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Sample records for chemotherapy including bortezomib

  1. Treatment of refractory/relapsed adult acute lymphoblastic leukemia with bortezomib- based chemotherapy

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    Zhao J

    2015-06-01

    Full Text Available Junmei Zhao,* Chao Wang,* Yongping Song, Yuzhang Liu, Baijun FangHenan Key Lab of Experimental Haematology, Henan Institute of Haematology, Henan Tumor Hospital, Zhengzhou University, Zhengzhou, People’s Republic of China  *These authors contributed equally to this work Abstract: Nine pretreated patients aged >19 years with relapsed/refractory acute lymphoblastic leukemia (ALL were treated with a combination of bortezomib plus chemotherapy before allogeneic hematopoietic stem cell transplantation (allo-HSCT. Eight (88.9% patients, including two Philadelphia chromosome-positive ALL patients, achieved a complete remission. Furthermore, the evaluable patients have benefited from allo-HSCT after response to this reinduction treatment. We conclude that bortezomib-based chemotherapy was highly effective for adults with refractory/relapsed ALL before allo-HSCT. Therefore, this regimen deserves a larger series within prospective trials to confirm these results. Keywords: acute lymphoblastic leukemia, refractory, relapsed, bortezomib

  2. Stem cell mobilization chemotherapy with gemcitabine is effective and safe in myeloma patients with bortezomib-induced neurotoxicity.

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    Mueller, Beatrice U; Keller, Sandra; Seipel, Katja; Mansouri Taleghani, Behrouz; Rauch, Daniel; Betticher, Daniel; Egger, Thomas; Pabst, Thomas

    2016-05-01

    Vinorelbine chemotherapy with granulocyte-colony stimulating factor (G-CSF) stimulation is a widely applied non-myelosuppressive mobilization regimen in Switzerland for myeloma patients, but its neurotoxic potential limits its use in patients with bortezomib-induced polyneuropathy. In this single-center study, we alternatively evaluated safety and effectiveness of gemcitabine chemotherapy with G-CSF for mobilization of autologous stem cells. Between March 2012 and February 2013, all bortezomib-pretreated myeloma patients planned to undergo first-line high-dose melphalan chemotherapy received a single dose of 1250 mg/m2 gemcitabine, with G-CSF started on day 4. The 24 patients in this study had received a median of four cycles of bortezomib-dexamethason-based induction. Bortezomib-related polyneuropathy was identified in 21 patients (88%) by clinical evaluation and a standardized questionnaire. Administration of gemcitabine mobilization did not induce new or aggravate pre-existing neuropathy. Stem cell mobilization was successful in all 24 patients, with a single day of apheresis being sufficient in 19 patients (78%). The median yield was 9.51×10(6) CD34+ cells/kg. Stem collection could be accomplished at day 8 in 67%. Our data suggest that single-dose gemcitabine together with G-CSF is an effective mobilization regimen in myeloma patients and a safe alternative non-myelosuppressive mobilization chemotherapy for myeloma patients with bortezomib-induced polyneuropathy.

  3. Successful treatment of primary advanced gastric plasmacytoma using a combination of surgical resection and chemotherapy with bortezomib: A case report

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    Sotaro Fukuhara

    2016-01-01

    Conclusions: This is the first reported case of advanced gastric plasmacytoma using adjuvant chemotherapy involving bortezomib and auto-PBSCT after the resection, and the patient has maintained a good course over a year. This protocol could be a new way to treat these tumors.

  4. Severe reversible cardiac failure after bortezomib treatment combined with chemotherapy in a non-small cell lung cancer patient: a case report

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    Giaccone Giuseppe

    2006-05-01

    Full Text Available Abstract Background Bortezomib (Velcade®, a dipeptide boronate proteasome inhibitor, is a novel anti-cancer agent registered for multiple myeloma (MM. It has also shown promising clinical activity in non-small cell lung cancer (NSCLC. Clinical experience with bortezomib so far indicates that overall incidence of cardiac failure associated with bortezomib therapy remains incidental. Nevertheless, acute development or exacerbation of congestive cardiac failure has been associated with bortezomib treatment. Case presentation We present here a case of severe, but reversible, congestive cardiac failure in a lung cancer patient who had no prior cardiac history, after receiving an experimental treatment of bortezomib combined with chemotherapy. Elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP, as retrospectively measured in archived serum samples, were suggestive of pre-existent (sub-clinical left ventricular dysfunction. Conclusion Based on literature, we hypothesize that baseline presence of sub clinical cardiomyopathy, characterized by a dysregulation of the ubiquitin-proteasome system, could have predisposed this patient for a cardiac side effect induced by systemic proteasome inhibition. Patients with heart disease or risk factors for it should be closely monitored when being submitted to treatment with proteasome inhibition therapy such as bortezomib. Caution is therefore warranted in lung cancer patients who often present with cardiac comorbidities.

  5. Proteasome subunit expression analysis and chemosensitivity in relapsed paediatric acute leukaemia patients receiving bortezomib-containing chemotherapy

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    Denise Niewerth

    2016-09-01

    Full Text Available Abstract Background Drug combinations of the proteasome inhibitor bortezomib with cytotoxic chemotherapy are currently evaluated in phase 2 and 3 trials for the treatment of paediatric acute myeloid leukaemia (AML and acute lymphocytic leukaemia (ALL. Methods We investigated whether expression ratios of immunoproteasome to constitutive proteasome in leukaemic cells correlated with response to bortezomib-containing re-induction chemotherapy in patients with relapsed and refractory acute leukaemia, enrolled in two Children’s Oncology Group phase 2 trials of bortezomib for ALL (COG-AALL07P1 and AML (COG-AAML07P1. Expression of proteasome subunits was examined in 72 patient samples (ALL n = 60, AML n = 12 obtained before start of therapy. Statistical significance between groups was determined by Mann-Whitney U test. Results Ratios of immunoproteasome to constitutive proteasome subunit expression were significantly higher in pre-B ALL cells than in AML cells for both β5i/β5 and β1i/β1 subunits (p = 0.004 and p < 0.001. These ratios correlated with therapy response in AML patients; β1i/β1 ratios were significantly higher (p = 0.028 between patients who did (n = 4 and did not reach complete remission (CR (n = 8, although for β5i/β5 ratios, this did not reach significance. For ALL patients, the subunit ratios were also higher for patients who showed a good early response to therapy but this relation was not statistically significant. Overall, for this study, the patients were treated with combination therapy, so response was not only attributed to proteasome inhibition. Moreover, the leukaemic blast cells were not purified for these samples. Conclusions These first ex vivo results encourage further studies into relative proteasome subunit expression to improve proteasome inhibition-containing therapy and as a potential indicator of bortezomib response in acute leukaemia.

  6. Combined chemotherapy including platinum derivatives for medulloblastoma. The usefulness as maintenance chemotherapy

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    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)

  7. Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib

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    Nijhof, I. S.; Groen, R. W. J.; Noort, W. A.;

    2015-01-01

    Purpose: Novel therapeutic agents have significantly improved the survival of patients with multiple myeloma. Nonetheless, the prognosis of patients with multiple myeloma who become refractory to the novel agents lenalidomide and bortezomib is very poor, indicating the urgent need for new...... with lenalidomide or bortezomib for the treatment of lenalidomide- and bortezomib-refractory patients. Experimental Design: In ex vivo assays, mainly evaluating antibody-dependent cell-mediated cytotoxicity, and in an in vivo xenograft mouse model, we evaluated daratumumab alone or in combination with lenalidomide...... or bortezomib as a potential therapy for lenalidomide- and bortezomib-refractory multiple myeloma patients. Results: Daratumumab induced significant lysis of lenalidomide/bortezomib-resistant multiple myeloma cell lines and of primary multiple myeloma cells in the bone marrow mononuclear cells derived from...

  8. Co-delivery of docetaxel and bortezomib based on a targeting nanoplatform for enhancing cancer chemotherapy effects.

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    Nie, Junpeng; Cheng, Wei; Peng, Yunmei; Liu, Gan; Chen, Yuhan; Wang, Xusheng; Liang, Chaoyu; Tao, Wei; Wei, Yinping; Zeng, Xiaowei; Mei, Lin

    2017-11-01

    Using facile polydopamine (PDA)-based surface modification and a pH-sensitive catechol-boronate binding mechanism, a novel drug delivery system was designed for the treatment of breast cancer. The system was able to achieve the following goals: active targeting, pH responsiveness, in vivo blood circulation for a prolonged period of time, and dual drug loading. After coating with PDA, the docetaxel (DTX)-loaded star-shaped copolymer cholic acid-poly(lactide-co-glycolide) nanoparticles (CA-PLGA@PDA/NPs) were functionalized with amino-poly(ethylene glycol)-folic acid (NH2-PEG-FA) and bortezomib (BTZ) to form the targeting composition, DTX-loaded CA-PLGA@PDA-PEG-FA + BTZ/NPs. The novel NPs exhibited similar drug release characteristics compared to unfunctionalized CA-PLGA/NPs. Meanwhile, the incorporated NH2-PEG-FA contributed to active targeting which was illustrated by cellular uptake experiments and biodistribution studies. Moreover, the pH responsive binding between BTZ and PDA was demonstrated to be effective to release BTZ at the tumor acidic environment for synergistic action with DTX. Both in vitro cytotoxicity and in vivo antitumor studies demonstrated that the novel nanoplatform exhibited the most suitable therapeutic effects. Taken together, the versatile PDA modified DTX-loaded CA-PLGA@PDA-PEG-FA + BTZ/NPs offered a promising chemotherapeutic strategy for enhancing breast cancer treatment.

  9. Phase I Trial Using the Proteasome Inhibitor Bortezomib and Concurrent Chemoradiotherapy for Head-and-Neck Malignancies

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    Kubicek, Gregory J. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Axelrod, Rita S. [Department of Medical Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Machtay, Mitchell [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH (United States); Ahn, Peter H.; Anne, Pramila R. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Fogh, Shannon [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States); Cognetti, David [Department of Otolaryngology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Myers, Thomas J. [EMD Serono, Rockland, MA (United States); Curran, Walter J. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Dicker, Adam P., E-mail: Adam.dicker@jeffersonhospital.org [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States)

    2012-07-15

    Purpose: Advanced head-and-neck cancer (HNC) remains a difficult disease to cure. Proteasome inhibitors such as bortezomib have the potential to improve survival over chemoradiotherapy alone. This Phase I dose-escalation study examined the potential of bortezomib in combination with cisplatin chemotherapy and concurrent radiation in the treatment of locally advanced and recurrent HNC. Methods and Materials: Eligible patients received cisplatin once weekly at 30 mg/m{sup 2} per week and bortezomib along with concurrent radiation. Bortezomib was given on Days 1, 4, 8, and 11 every 3 weeks, with an initial starting dose of 0.7 mg/m{sup 2} and escalation levels of 1.0 and 1.3 mg/m{sup 2}. Dose escalation was performed only after assessment to rule out any dose-limiting toxicity. Results: We enrolled 27 patients with HNC, including 17 patients with recurrent disease who had received prior irradiation. Patients received bortezomib dose levels of 0.7 mg/m{sup 2} (7 patients), 1.0 mg/m{sup 2} (10 patients), and 1.3 mg/m{sup 2} (10 patients). No Grade 5 toxicities, 3 Grade 4 toxicities (all hematologic and considered dose-limiting toxicities), and 39 Grade 3 toxicities (in 20 patients) were observed. With a median follow-up of 7.4 months, the overall median survival was 24.7 months (48.4 months for advanced HNC patients and 15.4 months for recurrent HNC patients). Conclusion: Bortezomib in combination with radiation therapy and cisplatin chemotherapy is safe in the treatment of HNC with a bortezomib maximum tolerated dose of 1.0 mg/m{sup 2} in patients previously treated for HNC and 1.3 mg/m{sup 2} in radiation-naive patients.

  10. Treatment outcome and prognostic factor analysis in transplant-eligible Chinese myeloma patients receiving bortezomib-based induction regimens including the staged approach, PAD or VTD

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    Chim Chor

    2012-06-01

    Full Text Available Abstract Background We have reported promising outcomes using a staged approach, in which bortezomib/thalidomide/dexamethasone was used only in 14 patients with suboptimal response to VAD (vincristine/adriamycin/dexamethasone before autologous stem cell transplantation (ASCT. Here we compared the outcomes of the staged approach with frontline PAD (bortezomib/doxorubicin/dexamethasone or VTD (bortezomib/thalidomide/dexamethasone induction, and analysed prognostic factors for outcome. Patients and methods Ninety-one transplant-eligible Chinese patients received three induction regimens prior to ASCT [staged approach (N = 25, PAD (N = 31, VTD (N = 35]. and received thalidomide maintenance for 2 years post-ASCT. Results 43 (47.3% patients had International Staging System (ISS III disease. By an intention-to-treat analysis, the overall CR/nCR rate were 37.4% post-induction, and 62.6% post-ASCT. Five-year overall (OS and event-free (EFS survivals were 66% and 45.1%. There was no difference of the post-induction CR/nCR rate, EFS or OS between patients induced by these three regimens. Moreover, ISS III disease did not affect CR/nCR rates. Multivariate analysis showed that ISS and post-ASCT CR/nCR impacted OS while ISS and post-induction CR/nCR impacted EFS. Conclusions These three induction regimens produced comparable and favorable outcomes in myeloma. The unfavorable outcome of ISS stage III persisted despite upfront/early use of bortezomib. CR/nCR predicted favorable survivals.

  11. ABT-199, a BH3 mimetic that specifically targets Bcl-2, enhances the antitumor activity of chemotherapy, bortezomib and JQ1 in "double hit" lymphoma cells.

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    Johnson-Farley, Nadine; Veliz, Jonny; Bhagavathi, S; Bertino, Joseph R

    2015-07-01

    Double hit lymphoma (DHL) is a recently recognized lymphoma with a survival of less than 2 years. Both ABT-737, a Bcl-2/Bcl-XL inhibitor, and ABT-199, which selectively targets Bcl-2, were potently cytotoxic against DHL cell lines Sc-1 and OcI-LY18, the RL cell line and primary human DHL cells, but not Ramos cells, which lack Bcl-2 expression. ABT-199 was more potent than ABT-737, and is the most promising of the BH3 mimetics to date. The DHL cell lines were also sensitive (DHL cell lines. Cells from a patient with DHL were also sensitive to JQ1 and bortezomib, providing a rationale for a clinical trial of these combinations in patients with relapsed DHL.

  12. Neoadjuvant multidrug chemotherapy including High-Dose Methotrexate modifies VEGF expression in Osteosarcoma: an immunohistochemical analysis

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    Rosa Michele A

    2010-02-01

    Full Text Available Abstract Background Angiogenesis plays a role in the progression of osteosarcoma, as well as in other mesenchymal tumors and carcinomas, and it is most commonly assessed by vascular endothelial growth factor (VEGF expression or tumor CD31-positive microvessel density (MVD. Tumor VEGF expression is predictive of poor prognosis, and chemotherapy can affect the selection of angiogenic pattern. The aim of the study was to investigate the clinical and prognostic significance of VEGF and CD31 in osteosarcoma, both at diagnosis and after neoadjuvant chemotherapy, in order to identify a potential role of chemotherapy in angiogenic phenotype. Methods A retrospective analysis was performed on 16 patients with high grade osteosarcoma. In each case archival pre-treatment biopsy tissue and post-chemotherapy tumor specimens were immunohistochemically stained against CD31 and VEGF, as markers of angiogenic proliferation both in newly diagnosed primary osteosarcoma and after multidrug chemotherapy including high-dose methotrexate (HDMTX. The correlation between clinicopathological parameters and the degree of tumor VEGF and CD31 expression was statistically assessed using the χ2 test verified with Yates' test for comparison of two groups. Significance was set at p Results Expression of VEGF was positive in 11 cases/16 of cases at diagnosis. Moreover, 8 cases/16 untreated osteosarcomas were CD31-negative, but the other 8 showed an high expression of CD31. VEGF expression in viable tumor cells after neoadjuvant chemotherapy was observed in all cases; in particular, there was an increased VEGF expression (post-chemotherapy VEGF - biopsy VEGF in 11 cases/16. CD31 expression increased in 11 cases/16 and decreased in 3 cases after chemotherapy. The data relating to the change in staining following chemotherapy appear statistically significant for VEGF expression (p p > 0,05. Conclusions Even if the study included few patients, these results confirm that VEGF and CD

  13. Bortezomib-Induced Bronchiolitis Obliterans Organizing Pneumonia

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    E. Vandeix

    2012-01-01

    Full Text Available Introduction. Bortezomib is a proteasome inhibitor indicated for the treatment of multiple myeloma patients. The most frequent side effects are gastrointestinal and neurological. Serious pulmonary complications have been described rarely. Observation. This case involves a 74-year-old man suffering from IgG Kappa myeloma treated with bortezomib, melphalan, and dexamethasone. After administering chemotherapy, the patient developed an acute respiratory distress syndrome (ARDS. A surgical pulmonary biopsy proved the existence of bronchiolitis obliterans organizing pneumonia (BOOP lesions. Systemic corticotherapy led to a rapid improvement in the patient’s condition. Conclusion. This is the first reported histologically confirmed case of bortezomid-induced BOOP. Faced with severe respiratory symptoms in the absence of other etiologies, complications due to bortezomid treatment should be evoked and corticotherapy considered.

  14. Treatment of multiple myeloma: thalidomide-, bortezomib-, and lenalidomide-induced peripheral neuropathy.

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    Koeppen, Susanne

    2014-01-01

    Over the last 15 years, substantial progress has been made in the treatment of patients with multiple myeloma (MM). New chemotherapeutic options with the immunomodulatory drugs thalidomide and lenalidomide and with the proteasome inhibitor bortezomib have increased the response rates before and after autologous hematopoietic stem cell transplantation (ASCT). Incorporation of the novel agents into the treatment of newly diagnosed MM and at relapse is now standard of care also for patients with MM not eligible for ASCT. However, the use of thalidomide and bortezomib is frequently associated with a dose-limiting peripheral neuropathy. In order to take full advantage of the therapeutic potential, a risk assessment for neurotoxicity is needed on a case-by-case basis. This assessment includes pre-existing neurological symptoms due to the MM, any comorbidities, and past or planned treatment regimens. The aim is to achieve maximum efficacy while minimizing the risk of developing chemotherapy-induced polyneuropathy (CIPN). This requires a neurological evaluation of the patient at regular intervals, the implementation of preventive measures, and the development of validated therapeutic strategies for emerging neurotoxic side effects. This review focuses on the incidence, prevention, and management of peripheral neurotoxicity due to thalidomide, bortezomib, and lenalidomide in the treatment of MM.

  15. Bortezomib in treatment of extramedullary plasmacytoma of the pancreas

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    Ju-Ying Wei; Hong-Yan Tong; Wei-Fang Zhu; Hui Liu; Feng-Juan Zhang; Wen-Juan Yu; Jie Jin

    2009-01-01

    BACKGROUND: Extramedullary pancreatic plasmacy-toma treated with bortezomib is rarely reported. METHODS: We admitted a 53-year-old woman with an asymptomatic mass above the left clavicle for over three months, then an asymptomatic swelling of the pancreas was found. A biopsy on the mass and a ifne needle aspiration of the pancreas were performed. The diagnosis of extramedullary plasmacytoma (EMP) was made. The patient was initially treated with combination chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD regimen). She progressed to painless jaundice during the chemotherapy. Then she was treated with bortezomib and hyper-dose dexamethasone. As a result, she had a near complete remission. RESULTS: The data demonstrated that the diagnosis was EMP of the pancreas. The patient responded very well to bortezomib, while failing to respond to the traditional chemotherapy regimen of VAD. CONCLUSION: EMP of the pancreas is rare. This case gives evidence for an excellent response of EMP of the pancreas to bortezomib.

  16. Bortezomib induces autophagic death in proliferating human endothelial cells

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    Belloni, Daniela; Veschini, Lorenzo [Myeloma Unit, Department of Oncology, IRCCS H San Raffaele, Milan (Italy); Foglieni, Chiara [Department of Cardiology, IRCCS H San Raffaele, Milan (Italy); Dell' Antonio, Giacomo [Department of Pathology, IRCCS H San Raffaele, Milan (Italy); Caligaris-Cappio, Federico [Myeloma Unit, Department of Oncology, IRCCS H San Raffaele, Milan (Italy); Universita Vita-Salute IRCCS H San Raffaele, Milan (Italy); Ferrarini, Marina [Myeloma Unit, Department of Oncology, IRCCS H San Raffaele, Milan (Italy); Ferrero, Elisabetta, E-mail: elisabetta.ferrero@hsr.it [Myeloma Unit, Department of Oncology, IRCCS H San Raffaele, Milan (Italy)

    2010-04-01

    The proteasome inhibitor Bortezomib has been approved for the treatment of relapsed/refractory multiple myeloma (MM), thanks to its ability to induce MM cell apoptosis. Moreover, Bortezomib has antiangiogenic properties. We report that endothelial cells (EC) exposed to Bortezomib undergo death to an extent that depends strictly on their activation state. Indeed, while quiescent EC are resistant to Bortezomib, the drug results maximally toxic in EC switched toward angiogenesis with FGF, and exerts a moderate effect on subconfluent HUVEC. Moreover, EC activation state deeply influences the death pathway elicited by Bortezomib: after treatment, angiogenesis-triggered EC display typical features of apoptosis. Conversely, death of subconfluent EC is preceded by ROS generation and signs typical of autophagy, including intense cytoplasmic vacuolization with evidence of autophagosomes at electron microscopy, and conversion of the cytosolic MAP LC3 I form toward the autophagosome-associated LC3 II form. Treatment with the specific autophagy inhibitor 3-MA prevents both LC3 I/LC3 II conversion and HUVEC cell death. Finally, early removal of Bortezomib is accompanied by the recovery of cell shape and viability. These findings strongly suggest that Bortezomib induces either apoptosis or autophagy in EC; interfering with the autophagic response may potentiate the antiangiogenic effect of the drug.

  17. Cost savings of home bortezomib injection in patients with multiple myeloma treated by a combination care in Outpatient Hospital and Hospital care at Home.

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    Touati, Mohamed; Lamarsalle, Ludovic; Moreau, Stéphane; Vergnenègre, Françoise; Lefort, Sophie; Brillat, Catherine; Jeannet, Laetitia; Lagarde, Aline; Daulange, Annick; Jaccard, Arnaud; Vergnenègre, Alain; Bordessoule, Dominique

    2016-12-01

    At home injectable chemotherapy for patients receiving treatment for hematological diseases is still in debate. Given the expense of new innovative medicines, at home treatment has been proposed as a suitable option for improving patient quality of life and decreasing treatment costs. We decided to assess the cost of bortezomib administration in France among multiple myeloma patients from an economic standpoint. Patients in this study were treated within a regional hematological network combining outpatient hospital care and Hospital care at Home administration. To make the cost comparison, our team simulated outpatient hospital care expenses. Fifty-four consecutive multiple myeloma patients who received at least one injection of bortezomib in Hospital care at Home from January 2009 to December 2011 were included in the study. The median number of injections was 12 (range 1-44) at home and 6 (range 0-30) in the outpatient care unit. When compared with the cost simulation of outpatient hospital care alone, bortezomib administration with combined care was significantly less expensive for the National Health Insurance (NHI) budget. The mean total cost per patient and per injection was 954.20 € for combined outpatient and Hospital care at Home vs 1143.42 € for outpatient hospital care alone. This resulted in an estimated 16.5 % cost saving (Wilcoxon signed-rank test, p multiple myeloma patients treated with bortezomib in routine practice in a large rural area.

  18. Differential impact of bortezomib on HL-60 and K562 cells.

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    Kliková, Katarína; Štefaniková, Andrea; Pilchová, Ivana; Hatok, Jozef; Chudý, Peter; Chudej, Juraj; Dobrota, Dušan; Račay, Peter

    2015-01-01

    Bortezomib (PS-341, or Velcade), reversible inhibitor of 20S proteasome approved for the treatment of multiple myeloma and mantle cell lymphoma, exhibited a cytotoxic effect toward other malignancies including leukaemia. In this study, we have documented that incubation of both HL-60 and K562 leukaemia cells with nanomolar concentrations of bortezomib is associated with the death of HL-60 cells observed within 24 hours of incubation with bortezomib and the death of K562 cells that were observed after 72 hours of incubation with bortezomib. The relative resistance of K562 cells to bortezomib correlated well with significantly higher expression of HSP27, HSP70, HSP90α, HSP90β and GRP75 in these cells. Incubation of both HL-60 and K562 cells with bortezomib induced a cleavage of HSP90β as well as expression of HSP70 and HSP90β but bortezomib did not affect levels of HSP27, HSP90α, GRP75 and GRP78. The death of both types of cells was accompanied with proteolytic activation of caspase 3 that was observed in HL-60 cells and proteolytic degradation of procaspase 3 in K562 cells. Our study has also pointed to essential role of caspase 8 in bortezomib-induced cleavage of HSP90β in both HL-60 and K562 cells. Finally, we have shown that bortezomib induced activation of caspase 9/caspase 3 axis in HL-60 cells, while the mechanism of death of K562 cells remains unknown.

  19. Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

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    Vangsted, Annette J.; Klausen, Tobias W.; Abildgaard, Niels;

    2011-01-01

    the impact on outcome of HDT, INF-α maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (−3737T...... carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (−3737T, −1464G...

  20. Mitotoxicity and bortezomib-induced chronic painful peripheral neuropathy.

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    Zheng, H; Xiao, W H; Bennett, G J

    2012-12-01

    Many of the most effective anti-cancer drugs induce a dose-limiting peripheral neuropathy that compromises therapy. Evidence from animal models of chemotherapy-induced painful peripheral neuropathy produced by the taxane agent, paclitaxel, and the platinum-complex agent, oxaliplatin, indicate that they produce neuropathy via a common mechanism-a toxic effect on the mitochondria in primary afferent sensory neurons. Bortezomib is from the proteasome-inhibitor class of chemotherapeutics. It also produces a dose-limiting peripheral neuropathy, but its effects on neuronal mitochondria are unknown. To investigate this, we developed a model of bortezomib-induced painful peripheral neuropathy in the rat and assessed mitochondrial function (respiration and ATP production) in sciatic nerve samples harvested at two time points: day 7, which is three days after treatment and before pain appears, and day 35, which is one month post-treatment and the time of peak pain severity. We found significant deficits in Complex I-mediated and Complex II-mediated respiration, and in ATP production at both time points. Prophylactic treatment with acetyl-L-carnitine, which has previously been shown to prevent paclitaxel- and oxaliplatin-induced mitochondrial dysfunction and pain, completely blocked bortezomib's effects on mitochondria and pain. These results suggest that mitotoxicity may be the core pathology for all chemotherapy-induced peripheral neuropathy and that drugs that protect mitochondrial function may be useful chemotherapy adjuncts.

  1. Bone building with bortezomib

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    Roodman, G. David

    2008-01-01

    In this issue of the JCI, Mukherjee et al. report that bortezomib, a clinically available proteasome inhibitor active against myeloma, induces the differentiation of mesenchymal stem/progenitor cells (MSCs) — rather than mature osteoprogenitor cells — into osteoblasts, resulting in new bone formation (see the related article beginning on page 491). These results were observed when MSCs were implanted subcutaneously in mice or were used to treat a mouse model of postmenopausal bone loss. Others have reported that immunomodulatory drugs (e.g., thalidomide and lenalidomide), which are active against myeloma, also block the activity of bone-resorbing osteoclasts. These results reflect the utility of targeting endogenous MSCs for the purpose of tissue repair and suggest that combining different classes of agents that are antineoplastic and also inhibit bone destruction and increase bone formation should be very beneficial for myeloma patients suffering from severe bone disease. PMID:18219395

  2. Population Pharmacokinetic Analysis of Bortezomib in Pediatric Leukemia Patients: Model-Based Support for Body Surface Area-Based Dosing Over the 2- to 16-Year Age Range.

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    Hanley, Michael J; Mould, Diane R; Taylor, Timothy J; Gupta, Neeraj; Suryanarayan, Kaveri; Neuwirth, Rachel; Esseltine, Dixie-Lee; Horton, Terzah M; Aplenc, Richard; Alonzo, Todd A; Lu, Xiaomin; Milton, Ashley; Venkatakrishnan, Karthik

    2017-09-01

    This population analysis described the pharmacokinetics of bortezomib after twice-weekly, repeat-dose, intravenous administration in pediatric patients participating in 2 clinical trials: the phase 2 AALL07P1 (NCT00873093) trial in relapsed acute lymphoblastic leukemia and the phase 3 AAML1031 (NCT01371981) trial in de novo acute myelogenous leukemia. The sources of variability in the pharmacokinetic parameters were characterized and quantified to support dosing recommendations. Patients received intravenous bortezomib 1.3 mg/m(2) twice-weekly, on days 1, 4, and 8 during specific blocks or cycles of both trials and on day 11 of block 1 of study AALL07P1, in combination with multiagent chemotherapy. Blood samples were obtained and the plasma was harvested on day 8 over 0-72 hours postdose to measure bortezomib concentrations by liquid chromatography-tandem mass spectrometry. Concentration-time data were analyzed by nonlinear mixed-effects modeling. Covariates were examined using forward addition (P < .01)/backward elimination (P < .001). Data were included from 104 patients (49%/51% acute lymphoblastic leukemia/acute myelogenous leukemia; 60%/40% aged 2-11 years/12-16 years). Bortezomib pharmacokinetics were described by a 3-compartment model with linear elimination. Body surface area adequately accounted for variability in clearance (exponent 0.97), supporting body surface area-based dosing. Stratified visual predictive check simulations verified that neither age group nor patient population represented sources of meaningful pharmacokinetic heterogeneity not accounted for by the final population pharmacokinetic model. Following administration of 1.3 mg/m(2) intravenous bortezomib doses, body surface area-normalized clearance in pediatric patients was similar to that observed in adult patients, thereby indicating that this dose achieves similar systemic exposures in pediatric patients. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley

  3. 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.)

  4. ABT-737 synergizes with Bortezomib to kill melanoma cells

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    Steven N. Reuland

    2012-02-01

    The BH3 mimetic ABT-737 is a potent inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-XL, and Bcl-w. The Bcl-2 family modulates sensitivity to anticancer drugs in many cancers, including melanomas. In this study, we examined whether ABT-737 is effective in killing melanoma cells either alone or in combination with a proteasome inhibitor already in clinical use (Bortezomib in vitro and in vivo, and further evaluated the mechanisms of action. Results showed that ABT-737 alone induced modest cytotoxicity in melanoma cells, but only at higher doses. Knock-down of the anti-apoptotic proteins Bcl-2, Bcl-XL, or Mcl-1 with siRNAs demonstrated that Mcl-1 is the critical mediator of melanoma's resistance to ABT-737 treatment. However, ABT-737 displayed strong synergistic lethality when combined with Bortezomib. Immunoblot analyses demonstrated that Bortezomib increased expression of Noxa, a pro-apoptotic Bcl-2 member that antagonizes Mcl-1. Additionally, siRNA-mediated inhibition of Noxa expression protected melanoma cells from cytotoxicity induced by the combination treatment. These results demonstrate that Bortezomib synergizes with ABT-737 by neutralizing Mcl-1's function via increased levels of Noxa. In a xenograft mouse model, although drug doses were limited due to toxicity, ABT-737 or Bortezomib slowed melanoma tumor growth compared to the control, and the drug combination significantly decreased growth compared to either drug alone. These data imply that less toxic drugs fulfilling a function similar to Bortezomib to neutralize Mcl-1 are promising candidates for combination with ABT-737 for treating melanomas.

  5. Bortezomib Induced Hepatitis B Reactivation

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    Salwa Hussain

    2014-01-01

    Full Text Available Background. It has recently been reported that hepatitis B (HBV reactivation often occurs after the use of rituximab and stem cell transplantation in patients with lymphoma who are hepatitis B surface antigen (HBsAg negative. However, clinical data on HBV reactivation in multiple myeloma (MM is limited to only a few reported cases. Bortezomib and lenalidomide have remarkable activity in MM with manageable toxicity profiles, but reactivation of viral infections may emerge as a problem. We present a case of MM that developed HBV reactivation after bortezomib and lenalidomide therapy. Case Report. A 73-year-old female with a history of marginal cell lymphoma was monitored without requiring therapy. In 2009, she developed MM, presenting as a plasmacytoma requiring vertebral decompression and focal radiation. While receiving radiation she developed renal failure and was started on bortezomib and liposomal doxorubicin. After a transient response to 5 cycles, treatment was switched to lenalidomide. Preceding therapy initiation, her serology indicated resolved infection. Serial monitoring for HBV displayed seroconversion one month after change in therapy. Conclusion. Bortezomib associated late HBV reactivation appears to be a unique event that requires further confirmation and brings to discussion whether hepatitis B core positive individuals would benefit from monitoring of HBV activation while on therapy.

  6. Curability of cancer by radiotherapy and chemotherapy, including in neuraxial neoplasms

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    Jalali Rakesh

    2009-01-01

    Full Text Available In the October of 1996, Lance Armstrong, celebrated cyclist and one of the greatest athletes the world has ever seen, at the age of 24, was diagnosed with metastatic testicular cancer with disease having already spread to his abdomen, lungs and brain. Lance underwent four cycles of chemotherapy, actually the pretty standard one, pioneered at the Indiana University and not only did he get completely cured of his cancer, he remains extremely well till date, 12 years later. He sure did have a few adverse effects during those cycles of chemotherapy in the form of nausea, vomiting, weakness and fall in blood count but he knew and experienced them only for a short transient time and emerged triumphant and strong. In fact, he went on to win six awe-inspiring and incredible successive Tours de France victories from 1999-2005, one of the most grueling sporting events testing the endurance of the very fittest. After his retirement, he has been so inspired that he has completely devoted himself to educate people about the common myths about cancer, and promised to raise awareness and generate money for furthering research into surgery, radiation therapy and chemotherapy for cancer through his foundation. He says "I am indebted to the doctors, nurses and medicine and would want to pay them back for all their energy and caring." In his successful journey of overcoming cancer, he captures the essence of its treatment so well by declaring "Pain is temporary, it may last a minute, or an hour, or a day, or a year, but eventually, it will subside and something else will take its place. If I quit, however, it will last forever".

  7. Chemotherapy

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    Ofer Merimsky

    2000-01-01

    Full Text Available Subjects and Methods: Seven patients with progressive localized or metastatic chemo-resistant osteosarcoma were treated by gemcitabine.The protocol included gemcitabine 1000 mg/m2/w for 7 consecutive weeks, followed by 1 week rest. If no progression was observed,maintenance by gemcitabine 1000 mg/m2/w for 3 weeks every 28 days was given until failure was clinically or radiologically evident.

  8. Desmoplastic small round cell tumor: review of therapy including surgery followed by continuous hyperthermic peritoneal perfusion of chemotherapy

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    Andrea Hayes-Jordan

    2011-12-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT is a very rare disease of children, adolescents, and young adults and involves the abdominal cavity. DSRCT has characteristic fusion gene involving EWS1 and WT1 translocation, t(11;22(p13;q12. Unlike Ewing’s sarcoma of bone, DSRCT usually presents with diffuse peritoneal implants that are prone to recur. The primary organ of origin of DSRCT is mesenchyme of the peritoneum. This makes it a very unique tumor that is difficult to treat because of the infiltrative and diffuse nature of the peritoneum. The challenge of local control is to remove dozens to hundreds of tumors studding the peritoneal cavity, and then eliminate microscopic disease. We review a sequential multimodality strategy to reduce macroscopic and microscopic disease including neoadjuvant chemotherapy, aggressive surgery including an emerging new therapy to use after surgery to treat microscopic residual disease: continuous hyperthermic peritoneal chemotherapy,

  9. Chemotherapy modulates intestinal immune gene expression including surfactant Protein-D and deleted in malignant brain tumors 1 in piglets

    DEFF Research Database (Denmark)

    Rathe, Mathias; Thomassen, Mads; Shen, René L.

    2016-01-01

    Background: Information about chemotherapy-induced intestinal gene expression may provide insight into the mechanisms underlying gut toxicity and help identify biomarkers and targets for intervention. Methods: We analyzed jejunal tissue from piglets subjected to two different, clinically relevant...... the upregulated genes for both treatments. Conclusion: In the developing intestine, chemotherapy increases the expression of genes related to innate immune functions involved in surveillance, protection, and homeostasis of mucosal surfaces....... the BUCY and DOX piglets. Selected genes of potential biological significance with a similar change in expression across the treatments were controlled by real-time polymerase chain reaction. Key innate defense molecules, including surfactant protein-D and deleted in malignant brain tumors 1, were among...

  10. Proteasome-based mechanisms of intrinsic and acquired bortezomib resistance in non-small cell lung cancer

    NARCIS (Netherlands)

    de Wilt, Leonie H. A. M.; Jansen, Gerrit; Assaraf, Yehuda G.; van Meerloo, Johan; Cloos, Jacqueline; Schimmer, Aaron D.; Chan, Elena T.; Kirk, Christopher J.; Peters, Godefridus J.; Kruyt, Frank A. E.

    2012-01-01

    The proteasome inhibitor bortezomib, registered for Multiple Myeloma treatment, is currently explored for activity in solid tumors including non-small cell lung cancer (NSCLC). Here we studied the proteasome-based mechanisms underlying intrinsic and acquired bortezomib resistance in NSCLC cells. Var

  11. Proteasome-based mechanisms of intrinsic and acquired bortezomib resistance in non-small cell lung cancer

    NARCIS (Netherlands)

    de Wilt, Leonie H. A. M.; Jansen, Gerrit; Assaraf, Yehuda G.; van Meerloo, Johan; Cloos, Jacqueline; Schimmer, Aaron D.; Chan, Elena T.; Kirk, Christopher J.; Peters, Godefridus J.; Kruyt, Frank A. E.

    2012-01-01

    The proteasome inhibitor bortezomib, registered for Multiple Myeloma treatment, is currently explored for activity in solid tumors including non-small cell lung cancer (NSCLC). Here we studied the proteasome-based mechanisms underlying intrinsic and acquired bortezomib resistance in NSCLC cells.

  12. Overexpression of salivary-type amylase reduces the sensitivity to bortezomib in multiple myeloma cells.

    Science.gov (United States)

    Mizuno, Shohei; Hanamura, Ichiro; Ota, Akinobu; Karnan, Sivasundaram; Narita, Tomoko; Ri, Masaki; Mizutani, Motonori; Goto, Mineaki; Gotou, Mayuko; Tsunekawa, Norikazu; Shikami, Masato; Iida, Shinsuke; Hosokawa, Yoshitaka; Miwa, Hiroshi; Ueda, Ryuzo; Nitta, Masakazu; Takami, Akiyoshi

    2015-11-01

    Amylase-producing myeloma exhibits refractoriness to chemotherapy and a dismal prognosis. In this study, we established a human myeloma cell line, 8226/AMY1, in which a lentivirally transfected AMY1 gene was stably expressed and explored its biological characteristics. 8226/AMY1 showed a survival advantage over mock control when treated with dexamethasone, bortezomib, and lenalidomide in vitro partly through inhibition of apoptosis induced by these reagents. In a xenograft murine model, 8226/AMY1 showed rapid tumor growth and reduced sensitivity to bortezomib compared with mock. A microarray gene expression analysis identified TCL1A, which functions as a coactivator of the cell survival kinase Akt, differentially up-regulated in 8226/AMY1. The expression of phosphorylated Akt was increased in the 8226/AMY1 cells following bortezomib treatment, but not in the mock cells. In addition, treatment with perifosine, an inhibitor of Akt phosphorylation, enhanced the anti-myeloma effect of bortezomib in the 8226/AMY1 cells. Our data suggest that amylase-producing myeloma reduced the sensitivity to bortezomib in vitro and in vivo, and the up-regulation of TCL1A may influence the drug susceptibility of 8226/AMY1 via the phosphorylation of Akt. These findings provide clues for developing treatment approaches for not only amylase-producing myeloma, but also relapsed and refractory myelomas.

  13. Prevalence of bortezomib-resistant constitutive NF-kappaB activity in mantle cell lymphoma

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    Kahl Brad S

    2008-05-01

    Full Text Available Abstract Background The proteasome inhibitor bortezomib can inhibit activation of the transcription factor NF-κB, a mechanism implicated in its anti-neoplastic effects observed in mantle cell lymphoma (MCL. However, NF-κB can be activated through many distinct mechanisms, including proteasome independent pathways. While MCL cells have been shown to harbor constitutive NF-κB activity, what fraction of this activity in primary MCL samples is sensitive or resistant to inhibition by bortezomib remains unclear. Results Proteasome activity in the EBV-negative MCL cell lines Jeko-1 and Rec-1 is inhibited by greater than 80% after exposure to 20 nM bortezomib for 4 hours. This treatment decreased NF-κB activity in Jeko-1 cells, but failed to do so in Rec-1 cells when assessed by electrophoretic mobility shift assay (EMSA. Concurrently, Rec-1 cells were more resistant to the cytotoxic effects of bortezomib than Jeko-1 cells. Consistent with a proteasome inhibitor resistant pathway of activation described in mouse B-lymphoma cells (WEHI231 and a breast carcinoma cell line (MDA-MB-468, the bortezomib-resistant NF-κB activity in Rec-1 cells is inhibited by calcium chelators, calmodulin inhibitors, and perillyl alcohol, a monoterpene capable of blocking L-type calcium channels. Importantly, the combination of perillyl alcohol and bortezomib is synergistic in eliciting Rec-1 cell cytotoxicity. The relevance of these results is illuminated by the additional finding that a considerable fraction of primary MCL samples (8 out of 10 displayed bortezomib-resistant constitutive NF-κB activity. Conclusion Our findings show that bortezomib-resistant NF-κB activity is frequently observed in MCL samples and suggest that this activity may be relevant to MCL biology as well as serve as a potential therapeutic target.

  14. Lambda Light Chain Myeloma with Oliguric Cast Nephropathy and Remission with Bortezomib, Doxorubicin and Dexamethasone

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    R Hada

    2012-12-01

    We report the clinical course and outcome of a patient presenting with acute kidney injury and oliguria, preceded by acute gastroenteritis and intake of Chinese medications and dialysis dependent state for eight weeks. Kidney biopsy revealed cast nephropathy with lambda light chain restriction and severe tubular injury. Serum protein electrophoresis was normal with no “M spike” but serum free light chain ratio was altered with very high lambda and normal kappa light chain levels. Bone marrow biopsy showed >85% atypical plasma cells. Haemodialysis was continued and chemotherapy with bortezomib, doxorubicin and dexamethasone was started. Kidney function gradually improved with discontinuation of dialysis after 1 month and complete remission of acute kidney injury and myeloma in 4 months of chemotherapy. Keywords: acute kidney injury; bortezomib; cast nephropathy; multiple myeloma.

  15. COMBINED MODALITY TREATMENT INCLUDING METHOTREXATE-BASED CHEMOTHERAPY FOR PRIMARY CEREBRAL NERVOUS SYSTEM LYMPHOMA: A SINGLE INSTITUTION EXPERIENCE

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    Giuseppina Massini

    2009-11-01

    Full Text Available

    Chemotherapy including high-dose methotrexate (HD-MTX, with or without radiotherapy, is standard treatment for primary cerebral nervous system lymphoma (PCNSL. It remains controversial whether addition of other drugs will add to therapeutic efficacy. We report here on 41 patients with PCNSL treated using a combined treatment modality, including HD-MTX (3.5 g/m2 for 2 cycles prior to whole brain radiotherapy (WBRT. In 22 patients, the chemotherapy was intensified by adding high-dose cytosine arabinoside (HD-AraC (2g/m2 for 4 doses for 2 cycles. Complete remission was obtained in 23 of 34 assessable patients (67%, and overall and disease-free survival rates were 24% and 46%, respectively, without differences between treatment groups. The addition of HD-AraC was complicated by severe infections in 17/22 (77% patients, resulting in 3 toxic deaths. Our study indicates that addition of HD-AraC may not improve clinical outcome in PCNSL, while it increases toxicity. More targeted and less toxic therapies are warranted.

  16. Herpes zoster in multiple myeloma patients during bortezomib treatment

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    I. N. Nazarova

    2011-01-01

    Full Text Available Recent advances in multiple myeloma (MM treatment associated with new drug use including bortezomib. Experiences in wide ambul atory drug use confirm therapy success for this serious disease, but at the same time reveals the most common side effects. One of th e most significant is the reactivation of Herpes zoster , which leads to decrease MM therapy results because of inability to perform standard therapy in these patients. Literature data and own experiences about reactivation of Herpes zoster during bortezomib therapy as monothe rapy and in combination, which varies from 7 to 34% according to different authors and 25% of own experiences, is presented. Treatment and preventive schedule of this complication are shown.

  17. Bortezomib, Ifosfamide, Carboplatin, and Etoposide in a Patient with HIV-Negative Relapsed Plasmablastic Lymphoma

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    Mehmet Akce

    2016-01-01

    Full Text Available Plasmablastic lymphoma (PBL is a rare subtype of diffuse large B cell lymphoma (DLBCL, often associated with HIV infection. We present a case of a 53-year-old HIV-negative man with untreated hepatitis C viral infection who presented with abdominal pain and lymphadenopathy. Lymph node and bone marrow biopsies were consistent with plasmablastic lymphoma. He had partial response (PR to 6 cycles of EPOCH but disease progressed seven weeks later. Repeat biopsy was consistent with plasmablastic lymphoma. Three cycles of bortezomib, ifosfamide, carboplatin, and etoposide (B-ICE chemotherapy resulted in a partial response (PR. Five months later, he presented with widespread lymphadenopathy and tumor lysis syndrome with circulating blasts. Flow cytometry revealed a different population of lymphoma cells, this time positive for CD5, CD19, CD20, and CD22, with dim expression of CD45 and CD38. The patient died on the first day of ESHAP chemotherapy. There are no treatment recommendations or standard of care for plasmablastic lymphoma. A literature search yielded 10 cases in which bortezomib was administered in either HIV-positive or HIV-negative PBL. Six reported a partial response, 3 reported a complete response, and 1 was a near-complete response. Bortezomib, in combination with chemotherapy, may be an effective treatment option in PBL as reported here.

  18. Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma.

    Science.gov (United States)

    Palumbo, Antonio; Ambrosini, Maria Teresa; Benevolo, Giulia; Pregno, Patrizia; Pescosta, Norbert; Callea, Vincenzo; Cangialosi, Clotilde; Caravita, Tommaso; Morabito, Fortunato; Musto, Pellegrino; Bringhen, Sara; Falco, Patrizia; Avonto, Ilaria; Cavallo, Federica; Boccadoro, Mario

    2007-04-01

    In multiple myeloma (MM), the addition of thalidomide or bortezomib to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter phase 1/2 trial, dosing, safety, and efficacy of the 4-drug combination, bortezomib, melphalan, prednisone, and thalidomide (VMPT) was determined. Bortezomib was administered at 3 dose levels (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2) on days 1, 4, 15, and 22; melphalan was given at a dose of 6 mg/m2 on days 1 through 5 and prednisone at 60 mg/m2 on days 1 through 5. Thalidomide was delivered at 50 mg on days 1 through 35. Each course was repeated every 35 days. The maximum tolerated dose of bortezomib was 1.3 mg/m2. Thirty patients with relapsed or refractory MM were enrolled; 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good PR. Among 14 patients who received VMPT as second-line treatment, the PR rate was 79% and the immunofixation-negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year survival from study entry was 84%. Grade 3 nonhematologic adverse events included infections (5 patients), fatigue (1), vasculitis (1), and peripheral neuropathy (2); no grade 4 toxicities were recorded. Initial results showed that VMPT is an effective salvage therapy with a very high proportion of responses. The incidence of neurotoxicities was unexpectedly low.

  19. Molecular mechanisms of bortezomib resistant adenocarcinoma cells.

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    Erika Suzuki

    Full Text Available Bortezomib (Velcade™ is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM. Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ~30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response.

