improve median survival among patients with completely resected stage Ⅱ-N2 non-small-cell lung cancer, but significantly improves the 1-year and 2-year overall survival. It neither decreases the incidence of brain metastasis but put off the time of brain metastasis.

  1. Are global and regional improvements in life expectancy and in child, adult and senior survival slowing?

    Directory of Open Access Journals (Sweden)

    Ryan J Hum

    Full Text Available Improvements in life expectancy have been considerable over the past hundred years. Forecasters have taken to applying historical trends under an assumption of continuing improvements in life expectancy in the future. A linear mixed effects model was used to estimate the trends in global and regional rates of improvements in life expectancy, child, adult, and senior survival, in 166 countries between 1950 and 2010. Global improvements in life expectancy, including both child and adult survival rates, decelerated significantly over the study period. Overall life expectancy gains were estimated to have declined from 5.9 to 4.0 months per year for a mean deceleration of -0.07 months/year2; annual child survival gains declined from 4.4 to 1.6 deaths averted per 1000 for a mean deceleration of -0.06 deaths/1000/year2; adult survival gains were estimated to decline from 4.8 to 3.7 deaths averted per 1000 per year for a mean deceleration of -0.08 deaths/1000/year2. Senior survival gains however increased from 2.4 to 4.2 deaths averted per 1000 per year for an acceleration of 0.03 deaths/1000/year2. Regional variation in the four measures was substantial. The rates of global improvements in life expectancy, child survival, and adult survival have declined since 1950 despite an increase in the rate of improvements among seniors. We postulate that low-cost innovation, related to the last half-century progress in health-primarily devoted to children and middle age, is reaping diminishing returns on its investments. Trends are uneven across regions and measures, which may be due in part to the state of epidemiological transition between countries and regions and disparities in the diffusion of innovation, accessible only in high-income countries where life expectancy is already highest.

  2. Background Parenchymal Enhancement on Preoperative Magnetic Resonance Imaging: Association With Recurrence-Free Survival in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Choi, Ji Soo; Ko, Eun Sook; Ko, Eun Young; Han, Boo-Kyung; Nam, Seok Jin

    2016-03-01

    To retrospectively investigate whether background parenchymal enhancement (BPE) of the contralateral breast on preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is associated with therapeutic outcomes following neoadjuvant chemotherapy (NAC) in unilateral invasive breast cancer. The institutional review board approved this study, and informed consent was waived. Between 2009 and 2011, 93 women with unilateral invasive breast cancer (43 premenopausal women who performed pre-NAC MRI between days 7 and 20 of the menstrual cycle and 50 postmenopausal women) underwent NAC with pre- and post-NAC DCE-MRI before surgery. MRI features (BPE [minimal, mild, moderate, marked] of the contralateral breast, lesion size and number, lesion kinetics, and changes in lesion size) and clinicopathologic features were analyzed. Patients were grouped according to BPE category (high [moderate or marked] or low [minimal or mild]). Cox regression modeling was used to determine associations between MRI features and recurrence-free survival (RFS) after controlling for clinicopathologic variables. The mean follow-up period was 48.2 months. Twenty-three recurrences occurred (2 ipsilateral breasts, 6 regional, and 15 distant). On multivariate analysis, high BPE on pre-NAC MRI (hazard ratio [HR] = 3.851, P = 0.006) and triple-negative cancer (HR = 3.192, P = 0.002) were independent factors associated with worse RFS. A greater reduction of lesion size on post-NAC MRI (HR = 0.984, P = 0.021) was associated with better RFS. High BPE on pre-NAC MRI is significantly associated with worse RFS in an NAC setting. This study suggests that BPE on pre-NAC DCE-MRI may have potential as a predictor of long-term outcomes in breast cancer patients who undergo NAC.

  3. Improvements in breast cancer survival between 1995 and 2012 in Denmark

    DEFF Research Database (Denmark)

    Jensen, Maj-Britt; Ejlertsen, Bent; Mouridsen, Henning T

    2016-01-01

    was extended considerable. Methods A population-based study of 68 842 breast cancer patients registered in the clinical database of the Danish Breast Cancer Cooperative Group in 1995-2012. Comprehensive data on prognostic factors, comorbidity and treatment together with complete follow-up for survival were....... The modified treatment strategies implemented by the use of nationwide guidelines seemed to have a major impact on the substantial survival improvements....

  4. Hydroxyapatite coating does not improve uncemented stem survival after total hip arthroplasty!

    DEFF Research Database (Denmark)

    Hailer, Nils P; Lazarinis, Stergios; Mäkelä, Keijo T

    2015-01-01

    Background and purpose - It is still being debated whether HA coating of uncemented stems used in total hip arthroplasty (THA) improves implant survival. We therefore investigated different uncemented stem brands, with and without HA coating, regarding early and long-term survival. Patients...... this surface treatment had no clinically relevant effect on their outcome, and we thus question whether HA coating adds any value to well-functioning stem designs....

  5. Nanoparticles carry chemotherapy drug deeper into solid tumors

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  6. Recent developments in the use of chemotherapy in brain tumours

    NARCIS (Netherlands)

    M.J. van den Bent (Martin); M.E. Hegi (Monika); R. Stupp (Roger)

    2006-01-01

    textabstractSeveral recent studies have further clarified the role of chemotherapy in newly diagnosed anaplastic glioma. For newly diagnosed glioblastoma, combined daily radiotherapy with daily temozolomide followed by six cycles of adjuvant temozolomide improves overall survival. This benefit is es

  7. Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana;

    2017-01-01

    Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated...

  8. Cancer Chemotherapy

    Science.gov (United States)

    ... controlled way. Cancer cells keep growing without control. Chemotherapy is drug therapy for cancer. It works by killing the cancer ... It depends on the type and amount of chemotherapy you get and how your body reacts. Some ...

  9. Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice.

    Directory of Open Access Journals (Sweden)

    Rachel E Sutherland

    Full Text Available Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2-4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient Kit(W-sh/Kit(W-sh mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to Kit(W-sh/Kit(W-sh mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host.

  10. Statin use is associated with improved survival in patients undergoing surgery for renal cell carcinoma

    DEFF Research Database (Denmark)

    Kaffenberger, Samuel D; Lin-Tsai, Opal; Stratton, Kelly L

    2015-01-01

    ) and disease-specific survival (DSS). Univariable survival analyses were performed using the Kaplan-Meier and the log-rank methods. Multivariable analysis was performed using a Cox proportional hazards model. The predictive discrimination of the models was assessed using the Harrell c-index. RESULTS......: 0.43-0.90; P = 0.011) and DSS (hazard ratio = 0.48; 95% CI: 0.28-0.83; P = 0.009). The multivariable model for DSS had excellent predictive discrimination with a c-index of 0.91. CONCLUSIONS: These data suggest that statin usage at time of surgery is independently associated with improved OS and DSS......PURPOSE: To determine whether statin use at time of surgery is associated with survival following nephrectomy or partial nephrectomy for renal cell carcinoma (RCC). Statins are thought to exhibit a protective effect on cancer incidence and possibly cancer survival in a number of malignancies...

  11. Adjuvant chemotherapy for completely resected non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Toyooka,Shinichi

    2009-10-01

    Full Text Available For many years, surgery alone was the standard treatment for patients with stage I-IIIA non-small-cell lung cancer (NSCLC. However, recent studies have demonstrated that adjuvant chemotherapy provides a survival benefit. The first adjuvant chemotherapy for NSCLC was performed in the 1960s using a key drug known as cyclophosphamide. In the 1980s and early 1990s, a new anti-cancer drug, cisplatin, was developed. The first meta-analysis of this drug was conducted by the Non-small Cell Lung Cancer Collaborative Group in 1995. This analysis comparing surgery with surgery plus chemotherapy containing cisplatin produced a hazard ratio of 0.87 and suggested an absolute benefit of chemotherapy of 5% at 5 years;this difference was not statistically significant (p0.08. Several clinical trials of adjuvant chemotherapy were planned after the meta-analysis conducted in 1995, but the efficacy of adjuvant chemotherapy remained a matter of controversy. However, useful evidence was reported after 2003. The International Adjuvant Lung Cancer Collaborative Group Trial (IALT demonstrated a 4.1% improvement in survival for patients with stage I to III NSCLC. The JBR. 10 trial demonstrated a 15% improvement in 5-year survival for the adjuvant chemotherapy arm in stage IB or II (excluding T3N0 patients. The Adjuvant Navelbine International Trialist Association (ANITA trial reported that the overall survival at 5 years improved by 8.6% in the chemotherapy arm and that this survival rate was maintained at 7 years (8.4% in stage II and IIIA patients. A meta-analysis based on collected and pooled individual patient data from the 5 largest randomized trials was conducted by the Lung Adjuvant Cisplatin Evaluation (LACE. This analysis demonstrated that cisplatin-based adjuvant chemotherapy improved survival in patients with stage II or III cancer. Alterna-tively, uracil-tegafur has been developed and tested in Japan. The Japan Lung Cancer Research Group (JLCRG on Postsurgical

  12. EFFECT OF NEOADJUVANT CHEMOTHERAPY USING PACLITAXEL COMBINED WITH CARBOPLATIN ON ADVANCED NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    XIONG Hong-chao; CHEN Jin-feng; ZHANG Li-jian

    2006-01-01

    Objective: To assess the therapeutic effectiveness of preoperative neoadjuvant chemotherapy using a combination of paclitaxel and carboplatin on local advanced non-small cell lung cancer (NSCLC). Methods: Twenty-five patients with advanced NSCLC were treated with paclitaxel and carboplatin for 2 to 4 cycles before undergoing tumor resection and then postoperative chemotherapy/radiotherapy therapy for 2 to 4 cycles. Results: Following neoadjuvant chemotherapy, the most prominent side-effect was bone marrow restraint. The overall response rate of preoperative chemotherapy was 56%. The mean survival time was 26.5 months, with 1-, 2- and 5-year survival rates of 55%, 25%, and 16%, respectively. All NSCLC patients survived the perioperative period. Conclusion: Preoperative neoadjuvant chemotherapy combining paclitaxel and carboplatin produced minimal side-effect while increasing the probability that advanced NSCLC patients would be able to undergo surgery thus improving their prognosis.

  13. Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657).

    Science.gov (United States)

    Esserman, Laura J; Berry, Donald A; Cheang, Maggie C U; Yau, Christina; Perou, Charles M; Carey, Lisa; DeMichele, Angela; Gray, Joe W; Conway-Dorsey, Kathleen; Lenburg, Marc E; Buxton, Meredith B; Davis, Sarah E; van't Veer, Laura J; Hudis, Clifford; Chin, Koei; Wolf, Denise; Krontiras, Helen; Montgomery, Leslie; Tripathy, Debu; Lehman, Constance; Liu, Minetta C; Olopade, Olufunmilayo I; Rugo, Hope S; Carpenter, John T; Livasy, Chad; Dressler, Lynn; Chhieng, David; Singh, Baljit; Mies, Carolyn; Rabban, Joseph; Chen, Yunni-Yi; Giri, Dilip; Au, Alfred; Hylton, Nola

    2012-04-01

    Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on recurrence-free survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ≥ 3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated. Categorization of breast cancer by molecular signatures enhanced the ability of pCR to predict improvement in RFS compared to the population as a whole. In multivariate analysis, the molecular signatures that added to the ability of HR and HER2 receptors, clinical stage, and pCR in predicting RFS included 70-gene signature, wound healing signature, p53 mutation signature, and PAM50 risk of recurrence. The low risk signatures were associated with significantly better prognosis, and also identified additional patients with a good prognosis within the no pCR group, primarily in the hormone receptor positive, HER-2 negative subgroup. The I-SPY 1 population is enriched for tumors with a poor prognosis but is still heterogeneous in terms of rates of pCR and RFS. The ability of pCR to predict RFS is better by subset than it is for the whole group. Molecular markers improve prediction of RFS by identifying additional patients with excellent prognosis within the no pCR group.

  14. Impact of adjuvant chemotherapy delay on survival in cancer breast patients%延迟辅助化疗对乳腺癌患者生存期的影响

    Institute of Scientific and Technical Information of China (English)

    Dalia Abdel Ghany

    2013-01-01

    Objective: The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. It is usually prescribed within 2-3 months after definitive surgery. The aim of this retrospective study was to assess the impact of adjuvant chemotherapy (CT) delay beyond 3 weeks ( 21 days) in premenopausal patients with ER-absent tumors being treated for early stages breast cancer on overall survival (OS) and disease-free survival (DFS). Methods: This retrospective study was conducted through revision of medical records of premenopausal patients diagnosed with early stage I-IIIA breast cancer and ER-absent tumors who received adjuvant CT after definitive surgery at the Department of Clinical Oncology, Ain-Shams University Hospitals. Results: Between 2005 and 2008, 105 patients were retrospectively analyzed and included. Patients were divided into 2 groups: Group A including 48 patients who started adjuvant CT < 21 days of surgery and group B which included 57 patients who had CT delay < 21 days. Both groups were matched demographically. Comparisons of overall survival, and disease-free survival between group A and group B patients all favored group A. At 5-year the OS rates were 87% and 73% for groups A and B respectively (P = 0.001), while DFS rates were 85% and 64% in groups A and B respectively (P = 0.001). Analysis of other prognostic factors (age, T, N, grade, HER2 status, surgery type, CT type, local radiotherapy received) were analyzed. Only nodal status predicted for worse DFS (P = 0.05) and OS (P = 0.006). Conclusion: Delay in initiating adjuvant chemotherapy for early stage breast cancer patients with ER-absent tumors was associated with a decrease in both OS and DFS rates.

  15. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2015-04-01

    had died. Published studies of melanoma therapies were tabled for comparison. Conclusion: The fact that 18 cases of exceptional survival in advanced melanoma were identified is remarkable in itself. Even with recent therapies, the factors for improved survival remain enigmatic; however, one apparent common denominator in most cases was the persistent use of repeated therapies to reduce tumor bulk, induce tumor necrosis, and/or cause immunostimulation. These cases are instructive, suggesting manipulation of an established, endogenous, existing immune response. These observations provide practical evidence that the course for any patient with advanced melanoma at the outset should be considered unpredictable, open to immunomanipulation, and thus not uniformly fatal. The findings were compared and interpreted with reported newer immunotherapeutic approaches. Keywords: advanced melanoma, clinical responses, immunotherapy, prolonged survival

  16. BCVPP chemotherapy for advanced Hodgkin's disease: evidence for greater duration of complete remission, greater survival, and less toxicity than with a MOPP regimen. Results of the Eastern Cooperative Oncology Group study.

    Science.gov (United States)

    Bakemeier, R F; Anderson, J R; Costello, W; Rosner, G; Horton, J; Glick, J H; Hines, J D; Berard, C W; DeVita, V T

    1984-10-01

    Two chemotherapy regimens for treatment of patients with advanced Hodgkin's disease, BCVPP (carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone) and MOPP (mechlorethamine hydrochloride, vincristine, procarbazine, and prednisone), were compared in a randomized prospective study. Two hundred ninety-three patients were evaluable in the induction phase of this study. The complete remission rate with BCVPP was 76% (112/147) and with MOPP, 73% (106/146) (p = 0.51). The duration of complete remissions for previously untreated patients given BCVPP was significantly longer than that for previously untreated patients given MOPP (p = 0.02). Although hematologic toxicities were similar, BCVPP caused less gastrointestinal (p = 0.0001) and neurologic toxicity (p = 0.01) than MOPP. Previously untreated patients achieving complete remission with BCVPP survived significantly longer than those receiving MOPP (p = 0.03). As primary induction chemotherapy for advanced Hodgkin's disease, BCVPP is an effective alternative to MOPP, having equal or greater therapeutic benefit with less toxicity.

  17.   Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525)

    DEFF Research Database (Denmark)

    Rasmussen, Anne-Sofie Schrohl; Look, Maxime P.; Meijer-van Gelder, Marion E.

    for the analysis of DFS. A similar pattern was seen in the analyses of OS. In the group treated with CMF, both TIMP-1 low and high patients had significantly better survival than untreated patients (Ppatients, those with TIMP-1 low tumors appear to benefit more from the adjuvant...... Predictive markers are needed to guide planning of adjuvant therapy for patients with breast cancer. We have recently shown that high tumor tissue levels of TIMP-1 are associated with decreased response to chemotherapy in metastatic breast cancer patients (Schrohl et al, Clin Cancer Res, 2006......) suggesting that TIMP-1 may be a predictive marker in breast cancer patients. Purpose: This study investigates the association of tumor tissue TIMP-1 levels with response to adjuvant chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil) or an anthracycline-containing regimen. Patients...

  18. Systemic chemotherapy for metastatic breast cancer

    Institute of Scientific and Technical Information of China (English)

    Yannan Zhao; Biyun Wang

    2015-01-01

    Breast cancer is the leading cause of cancer among women worldwide and the most common cancer in China. Many factors influence the treatment strategy for metastatic breast cancer (MBC). Chemotherapy should be administered to patients with hormone receptor-negative tumors, symptomatic visceral metastasis, and a short disease-free interval. Sequential single-agent chemotherapy has similar efficacy as combination agents in terms of overall survival and quality of life. Anthracyclines are the cornerstone of first-line treatment for MBC, and taxanes represent the second treatment option after resistance. When progression or intolerable toxicity occurs after optimal treatment, the alternative treatments include capecitabine, vinorel-bine, and gemcitabine. Ixabepilone and eribulin are relatively new effective single agents. A combination of cytotoxic agents for patients with rapid clinical progression can further improve the overall response rate and time to progression compared to single-agent treatment. For patients with MBC who were pretreated with anthracyclines in the neoadjuvant/adjuvant setting, a taxane-containing regimen such as docetaxel plus capecitabine or gemcitabine plus paclitaxel should be administered. Platinum-based therapies such as cisplatin or carboplatin have a role in the treatment of triple-negative breast cancer. Meanwhile, the efficacy of the addition of targeted drugs such as iniparib, bevacizumab, and cetuximab to chemotherapy remains unproven. Maintenance chemotherapy is routinely recommended in clinical practice at present. Patients who were previously treated with paclitaxel and gemcitabine have better progression-free and overall survival with maintenance chemotherapy according to a Korean phase Ⅲ clinical trial. Sequential maintenance treatment with capecitabine monotherapy after capecitabine-based combination chemotherapy (X-based X) appears favorable based on a series of domestic studies.

  19. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Science.gov (United States)

    2010-07-01

    ... quality of life. (Authority: 38 U.S.C. 501) Cross References: Improved pension. See § 3.1(w). Child. See... income of the veteran or surviving spouse. (Authority: 38 U.S.C. 1521, 1541) (c) Mexican border period and World War I veterans. The applicable maximum annual rate payable to a Mexican border period...

  20. Alpha (1,2)-fucosyltransferase M307A polymorphism improves piglet survival.

    Science.gov (United States)

    Kim, Kyungtae; Nguyen, Dinh Truong; Choi, Minkyung; Kim, Jin-Hoi; Seo, Han Geuk; Dadi, Hailu; Cha, Se-Yeoun; Seo, Kunho; Lee, Yun-Mi; Kim, Jong-Joo; Park, Chankyu

    2013-01-01

    To confirm the beneficial effects of alpha (1,2)-fucosyltransferase (FUT1) M307 (A) on piglet survival on commercial farms, we performed PCR-RFLP analysis of FUT1 M307 in successfully marketed (n = 245) and disease affected/deceased pigs during weaning (n = 252) at a commercial farm. We also evaluated the FUT1 genotypes of 190 healthy pigs from three different genetic backgrounds. The distribution of genotypes differed between the successfully marketed and disease affected/deceased pig groups. The frequency of the A allele, associated with resistance to edema and post-weaning diarrhea, was higher in the post-weaning survival group (0.21) than in the non-survival group (0.16, P piglet survival between AA and GG genotypes was 1.98; thus, piglet survival for individuals with the AA genotype was almost two-fold greater than for GG individuals. The FUT1 gene polymorphism can be used as an effective marker for selection programs to improve post-weaning piglet survival.

  1. Interact to survive: Phyllobacterium brassicacearum improves Arabidopsis tolerance to severe water deficit and growth recovery.

    Directory of Open Access Journals (Sweden)

    Justine Bresson

    Full Text Available Mutualistic bacteria can alter plant phenotypes and confer new abilities to plants. Some plant growth-promoting rhizobacteria (PGPR are known to improve both plant growth and tolerance to multiple stresses, including drought, but reports on their effects on plant survival under severe water deficits are scarce. We investigated the effect of Phyllobacterium brassicacearum STM196 strain, a PGPR isolated from the rhizosphere of oilseed rape, on survival, growth and physiological responses of Arabidopsis thaliana to severe water deficits combining destructive and non-destructive high-throughput phenotyping. Soil inoculation with STM196 greatly increased the survival rate of A. thaliana under several scenarios of severe water deficit. Photosystem II efficiency, assessed at the whole-plant level by high-throughput fluorescence imaging (Fv/Fm, was related to the probability of survival and revealed that STM196 delayed plant mortality. Inoculated surviving plants tolerated more damages to the photosynthetic tissues through a delayed dehydration and a better tolerance to low water status. Importantly, STM196 allowed a better recovery of plant growth after rewatering and stressed plants reached a similar biomass at flowering than non-stressed plants. Our results highlight the importance of plant-bacteria interactions in plant responses to severe drought and provide a new avenue of investigations to improve drought tolerance in agriculture.

  2. Prior infection does not improve survival against the amphibian disease Chytridiomycosis.

    Directory of Open Access Journals (Sweden)

    Scott D Cashins

    Full Text Available Many amphibians have declined globally due to introduction of the pathogenic fungus Batrachochytrium dendrobatidis (Bd. Hundreds of species, many in well-protected habitats, remain as small populations at risk of extinction. Currently the only proven conservation strategy is to maintain species in captivity to be reintroduced at a later date. However, methods to abate the disease in the wild are urgently needed so that reintroduced and wild animals can survive in the presence of Bd. Vaccination has been widely suggested as a potential strategy to improve survival. We used captive-bred offspring of critically endangered booroolong frogs (Litoria booroolongensis to test if vaccination in the form of prior infection improves survival following re exposure. We infected frogs with a local Bd isolate, cleared infection after 30 days (d using itraconazole just prior to the onset of clinical signs, and then re-exposed animals to Bd at 110 d. We found prior exposure had no effect on survival or infection intensities, clearly showing that real infections do not stimulate a protective adaptive immune response in this species. This result supports recent studies suggesting Bd may evade or suppress host immune functions. Our results suggest vaccination is unlikely to be useful in mitigating chytridiomycosis. However, survival of some individuals from all experimental groups indicates existence of protective innate immunity. Understanding and promoting this innate resistance holds potential for enabling species recovery.

  3. 139例晚期食管鳞状细胞癌的一线化疗及生存分析%First-line chemotherapy of patients with advanced esophageal squamous cell carcinoma:A survival analysis of 139 cases

    Institute of Scientific and Technical Information of China (English)

    闫晓杰; 夏学明; 刘钦兰; 白莉

    2015-01-01

    目的:研究晚期食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)一线化疗情况及影响预后的相关因素。方法回顾性分析2009年1月-2014年8月在我院初治Ⅳ期行一线化疗的139例ESCC患者的临床资料,其中男性124例,女性15例,年龄39~78岁,中位年龄为58岁。采用Kaplan-Meier法分析总生存时间(overall survival,OS),单因素和Cox回归多因素分析影响生存及预后的相关因素。结果139例患者化疗总有效率为46.8%,1年、3年、5年生存率分别为55.4%、15.8%、4.5%。一线化疗的中位OS为13.9个月,单因素及多因素分析显示,肝转移(P=0.028)、一线化疗疗效(P=0.001)、是否胸部放疗(P=0.000)与OS有关。结论有无肝转移、化疗是否有效、是否接受放疗对患者预后有重要影响,无肝转移患者的预后好,化疗评价有效、接受放疗有益于生存。%Objective To study the survival of patients with advanced esophageal squamous cell carcinoma (ESCC) in first-line chemotherapy and the factors related to the prognosis. Methods Clinical data about 139 advanced ESCC patients with 124 males and 15 females who received first-line chemotherapy in our hospital from January 2009 to August 2014 were retrospectively analyzed. The distribution of age range was 39 to 78 years old with median age of 58 years old. Kaplan-Meier method was used to calculate the overall survival (OS). Univariate analysis and Cox regression analysis were used to detect the influence factors of survival and prognosis. Results The response rate of 139 patients with chemotherapy was 46.8%with 1-year, 3-year, 5-year survival rates of 55.4%, 15.8%, 4.5%, respectively. The median OS of patients with advanced ESCC in first-line chemotherapy was 13.9 months. According to the results of univariate and COX multivariate analysis, OS of patients with advanced ESCC was closely associated with liver metastasis (P=0.028), curative effect of first

  4. Hepatic Artery Chemotherapy for Advanced Adenocarcinoma of the Pancreas

    Directory of Open Access Journals (Sweden)

    Robert Levin

    2016-08-01

    Full Text Available Context Seventy patients with adenocarcinoma of the pancreas with liver metastases, received chemotherapy every four weeks and their outcomes are reported in this retrospective series. Objective Advanced adenocarcinoma of the pancreas has a poor prognosis with only 2% 5-year survival reported by SEER (Surveillance, Epidemiology and End Results of the NCI. Chemotherapy given as intra-arterial perfusions is more intense than intravenous chemotherapy. Responses in perfused tumor is expected to be better than that obtained with only intravenous chemotherapy. Design Hepatic artery therapy is given monthly as a 5 hour perfusion of the hepatic artery using DDP and MIC. Also given is monthy Intravenous (IV therapy with four hours of Leucovorin (LV, with an injection of FUDR during the last hour of LV, daily x 5 days. Setting all therapy was given at Midwestern Regional Medical Center. Patients Thirty seven patients had no prior chemotherapy, while 33 patients had progressed after prior IV chemotherapy. Intervention Hepatic artery therapy with IV LV-FUDR was given for up to six months depending upon marrow tolerance and response. At that point, if response was ongoing or improving, therapy was continued monthly with only IV LV-FUDR; all therapy was stopped whenever progressive disease was evident. Results of those without prior chemotherapy, the mean overall survival (OS was 17.3 ± 30.2 months (mean±SD, ranging up to 13 years. Six patients survived more than three years with four are living in continuing complete remission for more than five years. Conclusion This therapy offers the opportunity for long term survival in a subset of patients with metastatic adenocarcinoma of the pancreas who have liver metastases, and some patients can be cured.

  5. Classification and Regression Tree Analysis of Clinical Patterns that Predict Survival in 127 Chinese Patients with Advanced Non-small Cell Lung Cancer Treated by Gefitinib Who Failed to Previous Chemotherapy

    Directory of Open Access Journals (Sweden)

    Ziping WANG

    2011-09-01

    Full Text Available Background and objective It has been proven that gefitinib produces only 10%-20% tumor regression in heavily pretreated, unselected non-small cell lung cancer (NSCLC patients as the second- and third-line setting. Asian, female, nonsmokers and adenocarcinoma are favorable factors; however, it is difficult to find a patient satisfying all the above clinical characteristics. The aim of this study is to identify novel predicting factors, and to explore the interactions between clinical variables and their impact on the survival of Chinese patients with advanced NSCLC who were heavily treated with gefitinib in the second- or third-line setting. Methods The clinical and follow-up data of 127 advanced NSCLC patients referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from March 2005 to March 2010 were analyzed. Multivariate analysis of progression-free survival (PFS was performed using recursive partitioning, which is referred to as the classification and regression tree (CART analysis. Results The median PFS of 127 eligible consecutive advanced NSCLC patients was 8.0 months (95%CI: 5.8-10.2. CART was performed with an initial split on first-line chemotherapy outcomes and a second split on patients’ age. Three terminal subgroups were formed. The median PFS of the three subsets ranged from 1.0 month (95%CI: 0.8-1.2 for those with progressive disease outcome after the first-line chemotherapy subgroup, 10 months (95%CI: 7.0-13.0 in patients with a partial response or stable disease in first-line chemotherapy and age <70, and 22.0 months for patients obtaining a partial response or stable disease in first-line chemotherapy at age 70-81 (95%CI: 3.8-40.1. Conclusion Partial response, stable disease in first-line chemotherapy and age ≥ 70 are closely correlated with long-term survival treated by gefitinib as a second- or third-line setting in advanced NSCLC. CART can be used to identify previously unappreciated patient

  6. How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart?

    Directory of Open Access Journals (Sweden)

    Liangpeng Li

    2016-01-01

    Full Text Available Mesenchymal stem cell (MSC is an intensely studied stem cell type applied for cardiac repair. For decades, the preclinical researches on animal model and clinical trials have suggested that MSC transplantation exerts therapeutic effect on ischemic heart disease. However, there remain major limitations to be overcome, one of which is the very low survival rate after transplantation in heart tissue. Various strategies have been tried to improve the MSC survival, and many of them showed promising results. In this review, we analyzed the studies in recent years to summarize the methods, effects, and mechanisms of the new strategies to address this question.

  7. Does Glucagon Improve Survival in a Porcine (Sus Scrofa) of Adult Asphyxial Cardiac Arrest in Addition to Standard Epinephrine Therapy?

    Science.gov (United States)

    2012-01-17

    UDIIILI: oa. I..UN I ItA!.. I NUMDI:It Does Glucagon improve survival in a porcine (Sus Scrofa ) of adult asphyxial cardiac arrest in addition to...EXPIRATION DATE: 25 Mar 13 PROTOCOL TITLE: Does Glucagon Improve Survival in a Porcine (Sus scrofa ) Model of Adult Asphyxial Cardiac Arrest in Addition...Additions: Deletions: 2 Protocol No: A-2007-03 Protocol Title: Does Glucagon Improve Survival in a Porcine (Sus scrofa ) Model of Adult Asphyxial

  8. Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy

    Science.gov (United States)

    Mangala, Lingegowda S.; Wang, Hongyu; Jiang, Dahai; Wu, Sherry Y.; Somasunderam, Anoma; Volk, David E.; Lokesh, Ganesh L. R.; Li, Xin; Pradeep, Sunila; Yang, Xianbin; Haemmerle, Monika; Nagaraja, Archana S; Bayraktar, Emine; Bayraktar, Recep; Li, Li; Tanaka, Takemi; Hu, Wei; Gharpure, Kshipra M; McGuire, Michael H.; Thiviyanathan, Varatharasa; Zhang, Xinna; Maiti, Sourindra N.; Bulayeva, Nataliya; Dorniak, Piotr L.; Cooper, Laurence J.N.; Rosenblatt, Kevin P.; Lopez-Berestein, Gabriel; Gorenstein, David G.; Sood, Anil K.

    2016-01-01

    Current antiangiogenesis therapy relies on inhibiting newly developed immature tumor blood vessels and starving tumor cells. This strategy has shown transient and modest efficacy. Here, we report a better approach to target cancer-associated endothelial cells (ECs), reverse permeability and leakiness of tumor blood vessels, and improve delivery of chemotherapeutic agents to the tumor. First, we identified deregulated microRNAs (miRs) from patient-derived cancer-associated ECs. Silencing these miRs led to decreased vascular permeability and increased maturation of blood vessels. Next, we screened a thioaptamer (TA) library to identify TAs selective for tumor-associated ECs. An annexin A2–targeted TA was identified and used for delivery of miR106b-5p and miR30c-5p inhibitors, resulting in vascular maturation and antitumor effects without inducing hypoxia. These findings could have implications for improving vascular-targeted therapy. PMID:27777972

  9. Parathyroid carcinoma survival: improvements in the era of intact parathyroid hormone monitoring?

    Directory of Open Access Journals (Sweden)

    Steve R. Martinez

    2013-02-01

    Full Text Available The intact parathyroid hormone (iPTH assay is a critical test in the diagnosis and management of PTH-mediated hypercalcemia, including parathyroid carcinoma (PCa. We hypothesized that the survival of patients diagnosed with PCa has improved since adoption of the iPTH assay into clinical practice. We identified all confirmed cases of PCa within the Surveillance, Epidemiology and End Results database from 1973 to 2006. Patients were categorized into two eras based upon introduction of the iPTH assay: 1973 to 1997 (era I and 1997 to 2006 (era II, when the iPTH assay was in standard use. We estimated overall survival (OS and disease-specific survival (DSS using the Kaplan-Meier method, with differences among survival curves assessed via log rank. Multivariate Cox proportional hazards models compared the survival rates between treatment eras while controlling for patient age, sex, race/ethnicity, tumor size, nodal status, extent of disease, and type of surgery. Multivariate models included patients undergoing potentially curative surgery and excluded those with dis- tant metastases. Risks of overall and disease-specific mortality were reported as hazard ratios with 95% confidence intervals. Study criteria were met by 370 patients. Median survival was 15.6 years. Five-year rates of OS and DSS were 78% and 88% for era I and 82% and 96% for era II. On multivariate analysis, age, black race, and unknown extent of disease predicted an increased risk of death from any cause. Treatment era did not predict OS. No factor predicted PCa-specific mortality. In multivariate analysis, neither OS nor DSS have improved in the current era that utilizes iPTH for the detection and management of PCa.

  10. Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Progression-Free Survival for Patients with Chronic Myelomonocytic Leukemia.

    Science.gov (United States)

    Kongtim, Piyanuch; Popat, Uday; Jimenez, Antonio; Gaballa, Sameh; El Fakih, Riad; Rondon, Gabriela; Chen, Julianne; Bueso-Ramos, Carlos; Borthakur, Gautam; Pemmaraju, Naveen; Garcia-Manero, Guillermo; Kantarjian, Hagop; Alousi, Amin; Hosing, Chitra; Anderlini, Paolo; Khouri, Issa F; Kebriaei, Partow; Andersson, Borje S; Oran, Betul; Rezvani, Katayoun; Marin, David; Shpall, Elizabeth J; Champlin, Richard E; Ciurea, Stefan O

    2016-01-01

    The treatment of patients with chronic myelomonocytic leukemia (CMML) with transplant has not been optimized. We retrospectively reviewed the data for 83 consecutive patients with CMML (47 with CMML-1/2 and 36 with CMML progressed to acute myeloid leukemia) who received an allogeneic stem cell transplant (allo-SCT) at our institution between April 1991 and December 2013 to identify factors associated with improved survival and determine whether treatment with hypomethylating agents before transplant improves progression-free survival (PFS). The median age of the cohort was 57 years. Seventy-eight patients received induction treatment before transplant, with 37 receiving hypomethylating agents and 41 receiving cytotoxic chemotherapy. Patients treated with a hypomethylating agent had a significantly lower cumulative incidence of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; P = .03), whereas treatment-related mortality at 1 year post-transplant did not significantly differ between the groups (27% and 30%, respectively; P = .84). The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a hypomethylating agent (43%) than in those treated with other agents (27%; P = .04). Our data support the use of hypomethylating agents before allo-SCT for patients with CMML to achieve morphologic remission and improve PFS of these patients. Future studies are needed to confirm these findings.

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

    Energy Technology Data Exchange (ETDEWEB)

    Urban, Damien [Department of Oncology, Sheba Medical Center, Ramat Gan (Israel); Mishra, Mark [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Onn, Amir [Department of Oncology, Sheba Medical Center, Ramat Gan (Israel); Dicker, Adam P. [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Symon, Zvi; Pfeffer, M. Raphael [Department of Oncology, Sheba Medical Center, Ramat Gan (Israel); Sackler School of Medicine, Tel Aviv University, Tel Aviv (Israel); Lawrence, Yaacov Richard, E-mail: yaacovla@gmail.com [Department of Oncology, Sheba Medical Center, Ramat Gan (Israel); Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Sackler School of Medicine, Tel Aviv University, Tel Aviv (Israel)

    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.

  12. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim;

    2007-01-01

    the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed...... with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management...... trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant...

  13. Decline in CA19-9 during chemotherapy predicts survival in four independent cohorts of patients with inoperable bile duct cancer

    DEFF Research Database (Denmark)

    Grunnet, Mie; Christensen, Ib J; Lassen, Ulrik;

    2015-01-01

    BACKGROUND: Carbohydrate associated antigen (CA19-9) has been approved by the FDA as a biomarker for monitoring treatment effect in pancreatic cancer. However, the value of serum CA19-9 as a biomarker of response to chemotherapy in bile duct cancer is unclear. The aim of this study was to determine...

  14. Selection criteria for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ingmar Konigsrainer

    2011-01-01

    Peritoneal carcinomatosis in gastric cancer is associated with a dismal prognosis. Systemic chemotherapy is not effective because of the existence of a blood-peritoneal barrier. Cytoreductive surgery and intraperitoneal chemotherapy can improve survival and quality of life in selected patients. Patient selection for this multimodal approach is one of the most critical issues, and calls for interdisciplinary evaluation by radiologists, medical and surgical oncologists, and anaesthetists. This article sets forth criteria for selection of gastric cancer patients suffering from peritoneal carcinomatosis.

  15. The development of advanced hydroelectric turbines to improve fish passage survival

    Energy Technology Data Exchange (ETDEWEB)

    Cada, Glenn F. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2001-09-01

    Recent efforts to improve the survival of hydroelectric turbine-passed juvenile fish have explored modifications to both operation and design of the turbines. Much of this research is being carried out by power producers in the Columbia River basin (U.S. Army Corps of Engineers and the public utility districts), while the development of low impact turbines is being pursued on a national scale by the U.S. Department of Energy. Fisheries managers are involved in all aspects of these efforts. Advanced versions of conventional Kaplan turbines are being installed and tested in the Columbia River basin, and a pilot scale version of a novel turbine concept is undergoing laboratory testing. Field studies in the last few years have shown that improvements in the design of conventional turbines have increased the survival of juvenile fish. There is still much to be learned about the causes and extent of injuries in the turbine system (including the draft tube and tailrace), as well as the significance of indirect mortality and the effects of turbine passage on adult fish. However, improvements in turbine design and operation, as well as new field, laboratory, and modeling techniques to assess turbine-passage survival, are contributing toward resolution of the downstream fish passage issue at hydroelectric power plants.

  16. Internal tandem duplication of the FLT3 gene confers poor overall survival in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: an International Consortium on Acute Promyelocytic Leukemia study.

    Science.gov (United States)

    Lucena-Araujo, Antonio R; Kim, Haesook T; Jacomo, Rafael H; Melo, Raul A; Bittencourt, Rosane; Pasquini, Ricardo; Pagnano, Katia; Fagundes, Evandro M; Chauffaille, Maria de Lourdes; Chiattone, Carlos S; Lima, Ana Silvia; Ruiz-Argüelles, Guillermo; Undurraga, Maria Soledad; Martinez, Lem; Kwaan, Hau C; Gallagher, Robert; Niemeyer, Charlotte M; Schrier, Stanley L; Tallman, Martin S; Grimwade, David; Ganser, Arnold; Berliner, Nancy; Ribeiro, Raul C; Lo-Coco, Francesco; Löwenberg, Bob; Sanz, Miguel A; Rego, Eduardo M

    2014-12-01

    Activating internal tandem duplication (ITD) mutations in the fms-like tyrosine kinase 3 (FLT3) gene (FLT3-ITD) are associated with poor outcome in acute myeloid leukemia, but their prognostic impact in acute promyelocytic leukemia (APL) remains controversial. Here, we screened for FLT3-ITD mutations in 171 APL patients, treated with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. We identified FLT3-ITD mutations in 35 patients (20 %). FLT3-ITD mutations were associated with higher white blood cell counts (P < 0.0001), relapse-risk score (P = 0.0007), higher hemoglobin levels (P = 0.0004), higher frequency of the microgranular morphology (M3v) subtype (P = 0.03), and the short PML/RARA (BCR3) isoform (P < 0.0001). After a median follow-up of 38 months, FLT3-ITD(positive) patients had a lower 3-year overall survival rate (62 %) compared with FLT3-ITD(negative) patients (82 %) (P = 0.006). The prognostic impact of FLT3-ITD on survival was retained in multivariable analysis (hazard ratio: 2.39, 95 % confidence interval [CI] 1.17-4.89; P = 0.017). Nevertheless, complete remission (P = 0.07), disease-free survival (P = 0.24), and the cumulative incidence of relapse (P = 0.94) rates were not significantly different between groups. We can conclude that FLT3-ITD mutations are associated with several hematologic features in APL, in particular with high white blood cell counts. In addition, FLT3-ITD may independently predict a shorter survival in patients with APL treated with ATRA and anthracycline-based chemotherapy.