  20. A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib

    Science.gov (United States)

    YERLIKAYA, AZMI; ERDOĞAN, ELIF; OKUR, EMRAH; YERLIKAYA, ŞERIFE; SAVRAN, BIRCAN

    2016-01-01

    Glucose-regulated protein 78 kDa/binding immunoglobulin protein (GRP78/BIP) is a well-known endoplasmic reticulum (ER) chaperone protein regulating ER stress by facilitating protein folding, assembly and Ca2+ binding. GRP78 is also a member of the heat shock protein 70 gene family and induces tumor cell survival and resistance to chemotherapeutics. Bortezomib is a highly specific 26S proteasome inhibitor that has been approved as treatment for patients with multiple myeloma. The present study first examined the dose- and time-dependent effects of bortezomib on GRP78 expression levels in the highly metastatic mouse breast cancer 4T1 cell line using western blot analysis. The analysis results revealed that GRP78 levels were significantly increased by bortezomib at a dose as low as 10 nM. Time-dependent experiments indicated that the accumulation of GRP78 was initiated after a 24 h incubation period following the addition of 10 nM bortezomib. Subsequently, the present study determined the half maximal inhibitory concentration of intracellular calcium chelator BAPTA-AM (13.6 µM) on 4T1 cells. The combination effect of BAPTA-AM and bortezomib on the 4T1 cells was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and WST-1 assays and an iCELLigence system. The results revealed that the combination of 10 nM bortezomib + 5 µM BAPTA-AM is more cytotoxic compared with monotherapies, including 10 nM bortezomib, 1 µM BAPTA-AM and 5 µM BAPTA-AM. In addition, the present results revealed that bortezomib + BAPTA-AM combination causes cell death through the induction of apoptosis. The present results also revealed that bortezomib + BAPTA-AM combination-induced apoptosis is associated with a clear increase in the phosphorylation of stress-activated protein kinase/Jun amino-terminal kinase SAPK/JNK. Overall, the present results suggest that bortezomib and BAPTA-AM combination therapy may be a novel therapeutic strategy for breast cancer treatment

  1. Blockade of NFκB activity by Sunitinib increases cell death in Bortezomib-treated endometrial carcinoma cells.

    Science.gov (United States)

    Sorolla, Anabel; Yeramian, Andrée; Valls, Joan; Dolcet, Xavier; Bergadà, Laura; Llombart-Cussac, Antoni; Martí, Rosa Maria; Matias-Guiu, Xavier

    2012-10-01

    Endometrial carcinoma is one of the most common malignancies in the female genital tract, usually treated by surgery and radiotherapy. Chemotherapy is used when endometrial carcinoma is associated with widespread metastasis or when the tumor recurs after radiation therapy. In the present study, we demonstrate that the tyrosine kinase receptor inhibitor Sunitinib reduces cell viability, proliferation, clonogenicity and induces apoptotic cell death in endometrial carcinoma cell lines, which is not due to its action through the most known targets like VEGFR, nor through EGFR as demonstrated in this work. Interestingly, Sunitinib reduces NFκB transcriptional activity either at basal level or activation by EGF or TNF-α. We observed that Sunitinib was able to inhibit the Bortezomib-induced NFκB transcriptional activity which correlates with a decrease of the phosphorylated levels of IKKα and β, p65 and IκBα. We evaluated the nature of the interaction between Sunitinib and Bortezomib by the dose effect method and identified a synergistic effect (combination index < 1). Analogously, silencing of p65 expression by lentiviral-mediated short-hairpin RNA delivery in Bortezomib treated cells leads to a strongly increased sensitivity to Bortezomib apoptotic cell death. Altogether our results suggest that the combination of Sunitinib and Bortezomib could be considered a promising treatment for endometrial carcinoma after failure of surgery and radiation. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  2. A Case of Undiagnosed HIV Infection in a 57-Year-Old Woman with Multiple Myeloma: Consequences on Chemotherapy Efficiency and Safety

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    I. Poizot-Martin

    2016-01-01

    Full Text Available Background. Non-AIDS-defining cancers represent a rising health issue among HIV-infected patients. Nevertheless, HIV testing is not systematic during the initial cancer staging. Here, we report a case of HIV infection diagnosed three years after chemotherapy initiation for multiple myeloma. Results. A 57-year-old woman diagnosed with multiple myeloma underwent a first round of chemotherapy by bortezomib/lenalidomide and then with bortezomib/liposomal-doxorubicine/dexamethasone, with partial remission, poor hematological tolerance, and multiple episodes of pneumococcal infection. Allogenic stem cell transplantation was proposed leading to HIV testing, which revealed seropositivity, with an HIV viral load of 5.5 Log10/mL and severe CD4 T cell depletion (24 cells/mm3. Chemotherapy by bendamustin was initiated. Multidisciplinary staff decided the initiation of antiretroviral therapy with tenofovir/emtricitabin/efavirenz and prophylaxis against opportunistic infections. After 34 months, patient achieved complete remission, sustained HIV suppression, and significant CD4 recovery (450 cells/mm3, allowing effective pneumococcal immunization without relapse. Conclusion. Our case illustrates the drawback that ignored HIV infection is still causing to cancer patients receiving chemotherapy and highlights the importance of early HIV testing in oncology. A multidisciplinary approach including oncologists/hematologists, virologists, and pharmacists is recommended in order to avoid drug interactions between chemotherapy and antiretroviral drugs. Moreover, prophylactic medication is recommended in these patients regardless of CD4+ cell count at the initiation of chemotherapy.

  3. Clinical efficacy of including capecitabine in neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis of randomized controlled trials.

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    Qiuyun Li

    Full Text Available BACKGROUND: Capecitabine has proven effective as a chemotherapy for metastatic breast cancer. Though several Phase II/III studies of capecitabine as neoadjuvant chemotherapy have been conducted, the results still remain inconsistent. Therefore, we performed a meta-analysis to obtain more precise understanding of the role of capecitabine in neoadjuvant chemotherapy for breast cancer patients. METHODS: The electronic database PubMed and online abstracts from ASCO and SABCS were searched to identify randomized clinical trials comparing neoadjuvant chemotherapy with or without capecitabine in early/operable breast cancer patients without distant metastasis. Risk ratios were used to estimate the association between capecitabine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool data in RevMan 5.1. RESULTS: Five studies were included in the meta-analysis. Neoadjuvant use of capecitabine with anthracycline and/or taxane based therapy was not associated with significant improvement in clinical outcomes including: pathologic complete response in breast (pCR; RR = 1.10, 95% CI 0.87-1.40, p = 0.43, pCR in breast tumor and nodes (tnpCR RR = 0.99, 95% CI 0.83-1.18, p = 0.90, overall response rate (ORR; RR = 1.00, 95% CI 0.94-1.07, p = 0.93, or breast-conserving surgery (BCS; RR = 0.98, 95% CI 0.93-1.04, p = 0.49. CONCLUSIONS: Neoadjuvant treatment of breast cancer involving capecitabine did not significantly improve pCR, tnpCR, BCS or ORR. Thus adding capecitabine to neoadjuvant chemotherapy regimes is unlikely to improve outcomes in breast cancer patients without distant metastasis. Further research is required to establish the condition that capecitabine may be useful in breast cancer neoadjuvant chemotherapy.

  4. Bortezomib partially improves laminin α2 chain-deficient muscular dystrophy.

    Science.gov (United States)

    Körner, Zandra; Fontes-Oliveira, Cibely C; Holmberg, Johan; Carmignac, Virginie; Durbeej, Madeleine

    2014-05-01

    Congenital muscular dystrophy, caused by mutations in LAMA2 (the gene encoding laminin α2 chain), is a severe and incapacitating disease for which no therapy is yet available. We have recently demonstrated that proteasome activity is increased in laminin α2 chain-deficient muscle and that treatment with the nonpharmaceutical proteasome inhibitor MG-132 reduces muscle pathology in laminin α2 chain-deficient dy(3K)/dy(3K) mice. Here, we explore the use of the selective and therapeutic proteasome inhibitor bortezomib (currently used for treatment of relapsed multiple myeloma and mantle cell lymphoma) in dy(3K)/dy(3K) mice and in congenital muscular dystrophy type 1A muscle cells. Outcome measures included quantitative muscle morphology, gene and miRNA expression analyses, proteasome activity, motor activity, and survival. Bortezomib improved several histological hallmarks of disease, partially normalized miRNA expression (miR-1 and miR-133a), and enhanced body weight, locomotion, and survival of dy(3K)/dy(3K) mice. In addition, bortezomib reduced proteasome activity in congenital muscular dystrophy type 1A myoblasts and myotubes. These findings provide evidence that the proteasome inhibitor bortezomib partially reduces laminin α2 chain-deficient muscular dystrophy. Investigation of the clinical efficacy of bortezomib administration in congenital muscular dystrophy type 1A clinical trials may be warranted.

  5. Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN

    Directory of Open Access Journals (Sweden)

    Yaqin eHan

    2013-12-01

    Full Text Available Chemotherapy induced peripheral neuropathy (CIPN is a type of neuropathic pain that is a major dose-limiting side-effect of potentially curative cancer chemotherapy treatment regimens that develops in a ‘stocking and glove’ distribution. When pain is severe, a change to less effective chemotherapy agents may be required, or patients may choose to discontinue treatment. Medications used to alleviate CIPN often lack efficacy and/or have unacceptable side-effects. Hence the unmet medical need for novel analgesics for relief of this painful condition has driven establishment of rodent models of CIPN. New insights on the pathobiology of CIPN gained using these models are discussed in this review. These include mitochondrial dysfunction and oxidative stress that are implicated as key mechanisms in the development of CIPN. Associated structural changes in peripheral nerves include neuronopathy, axonopathy and/or myelinopathy, especially intra-epidermal nerve fiber (IENF degeneration. In patients with CIPN, loss of heat sensitivity is a hallmark symptom due to preferential damage to myelinated primary afferent sensory nerve fibers in the presence or absence of demyelination. The pathobiology of CIPN is complex as cancer chemotherapy treatment regimens frequently involve drug combinations. Adding to this complexity, there are also subtle differences in the pathobiological consequences of commonly used cancer chemotherapy drugs, viz platinum compounds, taxanes, vincristine, bortezomib, thalidomide and ixabepilone, on peripheral nerves.

  6. Sequential treatment with bortezomib plus dexamethasone followed by autologous hematopoietic stem cell transplantation in patients with multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    ZHENG Dong; LI Juan; HUANG Bei-hui; LIU Jun-ru; ZOU Wai-yi; SU Chang

    2012-01-01

    Background Whether the sequential treatment with bortezomib plus dexamethasone (BD) followed by autologous hematopoietic stem cell transplantation (ASCT) could extend the overall survival period in multiple myeloma patients is still not clear.Few large case studies about this therapeutics in multiple myeloma were reported in China.Our purpose was to assess the efficacy and adverse effects of sequential treatment with BD chemotherapy and ASCT in patients with multiple myeloma.Methods Fifty-three patients with newly diagnosed or relapsed/refractory multiple myeloma received BD as induction therapy before ASCT.Stem-cell mobilization was undertaken with cyclophosphamide 3-5 g/m2 plus granulocyte colony-stimulating factor 300 μg/d.Target yield was 2.0×106 CD34+ cells/kg.Conditioning for ASCT consisted of melphalan 200 mg/m2.Thalidomide and/or α-interferon was used as post-transplantation maintenance treatment.Results The BD chemotherapy before transplantation was effective in 86.7% of the 53 patients,including 22.6% with complete remission (CR),39.6% with near complete remission (nCR),and 24.5% with partial remission (PR).The best effect was achieved after two treatment courses.Most bortezomib-related adverse effects were classes 1-2.All patients were successfully mobilized after BD for autologous peripheral blood stem cell transplantation.The ASCT was effective in 96.3% of patients,including 49.1% with CR,32.1% with nCR,and 15.1% with PR.The CR rate was significantly increased (49.1% vs.22.6%,P <0.05) by sequential ASCT.Within 27 (range,6-53) months of follow-up,the efficacy of ASCT was maintained in 29 patients and further enhanced by post-transplantation maintenance treatment in four patients.Eleven patients died after transplantation.Among the patients undergoing BD/ASCT treatment,overall survival (OS) was significantly better in newly diagnosed patients in comparison to relapsed/refractory patients (P=0.046).Conclusions BD chemotherapy can

  7. The challenge of relapsed/refractory myeloma: An emerging role of bortezomib

    Directory of Open Access Journals (Sweden)

    Bhargav Vyasa

    2012-01-01

    Full Text Available The treatment of multiple myeloma (MM has undergone significant developments in recent years. The availability of the novel agents includes thalidomide and its analogs, proteasome inhibitors, arsenic trioxide, farnesyltransferase inhibitors 2-methoxyestradiol and lenalidomide has extended treatment options and has improved the outcome and quality of life of patients with MM. This review presents the totality of evidence through a systematic review that assessed the efficacy, safety or toxicity of bortezomib in patients with relapsed/refractory myeloma with or without concomitant complications. This review has precisely covered the role of bortezomib in patients with relapsed/refractory myeloma and not the newly detected populace.

  8. Characterization of bortezomib-adapted I-45 mesothelioma cells

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    Peddaboina Chander

    2010-05-01

    Full Text Available Abstract Background Bortezomib, a proteasome-specific inhibitor, has emerged as a promising cancer therapeutic agent. However, development of resistance to bortezomib may pose a challenge to effective anticancer therapy. Therefore, characterization of cellular mechanisms involved in bortezomib resistance and development of effective strategies to overcome this resistance represent important steps in the advancement of bortezomib-mediated cancer therapy. Results The present study reports the development of I-45-BTZ-R, a bortezomib-resistant cell line, from the bortezomib-sensitive mesothelioma cell line I-45. I-45-BTZ-R cells showed no cross-resistance to the chemotherapeutic drugs cisplatin, 5-fluorouracil, and doxorubicin. Moreover, the bortezomib-adapted I-45-BTZ-R cells had decreased growth kinemics and did not over express proteasome subunit β5 (PSMB5 as compared to parental I-45 cells. I-45-BTZ-R cells and parental I-45 cells showed similar inhibition of proteasome activity, but I-45-BTZ-R cells exhibited much less accumulation of ubiquitinated proteins following exposure to 40 nm bortezomib. Further studies revealed that relatively low doses of bortezomib did not induce an unfolded protein response (UPR in the bortezomib-adapted cells, while higher doses induced UPR with concomitant cell death, as evidenced by higher expression of the mitochondrial chaperone protein Bip and the endoplasmic reticulum (ER stress-related pro-apoptotic protein CHOP. In addition, bortezomib exposure did not induce the accumulation of the pro-apoptotic proteins p53, Mcl-1S, and noxa in the bortezomib-adapted cells. Conclusion These results suggest that UPR evasion, together with reduced pro-apoptotic gene induction, accounts for bortezomib resistance in the bortezomib-adapted mesothelioma cell line I-45-BTZ-R.

  9. Why bortezomib cannot go with‘green’?

    Institute of Scientific and Technical Information of China (English)

    Li Jia; Feng-Ting Liu

    2013-01-01

    Eat more‘green’ or eat‘ifve a day’ is one of the most important healthy lifestyle behaviours in the 21 century. Aiming to ifght cancer effectively, more than half patients use vitamins or herbs concurrently with conventional anticancer treatment. Flavonoids or polyphenols existing in vegetables, fruits and green tea are common plant pigments with antioxidant properties and considered acting as cancer preventing or anti-cancer agents. Recently it was found that some lfavonoids and vitamin C in diet or supplements have antagonistic effect with the anti-cancer drug bortezomib. Bortezomib is a speciifc inhibitor for proteasome and is currently used for treatment of relapsed and refractory multiple myeloma. Despite its successful rates in treating multiple myeloma and other solid tumors, it is unable to kill leukemic cells in the blood. It was recently revealed that some lfavonoids and vitamin C present in green leaves and green teas in the blood can neutralize bortezomib by directly interaction between two chemicals. Here we summarize why dietary lfavonoids should be avoided in patients who take bortezomib as chemotherapeutic drug.

  10. Bortezomib in the management of multiple myeloma

    Directory of Open Access Journals (Sweden)

    Jacob P Laubach

    2009-09-01

    Full Text Available Jacob P Laubach, Constantine S Mitsiades, Teru Hideshima, Robert Schlossman, Dharminder Chauhan, Nikhil Munshi, Irene Ghobrial, Nicole Carreau, Kenneth C Anderson, Paul G RichardsonDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USAAbstract: Multiple myeloma (MM is a B-cell malignancy characterized by clonal expansion of plasma cells within the bone marrow, the presence of a serum and/or urine monoclonal protein, lytic bone lesions, and anemia. On a cellular level, the disease is characterized by complex interactions between tumor cells and the surrounding bone marrow microenvironment. Understanding of the relationship between malignant plasma cells and the microenvironment has sparked ongoing efforts to develop targeted therapeutic agents for treatment of this disease. The successful development of the first-in-class small-molecule proteasome inhibitor bortezomib occurred as a result of these efforts. This review focuses on the rationale for bortezomib therapy in the treatment of patients with newly diagnosed and relapsed MM, important treatment-related side effects, and future directions for use of bortezomib and other, emerging proteasome inhibitors.Keywords: multiple myeloma, bortezomib, stem cell transplantation, peripheral neuropathy

  11. Successful use of combined high cut-off haemodialysis and bortezomib for acute kidney injury associated with myeloma cast nephropathy.

    LENUS (Irish Health Repository)

    Ward, F

    2012-05-01

    We present the case of a 58-year old female with de novo dialysis-dependent acute kidney injury (AKI) secondary to myeloma cast nephropathy. The patient underwent extended high cut-off haemodialysis (HCO-HD), in conjunction with bortezomib-based chemotherapy, and soon became dialysis independent with normal renal function. To our knowledge, this is the first time this treatment strategy has been employed successfully in an Irish centre.

  12. Cytotoxic and apoptotic effects of bortezomib and gefitinib compared to alkylating agents on human glioblastoma cells.

    Science.gov (United States)

    Pédeboscq, Stéphane; L'Azou, Béatrice; Passagne, Isabelle; De Giorgi, Francesca; Ichas, François; Pometan, Jean-Paul; Cambar, Jean

    2008-01-01

    Glioblastoma is a malignant astrocytic tumor with a median survival of about 12 months for which new therapeutic strategies are required. We therefore examined the cytotoxicity of anticancer drugs with different mechanisms of action on two human glioblastoma cell lines expressing various levels of EGFR (epidermal growth factor receptor). Apoptosis induced by these anticancer agents was evaluated by flow cytometry. The cytotoxicity of alkylating drugs followed a dose-effect curve and cytotoxicity index values were lower with carboplatin than with BCNU and temozolomide. Anti-EGFR gefitinib (10 microM) cytotoxicity on DBTRG.05-MG expressing high levels of EGFR was significantly higher than on U87-MG expressing low levels of EGFR. Carboplatin and temozolomide cytotoxicity was potentiated with the addition of gefitinib on DBTRG.05-MG. Among the anticancer agents tested, the proteasome inhibitor bortezomib was the most cytotoxic with very low IC50 on the two cell lines. Moreover, all anticancer drugs tested induced apoptosis in a concentration-dependent manner. Bortezomib proved to be a more potent inductor of apoptosis than gefitinib and alkylating agents. These results show the efficacy of bortezomib and of the association between conventional chemotherapy and gefitinib on glioblastoma cells and therefore suggest the interest of these molecules in the treatment of glioblastoma.

  13. Is Bortezomib a Rare Cause of Acute Pancreatitis?

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    Tevfik Solakoglu

    2013-11-01

    Full Text Available Recently we have read an interesting case with bortezomib-induced pancreatitis in JOP. Journal of the Pancreas (Online by Elouni et al. [1]. To the best of our knowledge, this was the first reported case of bortezomib-induced acute pancreatitis in the English literature. We know that drug-induced pancreatitis is rare and each year the list of drugs associated with acute pancreatitis increases. Bortezomib is a new drug which is selective and reversible proteasome inhibitor used for the treatment of patients with multiple myeloma [2]. Herein we present a case of acute pancreatitis induced by bortezomib.

  14. Efficacy and safety of bortezomib maintenance in patients with newly diagnosed multiple myeloma: a meta-analysis.

    Science.gov (United States)

    Sun, Chun-Yan; Li, Jun-Ying; Chu, Zhang-Bo; Zhang, Lu; Chen, Lei; Hu, Yu

    2017-08-31

    Multiple myeloma (MM) is a B-cell neoplasm with a high incidence of relapse. Bortezomib has been extensively studied for the maintenance treatment of MM. Here, we carried out a meta-analysis to determine the efficacy and safety of maintenance therapy with bortezomib. We searched for clinical trials in PubMed (Medline), Embase (OVID), and the Cochrane Library. Two randomized controlled trials (RCTs) enrolling a total of 1338 patients were included. Bortezomib maintenance statistically significantly improved both progression-free survival (PFS) (hazard ratio (HR) 0.67, 95% confidence interval (CI) = 0.51 to 0.87, P=0.003) and overall survival (OS) (HR = 0.75 therapy, 95% CI = 0.63 to 0.89, P=0.001) more than did non-bortezomib maintenance therapy. Our analysis revealed higher incidence of neutropenia (risks ratios (RR) = 1.39; 95% CI = 1.08 to 1.79), peripheral neuropathy (PN) (RR = 2.23; 95% CI = 1.38 to 3.61, P=0.001), and cardiologic events (RR = 1.91; 95% CI = 1.12 to 3.28, P=0.02) in patients with bortezomib maintenance therapy. Our meta-analysis demonstrates OS and PFS benefits of bortezomib maintenance therapy in patients with newly diagnosed MM. However, the therapy is associated with increased risk of adverse events. Additionally, more RCTs are needed for better understanding and determination of optimal bortezomib maintenance therapy in MM. © 2017 The Author(s).

  15. A phase II study of bortezomib plus prednisone for initial therapy of chronic graft-versus-host disease.

    Science.gov (United States)

    Herrera, Alex F; Kim, Haesook T; Bindra, Bhavjot; Jones, Kyle T; Alyea, Edwin P; Armand, Philippe; Cutler, Corey S; Ho, Vincent T; Nikiforow, Sarah; Blazar, Bruce R; Ritz, Jerome; Antin, Joseph H; Soiffer, Robert J; Koreth, John

    2014-11-01

    Chronic graft-versus-host disease (GVHD) induces significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Corticosteroids are standard initial therapy, despite limited efficacy and long-term toxicity. Based on our experience using bortezomib as effective acute GVHD prophylaxis, we hypothesized that proteasome-inhibition would complement the immunomodulatory effects of corticosteroids to improve outcomes in chronic GVHD (cGVHD). We undertook a single-arm phase II trial of bortezomib plus prednisone for initial therapy of cGVHD. Bortezomib was administered at 1.3 mg/m(2) i.v. on days 1, 8, 15, and 22 of each 35-day cycle for 3 cycles (15 weeks). Prednisone was dosed at .5 to 1 mg/kg/day, with a suggested taper after cycle 1. All 22 enrolled participants were evaluable for toxicity; 20 were evaluable for response. Bortezomib plus prednisone therapy was well tolerated, with 1 occurrence of grade 3 sensory peripheral neuropathy possibly related to bortezomib. The overall response rate at week 15 in evaluable participants was 80%, including 2 (10%) complete and 14 (70%) partial responses. The organ-specific complete response rate was 73% for skin, 53% for liver, 75% for gastrointestinal tract, and 33% for joint, muscle, or fascia involvement. The median prednisone dose decreased from 50 mg/day to 20 mg/day at week 15 (P prednisone for initial treatment of cGVHD is feasible and well tolerated. We observed a high response rate to combined bortezomib and prednisone therapy; however, in this single-arm study, we could not directly measure the impact of bortezomib. Proteasome inhibition may offer benefit in the treatment of cGVHD and should be further evaluated.

  16. Apoptosis Induction and Gene Expression Profile Alterations of Cutaneous T-Cell Lymphoma Cells following Their Exposure to Bortezomib and Methotrexate

    Science.gov (United States)

    Kontsioti, Frieda; Konsta, Eugene; Vikentiou, Miriam; Spathis, Aris; Papageorgiou, Sotiris; Vasilatou, Diamantina; Gkontopoulos, Konstantinos; Mpazani, Efthimia; Karakitsos, Petros; Rigopoulos, Dimitrios; Dimitriadis, George

    2017-01-01

    Mycosis fungoides (MF) and its leukemic variant Sézary syndrome (SS) comprise the majority of CTCL, a heterogenous group of non-Hodgkins lymphomas involving the skin. The CTCL’s resistance to chemotherapy and the lack of full understanding of their pathogenesis request further investigation. With the view of a more targeted therapy, we evaluated in vitro the effectiveness of bortezomib and methotrexate, as well as their combination in CTCL cell lines, regarding apoptosis induction. Our data are of clinical value and indicate that the bortezomib/methotrexate combinational therapy has an inferior impact on the apoptosis of CTCL compared to monotherapy, with bortezomib presenting as the most efficient treatment option for SS and methotrexate for MF. Using PCR arrays technology, we also investigated the alterations in the expression profile of genes related to DNA repair pathways in CTCL cell lines after treatment with bortezomib or methotrexate. We found that both agents, but mostly bortezomib, significantly deregulate a large number of genes in SS and MF cell lines, suggesting another pathway through which these agents could induce apoptosis in CTCL. Finally, we show that SS and MF respond differently to treatment, verifying their distinct nature and further emphasizing the need for discrete treatment approaches. PMID:28107479

  17. Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma.

    Science.gov (United States)

    Sivaraj, Dharshan; Green, Michael M; Li, Zhiguo; Sung, Anthony D; Sarantopoulos, Stefanie; Kang, Yubin; Long, Gwynn D; Horwitz, Mitchell E; Lopez, Richard D; Sullivan, Keith M; Rizzieri, David A; Chao, Nelson J; Gasparetto, Cristina

    2017-02-01

    Comprehensive recommendations for maintenance therapy after autologous stem cell transplantation (ASCT) for patients with multiple myeloma (MM) have yet to be defined. Bortezomib has been utilized as maintenance therapy after ASCT, but data attesting to the safety and efficacy of this agent compared with lenalidomide in the post-ASCT setting are limited. Therefore, we retrospectively analyzed the outcomes of 102 patients with MM who received maintenance therapy with bortezomib after ASCT at Duke University's adult bone marrow transplant clinic between 2005 and 2015. Maintenance with bortezomib was initiated between 60 and 90 days after ASCT as a single agent 1.3 mg/m(2) once every 2 weeks (n = 92) or in combination with lenalidomide (10 mg/day) (n = 10). The median age at ASCT was 64 (range, 31 to 78). Of the 99 patients with molecular data available, 42% had high-risk cytogenetics (including d17p, t(4;14), +1q, and t(14;16) by fluorescein in situ hybridization). Overall, 46% of patients experienced side effects from maintenance therapy, with 31% of all patients experiencing peripheral neuropathy. In total, 2% of patients required discontinuation of bortezomib maintenance because of adverse events. No secondary malignancies were reported from the therapy. The median progression-free survival (PFS) for patients receiving maintenance therapy with bortezomib after ASCT was 36.5 months (95% confidence interval [CI], 21.3 to not available) and median overall survival was 72.7 months (95% CI, 63.9 to not available). The PFS of patients with high-risk cytogenetics was not statistically significantly different from those with standard-risk cytogenetics, suggesting that maintenance with bortezomib may help overcome the impact of high-risk cytogenetics on early progression. These results indicate that maintenance therapy with bortezomib represents a safe, well-tolerated, and efficacious option for patients with high-risk cytogenetics, renal insufficiency, an

  18. The choice of regimens based on bortezomib for patients with newly diagnosed multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Jingsong He

    Full Text Available INTRODUCTION: Bortezomib has significantly improved multiple myeloma (MM response rates, but strategies for choosing bortezomib-based regimens for initial MM therapy are not standardized. Here, we describe four bortezomib-based therapies in Chinese MM patients to determine the optimal chemotherapeutic approach. METHODS: Newly diagnosed symptomatic MM patients at three hematological centers between February 1, 2006 and May 31, 2013 were treated with therapies including bortezomib plus dexamethasone (PD or combinations of PD with either adriamycin (PAD, cyclophosphamide (PCD or thalidomide (PTD for every 28 days. RESULTS: The overall response rate of all the 215 eligible patients was 90.2%. The ORR for PCD, PAD, PTD and PD were 97.4%, 93.2%, 85.3% and 77.8% while the effects with VGPR or better were 63.7%, 62.7%, 44.2% and 37.8%, respectively. The effect of ORR, VGPR and CR/nCR for the PCD regimen was better than the PD protocol. Median PFS for all patients was 29.0 months with significant differences observed among treatment groups. Median OS of all the patients was not reached, but three-drug combinations were superior to PD alone. Frequently observed toxicities were neutropenia, thrombocytopenia, fatigue, infection, herpes zoster, and peripheral neuropathy. The incidence of peripheral neuropathy (PN in PTD group was significantly higher than other three groups, especially grade 2-3 PN. Treatment with anti-viral agent acyclovir significantly reduced the incidence of herpes zoster. CONCLUSIONS: Our experience indicated that bortezomib-based regimens were effective and well-tolerated in the Chinese population studied; three-drug combinations PCD, PAD were superior to PD, especially with respect to PCD.

  19. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth Carl)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  20. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

  1. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

  2. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth Carl)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  3. Bortezomib for refractory antibody-mediated cardiac allograft rejection.

    Science.gov (United States)

    Eckman, Peter M; Thorsgard, Marit; Maurer, David; Kim, Youngki; Alloway, Rita R; Woodle, E Steve

    2009-01-01

    This experience demonstrates that a bortezomib-based regimen provided effective therapy for late, refractory AMR in an adult heart transplant recipient and was well tolerated. This remarkably positive experience despite the refractory nature of the AMR episode argues strongly for continued evaluation of bortezomib use in this patient population.

  4. Bortezomib prevents acute doxorubicin ovarian insult and follicle demise, improving the fertility window and pup birth weight in mice.

    Directory of Open Access Journals (Sweden)

    Elon C Roti Roti

    Full Text Available Increasing numbers of female patients survive cancer, but succumb to primary ovarian insufficiency after chemotherapy. We tested the hypothesis that Bortezomib (Bort protects ovaries from doxorubicin (DXR chemotherapy by treating female mice with Bort 1 hour prior to DXR. By preventing DXR accumulation in the ovary, Bort attenuated DXR-induced DNA damage in all ovarian cell types, subsequent γH2AFX phosphorylation, and resulting apoptosis in preantral follicles. Bort pretreatment extended the number of litters per mouse, improved litter size and increased pup weight following DXR treatment, thus increasing the duration of post-chemotherapy fertility and improving pup health. As a promising prophylactic ovoprotective agent, Bort does not interfere with cancer treatment, and is currently used as a chemotherapy adjuvant. Bort-based chemoprotection may preserve ovarian function in a non-invasive manner that avoids surgical ovarian preservation, thus diminishing the health complications of premature menopause following cancer treatment.

  5. Chemotherapie-induzierte Neuropathien (CIN

    Directory of Open Access Journals (Sweden)

    Vass A

    2009-01-01

    Full Text Available Durch Chemotherapie induzierte Neuropathien manifestieren sich meist als überwiegend sensorische Neuropathien, die zu Koordinationsstörungen und neuropathischen Schmerzen führen. Da es keine kausale Therapie gibt, stellen sie eine dosislimitierende Nebenwirkung der Tumortherapie dar. Hervorgerufen werden sie durch fünf Substanzgruppen: Platinderivate, Taxane, Vinca-Alkaloide sowie Bortezomib und Thalidomid. In dieser Übersicht wird auf die kumulativen Dosen dieser Substanzen und die jeweilige Symptomatik und Häufigkeit der dadurch entstehenden Neuropathien eingegangen.

  6. Pooled analysis of the reports of pomalidomide after failure of lenalidomide and (or) bortezomib for multiple myeloma.

    Science.gov (United States)

    Sheng, Zhixin; Liu, Guangyu

    2016-06-01

    The use of pomalidomide after lenalidomide and (or) bortezomib failure in patients with multiple myeloma is not clearly clarified in clinical practice. We sought to compile the available clinical reports to better understand the effectiveness of pomalidomide after failure of lenalidomide and (or) bortezomib. We searched published reports including pomalidomide, lenalidomide and (or) bortezomib. Seven reports were identified. Pomalidomide-based regimen was pomalidomide plus low-dose dexamethasone (POM + LoDEX). Six randomized controlled trials enrolling a total of 641 patients that evaluated the treatment effects of pomalidomide after lenalidomide and (or) bortezomib failure in patients with multiple myeloma were included. Pooled results showed that the overall response rate (ORR) was 31% in the POM + LoDEX group. Analysis of heterogeneity showed very little (p = 0.997, I(2)  = 0%), suggesting that response rates of POM + LoDEX therapy were consistent across those included trials. Stable disease was achieved in 40% of 603 patients (heterogeneity: p = 0.980, I(2)  = 0%). In those >65 years, overall response was achieved in 32% of 71 patients (heterogeneity: p = 0.77, I(2)  = 0%). POM + LoDEX showed promising activity in the 95 patients with high-risk cytogenetic abnormalities: ORR was 27% (heterogeneity: p = 0.97, I(2)  = 0%). In the pooled analysis, toxicity consisted primarily of myelosuppression: Grade 3 or 4 neutropenia was seen in 53% (heterogeneity: p = 0.857, I(2)  = 0%). Pomalidomide may produce clinical benefits in patients who had shown refractory on prior lenalidomide and (or) bortezomib therapy. Moreover, elder patients and high-risk cytogenetic abnormalities were not negative predictors for pomalidomide response after lenalidomide and (or) bortezomib failure. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Bortezomib: the evidence of its clinical impact in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Simon Lancaster

    2006-06-01

    Full Text Available Simon LancasterSL Comm Ltd, Macclesfield, UKIntroduction: Multiple myeloma is a relatively common and incurable form of hematologic malignancy for which there is currently no single standard therapy. Bortezomib inhibits the 20S proteasome involved in the degradation of intracellular proteins, induces apoptosis, reverses drug resistance in multiple myeloma cells, and influences their microenvironment by blocking cytokine circuits, cell adhesion and angiogenesis in vivo.Aims: The objective of this review is to evaluate the evidence for the use of bortezomib in the treatment of multiple myeloma.Evidence review: In patients with relapsed multiple myeloma bortezomib significantly prolongs overall survival and time to progression, and improves response rates, duration of response, and quality of life compared with oral high-dose dexamethasone. Although the incidence of grade 4 adverse events was similar, grade 3 events and herpes zoster infections occur more frequently in patients treated with bortezomib than with high-dose dexamethasone. Evidence from a pharmacoeconomic study indicates that the benefits of bortezomib compared to thalidomide plus best standard care may be achieved at a reasonable cost.Clinical value: Bortezomib is a valuable treatment option in the management of relapsed multiple myeloma that improves survival and delays disease progression compared with oral high-dose dexamethasone treatment, albeit with an increased incidence of some adverse events such as grade 3 thrombocytopenia and neutropenia.Key words: bortezomib, evidence, multiple myeloma, outcomes, treatment

  8. [Reversal effect of LBH589 alone or in combination with bortezomib on drug-resistance in myeloid leukemia and its mechanism].

    Science.gov (United States)

    Jiang, Xue-Jie; Meng, Fan-Yi; Zhou, Hong-Sheng; Wang, Qiang; Wu, Fu-Qun; Huang, Kai-Kai; Huang, Ming; Wang, Zhi-Xiang; Chen, Wei-Wei

    2011-08-01

    To investigate reversal effect of histone deacetylase inhibitor LBH589 alone or in combination with proteasome inhibitor bortezomib on drug resistance in acute myeloid leukemia (AML) and its mechanism. Ex vivo cultures of HL-60/ADM cells and fresh refractory AML cells were treated with LBH589, bortezomib or their combination at varying concentrations. Proliferation capacity, apoptosis rate and reversal of drug resistance were evaluated by MTT assay, dual staining of Hoechst 33342 and Annexin VFITC/PI by flow cytometry, and adriamycin uptake rate with proliferation inhibition, respectively. The change of signal pathway at protein level was analyzed by Western blot. Synergistic cytotoxicity was observed in the combination treatment with LBH589 and bortezomib against HL-60/ADM cells, as well as the fresh AML cells, the most powerful synergy being observed at 21 nmol/L LBH589 plus 12 nmol/L bortezomib, with CI values of 0.531 and 0.498, respectively by Calcusyn software analysis. Moreover, the accumulation of adriamycin in HL-60/ADM cells was increased more in combination treatment [(64.81 +/- 3.69)%] than in either LBH589 [(28.96 +/- 2.52)%] or bortezomib [(37.29 +/- 3.71)%] alone (P kinase (PI3K)/Akt/nuclear factor-kappaB (NF-kappaB) signaling pathway. Combination treatment of drug resistant AML cells with LBH589 and bortezomib produces a synergistic effect of in creating sensitivity to chemotherapy. The mechanism may be mainly resulted from inhibition of PI3K/ Akt/NF-kappaB signaling pathway.

  9. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma

    DEFF Research Database (Denmark)

    San-Miguel, Jesús F; Hungria, Vânia T M; Yoon, Sung-Soo

    2014-01-01

    BACKGROUND: Panobinostat is a potent oral pan-deacetylase inhibitor that in preclinical studies has synergistic anti-myeloma activity when combined with bortezomib and dexamethasone. We aimed to compare panobinostat, bortezomib, and dexamethasone with placebo, bortezomib, and dexamethasone in pat...

  10. Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM

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    Offidani, Massimo; Pégourie, Brigitte; De La Rubia, Javier; Garderet, Laurent; Laribi, Kamel; Bosi, Alberto; Marasca, Roberto; Laubach, Jacob; Mohrbacher, Ann; Carella, Angelo Michele; Singhal, Anil K.; Tsao, L. Claire; Lynch, Mark; Bleickardt, Eric; Jou, Ying-Ming; Robbins, Michael; Palumbo, Antonio

    2016-01-01

    In this proof-of-concept, open-label, phase 2 study, patients with relapsed/refractory multiple myeloma (RRMM) received elotuzumab with bortezomib and dexamethasone (EBd) or bortezomib and dexamethasone (Bd) until disease progression/unacceptable toxicity. Primary endpoint was progression-free survival (PFS); secondary/exploratory endpoints included overall response rate (ORR) and overall survival (OS). Two-sided 0.30 significance level was specified (80% power, 103 events) to detect hazard ratio (HR) of 0.69. Efficacy and safety analyses were performed on all randomized patients and all treated patients, respectively. Of 152 randomized patients (77 EBd, 75 Bd), 150 were treated (75 EBd, 75 Bd). PFS was greater with EBd vs Bd (HR, 0.72; 70% confidence interval [CI], 0.59-0.88; stratified log-rank P = .09); median PFS was longer with EBd (9.7 months) vs Bd (6.9 months). In an updated analysis, EBd-treated patients homozygous for the high-affinity FcγRIIIa allele had median PFS of 22.3 months vs 9.8 months in EBd-treated patients homozygous for the low-affinity allele. ORR was 66% (EBd) vs 63% (Bd). Very good partial response or better occurred in 36% of patients (EBd) vs 27% (Bd). Early OS results, based on 40 deaths, revealed an HR of 0.61 (70% CI, 0.43-0.85). To date, 60 deaths have occurred (28 EBd, 32 Bd). No additional clinically significant adverse events occurred with EBd vs Bd. Grade 1/2 infusion reaction rate was low (5% EBd) and mitigated with premedication. In patients with RRMM, elotuzumab, an immunostimulatory antibody, appears to provide clinical benefit without added clinically significant toxicity when combined with Bd vs Bd alone. Registered to ClinicalTrials.gov as NCT01478048. PMID:27091875

  11. Bortezomib Inpatient Prescribing Practices in Free-Standing Children's Hospitals in the United States.

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    Amanda M DiNofia

    Full Text Available This study is a pharmacoepidemiologic description of pediatric bortezomib use. Exposure was identified through billing codes in patients admitted to US children's hospitals that participated with the Pediatric Health Information System between 2004 and 2013. Associated information on underlying diseases, demographics, institutional use, mortality, and physician type was collected. Exposure to bortezomib was identified in 314 patients. Hematologist/Oncologists prescribed half of the bortezomib used. Use increased during the study period. Inpatient volume was positively correlated with bortezomib utilization. Bortezomib use in pediatrics is increasing for a variety of diseases. Variation in use exists across institutions. Further studies are needed to characterize bortezomib's efficacy in pediatric diseases.

  12. Outcome of combined modality treatment including neoadjuvant chemotherapy of 128 cases of locally advanced breast cancer: Data from a tertiary cancer center in northern India

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    V Raina

    2011-01-01

    Full Text Available Background: Breast cancer is now the most common cancer in many parts of India and the incidence varies from 12 to 31/100000, and is rising. Locally advanced breast cancer (LABC accounts for 30 - 35% of all cases of breast cancers in India. LABC continues to present a challenge and imposes a major health impact in our country. Materials and Methods: We carried out a analysis of our LABC patients who received neoadjuvant chemotherapy (NACT at our hospital over a 10-year period, from January 1995 to December 2004. We analyzed the response to NACT, disease-free survival (DFS, and overall survival (OS. Results: Patients with stages IIIA, IIIB, and IIIC were included. LABC comprised of 26.24% (609 patients of new patients. One hundred and twenty-eight (31.1% patients received NACT. Median age was 48 years and estrogen receptor was positive in 64%. Chemotherapy protocol was an FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide regimen in the following doses: Cyclophosphamide 600 mg/m2, 5-FU 600 mg/m2, and Epirubicin 75 mg/m2 given every three weeks, six doses, followed by modified radical mastectomy (MRM and locoregional radiotherapy. The overall response rate (complete response (CR + partial response (PR was 84.4%, clinical CR (cCR was 13.3% and pathological CR (pCR was 7.8%. Median DFS and OS were 33 and 101 months, respectively. The disease-free survival (DFS and overall survival (OS at five years were 41 and 58%, respectively. Conclusions: This study analyzes the outcome in patients who received NACT, in the largest number of LABC patients from a single center in India, and our results are comparable to the results reported from other centers.

  13. Phase II Study of Bortezomib as a Single Agent in Patients with Previously Untreated or Relapsed/Refractory Acute Myeloid Leukemia Ineligible for Intensive Therapy

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    Chiara Sarlo

    2013-01-01

    Full Text Available We explored the safety and efficacy of bortezomib given as single agent in patients with untreated or relapsed/refractory acute myeloid leukemia (AML, unfit for conventional chemotherapy. Fourteen patients were treated with bortezomib 1.5 mg/m2 administered twice weekly for two weeks, every 3 weeks. Median age was 70 years (range 60–81 and the median number of cycles delivered was 2 (range 1–4. Of 13 evaluable patients, in 8 (61%, the administration of bortezomib resulted in an antileukemic effect as demonstrated by peripheral blood and/or bone marrow blast reduction. In 4 (50% of these 8, a decrease by 37% of transfusion requirement was also observed . Overall median survival was 4 months (range 0.25–10. Neurotoxicity was the most frequent adverse event with 7 of 13 (54% patients experiencing grades 3-4 peripheral neuropathy. Neurotoxicity led to treatment discontinuation in 4 (57% of 7. In conclusion, the observed anti-leukemic activity of bortezomib indicates that there is room for designing additional studies in which combination with other chemotherapeutic agents should be considered. Clinical registration no.: EUDRACT 2006-006923-38.

  14. Retrospective study comparing low-dose versus standard dose of bortezomib in patients with multiple myeloma

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    Marcela Espinoza Zelada

    2015-03-01

    Full Text Available INTRODUCTION Bortezomib is a selective inhibitor of the proteosoma that is used in multiple myeloma. In combination with other antineoplastic drugs, it has a well-documented impact in progression-free survival rates and overall survival rates with standard doses (1.3-1.5 mg/m2. However, up to 88% of patients on standard doses have unwanted side effects (neutropenia, neuropathy or anemia. Standard dose (1.3 mg/m2 is used in almost all patients and low dose (0.7-0.8 mg/m2 is reserved for patients with kidney disease and neuropathy. OBJECTIVE We aim to describe clinical, cytological, and cytometric outcomes, as well as overall survival and side effects of low dose versus standard dose of bortezomib in our institution. METHODS Retrospective, descriptive study based on data recovered from clinical charts of 48 multiple myeloma patients treated in our hospital between 2011 and 2013. We included data on age, gender, type of multiple myeloma, serum albumin, serum creatinine, beta 2 microglobulin, calcemia, imaging studies, disease stage, pre-and post-therapy bone marrow studies, adverse events and rate of progression. We also recorded events like date of death or of the last medical appointment. RESULTS Forty-eight multiple myeloma patients were treated with bortezomib-cyclophosphamide-dexamethasone. Twenty-one patients received low dose and 27 patients were treated with the standard dose. No statistical differences between the two groups were found for clinical response (p=0.6, cytological response (p=0.28, flow cytometric response (p= 0.3, rate of adverse effects and overall survival rates. CONCLUSION This retrospective analysis suggests that lower doses of bortezomib have similar effects in disease control measured by flow cytometry and cytology compared to standard doses in multiple myeloma patients.

  15. Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide

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    T.B.M. Castro

    2016-01-01

    Full Text Available In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61% vs 23 (39% males, and of whites, 49 (83.1% vs 10 (16.9% blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6. Regarding staging at diagnosis, 27 (45.7% patients were in stage III-A, with 12 (20.3% patients having serum creatinine ≥2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40 were: neutropenia (42.5%, diarrhea (47.5%, and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26 and sc (n=14 administration routes (P=0.343. In the group treated with thalidomide (n=19, 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038. Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%. Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines.

  16. Deletion of Chromosomal Region 8p21 Confers Resistance to Bortezomib and Is Associated with Upregulated Decoy TRAIL Receptor Expression in Patients with Multiple Myeloma.

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    Adil Doganay Duru

    Full Text Available Loss of the chromosomal region 8p21 negatively effects survival in patients with multiple myeloma (MM that undergo autologous stem cell transplantation (ASCT. In this study, we aimed to identify the immunological and molecular consequences of del(8(p21 with regards to treatment response and bortezomib resistance. In patients receiving bortezomib as a single first line agent without any high-dose therapy, we have observed that patients with del(8(p21 responded poorly to bortezomib with 50% showing no response while patients without the deletion had a response rate of 90%. In vitro analysis revealed a higher resistance to bortezomib possibly due to an altered gene expression profile caused by del(8(p21 including genes such as TRAIL-R4, CCDC25, RHOBTB2, PTK2B, SCARA3, MYC, BCL2 and TP53. Furthermore, while bortezomib sensitized MM cells without del(8(p21 to TRAIL/APO2L mediated apoptosis, in cells with del(8(p21 bortezomib failed to upregulate the pro-apoptotic death receptors TRAIL-R1 and TRAIL-R2 which are located on the 8p21 region. Also expressing higher levels of the decoy death receptor TRAIL-R4, these cells were largely resistant to TRAIL/APO2L mediated apoptosis. Corroborating the clinical outcome of the patients, our data provides a potential explanation regarding the poor response of MM patients with del(8(p21 to bortezomib treatment. Furthermore, our clinical analysis suggests that including immunomodulatory agents such as Lenalidomide in the treatment regimen may help to overcome this negative effect, providing an alternative consideration in treatment planning of MM patients with del(8(p21.

  17. Bortezomib sensitizes human osteosarcoma cells to adriamycin-induced apoptosis through ROS-dependent activation of p-eIF2α/ATF4/CHOP axis.

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    Xian, Miao; Cao, Handi; Cao, Ji; Shao, Xuejing; Zhu, Difeng; Zhang, Ning; Huang, Ping; Li, Weixu; Yang, Bo; Ying, Meidan; He, Qiaojun

    2017-09-01

    Osteosarcoma is the most common bone cancer, and chemotherapy is currently indispensable for its treatment. Adriamycin has been claimed to be the most effective agent for osteosarcoma, however, the outcome of adriamycin chemotherapy remains unsatisfactory. Here, we reported a potent combination therapy that bortezomib, a proteasome inhibitor, enhances adriamycin-induced apoptosis to eliminate osteosarcoma cells and we revealed that the activation of p-eIF2α/ATF4/CHOP axis is the underlying associated mechanisms. First, we observed that bortezomib enhances adriamycin-mediated inhibition of cell proliferation and enhances the apoptosis in osteosarcoma cell lines. Moreover, this drug combination produced more potent tumor-growth inhibitory effects in human osteosarcoma cell line KHOS/NP xenografts. Our study showed that reactive oxygen species (ROS) plays an important role in apoptosis induced by adriamycin plus bortezomib, whereas ROS scavenger NAC could almost completely block the apoptosis induced by the combination treatment. Meanwhile, p-eIF2α is remarkably elevated in the combination group. As a result, ATF4 exhibits strong activation which consequently induces the activation of CHOP and leads to the cell death. Finally, 13 primary osteosarcoma cells demonstrated potent response to the combination treatment. In a human osteosarcoma patient-derived xenograft (PDX) model, our finding suggests that when combined with bortezomib, a relatively low dose of adriamycin produced more potent tumor-growth inhibitory effects without increased toxicity. Thus, our findings not only provide a promising combination strategy to overcome osteosarcoma but also shed new light on the strategy of combining increased ROS and inhibited proteasome to open up new opportunities for the clinical development of chemotherapy regimens. © 2017 UICC.

  18. Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment.

    Science.gov (United States)

    Morabito, Fortunato; Gentile, Massimo; Mazzone, Carla; Rossi, Davide; Di Raimondo, Francesco; Bringhen, Sara; Ria, Roberto; Offidani, Massimo; Patriarca, Francesca; Nozzoli, Chiara; Petrucci, Maria Teresa; Benevolo, Giulia; Vincelli, Iolanda; Guglielmelli, Tommasina; Grasso, Mariella; Marasca, Roberto; Baldini, Luca; Montefusco, Vittorio; Musto, Pellegrino; Cascavilla, Nicola; Majolino, Ignazio; Musolino, Caterina; Cavo, Michele; Boccadoro, Mario; Palumbo, Antonio

    2011-11-24

    We assessed efficacy, safety, and reversal of renal impairment (RI) in untreated patients with multiple myeloma given bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide (VMPT-VT) maintenance or bortezomib-melphalan-prednisone (VMP). Exclusion criteria included serum creatinine ≥ 2.5 mg/dL. In the VMPT-VT/VMP arms, severe RI (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min), moderate RI (eGFR 31-50 mL/min), and normal renal function (eGFR > 50 mL/min), were 6%/7.9%, 24.1%/24.9%, and 69.8%/67.2%, respectively. Statistically significant improvements in overall response rates and progression-free survival were observed in VMPT-VT versus VMP arms across renal cohorts, except in severe RI patients. In the VMPT group, severe RI reduced overall survival (OS). RI was reversed in 16/63 (25.4%) patients receiving VMPT-VT versus 31/77 (40.3%) receiving VMP. Multivariate analysis showed male sex (P = .022) and moderate RI (P = .003) significantly predicted RI recovery. VMP patients achieving renal response showed longer OS. In both arms, greater rates of severe hematologic adverse events were associated with RI (eGFR < 50 mL/min), however, therapy discontinuation rates were unaffected. VMPT-VT was superior to VMP for cases with normal renal function and moderate RI, whereas VMPT-VT failed to outperform VMP in patients with severe RI, although the relatively low number of cases analyzed preclude drawing definitive conclusions. VMPT-VT had no advantage in terms of RI reversal over VMP.

  19. Bortezomib-thalidomide-based regimens improved clinical outcomes without increasing toxicity as induction treatment for untreated multiple myeloma: a meta-analysis of phase III randomized controlled trials.

    Science.gov (United States)

    Huang, Hejing; Zhou, Lili; Peng, Lihui; Fu, Weijun; Zhang, Chunyang; Hou, Jian

    2014-09-01

    Novel agents thalidomide and bortezomib have significantly improved myeloma treatment. However, it remains unclear whether patients will benefit more from the combination therapy of these two agents. Our meta-analysis aims to compare the efficiency, and more importantly, the safety of bortezomib-thalidomide-based (VT-based) versus bortezomib-based or thalidomide-based (V-based/T-based) regimens as induction therapy in patients with previously untreated myeloma. Overall, five phase III RCTs including 1765 patients were identified. Compared with V-based or T-based regimens, VT-based regimens significantly improved CR (OR=2.22, 95% CI [1.44, 3.43]), ORR (OR=2.19, 95% CI [1.51, 3.19]) as well as PFS (HR=0.69, 95% CI [0.54, 0.88]), but not OS (HR=1.04, 95% CI [0.91, 1.19]). Notably, most expected side effects of bortezomib or thalidomide were comparable in both groups, including hematologic (anemia, neutropenia, thrombocytopenia), nonhematologic (peripheral neuropathy, deep venous thrombosis, infections, gastrointestinal events) side effects and discontinuation during or after induction therapy. These results suggest that combination of thalidomide and bortezomib might be a better first-line choice for patients with untreated myeloma.

  20. Nutritional status and feeding-tube placement in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy-based larynx preservation program.

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    Bozec, Alexandre; Benezery, Karen; Chamorey, Emmanuel; Ettaiche, Marc; Vandersteen, Clair; Dassonville, Olivier; Poissonnet, Gilles; Riss, Jean-Christophe; Hannoun-Lévi, Jean-Michel; Chand, Marie-Eve; Leysalle, Axel; Saada, Esma; Sudaka, Anne; Haudebourg, Juliette; Hebert, Christophe; Falewee, Marie-Noelle; Demard, François; Santini, José; Peyrade, Frédéric

    2016-09-01

    The objective of the study is to evaluate the nutritional status and determine its impact on clinical outcomes in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program without prophylactic feeding-tube placement. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngolaryngectomy, treated by docetaxel, cisplatin and 5-fluorouracil (TPF)-ICT for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Patients' nutritional status was closely monitored. Enteral nutrition was used if and when a patient was unable to sustain per-oral nutrition and hydration. The impact of nutritional status on clinical outcomes was investigated in univariate and multivariate analysis. A total of 53 patients (42 men and 11 women, mean age = 58.6 ± 8.2 years) were included in this study. Six (11.3 %) patients had lost more than 10 % of their usual body weight before therapy. Compared with patients' usual weight, the mean maximum patient weight loss during therapeutic management was 8.7 ± 4.5 kg. Enteral nutrition was required in 17 patients (32 %). We found no influence of the tested nutritional status-related factors on response to ICT, toxicity of ICT, overall, cause-specific and recurrence-free survival, and on post-therapeutic swallowing outcome. Maximum weight loss was significantly associated with a higher risk of enteral tube feeding during therapy (p = 0.03) and of complications (grade ≥3, p = 0.006) during RT. Without prophylactic feeding-tube placement, approximately one-third of the patients required enteral nutrition. There was no significant impact of nutritional status on oncologic or functional outcomes.

  1. Bortezomib resistance in mantle cell lymphoma is associated with plasmacytic differentiation

    DEFF Research Database (Denmark)

    Pérez-Galán, Patricia; Mora-Jensen, Helena; Weniger, Marc A

    2011-01-01

    Bortezomib induces remissions in 30%-50% of patients with relapsed mantle cell lymphoma (MCL). Conversely, more than half of patients' tumors are intrinsically resistant to bortezomib. The molecular mechanism of resistance has not been defined. We generated a model of bortezomib-adapted subclones...

  2. 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 ...

  3. Bortezomib for the treatment of mantle cell lymphoma: an update.

    Science.gov (United States)

    Hambley, Bryan; Caimi, Paolo F; William, Basem M

    2016-08-01

    Bortezomib is a first in class proteasome inhibitor, initially approved by the US Food and Drug Administration for the treatment of plasma cell myeloma. Bortezomib has been approved for the treatment of relapsed and refractory mantle cell lymphoma (MCL) and, more recently, in the upfront setting as well. Treatment algorithms for MCL have rapidly evolved over the past two decades, and the optimal regimen remains to be defined. The choice of treatment regimen is based on disease risk stratification models, the expected toxicity of antineoplastic agents, the perceived patient ability to tolerate the planned treatments and the availability of novel agents. As new drugs with novel mechanisms of action and variable toxicity profiles come into use, treatment decisions for a given patient have become increasingly complex. This article provides an overview of the evolving use of bortezomib in the rapidly changing management landscape of MCL.

  4. Changes in circulating endothelial progenitor cells predict responses of multiple myeloma patients to treatment with bortezomib and dexamethasone

    Directory of Open Access Journals (Sweden)

    L. Wang

    2015-08-01

    Full Text Available Four cycles of chemotherapy are required to assess responses of multiple myeloma (MM patients. We investigated whether circulating endothelial progenitor cells (cEPCs could be a biomarker for predicting patient response in the first cycle of chemotherapy with bortezomib and dexamethasone, so patients might avoid ineffective and costly treatments and reduce exposure to unwanted side effects. We measured cEPCs and stromal cell-derived factor-1α (SDF-1α in 46 MM patients in the first cycle of treatment with bortezomib and dexamethasone, and investigated clinical relevance based on patient response after four 21-day cycles. The mononuclear cell fraction was analyzed for cEPC by FACS analysis, and SDF-1α was analyzed by ELISA. The study population was divided into 3 groups according to the response to chemotherapy: good responders (n=16, common responders (n=12, and non-responders (n=18. There were no significant differences among these groups at baseline day 1 (P>0.05. cEPC levels decreased slightly at day 21 (8.2±3.3 cEPCs/μL vs day 1 (8.4±2.9 cEPCs/μL in good responders (P>0.05. In contrast, cEPC levels increased significantly in the other two groups (P<0.05. SDF-1α changes were closely related to changes in cEPCs. These findings indicate that change in cEPCs at day 21 in the first cycle might be considered a noninvasive biomarker for predicting a later response, and extent of change could help decide whether to continue this costly chemotherapy. cEPCs and the SDF-1α/CXCR4 axis are potential therapeutic targets for improved response and outcomes in MM patients.

  5. Efficacy of lenalidomide, bortezomib, and prednisolone in patients with relapsed or refractory multiple myeloma

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    T. A. Мitinа

    2015-01-01

    Full Text Available 49 patients aged 28 to 81 years old (median age of 55 years old with relapsed or refractory multiple myeloma (MM were enrolled in the study. The relapse was diagnosed in 25 (51 % patients, the refractory disease was determined in 24 (49 % patients (including primary refractory disease in 14 (28.6 % patients. The prior therapy for all patients included bortezomib-based treatment in combination with thalidomide and autologus stem cell transplantation (8.1 %. Lenalidomide had not been used in the previous therapeutic regimens. All patients were given the original treatment regimen, which included lenalidomide, bortezomib, and prednisolone (RVP. The therapy was made up of seven induction cycles with each one lasting for 48 days. Length of courses was 14 days. After seven cycles of RVP therapy were over, such results were achieved: complete response (CR in 1 (2 % patient; very good partial response (VGPR in 4 (8 % patients; partial response (PR in 26 (53 % patients; minimal response (MR in 2 (4 % patients; stable disease (SD in 8 (16.3 % patients, and progressive disease (PD in 8 (16.3 % patients. The objective response rate, including CR+VGPR+PR, was obtained in 31 (63.1 % patients. The objective response rate, including MR, was seen in 33 (67.1 % patients. Hematological and non-hematological toxicities were moderate. Taking into account the above, the RVP therapeutic regimen has demonstrated its efficacy as a second-line therapy for MM, and its clinical use can solve the problem of relapsed/refractory to bortezomib-based regimens MM management.

  6. Liposomal bortezomib nanoparticles via boronic ester prodrug formulation for improved therapeutic efficacy in vivo.

    Science.gov (United States)

    Ashley, Jonathan D; Stefanick, Jared F; Schroeder, Valerie A; Suckow, Mark A; Kiziltepe, Tanyel; Bilgicer, Basar

    2014-06-26

    In this study, we describe the development of liposomal bortezomib nanoparticles, which was accomplished by synthesizing bortezomib prodrugs with reversible boronic ester bonds and then incorporating the resulting prodrugs into the nanoparticles via surface conjugation. Initially, several prodrug candidates were screened based upon boronic ester stability using isobutylboronic acid as a model boronic acid compound. The two most stable candidates were then selected to create surface conjugated bortezomib prodrugs on the liposomes. Our strategy yielded stable liposomal bortezomib nanoparticles with a narrow size range of 100 nm and with high reproducibility. These liposomal bortezomib nanoparticles demonstrated significant proteasome inhibition and cytotoxicity against multiple myeloma cell lines in vitro and remarkable tumor growth inhibition with reduced systemic toxicity compared to free bortezomib in vivo. Taken together, this study demonstrates the incorporation of bortezomib into liposomal nanoparticles via reversible boronic ester bond formation to enhance the therapeutic index for improved patient outcome.

  7. HIV-Associated Burkitt Lymphoma: Good Efficacy and Tolerance of Intensive Chemotherapy Including CODOX-M/IVAC with or without Rituximab in the HAART Era

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    J. A. Rodrigo

    2012-01-01

    Full Text Available Background. The outcome of HIV-associated non-Hodgkin lymphoma (NHL has improved substantially in the highly active antiretroviral therapy (HAART era. However, HIV-Burkitt lymphoma (BL, which accounts for up to 20% of HIV-NHL, has poor outcome with standard chemotherapy. Patients and Methods. We retrospectively reviewed HIV-BL treated in the HAART era with the Magrath regimen (CODOX-M/IVAC±R at four Canadian centres. Results. Fourteen patients with HIV-BL received at least one CODOX-M/IVAC±R treatment. Median age at BL diagnosis was 45.5 years, CD4 count 375 cells/mL and HIV viral load (VL 250 cells/mL and undetectable, respectively, in 4. Conclusion. Intensive chemotherapy with CODOX-M/IVAC±R yielded acceptable toxicity and good survival rates in patients with HIV-associated Burkitt lymphoma receiving HAART.

  8. Bortezomib in mantle cell lymphoma: comparative therapeutic outcomes

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    Vallumsetla N

    2015-11-01

    Full Text Available Nishanth Vallumsetla, Jonas Paludo, Prashant Kapoor Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA Abstract: Mantle cell lymphoma (MCL is an incurable, typically aggressive subtype of non-Hodgkin lymphoma, accounting for 4%–7% of newly diagnosed non-Hodgkin lymphoma cases. Chemoresistance commonly ensues in MCL, and patients with this heterogeneous disease invariably relapse, underscoring the unmet need for better therapies. Over the past few years, several novel agents with promising activity and unique mechanisms of action have been deemed effective in MCL. Bortezomib is a reversible proteasome inhibitor, approved as a single agent for patients with relapsed/refractory MCL who have received at least one prior line of therapy. Addition of bortezomib to chemoimmunotherapies has demonstrated good tolerability and superior efficacy, both in the upfront and salvage settings, and recently one such combination of bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone was approved as a frontline regimen in untreated patients with MCL. This review examines the role of bortezomib in a multitude of clinical settings and ongoing clinical trials designed to optimize its integration in the current treatment paradigms of MCL. Keywords: non-Hodgkin lymphoma, proteosome inhibitor, treatment

  9. 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 ...

  10. Chalazia development in multiple myeloma: a new complication associated with bortezomib therapy

    Directory of Open Access Journals (Sweden)

    Charles Yun

    2015-06-01

    Full Text Available Multiple myeloma (MM is a neoplasm of plasma cells within the bone marrow. A major impact on improving survival in MM has been the use of the boronic acid-derived proteasome inhibitor bortezomib, a first-in-class selective inhibitor of the 26S proteasome. Ocular side effects of bortezomib are rare. In this report, we present 2 patients with active MM in whom persistent chalazia became a therapy-interfering complication of treatment with bortezomib. Both patients had relapsed ISS III B kappa light chain myeloma, and they were responding to treatment with bortezomib until chalazia − which caused intolerable discomfort − started. In both patients discontinuation of bortezomib was necessary for chalazia to heal, and restarting of bortezomib was associated with relapse of chalazia.

  11. Trypanocidal activity of the proteasome inhibitor and anti-cancer drug bortezomib

    Directory of Open Access Journals (Sweden)

    Wang Xia

    2009-07-01

    Full Text Available Abstract The proteasome inhibitor and anti-cancer drug bortezomib was tested for in vitro activity against bloodstream forms of Trypanosoma brucei. The concentrations of bortezomib required to reduce the growth rate by 50% and to kill all trypanosomes were 3.3 nM and 10 nM, respectively. In addition, bortezomib was 10 times more toxic to trypanosomes than to human HL-60 cells. Moreover, exposure of trypanosomes to 10 nM bortezomib for 16 h was enough to kill 90% of the parasites following incubation in fresh medium. However, proteasomal peptidase activities of trypanosomes exposed to bortezomib were only inhibited by 10% and 30% indicating that the proteasome is not the main target of the drug. The results suggest that bortezomib may be useful as drug for the treatment of human African trypanosomiasis.

  12. Primary Therapy of Waldenström Macroglobulinemia With Bortezomib, Dexamethasone, and Rituximab: WMCTG Clinical Trial 05-180

    Science.gov (United States)

    Treon, Steven P.; Ioakimidis, Leukothea; Soumerai, Jacob D.; Patterson, Christopher J.; Sheehy, Patricia; Nelson, Marybeth; Willen, Michael; Matous, Jeffrey; Mattern, John; Diener, Jakow G.; Keogh, George P.; Myers, Thomas J.; Boral, Andy; Birner, Ann; Esseltine, Dixie L.; Ghobrial, Irene M.

    2009-01-01

    Purpose We examined the activity of bortezomib, dexamethasone, and rituximab (BDR) in patients with symptomatic, untreated Waldenström macroglobulinemia (WM). Patients and Methods A cycle of therapy consisted of bortezomib 1.3 mg/m2 intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m2 on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy. Twenty-three patients received a median of seven cycles of treatment. Results Median bone marrow disease involvement declined from 55% to 10% (P = .0004), serum immunoglobulin M levels declined from 4,830 to 1,115 mg/dL (P < .0001), and hematocrit increased from 29.8% to 38.2% (P = .0002) at best response. The overall response rates and major response rates were 96% and 83% with three complete responses, two near complete responses, three very good partial responses, 11 partial responses, and three minor responses. Responses occurred at a median of 1.4 months. With a median follow-up of 22.8 months, 18 of 23 patients remained free of disease progression. Peripheral neuropathy was the most common toxicity, and it resolved to grade ≤ 1 in 13 of 16 patients at a median of 6.0 months. Four of the first seven treated patients developed herpes zoster, resulting in the institution of prophylactic antiviral therapy. Conclusion The results demonstrate that BDR produces rapid and durable responses, along with high rates of response and complete remissions in WM. Herpes zoster prophylaxis is necessary with BDR, and reversible peripheral neuropathy was the most common toxicity leading to premature discontinuation of bortezomib in 61% of patients. Exploration of alternative schedules for bortezomib administration that includes weekly dosing should be pursued. PMID:19506160

  13. Synthesis and Characterization of Organic Impurities in Bortezomib Anhydride Produced by a Convergent Technology

    Science.gov (United States)

    Ivanov, Andrey S.; Shishkov, Sergey V.; Zhalnina, Anna A.

    2012-01-01

    A profile of impurities in bortezomib anhydride, produced by a recently developed convergent technology, has been characterized. HPLC-MS analysis of the drug essence revealed three impurities: an epimer of bortezomib, resulting from partial racemization of l-phenylalanine’s stereogenic center during the chemical synthesis, and two epimeric products of oxidative degradation of bortezomib, in which boron is replaced by the OH group. The impurities were obtained by chemical synthesis and characterized by physical methods. PMID:22396904

  14. Synergistic anti-proliferative and pro-apoptotic activity of combined therapy with bortezomib, a proteasome inhibitor, with anti-epidermal growth factor receptor (EGFR) drugs in human cancer cells.

    Science.gov (United States)

    Cascone, Tina; Morelli, Maria Pia; Morgillo, Floriana; Kim, Woo-Young; Rodolico, Gabriella; Pepe, Stefano; Tortora, Giampaolo; Berrino, Liberato; Lee, Ho-Young; Heymach, John V; Ciardiello, Fortunato

    2008-09-01

    The proteasome plays a pivotal role in the turnover of regulatory transduction proteins induced by activated cell membrane growth factor receptors. The epidermal growth factor receptor (EGFR) pathway is crucial in the development and progression of human epithelial cancers. Proteasome inhibition may sensitize human cancer cell lines to EGFR inhibitors. We investigated the growth inhibitory and pro-apoptotic effects of the proteasome inhibitor bortezomib in combination with anti-EGFR drugs, such as gefitinib, vandetanib, and cetuximab in EGFR-expressing human cancer cell lines. Bortezomib determined dose-dependent growth inhibition in a nine cancer cell line panel (IC(50) values, range 6-42 nM). A significant synergistic growth inhibitory effect was observed with the combination of bortezomib and each EGFR inhibitor in all cell lines (combination index, CI, range 0.10-0.55), which was accompanied by a significant induction in apoptosis by the combined treatment with bortezomib, cetuximab and vandetanib. In HCT-116 colon cancer and A549 lung adenocarcinoma cells, bortezomib plus EGFR inhibitor treatment induced a more effective inhibition of EGFR-activated down-stream signals, including a marked suppression in activated, phosphorylated Akt (P-Akt). In contrast, overexpression of a constitutively active P-Akt protected A549 cells by cell growth inhibition and apoptosis following treatment with bortezomib and EGFR inhibitors. The combined treatment with bortezomib and EGFR inhibitors has a synergistic growth inhibitory and pro-apoptotic activity in different human cancer cells which possess a functional EGFR-dependent autocrine growth pathway through to a more efficient and sustained inhibition of Akt.

  15. A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma.

    Science.gov (United States)

    Larocca, A; Bringhen, S; Petrucci, M T; Oliva, S; Falcone, A P; Caravita, T; Villani, O; Benevolo, G; Liberati, A M; Morabito, F; Montefusco, V; Passera, R; De Rosa, L; Omedé, P; Vincelli, I D; Spada, S; Carella, A M; Ponticelli, E; Derudas, D; Genuardi, M; Guglielmelli, T; Nozzoli, C; Aghemo, E; De Paoli, L; Conticello, C; Musolino, C; Offidani, M; Boccadoro, M; Sonneveld, P; Palumbo, A

    2016-06-01

    This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients ⩾75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade ⩾3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade ⩾3 AEs included infections (8-20%), and constitutional (10-14%) and cardiovascular events (4-12%); peripheral neuropathy was limited (4-6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients.

  16. A phase I study of bortezomib, etoposide and carboplatin in patients with advanced solid tumors refractory to standard therapy

    NARCIS (Netherlands)

    Lieu, Christopher; Chow, Laura; Pierson, A. Scott; Eckhardt, S. Gail; O'Bryant, Cindy L.; Morrow, Mark; Tran, Zung Vu; Wright, John J.; Gore, Lia

    2009-01-01

    Purpose: To evaluate the toxicity, pharmacological, and biological properties of the combination of bortezomib, etoposide, and carboplatin in adults with advanced solid malignancies. Patients and methods: Patients received escalating doses of bortezomib, etoposide, and carboplatin every 21 days. Sur

  17. [A case of recurrent non-small cell lung cancer successfully treated with multiple modality therapies including S-1 monotherapy as fifth-line chemotherapy hospital)].

    Science.gov (United States)

    Yokosuka, Tetsuya; Kobayashi, Toshiko; Enomoto, Tatsuji; Takeda, Atsuya

    2013-09-01

    An 80-year-old man with no complaint was referred to our department because of high serum CEA level. He was diagnosed as non-small cell lung cancer(adenocarcinoma)of the left lower lobe(c-T2aN0M0, stage I B), and therefore the left lower lobectomy with lymph node dissection was performed. Pathological staging was p-T2aN1(#10)M0, stage II A, and EGFR mutation was negative. Adjuvant chemotherapy with UFT was started, but multiple hilar and mediastinal lymph nodes metastases soon appeared. Carboplatin(CBDCA)+paclitaxel(PTX), erlotinib, and docetaxel(DOC)were attempted after that, but the lymph nodes increased in size and the CEA level was up to 159.8 ng/mL. At about the same time, brain and pulmonary metastases were recognized. After radiation for the chest lymph nodes and stereotactic radiosurgery(SRS)for the brain metastasis, oral S-1 monotherapy was introduced. Soon after, the lymph nodes shrinked and the CEA level decreased. Also, the pulmonary metastasis disappeared. Although a right supraclavicular lymph node metastasis was resected during the clinical course, the S-1 monotherapy has been continued with no serious adverse event. He is well(PS 0)without recurrent lesion, and his serum CEA level is within the normal limit.

  18. Guillain Barré Syndrome in a multiple myeloma patient after the first course of bortezomib therapy: A case report

    OpenAIRE

    2015-01-01

    Bortezomib is approved for treating relapsed multiple myeloma (MM) and mantle cell lymphoma, and clinical evidence has shown complete clinical responses in MM patients. Peripheral neuropathy is one of the most common adverse effects of bortezomib. However, rare evidence has shown that bortezomib is associated with Guillain-Barré syndrome (GBS). In the present study, a case of GBS is reported in an MM patient finishing the first course of bortezomib therapy. Based on a bone marrow cell examina...

  19. Targeting the insulin-like growth factor-1 receptor to overcome bortezomib resistance in preclinical models of multiple myeloma.

    Science.gov (United States)

    Kuhn, Deborah J; Berkova, Zuzana; Jones, Richard J; Woessner, Richard; Bjorklund, Chad C; Ma, Wencai; Davis, R Eric; Lin, Pei; Wang, Hua; Madden, Timothy L; Wei, Caimiao; Baladandayuthapani, Veerabhadran; Wang, Michael; Thomas, Sheeba K; Shah, Jatin J; Weber, Donna M; Orlowski, Robert Z

    2012-10-18

    Proteasome inhibition with bortezomib is a validated approach to the treatment of multiple myeloma, but drug resistance often emerges and limits its utility in the retreatment setting. To begin to identify some of the mechanisms involved, we developed bortezomib-resistant myeloma cell lines that, unlike previously reported models, showed no β5 subunit mutations. Instead, up-regulation of the insulin-like growth factor (IGF)-1 axis was identified, with increased autocrine and paracrine secretion of IGF-1, leading to increased activation of the IGF-1 receptor (IGF-1R). Exogenous IGF-1 reduced cellular sensitivity to bortezomib, whereas pharmacologic or small hairpin RNA-mediated IGF-1R suppression enhanced bortezomib sensitivity in cell lines and patient samples. In vitro studies with OSI-906, a clinically relevant dual IGF-1R and insulin receptor inhibitor, showed it acted synergistically with bortezomib, and potently resensitized bortezomib-resistant cell lines and patient samples to bortezomib. Importantly, OSI-906 in combination with bortezomib also overcame bortezomib resistance in an in vivo model of myeloma. Taken together, these data support the hypothesis that signaling through the IGF-1/IGF-1R axis contributes to acquired bortezomib resistance, and provide a rationale for combining bortezomib with IGF-1R inhibitors like OSI-906 to overcome or possibly prevent the emergence of bortezomib-refractory disease in the clinic.

  20. p53 Expression in Pretreatment Specimen Predicts Response to Neoadjuvant Chemotherapy Including Anthracycline and Taxane in Patients with Primary Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Shien,Tadahiko

    2013-06-01

    Full Text Available While clinical and pathologic responses are important prognostic parameters, biological markers from core needle biopsy (CNB are needed to predict neoadjuvant chemotherapy (NAC response, to individualize treatment, and to achieve maximal efficacy. We retrospectively evaluated the cases of 183 patients with primary breast cancer who underwent surgery after NAC (anthracycline and taxane at the National Cancer Center Hospital (NCCH. We analyzed EGFR, HER2, and p53 expression and common clinicopathological features from the CNB and surgical specimens of these patients. These biological markers were compared between sensitive patients (pathological complete response;pCR and insensitive patients (clinical no change;cNC and clinical progressinve disease;cPD. In a comparison between the 9 (5% sensitive patients and 30 (16% insensitive patients, overexpression of p53 but not overexpression of either HER2 or EGFR was associated with a good response to NAC. p53 (p=0.045 and histological grade 3 (p=0.011 were important and significant predictors of the response to NAC. The correspondence rates for histological type, histological grade 3, ER, PgR, HER2, p53, and EGFR in insensitive patients between CNB and surgical specimens were 70%, 73%, 67%, 70%, 80%, 93%, and 73%. The pathologic response was significantly associated with p53 expression and histological grade 3. The correspondence rate of p53 expression between CNB and surgical specimens was higher than that of other factors. We conclude that the level of p53 expression in the CNB was an effective and reliable predictor of treatment response to NAC.

  1. Combined effects of lapatinib and bortezomib in human epidermal receptor 2 (HER2)-overexpressing breast cancer cells and activity of bortezomib against lapatinib-resistant breast cancer cells.

    Science.gov (United States)

    Ma, Chuandong; Niu, Xiuqing; Luo, Jianmin; Shao, Zhimin; Shen, Kunwei

    2010-10-01

    Lapatinib and bortezomib are highly active against breast cancer cells. Breast cancer patients who initially respond to lapatinib may eventually manifest acquired resistance to this treatment. Thus, the identification of novel agents that may prevent or delay the development of acquired resistance to lapatinib is critical. In the current study, we show that the combination of lapatinib and bortezomib results in a synergistic growth inhibition in human epidermal receptor 2 (HER2)-overexpressing breast cancer cells and that the combination enhances apoptosis of SK-BR-3 cells. Importantly, we found that the combination of lapatinib plus bortezomib more effectively blocked activation of the HER2 pathway in SK-BR-3 cells, compared with monotherapy. In addition, we established a model of acquired resistance to lapatinib by chronically challenging SK-BR-3 breast cancer cells with increasing concentrations of lapatinib. Here, we showed that bortezomib notably induced apoptosis of lapatinib-resistant SK-BR-3 pools and further inhibited HER2 signaling in the resistant cells. Taken together, the current data indicate a synergistic interaction between lapatinib and bortezomib in HER2-overexpressing breast cancer cells and provide the rationale for the clinical evaluation of these two noncross-resistant targeted therapies. The combination of lapatinib and bortezomib may be a potentially novel approach to prevent or delay the onset of acquired resistance to lapatinib in HER2-overxpressing/estrogen receptor (ER)-negative breast cancers.

  2. Regulating Prostate Cancer Sensitivity to Chemotherapy through Translational Control of CCAAT/Enhancer Binding Proteins

    Science.gov (United States)

    2016-10-01

    2016.03.005. PMID: 26968249 Page !26 11. APPENDICES: Page !27 Original Articles C/EBPβ regulates sensitivity to bortezomib in prostate cancer ...2016) 152–161 ORIGINAL ARTICLE CCAAT/Enhancer binding protein β controls androgen- deprivation-induced senescence in prostate cancer cells DJ Barakat1, J...AWARD NUMBER: W81XWH-14-1-0209 TITLE: Regulating Prostate Cancer Sensitivity to Chemotherapy through Translational Control of CCAAT/Enhancer

  3. [Cellulitis due to Achromobacter xylosoxidans during bortezomib therapy for multiple myeloma].

    Science.gov (United States)

    Kikuchi, Taku; Mori, Takehiko; Kohashi, Sumiko; Yamane, Yusuke; Okayama, Mikio; Mashima, Eri; Murakami, Koichi; Shimizu, Takayuki; Kurihara, Yuichi; Ueda, Tomomi; Suzuki, Takeshi; Okamoto, Shinichiro

    2016-02-01

    Achromobacter xylosoxidans (A. xylosoxidans) is a non-fermentative gram-negative rod. This organism is reportedly a causative pathogen of bacteremia mainly in patients with hematological disorders. However, only one case of cellulitis due to A. xylosoxidans associated with hematological malignancy has been reported. An 80-year-old man developed cellulitis and subsequent bacteremia due to A. xylosoxidans during bortezomib therapy for multiple myeloma. Although his condition was serious enough to require intensive care, he fully recovered with appropriate antimicrobial agents and supportive care. The isolate was broadly resistant to antimicrobial agents, including cefepime, amikacin, and ciprofloxacin. Therefore, the identification and selection of appropriate antimicrobial agents were considered to have contributed to the successful outcome in this case. Physicians should recognize A. xylosoxidans as a possible pathogen causing cellulitis and secondary bacteremia, as well as being aware of its broad resistance to antimicrobial agents.

  4. Neurotoxicity of cancer chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Miyoung Yang; Changjong Moon

    2013-01-01

    There is accumulating clinical evidence that chemotherapeutic agents induce neurological side effects, including memory deficits and mood disorders, in cancer patients who have undergone chemotherapeutic treatments. This review focuses on chemotherapy-induced neurodegeneration and hippocampal dysfunctions and related mechanisms as measured by in vivo and in vitro approaches. These investigations are helpful in determining how best to further explore the causal mechanisms of chemotherapy-induced neurological side effects and in providing direction for the future development of novel optimized chemotherapeutic agents.

  5. Effect of bortezomib on migration and invasion in cervical carcinoma HeLa cell

    Institute of Scientific and Technical Information of China (English)

    Chong Shi; Guo-Bin Zhang; Shu-Wang Yin

    2015-01-01

    Objective: To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism. Methods:The effect of bortezomib on the viability of HeLa cell was measured by MTT assay. The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively. The activation of Akt/mTOR signaling pathway and expression level of MMP2, MMP9 were assayed by western blot. Results:MTT assay indicated bortezomib (2.5μM, 5μM, 10μM) could inhibit HeLa cell viability, and the inhibitory rate was highest at 48 h. Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion. Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR, and down-regulate the expression of MMP2 and MMP9. Conclusions:These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell, which might be related to Akt/mTOR signal pathway.

  6. Rapid improvement in renal function in patients with multiple myeloma and renal failure treated with bortezomib

    Directory of Open Access Journals (Sweden)

    Qayum Abdul

    2010-01-01

    Full Text Available Multiple Myeloma (MM frequently presents with renal dysfunction apart from other manifestations. Development of renal failure in patients with MM carries a poor prognosis. Bortezo-mib is a new addition to drugs used in MM and has shown good efficacy and safety profiles. Previous trials have shown its efficacy in relapsed and refractory MM as well. Studies have also shown that bortezomib is also effective in patients with MM who present with renal failure. We report here six cases of renal failure secondary to MM treated with bortezomib. All patients had poor performance status of 3-4 on ECOG scale. Five out of six patients showed satisfactory anti-myeloma response to bortezomib. Reversal of renal failure was observed in all six patients. Adverse effects to bortezomib were mild and manageable. Reversal of renal failure persisted despite incomplete response to MM in two cases, and progression of disease in one patient. It appears that bortezomib may have an effect on the kidneys in reversal of renal failure, other than its anti-myeloma effect. In conclusion, borte-zomib appears to be an effective treatment for patients with advanced MM and renal failure irres-pective of performance status and age.

  7. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients.

    Science.gov (United States)

    Palumbo, Antonio; Gay, Francesca; Falco, Patrizia; Crippa, Claudia; Montefusco, Vittorio; Patriarca, Francesca; Rossini, Fausto; Caltagirone, Simona; Benevolo, Giulia; Pescosta, Norbert; Guglielmelli, Tommasina; Bringhen, Sara; Offidani, Massimo; Giuliani, Nicola; Petrucci, Maria Teresa; Musto, Pellegrino; Liberati, Anna Marina; Rossi, Giuseppe; Corradini, Paolo; Boccadoro, Mario

    2010-02-10

    PURPOSE To evaluate the effect of bortezomib as induction therapy before autologous transplantation, followed by lenalidomide as consolidation-maintenance in myeloma patients. PATIENTS AND METHODS Newly diagnosed patients age 65 to 75 years were eligible. Induction (bortezomib, doxorubicin, and dexamethasone [PAD]) included four 21-day cycles of bortezomib (1.3 mg/m(2) on days 1, 4, 8, and 11), pegylated liposomal doxorubicin (30 mg/m(2) on day 4), and dexamethasone (40 mg/d; cycle 1: days 1 to 4, 8 to 11, and 15 to 18; cycles 2 to 4: days 1 to 4). Autologous transplantation was tandem melphalan 100 mg/m(2) (MEL100) and stem-cell support. Consolidation included four 28-day cycles of lenalidomide (25 mg/d on days 1 to 21 every 28 days) plus prednisone (50 mg every other day), followed by maintenance with lenalidomide (LP-L; 10 mg/d on days 1 to 21) until relapse. Primary end points were safety (incidence of grade 3 to 4 adverse events [AEs]) and efficacy (response rate). Results A total of 102 patients were enrolled. In a per-protocol analysis, after PAD, 58% of patients had very good partial response (VGPR) or better, including 13% with complete response (CR); after MEL100, 82% of patients had at least VGPR and 38% had CR; and after LP-L, 86% of patients had at least VGPR and 66% had CR. After median follow-up time of 21 months, the 2-year progression-free survival rate was 69%, and the 2-year overall survival rate was 86%. During induction, treatment-related mortality was 3%; grade 3 to 4 AEs included thrombocytopenia (17%), neutropenia (10%), peripheral neuropathy (16%), and pneumonia (10%). During consolidation-maintenance, grade 3 to 4 AEs were neutropenia (16%), thrombocytopenia (6%), pneumonia (5%), and cutaneous rash (4%). CONCLUSION Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance, is an effective regimen.

  8. Bortezomib protects from varicose-like venous remodeling.

    Science.gov (United States)

    Pfisterer, Larissa; Meyer, Ralph; Feldner, Anja; Drews, Oliver; Hecker, Markus; Korff, Thomas

    2014-08-01

    Despite the high prevalence of venous diseases that are associated with and based on the structural reorganization of the venous vessel wall, not much is known about their mechanistic causes. In this context, we demonstrated that the quantity of myocardin, a transcriptional regulator of the contractile and quiescent smooth muscle cell phenotype, was diminished in proliferating synthetic venous smooth muscle cells (VSMCs) of human and mouse varicose veins by 51 and 60%, respectively. On the basis of the relevance of proteasomal activity for such phenotypic changes, we hypothesized that the observed VSMC activation is attenuated by the proteasome inhibitor bortezomib. This drug fully abolished VSMC proliferation and loss of myocardin in perfused mouse veins and blocked VSMC invasion in collagen gels by almost 80%. In line with this, topical transdermal treatment with bortezomib diminished VSMC proliferation by 80%, rescued 90% of VSMC myocardin abundance, and inhibited varicose-like venous remodeling by 67 to 72% in a mouse model. Collectively, our data indicate that the proteasome plays a pivotal role in VSMC phenotype changes during venous remodeling processes. Its inhibition protects from varicose-like vein remodeling in mice and may thus serve as a putative therapeutic strategy to treat human varicose veins.

  9. Novel therapeutic strategy to prevent chemotherapy-induced persistent sensory neuropathy by TRPA1 blockade.

    Science.gov (United States)

    Trevisan, Gabriela; Materazzi, Serena; Fusi, Camilla; Altomare, Alessandra; Aldini, Giancarlo; Lodovici, Maura; Patacchini, Riccardo; Geppetti, Pierangelo; Nassini, Romina

    2013-05-15

    Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and painful adverse reaction of cancer treatment in patients that is little understood or treated. Cytotoxic drugs that cause CIPN exert their effects by increasing oxidative stress, which activates the ion channel TRPA1 expressed by nociceptors. In this study, we evaluated whether TRPA1 acted as a critical mediator of CIPN by bortezomib or oxaliplatin in a mouse model system. Bortezomib evoked a prolonged mechanical, cold, and selective chemical hypersensitivity (the latter against the TRPA1 agonist allyl isothiocyanate). This CIPN hypersensitivity phenotype that was stably established by bortezomib could be transiently reverted by systemic or local treatment with the TRPA1 antagonist HC-030031. A similar effect was produced by the oxidative stress scavenger α-lipoic acid. Notably, the CIPN phenotype was abolished completely in mice that were genetically deficient in TRPA1, highlighting its essential role. Administration of bortezomib or oxaliplatin, which also elicits TRPA1-dependent hypersensitivity, produced a rapid, transient increase in plasma of carboxy-methyl-lysine, a by-product of oxidative stress. Short-term systemic treatment with either HC-030031 or α-lipoic acid could completely prevent hypersensitivity if administered before the cytotoxic drug. Our findings highlight a key role for early activation/sensitization of TRPA1 by oxidative stress by-products in producing CIPN. Furthermore, they suggest prevention strategies for CIPN in patients through the use of early, short-term treatments with TRPA1 antagonists.

  10. Data for a proteomic analysis of p53-independent induction of apoptosis by bortezomib

    OpenAIRE

    2014-01-01

    This data article contains data related to the research article entitled, “A proteomic analysis of p53-independent induction of apoptosis by bortezomib in 4T1 breast cancer cell line” by Yerlikaya et al. [1]. The research article presented 2-DE and nLC-MS/MS based proteomic analysis of proteasome inhibitor bortezomib-induced changes in the expression of cellular proteins. The report showed that GRP78 and TCEB2 were over-expressed in response to treatment with bortezomib for 24 h. In addition,...

  11. Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory B-cell Neoplasms

    Science.gov (United States)

    Holkova, Beata; Perkins, E. Brent; Ramakrishnan, Viswanathan; Tombes, Mary Beth; Shrader, Ellen; Talreja, Neha; Wellons, Martha D.; Hogan, Kevin T.; Roodman, G. David; Coppola, Domenico; Kang, Loveleen; Dawson, Jana; Stuart, Robert K.; Peer, Cody; Figg, William D.; Kolla, Sarah; Doyle, Austin; Wright, John; Sullivan, Daniel M.; Roberts, John D.; Grant, Steven

    2011-01-01

    Purpose A phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximally tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B cell malignancies (multiple myeloma, indolent and mantle cell lymphoma). Experimental Design Patients received bortezomib by IV push on days 1, 4, 8 and 11. Patients also received alvocidib on days 1 and 8 by 30 min bolus infusion followed by a 4 hour continuous infusion. Treatment was on a 21 day cycle, with indefinite continuation for patients experiencing responses or stable disease. Dose escalation employed a standard 3+3 design until the MTD was identified based upon DLTs. Pharmacokinetic studies and pharmacodynamic studies were performed. Results Sixteen patients were treated. The MTD was established as 1.3 mg/m2 for bortezomib and 30 mg/m2 for alvocidib (both the 30 min bolus and 4 hour infusions). Common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. Common non-hematologic toxicities included fatigue and febrile neutropenia. DLTs included fatigue, febrile neutropenia, and elevated aspartate aminotransferase (AST) levels. Two complete responses (CR; 12%) and five partial responses (PR; 31%) were observed at the MTD (overall response rate 44%). Pharmacokinetic results were typical for alvocidib, and pharmacodynamic studies yielded variable results. Conclusions The combination of bortezomib and alvocidib is tolerable and an MTD has been established for the tested schedule. The regimen appears active in patients with relapsed and/or refractory multiple myeloma or non-Hodgkin’s lymphoma, justifying phase II studies to determine the activity of this regimen more definitively. PMID:21447728

  12. Successful Use of Cyclophosphamide as an Add-On Therapy for Multiple Myeloma Patients with Acquired Resistance to Bortezomib or Lenalidomide

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    Shigeki Ito

    2013-01-01

    Full Text Available Novel agents such as thalidomide, lenalidomide, and bortezomib have been shown to possess potent activity against multiple myeloma. However, the treatment strategy for patients who acquired resistance to these agents has not been established. In addition to switching drug classes, intensified treatment strategy, including increase in the dosage of current agents and addition of other agents, may be considered for these patients. We here describe 2 myeloma patients with acquired resistance to bortezomib or lenalidomide, in whom add-on therapy with low-dose cyclophosphamide was effective and tolerable. These cases suggest that add-on therapy with cyclophosphamide is one of the treatment options to overcome resistance to novel agents in patients with multiple myeloma. A larger prospective study is needed to clarify the efficacy and safety of this strategy for novel agent-resistant multiple myeloma.

  13. Ventricular fibrillation after bortezomib therapy in a patient with systemic amyloidosis

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    Satoshi Yamasaki

    2013-09-01

    Full Text Available A 64-year-old female was diagnosed with systemic amyloidosis associated with multiple myeloma. Bortezomib and dexamethasone-therapy was initiated; however, she developed lethal ventricular fibrillation (VF and cardiac arrest after 84 hours of therapy. Cardiopulmonary resuscitation using direct current shocks with epinephrine and amiodarone was initiated but failed to receive cardiac function. Although her arterial pulsations recovered immediately after the injection of vasopressin, she died of heart failure 8 hours after the onset of VF. Cardiac amyloidosis was verified by autopsy. Although the direct association of bortezomib with lethal VF remained to be clarified in our patient, the current report emphasizes on bortezomib as a substantial risk factor for cardiomyocyte damage. The potential risk of lethal events associated with cardiac amyloidosis should be carefully considered during bortezomib treatment for patients with AL amyloidosis.

  14. Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma

    DEFF Research Database (Denmark)

    Hjorth, Martin; Hjertner, Øyvind; Knudsen, Lene Meldgaard

    2012-01-01

    Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives....

  15. Bortezomib partially protects the rat diaphragm from ventilator-induced diaphragm dysfunction

    NARCIS (Netherlands)

    Agten, A.; Maes, K.; Thomas, D.; Cielen, N.; Hees, H.W. van; Dekhuijzen, R.; Decramer, M.; Gayan-Ramirez, G.

    2012-01-01

    OBJECTIVE: Controlled mechanical ventilation leads to diaphragmatic contractile dysfunction and atrophy. Since proteolysis is enhanced in the diaphragm during controlled mechanical ventilation, we examined whether the administration of a proteasome inhibitor, bortezomib, would have a protective effe

  16. cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas.

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    Valentina Manfè

    Full Text Available Successful/effective cancer therapy in low grade lymphoma is often hampered by cell resistance to anti-neoplastic agents. The crucial mechanisms responsible for this phenomenon are poorly understood. Overcoming resistance of tumor cells to anticancer agents, such as proteasome inhibitors, could improve their clinical efficacy. Using cutaneous T-cell lymphoma (CTCL as a model of the chemotherapy-resistant peripheral lymphoid malignancy, we demonstrated that resistance to proteasome inhibition involved a signaling between the oncogene cMyc and miR-125b-5p. Bortezomib repressed cMyc and simultaneously induced miR-125b-5p that exerted a cytoprotective effect through the downmodulation of MAD4. Overexpression of cMyc repressed miR-125b-5p transcription and sensitized lymphoma cells to bortezomib. The central role of miR-125b-5p was further confirmed in a mouse model of T-cell lymphoma, where xenotransplantation of human CTCL cells overexpressing miR-125b-5p resulted in enhanced tumor growth and a shorter median survival. Our findings describe a novel mechanism through which miR-125b-5p not only regulates tumor growth in vivo, but also increases cellular resistance to proteasome inhibitors via modulation of MAD4.

  17. Visualizing the antivascular effect of bortezomib on the hypoxic tumor microenvironment

    Science.gov (United States)

    Sun, Xiaorong; Ackerstaff, Ellen; He, Fuqiu; Xing, Ligang; Hsiao, Hung Tsung; Koutcher, Jason A.; Ling, C. Clifton; Li, Gloria C.

    2015-01-01

    Bortezomib, a novel proteasome inhibitor, has been approved for treating multiple myeloma and mantle cell lymphoma and studied pre-clinically and clinically for solid tumors. Preferential cytotoxicity of bortezomib was found toward hypoxic tumor cells and endothelial cells in vitro. The purpose of this study is to investigate the role of a pretreatment hypoxic tumor microenvironment on the effects of bortezomib in vitro and ex vivo, and explore the feasibility of dynamic contrast enhanced magnetic resonance imaging (DCE MRI) to noninvasively evaluate the biological effects of bortezomib. It was shown in vitro by Western blot, flow cytometry, and ELISA that bortezomib accumulated HIF-1α in non-functional forms and blocks its hypoxia response in human colorectal cancer cell lines. Ex vivo experiments were performed with fluorescent immunohistochemical staining techniques using multiple endogenous and exogenous markers to identify hypoxia (pimonidazole, HRE-TKeGFP), blood flow/permeability (Hoechst 33342), micro-vessels (CD31 and SMA), apoptosis (cleaved caspase 3) and hypoxia response (CA9). After bortezomib administration, overall apoptosis index was significantly increased and blood perfusion was dramatically decreased in tumor xenografts. More importantly, apoptosis signals were found preferentially located in moderate and severe pretreatment hypoxic regions in both tumor and endothelial cells. Meanwhile, DCE MRI examinations showed that the tumor blood flow and permeability decreased significantly after bortezomib administration. The present study revealed that bortezomib reduces tumor hypoxia response and blood perfusion, thus, presenting antivascular properties. It will be important to determine the hypoxic/perfusion status pre- and during treatment at further translational studies. PMID:26416246

  18. Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats

    Directory of Open Access Journals (Sweden)

    Shota Yamamoto

    2015-09-01

    Full Text Available Bortezomib, an effective anticancer drug for multiple myeloma, often causes peripheral neuropathy which is mainly characterized by numbness and painful paresthesia. Nevertheless, there is no effective strategy to escape or treat bortezomib-induced peripheral neuropathy (BIPN, because we have understood few mechanism of this side effect. In this study, we evaluated behavioral and pathological characteristics of BIPN, and investigated pharmacological efficacy of various analgesic drugs and adjuvants on mechanical allodynia induced by bortezomib treatment in rats. The repeated administration of bortezomib induced mechanical and cold allodynia. There was axonal degeneration of sciatic nerve behind these neuropathic symptoms. Furthermore, the exposure to bortezomib shortened neurite length in PC12 cells. Finally, the result of evaluation of anti-allodynic potency, oral administration of tramadol (10 mg/kg, pregabalin (3 mg/kg, duloxetine (30 mg/kg or mexiletine (100 mg/kg, but not amitriptyline or diclofenac, transiently relieved the mechanical allodynia induced by bortezomib. These results suggest that axonal degeneration of the sciatic nerve is involved in BIPN and that some analgesic drugs and adjuvants are effective in the relief of painful neuropathy.

  19. Acupuncture for neuropathic pain due to bortezomib in a patient with multiple myeloma.

    Science.gov (United States)

    Mandıroğlu, Sibel; Cevik, Cemal; Aylı, Meltem

    2014-04-01

    Multiple myeloma (MM) is characterised by an increase in plasma cells, particularly in the bone marrow but also in other organs and systems, and with the abnormal production of immunoglobulin. Bortezomib, a current treatment option, inhibits angiogenesis by proteasome inhibition and is known to be effective in the treatment of MM. Peripheral neuropathy (PN) is a common dose-related side effect of bortezomib in patients with MM. We describe a case of PN due to bortezomib treatment which responded dramatically to acupuncture treatment, enabling his bortezomib treatment to continue. The patient was a 74-year-old man with pain, numbness, tingling and weakness in his hands and feet after 22 days of bortezomib treatment given by the haematology clinic. His neuropathic pain score was 8/10. There were no autonomic symptoms. Electroneurophysiological testing confirmed sensorimotor PN. Acupuncture treatment was planned as his neuropathic pain continued. Acupuncture was administered bilaterally to ST36, SP6 and LI4 15 times (every other day in the first five sessions and then twice a week). The numbness, tingling and pain symptoms substantially decreased after the first two treatments. After the 15th session acupuncture treatment was continued once a month. At the end of the sixth month the neuropathic pain assessment score was 0/10. There was no side effect of acupuncture treatment. Acupuncture seems promising as a complementary medical treatment for neuropathic pain from bortezomib-induced PN. Clinical studies involving more cases and electrophysiological studies are necessary to investigate the effectiveness of acupuncture.

  20. BAK and NOXA are critical determinants of mitochondrial apoptosis induced by bortezomib in mesothelioma.

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    Sara Busacca

    Full Text Available Based on promising preclinical efficacy associated with the 20S proteasome inhibitor bortezomib in malignant pleural mesothelioma (MPM, two phase II clinical trials have been initiated (EORTC 08052 and ICORG 05-10. However, the potential mechanisms underlying resistance to this targeted drug in MPM are still unknown. Functional genetic analyses were conducted to determine the key mitochondrial apoptotic regulators required for bortezomib sensitivity and to establish how their dysregulation may confer resistance. The multidomain proapoptotic protein BAK, but not its orthologue BAX, was found to be essential for bortezomib-induced apoptosis in MPM cell lines. Immunohistochemistry was performed on tissues from the ICORG-05 phase II trial and a TMA of archived mesotheliomas. Loss of BAK was found in 39% of specimens and loss of both BAX/BAK in 37% of samples. However, MPM tissues from patients who failed to respond to bortezomib and MPM cell lines selected for resistance to bortezomib conserved BAK expression. In contrast, c-Myc dependent transactivation of NOXA was abrogated in the resistant cell lines. In summary, the block of mitochondrial apoptosis is a limiting factor for achieving efficacy of bortezomib in MPM, and the observed loss of BAK expression or NOXA transactivation may be relevant mechanisms of resistance in the clinic.