  17. Prognostic signiifcance ofthe pre-chemotherapy lymphocyte-to-monocyte ratio inpatients withpreviously untreated metastatic colorectal cancer receiving FOLFOX chemotherapy

    Institute of Scientific and Technical Information of China (English)

    GuiNanLin; PanPanLiu; DongYingLiu; JieWenPeng; JianJunXiao; ZhongJunXia

    2016-01-01

    Background:As a surrogate marker of systemic inlfammation, the lymphocyte‑to‑monocyte ratio (LMR) is an independent prognostic factor for various malignancies. This study investigated the prognostic signiifcance of the pre‑chemotherapy LMR in patients with previously untreated metastatic colorectal cancer (mCRC) receiving chemotherapy. Methods:The present study included newly diagnosed mCRC patients treated between January 2005 and Decem‑ber 2013 with FOLFOX chemotherapy, speciifcally oxaliplatin 180mg/m2 on day 1, with leucovorin 400mg/m2 administered as a 2‑hour infusion before the administration of 5‑lfuorouracil 400mg/m2 as an intravenous bolus injection, and 5‑lfuorouracil 2400mg/m2 as a 46‑h infusion immediately after 5‑lfuorouracil bolus injection. The LMR was calculated as the absolute count of lymphocytes divided by the absolute count of monocytes. COX proportional hazards analysis was performed to evaluate the association of LMR with survival outcomes. Results:A total of 488 patients were included. Patients with high pre‑chemotherapy LMR experienced signiif‑cant improvements in progression‑free survival (PFS, 9.2 vs. 7.6months,P<0.001) and overall survival (OS, 19.4 vs. 16.6months,P<0.001) compared with patients with low pre‑chemotherapy LMR. Subsequent COX multivariate analysis showed that high pre‑chemotherapy LMR (≥3.11) was an independent favorable prognostic factor for PFS and OS. Additionally, patients whose LMR remained high (high–high subgroup), increased (low–high subgroup), or decreased (high–low subgroup) following chemotherapy showed better results in terms of PFS and OS than patients whose LMR remained low (low–low subgroup) after chemotherapy. Conclusions:For patients with previously untreated mCRC receiving FOLFOX chemotherapy, an elevated pre‑chem‑otherapy LMR is an independent favorable prognostic factor for PFS and OS, and changes in the LMR before and after chemotherapy seem to predict the

  18. Metformin use improves survival of diabetic liver cancer patients: systematic review and meta-analysis

    Science.gov (United States)

    Ma, Shu-Juan; Zheng, Yi-Xiang; Zhou, Peng-Cheng; Xiao, Yan-Ni; Tan, Hong-Zhuan

    2016-01-01

    Metformin has garnered considerable interest as a chemo-preventive and chemo-therapeutic agent given the increased risk of liver cancer among diabetic patients. This work was performed to illustrate the association between metformin use and survival of diabetic liver cancer patients. We conducted a comprehensive literature search of PubMed, Web of Science, Embase, BIOSIS Previews, Cochrane Library from inception to 12 May 2016. Meta-analyses were performed using Stata (version 12.0), with hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) as effect measures. Eleven cohort studies involving 3452 liver cancer patients fulfilled the inclusion criteria. Meta-analyses showed that metformin use was associated with better survival (HR = 0.59; 95% CI, 0.42-0.83; p = 0.002) of liver cancer patients, and the beneficial effect persisted (HR = 0.64; 95% CI, 0.42-0.97; p = 0.035) when the population was restricted to diabetic liver cancer patients. After adjusting for age, etiology, index of tumor severity and treatment of liver cancer, the association between metformin use and better survival of liver cancer patients was stable, pooled HR ranged from 0.47 to 0.57. The results indicated that metformin use improved survival of diabetic liver cancer patients. However, the results should be interpreted with caution given the possibility of residual confounding. Further prospective studies are still needed to confirm the prognostic benefit of metformin use. PMID:27494848

  19. Improvement in initial survival of spinal injuries: a 10-year audit.

    Science.gov (United States)

    Tan, H B; Sloan, J P; Barlow, I F

    2005-08-01

    A 10-year retrospective study of all spinal injuries presenting to the Leeds Teaching Hospitals between 1991 and 2001. The hospitals provide secondary care to a population of 750,000 and tertiary care to a population of 2-3 million. In total 1119 spinal injuries were studied. The overall survival rate was 89%. The commonest age group for presentation was 25-29 years with a secondary peak in the seventh decade, a mean overall of 43 years. 66% of injuries occurred in males. The commonest cause was a fall from a height (44%), with road traffic accidents (RTA) causing 43%. Pedestrians were most at risk within the road traffic group, making up 63% of cases. Isolated cervical spine injuries made up 37% of all cases. Cervical fractures were most associated with neurological injury (50%). Immediate survival has increased over the decade from 83% in 1991 to 93% in 2001. The probability of survival was significant at P = 0.006 and actual survival at P = 0.012 (Pearson correlation). The causal analysis has not been carried out but it is thought likely that improved quality of care is responsible.

  20. Rac1 selective activation improves retina ganglion cell survival and regeneration.

    Directory of Open Access Journals (Sweden)

    Erika Lorenzetto

    Full Text Available In adult mammals, after optic nerve injury, retinal ganglion cells (RGCs do not regenerate their axons and most of them die by apoptosis within a few days. Recently, several strategies that activate neuronal intracellular pathways were proposed to prevent such degenerative processes. The rho-related small GTPase Rac1 is part of a complex, still not fully understood, intracellular signaling network, mediating in neurons many effects, including axon growth and cell survival. However, its role in neuronal survival and regeneration in vivo has not yet been properly investigated. To address this point we intravitreally injected selective cell-penetrating Rac1 mutants after optic nerve crush and studied the effect on RGC survival and axonal regeneration. We injected two well-characterized L61 constitutively active Tat-Rac1 fusion protein mutants, in which a second F37A or Y40C mutation confers selectivity in downstream signaling pathways. Results showed that, 15 days after crush, both mutants were able to improve survival and to prevent dendrite degeneration, while the one harboring the F37A mutation also improved axonal regeneration. The treatment with F37A mutant for one month did not improve the axonal elongation respect to 15 days. Furthermore, we found an increase of Pak1 T212 phosphorylation and ERK1/2 expression in RGCs after F37A treatment, whereas ERK1/2 was more activated in glial cells after Y40C administration. Our data suggest that the selective activation of distinct Rac1-dependent pathways could represent a therapeutic strategy to counteract neuronal degenerative processes in the retina.

  1. Comparative Study on Rituximab Combined with Chemotherapy and Single Chemotherapy for Diffuse Large B Cell Lymphoma

    Institute of Scientific and Technical Information of China (English)

    FENG Ji-feng

    2015-01-01

    Objective:To explore the clinical efifcacy and safety of rituximab combined with chemotherapy and single chemotherapy for diffuse large B cell lymphoma (DLBCL). Methods:A total of 97 patients with DLBCL were selected. Patients treated by single chemotherapy were designed as control group, while those by rituximab combined with chemotherapy as observational group. All patients were treated for at least 4 cycles. The short-term and long-term efifcacy and related adverse reactions of 2 groups were observed. Results:The rate of complete remission (CR) in observational group was signiifcantly higher than in control group (χ2=4.6589,P=0.0309). However, there was no signiifcant difference in objective remission rate (ORR) between 2 groups (P=0.3651). The rates of 3-year overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were 80.30% (53/66), 69.70% (46/66) and 59.09% (39/66) in observational group, and 61.29% (19/31), 58.06% (18/31) and 58.06% (18/31) in control group, respectively. The OS in observational group was signiifcantly longer than in control group (P=0.035). However, there was no signiifcant difference in PFS, DFS and rate adverse reactions between 2 groups (P=0.089;P=0.438;χ2=0.1562,P=0.6927). Conclusion: Rituximab combined with chemotherapy can improve the efficacy of DLBCL without increasing the adverse reactions, which can be used as the ifrst-line treatment for DLBCL, thus deserving to be widely applied in clinic.

  2. Comparative Study on Rituximab Combined with Chemotherapy and Single Chemotherapy for Diffuse Large B Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Ji-feng FENG

    2015-06-01

    Full Text Available Objective: To explore the clinical efficacy and safety of rituximab combined with chemotherapy and single chemotherapy for diffuse large B cell lymphoma (DLBCL. Methods: A total of 97 patients with DLBCL were selected. Patients treated by single chemotherapy were designed as control group, while those by rituximab combined with chemotherapy as observational group. All patients were treated for at least 4 cycles. The short-term and long-term efficacy and related adverse reactions of 2 groups were observed. Results: The rate of complete remission (CR in observational group was significantly higher than in control group (χ2=4.6589, P=0.0309. However, there was no significant difference in objective remission rate (ORR between 2 groups (P=0.3651. The rates of 3-year overall survival (OS, progression-free survival (PFS and disease-free survival (DFS were 80.30% (53/66, 69.70% (46/66 and 59.09% (39/66 in observational group, and 61.29% (19/31, 58.06% (18/31 and 58.06% (18/31 in control group, respectively. The OS in observational group was significantly longer than in control group (P=0.035. However, there was no significant difference in PFS, DFS and rate adverse reactions between 2 groups (P=0.089; P=0.438; χ2=0.1562, P=0.6927. Conclusion: Rituximab combined with chemotherapy can improve the efficacy of DLBCL without increasing the adverse reactions, which can be used as the first-line treatment for DLBCL, thus deserving to be widely applied in clinic.

  3. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial.

    Science.gov (United States)

    Burnett, A K; Hills, R K; Grimwade, D; Jovanovic, J V; Craig, J; McMullin, M F; Kell, J; Wheatley, K; Yin, J A L; Hunter, A; Milligan, D; Russell, N H

    2013-04-01

    Two hundred eighty-five patients, median age 42, with PML-RARα-positive acute promyelocytic leukaemia were randomised to Ara-C-containing 'Medical Research Council (MRC) Chemotherapy'+ATRA (All-trans-retinoic acid) or anthracycline+ATRA (modified 'Spanish') therapy. MRC treatment comprised four courses with ATRA in courses 1-2. Spanish treatment comprised four anthracycline-based courses with ATRA in courses 1-3. In course 3 patients were randomised to gemtuzumab ozogamicin (GO) or not. The Spanish arm received 24-month maintenance. Patients were sequentially molecularly monitored. Quality of life was assessed at baseline, 3, 6, 9, 12, 24 months. Remission rates were similar in both arms (93%): cumulative incidence of haematological relapse (CIHR) was 6% at 5 years; 5 patients relapsed molecularly. Survival post relapse was 80%. There were more deaths in remission in the MRC arm (4% vs 10%: P=0.2). The overall 5-year relapse-free and overall survival was similar between arms (81% vs 82% and 84% vs 83%, respectively). More supportive care and hospitalisation (81.8 vs 63 days, P10 × 10(9)/l) was not prognostic overall, or within treatment arms. Both approaches deliver similar results with minor differences in quality of life. MRC treatment required more hospitalisation. This suggests that additional chemotherapy, Ara-C in particular, is not required.

  4. Ovarian cancer stem cells: Can targeted therapy lead to improved progression-free survival?

    Institute of Scientific and Technical Information of China (English)

    Christen; L; Walters; Haygood; Rebecca; C; Arend; J; Michael; Straughn; Donald; J; Buchsbaum

    2014-01-01

    Despite significant effort and research funds, epithelial ovarian cancer remains a very deadly disease. There are no effective screening methods that discover early stage disease; the majority of patients are diagnosed with advanced disease. Treatment modalities consist primarily of radical debulking surgery followed by taxane and platinum-based chemotherapy. Newer therapies including limited targeted agents and intraperitoneal delivery of chemotherapeutic drugs have improved disease-free intervals, but failed to yield longlasting cures in most patients. Chemotherapeutic resistance, particularly in the recurrent setting, plagues the disease. Targeting the pathways and mechanisms behind the development of chemoresistance in ovarian cancer could lead to significant improvement in patient outcomes. In many malignancies, including blood and other solid tumors, there is a subgroup of tumor cells, separate from the bulk population, called cancer stem cells(CSCs). These CSCs are thought to be the cause of metastasis, recurrence and resistance. However, todate, ovarian CSCs have been difficult to identify, isolate, and target. It is felt by many investigators that finding a putative ovarian CSC and a chemotherapeutic agent to target it could be the key to a cure for this deadly disease. This review will focus on recent advances in this arena and discuss some of the controversies surrounding the concept.

  5. Short-term Effect of Chemotherapy Concomitant with Multiple Autologous Immunocytes on Patients with Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Junquan Liu

    2013-12-01

    : Chemotherapy concomitant with multiple autologous immunocytes can improve the immunological function and prolong survival time for patients with advanced colorectal carcinoma.

  6. Clinical significance of preoperative regional intra-arterial infusion chemotherapy for advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Cheng-Wu Zhang; Shou-Chun Zou; Dun Shi; Da-Jian Zhao

    2004-01-01

    AIM: Preoperative intra-arterial infusion chemotherapy could increase the radical resection rate of advanced gastric cancer, but its effect on the long-term survival has not been assessed. This study was designed to evaluate the clinical significance of preoperative intra-arterial infusion chemotherapy for advanced gastric cancer.METHODS: Clinicopathological data of 91 patients who underwent curative resection for advanced gastric cancer were collected. Among them, 37 patients undertaken preoperative intra-arterial infusion chemotherapy were used as the interventional chemotherapy group, and the remaining 54 patients as the control group. Eleven factors including clinicopathological variables, treatment procedures and molecular biological makers that might contribute to the long-term survival rate were analyzed using Cox multivariate regression analysis.RESULTS: The 5-year survival rate was 52.5% and 39.8%,respectively, for the interventional group and the control group (P<0.05). Cox multivariate regression analysis revealed that the TNM stage (P<0.001), preoperative intraarterial infusion chemotherapy (P = 0.029) and growth pattern (P = 0.042) were the independent factors for the long-term survival of patients with advanced gastric cancer.CONCLUSION: Preoperative intra-arterial infusion chemotherapy plays an important role in improving the prognosis of advanced gastric cancer.

  7. Bypass system modification at Bonneville Dam on the Columbia River improved the survival of juvenile salmon

    Science.gov (United States)

    Ferguson, J.W.; Sandford, B.P.; Reagan, R.E.; Gilbreath, L.G.; Meyer, E.B.; Ledgerwood, R.D.; Adams, N.S.

    2007-01-01

    From 1987 to 1992, we evaluated a fish bypass system at Bonneville Dam Powerhouse 2 on the Columbia River. The survival of subyearling Chinook salmon Oncorhynchus tshawytscha released into the system ranged from 0.774 to 0.911 and was significantly lower than the survival of test fish released into turbines and the area immediately below the powerhouse where bypass system flow reentered the river. Yearling and subyearling Chinook salmon and yearling coho salmon O. kisutch released into the bypass system were injured or descaled. Also, levels of blood plasma cortisol and lactate were significantly higher in yearling and subyearling Chinook salmon that passed through the bypass system than in fish released directly into a net located over the bypass exit. This original system was then extensively modified using updated design criteria, and the site where juvenile fish reentered the river was relocated 2.8 km further downstream to reduce predation on bypassed fish by northern pikeminnow Ptychocheilus oregonensis. Based on studies conducted from 1999 to 2001, the new bypass system resulted in high fish survival, virtually no injuries to fish, fish passage times that were generally similar to water travel times, and mild stress responses from which fish recovered quickly. The mean estimated survival of subyearling Chinook salmon passing through the new bypass system was 0.946 in 2001, which was an usually low-flow year. Survival, physical condition, passage timing, and blood physiological indicators of stress were all useful metrics for assessing the performance of both bypass systems and are discussed. The engineering and hydraulic criteria used to design the new bypass system that resulted in improved fish passage conditions are described.

  8. Application of bacterial lipopolysaccharide to improve survival of the black tiger shrimp after Vibrio harveyi exposure.

    Science.gov (United States)

    Rungrassamee, Wanilada; Maibunkaew, Sawarot; Karoonuthaisiri, Nitsara; Jiravanichpaisal, Pikul

    2013-10-01

    This study investigates an effect of bacterial lipopolysaccharide (LPS) as feed supplement to improve immunity of the black tiger shrimp (Penaeus monodon). LPS was coated to commercial feed pellets and given to the shrimp once or twice a day for 10 days before an exposure with shrimp pathogenic bacterium Vibrio harveyi. The growth rates, percent weight gains, total hemocyte and granulocyte counts and survival rates of shrimp between the LPS-coated pellet fed groups and a control group where shrimp fed with commercial feed pellets were compared. After 10 days of the feeding trials, growth rates were not significantly different in all groups, suggesting no toxicity from LPS supplement. To determine beneficial effect of LPS diets, each group was subsequently exposed to V. harveyi by immersion method and the survival rates were recorded for seven days after the immersion. Regardless of the dosages of LPS, the shrimp groups fed with LPS-coated pellets showed higher survival rates than the control group. There was no significant difference in survival rates between the two LPS dosages groups. In addition to survival under pathogen challenge, we also determine effect of LPS on immune-related genes after 10-day feeding trial. Gene expression analysis in the P. monodon intestines revealed that antilipopolysaccharide factor isoform 3 (ALF3), C-type lectin, and mucine-like peritrophin (mucin-like PM) were expressed significantly higher in a group fed with LPS supplemental diet once or twice a day than in a control group. The transcript levels of C-type lectin and mucin-like PM had increased significantly when LPS was given once a day, while significant induction of ALF3 transcripts was observed when shrimp were fed with LPS twice a day. The up-regulation of the immune gene levels in intestines and higher resistance to V. harveyi of the shrimp fed with LPS provide the evidence for potential application of LPS as an immunostimulant in P. monodon farming.

  9. Nanoshell-mediated photothermal therapy improves survival in a murine glioma model.

    Science.gov (United States)

    Day, Emily S; Thompson, Patrick A; Zhang, Linna; Lewinski, Nastassja A; Ahmed, Nabil; Drezek, Rebekah A; Blaney, Susan M; West, Jennifer L

    2011-08-01

    We are developing a novel treatment for high-grade gliomas using near infrared-absorbing silica-gold nanoshells that are thermally activated upon exposure to a near infrared laser, thereby irreversibly damaging cancerous cells. The goal of this work was to determine the efficacy of nanoshell-mediated photothermal therapy in vivo in murine xenograft models. Tumors were induced in male IcrTac:ICR-Prkdc(SCID) mice by subcutaneous implantation of Firefly Luciferase-labeled U373 human glioma cells and biodistribution and survival studies were performed. To evaluate nanoparticle biodistribution, nanoshells were delivered intravenously to tumor-bearing mice and after 6, 24, or 48 h the tumor, liver, spleen, brain, muscle, and blood were assessed for gold content by inductively coupled plasma-mass spectrometry (ICP-MS) and histology. Nanoshell concentrations in the tumor increased for the first 24 h and stabilized thereafter. Treatment efficacy was evaluated by delivering saline or nanoshells intravenously and externally irradiating tumors with a near infrared laser 24 h post-injection. Success of treatment was assessed by monitoring tumor size, tumor luminescence, and survival time of the mice following laser irradiation. There was a significant improvement in survival for the nanoshell treatment group versus the control (P nanoshell treatment group remained tumor free at the end of the 90-day study period. By comparison, none of the mice in the control group survived beyond 24 days and mean survival was only 13.3 days. The results of these studies suggest that nanoshell-mediated photothermal therapy represents a promising novel treatment strategy for malignant glioma.

  10. Abiraterone acetate plus prednisone versus prednisone alone in chemotherapy-naive men with metastatic castration-resistant prostate cancer: patient-reported outcome results of a randomised phase 3 trial

    NARCIS (Netherlands)

    Basch, E.; Autio, K.; Ryan, C.J.; Mulders, P.; Shore, N.; Kheoh, T.; Fizazi, K.; Logothetis, C.J.; Rathkopf, D.; Smith, M.R.; Mainwaring, P.N.; Hao, Y.; Griffin, T.; Li, S.; Meyers, M.L.; Molina, A.; Cleeland, C.

    2013-01-01

    BACKGROUND: Abiraterone acetate plus prednisone significantly improves radiographic progression-free survival in asymptomatic or mildly symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer compared with prednisone alone. We describe analyses of data for patie

  11. A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation

    Directory of Open Access Journals (Sweden)

    Brian G. Ballios

    2015-06-01

    Full Text Available The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs. The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.

  12. Chemotherapy options for the elderly patient with advanced non-small cell lung cancer.

    LENUS (Irish Health Repository)

    Hennessy, B T

    2012-02-03

    Combination chemotherapy has been shown to improve overall survival compared with best supportive care in patients with advanced non-small cell lung cancer (NSCLC). The survival advantage is modest and was initially demonstrated with cisplatin-containing regimens in a large meta-analysis of randomized trials reported in 1995. Newer chemotherapy combinations have been shown to be better tolerated than older cisplatin-based combinations, and some trials have also shown greater efficacy and survival benefits with these newer combinations. Combination chemotherapy is, therefore, the currently accepted standard of care for patients with good performance statuses aged less than 70 years with advanced NSCLC. However, there are limited data from clinical trials to support the use of combination chemotherapy in elderly patients over 70 years of age with advanced NSCLC. Subgroup analyses of large randomized phase III trials suggest that elderly patients with good performance statuses do as well as younger patients treated with combination chemotherapy. There are few randomized trials reported that evaluate chemotherapy in patients aged greater than 70 years only. Based on data from trials performed by an Italian group, single-agent vinorelbine has been shown to have significant activity in elderly patients with advanced NSCLC and to be well tolerated by those patients with Eastern Cooperative Oncology Group performance statuses of two or less, with associated improvements in measures of global health.

  13. Side effects of chemotherapy in musculoskeletal oncology.

    Science.gov (United States)

    Mavrogenis, Andreas F; Papagelopoulos, Panayiotis J; Romantini, Matteo; Angelini, Andrea; Ruggieri, Pietro

    2010-01-01

    With recent advances in medical and orthopedic oncology, radiation therapy and single- or multiple-agent perioperative chemotherapy are currently applied as an essential part of the multidisciplinary treatment to improve disease-free and overall survival of patients with primary and metastatic bone and soft tissue tumors. However, these treatments have led to unwanted complications. A better understanding of the effects of various antineoplastic agents on bone, soft tissue, and organs may provide the basis for the more efficacious use of antiproliferative drugs when fracture healing or allograft incorporation is required. This knowledge may also provide a rationale for concurrent treatment with drugs that protect against or compensate for adverse effects in osseous repair resulting from chemotherapy.

  14. Radiation Therapy Improves Survival Outcome in Pancreatic Adenocarcinoma: Comparison of a 15-Year Institutional Experience at the University of Nebraska Medical Center with SEER Data

    Directory of Open Access Journals (Sweden)

    Michael J. Baine

    2014-01-01

    Full Text Available Objectives. We examined the role of radiation therapy (RT in pancreatic adenocarcinoma (PA treatment through a 15-year retrospective analysis of patients treated at University of Nebraska Medical Center (UNMC as well as those from the SEER database. Methods. A total of 561 patients diagnosed with PA at UNMC between 1995 and 2011 and 60,587 patients diagnosed between 1995 and 2009 from the SEER were included. Examined prognostic factors for overall survival (OS were age, gender, race, stage, year of diagnosis, and treatment with surgery, chemotherapy (CT, or RT. Time to death was plotted by Kaplan-Meier method. A Cox proportional hazards model was used to evaluate prognostic factors for OS. Results. The median OS was 7.3 and 5 months for patients from UNMC and the SEER database, respectively. A Cox model of patients from UNMC showed that RT was associated with improved OS (HR 0.77, P=0.018 after adjusting for factors including age, race, gender, stage, year of diagnosis, having surgery, or having CT. Cox analysis of patients from the SEER showed similar results (HR 0.65, P<0.0001. Conclusions. RT confers an independent survival advantage in patients being treated for PA which is apparent both at UNMC and through SEER data.

  15. 动脉持续灌注化疗与静脉全身化疗治疗中晚期胰腺癌的疗效分析%A clinical study on continuous transarterial infusion chemotherapy and systemic venous chemotherapy with gemcitabine and 5-fiuorouracil in treating patients with advanced pancreatic carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To compare the curative effectiveness of continuous transarterial infusion chemotherapy and systemic venous chemotherapy in treating patients with advanced pancreatic cancer, and to evaluate the value of selective continuous transarterial infusion chemotherapy in treating advanced pancreatic cancer. Methods: Of the 51 patients with advanced pancreatic cancer receiving chemotherapy with gemcitabine and 5-fluorouracil, 25 patients were treated with selective continuous transarterial infusion chemotherapy, 26 were treated with systemic venous chemotherapy, and curative effectiveness was analyzed retrospectively. Curative effectiveness included tumor volume, clinical benefit response (CBR), acute and subacute toxic reactions of antitumor drugs, survival rate and median survival time. Results: The objective effective rate in transarterial group was 32.0% versus 23.1% in systemic group without any significant difference (P = 0.475). Clinical benefit rates in transarterial group and systemic group were 80.0% and 50.0% respectively (P = 0.025). The 6-, 9- and 12-month accumulated survival rates and median survival time in transarterial group were higher than those of the systemic group (P = 0.002), the differences were statistically significant. However, the adverse reactions between the two groups were not statistically significant. Conclusion: Compared with systemic chemotherapy, continuous transarterial infusion chemotherapy with gemcitabine and 5-fluorouracil could improve clinical benefit rate and survival time of patients with advanced pancreatic cancer, it is safe and reliable, and the adverse reactions is less.

  16. Exenatide improves glucose homeostasis and prolongs survival in a murine model of dilated cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Arpita Kalla Vyas

    Full Text Available BACKGROUND: There is growing awareness of secondary insulin resistance and alterations in myocardial glucose utilization in congestive heart failure. Whether therapies that directly target these changes would be beneficial is unclear. We previously demonstrated that acute blockade of the insulin responsive facilitative glucose transporter GLUT4 precipitates acute decompensated heart failure in mice with advanced dilated cardiomyopathy. Our current objective was to determine whether pharmacologic enhancement of insulin sensitivity and myocardial glucose uptake preserves cardiac function and survival in the setting of primary heart failure. METHODOLOGY/PRINCIPAL FINDINGS: The GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9 starting at 56 days of life. TG9 mice develop congestive heart failure and secondary insulin resistance in a highly predictable manner with death by 12 weeks of age. Glucose homeostasis was assessed by measuring glucose tolerance at 8 and 10 weeks and tissue 2-deoxyglucose uptake at 75 days. Exenatide treatment improved glucose tolerance, myocardial GLUT4 expression and 2-deoxyglucose uptake, cardiac contractility, and survival over control vehicle-treated TG9 mice. Phosphorylation of AMP kinase and AKT was also increased in exenatide-treated animals. Total myocardial GLUT1 levels were not different between groups. Exenatide also abrogated the detrimental effect of the GLUT4 antagonist ritonavir on survival in TG9 mice. CONCLUSION/SIGNIFICANCE: In heart failure secondary insulin resistance is maladaptive and myocardial glucose uptake is suboptimal. An incretin-based therapy, which addresses these changes, appears beneficial.

  17. Improved survival with an ambulatory model of non-invasive ventilation implementation in motor neuron disease.

    Science.gov (United States)

    Sheers, Nicole; Berlowitz, David J; Rautela, Linda; Batchelder, Ian; Hopkinson, Kim; Howard, Mark E

    2014-06-01

    Non-invasive ventilation (NIV) increases survival and quality of life in motor neuron disease (MND). NIV implementation historically occurred during a multi-day inpatient admission at this institution; however, increased demand led to prolonged waiting times. The aim of this study was to evaluate the introduction of an ambulatory model of NIV implementation. A prospective cohort study was performed. Inclusion criteria were referral for NIV implementation six months pre- or post-commencement of the Day Admission model. This model involved a 4-h stay to commence ventilation with follow-up in-laboratory polysomnography titration and outpatient attendance. Outcome measures included waiting time, hospital length of stay, adverse events and polysomnography data. Results indicated that after changing to the Day Admission model the median waiting time fell from 30 to 13.5 days (p Survival was also prolonged (median (IQR) 278 (51-512) days pre- vs 580 (306-1355) days post-introduction of the Day Admission model; hazard ratio 0.41, p = 0.04). Daytime PaCO2 was no different. In conclusion, reduced waiting time to commence ventilation and improved survival were observed following introduction of an ambulatory model of NIV implementation in people with MND, with no change in the effectiveness of ventilation.

  18. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    Directory of Open Access Journals (Sweden)

    Stéphanie Rimbaud

    Full Text Available Heart failure (HF is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT. Resveratrol (18 mg/kg/day; HS-RSV was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition. Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001, and prevented the 25% reduction in body weight in HS-NT (P<0.001. Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF.

  19. PEGylated dendritic nanoarchitechture improves mean survival time of BDF1mice bearing myelogenous k -562 leukemia

    Institute of Scientific and Technical Information of China (English)

    Ramadoss Karthikeyan; Pureti Madhu Kumar; Palanirajan Vijayaraj Kumar

    2013-01-01

    Objective:To developing and exploring the use ofPEGylated poly(propylene imine) dendritic architecture for the delivery of an anti leukemic activity ofPrednisolone.Methods:For this study,PEGylated poly(propylene imine) dendritic architecture was synthesized and loaded with Prednisolone and targeted to the ascetic form of myelogenous leukemia k-562 cellines in hybrid miceBDF1, was used as tumor model.Theantileukemic activity was assessed by use of the criterionT/C%, whereT was the mean survival time(MST, days) of the drug treated mice, bearing k-562 leukemia andC- the mean survival time(MST, days) of untreated control animals, bearing the same leukemia cellines.Results:An antileukemic activity of the studiedPrednisolone loaded PEGylatedPolypropyleneimine(PPI) dendrimer was found to have increasing the mean survival time of the k-562 myelogenous leukemia cellines bearingBDF1 mice.The criterion“increase of life span”(ILS%) reached maximally270.1% for the drug loaded dendrimer.Conclusion:The studied dendrimer withPrednisolone showed lower toxicity with improved antileukemic activity in comparison with freePrednisolone.The further experiments in this field are in progress, aiming to design better dendritic formulations, with potential clinical use.

  20. Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

    Science.gov (United States)

    2014-10-01

    had more severe outcomes and measures . Therefore, improved outcomes are not associated with a higher dose of BHB/M and in fact would appear...animals survived until end of experiment (Figure 1).   4   Figure 1. Kaplan Meier Curve for observation of Maximum Tolerated Dose (MTD...2X or 4X BHB/M 0 10 20 30 40 50 Ba se lin e Sh oc k 35 LR 1 FR 2 FR 1 90 FR 7 FR 2 0 BHB-2X (n=6) BHB-4X (n=5) BH B co nc en tr at io n

  1. Improved survival in patients obtaining remission of nephrotic range albuminuria in diabetic nephropathy

    DEFF Research Database (Denmark)

    Hovind, Peter; Tarnow, Lise; Rossing, Peter

    2004-01-01

    BACKGROUND: The level of albuminuria is related to progression of diabetic nephropathy, and patients with nephrotic range albuminuria have advanced renal structural changes and the fastest decline in glomerular filtration rate (GFR). We have previously demonstrated that the rate of decline in GFR...... risk of reaching the end point, 1.42 (1.08 to 1.87), P= 0.01. CONCLUSION: Our prospective study suggests that remission of nephrotic range albuminuria in type 1 diabetic patients, induced by aggressive antihypertensive treatment with and without ACE inhibitors, is associated with a slower progression...... in diabetic nephropathy and a substantially improved survival....

  2. Mesenteric lymph duct ligation improves survival in a lethal shock model.

    Science.gov (United States)

    Badami, Chirag D; Senthil, Maheswari; Caputo, Francis J; Rupani, Bobby J; Doucet, Danielle; Pisarenko, Vadim; Xu, Da-Zhong; Lu, Qi; Feinman, Rena; Deitch, Edwin A

    2008-12-01

    The goal of this study was to test the hypothesis that factors released from the gut and carried in the mesenteric lymph contribute to mortality in a lethal gut I/R model. To test this hypothesis, a lethal splanchnic artery occlusion (SAO) shock model was used in male Sprague-Dawley rats. In the first set of experiments, ligation of the mesenteric lymph duct (LDL), which prevents gut-derived factors carried in the intestinal lymphatics from reaching the systemic circulation, significantly improved 24-h survival after a 20-min SAO insult (0% vs. 60% survival; P < 0.05). This increase in survival in the LDL-treated rats was associated with a blunted hypotensive response. Because increased iNOS-induced NO levels have been implicated in SAO-induced shock, we measured plasma nitrite/nitrate levels and liver iNOS protein levels in a second group of animals. Ligation of the mesenteric lymph duct significantly abrogated the SAO-induced increase in plasma nitrite/nitrate levels and the induction of hepatic iNOS (P < 0.05). In an additional series of studies, we documented that LDL increased not only 24-h but also long-term 7-day survival. During the course of these studies, we made the unexpected finding that Sprague-Dawley rats from different animal vendors had differential resistance to SAO, and that the time of the year that the experiments were carried out also influenced the results. Nonetheless, in conclusion, these studies support the hypothesis that factors carried in the mesenteric lymph significantly contribute to the development of irreversible shock after SAO.

  3. Dipyridamole treatment is associated with improved renal outcome and patient survival in advanced chronic kidney disease.

    Science.gov (United States)

    Hung, Chi-Chih; Yang, Mei-Li; Lin, Ming-Yen; Lin, Hugo You-Hsien; Lim, Lee-Moay; Kuo, Hung-Tien; Hwang, Shang-Jyh; Tsai, Jer-Chia; Chen, Hung-Chun

    2014-12-01

    Dipyridamole has been shown to decrease proteinuria and improve renal function progression especially in early chronic kidney disease (CKD) patients with glomerulonephropathy. A combination therapy of dipyridamole with aspirin could prevent second strokes in the general population. Whether these effects of dipyridamole are also true in advanced CKD patients and whether dipyridamole could improve renal outcomes or patient survival is unknown. We retrospectively analyzed an observational cohort of 3074 participants with CKD stage 3-5 from southern Taiwan, of whom 871 (28.3%) had received dipyridamole treatment ≥50 mg/d for ≥3 months and more than half of the observation period. The mean age was 63.6 ± 13.4 years and the mean estimated glomerular filtration rate (eGFR) was 25.5 mL/min/1.73 m(2). After inverse probability of treatment weighted adjustment by propensity score, there were no differences between the dipyridamole-treated and untreated groups. Dipyridamole treatment was associated with decreased odds for rapid eGFR decline [odds ratio, 0.755; 95% confidence interval (CI), 0.595-0.958; p = 0.007] and progression of urine protein-to-creatinine ratio (odds ratio, 0.655; 95% CI, 0.517-0.832; p = 0.002). In survival analysis, the dipyridamole-treated group was also associated with a decreased risk for end-stage renal disease (hazard ratio, 0.847; 95% CI, 0.733-0.980; p = 0.011) and all-cause mortality (hazard ratio, 0.765; 95% CI, 0.606-0.971; p = 0.001) but not for cardiovascular events. Our findings demonstrate that dipyridamole treatment is significantly associated with better renal outcomes and patient survival in patients with CKD stage 3-5. Further investigations are warranted to confirm these independent positive effects.

  4. Human hepatocyte growth factor (hHGF-modified hepatic oval cells improve liver transplant survival.

    Directory of Open Access Journals (Sweden)

    Zhu Li

    Full Text Available Despite progress in the field of immunosuppression, acute rejection is still a common postoperative complication following liver transplantation. This study aims to investigate the capacity of the human hepatocyte growth factor (hHGF in modifying hepatic oval cells (HOCs administered simultaneously with orthotopic liver transplantation as a means of improving graft survival. HOCs were activated and isolated using a modified 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH model in male Lewis rats. A HOC line stably expressing the HGF gene was established following stable transfection of the pBLAST2-hHGF plasmid. Our results demonstrated that hHGF-modified HOCs could efficiently differentiate into hepatocytes and bile duct epithelial cells in vitro. Administration of HOCs at the time of liver transplantation induced a wider distribution of SRY-positive donor cells in liver tissues. Administration of hHGF-HOC at the time of transplantation remarkably prolonged the median survival time and improved liver function for recipients compared to these parameters in the other treatment groups (P<0.05. Moreover, hHGF-HOC administration at the time of liver transplantation significantly suppressed elevation of interleukin-2 (IL-2, tumor necrosis factor-α (TNF-α and interferon-γ (IFN-γ levels while increasing the production of IL-10 and TGF-β1 (P<0.05. HOC or hHGF-HOC administration promoted cell proliferation, reduced cell apoptosis, and decreased liver allograft rejection rates. Furthermore, hHGF-modified HOCs more efficiently reduced acute allograft rejection (P<0.05 versus HOC transplantation only. Our results indicate that the combination of hHGF-modified HOCs with liver transplantation decreased host anti-graft immune responses resulting in a reduction of allograft rejection rates and prolonging graft survival in recipient rats. This suggests that HOC-based cell transplantation therapies can be developed as a means of treating severe liver

  5. Lack of survival advantage in patients with advanced, resectable squamous cell carcinoma of the oral cavity receiving induction chemotherapy with cisplatin (CDDP), docetaxel (TXT) and 5-fluorouracil (5FU).

    Science.gov (United States)

    Umeda, Masahiro; Komatsubara, Hideki; Ojima, Yasutaka; Minamikawa, Tsutomu; Shigeta, Takashi; Shibuya, Yasuyuki; Yokoo, Satoshi; Komori, Takahide

    2004-01-01

    Cisplatin-based neoadjuvant chemotherapy (NAC) has been reported to increase survival of patients with nasopharyngeal carcinoma, and organ preservation in those with laryngeal carcinoma, but its efficacy for other head and neck carcinomas is still controversial. We examined the effects of NAC for patients with stage III-IV squamous cell carcinoma of the oral cavity. The patients were divided into two groups; 9 patients who underwent NAC consisting of one course of cisplatin (CDDP), docetaxel (TXT) and 5-fluorouracil (5FU) followed by surgery (NAC group), and 18 patients who underwent surgery alone (control group). Complete response (CR) was not observed, but partial response (PR) was obtained in 6 of 9 patients (33%) of the NAC group. The 3-year survival rate was 29.6% in the NAC group and 81.5% in the control group. Although any valid conclusions could not be drawn because of the small number of patients examined here, NAC with CDDP, TXT and 5FU offered no advantages over standard treatment for advanced oral cancer in terms of survival.

  6. Anti-inflammatory thalidomide improves islet grafts survival and functions in a xenogenic environment.

    Directory of Open Access Journals (Sweden)

    Chunguang Chen

    Full Text Available Thalidomide possesses both anti-inflammatory and anti-angiogenic properties. This study investigates its potential application in islet transplantation with a xenogenic transplantation model. Transplantation was performed using C57Bl/6 mice and NMRI nu/nu mice as recipients of porcine islets. Moreover, islet graft vasculature and inflammation were investigated to identify the mechanisms of thalidomide action. In the immunocompetent environment of C57Bl/6 mice, a fast graft rejection was observed. The group treated with thalidomide 200 mg/kg BW per day achieved and maintained euglycemia in the complete observation period for 42 days. The treated mice had more functional islet graft mass with less leukocyte infiltration. The pro-inflammatory TNF-alpha and VEGF content in islet grafted kidneys was significantly lowered by the treatment. By comparison, thalidomide was not effective in improving graft survival in immunocompromised nude mice. It strongly inhibited the VEGF and TNF-alpha-induced endothelial proliferation of isolated pig islets in a dose dependent manner. The magnitude of thalidomide's inhibitory effect was nearly identical to the effect of VEGF- receptor 2 inhibitor SU416 and anti-TNF-receptor 1 neutralizing antibody, and was reversed by sphingosine-1-phosphate. In conclusion, the anti-inflammatory effect of thalidomide improved islet graft survival and function in a transplantation model with a maximum immune barrier.

  7. Significant Improvement in Survival after Unrelated Donor Hematopoietic Cell Transplantation in the Recent Era

    Science.gov (United States)

    Majhail, Navneet S; Chitphakdithai, Pintip; Logan, Brent; King, Roberta; Devine, Steven; Rossmann, Susan N; Hale, Gregory; Hartzman, Robert J; Karanes, Chatchada; Laport, Ginna G; Nemecek, Eneida; Snyder, Edward L; Switzer, Galen E; Miller, John; Navarro, Willis; Confer, Dennis L; Levine, John E

    2014-01-01

    Patients and physicians may defer unrelated donor hematopoietic cell transplantation (HCT) as curative therapy due to mortality risk associated with the procedure. Therefore, it is important for physicians to know the current outcomes data when counseling potential candidates. To provide this information, we evaluated 15,059 unrelated donor HCT recipients between 2000-2009. We compared outcomes before and after 2005 for four cohorts: age <18 years with malignant diseases (N=1,920), 18-59 years with malignant diseases (N=9,575), ≥60 years with malignant diseases (N=2,194), and non-malignant diseases (N=1,370). Three-year overall survival in 2005-2009 was significantly better in all four cohorts (<18 years: 55% vs. 45%, 18-59 years: 42% vs. 35%, ≥60 years: 35% vs. 25%, non-malignant diseases: 69% vs. 60%, P<0.001 for all comparisons). Multivariate analyses in leukemia patients receiving HLA 7-8/8 matched transplants showed significant reduction in overall and non-relapse mortality in the first 1-year after HCT among patients transplanted in 2005-2009; however, risks for relapse did not change over time. Significant survival improvements after unrelated donor HCT have occurred over the recent decade and can be partly explained by better patient selection (e.g., HCT earlier in the disease course and lower disease risk), improved donor selection (e.g., more precise allele-level matched unrelated donors) and changes in transplant practices. PMID:25445638

  8. Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

    Science.gov (United States)

    Djoumerska-Alexieva, Iglika; Roumenina, Lubka; Pashov, Anastas; Dimitrov, Jordan; Hadzhieva, Maya; Lindig, Sandro; Voynova, Elisaveta; Dimitrova, Petya; Ivanovska, Nina; Bockmeyer, Clemens; Stefanova, Zvetanka; Fitting, Catherine; Bläss, Markus; Claus, Ralf; von Gunten, Stephan; Kaveri, Srini; Cavaillon, Jean-Marc; Bauer, Michael; Vassilev, Tchavdar

    2015-01-01

    Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as “genomic storm” in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous “danger” signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes. PMID:26701312

  9. Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving dose-intensive or standard dose chemotherapy for high-risk primary breast cancer.

    Science.gov (United States)

    Bernhard, J; Zahrieh, D; Zhang, J J; Martinelli, G; Basser, R; Hürny, C; Forbes, J F; Aebi, S; Yeo, W; Thürlimann, B; Green, M D; Colleoni, M; Gelber, R D; Castiglione-Gertsch, M; Price, K N; Goldhirsch, A; Coates, A S

    2008-01-15

    Quality of life (QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients scored QL indicators. Mean durations for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden (month 3: PQ-TWiST was 1.8 months longer for patients receiving DI-EC (95% CI, -2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy.

  10. Primary parotid B-cell lymphoma successfully treated with chemotherapy plus highly active antiretroviral therapy with prolonged survival and immune reconstitution in an acquired immunodeficiency syndrome patient: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Marcelo Corti

    2014-01-01

    Full Text Available Non-Hodgkin′s lymphoma (NHL is the second most common acquired immunodeficiency syndrome (AIDS-defining cancer. In this population, up to 70-80% of cases may present as extranodal location as the primary clinical manifestation of the neoplasm disease. Gastrointestinal tract is the most frequent location of AIDS-associated NHL. However, salivary gland involvement, including the parotid gland is a rare complication in human immunodeficiency virus (HIV-patients. Here, we describe a patient seropositive for the HIV, who developed a primary NHL of the parotid gland histologically classified as a high-grade diffuse large B-cell lymphoma. Patient was treated with a combination of chemotherapy plus highly active antiretroviral therapy with a good clinical, virological and immunological response and a prolonged survival, more than 5 years, without evidence of neoplasm relapse.

  11. Chemotherapy of prostate cancer: present and future.

    Science.gov (United States)

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

    The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved.

  12. Palliative chemotherapy beyond three courses conveys no survival or consistent quality-of-life benefits in advanced non-small-cell lung cancer

    DEFF Research Database (Denmark)

    von Plessen, C; Bergman, B; Andresen, O;

    2006-01-01

    and 8 of a 3-week cycle. Key end points were QoL at 18 weeks, measured with EORTC Quality of Life Questionnaire (QLQ)-C30 and QLQ-LC13, and overall survival. Secondary end points were progression-free survival and need of palliative radiotherapy. Two hundred and ninety-seven patients were randomised (C3...... of life (QoL) and survival. Patients with stage IIIB or IV NSCLC and WHO performance status (PS) 0-2 were randomised to receive three (C3) or six (C6) courses of carboplatin (area under the curve (AUC) 4, Chatelut's formula, equivalent to Calvert's AUC 5) on day 1 and vinorelbine 25 mg m(-2) on days 1...

  13. Improved survival and renal prognosis of patients with type 2 diabetes and nephropathy with improved control of risk factors

    DEFF Research Database (Denmark)

    Andrésdóttir, Gudbjörg; Jensen, Majken; Carstensen, Bendix

    2014-01-01

    OBJECTIVE: To evaluate long-term survival, development of renal end points, and decline in glomerular filtration rate (GFR) in patients with type 2 diabetes and diabetic nephropathy (DN) after renin-angiotensin system (RAS) inhibition and multifactorial treatment of cardiovascular risk factors have...... and lower GFR were predictors of mortality, whereas albuminuria, HbA1c, and low GFR predicted ESRD. CONCLUSIONS: Overall prognosis has improved considerably with current multifactorial treatment of DN in type 2 diabetes, including long-term RAS inhibition....... become standard of care. RESEARCH DESIGN AND METHODS: All patients with type 2 diabetes and DN (n = 543) at the Steno Diabetes Center were followed during 2000-2010. GFR was measured yearly with 51Cr-EDTA plasma clearance. Annual decline in GFR was determined in patients with at least three measurements...

  14. Gastric infiltration of diffuse large B-cell lymphoma: Endoscopic diagnosis and improvement of lesions after chemotherapy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of the non-Hodgkin's lymphoma (NHL) accounting for about 40% of all NHLs. This is a case report about the endoscopic appearance of a DLBCL with infiltration to the stomach in a 39-year-old female. She had a 6-me history of lumbar and left upper quadrant pain with intermittent episodes of melena. A computer tomograghy (CT) scan showed mural thickening of the gastric antrum. Endoscopic examination revealed multiple gastric ulcers. Definite diagnosis could be made by endoscopic biopsies and the patient had a good response to chemotherapy. This response correlated well with a further endoscopic follow-up. A follow-up endoscopic examination could be considered to evaluate a good response to chemotherapy in DLBCL patients with secondary gastric dissemination.

  15. Tumor site- and stage-specific associations between allelic variants of glutathione S-transferase and DNA-repair genes and overall survival in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy.

    Directory of Open Access Journals (Sweden)

    Ching-Yu Lai

    Full Text Available INTRODUCTION: Our retrospective cohort study investigated the effect of tumor site and stage on the associations between the allelic variants of glutathione S-transferase (GST and DNA-repair genes and overall survival (OS in CRC patients treated with 5-fluorouracil (5-FU-based adjuvant chemotherapy. MATERIAL AND METHODS: We genotyped GSTM1, GSTT1, GSTP1 Ile105Val, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln in 491 CRC patients between 1995 and 2001. A Cox proportional-hazards model was used to calculate the hazard ratios (HRs and 95% confidence intervals (CIs for the relationships between the allelic variants and OS. Survival analyses were performed for each allelic variant by using the log-rank test and Kaplan-Meier analysis. RESULTS: The CRC patients with the XPD Gln allelic variants had poorer survival than patients with the Lys/Lys genotype (HR  =1.38, 95% CI  =1.02-1.87, and rectal cancer patients had the poorest survival among them (HR  =1.87, 95% CI  =1.18-2.95. A significantly shorter OS was observed among stage II/III colon cancer patients with the XRCC1 Gln allelic variants (HR  =1.69, 95% CI  =1.06-2.71, compared to those with XRCC1 Arg/Arg genotype. In the combined analysis of the XRCC1 and XPD genes patients with stage II/III tumors, the poorest OS occurred in colon cancer patients with the XRCC1 Gln and XPD Gln allelic variants (HR  =2.60, 95% CI  =1.19-5.71 and rectal cancer patients with the XRCC1 Arg/Arg and XPD Gln allelic variants (HR  =2.77, 95% CI  =1.25-6.17. CONCLUSION: The XPD and XRCC1 allelic variants may be prognostic markers for CRC patients receiving 5-FU based chemotherapy. The contributions of the XPD and XRCC1 allelic variants to OS are tumor site- and/or stage-dependent.

  16. Trehalose does not improve neuronal survival on exposure to alpha-synuclein pre-formed fibrils

    Directory of Open Access Journals (Sweden)

    Matthew Redmann

    2017-04-01

    Full Text Available Parkinson's disease is a debilitating neurodegenerative disorder that is pathologically characterized by intracellular inclusions comprised primarily of alpha-synuclein (αSyn that can also be transmitted from neuron to neuron. Several lines of evidence suggest that these inclusions cause neurodegeneration. Thus exploring strategies to improve neuronal survival in neurons with αSyn aggregates is critical. Previously, exposure to αSyn pre-formed fibrils (PFFs has been shown to induce aggregation of endogenous αSyn resulting in cell death that is exacerbated by either starvation or inhibition of mTOR by rapamycin, both of which are able to induce autophagy, an intracellular protein degradation pathway. Since mTOR inhibition may also inhibit protein synthesis and starvation itself can be detrimental to neuronal survival, we investigated the effects of autophagy induction on neurons with αSyn inclusions by a starvation and mTOR-independent autophagy induction mechanism. We exposed mouse primary cortical neurons to PFFs to induce inclusion formation in the presence and absence of the disaccharide trehalose, which has been proposed to induce autophagy and stimulate lysosomal biogenesis. As expected, we observed that on exposure to PFFs, there was increased abundance of pS129-αSyn aggregates and cell death. Trehalose alone increased LC3-II levels, consistent with increased autophagosome levels that remained elevated with PFF exposure. Interestingly, trehalose alone increased cell viability over a 14-d time course. Trehalose was also able to restore cell viability to control levels, but PFFs still exhibited toxic effects on the cells. These data provide essential information regarding effects of trehalose on αSyn accumulation and neuronal survival on exposure to PFF.

  17. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival : an overview of the randomised trials

    NARCIS (Netherlands)

    Abe, O; Abe, R; Enomoto, K; Kikuchi, K; Koyama, H; Masuda, H; Nomura, Y; Sakai, K; Sugimachi, K; Tominaga, T; Uchino, J; Yoshida, M; Haybittle, JL; Davies, C; Harvey, VJ; Holdaway, TM; Kay, RG; Mason, BH; Forbes, JF; Wilcken, N; Gnant, M; Jakesz, R; Ploner, M; Yosef, HMA; Focan, C; Lobelle, JP; Peek, U; Oates, GD; Powell, J; Durand, M; Mauriac, L; Di Leo, A; Dolci, S; Piccart, MJ; Masood, MB; Parker, D; Price, JJ; Hupperets, PSGJ; Jackson, S; Ragaz, J; Berry, D; Broadwater, G; Cirrincione, C; Muss, H; Norton, L; Weiss, RB; Abu-Zahra, HT; Portnoj, SM; Baum, M; Cuzick, J; Houghton, J; Riley, D; Gordon, NH; Davis, HL; Beatrice, A; Mihura, J; Naja, A; Lehingue, Y; Romestaing, P; Dubois, JB; Delozier, T; Mace-Lesec'h, J; Rambert, P; Andrysek, O; Barkmanova, J; Owen, [No Value; Meier, P; Howell, A; Ribeiro, GC; Swindell, R; Alison, R; Boreham, J; Clarke, M; Collins, R; Darby, S; Davies, C; Elphinstone, P; Evans, [No Value; Godwin, J; Gray, R; Harwood, C; Hicks, C; James, S; MacKinnon, E; McGale, P; McHugh, T; Mead, G; Peto, R; Wang, Y; Albano, J; de Oliveira, CF; Gervasio, H; Gordilho, J; Johansen, H; Mouridsen, HT; Gelman, RS; Harris, [No Value; Henderson, IC; Shapiro, CL; Andersen, KW; Axelsson, CK; Blichert-Toft, M; Moller, S; Mouridsen, HT; Overgaard, J; Overgaard, M; Rose, C; Cartensen, B; Palshof, T; Trampisch, HJ; Dalesio, O; de Vries, EGE; Rodenhuis, S; van Tinteren, H; Comis, RL; Davidson, NE; Gray, R; Robert, N; Sledge, G; Tormey, DC; Wood, W; Cameron, D; Chetty, U; Forrest, P; Jack, W; Rossbach, J; Klijn, JGM; Treurniet-Donker, AD; van Putten, WLJ; Costa, A; Veronesi, U; Bartelink, H; Duchateau, L; Legrand, C; Sylvester, R; van der Hage, JA; van de Velde, CJH; Cunningham, MP; Catalano, R; Creech, RH; Bonneterre, J; Fargeot, P; Fumoleau, P; Kerbrat, P; Namer, M; Jonat, W; Kaufmann, M; Schumacher, M; von Minckwitz, G; Bastert, G; Rauschecker, H; Sauer, R; Sauerbrei, W; Schauer, A; Schumacher, M; de Schryver, A; Vakaet, L; Belfiglio, M; Nicolucci, A; Pellegrini, F; Sacco, M; Valentini, M; McArdle, CS; Smith, DC; Galligioni, E; Boccardo, F; Rubagotti, A; Dent, DM; Gudgeon, CA; Hacking, A; Erazo, A; Medina, JY; Izuo, M; Morishita, Y; Takei, H; Fentiman, IS; Hayward, JL; Rubens, RD; Skilton, D; Graeff, H; Janicke, F; Meisner, C; Scheurlen, H; Kaufmann, M; von Fournier, D; Dafni, U; Fountzilas, G; Klefstrom, P; Blomqvist, C; Saarto, T; Margreiter, R; Asselain, B; Salmon, RJ; Vilcoq, [No Value; Arriagada, R; Hill, C; Laplanche, A; Le, MG; Spielmann, M; Bruzzi, P; Montanaro, E; Rosso, R; Sertoli, MR; Venturini, M; Amadori, D; Benraadt, J; Kooi, M; van de Velde, AO; van Dongen, JA; Vermorken, JB; Castiglione, M; Cavalli, F; Coates, A; Collins, J; Forbes, J; Gelber, RD; Goldhirsch, A; Lindtner, J; Price, KN; Rudenstam, CM; Senn, HJ; Bliss, JM; Chilvers, CED; Coombes, RC; Hall, E; Marty, M; Borovik, R; Brufman, G; Hayat, H; Robinson, E; Wigler, N; Bonadonna, G; Camerini, T; De Palo, G; Del Vecchio, M; Formelli, F; Valagussa, P; Martoni, A; Pannuti, F; Cocconi, G; Colozza, A; Camisa, R; Aogi, K; Takashima, S; Abe, O; Ikeda, T; Inokuchi, K; Kikuchi, K; Sawa, K; Sonoo, H; Korzeniowski, S; Skolyszewski, J; Ogawa, M; Yamashita, J; Bonte, J; Christiaens, R; Paridaens, R; Van den Boegart, W; Martin, P; Romain, S; Hakes, T; Hudis, CA; Norton, L; Wittes, R; Giokas, G; Kondylis, D; Lissaios, B; de la Huerta, R; Sainz, MG; Altemus, R; Cowan, K; Danforth, D; Lichter, A; Lippman, M; O'Shaughnessy, J; Pierce, LJ; Steinberg, S; Venzon, D; Zujewski, J; Paradiso, A; De Lena, M; Schittulli, F; Myles, JD; Pater, JL; Pritchard, KI; Nomura, Y; Anderson, S; Bass, G; Brown, A; Bryant, J; Costantino, J; Dignam, J; Fisher, B; Redmond, C; Wieand, S; Wolmark, N; Baum, M; Jackson, IM; Palmer, MK; Ingle, JN; Suman, VJ; Bengtsson, NO; Jonsson, H; Larsson, LG; Lythgoe, JP; Swindell, R; Kissin, M; Erikstein, B; Hannisdal, E; Jacobsen, AB; Varhaug, JE; Erikstein, B; Gundersen, S; Hauer-Jensen, M; Host, H; Jacobsen, AB; Nissen-Meyer, R; Blamey, RW; Mitchell, AK; Morgan, DAL; Robertson, JFR; Di Palma, M; Mathe, G; Misset, JL; Clark, RM; Levine, M; Morimoto, K; Sawa, K; Takatsuka, Y; Crossley, E; Harris, A; Talbot, D; Taylor, M; Cocconi, G; di Blasio, B; Ivanov, [No Value; Semiglazov, [No Value; Brockschmidt, J; Cooper, MR; Ueo, H; Falkson, CI; A'Hern, R; Ashley, S; Powles, TJ; Smith, IE; Yarnold, [No Value; Gazet, JC; Cocoran, N; Deshpande, N; di Martino, L; Douglas, P; Hacking, A; Host, H; Lindtner, A; Notter, G; Bryant, AJS; Ewing, GH; Firth, LA; Krushen-Kosloski, JL; Nissen-Meyer, R; Foster, L; George, WD; Stewart, HJ; Stroner, P; Malmstrom, P; Moller, TR; Ryden, S; Tengrup, [No Value; Tennvall-Nittby, L; Carstenssen, J; Dufmats, M; Hatschek, T; Nordenskjold, B; Soderberg, M; Carpenter, JT; Albain, K; Crowley, J; Green, S; Martino, S; Osborne, CK; Ravdin, PM; Glas, U; Johansson, U; Rutqvist, LE; Singnomklao, T; Wallgren, A; Castiglione, M; Goldhirsch, A; Maibach, R; Senn, HJ; Thurlimann, B; Brenner, H; Hercbergs, A; Yoshimoto, M; DeBoer, G; Paterson, AHG; Pritchard, KI; Meakin, JW; Panzarella, T; Pritchard, KI; Shan, Y; Shao, YF; Wang, [No Value; Zhao, DB; Boreham, J; Chen, ZM; Pan, HC; Peto, R; Bahi, J; Reid, M; Spittle, M; Deutsch, GP; Senanayake, F; Kwong, DLW; Bianco, AR; Carlomagno, C; De Laurentiis, M; De Placido, S; Buzdar, AU; Smith, T; Bergh, J; Holmberg, L; Liljegren, G; Nilsson, J; Seifert, M; Sevelda, P; Zielinsky, CC; Buchanan, RB; Cross, M; Royle, GT; Dunn, JA; Hills, RK; Lee, M; Morrison, JM; Spooner, D; Litton, A; Chlebowski, RT; Caffier, H

    2005-01-01

    Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-anal

  18. Application of Postoperative Chemotherapy on Thymomas and Its Prognostic Effect

    Directory of Open Access Journals (Sweden)

    Ke MA

    2016-07-01

    Full Text Available Background and objective To study the role of postoperative chemotherapy and its prognostic effect in Masaoka-Koga stage III and IV thymic tumors. Methods Between 1994 and 2012, 1,700 patients with thymic tumors who underwent surgery without neoajuvant therapy were enrolled for the study. Among them, 665 patients in Masaoka-Koga stage III and IV were further analyzed to evaluate the clinical value of postoperative chemotherapy. The Kaplan-Meier method was used to obtain the survival curve of the patients divided into different subgroups, and the Cox regression analysis was used to make multivariate analysis on the factors affecting prognosis. A Propensity-Matched Study was used to evaluate the clinical value of chemotherapy. Results Two-hundred-twenty-one patients were treated with postoperative chemotherapy, while the rest 444 cases were not. The two groups showed significant differences (P<0.05 regarding the incidence of myasthenia gravis, World Health Organization (WHO histological subtypes, pathological staging, resection status and the use of postoperative radiotherapy. WHO type C tumors, incomplete resection, and postoperative radiotherapy were significantly related to increased recurrence and worse survival (P<0.05. Five-year and 10-year disease free survivals (DFS and recurrence rates in patients who underwent surgery followed by postoperative chemotherapy were 51% and 30%, 46% and 68%, comparing with 73% and 58%, 26% and 40% in patients who had no adjuvant chemotherapy after surgery (P=0.001, P=0.001, respectively. In propensity-matched study, 158 pairs of patients with or without postoperative chemotherapy (316 patients in total were selected and compared accordingly. Similar 5-year survival rates were detected between the two groups (P=0.332. Conclusion Pathologically higher grade histology, incomplete resection, and postoperative radiotherapy were found to be associated with worse outcomes in advanced stage thymic tumors. At present

  19. Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer

    NARCIS (Netherlands)

    Frielink, L.M.; Pijlman, B.M.; Ezendam, N.P.; Pijnenborg, J.M.A.

    2016-01-01

    BACKGROUND: Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. METHODS: All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The perc

  20. Outcome of combination chemotherapy in extensive stage small-cell lung cancer

    DEFF Research Database (Denmark)

    Lassen, U N; Hirsch, F R; Osterlind, K

    1998-01-01

    During the past two decades many different treatment regimens of combination chemotherapy have been applied in extensive stage small-cell lung cancer (SCLC). This study was carried out to identify whether these modifications have resulted in an improved overall survival for extensive stage during...

  1. Trastuzumab after Chemotherapy Is Effective in HER2-Positive Breast Cancer

    Science.gov (United States)

    Treatment with trastuzumab for 1 year following standard chemotherapy improved disease-free survival in women with HER2-positive early breast cancer, according to 4-year follow-up results of the Herceptin Adjuvant (HERA) trial reported February 25, 2011,

  2. Significant improvement of survival by intrasplenic hepatocyte transplantation in totally hepatectomized rats.

    Science.gov (United States)

    Vogels, B A; Maas, M A; Bosma, A; Chamuleau, R A

    1996-01-01

    The effect of intrasplenic hepatocyte transplantation (HTX) was studied in an experimental model of acute liver failure in rats with chronic liver atrophy. Rats underwent a portacaval shunt operation on Day -14 to induce liver atrophy, and underwent total hepatectomy on Day 0 as a start of acute liver failure. Intrasplenic hepatocyte or sham transplantation was performed on Day -7,-3, or -1 (n = 4 to 6 per group). During the period following hepatectomy, mean arterial blood pressure was maintained above 80 mm Hg and hypoglycaemia was prevented. Severity of hepatic encephalopathy was assessed by clinical grading and EEG spectral analysis, together with determination of blood ammonia and plasma amino acid concentrations, and "survival" time. Histological examination of the spleen and lungs was performed after sacrifice. Intrasplenic hepatocyte transplantation resulted in a significant improvement in clinical grading in all transplanted groups (p 0.05), HTX at Day -3: 19.7 +/- 3.7 h vs. 6.5 +/- 0.3 h (p ammonia concentrations after total hepatectomy (p spleens after sacrifice showed clusters of hepatocytes in the red pulp. Hepatocytes present in the spleen for 3 and 7 days showed bile accumulation and spots of beginning necrosis. The present data show that in a hard model of complete liver failure in portacaval shunted rats, intrasplenic hepatocyte transplantation is able to prolong "survival" time significantly 2- to 3-fold. The relevance of this observation for human application is discussed.

  3. Single Agent Polysaccharopeptide Delays Metastases and Improves Survival in Naturally Occurring Hemangiosarcoma

    Directory of Open Access Journals (Sweden)

    Dorothy Cimino Brown

    2012-01-01

    Full Text Available The 2008 World Health Organization World Cancer Report describes global cancer incidence soaring with many patients living in countries that lack resources for cancer control. Alternative treatment strategies that can reduce the global disease burden at manageable costs must be developed. Polysaccharopeptide (PSP is the bioactive agent from the mushroom Coriolus versicolor. Studies indicate PSP has in vitro antitumor activities and inhibits the growth of induced tumors in animal models. Clear evidence of clinically relevant benefits of PSP in cancer patients, however, is lacking. The investment of resources required to complete large-scale, randomized controlled trials of PSP in cancer patients is more easily justified if antitumor and survival benefits are documented in a complex animal model of a naturally occurring cancer that parallels human disease. Because of its high metastatic rate and vascular origin, canine hemangiosarcoma is used for investigations in antimetastatic and antiangiogenic therapies. In this double-blind randomized multidose pilot study, high-dose PSP significantly delayed the progression of metastases and afforded the longest survival times reported in canine hemangiosarcoma. These data suggest that, for those cancer patients for whom advanced treatments are not accessible, PSP as a single agent might offer significant improvements in morbidity and mortality.

  4. Association of GWAS-identified lung cancer susceptibility loci with survival length in patients with small-cell lung cancer treated with platinum-based chemotherapy.

    Directory of Open Access Journals (Sweden)

    Dong Li

    Full Text Available Genetic variants have been shown to affect length of survival in cancer patients. This study explored the association between lung cancer susceptibility loci tagged by single-nucleotide polymorphisms (SNPs identified in the genome-wide association studies and length of survival in small-cell lung cancer (SCLC. Eighteen SNPs were genotyped among 874 SCLC patients and Cox proportional hazards regression was used to examine the effects of genotype on survival length under an additive model with age, sex, smoking status and clinical stage as covariates. We identified 3 loci, 20q13.2 (rs4809957G >A, 22q12.2 (rs36600C >T and 5p15.33 (rs401681C >T, significantly associated with the survival time of SCLC patients. The adjusted hazard ratio (HR for patients with the rs4809957 GA or AA genotype was 0.80 (95% CI, 0.66-0.96; P = 0.0187 and 0.73 (95% CI, 0.55-0.96; P = 0.0263 compared with the GG genotype. Using the dominant model, the adjusted HR for patients carrying at least one T allele at rs36600 or rs401681 was 0.78 (95% CI, 0.63-0.96; P = 0.0199 and 1.29 (95% CI, 1.08-1.55; P = 0.0047, respectively, compared with the CC genotype. Stratification analyses showed that the significant associations of these 3 loci were only seen in smokers and male patients. The rs4809957 SNP was only significantly associated with length of survival of patients with extensive-stage but not limited-stage tumor. These results suggest that some of the lung cancer susceptibility loci might also affect the prognosis of SCLC.

  5. ADJUVANT CHEMOTHERAPY FOLLOWING RADICAL SURGERY FOR NON-SMALL CELL LUNG CANCER:A RANDOMIZED STUDY

    Institute of Scientific and Technical Information of China (English)

    XU Guang-chuan; RONG Tie-hua; LIN Peng

    1999-01-01

    Objective: To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small cell lung cancer (NSCLC). Methods: Seventy patients with NSCLC (stage Ⅰ-Ⅲ) undergone radical surgery were randomized into two groups: 35 patients received adjuvant chemotherapy with cyclophosphamide (CTX)300 mg/m2, vincristine (VCR) 1.4% mg/m2, adriamycin (ADM) 50 mg/m2, lomustine (CCNU) 50 mg/m2 d1,cisplatin (DDP) 20 mg/m2, d1-5, for 4 cycles, and followed by oral Ftorafur (FT-207) 600-900 mg/d for 1year (adjuvant chemotherapy group). The other 35patients received surgical treatment only (surgery group). Results: The overall 5-year survival rate was 48.6% in the adjuvant chemotherapy group, and 31.4%in the surgery group, respectively. The difference between the two groups was not statistically significant (P>0.05). The 5-year survival rate of patients in stage Ⅲwas 44.0% and 20.8% received surgery with and without adjuvant chemotherapy, respectively. The difference between the two groups was statistically significant (P<0.025). The 5-year survival rate of patients in stage Ⅰ-Ⅱ in the two groups was 60.0% and 54.5%, respectively (P>0.75). Conclusion: Postoperative adjuvant chemotherapy in NSCLC can improve survival, for those patients in stage Ⅲ, it suggests significantly 5-year survival rate in the adjuvant chemotherapy group was higher than that in the surgery alone group.

  6. Life expectancy with perioperative chemotherapy and chemoradiotherapy for locally advanced gastric adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Sadighi S

    2008-12-01

    Full Text Available "nBackground: Although postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach, curative surgery occurs in less than 50% of nonmetastatic gastric cancers. A regimen of docetaxel, cisplatin and infusional fluorouracil improves survival of patients with incurable locally-advanced gastric adenocarcinoma. So we assessed the perioperative regimen of docetaxel, cisplatin and infusions 5FU (TCF and postoperative chemoradiotherapy to improve outcomes in patients with potentially resectable gastric adenocarcinoma. "nMethods: Between March 2005 and March 2008, we 100 enrolled patients with stage II to IV (M0 adenocarcinoma of the stomach who had not been treated previously. Treatment consisted of three preoperative and one postoperative cycles of TCF followed by chemoradiotherapy. The primary end point was overall survival. The secondary end points were progression-free survival and toxicity of treatment. "nResults: A total of 100 patients participated, 83 of whom received neoadjuvant and 17 received adjuvant chemotherapy. Seventy-five patients underwent at least D0 gastrectomy. After chemotherapy, tumor stages were significantly lower than before beginning the protocol. Out of 100 patients, 44 had stage IV before chemotherapy versus 15 after the treatment. Three patients showed complete pathologic response. The median survival time was 25 months. "nConclusion: Docetaxel, cisplatin and 5FU combination chemotherapy is an active preoperative treatment in locally advanced gastric cancer. Perioperative chemoradio-therapy should be considered as an option to lengthen patient survival.

  7. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Lindvall, O.; Brundin, P.; Widner, H.; Rehncrona, S.; Gustavii, B.; Frackowiak, R.; Leenders, K.L.; Sawle, G.; Rothwell, J.C.; Marsden, C.D. (University Hospital, Lund (Sweden))

    1990-02-02

    Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-L-({sup 18}F)fluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the on-off phenomenon). The clinical improvement was most marked on the side contralateral to the transplant.

  8. Rituximab and escalated chemotherapy in elderly patients with aggressive diffuse large-cell lymphoma: a controlled clinical trial.

    Science.gov (United States)

    Avilés, Agustin; Nambo, María Jesus; Castañeda, Claudia; Cleto, Sergio; Neri, Natividad; Murillo, Edgar; Huerta-Guzmán, Judith; Contreras, Margarita

    2007-04-01

    The treatment of elderly patients with aggressive malignant lymphoma has not been defined. The addition of rituximab to conventional chemotherapy has been reported to improve the outcome, but most patients have good prognostic factors (performance status < 2, no severe associated diseases, low or low-intermediate clinical risk). Thus, we developed a combined regimen, including escalated doses of anthracycline and rituximab. The endpoint was to improve event-free survival (EFS) and overall survival. Two hundred and four (204) patients were randomly assigned to receive an escalated chemotherapy regimen (CEOP) with escalated dose of epirubicin, compared to the same regimen and addition of rituximab. All patients had poor prognostic factors: high- or high-intermediate clinical risk, poor performance status, bulky disease, and more than 2 with extranodal involvement. In an intent-to-treat analysis, all patients were evaluable for efficacy and toxicity. The complete response rates were similar in both arms: 74% in chemotherapy and 78% in the rituximab + chemotherapy program. EFS and overall survival were similar: 77% and 84%, respectively, in combined chemotherapy and 75% and 81% in the rituximab-chemotherapy regimen. Toxicity was mild and well tolerated. In elderly patients with diffuse large-cell lymphoma and poor prognostic factors, rituximab did not improve their outcome.

  9. Gacyclidine improves the survival and reduces motor deficits in a mouse model of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Yannick Nicolas Gerber

    2013-12-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder typified by a massive loss of motor neurons with few therapeutic options. The exact cause of neuronal degeneration is unknown but it is now admitted that ALS is a multifactorial disease with several mechanisms involved including glutamate excitotoxicity. More specifically, N-methyl-D-aspartate (NMDA-mediated cell death and impairment of the glutamate-transport has been suggested to play a key role in ALS pathophysiology. Thus, evaluating NMDAR antagonists is of high therapeutic interest. Gacyclidine, also named GK11, is a high affinity non-competitive NMDAR antagonist that may protect against motor neuron death in an ALS context. Moreover, GK11 presents a low intrinsic neurotoxicity and has already been used in two clinical trials for CNS lesions. In the present study, we investigated the influence of chronic administration of two doses of GK11 (0.1 and 1 mg/kg on the survival and the functional motor activity of hSOD1G93A mice, an animal model of ALS. Treatment started at early symptomatic age (60 days and was applied bi-weekly until the end stage of the disease. We first confirmed that functional alteration of locomotor activity was evident in the hSOD1G93A transgenic female mice by 60 days of age. A low dose of GK11 improved the survival of the mice by 4.3% and partially preserved body weight. Improved life span was associated with a delay in locomotor function impairment. Conversely, the high dose treatment worsened motor functions. These findings suggest that chronic administration of GK11beginning at early symptomatic stage may be beneficial for patients with ALS.

  10. Improved Survival with T Cell Clonotype Stability After Anti–CTLA-4 Treatment in Cancer Patients

    Science.gov (United States)

    Cha, Edward; Klinger, Mark; Hou, Yafei; Cummings, Craig; Ribas, Antoni; Faham, Malek; Fong, Lawrence

    2015-01-01

    Cytotoxic T lymphocyte–associated antigen-4 (CTLA-4) blockade can promote antitumor T cell immunity and clinical responses. The mechanism by which anti–CTLA-4 antibodies induces antitumor responses is controversial. To determine the effects of CTLA-4 blockade on the T cell repertoire, we used next-generation deep sequencing to measure the frequency of individual rearranged T cell receptor β (TCRβ) genes, thereby characterizing the diversity of rearrangements, known as T cell clonotypes. CTLA-4 blockade in patients with metastatic castration-resistant prostate cancer and metastatic melanoma resulted in both expansion and loss of T cell clonotypes, consistent with a global turnover of the T cell repertoire. Overall, this treatment increased TCR diversity as reflected in the number of unique TCR clonotypes. The repertoire of clonotypes continued to evolve over subsequent months of treatment. Whereas the number of clonotypes that increased with treatment was not associated with clinical outcome, improved overall survival was associated with maintenance of high-frequency clones at baseline. In contrast, the highest-frequency clonotypes fell with treatment in patients with short overall survival. Stably maintained clonotypes included T cells having high-avidity TCR such as virus-reactive T cells. Together, these results suggest that CTLA-4 blockade induces T cell repertoire evolution and diversification. Moreover, improved clinical outcomes are associated with less clonotype loss, consistent with the maintenance of high-frequency TCR clonotypes during treatment. These clones may represent the presence of preexisting high-avidity T cells that may be relevant in the antitumor response. PMID:24871131

  11. Chemotherapy (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Chemotherapy KidsHealth > For Parents > Chemotherapy Print A A A ... have many questions and concerns about it. About Chemotherapy Chemotherapy (often just called "chemo") refers to medications ...

  12. Can survival prediction be improved by merging gene expression data sets?

    Directory of Open Access Journals (Sweden)

    Haleh Yasrebi

    Full Text Available BACKGROUND: High-throughput gene expression profiling technologies generating a wealth of data, are increasingly used for characterization of tumor biopsies for clinical trials. By applying machine learning algorithms to such clinically documented data sets, one hopes to improve tumor diagnosis, prognosis, as well as prediction of treatment response. However, the limited number of patients enrolled in a single trial study limits the power of machine learning approaches due to over-fitting. One could partially overcome this limitation by merging data from different studies. Nevertheless, such data sets differ from each other with regard to technical biases, patient selection criteria and follow-up treatment. It is therefore not clear at all whether the advantage of increased sample size outweighs the disadvantage of higher heterogeneity of merged data sets. Here, we present a systematic study to answer this question specifically for breast cancer data sets. We use survival prediction based on Cox regression as an assay to measure the added value of merged data sets. RESULTS: Using time-dependent Receiver Operating Characteristic-Area Under the Curve (ROC-AUC and hazard ratio as performance measures, we see in overall no significant improvement or deterioration of survival prediction with merged data sets as compared to individual data sets. This apparently was due to the fact that a few genes with strong prognostic power were not available on all microarray platforms and thus were not retained in the merged data sets. Surprisingly, we found that the overall best performance was achieved with a single-gene predictor consisting of CYB5D1. CONCLUSIONS: Merging did not deteriorate performance on average despite (a The diversity of microarray platforms used. (b The heterogeneity of patients cohorts. (c The heterogeneity of breast cancer disease. (d Substantial variation of time to death or relapse. (e The reduced number of genes in the merged data

  13. Long-term albumin infusion improves survival in patients with cirrhosis and ascites: An unblinded randomized trial

    Institute of Scientific and Technical Information of China (English)

    Roberto Giulio Romanelli; Paolo Gentilini; Giacomo Laffi; Giorgio La Villa; Giuseppe Barletta; Francesco Vizzutti; Fabio Lanini; Umberto Arena; Vieri Boddi; Roberto Tarquini; Pietro Pantaleo

    2006-01-01

    AIM: To investigate the effects of long-term albumin administration on survival, recurrence of ascites and onset of other complications.METHODS: One hundred consecutive patients admitted for first-onset ascites were randomized to receive diuretics plus human albumin 25 g/wk in the first year and 25g every two wk thereafter (group 1) or diuretics alone (group 2). The primary endpoint was survival without liver transplantation. Secondary endpoints were recurrence of ascites and occurrence of other complications.RESULTS: Median follow-up was 84 (2-120) mo. Albumin-treated patients had significantly greater cumulative survival rate (Breslow test= 7.05, P= 0.0078) and lower probability of ascites recurrence (51% versus 94%,P<0.0001). Chronic albumin infusion resulted in a mean increase in survival of 16 mo.CONCLUSION: Long-term albumin administration after first-onset ascites significantly improves patients' survival and decreases the risk of ascites recurrence.

  14. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Science.gov (United States)

    2010-07-01

    ... elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and... spouses of Spanish-American War veterans. (a) General. A surviving spouse of a Spanish-American War... and attendance. A surviving spouse of a Spanish-American War veteran who is receiving or entitled...

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

    Science.gov (United States)

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

  16. Improved survival for patients diagnosed with chronic lymphocytic leukemia in the era of chemo-immunotherapy

    DEFF Research Database (Denmark)

    da Cunha-Bang, C; Simonsen, J; Rostgaard, K

    2016-01-01

    The treatment of chronic lymphocytic leukemia (CLL) is in rapid transition, and during recent decades both combination chemotherapy and immunotherapy have been introduced. To evaluate the effects of this development, we identified all CLL patients registered in the nation-wide Danish Cancer...... for patients treated with chemo-immunotherapy demonstrated in clinical studies....

  17. Improved survival of patients with hepatocellular carcinoma and disparities by age, race, and socioeconomic status by decade, 1983–2012

    Science.gov (United States)

    Li, Jie; Hong, Guobin; Li, Dan; Mallampati, Saradhi; Zhou, Xiuling; Zhou, Cuiling; Zhang, Hongyu; Cheng, Zhibin; Shan, Hong; Ma, Haiqing

    2016-01-01

    Hepatocellular carcinoma (HCC), accounting for the majority of liver cancer, is a highly aggressive malignancy with poor prognosis and therefore adds up the financial burden. Incidence data of HCC in three decades during 1983-2012 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database with incidence rates of 1.9, 3.1 and 4.9 per 100,000 respectively. In addition, to evaluate the survival changes in the same period, a total of 63,640 HCC cancer cases were accessed from SEER database. The six-month relative survival rates improved each decade from 31.0% to 42.9% to 57.2% and the higher increase can be seen in the last two decades. More importantly, the disparities of survival among different racial groups and socioeconomic status (SES) were confirmed by the inferiority of survival in Black race and high-poverty group respectively. This research analyzed the incidence and survival data of HCC in the past three decades and may help predict the future trends of incidence and survival. Furthermore, this study may help better design healthcare policies and clinical management programs to balance the disparities of survival between SES groups, races, ages and sexes confirmed in this study and thereby improve the clinical management of HCC. PMID:27486977

  18. Survival benefit and phenotypic improvement by hamartin gene therapy in a tuberous sclerosis mouse brain model.

    Science.gov (United States)

    Prabhakar, Shilpa; Zhang, Xuan; Goto, June; Han, Sangyeul; Lai, Charles; Bronson, Roderick; Sena-Esteves, Miguel; Ramesh, Vijaya; Stemmer-Rachamimov, Anat; Kwiatkowski, David J; Breakefield, Xandra O

    2015-10-01

    We examined the potential benefit of gene therapy in a mouse model of tuberous sclerosis complex (TSC) in which there is embryonic loss of Tsc1 (hamartin) in brain neurons. An adeno-associated virus (AAV) vector (serotype rh8) expressing a tagged form of hamartin was injected into the cerebral ventricles of newborn pups with the genotype Tsc1(cc) (homozygous for a conditional floxed Tsc1 allele) SynI-cre(+), in which Tsc1 is lost selectively in neurons starting at embryonic day 12. Vector-treated Tsc1(cc)SynIcre(+) mice showed a marked improvement in survival from a mean of 22 days in non-injected mice to 52 days in AAV hamartin vector-injected mice, with improved weight gain and motor behavior in the latter. Pathologic studies showed normalization of neuron size and a decrease in markers of mTOR activation in treated as compared to untreated mutant littermates. Hence, we show that gene replacement in the brain is an effective therapeutic approach in this mouse model of TSC1. Our strategy for gene therapy has the advantages that therapy can be achieved from a single application, as compared to repeated treatment with drugs, and that AAV vectors have been found to have minimal to no toxicity in clinical trials for other neurologic conditions. Although there are many additional issues to be addressed, our studies support gene therapy as a useful approach in TSC patients.

  19. Simvastatin Treatment Improves Survival in a Murine Model of Burn Sepsis

    Science.gov (United States)

    Beffa, David C; Fischman, Alan J.; Fagan, Shawn P.; Hamrahi, Victoria F.; Kaneki, Masao; Yu, Yong-Ming; Tompkins, Ronald G.; Carter, Edward A.

    2014-01-01

    Infection is the most common and most serious complication of a major burn injury related to burn size. Despite improvements in antimicrobial therapies sepsis still accounts for 50–60% of deaths in burn patients. Given the acute onset and unpredictable nature of sepsis, primary prevention was rarely attempted in its management. However, recent studies have demonstrated that statin treatment can decrease mortality is a murine model of sepsis by preservation of cardiac function and reversal of inflammatory alterations. In addition, it has been shown that treatment with statins is associated with reduced incidence of sepsis in human patients. In the current study groups of CD1 male mice (n=12) were anesthetized and subjected to a dorsal 30% TBSA scald burn injury. Starting 2 hours post burn, the animals were divided into a treatment group receiving 0.2 µ/g simvastatin or a sham group receiving placebo. Simvastatin and placebo were administered by intraperitoneal injection with two dosing regimens; once daily and every 12 hours. On Post burn day 7 cecal ligation and puncture with a 21-gauge needle was performed under ketamine/xylazine anesthesia and the two different dosing schedules were continued. A simvastatin dose dependant improvement in survival was observed in the burn sepsis model. PMID:21145172

  20. Pretreatment with octreotide modulates iNOS gene expression, mimics surgical delay, and improves flap survival.

    Science.gov (United States)

    Gözü, Aydin; Poda, Mehveş; Taşkin, Elif I; Turgut, Hürriyet; Erginel-Unaltuna, Nihan; Doğruman, Hüsniye; Ozsoy, Zafer

    2010-08-01

    We aimed to evaluate the role of a synthetic somatostatin analogue in delay procedure of experimental skin flaps. Thirty-six rats were randomly divided into 2 groups of 18 each to compare the possible local ischemic effect of octreotide with that of surgical delay in the dorsal random pattern skin flap model. The inducible nitric oxide synthase gene expression was assessed in the flap territory at intervals of immediate, 24 and 48 hours after preconditioning. Histologic analysis was performed in rats at 48th hour and 3 additional rats were used for microangiography. A gradual increase of daily transcript levels was detected in both groups (P < 0.05). The differences of molecular and histologic findings between the groups were not distinctive. Pharmacologically preconditioned rat displayed relevant microvascular features. Forty rats were further grouped randomly into 4 groups of 10 each. In group 1 rats, flaps were raised and reinserted without any prior intervention. Group 2 rats underwent surgical delay procedure, whereas flap territories of the others received either saline solution or octreotide 1 week before the ultimate flap harvest. After another 7-day period, both delay procedures were found effective in improving flap viability (P < 0.01). Ischemia induced by octreotide favored to investigate its utility in delay phenomenon. Although it was not as effective as the surgical delay procedure, it may be a safe pharmacologic alternative to improve the flap survival.

  1. Improving breast cancer survival analysis through competition-based multidimensional modeling.

    Directory of Open Access Journals (Sweden)

    Erhan Bilal

    Full Text Available Breast cancer is the most common malignancy in women and is responsible for hundreds of thousands of deaths annually. As with most cancers, it is a heterogeneous disease and different breast cancer subtypes are treated differently. Understanding the difference in prognosis for breast cancer based on its molecular and phenotypic features is one avenue for improving treatment by matching the proper treatment with molecular subtypes of the disease. In this work, we employed a competition-based approach to modeling breast cancer prognosis using large datasets containing genomic and clinical information and an online real-time leaderboard program used to speed feedback to the modeling team and to encourage each modeler to work towards achieving a higher ranked submission. We find that machine learning methods combined with molecular features selected based on expert prior knowledge can improve survival predictions compared to current best-in-class methodologies and that ensemble models trained across multiple user submissions systematically outperform individual models within the ensemble. We also find that model scores are highly consistent across multiple independent evaluations. This study serves as the pilot phase of a much larger competition open to the whole research community, with the goal of understanding general strategies for model optimization using clinical and molecular profiling data and providing an objective, transparent system for assessing prognostic models.