  1. BAK and NOXA are critical determinants of mitochondrial apoptosis induced by bortezomib in mesothelioma.

    Science.gov (United States)

    Busacca, Sara; Chacko, Alex D; Klabatsa, Astero; Arthur, Kenneth; Sheaff, Michael; Barbone, Dario; Mutti, Luciano; Gunasekharan, Vignesh K; Gorski, Julia J; El-Tanani, Mohamed; Broaddus, V Courtney; Gaudino, Giovanni; Fennell, Dean A

    2013-01-01

    Based on promising preclinical efficacy associated with the 20S proteasome inhibitor bortezomib in malignant pleural mesothelioma (MPM), two phase II clinical trials have been initiated (EORTC 08052 and ICORG 05-10). However, the potential mechanisms underlying resistance to this targeted drug in MPM are still unknown. Functional genetic analyses were conducted to determine the key mitochondrial apoptotic regulators required for bortezomib sensitivity and to establish how their dysregulation may confer resistance. The multidomain proapoptotic protein BAK, but not its orthologue BAX, was found to be essential for bortezomib-induced apoptosis in MPM cell lines. Immunohistochemistry was performed on tissues from the ICORG-05 phase II trial and a TMA of archived mesotheliomas. Loss of BAK was found in 39% of specimens and loss of both BAX/BAK in 37% of samples. However, MPM tissues from patients who failed to respond to bortezomib and MPM cell lines selected for resistance to bortezomib conserved BAK expression. In contrast, c-Myc dependent transactivation of NOXA was abrogated in the resistant cell lines. In summary, the block of mitochondrial apoptosis is a limiting factor for achieving efficacy of bortezomib in MPM, and the observed loss of BAK expression or NOXA transactivation may be relevant mechanisms of resistance in the clinic.

  2. Rare occurrence of bortezomib-induced Sweet′s syndrome in multiple myeloma

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    Chaturbhuj Agrawal

    2016-01-01

    Full Text Available Sweet′s syndrome (SS (acute neutrophilic dermatosis has already been described in cases of acute leukemia. It has been rarely reported in patients receiving bortezomib therapy for multiple myeloma (MM. A 65-year-old male, who was diagnosed as a case of MM 3 years back, initially received lenalidomide- and dexamethasone-based regimen, followed by lenalidomide maintenance, but subsequently had progressive disease with increasing monoclonal M-spike on serum protein electrophoresis, so shifted to bortezomib and dexamethasone along with monthly zoledronic acid-based treatment. He developed itching over face and neck with darkening and thickening of the skin. Examination revealed hyperpigmentation of face along with excoriation and erosions with involvement of "V" of neck with relative sparing of upper eyelid, postauricular area, and nasolabial folds. Histopathological examination of skin biopsy revealed neutrophilic infiltration of dermis suggestive of SS. A wide variety of cutaneous complications has been described in 10-20% of patients receiving bortezomib. However, SS has rarely been described in such patients with only a few case reports reported so far. Our patient developed features of SS while on bortezomib therapy and had shown dramatic response to bortezomib withdrawal and treatment with oral and topical steroids showing temporal association of this rare syndrome with bortezomib therapy.

  3. Breast Cancer Chemotherapy and Your Heart

    Science.gov (United States)

    ... American Heart Association Cardiology Patient Page Breast Cancer Chemotherapy and Your Heart Christine Unitt , Kamaneh Montazeri , Sara ... cancer treatments. Breast cancer treatments include the following: Chemotherapy involves drugs that are intended to kill the ...

  4. Interferon-γ-induced upregulation of immunoproteasome subunit assembly overcomes bortezomib resistance in human hematological cell lines

    OpenAIRE

    2014-01-01

    Background Despite encouraging results with the proteasome inhibitor bortezomib in the treatment of hematologic malignancies, emergence of resistance can limit its efficacy, hence calling for novel strategies to overcome bortezomib-resistance. We previously showed that bortezomib-resistant human leukemia cell lines expressed significantly lower levels of immunoproteasome at the expense of constitutive proteasomes, which harbored point mutations in exon 2 of the PSMB5 gene encoding the β5 subu...

  5. Therapeutic effect of bortezomib for primary plasma cell leukemia followed by auto/allo stem cell transplantation

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    Ozasa R

    2012-07-01

    Full Text Available Ryotaro Ozasa, Masaaki Hotta, Hideaki Yoshimura, Takahisa Nakanishi, Takeshi Tamaki, Shinya Fujita, Naoto Nakamichi, Michihiko Miyaji, Kazuyoshi Ishii, Tomoki Ito, Shosaku NomuraFirst Department of Internal Medicine, Kansai Medical University, Osaka, JapanAbstract: Plasma cell leukemia (PCL is a rare disease that represents approximately 4% of plasma cell malignant disorders. PCL consists of two variants: primary PCL presents in patients with no previous history of multiple myeloma, while secondary PCL consists of a leukemic transformation in a previously recognized multiple myeloma. Primary PCL is an extremely resistant, rapidly progressive, fatal disease, with a median overall survival of 6.8 months. There is no standard therapeutic strategy, because no treatment option has been prospectively evaluated. We describe a successful case of newly diagnosed primary PCL, treated with a regimen that included bortezomib, followed by auto stem cell transplantation and nonmyeloablative allogeneic stem cell transplantation. Our patient has maintained remission status for over 12 months since undergoing the allogeneic stem cell transplantation. This strategy is promising for PCL, which, though an extremely resistant disease, may become curable.Keywords: plasma cell leukemia, multiple myeloma, bortezomib, stem cell transplantation

  6. Severe Acute Hepatitis B in HBV-Vaccinated Partner of a Patient with Multiple Myeloma Treated with Cyclophosphamide, Bortezomib, and Dexamethasone and Autologous Stem Cell Transplant

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    Majed M. Almaghrabi

    2017-01-01

    Full Text Available Hepatitis B reactivation can occur with various forms of immunosuppression. Cyclophosphamide, Bortezomib, and Dexamethasone (CYBOR-D chemotherapy is commonly used for the treatment of multiple myeloma and has not been noted in guidelines to be causative in HBV reactivation. Indeed, current guidelines do not recommend providing antiviral prophylaxis to patients with prior HBV infection. We present a case of HBV reactivation as a result of CYBOR-D and autologous stem cell transplant which is complicated by the patient’s partner who developed acute hepatitis B. Our case highlights the need to review the role of antiviral prophylaxis for patients undergoing treatment of multiple myeloma and also the role of ensuring immunity for close contacts of these patients who may also be at risk.

  7. Combination Chemotherapy for Influenza

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    Robert G. Webster

    2010-07-01

    Full Text Available The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir and to M2 ion channel blockers (amantadine and rimantadine, although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease, the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets.

  8. Bortezomib sensitizes primary human esthesioneuroblastoma cells to TRAIL-induced apoptosis.

    Science.gov (United States)

    Koschny, Ronald; Holland, Heidrun; Sykora, Jaromir; Erdal, Hande; Krupp, Wolfgang; Bauer, Manfred; Bockmuehl, Ulrike; Ahnert, Peter; Meixensberger, Jürgen; Stremmel, Wolfgang; Walczak, Henning; Ganten, Tom M

    2010-04-01

    TNF-related apoptosis-inducing ligand (TRAIL), a promising novel anti-cancer cytokine of the TNF superfamily, and Bortezomib, the first-in-class clinically used proteasome inhibitor, alone or in combination have been shown to efficiently kill numerous tumor cell lines. However, data concerning primary human tumor cells are very rare. Using primary esthesioneuroblastoma cells we analyzed the anti-tumor potential and the mechanism employed by Bortezomib in combination with TRAIL for the treatment of this rare but aggressive tumor. Expression of components of the TRAIL pathway was analyzed in tumor specimens and isolated primary tumor cells at the protein level. Cells were treated with TRAIL, Bortezomib, and a combination thereof, and apoptosis induction was quantified. Clonogenicity assays were performed to elucidate the long-term effect of this treatment. Despite expressing all components of the TRAIL pathway, freshly isolated primary esthesioneuroblastoma cells were completely resistant to TRAIL-induced apoptosis. They could, however, be very efficiently sensitized by subtoxic doses of Bortezomib. The influence of Bortezomib on the TRAIL pathway was analyzed and showed upregulation of TRAIL death receptor expression, enhancement of the TRAIL death-inducing signaling complex (DISC), and downregulation of anti-apoptotic proteins of the TRAIL pathway. Of clinical relevance, TRAIL-resistant primary tumor cells could be repeatedly sensitized by Bortezomib, providing the basis for repeated clinical application schedules. This is the first report on the highly synergistic induction of apoptosis in primary esthesioneuroblastoma cells by Bortezomib and TRAIL. This combination, therefore, represents a promising novel therapeutic option for esthesioneuroblastoma.

  9. Arterial occlusion precipitated by cisplatinbased chemotherapy

    OpenAIRE

    2010-01-01

    Cisplatin-based therapy is curative in testicular cancer. Adverse effects of cisplatin-based chemotherapy include dose-dependent myelosuppression, nephrotoxicity, neurotoxicity, and ototoxicity. By contrast, chemotherapy-associated vascular complications are unpredictable. Few incidents of digital gangrene with cisplatin have been reported. Here, we present a patient who developed arterial occlusion leading to gangrene of the toe after cisplatinbased chemotherapy.

  10. Glutamine: A novel approach to chemotherapy-induced toxicity

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    Kumar Gaurav

    2012-01-01

    Full Text Available Treatment of cancer is associated with short- and long-term side-effects. Cancer produces a state of glutamine deficiency, which is further aggravated by toxic effects of chemotherapeutic agents leading to increased tolerance of tumor to chemotherapy as well as reduced tolerance of normal tissues to the side-effects of chemotherapy. This article reviews the possible role of glutamine supplementation in reducing the serious adverse events in patients treated with anticancer drugs. The literature related to the possible role of glutamine in humans with cancer and the supportive evidence from animal studies was reviewed. Searches were made and the literature was retrieved using PUBMED, MEDLINE, COCHRANE LIBRARY, CENAHL and EMBASE, with a greater emphasis on the recent advances and clinical trials. Glutamine supplementation was found to protect against radiation-induced mucositis, anthracycline-induced cardiotoxicity and paclitaxel-related myalgias/arthralgias. Glutamine may prevent neurotoxicity of paclitaxel, cisplatin, oxaplatin bortezomib and lenolidamide, and is beneficial in the reduction of the dose-limiting gastrointestinal toxic effects of irinotecan and 5-FU-induced mucositis and stomatitis. Dietary glutamine reduces the severity of the immunosuppressive effect induced by methotrexate and improves the immune status of rats recovering from chemotherapy. In patients with acute myeloid leukemia requiring parenteral nutrition, glycyl-glutamine supplementation could hasten neutrophil recovery after intensive myelosuppressive chemotherapy. Current data supports the usefulness of glutamine supplementation in reducing complications of chemotherapy; however, paucity of clinical trials weakens the clear interpretation of these findings.

  11. Cytotoxic effects of bortezomib in myelodysplastic syndrome/acute myeloid leukemia depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1

    NARCIS (Netherlands)

    Fang, Jing; Rhyasen, Garrett; Bolanos, Lyndsey; Rasch, Christopher; Varney, Melinda; Wunderlich, Mark; Goyama, Susumu; Jansen, Gerrit; Cloos, Jacqueline; Rigolino, Carmela; Cortelezzi, Agostino; Mulloy, James C.; Oliva, Esther N.; Cuzzola, Maria; Starczynowski, Daniel T.

    2012-01-01

    Bortezomib (Velcade) is used widely for the treatment of various human cancers; however, its mechanisms of action are not fully understood, particularly in myeloid malignancies. Bortezomib is a selective and reversible inhibitor of the proteasome. Paradoxically, we find that bortezomib induces prote

  12. Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT

    DEFF Research Database (Denmark)

    Gimsing, P; Hjertner, Ø; Abildgaard, N

    2015-01-01

    Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib i...

  13. Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors.

    Science.gov (United States)

    Golden, Encouse B; Lam, Philip Y; Kardosh, Adel; Gaffney, Kevin J; Cadenas, Enrique; Louie, Stan G; Petasis, Nicos A; Chen, Thomas C; Schönthal, Axel H

    2009-06-04

    The anticancer potency of green tea and its individual components is being intensely investigated, and some cancer patients already self-medicate with this "miracle herb" in hopes of augmenting the anticancer outcome of their chemotherapy. Bortezomib (BZM) is a proteasome inhibitor in clinical use for multiple myeloma. Here, we investigated whether the combination of these compounds would yield increased antitumor efficacy in multiple myeloma and glioblastoma cell lines in vitro and in vivo. Unexpectedly, we discovered that various green tea constituents, in particular (-)-epigallocatechin gallate (EGCG) and other polyphenols with 1,2-benzenediol moieties, effectively prevented tumor cell death induced by BZM in vitro and in vivo. This pronounced antagonistic function of EGCG was evident only with boronic acid-based proteasome inhibitors (BZM, MG-262, PS-IX), but not with several non-boronic acid proteasome inhibitors (MG-132, PS-I, nelfinavir). EGCG directly reacted with BZM and blocked its proteasome inhibitory function; as a consequence, BZM could not trigger endoplasmic reticulum stress or caspase-7 activation, and did not induce tumor cell death. Taken together, our results indicate that green tea polyphenols may have the potential to negate the therapeutic efficacy of BZM and suggest that consumption of green tea products may be contraindicated during cancer therapy with BZM.

  14. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients.

    Science.gov (United States)

    Bringhen, Sara; Larocca, Alessandra; Rossi, Davide; Cavalli, Maide; Genuardi, Mariella; Ria, Roberto; Gentili, Silvia; Patriarca, Francesca; Nozzoli, Chiara; Levi, Anna; Guglielmelli, Tommasina; Benevolo, Giulia; Callea, Vincenzo; Rizzo, Vincenzo; Cangialosi, Clotilde; Musto, Pellegrino; De Rosa, Luca; Liberati, Anna Marina; Grasso, Mariella; Falcone, Antonietta P; Evangelista, Andrea; Cavo, Michele; Gaidano, Gianluca; Boccadoro, Mario; Palumbo, Antonio

    2010-12-02

    In a recent phase 3 trial, bortezomib-melphalan-prednisone-thalidomide followed by maintenance treatment with bortezomib-thalidomide demonstrated superior efficacy compared with bortezomib-melphalan-prednisone. To decrease neurologic toxicities, the protocol was amended and patients in both arms received once-weekly instead of the initial twice-weekly bortezomib infusions: 372 patients received once-weekly and 139 twice-weekly bortezomib. In this post-hoc analysis we assessed the impact of the schedule change on clinical outcomes and safety. Long-term outcomes appeared similar: 3-year progression-free survival rate was 50% in the once-weekly and 47% in the twice-weekly group (P > .999), and 3-year overall survival rate was 88% and 89%, respectively (P = .54). The complete response rate was 30% in the once-weekly and 35% in the twice-weekly group (P = .27). Nonhematologic grade 3/4 adverse events were reported in 35% of once-weekly patients and 51% of twice-weekly patients (P = .003). The incidence of grade 3/4 peripheral neuropathy was 8% in the once-weekly and 28% in the twice-weekly group (P < .001); 5% of patients in the once-weekly and 15% in the twice-weekly group discontinued therapy because of peripheral neuropathy (P < .001). This improvement in safety did not appear to affect efficacy. This study is registered at http://www.clinicaltrials.gov as NCT01063179.

  15. Bortezomib in plasmablastic lymphoma: A glimpse of hope for a hard-to-treat disease.

    Science.gov (United States)

    Guerrero-Garcia, Thomas A; Mogollon, Renzo J; Castillo, Jorge J

    2017-09-27

    Plasmablastic lymphoma (PBL) is a rare and hard to treat disease. With current standard chemotherapeutic regimens, PBL is associated with a median overall survival of 12-15 months. We performed a systematic review of the literature through March 31, 2017 looking for patients with a diagnosis of PBL who were treated with bortezomib, alone or in combination. We identified 21 patients, of which 11 received bortezomib in the frontline setting and 10 received bortezomib in the relapsed setting. Eleven patients were HIV-positive and 10 were HIV-negative. The overall response rate to bortezomib-containing regimens was 100% in the frontline setting and 90% in the relapsed setting. Furthermore, the 2-year overall survival of patients treated upfront was 55%, and the median OS in relapsed patients was 14 months. Although the sample size is small, we believe our results are encouraging and should serve as rationale to investigate bortezomib-based regimens in patients with PBL. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Therapeutic trial of metformin and bortezomib in a mouse model of tuberous sclerosis complex (TSC.

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    Neil Auricchio

    Full Text Available Tuberous sclerosis complex (TSC is a human genetic disorder in which loss of either TSC1 or TSC2 leads to development of hamartoma lesions, which can progress and be life-threatening or fatal. The TSC1/TSC2 protein complex regulates the state of activation of mTORC1. Tsc2(+/- mice develop renal cystadenoma lesions which grow progressively. Both bortezomib and metformin have been proposed as potential therapeutics in TSC. We examined the potential benefit of 1 month treatment with bortezomib, and 4 month treatment with metformin in Tsc2(+/- mice. Results were compared to vehicle treatment and treatment with the mTORC1 inhibitor rapamycin for 1 month. We used a quantitative tumor volume measurement on stained paraffin sections to assess the effect of these drugs. The median tumor volume per kidney was decreased by 99% in mice treated with rapamycin (p = 0.0004. In contrast, the median tumor volume per kidney was not significantly reduced for either the bortezomib cohort or the metformin cohort. Biochemical studies confirmed that bortezomib and metformin had their expected pharmacodynamic effects. We conclude that neither bortezomib nor metformin has significant benefit in this native Tsc2(+/- mouse model, which suggests limited benefit of these compounds in the treatment of TSC hamartomas and related lesions.

  17. Bortezomib and lenalidomide as front-line therapy for multiple myeloma.

    Science.gov (United States)

    Zou, Yandun; Lin, Mingzhen; Sheng, Zhixin; Niu, Shaona

    2014-09-01

    The objective of the study was to investigate the effects and safety of novel agents such as bortezomib and lenalidomide in the treatment of newly diagnosed patients with multiple myeloma. We performed a comprehensive meta-analysis of randomized controlled trials (RCTs). An initial search yielded 627 citations, of which 10 RCTs enrolling 4534 patients met the inclusion criteria. The addition of bortezomib to first-line therapy significantly prolonged overall survival (OS) (hazard ratio [HR], 0.75 [0.65, 0.87], p lenalidomide had no impact on survival (HR, 0.88 [0.65, 1.20], p = 0.42). Both lenalidomide and bortezomib consistently improved progression-free survival (PFS) compared with conventional therapy alone. The corresponding HRs were 0.65, 95% confidence interval (CI) [0.55, 0.77] (p lenalidomide, respectively. Some of the increased adverse events reported were herpes zoster (relative risk [RR], 3.64 [2.23, 5.94], p lenalidomide. Interestingly, treatment with bortezomib seemed to be associated with a lower rate of treatment related mortality (RR, 0.39 [0.18, 0.85], p = 0.02). An increased incidence of second primary cancers was observed in the lenalidomide group (RR 2.61 [1.60, 4.27], p lenalidomide and bortezomib consistently improved PFS of patients with newly diagnosed myeloma when it was added to standard therapy.

  18. Analysis of the efficacy and toxicity of bortezomib for treatment of relapsed or refractory multiple myeloma in community practice

    NARCIS (Netherlands)

    Wu, KL; van Wieringen, W; Vellenga, E; Zweegman, S; Lokhorst, HM; Sonneveld, P

    The clinical data on the efficacy and toxicity of bortezomib as treatment for multiple myeloma patients are restricted to prospective phase II studies in expert myeloma centers. Here we report a multi-institutional analysis of the efficacy and toxicity of bortezomib in patients with relapsed or

  19. Long-term outcomes of primary systemic light chain (AL) amyloidosis in patients treated upfront with bortezomib or lenalidomide and the importance of risk adapted strategies.

    Science.gov (United States)

    Kastritis, Efstathios; Roussou, Maria; Gavriatopoulou, Maria; Migkou, Magdalini; Kalapanida, Despina; Pamboucas, Constantinos; Kaldara, Elisavet; Ntalianis, Argyrios; Psimenou, Erasmia; Toumanidis, Savvas T; Tasidou, Anna; Terpos, Evangelos; Dimopoulos, Meletios A

    2015-04-01

    Bortezomib and lenalidomide are increasingly used in patients with AL amyloidosis, but long term data on their use as primary therapy in AL amyloidosis are lacking while early mortality remains significant. Thus, we analyzed the long term outcomes of 85 consecutive unselected patients, which received primary therapy with bortezomib or lenalidomide and we prospectively evaluated a risk adapted strategy based on bortezomib/dexamethasone to reduce early mortality. Twenty-six patients received full-dose bortezomib/dexamethasone, 36 patients lenalidomide with oral cyclophosphamide and low-dose dexamethasone and 23 patients received bortezomib/dexamethasone at a dose and schedule adjusted to the risk of early death. On intent to treat, 67% of patients achieved a hematologic response (24% hemCRs) and 34% an organ response; both were more frequent with bortezomib. An early death occurred in 20%: in 36% of those treated with full-dose bortezomib/dexamethasone, in 22% of lenalidomide-treated patients but only in 4.5% of patients treated with risk-adapted bortezomib/dexamethasone. Activity of full vs. adjusted dose bortezomib/dexamethasone was similar; twice weekly vs. weekly administration of bortezomib also had similar activity. After a median follow up of 57 months, median survival is 47 months and is similar for patients treated with bortezomib vs. lenalidomide-based regimens. However, risk adjusted-bortezomib/dexamethasone was associated with improved 1-year survival vs. full-dose bortezomib/dexamethasone or lenalidomide-based therapy (81% vs. 56% vs. 53%, respectively). In conclusion, risk-adapted bortezomib/dexamethasone may reduce early mortality and preserve activity while long term follow up indicates that remissions obtained with lenalidomide or bortezomib may be durable, even without consolidation with alkylators. © 2015 Wiley Periodicals, Inc.

  20. Bortezomib reduces the tumorigenicity of multiple myeloma via downregulation of upregulated targets in clonogenic side population cells.

    Directory of Open Access Journals (Sweden)

    Miho Nara

    Full Text Available Side population (SP cells in cancers, including multiple myeloma, exhibit tumor-initiating characteristics. In the present study, we isolated SP cells from human myeloma cell lines and primary tumors to detect potential therapeutic targets specifically expressed in SP cells. We found that SP cells from myeloma cell lines (RPMI 8226, AMO1, KMS-12-BM, KMS-11 express CD138 and that non-SP cells include a CD138-negative population. Serial transplantation of SP and non-SP cells into NOD/Shi-scid IL-2γnul mice revealed that clonogenic myeloma SP cells are highly tumorigenic and possess a capacity for self-renewal. Gene expression analysis showed that SP cells from five MM cell lines (RPMI 8226, AMO1, KMS-12-BM, KMS-11, JJN3 express genes involved in the cell cycle and mitosis (e.g., CCNB1, CDC25C, CDC2, BIRC5, CENPE, SKA1, AURKB, KIFs, TOP2A, ASPM, polycomb (e.g., EZH2, EPC1 and ubiquitin-proteasome (e.g., UBE2D3, UBE3C, PSMA5 more strongly than do non-SP cells. Moreover, CCNB1, AURKB, EZH2 and PSMA5 were also upregulated in the SPs from eight primary myeloma samples. On that basis, we used an aurora kinase inhibitor (VX-680 and a proteasome inhibitor (bortezomib with RPMI 8226 and AMO1 cells to determine whether these agents could be used to selectively target the myeloma SP. We found that both these drugs reduced the SP fraction, though bortezomib did so more effectively than VX-680 due to its ability to reduce levels of both phospho-histone H3 (p-hist. H3 and EZH2; VX-680 reduced only p-hist. H3. This is the first report to show that certain oncogenes are specifically expressed in the myeloma SP, and that bortezomib effectively downregulates expression of their products. Our approach may be useful for screening new agents with which to target a cell population possessing strong tumor initiating potential in multiple myeloma.

  1. Antiproliferative effects of Bortezomib in endothelial cells transformed by viral G protein-coupled receptor associated to Kaposi's sarcoma.

    Science.gov (United States)

    Suares, A; Mori Sequeiros Garcia, M; Paz, C; González-Pardo, V

    2017-04-01

    The Kaposi's Sarcoma-associated Herpes virus G Protein-Coupled Receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi Sarcoma. We have previously demonstrated that the proteasome inhibitor Bortezomib inhibits NF-κB pathway, which is required for tumor maintenance in endothelial cells that express vGPCR (vGPCR cells). In this work, we further investigated Bortezomib anti-proliferative mechanism of action. We demonstrated that Bortezomib decreases vGPCR cell number in a dose-dependent manner and induces cell morphology changes. Bortezomib decreases ERK1/2 phosphorylation whereas induces the accumulation of MKP-3 - a specific ERK1/2 MAP kinase phosphatase - in time and concentration dependent manner (1.5-32h; 0.25-1nM). The transcription factor FOXO1 is activated by dephosphorylation and regulates p21 expression. Here, we demonstrated that Bortezomib increases FOXO1 protein and decreases its phosphorylation in a concentration dependent manner (0.25-1nM). Bortezomib (0.5nM, 24h) also increase nuclear FOXO1 protein, in line with FOXO1 dephosphorylation induced by the drug. Consistent with FOXO1 dephosphorylation/activation, p21 mRNA expression is increased by Bortezomib in a MKP-3-dependent way. Bortezomib (0.5nM, 24h) also decreases VEGF, an ERK1/2 -dependent effect. It is concluded that in vGPCR cells, Bortezomib decreases ERK1/2 and FOXO1 phosphorylation through MKP-3 accumulation, leading ERK1/2 deactivation and FOXO1 activation respectively and, consequently, to cell proliferation inhibition, p21 induction and VEGF repression. Taken together, all these events contribute to the anti-tumoral effect of Bortezomib.

  2. The protective effects of the proteasome inhibitor bortezomib (velcade on ischemia-reperfusion injury in the rat retina.

    Directory of Open Access Journals (Sweden)

    Fang-Ting Chen

    Full Text Available PURPOSE: To evaluate the protective effects of bortezomib (Velcade on ischemia-reperfusion (IR injury in the rat retina. METHODS: The rats were randomized to receive treatment with saline, low-dose bortezomib (0.05 mg/kg, or high-dose bortezomib (0.2 mg/kg before the induction of IR injury. Electroretinography (ERG was used to assess functional changes in the retina. The expression of inflammatory mediators (iNOS, ICAM-1, MCP-1, TNF-α, anti-oxidant proteins (heme oxygenase, thioredoxin, peroxiredoxin, and pro-apoptotic proteins (p53, bax were quantified by PCR and western blot analysis. An immunofluorescence study was performed to detect the expression of iNOS, oxidative markers (nitrotyrosine, 8-OHdG, acrolein, NF-κB p65, and CD 68. Apoptosis of retinal cells was labeled with in situ TUNEL staining. Neu-N staining was performed in the flat-mounted retina to evaluate the density of retinal ganglion cells. RESULTS: ERG showed a decreased b-wave after IR injury, and pretreatment with bortezomib, especially the high dosage, reduced the functional impairment. Bortezomib successfully reduced the elevation of inflammatory mediators, anti-oxidant proteins, pro-apoptotic proteins and oxidative markers after IR insult in a dose-dependent manner. In a similar fashion, NF-κB p65- and CD 68-positive cells were decreased by bortezomib treatment. Retinal cell apoptosis in each layer was attenuated by bortezomib. The retinal ganglion cell density was markedly decreased in the saline and low-dose bortezomib groups but was not significantly changed in the high-dose bortezomib group. CONCLUSIONS: Bortezomib had a neuro-protective effect in retinal IR injury, possibly by inhibiting the activation of NF-κB related to IR insult and reducing the inflammatory signals and oxidative stress in the retina.

  3. Monoclonal gammopathy-associated pauci-immune extracapillary-proliferative glomerulonephritis successfully treated with bortezomib.

    Science.gov (United States)

    Grundmann, Franziska; Witthus, Marco; Göbel, Heike; Kisner, Tuelay; Siewert, Rainer; Benzing, Thomas; Kurschat, Christine E

    2013-06-01

    Extracapillary-proliferative glomerulonephritis is a rare complication of multiple myeloma. Partial remission of kidney involvement with cyclophosphamide therapy has previously been described. We report the case of a 60-year-old male patient diagnosed with rapidly progressive glomerulonephritis associated with IgG kappa monoclonal gammopathy. His kidney biopsy revealed pauci-immune extracapillary-proliferative glomerulonephritis without cryoglobulinaemia. Treatment with the proteasome inhibitor bortezomib induced rapid clinical and histological remission of his kidney disease. The patient's renal function remained stable on bortezomib maintenance therapy. Our findings suggest that bortezomib is a promising therapeutic approach to ameliorate severe kidney damage in monoclonal gammopathy- and myeloma-associated pauci-immune extracapillary-proliferative glomerulonephritis.

  4. Pulse treatment with the proteasome inhibitor bortezomib inhibits osteoclast resorptive activity in clinically relevant conditions

    DEFF Research Database (Denmark)

    Boissy, P; Levin Andersen, Thomas; Lund, T

    2008-01-01

    Myeloma bone disease is due to bone degradation by osteoclasts, and absence of repair by bone forming osteoblasts. Recent observations suggest that the anti-myeloma drug bortezomib, a proteasome inhibitor, stimulates bone formation and may inhibit bone resorption. Here, we tested bortezomib...... on cultured osteoclasts in conditions mimicking the pulse treatment used in the clinic, thereby avoiding continuous proteasome inhibition and unselective toxicity. A 3h pulse with 25nM bortezomib followed by a 3-day culture in its absence markedly inhibited osteoclast activity as evaluated through bone...... resorption, TRAcP release, and RANKL-induced NF-kappaB translocation into nuclei, an event dependent on proteasomes and critical for osteoclast function. The effect on TRAcP was maximal during the first 24h post-pulse, and then tended to subside. Importantly, applying this pulse treatment to cultured myeloma...

  5. Lenalidomide (Revlimid), bortezomib (Velcade) and dexamethasone for heavily pretreated relapsed or refractory multiple myeloma.

    Science.gov (United States)

    Jimenez-Zepeda, Victor H; Reece, Donna E; Trudel, Suzanne; Chen, Christine; Tiedemann, Rodger; Kukreti, Vishal

    2013-03-01

    The combination of lenalidomide, bortezomib and dexamethasone (RVD) has shown excellent efficacy in patients with relapsed or refractory multiple myeloma (RRMM). The aim of our study was to assess the efficacy and toxicity profile of RVD for patients with advanced RRMM. We retrospectively reviewed the records of all patients with RRMM treated with RVD between March 2009 and December 2011. Thirty patients received ≥ 1 full cycle of RVD. Primary endpoints were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). After a median of 5 cycles (1-16), a very good partial response (VGPR) was seen in 10%, partial response (PR) in 36.7% and stable disease (SD) in 13.3% (ORR of 46.7%). Disease progression occurred in 21 patients at a median of 3 months (range 1.41-4.59). Eight patients (26%) experienced grade 3/4 adverse events, including anemia, neutropenia, muscle weakness and pneumonia. No patient experienced worsening peripheral neuropathy. Although RVD has been previously shown to be effective in RRMM, the ORR and PFS we observed were affected by very advanced disease status and heavy prior exposure to novel agents. Nevertheless, six of these patients with RRMM experienced a benefit of ≥ 6 months, suggesting synergism of this immunomodulatory derivative/proteasome inhibitor combination and/or re-establishment of drug sensitivity by an emergent myeloma clone.

  6. 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 ...

  7. 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 ...

  8. 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 ...

  9. 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 ...

  10. 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 ...

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

    Science.gov (United States)

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

    2007-12-01

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

  12. Interferon-γ-induced upregulation of immunoproteasome subunit assembly overcomes bortezomib resistance in human hematological cell lines.

    Science.gov (United States)

    Niewerth, Denise; Kaspers, Gertjan J L; Assaraf, Yehuda G; van Meerloo, Johan; Kirk, Christopher J; Anderl, Janet; Blank, Jonathan L; van de Ven, Peter M; Zweegman, Sonja; Jansen, Gerrit; Cloos, Jacqueline

    2014-01-13

    Despite encouraging results with the proteasome inhibitor bortezomib in the treatment of hematologic malignancies, emergence of resistance can limit its efficacy, hence calling for novel strategies to overcome bortezomib-resistance. We previously showed that bortezomib-resistant human leukemia cell lines expressed significantly lower levels of immunoproteasome at the expense of constitutive proteasomes, which harbored point mutations in exon 2 of the PSMB5 gene encoding the β5 subunit. Here we investigated whether up-regulation of immunoproteasomes by exposure to interferon-γ restores sensitivity to bortezomib in myeloma and leukemia cell lines with acquired resistance to bortezomib. RPMI-8226 myeloma, THP1 monocytic/macrophage and CCRF-CEM (T) parental cells and sub lines with acquired resistance to bortezomib were exposed to Interferon-γ for 24-48 h where after the effects on proteasome subunit expression and activity were measured, next to sensitivity measurements to proteasome inhibitors bortezomib, carfilzomib, and the immunoproteasome selective inhibitor ONX 0914. At last, siRNA knockdown experiments of β5i and β1i were performed to identify the contribution of these subunits to sensitivity to proteasome inhibition. Statistical significance of the differences were determined using the Mann-Whitney U test. Interferon-γ exposure markedly increased immunoproteasome subunit mRNA to a significantly higher level in bortezomib-resistant cells (up to 30-fold, 10-fold, and 6-fold, in β1i, β5i, and β2i, respectively) than in parental cells. These increases were paralleled by elevated immunoproteasome protein levels and catalytic activity, as well as HLA class-I. Moreover, interferon-γ exposure reinforced sensitization of bortezomib-resistant tumor cells to bortezomib and carfilzomib, but most prominently to ONX 0914, as confirmed by cell growth inhibition studies, proteasome inhibitor-induced apoptosis, activation of PARP cleavage and accumulation of

  13. 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.

  14. 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.

  15. Partial remission of acute myeloid leukemia complicating multiple myeloma following COAP chemotherapy: A case report.

    Science.gov (United States)

    Shen, Man; Sun, Wan-Jun; Huang, Zhong-Xia; Zhang, Jia-Jia; An, Na; Li, Xin

    2015-03-01

    A 77-year-old male was admitted to hospital after complaining of fever and a cough for three days. A diagnosis of multiple myeloma was confirmed following M protein identification and a bone marrow biopsy. The patient received chemotherapy regimens of bortezomib plus dexamethasone, cyclophosphamide, thalidomide and dexamethasone, and thalidomide and dexamethasone, and was prescribed thalidomide (100 mg/d) to be taken orally for maintenance therapy. After a further two years the patient was subsequently diagnosed with acute myeloid leukemia. Chemotherapy regimens of cytarabine, aclacinomycin and daunorubicin, homoharringtonine and etoposide, and mitoxantrone and cytarabine resulted in no remission. Partial remission was obtained with a course of ifosfamide, vindesine, cytarabine and prednisone chemotherapy. This therapy may be an alternative treatment for secondary leukemia, particularly in elderly patients.

  16. Acute emesis: moderately emetogenic chemotherapy

    DEFF Research Database (Denmark)

    Herrstedt, Jørn; Rapoport, Bernardo; Warr, David

    2011-01-01

    This paper is a review of the recommendations for the prophylaxis of acute emesis induced by moderately emetogenic chemotherapy as concluded at the third Perugia Consensus Conference, which took place in June 2009. The review will focus on new studies appearing since the Second consensus conference...... receiving multiple cycles of moderately emetogenic chemotherapy will be reviewed. Consensus statements are given, including optimal dose and schedule of serotonin(3) receptor antagonists, dexamethasone, and neurokinin(1) receptor antagonists. The most significant recommendations (and changes since the 2004...... version of the guidelines) are as follows: the best prophylaxis in patients receiving moderately emetogenic chemotherapy (not including a combination of an anthracycline plus cyclophosphamide) is the combination of palonosetron and dexamethasone on the day of chemotherapy, followed by dexamethasone...

  17. A Bim-targeting strategy overcomes adaptive bortezomib resistance in myeloma through a novel link between autophagy and apoptosis.

    Science.gov (United States)

    Chen, Shuang; Zhang, Yu; Zhou, Liang; Leng, Yun; Lin, Hui; Kmieciak, Maciej; Pei, Xin-Yan; Jones, Richard; Orlowski, Robert Z; Dai, Yun; Grant, Steven

    2014-10-23

    Bim contributes to resistance to various standard and novel agents. Here we demonstrate that Bim plays a functional role in bortezomib resistance in multiple myeloma (MM) cells and that targeting Bim by combining histone deacetylase inhibitors (HDACIs) with BH3 mimetics (eg, ABT-737) overcomes bortezomib resistance. BH3-only protein profiling revealed high Bim levels (Bim(hi)) in most MM cell lines and primary CD138(+) MM samples. Whereas short hairpin RNA Bim knockdown conferred bortezomib resistance in Bim(hi) cells, adaptive bortezomib-resistant cells displayed marked Bim downregulation. HDACI upregulated Bim and, when combined with ABT-737, which released Bim from Bcl-2/Bcl-xL, potently killed bortezomib-resistant cells. These events were correlated with Bim-associated autophagy attenuation, whereas Bim knockdown sharply increased autophagy in Bim(hi) cells. In Bim(low) cells, autophagy disruption by chloroquine (CQ) was required for HDACI/ABT-737 to induce Bim expression and lethality. CQ also further enhanced HDACI/ABT-737 lethality in bortezomib-resistant cells. Finally, HDACI failed to diminish autophagy or potentiate ABT-737-induced apoptosis in bim(-/-) mouse embryonic fibroblasts. Thus, Bim deficiency represents a novel mechanism of adaptive bortezomib resistance in MM cells, and Bim-targeting strategies combining HDACIs (which upregulate Bim) and BH3 mimetics (which unleash Bim from antiapoptotic proteins) overcomes such resistance, in part by disabling cytoprotective autophagy.

  18. Bendamustine, bortezomib and prednisone for the treatment of patients with newly diagnosed multiple myeloma: results of a prospective phase 2 Spanish/PETHEMA trial

    Science.gov (United States)

    Mateos, María-Victoria; Oriol, Albert; Rosiñol, Laura; de Arriba, Felipe; Puig, Noemí; Martín, Jesús; Martínez-López, Joaquín; Echeveste, María Asunción; Sarrá, Josep; Ocio, Enrique; Ramírez, Gemma; Martínez, Rafael; Palomera, Luis; Payer, Angel; Iglesias, Rebeca; de la Rubia, Javier; Alegre, Adrian; Chinea, Ana Isabel; Bladé, Joan; Lahuerta, Juan José; Miguel, Jesús-F. San

    2015-01-01

    Bendamustine is a bifunctional alkylating agent with proven activity in myeloma. In this study 60 newly diagnosed myeloma patients were given bendamustine plus bortezomib and prednisone in a regimen consisting of one cycle of bortezomib twice weekly for 6 weeks (1.3 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32), plus bendamustine (90 mg/m2 on days 1 and 4) and prednisone. The following cycles included bortezomib once weekly. Patients who were transplant candidates proceeded to stem cell collection after four cycles and the transplant was performed after six cycles. Patients who were not candidates for transplantation received up to nine cycles. Forty-two patients were transplant candidates and after six cycles, 50% achieved at least a very good partial response, with 24% having complete responses; 35 proceeded to a transplant, and the complete response rate was 54%. Seventeen patients continued up to nine cycles, and 57% achieved at least a very good partial response, including 26% with complete responses. The 2-year progression-free survival and overall survival rates were 62% and 86%, respectively. The safety profile was manageable, but stem cell mobilization was compromised in 35% of patients. In summary, this combination is effective in untreated patients, with an acceptable toxicity profile, but given the introduction of second-generation novel agents and monoclonal antibodies, the combination will probably be better reserved for relapsing patients, in whom stem cell collection is not needed, while cost-effective combinations with non-cross-resistant drugs continue to represent a medical need. This trial was registered with ClinicalTrials.gov, number NCT01376401. PMID:25911554

  19. Preferential cytotoxicity of bortezomib toward highly malignant human liposarcoma cells via suppression of MDR1 expression and function

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Yamei; Wang, Lingxian; Wang, Lu; Wu, Xuefeng; Wu, Xudong [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Gu, Yanhong; Shu, Yongqian [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Sun, Yang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Shen, Yan, E-mail: shenyan@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

    2015-02-15

    Liposarcoma is the most common soft tissue sarcoma with a high risk of relapse. Few therapeutic options are available for the aggressive local or metastatic disease. Here, we report that the clinically used proteasome inhibitor bortezomib exhibits significantly stronger cytotoxicity toward highly malignant human liposarcoma SW872-S cells compared with its parental SW872 cells, which is accompanied by enhanced activation of apoptotic signaling both in vitro and in vivo. Treatment of cells with Jun-N-terminal kinase (JNK) inhibitor SP60015 or the translation inhibitor cycloheximide ameliorated this enhanced apoptosis. Bortezomib inhibited MDR1 expression and function more effectively in SW872-S cells than in SW872 cells, indicating that the increased cytotoxicity relies on the degree of proteasome inhibition. Furthermore, the pharmacological or genetic inhibition of sarco/endoplasmic reticulum calcium-ATPase (SERCA) 2, which is highly expressed in SW872-S cells, resulted in partial reversal of cell growth inhibition and increase of MDR1 expression in bortezomib-treated SW872-S cells. These results show that bortezomib exhibits preferential cytotoxicity toward SW872-S cells possibly via highly expressed SERCA2-associated MDR1 suppression and suggest that bortezomib may serve as a potent agent for treating advanced liposarcoma. - Highlights: • We compare the cytotoxicity of different drugs between SW872-S and SW872 cells. • Highly malignant liposarcoma cells SW872-S show hypersensitivity to bortezomib. • Apoptotic signaling is robustly enhanced in bortezomib-treated SW872-S cells. • Bortezomib has strong suppression on MDR1 expression and function in SW872-S cells. • Inhibition of SERCA2 protects SW872-S cells from bortezomib.

  20. The Effect of Neoadjuvant Chemotherapy Compared to Adjuvant Chemotherapy in Healing after Nipple-Sparing Mastectomy.

    Science.gov (United States)

    Frey, Jordan D; Choi, Mihye; Karp, Nolan S

    2017-01-01

    Nipple-sparing mastectomy is the latest advancement in the treatment of breast cancer. The authors aimed to investigate the effects of neoadjuvant and adjuvant chemotherapy in nipple-sparing mastectomy. Patients undergoing nipple-sparing mastectomy from 2006 to June of 2015 were identified. Results were stratified by presence of neoadjuvant or adjuvant chemotherapy. A total of 840 nipple-sparing mastectomies were performed. Twenty-eight were in those who received neoadjuvant chemotherapy and 93 were in patients receiving adjuvant chemotherapy. Patients receiving both neoadjuvant and adjuvant chemotherapy were included in the neoadjuvant group. Nipple-sparing mastectomies that received neoadjuvant (with or without adjuvant) chemotherapy were compared to those in patients who received adjuvant chemotherapy. Those with neoadjuvant (with or without adjuvant) chemotherapy were more likely to have explantation (p = 0.0239) and complete nipple-areola complex necrosis (p = 0.0021). Those with neoadjuvant (with or without adjuvant) chemotherapy were more likely to have implant explantation (p = 0.0015) and complete nipple-areola complex necrosis (p = 0.0004) compared to those with no chemotherapy. Compared to nipple-sparing mastectomies in patients with no chemotherapy, those with adjuvant chemotherapy were more likely to have a hematoma (p = 0.0021). Those that received both neoadjuvant and adjuvant chemotherapy were more likely to have complete nipple-areola complex necrosis compared with both the neoadjuvant chemotherapy-only and adjuvant chemotherapy-only groups (p < 0.0001). Nipple-sparing mastectomy is safe to perform in the setting of neoadjuvant and adjuvant chemotherapy. As a whole, neoadjuvant (with or without adjuvant) chemotherapy increases risk of complications. Therapeutic, III.

  1. [Severe bortezomib-induced peripheral neuropathy in a patient with multiple myeloma].

    Science.gov (United States)

    Sanada, Yukinari; Nakazato, Tomonori; Suzuki, Kazuhito; Mihara, Ai; Aisa, Yoshinobu; Iwabuchi, Michio; Kakimoto, Tsunayuki

    2010-04-01

    A 59-year-old man was diagnosed with IgA-kappa multiple myeloma in October 2005. He was treated with 4 courses of VAD and autologous peripheral blood stem cell transplantation (auto-PBSCT) after 200 mg/m(2) melphalan in September 2006, followed by a second auto-PBSCT after 200 mg/m(2) melphalan in February 2007. However, he did not achieve a very good partial response (VGPR). Laboratory examinations showed increased serum IgA level and renal dysfunction gradually progressed. Bortezomib was then started at a dose of 1.3 mg/m(2) in November 2008. After three cycles of bortezomib, the patient developed numbness, pain and weakness of his upper and lower extremities. The sensation of position and vibration was diminished in the fingers and toes. He developed left foot drop and gait disturbance due to left peroneal nerve palsy. Autonomic dysfunction such as orthostatic hypotension and urinary retention also occurred. Nerve conduction studies showed severe sensorimotor polyneuropathy particularly in the lower extremities. He developed grade 4 motor neuropathy and severe painful neuralgia. Six months after the cessation of bortezomib, these symptoms gradually improved and he was able to walk with support and discharged. Close monitoring of neurological symptoms and prompt dose-reduction or cessation of bortezomib are important to prevent the progression of irreversible peripheral neuropathy.

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

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    Salzer Shanta

    2007-12-01

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

  3. Thrombotic microangiopathy associated with bortezomib treatment in a patient with relapsed multiple myeloma

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    Urpu Salmenniemi

    2012-06-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP and hemolytic-uremic syndrome (HUS describe microvascular occlusive disorders characterized by thrombocytopenia due to increased platelet aggregation and fragmentation hemolysis. We report here what to our knowledge is the second case of TTP/HUS associated with bortezomib treatment.

  4. Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients

    DEFF Research Database (Denmark)

    Morabito, Fortunato; Bringhen, Sara; Larocca, Alessandra

    2014-01-01

    Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty...

  5. Data for a proteomic analysis of p53-independent induction of apoptosis by bortezomib

    Science.gov (United States)

    Yerlikaya, Azmi; Okur, Emrah; Tarık Baykal, Ahmet; Acılan, Ceyda; Boyacı, İhsan; Ulukaya, Engin

    2014-01-01

    This data article contains data related to the research article entitled, “A proteomic analysis of p53-independent induction of apoptosis by bortezomib in 4T1 breast cancer cell line” by Yerlikaya et al. [1]. The research article presented 2-DE and nLC-MS/MS based proteomic analysis of proteasome inhibitor bortezomib-induced changes in the expression of cellular proteins. The report showed that GRP78 and TCEB2 were over-expressed in response to treatment with bortezomib for 24 h. In addition, the report demonstrated that Hsp70, the 26S proteasome non-ATPase regulatory subunit 14 and sequestosome 1 were increased at least 2 fold in p53-deficient 4T1 cells. The data here show for the first time the increased expressions of Card10, Dffb, Traf3 and Trp53bp2 in response to inhibition of the 26S proteasome. The information presented here also shows that both Traf1 and Xiap (a member of IAPs) are also downregulated simultaneously upon proteasomal inhibition. The increases in the level of Card10 and Trp53bp2 proteins were verified by Western blot analysis in response to varying concentrations of bortezomib for 24 h. PMID:26217687

  6. Data for a proteomic analysis of p53-independent induction of apoptosis by bortezomib

    Directory of Open Access Journals (Sweden)

    Azmi Yerlikaya

    2014-12-01

    Full Text Available This data article contains data related to the research article entitled, “A proteomic analysis of p53-independent induction of apoptosis by bortezomib in 4T1 breast cancer cell line” by Yerlikaya et al. [1]. The research article presented 2-DE and nLC-MS/MS based proteomic analysis of proteasome inhibitor bortezomib-induced changes in the expression of cellular proteins. The report showed that GRP78 and TCEB2 were over-expressed in response to treatment with bortezomib for 24 h. In addition, the report demonstrated that Hsp70, the 26S proteasome non-ATPase regulatory subunit 14 and sequestosome 1 were increased at least 2 fold in p53-deficient 4T1 cells. The data here show for the first time the increased expressions of Card10, Dffb, Traf3 and Trp53bp2 in response to inhibition of the 26S proteasome. The information presented here also shows that both Traf1 and Xiap (a member of IAPs are also downregulated simultaneously upon proteasomal inhibition. The increases in the level of Card10 and Trp53bp2 proteins were verified by Western blot analysis in response to varying concentrations of bortezomib for 24 h.