  2. Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lim Yiting [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Kastan, Michael B. [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina (United States); Matsui, William, E-mail: matsuwi@jhmi.edu [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); DeWeese, Theodore L., E-mail: deweete@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2012-11-01

    Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 {mu}g per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

  3. Bortezomib improves progression-free survival in multiple myeloma patients overexpressing preferentially expressed antigen of melanoma

    Institute of Scientific and Technical Information of China (English)

    Qin Yazhen; Lu Jin; Bao Li; Zhu Honghu; Li Jinlan; Li Lingdi; Lai Yueyun

    2014-01-01

    Background Significant efforts have been made to identify factors that differentiate patients treated with novel therapies,such as bortezomib in multiple myeloma (MM).The exact expression pattern and prognostic value of the cancer/testis antigen preferentially expressed antigen of melanoma (PRAME) in MM are unknown and were explored in this study.Methods The transcript level of PRAME was detected in bone marrow specimens from 100 newly diagnosed MM patients using real-time quantitative polymerase chain reaction,and the prognostic value of PRAME was determined through retrospective survival analysis.PRAME expression higher than the upper limit of normal bone marrow was defined as PRAME overexpression or PRAME (+).Results Sixty-two patients (62.0%) overexpressed PRAME.PRAME overexpression showed no prognostic significance to either overall survival (n=100) or progression-free survival (PFS,n=96,all P >0.05) of patients.The patients were also categorized according to regimens with or without bortezomib.PRAME overexpression tended to be associated with a lower two-year PFS rate in patients treated with non-bortezomib-containing regimens (53.5% vs.76.9%,P=0.071).By contrast,it was not associated with the two-year PFS rate in patients with bortezomib-containing regimens (77.5% vs.63.9%,P >0.05).When the patients were categorized into PRAME (+) and PRAME (-) groups,treatment with bortezomib-containing regimens predicted a higher two-year PFS rate in PRAME (+) patients (77.5% vs.53.5%,P=0.027) but showed no significant effect on two-year PFS rate in PRAME (-) patients (63.9% vs.76.9%,P >0.05).Conclusion PRAME overexpression might be an adverse prognostic factor of PFS in MM patients treated with non-bortezomib-containing regimens.Bortezomib improves PFS in patients overexpressing PRAME.

  4. HLA-E expression in cervical adenocarcinomas: association with improved long-term survival

    Directory of Open Access Journals (Sweden)

    Spaans Vivian M

    2012-09-01

    .001, respectively. Conclusion High expression of HLA-E occurred in the majority of all histopathological subtypes of cervical cancer; especially in cervical AC. High HLA-E expression in cervical AC was associated with improved patient survival. This study also highlights the importance of careful evaluation of cervical carcinomas to distinguish histopathological subtypes. In the future, insight into the biological behaviour and distinct molecular carcinogenetic processes of the AC, ASC, and SCC subtypes may contribute to the development of more tumour-specific treatment strategies.

  5. Immunotherapy improves immune homeostasis and increases survival rate of septic patients

    Institute of Scientific and Technical Information of China (English)

    HUANG Shun-wei; CHEN Juan; OUYANG Bin; YANG Chun-hua; CHEN Min-ying; GUAN Xiang-dong

    2009-01-01

    Objective: To investigate the efficacy of immunotherapy on septic patients with Ulinastatin plus Thymosin-α1. Methods: Seventy postoperative septic patients were divided into two groups at random: the immunotherapy group (n=36) and the conventional therapy group (n=34). Patients in the immunotherapy group received intravenous Ulinastatin of 200 000 U, 3 times per day for 3 days, Ulinastatin of 100 000 U, 3 times per day for 4 days, and subcutaneous injection of Thymosin-α1 of 1.6 mg, twice per day for 3 days, then once per day for 4 days. While conventional therapies such as antibiotics and fluid resuscitation were undertaken in both groups. The expression levels of serum tumor necrosis factor-α (TNF-α), interleukin- 10 (IL-10), IgG, C3, T lymphocyte subsets, CD14+ monocyte human leukocyte antigen (locus) DR (HLA-DR) and patients' 28-day survival rate of the two groups were observed and evaluated. Results: The survival rate was significantly higher in the immunotherapy group (63.9%; 23/36) compared with the conventional therapy group (41.2%; 14/34). The serum TNF-α levels [(1.38±0.50) ng/ml in the immunotherapy group vs (1.88±0.53) ng/ml in the conventional group, P<0.05] and the serum IL- 10 levels [(217.52±15.71) ng/ml vs (101.53±16.57) ng/ml, P<0.05] were significantly different between the two groups. The serum IgG levels in the immunotherapy group [(17.65±6.81) g/L] were significantly higher than in the conventional group [(11.94±5.32) g/L]. There were also significant differences in the expression levels of CD4+ T lymphocyte (35%±13% in the immunotherapy group vs 21%±7% in the conventional group, P<0.05) and CD14+ monocyte HLA-DR (50%±5% in the former vs 35%±4% in the latter, P<0.05). Conclusions: Immunotherapy with Ulinastatin plus Thymosin-α1 can enhance the inflammatory response, improve the immune homeostasis, and increase the survival rate of septic patients.

  6. Prescription dose and fractionation predict improved survival after stereotactic radiotherapy for brainstem metastases

    Directory of Open Access Journals (Sweden)

    Leeman Jonathan E

    2012-07-01

    nausea (n = 1 and headaches (n = 2 that resolved with a short-course of dexamethasone. Conclusion SRT/SRS for brainstem metastases is safe and achieves a high rate of local control. We found higher GPA as well as greater number of treatment fractions and higher prescription dose to be correlated with improved overall survival. Despite this approach, prognosis remains poor and distant intracranial control remains an issue, even in patients previously treated with WBRT.

  7. Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension.

    Science.gov (United States)

    Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

  8. Renal Transplant Immunology in the Last 20 Years: A Revolution Towards Graft and Patient Survival Improvement.

    Science.gov (United States)

    Sá, Helena; Leal, Rita; Rosa, Manuel Santos

    2016-09-28

    To deride the hope of progress is the ultimate fatuity, the last word in poverty of spirit and meanness of mind. There is no need to be dismayed by the fact that we cannot yet envisage a definitive solution of our problems, a resting-place beyond which we need not try to go. -P.B. Medawar, 1969* [Formula: see text] Thomas E. Starlz, also known as the Father of Clinical Transplantation, once said that organ transplantation was the supreme exception to the rule that most major advances in medicine spring from discoveries in basic science [Starzl T. The mystique of organ transplantation. J Am Coll Surg 2005 Aug;201(2):160-170]. In fact, the first successful identical-twin kidney transplantation performed by Murray's team in December 1954 (Murray J et al. Renal homotransplantations in identical twins. Surg Forum 1955;6:432-436) was the example of an upside down translation medicine: Human clinical transplantation began and researchers tried to understand the underlying immune response and how to control the powerful rejection pathways through experimental models. In the last 20 years, we have witnessed an amazing progress in the knowledge of immunological mechanisms regarding alloimmune response and an outstanding evolution on the identification and characterization of major and minor histocompatibility antigens. This review presents an historical and clinical perspective of those important advances in kidney transplantation immunology in the last 20 years, which contributed to the improvement in patients' quality of life and the survival of end-stage renal patients. In spite of these significant progresses, some areas still need substantial progress, such as the definition of non-invasive biomarkers for acute rejection; the continuous reduction of immunosuppression; the extension of graft survival, and finally the achievement of real graft tolerance extended to HLA mismatch donor: recipient pairs.

  9. A Review of NEPA, a Novel Fixed Antiemetic Combination with the Potential for Enhancing Guideline Adherence and Improving Control of Chemotherapy-Induced Nausea and Vomiting

    Directory of Open Access Journals (Sweden)

    Paul J. Hesketh

    2015-01-01

    Full Text Available Combination antiemetic regimens targeting multiple molecular pathways associated with emesis have become the standard of care for prevention of chemotherapy-induced nausea and vomiting (CINV related to highly and moderately emetogenic chemotherapies. Antiemetic consensus guidelines from several professional societies are widely available and updated regularly as new data emerges. Unfortunately, despite substantial research supporting the notion that guideline conformity improves CINV control, adherence to antiemetic guidelines is unsatisfactory. While studies are needed to identify specific barriers to guideline use and explore measures to enhance adherence, a novel approach has been taken to improve clinician adherence and patient compliance, with the development of a new combination antiemetic. NEPA is an oral fixed combination of a new highly selective NK1 receptor antagonist (RA, netupitant, and the pharmacologically and clinically distinct 5-HT3 RA, palonosetron. This convenient antiemetic combination offers guideline-consistent prophylaxis by targeting two critical pathways associated with CINV in a single oral dose administered only once per cycle. This paper will review and discuss the NEPA data in the context of how this first combination antiemetic may overcome some of the barriers interfering with adherence to antiemetic guidelines, enhance patient compliance, and offer a possible advance in the prevention of CINV for patients.

  10. Topoisomerase II alpha expression and the benefit of adjuvant chemotherapy for postoperative patients with non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Jie Li

    2010-11-01

    Full Text Available Abstract Background Adjuvant chemotherapy has been shown to improve survival rates of postoperative patients with non-small cell lung cancer (NSCLC. Biomarkers could help select an appropriate chemotherapy for NSCLC patients or predict the efficacy of chemotherapy. The objective of this study was to explore the possible prognostic and predictive role of topoisomerase II alpha (TopIIα expression level in postoperative NSCLC patients who received adjuvant chemotherapy. Methods Patients with stage I-III NSCLC, who underwent surgery in our hospital from January 2004 to December 2007 and who also received adjuvant chemotherapy after surgery, were analyzed in this study. Expression of TopIIα and Ki67 in paraffin-embedded tissues was detected by immunohistochemistry (IHC. The relationships between clinicopathological characteristics, chemotherapy regimens, the expression of biomarkers and disease free survival (DFS were analyzed. Results TopIIα and Ki67 were highly expressed in 22.5% and 36.4% of the 151 patients, respectively. Univariate survival analysis showed that male sex (P = 0.036, non-adenocarcinoma (P = 0.004, earlier pathological TNM stage (P = 0.001 or pathological N stage (P Conclusions High TopIIα expression was discovered to be correlated with better DFS for postoperative NSCLC patients who received adjuvant chemotherapy. The NVB-containing chemotherapy regimen was more effective than the TXT-containing regimen in improving DFS in patients with low TopIIα expression. TopIIα could be considered to be an independent prognostic biomarker of DFS in postoperative NSCLC patients who received adjuvant chemotherapy.

  11. Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients?

    Science.gov (United States)

    Franceschi, E; Bartolotti, M; Paccapelo, A; Marucci, G; Agati, R; Volpin, L; Danieli, D; Ghimenton, C; Gardiman, M P; Sturiale, C; Poggi, R; Mascarin, M; Balestrini, D; Masotto, B; Brandes, A A

    2016-06-01

    The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm(2)) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8-13), median survival was 18 years (95 % CI 9-28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0-97.2 %) and 60.2 % (95 % CI 36.9-83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group).

  12. Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo.

    Science.gov (United States)

    Giladi, Moshe; Weinberg, Uri; Schneiderman, Rosa S; Porat, Yaara; Munster, Michal; Voloshin, Tali; Blatt, Roni; Cahal, Shay; Itzhaki, Aviran; Onn, Amir; Kirson, Eilon D; Palti, Yoram

    2014-10-01

    Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. Common treatment modalities for NSCLC include surgery, radiotherapy, chemotherapy, and, in recent years, the clinical management paradigm has evolved with the advent of targeted therapies. Despite such advances, the impact of systemic therapies for advanced disease remains modest, and as such, the prognosis for patients with NSCLC remains poor. Standard modalities are not without their respective toxicities and there is a clear need to improve both efficacy and safety for current management approaches. Tumor-treating fields (TTFields) are low-intensity, intermediate-frequency alternating electric fields that disrupt proper spindle microtubule arrangement, thereby leading to mitotic arrest and ultimately to cell death. We evaluated the effects of combining TTFields with standard chemotherapeutic agents on several NSCLC cell lines, both in vitro and in vivo. Frequency titration curves demonstrated that the inhibitory effects of TTFields were maximal at 150 kHz for all NSCLC cell lines tested, and that the addition of TTFields to chemotherapy resulted in enhanced treatment efficacy across all cell lines. We investigated the response of Lewis lung carcinoma and KLN205 squamous cell carcinoma in mice treated with TTFields in combination with pemetrexed, cisplatin, or paclitaxel and compared these to the efficacy observed in mice exposed only to the single agents. Combining TTFields with these therapeutic agents enhanced treatment efficacy in comparison with the respective single agents and control groups in all animal models. Together, these findings suggest that combining TTFields therapy with chemotherapy may provide an additive efficacy benefit in the management of NSCLC.

  13. A comparison of intravenous plus intraperitoneal chemotherapy with intravenous chemotherapy alone for the treatment of gastric cancer:a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Objective:We aimed to evaluate the effectiveness and safety of intravenous (IV) plus intraperitoneal (IP) chemotherapy compared to IV chemotherapy alone for patients with gastric cancer.Methods: Electronic databases were searched up to June 2013. Two authors independently assessed the quality of included studies. hTe GARDE System was adopted to rate the level of evidence. Of 392 citations, ifve RCTs involving 1, 072 patients were included.Results:Overall, a signiifcant improvement in in 1- and 3- and 5-year survival rate was observed in the IV plus IP chemotherapy group (3 RCTs,n=360, RR=1.10, 95% CI, 1.04~1.17), (5 RCTs,n=953, RR=1.22, 95% CI, 1.11~1.35) and (3 RCTs, n=347, RR=1.42, 95% CI, 1.12~1.80), respectively. Results supported a signiifcant decrease in the rate of metastases (1 RCT,n=85, RR=0.41 95% CI, 0.19~0.89) and peritoneal recurrence (2 RCTs,n=297, RR=0.41, 95% CI, 0.26~0.62) in the IV plus IP chemotherapy group, however, the incidence of adverse events was increased.Conclusion:For patients with gastric cancer, IV plus IP chemotherapy can improve the overall survival rate and prevent the distant or peritoneal metastases. An increased risk of neutropenia, peripheral edema and neuropathy was observed.

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

    Directory of Open Access Journals (Sweden)

    Michal Lotem

    2016-01-01

    Full Text Available 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.

  15. Investigation of the Effect of Neoadjuvant Chemotherapy on Stage II Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Yanli Song; Dong Wang

    2007-01-01

    OBJECTIVE To investigate the effect of neoadjuvant chemotherapy in treatment of Stage II breast cancer.METHODS The data from 113 patients with breast cancer of the same pathologic type in Stage II, during the period of 1995 to 2001, were analyzed retrospectively. Among the patients, 47 were treated with neoadjuvant chemotherapy, and 66 received no adjuvant therapy before surgery (control group). After the patients of the neoadjuvant chemotherapy group had received 2 courses of chemotherapy with the CMF regimen, the surgical procedure was conducted.RESULTS Complete remission (CR) was attained in 9 of the 47 cases receiving neoadjuvant chemotherapy and partial remission (PR) was reached for 22 cases. The rate of breast-conserving surgery was enhanced from 22.73% to 46.81% (P<0.05) in the neoadjuvant treatment group. There was no difference in the 5-year overall survival (OS) and disease-free survival (DFS) rate between the two groups (P>0.05), but the 5-year OS and DFS of the cases with clinical tumor remission was higher compared to the control group (P<0.05).CONCLUSION Neoadjuvant chemotherapy can enhance the rate of breast conservation for Stage II breast cancer and may improve the prognosis of the cases with clinical remission.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-04

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

  17. Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

    DEFF Research Database (Denmark)

    Herbst, Christine; Rehan, Fareed A; Brillant, Corinne;

    2010-01-01

    Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin's lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication...

  18. Reducing the iron burden and improving survival in transfusion-dependent thalassemia patients: current perspectives

    Directory of Open Access Journals (Sweden)

    Bayanzay K

    2016-08-01

    Full Text Available Karim Bayanzay, Lama Alzoebie Department of Hematology, Gulf Medical University, Ajman, United Arab Emirates Abstract: Hypertransfusion regimens for thalassemic patients revolutionized the management of severe thalassemia; transforming a disease which previously led to early infant death into a chronic condition. The devastating effect of the accrued iron from chronic blood transfusions necessitates a more finely tuned approach to limit the complications of the disease, as well as its treatment. A comprehensive approach including carefully tailored transfusion protocol, continuous monitoring and assessment of total body iron levels, and iron chelation are currently the mainstay in treating iron overload. There are also indications for ancillary treatments, such as splenectomy and fetal hemoglobin induction. The main cause of death in iron overload continues to be related to cardiac complications. However, since the widespread use of iron chelation started in the 1970s, there has been a general improvement in survival in these patients. Keywords: hematology, chelators, deferoxamine, deferiserox, deferiprone, liver iron concentration, iron overload, serum ferritin concentration, hepatic iron storage, iron chelation therapy

  19. Incorporating movement patterns to improve survival estimates for juvenile bull trout

    Science.gov (United States)

    Bowerman, Tracy; Budy, Phaedra

    2012-01-01

    Populations of many fish species are sensitive to changes in vital rates during early life stages, but our understanding of the factors affecting growth, survival, and movement patterns is often extremely limited for juvenile fish. These critical information gaps are particularly evident for bull trout Salvelinus confluentus, a threatened Pacific Northwest char. We combined several active and passive mark–recapture and resight techniques to assess migration rates and estimate survival for juvenile bull trout (70–170 mm total length). We evaluated the relative performance of multiple survival estimation techniques by comparing results from a common Cormack–Jolly–Seber (CJS) model, the less widely used Barker model, and a simple return rate (an index of survival). Juvenile bull trout of all sizes emigrated from their natal habitat throughout the year, and thereafter migrated up to 50 km downstream. With the CJS model, high emigration rates led to an extreme underestimate of apparent survival, a combined estimate of site fidelity and survival. In contrast, the Barker model, which allows survival and emigration to be modeled as separate parameters, produced estimates of survival that were much less biased than the return rate. Estimates of age-class-specific annual survival from the Barker model based on all available data were 0.218±0.028 (estimate±SE) for age-1 bull trout and 0.231±0.065 for age-2 bull trout. This research demonstrates the importance of incorporating movement patterns into survival analyses, and we provide one of the first field-based estimates of juvenile bull trout annual survival in relatively pristine rearing conditions. These estimates can provide a baseline for comparison with future studies in more impacted systems and will help managers develop reliable stage-structured population models to evaluate future recovery strategies.

  20. The proneural molecular signature is enriched in oligodendrogliomas and predicts improved survival among diffuse gliomas.

    Directory of Open Access Journals (Sweden)

    Lee A D Cooper

    Full Text Available The Cancer Genome Atlas Project (TCGA has produced an extensive collection of '-omic' data on glioblastoma (GBM, resulting in several key insights on expression signatures. Despite the richness of TCGA GBM data, the absence of lower grade gliomas in this data set prevents analysis genes related to progression and the uncovering of predictive signatures. A complementary dataset exists in the form of the NCI Repository for Molecular Brain Neoplasia Data (Rembrandt, which contains molecular and clinical data for diffuse gliomas across the full spectrum of histologic class and grade. Here we present an investigation of the significance of the TCGA consortium's expression classification when applied to Rembrandt gliomas. We demonstrate that the proneural signature predicts improved clinical outcome among 176 Rembrandt gliomas that includes all histologies and grades, including GBMs (log rank test p = 1.16e-6, but also among 75 grade II and grade III samples (p  =  2.65e-4. This gene expression signature was enriched in tumors with oligodendroglioma histology and also predicted improved survival in this tumor type (n =  43, p  =  1.25e-4. Thus, expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for lower grade oligodendrogliomas, and likely represent important differences in tumor biology with implications for treatment and therapy. Integrated DNA and RNA analysis of low-grade and high-grade proneural gliomas identified increased expression and gene amplification of several genes including GLIS3, TGFB2, TNC, AURKA, and VEGFA in proneural GBMs, with corresponding loss of DLL3 and HEY2. Pathway analysis highlights the importance of the Notch and Hedgehog pathways in the proneural subtype. This demonstrates that the expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for low-grade oligodendrogliomas, and likely represent important differences in tumor

  1. Improved survival rate in patients with diabetes and end-stage renal disease in Denmark

    DEFF Research Database (Denmark)

    Sørensen, V R; Mathiesen, E R; Heaf, J;

    2007-01-01

    AIMS/HYPOTHESIS: We investigated the survival rate of Danish diabetic patients with end-stage renal disease (ESRD) between 1990 and 2005 and evaluated possible predictors of survival rate. MATERIALS AND METHODS: Data were obtained from the Danish National Register on Dialysis and Transplantation...

  2. Oesophageal cancer in The Netherlands : Increasing incidence and mortality but improving survival

    NARCIS (Netherlands)

    Crane, Lucia M. A.; Schaapveld, Michael; Visser, Otto; Louwmand, Marieke W. J.; Plukker, John T. M.; van Dam, Gooitzen M.

    2007-01-01

    Aim: Oesophageal cancer is highly lethal with a 5-year relative survival of 10-15%. An increasing incidence has been reported for several parts bf the Western world. We studied time trends in incidence, mortality and survival for oesophageal cancer in the Netherlands during 1989-2003. Methods: Data

  3. Stereotactic Body Radiotherapy for Pulmonary Metastases From Soft-Tissue Sarcomas: Excellent Local Lesion Control and Improved Patient Survival

    Energy Technology Data Exchange (ETDEWEB)

    Dhakal, Sughosh [Department of Radiation Oncology, University of Rochester, Rochester, NY (United States); Corbin, Kimberly S. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL (United States); Milano, Michael T.; Philip, Abraham [Department of Radiation Oncology, University of Rochester, Rochester, NY (United States); Sahasrabudhe, Deepak [Department of Medicine, Division of Hematology and Oncology, University of Rochester, Rochester, NY (United States); Jones, Carolyn [Department of Surgery, Division of Thoracic/Foregut, University of Rochester, Rochester, NY (United States); Constine, Louis S., E-mail: louis_constine@urmc.rochester.edu [Department of Radiation Oncology, University of Rochester, Rochester, NY (United States)

    2012-02-01

    Purpose: Patients with pulmonary metastases (PM) from soft-tissue sarcomas (STS) have historically been treated with surgery and/or chemotherapy. Since 2001, we have treated PM with stereotactic body radiation therapy (SBRT). We postulated that SBRT for PM from STS would yield excellent local control (LC) and overall survival (OS). Methods and Materials: Fifty-two patients with PM from STS, diagnosed between 1990 and 2006 at University of Rochester, were retrospectively reviewed. Most patients received multimodality treatment comprising of surgery, chemotherapy, and/or radiation. SBRT used the Novalis ExacTrac patient positioning platform, vacuum bag immobilization, and relaxed end-expiratory breath hold techniques. Results: Leiomyosarcoma (23%), malignant fibrous histiocytoma (19%), and synovial sarcoma (15%) were the most common histologies. Forty-eight percent initially presented with PM, whereas 52% developed PM at a median of 0.7 (0.3-7.3) years after initial diagnosis. Median follow-up from diagnosis of PM was 0.9 (0.3-7.3) years. Fifteen patients underwent SBRT to 74 lesions. Median number of lesions treated was 4 (1-16) per patient and 3.5 (1-6) per session. Preferred dose and fractionation was 50 Gy in 5 Gy fractions. Three-year LC was 82%. No patients experienced Grade {>=}3 toxicity. Median OS was 2.1 (0.8-11.5) years for patients treated with SBRT, and 0.6 (0.1-7.8) years for those who never received SBRT (p = 0.002). Conclusions: SBRT provides excellent LC of PM and may extend OS. SBRT should be considered for all patients with PM from STS, particularly those who are not surgical candidates. Further investigation is warranted to establish criteria for the use of SBRT for STS patients with PM.

  4. Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain.

    Science.gov (United States)

    Upadhyay, Urvashi M; Tyler, Betty; Patta, Yoda; Wicks, Robert; Spencer, Kevin; Scott, Alexander; Masi, Byron; Hwang, Lee; Grossman, Rachel; Cima, Michael; Brem, Henry; Langer, Robert

    2014-11-11

    Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood-brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.

  5. Is adjuvant chemotherapy necessary for patients with microinvasive breast cancer after surgery?

    Institute of Scientific and Technical Information of China (English)

    Hai-Fei Niu; Li-Juan Wei; Jin-Pu Yu; Zhen Lian; Jing Zhao; Zi-Zheng Wu; Jun-Tian Liu

    2016-01-01

    Objective:Survival and treatment of patients with microinvasive breast cancer (MIBC) remain controversial. In this paper, we evaluated whether adjuvant chemotherapy is necessary for patients with MIBC to identify risk factors influencing its prognosis and decide the indication for adjuvant chemotherapy. Methods:In this retrospective study, 108 patients with MIBC were recruited according to seventh edition of the staging manual of the American Joint Committee on Cancer (AJCC). The subjects were divided into chemotherapy and non-chemotherapy groups. We compared the 5-year disease-free survival (DFS) and overall survival (OS) rates between groups. Furthermore, we analyzed the factors related to prognosis for patients with MIBC using univariate and multivariate analyses. We also evaluated the impact of adjuvant chemotherapy on the prognostic factors by subgroup analysis after median follow-up time of 33 months (13-104 months). Results:The 5-year DFS and OS rates for the chemotherapy group were 93.7% and 97.5%, whereas those for the non-chemotherapy group were 89.7% and 100%. Results indicate that 5-year DFS was superior, but OS was inferior, in the former group compared with the latter group. However, no statistical significance was observed in the 5-year DFS (P=0.223) or OS (P=0.530) rate of the two groups. Most relevant poor-prognostic factors were Ki-67 overexpression and negative hormonal receptors. Cumulative survival was 98.2%vs. 86.5% between low Ki-67 (≤20%) and high Ki-67 (>20%). The hazard ratio of patients with high Ki-67 was 16.585 [95% confidence interval (CI), 1.969-139.724;P=0.010]. Meanwhile, ER(-)/PR(-) patients with MIBC had cumulative survival of 79.3% compared with 97.5% for ER(+) or PR(+) patients with MIBC. The hazard ratio for ER(-)/PR(-) patients with MIBC was 19.149 (95% CI, 3.702-99.057;P<0.001). Subgroup analysis showed that chemotherapy could improve the outcomes of ER(-)/PR(-) patients (P=0.014), but not those who overexpress Ki-67 (P=0

  6. A clinical review of treatment outcomes in glioblastoma multiforme - the validation in a non-trial population of the results of a randomised Phase III clinical trial: has a more radical approach improved survival?

    LENUS (Irish Health Repository)

    Rock, K

    2012-01-03

    Objective: Glioblastoma multiforme (GBM) accounts for up to 60% of all malignant primary brain tumours in adults, occurring in 2-3 cases per 100 000 in Europe and North America. In 2005, a Phase III clinical trial demonstrated a significant improvement in survival over 2, and subsequently, 5 years with the addition of concurrent and adjuvant temozolomide (TMZ) to radical radiotherapy (RT) (Stupp R, Hegi M, van den Bent M, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009:10:459-66). The aim of this study was to investigate if the demonstrated improved survival in the literature translated to clinical practice.Methods: This was a retrospective study including all patients with histologically proven GBM diagnosed from 1999 to 2008 and treated with adjuvant RT at our institution. A total of 273 patients were identified. Statistical analysis was carried out using SPSS v18.Results: The median survival for the whole group (n = 273) over the 10-year period was 7.6 months (95% confidence interval 6.7-8.4 months). Overall, the cumulative probability of survival at 1 and 2 years was 31.5 and 9.4%, respectively. In total, 146 patients received radical RT. 103 patients were treated with radical RT and TMZ and 43 patients received radical RT alone. The median survival for patients receiving radical RT with TMZ was 13.4 months (95% CI 10.9-15.8 months) vs 8.8 months for radical RT alone (95% CI 6.9 - 10.7 months, p = 0.006). 2-year survival figures were 21.2 vs 4.7%, respectively. On multivariate analysis, independent predictors of survival included KPS, RT dose, TMZ and extent of surgery. The strongest predictors of poorer outcome based on the hazard ratio were palliative RT, followed by not receiving TMZ chemotherapy, then KPS <90 and a biopsy only surgical approach.Conclusion: This paper demonstrates

  7. A clinical review of treatment outcomes in glioblastoma multiforme - the validation in a non-trial population of the results of a randomised Phase III clinical trial: has a more radical approach improved survival?

    LENUS (Irish Health Repository)

    2012-02-01

    Objective: Glioblastoma multiforme (GBM) accounts for up to 60% of all malignant primary brain tumours in adults, occurring in 2-3 cases per 100 000 in Europe and North America. In 2005, a Phase III clinical trial demonstrated a significant improvement in survival over 2, and subsequently, 5 years with the addition of concurrent and adjuvant temozolomide (TMZ) to radical radiotherapy (RT) (Stupp R, Hegi M, van den Bent M, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009:10:459-66). The aim of this study was to investigate if the demonstrated improved survival in the literature translated to clinical practice.Methods: This was a retrospective study including all patients with histologically proven GBM diagnosed from 1999 to 2008 and treated with adjuvant RT at our institution. A total of 273 patients were identified. Statistical analysis was carried out using SPSS v18.Results: The median survival for the whole group (n = 273) over the 10-year period was 7.6 months (95% confidence interval 6.7-8.4 months). Overall, the cumulative probability of survival at 1 and 2 years was 31.5 and 9.4%, respectively. In total, 146 patients received radical RT. 103 patients were treated with radical RT and TMZ and 43 patients received radical RT alone. The median survival for patients receiving radical RT with TMZ was 13.4 months (95% CI 10.9-15.8 months) vs 8.8 months for radical RT alone (95% CI 6.9 - 10.7 months, p = 0.006). 2-year survival figures were 21.2 vs 4.7%, respectively. On multivariate analysis, independent predictors of survival included KPS, RT dose, TMZ and extent of surgery. The strongest predictors of poorer outcome based on the hazard ratio were palliative RT, followed by not receiving TMZ chemotherapy, then KPS <90 and a biopsy only surgical approach.Conclusion: This paper demonstrates improved

  8. Treatment of Nausea and Vomiting During Chemotherapy.

    Science.gov (United States)

    Mustian, Karen M; Devine, Katie; Ryan, Julie L; Janelsins, Michelle C; Sprod, Lisa K; Peppone, Luke J; Candelario, Grace D; Mohile, Supriya G; Morrow, Gary R

    2011-01-01

    Nausea and vomiting are two of the most troubling side effects patients experience during chemotherapy. While newly available treatments have improved our ability to manage nausea and vomiting, anticipatory and delayed nausea and vomiting are still a major problem for patients receiving chemotherapy. Many cancer patients will delay or refuse future chemotherapy treatments and contemplate stopping chemotherapy altogether because of their fear of experiencing further nausea and vomiting. The purpose of this article is to provide an overview of the patho-psychophysiology of chemotherapy-induced nausea and vomiting and the recommended guidelines for treatment.

  9. Improving long-term survival of patients with acute myocardial infarction from 1977-1988 in a region of Denmark

    DEFF Research Database (Denmark)

    Torp-Pedersen, C; Hildebrandt, P; Køber, L;

    1995-01-01

    The aim of this investigation was to study secular trends in long-term survival following myocardial infarction (MI). Five thousand one hundred and fifty-seven consecutive cases of MI in 3942 patients were recorded in a well-defined region in the study period 1977-1988. The study period ended...... significant (P infarction was an independent predictor of survival. Patients were subdivided into a high risk group suffering from either congestive heart failure or cardiac arrest during hospitalization, and a low risk group without these complications....... Year of infarction was without importance in the high risk group but highly significant in the low risk group. Long-term survival following MI gradually improved prior to the introduction of thrombolytic therapy. The improvement was confined to low risk patients without cardiac arrest or congestive...

  10. Practical use of perioperative chemotherapy for muscle-invasive bladder cancer: summary of session at the Society of Urologic Oncology annual meeting.

    Science.gov (United States)

    Apolo, Andrea B; Grossman, Herbert Barton; Bajorin, Dean; Steinberg, Gary; Kamat, Ashish M

    2012-01-01

    At the 11th annual meeting of the Society of Urologic Oncology, an expert panel was convened to discuss the practical use of perioperative chemotherapy for muscle-invasive bladder cancer. The discussion was structured as a case-based debate among the panelists. The topics included: neoadjuvant chemotherapy with a focus on T2 disease, pros and cons, survival data, tolerability of cisplatin-based therapy, can we avoid radical cystectomy in complete responders, limitations and alternatives to cisplatin-based therapy, management of 'suboptimal' chemotherapy, residual disease after neoadjuvant chemotherapy, adjuvant chemotherapy, and key aspects of radical cystectomy and lymph-node dissection in multimodal therapy. The presentations were derived from published literature. The panelists agreed that patients with muscle-invasive bladder cancer should be managed with a multidisciplinary team, including urologist and medical oncologist. Cisplatin-based neoadjuvant chemotherapy has demonstrated improved survival and should be incorporated into the management of all eligible patients with muscle-invasive bladder cancer. However, in some centers, neoadjuvant chemotherapy is reserved for patients with >T2 disease or high-risk features. There are no data for the administration of non-cisplatin-based neoadjuvant chemotherapy, such as carboplatin-combinations. Cisplatin-ineligible patients should proceed directly to surgical extirpation with adjuvant cisplatin-based chemotherapy considered based on pathologic findings. However, the data for adjuvant chemotherapy is less compelling. As our refinement of the selection process continues, we may be able to better identify subsets of patients who may be spared chemotherapy, but much work remains to be done in this arena. The current standard for muscle-invasive bladder cancer patients is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy and pelvic lymph-node dissection.

  11. Use of Cox's Cure Model to Establish Clinical Determinants of Long-Term Disease-Free Survival in Neoadjuvant-Chemotherapy-Treated Breast Cancer Patients without Pathologic Complete Response.

    Science.gov (United States)

    Asano, Junichi; Hirakawa, Akihiro; Hamada, Chikuma; Yonemori, Kan; Hirata, Taizo; Shimizu, Chikako; Tamura, Kenji; Fujiwara, Yasuhiro

    2013-01-01

    In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC), the ordinary Cox proportional-hazards (PH) model has been often used to identify prognostic factors for disease-free survival (DFS). This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years) and may be considered clinically "cured." Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure.

  12. Use of Cox’s Cure Model to Establish Clinical Determinants of Long-Term Disease-Free Survival in Neoadjuvant-Chemotherapy-Treated Breast Cancer Patients without Pathologic Complete Response

    Directory of Open Access Journals (Sweden)

    Junichi Asano

    2013-01-01

    Full Text Available In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC, the ordinary Cox proportional-hazards (PH model has been often used to identify prognostic factors for disease-free survival (DFS. This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years and may be considered clinically “cured.” Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure.

  13. Chemotherapy e-prescribing: opportunities and challenges

    Directory of Open Access Journals (Sweden)

    Elsaid KA

    2015-05-01

    Full Text Available Khaled A Elsaid,1,2 Steven Garguilo,1 Christine M Collins2 1Department of Pharmaceutical Sciences, School of Pharmacy, MCPHS University, Boston, MA, 2Pharmacy Services, Rhode Island Hospital, Providence, RI, USA Abstract: Chemotherapy drugs are characterized by low therapeutic indices and significant toxicities at clinically prescribed doses, raising serious issues of drug safety. The safety of the chemotherapy medication use process is further challenged by regimen complexity and need to tailor treatment to patient status. Errors that occur during chemotherapy prescribing are associated with serious and life-threatening outcomes. Computerized provider order entry (CPOE systems were shown to reduce overall medication errors in ambulatory and inpatient settings. The adoption of chemotherapy CPOE is lagging due to financial cost and cultural and technological challenges. Institutions that adopted infusional or oral chemotherapy electronic prescribing modified existing CPOE systems to allow chemotherapy prescribing, implemented chemotherapy-specific CPOE systems, or developed home-grown chemotherapy electronic prescribing programs. Implementation of chemotherapy electronic prescribing was associated with a significant reduction in the risk of prescribing errors, most significantly dose calculation and adjustment errors. In certain cases, implementation of chemotherapy CPOE was shown to improve the chemotherapy use process. The implementation of chemotherapy CPOE may increase the risk of new types of errors, especially if processes are not redesigned and adapted to CPOE. Organizations aiming to implement chemotherapy CPOE should pursue a multidisciplinary approach engaging all stakeholders to guide system selection and implementation. Following implementation, organizations should develop and use a risk assessment process to identify and evaluate unanticipated consequences and CPOE-generated errors. The results of these analyses should serve to

  14. Positive end-expiratory pressure improves survival in a rodent model of cardiopulmonary resuscitation using high-dose epinephrine.

    LENUS (Irish Health Repository)

    McCaul, Conán

    2009-10-01

    Multiple interventions have been tested in models of cardiopulmonary resuscitation (CPR) to optimize drug use, chest compressions, and ventilation. None has studied the effects of positive end-expiratory pressure (PEEP) on outcome. We hypothesized that because PEEP can reverse pulmonary atelectasis, lower pulmonary vascular resistance, and potentially improve cardiac output, its use during CPR would increase survival.

  15. Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan

    Directory of Open Access Journals (Sweden)

    Chou Pesus

    2011-08-01

    Full Text Available Abstract Background Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC. Methods Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads. Results As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p p = 0.001 after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p Conclusions Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate.

  16. Neoadjuvant Chemotherapy Creates Surgery Opportunities For Inoperable Locally Advanced Breast Cancer

    Science.gov (United States)

    Wang, Minghao; Hou, Lingmi; Chen, Maoshan; Zhou, Yan; Liang, Yueyang; Wang, Shushu; Jiang, Jun; Zhang, Yi

    2017-01-01

    Neoadjuvant chemotherapy (NAC), the systematic chemotherapy given to patients with locally advanced and inoperable breast caner, has been proven to be of great clinical values. Many scientific reports confirmed NAC could effectively eliminate sub-clinical disseminated lesions of tumor, and improve long-term and disease-free survival rate of patients with locally advanced breast cancer (LABC); however, up to now, LABC is still a serious clinical issue given improved screening and early diagnosis. This study, with main focus on inoperable LABC, investigated the values of NAC in converting inoperable LABC into operable status and assessed the prognosis. Sixty-one patients with inoperable LABC were initially treated with neoadjuvant chemotherapy; their local conditions were improved to operable status. Radical surgery was exerted on 49 patients. Original chemotherapy was performed after surgery, followed by local radiotherapy. And endocrine therapy was optional according to the hormone receptor status. The quality of life for most patients with skin diabrosis was obviously improved because their local conditions were under control. For all recruited cases, the survival duration and life quality were significantly improved in patients who finished both NAC and surgery compared to those who did not. Further more, this study demonstrates improved prognostic consequences.

  17. Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Christopher A., E-mail: barkerc@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bishop, Andrew J.; Chang, Maria; Beal, Kathryn; Chan, Timothy A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-07-01

    Purpose: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Methods and Materials: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. Results: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, −0.09 to 1.17), independently of RTOG RPA class and seizure history. Conclusions: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.

  18. Improving the Survival of Arthrobacter sp., CW9 during Spray Drying Monitored by Scan Electric Microscope

    OpenAIRE

    Zhenqiang Xia; Ming Zhu; Yanqiu Zhang

    2014-01-01

    The culture of an aquaculture probiotic, i.e., Arthrobacter sp., CW9, was spray dried with different carriers/protectants, in which Scan Electric Microscope (SEM) was used to analyze the surface of micro-paticles produced by spray-drying. Matrix of protectants, inlet temperature and feed rate were optimized according to the survival rate after spray drying. Scanning electron micrographs showed that cracks formed on the particle surface were a key factor in enhancing bacteria survival during s...

  19. High procedure volume is strongly associated with improved survival after lung cancer surgery

    DEFF Research Database (Denmark)

    Lüchtenborg, Margreet; Riaz, Sharma P; Coupland, Victoria H

    2013-01-01

    Studies have reported an association between hospital volume and survival for non-small-cell lung cancer (NSCLC). We explored this association in England, accounting for case mix and propensity to resect.......Studies have reported an association between hospital volume and survival for non-small-cell lung cancer (NSCLC). We explored this association in England, accounting for case mix and propensity to resect....

  20. Types of chemotherapy

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000910.htm Types of chemotherapy To use the sharing features on this page, ... or on cancer cells. How Doctors Choose Your Chemotherapy The type and dose of chemotherapy your doctor ...

  1. Chemotherapy for Thyroid Cancer

    Science.gov (United States)

    ... Type and Stage Thyroid Cancer Treating Thyroid Cancer Chemotherapy for Thyroid Cancer Chemotherapy (chemo) uses anti-cancer drugs that are injected ... vein or muscle, or are taken by mouth. Chemotherapy is systemic therapy, which means that the drug ...

  2. Chemotherapy for Testicular Cancer

    Science.gov (United States)

    ... Type and Stage Testicular Cancer Treating Testicular Cancer Chemotherapy for Testicular Cancer Chemotherapy (chemo) is the use of drugs to treat ... that is only in the testicle. Doctors give chemotherapy in cycles, with each period of treatment followed ...

  3. Side Effects of Chemotherapy

    Science.gov (United States)

    ... Jacket Fashion Show Contact Us Side Effects of Chemotherapy Each of the chemotherapy drugs available today works in a slightly different ... few rules of thumb when it comes to chemotherapy that should always be kept in mind. Ignore ...

  4. Chemotherapy and Your Mouth

    Science.gov (United States)

    ... Treatment and Oral Health > Chemotherapy and Your Mouth Chemotherapy and Your Mouth Main Content Are You Being ... Problems Too? Remember Are You Being Treated With Chemotherapy for Cancer? If so, this booklet can help ...

  5. Advanced duodenal carcinoma:Chemotherapy efficacy and analysis of prognostic factors

    Institute of Scientific and Technical Information of China (English)

    Junbao Liu; Nan Wang; Wei Liu; Chengxu Cui; Lifang Yuan; Jinwan Wang; Shuping Shi; Zhujun Shao; Haijian Tang; Tingting Yang; Chunhui Gao

    2016-01-01

    Objective This study aimed to determine the ef icacy of chemotherapy and to identify potential chemo-therapy agents to treat advanced primary duodenal carcinoma (PDC). Methods Seventy-three patients with advanced PDC were included in the study. Response rate (RR), disease control rate (DCR), progression-free survival (PFS), overal survival (OS) and prognosis were com-pared among patients using the Cox proportional hazards model. Results The overal RR and DCR of 52 patients were 21.15% and 69.23%, respectively. The median PFS and OS times were 4.51 and 11.47 months, respectively. Pal iative chemotherapy improved the OS of patients with advanced PDC compared with patients who did not receive chemotherapy (14.28 months vs. 5.20 months, HR = 0.205, 95% CI: 0.077 to 0.547, P = 0.0016). Multivariate analysis indicated mucinous histology and liver metastasis as factors predictive of poor prognosis in patients with advanced PDC. Conclusion Pal iative chemotherapy may improve the OS of patients with advanced PDC. Mucinous histology and liver metastasis were the main prognostic factors in patients with advanced PDC.

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

    Directory of Open Access Journals (Sweden)

    Thamm Reinhard

    2006-06-01

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

  7. Comparison of Postoperative Survival and Quality of Life among Primary Bladder Cancer Patients Received Different Chemotherapy Regimens%不同化疗方案治疗原发性膀胱癌术后患者生存期与生活质量的比较

    Institute of Scientific and Technical Information of China (English)

    贾书雷; 杨东; 贾巍伟; 刘东

    2011-01-01

    Objective To observe the postoperative survival and quality of life in patients with primary bladder cancer receiving different chemotherapy regimens.Methods A total of 116 patients who met the inclusion criteria were randomized into two groups ( 58 cases each ), with the observation group underwent a long - term postoperative infusion chemotherapy regimen and the control group underwent a short - term infusion chemotherapy.The drugs were diluted to 50 mL with distilled water and in-travesical chemotherapy was performed after emptying the bladder with the drugs retained for 60 minutes.The patients were told to change the position every 15 minutes.Clinical efficacy, survival, adverse effects and quality of life improvement were compared between the two groups.Results Clinical efficacy between the two groups showed significant differences ( P < 0.05 ).Five -year survival rate was 48.3% for the observation group and 22.4% for the control group ( P <0.05 ).Quality of life score between the both groups showed no significant differences ( P > 0.05 ) before treatment; quality of life score between the both groups showed significant differences ( P < 0.05 ) after treatment.Hematologic toxicity and gastrointestinal reactions, represented by leukopenia, thrombocytopenia, anemia, nausea, vomiting, liver dysfunction, renal dysfunction, peripheral nerve toxicity, and alopecia, were the main side effects for both groups.Incidence of leukopenia, anemia recurrence, and peripheral nerve toxicity were higher in the control group than the observation group ( P < 0.05 ).Conclusion The modified long - term infusion chemotherapy can improve the clinical efficacy, quality of life, as well as survival status of the patients.%目的 探讨不同化疗方案治疗原发性膀胱癌术后患者对其生存期与生活质量的影响.方法 将符合纳入标准的116例原发性膀胱癌患者随机分为观察组、对照组,每组58例.观察组于术后行改良长期灌注

  8. Chemotherapy of ovarian cancer in elderly patients

    Institute of Scientific and Technical Information of China (English)

    Tiffany A. Troso-Sandoval; Stuart M. Lichtman

    2015-01-01

    Epithelial ovarian cancer is primarily a disease of older women. Advanced age is risk factor for decreased survival. Optimal surgery and the safe and effective administration of chemotherapy are essential for prolonged progression-free and overall survival (OS). In this article, the available regimens in both the primary treatment and relapsed setting are reviewed.

  9. Association of Metformin Use with Outcomes in Advanced Endometrial Cancer Treated with Chemotherapy.

    Science.gov (United States)

    Ezewuiro, Obiageli; Grushko, Tatyana A; Kocherginsky, Masha; Habis, Mohammed; Hurteau, Jean A; Mills, Kathryn A; Hunn, Jessica; Olopade, Olufunmilayo I; Fleming, Gini F; Romero, Iris L

    2016-01-01

    There is increasing evidence that metformin, a commonly used treatment for diabetes, might have the potential to be repurposed as an economical and safe cancer therapeutic. The aim of this study was to determine whether stage III-IV or recurrent endometrial cancer patients who are using metformin during treatment with chemotherapy have improved survival. To test this we analyzed a retrospective cohort of subjects at two independent institutions who received chemotherapy for stage III-IV or recurrent endometrial cancer from 1992 to 2011. Diagnosis of diabetes, metformin use, demographics, endometrial cancer clinico-pathologic parameters, and survival duration were abstracted. The primary outcome was overall survival. The final cohort included 349 patients, 31 (8.9%) had diabetes and used metformin, 28 (8.0%) had diabetes but did not use metformin, and 291 (83.4%) did not have diabetes. The results demonstrate that the median overall survival was 45.6 months for patients with diabetes who used metformin compared to 12.5 months for patients with diabetes who did not use metformin and 28.5 months for patients without diabetes (log-rank test comparing the three groups P = 0.006). In a model adjusted for confounders, the difference in survival between the three groups remained statistically significant (P = 0.023). The improvement in survival among metformin users was not explained by better baseline health status or more aggressive use of chemotherapy. Overall, the findings in this retrospective cohort of endometrial cancer patients with stage III-IV or recurrent disease treated with chemotherapy indicate that patients with diabetes who were concurrently treated with metformin survived longer than patients with diabetes who did not use metformin.

  10. High-dose Helical Tomotherapy With Concurrent Full-dose Chemotherapy for Locally Advanced Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Jee Suk [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Wang, Michael L.C. [Department of Radiation Oncology, National Cancer Centre (Singapore); Koom, Woong Sub; Yoon, Hong In; Chung, Yoonsun [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Song, Si Young [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Seong, Jinsil, E-mail: jsseong@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-08-01

    Purpose: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high-dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods and Materials: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between 2006 and 2009. Radiotherapy was directed to the primary tumor with a 0.5-cm margin without prophylactic nodal coverage. Twenty-nine patients (79%) received full-dose (1000 mg/m{sup 2}) gemcitabine-based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range, 3.4-43.9) for the entire cohort, and 22.5 months (range, 12.0-43.9) for the surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (21%) were converted to resectable status, including 1 with a pathological complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than Grade 3. Severe late GI toxicity ({>=}Grade 3) occurred in 10 patients (26%); 1 treatment-related death from GI bleeding was observed. Conclusion: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.

  11. Codelivery of doxorubicin and curcumin with lipid nanoparticles results in improved efficacy of chemotherapy in liver cancer.

    Science.gov (United States)

    Zhao, Xiaojing; Chen, Qi; Liu, Wei; Li, Yusang; Tang, Hebin; Liu, Xuhan; Yang, Xiangliang

    2015-01-01

    Liver cancer is a leading cause of cancer deaths worldwide. The combination therapy of cytotoxic and chemosensitizing agents loaded in nanoparticles has been highlighted as an effective treatment for different cancers. However, such studies in liver cancer remain very limited. In our study, we aim to develop a novel lipid nanoparticles loaded with doxorubicin (DOX) (an effective drug for liver cancer) and curcumin (Cur) (a chemosensitizer) simultaneously, and we examined the efficacy of chemotherapy in liver cancer. DOX and Cur codelivery lipid nanoparticles (DOX/Cur-NPs) were successfully prepared using a high-pressure microfluidics technique, showing a mean particle size of around 90 nm, a polydispersity index 90% for both DOX and Cur. The blank lipid nanoparticles were nontoxic, as determined by a cell cytotoxicity study in human normal liver cells L02 and liver cancer cells HepG2. In vitro DOX release studies revealed a sustained-release pattern until 48 hours in DOX/Cur-NPs. We found enhanced cytotoxicity and decreased inhibitory concentration (IC)50 in HepG2 cells and reduced cytotoxicity in L02 cells treated with DOX/Cur-NPs, suggesting the synergistic effects of DOX/Cur-NPs compared with free DOX and DOX nanoparticles (NPs). The optimal weight ratio of DOX and Cur was 1:1. Annexin-V-fluorescein isothiocyanate/propidium iodide double staining showed enhanced apoptosis in HepG2 cells treated with DOX/Cur-NPs compared with free DOX and DOX-NPs. An in vivo experiment showed the synergistic effect of DOX/Cur-NPs compared with DOX-NPs on liver tumor growth inhibition. Taken together, the simultaneous delivery of DOX and Cur by DOX/Cur-NPs might be a promising treatment for liver cancer.

  12. Improved renal allograft survival using the mixed lymphocyte culture for selection of nonidentical living related donors.

    Science.gov (United States)

    Riggio, R R; Saal, S D; Katz, E B; Tapia, L; White, R; Chami, J; Sheigh, J S; Sullivan, J F; Stenzel, K H; Stubenbord, W T; Whitsell, J C; Rubin, A L

    1975-01-01

    Our results concur with earlier published work, by other groups, showing that LRD-recipient pairs with low MLC stimulation usually have better and more prolonged graft success than do those with higher stimulation. Specific HL-A compatibilities or incompatibilities did not seem to affect these results, nor did the presence of an increased number of common loci, short of increasing the apparent chromosome compatibility. The presence of pre-transplant cytotoxic antibodies, in patients with a high MI, however, may unfavorably affect the LRD transplant. The overall results of our LRD transplant experience is shown in Figure 1, and superimposed upon Figure 2, is the current extrapolation of data showing MLC stimulation and haplotype success. Thus, it appears that graft survival may be improved and more closely approach the levels seen in a full-house, diplotype match, by using the MLC results in considering patients for transplantation. Not all patients with a high MLC, however, (see table) reject their grafts and it is impossible to predict pre-transplant who will develop specific allograft enhancement. Before the MI becomes a specific criteria for transplant selection, additional studies of patient stimulation in MLC should be done. Suppression of stimulation by donor cells in autologous serum, as compared to the response to unrelated controls, might provide pre-transplant clues to the presence of enhancing factors. Such studies could provide an index that would be more meaningful than the MI in AB sera alone. Since overall results from both our series and from the Transplant Registry continue to indicate better long term graft survival for LRD than for cadaver transplants, and since the evidence suggests that a successful transplant offers a patient a better quality of life, as well as decreased morbidity and mortality compared to concomitant time spent on hemodialysis, continued LRD transplants with high MI is warranted in some circumstances with the patient

  13. Neoadjuvant chemotherapy of cisplatin and fluorouracil regimen in head and neck squamous cell carcinoma: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    SU Yu-xiong; ZHENG Jia-wei; ZHENG Guang-sen; LIAO Gui-qing; ZHANG Zhi-yuan

    2008-01-01

    Background The benefit of neoadjuvant chemotherapy in the management of head and neck squamous cell carcinomas (HNSCC) still remains controversial. The aim of this meta-analysis is to evaluate the role of the neoadjuvant chemotherapy with the cisplatin and fluororacil (PF) regimen in enhancing the overall survival of and decreasing locoregional relapse and distant metastasis in HNSCC patients.Methods Medline and manual searches were performed to identify all published randomized controlled trials (RCTs) investigating the efficacy of the neoadjuvant chemotherapy with the PF regimen. Outcomes assessed by meta-analysis included Iocoregional relapse, distant metastasis, and overall survival. The odds ratio was the principle measurement of effect, which was calculated as the treatment group (chemotherapy plus Iocoregional treatment) versus the control group (Iocoregional treatment alone) and was presented as a point estimate with 95% confidence intervals (Cl).Results Eight RCTs were adopted for analysis. The meta-analysis showed that the odds ratio for the Iocoregional relapse was 0.92 (0.70-1.22, 95%Cl), which was not statistically significant. The odds ratios for distant metastasis and overall survival were 0.47 (0.33-0.68, 95% Cl) and 1.28 (1.01-1.62, 95% Cl) respectively, which were both statistically significant.Conclusions Neoadjuvant chemotherapy with the PF regimen in HNSCC patients has no effect on Iocoregional relapse. However, it shows a small but significant benefit in reducing distant metastasis and improving the overall survival.

  14. Improved tumor response and survival outcomes with post-transplant bortezomib (Btz) consolidation versus observation (Obs) alone in patients with newly diagnosed multiple myeloma (MM)

    DEFF Research Database (Denmark)

    Sezer, O.; Terpos, E.; Hajek, R.;

    2015-01-01

    Background: Induction therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a standard frontline treatment for eligible MM patients (pts). Post- ASCT consolidation can improve depth of response and long-term outcomes. This phase 2 study evaluated the effect...

  15. chemotherapy patients

    Directory of Open Access Journals (Sweden)

    Katarzyna Augustyniuk

    2016-02-01

    Full Text Available Background . Complementary and alternative medicine (CAM practices for cancer have become popular among oncology patients. An increasing interest in alternative medicine can be explained by the inefficiency of conventional treatment, dissatisfaction with treating patients like objects, and the will to use all available treatment methods. Objectives . The authors assessed how often patients use CAM methods, and which of them are most popular. Material and methods . The study was conducted in Military Hospital no. 109 and the Independent Public Clinical Hospital no. 1 in Szczecin among 100 chemotherapy patients. This survey-based study was performed using an original questionnaire. Results. Most respondents (68% did not use alternative methods to fight the disease. The most popular treatment methods were: herbal medicine (50%, alternative medicine preparations (38% and diet (25%, and the least common: hypnosis (3% and aromatherapy (3%. Analyzed sociodemographic factors had no effects on a choice of a CAM method. Patients obtained information about CAM methods mainly from the Internet (40%, medical staff (37% and literature (31%. Conclusions . 1. Using CAM by patients receiving chemotherapy for neoplasms is quite a common phenomenon. 2. CAM were more often chosen by women. Neither the duration of the disease nor sociodemographic data had effects on making the decision to use CAM methods. 3. The most popular CAM were: herbal medicine, alternative medicine preparations, and diet. 4. Cancer patients should receive special support from nurses and doctors as well as other members of the therapeutic team. Oncology patients should never be left on their own so that they were forced to seek help and support in therapies unconfirmed by scientific investigation.

  16. Hypoxic preconditioning improves survival of cardiac progenitor cells: role of stromal cell derived factor-1α-CXCR4 axis.

    Directory of Open Access Journals (Sweden)

    Fengdi Yan

    Full Text Available BACKGROUND: Cardiac progenitor cells (CPCs have been shown to be suitable in stem cell therapy for resurrecting damaged myocardium, but poor retention of transplanted cells in the ischemic myocardium causes ineffective cell therapy. Hypoxic preconditioning of cells can increase the expression of CXCR4 and pro-survival genes to promote better cell survival; however, it is unknown whether hypoxia preconditioning will influence the survival and retention of CPCs via the SDF-1α/CXCR4 axis. METHODS AND RESULTS: CPCs were isolated from adult mouse hearts and purified by magnetic activated cell sorting using c-kit magnetic beads. These cells were cultured at various times in either normoxic or hypoxic conditions, and cell survival was analyzed using flow cytometry and the expression of hypoxia-inducible factor-1α (HIF-1α, CXCR4, phosphorylated Akt and Bcl-2 were measured by Western blot. Results showed that the expression of pro-survival genes significantly increased after hypoxia treatment, especially in cells cultured in hypoxic conditions for six hours. Upon completion of hypoxia preconditioning from c-kit+ CPCs for six hours, the anti-apoptosis, migration and cardiac repair potential were evaluated. Results showed a significant enhancement in anti-apoptosis and migration in vitro, and better survival and cardiac function after being transplanted into acute myocardial infarction (MI mice in vivo. The beneficial effects induced by hypoxia preconditioning of c-kit+ CPCs could largely be blocked by the addition of CXCR4 selective antagonist AMD3100. CONCLUSIONS: Hypoxic preconditioning may improve the survival and retention of c-kit+ CPCs in the ischemic heart tissue through activating the SDF-1α/CXCR4 axis and the downstream anti-apoptosis pathway. Strategies targeting this aspect may enhance the effectiveness of cell-based cardiac regenerative therapy.

  17. Clinical Studies of Postoperative Arterial Infusion Chemotherapy in Patients with Pathologic T3 Esophageal Squamous Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Baodong Liu; Zongjun Dong; Xiuyi Zhi; Qingsheng Xu

    2006-01-01

    OBJECTIVE To evaluate how arterial infusion chemotherapy after radical surgery influences long-term survival of patients with pathologic T3 (pT3) esophageal squamous carcinoma.METHODS We divided 190 patients with pathologic pT3 esophageal squamous carcinoma, confirmed by consecutive radical surgery, into an experimental group (surgery + intra-arterial infusion, 56 T3N0M0 and 52 T3N1M0 cases), and the remaining patients into a control group (surgery alone, 48 T3N0M0 and 34 T3N1M0 cases). The experimental group was sub-grouped into 56 cases (26 T3N0M0 and 30 T3N1M0 cases) receiving 1 or 2 periods of chemotherapy, while 52 cases (30 T3N0M0 and 22 T3N1M0 cases) underwent 3 or more than 3 periods of chemotherapy. We used one to seven courses of selected arterial infusion chemotherapy of cisplatin (80 mg/m2 of body-surface area) and fluorouracil (800 mg/m2) with or without epirubicin at 3~4 weeks post operation. The interval between each period was 3~4 weeks. All cases were followed-up for more than 5 years. Survival rates were calculated by the Kaplan-Meier methods and survival differences between patients with and without selected arterial infusion chemotherapy were compared with the Log-rank test. Prognostic variables were entered into a Cox regression analysis model controlling for age, site, lymph node status, and treatment received.RESULTS The overall survival rates were not significantly different between the experimental group and the control group, but there was better survival for patients who received 3 or more than 3 courses of chemotherapy. Lymph node status (N) was an important factor in the prognosis.CONCLUSION Trans-catheter arterial infusion chemotherapy is a safe and effective method of therapy. Postoperative selective arterial infusion chemotherapy can improve the survival rate in patients with esophageal squamous carcinoma who were previously treated by radical surgery.However, this modality of therapy needs further investigation.

  18. Colorectal cancers detected through screening are associated with lower stages and improved survival

    DEFF Research Database (Denmark)

    Lindebjerg, Jan; Osler, Merete; Bisgaard, Claus

    2014-01-01

    detected through screening were diagnosed at significantly lower stages than among screening non-responders. There were relatively fewer locally advanced rectal cancers among patients diagnosed through positive FOBT than among non-responders. Survival among screening cancer patients was superior...... to that of all other screening groups. No effect of lead time was detected. Neither stage nor survival among patients who had a negative FOBT was inferior to the unscreened Danish population. CONCLUSION: The positive effect on survival among screening cancer patients is neither outbalanced by more advanced......INTRODUCTION: Population screening for colorectal cancer (CRC) using faecal occult blood test (FOBT) will be introduced in Denmark in 2014. Prior to the implementation of the screening programme, a feasibility study was performed in 2005-2006. In this paper, occurrences of colorectal cancer...

  19. Colorectal cancers detected through screening are associated with lower stages and improved survival

    DEFF Research Database (Denmark)

    Lindebjerg, Jan; Osler, Merete; Bisgaard, Claus Hedebo

    2014-01-01

    in the distribution of colon cancer stages and rectal cancer groups between the various screening categories were analysed through χ(2)-tests. Survival analysis with respect to screening groups was done by Kaplan-Meier and Cox-Mantel hazard ratios, and survival was corrected for lead time. RESULTS: Colon cancers......INTRODUCTION: Population screening for colorectal cancer (CRC) using faecal occult blood test (FOBT) will be introduced in Denmark in 2014. Prior to the implementation of the screening programme, a feasibility study was performed in 2005-2006. In this paper, occurrences of colorectal cancer...... in the feasibility study cohort were reviewed with respect to the effect of screening participation on stages and survival. MATERIAL AND METHODS: All cases of CRC in a feasibility study cohort diagnosed from the beginning of the study until two years after the study ended were identified. Differences...

  20. Improving the Survival of Arthrobacter sp., CW9 during Spray Drying Monitored by Scan Electric Microscope

    Directory of Open Access Journals (Sweden)

    Zhenqiang Xia

    2014-03-01

    Full Text Available The culture of an aquaculture probiotic, i.e., Arthrobacter sp., CW9, was spray dried with different carriers/protectants, in which Scan Electric Microscope (SEM was used to analyze the surface of micro-paticles produced by spray-drying. Matrix of protectants, inlet temperature and feed rate were optimized according to the survival rate after spray drying. Scanning electron micrographs showed that cracks formed on the particle surface were a key factor in enhancing bacteria survival during spray-drying. Span-60 had synergism with Skim Milk Powder (SMP: trehalose (7.5%: 7.5%, w/v in protecting Arthrobacter sp., CW9 bacteria from heat injury, unlike SMP with trehalose. Particle size is an important factor influencing bacteria survival during spray drying and particle size itself was influenced by certain additives.

  1. Improved survival prediction from lung function data in a large population sample

    DEFF Research Database (Denmark)

    Miller, M.R.; Pedersen, O.F.; Lange, P.

    2008-01-01

    mortality in the Copenhagen City Heart Study data. Cox regression models were derived for survival over 25 years in 13,900 subjects. Age on entry, sex, smoking status, body mass index, previous myocardial infarction and diabetes were putative predictors together with FEV1 either as raw data, standardised....... In univariate predictions of all cause mortality the HR for FEV1/ht(2) categories was 2-4 times higher than those for FEV1PP and 3-10 times higher for airway related tung disease mortality. We conclude that FEV1/ht(2) is superior to FEV1PP for predicting survival. in a general population and this method...

  2. Chemotherapy or radio-chemotherapy for advanced adenocarcinoma of the oesophagus and cardiac orifice; Adenocarcinomes du bas oesophage et du cardia: quelle chimiotherapie ou chimioradiotherapie dans le traitement des recidives et des metastases

    Energy Technology Data Exchange (ETDEWEB)

    Seitz, J.F.; Duffaud, F.; Dahan, L.; Ries, P.; Ville, E.; Laugier, R. [Centre Hospitalier Universitaire de la Timone, 13 - Marseille (France)

    2001-11-01

    Adenocarcinomas of esophagus and cardia represent in France approximately 20 to 40% of the esophagus cancers. They have a high risk to develop lymph nodes metastases and liver metastases. Currently, only 50 to 70% of patients may benefit from surgical curative resection at diagnosis, but more than 50% of them will recur. The standard of treatment of these metastatic adenocarcinomas is chemotherapy. Three large randomized comparative studies, between chemotherapy and supportive care, showed that chemotherapy significantly extends the median of survival (from 3-4 months to 10-12 months) and improves the quality of life. Currently, the combination of epirubicin-cisplatin-continuous 5FU (ECF) is the most effective regimen but it is difficult to administer and tolerate because of the long continuous 5FU infusion. In France, the most commonly used combination regimen still associates 5FU and cisplatin. New drugs (such as docetaxel, CPT11, oxaliplatin) used alone or in combination, especially with 5U, are very promising. Radio-chemotherapy is the preferred treatment for locoregional recurrences, because it improves dysphagia and enables to obtain complete tumor responses. Current results from concomitant radio-chemotherapy studies for esophagus cancer, based on 5FU alone, 5FU-cisplatin or 5FU-mitomycin, given as preoperative treatment or as exclusive treatment, support to use radio-chemotherapy for the treatment of loco-regional recurrences after surgical resection. Nevertheless, the optimal radio-chemotherapy schedule still remain to be defined (dose, duration, splitting of radiotherapy, choice of anticancer drugs). (authors)

  3. Quinic Acid Could Be a Potential Rejuvenating Natural Compound by Improving Survival of Caenorhabditis elegans under Deleterious Conditions

    Science.gov (United States)

    Zhang, Longze; Zhang, Junjing

    2012-01-01

    Abstract Quinic acid (QA) is an active ingredient of Cat's Claw (Uncaria tomentosa), which is found to be active in enhancing DNA repair and immunity in model systems and able to generate neuroprotective effects in neurons. However, QA's role in improving survival is not well studied. Here we report that QA can provide protection in Caenorhabidits elegans and improve worm survival under stress. Under heat stress and oxidative stress, QA-treated wild-type C. elegans N2 (N2) survived 17.8% and 29.7% longer, respectively, than the control worms. Our data suggest that under heat stress, QA can upregulate the expression of the small heat shock protein hsp-16.2 gene, which could help the worms survive a longer time. We also found that QA extended the C. elegans mutant VC475 [hsp-16.2 (gk249)] life span by 15.7% under normal culture conditions. However, under normal culture conditions, QA did not affect hsp-16.2 expression, but upregulated the expression of daf-16 and sod-3 in a DAF-16–dependent manner, and downregulated the level of reactive oxygen species (ROS), suggesting that under normal conditions QA acts in different pathways. As a natural product, QA demonstrates great potential as a rejuvenating compound. PMID:22950425

  4. The clinical effects of DC-CIK cells combined with chemotherapy in the treatment of advanced NSCLC%DC-CIK联合化疗治疗非小细胞肺癌的临床疗效评价

    Institute of Scientific and Technical Information of China (English)

    Junping Zhang; Jiangtao Wang; Tianliang Shi; Guanghua Mao; Yaping Han; Xiaoling Yang; Huijing Feng; Linzi Jia; Ting Zhi; Yan Xiao; Libin Zhang

    2012-01-01

    Objective: The aim of the study was to evaluate the safety and therapeutic effects of autologous dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) combined with chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Methods: Fifty patients with advanced NSCLC (stages III to IV), who had received therapies in our Center (Department of Biotherapy, Affiliated to Cancer Hospital of Shanxi Medical University, Taiyuan, China) from August 2008 to January 2010, were treated by DC-CIK + chemotherapy as the combined treatment group; fifty advanced NSCLC patients treated with chemotherapy at the same time served as controls. The immunologic function, short-term therapeutic effects, the 1-year survival rate, the life quality, the chemotherapy side effects were compared between the two groups, the safety and therapeutic effects of DC-CIK cells therapy were observed too. Results: There was no obvious change of subsets of T cells in peripheral blood before and after therapy in DC-CIK + chemotherapy group, and IFN-γ was improved after therapy in this group (P < 0.05); in chemotherapy alone group, the ratios of CD3+CD4+, CD3+CD8+, CD3-CD56+ cells and the secretion of IL-2, TNF-α decreased significantly after therapy (P < 0.05); the ratios of CD3+CD8+, CD3+CD56+ were improved after cell culture (P < 0.05). The disease control rate (DCR) of DC-CIK + chemotherapy group was higher than that in the chemotherapy alone group (78.0% vs 56.0%, P < 0.05); the 1-year survival rates of DC-CIK + chemotherapy group and chemotherapy alone group were 50% and 44% respectively, had no significant difference. Compared with chemotherapy alone group, the occurrence of chemotherapy side effects (including bone marrow suppression, nausea and vomiting, peripheral nerve toxicity) was less in the DC-CIK + chemotherapy group (P < 0.05). The physical and appetite were better in DC-CIK + chemotherapy group after therapy. Conclusion: To compare with simple chemotherapy, DC

  5. Centralized treatment of advanced stages of ovarian cancer improves survival: a nationwide Danish survey

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Høgdall, Claus; Kehlet, Henrik;

    2011-01-01

    Objective. This retrospective, nationwide, observational study was designed to compare treatment in tertiary referral centers vs. regional hospitals on overall survival for patients with stage IIIC and IV ovarian cancer. Material and methods. The study took place in all gynecological departments ...

  6. [Clinical efficacy of decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen on elderly patients with high risk myelodysplastic syndrome and acute myeloid leukemia].

    Science.gov (United States)

    Dou, Li-Ping; Jing, Yu; Wang, Quan-Shun; Mei, Jun-Hui; Yu, Li

    2013-06-01

    This study was aimed to observe the clinical efficacy and adverse effects of decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen on elderly patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Five elderly patients with MDS and AML were treated with decitabine plus improved CAG chemotherapy and donor peripheral lymphocyte infusion regimen. Examinations on liver and renal function, electrocardiogram and bone marrow analysis were performed before and after treatment, and adverse effects were observed. The results indicated that after a course of treatment by decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen, the total effective rate was 100%, and 4 patients (80%) achieved complete remission, 1 patient achieved partial remission. The dominant clinical adverse effect was bone marrow depression, the median time of neutrophil>0.5×10(9)/L and platelet>20×10(9)/L was 15 d and 16 d respectively for patients without previous MDS. It is concluded that decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen may be effective with less adverse effects for elderly primary AML and high risk MDS patients, it is a promising therapeutic methods and worthy to deeply study.

  7. Modelling p-value distributions to improve theme-driven survival analysis of cancer transcriptome datasets

    Directory of Open Access Journals (Sweden)

    Brors Benedikt

    2010-01-01

    Full Text Available Abstract Background Theme-driven cancer survival studies address whether the expression signature of genes related to a biological process can predict patient survival time. Although this should ideally be achieved by testing two separate null hypotheses, current methods treat both hypotheses as one. The first test should assess whether a geneset, independent of its composition, is associated with prognosis (frequently done with a survival test. The second test then verifies whether the theme of the geneset is relevant (usually done with an empirical test that compares the geneset of interest with random genesets. Current methods do not test this second null hypothesis because it has been assumed that the distribution of p-values for random genesets (when tested against the first null hypothesis is uniform. Here we demonstrate that such an assumption is generally incorrect and consequently, such methods may erroneously associate the biology of a particular geneset with cancer prognosis. Results To assess the impact of non-uniform distributions for random genesets in such studies, an automated theme-driven method was developed. This method empirically approximates the p-value distribution of sets of unrelated genes based on a permutation approach, and tests whether predefined sets of biologically-related genes are associated with survival. The results from a comparison with a published theme-driven approach revealed non-uniform distributions, suggesting a significant problem exists with false positive rates in the original study. When applied to two public cancer datasets our technique revealed novel ontological categories with prognostic power, including significant correlations between "fatty acid metabolism" with overall survival in breast cancer, as well as "receptor mediated endocytosis", "brain development", "apical plasma membrane" and "MAPK signaling pathway" with overall survival in lung cancer. Conclusions Current methods of theme

  8. Improved Auditory Nerve Survival with Nanoengineered Supraparticles for Neurotrophin Delivery into the Deafened Cochlea

    Science.gov (United States)

    Tan, Justin; Wang, Yajun; Caruso, Frank; Shepherd, Robert K.

    2016-01-01

    Cochlear implants electrically stimulate spiral ganglion neurons (SGNs) in order to provide speech cues to severe-profoundly deaf patients. In normal hearing cochleae the SGNs depend on endogenous neurotrophins secreted by sensory cells in the organ of Corti for survival. SGNs gradually degenerate following deafness and consequently there is considerable interest in developing clinically relevant strategies to provide exogenous neurotrophins to preserve SGN survival. The present study investigated the safety and efficacy of a drug delivery system for the cochlea using nanoengineered silica supraparticles. In the present study we delivered Brain-derived neurotrophic factor (BDNF) over a period of four weeks and evaluated SGN survival as a measure of efficacy. Supraparticles were bilaterally implanted into the basal turn of cochleae in profoundly deafened guinea pigs. One ear received BDNF-loaded supraparticles and the other ear control (unloaded) supraparticles. After one month of treatment the cochleae were examined histologically. There was significantly greater survival of SGNs in cochleae that received BDNF supraparticles compared to the contralateral control cochleae (repeated measures ANOVA, p = 0.009). SGN survival was observed over a wide extent of the cochlea. The supraparticles were well tolerated within the cochlea with a tissue response that was localised to the site of implantation in the cochlear base. Although mild, the tissue response was significantly greater in cochleae treated with BDNF supraparticles compared to the controls (repeated measures ANOVA, p = 0.003). These data support the clinical potential of this technology particularly as the supraparticles can be loaded with a variety of therapeutic drugs. PMID:27788219

  9. Palliative resection of the primary tumor is associated with improved overall survival in incurable stage IV colorectal cancer: A nationwide population-based propensity-score adjusted study in the Netherlands.

    Science.gov (United States)

    't Lam-Boer, Jorine; Van der Geest, Lydia G; Verhoef, Cees; Elferink, Marloes E; Koopman, Miriam; de Wilt, Johannes H

    2016-11-01

    As the value of palliative primary tumor resection in stage IV colorectal cancer (CRC) is still under debate, the purpose of this population-based study was to investigate if palliative primary tumor resection as the initial treatment after diagnosis was associated with improved overall survival. All patients with stage IV colorectal adenocarcinoma (2008-2011) were selected from the Netherlands Cancer Registry, and patients undergoing treatment with curative intent (i.e., metastasectomy, radiofrequency ablation and/or hyperthermic intraperitoneal chemotherapy), or best supportive care were excluded. After propensity score matching, a multivariable Cox proportional hazard model was performed to determine the association between treatment strategy and mortality. From a total group of 10,371 patients with stage IV CRC, 2,746 patients (26%) underwent an elective palliative resection of the primary tumor, whether or not followed by systemic therapy, and 3,345 patients (32%) were initially treated with palliative systemic therapy. After propensity score matching, median overall survival in these groups was 17.2 months (95% CI 16.3-18.1) and 11.5 months (95% CI 11.0-12.0), respectively. In Cox regression analysis, primary tumor resection was significantly associated with improved overall survival (hazard ratio of death = 0.44 [95% CI 0.35-0.55], p population-based study shows an overall survival benefit for patients with incurable stage IV CRC who underwent primary tumor resection as the initial treatment after diagnosis, compared to patients who started systemic therapy with the primary tumor in situ. This result is an argument in favor of resection of the primary tumor, even when patients have little to no symptoms.

  10. Neoadjuvant intraarterial chemotherapy and embolization in treatment of advanced ovarian epithelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    刘恩令; 糜若然

    2004-01-01

    Background The purpose of the study was to evaluate the role of neoadjuvant chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries in treating patients with advanced ovarian epithelial carcinoma.Methods Forty-two patients with advanced ovarian epithelial carcinoma (study group) were treated via the anterior branches of the bilateral internal iliac arteries after cytoreductive surgery and 7 courses of adjuvant platinum-based combination chemotherapy. Primary cytoreductive surgery was performed in 43 patients with advanced ovarian epithelial carcinoma (control group), and then followed by 8 courses of adjuvant platinum-based combination chemotherapy. The rate of optimal cytoreductive surgery, survival rate, blood loss during operation and operative time were investigated in the two groups. Statistical significance was asessed using Student's t test, the Chi-squre test and the log-rank test. Results In the study group, the rate of optimum debulking after platinum-based chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries was 71.43%(30/42) (χ2=10.06, P0.05).Conclusions Neoadjuvant platinum-based combination chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries is an alternative treatment for patients with advanced ovarian epithelial carcinoma, in whom the chance of optimal cytoreductive surgery is low. The treatment can reduce blood loss, decrease operative time, and increase the rate of optimal cytoreductive surgery; but the median survival can't be improved significantly.

  11. Chemotherapy Plus Cetuximab versus Chemotherapy Alone for Patients with KRAS Wild Type Unresectable Liver-Confined Metastases Colorectal Cancer: An Updated Meta-Analysis of RCTs

    Science.gov (United States)

    Lv, W.; Zhang, G. Q.; Jiao, A.; Zhao, B. C.; Shi, Y.; Chen, B. M.

    2017-01-01

    Purpose. Our study analyses clinical trials and evaluates the efficacy of adding cetuximab in systematic chemotherapy for unresectable colorectal cancer liver-confined metastases patients. Materials and Methods. Search EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials for RCTs comparing chemotherapy plus cetuximab with chemotherapy alone for KRAS wild type patients with colorectal cancer liver metastases (CRLMs). We calculated the relative risks (RRs) with 95% confidence interval and performed meta-analysis of hazard ratios (HRs) for the R0 resection rate, the overall response rate (ORR), the progression-free survival (PFS) and overall survival (OS). Results. 1173 articles were retrieved and 4 RCTs were available for our study. The four studies involved 504 KRAS wild type patients with CRLMs. The addition of cetuximab significantly improved all the 4 outcomes: the R0 resection rate (RR 2.03, p = 0.004), the ORR (RR 1.76, p < 0.00001), PFS (HR 0.63, p < 0.0001), and also OS (HR 0.74, p = 0.04); the last outcome is quite different from the conclusion published before. Conclusions. Although the number of patients analysed was limited, we found that the addition of cetuximab significantly improves the outcomes in KRAS wild type patients with unresectable colorectal cancer liver-confined metastases. Cetuximab combined with systematic chemotherapy perhaps suggests a promising choice for KRAS wild type patients with unresectable liver metastases. PMID:28167959

  12. Adipose-derived mesenchymal stem cell administration does not improve corneal graft survival outcome.

    Directory of Open Access Journals (Sweden)

    Sherezade Fuentes-Julián

    Full Text Available The effect of local and systemic injections of mesenchymal stem cells derived from adipose tissue (AD-MSC into rabbit models of corneal allograft rejection with either normal-risk or high-risk vascularized corneal beds was investigated. The models we present in this study are more similar to human corneal transplants than previously reported murine models. Our aim was to prevent transplant rejection and increase the length of graft survival. In the normal-risk transplant model, in contrast to our expectations, the injection of AD-MSC into the graft junction during surgery resulted in the induction of increased signs of inflammation such as corneal edema with increased thickness, and a higher level of infiltration of leukocytes. This process led to a lower survival of the graft compared with the sham-treated corneal transplants. In the high-risk transplant model, in which immune ocular privilege was undermined by the induction of neovascularization prior to graft surgery, we found the use of systemic rabbit AD-MSCs prior to surgery, during surgery, and at various time points after surgery resulted in a shorter survival of the graft compared with the non-treated corneal grafts. Based on our results, local or systemic treatment with AD-MSCs to prevent corneal rejection in rabbit corneal models at normal or high risk of rejection does not increase survival but rather can increase inflammation and neovascularization and break the innate ocular immune privilege. This result can be partially explained by the immunomarkers, lack of immunosuppressive ability and immunophenotypical secretion molecules characterization of AD-MSC used in this study. Parameters including the risk of rejection, the inflammatory/vascularization environment, the cell source, the time of injection, the immunosuppression, the number of cells, and the mode of delivery must be established before translating the possible benefits of the use of MSCs in corneal transplants to clinical

  13. Palliative Care Improves Survival, Quality of Life in Advanced Lung Cancer | Division of Cancer Prevention

    Science.gov (United States)

    Results from the first randomized clinical trial of its kind have revealed a surprising and welcome benefit of early palliative care for patients with advanced lung cancer—longer median survival. Although several researchers said that the finding needs to be confirmed in other trials of patients with other cancer types, they were cautiously optimistic that the trial results could influence oncologists’ perceptions and use of palliative care. |

  14. Encapsulated Whole Bone Marrow Cells Improve Survival in Wistar Rats after 90% Partial Hepatectomy

    Directory of Open Access Journals (Sweden)

    Carolina Uribe-Cruz

    2016-01-01

    Full Text Available Background and Aims. The use of bone marrow cells has been suggested as an alternative treatment for acute liver failure. In this study, we investigate the effect of encapsulated whole bone marrow cells in a liver failure model. Methods. Encapsulated cells or empty capsules were implanted in rats submitted to 90% partial hepatectomy. The survival rate was assessed. Another group was euthanized at 6, 12, 24, 48, and 72 hours after hepatectomy to study expression of cytokines and growth factors. Results. Whole bone marrow group showed a higher than 10 days survival rate compared to empty capsules group. Gene expression related to early phase of liver regeneration at 6 hours after hepatectomy was decreased in encapsulated cells group, whereas genes related to regeneration were increased at 12, 24, and 48 hours. Whole bone marrow group showed lower regeneration rate at 72 hours and higher expression and activity of caspase 3. In contrast, lysosomal-β-glucuronidase activity was elevated in empty capsules group. Conclusions. The results show that encapsulated whole bone marrow cells reduce the expression of genes involved in liver regeneration and increase those responsible for ending hepatocyte division. In addition, these cells favor apoptotic cell death and decrease necrosis, thus increasing survival.

  15. Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

    Directory of Open Access Journals (Sweden)

    Xiaojie Wang

    2015-01-01

    Full Text Available Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1 or fibroblasts (FB, group 2 under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P<0.001 without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation.

  16. Hair follicle dermal sheath derived cells improve islet allograft survival without systemic immunosuppression.

    Science.gov (United States)

    Wang, Xiaojie; Hao, Jianqiang; Leung, Gigi; Breitkopf, Trisia; Wang, Eddy; Kwong, Nicole; Akhoundsadegh, Noushin; Warnock, Garth L; Shapiro, Jerry; McElwee, Kevin J

    2015-01-01

    Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1) or fibroblasts (FB, group 2) under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P < 0.001) without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation.

  17. Tumour infiltrating lymphocytes correlate with improved survival in patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Jiang, Dongxian; Liu, Yalan; Wang, Hao; Wang, Haixing; Song, Qi; Sujie, Akesu; Huang, Jie; Xu, Yifan; Zeng, Haiying; Tan, Lijie; Hou, Yingyong; Xu, Chen

    2017-03-21

    We undertook a study of tumour infiltrating lymphocytes (TILs) in a large and relatively homogeneous group of patients with completely resected esophageal squamous cell carcinoma (ESCC). Hematoxylin and eosin-stained sections of 235 ESCC tumours were evaluated for density of TILs in intratumoural (iTIL) and stromal compartments (sTIL). Foxp3+, CD4+, and CD8+ T cells in tumoural and stromal areas were evaluated by immunohistochemistry. Of the 235 tumours, high sTIL (>10%), and iTIL (>10%) were observed in 101 (43.0%) and 98 (41.7%), respectively. The median follow-up period was 36.0 months (95% CI 29.929-42.071). Univariate analysis revealed that sTIL (>10%), iTIL (>20%), vessels involvement, lymph node metastasis, and clinical stage were significantly associated with postoperative outcome. In multivariate analysis, high sTIL (HR: 0.664, P = 0.019 for Disease free survival; HR: 0.608, P = 0.005 for Overall survival) was identified as independent better prognostic factor. Further analysis, sTIL was identified as independently prognostic factor in Stage III-IVa disease, which was not found in Stage I-II disease. Our study demonstrated that sTIL was associated with better ESCC patients' survival, especially in Stage III-IVa disease. Assessment of sTIL could be useful to discriminate biological behavior for ESCC patients.