  7. Synergistic Effect and Molecular Mechanism of Homoharringtonine and Bortezomib on SKM-1 Cell Apoptosis.

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    Jing Zhang

    Full Text Available Myelodysplastic syndromes (MDS are clonal marrow stem-cell disorders with a high risk of progression to acute myeloid leukemia (AML. Treatment options are limited and targeted therapies are not available for MDS. In the present study, we investigated the cytotoxicity and the molecular mechanism of Homoharringtonine (HHT and Bortezomib towards high-risk MDS cell line SKM-1 in vitro and the role of miR-3151 was first evaluated in SKM-1 cells.SKM-1 cells were treated with different concentrations of HHT or Bortezomib, and cell viability was analyzed with CCK-8 assay. The influence on cell proliferation, cell cycle distribution and the percentage of apoptosis cells were analyzed by flow cytometry. Calcusyn software was used to calculate combination index (CI values. Western blot was used to analysis phosphorylation of Akt and nuclear NF-κB protein expression in SKM-1 cells. Mature miR-3151 level and p53 protein level were detected after HHT or Bortezomib treatment. The cell proliferation and p53 protein level were reassessed in SKM-1 cells infected with lentivirus to overexpress miR-3151.Simultaneous exposure to HHT and Bortezomib (10.4:1 resulted in a significant reduction of cell proliferation in SKM-1 cells (P < 0.05. Cell cycle arrest at G0/G1 and G2/M phase was observed (P < 0.05. HHT and Bortezomib synergistically induced cell apoptosis by regulating members of caspase 9, caspase 3 and Bcl-2 family (P < 0.01. The mechanisms of the synergy involved Akt and NF-κB signaling pathway inhibition, downregulation of mature miR-3151 and increment of downstream p53 protein level. Overexpression of miR-3151 promoted cell proliferation and inhibited p53 protein expression in SKM-1 (P < 0.01.HHT and Bortezomib synergistically inhibit SKM-1 cell proliferation and induce apoptosis in vitro. Inhibition of Akt and NF-κB pathway signaling contribute to molecular mechanism of HHT and Bortezomib. miR-3151 abundance is implicated in SKM-1 cell viability, cell

  8. 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.

  9. Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study

    Science.gov (United States)

    Campbell, Toby C.; Zhang, Chong; Kim, KyungMann; Kolesar, Jill M.; Oettel, Kurt R.; Blank, Jules H.; Robinson, Emily G.; Ahuja, Harish G.; Kirschling, Ron J.; Johnson, Peter H.; Huie, Michael S.; Wims, Mary E.; Larson, Martha M.; Hernan, Hilary R.; Traynor, Anne M.

    2014-01-01

    Summary Introduction The primary objective of this phase II trial was to evaluate the efficacy and tolerability of vorinostat and bortezomib as third-line therapy in advanced non-small cell lung cancer (NSCLC) patients. Methods Eligibility criteria included recurrent/metastatic NSCLC, having received 2 prior systemic regimens, and performance status 0–2. Patients took vorinostat 400 mg PO daily days 1–14 and bortezomib 1.3 mg/m2 IV day 1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS), with a goal of at least 40 % of patients being free of progression at that time point. This study followed a two-stage minimax design. Results Eighteen patients were enrolled in the first stage. All patients had two prior lines of treatment. Patients received a median of two treatment cycles (range: 1–6) on study. There were no anti-tumor responses; stable disease was observed in 5 patients (27.8 %). Median PFS was 1.5 months, 3m-PFS rate 11.1 %, and median overall survival 4.7 months. The most common grade 3/4 toxicities were thrombocytopenia and fatigue. Two patients who had baseline taxane-related grade 1 peripheral neuropathy developed grade 3 neuropathy. The study was closed at its first interim analysis for lack of efficacy. Conclusions Bortezomib and vorinostat displayed minimal anti-tumor activity as third-line therapy in NSCLC. We do not recommend this regimen for further investigation in unselected patients. PMID:23728919

  10. Pre-clinical efficacy of PU-H71, a novel HSP90 inhibitor, alone and in combination with bortezomib in Ewing sarcoma.

    Science.gov (United States)

    Ambati, Srikanth R; Lopes, Eloisi Caldas; Kosugi, Kohji; Mony, Ullas; Zehir, Ahmet; Shah, Smit K; Taldone, Tony; Moreira, Andre L; Meyers, Paul A; Chiosis, Gabriela; Moore, Malcolm A S

    2014-03-01

    Ewing sarcoma is characterized by multiple deregulated pathways that mediate cell survival and proliferation. Heat shock protein 90 (HSP90) is a critical component of the multi-chaperone complexes that regulate the disposition and activity of a large number of proteins involved in cell-signaling systems. We tested the efficacy of PU-H71, a novel HSP90 inhibitor in Ewing sarcoma cell lines, primary samples, benign mesenchymal stromal cells and hematopoietic stem cells. We performed cell cycle analysis, clonogenic assay, immunoblot analysis and reverse phase protein array in Ewing cell lines and in vivo experiments in NSG and nude mice using the A673 cell line. We noted a significant therapeutic window in the activity of PU-H71 against Ewing cell lines and benign cells. PU-H71 treatment resulted in G2/M phase arrest. Exposure to PU-H71 resulted in depletion of critical proteins including AKT, pERK, RAF-1, c-MYC, c-KIT, IGF1R, hTERT and EWS-FLI1 in Ewing cell lines. Our results indicated that Ewing sarcoma tumor growth and the metastatic burden were significantly reduced in the mice injected with PU-H71 compared to the control mice. We also investigated the effects of bortezomib, a proteasome inhibitor, alone and in combination with PU-H71 in Ewing sarcoma. Combination index (CI)-Fa plots and normalized isobolograms indicated synergism between PU-H71 and bortezomib. Ewing sarcoma xenografts were significantly inhibited when mice were treated with the combination compared to vehicle or either drug alone. This provides a strong rationale for clinical evaluation of PU-H71 alone and in combination with bortezomib in Ewing sarcoma.

  11. Glycogen Synthase Kinase-3 regulates multiple myeloma cell growth and bortezomib-induced cell death

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    Colpo Anna

    2010-10-01

    Full Text Available Abstract Background Glycogen Synthase Kinase-3 (GSK-3 α and β are two serine-threonine kinases controlling insulin, Wnt/β-catenin, NF-κB signaling and other cancer-associated transduction pathways. Recent evidence suggests that GSK-3 could function as growth-promoting kinases, especially in malignant cells. In this study, we have investigated GSK-3α and GSK-3β function in multiple myeloma (MM. Methods GSK-3 α and β expression and cellular localization were investigated by Western blot (WB and immunofluorescence analysis in a panel of MM cell lines and in freshly isolated plasma cells from patients. MM cell growth, viability and sensitivity to bortezomib was assessed upon treatment with GSK-3 specific inhibitors or transfection with siRNAs against GSK-3 α and β isoforms. Survival signaling pathways were studied with WB analysis. Results GSK-3α and GSK-3β were differently expressed and phosphorylated in MM cells. Inhibition of GSK-3 with the ATP-competitive, small chemical compounds SB216763 and SB415286 caused MM cell growth arrest and apoptosis through the activation of the intrinsic pathway. Importantly, the two inhibitors augmented the bortezomib-induced MM cell cytotoxicity. RNA interference experiments showed that the two GSK-3 isoforms have distinct roles: GSK-3β knock down decreased MM cell viability, while GSK-3α knock down was associated with a higher rate of bortezomib-induced cytotoxicity. GSK-3 inhibition caused accumulation of β-catenin and nuclear phospho-ERK1, 2. Moreover, GSK-3 inhibition and GSK-3α knockdown enhanced bortezomib-induced AKT and MCL-1 protein degradation. Interestingly, bortezomib caused a reduction of GSK-3 serine phosphorylation and its nuclear accumulation with a mechanism that resulted partly dependent on GSK-3 itself. Conclusions These data suggest that in MM cells GSK-3α and β i play distinct roles in cell survival and ii modulate the sensitivity to proteasome inhibitors.

  12. Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Non-Hybrid “(Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms

    Science.gov (United States)

    Holkova, Beata; Kmieciak, Maciej; Perkins, E. Brent; Bose, Prithviraj; Baz, Rachid C.; Roodman, G. David; Stuart, Robert K.; Ramakrishnan, Viswanathan; Wan, Wen; Peer, Cody J; Dawson, Jana; Kang, Loveleen; Honeycutt, Connie; Tombes, Mary Beth; Shrader, Ellen; Weir-Wiggins, Caryn; Wellons, Martha; Sankala, Heidi; Hogan, Kevin T.; Colevas, A. Dimitrios; Doyle, L. Austin; Figg, William D.; Coppola, Domenico; Roberts, John D.; Sullivan, Daniel; Grant, Steven

    2014-01-01

    Purpose This phase I study was conducted to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma [MM], indolent lymphoma, Waldenstrom's macroglobulinemia, and mantle cell lymphoma). Experimental Design Patients received bortezomib (intravenous push), followed by alvocidib (1-hour infusion), on days 1, 4, 8, and 11 of a 21-day treatment cycle. Patients experiencing responses or stable disease continued on treatment at the investigator's discretion. A standard 3+3 dose-escalation design was used to identify the MTD based on DLTs, and pharmacokinetic and pharmacodynamic studies were conducted. Results A total of 44 patients were enrolled, with 39 patients assessed for response. The MTD was established as 1.3 mg/m2 for bortezomib and 40 mg/m2 for alvocidib. The most common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common non-hematologic toxicities included diarrhea, fatigue, and sensory neuropathy. Three complete remissions (8%) and 10 partial remissions (26%) were observed for a total response rate of 33%. Pharmacokinetic findings with the current dosing regimen were consistent with the comparable literature and the hybrid dosing regimen. Pharmacodynamic study results did not correlate with clinical responses. Conclusions The combination of bortezomib and alvocidib is tolerable and an MTD has been established for this schedule. The regimen appears to be efficacious in patients with relapsed/refractory MM or indolent non-Hodgkin's lymphoma. As the non-hybrid regimen is less cumbersome than the previous hybrid dosing schedule regimen, the current schedule is recommended for successor studies. PMID:25248382

  13. Curative effect observation of patients with primary systemic amyloidosis treated by the combination of bortezomib with dexmethasone and cyclophosphamide

    Institute of Scientific and Technical Information of China (English)

    路瑾

    2013-01-01

    Objective To analyze the efficacy and side effects of the combination regimen containing bortezomib,cyclophosphamide and dexamethasone(BCD)in the treatment of primary systemic amyloidosis(PSA).Methods

  14. miR-122 regulates p53/Akt signalling and the chemotherapy-induced apoptosis in cutaneous T-cell lymphoma.

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    Valentina Manfè

    Full Text Available Advanced cutaneous T-cell lymphoma (CTCL is resistant to chemotherapy and presents a major area of medical need. In view of the known role of microRNAs (miRNAs in the regulation of cellular signalling, we aimed to identify the functionally important miRNA species, which regulate apoptosis in CTCL. Using a recently established model in which apoptosis of CTCL cell lines is induced by Notch-1 inhibition by γ-secretase inhibitors (GSIs, we found that miR-122 was significantly increased in the apoptotic cells. miR-122 up-regulation was not specific for GSI-1 but was also seen during apoptosis induced by chemotherapies including doxorubicin and proteasome blockers (bortezomib, MG132. miR-122 was not expressed in quiescent T-cells, but was detectable in CTCL: in lesional skin in mycosis fungoides and in Sézary cells purified from peripheral blood. In situ hybridization results showed that miR-122 was expressed in the malignant T-cell infiltrate and increased in the advanced stage mycosis fungoides. Surprisingly, miR-122 overexpression decreased the sensitivity to the chemotherapy-induced apoptosis via a signaling circuit involving the activation of Akt and inhibition of p53. We have also shown that induction of miR-122 occurred via p53 and that p53 post-transcriptionally up-regulated miR-122. miR-122 is thus an amplifier of the antiapoptotic Akt/p53 circuit and it is conceivable that a pharmacological intervention in this pathway may provide basis for novel therapies for CTCL.

  15. miR-122 Regulates p53/Akt Signalling and the Chemotherapy-Induced Apoptosis in Cutaneous T-Cell Lymphoma

    Science.gov (United States)

    Manfè, Valentina; Biskup, Edyta; Rosbjerg, Anne; Kamstrup, Maria; Skov, Anne Guldhammer; Lerche, Catharina Margrethe; Lauenborg, Britt Thyssing; Ødum, Niels; Gniadecki, Robert

    2012-01-01

    Advanced cutaneous T-cell lymphoma (CTCL) is resistant to chemotherapy and presents a major area of medical need. In view of the known role of microRNAs (miRNAs) in the regulation of cellular signalling, we aimed to identify the functionally important miRNA species, which regulate apoptosis in CTCL. Using a recently established model in which apoptosis of CTCL cell lines is induced by Notch-1 inhibition by γ-secretase inhibitors (GSIs), we found that miR-122 was significantly increased in the apoptotic cells. miR-122 up-regulation was not specific for GSI-1 but was also seen during apoptosis induced by chemotherapies including doxorubicin and proteasome blockers (bortezomib, MG132). miR-122 was not expressed in quiescent T-cells, but was detectable in CTCL: in lesional skin in mycosis fungoides and in Sézary cells purified from peripheral blood. In situ hybridization results showed that miR-122 was expressed in the malignant T-cell infiltrate and increased in the advanced stage mycosis fungoides. Surprisingly, miR-122 overexpression decreased the sensitivity to the chemotherapy-induced apoptosis via a signaling circuit involving the activation of Akt and inhibition of p53. We have also shown that induction of miR-122 occurred via p53 and that p53 post-transcriptionally up-regulated miR-122. miR-122 is thus an amplifier of the antiapoptotic Akt/p53 circuit and it is conceivable that a pharmacological intervention in this pathway may provide basis for novel therapies for CTCL. PMID:22235305

  16. Hepatitis C-Induced Hepatitis Flare in a Patient with Non-Hodgkin B-Cell Lymphoma Treated by Rituximab Including Chemotherapy (Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin - Vincristine, Prednisolone Regimen

    Directory of Open Access Journals (Sweden)

    Asim Ulcay

    2014-06-01

    Full Text Available Hepatitis virus infections can lead to more critical outcomes such as severe hepatic dysfunction, failure and fulminancy in immunosuppressive patients compared to immunocompetent individuals. It is globally accepted that reactivation of both Hepatitis B virus [HBV ] and Hepatitis C virus [HCV] occurs after chemotherapy and antibody treatments of malignant diseases or solid organ/ bone marrow transplant in recipient patients. Especially among B-cell Non Hodgkin Lymphoma [NHL] patients, according to various studies, the seroprevelance of HCV is higher than that of the general population. On the other hand the role of HCV in the pathogenesis and etiology of NHL has been suggested. Today, cytotoxic drugs, corticosteroids, rituximab and hepatotoxic regimens are administered to NHL patients. Specifically, it has been emphasized that the utilization of rituximab [Anti CD20 antibody ] regiments for B-cell NHL patients may result with flares in HCV patients conspicuously. Here, we report the case of an acute flare up due to HCV infection in a patient who underwent a 4 month course of rituximab containing chemotherapy against a B cell NHL [CD20+ ] disease and a dramatic recovery from HCV infection at the end. [Dis Mol Med 2014; 2(3.000: 51-54

  17. Pilot study of Bortezomib for Patients with Imatinib-Refractory Chronic Myeloid Leukemia in Chronic or Accelerated Phase

    Science.gov (United States)

    Santos, Fabio P S; Kantarjian, Hagop; McConkey, David; O'Brien, Susan; Faderl, Stefan; Borthakur, Gautam; Ferrajoli, Alessandra; Wright, John; Cortes, Jorge

    2015-01-01

    Background Proteasome inhibitors are anticancer compounds that disrupt the proteolytic activity of the proteasome and lead to tumor cell growth arrest and apoptosis. Bortezomib is a proteasome inhibitor that is currently approved for use in multiple myeloma and mantle cell lymphoma. It induces apoptosis of chronic myeloid leukemia (CML) cells in vitro, but the activity of bortezomib in patients with imatinib-resistant CML is unknown. Methods We conducted a pilot trial to evaluate the activity of single agent bortezomib in CML. Seven patients with imatinib-refractory CML were treated with bortezomib at a dose of 1.5 mg/m2 on days 1, 4, 8 and 11 every 3 weeks. Results The median number of cycles received was 2. No patient had a hematologic or cytogenetic response. Three patients had a temporary decrease in basophil counts associated with therapy with bortezomib. Six patients developed grade 3-4 nonhematological toxicities. Conclusion Bortezomib had minimal efficacy and considerable toxicity in patients with imatinib-refractory CML. Further studies should focus on alternative approaches to employ proteasome inhibitors in the treatment of CML, such as in combination with tyrosine kinase inhibitors or as a strategy to eradicate leukemic stem cells. PMID:21816374

  18. Atg3 Overexpression Enhances Bortezomib-Induced Cell Death in SKM-1 Cell.

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    Lin Zhuang

    Full Text Available Myelodysplastic syndrome (MDS is a group of heterogeneous hematopoietic stem cell malignancies with a high risk of transformation into acute myeloid leukemia (AML. Clonal evolutions are significantly associated with transformation to AML. According to a gene expression microarray, atg3 is downregulated in MDS patients progressing to leukemia, but less is known about the function of Atg3 in the survival and death of MSD/AML cells. Moreover, the role of autophagy as a result of bortezomib treatment is controversial. The current study was designed to investigate the function of Atg3 in SKM-1 cells and to study the effect of Atg3 on cell viability and cell death following bortezomib treatment.Four leukemia cell lines (SKM-1, THP-1, NB4 and K562 and two healthy patients' bone marrow cells were analyzed for Atg3 expression via qRT-PCR and Western blotting analysis. The role of Atg3 in SKM-1 cell survival and cell death was analyzed by CCK-8 assay, trypan blue exclusion assay, DAPI staining and Annexin V/PI dual staining with or without bortezomib treatment. Western blotting analysis was used to detect proteins in autophagic and caspase signaling pathways. Electron microscopy was used to observe ultrastructural changes after Atg3 overexpression.Downregulation of Atg3 expression was detected in four leukemia cell lines compared with healthy bone marrow cells. Atg3 mRNA was significantly decreased in MDS patients' bone marrow cells. Overexpression of Atg3 in SKM-1 cells resulted in AKT-mTOR-dependent autophagy, a significant reduction in cell proliferation and increased cell death, which could be overcome by the autophagy inhibitor 3-MA. SKM-1 cells overexpressing Atg3 were hypersensitive to bortezomib treatment at different concentrations via autophagic cell death and enhanced sensitivity to apoptosis in the SKM-1 cell line. Following treatment with 3-MA, the sensitivity of Atg3-overexpressing cells to bortezomib treatment was reduced. Atg3 knockdown

  19. Chemotherapy (For Parents)

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    ... Getting Involved Teaching Kids to Be Smart About Social Media Chemotherapy KidsHealth ... and Where Chemo Is Given Common Side Effects of Chemotherapy Common Side Effects (continued) Common Side ...

  20. 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.

  1. Chemotherapy Side Effects: A Cause of Heart Disease?

    Science.gov (United States)

    ... Can chemotherapy side effects increase the risk of heart disease? Answers from Timothy J. Moynihan, M.D. Chemotherapy side effects may increase the risk of heart disease, including weakening of the heart muscle (cardiomyopathy) and ...

  2. 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 ...

  3. Dorsal Column Degeneration after Bortezomib Therapy in a Patient with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Tatsuro Joh

    2009-10-01

    Full Text Available We present here a case of dorsal column degeneration in a female patient with multiple myeloma following exposure to bortezomib. Two days after intravenous administration of a first course of bortezomib 1 mg/m2, the patient developed rapidly-progressive numbness, pain and muscle weakness in the bilateral upper and lower limbs. Following gancyclovir treatment of subsequent cytomegalovirus viremia, the patient went on to receive a course of EPOCH (etoposide 50 mg/m2/day on days 1–4, vincristine 0.4 mg/m2/day on days 1–4, doxorubicin 10 mg/m2/day on days 1–4, cyclophosphamide 750 mg/m2/day on day 6, and prednisolone 60 mg/m2/day on days 1–6. Shortly thereafter, the patient developed bilateral Aspergillus pneumonia. Despite treatment with appropriate antifungal agents, the patient died from respiratory failure due to bilateral diffuse alveolar damage of the lungs and without recovery of severe sensory and motor neuropathy prior to her death. Post mortem examination revealed spongy degeneration of the dorsal column from the medulla oblongata to the cervical spinal cord. Bortezomib-associated peripheral neuropathy in patients with multiple myeloma has been commonly reported but appears to resolve in a majority of these patients after dose reduction or discontinuation. We believe this to be the first report of spinal cord abnormalities in a patient with multiple myeloma treated with bortezomib. Further investigation is required to ascertain the exact mechanism of this central neurotoxic effect and to identify appropriate neuroprotective strategies.

  4. A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib

    OpenAIRE

    2016-01-01

    Glucose-regulated protein 78 kDa/binding immunoglobulin protein (GRP78/BIP) is a well-known endoplasmic reticulum (ER) chaperone protein regulating ER stress by facilitating protein folding, assembly and Ca2+ binding. GRP78 is also a member of the heat shock protein 70 gene family and induces tumor cell survival and resistance to chemotherapeutics. Bortezomib is a highly specific 26S proteasome inhibitor that has been approved as treatment for patients with multiple myeloma. The present study...

  5. Management of Multiple Myeloma and Usage of Bortezomib: Perspective from India and Ukraine

    Directory of Open Access Journals (Sweden)

    India and Ukraine Haemato-oncology Group

    2016-11-01

    Full Text Available Novel treatment strategies have remarkably improved the multiple myeloma (MM patients’ survival, with associated increased costs.A joint panel meet of international experts from India and Ukraine was held in New Delhi on 19th May 2016 focusing on: MM management, bortezomib role, unmet medical needs, and current challenges.The healthcare system for oncology in India is majorly private versus government-based in Ukraine. In India, electrophoresis, serum-free light chain assays, bone marrow tests, and X-rays are available modes of diagnosis. Despite of the numerous cancer centers and stem cell transplant centers, most patients do not prefer transplant owing to its high-cost and social stigma. Majority of the patients are treated with bortezomib or lenalidomide-based regimens. Most patients buy drug themselves. The expanding generic drugs market is a ray of hope for the affordable drugs.In Ukraine, immuno-fixation, bone-marrow analysis, and magnetic-resonance-imaging are common diagnostic modalities. Due to high-cost, only few patients undergo transplant. Bortezomib-based regimens are preferred in most of the patients, however usage is limited due to high costs and lack of funds. Thalidomide-based regimens are used for maintenance therapy due to affordability. In case of relapsed MM, bortezomib is preferred in triple therapy, however more affordable option is cyclophosphamide, thalidomide, and dexamethasone (CTD. Issues such as cost containment, common treatment strategies, enhanced collaboration, and improved healthcare access need immediate attention. High-quality generics access will improve outcomes and support healthcare cost containment. Pharmacoeconomic studies and head-to-head trials are warranted to determine the cost-effectiveness and benefit of novel therapies in MM.

  6. [History of cancer and chemotherapy before chemotherapy].

    Science.gov (United States)

    Bonnichon, Philippe; Berger, J P; Bonni, N; Fontaine, M; Pion-Graff, J

    2014-01-01

    Chemotherapy stands today for cancer. In 1909, Paul Ehrlich (1854-1915) advocates the use of arsphenamine by infusion. So, he is considered as the father of chemotherapy. In fact, the first to have thought through chemotherapy was Sir Christopher Wren (1632-1723). In 1676, ideas and experiments on animals had sufficiently progressed to allow Michel Ettmuller (1644-1683) to publish the first edition of his book and several others were printed until 1753. In this book, he describes the first intravenous treatment, it sets the first indications, dosages and different products which can be used. However this method has been forgotten until the late 19th century.

  7. Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651.

    Science.gov (United States)

    Goorin, Allen M; Schwartzentruber, Douglas J; Devidas, Meenakshi; Gebhardt, Mark C; Ayala, Alberto G; Harris, Michael B; Helman, Lee J; Grier, Holcombe E; Link, Michael P

    2003-04-15

    Successful therapeutic interventions to prevent disease progression in patients with nonmetastatic osteosarcoma have included surgery with adjuvant chemotherapy. Presurgical chemotherapy has been advocated for these patients because of putative improvement in event-free survival (EFS). The advantages of presurgical chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups. The theoretic disadvantage is that it exposes a large tumor burden to marginally effective chemotherapy. The contribution of chemotherapy and surgery timing has not been tested rigorously. Between 1986 and 1993, we conducted a prospective trial in patients with nonmetastatic osteosarcoma who were assigned randomly to immediate surgery or presurgical chemotherapy. Except for the timing of surgery (week 0 or 10), patients received 44 weeks of identical combination chemotherapy that included high-dose methotrexate with leucovorin rescue, doxorubicin, cisplatin, bleomycin, cyclophosphamide, and dactinomycin. One hundred six patients were enrolled onto this study. Six were excluded from analysis. Of the remaining 100 patients, 45 were randomly assigned to immediate chemotherapy, and 55 were randomly assigned to immediate surgery. Sixty-seven patients remain disease-free. At 5 years, the projected EFS +/- SE is 65% +/- 6% (69% +/- 8% for immediate surgery and 61% +/- 8% for presurgical chemotherapy; P =.8). The treatment arms had similar incidence of limb salvage (55% for immediate surgery and 50% for presurgical chemotherapy). Chemotherapy was effective in both treatment groups. There was no advantage in EFS for patients given presurgical chemotherapy.

  8. Obesity Is an Independent Predictor of Poor Survival in Metastatic Breast Cancer: Retrospective Analysis of a Patient Cohort Whose Treatment Included High-Dose Chemotherapy and Autologous Stem Cell Support

    Directory of Open Access Journals (Sweden)

    A. von Drygalski

    2011-01-01

    Full Text Available The purpose of the study was to identify predictors of long-term survival in metastatic breast cancer (MBC. A cohort of 96 patients, who received high-dose chemotherapy with autologous stem cell support (HD-ASCT as part of their treatment, was analyzed. Percent long-term survival at 10 years was 24.5% (CI 17.2–34.9% when metastasis was diagnosed and 14.4% (CI 8.7–23.9% when MBC was diagnosed. Survival was impacted significantly by body mass index (BMI. Median overall survival from initial diagnosis or from time of metastasis for patients with BMIs ≤30 and >30 (obese was 7.1 (CI 4.4–8.7 and 3.2 years (2.41–6.75, respectively, or 3.2 or 2.3 years (all =0.02. Also, obesity was the only independent patient-related predictor of time to metastasis and of survival. While obesity is linked with poor outcomes in earlier stages of breast cancer, this has not been previously reported for MBC.

  9. [Chemotherapy-induced stomatitis and diarrhea].

    Science.gov (United States)

    Kadowaki, Shigenori; Yamaguchi, Kensei

    2011-11-01

    Chemotherapy-induced mucositis is a clinically important and sometimes dose-limiting toxicity of cancer treatment, including standard-dose chemotherapy, high-dose chemotherapy and chemoradiotherapy. Consequently, dose reductions or treatment delays resulting from mucositis may impair treatment effectiveness. Symptoms are oral mucositis, dysphagia, abdominal pain and diarrhea, depending on the affected site. Although the underlying pathobiology of oral mucositis has been considerably elucidated over the past decade, there are few interventions for the prevention or treatment validated by randomized trials. The most commonly accepted intervention is basic oral care. Diarrhea is most common in patients treated with irinotecan and in some cases, life-threatening. No definitive interventions for the prevention of diarrhea exist, but there is evidence that loperamide and octreotide are effective for chemotherapy-induced diarrhea. In future, there is a need for well designed trials, preferably including a placebo or no treatment control, validating more effective interventions for managing chemotherapy- induced mucositis.

  10. Profound activity of the anti-cancer drug bortezomib against Echinococcus multilocularis metacestodes identifies the proteasome as a novel drug target for cestodes.

    Directory of Open Access Journals (Sweden)

    Britta Stadelmann

    2014-12-01

    Full Text Available A library of 426 FDA-approved drugs was screened for in vitro activity against E. multilocularis metacestodes employing the phosphoglucose isomerase (PGI assay. Initial screening at 20 µM revealed that 7 drugs induced considerable metacestode damage, and further dose-response studies revealed that bortezomib (BTZ, a proteasome inhibitor developed for the chemotherapy of myeloma, displayed high anti-metacestodal activity with an EC50 of 0.6 µM. BTZ treatment of E. multilocularis metacestodes led to an accumulation of ubiquinated proteins and unequivocally parasite death. In-gel zymography assays using E. multilocularis extracts demonstrated BTZ-mediated inhibition of protease activity in a band of approximately 23 kDa, the same size at which the proteasome subunit beta 5 of E. multilocularis could be detected by Western blot. Balb/c mice experimentally infected with E. multilocularis metacestodes were used to assess BTZ treatment, starting at 6 weeks post-infection by intraperitoneal injection of BTZ. This treatment led to reduced parasite weight, but to a degree that was not statistically significant, and it induced adverse effects such as diarrhea and neurological symptoms. In conclusion, the proteasome was identified as a drug target in E. multilocularis metacestodes that can be efficiently inhibited by BTZ in vitro. However, translation of these findings into in vivo efficacy requires further adjustments of treatment regimens using BTZ, or possibly other proteasome inhibitors.

  11. Profound activity of the anti-cancer drug bortezomib against Echinococcus multilocularis metacestodes identifies the proteasome as a novel drug target for cestodes.

    Science.gov (United States)

    Stadelmann, Britta; Aeschbacher, Denise; Huber, Cristina; Spiliotis, Markus; Müller, Joachim; Hemphill, Andrew

    2014-12-01

    A library of 426 FDA-approved drugs was screened for in vitro activity against E. multilocularis metacestodes employing the phosphoglucose isomerase (PGI) assay. Initial screening at 20 µM revealed that 7 drugs induced considerable metacestode damage, and further dose-response studies revealed that bortezomib (BTZ), a proteasome inhibitor developed for the chemotherapy of myeloma, displayed high anti-metacestodal activity with an EC50 of 0.6 µM. BTZ treatment of E. multilocularis metacestodes led to an accumulation of ubiquinated proteins and unequivocally parasite death. In-gel zymography assays using E. multilocularis extracts demonstrated BTZ-mediated inhibition of protease activity in a band of approximately 23 kDa, the same size at which the proteasome subunit beta 5 of E. multilocularis could be detected by Western blot. Balb/c mice experimentally infected with E. multilocularis metacestodes were used to assess BTZ treatment, starting at 6 weeks post-infection by intraperitoneal injection of BTZ. This treatment led to reduced parasite weight, but to a degree that was not statistically significant, and it induced adverse effects such as diarrhea and neurological symptoms. In conclusion, the proteasome was identified as a drug target in E. multilocularis metacestodes that can be efficiently inhibited by BTZ in vitro. However, translation of these findings into in vivo efficacy requires further adjustments of treatment regimens using BTZ, or possibly other proteasome inhibitors.

  12. Bortezomib combined with lenalidomide as the first-line treatment for the rare synchronous occurrence of multiple myeloma and pulmonary adenocarcinoma

    Science.gov (United States)

    Zuo, Wenli; Zhu, Xinghu; Yang, Jingke; Mei, Zhenyang; Deng, Mei; Lin, Quande; Song, Yongping; Yin, Qingsong

    2017-01-01

    Abstract Background: Simultaneous multiple myeloma (MM) and pulmonary adenocarcinoma is a rare occurrence, and thus, treatment is a challenge. This study reports on 1 such case of MM with concurrent lung cancer, where an accurate diagnosis was made and the patient underwent treatment for both cancers. Case summary: A 68-year-old man presented with 2 months of progressive lower back pain. Visualization with magnetic resonance imaging (MRI) revealed multiple collapsed vertebrae from T12 to S3, as well as an altered signal intensity at the T3 vertebra. The patient was diagnosed with MM upon examination. A chest computed tomography (CT) scan revealed a round mass in the left lower lobe of the lungs, and a CT-guided needle biopsy uncovered a moderately differentiated adenocarcinoma. There were no additional notable findings in the left lung using positron emission tomography computed tomography (PET-CT). Therefore, a diagnosis of MM with pulmonary adenocarcinoma was made. Surgery was performed to excise the lung cancer. Bortezomib was used as first-line induction therapy against both tumors and lenalidomide was used for maintenance. The patient went into complete remission. Using this combined chemotherapy, the patient has survived for over 3 years since a diagnosis was made despite relapsing twice after the first year. Conclusion: This report clearly delineates the diagnosis and treatment of a rare case of synchronous MM and pulmonary adenocarcinoma, as well as depicts a potentially positive outcome for the patient. It also overviews some diagnostic and therapeutic implications for clinicians. PMID:28072730

  13. Curcumin and Its Analogue Induce Apoptosis in Leukemia Cells and Have Additive Effects with Bortezomib in Cellular and Xenograft Models

    Directory of Open Access Journals (Sweden)

    L. I. Nagy

    2015-01-01

    Full Text Available Combination therapy of bortezomib with other chemotherapeutics is an emerging treatment strategy. Since both curcumin and bortezomib inhibit NF-κB, we tested the effects of their combination on leukemia cells. To improve potency, a novel Mannich-type curcumin derivative, C-150, was synthesized. Curcumin and its analogue showed potent antiproliferative and apoptotic effects on the human leukemia cell line, HL60, with different potency but similar additive properties with bortezomib. Additive antiproliferative effects were correlated well with LPS-induced NF-κB inhibition results. Gene expression data on cell cycle and apoptosis related genes, obtained by high-throughput QPCR, showed that curcumin and its analogue act through similar signaling pathways. In correlation with in vitro results similar additive effect could be obsereved in SCID mice inoculated systemically with HL60 cells. C-150 in a liposomal formulation given intravenously in combination with bortezomib was more efficient than either of the drugs alone. As our novel curcumin analogue exerted anticancer effects in leukemic cells at submicromolar concentration in vitro and at 3 mg/kg dose in vivo, which was potentiated by bortezomib, it holds a great promise as a future therapeutic agent in the treatment of leukemia alone or in combination.

  14. Bortezomib Treatment Produces Nocifensive Behavior and Changes in the Expression of TRPV1, CGRP, and Substance P in the Rat DRG, Spinal Cord, and Sciatic Nerve

    Directory of Open Access Journals (Sweden)

    M. Quartu

    2014-01-01

    Full Text Available To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN, we examined the effects of a single-dose intravenous administration of bortezomib and a well-established “chronic” schedule in a rat model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP and substance P (SP were studied in L4-L5 dorsal root ganglia (DRGs, spinal cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold, whereas no difference occurred in thermal withdrawal latency. Western blot analysis showed a relative increase of TRPV1 in DRG and spinal cord after both acute and chronic bortezomib administration. Reverse transcriptase-polymerase chain reaction revealed a decrease of TRPV1 and CGRP mRNA relative levels after chronic treatment. Immunohistochemistry showed that in the DRGs, TRPV1-, CGRP-, and SP-immunoreactive neurons were mostly small- and medium-sized and the proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A bortezomib-induced increase in density of TRPV1- and CGRP-immunoreactive innervation in the dorsal horn was also observed. Our findings show that bortezomib-treatment selectively affects subsets of DRG neurons likely involved in the processing of nociceptive stimuli and that neurochemical changes may contribute to development and persistence of pain in bortezomib-induced PN.

  15. 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.

  16. Depletion of alloreactive T-cells in vitro using the proteasome inhibitor bortezomib preserves the immune response against pathogens.

    Science.gov (United States)

    Blanco, Belén; Sánchez-Abarca, Luis Ignacio; Caballero-Velázquez, Teresa; Santamaría, Carlos; Inogés, Susana; Pérez-Simón, José Antonio

    2011-10-01

    Current graft-versus-host disease (GVHD) inhibition approaches lead to abrogation of pathogen-specific T-cell responses. We propose an approach to inhibit GVHD without hampering immunity against pathogens: in vitro depletion of alloreactive T cells with the preoteasome inhibitor bortezomib. We show that PBMCs stimulated with allogeneic cells and treated with bortezomib greatly reduce their ability to produce IFN-γ when re-stimulated with the same allogeneic cells, but mainly preserve their ability to respond to citomegalovirus stimulation. Unlike in vivo administration of immunosuppressive drugs or other strategies of allodepletion, in vitro allodepletion with bortezomib maintains pathogen-specific T cells, representing a promising alternative for GVHD prophylaxis.

  17. SIE, SIES, GITMO evidence-based guidelines on novel agents (thalidomide, bortezomib, and lenalidomide) in the treatment of multiple myeloma.

    Science.gov (United States)

    Barosi, Giovanni; Merlini, Giampaolo; Billio, Atto; Boccadoro, Mario; Corradini, Paolo; Marchetti, Monia; Massaia, Massimo; Tosi, Patrizia; Palumbo, Antonio; Cavo, Michele; Tura, Sante

    2012-06-01

    In this project, we produced drug-specific recommendations targeting the use of new agents for multiple myeloma (MM). We used the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system which separates the judgments on quality of evidence from the judgment about strength of recommendations. We recommended thalidomide and bortezomib in MM patients candidates to autologous stem cell transplantation (ASCT) (weak positive). We did not recommend novel agents as maintenance therapy after ASCT (weak negative). In patients not candidate to ASCT, thalidomide or bortezomib (strong positive) associated with melphalan and prednisone were recommended. In these patients, no specific course of action could be recommended as for maintenance therapy. In patients who are refractory or relapsing after first-line therapy, we recommended bortezomib and pegylated liposomal doxorubicin, or lenalidomide and dexamethasone combinations (weak positive).

  18. Successful treatment of refractory systemic lupus erythematosus using proteasome inhibitor bortezomib followed by belimumab: description of two cases.

    Science.gov (United States)

    Sjöwall, C; Hjorth, M; Eriksson, P

    2017-01-01

    Although the putative therapeutic options for patients with systemic lupus erythematosus (SLE) are steadily increasing, refractory disease is indeed a major challenge to many clinicians and patients. The proteasome inhibitor bortezomib - approved for the treatment of multiple myeloma since the beginning of this century - was recently reported successful in twelve cases of refractory SLE by German colleagues. Herein, we describe two Swedish SLE cases with refractory renal and pulmonary manifestations that were rescued by bortezomib as induction of remission followed by monthly doses of belimumab. The patients were carefully monitored with regard to disease activity and renal function. Anti-dsDNA and anti-C1q antibodies, complement proteins and lymphocyte subsets were analysed in consecutive samples. In December 2016, the patients had been in clinical remission post bortezomib administration for a period of 28 and 22 months, respectively. Potential benefits of using belimumab as maintenance therapy to prevent regeneration of autoreactive B cell clones are discussed.

  19. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma.

    Science.gov (United States)

    Kumar, Shaji; Flinn, Ian; Richardson, Paul G; Hari, Parameswaran; Callander, Natalie; Noga, Stephen J; Stewart, A Keith; Turturro, Francesco; Rifkin, Robert; Wolf, Jeffrey; Estevam, Jose; Mulligan, George; Shi, Hongliang; Webb, Iain J; Rajkumar, S Vincent

    2012-05-10

    Combinations of bortezomib (V) and dexamethasone (D) with either lenalidomide (R) or cyclophosphamide (C) have shown significant efficacy. This randomized phase 2 trial evaluated VDC, VDR, and VDCR in previously untreated multiple myeloma (MM). Patients received V 1.3 mg/m2 (days 1, 4, 8, 11) and D 40 mg (days 1, 8, 15), with either C 500 mg/m2 (days 1, 8) and R 15 mg (days 1-14; VDCR), R 25 mg (days 1-14; VDR), C 500 mg/m2 (days 1, 8; VDC) or C 500 mg/m2 (days 1, 8, 15; VDC-mod) in 3-week cycles (maximum 8 cycles), followed by maintenance with V 1.3 mg/m2 (days 1, 8, 15, 22) for four 6-week cycles (all arms)≥very good partial response was seen in 58%, 51%, 41%, and 53% (complete response rate of 25%, 24%, 22%, and 47%) of patients (VDCR, VDR, VCD, and VCD-mod, respectively); the corresponding 1-year progression-free survival was 86%, 83%, 93%, and 100%, respectively. Common adverse events included hematologic toxicities, peripheral neuropathy, fatigue, and gastrointestinal disturbances. All regimens were highly active and well tolerated in previously untreated MM, and, based on this trial, VDR and VCD-mod are preferred for clinical practice and further comparative testing. No substantial advantage was noted with VDCR over the 3-drug combinations. This trial is registered at www.clinicaltrials.gov (NCT00507442).

  20. Bortezomib (PS-341 treatment decreases inflammation and partially rescues the expression of the dystrophin-glycoprotein complex in GRMD dogs.

    Directory of Open Access Journals (Sweden)

    Karla P C Araujo

    Full Text Available Golden retriever muscular dystrophy (GRMD is a genetic myopathy corresponding to Duchenne muscular dystrophy (DMD in humans. Muscle atrophy is known to be associated with degradation of the dystrophin-glycoprotein complex (DGC via the ubiquitin-proteasome pathway. In the present study, we investigated the effect of bortezomib treatment on the muscle fibers of GRMD dogs. Five GRMD dogs were examined; two were treated (TD- Treated dogs with the proteasome inhibitor bortezomib, and three were control dogs (CD. Dogs were treated with bortezomib using the same treatment regimen used for multiple myeloma. Pharmacodynamics were evaluated by measuring the inhibition of 20S proteasome activity in whole blood after treatment and comparing it to that in CD. We performed immunohistochemical studies on muscle biopsy specimens to evaluate the rescue of dystrophin and dystrophin-associated proteins in the muscles of GRMD dogs treated with bortezomib. Skeletal tissue from TD had lower levels of connective tissue deposition and inflammatory cell infiltration than CD as determined by histology, collagen morphometry and ultrastructural analysis. The CD showed higher expression of phospho-NFκB and TGF-β1, suggesting a more pronounced activation of anti-apoptotic factors and inflammatory molecules and greater connective tissue deposition, respectively. Immunohistochemical analysis demonstrated that dystrophin was not present in the sarcoplasmic membrane of either group. However, bortezomib-TD showed higher expression of α- and β-dystroglycan, indicating an improved disease histopathology phenotype. Significant inhibition of 20S proteasome activity was observed 1 hour after bortezomib administration in the last cycle when the dose was higher. Proteasome inhibitors may thus improve the appearance of GRMD muscle fibers, lessen connective tissue deposition and reduce the infiltration of inflammatory cells. In addition, proteasome inhibitors may rescue some

  1. Tolerability of Velcade (Bortezomib) subcutaneous administration using a maximum volume of 3 mL per injection site.

    Science.gov (United States)

    Ng, Pamela; Incekol, Diana; Lee, Roy; Paisley, Emma; Dara, Celina; Brandle, Ian; Kaufman, Marina; Chen, Christine; Trudel, Suzanne; Tiedemann, Rodger; Reece, Donna; Kukreti, Vishal

    2015-08-01

    Subcutaneous injection is now commonly used as a standard for bortezomib administration. The bortezomib (Velcade(®)) product monograph recommends that intravenous injections be prepared at a concentration of 1 mg/mL, while subcutaneous injections may be prepared at a concentration of 2.5 mg/mL. Many institutions and subcutaneous administration guidelines use 2 mL as the maximum volume for subcutaneous injection. Using 2 mL as the maximum volume for injection would mean that many patients receiving bortezomib will receive two injections during each visit with common dosing parameters. In this prospective study evaluating a change to subcutaneous administration, bortezomib 1 mg/mL was administered subcutaneously at a higher maximum of 3 mL per injection site. For 57 individual patients, 339 doses were administered. Skin reactions were noted in 42% with all reactions being Grade 1 or 2. Patients tolerated subcutaneous injections well and only four patients were switched back to intravenous route. This is the first time that subcutaneous bortezomib of a volume up to a maximum of 3 mL (bortezomib 3 mg) per injection site has been reported. This higher single dose is well tolerated with limited skin reactions, no significant hypotension and facilitates ease of administration with only 5 patients needing two injections per visit. If the maximum volume for injection was kept at 2 mL, a total of 46 patients would have received two injections per visit. © The Author(s) 2014.

  2. Congenital sacrococcygeal PNET and chemotherapy

    Directory of Open Access Journals (Sweden)

    Colin Patrick Hawkes

    2012-01-01

    Full Text Available We present the case of a congenital localised sacrococcygeal primitive neuroectodermal tumor treated aggressively with surgical resection and modified age-appropriate adjuvant chemotherapy. The conventional combination chemotherapy of vincristine, adriamycin, cyclophosphamide, ifosfamide and etoposide was modified to a regimen including vincristine, adriamicin, cyclophosphamide and actinomycin in order to minimise the predicted toxicity in this age group. Adjuvant "induction" chemotherapy commenced at 4 weeks of age and consisted of four cycles of vincristine, adriamycin and cyclophosphamide at 50%, 75%, 75% and 100% of recommended doses (vincristine 0.05 mg/kg, adriamycin 0.83 mg/kg daily × 2, cyclophosphamide 40 mg/kg at 3-weekly intervals. This was followed by four cycles of "maintenance" chemotherapy with vincristine (0.025 mg/kg, actinomycin (0.025 mg/kg and cyclophosphamide (36 mg/kg at full recommended doses. Cardioxane at a dose of 16.6 mg/kg was infused immediately prior to the adriamycin. Our patient is thriving at 19 months out from end of treatment.

  3. Cutaneous localization in multiple myeloma in the context of bortezomib-based treatment: how do myeloma cells escape from the bone marrow to the skin?

    Science.gov (United States)

    Marchica, Valentina; Accardi, Fabrizio; Storti, Paola; Mancini, Cristina; Martella, Eugenia; Dalla Palma, Benedetta; Bolzoni, Marina; Todoerti, Katia; Marcatti, Magda; Schifano, Chiara; Bonomini, Sabrina; Sammarelli, Gabriella; Neri, Antonino; Ponzoni, Maurilio; Aversa, Franco; Giuliani, Nicola

    2017-01-01

    The skin is a possible site of extramedullary localization in multiple myeloma (MM) patients; however, the mechanisms involved in this process are poorly understood. We describe the case of a refractory MM patient who developed a cutaneous localization under bortezomib treatment and we further expanded observations in other eight MM patients. We focused on the expression of genes involved in plasma cell skin homing, including CCR10, which was highly expressed. Moreover, we observed a lack of CXCR4 surface expression and the down-regulation of ICAM1/CD54 throughout the progression of the disease, suggesting a possible mechanism driving the escape of MM cells from the bone marrow into the skin.

  4. Extravasation of chemotherapy

    DEFF Research Database (Denmark)

    Langer, Seppo W

    2010-01-01

    Extravasation of chemotherapy is a feared complication of anticancer therapy. The accidental leakage of cytostatic agents into the perivascular tissues may have devastating short-term and long-term consequences for patients. In recent years, the increased focus on chemotherapy extravasation has led...

  5. Chemotherapy for Soft Tissue Sarcomas

    Science.gov (United States)

    ... Stage Soft Tissue Sarcoma Treating Soft Tissue Sarcomas Chemotherapy for Soft Tissue Sarcomas Chemotherapy (chemo) is the use of drugs given into ... Depending on the type and stage of sarcoma, chemotherapy may be given as the main treatment or ...

  6. Overview, prevention and management of chemotherapy extravasation.

    Science.gov (United States)

    Kreidieh, Firas Y; Moukadem, Hiba A; El Saghir, Nagi S

    2016-02-10

    Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, prevention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non-pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused.

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

    Science.gov (United States)

    2013-07-01

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

  8. The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Dijk, Marianne van; Murphy, Eoin [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); Morrell, Ruth [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Knapper, Steven [Department of Haematology, School of Medicine, Cardiff University, Heath Park, CF14 4XN Cardiff (United Kingdom); O' Dwyer, Michael [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Samali, Afshin; Szegezdi, Eva, E-mail: eva.szegezdi@nuigalway.ie [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland)

    2011-03-15

    Acute myeloid leukemia (AML) is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents are urgently required which can overcome drug resistance whilst avoiding unnecessary toxicity. Among newer targeted agents, both tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and proteasome inhibitors show particular promise. In this report we show that a combination of the proteasome inhibitor bortezomib and TRAIL is effective against AML cell lines, in particular, AML cell lines displaying myelomonocytic/monocytic phenotype (M4/M5 AML based on FAB classification), which account for 20-30% of AML cases. We show that the underlying mechanism of sensitization is at least in part due to bortezomib mediated downregulation of c-FLIP and XIAP, which is likely to be regulated by NF-κB. Blockage of NF-κB activation with BMS-345541 equally sensitized myelomonocytic AML cell lines and primary AML blasts to TRAIL.

  9. The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis

    Directory of Open Access Journals (Sweden)

    Eva Szegezdi

    2011-03-01

    Full Text Available Acute myeloid leukemia (AML is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents are urgently required which can overcome drug resistance whilst avoiding unnecessary toxicity. Among newer targeted agents, both tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL and proteasome inhibitors show particular promise. In this report we show that a combination of the proteasome inhibitor bortezomib and TRAIL is effective against AML cell lines, in particular, AML cell lines displaying myelomonocytic/monocytic phenotype (M4/M5 AML based on FAB classification, which account for 20-30% of AML cases. We show that the underlying mechanism of sensitization is at least in part due to bortezomib mediated downregulation of c-FLIP and XIAP, which is likely to be regulated by NF-κB. Blockage of NF-κB activation with BMS-345541 equally sensitized myelomonocytic AML cell lines and primary AML blasts to TRAIL.

  10. [Combined radio- and chemotherapy of anal cancer].