  18. Antibody/doxycycline combined therapy for pulmonary ricinosis: Attenuation of inflammation improves survival of ricin-intoxicated mice

    Directory of Open Access Journals (Sweden)

    Yoav Gal

    2014-01-01

    Full Text Available Ricin, a highly toxic plant-derived toxin, is considered a potential weapon in biological warfare due to its high availability and ease of preparation. Pulmonary exposure to ricin results in the generation of an acute edematous inflammation followed by respiratory insufficiency and death. Passive immunization with polyclonal anti-ricin antibodies conferred protection against pulmonary ricinosis, however, at clinically-relevant time points for treatment, survival rates were limited. In this study, intranasal instillation of a lethal dose of ricin to mice, served as a lung challenge model for the evaluation and comparison of different therapeutic modalities against pulmonary ricinosis. We show that treatment with doxycycline resulted in a significant reduction of pro-inflammatory cytokines, markers of oxidative stress and capillary permeability in the lungs of the mice. Moreover, survival rates of mice intoxicated with ricin and treated 24 h later with anti-ricin antibody were significantly improved by co-administration of doxycycline. In contrast, co-administration of the steroid drug dexamethasone with anti-ricin antibodies did not increase survival rates when administered at late hours after intoxication, however dexamethasone did exert a positive effect on survival when applied in conjunction with the doxycycline treatment. These studies strongly suggest that combined therapy, comprised of neutralizing anti-ricin antibodies and an appropriate anti-inflammatory agent, can promote high-level protection against pulmonary ricinosis at clinically-relevant time points post-exposure.

  19. Change of SPARC expression after chemotherapy in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Yong-Yin Gao; Xin-Yuan Zhang; Yi Ba; Ding-Zhi Huang; Ru-Bing Han; Xia Wang; Shao-Hua Ge; Hong-Li Li; Ting Deng; Rui Liu; Ming Bai; Li-Kun Zhou

    2015-01-01

    Objective:The expression of tumor biomarkers may change after chemotherapy. However, whether secreted protein acidic and rich in cysteine (SPARC) expression changes atfer chemotherapy in gastric cancer (GC) is unclear. hTis study investigated the inlfuence of chemotherapy on SPARC expression in GC. Methods:Immunohistochemistry was used to analyze SPARC expression in 132 GC cases (including 54 cases with preoperative chemotherapy and 78 cases without preoperative chemotherapy). SPARC expression of postoperative specimens with and without preoperative chemotherapy was assessed to analyze the inlfuence of chemotherapy on SPARC expression. Results:SPARC was highly expressed in GC compared with the desmoplastic stroma surrounding tumor cells and noncancerous tissues. High SPARC expression was correlated with invasion depth, lymph node, and TNM stage. After chemotherapy, a lower proportion of high SPARC expression was observed in patients with preoperative chemotherapy than in the controls. For 54 patients with preoperative chemotherapy, gross type, histology, depth of invasion, lymph node, TNM stage, and SPARC expression were related to overall survival. Further multivariate analysis showed that lymph node, histology, and SPARC expression atfer chemotherapy were independent prognostic factors. Conclusion:SPARC expression may change after chemotherapy in GC. SPARC expression should be reassessed for patients with GC atfer chemotherapy.

  20. Surgical salvage improves overall survival for HPV-positive and HPV-negative recurrent locoregional and distant metastatic oropharyngeal cancer

    Science.gov (United States)

    Guo, Theresa; Qualliotine, Jesse R.; Ha, Patrick K.; Califano, Joseph A.; Kim, Young; Saunders, John R.; Blanco, Ray; D'Souza, Gypsyamber; Zhang, Zhe; Chung, Christine H.; Kiess, Ana; Gourin, Christine G.; Koch, Wayne; Richmon, Jeremy D.; Agrawal, Nishant; Eisele, David W.; Fakhry, Carole

    2015-01-01

    Background Human papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for distant metastatic disease are limited. Methods A retrospective analysis of patients with recurrent OPSCC from two institutions between 2000-2012 was performed. P16 immunohistochemistry and/or in situ hybridization, as clinically available, were used to determine HPV tumor status. Clinical characteristics, distribution of recurrence site and treatment modalities were compared by HPV tumor status. Overall survival was examined by Kaplan-Meier and Cox proportional hazards methods. Results The study included 108 patients with 65 locoregional and 43 distant metastatic first recurrences. The majority were HPV-positive (n=80). HPV-positive tumor status was associated with longer time to recurrence (p<0.01). Anatomic site distribution of recurrences did not differ by HPV tumor status. HPV-positive tumor status (adjusted HR [aHR] 0.23 (95%CI 0.09-0.58), p=0.002), longer time to recurrence (≥1 year; aHR 0.36 (0.18-0.74), p=0.006), and surgical salvage (aHR 0.26 (0.12-0.61), p=0.002) were independently associated with overall survival after recurrence. Surgical salvage was independently associated with improved overall survival compared to non-surgical treatment in both locoregional (aHR 0.15 (0.04-0.56), p=0.005) and distant metastatic recurrence (aHR 0.19 (0.05-0.75), p=0.018). Conclusions Surgical salvage is associated with improved overall survival for recurrent locoregional and distant metastatic OPSCC, independent of HPV tumor status. Further prospective data is needed to confirm the role of surgical salvage for distant metastases. PMID:25782027

  1. Effectiveness of early antiretroviral therapy initiation to improve survival among HIV-infected adults with tuberculosis: a retrospective cohort study.

    Directory of Open Access Journals (Sweden)

    Molly F Franke

    2011-05-01

    Full Text Available BACKGROUND: Randomized clinical trials examining the optimal time to initiate combination antiretroviral therapy (cART in HIV-infected adults with sputum smear-positive tuberculosis (TB disease have demonstrated improved survival among those who initiate cART earlier during TB treatment. Since these trials incorporated rigorous diagnostic criteria, it is unclear whether these results are generalizable to the vast majority of HIV-infected patients with TB, for whom standard diagnostic tools are unavailable. We aimed to examine whether early cART initiation improved survival among HIV-infected adults who were diagnosed with TB in a clinical setting. METHODS AND FINDINGS: We retrospectively reviewed charts for 308 HIV-infected adults in Rwanda with a CD4 count ≤ 350 cells/µl and a TB diagnosis. We estimated the effect of cART on survival using marginal structural models and simulated 2-y survival curves for the cohort under different cART strategies:start cART 15, 30, 60, or 180 d after TB treatment or never start cART. We conducted secondary analyses with composite endpoints of (1 death, default, or lost to follow-up and (2 death, hospitalization, or serious opportunistic infection. Early cART initiation led to a survival benefit that was most marked for individuals with low CD4 counts. For individuals with CD4 counts of 50 or 100 cells/µl, cART initiation at day 15 yielded 2-y survival probabilities of 0.82 (95% confidence interval: [0.76, 0.89] and 0.86 (95% confidence interval: [0.80, 0.92], respectively. These were significantly higher than the probabilities computed under later start times. Results were similar for the endpoint of death, hospitalization, or serious opportunistic infection. cART initiation at day 15 versus later times was protective against death, default, or loss to follow-up, regardless of CD4 count. As with any observational study, the validity of these findings assumes that biases from residual confounding by

  2. Response of a patient with pleural and peritoneal mesothelioma after second-line chemotherapy with lipoplatin and gemcitabine.

    Science.gov (United States)

    Karpathiou, Georgia; Argiana, Evangelia; Koutsopoulos, Anastassios; Froudarakis, Marios E

    2007-01-01

    We report the case of a 56-year-old patient with malignant pleural mesothelioma of epithelial type, who responded to second-line chemotherapy with lipoplatin plus gemcitabine. Diagnosis and staging of the disease was done by medical thoracoscopy with biopsies of the right pleura in December 2003, when he was treated with talc pleurodesis. Eighteen months later, he presented with pleural effusion of the left side and underwent first-line chemotherapy with cisplatin plus vinorelbine. After 8 cycles, the patient presented renal toxicity limiting further cisplatinum chemotherapy and disease progression with peritoneal invasion of the tumor and ascites. Treatment with lipoplatin-gemcitabine was decided on in November 2006, and the patient showed important improvement in the clinical status and peritoneal effusion. He survived for 36 weeks, with symptom-free survival of 34 weeks.

  3. Preoperative docetaxel/cisplatin/5-fluorouracil chemotherapy in patients with locally advanced gastro-esophageal adenocarcinoma.

    Science.gov (United States)

    Bayraktar, Ulas Darda; Bayraktar, Soley; Hosein, Peter; Chen, Emerson; Koniaris, Leonidas G; Rocha-Lima, Caio Max S; Montero, Alberto J

    2012-09-01

    Perioperative chemotherapy plus surgery improves survival compared to surgery alone in GE junctional (GEJ) and gastric adenocarcinomas. The docetaxel/cisplatin/5-fluorouracil (DCF) combination is superior to CF in patients with metastatic gastric cancer. We retrospectively evaluated the safety and efficacy of preoperative DCF chemotherapy in patients with locally advanced gastric and GEJ cancer. Twenty-one gastric and 10 gastroesophageal junctional (GEJ) cancer patients received 2-3 cycles of preoperative docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1, 5-FU 750 mg/m(2) (continuous infusion) on days 1-5 every 3 weeks. Clinical response was evaluated by comparing pre- and postchemotherapy CT scans. Overall survival (OS) and progression-free survival (PFS) were calculated from the initiation of chemotherapy. None of the patients achieved complete clinical remission while 11 (35%) patients achieved partial clinical remission. Ten patients with GEJ cancer (100%) and 13 with gastric cancer (62%) underwent curative surgery (P = 0.023). Seventeen (55%) patients experienced grade 3-4 chemotherapy-related adverse events. The most common adverse events were anemia, nausea/vomiting, diarrhea, and febrile neutropenia. At a median follow-up of 17.0 months, median OS and PFS were 26.1 months (95% CI: 22.7-29.5) and 18.8 months (95% CI: 9.9-27.7), respectively. The DCF regimen is active in patients with gastric and GEJ adenocarcinoma in the preoperative setting.

  4. Hepatic arterial infusion pump chemotherapy for colorectal liver metastases: an old technology in a new era.

    Science.gov (United States)

    Ko, Y J; Karanicolas, P J

    2014-02-01

    Aggressive treatment of colorectal cancer (crc) liver metastases can yield long-term survival and cure. Unfortunately, most patients present with technically unresectable metastases; conventional therapy in such patients consists of systemic therapy. Despite advances in the effectiveness of systemic therapy in the first-line setting, the tumour response rate and median survival remain low in the second-line setting. The preferential blood supply from the hepatic artery to crc liver metastases allows for excellent regional delivery of chemotherapy. Here, we review efficacy and safety data for hepatic artery infusion (hai) pump chemotherapy in patients with metastatic crc from the 5-fluorouracil era and from the era of modern chemotherapy. In selected patients with liver-only or liver-dominant disease who have progressed on first-line chemotherapy, hai combined with systemic agents is a viable therapeutic option when performed at experienced centres. Furthermore, significantly improved survival has been demonstrated with adjuvant hai therapy after liver resection in the phase iii setting. The complication rates and local toxicities associated with hai pump therapy are infrequent at experienced centres and can be managed with careful follow-up and early intervention. The major obstacles to the wide adoption of hai therapy include technical expertise for pump insertion and maintenance, and for floxuridine dose modification. The creation of formal preceptor-focused education and training in hai therapy for interdisciplinary medical professionals might encourage the creation and expansion of this liver-directed approach.

  5. Clinical Benefit of Second-Line Palliative Chemotherapy in Advanced Soft-Tissue Sarcoma

    Directory of Open Access Journals (Sweden)

    Anna Minchom

    2010-01-01

    Full Text Available Background. This paper aimed to assess the utility of second-line chemotherapy in patients with advanced soft-tissue sarcoma. Materials and Methods. A retrospective search of a prospectively maintained database identified patients treated between 1991 and 2005. Patients with gastrointestinal stromal tumours, small round cell tumours, and Ewing's sarcoma were excluded. Response was assessed using WHO and RECIST. Patients who achieved stable disease for 6 months or more were classified as having disease control. Results. Three hundred and seventy-nine patients received second-line chemotherapy. Eighty-six (22.7% achieved disease control. Median duration of response was 11 months (95% CI: 9–13. On multivariate analysis, pathological subtype, absence of lung metastases, and the use of combination chemotherapy were independent predictors of disease control. Twenty-eight (16.1% patients who failed to respond to first-line therapy achieved disease control. Eight (2.1% patients had sufficient downstaging to enable complete surgical resection. Progression-free survival was 23% at 6 months. Median overall survival was 8 months (95% CI: 7–10 months. On multivariate analysis, synovial histology and absence of lung metastases were associated with improved survival. Conclusion. Second-line chemotherapy can provide clinical benefit in over 20% of soft-tissue sarcoma patients.

  6. Chemotherapy versus support cancer treatment in advanced gastric cancer: a meta-analysis

    Directory of Open Access Journals (Sweden)

    L. Casaretto

    2006-04-01

    Full Text Available The aim of the present study was to compare the efficacy of chemotherapy and support treatment in patients with advanced non-resectable gastric cancer in a systematic review and meta-analysis of randomized clinical trials that included a comparison of chemotherapy and support care treatment in patients diagnosed with gastric adenocarcinoma, regardless of their age, gender or place of treatment. The search strategy was based on the criteria of the Cochrane Base, using the following key words: 1 randomized clinical trials and antineoplastic combined therapy or gastrointestinal neoplasm, 2 stomach neoplasm and drug therapy, 3 clinical trial and multi-modality therapy, 4 stomach neoplasm and drug therapy or quality of life, 5 double-blind method or clinical trial. The search was carried out using the Cochrane, Medline and Lilacs databases. Five studies fulfilled the inclusion criteria, for a total of 390 participants, 208 (53% receiving chemotherapy, 182 (47% receiving support care treatment and 6 losses (1.6%. The 1-year survival rate was 8% for support care and 20% for chemotherapy (RR = 2.14, 95% CI = 1.00-4.57, P = 0.05; 30% of the patients in the chemotherapy group and 12% in the support care group attained a 6-month symptom-free period (RR = 2.33, 95% CI = 1.41-3.87, P < 0.01. Quality of life evaluated after 4 months was significantly better for the chemotherapy patients (34%; RR = 2.07, 95% CI = 1.31-3.28, P < 0.01 with tumor mass reduction (RR = 3.32, 95% CI = 0.77-14.24, P = 0.1. Chemotherapy increased the 1-year survival rate of the patients and provided a longer symptom-free period of 6 months and an improvement in quality of life.

  7. "Coming to grips" with chemotherapy-induced premature menopause.

    Science.gov (United States)

    Knobf, M Tish

    2008-04-01

    Chemotherapy for early stage breast cancer has significantly improved survival outcomes but is associated with ovarian toxicity, resulting in early menopause for many premenopausal women. A qualitative study was conducted that generated a grounded theory explaining how women carried on with life in response to breast cancer and menopause. My purpose in this article is to describe three distinct types of responses from women in that study: making the best of it, struggling and barely noticing. The degree of menopausal symptom distress and perceived level of preparation for the menopause experience had the greatest influence on the type of response.

  8. RGDS-fuctionalized alginates improve the survival rate of encapsulated embryonic stem cells during cryopreservation.

    Science.gov (United States)

    Sambu, S; Xu, X; Schiffer, H A; Cui, Z F; Ye, H

    2011-01-01

    Cryopreservation of stem cells, especially embryonic stem cells, is problematic because of low post-thaw cell survival rates and spontaneous differentiation following recovery. In this investigation, mouse embryonic stem cells (mESCs) were encapsulated in arginine-glycine-aspartic acid-serine (RGDS)-coupled calcium alginates (1.2 percent, w/v), allowed to attach to the substratum and then cryopreserved in 10 percent (v/v) dimethyl sulfoxide (DMSO) solution at a slow cooling rate of 1 C per min. RGDS coupling to alginate was confirmed by Transmission Fourier Transform Infra-Red spectroscopy (T-FTIR) and quantified by using ninhydrin-Ultraviolet/Visible light (ninhydrin-UV/VIS) assay. Flow cytometry data showed that mESCs cryopreserved in RGDS-alginate beads had a higher expression of stem cell markers compared with cells cryopreserved in suspension or cells cryopreserved in unmodified alginates. Cell viability after thawing was assessed using trypan blue exclusion assay and monitored using Alamar blue assay for 6 hours. It was shown that post-thaw cell survival rate was significantly higher for cells encapsulated in RGDS-modified alginate (93 ± 2 percent, mean and standard error) than those in suspension (52 ± 2 percent) or in unmodified alginates (62 ± 3 percent). These results showed that cells encapsulated and attached to a substratum have better survival rate and stem cell marker expression 24 hours after cryopreservation than those in suspension. Encapsulation in RGDS-alginate was optimized for peptide concentration, cryoprotective agent loading time and cooling rate. The best result was obtained when using 12.5 mg peptide per g alginate, 30 minutes loading time and 1 C per min cooling rate.

  9. Fasudil improves survival and promotes skeletal muscle development in a mouse model of spinal muscular atrophy

    OpenAIRE

    Bowerman Melissa; Murray Lyndsay M; Boyer Justin G; Anderson Carrie L; Kothary Rashmi

    2012-01-01

    Abstract Background Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. It is caused by mutations/deletions of the survival motor neuron 1 (SMN1) gene and is typified by the loss of spinal cord motor neurons, muscular atrophy, and in severe cases, death. The SMN protein is ubiquitously expressed and various cellular- and tissue-specific functions have been investigated to explain the specific motor neuron loss in SMA. We have previously shown that the RhoA/Rho kinase (...

  10. Slow and stepped re-warming after acute low temperature exposure do not improve survival of Drosophila melanogaster larvae.

    Science.gov (United States)

    Sinclair, Brent J; Rajamohan, Arun

    2008-01-01

    We tested that hypothesis that slow re-warming rates would improve the ability of Drosophila melanogaster Meigen larvae to survive acute low temperature exposure. Four larval stages (1(st), 2(nd), 3(rd) instars and wandering stage 3(rd) instars) of four wild-type strains were exposed to -7 degrees C for periods of time expected to result in 90 % mortality. Larvae were then either directly transferred to their rearing temperature (21 degrees C), or returned to this temperature in a stepwise fashion (pausing at 0 and 15 degrees C) or by slow warming at 1 or 0.1 degrees C/min. We observed a reduced rapid cold-hardening effect and no general increase in survival of acute chilling in larvae re-warmed in a stepwise or slow fashion, and hypothesise that slow re-warming may result in accumulation of further chill injuries.

  11. Toxicity during l-LV/5FU adjuvant chemotherapy as a modified RPMI regimen for patients with colorectal cancer.

    Science.gov (United States)

    Hotta, Tsukasa; Takifuji, Katsunari; Arii, Kazuo; Yokoyama, Shozo; Matsuda, Kenji; Higashiguchi, Takashi; Tominaga, Toshiji; Oku, Yoshimasa; Yamaue, Hiroki

    2005-08-01

    l-leucovorin (LV)/5-fluorouracil (5FU) may play an important role, as an adjuvant chemotherapy, in improving the survival of patients with stage III colorectal cancer. However, severe toxicity of the chemotherapeutic agent could be fatal. Adverse effects, including bone marrow suppression, liver damage, renal damage, and glucose tolerance, were evaluated daily during 3 courses of l-LV/5FU-modified RPMI regimen adjuvant chemotherapy for 22 patients with stage III colorectal cancer. Decrease in the serum levels of neutrophils and platelets occurred in the 1st course, which became more obvious after three or four administrations of l-LV/5FU in the 1st course. Furthermore, serum levels of leukocytes, neutrophils, and platelets on the re-start day of this chemotherapy after 2-week intervals were lower than those on the start day of this chemotherapy. In the evaluation of liver damage, renal damage, and glucose tolerance; serum alanine aminotransferase level in the 2nd course, serum total bilirubin (T.Bil) level in the 1st course, and serum creatinine level in the 1st course deteriorated during the course. T.Bil levels on the re-start day of this chemotherapy after 2-week intervals were especially high compared to that on the start day. The more courses of this chemotherapy we perform, the more attention we must pay to bone marrow suppression and hyperbilirubinemia. Thus, we clarified the attentive point of side effect of l-LV/5FU adjuvant chemotherapy for colorectal cancer.

  12. Significant survival improvement of patients with recurrent breast cancer in the periods 2001-2008 vs. 1992-2000

    Directory of Open Access Journals (Sweden)

    Nishimura Sumiko

    2011-03-01

    Full Text Available Abstract Background It is unclear whether individualized treatments based on biological factors have improved the prognosis of recurrent breast cancer. The purpose of this study is to evaluate the survival improvement of patients with recurrent breast cancer after the introduction of third generation aromatase inhibitors (AIs and trastuzumab. Methods A total of 407 patients who received first diagnosis of recurrent breast cancer and treatment at National Kyushu Cancer Center between 1992 and 2008 were retrospectively evaluated. As AIs and trastuzumab were approved for clinical use in Japan in 2001, the patients were divided into two time cohorts depending on whether the cancer recurred before or after 2001. Cohort A: 170 patients who were diagnosed between 1992 and 2000. Cohort B: 237 patients who were diagnosed between 2001 and 2008. Tumor characteristics, treatments, and outcome were compared. Results Fourteen percent of cohort A and 76% of cohort B received AIs and/or trastuzumab (P Conclusions The prognosis of patients with recurrent breast cancer was improved over time following the introduction of AIs and trastuzumab and the survival improvement was apparent in HR- and/or HER-2-positive tumors.

  13. Codelivery of curcumin and doxorubicin by MPEG-PCL results in improved efficacy of systemically administered chemotherapy in mice with lung cancer

    Science.gov (United States)

    Wang, Bi-Lan; Shen, Yong-mei; Zhang, Qiong-wen; Li, Yu-li; Luo, Min; Liu, Ze; Li, Yan; Qian, Zhi-yong; Gao, Xiang; Shi, Hua-shan

    2013-01-01

    Systemic administration of chemotherapy for cancer often has toxic side effects, limiting the doses that can be used in its treatment. In this study, we developed methoxy poly(ethylene glycol)-poly(caprolactone) (MPEG-PCL) micelles loaded with curcumin and doxorubicin (Cur-Dox/MPEG-PCL) that were tolerated by recipient mice and had enhanced antitumor effects and fewer side effects. It was shown that these Cur-Dox/MPEG-PCL micelles could release curcumin and doxorubicin slowly in vitro. The long circulation time of MPEG-PCL micelles and the slow rate of release of curcumin and doxorubicin in vivo may help to maintain plasma concentrations of active drug. We also demonstrated that Cur-Dox/MPEG-PCL had improved antitumor effects both in vivo and in vitro. The mechanism by which Cur-Dox/MPEG-PCL micelles inhibit lung cancer might involve increased apoptosis of tumor cells and inhibition of tumor angiogenesis. We found advantages using Cur-Dox/MPEG-PCL micelles in the treatment of cancer, with Cur-Dox/MPEG-PCL achieving better inhibition of LL/2 lung cancer growth in vivo and in vitro. Our study indicates that Cur-Dox/MPEG-PCL micelles may be an effective treatment strategy for cancer in the future. PMID:24101869

  14. Beneficial native bacteria improve survival and mycorrhization of desert truffle mycorrhizal plants in nursery conditions.

    Science.gov (United States)

    Navarro-Ródenas, Alfonso; Berná, Luis Miguel; Lozano-Carrillo, Cecilia; Andrino, Alberto; Morte, Asunción

    2016-10-01

    Sixty-four native bacterial colonies were isolated from mycorrhizal roots of Helianthemum almeriense colonized by Terfezia claveryi, mycorrhizosphere soil, and peridium of T. claveryi to evaluate their effect on mycorrhizal plant production. Based on the phylogenetic analysis of the 16S rDNA partial sequence, 45 different strains from 17 genera were gathered. The largest genera were Pseudomonas (40.8 % of the isolated strains), Bacillus (12.2 % of isolated strains), and Varivorax (8.2 % of isolated strains). All the bacteria were characterized phenotypically and by their plant growth-promoting rhizobacteria (PGPR) traits (auxin and siderophore production, phosphate solubilization, and ACC deaminase activity). Only bacterial combinations with several PGPR traits or Pseudomonas sp. strain 5, which presents three different PGPR traits, had a positive effect on plant survival and growth. Particularly relevant were the bacterial treatments involving auxin release, which significantly increased the root-shoot ratio and mycorrhizal colonization. Moreover, Pseudomonas mandelii strain 29 was able to considerably increase mycorrhizal colonization but not plant growth, and could be considered as mycorrhiza-helper bacteria. Therefore, the mycorrhizal roots, mycorrhizosphere soil, and peridium of desert truffles are environments enriched in bacteria which may be used to increase the survival and mycorrhization in the desert truffle plant production system at a semi-industrial scale.

  15. Hormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans

    Science.gov (United States)

    Kumsta, Caroline; Chang, Jessica T.; Schmalz, Jessica; Hansen, Malene

    2017-01-01

    Stress-response pathways have evolved to maintain cellular homeostasis and to ensure the survival of organisms under changing environmental conditions. Whereas severe stress is detrimental, mild stress can be beneficial for health and survival, known as hormesis. Although the universally conserved heat-shock response regulated by transcription factor HSF-1 has been implicated as an effector mechanism, the role and possible interplay with other cellular processes, such as autophagy, remains poorly understood. Here we show that autophagy is induced in multiple tissues of Caenorhabditis elegans following hormetic heat stress or HSF-1 overexpression. Autophagy-related genes are required for the thermoresistance and longevity of animals exposed to hormetic heat shock or HSF-1 overexpression. Hormetic heat shock also reduces the progressive accumulation of PolyQ aggregates in an autophagy-dependent manner. These findings demonstrate that autophagy contributes to stress resistance and hormesis, and reveal a requirement for autophagy in HSF-1-regulated functions in the heat-shock response, proteostasis and ageing. PMID:28198373

  16. Survival and longevity improvements at extreme ages: an interpretation assuming an ecological stress theory of aging.

    Science.gov (United States)

    Parsons, Peter A

    2007-04-01

    The primary determinant of survival during aging is the energetic efficiency and metabolic stability required to counter the accumulated internal and external stresses of a lifetime. Hence, genetically stress-resistant individuals should accumulate with age; frailer, less robust, less energetically efficient and less metabolically stable individuals should succumb in parallel. This selection process implies the accumulation of energetically efficient stress-resistant individuals with age to the exclusion of all others. High additive genetic variability for survival is expected under extreme circumstances, however there is limited evidence close to the absolute extremes of life that diversity may fall. At this stage, only a few highly adaptive, oxidative-stress-resistant and presumably somewhat homozygous genotypes should remain. Therefore a fall in variability may occur in these outliers, when frailer individuals are unable to cope and are eliminated at extreme ages. This process could provide an explanation of mortality-rate declines in domesticated (laboratory) and free-living populations of the extremely old. That is, mortality-rate declines may be an expectation from a process of genetic sorting resulting from the accumulated responses to environmental stress over time. Application of an ecological stress theory of aging, which combines the external stresses to which organisms are exposed with internal stresses, appears to be the prerequisite for this conclusion.

  17. Does adding risk-trends to survival models improve in-hospital mortality predictions? A cohort study

    Directory of Open Access Journals (Sweden)

    Forster Alan J

    2011-07-01

    Full Text Available Abstract Background Clinicians informally assess changes in patients' status over time to prognosticate their outcomes. The incorporation of trends in patient status into regression models could improve their ability to predict outcomes. In this study, we used a unique approach to measure trends in patient hospital death risk and determined whether the incorporation of these trend measures into a survival model improved the accuracy of its risk predictions. Methods We included all adult inpatient hospitalizations between 1 April 2004 and 31 March 2009 at our institution. We used the daily mortality risk scores from an existing time-dependent survival model to create five trend indicators: absolute and relative percent change in the risk score from the previous day; absolute and relative percent change in the risk score from the start of the trend; and number of days with a trend in the risk score. In the derivation set, we determined which trend indicators were associated with time to death in hospital, independent of the existing covariates. In the validation set, we compared the predictive performance of the existing model with and without the trend indicators. Results Three trend indicators were independently associated with time to hospital mortality: the absolute change in the risk score from the previous day; the absolute change in the risk score from the start of the trend; and the number of consecutive days with a trend in the risk score. However, adding these trend indicators to the existing model resulted in only small improvements in model discrimination and calibration. Conclusions We produced several indicators of trend in patient risk that were significantly associated with time to hospital death independent of the model used to create them. In other survival models, our approach of incorporating risk trends could be explored to improve their performance without the collection of additional data.

  18. Comparison of efficacy of different route of administration of chemotherapy on unresectable, advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Zhang Caihua

    2012-08-01

    Full Text Available Abstract Background The aim of this study was to compare the efficacy of two neoadjuvant chemotherapies (FLEEOX and XELOX with different routes of administration for unresectable gastric cancer. Methods A total of 85 patients with unresectable gastric cancer hospitalized from January 2007 to December 2009 received neoadjuvant chemotherapy. The FLEEOX group (48 patients received the FLEEOX regimen(fluorouracil, leucovorin, http://epirubicin, epotoside, and oxaliplatin, which combined arterial with venous administration for one or two cycles, while the XELOX group (37 patients received XELOX (capecitabine plus oxaliplatin via venous administration for two to four cycles. The clinical response and overall survival of the two groups were compared. Results In the FLEEOX group, the clinical response rate (RR of chemotherapy was 85.4% (41 of 48 patients and the median survival time was 25 months. The 1-year and 2-year disease-free survival (DFS rates were 85.4% and 45.8%, respectively. In the XELOX group, the clinical RR was 59.5% and the median survival time was 9 months, while the 1-year and 2-year survival rates were 35.2% and 8.3%, respectively. The clinical RR, the R0 resection rate, the median survival time, and the 1-year and 2-year DFS rates were significantly better (P 0.05 in the FLEEOX group than in the XELOX group. In addition, there were no significant differences in the rates of toxic and adverse reactions or post-operative complications between the two groups. Conclusions For patients with a preoperative diagnosis of unresectable gastric cancer, the efficacy of the FLEEOX regimen, which combines arterial with venous administration, was better than that of the XELOX regimen, using venous administration only. This combination of arterial and venous administration could be useful for improving the efficacy of neoadjuvant chemotherapy for gastric cancer.

  19. Cold stress improves the ability of Lactobacillus plantarum L67 to survive freezing.

    Science.gov (United States)

    Song, Sooyeon; Bae, Dong-Won; Lim, Kwangsei; Griffiths, Mansel W; Oh, Sejong

    2014-11-17

    The stress resistance of bacteria is affected by the physiological status of the bacterial cell and environmental factors such as pH, salts and temperature. In this study, we report on the stress response of Lactobacillus plantarum L67 after four consecutive freeze-thaw cycles. The cold stress response of the cold-shock protein genes (cspC, cspL and cspP) and ATPase activities were then evaluated. The cold stress was adjusted to 5 °C when the bacteria were growing at the mid-exponential phase. A comparative proteomic analysis was performed with two-dimensional gel electrophoresis (2D SDS-PAGE) and a matrix assisted laser desorption/ionization-mass spectrometer. Only 56% of the L. plantarum L67 cells without prior exposure to cold stress survived after four consecutive freeze-thaw cycles. However, 78% of the L. plantarum L67 cells that were treated with cold stress at 5 °C for 6 h survived after freeze-thaw conditions. After applying cold stress to the culture for 6h, the cells were then stored for 60 days at 5 °C, 25 °C and 35 °C separately. The cold-stressed culture of L. plantarum L67 showed an 8% higher viability than the control culture. After applying cold stress for 6h, the transcript levels of two genes (cspP and cspL) were up-regulated 1.4 (cspP) and 1.2 (cspL) times compared to the control. However, cspC was not up-regulated. A proteomic analysis showed that the proteins increased after a reduction of the incubation temperature to 5 °C. The importance of the expression of 13 other relevant proteins was also determined through the study. The exposure of L. plantarum cells to low temperatures aids their ability to survive through subsequent freeze-thaw processes and lyophilization.

  20. Combined chemotherapy including platinum derivatives for medulloblastoma. The usefulness as maintenance chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Hikaru; Otani, Mitsuhiro; Yoshida, Kazunari; Kagami, Hiroshi; Shimazaki, Kenji; Toya, Shigeo; Kawase, Takeshi [Keio Univ., Tokyo (Japan). School of Medicine

    1997-02-01

    The authors reviewed 24 cerebellar medulloblastoma patients treated at Keio University to determine usefulness of combined chemotherapy including platinum derivatives (cisplatin, carboplatin) as the induction and maintenance treatment. All patients underwent radical surgery and craniospinal irradiation. Ten received adjuvant chemotherapy other than platinum derivatives (mainly with nitrosourea compounds), five were treated by induction and maintenance chemotherapy including platinum derivatives, and nine patients did not undergo chemotherapy. The progression-free survival rate of patients treated with platinum derivatives was better than that of patients treated with other modes of chemotherapy and also that of patients who did not receive chemotherapy. The results were especially good in the case of four patients treated with maintenance chemotherapy consisting of carboplatin and etoposide, two of whom had been free from relapse beyond the risk period of Collins. The occurrences of toxicity in maintenance chemotherapy with carboplatin and etoposide were limited to transient leucopenia. The present study indicates combined chemotherapy including platinum derivatives benefits patients with medulloblastoma, and could be useful, especially as maintenance treatment. (author)

  1. Angiotensin AT2-receptor stimulation improves survival and neurological outcome after experimental stroke in mice

    DEFF Research Database (Denmark)

    Schwengel, Katja; Namsolleck, Pawel; Lucht, Kristin;

    2016-01-01

    of C21 on neurological outcome, infarct size and expression of BDNF or GAP-43 in AT2-KO mice. From these data, it can be concluded that AT2R stimulation attenuates early mortality and neurological deficits after experimental stroke through neuroprotective mechanisms in an AT2R-specific way. Key message......This study investigated the effect of post-stroke, direct AT2-receptor (AT2R) stimulation with the non-peptide AT2R-agonist compound 21 (C21) on infarct size, survival and neurological outcome after middle cerebral artery occlusion (MCAO) in mice and looked for potential underlying mechanisms. C57...... • AT2R stimulation after MCAO in mice reduces mortality and neurological deficits.• AT2R stimulation increases BDNF synthesis and protects neurons from apoptosis.• The AT2R-agonist C21 acts protectively when applied post-stroke and peripherally....

  2. Intracellular trehalose improves the survival of human red blood cells by freeze-drying

    Institute of Scientific and Technical Information of China (English)

    HE Hui; LIU Baolin; HUA Zezhao; LI Chuan; WU Zhengzheng

    2007-01-01

    Freeze-drying of human red blood cells has a potential important application for blood transfusion.The aim of this study was to investigate the effects ofintracellular trehalose on the survival of red blood cells after freeze-drying and rehydration.Fresh red blood cells were incubated in trehalose solutions of various concentrations at 37℃ for 7 h following freeze-drying.Polyvinylpyrrolidone,Trehalose,sodium citrate,and human serum albumin were used as extracellular protective agents for the freeze-drying of red blood cells.The results indicated that the intracellular trehalose concentration was increased with increasing concentration of extracellular trehalose solution,and the maximum concen tration of intracellular trehalose reached 35 mmol/L.The viability of freeze-dried red blood cells increased with the increment of intracellular trehalose concentration.

  3. Improving pharmacokinetic-pharmacodynamic modeling to investigate anti-infective chemotherapy with application to the current generation of antimalarial drugs.

    Directory of Open Access Journals (Sweden)

    Katherine Kay

    poorly reported in the malaria literature, severely reducing its value for subsequent re-application, and we make specific recommendations to improve this situation.

  4. Chemically modified tetracycline (COL-3) improves survival if given 12 but not 24 hours after cecal ligation and puncture.

    Science.gov (United States)

    Halter, Jeffrey M; Pavone, Lucio A; Steinberg, Jay M; Gatto, Louis A; DiRocco, Joseph; Landas, Steve; Nieman, Gary F

    2006-12-01

    Sepsis can result in excessive and maladaptive inflammation that is responsible for more than 215,00 deaths per year in the United State alone. Current strategies for reducing the morbidity and mortality associated with sepsis rely on treatment of the syndrome rather than prophylaxis. We have been investigating a modified tetracycline, COL-3, which can be given prophylactically to patients at high risk for developing sepsis. Our group has shown that COL-3 is very effect at preventing the sequelae of sepsis if given before or immediately after injury in both rat and porcine sepsis models. In this study, we wanted to determine the "treatment window" for COL-3 after injury at which it remains protective. Sepsis was induced by cecal ligation and puncture (CLP). Rats were anesthetized and placed into five groups: CLP (n = 20) = CLP without COL-3, sham (n = 5) = surgery without CLP or COL-3, COL3@6h (n = 10) = COL-3 given by gavage 6 h after CLP, COL3@12h (n = 10) = COL-3 given by gavage 12 h after CLP, and COL3@24h (n = 20) = COL-3 given by gavage 24 h after CLP. COL-3 that was given at 6 and 12 h after CLP significantly improved survival as compared with the CLP and the CLP@24h groups. Improved survival was associated with a significant improvement in lung pathology assessed morphologically. These data suggest that COL-3 can be given up to 12 h after trauma and remain effective.

  5. Cell of origin predicts outcome to treatment with etoposide-containing chemotherapy in young patients with high-risk diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Gang, Anne O; Pedersen, Mette Ø; Knudsen, Helle;

    2015-01-01

    Addition of etoposide to the R-CHOP chemotherapy regimen with cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab (R-CHOEP) has resulted in improved survival in young patients with high-risk diffuse large B-cell lymphoma (DLBCL). It is not known whether biological factors can...

  6. Increased proliferation activity measured by immunoreactive Ki67 is associated with survival improvement in rectal/recto sigmoid cancer

    Institute of Scientific and Technical Information of China (English)

    Eeva Salminen; Salla Palmu; Tero Vahlberg; Peter J. Roberts; Karl-Owe S(o)derstr(o)m

    2005-01-01

    AIM: To assess the expression of Ki67 as prognosticator in rectal/recto sigmoid cancer.METHODS: Samples from 146 patients with rectal and recto sigmoid cancer were studied for expression of Ki67 and its prognostic significance in comparison with clinicopathological predictors of survival. Formalin-fixed, paraffin-embedded tissues from 6 (4.1%) patients with T1, 26 (17.8%) with T2, 94 (64.4%) with T3, and 20 (13.7%) with T4 tumors were studied. Ki67 expression was determined immunohistochemically. Samples were divided according to mean value into high (>40%) and low (≤40%) expression. Areas of extensive proliferation (>50%) were defined as 'hot spot' areas. RESULTS: Hot spot areas were present in samples regardless of histopathological grade. Lower TNM and Dukes stage and higher expression of Ki67 and presence of Ki67 hot spot areas in histopathological samples were associated with better survival, whereas no association was observed with histopathological grade (P = 0.78). In Cox multivariate regression analysis, significant prognostic factors were Dukes stage (P<0.001), presence of lymph node metastases (P = 0.015), age (P = 0.035) andpresence of Ki67 hot spot areas (P = 0.044). CONCLUSION: Proliferative activity as measured by Ki67 in rectal cancer is associated with survival improvement compared with patients with low Ki67. Areas of prognostically significant increased proliferation were found independently of histopathological tumor grade.

  7. Third-Line Chemotherapy for Metastatic Urothelial Cancer: A Retrospective Observational Study.

    Science.gov (United States)

    Di Lorenzo, Giuseppe; Buonerba, Carlo; Bellelli, Teresa; Romano, Concetta; Montanaro, Vittorino; Ferro, Matteo; Benincasa, Alfonso; Ribera, Dario; Lucarelli, Giuseppe; De Cobelli, Ottavio; Sonpavde, Guru; De Placido, Sabino

    2015-12-01

    The prognosis of locally advanced (T3/T4 or N1) and metastatic disease urothelial carcinoma is poor. In this retrospective study, we reviewed data about patients receiving third-line chemotherapy for metastatic disease, in view of the lack of data in this setting.We retrospectively analyzed medical records of patients with a pathologic diagnosis of urothelial carcinoma treated with systemic chemotherapy for metastatic disease at 4 participating Institutions between January, 2010, and January, 2015. Cox proportional hazards regression was used to evaluate the association of the chemotherapy agent used versus others with overall survival, adjusted for 5 externally validated prognostic factors in advanced urothelial carcinoma.Of 182 patients that received first-line chemotherapy/adjuvant chemotherapy as defined above, 116 patients (63.73%) received second-line salvage treatment. Fifty-two patients were finally included in this analysis, whereas 9 were excluded due to missing data. Third-line chemotherapy was based on cyclophosphamide, platinum, vinflunine, taxanes, and gemcitabine in 16, 12, 11, 10, and 3 patients, respectively. Median PFS (progression-free survival) and OS (overall survival) of the population were 13 (10-17) and 31 (28-36) weeks. Single-agent cyclophosphamide was associated with a PFS of 18 (13-22) and an OS of 38 (33-41) weeks, whereas platinum-based combinations were associated with a PFS of 5 weeks and an OS of 8 weeks. Multivariate analysis showed improved survival in patients treated with cyclophosphamide (hazard ratio (HR) = 0.42; 95% CI: 0.20-0.89; P = 0.025) and a worse survival in those treated with platinum-based regimens (HR: 4.37; 95% CI = 1.95-9.77; P < 0.01).We observed a significantly longer overall survival in patients receiving single-agent cyclophosphamide, with few grade 3 to 4 toxicities. Further studies should assess the efficacy of metronomic single-agent cyclophosphamide in advanced lines of treatment, as it may

  8. Implantable defibrillators improve survival in patients with mildly symptomatic heart failure receiving cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Gold, Michael R; Daubert, Jean-Claude; Abraham, William T;

    2013-01-01

    Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure. These benefits have been noted with both CRT-pacemakers as well as those devices with defibrillator backup (CRT...

  9. Improved late survival and disability after stroke with therapeutic anticoagulation for atrial fibrillation: a population study.

    LENUS (Irish Health Repository)

    Hannon, Niamh

    2011-09-01

    Although therapeutic anticoagulation improves early (within 1 month) outcomes after ischemic stroke in hospital-admitted patients with atrial fibrillation, no information exists on late outcomes in unselected population-based studies, including patients with all stroke (ischemic and hemorrhagic).

  10. Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab.