    Science.gov (United States)

    Dobrowsky, W

    1986-05-30

    The treatment regime in anal carcinoma is changing from being a mainly surgical problem. Combined radio-chemotherapy is of increasing interest as treatment of choice. The new treatment modality, including chemotherapy with Mitomycin C and 5-fluorouracil combined with percutaneous and interstitial radiotherapy is presented. The treatment regimes performed at the University Department for Radiotherapy and Radiobiology Vienna is discussed with regard to tolerance, side effects and local control.

  11. Caveolin-1 is required for vascular endothelial growth factor-triggered multiple myeloma cell migration and is targeted by bortezomib.

    Science.gov (United States)

    Podar, Klaus; Shringarpure, Reshma; Tai, Yu-Tzu; Simoncini, Melissa; Sattler, Martin; Ishitsuka, Kenji; Richardson, Paul G; Hideshima, Teru; Chauhan, Dharminder; Anderson, Kenneth C

    2004-10-15

    We recently demonstrated that caveolae, vesicular flask-shaped invaginations of the plasma membrane, represent novel therapeutic targets in multiple myeloma. In the present study, we demonstrate that vascular endothelial growth factor (VEGF) triggers Src-dependent phosphorylation of caveolin-1, which is required for p130(Cas) phosphorylation and multiple myeloma cell migration. Conversely, depletion of caveolin-1 by antisense methodology abrogates p130(Cas) phosphorylation and VEGF-triggered multiple myeloma cell migration. The proteasome inhibitor bortezomib both inhibited VEGF-triggered caveolin-1 phosphorylation and markedly decreased caveolin-1 expression. Consequently, bortezomib inhibited VEGF-induced multiple myeloma cell migration. Bortezomib also decreased VEGF secretion in the bone marrow microenvironment and inhibited VEGF-triggered tyrosine phosphorylation of caveolin-1, migration, and survival in human umbilical vascular endothelial cells. Taken together, these studies demonstrate the requirement of caveolae for VEGF-triggered multiple myeloma cell migration and identify caveolin-1 in multiple myeloma cells and human umbilical vascular endothelial cells as a molecular target of bortezomib.

  12. Safety and effectiveness of low-dose lenalidomide therapy for multiple myeloma complicated with bortezomib-associated interstitial pneumonia.

    Science.gov (United States)

    Nagamachi, Yasuhiro; Yamauchi, Naofumi; Muramatsu, Hirohito; Okamoto, Tetsuro; Inomata, Hidetoshi; Nozawa, Eri; Koyama, Ryuzo; Ihara, Koji; Nishisato, Takuji; Yamada, Hideyuki; Yano, Tomohiro; Tanaka, Shingo; Ono, Kaoru; Kikuchi, Shohei; Kato, Junji

    2013-05-01

    A 78-year-old woman was diagnosed with multiple myeloma (MM: IgG κ type, stage IIIA, ISS III) at a nearby hospital in August 2010. High-dose dexamethasone therapy was ineffective, and she was treated with 2 courses of bortezomib. She was referred to our hospital with back pain and dyspnea in November. She was diagnosed with interstitial pneumonia (IP) and improved rapidly with steroid pulse therapy. Because the involvement of bortezomib was suspected in IP, lenalidomide therapy was selected for MM. Lenalidomide (15 mg) was administered for 2 courses. The patient achieved a PR and the treatment is still ongoing with a good response. According to the interim report on PMS (post-marketing surveillance), 3 of the 1,177 patients treated with lenalidomide developed IP. The dose level was 25 mg in 2 cases and 10 mg in 1 case. The outcomes of these patients were death in 1 case, not recovered in 1 case, and unknown in 1 case. When lenalidomide is used to treat bortezomib-induced IP, there are no rules or regulations about its dose level. In the present case, the dose of lenalidomide (15 mg) was based on the retreatment dose after bone marrow suppression. Low-dose lenalidomide therapy was effective and safe against MM with a bortezomib-associated lung disorder.

  13. Effects of single-agent bortezomib as post-transplant consolidation therapy on multiple myeloma-related bone disease

    DEFF Research Database (Denmark)

    Sezer, Orhan; Beksac, Meral; Hajek, Roman

    2017-01-01

    This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycl...

  14. Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia.

    Science.gov (United States)

    Ghobrial, I M; Redd, R; Armand, P; Banwait, R; Boswell, E; Chuma, S; Huynh, D; Sacco, A; Roccaro, A M; Perilla-Glen, A; Noonan, K; MacNabb, M; Leblebjian, H; Warren, D; Henrick, P; Castillo, J J; Richardson, P G; Matous, J; Weller, E; Treon, S P

    2015-12-01

    We examined the combination of the mammalian target of rapamycin inhibitor everolimus with bortezomib and rituximab in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM) in a phase I/II study. All patients received six cycles of the combination of everolimus/rituximab or everolimus/bortezomib/rituximab followed by maintenance with everolimus until progression. Forty-six patients were treated; 98% received prior rituximab and 57% received prior bortezomib. No dose-limiting toxicities were observed in the phase I. The most common treatment-related toxicities of all grades were fatigue (63%), anemia (54%), leucopenia (52%), neutropenia (48%) and diarrhea (43%). Thirty-six (78%) of the 46 patients received full dose therapy (FDT) of the three drugs. Of these 36, 2 (6%) had complete response (90% confidence interval (CI): 1-16). In all, 32/36 (89%) of patients experienced at least a minimal response (90% CI: 76-96%). The observed partial response or better response rate was 19/36 (53, 90 CI: 38-67%). For the 36 FDT patients, the median progression-free survival was 21 months (95% CI: 12-not estimable). In summary, this study demonstrates that the combination of everolimus, bortezomib and rituximab is well tolerated and achieved 89% response rate even in patients previously treated, making it a possible model of non-chemotherapeutic-based combination therapy in WM.

  15. Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells.

    Science.gov (United States)

    Bista, Ranjan; Lee, David W; Pepper, Oliver B; Azorsa, David O; Arceci, Robert J; Aleem, Eiman

    2017-02-01

    Children with Down syndrome (DS) have increased risk for developing AML (DS-AMKL), and they usually experience severe therapy-related toxicities compared to non DS-AMKL. Refractory/relapsed disease has very poor outcome, and patients would benefit from novel, less toxic, therapeutic strategies that overcome resistance. Relapse/resistance are linked to cancer stem cells with high aldehyde dehydrogenase (ALDH) activity. The purpose of the present work was to study less toxic alternative therapeutic agents for relapsed/refractory DS-AMKL. Fourteen AML cell lines including the DS-AMKL CMY and CMK from relapsed/refractory AML were used. Cytarabine (Ara-C), bortezomib (BTZ), disulfiram/copper (DSF/Cu(2+)) were evaluated for cytotoxicity, depletion of ALDH-positive cells, and resistance. BTZ-resistant CMY and CMK variants were generated by continuous BTZ treatment. Cell viability was assessed using CellTiter-Glo®, ALDH activity by ALDELUOR(TM), and proteasome inhibition by western blot of ubiquitinated proteins and the Proteasome-Glo™ Chymotrypsin-Like (CT-like) assay, apoptosis by Annexin V Fluos/Propidium iodide staining, and mutations were detected using PCR, cloning and sequencing. Ara-C-resistant AML cell lines were sensitive to BTZ and DSF/Cu(2+). The Ara-C-resistant DS-AMKL CMY cells had a high percentage of ALDH(bright) "stem-like" populations that may underlie Ara-C resistance. One percent of these cells were still resistant to BTZ but sensitive to DSF/Cu(2+). To understand the mechanism of BTZ resistance, BTZ resistant (CMY-BR) and (CMK-BR) were generated. A novel mutation PSMB5 Q62P underlied BTZ resistance, and was associated with an overexpression of the β5 proteasome subunit. BTZ-resistance conferred increased resistance to Ara-C due to G1 arrest in the CMY-BR cells, which protected the cells from S-phase damage by Ara-C. CMY-BR and CMK-BR cells were cross-resistant to CFZ and MG-132 but sensitive to DSF/Cu(2+). In this setting, DSF/Cu(2+) induced

  16. 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.

  17. 盐酸帕洛诺司琼对预防含顺铂方案化疗所致恶心呕吐患者的疗效观察%Effect observation of Palonosetron hydrochloride on preventing nausea and vomiting with chemotherapy including cisplatin

    Institute of Scientific and Technical Information of China (English)

    段琼玉; 吴荣

    2012-01-01

    目的 探讨分别应用盐酸帕洛诺司琼、盐酸格拉司琼预防含顺铂方案化疗所致恶心呕吐的疗效.方法 将60例接受含顺铂方案化疗的肿瘤患者随机分为观察组(盐酸帕洛诺司琼组)及对照组(盐酸格拉司琼组),每组各30例,比较两组对预防化疗所致呕吐的临床疗效、用药后不同时间恶心的完全控制率以及恶心治疗后的有效率.结果 观察组急性呕吐的总有效率(83.3%)明显高于对照组(66.7%),两组延迟性呕吐的总有效率分别为70.0%和53.3%,差异有统计学意义(χ2=14.127,P 0.05).结论 盐酸帕洛诺司琼在预防含顺铂方案化疗所引起的恶心呕吐的疗效优于盐酸格拉司琼,安全性好,值得临床推广.%Obejective To investigate and compare effects of Palonosetron hydrochloride and granisetron hydrochloride were used to prevent the nausea and vomiting caused by chemotherapy with cisplatin. Methods 60 patients receiving chemotherapy including cisplatin were randomly divided into the observation group (palonosetron hydrochloride Group)and the control group(granisetron hydrochloride group),each group contained 30 cases. The occurrence of acute emesis, delayed vomiting, and Nausea complete control rate, nausea treatment efficiency after treatment different times were compared between two groups. Results The acute vomiting total effective rate in observation group (83.3%) was significantly higher than the control group (66.7%). Delayed vomiting total efficiency of two groups was 70.0% and 53.3% respectively, the difference was statistically significance (x2=14.127, P 0.05). Conclusion The efficacy of Palonosetron hydrochloride in the prevention and treatment of nausea and vomiting caused by chemotherapy including cisplatin is superior to the efficacy of aranisetron hydrochloride, and Palonosetron hydrochloride has its own priorities, such as convenient use, good safety and worthy of clinical application.

  18. Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation.

    Science.gov (United States)

    Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

    2016-02-01

    Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2  g/kg), a single dose of rituximab (375  mg/m), and 4 doses of bortezomib (1.3  mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83  ±  16.0 (14952  ±  5820) and 63  ±  36.0 (10321  ±  7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.

  19. Symptoms in Children After Chemotherapy

    Directory of Open Access Journals (Sweden)

    Sevcan Atay Turan

    2016-08-01

    Full Text Available Introduction: Identification of symptoms resulted from chemotherapy in children. Materials and Methods: In this study 46 children and adolescents who had chemotherapy in a pediatric oncology clinic of an oncology hospital were included. Sociodemographic questionnaire and Memorial Symptom Assessment Scale (10-18 years were used as data collection tool. Results: In this survey the mean age of children with cancer was 13.47±2.14 years and the majority of them (41.3% were monitored with non-Hodgkin’s lymphoma diagnosis. The most common symptoms in children who had chemotherapy in hospital were fatigue (76.1%, feeling nervous (69.6%, alopecia (65.2%, nausea (60.9% and feeling sad (60.9%, while the least common symptoms were swelling in the arms/legs (8.7% and problems in urination (6.5%. The most troublesome symptoms were dizziness (66.6%, difficulty in swallowing (64.3%, pain (47.8% and hair loss (43.4%. Conclusions: It was seen that the children still experience high prevalence of post-treatment symptoms, they had more intense psychological symptoms and physical symptoms caused more discomfort.

  20. Impact of C-Myc gene-related aberrations in newly diagnosed myeloma with bortezomib/dexamethasone therapy.

    Science.gov (United States)

    Sekiguchi, Naohiro; Ootsubo, Kaori; Wagatsuma, Miyuki; Midorikawa, Kiyoe; Nagata, Akihisa; Noto, Satoshi; Yamada, Kazuaki; Takezako, Naoki

    2014-03-01

    Recent studies have suggested that c-Myc over-expression may be a factor indicating poor prognosis in multiple myeloma (MM), although c-Myc gene-related abnormalities, including translocation and gene amplification, have not been fully investigated in the novel agent era. Additional chromosome 8 may be considered as aggressive disease in the 1990s. To clarify the impact of these aberrations, we retrospectively analyzed newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM) with bortezomib and dexamethasone induction therapy. In the present study, the high-risk group was defined as having at least one of the following present: non-hyperdiploidy, IgH/FGFR3, and del p53. Forty NDMM cases were analyzed. At the median follow-up duration of 14.1 months, 14 RRMM were recognized. The proportions of patients in the high-risk, c-Myc gene-related aberrations, and additional chromosome 8 groups at diagnosis were 45.5, 22.5, and 10 %, respectively. The proportions of patients who developed RRMM in the high-risk, c-Myc gene-related aberrations, and additional chromosome 8 groups were 41.7, 77.7, and 50 %, respectively. Furthermore, patients with c-Myc gene-related abnormalities tended to exhibit inferior progression-free survival (PFS), and those with c-Myc gene-related abnormalities and/or additional chromosome 8 showed statistically shorter PFS. Therefore, c-Myc gene-related abnormalities and additional chromosome 8 may be related to a poorer prognosis.

  1. 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.

  2. 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.

  3. Fasting and differential chemotherapy protection in patients.

    Science.gov (United States)

    Raffaghello, Lizzia; Safdie, Fernando; Bianchi, Giovanna; Dorff, Tanya; Fontana, Luigi; Longo, Valter D

    2010-11-15

    Chronic calorie restriction has been known for decades to prevent or retard cancer growth, but its weight-loss effect and the potential problems associated with combining it with chemotherapy have prevented its clinical application. Based on the discovery in model organisms that short term starvation (STS or fasting) causes a rapid switch of cells to a protected mode, we described a fasting-based intervention that causes remarkable changes in the levels of glucose, IGF-I and many other proteins and molecules and is capable of protecting mammalian cells and mice from various toxins, including chemotherapy. Because oncogenes prevent the cellular switch to this stress resistance mode, starvation for 48 hours or longer protects normal yeast and mammalian cells and mice but not cancer cells from chemotherapy, an effect we termed Differential Stress Resistance (DSR). In a recent article, 10 patients who fasted in combination with chemotherapy, reported that fasting was not only feasible and safe but caused a reduction in a wide range of side effects accompanied by an apparently normal and possibly augmented chemotherapy efficacy. Together with the remarkable results observed in animals, these data provide preliminary evidence in support of the human application of this fundamental biogerontology finding, particularly for terminal patients receiving chemotherapy. Here we briefly discuss the basic, pre-clinical, and clinical studies on fasting and cancer therapy.

  4. A network biology approach evaluating the anticancer effects of bortezomib identifies SPARC as a therapeutic target in adult T-cell leukemia cells

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2008-10-01

    Full Text Available Junko H Ohyashiki1, Ryoko Hamamura2, Chiaki Kobayashi2, Yu Zhang2, Kazuma Ohyashiki21Intractable Immune System Disease Research Center, Tokyo Medical University, Tokyo, Japan; 2First Department of Internal Medicine, Tokyo Medical University, Tokyo, JapanAbstract: There is a need to identify the regulatory gene interaction of anticancer drugs on target cancer cells. Whole genome expression profiling offers promise in this regard, but can be complicated by the challenge of identifying the genes affected by hundreds to thousands of genes that induce changes in expression. A proteasome inhibitor, bortezomib, could be a potential therapeutic agent in treating adult T-cell leukemia (ATL patients, however, the underlying mechanism by which bortezomib induces cell death in ATL cells via gene regulatory network has not been fully elucidated. Here we show that a Bayesian statistical framework by VoyaGene® identified a secreted protein acidic and rich in cysteine (SPARC gene, a tumor-invasiveness related gene, as a possible modulator of bortezomib-induced cell death in ATL cells. Functional analysis using RNAi experiments revealed that inhibition of the expression SPARC by siRNA enhanced the apoptotic effect of bortezomib on ATL cells in accordance with an increase of cleaved caspase 3. Targeting SPARC may help to treat ATL patients in combination with bortezomib. This work shows that a network biology approach can be used advantageously to identify the genetic interaction related to anticancer effects.Keywords: network biology, adult T cell leukemia, bortezomib, SPARC

  5. Noxa/Bcl-2 protein interactions contribute to bortezomib resistance in human lymphoid cells.

    Science.gov (United States)

    Smith, Alyson J; Dai, Haiming; Correia, Cristina; Takahashi, Rie; Lee, Sun-Hee; Schmitz, Ingo; Kaufmann, Scott H

    2011-05-20

    Previous studies have suggested that the BH3 domain of the proapoptotic Bcl-2 family member Noxa only interacts with the anti-apoptotic proteins Mcl-1 and A1 but not Bcl-2. In view of the similarity of the BH3 binding domains of these anti-apoptotic proteins as well as recent evidence that studies of isolated BH3 domains can potentially underestimate the binding between full-length Bcl-2 family members, we examined the interaction of full-length human Noxa with anti-apoptotic human Bcl-2 family members. Surface plasmon resonance using bacterially expressed proteins demonstrated that Noxa binds with mean dissociation constants (K(D)) of 3.4 nm for Mcl-1, 70 nm for Bcl-x(L), and 250 nm for wild type human Bcl-2, demonstrating selectivity but not absolute specificity of Noxa for Mcl-1. Further analysis showed that the Noxa/Bcl-2 interaction reflected binding between the Noxa BH3 domain and the Bcl-2 BH3 binding groove. Analysis of proteins expressed in vivo demonstrated that Noxa and Bcl-2 can be pulled down together from a variety of cells. Moreover, when compared with wild type Bcl-2, certain lymphoma-derived Bcl-2 mutants bound Noxa up to 20-fold more tightly in vitro, pulled down more Noxa from cells, and protected cells against killing by transfected Noxa to a greater extent. When killing by bortezomib (an agent whose cytotoxicity in Jurkat T-cell leukemia cells is dependent on Noxa) was examined, apoptosis was enhanced by the Bcl-2/Bcl-x(L) antagonist ABT-737 or by Bcl-2 down-regulation and diminished by Bcl-2 overexpression. Collectively, these observations not only establish the ability of Noxa and Bcl-2 to interact but also identify Bcl-2 overexpression as a potential mechanism of bortezomib resistance.

  6. Proteasome inhibitor bortezomib is a novel therapeutic agent for focal radiation-induced osteoporosis.

    Science.gov (United States)

    Chandra, Abhishek; Wang, Luqiang; Young, Tiffany; Zhong, Leilei; Tseng, Wei-Ju; Levine, Michael A; Cengel, Keith; Liu, X Sherry; Zhang, Yejia; Pignolo, Robert J; Qin, Ling

    2017-08-31

    Bone atrophy and its related fragility fractures are frequent, late side effects of radiotherapy in cancer survivors and have a detrimental impact on their quality of life. In another study, we showed that parathyroid hormone 1-34 and anti-sclerostin antibody attenuates radiation-induced bone damage by accelerating DNA repair in osteoblasts. DNA damage responses are partially regulated by the ubiquitin proteasome pathway. In the current study, we examined whether proteasome inhibitors have similar bone-protective effects against radiation damage. MG132 treatment greatly reduced radiation-induced apoptosis in cultured osteoblastic cells. This survival effect was owing to accelerated DNA repair as revealed by γH2AX foci and comet assays and to the up-regulation of Ku70 and DNA-dependent protein kinase, catalytic subunit, essential DNA repair proteins in the nonhomologous end-joining pathway. Administration of bortezomib (Bzb) reversed the loss of trabecular bone structure and strength in mice at 4 wk after focal radiation. Histomorphometry revealed that Bzb significantly increased the number of osteoblasts and activity in the irradiated area and suppressed the number and activity of osteoclasts, regardless of irradiation. Two weeks of Bzb treatment accelerated DNA repair in bone-lining osteoblasts and thus promoted their survival. Meanwhile, it also inhibited bone marrow adiposity. Taken together, we demonstrate a novel role of proteasome inhibitors in treating radiation-induced osteoporosis.-Chandra, A., Wang, L., Young, T., Zhong, L., Tseng, W.-J., Levine, M. A., Cengel, K., Liu, X. S., Zhang, Y., Pignolo, R. J., Qin, L. Proteasome inhibitor bortezomib is a novel therapeutic agent for focal radiation-induced osteoporosis. © FASEB.

  7. [Adapting immunisation schedules for children undergoing chemotherapy].

    Science.gov (United States)

    Fernández-Prada, María; Rodríguez-Martínez, María; García-García, Rebeca; García-Corte, María Dolores; Martínez-Ortega, Carmen

    2016-10-20

    Children undergoing chemotherapy for cancer have special vaccination needs after completion of the treatment. The aim of this study was to evaluate the adaptation of post-chemotherapy vaccination schedules. An observational study was performed on a retrospective cohort that included all children aged from 0 to 14 years, who completed chemotherapy in a tertiary hospital between 2009 and 2015. Inclusion and exclusion criteria were applied. Immunisation was administered in accordance with the guidelines of the Vaccine Advisory Committee of the Spanish Association of Paediatrics. Primary Care immunisation and clinical records of the Preventive Medicine and Public Health Department were reviewed. Of the 99 children who had received chemotherapy, 51 (70.6% males) were included in the study. As regards the type of tumour, 54.9% had a solid organ tumour, and 45.1% had a haematological tumour. Post-chemotherapy immunisation was administered to 70.6%. The most common vaccines received were: diphtheria-tetanus-pertussis or diphtheria-tetanus (54.9%), meningococcus C (41.2%), and seasonal influenza (39.2%). The rate of adaptation of the immunisation schedule after chemotherapy was 9.8%. The pneumococcal conjugate vaccine against 7v or 13v was administered to 21.6% of study subjects. However, only 17.6% received polysaccharide 23v. None received vaccination against hepatitis A. No statistically significant differences were observed between adherence to immunisation schedules and type of tumour (P=.066), gender (P=.304), or age (P=.342). Post-chemotherapy immunisation of children with cancer is poor. The participation of health professionals in training programs and referral of paediatric cancer patients to Vaccine Units could improve the rate of schedule adaptation and proper immunisation of this population. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  8. Chemotherapy, cognitive impairment and hippocampal toxicity.

    Science.gov (United States)

    Dietrich, J; Prust, M; Kaiser, J

    2015-11-19

    Cancer therapies can be associated with significant central nervous system (CNS) toxicity. While radiation-induced brain damage has been long recognized both in pediatric and adult cancer patients, CNS toxicity from chemotherapy has only recently been acknowledged. Clinical studies suggest that the most frequent neurotoxic adverse effects associated with chemotherapy include memory and learning deficits, alterations of attention, concentration, processing speed and executive function. Preclinical studies have started to shed light on how chemotherapy targets the CNS both on cellular and molecular levels to disrupt neural function and brain plasticity. Potential mechanisms include direct cellular toxicity, alterations in cellular metabolism, oxidative stress, and induction of pro-inflammatory processes with subsequent disruption of normal cellular and neurological function. Damage to neural progenitor cell populations within germinal zones of the adult CNS has been identified as one of the key mechanisms by which chemotherapy might exert long-lasting and progressive neurotoxic effects. Based on the important role of the hippocampus for maintenance of brain plasticity throughout life, several experimental studies have focused on the study of chemotherapy effects on hippocampal neurogenesis and associated learning and memory. An increasing body of literature from both animal studies and neuroimaging studies in cancer patients suggests a possible relationship between chemotherapy induced hippocampal damage and the spectrum of neurocognitive deficits and mood alterations observed in cancer patients. This review aims to briefly summarize current preclinical and neuroimaging studies that are providing a potential link between the neurotoxic effects of chemotherapy and hippocampal dysfunction, highlighting challenges and future directions in this field of investigation.

  9. 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.

  10. Chemotherapy of herpesvirus infections.

    Science.gov (United States)

    Jawetz, E

    1975-07-01

    Herpesviruses commonly produce lesions that come to the attention of physicians. Many different chemicals are known to suppress the growth of herpesviruses in vitro, but only a few of these have found application in clinical practice. A critical assessment of the place of some of these forms of chemotherapy was briefly presented.

  11. Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

    Directory of Open Access Journals (Sweden)

    Shenghao Wu

    2015-01-01

    Full Text Available Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM patients with the therapy of subcutaneous (subQ administration of bortezomib and dexamethasone plus thalidomide (VTD regimen. Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group.The efficacy and safety of two groups were analyzed retrospectively. Results. The overall remission (OR after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05. No significant differences in time to 1-year estimate of overall survival (72% versus 75%, P=0.848 and progression-free survival (median 22 months versus 25 months; P=0.725 between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50% than VTD group (80%, P=0.015. Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

  12. Target Mechanism-Based Whole-Cell Screening Identifies Bortezomib as an Inhibitor of Caseinolytic Protease in Mycobacteria

    Science.gov (United States)

    Moreira, Wilfried; Ngan, Grace J. Y.; Low, Jian Liang; Poulsen, Anders; Chia, Brian C. S.; Ang, Melgious J. Y.; Yap, Amelia; Fulwood, Justina; Lakshmanan, Umayal; Lim, Jolander; Khoo, Audrey Y. T.; Flotow, Horst; Hill, Jeffrey; Raju, Ravikiran M.; Rubin, Eric J.

    2015-01-01

    ABSTRACT A novel type of antibacterial screening method, a target mechanism-based whole-cell screening method, was developed to combine the advantages of target mechanism- and whole-cell-based approaches. A mycobacterial reporter strain with a synthetic phenotype for caseinolytic protease (ClpP1P2) activity was engineered, allowing the detection of inhibitors of this enzyme inside intact bacilli. A high-throughput screening method identified bortezomib, a human 26S proteasome drug, as a potent inhibitor of ClpP1P2 activity and bacterial growth. A battery of secondary assays was employed to demonstrate that bortezomib indeed exerts its antimicrobial activity via inhibition of ClpP1P2: Down- or upmodulation of the intracellular protease level resulted in hyper- or hyposensitivity of the bacteria, the drug showed specific potentiation of translation error-inducing aminoglycosides, ClpP1P2-specific substrate WhiB1 accumulated upon exposure, and growth inhibition potencies of bortezomib derivatives correlated with ClpP1P2 inhibition potencies. Furthermore, molecular modeling showed that the drug can bind to the catalytic sites of ClpP1P2. This work demonstrates the feasibility of target mechanism-based whole-cell screening, provides chemical validation of ClpP1P2 as a target, and identifies a drug in clinical use as a new lead compound for tuberculosis therapy. PMID:25944857

  13. Liver Injury Induced by Anticancer Chemotherapy and Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Y. Maor

    2013-01-01

    Full Text Available Cytotoxic chemotherapy prolongs survival of patients with advanced and metastatic tumors. This is, however, a double-edged sword with many adverse effects. Since the liver has a rich blood supply and plays an active role in the metabolism of medications, it is not surprising that there can be hepatic injury related to chemotherapy. In addition, radioembolization may affect the parenchyma of normal and cirrhotic livers. We review chemotherapy-associated liver injury in patients with colorectal liver metastases, including downsizing chemotherapy and neoadjuvant chemotherapy. We discuss the mechanism of the hepatic injury, secondary to reactive oxygen species, and the spectrum of hepatic injury including, steatosis, steatohepatitis, hepatic sinusoidal injury and highlight the pharmacogenomics of such liver insults. Methods for reducing and treating the hepatotoxicity are discussed for specific agents including tamxifen and the newly introduced targeted antibodies.

  14. Pregnancy outcomes after chemotherapy for trophoblastic neoplasia

    Directory of Open Access Journals (Sweden)

    MILA TREMENTOSA GARCIA

    Full Text Available SUMMARY Introduction The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. Objective To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Method Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms “gestational trophoblastic disease” and “pregnancy outcome”. Results A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. Conclusion The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

  15. Preoperative Arterial Interventional Chemotherapy on Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    WANG Hui; LING HU-Hua; TANG Liang-dan; ZHANG Xing-hua

    2008-01-01

    Objective:To discuss the therapeutic effect of preoperative interventional chemotherapy on cervical cancer.Methods:Preoperative interventional chemotherapy by femoral intubation was performed in 25 patients with bulky cervical cancer.The patients received bleomycin 45 mg and cisplatin or oxaliplatin 80 mg/m2.Results:25 cases(including 8 cases with stage Ⅰ and 17 cases with stage Ⅱ)received one or two courses of preoperative interventional chemotherapy.The size of the focal lesions was decreased greatly and radical hysterectomy and lymphadenectomy were performed successfully in all the patients.All of the specimens were sent for pathological examination.Lymphocyte infiltration was found more obvious in the cancer tissues as compared with their counterpart before treatment.As a result,relevant vaginal bleeding was stopped completely shortly after the treatment.Conclusion:Arterial interventional chemotherapy was proved to reduce the local size of cervical cancer and thus control the hemorrhage efficiently.The patients with cervical cancer can receive radical hysterectomy therapy after the interventional chemotherapy.

  16. Prevent Infections During Chemotherapy

    Centers for Disease Control (CDC) Podcasts

    2011-10-24

    This podcast discusses the importance of preventing infections in cancer patients who are undergoing chemotherapy. Dr. Lisa Richardson, CDC oncologist, talks about a new Web site for cancer patients and their caregivers.  Created: 10/24/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 10/24/2011.

  17. Chemotherapy of Leishmaniasis.

    Science.gov (United States)

    1978-12-01

    NOTES 1S. KEY WORDS (Continue on reverse side linscoeawy and identiIIy by block number) LEISHMANIA LEISHMANIASIS CHEMOTHERAPY ANTILEISHMANIAL PENTOSTAM...number of compounds was supplied by WRAIR for testing on four strains of Leishmania in December 1977. Preliminary data were supplied to WRAIR by the...j_ = L. tropica major (Strain LV39 from USSR) and the New World cutaneous leishmaniasis by L. mexicana amazonensis (Strain LV78 from Brazil). The test

  18. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    Science.gov (United States)

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  19. The Cost-Effectiveness of Initial Treatment of Multiple Myeloma in the U.S. With Bortezomib Plus Melphalan and Prednisone Versus Thalidomide Plus Melphalan and Prednisone or Lenalidomide Plus Melphalan and Prednisone With Continuous Lenalidomide Maintenance Treatment

    OpenAIRE

    2013-01-01

    A detailed pharmacoeconomic analysis was conducted to estimate the incremental cost-effectiveness of bortezomib, melphalan, and prednisone versus thalidomide, melphalan, and prednisone versus lenalidomide, melphalan, and prednisone with lenalidomide maintenance as therapy for previously untreated transplant-ineligible multiple myeloma patients. Bortezomib, melphalan, and prednisone was found to be the cost-effective option in the U.S. setting.

  20. Primary therapy of Waldenström macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BDR): Long-term results of a phase 2 study of the European Myeloma Network (EMN)

    NARCIS (Netherlands)

    M.A. Dimopoulos (Meletios); R. Garcia-Sanz (Ramon); M. Gavriatopoulou (Maria); P. Morel; M.-C. Kyrtsonis (Marie-Christine); L.K. Michalis (Lampros); Z. Kartasis (Zafiris); X. Leleu; G. Palladini (Giovanni); A. Tedeschi (Alessandra); D. Gika (Dimitra); G. Merlini; E. Kastritis (Efstathios); P. Sonneveld (Pieter)

    2013-01-01

    textabstractIn this phase 2 multicenter trial, we evaluated the activity of bortezomib, dexamethasone, and rituximab (BDR) combination in previously untreated symptomatic patients with Waldenström macroglobulinemia (WM). To prevent immunoglobulin M (IgM) "flare," single agent bortezomib (1.3 mg/m 2

  1. Harnessing Noxa demethylation to overcome Bortezomib resistance in mantle cell lymphoma.

    Science.gov (United States)

    Leshchenko, Violetta V; Kuo, Pei-Yu; Jiang, Zewei; Weniger, Marc A; Overbey, Jessica; Dunleavy, Kieron; Wilson, Wyndham H; Wiestner, Adrian; Parekh, Samir

    2015-09-29

    Bortezomib (BZM) is the first proteasome inhibitor approved for relapsed Mantle Cell Lymphoma (MCL) with durable responses seen in 30%-50% of patients. Given that a large proportion of patients will not respond, BZM resistance is a significant barrier to use this agent in MCL. We hypothesized that a subset of aberrantly methylated genes may be modulating BZM response in MCL patients. Genome-wide DNA methylation analysis using a NimbleGen array platform revealed a striking promoter hypomethylation in MCL patient samples following BZM treatment. Pathway analysis of differentially methylated genes identified molecular mechanisms of cancer as a top canonical pathway enriched among hypomethylated genes in BZM treated samples. Noxa, a pro-apoptotic Bcl-2 family member essential for the cytotoxicity of BZM, was significantly hypomethylated and induced following BZM treatment. Therapeutically, we could demethylate Noxa and induce anti-lymphoma activity using BZM and the DNA methytransferase inhibitor Decitabine (DAC) and their combination in vitro and in vivo in BZM resistant MCL cells. These findings suggest a role for dynamic Noxa methylation for the therapeutic benefit of BZM. Potent and synergistic cytotoxicity between BZM and DAC in vitro and in vivo supports a strategy for using epigenetic priming to overcome BZM resistance in relapsed MCL patients.

  2. Copper–zinc superoxide dismutase-mediated redox regulation of bortezomib resistance in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Kelley Salem

    2015-04-01

    Full Text Available Multiple myeloma (MM is an incurable B-cell malignancy. The proteasome inhibitor bortezomib (BTZ is a frontline MM drug; however, intrinsic or acquired resistance to BTZ remains a clinical hurdle. As BTZ induces oxidative stress in MM cells, we queried if altered redox homeostasis promotes BTZ resistance. In primary human MM samples, increased gene expression of copper–zinc superoxide dismutase (CuZnSOD or SOD1 correlated with cancer progression, high-risk disease, and adverse overall and event-free survival outcomes. As an in vitro model, human MM cell lines (MM.1S, 8226, U266 and the BTZ-resistant (BR lines (MM.1SBR, 8226BR were utilized to determine the role of antioxidants in intrinsic or acquired BTZ-resistance. An up-regulation of CuZnSOD, glutathione peroxidase-1 (GPx-1, and glutathione (GSH were associated with BTZ resistance and attenuated prooxidant production by BTZ. Enforced overexpression of SOD1 induced BTZ resistance and pharmacological inhibition of CuZnSOD with disulfiram (DSF augmented BTZ cytotoxicity in both BTZ-sensitive and BTZ-resistant cell lines. Our data validates CuZnSOD as a novel therapeutic target in MM. We propose DSF as an adjuvant to BTZ in MM that is expected to overcome intrinsic and acquired BTZ resistance as well as augment BTZ cytotoxicity.

  3. Copper-zinc superoxide dismutase-mediated redox regulation of bortezomib resistance in multiple myeloma.

    Science.gov (United States)

    Salem, Kelley; McCormick, Michael L; Wendlandt, Erik; Zhan, Fenghuang; Goel, Apollina

    2015-01-01

    Multiple myeloma (MM) is an incurable B-cell malignancy. The proteasome inhibitor bortezomib (BTZ) is a frontline MM drug; however, intrinsic or acquired resistance to BTZ remains a clinical hurdle. As BTZ induces oxidative stress in MM cells, we queried if altered redox homeostasis promotes BTZ resistance. In primary human MM samples, increased gene expression of copper-zinc superoxide dismutase (CuZnSOD or SOD1) correlated with cancer progression, high-risk disease, and adverse overall and event-free survival outcomes. As an in vitro model, human MM cell lines (MM.1S, 8226, U266) and the BTZ-resistant (BR) lines (MM.1SBR, 8226BR) were utilized to determine the role of antioxidants in intrinsic or acquired BTZ-resistance. An up-regulation of CuZnSOD, glutathione peroxidase-1 (GPx-1), and glutathione (GSH) were associated with BTZ resistance and attenuated prooxidant production by BTZ. Enforced overexpression of SOD1 induced BTZ resistance and pharmacological inhibition of CuZnSOD with disulfiram (DSF) augmented BTZ cytotoxicity in both BTZ-sensitive and BTZ-resistant cell lines. Our data validates CuZnSOD as a novel therapeutic target in MM. We propose DSF as an adjuvant to BTZ in MM that is expected to overcome intrinsic and acquired BTZ resistance as well as augment BTZ cytotoxicity.

  4. Magnetic fluid hyperthermia enhances cytotoxicity of bortezomib in sensitive and resistant cancer cell lines.

    Science.gov (United States)

    Alvarez-Berríos, Merlis P; Castillo, Amalchi; Rinaldi, Carlos; Torres-Lugo, Madeline

    2014-01-01

    The proteasome inhibitor bortezomib (BZ) has shown promising results in some types of cancer, but in others it has had minimal activity. Recent studies have reported enhanced efficacy of BZ when combined with hyperthermia. However, the use of magnetic nanoparticles to induce hyperthermia in combination with BZ has not been reported. This novel hyperthermia modality has shown better potentiation of chemotherapeutics over other types of hyperthermia. We hypothesized that inducing hyperthermia via magnetic nanoparticles (MFH) would enhance the cytotoxicity of BZ in BZ-sensitive and BZ-resistant cancer cells more effectively than hyperthermia using a hot water bath (HWH). Studies were conducted using BZ in combination with MFH in two BZ-sensitive cell lines (MDA-MB-468, Caco-2), and one BZ-resistant cell line (A2780) at two different conditions, ie, 43°C for 30 minutes and 45°C for 30 minutes. These experiments were compared with combined application of HWH and BZ. The results indicate enhanced potentiation between hyperthermic treatment and BZ. MFH combined with BZ induced cytotoxicity in sensitive and resistant cell lines to a greater extent than HWH under the same treatment conditions. The observation that MFH sensitizes BZ-resistant cell lines makes this approach a potentially effective anticancer therapy platform.

  5. Synergistic DNA-damaging effect in multiple myeloma with the combination of zalypsis, bortezomib and dexamethasone

    Science.gov (United States)

    López-Iglesias, Ana-Alicia; González-Méndez, Lorena; San-Segundo, Laura; Herrero, Ana B.; Hernández-García, Susana; Martín-Sánchez, Montserrat; Gutiérrez, Norma C.; Paíno, Teresa; Avilés, Pablo; Mateos, María-Victoria; San-Miguel, Jesús F.; Garayoa, Mercedes; Ocio, Enrique M.

    2017-01-01

    Despite new advances in multiple myeloma treatment and the consequent improvement in overall survival, most patients relapse or become refractory to treatment. This suggests that new molecules and combinations that may further inhibit important survival pathways for these tumor cells are needed. In this context, zalypsis is a novel compound, derived from marine organisms, with a powerful preclinical anti-myeloma effect based on the sensitivity of malignant plasma cells to DNA-damage induction; and it has already been tested in a phase I/II clinical trial in multiple myeloma. We hypothesized that the addition of this compound to the combination of bortezomib plus dexamethasone may improve efficacy with acceptable toxicity. The triple combination demonstrated strong synergy and higher efficacy compared with double combinations; not only in vitro, but also ex vivo and, especially, in in vivo experiments. The triple combination triggers cell death, mainly through a synergistic induction of DNA damage and a decrease in the nuclear localization of nuclear factor kappa B. Our findings support the clinical evaluation of this combination for relapsed and refractory myeloma patients. PMID:27540138

  6. WE-D-BRE-04: Modeling Optimal Concurrent Chemotherapy Schedules

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, J; Deasy, J O [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2014-06-15

    Purpose: Concurrent chemo-radiation therapy (CCRT) has become a more common cancer treatment option with a better tumor control rate for several tumor sites, including head and neck and lung cancer. In this work, possible optimal chemotherapy schedules were investigated by implementing chemotherapy cell-kill into a tumor response model of RT. Methods: The chemotherapy effect has been added into a published model (Jeong et al., PMB (2013) 58:4897), in which the tumor response to RT can be simulated with the effects of hypoxia and proliferation. Based on the two-compartment pharmacokinetic model, the temporal concentration of chemotherapy agent was estimated. Log cell-kill was assumed and the cell-kill constant was estimated from the observed increase in local control due to concurrent chemotherapy. For a simplified two cycle CCRT regime, several different starting times and intervals were simulated with conventional RT regime (2Gy/fx, 5fx/wk). The effectiveness of CCRT was evaluated in terms of reduction in radiation dose required for 50% of control to find the optimal chemotherapy schedule. Results: Assuming the typical slope of dose response curve (γ50=2), the observed 10% increase in local control rate was evaluated to be equivalent to an extra RT dose of about 4 Gy, from which the cell-kill rate of chemotherapy was derived to be about 0.35. Best response was obtained when chemotherapy was started at about 3 weeks after RT began. As the interval between two cycles decreases, the efficacy of chemotherapy increases with broader range of optimal starting times. Conclusion: The effect of chemotherapy has been implemented into the resource-conservation tumor response model to investigate CCRT. The results suggest that the concurrent chemotherapy might be more effective when delayed for about 3 weeks, due to lower tumor burden and a larger fraction of proliferating cells after reoxygenation.

  7. Oculomotor Deficits after Chemotherapy in Childhood.

    Directory of Open Access Journals (Sweden)

    Einar-Jón Einarsson

    Full Text Available Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years. Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy was markedly poorer (p<0.001 and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence (p = 0.004, whereas smooth pursuit and saccade onset times were shorter (p = 0.004 in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%, unsteadiness, light-headedness and that things around them were spinning or moving (87%. Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects' self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of

  8. 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.

  9. Weight changes during chemotherapy for breast cancer

    Directory of Open Access Journals (Sweden)

    Luciano José Megale Costa

    Full Text Available CONTEXT: Patients receiving adjuvant chemotherapy for breast cancer have a tendency to gain weight. This tendency has determining factors not completely defined and an unknown prognostic impact. OBJECTIVE: To evaluate weight change during chemotherapy for breast cancer in a defined population and to identify its predisposing factors and possible prognostic significance. DESIGN: Observational, retrospective cohort study. SETTING: Private clinical oncology service. PARTICIPANTS: 106 consecutive patients with breast cancer treated between June 1994 and April 2000, who received neoadjuvant (n = 8, adjuvant (n = 74 or palliative (n = 24 chemotherapy. INTERVETION: Review of medical records and gathering of clinical information, including patients’ body weights before treatment and at follow-up reviews. MAIN MEASUREMENTS: Body weight change, expressed as percentage of body weight per month in treatment; role of clinical data in weight change; and influence of weight change in overall survival and disease-free survival. RESULTS: There was a mean increase of 0.50 ± 1.42% (p = 0.21 of body weight per month of treatment. We noted a negative correlation between metastatic disease and weight gain (r = -0.447, p < 0.0001. In the adjuvant and neoadjuvant therapy groups there was a mean weight gain of 0.91 ± 1.19 % (p < 0.00001 per month, whereas in the metastatic (palliative group, we observed a mean loss of 0.52 ± 1.21% (p = 0.11 of body weight per month during the treatment. We did not observe any statistically significant correlation between weight changes and disease-free survival or overall survival. CONCLUSIONS: Women with breast cancer undergoing adjuvant or neoadjuvant chemotherapy gain weight, whereas metastatic cancer patients will probably lose weight during palliative chemotherapy. Further studies are needed in order to evaluate the prognostic significance of weight changes during chemotherapy.

  10. Association between bortezomib dose intensity and overall survival in mantle cell lymphoma patients on frontline VR-CAP in the phase 3 LYM-3002 study().

    Science.gov (United States)

    Robak, Tadeusz; Huang, Huiqiang; Jin, Jie; Zhu, Jun; Liu, Ting; Samoilova, Olga; Pylypenko, Halyna; Verhoef, Gregor; Siritanaratkul, Noppadol; Osmanov, Evgenii; Pereira, Juliana; Mayer, Jiri; Hong, Xiaonan; Okamoto, Rumiko; Pei, Lixia; Rooney, Brendan; van de Velde, Helgi; Cavalli, Franco

    2017-06-05

    The pivotal LYM-3002 study compared frontline rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients for whom stem cell transplantation was not an option. This post hoc subanalysis of the VR-CAP data from LYM-3002 evaluated the effect of bortezomib dose intensity on OS in patients who completed ≥6 cycles of treatment. From the end of cycle 6, patients receiving ≥4.6 mg/m(2)/cycle of bortezomib had significantly longer OS (but not PFS) compared with those receiving VR-CAP. Clinicaltrials.gov identifier: NCT00722137.

  11. Dietetic management in gastrointestinal complications from antimalignant chemotherapy.

    Science.gov (United States)

    Calixto-Lima, L; Martins de Andrade, E; Gomes, A P; Geller, M; Siqueira-Batista, R

    2012-01-01

    Antineoplastic chemotherapy (CT) represents the systemic treatment of malignant tumors. It can be used alone or combined with surgery and / or radiotherapy. The cytotoxic agents used in chemotherapy work on both cancerous cells and noncancerous cells of the body, generally resulting in high toxicity. The biological aggressiveness of chemotherapy particularly affects rapidly replicating cells, such as those of the digestive tract, resulting in adverse effects that impair food intake, leading to compromised nutritional status and which may lead to cachexia. The main toxic effects of chemotherapy in the gastrointestinal tract include nausea, vomiting -these are the most frequent- constipation, diarrhea, xerostomia, mucositis, dysphagia and anorexia. Given the high frequency of such effects, nutritional intervention should be an integral part of cancer treatment, to maintain and/or improve the patient's nutritional status and reduce or minimize the side effects caused by treatment. Accordingly, the goal of this study is to review dietetic conduct in the process of caring for patients undergoing cancer chemotherapy.

  12. Near-tetraploidy clone can evolve from a hyperdiploidy clone and cause resistance to lenalidomide and bortezomib in a multiple myeloma patient.

    Science.gov (United States)

    Yuan, Ji; Shah, Radhika; Kulharya, Anita; Ustun, Celalettin

    2010-07-01

    Aneuploidy is a very common prognostic factor in multiple myeloma (MM). Nonhyperdiploidy including near-tetraploidy (NT) is a poor prognostic indicator, compared to hyperdiploidy in multiple myeloma (MM). NT results from endoduplication of hypodiploidy. We report of a 55-year-old female patient diagnosed with advanced stage MM with hyperdiploidy and t(8;14)(q24;q32). The patient responded well to lenalidomide and dexamethasone for approximately 1 year. At the time of progression, she had become unresponsive to lenalidomide and subsequently bortezomib, and was found to have NT and loss of choromosome 13. There is another reported patient who had a possible interchange from nonhyperdiploidy to hyperdiploidy status, however, artifact could not be ruled out. To our knowledge, this is the first patient in whom evolution of an abnormal clone from a hyperdiploidy to a NT abnormal clone has been confirmed during the natural course of MM. This evolution is associated with resistance to novel drugs and poor prognosis in MM.

  13. 硼替佐米联合地塞米松治疗多发性骨髓瘤52例疗效分析%Clinical Efficacy Analysis of Bortezomib Combined with Dexamethasone in Treatment of Multiple Myeloma

    Institute of Scientific and Technical Information of China (English)

    王平

    2013-01-01

    目的 探讨硼替佐米联合地塞米松对多发性骨髓瘤的治疗效果和不良反应.方法 根据入组的多发性骨髓瘤患者个体情况制定硼替佐米和地塞米松的用量,在治疗过程中监测患者的各项生理指标,详细记录不良反应,治疗结束后随访6个月,观察存活率及用药依从性.结果 所有参与实验的患者均完成了规定的治疗周期,总有效率为78.85%,取得最佳化疗效果的疗程为2个疗程,复发率为11.54%,治疗后仅1例患者死亡.结论 利用硼替佐米联合地塞米松治疗多发性骨髓瘤疗效显著,有效率较高,不良反应在可控范围内,近期存活率也较满意.%Objective To explore the curative effect of bortezomib combined with dexamethasone on multiple myeloma and adverse reaction.Method According to the individual condition of patients develop boron for Zomi and dexamethasone dosage,various physiological indexes of patients during process of treatment were monitored,a detailed record of adverse reactions after the end of treatment were followed up for 6 months to observe the survival rate and medication compliance.Results All the patients in the experiment were completed the prescribed treatment cycle,the total efficiency was 78.85%,to achieve the best effect of chemotherapy for the treatment of 2 courses,the recurrence rate was 11.54%,1 patients died after treatment.Conclusion The use of bortezomib combined with dexamethasone in the treatment of multiple myeloma had high efficiency,adverse reactions in the controlled range,the short-term survival rate is satisfied.

  14. Chemotherapy of metastatic colon cancer

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2012-01-01

    Full Text Available Colorectal cancer is one of the leading causes of cancer incidence and mortality. In 2008 inRussian Federation55 719 new cases of colorectal cancer were diagnosed and 37 911 patients died of this disease. A significant progress was achieved in metastatic colorectal cancer treatment during the last decades. A lot of treatment options became available: from 5-fluoruracil monotherapy to combined treatment treatment schemes including surgery. A group of patients with isolated liver metastases was distinguished, who can achieve 5-year survival rate of 40 % after systemic treatment and surgery. Today, based on clinical data and molecular analysis, we come close to individualized treatment of this patient group. In this literature review results of metastatic colorectal cancer chemotherapy are being analyzed and rational treatment tactic is proposed based on therapy goals. 