    Science.gov (United States)

    Eefsen, Rikke Løvendahl; Engelholm, Lars; Willemoe, Gro L; Van den Eynden, Gert G; Laerum, Ole Didrik; Christensen, Ib Jarle; Rolff, Hans Christian; Høyer-Hansen, Gunilla; Osterlind, Kell; Vainer, Ben; Illemann, Martin

    2016-04-01

    The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing differences in angiogenesis. To identify possible response markers, histological markers of angiogenesis were assessed. Patients who underwent resection of colorectal liver metastasis at Rigshospitalet, Copenhagen, Denmark from 2007 to 2011 were included (n = 254) including untreated and patients treated with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p chemotherapy-treated patients (p = 0.006/p = 0.002). Tumour cell proliferation assessed by Ki67 expression correlated to a shorter recurrence free survival in the total patient cohort. In conclusion, liver metastases from patients treated with neo-adjuvant chemotherapy and bevacizumab had significantly lower microvessel densities and tumour regression grades when compared to liver metastases from untreated or chemotherapy treated patients. This may indicate that bevacizumab treatment results in altered vascular biology and tumour viability, with possible tumour reducing effect.

  11. Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Herbst, Christine; Rehan, Fareed Ahmed; Skoetz, Nicole

    2011-01-01

    BACKGROUND: Combined modality treatment (CMT) consisting of chemotherapy followed by localised radiotherapy is standard treatment for patients with early stage Hodgkin lymphoma (HL). However, due to long term adverse effects such as secondary malignancies, the role of radiotherapy has been...... questioned recently and some clinical study groups advocate chemotherapy only for this indication. OBJECTIVES: We performed a systematic review with meta-analysis of randomised controlled trials (RCTs) comparing chemotherapy alone with CMT in patients with early stage Hodgkin lymphoma with respect...... to response rate, progression-free survival (alternatively tumour control) and overall survival (OS). SEARCH STRATEGY: We searched MEDLINE, EMBASE and CENTRAL as well as conference proceedings from January 1980 to November 2010 for randomised controlled trials comparing chemotherapy alone to the same...

  12. Chemotherapy | Smokefree.gov

    Science.gov (United States)

    Chemotherapy works by killing cancer cells, but healthy cells get attacked too. Damage to healthy cells can cause uncomfortable side effects. Use this action deck to get information on common chemotherapy side effects and learn how to manage them.

  13. Uterine/Endometrial Cancer: Chemotherapy

    Science.gov (United States)

    ... Types of Gynecologic Cancers Uterine/Endometrial Cancer Chemotherapy Chemotherapy Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy for endometrial cancer is usually given intravenously (injected ...

  14. Immunomodulatory and Antimicrobial Activity of Babassu Mesocarp Improves the Survival in Lethal Sepsis.

    Science.gov (United States)

    Barroqueiro, Elizabeth S B; Prado, Dayanna S; Barcellos, Priscila S; Silva, Tonicley A; Pereira, Wanderson S; Silva, Lucilene A; Maciel, Márcia C G; Barroqueiro, Rodrigo B; Nascimento, Flávia R F; Gonçalves, Azizedite G; Guerra, Rosane N M

    2016-01-01

    Attalea speciosa syn Orbignya phalerata Mart. (babassu) has been used in the treatment of inflammatory and infectious diseases. Aim of the study. To investigate the antimicrobial and immunological activity of babassu mesocarp extract (EE). Material and Methods. The in vitro antimicrobial activity was evaluated by disk diffusion assay and by determination of the minimum inhibitory concentration (MIC) to Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA). The flavonoids and phenolic acids content were determined by chromatography. The in vivo assays were performed in Swiss mice submitted to sepsis by cecal ligation and puncture (CLP). The mice received EE subcutaneously (125 or 250 mg/Kg), 6 hours after the CLP. The number of lymphoid cells was quantified and the cytokines production was determined by ELISA after 12 h. Results. EE was effective as antimicrobial to E. faecalis, S. aureus, and MRSA. EE is rich in phenolic acids, a class of compounds with antimicrobial and immunological activity. An increased survival can be observed in those groups, possibly due to a significant inhibition of TNF-α and IL-6. Conclusions. The EE showed specific antimicrobial activity in vitro and an important antiseptic effect in vivo possibly due to the antimicrobial and immunomodulatory activity.

  15. Immunomodulatory and Antimicrobial Activity of Babassu Mesocarp Improves the Survival in Lethal Sepsis

    Directory of Open Access Journals (Sweden)

    Elizabeth S. B. Barroqueiro

    2016-01-01

    Full Text Available Attalea speciosa syn Orbignya phalerata Mart. (babassu has been used in the treatment of inflammatory and infectious diseases. Aim of the study. To investigate the antimicrobial and immunological activity of babassu mesocarp extract (EE. Material and Methods. The in vitro antimicrobial activity was evaluated by disk diffusion assay and by determination of the minimum inhibitory concentration (MIC to Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA. The flavonoids and phenolic acids content were determined by chromatography. The in vivo assays were performed in Swiss mice submitted to sepsis by cecal ligation and puncture (CLP. The mice received EE subcutaneously (125 or 250 mg/Kg, 6 hours after the CLP. The number of lymphoid cells was quantified and the cytokines production was determined by ELISA after 12 h. Results. EE was effective as antimicrobial to E. faecalis, S. aureus, and MRSA. EE is rich in phenolic acids, a class of compounds with antimicrobial and immunological activity. An increased survival can be observed in those groups, possibly due to a significant inhibition of TNF-α and IL-6. Conclusions. The EE showed specific antimicrobial activity in vitro and an important antiseptic effect in vivo possibly due to the antimicrobial and immunomodulatory activity.

  16. Immunomodulatory and Antimicrobial Activity of Babassu Mesocarp Improves the Survival in Lethal Sepsis

    Science.gov (United States)

    Prado, Dayanna S.; Barcellos, Priscila S.; Gonçalves, Azizedite G.

    2016-01-01

    Attalea speciosa syn Orbignya phalerata Mart. (babassu) has been used in the treatment of inflammatory and infectious diseases. Aim of the study. To investigate the antimicrobial and immunological activity of babassu mesocarp extract (EE). Material and Methods. The in vitro antimicrobial activity was evaluated by disk diffusion assay and by determination of the minimum inhibitory concentration (MIC) to Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA). The flavonoids and phenolic acids content were determined by chromatography. The in vivo assays were performed in Swiss mice submitted to sepsis by cecal ligation and puncture (CLP). The mice received EE subcutaneously (125 or 250 mg/Kg), 6 hours after the CLP. The number of lymphoid cells was quantified and the cytokines production was determined by ELISA after 12 h. Results. EE was effective as antimicrobial to E. faecalis, S. aureus, and MRSA. EE is rich in phenolic acids, a class of compounds with antimicrobial and immunological activity. An increased survival can be observed in those groups, possibly due to a significant inhibition of TNF-α and IL-6. Conclusions. The EE showed specific antimicrobial activity in vitro and an important antiseptic effect in vivo possibly due to the antimicrobial and immunomodulatory activity. PMID:27630733

  17. An anti-apoptotic peptide improves survival in lethal total body irradiation.

    Science.gov (United States)

    McDunn, Jonathan E; Muenzer, Jared T; Dunne, Benjamin; Zhou, Anthony; Yuan, Kevin; Hoekzema, Andrew; Hilliard, Carolyn; Chang, Katherine C; Davis, Christopher G; McDonough, Jacquelyn; Hunt, Clayton; Grigsby, Perry; Piwnica-Worms, David; Hotchkiss, Richard S

    2009-05-15

    Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5-10 microM) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation.

  18. Increased androgen receptor expression in serous carcinoma of the ovary is associated with an improved survival

    Directory of Open Access Journals (Sweden)

    Nodin Björn

    2010-06-01

    Full Text Available Abstract Background Altered androgen hormone homeostasis and androgen receptor (AR activity have been implicated in ovarian carcinogenesis but the relationship between AR expression in ovarian cancer and clinical outcome remains unclear. Methods In this study, the prognostic impact of AR expression was investigated using immunohistochemistry in tissue microarrays from 154 incident cases of epithelial ovarian cancer (EOC in the prospective, population-based cohorts Malmö Diet and Cancer Study and Malmö Preventive Project. A subset of corresponding fallopian tubes (n = 36 with no histopathological evidence of disease was also analysed. Results While abundantly expressed in the majority of fallopian tubes with more than 75% positive nuclei in 16/36 (44% cases, AR was absent in 108/154 (70% of EOC cases. AR expression was not related to prognosis in the entire cohort, but in the serous subtype (n = 90, AR positivity (> 10% positive nuclei was associated with a prolonged disease specific survival in univariate (HR= 0.49; 95% CI 0.25-0.96; p= 0.038 and multivariate (HR= 0.46; 95% CI 0.22-0.97; p= 0.042 analysis, adjusted for age, grade and clinical stage. Conclusions AR expression is considerably reduced in EOC as compared to fallopian tubes, and in EOC of the serous subtype, high AR expression is a favourable prognostic factor. These results indicate that assessment of AR expression might be of value for treatment stratification of EOC patients with serous ovarian carcinoma.

  19. Soluble guanylate cyclase stimulation prevents fibrotic tissue remodeling and improves survival in salt-sensitive Dahl rats.

    Directory of Open Access Journals (Sweden)

    Sandra Geschka

    Full Text Available BACKGROUND: A direct pharmacological stimulation of soluble guanylate cyclase (sGC is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521, have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension. METHODS AND RESULTS: Mortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 and plasminogen activator inhibitor-1 (PAI-1 in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1. CONCLUSIONS: Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions.

  20. Prognostic Impact of CT-Quantified Muscle and Fat Distribution before and after First-Line-Chemotherapy in Lung Cancer Patients

    Science.gov (United States)

    Nattenmüller, Johanna; Wochner, Raoul; Muley, Thomas; Steins, Martin; Hummler, Simone; Teucher, Birgit; Wiskemann, Joachim; Kauczor, Hans-Ulrich; Wielpütz, Mark Oliver; Heussel, Claus Peter

    2017-01-01

    Introduction Cachexia and sarcopenia are associated with poor outcome and increased chemotherapy-induced toxicity in lung cancer patients. However, the complex interplay of obesity, sarcopenia and cachexia, and its impact on survival in the context of first-line-chemotherapy is not yet understood. Methods In 200 consecutively recruited lung cancer patients (70 female, mean age 62y; mean BMI 25 kg/m2; median follow-up 15.97 months) with routine staging-CT before and after chemotherapy (CTX, mean interval: 4.3 months), densitometric quantification of total (TFA), visceral (VFA), and subcutaneous-fat-area (SFA), inter-muscular-fat-area (IMFA), muscle-density (MD), muscle-area (MA) and skeletal-muscle-index (SMI) was performed retrospectively to evaluate changes under chemotherapy and the impact on survival. Results We observed increases in TFA, VFA, SFA, VFA/SFA, and IMFA (p<0.05–0.001), while there were decreases in MA, MD and BMI (p<0.05–0.001) after chemotherapy. High pre-therapeutic VFA/SFA was a predictive factor for poor survival (HR = 1.272; p = 0.008), high pre-therapeutic MD for improved survival (HR = 0.93; p<0.05). Decrease in BMI (HR = 1.303; p<0.001), weight (HR = 1.067; p<0.001) and SMI (HR = 1.063; p<0.001) after chemotherapy were associated with poor survival. Patients with ≥4 CTX-cycles showed increased survival (17.6 vs. 9.1months), less muscle depletion (SMIdifference: p<0.05) and no BMI loss (BMIdifference: p<0.001). Conclusions After chemotherapy, patients exhibited sarcopenia with decreased muscle and increased adipose tissue compartments, which was not adequately mirrored by BMI and weight loss but by imaging. Particularly sarcopenic patients received less CTX-cycles and had poorer survival. As loss of BMI, weight and muscle were associated with poor survival, early detection (via imaging) and prevention (via physical exercise and nutrition) of sarcopenia may potentially improve outcome and reduce chemotherapy-induced toxicity. PMID

  1. Improved survival for elderly married glioblastoma patients. Better treatment delivery, less toxicity, and fewer disease complications

    Energy Technology Data Exchange (ETDEWEB)

    Putz, Florian; Goerig, Nicole; Knippen, Stefan; Gryc, Thomas; Semrau, Sabine; Lettmaier, Sebastian; Fietkau, Rainer [Friedrich-Alexander-University Erlangen-Nuremberg, Department of Radiation Oncology, Erlangen (Germany); Putz, Tobias [University of Bamberg, Professorship of Demography, Bamberg (Germany); Eyuepoglu, Ilker; Roessler, Karl [Friedrich-Alexander-University Erlangen-Nuremberg, Department of Neurosurgery, Erlangen (Germany)

    2016-11-15

    Marital status is a well-described prognostic factor in patients with gliomas but the observed survival difference is unexplained in the available population-based studies. A series of 57 elderly glioblastoma patients (≥70 years) were analyzed retrospectively. Patients received radiotherapy or chemoradiation with temozolomide. The prognostic significance of marital status was assessed. Disease complications, toxicity, and treatment delivery were evaluated in detail. Overall survival was significantly higher in married than in unmarried patients (median, 7.9 vs. 4.0 months; p = 0.006). The prognostic significance of marital status was preserved in the multivariate analysis (HR, 0.41; p = 0.011). Married patients could receive significantly higher daily temozolomide doses (mean, 53.7 mg/m{sup 2} vs. 33.1 mg/m{sup 2}; p = 0.020), were more likely to receive maintenance temozolomide (45.7 % vs. 11.8 %; p = 0.016), and had to be hospitalized less frequently during radiotherapy (55.0 % vs. 88.2 %; p = 0.016). Of the patients receiving temozolomide, married patients showed significantly lower rates of hematologic and liver toxicity. Most complications were infectious or neurologic in nature. Complications of any grade were more frequent in unmarried patients (58.8 % vs. 30.0 %; p = 0.041) with the incidence of grade 3-5 complications being particularly elevated (47.1 % vs. 15.0 %; p = 0.004). We found poorer treatment delivery as well as an unexpected severe increase in toxicity and disease complications in elderly unmarried glioblastoma patients. Marital status may be an important predictive factor for clinical decision-making and should be addressed in further studies. (orig.) [German] Fuer verheiratete Patienten mit malignen Gliomen ist ein verbessertes Gesamtueberleben gut beschrieben. Die zugrunde liegenden Mechanismen konnten bislang jedoch in den verfuegbaren bevoelkerungsbezogenen Arbeiten nicht erklaert werden. Eine Serie von 57 aelteren Patienten mit

  2. Collagen IV-modified scaffolds improve islet survival and function and reduce time to euglycemia.

    Science.gov (United States)

    Yap, Woon Teck; Salvay, David M; Silliman, Michael A; Zhang, Xiaomin; Bannon, Zachary G; Kaufman, Dixon B; Lowe, William L; Shea, Lonnie D

    2013-11-01

    Islet transplantation on extracellular matrix (ECM) protein-modified biodegradable microporous poly(lactide-co-glycolide) scaffolds is a potential curative treatment for type 1 diabetes mellitus (T1DM). Collagen IV-modified scaffolds, relative to control scaffolds, significantly decreased the time required to restore euglycemia from 17 to 3 days. We investigated the processes by which collagen IV-modified scaffolds enhanced islet function and mediated early restoration of euglycemia post-transplantation. We characterized the effect of collagen IV-modified scaffolds on islet survival, metabolism, and insulin secretion in vitro and early- and intermediate-term islet mass and vascular density post-transplantation and correlated these with early restoration of euglycemia in a syngeneic mouse model. Control scaffolds maintained native islet morphologies and architectures as well as collagen IV-modified scaffolds in vivo. The islet size and vascular density increased, while β-cell proliferation decreased from day 16 to 113 post-transplantation. Collagen IV-modified scaffolds promoted islet cell viability and decreased early-stage apoptosis in islet cells in vitro-phenomena that coincided with enhanced islet metabolic function and glucose-stimulated insulin secretion. These findings suggest that collagen IV-modified scaffolds promote the early restoration of euglycemia post-transplantation by enhancing islet metabolism and glucose-stimulated insulin secretion. These studies of ECM proteins, in particular collagen IV, and islet function provide key insights for the engineering of a microenvironment that would serve as a platform for enhancing islet transplantation as a viable clinical therapy for T1DM.

  3. Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours

    DEFF Research Database (Denmark)

    Sengeløv, Lisa; von der Maase, Hans; Lundbeck, Finn

    2002-01-01

    This prospective, randomized study based on two associated trials was designed to evaluate the effect of neoadjuvant chemotherapy with cisplatin and methotrexate with folinic acid rescue or no chemotherapy prior to local treatment in patients with T2-T4b, NX-3, MO transitional cell carcinoma...... was 12.9 months. Median time to progression was 14.2 months with chemotherapy and 11.4 months without chemotherapy. The actuarial 5-year overall survival rate for all 153 patients was 29%, and 29% for both treatment groups. Multivariate analyses showed that T-stage, tumour size and serum creatinine were...... independent prognostic factors for survival. The cystectomy trial included 33 patients. Median survival was 78.9 months, 82.5 months with chemotherapy and 45.8 months without chemotherapy (p = 0.76). The radiotherapy trial included 120 patients. The median survival was 17.6 months. Median survival was 19...

  4. Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

    Science.gov (United States)

    Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

    1999-10-01

    In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

  5. Simvastatin Treatment Improves Survival in a Murine Model of Burn Sepsis

    OpenAIRE

    2010-01-01

    Infection is the most common and most serious complication of a major burn injury related to burn size. Despite improvements in antimicrobial therapies sepsis still accounts for 50–60% of deaths in burn patients. Given the acute onset and unpredictable nature of sepsis, primary prevention was rarely attempted in its management. However, recent studies have demonstrated that statin treatment can decrease mortality is a murine model of sepsis by preservation of cardiac function and reversal of ...

  6. Electroporation enhances mitomycin C cytotoxicity on T24 bladder cancer cell line: a potential improvement of intravesical chemotherapy in bladder cancer.

    Science.gov (United States)

    Vásquez, Juan L; Gehl, Julie; Hermann, Gregers G

    2012-12-01

    Intravesical mitomycin instillation combined with electric pulses is being used experimentally for the treatment of T1 bladder tumors, in patients unfit for surgery. Electroporation may enhance the uptake of chemotherapeutics by permeabilization of cell membranes. We investigated if electroporation improves the cytotoxicity of mitomycin. In two cell lines, T24 (bladder cancer cell line) and DC3F (Chinese hamster fibroblast), exposure to different concentrations of mitomycin (0.01-2000μM) was tested with and without electroporation (6 pulses of 1kV/cm, duration: 99μs, frequency: 1Hz). Cell viability was assessed by colorimetric assay (MTT). For both cell lines, mitomycin's IC_50 was approximately 1000μM in both pulsed and unpulsed cells. On T24 cells, electroporation and mitomycin caused (relative reduction) RR of survival of: 25%, 31% and 29%, by concentrations 0μM, 500μM and 1000μM respectively. For DC3F cells, the RRs of survival were: 28%, 29%, and 33%, by concentrations 0μM, 500μM and 1000μM respectively. In conclusion, electroporation and mitomycin together are about 30% more effective than mitomycin alone. The results help to elucidate the additive effect of mitomycin and electric pulses and support the use of this combination in the treatment of bladder cancer.

  7. Outcome following incomplete surgical cytoreduction combined with intraperitoneal chemotherapy for colorectal peritoneal metastases

    Institute of Scientific and Technical Information of China (English)

    Roisin; Mary; Heaney; Conor; Shields; Jurgen; Mulsow

    2015-01-01

    Cytoreductive surgery combined with intraperitoneal chemotherapy can improve survival in appropriately selected patients with colorectal peritoneal metastases. Outcomes are best in those patients in whom a complete cytoreduction can be achieved. Unresectabledisease is however encountered in approximately one-quarter of patients at laparotomy. The merits, or otherwise, of proceeding with an incomplete cytoreduction in this setting are unclear. We performed a review of published outcomes following incomplete cytoreduction for colorectal peritoneal metastases. Using the electronic databases, Pub Med and MEDLINE, a systematic search of available literature published during the period January 1997 to September 2014 was conducted. Following application of exclusion criteria, 19 papers were identified and included in this review. These comprised fifteen case series, 3 case control studies and one randomised control trial. In the nineteen studies included in this review, 2790 patients underwent cytoreductive surgery with or without intraperitoneal chemotherapy for peritoneal metastases of colorectal origin. Of these, 1732(62%) underwent a complete cytoreduction while 986(35%) patients underwent an incomplete cytoreduction. Median survival in the complete cytoreduction group ranged from 11 to 62 mo while survival in the latter group ranged from 2.4 to 32 mo. Of the 986 patients with an incomplete cytoreduction, 331 patients received intraperitoneal chemotherapy and survival in this cohort ranged from 4.5 to 32 mo. An incomplete cytoreduction, with or without intraperitoneal chemotherapy, does not appear to confer a survival benefit. The limited available data points to a palliative benefit in a subset of patients. In the absence of high quality data, the decision as to whether or not to proceed with surgery should be made on an individual patient basis.

  8. Sufficient virus-neutralizing antibody in the central nerve system improves the survival of rabid rats

    Directory of Open Access Journals (Sweden)

    Liao Pi-Hung

    2012-06-01

    Full Text Available Abstract Background Rabies is known to be lethal in human. Treatment with passive immunity for the rabies is effective only when the patients have not shown the central nerve system (CNS signs. The blood–brain barrier (BBB is a complex functional barrier that may compromise the therapeutic development in neurological diseases. The goal of this study is to determine the change of BBB integrity and to assess the therapeutic possibility of enhancing BBB permeability combined with passive immunity in the late stage of rabies virus infection. Methods The integrity of BBB permeability in rats was measured by quantitative ELISA for total IgG and albumin levels in the cerebrospinal fluid (CSF and by exogenously applying Evans blue as a tracer. Western blotting of occludin and ZO-1, two tight junction proteins, was used to assess the molecular change of BBB structure. The breakdown of BBB with hypertonic arabinose, recombinant tumor necrosis factor-alpha (rTNF-γ, and focused ultrasound (FUS were used to compare the extent of BBB disruption with rabies virus infection. Specific humoral immunity was analyzed by immunofluorescent assay and rapid fluorescent focus inhibition test. Virus-neutralizing monoclonal antibody (mAb 8-10E was administered to rats with hypertonic breakdown of BBB as a passive immunotherapy to prevent the death from rabies. Results The BBB permeability was altered on day 7 post-infection. Increased BBB permeability induced by rabies virus infection was observed primarily in the cerebellum and spinal cord. Occludin was significantly decreased in both the cerebral cortex and cerebellum. The rabies virus-specific antibody was not strongly elicited even in the presence of clinical signs. Disruption of BBB had no direct association with the lethal outcome of rabies. Passive immunotherapy with virus-neutralizing mAb 8-10E with the hypertonic breakdown of BBB prolonged the survival of rabies virus-infected rats. Conclusions We demonstrated

  9. Sarcopenia and chemotherapy-mediated toxicity

    Science.gov (United States)

    Vega, Maria Cecília Monteiro Dela; Laviano, Alessandro; Pimentel, Gustavo Duarte

    2016-01-01

    ABSTRACT This narrative review focuses on the role of sarcopenia and chemotherapy-induced toxicity in cancer patients. Consistent evidence shows that sarcopenia in cancer patients leads to decreased overall survival by influencing treatment discontinuation and dose reduction. Therefore, sarcopenia should be considered a robust prognostic factor of negative outcome as well as a determinant of increased healthcare costs. PMID:28076611

  10. Sarcopenia and chemotherapy-mediated toxicity

    OpenAIRE

    Vega,Maria Cecília Monteiro Dela; Laviano, Alessandro; Pimentel, Gustavo Duarte

    2016-01-01

    ABSTRACT This narrative review focuses on the role of sarcopenia and chemotherapy-induced toxicity in cancer patients. Consistent evidence shows that sarcopenia in cancer patients leads to decreased overall survival by influencing treatment discontinuation and dose reduction. Therefore, sarcopenia should be considered a robust prognostic factor of negative outcome as well as a determinant of increased healthcare costs.

  11. Effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shu-Hui Yao

    2016-01-01

    Objective:To evaluate the effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer.Methods:A total of 39 cases with advanced non-small cell lung cancer who received cryoablation sequential chemotherapy and 39 cases with advanced non-small cell lung cancer who received chemotherapy alone were selected and enrolled in sequential group and control group, disease progression and survival of two groups were followed up, and contents of tumor markers and angiogenesis molecules in serum as well as contents of T-lymphocyte subsets in peripheral blood were detected.Results:Progression-free survival and median overall survival (mOS) of sequential group were longer than those of control group, and cumulative cases of tumor progression at various points in time were significantly less than those of control group (P<0.05); 1 month after treatment, serum tumor markers CEA, CYFRA21-1 and NSE contents, serum angiogenesis molecules PCDGF, VEGF and HDGF contents as well as CD3+CD4-CD8+CD28-T cell content in peripheral blood of sequential group were significantly lower than those of control group (P<0.05), and contents of CD3+CD4+CD8-T cell and CD3+CD4-CD8+CD28+T cell in peripheral blood were higher than those of control group (P<0.05).Conclusions:Cryoablation sequential chemotherapy can improve the prognosis of patients with advanced non-small cell lung cancer, delay disease progression, prolong survival time, inhibit angiogenesis and improve immune function.

  12. Enhancing bile tolerance improves survival and persistence of Bifidobacterium and Lactococcus in the murine gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Hill Colin

    2008-10-01

    Full Text Available Abstract Background The majority of commensal gastrointestinal bacteria used as probiotics are highly adapted to the specialised environment of the large bowel. However, unlike pathogenic bacteria; they are often inadequately equipped to endure the physicochemical stresses of gastrointestinal (GI delivery in the host. Herein we outline a patho-biotechnology strategy to improve gastric delivery and host adaptation of a probiotic strain Bifidobacterium breve UCC2003 and the generally regarded as safe (GRAS organism Lactococcus lactis NZ9000. Results In vitro bile tolerance of both strains was significantly enhanced (P Listeria monocytogenes bile resistance mechanism BilE. Strains harbouring bilE were also recovered at significantly higher levels (P n = 5, following oral inoculation. Furthermore, a B. breve strain expressing bilE demonstrated increased efficacy relative to the wild-type strain in reducing oral L. monocytogenes infection in mice. Conclusion Collectively the data indicates that bile tolerance can be enhanced in Bifidobacterium and Lactococcus species through rational genetic manipulation and that this can significantly improve delivery to and colonisation of the GI tract.

  13. A review of topotecan in combination chemotherapy for advanced cervical cancer

    Directory of Open Access Journals (Sweden)

    Minoo Robati

    2008-03-01

    Full Text Available Minoo Robati, David Holtz, Charles J DuntonDepartment of Obstetrics and Gynecology, Main Line Gynecologic Oncology, Lankenau Hospital, Wynnewood, PA, USAAbstract: Treatment of advanced, recurrent or persistent cervical cancer includes radiotherapy and chemotherapy. Radiation has been the primary treatment modality for locoregionally advanced cervical cancer. Concomitant systemic cisplatin chemotherapy and radiation have shown high response rates with improvements in durable remissions and overall survival. Cisplatin has been the standard medication for the treatment of advanced cervical cancer. Combinations with other chemotherapeutic agents have been the subject of clinical trials with varying results. The toxicity of combination chemotherapy and tolerability of patients are other factors that should be considered in the management of patients with advanced disease. Recently topotecan, in combination with cisplatin, achieved increased response and overall survival rates without further compromising the patients’ quality of life. This review focuses on the mechanism of action and toxicities of topotecan, as well as its role as a radio-sensitizer and chemotherapeutic agent in the management of advanced, recurrent, or persistent cervical cancer. Other combination modalities and dosages are also discussed.Keywords: topotecan, combination chemotherapy, advanced cervical cancer

  14. Improvement in autologous human fat transplant survival with SVF plus VEGF-PLA nano-sustained release microspheres.

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    Li, Liqun; Pan, Shengsheng; Ni, Binting; Lin, Yuanshao

    2014-08-01

    Early neovascularization is important for autologous fat transplant survival. SVF cells are ideal seed cells. Both vascular endothelial growth factor (VEGF) and SVF cells can promote neovascularization. However, the half-life (about 50 min) of VEGF is too short to sustain an adequate local concentration. We have investigated whether VEGF-polylactic acid (PLA) nano-sustained release microspheres plus SVF cells can improve neovascularization and survival of transplanted fat tissues. SVF cells were harvested and constructed VEGF-PLA nano-sustained release microspheres in vitro. Human fat tissues was mixed with SVF cells plus VEGF-PLA, SVF cells alone or Dulbecco's modified Eagle's medium as the control. These three mixtures were injected into random sites in 18 nude mice. Two months later, the transplants were weighed and examined histologically; and capillaries were counted to quantify neovascularization. Hematoxylin-eosin (HE) and anti-VEGF stains were applied to reveal cell infiltration. The mean wet weight of fat in the SVF plus VEGF-PLA, SVF alone, and control transplants were 0.18 ± 0.013 g, 0.16 ± 0.015 g, and 0.071 ± 0.12 g, respectively; the differences between groups were statistically significant. More vessels were present in the SVF plus VEGF-PLA transplants than in the other two types. Transplants mixed with SVF cells also had an acceptable density of capillaries. Histological analysis revealed that both the SVF plus VEGF-PLA and SVF alone transplants, but not the control transplants, were composed of adipose tissue, and had less fat necrosis and less fibrosis than control specimens. SVF plus VEGF-PLA transplants had significantly greater capillary density and VEGF expression than the other two transplant groups. Thus transplanted fat tissue survival and quality can be enhanced by the addition of VEGF-PLA nano-sustained release microspheres plus SVF cells.

  15. Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy

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    Kinuya, Seigo; Yokoyama, Kunihiko; Bai, Jingming; Michigishi, Takatoshi; Tonami, Norihisa [Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa (Japan); Koshida, Kiyoshi [Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa (Japan); Mori, Hirofumi; Shiba, Kazuhiro [Radioisotope Center, Kanazawa University, Kanazawa, Ishikawa (Japan); Watanabe, Naoto [Department of Radiology, Toyama Medical and Pharmaceutical University, Toyama (Japan); Shuke, Noriyuki [Department of Radiology, Asahikawa Medical College, Asahikawa, Hokkaido (Japan)

    2004-07-01

    We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of {sup 131}I-A7, an IgG1 anti-colorectal monoclonal antibody, or {sup 131}I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation (n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice (n=8) (P<0.05). {sup 131}I-A7 RIT displayed a marked therapeutic effect (n=8) (P<0.001); however, all animals eventually died due to metastases by 99 days. The combined regimen of {sup 131}I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy (n=10) (P<0.05); three mice survived the entire 160-day observation period. The combination of antiangiogenic therapy and {sup 131}I-HPMS-1 RIT failed to provide an appreciable benefit (n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases. (orig.)

  16. Extracellular administration of BCL2 protein reduces apoptosis and improves survival in a murine model of sepsis.

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    Akiko Iwata

    Full Text Available BACKGROUND: Severe sepsis and septic shock are major causes of morbidity and mortality worldwide. In experimental sepsis there is prominent apoptosis of various cell types, and genetic manipulation of death and survival pathways has been shown to modulate organ injury and survival. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effect of extracellular administration of two anti-apoptotic members of the BCL2 (B-cell lymphoma 2 family of intracellular regulators of cell death in a murine model of sepsis induced by cecal ligation and puncture (CLP. We show that intraperitoneal injection of picomole range doses of recombinant human (rh BCL2 or rhBCL2A1 protein markedly improved survival as assessed by surrogate markers of death. Treatment with rhBCL2 or rhBCL2A1 protein significantly reduced the number of apoptotic cells in the intestine and heart following CLP, and this was accompanied by increased expression of endogenous mouse BCL2 protein. Further, mice treated with rhBCL2A1 protein showed an increase in the total number of neutrophils in the peritoneum following CLP with reduced neutrophil apoptosis. Finally, although neither BCL2 nor BCL2A1 are a direct TLR2 ligand, TLR2-null mice were not protected by rhBCL2A1 protein, indicating that TLR2 signaling was required for the protective activity of extracellularly adminsitered BCL2A1 protein in vivo. CONCLUSIONS/SIGNIFICANCE: Treatment with rhBCL2A1 or rhBCL2 protein protects mice from sepsis by reducing apoptosis in multiple target tissues, demonstrating an unexpected, potent activity of extracellularly administered BCL2 BH4-domain proteins.

  17. Epoetin beta for the treatment of chemotherapy-induced anemia: an update

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    Galli L

    2015-03-01

    Full Text Available Luca Galli,1 Clara Ricci,2 Colin Gerard Egan2 1Oncology Unit 2, University Hospital of Pisa, Pisa, Italy; 2Primula Multimedia SRL, Pisa, Italy Abstract: Epoetin beta belongs to the class of erythropoiesis-stimulating agents (ESAs that are currently available to treat anemic patients receiving chemotherapy. Chemotherapy-induced anemia affects a high percentage of cancer patients and, due to its negative effects on disease outcome and the patient’s quality of life, should be treated when first diagnosed. Initial trials with ESAs have shown efficacy in improving quality of life and reducing the need for blood transfusions in patients with chemotherapy-induced anemia. However, recent meta-analyses have provided conflicting data on the impact of ESAs on survival and tumor progression. Here we provide an overview of these recent data and review the role of epoetin beta in the treatment of chemotherapy-induced anemia over the past 20 years. Keywords: epoetin beta, erythropoietin, chemotherapy, cancer, anemia, treatment

  18. Nanoscale Quantifying the Effects of Targeted Drug on Chemotherapy in Lymphoma Treatment Using Atomic Force Microscopy.

    Science.gov (United States)

    Li, Mi; Xiao, Xiubin; Liu, Lianqing; Xi, Ning; Wang, Yuechao

    2016-10-01

    The applications of targeted drugs in treating cancers have significantly improved the survival rates of patients. However, in the clinical practice, targeted drugs are commonly combined with chemotherapy drugs, causing that the exact contribution of targeted drugs to the clinical outcome is difficult to evaluate. Quantitatively investigating the effects of targeted drugs on chemotherapy drugs on cancer cells is useful for us to understand drug actions and design better drugs. The advent of atomic force microscopy (AFM) provides a powerful tool for probing the nanoscale physiological activities of single live cells. In this paper, the detailed changes in cell morphology and mechanical properties were quantified on single lymphoma cells during the actions of rituximab (a monoclonal antibody targeted drug) and two chemotherapy drugs (cisplatin and cytarabine) by AFM. AFM imaging revealed the distinct changes of cellular ultramicrostructures induced by the drugs. The changes of cellular mechanical properties after the drug stimulations were measured by AFM indenting. The statistical histograms of cellular surface roughness and mechanical properties quantitatively showed that rituximab could remarkably strengthen the killing effects of chemotherapy drugs. The study offers a new way to quantify the synergistic interactions between targeted drugs and chemotherapy drugs at the nanoscale, which will have potential impacts on predicting the efficacies of drug combinations before clinical treatments.

  19. Electrical vagus nerve stimulation attenuates systemic inflammation and improves survival in a rat heatstroke model.

    Science.gov (United States)

    Yamakawa, Kazuma; Matsumoto, Naoya; Imamura, Yukio; Muroya, Takashi; Yamada, Tomoki; Nakagawa, Junichiro; Shimazaki, Junya; Ogura, Hiroshi; Kuwagata, Yasuyuki; Shimazu, Takeshi

    2013-01-01

    This study was performed to gain insights into novel therapeutic approaches for the treatment of heatstroke. The central nervous system regulates peripheral immune responses via the vagus nerve, the primary neural component of the cholinergic anti-inflammatory pathway. Electrical vagus nerve stimulation (VNS) reportedly suppresses pro-inflammatory cytokine release in several models of inflammatory disease. Here, we evaluated whether electrical VNS attenuates severe heatstroke, which induces a systemic inflammatory response. Anesthetized rats were subjected to heat stress (41.5°C for 30 minutes) with/without electrical VNS. In the VNS-treated group, the cervical vagus nerve was stimulated with constant voltage (10 V, 2 ms, 5 Hz) for 20 minutes immediately after completion of heat stress. Sham-operated animals underwent the same procedure without stimulation under a normothermic condition. Seven-day mortality improved significantly in the VNS-treated group versus control group. Electrical VNS significantly suppressed induction of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-6 in the serum 6 hours after heat stress. Simultaneously, the increase of soluble thrombomodulin and E-selectin following heat stress was also suppressed by VNS treatment, suggesting its protective effect on endothelium. Immunohistochemical analysis using tissue preparations obtained 6 hours after heat stress revealed that VNS treatment attenuated infiltration of inflammatory (CD11b-positive) cells in lung and spleen. Interestingly, most cells with increased CD11b positivity in response to heat stress did not express α7 nicotinic acetylcholine receptor in the spleen. These data indicate that electrical VNS modulated cholinergic anti-inflammatory pathway abnormalities induced by heat stress, and this protective effect was associated with improved mortality. These findings may provide a novel therapeutic strategy to combat severe heatstroke in the critical care

  20. Adjuvant 5FU plus levamisole in colonic or rectal cancer: improved survival in stage II and III.

    Science.gov (United States)

    Taal, B G; Van Tinteren, H; Zoetmulder, F A

    2001-11-16

    Based on the first favourable results of adjuvant therapy of 5FU plus levamisole in Dukes C colonic cancer in 1990, we conducted a prospective trial. 1029 patients were randomised to receive one year 5FU plus levamisole or no further treatment following curative surgery for stage II or III colon (n = 730) or rectal cancer (n = 299). 45% were in stage II and 55% in stage III. With a median follow-up of 4 years and 9 months a significant reduction in odds of death (25%, SD 9%, P = 0.007) was observed for those with adjuvant treatment (65% at 5 year) compared to the observation group (55%). Improved relative survival was present in stage III (56% vs 44%), and in stage II patients (78% vs 70%). In rectal cancer a non-significant difference in disease-free or overall survival was observed. Distant metastases developed in 76%, while local recurrence alone occurred in 14%. An early start of adjuvant treatment (5FU plus levamisole was 69%. Severe toxicity did not occur. In conclusion, one year 5FU plus levamisole was of benefit in stage II and III colonic cancer; in rectal cancer a significant positive effect could not be demonstrated.

  1. Inoculation of somatic embryos of sweet potato with an arbuscular mycorrhizal fungus improves embryo survival and plantlet formation.

    Science.gov (United States)

    Bressan, W; de Carvalho, C H; Sylvia, D M

    2000-08-01

    Responses of somatic embryos of sweet potato (Ipomoea batata (L.) Poir., cv. White Star) at different developmental stages to in vitro inoculation with Glomus etunicatum (Becker and Gerdemann) (isolate INVAM FL329) were evaluated. Somatic embryos were grown in glass tubes containing sterilized vermiculite and sand. A layer of natrosol plus White's medium was used as a carrier for arbuscular mycorrhizal (AM) fungal spores. Survival of embryos inoculated with AM fungi was significantly (P < 0.05) greater than that of noninoculated embryos at the rooted-cotyledonary-torpedo and rooted-elongated-torpedo developmental stages. Mycorrhizae significantly (P < 0.05) increased plantlet formation only when inoculation occurred at the rooted-elongated-torpedo developmental stage. The growth stage at which the embryos were inserted into the glass tubes exerted a significant influence upon plantlet formation, and plantlet formation was further enhanced by inoculation with G. etunicatum. Plantlet formation was greatest at the rooted-elongated-torpedo stage. These results demonstrate that inoculation of somatic embryos with AM fungi improves embryo survival and plantlet formation, and could enhance use of somatic embryos as synthetic seeds.

  2. Reduction in plasma cell proliferation after initial therapy in newly diagnosed multiple myeloma measures treatment response and predicts improved survival.

    Science.gov (United States)

    Larsen, Jeremy T; Chee, Cheng E; Lust, John A; Greipp, Philip R; Rajkumar, S Vincent

    2011-09-08

    Standard myeloma treatment response criteria are determined principally by changes in the monoclonal protein. Reduction in the size of the proliferative component of malignant plasma cells may be an additional metric of assessing response to therapy. We retrospectively analyzed 176 patients with newly diagnosed myeloma with a measurable plasma cell labeling index (PCLI) at diagnosis and repeat measurement 4 months after initiation of therapy. PCLI response was defined as a ≥ 60% reduction. Baseline PCLI is an independent prognostic factor; therefore, we categorized patients into 3 groups: PCLI ≥ 3% (high), ≥ 1% (intermediate), and compared with 29 months in nonresponders (P = .02). Improved median overall survival with PCLI response occurred in the high initial PCLI group (28 vs 7 months; P = .003) and intermediate group (64 vs 24 months; P = .002). The application of PCLI response and serum M-spike response together provided further prognostic information. On multivariate analysis, the prognostic value of PCLI response was independent of β(2)-microglobulin, elevated creatinine, serum M-spike response, and baseline PCLI. We conclude that a significant reduction in plasma cell proliferation in patients with newly diagnosed myeloma is an important predictor of survival.

  3. Does hyperthermic intraoperative chemotherapy lead to improved outcomes in patients with ovarian cancer? A single center cohort study in 111 consecutive patients

    Directory of Open Access Journals (Sweden)

    Warschkow Rene

    2012-06-01

    Full Text Available Abstract Background For recurrent disease or primary therapy of advanced ovarian cancer, cytoreductive surgery (CRS followed by adjuvant chemotherapy is a therapeutic option. The aim of this study was to evaluate the outcome for patients with epithelial ovarian cancer treated with hyperthermic intraoperative chemotherapy (HIPEC and completeness of cytoreduction (CC. Methods Data were retrospectively collected from 111 patients with recurrent or primary ovarian cancer operated with the contribution of visceral surgical oncologists between 1991 and 2006 in a tertiary referral hospital. Results Ninety patients received CRS and 21 patients CRS plus HIPEC with cisplatin. Patients with complete cytoreduction (CC0 were more likely to receive HIPEC. Overall, 19 of 21 patients (90.5 % with HIPEC and 33 of 90 patients (36.7 % with CRS had a complete cytoreduction (P  Conclusions Completeness of cytoreduction was proved to be crucial for long-term outcome. HIPEC procedures in ovarian cancer should be performed in clinical trials to compare CRS, HIPEC and systemic chemotherapy against CRS with systemic chemotherapy. Concerning the safety of HIPEC with cisplatin, the risk of persistent renal failure must be considered when dosage is based on body surface.

  4. Role of Chemotherapy and Mechanisms of Resistance to Chemotherapy in Metastatic Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Lohiya, Vipin; Aragon-Ching, Jeanny B.; Sonpavde, Guru

    2016-01-01

    Chemotherapy using the taxanes, docetaxel and cabazitaxel, remains an important therapeutic option in metastatic castration-resistant prostate cancer (CRPC). However, despite the survival benefits afforded by these agents, the survival increments are modest and resistance occurs universally. Efforts to overcome resistance to docetaxel by combining with biologic agents have heretofore been unsuccessful. Indeed, resistance to these taxanes is also associated with cross-resistance to the antiandrogen drugs, abiraterone and enzalutamide. Here, we discuss the various mechanisms of resistance to chemotherapy in metastatic CRPC and the potential role of emerging regimens and agents in varying clinical phases of development.

  5. Improved survival in rats with glioma using MRI-guided focused ultrasound and microbubbles to disrupt the blood-brain barrier and deliver Doxil

    Science.gov (United States)

    Aryal, Muna; Zhi Zhang, Yong; Vykhodtseva, Natalia; Park, Juyoung; Power, Chanikarn; McDannold, Nathan

    2012-02-01

    Blood-brain-barrier (BBB) limits the transportation of most neuropeptides, proteins (enzymes, antibodies), chemotherapeutic agents, and genes that have therapeutic potential for the treatment of brain diseases. Different methods have been used to overcome this limitation, but they are invasive, non-targeted, or require the development of new drugs. We have developed a method that uses MRI-guided focused ultrasound (FUS) combined with circulating microbubbles to temporarily open BBB in and around brain tumors to deliver chemotherapy agents. Here, we tested whether this noninvasive technique could enhance the effectiveness of a chemotherapy agent (Doxil). Using 690 kHz FUS transducer and microbubble (Definity), we induced BBB disruption in intracranially-implanted 9L glioma tumors in rat's brain in three weekly sessions. Animals who received BBB disruption and Doxil had a median survival time of 34.5 days, which was significantly longer than that found in control animals which is 16, 18.5, 21 days who received no treatment, BBB disruption only and Doxil only respectively This work demonstrates that FUS technique has promise in overcoming barriers to drug delivery, which are particularly stark in the brain due to the BBB.

  6. Treatment of primary brain lymphoma without immune deficiency, The importance of chemotherapy before radiotherapy

    Directory of Open Access Journals (Sweden)

    Keihani M

    1999-09-01

    patients were evaluated for disease free survival and relaps based on the different treatment groups. Results: Median follow-up time was 19 months. Ten patients relapsed. These patients initially received radiotherapy (Group I. In this time period there were no relapses in Group II patients. The median DFS was 24 months with a chance of survival in 3 years of 45.95+11.95% for both groups. Chemotherapy followed by radiotherapy was more efficacious than radiotherapy prior to chemotherapy. Two years survival was 9% in contrast to 100% in favor of chemotherapy followed by radiotherapy. Conclusion: The above model demonstrated that treatment using a protocol consisting of chemotherapy prior to radiation provides improved disease free survival over a treatment regimen consisting of radiotherapy followed by chemotherapy.

  7. Differential distribution improves gene selection stability and has competitive classification performance for patient survival.

    Science.gov (United States)

    Strbenac, Dario; Mann, Graham J; Yang, Jean Y H; Ormerod, John T

    2016-07-27

    A consistent difference in average expression level, often referred to as differential expression (DE), has long been used to identify genes useful for classification. However, recent cancer studies have shown that when transcription factors or epigenetic signals become deregulated, a change in expression variability (DV) of target genes is frequently observed. This suggests that assessing the importance of genes by either differential expression or variability alone potentially misses sets of important biomarkers that could lead to improved predictions and treatments. Here, we describe a new approach for assessing the importance of genes based on differential distribution (DD), which combines information from differential expression and differential variability into a unified metric. We show that feature ranking and selection stability based on DD can perform two to three times better than DE or DV alone, and that DD yields equivalent error rates to DE and DV. Finally, assessing genes via differential distribution produces a complementary set of selected genes to DE and DV, potentially opening up new categories of biomarkers.

  8. Chemotherapy-induced monoamine oxidase expression in prostate carcinoma functions as a cytoprotective resistance enzyme and associates with clinical outcomes.

    Directory of Open Access Journals (Sweden)

    Ryan R Gordon

    Full Text Available To identify molecular alterations in prostate cancers associating with relapse following neoadjuvant chemotherapy and radical prostatectomy patients with high-risk localized prostate cancer were enrolled into a phase I-II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pre-treatment prostate tissue was acquired by needle biopsy and post-treatment tissue was acquired by prostatectomy. Prostate cancer gene expression measurements were determined in 31 patients who completed 4 cycles of neoadjuvant chemotherapy. We identified 141 genes with significant transcript level alterations following chemotherapy that associated with subsequent biochemical relapse. This group included the transcript encoding monoamine oxidase A (MAOA. In vitro, cytotoxic chemotherapy induced the expression of MAOA and elevated MAOA levels enhanced cell survival following docetaxel exposure. MAOA activity increased the levels of reactive oxygen species and increased the expression and nuclear translocation of HIF1α. The suppression of MAOA activity using the irreversible inhibitor clorgyline augmented the apoptotic responses induced by docetaxel. In summary, we determined that the expression of MAOA is induced by exposure to cytotoxic chemotherapy, increases HIF1α, and contributes to docetaxel resistance. As MAOA inhibitors have been approved for human use, regimens combining MAOA inhibitors with docetaxel may improve clinical outcomes.

  9. Alpha B-crystallin improved survival of retinal ganglion cells in a rat model of acute ocular hypertension

    Institute of Scientific and Technical Information of China (English)

    Zhihong Wu; Layi Wang; Shike Hou

    2012-01-01

    Increased endogenous αB-crystallin protein levels have been shown to reduce cell apoptosis,although the effects of exogenous αB-crystallin protein remain poorly understood.The present study established an acute ocular hypertension model in the right eye of Sprague-Dawley rats.Fluorogold retrograde tracing and immunofluorescence methods showed that the number of retinal ganglion cells decreased in the right eyes and caspase-3 expression increased following acute ocular hypertension.Intravitreal injection of αB-crystallin in the right eye increased the number of retinal ganglion cells and reduced caspase-3 expression.Results demonstrated that exogenous αB-crystallin protein inhibited caspase-3 expression and improved retinal ganglion cell survival following acute ocular hypertension.

  10. Locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy plus concurrent weekly cisplatin with or without neoadjuvant chemotherapy

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    Wee, Chan Woo; Keam, Bhum Suk; Heo, Dae Seog; Sung, Myung Whun; Won, Tae Bin; Wu, Hong Gyun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    The outcomes of locoregionally advanced nasopharyngeal carcinoma patients treated with concurrent chemoradiation (CCRT) using intensity-modulated radiotherapy (IMRT) with/without neoadjuvant chemotherapy (NCT) were evaluated. Eighty-three patients who underwent NCT followed by CCRT (49%) or CCRT with/without adjuvant chemotherapy (51%) were reviewed. To the gross tumor, 67.5 Gy was prescribed. Weekly cisplatin was used as concurrent chemotherapy. With a median follow-up of 49.4 months, the 5-year local control, regional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival rates were 94.7%, 89.3%, 77.8%, 68.0%, and 81.8%, respectively. In multivariate analysis, the American Joint Committee on Cancer stage (p = 0.016) and N stage (p = 0.001) were negative factors for DMFS and DFS, respectively. Overall, NCT demonstrated no benefit and an increased risk of severe hematologic toxicity. However, compared to patients treated with CCRT alone, NCT showed potential of improving DMFS in stage IV patients. CCRT using IMRT resulted in excellent local control and survival outcome. Without evidence of survival benefit from phase III randomized trials, NCT should be carefully administered in locoregionally advanced nasopharyngeal carcinoma patients who are at high-risk of developing distant metastasis and radiotherapy-related mucositis. The results of ongoing trials are awaited.

  11. Evaluation of Best Supportive Care and Systemic Chemotherapy as Treatment Stratified According to the Retrospective Peritoneal Surface Disease Severity Score (PSDSS) for Peritoneal Carcinomatosis of Colorectal Origin

    Science.gov (United States)

    2010-12-22

    median survival after systemic 5-Fluorouracil/Leucovorin ( 5FU /L) based chemotherapy for PC of colorectal cancer can, under the best of circumstances...type of systemic chemotherapy regimen; no chemotherapy (best supportive care), 5-Fluorouracil/Leucovorin ( 5FU /L), or modern chemotherapy...Eighty-three patients (50%) had no chemotherapy treatment and received best supportive care only. Forty-two patients (25%) received 5FU /L chemotherapy

  12. Salvianolic acid B enhances in vitro angiogenesis and improves skin flap survival in Sprague-Dawley rats.

    Science.gov (United States)

    Lay, Ing-Shiow; Hsieh, Cheng-Chu; Chiu, Jen-Hwey; Shiao, Ming-Shi; Lui, Wing-Yiu; Wu, Chew-Wun

    2003-12-01

    Insufficient angiogenesis and microcirculatory intravascular clotting have been implicated in the pathophysiology of skin flap failure. Salvianolic acid B (Sal B), isolated from Salvia miltiorrhiza, has been reported to enhance angiogenesis in vitro. This study was aimed to determine the efficacy of Sal B on ischemia-reperfusion injury of the skin flap in Sprague-Dawley rats. Sal B was administered intraperitoneally 2 h before operation, and on the 2nd and 4th days after surgical elevation of an extended epigastric adipocutaneous flap (5 x 7 cm) in ketamine-anesthetized rats. Flap ischemia was achieved by ligating the right superficial epigastric artery and vein and clamping the left superficial epigastric artery and vein for 3 h and then released. Percentage of flap necrosis area (FNA) and plasma levels of aspartate aminotransferase, alanine aminotransferase, creatinine, and malondialdehyde were measured at 7 days after the operation. Animals were divided into six groups, including: vehicle, Sal B low dose (5 mg/kg), Sal B high dose (50 mg/kg) and each with [mesh(+)] or without mesh [mesh(-)] placement. In the three groups with mesh(+), FNA in control flaps was 53.7 +/- 6.9%, whereas low-dose and high-dose Sal B significantly improved flap survival with FNA 27.4 +/- 3.8% and 25.3 +/- 4.3%, respectively (P mesh(-), control flaps were 35.9 +/- 4.5%, whereas high-dose Sal B also significantly improved flap survival with FNA 17.9 +/- 4.7% (P < 0.05, one-way ANOVA). There were no differences in aspartate aminotransferase, alanine aminotransferase, creatinine, or malondialdehyde between groups. We conclude that Sal B attenuates ischemia-reperfusion injury of skin flap, and provides therapeutic potential in reconstructive plastic surgery.

  13. Hemo oxygenase-1 induction in vitro and in vivo can yield pancreas islet xenograft survival and improve islet function

    Institute of Scientific and Technical Information of China (English)

    CHEN Xi; SU Chang; ZHANG Zheng-yun; ZHANG Ming-jun; GU Wei-qiong; LI Xiao-ying; LI Hong-wei; ZHOU Guang-wen

    2011-01-01

    Background The induced expression of heme oxygenase-1 (HO-1) in donor islets improves allograft survival.Cobalt protoporphyrin (CoPP) could significantly enhance the expression of HO-1 mRNA and protein in rat islet safely.Our work was to study how to protect pancreatic islet xenograft by CoPP-induction.Methods Islet xenografts treated with CoPP-induction and CoPP+ Zinc protoporphyrin (ZnPP) in vitro and in vivo were randomly transplanted into murine subrenal capsule; then the graft survival time was compared by blood glucose level and pathological examination and meanwhile the interferon γ (IFN-γ),tumor necrosis factor a (TNF-α),interleukin 10 (IL-10) and IL-1β level in serum and their mRNA and HO-1 mRNA and protein expression were examined.Results Islets with CoPP-induction under low- and high-glucose stimulation exhibited much higher insulin secretion compared with other three groups.CoPP-induction could increase higher expression of HO-1 (mRNA:3.33- and 76.09-fold in vitro and in vivo; protein:2.85- and 58.72-fold).The normoglycemia time in induction groups ((14.63±1.19) and (16.88+1.64) days) was significantly longer.The pathological examination showed less lymphocyte infiltration in induction groups.The IL-10 level and its mRNA in induction groups were significantly higher.Conclusions The HO-1 induced by CoPP would significantly improve function,prolong normoglycemia time and reduce lymphocyte infiltration.Meanwhile CoPP-induction in vivo had more beneficial effects than in vitro.Its mechanism could be related to immune-modulation of IL-10.

  14. Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia.

    Science.gov (United States)

    Müller-Tidow, C; Tschanter, P; Röllig, C; Thiede, C; Koschmieder, A; Stelljes, M; Koschmieder, S; Dugas, M; Gerss, J; Butterfaß-Bahloul, T; Wagner, R; Eveslage, M; Thiem, U; Krause, S W; Kaiser, U; Kunzmann, V; Steffen, B; Noppeney, R; Herr, W; Baldus, C D; Schmitz, N; Götze, K; Reichle, A; Kaufmann, M; Neubauer, A; Schäfer-Eckart, K; Hänel, M; Peceny, R; Frickhofen, N; Kiehl, M; Giagounidis, A; Görner, M; Repp, R; Link, H; Kiani, A; Naumann, R; Brümmendorf, T H; Serve, H; Ehninger, G; Berdel, W E; Krug, U

    2016-03-01

    DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.

  15. Induction chemotherapy before chemoradiotherapy and surgery for locally advanced rectal cancer. Is it time for a randomized phase III trial?

    Energy Technology Data Exchange (ETDEWEB)

    Roedel, Claus [Frankfurt Univ. (Germany). Klinik fuer Strahlentherapie und Onkologie; Arnold, Dirk [Halle Univ. (Germany). Klinik und Poliklinik fuer Innere Medizin IV; Becker, Heinz; Ghadimi, Michael; Liersch, Torsten [Goettingen Univ. (Germany). Klinik fuer Allgemein- und Visceralchirurgie; Fietkau, Rainer; Sauer, Rolf [Erlangen Univ. (Germany). Strahlenklinik; Graeven, Ullrich [Kliniken Maria Hilf GmbH, Moenchengladbach (Germany). Klinik fuer Haematologie, Onkologie und Gastroenterologie; Hess, Clemens [Goettingen Univ. (Germany). Klinik fuer Strahlentherapie und Radioonkologie; Hofheinz, Ralf [Universitaetsmedizin Mannheim (Germany). III. Medizinische Klinik Haematologie und Internistische Onkologie; Hohenberger, Werner [Erlangen Univ. (Germany). Chirurgische Klinik; Post, Stefan [Universitaetsmedizin Mannheim (Germany). Chirurgische Klinik; Raab, Rudolf [Klinikum Oldenburg (Germany). Klinik fuer Allgemein- und Visceralchirurgie; Wenz, Frederick [Universitaetsmedizin Mannheim (Germany). Klinik fuer Strahlentherapie und Radioonkologie

    2010-12-15

    Background: In the era of preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), the development of distant metastases is the predominant mode of failure in rectal cancer patients today. Integrating more effective systemic therapy into combined modality programs is the challenge. The question that needs to be addressed is how and when to apply systemic treatment with adequate dose and intensity. Material and Methods: This review article focuses on phase II-III trials designed to improve 5-fluorouracil (5-FU)-based combined modality treatment for rectal cancer patients through the inclusion of concurrent, adjuvant or, most recently, induction combination chemotherapy. Computerized bibliographic searches of PubMed were supplemented with hand searches of reference lists and abstracts of ASCO/ASTRO/ESTRO meetings. Results: After preoperative CRT and surgical resection, approximately one third of patients do not receive adjuvant chemotherapy, mainly due to surgical complications, patients' refusal, or investigator's discretion. In order to be able to apply chemotherapy with sufficient dose and intensity, an innovative approach is to deliver systemic therapy prior to preoperative CRT rather than adjuvant chemotherapy. Emerging evidence from several phase II trials and, recently, randomized phase II trials indicate that induction chemotherapy is feasible, does not compromise CRT or surgical resection, and enables the delivery of chemotherapy in adequate dose and intensity. Although this approach did not increase local efficacy in recent trials (e.g., pathological complete response rates, tumor regression, R0 resection rates, local control), it may help to improve control of distant disease. Conclusion: Whether this improvement in applicability and dose density of chemotherapy will ultimately translate into improved disease-free survival will have to be tested in a larger phase III trial. (orig.)

  16. De-escalation empirical antibiotic therapy improved survival for patients with severe aplastic anemia treated with antithymocyte globulin.

    Science.gov (United States)

    Fu, Rong; Chen, Tong; Song, Jia; Wang, Guojin; Li, Lijuan; Ruan, Erbao; Liu, Hui; Wang, Yihao; Wang, Huaquan; Xing, Limin; Wu, Yuhong; Liu, Hong; Qu, Wen; Shao, Zonghong

    2017-02-01

    We aimed to investigate the efficacy and safety of de-escalation empirical therapy for controlling infection in patients with severe aplastic anaemia (SAA) treated with antithymocyte globulin (ATG). Eighty-seven ATG-treated SAA patients who had microbiological culture-confirmed infections from 2006 to 2015 in our center were retrospectively analyzed. The efficacy of de-escalation and non-de-escalation therapy was compared. Among all 87 patients, 63 patients were treated with de-escalation therapy and 24 patients with non-de-escalation therapy. More patients showed response to anti-infection treatment in de-escalation group than in non-de-escalation group both on day 7 (60.32% vs. 25.00%, P = 0.003) and on day 30 (79.37% vs. 58.33%, P = 0.047) since the initial antimicrobial therapy. On day 30, more patients had increased absolute neutrophil count in de-escalation group compared with non-de-escalation group (76.19% vs. 45.83%, P = 0.007), and de-escalation group had lower morality rate (17.46% vs. 37.50%, P = 0.047) and better survival outcome (P = 0.023) on day 90. Twenty-three patients in de-escalation group and 5 patients in non-escalation group received granulocyte transfusions. Granulocyte transfusions helped to control infections in both de-escalation group (P = 0.027) and non-de-escalation group (P = 0.042) on day 7, but did not improve survival on day 90. We concluded that de-escalation antibiotics improved survival in SAA patients after ATG treatment. Early administration of broad-spectrum antibiotics pending microbiological cultures combined with a commitment to change to narrow-spectrum antibiotics should be recommended for controlling infections in SAA patients treated with ATG. Granulocyte transfusions might be an adjunctive therapy in controlling infections.

  17. Baicalin improves survival in a murine model of polymicrobial sepsis via suppressing inflammatory response and lymphocyte apoptosis.

    Directory of Open Access Journals (Sweden)

    Jiali Zhu

    Full Text Available BACKGROUND: An imbalance between overwhelming inflammation and lymphocyte apoptosis is the main cause of high mortality in patients with sepsis. Baicalin, the main active ingredient of the Scutellaria root, exerts anti-inflammatory, anti-apoptotic, and even antibacterial properties in inflammatory and infectious diseases. However, the therapeutic effect of baicalin on polymicrobial sepsis remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP in C57BL/6 mice. Mice were infused with baicalin intraperitoneally at 1 h, 6 h and 12 h after CLP. Survival rates were assessed over the subsequent 8 days. Bacterial burdens in blood and peritoneal cavity were calculated to assess the bacterial clearance. Neutrophil count in peritoneal lavage fluid was also calculated. Injuries to the lung and liver were detected by hematoxylin and eosin staining. Levels of cytokines, including tumor necrosis factor (TNF-alpha, interleukin (IL-6, IL-10 and IL-17, in blood and peritoneum were measured by enzyme-linked immunosorbent assay. Adaptive immune function was assessed by apoptosis of lymphocytes in the thymus and counts of different cell types in the spleen. Baicalin significantly enhanced bacterial clearance and improved survival of septic mice. The number of neutrophils in peritoneal lavage fluid was reduced by baicalin. Less neutrophil infiltration of the lung and liver in baicalin-treated mice was associated with attenuated injuries to these organs. Baicalin significantly reduced the levels of proinflammatory cytokines but increased the level of anti-inflammatory cytokine in blood and peritoneum. Apoptosis of CD3(+ T cell was inhibited in the thymus. The numbers of CD4(+, CD8(+ T lymphocytes and dendritic cells (DCs were higher, while the number of CD4(+CD25(+ regulatory T cells was lower in the baicalin group compared with the CLP group. CONCLUSIONS/SIGNIFICANCE: Baicalin improves survival of mice

  18. Codelivery of curcumin and doxorubicin by MPEG-PCL results in improved efficacy of systemically administered chemotherapy in mice with lung cancer

    Directory of Open Access Journals (Sweden)

    Wang BL

    2013-09-01

    Full Text Available Bi-Lan Wang,1,* Yong-mei Shen,1,3,* Qiong-wen Zhang,1,* Yu-li Li,1 Min Luo,1 Ze Liu,1,2 Yan Li,1 Zhi-yong Qian,1 Xiang Gao,1 Hua-shan Shi1,2 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, 2State Key Laboratory of Biotherapy and Department of Head and Neck Oncology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, 3Sichuang Haoyisheng Pharmacy, Chengdu, People’s Republic of China *These authors contributed equally to this work Abstract: Systemic administration of chemotherapy for cancer often has toxic side effects, limiting the doses that can be used in its treatment. In this study, we developed methoxy poly(ethylene glycol-poly(caprolactone (MPEG-PCL micelles loaded with curcumin and doxorubicin (Cur-Dox/MPEG-PCL that were tolerated by recipient mice and had enhanced antitumor effects and fewer side effects. It was shown that these Cur-Dox/MPEG-PCL micelles could release curcumin and doxorubicin slowly in vitro. The long circulation time of MPEG-PCL micelles and the slow rate of release of curcumin and doxorubicin in vivo may help to maintain plasma concentrations of active drug. We also demonstrated that Cur-Dox/MPEG-PCL had improved antitumor effects both in vivo and in vitro. The mechanism by which Cur-Dox/MPEG-PCL micelles inhibit lung cancer might involve increased apoptosis of tumor cells and inhibition of tumor angiogenesis. We found advantages using Cur-Dox/MPEG-PCL micelles in the treatment of cancer, with Cur-Dox/MPEG-PCL achieving better inhibition of LL/2 lung cancer growth in vivo and in vitro. Our study indicates that Cur-Dox/MPEG-PCL micelles may be an effective treatment strategy for cancer in the future. Keywords: methoxy poly(ethylene glycol, poly(caprolactone, curcumin, doxorubicin, micelles, cancer, treatment

  19. Survival of multiple myeloma patients in the era of novel therapies confirms the improvement in patients younger than 75 years: a population-based analysis.

    Science.gov (United States)

    Pozzi, Samantha; Marcheselli, Luigi; Bari, Alessia; Liardo, Eliana V; Marcheselli, Raffaella; Luminari, Stefano; Quaresima, Micol; Cirilli, Claudia; Ferri, Paola; Federico, Massimo; Sacchi, Stefano

    2013-10-01

    Novel treatments for multiple myeloma (MM) have shown promising results in clinical trials, but the advantage in unselected patients is still unclear. In order to evaluate whether novel therapies impact survival of MM patients, we performed a population-based analysis on data collected by the Modena Cancer Registry from 1989 to 2009. The analysis evaluated 1206 newly diagnosed MM patients collected in the years 1988-96 (conventional therapy), 1997-05 (high dose melphalan and autologous transplant), and 2006-09 (novel agents era). Both relative survival (RS) and overall survival (OS) improved over the years, but not equally in the three groups. For patients aged survival of MM patients aged survival. Despite the limits of this study, these data refer to an unselected population, giving a picture of every day clinical practice.

  20. Efficacy and safety of ifosfamide-based chemotherapy for osteosarcoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Fan XL

    2015-11-01

    Full Text Available Xiao-Liang Fan,1,* Guo-Ping Cai,2,* Liu-Long Zhu,1 Guo-Ming Ding1 1Department of Orthopaedics, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou, 2Department of Orthopaedics, Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The efficacy of ifosfamide-based chemotherapy in the treatment of osteosarcoma has been investigated; however, results are inconsistent. Therefore, we reviewed the relevant studies and conducted a meta-analysis to assess the efficacy of ifosfamide-based chemotherapy in patients with osteosarcoma.Methods: A systematic literature search on PubMed, Embase, and Web of Science databases was performed. Eligible studies were clinical trials of patients with osteosarcoma who received ifosfamide-based chemotherapy. Hazard ratios (HRs were pooled to compare event-free survival (EFS and overall survival (OS. Risk ratios (RRs were pooled to compare good histologic response rates and adverse event incidence. Meta-analysis was performed using a fixed-effects model or a random-effects model according to heterogeneity.Results: A total of seven randomized controlled trials were included in this meta-analysis. Pooled results showed that ifosfamide-based chemotherapy significantly improved EFS (HR=0.72, 95% confidence interval [CI]: 0.63, 0.82; P=0.000 and OS (HR=0.83, 95% CI: 0.70, 0.99; P=0.034; furthermore, this form of chemotherapy increased good histologic response rate (RR=1.27, 95% CI: 1.10, 1.46; P=0.001. In addition, patients in the ifosfamide group exhibited a significantly higher incidence of fever (RR=2.23, 95% CI: 1.42, 3.50; P=0.000 and required more frequent platelet transfusion (RR=1.92, 95% CI: 1.23, 3.01; P=0.004.Conclusion: This meta-analysis confirmed that ifosfamide-based chemotherapy can significantly improve EFS and OS; this chemotherapy can also increase good histologic response rate in patients with osteosarcoma

  1. Which is better for gastric cancer patients, perioperative or adjuvant chemotherapy: a meta-analysis

    OpenAIRE

    2016-01-01

    Background The preferred chemotherapy method for gastric cancer continues to be matter of debate. We performed a meta-analysis to comparing prognosis and safety between perioperative chemotherapy and adjuvant chemotherapy to identify the better chemotherapy option for gastric cancer. Methods We searched the PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies until February 2016. The main endpoints were prognostic value (hazard ratio [HR] for overall survival [OS] and 1-,...

  2. Combining etoposide and dexrazoxane synergizes with radiotherapy and improves survival in mice with central nervous system tumors

    DEFF Research Database (Denmark)

    Hofland, Kenneth Francis; Thougaard, Annemette Vinding; Dejligbjerg, Marielle;

    2005-01-01

    : Mice with cerebrally inoculated Ehrlich ascites tumor (EHR2) cells were treated with combinations of etoposide + dexrazoxane + cerebral radiotherapy. Similar chemotherapy and radiation combinations were investigated by clonogenic assays using EHR2 cells, and by DNA double-strand break assay through...

  3. Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management

    OpenAIRE

    SMITH, J. JOSHUA; Chow, Oliver S; Gollub, Marc J.; Nash, Garrett M.; Temple, Larissa K.; Weiser, Martin R.; Guillem, José G.; Paty, Philip B.; Avila, Karin; Garcia-Aguilar, Julio; ,

    2015-01-01

    Background Treatment of patients with non-metastatic, locally advanced rectal cancer (LARC) includes pre-operative chemoradiation, total mesorectal excision (TME) and post-operative adjuvant chemotherapy. This trimodality treatment provides local tumor control in most patients; but almost one-third ultimately die from distant metastasis. Most survivors experience significant impairment in quality of life (QoL), due primarily to removal of the rectum. A current challenge lies in identifying pa...

  4. Maintenance Chemotherapy of Stage Ⅲ Epithelial Ovarian Carcinoma-Focusing on Individualized Maintenance Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Zhao; Yi Zhang; Qiao Zhang

    2005-01-01

    OBJECTIVE To investigate the role of maintenance chemotherapy on stage Ⅲ ovarian carcinoma.METHODS A retrospective analysis was conducted of 47 stage Ⅲ ovarian carcinoma patients with clinical complete remission after first-line chemotherapy. Among these patients, 21 cases were treated with maintenance chemotherapy, while the other 26 cases were free of treatment until progression. The 2 groups were compared with respect to progression-free survival (PFS) and overall survival(OS).RESULTS The median PFS and OS were not significantly different between the 2 groups. For those patients, in a subgroup of suboptimal surgery (residual disease >2 cm), the median PFS was 110 weeks and 56 weeks and the median OS was 223 weeks and 157 weeks for the maintenance and non-treated respectively. Both PFS and OS values favoured the maintenance group, P=0.004 and P=0.015 respectively. In a subgroup of optimal surgery (residual disease ≤2 cm), the differences were not significant.CONCLUSION Patients with stage Ⅲ ovarian carcinoma with clinical complete remission may benefit from maintenance chemotherapy, if the residual disease is >2 cm. To those with a residual disease ≤2 cm, the maintenance chemotherapy maybe of no value. So "individualized maintenance chemotherapy" should be conducted in the clinical setting.

  5. Safe chemotherapy in the home environment.

    Science.gov (United States)

    Chavis-Parker, Paula

    2015-05-01

    The Oncology Nursing Society and the American Society of Clinical Oncology have established guidelines for the safe and effective use of chemotherapeutic medications in the acute and outpatient care settings. A review of literature was performed to determine the safe and effective administration of chemotherapy in the home environment. The administration of oral and intravenous chemotherapy in the home has become a common intervention for patients being treated for cancer based on patient preference, cost-effectiveness of healthcare delivery, and increasing demand for oncology services. Home healthcare nurses can greatly impact the management of adverse effects of chemotherapy in the home, increasing the quality of life and improving patient outcomes.

  6. Five-Year Survival Among Stage IIIA Lung Cancer Patients Receiving Two Different Treatment Modalities.

    Science.gov (United States)

    Bilfinger, Thomas; Keresztes, Roger; Albano, Denise; Nemesure, Barbara

    2016-07-21

    BACKGROUND Five-year survival rates among stage IIIA lung cancer patients range between 2% and 15%, and there is currently no consensus regarding optimal treatment approaches for these patients. The current investigation evaluated survival outcomes among stage IIIA lung cancer patients receiving 2 different treatment modalities, neoadjuvant chemotherapy followed by resection versus chemoradiation alone. MATERIAL AND METHODS This retrospective study is based on 127 patients attending the Lung Cancer Evaluation Center at Stony Brook Cancer Center between 2002 and 2014. Patients were treated either with neoadjuvant chemotherapy followed by resection or a regimen of chemoradiation alone. Kaplan-Meier curves were used to compare survival outcomes between groups and Cox proportional hazard models were used to evaluate treatment effects on survival, while adjusting for possible confounders. RESULTS Approximately one-fourth (n=33) of patients received neoadjuvant chemotherapy followed by surgery, whereas 94 patients received definitive chemoradiation. Patients in the surgical group were found to be significantly younger than those receiving chemoradiation alone (60.1 vs. 67.9 years, respectively; p=0.001). Five-year survival among patients receiving preoperative chemotherapy followed by resection was significantly higher than that among patients receiving chemoradiation alone (63% vs. 19%, respectively; p<0.001), whereas the hazard ratio (HR) was 3-4 times greater in the latter group (HR=3.77, 95% confidence interval=1.87, 7.61). CONCLUSIONS Findings from this study indicate that preoperative chemotherapy followed by resection can improve survival outcomes for stage IIIA lung cancer patients compared with chemoradiation alone. The results reflect a select surgical group of patients; thus, the data highlight the need to develop new therapies that may result in more patients being viable surgical candidates.

  7. Mechanisms of chemotherapy-induced behavioral toxicities

    Directory of Open Access Journals (Sweden)

    Elisabeth G Vichaya

    2015-04-01

    Full Text Available While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms of chemotherapy include (i cognitive deficiencies such as problems with attention, memory and executive functioning; (ii fatigue and motivational deficit; and (iii neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients.

  8. Mechanisms of chemotherapy-induced behavioral toxicities.

    Science.gov (United States)

    Vichaya, Elisabeth G; Chiu, Gabriel S; Krukowski, Karen; Lacourt, Tamara E; Kavelaars, Annemieke; Dantzer, Robert; Heijnen, Cobi J; Walker, Adam K

    2015-01-01

    While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence, neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs) activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients.

  9. Novel inhibitors of neurotropic alphavirus replication that improve host survival in a mouse model of acute viral encephalitis.

    Science.gov (United States)

    Sindac, Janice A; Yestrepsky, Bryan D; Barraza, Scott J; Bolduc, Kyle L; Blakely, Pennelope K; Keep, Richard F; Irani, David N; Miller, David J; Larsen, Scott D

    2012-04-12

    Arboviral encephalitis is a potentially devastating human disease with no approved therapies that target virus replication. We previously discovered a novel class of thieno[3,2-b]pyrrole-based inhibitors active against neurotropic alphaviruses such as western equine encephalitis virus (WEEV) in cultured cells. In this report, we describe initial development of these novel antiviral compounds, including bioisosteric replacement of the 4H-thieno[3,2-b]pyrrole core with indole to improve metabolic stability and the introduction of chirality to assess target enantioselectivity. Selected modifications enhanced antiviral activity while maintaining low cytotoxicity, increased stability to microsomal metabolism, and also revealed striking enantiospecific activity in cultured cells. Furthermore, we demonstrate improved outcomes (both symptoms and survival) following treatment with indole analogue 9h (CCG-203926) in an in vivo mouse model of alphaviral encephalitis that closely correlate with the enantiospecific in vitro antiviral activity. These results represent a substantial advancement in the early preclinical development of a promising class of novel antiviral drugs against virulent neurotropic alphaviruses.

  10. FIRST LINE 5-FU-BASED CHEMOTHERAPY WITH/WITHOUT BEVACIZUMAB FOR METASTATIC COLORECTAL CANCER: TISSUE BIOMARKER CANDIDATES

    OpenAIRE

    Assia Konsoulova; Ivan Donev; Nikolay Conev; Sonya Draganova; Nadezhda Petrova; Eleonora Dimitrova; Hristo Popov; Kameliya Bratoeva; Petar Ghenev

    2016-01-01

    Purpose: Colorectal cancer is the second leading cause of cancer mortality in the USA. According to Bulgarian National Statistics Institute, 2370 colon and 1664 rectal cancer cases were diagnosed in 2012 with total number of patients 29995. Adding bevacizumab to chemotherapy in patients with metastatic disease improves progression-free survival (PFS) but no predictive markers have been proven in the clinical practice. In our study we examined two tissue biomarkers that may correlate with resp...

  11. Dietary Curcumin Increases Antioxidant Defenses in Lung, Ameliorates Radiation-Induced Pulmonary Fibrosis, and Improves Survival in Mice

    Science.gov (United States)

    Lee, James C.; Kinniry, Paul A.; Arguiri, Evguenia; Serota, Matthew; Kanterakis, Stathis; Chatterjee, Shampa; Solomides, Charalambos C.; Javvadi, Prashanthi; Koumenis, Constantinos; Cengel, Keith A.; Christofidou-Solomidou, Melpo

    2010-01-01

    The effectiveness of lung radiotherapy is limited by radiation tolerance of normal tissues and by the intrinsic radiosensitivity of lung cancer cells. The chemopreventive agent curcumin has known antioxidant and tumor cell radiosensitizing properties. Its usefulness in preventing radiation-induced pneumonopathy has not been tested previously. We evaluated dietary curcumin in radiation-induced pneumonopathy and lung tumor regression in a murine model. Mice were given 1%or 5%(w/w) dietary curcumin or control diet prior to irradiation and for the duration of the experiment. Lungs were evaluated at 3 weeks after irradiation for acute lung injury and inflammation by evaluating bronchoalveolar lavage (BAL) fluid content for proteins, neutrophils and at 4 months for pulmonary fibrosis. In a separate series of experiments, an orthotopic model of lung cancer using intravenously injected Lewis lung carcinoma (LLC) cells was used to exclude possible tumor radioprotection by dietary curcumin. In vitro, curcumin boosted antioxidant defenses by increasing heme oxygenase 1 (HO-1) levels in primary lung endothelial and fibroblast cells and blocked radiation-induced generation of reactive oxygen species (ROS). Dietary curcumin significantly increased HO-1 in lungs as early as after 1 week of feeding, coinciding with a steady-state level of curcumin in plasma. Although both 1% and 5% w/w dietary curcumin exerted physiological changes in lung tissues by significantly decreasing LPS-induced TNF-α production in lungs, only 5%dietary curcumin significantly improved survival of mice after irradiation and decreased radiation-induced lung fibrosis. Importantly, dietary curcumin did not protect LLC pulmonary metastases from radiation killing. Thus dietary curcumin ameliorates radiation-induced pulmonary fibrosis and increases mouse survival while not impairing tumor cell killing by radiation. PMID:20426658

  12. Grape seed extract protects IEC-6 cells from chemotherapy-induced cytotoxicity and improves parameters of small intestinal mucositis in rats with experimentally-induced mucositis.

    Science.gov (United States)

    Cheah, Ker Y; Howarth, Gordon S; Yazbeck, Roger; Wright, Tessa H; Whitford, Eleanor J; Payne, Caroline; Butler, Ross N; Bastian, Susan E P

    2009-02-01

    Mucositis is a common side-effect of high-dose chemotherapy regimens. Grape seed extract (GSE) represents a rich source of proanthocyanidins with the potential to decrease oxidative damage and inflammation within the gastrointestinal tract. We evaluated GSE for its capacity to decrease the severity of chemotherapy-induced mucositis in vitro and in vivo. In vitro: GSE was administered to IEC-6 intestinal epithelial cells prior to damage induced by 5-Fluorouracil (5-FU). Cell viability was determined by neutral red assay. In vivo: Female Dark Agouti rats (130-180 g) were gavaged with 1 ml GSE (400 mg/kg) daily (day 3-11) and received 5-FU (150 mg/kg) by intraperitoneal (i.p.) injection on day nine to induce mucositis. Rats were sacrificed at day 12 and intestinal tissues collected for myeloperoxidase and sucrase activity assays and histological analyses. Statistical analysis was performed by one-way ANOVA. GSE prevented the decrease in IEC-6 cell viability induced by 5-FU (p IEC-6 cells from 5-FU-induced cytotoxicity and ameliorated intestinal damage induced by 5-FU in rats. GSE may represent a promising prophylactic adjunct to conventional chemotherapy for preventing intestinal mucositis.

  13. Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma?

    Science.gov (United States)

    Clarke, Jennifer L; Ennis, Michele M; Yung, W K Alfred; Chang, Susan M; Wen, Patrick Y; Cloughesy, Timothy F; Deangelis, Lisa M; Robins, H Ian; Lieberman, Frank S; Fine, Howard A; Abrey, Lauren; Gilbert, Mark R; Mehta, Minesh; Kuhn, John G; Aldape, Kenneth D; Lamborn, Kathleen R; Prados, Michael D

    2011-10-01

    Historically, the North American Brain Tumor Consortium used 6-month progression-free survival (PFS6) as the primary outcome for recurrent glioma phase II clinical trials. In some trials, a subset of patients received the trial treatment before surgery to assess tumor uptake and biological activity. We compared PFS6 and overall survival (OS) for patients with glioblastoma undergoing surgery at progression to results for those without surgery to evaluate the impact of surgical intervention on these outcomes. Two data sets were analyzed. The first included 511 patients enrolled during the period 1998-2005, 105 of whom had surgery (excluding biopsies) during the study or ≤ 30 days prior to registration. Analysis was stratified on the basis of whether temozolomide was part of the protocol treatment regimen. The second data set included 247 patients enrolled during 2005-2008, 103 of whom underwent surgery during the clinical trial or immediately prior to study registration. A combined data set consisting of all patients who did not receive temozolomide was also compiled. No statistically significant difference in PFS6 or OS was found between the surgery and nonsurgery groups in either data set alone or in the combined data set (P > .45). We conclude that PFS6 and OS results for patients with and without surgical intervention at the time of progression are similar, allowing data from these patients to be combined in assessing the benefit of new treatments without the need for stratification or other statistical adjustment.

  14. Efficacy of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yang Hyun Baek; Kyoung Tae Kim; Sung Wook Lee; Jin Sook Jeong; Byeong Ho Park; Kyung Jin Nam; Jin Han Cho

    2012-01-01

    AIM:To investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) using floxuridine (FUDR)in patients with advanced hepatocellular carcinoma (HCC) confined to the liver.METHODS:Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at our hospital between March 2005 and May 2008.Among the 34 patients,9 patients were classified as Child class C,and 18 patients had portal vein tumor thrombus (PVTT).One course of chemotherapy consisted of continuous infusion of FUDR (0.3 mg/kg during day 1-14) and dexamethasone (10 mg on day 1,4,7 and 11),and this treatment was repeated every 28 d.RESULTS:Two patients (5.9%) displayed a complete response,and 12 patients (35.3%) had a partial response.The tumor control rate was 61.8%.The median overall survival times were 15.3 mo,12.4 mo and 4.3 mo for the patients who were classified as Child class A,Child class B and Child class C,respectively (P =0.0392).The progression-free survival was 12.9mo,7.7 mo and 2.6 mo for the patients who were classified as Child class A,Child class B and Child class C,respectively (P =0.0443).The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT.In addition to hepatic reserve capacity and PVTT,the extent of HCC was an independent factor in determining a poor prognosis.The most common adverse reactions to HAIC were mucositis,diarrhea and peptic ulcer disease,but most of these complications were improved by medical treatment and/or a delay of HAIC.CONCLUSION:The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities,even in patients with advanced cirrhosis.

  15. Intrathecal enzyme replacement therapy improves motor function and survival in a preclinical mouse model of infantile neuronal ceroid lipofuscinosis.

    Science.gov (United States)

    Lu, Jui-Yun; Nelvagal, Hemanth R; Wang, Lingling; Birnbaum, Shari G; Cooper, Jonathan D; Hofmann, Sandra L

    2015-01-01

    The neuronal ceroid lipofuscinoses (NCLs) are a group of related hereditary lysosomal storage disorders characterized by progressive loss of neurons in the central nervous system resulting in dementia, loss of motor skills, seizures and blindness. A characteristic intralysosomal accumulation of autofluorescent storage material