  15. Randomized Phase II Study of R-CHOP With or Without Bortezomib in Previously Untreated Patients With Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Leonard, John P; Kolibaba, Kathryn S; Reeves, James A; Tulpule, Anil; Flinn, Ian W; Kolevska, Tatjana; Robles, Robert; Flowers, Christopher R; Collins, Robert; DiBella, Nicholas J; Papish, Steven W; Venugopal, Parameswaran; Horodner, Andrew; Tabatabai, Amir; Hajdenberg, Julio; Park, Jaehong; Neuwirth, Rachel; Mulligan, George; Suryanarayan, Kaveri; Esseltine, Dixie-Lee; de Vos, Sven

    2017-09-01

    Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m(2) intravenously on days 1 and 4 (VR-CHOP). The primary end point, progression-free survival (PFS), was evaluated in 183 patients with centrally confirmed non-GCB DLBCL who received one or more doses of study drug (91 R-CHOP, 92 VR-CHOP). Results After a median follow-up of 34 months, with 25% (R-CHOP) and 18% (VR-CHOP) of patients having had PFS events, the hazard ratio (HR) for PFS was 0.73 (90% CI, 0.43 to 1.24) with VR-CHOP ( P = .611). Two-year PFS rates were 77.6% with R-CHOP and 82.0% with VR-CHOP; they were 65.1% versus 72.4% in patients with high-intermediate/high IPI (HR, 0.67; 90% CI, 0.34 to 1.29), and 90.0% versus 88.9% (HR, 0.85; 90% CI, 0.35 to 2.10) in patients with low/low-intermediate IPI. Overall response rate with R-CHOP and VR-CHOP was 98% and 96%, respectively. The overall survival HR was 0.75 (90% CI, 0.38 to 1.45); 2-year survival rates were 88.4% and 93.0%, respectively. In the safety population (100 R-CHOP and 101 VR-CHOP patients), grade ≥ 3 adverse events included neutropenia (53% v 49%), thrombocytopenia (13% v 29%), anemia (7% v 15%), leukopenia (26% v 25%), and neuropathy (1% v 5%). Conclusion Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.

  16. Evolution of radiotherapy and chemotherapy practice in malignant gliomas

    Directory of Open Access Journals (Sweden)

    Anusheel Munshi

    2013-01-01

    Full Text Available Malignant astrocytomas of the brain carry a poor prognosis. This article traces the evolution of radiotherapy and chemotherapy practice including the development of concurrent chemo-radiation schedules in the context of these tumors.

  17. Phase I trial of dose-escalating metronomic temozolomide plus bevacizumab and bortezomib for patients with recurrent glioblastoma.

    Science.gov (United States)

    McCracken, D Jay; Celano, Emma C; Voloschin, Alfredo D; Read, William L; Olson, Jeffrey J

    2016-10-01

    The average survival time for patients with recurrent glioblastoma is between 5 and 9 months. Phase I and II trials have shown a modest survival benefit with combination temozolomide and other chemotherapeutics. We conducted a phase I trial of dose-escalating temozolomide with bevacizumab and the proteasome inhibitor bortezomib for patients with recurrent disease. Three groups of three patients were scheduled to receive daily doses of temozolomide at 25, 50, and 75 mg/m(2). Fixed doses of bortezomib and bevacizumab were given at standard intervals. Patients were monitored for dose-limiting toxicities (DLT) to determine the maximum-tolerated dose (MTD) of temozolomide with this regimen. No DLT were seen in the first two groups (25 and 50 mg/m(2) temozolomide). One patient in the 75 mg/m(2) group experienced a grade 4 elevation of ALT and three more patients were accrued for a total of six patients at that dose level. No other DLT occurred, thus making 75 mg/m(2) the MTD. Progression-free survival was 3.27 months for all patients and mean overall survival was 20.75 months. The MTD of temozolomide was 75 mg/m(2) in combination with bevacizumab and bortezomib for recurrent glioblastoma. Only one patient experienced a severe (Grade 4) elevation of ALT. This study will provide the framework for further studies to elicit effectiveness and better determine a safety profile for this drug combination.

  18. 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.

  19. An NMR Study of the Bortezomib Degradation under Clinical Use Conditions

    Directory of Open Access Journals (Sweden)

    Adele Bolognese

    2009-01-01

    Full Text Available The (R-3-methyl-1-((S-3-phenyl-2-(pyrazine-2-carboxamidopropanamidobutyl-boronic acid, bortezomib (BTZ, which binds the 20S proteasome subunit and causes a large inhibition of its activity, is a peptidomimetic boronic drug mainly used for the treatment of multiple myeloma. Commercial BTZ, stabilized as mannitol derivative, has been investigated under the common conditions of the clinical use because it is suspected to be easily degradable in the region of its boronic moiety. Commercial BTZ samples, reconstituted according to the reported commercial instructions and stored at 4∘C, were analyzed by high-field nuclear magnetic resonance spectroscopy in comparison with identical samples bubbled with air and argon, respectively. All the samples remained unchanged for a week. After a month, the air filled samples showed the presence of two main degradation products (6% of starting material, the N-(1-(1-hydroxy-3-methylbutylamino-1-oxo-3-phenylpropan-2-yl pyrazine-2-carboxamide (BTZ1; 5%, determined from NMR integration and the (S-N-(1-(3-methylbutanamido-1-oxo-3-phenylpropan-2-ylpyrazine-2-carboxamide (BTZ2; 1%, determined from NMR integration, identified on the basis of their chemical and spectroscopic properties. The BTZ1 and BTZ2 finding suggests that, under the common condition of use and at 4∘C, commercial BTZ-mannitol is stable for a week, and that, in time, it undergoes slow oxidative deboronation which partially inactivates the product. Low temperature and scarce contact with air decrease the degradation process.

  20. Palliative chemotherapy: oxymoron or misunderstanding?

    Science.gov (United States)

    Roeland, E J; LeBlanc, T W

    2016-03-21

    Oncologists routinely prescribe chemotherapy for patients with advanced cancer. This practice is sometimes misunderstood by palliative care clinicians, yet data clearly show that chemotherapy can be a powerful palliative intervention when applied appropriately. Clarity regarding the term "palliative chemotherapy" is needed: it is chemotherapy given in the non-curative setting to optimize symptom control, improve quality of life, and sometimes to improve survival. Unfortunately, oncologists lack adequate tools to predict which patients will benefit. In a study recently published in BMC Palliative Care, Creutzfeldt et al. presented an innovative approach to advancing the science in this area: using patient reported outcomes to predict responses to palliative chemotherapy. With further research, investigators may be able to develop predictive models for use at the bedside to inform clinical decision-making about the risks and benefits of treatment. In the meantime, oncologists and palliative care clinicians must work together to reduce the use of "end-of-life chemotherapy"-chemotherapy given close to death, which does not improve longevity or symptom control-while optimizing the use of chemotherapy that has true palliative benefits for patients.

  1. 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

  2. A history of cancer chemotherapy.

    Science.gov (United States)

    DeVita, Vincent T; Chu, Edward

    2008-11-01

    The use of chemotherapy to treat cancer began at the start of the 20th century with attempts to narrow the universe of chemicals that might affect the disease by developing methods to screen chemicals using transplantable tumors in rodents. It was, however, four World War II-related programs, and the effects of drugs that evolved from them, that provided the impetus to establish in 1955 the national drug development effort known as the Cancer Chemotherapy National Service Center. The ability of combination chemotherapy to cure acute childhood leukemia and advanced Hodgkin's disease in the 1960s and early 1970s overcame the prevailing pessimism about the ability of drugs to cure advanced cancers, facilitated the study of adjuvant chemotherapy, and helped foster the national cancer program. Today, chemotherapy has changed as important molecular abnormalities are being used to screen for potential new drugs as well as for targeted treatments.

  3. Interstitial pneumonitis following intrapleural chemotherapy

    Directory of Open Access Journals (Sweden)

    Humphries Gary N

    2009-02-01

    Full Text Available Abstract Background Mucinous neoplasms within the abdomen may disseminate by direct extension through the diaphragm to involve the pleural space. Treatment of this condition is by parietal and visceral pleurectomy followed by hyperthermic intrapleural chemotherapy. Case presentation In this case report a patient developed persistent right upper lobe interstitial pneumonitis and progressive parenchymal fibrosis following intrapleural chemotherapy treatment with mitomycin C and doxrubicin. The condition persisted until death 28 months later. Death was from progressive intraabdominal disease with intestinal obstruction and sepsis associated with progressive pulmonary parenchymal disease. The right pleural space disease did not recur. Conclusion This manuscript is the first case report describing interstitial pneumonitis and lung fibrosis following intrapleural chemotherapy. Since pulmonary toxicity from chemotherapy is a dose-dependent phenomenon, dose reduction of intrapleural as compared to intraperitoneal hyperthermic chemotherapy may be necessary.

  4. Protein kinase CK2 inhibition down modulates the NF-κB and STAT3 survival pathways, enhances the cellular proteotoxic stress and synergistically boosts the cytotoxic effect of bortezomib on multiple myeloma and mantle cell lymphoma cells.

    Science.gov (United States)

    Manni, Sabrina; Brancalion, Alessandra; Mandato, Elisa; Tubi, Laura Quotti; Colpo, Anna; Pizzi, Marco; Cappellesso, Rocco; Zaffino, Fortunato; Di Maggio, Speranza Antonia; Cabrelle, Anna; Marino, Filippo; Zambello, Renato; Trentin, Livio; Adami, Fausto; Gurrieri, Carmela; Semenzato, Gianpietro; Piazza, Francesco

    2013-01-01

    CK2 is a pivotal pro-survival protein kinase in multiple myeloma that may likely impinge on bortezomib-regulated cellular pathways. In the present study, we investigated CK2 expression in multiple myeloma and mantle cell lymphoma, two bortezomib-responsive B cell tumors, as well as its involvement in bortezomib-induced cytotoxicity and signaling cascades potentially mediating bortezomib resistance. In both tumors, CK2 expression correlated with that of its activated targets NF-κB and STAT3 transcription factors. Bortezomib-induced proliferation arrest and apoptosis were significantly amplified by the simultaneous inhibition of CK2 with two inhibitors (CX-4945 and K27) in multiple myeloma and mantle cell lymphoma cell lines, in a model of multiple myeloma bone marrow microenvironment and in cells isolated from patients. CK2 inhibition empowered bortezomib-triggered mitochondrial-dependent cell death. Phosphorylation of NF-κB p65 on Ser529 (a CK2 target site) and rise of the levels of the endoplasmic reticulum stress kinase/endoribonuclease Ire1α were markedly reduced upon CK2 inhibition, as were STAT3 phospho Ser727 levels. On the contrary, CK2 inhibition increased phospho Ser51 eIF2α levels and enhanced the bortezomib-dependent accumulation of poly-ubiquitylated proteins and of the proteotoxic stress-associated chaperone Hsp70. Our data suggest that CK2 over expression in multiple myeloma and mantle cell lymphoma cells might sustain survival signaling cascades and can antagonize bortezomib-induced apoptosis at different levels. CK2 inhibitors could be useful in bortezomib-based combination therapies.

  5. Bortezomib-based triplets are associated with a high probability of dialysis independence and rapid renal recovery in newly diagnosed myeloma patients with severe renal failure or those requiring dialysis.

    Science.gov (United States)

    Dimopoulos, Meletios A; Roussou, Maria; Gavriatopoulou, Maria; Psimenou, Erasmia; Eleutherakis-Papaiakovou, Evangelos; Migkou, Magdalini; Matsouka, Charis; Mparmparousi, Despoina; Gika, Dimitra; Kafantari, Eftychia; Ziogas, Dimitrios; Fotiou, Despoina; Panagiotidis, Ioannis; Terpos, Evangelos; Kastritis, Efstathios

    2016-05-01

    Renal failure (RF) is a common and severe complication of symptomatic myeloma, associated with significant morbidity and mortality. Such patients are commonly excluded from clinical trials. Bortezomib/dexamethasone (VD)-based regimens are the backbone of the treatment of newly diagnosed MM patients who present with severe RF even those requiring dialysis. We analyzed the outcomes of 83 consecutive bortezomib-treated patients with severe RF (eGFR dialysis. By IMWG renal response criteria, 54 (65%) patients achieved at least MRrenal, including CRrenal in 35% and PRrenal in 12%. Triplet combinations (i.e., VD plus a third agent) versus VD alone were associated with higher rates of renal responses (72 vs. 50%; P = 0.06). Fifteen of the 31 (48%) patients became dialysis independent within a median of 217 days (range 11-724). Triplets were associated with a higher probability of dialysis discontinuation (57 vs. 35%). Serum free light chain (sFLC) level ≥11,550 mg/L was associated with lower rates of major renal response, longer time to major renal response, lower probability, and longer time to dialysis discontinuation. Rapid myeloma response (≥PR within the first month) was also associated with higher rates of renal response. Patients who became dialysis-independent had longer survival than those remaining on dialysis. In conclusion, VD-based triplets are associated with a significant probability of renal response and dialysis discontinuation, improving the survival of patients who became dialysis independent. Rapid disease response is important for renal recovery and sFLCs are predictive of the probability and of the time required for renal response.

  6. Induction of potent NK cell-dependent anti-myeloma cytotoxic T cells in response to combined mapatumumab and bortezomib.

    Science.gov (United States)

    Neeson, Paul J; Hsu, Andy K; Chen, Yin R; Halse, Heloise M; Loh, Joanna; Cordy, Reece; Fielding, Kate; Davis, Joanne; Noske, Josh; Davenport, Alex J; Lindqvist-Gigg, Camilla A; Humphreys, Robin; Tai, Tsin; Prince, H Miles; Trapani, Joseph A; Smyth, Mark J; Ritchie, David S

    2015-09-01

    There is increasing evidence that some cancer therapies can promote tumor immunogenicity to boost the endogenous antitumor immune response. In this study, we used the novel combination of agonistic anti-TRAIL-R1 antibody (mapatumumab, Mapa) with low dose bortezomib (LDB) for this purpose. The combination induced profound myeloma cell apoptosis, greatly enhanced the uptake of myeloma cell apoptotic bodies by dendritic cell (DC) and induced anti-myeloma cytotoxicity by both CD8(+) T cells and NK cells. Cytotoxic lymphocyte expansion was detected within 24 h of commencing therapy and was maximized when myeloma-pulsed DC were co-treated with low dose bortezomib and mapatumumab (LDB+Mapa) in the presence of NK cells. This study shows that Mapa has two distinct but connected modes of action against multiple myeloma (MM). First, when combined with LDB, Mapa produced powerful myeloma cell apoptosis; secondly, it promoted DC priming and an NK cell-mediated expansion of anti-myeloma cytotoxic lymphocyte (CTL). Overall, this study indicates that Mapa can be used to drive potent anti-MM immune responses.

  7. Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Viola Baradari; Michael H(o)pfner; Alexander Huether; Detlef Schuppan; Hans Scherübl

    2007-01-01

    AIM: To investigate the antiproliferative effect of the histone deacetylase (HDAC) inhibitor MS-275 on cholangiocarcinoma cells alone and in combination with conventional cytostatic drugs (gemcitabine or doxorubicin)or the novel anticancer agents sorafenib or bortezomib.METHODS: Two human bile duct adenocarcinoma cell lines (EGI-1 and TFK-1) were studied. Crystal violet staining was used for detection of cell number changes.Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydrogenase (LDH).Apoptosis was determined by measuring the enzyme activity of caspase-3. Cell cycle status reflected by the DNA content was detected by flow cytometry.RESULTS: MS-275 treatment potently inhibited the proliferation of EGI-1 and TFK-1 cholangiocarcinoma cells by inducing apoptosis and cell cycle arrest. MS-275-induced apoptosis was characterized by activation of caspase-3, up-regulation of Bax and down-regulation of Bcl-2. Cell cycle was predominantly arrested at the G1/S checkpoint, which was associated with induction of the cyclin-dependent kinase inhibitor p21Waf/CIP1. Furthermore,additive anti-neoplastic effects were observed when MS-275 treatment was combined with gemcitabine or doxorubicin, while combination with the multikinase inhibitor sorafenib or the proteasome inhibitor bortezomib resulted in overadditive anti-neoplastic effects.CONCLUSION: The growth of human cholangiocarcinoma cells can be potently inhibited by MS-275 alone or in combination with conventional cytostatic drugs or new,targeted anticancer agents.

  8. Polymorphisms of nuclear factor-κB family genes are associated with development of multiple myeloma and treatment outcome in patients receiving bortezomib-based regimens.

    Science.gov (United States)

    Du, Juan; Huo, Jun; Shi, Jun; Yuan, Zhengang; Zhang, Chunyang; Fu, Weijun; Jiang, Hua; Yi, Qing; Hou, Jian

    2011-05-01

    The nuclear factor-κB pathway is an important signaling pathway activated in multiple myeloma cells. Bortezomib inhibits nuclear factor-κB activation and is an important antimyeloma agent. Nevertheless, patients treated with this drug eventually relapse. We hypothesized that the nuclear factor-κB pathway may be associated with multiple myeloma and patients' responses to bortezomib. In this study we analyzed 26 polymorphism sites of nuclear factor-κB family member genes, IKBα, NFKB2, and TRAF3, in 527 unrelated Chinese Han subjects (252 with multiple myeloma and 275 controls) using a Sequenom MassARRAY genotyping assay, and examined the outcome of 83 patients treated with a bortezomib-based regimen. Single nucleotide polymorphisms in the TRAF3 rs12147254 A allele and a specific haplotype 1 of TRAF3 [GAACAG] are associated with a decreased risk of multiple myeloma (odds ratio 0.709, PNuclear factor-κB family member gene polymorphisms play a role in the development of multiple myeloma and in the response to bortezomib therapy.

  9. First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro

    DEFF Research Database (Denmark)

    Lund, Thomas; Søe, Kent; Abildgaard, Niels

    2010-01-01

    OBJECTIVES: The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma. METHODS: Twenty newly diagnosed patients recei...

  10. Prospective longitudinal study on quality of life in relapsed/refractory multiple myeloma patients receiving second- or third-line lenalidomide or bortezomib treatment.

    Science.gov (United States)

    Leleu, X; Kyriakou, C; Vande Broek, I; Murphy, P; Bacon, P; Lewis, P; Gilet, H; Arnould, B; Petrucci, M T

    2017-03-17

    Treatment advances for multiple myeloma (MM) that have prolonged survival emphasise the importance of measuring patients' health-related quality of life (HRQoL) in clinical studies. HRQoL/functioning and symptoms of patients with relapsed/refractory MM (RRMM) receiving second- or third-line lenalidomide or bortezomib treatment were measured in a prospective European multicentre, observational study at different time points. At baseline, patients in the lenalidomide cohort were frailer than in the bortezomib cohort with more rapid disease progression at study entry (more patients with Eastern Cooperative Oncology Group performance status >2, shorter time from diagnosis, more chronic heart failure, higher serum creatinine levels, more patients with dialysis required). About 40% of the patients receiving lenalidomide discontinued the study in Life Core domains of Diarrhoea and Global Health Status/QoL had worsened in the lenalidomide and bortezomib cohorts, respectively. A clinically meaningful deterioration in HRQoL was more often observed for patients who discontinued the study prior to 6 months in the bortezomib cohort than in the lenalidomide cohort.

  11. Bortezomib for antibody mediated rejection treatment: experience at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City.

    Science.gov (United States)

    Leyva, Sergio; Marino-Vázquez, Lluvia A; Reyes-Loaeza, Jorge A; Vega, Olynka; Uribe-Uribe, Norma; Alberú, Josefina; Morales-Buenrostro, Luis E

    2009-01-01

    The use of bortezomib as a treatment modality of AHR improved and stabilized graft function (clinical response) in the majority of patients. Its use in single dose, even combined with rituximab, does not seem to be useful to obtain a sustained clinical response neither to reduce HLAabs level. The use of 4 doses of bortezomib in days 1, 4, 7, and 10 (1.3 mg/m2 BSA each) plus plasmapheresis produced both a good clinical response and a reduction in DSA. Moving forward, it will necessary to define the long-term effectiveness of bortezomib and whether rituximab administration is indispensable to achieve this goal.

  12. Mechanisms of chemotherapy-induced behavioral toxicities

    OpenAIRE

    Vichaya, Elisabeth G.; Chiu, Gabriel S.; Karen eKrukowski; Lacourt, Tamara E.; Annemieke eKavelaars; Robert eDantzer; Cobi J Heijnen; Adam K. Walker

    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 tre...

  13. Paul Ehrlich: From magic bullets to chemotherapy

    Directory of Open Access Journals (Sweden)

    Juan Fernando Cediel

    2008-09-01

    Full Text Available Paul Ehrlich is one of the most notable figures in the world of science. Considered by many as the father of chemotherapy, he was awarded the Nobel Prize in Physiology and Medicine in 1908 for his contributions to immunology. This document outlines some of his most important findings, including those who led him to create his famous «magic bullets», precursors of current chemotherapeutic agents.

  14. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Vogel Ulla

    2010-08-01

    Full Text Available Abstract Background The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Methods Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion, *6, and CYP2D6 gene duplication. Results In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome.

  15. High throughput chemical library screening identifies a novel p110-δ inhibitor that potentiates the anti-myeloma effect of bortezomib.

    Science.gov (United States)

    Malek, Ehsan; Driscoll, James J

    2016-06-21

    Multiple myeloma (MM) remains an incurable plasma cell malignancy and drug resistance persists as the major cause of treatment failure leading to fatal outcomes. The phosphatidyl-inositol-3-kinase (PI3K) pathway is constitutively hyperactivated in MM to promote disease progression and drug resistance. While inhibiting PI3K induces apoptosis in MM and is predicted to increase tumor susceptibility to anticancer therapy, early-generation pan-PI3K inhibitors display poor clinical efficacy as well as intolerable side effects. Here, we found that PI3K activity is significantly upregulated in MM cell lines and patient tumor cells resistant to bortezomib and that the majority of PI3K activity in MM cells is dependent upon the p110-δ isoform. Genetic or pharmacologic inhibition of p110-δ substantially reduced myeloma viability and enhanced cellular sensitivity to bortezomib. Chemical library screens then identified a novel compound, DT97, that potently inhibited p110-δ kinase activity and induced apoptosis in MM cells. DT97 was evaluated in the NCI-60 panel of human cancer cell types and anticancer activity was greatest against MM, leukemia and lymphoma cells. Co-treatment with DT97 and bortezomib synergistically induced apoptosis in MM patient cells and overcame bortezomib-resistance. Although bone marrow stromal cells (BMSCs) promote MM growth, the pro-survival effects of BMSCs were significantly reduced by DT97 treatment. Co-treatment with bortezomib and DT97 reduced the growth of myeloma xenotransplants in murine models and prolonged host survival. Taken together, the results provide the basis for further clinical evaluation of p110-δ inhibitors, as monotherapy or in synergistic combinations, for the benefit of MM patients.

  16. Inhibition of activated receptor tyrosine kinases by Sunitinib induces growth arrest and sensitizes melanoma cells to Bortezomib by blocking Akt pathway.

    Science.gov (United States)

    Yeramian, Andree; Sorolla, Anabel; Velasco, Ana; Santacana, Maria; Dolcet, Xavier; Valls, Joan; Abal, Leandre; Moreno, Sara; Egido, Ramón; Casanova, Josep M; Puig, Susana; Vilella, Ramón; Llombart-Cussac, Antonio; Matias-Guiu, Xavier; Martí, Rosa M

    2012-02-15

    Despite the use of multiple therapeutic strategies, metastatic melanoma remains a challenge for oncologists. Thus, new approaches using combinational treatment may be used to try to improve the prognosis of this disease. In this report, we have analyzed the expression of receptor tyrosine kinases (RTKs) in melanoma specimens and in four metastatic melanoma cell lines. Both melanoma specimens and cell lines expressed RTKs, suggesting that they may represent eventual targets for multitargeted tyrosine kinase inhibitor, Suntinib. Sunitinib reduced the proliferation of two melanoma cell lines (M16 and M17) and increased apoptosis in one of them (M16). Moreover, the two metastatic melanoma cell lines harbored an activated receptor (PDGFRα and VEGFR, respectively), and Sunitinib suppressed the phosphorylation of the RTKs and their downstream targets Akt and ribosomal protein S6, in these two cell lines. Similar results were obtained when either PDGFRα or VEGFR2 expression was silenced by lentiviral-mediated short-hairpin RNA delivery in M16 and M17, respectively. To evaluate the interaction between Sunitinib and Bortezomib, median dose effect analysis using MTT assay was performed, and combination index was calculated. Bortezomib synergistically enhanced the Sunitinib-induced growth arrest in Sunitinib-sensitive cells (combination index < 1). Moreover, LY294002, a PI3K inhibitor, sensitized melanoma cells to Bortezomib treatment, suggesting that downregulation of phospho-Akt by Sunitinib mediates the synergy obtained by Bortezomib + Sunitinib cotreatment. Altogether, our results suggest that melanoma cells harboring an activated RTK may be clinically responsive to pharmacologic RTK inhibition by Sunitinib, and a strategy combining Sunitinib and Bortezomib, may provide therapeutic benefit. Copyright © 2011 UICC.

  17. Subcutaneous bortezomib in multiple myeloma patients induces similar therapeutic response rates as intravenous application but it does not reduce the incidence of peripheral neuropathy.

    Directory of Open Access Journals (Sweden)

    Jiri Minarik

    Full Text Available Subcutaneous (SC application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM patients treated using either intravenous (IV or subcutaneous (SC route of administration.During January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly - 63% or twice weekly - 27% in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration.The response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥ 3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN. PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥ 2 was present in 20% vs 18% and PN grade ≥ 3 was present in 6% vs 4%.We conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration.

  18. Neoadjuvant chemotherapy as ovarian cancer treatment

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Ottesen, Bent; Kehlet, Henrik

    2012-01-01

    INTRODUCTION: The traditional first-line treatment for patients with advanced ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is controversial as some authors report a potential benefit from the alternative treatment with neoadjuvant chemotherapy (NACT) and interval...... debulking surgery. The aim of this study was to investigate the use of NACT in Denmark in regard to increased use and regional differences. MATERIAL AND METHODS: Stage IIIC and IV ovarian cancer patients treated in the five Danish tertiary referral centres in the 2005-2010-period were included. The study...... is based on validated data from The Danish Gynaecological Cancer Database. RESULTS: Of the 1,367 eligible patients 1,069 were treated with PDS and 298 with NACT. In 2005-2007, 11% of patients were treated with NACT. In 2008-2010, this percentage had risen to 30% (p

  19. Neoadjuvant chemotherapy as ovarian cancer treatment

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Ottesen, Bent; Kehlet, Henrik;

    2012-01-01

    INTRODUCTION: The traditional first-line treatment for patients with advanced ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is controversial as some authors report a potential benefit from the alternative treatment with neoadjuvant chemotherapy (NACT) and interval...... debulking surgery. The aim of this study was to investigate the use of NACT in Denmark in regard to increased use and regional differences. MATERIAL AND METHODS: Stage IIIC and IV ovarian cancer patients treated in the five Danish tertiary referral centres in the 2005-2010-period were included. The study...... is based on validated data from The Danish Gynaecological Cancer Database. RESULTS: Of the 1,367 eligible patients 1,069 were treated with PDS and 298 with NACT. In 2005-2007, 11% of patients were treated with NACT. In 2008-2010, this percentage had risen to 30% (p

  20. Using Epigenetic Therapy to Overcome Chemotherapy Resistance.

    Science.gov (United States)

    Strauss, Julius; Figg, William D

    2016-01-01

    It has been known for decades that as cancer progresses, tumors develop genetic alterations, making them highly prone to developing resistance to therapies. Classically, it has been thought that these acquired genetic changes are fixed. This has led to the paradigm of moving from one cancer therapy to the next while avoiding past therapies. However, emerging data on epigenetic changes during tumor progression and use of epigenetic therapies have shown that epigenetic modifications leading to chemotherapy resistance have the potential to be reversible with epigenetic therapy. In fact, promising clinical data exist that treatment with epigenetic agents can diminish chemotherapy resistance in a number of tumor types including chronic myelogenous leukemia, colorectal, ovarian, lung and breast cancer. The potential for epigenetic-modifying drugs to allow for treatment of resistant disease is exciting and clinical trials have just begun to evaluate this area.

  1. Adjuvant chemotherapy for advanced endometrial cancer.

    Science.gov (United States)

    Galaal, Khadra; Al Moundhri, Mansour; Bryant, Andrew; Lopes, Alberto D; Lawrie, Theresa A

    2014-05-15

    Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective. To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV). We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials. Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer. Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software. We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data

  2. Metronomic chemotherapy regimens in oncology

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2016-01-01

    Full Text Available Metronomic chemotherapy implies the regular use of cytotoxic agents in doses much smaller than the maximum tolerable doses for a long time. Preclinical experiments show that this treatment option has a many-sided (antiangiogenic, immunostimulating, and direct cytotoxic effect on tumor. Moreover, this approach has gained the widest acceptance in treating patients with metastatic breast cancer in clinical practice. By taking into account the high activity of angiogenesis in colon cancer progression, it is interesting to study the impact of metronomic chemotherapy regimens for this nosological entity as well. This literature review considers not only the history of metronomic chemotherapy, the mechanisms of action, and a range of drugs having an antitumor effect in the metronomic regimens, but also analyzes clinical trials of metronomic chemotherapy regimens in patients with metastatic colon cancer.

  3. Managing Chemotherapy Side Effects: Constipation

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Constipation Take these steps: Eat high-fiber foods such as: ● ● Whole-grain breads and cereals ● ● Fruits and vegetables ● ● Nuts and seeds ...

  4. INTERVENTION CHEMOTHERAPY IN COMPREHENSIVE TREATMENT OF ADVANCED NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the use of interventional chemotherapy in comprehensive treatment for advanced nasopharyngeal carcinoma. Methods: Interventional chemotherapy with multi-drugs including cisplatin (DDP) 100 mg, 5-fluorouracil (5-FU) 1000 mg and bleomycin (BLM) 16 mg was used to treat 30 cases with advanced nasopharyngeal carcinoma before radiotherapy. 50 cases that received radiotherapy alone were used as a control group. The methods, time and dose schedule of radiotherapy were similar in the two groups. Results: The primary lesions in 16 cases and the cervical lymph nodes in 12 cases were reduced in size after interventional chemotherapy. Radiation doses of those in complete response in their primary lesion and cervical lymph nodes were lower than that of the control group (P<0.05). The complete response rate of study group was 83.3% and that of control group was 72.0% (P<0.05). Conclusion: Interventional chemotherapy plus radiotherapy is a valuable treatment method in advanced nasopharyngeal carcinoma.

  5. Clinical overview of metronomic chemotherapy in breast cancer.

    Science.gov (United States)

    Munzone, Elisabetta; Colleoni, Marco

    2015-11-01

    Over 15 years ago, low-dose metronomic chemotherapy was shown to induce disease control in patients with advanced-stage breast cancer with a lower incidence of adverse events compared with conventional maximum tolerated dose chemotherapy. Good response rates have been seen in heavily pre-treated patients for whom limited treatment options are available. Most patients prefer oral therapy and metronomic chemotherapy is a convenient alternative in patients with advanced-stage disease in which minimal toxicity and good tumour control are the overall aims of treatment. The addition of metronomic protocols to standard neoadjuvant chemotherapy regimens has produced promising pathological complete response rates. Ongoing trials including the SYSUCC-001 trial in patients with triple-negative breast cancer and the IBCSG 22-00 trial that is assessing a cyclophosphamide-methotrexate maintenance regimen after standard adjuvant therapy in hormone receptor-negative disease, will clarify the value of adding this approach to conventional therapies. The low cost associated with metronomic chemotherapy represents an opportunity for the utilization of this treatment option, especially in developing countries, and poses a challenge for the launch of large trials sponsored by industry. Using breast cancer as the principal example, we discuss the key clinical advances in this area, including new trial design, appropriate patient and end point selection, as well as the evolving rationale for metronomic chemotherapy combinations.

  6. Chemotherapy-induced sclerosing cholangitis

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    Sandrasegaran, K.; Alazmi, W.M.; Tann, M.; Fogel, E.L.; McHenry, L.; Lehman, G.A

    2006-08-15

    Aim: To review the computed tomography (CT), magnetic resonance imaging (MRI) and cholangiographic findings of chemotherapy-induced sclerosing cholangitis (CISC). Methods: Between January 1995 and December 2004, 11 patients in the endoscopic retrograde cholangiography database were identified with CISC. Twelve CT, four MRI, 69 endoscopic and nine antegrade cholangiographic studies in these patients were reviewed. Serial change in appearance and response to endoscopic treatment were recorded. Results: CISC showed segmental irregular biliary dilatation with strictures of proximal extrahepatic bile ducts. The distal 5 cm of common bile duct was not affected in any patient. CT and MRI findings included altered vascular perfusion of one or more liver segments, liver metastases or peritoneal carcinomatosis. Biliary strictures needed repeated stenting in 10 patients (mean: every 4.7 months). Cirrhosis (n = 1) or confluent fibrosis (n = 0) were uncommon findings. Conclusion: CISC shares similar cholangiographic appearances to primary sclerosing cholangitis (PSC). Unlike PSC, biliary disease primarily involved ducts at the hepatic porta rather than intrahepatic ducts. Multiphasic contrast-enhanced CT or MRI may show evidence of perfusion abnormalities, cavitary liver lesions, or metastatic disease.

  7. [Buccal manifestations in patients submitted to chemotherapy].

    Science.gov (United States)

    Hespanhol, Fernando Luiz; Tinoco, Eduardo Muniz Barretto; Teixeira, Henrique Guilherme de Castro; Falabella, Márcio Eduardo Vieira; Assis, Neuza Maria de Souza Picorelli

    2010-06-01

    Several changes in the oral cavity due to chemotherapy can be observed and can lead to important systemic complications, increasing the time of the patient in hospital and the costs of the treatment as well as affect the quality of life of the patients. The aim of this study was to assess the oral manifestation in patients treated with chemotherapy according to sex, age and tumor type. Data was collected in an oncology hospital in Juiz de Fora, Minas Gerais State, from patients' records that were submitted to oncologic treatment. It was possible to verify that mucositis, associated or not to other type of lesions, was the most common lesion in both sex of all ages (15.5%). Xerostomia and other lesions, such as Candida infection and aphthous lesions, were also present. It is possible to improve the quality of life of the patient during and after anti-neoplastic therapies through a protocol of odontological assistance that includes changes of the oral environment previous to chemotherapy such as profilaxis, caries removal, treatment of periodontal and periapical lesions, oral hygiene instructions, diet orientation and laser therapy. It is very important the insertion of the dentist in the oncologic medical team for the early diagnosis of the oral manifestation and follow-up during treatment time.

  8. Effect of systemic vein chemotherapy and internal iliac arterial embolization infusion chemotherapy on angiogenesis and malignant degree of cervical cancer

    Institute of Scientific and Technical Information of China (English)

    Gang Chen

    2016-01-01

    Objective:To analyze the effect of systemic vein chemotherapy and internal iliac arterial chemoembolization on angiogenesis and malignant degree of cervical cancer.Methods: A total of 108 cases of patients with middle and advanced cervical cancer were included in the research, and the time range of the research was from February 2014 to December 2015. According to different means of chemotherapy, included patients were divided into observation group 54 cases and control group 54 cases, control group received systemic vein chemotherapy, observation group received internal iliac arterial infusion chemotherapy and embolization treatment, and then differences in the levels of angiogenesis-related indicators, blood flow parameters within tumor, serum illness-related indicators, cervical tumor tissue proliferation-related indicators,etc. were compared between two groups after treatment.Results:Serum VEGFR-2, HIF-1α, vWF and Lam values of observation group after chemotherapy were lower than those of control group; PI, VI, FI, VFI and Vmax values of observation group after treatment were lower than those of control group while RI value was higher than that of control group; serum SCC-Ag, TK1, HE4, CYFRA21-1, IGF-Ⅱ and Gal-9 values of observation group after chemotherapy were lower than those of control group; miR-26b, SCD-1, Cyclin D1 and TLR4 protein expression levels in tumor tissue of observation group after treatment were lower than those of control group while miR-99b protein expression level was higher than that of control group.Conclusions: Internal iliac arterial infusion chemotherapy and embolization can significantly decrease tumor angiogenesis and inhibit tumor cell proliferation, and it is a perfect means of interventional chemotherapy.

  9. To Explore the Effect of Trinity Comprehensive Treatment Including Abdominal Cavity Perfusion Chemotherapy, RF Deep Thermal Therapy and the Immune Therapy in the Treatment of Advanced Ovarian Cancer%腹腔热灌注化疗、体外射频深部热疗、免疫治疗三位一体综合治疗在晚期卵巢癌中的临床应用

    Institute of Scientific and Technical Information of China (English)

    王俊芳; 崔萍; 毛莉; 张延志; 程丽娟

    2015-01-01

    Objective To evaluate the effect of the trinity comprehensive treatment including the peritoneal cavity hot perfusion chemotherapy, the deep in vitro rf heat therapy and the immune therapy of the treatment for the patients with advanced ovarian cancer.Methods42 cases of patients with advanced epithelial ovarian cancer in our department were selected as the research object. The patients were randomly divided into treatment group and intraperitoneal chemotherapy group. The indicators including the ascites control, KPS score after treatment, CA125 half-life and the incidence of bone marrow suppression were analyzed. Results42 cases of patients had complete 6 courses of chemotherapy. The results of the indicators were: control of ascites (90.9%: 90.9%), KPS score comparison after treatment (31.8%: 60.0%), CA125 half-life (17.3 +/- 5.1 days, 13.4 +/- 4.5 days) and the incidence of bone marrow suppression (18.2%: 40.0%). Conclusion The trinity comprehensive therapy "Hot perfusion chemotherapy combined with abdominal cavity with deep in vitro rf heat therapy, immune therapy" in the treatment of advanced ovarian cancer can signiifcantly improve the ascites control, increase the KPS score, shorten the CA125 half-life and reduce the incidence of bone marrow suppression. This method can improve the body immunity, promote hemopoietic function which is a kind of effective treatment for advanced ovarian cancer. It can improve the survival rate and life quality of advanced ovarian cancer patients.%目的:评价腹腔热灌注化疗联合体外射频深部热疗、免疫治疗三位一体综合治疗在晚期卵巢癌中的临床应用。方法将我科收治晚期上皮性卵巢癌患者42例作为研究对象。将其随机分为综合治疗组和腹腔化疗组。分析两组腹水控制率、治疗后KPS评分、CA125半衰期、骨髓抑制发生率。结果42例病人均完成全部6疗程化疗,两组观察指标分别是:腹水控制率(90.9%:75.0%

  10. 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

  11. 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...

  12. Present situation and development of chemotherapy of nasopharyngeal carcinoma%鼻咽癌化疗现状及进展

    Institute of Scientific and Technical Information of China (English)

    冼献清; 谢民强; 江刚

    2013-01-01

    Chemotherapy is one of main treatments for nasopharyngeal carcinoma (NPC) except radiation therapy. Improving and optimizing chemotherapeutic regimen are helpful to improve the therapeutic effects and reduce side effects. At present, concurrent chemoradiotherapy still is the standard treatment for advanced nasopharyngeal carcinoma. Induced chemotherapy has been shown superiority, but the effect of adjuvant chemotherapy needs further study. This paper analyzed the superior and inferior, effect and side effect of all kinds of chemotherapeutic methods or scheme including induced chemotherapy,concurrent chemotherapy, adjuvant chemotherapy and palliative chemotherapy and introduced simply the mechanism and clinical effect of new drugs of anticancer. It was hoped to offer some reference for the selection of chemotherapy for NPC.

  13. The Impact of Breast Reconstruction on the Delivery of Chemotherapy

    Science.gov (United States)

    Alderman, Amy K.; Collins, E. Dale; Schott, Anne; Hughes, Melissa E.; Ottesen, Rebecca A.; Theriault, Richard L.; Wong, Yu-Ning; Weeks, Jane C.; Niland, Joyce C.; Edge, Stephen B.

    2009-01-01

    Purpose Our purpose was to evaluate the impact of post-mastectomy breast reconstruction on the timing of chemotherapy. Methods We included Stage I–III breast cancer patients from eight National Comprehensive Cancer Network institutions for whom guidelines recommended chemotherapy. Surgery type was categorized as breast conserving surgery (BCS), mastectomy alone, mastectomy with immediate reconstruction (M+IR), or mastectomy with delayed reconstruction (M+DR). A Cox regression analysis was used to assess the association between surgery type and timing of chemotherapy initiation. Results Of the 3,643 patients, only 5.1% received it ≥ 8 weeks from surgery. In the multivariate analysis, higher stage, Caucasian and Hispanic race/ethnicity, lower body-mass index and absence of comorbid conditions were all significantly associated with earlier time to chemotherapy. There was also significant interaction between age, surgery and chemotherapy delivery. Among women breast reconstruction does not appear to lead to omission of chemotherapy, but it is associated with a modest, but statistically significant, delay in initiating treatment. For most, it is unlikely that this delay has any clinical significance. PMID:20143440

  14. [Efficacy of Levofloxacin Hydrate in Febrile Neutropenia for Outpatient Chemotherapy].

    Science.gov (United States)

    Inagaki, Manato; Sato, Junya; Nihei, Satoru; Kashiwaba, Masahiro; Kudo, Kenzo

    2016-05-01

    Management of febrile neutropenia (FN) is important for the safety of patients undergoing outpatient chemotherapy. Oral antimicrobials are usually prescribed as the initial treatment for FN, and outpatients are instructed to begin medication prior to chemotherapy. However, the effectiveness and safety of the use of these oral antibiotics have not yet been established. In this study, we investigated the effectiveness and safety of levofloxacin hydrate (LVFX) for breast cancer patients with FN, and the factors associated with the onset of FN in 134 breast cancer patients who underwent chemotherapy including the anticancer drug anthracycline (total, 513 courses), in an outpatient chemotherapy department. The effectiveness and safety of LVFX were defined respectively as defervescence within 5 days, and the appearance of side effects such as diarrhea and rashes. Fever was observed in 89 (66%) of the 134 patients, and during 164 (32%) of 513 courses. Defervescence was observed with the LVFX medication in 149 (93%) of 160 courses. The primary side effect was the development of rashes, and only 2 (1%) of the 160 courses were discontinued. Onset of stomatitis during chemotherapy was observed as a factor of FN (odds ratio: 1.36, p<0.05). Our results suggest that the use of LVFX according to the patients' discretion might be an effective and safe option for the management of FN during outpatient chemotherapy.

  15. The effects of a six-week supervised multimodal exercise intervention during chemotherapy on cancer-related fatigue

    DEFF Research Database (Denmark)

    Andersen, Christina; Rørth, Mikael; Ejlertsen, Bent

    2013-01-01

    Cancer related fatigue (CRF) is a common problem for cancer patients across diagnoses during chemotherapy and is associated with physical inactivity, lower functional level and lack of energy. Few RCT exercise intervention studies have included cancer patients undergoing chemotherapy. The objecti...... of this study is to evaluate whether a six-week supervised multimodal exercise intervention, adjunct to chemotherapy and standard care, can reduce the patient's CRF level.......Cancer related fatigue (CRF) is a common problem for cancer patients across diagnoses during chemotherapy and is associated with physical inactivity, lower functional level and lack of energy. Few RCT exercise intervention studies have included cancer patients undergoing chemotherapy. The objective...

  16. Quality of life assessment in dogs and cats receiving chemotherapy

    DEFF Research Database (Denmark)

    Vøls, Kåre Kryger; Heden, Martin A.; Kristensen, Annemarie Thuri

    2017-01-01

    comparative analysis of published papers on the effects of chemotherapy on QoL in dogs and cats were conducted. This was supplemented with a comparison of the parameters and domains used in veterinary QoL-assessments with those used in the Pediatric Quality of Life Inventory (PedsQL™) questionnaire designed...... to assess QoL in toddlers. Each of the identified publications including QoL-assessment in dogs and cats receiving chemotherapy applied a different method of QoL-assessment. In addition, the veterinary QoL-assessments were mainly focused on physical clinical parameters, whereas the emotional (6/11), social...... (4/11) and role (4/11) domains were less represented. QoL-assessment of cats and dogs receiving chemotherapy is in its infancy. The most commonly reported method to assess QoL was questionnaire based and mostly included physical and clinical parameters. Standardizing and including a complete range...

  17. Quality of life assessment in dogs and cats receiving chemotherapy

    DEFF Research Database (Denmark)

    Vøls, Kåre K.; Heden, Martin A.; Kristensen, Annemarie Thuri;

    2016-01-01

    comparative analysis of published papers on the effects of chemotherapy on QoL in dogs and cats were conducted. This was supplemented with a comparison of the parameters and domains used in veterinary QoL-assessments with those used in the Pediatric Quality of Life Inventory (PedsQL™) questionnaire designed...... to assess QoL in toddlers. Each of the identified publications including QoL-assessment in dogs and cats receiving chemotherapy applied a different method of QoL-assessment. In addition, the veterinary QoL-assessments were mainly focused on physical clinical parameters, whereas the emotional (6/11), social...... (4/11) and role (4/11) domains were less represented. QoL-assessment of cats and dogs receiving chemotherapy is in its infancy. The most commonly reported method to assess QoL was questionnaire based and mostly included physical and clinical parameters. Standardizing and including a complete range...

  18. Down-regulation of 11β-hydroxysteroid dehydrogenase type 2 by bortezomib sensitizes Jurkat leukemia T cells against glucocorticoid-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Yi Tao

    Full Text Available 11β-Hydroxysteroid dehydrogenases type 2 (11β-HSD2, a key regulator for pre-receptor metabolism of glucocorticoids (GCs by converting active GC, cortisol, to inactive cortisone, has been shown to be present in a variety of tumors. But its expression and roles have rarely been discussed in hematological malignancies. Proteasome inhibitor bortezomib has been shown to not only possess antitumor effects but also potentiate the activity of other chemotherapeutics. In this study, we demonstrated that 11β-HSD2 was highly expressed in two GC-resistant T-cell leukemic cell lines Jurkat and Molt4. In contrast, no 11β-HSD2 expression was found in two GC-sensitive non-hodgkin lymphoma cell lines Daudi and Raji as well as normal peripheral blood T cells. Inhibition of 11β-HSD2 by 11β-HSD inhibitor 18β-glycyrrhetinic acid or 11β-HSD2 shRNA significantly increased cortisol-induced apoptosis in Jurkat cells. Additionally, pretreatment of Jurkat cells with low-dose bortezomib resulted in increased cellular sensitivity to GC as shown by elevated induction of apoptosis, more cells arrested at G1 stage and up-regulation of GC-induced leucine zipper which is an important mediator of GC action. Furthermore, we clarified that bortezomib could dose-dependently inhibit 11β-HSD2 messenger RNA and protein levels as well as activity (cortisol-cortisone conversion through p38 mitogen-activated protein kinase signaling pathway. Therefore, we suggest 11β-HSD2 is, at least partially if not all, responsible for impaired GC suppression in Jurkat cells and also indicate a novel mechanism by which proteasome inhibitor bortezomib may influence GC action.

  19. Bortezomib and Fenretinide Induce Synergistic Cytotoxicity in Mantle Cell Lymphoma Via Apoptosis, Cell Cycle Dysregulation, and IκBα Kinase Down-regulation

    Science.gov (United States)

    Cowan, Andrew J.; Frayo, Shani L.; Press, Oliver W.; Palanca-Wessels, Maria C.; Pagel, John M.; Green, Damian J.; Gopal, Ajay K.

    2015-01-01

    Background Mantle cell lymphoma (MCL) remains incurable for most patients and proteasome inhibitors like bortezomib induce responses in a minority of patients with relapsed disease. Fenretinide is a retinoid that has shown preclinical activity in B-cell lymphomas. We hypothesized that these agents could yield augmented anti-tumor activity. Methods Mantle cell lymphoma lines (Granta-519, Jeko-1, Rec-1) were treated with escalating concentrations of bortezomib and fenretinide singly and in combination. Cytotoxicity was assessed using the MTT assay. Flow cytometric methods assessed apoptosis and necrosis with annexin V-FITC/propidium iodide and G1 and G2 cell cycle changes with DAPI staining. Changes in Cyclin D1, Cyclin B, IκBα, and IKKα expression were quantified by Western blot. Results Cytotoxicity was mediated via apoptosis; both agents showed observed vs expected cytotoxicity in Granta-519 of 92.2% vs 55.1%, in Jeko-1 of 87.6% vs 36.3%, and in Rec-1 of 63.2% vs 29.8%. Isobolographic analysis confirmed synergy in Jeko-1 and Rec-1. Bortezomib induced G2 phase arrest with a 1.7 fold-increase over control, and fenretinide resulted in G1 phase arrest, with an increase of 1.3 fold over control. In combination G2 phase arrest predominated, with a 1.4 fold-increase compared to control, and reduced expression of Cyclin D1 to 24%, Cyclin B to 52% and 64%, Cyclin D3 to 25% and 43%, IκBα to 23% and 46%, and IκBα kinase to 34% and 44%. Conclusions Bortezomib and fenretinide exhibit synergistic cytotoxicity against MCL cell lines. This activity is mediated by IκBα kinase modulation, decreased cyclin expression, cell cycle dysregulation, and apoptotic cell death. PMID:26237500

  20. Good clinical activity and favorable toxicity profile of once weekly bortezomib, fotemustine, and dexamethasone (B-MuD) for the treatment of relapsed multiple myeloma.

    Science.gov (United States)

    Mangiacavalli, Silvia; Pochintesta, Lara; Pascutto, Cristiana; Cocito, Federica; Pompa, Alessandra; Cazzola, Mario; Corso, Alessandro

    2013-02-01

    Since multiple myeloma (MM) is still not-curable, the management of relapse remains challenging. Given the known efficacy of alkylating agents in MM, we conducted a phase I/II study to test a new three drug combination in which Fotemustine (Muphoran), an alkylating agent of nitrosurea family, was added to bortezomib + dexamethasone backbone (B-MuD) for the treatment of MM relapsed patients. Fotemustine was administered at two dose levels (80-100 mg/m² i.v.) on day 1. The original 21-day schedule was early amended for extra-hematological toxicity and a 35-day schedule was adopted (Bortezomib 1.3 mg/m² i.v. on days 1, 8, 15, and 22, Dexamethasone 20 mg i.v. on days 1, 8, 15, and 22) for a total of six courses. Twenty-four patients were enrolled. The maximum tolerated dose of Fotemustine was 100 mg/m². The overall response rate was of 62% (CR 8%, VGPR 33%, and PR 21%). The median OS was 28.5 months, the median progression-free survival (PFS) was 19.1 months. B-MuD resulted effective in patients previous exposed to bortezomib without difference of response (P = 0.25) and PFS (P = 0.87) when compared to bortezomib-naive patients. Thrombocytopenia was the most common AE overall. In conclusion, B-MuD is an effective and well tolerated combination in relapsed MM patients even in advanced disease phase.

  1. Variation in drug sensitivity of malignant mesothelioma cell lines with substantial effects of selenite and bortezomib, highlights need for individualized therapy.

    Directory of Open Access Journals (Sweden)

    Adam Szulkin

    Full Text Available BACKGROUND: Malignant mesothelioma cells have an epithelioid or sarcomatoid morphology, both of which may be present in the same tumor. The sarcomatoid phenotype is associated with worse prognosis and heterogeneity of mesothelioma cells may contribute to therapy resistance, which is often seen in mesothelioma. This study aimed to investigate differences in sensitivity between mesothelioma cell lines to anti-cancer drugs. We studied two novel drugs, selenite and bortezomib and compared their effect to four conventional drugs. We also investigated the immunoreactivity of potential predictive markers for drug sensitivity; Pgp, MRP-1, ERCC1, RRM1, TS, xCT and proteasome 20S subunit. MATERIALS AND METHODS: We treated six mesothelioma cell lines with selenite, bortezomib, carboplatin, pemetrexed, doxorubicin or gemcitabine as single agents and in combinations. Viability was measured after 24 and 48 hours. Immunocytochemistry was used to detect predictive markers. RESULTS: As a single agent, selenite was effective on four out of six cell lines, and in combination with bortezomib yielded the greatest response in the studied mesothelioma cell lines. Cells with an epithelioid phenotype were generally more sensitive to the different drugs than the sarcomatoid cells. Extensive S-phase arrest was seen in pemetrexed-sensitive cell lines. MRP-1 predicted sensitivity of cell lines to treatment with carboplatin and xCT predicted pemetrexed effect. CONCLUSIONS: The observed heterogeneity in sensitivity of mesothelioma cell lines with different morphology highlights the need for more individualized therapy, requiring development of methods to predict drug sensitivity of individual tumors. Selenite and bortezomib showed a superior effect compared to conventional drugs, motivating clinical testing of these agents as future treatment regime components for patients with malignant mesothelioma.

  2. Anaphylaxis to chemotherapy and monoclonal antibodies.

    Science.gov (United States)

    Castells, Mariana C

    2015-05-01

    Hypersensitivity reactions are increasingly prevalent, although underrecognized and underreported. Platins induce immunoglobulin E-mediated sensitization; taxenes and some monoclonal antibodies can induce reactions at first exposure. Severe hypersensitivity can preclude first-line therapy. Tryptase level at the time of a reaction is a useful diagnostic tool. Skin testing provides a specific diagnosis. Newer tests are promising diagnostic tools to help identify patients at risk before first exposure. Safe management includes rapid drug desensitization. This review provides information regarding the scope of hypersensitivity and anaphylactic reactions induced by chemotherapy and biological drugs, as well as diagnosis, management, and treatment options.

  3. Transient focal liver scan defects in children receiving chemotherapy (pseudometastases): work in progress

    Energy Technology Data Exchange (ETDEWEB)

    Abramson, S.J.; Barash, F.S.; Seldin, D.W.; Berdon, W.E.

    1984-03-01

    Three pediatric patients with tumors (two rhabdomyosarcoma, one Wilms tumor) had significant focal defects on Tc-99m sulfur colloid scans while receiving chemotherapy (all three had received chemotherapy, including actinomycin D, within ten days prior to scanning). In all three, the defects resolved spontaneously; one biopsy showed fibrosis of a mild degree. The finding of defects on liver scans of pediatric patients receiving chemotherapy must not be automatically assumed to be metastatic disease; the changes may relate to hepatic response to recently administered chemotherapy.

  4. Chemotherapy-Induced Perforation of Gastric Burkitt Lymphoma; A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Shahram Bolandparvaz

    2014-07-01

    Full Text Available Burkitt lymphoma of stomach is among the most rapidly growing gastric cancersassociated with several gasterointestinal symptoms including hematemesis, anorexia, vomiting and etc. Gastric perforation in patients with Burkitt lymphoma of stomach is a very rare condition especially after chemotherapy. We herein present a 21-year old man who was kwon case of gastric Burkitt lymphoma who had undergone chemotherapy and presented with acute onset gastric pain and tenderness. He was diagnosed to suffer from perforated gastric lymphoma for which laparotomy and total gastrectomy was performed. Treatment was continued by chemotherapy. Closed observation is thus recommended for those patients with gastric Burkitt lymphoma undergoing chemotherapy.

  5. Combination of bortezomib and mitotic inhibitors down-modulate Bcr-Abl and efficiently eliminates tyrosine-kinase inhibitor sensitive and resistant Bcr-Abl-positive leukemic cells.

    Science.gov (United States)

    Bucur, Octavian; Stancu, Andreea Lucia; Goganau, Ioana; Petrescu, Stefana Maria; Pennarun, Bodvael; Bertomeu, Thierry; Dewar, Rajan; Khosravi-Far, Roya

    2013-01-01

    Emergence of resistance to Tyrosine-Kinase Inhibitors (TKIs), such as imatinib, dasatinib and nilotinib, in Chronic Myelogenous Leukemia (CML) demands new therapeutic strategies. We and others have previously established bortezomib, a selective proteasome inhibitor, as an important potential treatment in CML. Here we show that the combined regimens of bortezomib with mitotic inhibitors, such as the microtubule-stabilizing agent Paclitaxel and the PLK1 inhibitor BI2536, efficiently kill TKIs-resistant and -sensitive Bcr-Abl-positive leukemic cells. Combined treatment activates caspases 8, 9 and 3, which correlate with caspase-induced PARP cleavage. These effects are associated with a marked increase in activation of the stress-related MAP kinases p38MAPK and JNK. Interestingly, combined treatment induces a marked decrease in the total and phosphorylated Bcr-Abl protein levels, and inhibits signaling pathways downstream of Bcr-Abl: downregulation of STAT3 and STAT5 phosphorylation and/or total levels and a decrease in phosphorylation of the Bcr-Abl-associated proteins CrkL and Lyn. Moreover, we found that other mitotic inhibitors (Vincristine and Docetaxel), in combination with bortezomib, also suppress the Bcr-Abl-induced pro-survival signals and result in caspase 3 activation. These results open novel possibilities for the treatment of Bcr-Abl-positive leukemias, especially in the imatinib, dasatinib and nilotinib-resistant CML cases.

  6. The Applicability of the International Staging System in Chinese Patients with Multiple Myeloma Receiving Bortezomib or Thalidomide-Based Regimens as Induction Therapy: A Multicenter Analysis

    Directory of Open Access Journals (Sweden)

    Jing Lu

    2015-01-01

    Full Text Available The International Staging System (ISS is the most important prognostic system for multiple myeloma (MM. It was identified in the era of conventional agents. The outcome of MM has significantly changed by novel agents. Thus the applicability of ISS system in the era of novel agents in Chinese patients needs to be demonstrated. We retrospectively analyzed the clinical outcomes and prognostic significance of ISS system in 1016 patients with newly diagnosed multiple myeloma in Chinese patients between 2008 and 2012, who received bortezomib- or thalidomide-based regimens as first-line therapy. The median overall survival (OS of patients for ISS stages I/II/III was not reached/55.4 months/41.7 months (p<0.001, and the median progression-free survival (PFS was 30/29.5/25 months (p=0.072, respectively. Statistically significant difference in survival was confirmed among three ISS stages in thalidomide-based group, but not between ISS stages I and II in bortezomib-based group. These findings suggest that ISS system can predict the survival in the era of novel agents in Chinese MM patients, and bortezomib may have the potential to partially overcome adverse effect of risk factors on survival, especially in higher stage of ISS system.

  7. Fertility preservation after chemotherapy for Hodgkin lymphoma

    NARCIS (Netherlands)

    van der Kaaij, Marleen A. E.; van Echten-Arends, Jannie; Simons, Arnold H. M.; Kluin-Nelemans, Hanneke C.

    2010-01-01

    Treatment for Hodgkin lymphoma can negatively affect fertility. This review summarizes data on fertility after chemotherapy in adult patients. Alkylating chemotherapy, especially if containing procarbazine and/or cyclophosphamide, is most harmful to gonadal functioning. Alkylating regimens cause pro

  8. Chemotherapy of human african trypanosomiasis.

    Science.gov (United States)

    Bacchi, Cyrus J

    2009-01-01

    Human Africa trypanosomiasis is a centuries-old disease which has disrupted sub-Saharan Africa in both physical suffering and economic loss. This article presents an update of classic chemotherapeutic agents, in use for >50 years and the recent development of promising non-toxic combination chemotherapy suitable for use in rural clinics.

  9. Chemotherapy of Human African Trypanosomiasis

    Directory of Open Access Journals (Sweden)

    Cyrus J. Bacchi

    2009-01-01

    Full Text Available Human Africa trypanosomiasis is a centuries-old disease which has disrupted sub-Saharan Africa in both physical suffering and economic loss. This article presents an update of classic chemotherapeutic agents, in use for >50 years and the recent development of promising non-toxic combination chemotherapy suitable for use in rural clinics.

  10. Managing Chemotherapy Side Effects: Diarrhea

    Science.gov (United States)

    ... such as Pedialyte ® ••Tea (without caffeine) ••Water ••Applesauce ••Bananas ••Crackers ••Cream of wheat or rice cereal ••Eggs •• ... has a series of 18 Chemotherapy Side Effects Sheets at: www.cancer.gov/chemo-side-effects

  11. Cost-effectiveness of lenalidomide plus dexamethasone vs. bortezomib plus melphalan and prednisone in transplant-ineligible U.S. patients with newly-diagnosed multiple myeloma.

    Science.gov (United States)

    Usmani, S Z; Cavenagh, J D; Belch, A R; Hulin, C; Basu, S; White, D; Nooka, A; Ervin-Haynes, A; Yiu, W; Nagarwala, Y; Berger, A; Pelligra, C G; Guo, S; Binder, G; Gibson, C J; Facon, T

    2016-01-01

    To conduct a cost-effectiveness assessment of lenalidomide plus dexamethasone (Rd) vs bortezomib plus melphalan and prednisone (VMP) as initial treatment for transplant-ineligible patients with newly-diagnosed multiple myeloma (MM), from a U.S. payer perspective. A partitioned survival model was developed to estimate expected life-years (LYs), quality-adjusted LYs (QALYs), direct costs and incremental costs per QALY and LY gained associated with use of Rd vs VMP over a patient's lifetime. Information on the efficacy and safety of Rd and VMP was based on data from multinational phase III clinical trials and a network meta-analysis. Pre-progression direct costs included the costs of Rd and VMP, treatment of adverse events (including prophylaxis) and routine care and monitoring associated with MM. Post-progression direct costs included costs of subsequent treatment(s) and routine care and monitoring for progressive disease, all obtained from published literature and estimated from a U.S. payer perspective. Utilities were obtained from the aforementioned trials. Costs and outcomes were discounted at 3% annually. Relative to VMP, use of Rd was expected to result in an additional 2.22 LYs and 1.47 QALYs (discounted). Patients initiated with Rd were expected to incur an additional $78,977 in mean lifetime direct costs (discounted) vs those initiated with VMP. The incremental costs per QALY and per LY gained with Rd vs VMP were $53,826 and $35,552, respectively. In sensitivity analyses, results were found to be most sensitive to differences in survival associated with Rd vs VMP, the cost of lenalidomide and the discount rate applied to effectiveness outcomes. Rd was expected to result in greater LYs and QALYs compared with VMP, with similar overall costs per LY for each regimen. Results of this analysis indicated that Rd may be a cost-effective alternative to VMP as initial treatment for transplant-ineligible patients with MM, with an incremental cost-effectiveness ratio

  12. Chemotherapy-associated recurrent pneumothoraces in lymphangioleiomyomatosis.

    LENUS (Irish Health Repository)

    Kelly, Emer

    2012-02-01

    Lymphangioleiomyomatosis is a rare cause of pneumothorax in women. We present the case of a 48-year-old woman with lymphangioleiomyomatosis, who had never had a pneumothorax prior to commencing chemotherapy for breast cancer. During chemotherapy she developed 3 pneumothoraces and 2 episodes of pneumomediastinum. We suggest that the pneumothoraces were caused by the chemotherapy. To our knowledge, this is the first reported case of chemotherapy triggering pneumothoraces in a woman with lymphangioleiomyomatosis.

  13. Chemotherapy and You: Support for People with Cancer

    Science.gov (United States)

    ... Terms Blogs and Newsletters Health Communications Publications Reports Chemotherapy and You: Support for People With Cancer Chemotherapy ... ePub This booklet covers: Questions and answers about chemotherapy. Answers common questions, such as what chemotherapy is ...

  14. Adjuvant chemotherapy for early-stage cervical cancer.

    Science.gov (United States)

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-04-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  15. Thalidomide-based induction regimens are as effective as bortezomib-based regimens in elderly patients with multiple myeloma with cereblon expression.

    Science.gov (United States)

    Jung, Sung-Hoon; Choi, Hyun-Jung; Shin, Myung-Geun; Lee, Seung-Shin; Hwang, Eu Chang; Jung, Tae-Young; Cho, Min-Seok; Yang, Deok-Hwan; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Kim, Hyeoung-Joon; Lee, Je-Jung

    2016-10-01

    Cereblon (CRBN) has been identified as a primary target of immunomodulatory drugs and is considered a biomarker for the prediction of outcomes after thalidomide- or lenalidomide-based treatments. In this study, we evaluated CRBN expression in bone marrow (BM) tissue at diagnosis and investigated the relationship between CRBN expression and treatment outcomes after thalidomide- or bortezomib-based front-line therapies in 89 elderly patients with multiple myeloma (MM). CRBN expression at the time of diagnosis was evaluated with immunohistochemical (IHC) staining for myeloma cells in paraffin wax-embedded BM tissue. CRBN-immunostained slides were scored by intensity and diffuseness, and a total score of >6 was defined as CRBN-positive (CRBN(+)). Thirty-eight patients (45.2 %) were CRBN(+). Among patients treated with thalidomide-based regimens, CRBN(+) patients showed a better treatment response than did CRBN-negative patients (35.0 vs. 11.8 % complete response rate, respectively; HR = 4.038, P = 0.137). During a median follow-up of 31.8 months, patients treated with bortezomib-based regimens had a longer time to progression (TTP) than did patients treated with thalidomide-based regimens (15.6 vs. 13.2 months, respectively; P = 0.047), but early mortality occurred frequently in patients treated with bortezomib-based regimens. Additionally, there was no significant difference in survival outcomes between thalidomide- and bortezomib-based regimens in CRBN(+) patients (median TTP, 13.8 vs. 15.6 months, respectively; P = 0.842 and median OS, 39.3 vs. 30.1 months, respectively; P = 0.074). These data suggest that thalidomide-based regimens are as effective as bortezomib-based regimens in elderly patients with MM who are CRBN(+). Thus, CRBN positivity, by IHC staining, may be useful in deciding appropriate treatment options in elderly patients with MM.

  16. 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

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review th...

  17. 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

  18. CR4056, a new analgesic I2 ligand, is highly effective against bortezomib-induced painful neuropathy in rats

    Directory of Open Access Journals (Sweden)

    Meregalli C

    2012-06-01

    Full Text Available Cristina Meregalli,1 Cecilia Ceresa,1 Annalisa Canta,1 Valentina Alda Carozzi,1 Alessia Chiorazzi,1 Barbara Sala,1 Norberto Oggioni,1 Marco Lanza,2 Ornella Letar,i2 Flora Ferrari,2 Federica Avezza,1 Paola Marmiroli,1 GianFranco Caselli,2 Guido Cavaletti11Department of Neuroscience and Biomedical Technologies, University of Milan-Bicocca, 2Pharmacology and Toxicology Department, Rottapharm | Madaus Research Center, Monza, ItalyAbstract: Although bortezomib (BTZ is the frontline treatment for multiple myeloma, its clinical use is limited by the occurrence of painful peripheral neuropathy, whose treatment is still an unmet clinical need. Previous studies have shown chronic BTZ administration (0.20 mg/kg intravenously three times a week for 8 weeks to female Wistar rats induced a peripheral neuropathy similar to that observed in humans. In this animal model of BTZ-induced neurotoxicity, the present authors evaluated the efficacy of CR4056, a novel I2 ligand endowed with a remarkable efficacy in several animal pain models. CR4056 was administered in a wide range of doses (0.6–60 mg/kg by gavage every day for 2–3 weeks in comparison with buprenorphine (Bupre (28.8 µg/kg subcutaneously every day for 2 weeks and gabapentin (Gaba (100 mg/kg by gavage every day for 3 weeks. Chronic administration of BTZ reduced nerve conduction velocity and induced allodynia. CR4056, Bupre, or Gaba did not affect the impaired nerve conduction velocity. Conversely, CR4056 dose-dependently reversed BTZ-induced allodynia (minimum effective dose 0.6 mg/kg. The optimal dose found, 6 mg/kg, provided a constant pain relief throughout the treatment period and without rebound after suspension, being effective when coadministered with BTZ, starting before or after allodynia was established, or when administered alone after BTZ cessation. A certain degree of tolerance was seen after 7 days of administration, but only at the highest doses (20 and 60 mg/kg. Bupre was effective

  19. Resection after preoperative chemotherapy versus synchronous liver resection of colorectal cancer liver metastases

    Science.gov (United States)

    Kim, Chan W.; Lee, Jong L.; Yoon, Yong S.; Park, In J.; Lim, Seok-Byung; Yu, Chang S.; Kim, Tae W.; Kim, Jin C.

    2017-01-01

    Abstract This study aimed to determine the prognostic effects of preoperative chemotherapy for colorectal cancer liver metastasis (CLM). We retrospectively evaluated 2 groups of patients between January 2006 and August 2012. A total of 53 patients who had ≥3 hepatic metastases underwent resection after preoperative chemotherapy (preoperative chemotherapy group), whereas 96 patients who had ≥3 hepatic metastases underwent resection with a curative intent before chemotherapy for CLM (primary resection group). A propensity score (PS) model was used to compare the both groups. The 3-year disease-free survival (DFS) rates were 31.7% and 20.4% in the preoperative chemotherapy and primary resection groups, respectively (log-rank = 0.015). Analyzing 32 PS matched pairs, we found that the DFS rate was significantly higher in the preoperative chemotherapy group than in the primary resection group (3-year DFS rates were 34.2% and 16.8%, respectively [log-rank = 0.019]). Preoperative chemotherapy group patients had better DFSs than primary resection group patients in various multivariate analyses, including crude, multivariable, average treatment effect with inverse probability of treatment weighting model and PS matching. Responses to chemotherapy are as important as achieving complete resection in cases of multiple hepatic metastases. Preoperative chemotherapy may therefore be preferentially considered for patients who experience difficulty undergoing complete resection for multiple hepatic metastases. PMID:28207557

  20. Cancer chemotherapy and cardiac arrhythmias: a review.

    Science.gov (United States)

    Tamargo, Juan; Caballero, Ricardo; Delpón, Eva

    2015-02-01

    Cardiovascular toxicity is a potential complication of cancer chemotherapy (CC) that increases the morbidity and mortality of cancer patients. Cardiac arrhythmias have been reported as an adverse effect of many chemotherapeutic drugs, including novel targeted therapies. The relationship between chemotherapy and arrhythmias has not been well-established and the proarrhythmogenic mechanisms remain uncertain as they can be the result of a direct electrophysiological effect or of changes in cardiac structure and function, including myocardial ischaemia and heart failure, which create an arrhythmogenic substrate. In this review we summarise available evidence of proarrhythmia induced by CC, discuss the possible mechanisms involved in this adverse effect and emphasise the importance of cardiac monitoring for the early diagnosis, intervention and surveillance of those patients more susceptible to develop proarrhythmia in an attempt to reduce the morbidity and mortality. Oncologists should be fully aware of proarrhythmia and the close collaboration between cardiologists and oncologists would result in a better cardiovascular assessment, risk stratification, cardiac monitoring and treatment during CC and during the follow-up. The final objective is to understand the mechanisms of proarrhythmia and evaluate its real incidence and clinical relevance so as to select the safest and most effective treatment for cancer patients.

  1. 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.

  2. Progress in adjuvant chemotherapy for breast cancer: an overview.

    Science.gov (United States)

    Anampa, Jesus; Makower, Della; Sparano, Joseph A

    2015-01-01

    Breast cancer is the most common cause of cancer and cancer death worldwide. Although most patients present with localized breast cancer and may be rendered disease-free with local therapy, distant recurrence is common and is the primary cause of death from the disease. Adjuvant systemic therapies are effective in reducing the risk of distant and local recurrence, including endocrine therapy, anti-HER2 therapy, and chemotherapy, even in patients at low risk of recurrence. The widespread use of adjuvant systemic therapy has contributed to reduced breast cancer mortality rates. Adjuvant cytotoxic chemotherapy regimens have evolved from single alkylating agents to polychemotherapy regimens incorporating anthracyclines and/or taxanes. This review summarizes key milestones in the evolution of adjuvant systemic therapy in general, and adjuvant chemotherapy in particular. Although adjuvant treatments are routinely guided by predictive factors for endocrine therapy (hormone receptor expression) and anti-HER2 therapy (HER2 overexpression), predicting benefit from chemotherapy has been more challenging. Randomized studies are now in progress utilizing multiparameter gene expression assays that may more accurately select patients most likely to benefit from adjuvant chemotherapy.

  3. Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

    Energy Technology Data Exchange (ETDEWEB)

    Weir, Genevieve M. [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada); Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Liwski, Robert S. [Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Room 206E, Dr. D. J. Mackenzie Building, Department of Pathology, Dalhousie University, 5788 University Avenue, Halifax, NS, B3H 2Y9 (Canada); Mansour, Marc [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada)

    2011-08-05

    Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

  4. Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

    Directory of Open Access Journals (Sweden)

    Marc Mansour

    2011-08-01

    Full Text Available Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

  5. Myelopathy due to intrathecal chemotherapy: report of six cases.

    Science.gov (United States)

    Bay, Ali; Oner, Ahmet Faik; Etlik, Omer; Yilmaz, Cahide; Caksen, Huseyin

    2005-05-01

    Intrathecal chemotherapy and systemic chemotherapy are used for both prophylaxis and treatment of central nervous system disease in hematologic malignancies. However, intrathecal treatment has some adverse effects, such as arachnoiditis, progressive myelopathy, and leukoencephalopathy. The authors describe six children in whom myelopathy and adhesive arachnoiditis developed after administration of intrathecal chemotherapy including methotrexate, cytosine arabinoside, and prednisolone. Urinary retention and incontinence, the main presenting complaints in all patients, developed within 12 hours after intrathecal therapy and spontaneously resolved within 7 days. Two patients were unable to walk. In these two, weakness in the lower extremities gradually recovered by 1 month but urinary incontinence did not improve. None of the children had sensory loss. On follow-up periodic recurrent urinary tract infection was noted in four patients. MRI findings corresponded to arachnoiditis. No response was recorded on tibial nerve somatosensory evoked potentials in all patients. Intrathecal chemotherapy, especially methotrexate, can cause spinal cord dysfunction in children with acute lymphoblastic leukemia and non-Hodgkin's lymphoma. Arachnoiditis should be kept in mind as a causative factor in recurrent urinary tract infection in patients receiving intrathecal chemotherapy.

  6. The anti-apoptotic protein BCL2L1/Bcl-xL is neutralized by pro-apoptotic PMAIP1/Noxa in neuroblastoma, thereby determining bortezomib sensitivity independent of prosurvival MCL1 expression.

    Science.gov (United States)

    Hagenbuchner, Judith; Ausserlechner, Michael J; Porto, Verena; David, Reinhard; Meister, Bernhard; Bodner, Martin; Villunger, Andreas; Geiger, Kathrin; Obexer, Petra

    2010-03-05

    Neuroblastoma is the most frequent extracranial solid tumor in children. Here, we report that the proteasome inhibitor bortezomib (PS-341, Velcade) activated the pro-apoptotic BH3-only proteins PMAIP1/Noxa and BBC3/Puma and induced accumulation of anti-apoptotic MCL1 as well as repression of anti-apoptotic BCL2L1/Bcl-xL. Retroviral expression of Bcl-xL, but not of MCL1, prevented apoptosis by bortezomib. Gene knockdown of Noxa by shRNA technology significantly reduced apoptosis, whereas Puma knockdown did not affect cell death kinetics. Immunoprecipitation revealed that endogenous Noxa associated with both, Bcl-xL and MCL1, suggesting that in neuronal cells Noxa can neutralize Bcl-xL, explaining the pronounced protective effect of Bcl-xL. Tetracycline-regulated Noxa expression did not trigger cell death per se but sensitized to bortezomib treatment in a dose-dependent manner. This implies that the induction of Noxa is necessary but not sufficient for bortezomib-induced apoptosis. We conclude that MCL1 steady-state expression levels do not affect sensitivity to proteasome-inhibitor treatment in neuronal tumor cells, and that both the repression of Bcl-xL and the activation of Noxa are necessary for bortezomib-induced cell death.

  7. Alternative Methods to Treat Nausea and Vomiting from Cancer Chemotherapy

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Sheikhi

    2015-01-01

    Full Text Available Chemotherapy Induced Nausea and Vomiting (CINV is among the most intensive side effects and critical concerns for patients with cancer. Most of these patients experience nausea and vomiting after chemotherapy. Sometimes, this is so annoying that it may prevent them from continuing the therapy. With the recent advances, a variety of therapeutic methods are innovated and applied to control CINV. Among them, the main methods include medicinal therapy, relaxation, and herbal therapy. Yet, using dexamethasone together with massage therapy and ginger is identified as the most effective method.

  8. Chemotherapy-induced Peripheral Neuropathy | Division of Cancer Prevention

    Science.gov (United States)

    It usually starts in the hands and/or feet and creeps up the arms and legs. Sometimes it feels like a tingling or numbness. Other times, it’s more of a shooting and/or burning pain or sensitivity to temperature. It can include sharp, stabbing pain, and it can make it difficult to perform normal day-to-day tasks like buttoning a shirt, sorting coins in a purse, or walking. An estimated 30 to 40 percent of cancer patients treated with chemotherapy experience these symptoms, a condition called chemotherapy-induced peripheral neuropathy (CIPN). |

  9. Mathematical modeling of brain tumors: effects of radiotherapy and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Powathil, G [Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, N2L 3G1 (Canada); Kohandel, M [Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, N2L 3G1 (Canada); Sivaloganathan, S [Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, N2L 3G1 (Canada); Oza, A [Center for Mathematical Medicine, Fields Institute for Research in Mathematical Sciences, Toronto, Ontario M5T 3J1 (Canada); Milosevic, M [Radiation Medicine Program, Princess Margaret Hospital, and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9 (Canada)

    2007-06-07

    Gliomas, the most common primary brain tumors, are diffusive and highly invasive. The standard treatment for brain tumors consists of a combination of surgery, radiation therapy and chemotherapy. Over the past few years, mathematical models have been applied to study untreated and treated brain tumors. In an effort to improve treatment strategies, we consider a simple spatio-temporal mathematical model, based on proliferation and diffusion, that incorporates the effects of radiotherapeutic and chemotherapeutic treatments. We study the effects of different schedules of radiation therapy, including fractionated and hyperfractionated external beam radiotherapy, using a generalized linear quadratic (LQ) model. The results are compared with published clinical data. We also discuss the results for combination therapy (radiotherapy plus temozolomide, a new chemotherapy agent), as proposed in recent clinical trials. We use the model to predict optimal sequencing of the postoperative (combination of radiotherapy and adjuvant, neo-adjuvant or concurrent chemotherapy) treatments for brain tumors.

  10. Chemotherapy and quality of life in NSCLC PS 2 patients

    DEFF Research Database (Denmark)

    Helbekkmo, Nina; Strøm, Hans H; Sundstrøm, Stein H

    2009-01-01

    INTRODUCTION: Nearly 40% of patients with advanced NSCLC are in performance status (PS) 2. These patients have a shorter life expectancy than PS 0/1 patients and they are underrepresented in clinical trials. Data on how platinum-based combination chemotherapy affects Health Related Quality of Life...... (HRQOL) of patients with PS 2 are scarce and the treatment of this important group of patients is controversial. METHODS: A national multicenter phase III study on platinum based chemotherapy to 432 advanced NSCLC patients included 123 patients with PS 2. To explore the treatment impact on HRQOL......: Whereas the demographic data at baseline were well balanced between the groups, the PS 2 patients had significantly worse function and more severe symptoms than the PS 0/1 patients. In response to combination chemotherapy, the PS 2 patients had a more profound improvement of global QOL, cognitive function...

  11. Myoepithelial Carcinoma of the Breast Treated with Surgery and Chemotherapy

    Directory of Open Access Journals (Sweden)

    Yumi Endo

    2013-01-01

    Full Text Available Myoepithelial carcinoma (malignant myoepithelioma of the breast is a rare tumor, for which only a limited number of reports have been published. Most of the reports emphasized diagnosis and pathology but not biological behavior and treatment. We report a 61-year-old patient with breast myoepithelial carcinoma who developed locoregional and distant metastases and received many chemotherapy regimens. She presented with an elastic hard mass of the left breast. Breast conserving surgery was performed as part of both diagnosis and treatment. From the results of histological and immunohistochemical examinations, this case was considered to be a myoepithelial carcinoma. Fifteen months after the completion of adjuvant radiotherapy, distant metastasis of the left parasternal lymph node metastasis developed. She was treated by further excision and received a total of four regimens of chemotherapy including a combination of doxorubicin and cyclophosphamide. She received chemotherapy for 20 months after the diagnosis of metastasis.

  12. Bursectomy, Curettage, and Chemotherapy in Tuberculous Trochanteric Bursitis.

    Science.gov (United States)

    Ramos-Pascua, Luis R; Carro-Fernández, José A; Santos-Sánchez, José A; Casas Ramos, Paula; Díez-Romero, Luis J; Izquierdo-García, Francisco M

    2016-03-01

    We presented three patients with trochanteric tuberculosis and described the clinical and imaging findings of the infection. Histology revealed a necrotizing granulomatous bursitis and microbiology confirmed tuberculosis. All cases were successfully treated with bursectomy and curettage of the trochanteric lesion and antituberculous chemotherapy including isoniazid, pyrazinamide, rifampicin, and ethambutol.

  13. Pulmonary blastoma: remission with chemotherapy

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Jacobsen, M; Vindeløv, L

    1984-01-01

    A 59-year-old man with pulmonary blastoma, who had undergone right-sided pneumonectomy, had a relapse of the tumour 7 months later. Light-microscopic and ultrastructural studies were consistent with recurrence from the primary tumour. Cell kinetic studies revealed a high fraction of tumour cells ...... in the S-phase. Complete remission of the recurrence was obtained within 16 days after initiation of combination chemotherapy consisting of CCNU, vincristine, VP-16 and cyclophosphamide....

  14. Change in ploidy status from hyperdiploid to near-tetraploid in multiple myeloma associated with bortezomib/lenalidomide resistance.

    Science.gov (United States)

    Pavlistova, Lenka; Zemanova, Zuzana; Sarova, Iveta; Lhotska, Halka; Berkova, Adela; Spicka, Ivan; Michalova, Kyra

    2014-01-01

    Ploidy is an important prognostic factor in the risk stratification of multiple myeloma (MM) patients. Patients with MM can be divided into two groups according to the modal number of chromosomes: nonhyperdiploid (NH-MM) and hyperdiploid (H-MM), which has a more favorable outcome. The two ploidy groups represent two different oncogenetic pathways determined at the premalignant stage. The ploidy subtype also persists during the course of the disease, even during progression after the therapy, with only very rare cases of ploidy conversion. The clinical significance of ploidy conversion and its relation to drug resistance have been previously discussed. Here, we describe a female MM patient with a rare change in her ploidy status from H-MM to NH-MM, detected by cytogenetic and molecular cytogenetic examinations of consecutive bone marrow aspirates. We hypothesize that ploidy conversion (from H-MM to NH-MM) is associated with disease progression and acquired resistance to bortezomib/lenalidomide therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. The role of bortezomib, thalidomide and lenalidomide in the management of multiple myeloma: an overview of clinical and economic information.

    Science.gov (United States)

    Messori, Andrea; Maratea, Dario; Nozzoli, Chiara; Bosi, Alberto

    2011-04-01

    Bortezomib, thalidomide and lenalidomide can be aimed at treating patients with newly diagnosed multiple myeloma (both eligible and ineligible for transplantation) as well as those with relapsed or refractory disease. This review analysed the available clinical and economic data on these three drugs. Irrespective of which of the three agents is considered, the magnitude of the benefit in newly diagnosed cases (transplanted or non-transplanted) tends to be between 10 and 20 months per patient in terms of progression-free survival or survival; the survival benefit is smaller in relapsed or refractory disease. In addition, a single-institution observational analysis evaluated the outcomes in nearly 3000 consecutive patients examined between 1971 and 2006. The survival in patients diagnosed between 2001 and 2006 was longer than that observed in patients diagnosed between 1994 and 2000. This finding supports the conclusion that novel agents provide a survival improvement compared with traditional therapy. Formal cost-effectiveness studies on these three agents are still lacking. A MEDLINE search retrieved only four short papers or letters and no full-length analysis. Hence, the cost effectiveness of these agents needs further investigation, with separate assessments of the different therapeutic settings. In a simplified analysis, we tried to contrast the average cost of treatment for each of the novel agents versus their respective benefit, expressed in quality-adjusted survival. Despite its preliminary nature, our assessment indicates that the cost effectiveness of these three agents is likely to be within commonly accepted pharmacoeconomic thresholds.

  16. Higher incidence of injection site reactions after subcutaneous bortezomib administration on the thigh compared with the abdomen.

    Science.gov (United States)

    Kamimura, Tomohiko; Miyamoto, Toshihiro; Yokota, Noriko; Takashima, Shuichiro; Chong, Yong; Ito, Yoshikiyo; Akashi, Koichi

    2013-02-01

    Subcutaneous (sc) rather than intravenous administration of bortezomib (Bor) is becoming more common for treating multiple myeloma (MM) because scBor results in lower incidence and severity of peripheral neuropathy and has equivalent efficacy. Bor is an irritant cytotoxic agent when it leaks out; therefore, it is recommended that injections of scBor should be rotated among eight different sites on the abdomen and thigh. However, detailed information about injection site reaction (ISR) has not been sufficiently documented. We retrospectively analyzed the incidence and severity of ISR following scBor administration in 15 Japanese patients with MM. Grade 1 ISR occurred following 40 of 158 (25.3%) scBor injections in ten patients, whereas grade 2 ISRs occurred following seven injections (4.4%) in five patients. Five patients did not develop ISR. Of note, grade 2 ISR was documented in 6 of 65 (9.2%) thigh injections but only in 1 of 93 (1.1%) abdominal injections. These data show that grade 2 ISRs were more common in the thigh compared with the abdomen possibly because the thigh contains lesser adipose tissue than the abdomen. Grade 2 ISRs resolved without any sequela within a median of 7 d. scBor administration on the abdomen instead of the thigh should be considered, especially for emaciated patients, because ISR rapidly resolves within the interval before the next injection even if it occurs. © 2012 John Wiley & Sons A/S.

  17. Therapeutic potential of the proteasome inhibitor Bortezomib on titanium particle-induced inflammation in a murine model.

    Science.gov (United States)

    Mao, Xin; Pan, Xiaoyun; Cheng, Tao; Zhang, Xianlong

    2012-06-01

    Wear particle-induced aseptic loosening has been recognized as a harmful inflammatory process that jeopardizes the longevity of total joint replacement. The proteasome controls the activation of NF-κB and subsequent inflammatory mediators, such as TNF-α and IL-1β; thus, we investigated whether proteasome inhibition can ameliorate wear particle-induced inflammation in a murine model. A total of 48 BALB/C mice were divided into four groups. Titanium (Ti) particles were injected into the established air pouches of all mice (except negative controls) to provoke inflammation, and then 0.1 or 0.5 mg/kg of Bortezomib (Bzb, a proteasome inhibitor) was administered to ameliorate the inflammation response, while air pouches without Bzb administration were used as loading controls. The air pouches were harvested 2 or 7 days after Bzb injection for molecular and histological analyses. Inflammation responses in the air pouch tissues of Bzb treatment groups are lower than those in the Ti-stimulated group, and this occurs in a dose-dependent manner. Bzb can significantly attenuate the severity of Ti-induced inflammation in air pouches.

  18. The role of intravitreal chemotherapy for retinoblastoma

    Directory of Open Access Journals (Sweden)

    Fairooz P Manjandavida

    2015-01-01

    Full Text Available Targeted therapy in retinoblastoma (RB is widely accepted as the current management tool with an aim of increasing drug availability at the tumor location. Inevitably the effect is several times higher compared to systemic delivery of chemotherapeutic drugs and carries less systemic toxicity. Despite tremendous advancement in saving life, eye salvage in advanced RB especially with active vitreous seeds remains a challenge. The hypoxic environment of the vitreous and reduced vitreous concentration of the drugs delivered makes these tumor seeds resistant to chemotherapy. Direct delivery of chemotherapeutic drugs into the vitreous cavity aids to overcome these challenges and is progressively being accepted worldwide. However, intraocular procedure in RB was abandoned due to high risk of extraocular tumor dissemination. Recently, the forbidden therapeutic technique was re-explored and modified for safe use. Although eye salvage rate has tremendously improved after intravitreal chemotherapy (IVitC, retinal toxicity, and vision salvage are yet to be validated. In our preliminary report of intravitreal melphalan in 11 eyes, we reported 100% eye salvage and 0% recurrence with an extended 15 months mean follow-up. In this review, we analyzed published reports on IVitC in RB via PubMed, Medline, and conference proceedings citation index, electronic database search, without language restriction that included case series and reports of humans and experimental animal eyes with RB receiving IVitC.

  19. Chemotherapy of enterobiasis (oxyuriasis).

    Science.gov (United States)

    St Georgiev, V

    2001-02-01

    Enterobius vermicularis (syn. Oxyurus vermicularis), also known as pinworm or seatworm, is the causative agent of human enterobiasis (oxyuriasis). The disease is more prevalent in temperate regions and is facilitated by factors such as overcrowding in schools and family groupings, as well as inadequate personal and community hygiene. Although the infection is more likely to occur in lower socioeconomic groups, enterobiasis has been reported to affect virtually every level of the general population and especially children. In the great majority of cases, enterobiasis is asymptomatic. One common symptom is intense pruritus ani that in some patients can lead to insomnia, restlessness and irritability. Scratching may cause skin irritation, and in more serious cases, eczematous dermatitis, haemorrhage or secondary bacterial infections. Ectopic migration of E. vermicularis often results in pinworm infestation of the female genital tract often causing granulomas of the uterus, ovary and the fallopian tubes and pelvic peritoneum. Anthelmintic therapies for enterobiasis are successful and include mebendazole, albendazole and pyrantel pamoate. Mass medication of affected groups reduced symptoms rapidly, progressively and in a cost-effective way.

  20. Anticipatory nausea and vomiting due to chemotherapy.

    Science.gov (United States)

    Kamen, Charles; Tejani, Mohamedtaki A; Chandwani, Kavita; Janelsins, Michelle; Peoples, Anita R; Roscoe, Joseph A; Morrow, Gary R

    2014-01-05

    As a specific variation of chemotherapy-induced nausea and vomiting, anticipatory nausea and vomiting (ANV) appears particularly linked to psychological processes. The three predominant factors related to ANV are classical conditioning; demographic and treatment-related factors; and anxiety or negative expectancies. Laboratory models have provided some support for these underlying mechanisms for ANV. ANV may be treated with medical or pharmacological interventions, including benzodiazepines and other psychotropic medications. However, behavioral treatments, including systematic desensitization, remain first line options for addressing ANV. Some complementary treatment approaches have shown promise in reducing ANV symptoms. Additional research into these approaches is needed. This review will address the underlying models of ANV and provide a discussion of these various treatment options.

  1. Gastrointestinal symptoms and weight loss in cancer patients receiving chemotherapy.

    Science.gov (United States)

    Sánchez-Lara, Karla; Ugalde-Morales, Emilio; Motola-Kuba, Daniel; Green, Dan

    2013-03-14

    Cancer patients receiving chemotherapy have a high risk of malnutrition secondary to the disease and treatment, and 40-80 % of cancer patients suffer from different degrees of malnutrition, depending on tumour subtype, location, staging and treatment strategy. Malnutrition in cancer patients affects the patient's overall condition, and it increases the number of complications, the adverse effects of chemotherapy and reduces the quality of life. The aim of the present study was to evaluate weight-loss prevalence depending on the tumour site and the gastrointestinal (GI) symptoms of oncology patients receiving chemotherapy. We included 191 cancer patients receiving chemotherapy. Files of all patients were reviewed to identify symptoms that might potentially influence weight loss. The nutritional status of all patients was also determined. The cancer sites in the patients were as follows: breast (31·9 %); non-colorectal GI (18·3 %); colorectal (10·4 %); lung (5·8 %); haematological (13·1 %); others (20·5 %). Of these patients, 58 % experienced some degree of weight loss, and its prevalence was higher among the non-colorectal GI and lung cancer patients. Common symptoms included nausea (59·6 %), anorexia (46 %) and constipation (31·9 %). A higher proportion of patients with ≥ 5 % weight loss experienced anorexia, nausea and vomiting (OR 9·5, 2·15 and 6·1, respectively). In conclusion, these results indicate that GI symptoms can influence weight loss in cancer patients, and they should be included in early nutritional evaluations.

  2. Bortezomib for acute humoral rejection treatment at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City: an update.

    Science.gov (United States)

    Leyva, Sergio; Marino, Lluvia A; Alberú, Josefina; Morales-Buenrostro, Luis E

    2010-01-01

    The use of bortezomib as a treatment modality of AHR improved and stabilized graft function (clinical response) in the majority of patients. Its use in single dose, even combined with rituximab, does not seem to be useful to obtain a sustained clinical response, or to reduce HLAabs level. The use of 4 doses of bortezomib in days 1, 4, 7, and 10 (1.3 mg/m2 BSA each) plus plasmapheresis produced both a good clinical response and a reduction in DSA. Moving forward, it will be necessary to define the long-term effectiveness of bortezomib and whether rituximab administration is indispensable to achieve this goal. Until now, it is evident that many patients needed retreatment and they were well tolerated.

  3. Use of allogeneic platelet gel in the management of chemotherapy extravasation injuries: a case report

    Directory of Open Access Journals (Sweden)

    Di Costanzo G

    2015-02-01

    Full Text Available Gaetano Di Costanzo,1 Giovanna Loquercio,1 Gianpaolo Marcacci,2 Vincenzo Iervolino,1 Stefano Mori,3 Arnolfo Petruzziello,1 Pasquale Barra,1 Carmela Cacciapuoti1 1Transfusion Service, Department of Haematology, National Cancer Institute “G Pascale” Foundation, IRCCS, Naples, Italy; 2Hematology-Oncology and Stem Cell Transplantation Unit, National Cancer Institute “G Pascale” Foundation, IRCCS, Naples, Italy; 3Department of Surgery, Melanoma – Soft Tissues – Head and Neck – Skin Cancers, National Cancer Institute “G Pascale” Foundation, IRCCS, Naples, Italy Abstract: The allogeneic platelet (PLT gel offers to be a valid supportive measure in the management of chemotherapy extravasation injuries. We report a case of a 58-year-old patient with multiple myeloma enrolled for high-dose chemotherapy and autologous stem cell transplantation. As pretransplant therapy, the patient received induction therapy with bortezomib, adriblastina, and desametazone. A port was inserted in the vein on the back of the hand. After three cycles, the patient reported rapid development of redness, pain, and necrotic tissue in the left hand, and a diagnosis of extravasation was addressed. The patient presented a raw area on the back of the hand caused by cytotoxic/chemotherapeutic drug leakage because of the malposition of venous access devices. Skin ulcer was debrided, and the wound was reconstructed with a combination of local random rotational flap and abdomen skin graft. Two weeks later, a 20% skin flap necrosis was observed. In the context of wound healing, topical plasma-rich PLT gel is able to accelerate the regeneration and repair of tissue, so it was set out to assess PLT gel efficacy in this case. The PLT gel was applied topically once every 5 days, for a duration of 60 days on average. There were no adverse reactions observed during the topical therapy. Complete wound healing was observed after 12 PLT-rich plasma applications. No ulcer

  4. MRI diagnosis of and follow-up after humoral head necrosis as complication after chemotherapy; MRT-Diagnose und Verlauf beidseitiger Humeruskopfnekrosen aus Komplikation nach Chemotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Morakkabati, N. [Bonn Univ. (Germany). Radiologische Klinik; Strunk, H. [Bonn Univ. (Germany). Radiologische Klinik; Gutjahr, P. [Mainz Univ. (Germany). Kinderklinik

    1997-01-01

    A 14-year old female patient was treated with chemotherapy including cortisone for malignant T-cell lymphoma. After chemotherapy she complained of pain in both hips and shoulders. Bone scientigraphy failed to show any abnormality. However, bilateral femoral and humeral head necrosis was seen with MR imaging, which was also useful for follow up. (orig.) [Deutsch] Eine 14jaehrige Patientin wurde aufgrund eines malignen Non-Hodgkin-Lymphoms zystostatisch behandelt, unter anderem mit Cortison. Nach dieser Chemotherapie traten Schmerzen in der Huefte und in beiden Schultern auf. Skelettszintigraphie und Roentgenuebersichtsaufnahme zeigten zunaechst keinen pathologischen Befund. In der MRT konnten jedoch beidseitige Humerus- und Femurkopfnekrosen nachgewiesen sowie im Verlauf kontrolliert werden. (orig.)

  5. Post-chemotherapy arthralgia and arthritis in lung cancer

    Directory of Open Access Journals (Sweden)

    Aref H Amiri

    2012-01-01

    Full Text Available Objective: Evaluate the characteristics of arthritis, arthralgia and musculoskeletal pain after chemotherapy in patients with lung cancer. Materials and Methods: In this study, we evaluate the characteristics of 17 patients with joint symptoms following receiving chemotherapy for lung cancer. Demographic information of patients including sex, age, time of rheumatologic findings after starting of chemotherapy, time of improvement after starting of medication, and relevant laboratory findings for each patient. Results: A total of seventeen patients (six women with mean age 41.2 ± 5.2 years and 11 men with mean age 42.5 ± 8.2 that received standard chemotherapy for lung cancer according to stage of disease. Joint symptoms usually began about seven months after the first session of chemotherapy. Patients had an average of two tender joints and 1 hr of morning stiffness. Four patients were positive for anti-nuclear antibody, and none of patient was positive for rheumatoid factor. Non-steroidal anti-inflammatory drugs, disease modifying anti-rheumatic drugs (DMARD, corticosteroids, and venlafaxine were prescribed. Four patients did not show an improvement. Follow-up was available for all patients. 11 patients showed favorable responses, characterized by a significant decrease (more than 50% in morning stiffness, pain, and tender joint counts after a mean of three months′ treatment. Two patients had complete resolution of symptoms and did not required further medications for arthritis, arthralgia or musculoskeletal pain. Conclusion: Chemotherapy-related arthropathy in lung cancer is not uncommon. Early treatment with NSAID, DMARD, and corticosteroids is effective in the majority of patients.

  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. Bortezomib interferes with adhesion of B cell precursor acute lymphoblastic leukemia cells through SPARC up-regulation in human bone marrow mesenchymal stromal/stem cells.

    Science.gov (United States)

    Iwasa, Masaki; Miura, Yasuo; Fujishiro, Aya; Fujii, Sumie; Sugino, Noriko; Yoshioka, Satoshi; Yokota, Asumi; Hishita, Terutoshi; Hirai, Hideyo; Andoh, Akira; Ichinohe, Tatsuo; Maekawa, Taira

    2017-05-01

    The poor prognosis of adults with B cell precursor acute lymphoblastic leukemia (BCP-ALL) is attributed to leukemia cells that are protected by the bone marrow (BM) microenvironment. In the present study, we explored the pharmacological targeting of mesenchymal stromal/stem cells in BM (BM-MSCs) to eliminate chemoresistant BCP-ALL cells. Human BCP-ALL cells (NALM-6 cells) that adhered to human BM-MSCs (NALM-6/Ad) were highly resistant to multiple anti-cancer drugs, and exhibited pro-survival characteristics, such as an enhanced Akt/Bcl-2 pathway and increased populations in the G0 and G2/S/M cell cycle stages. Bortezomib, a proteasome inhibitor, interfered with adhesion between BM-MSCs and NALM-6 cells and up-regulated the matricellular protein SPARC (secreted protein acidic and rich in cysteine) in BM-MSCs, thereby reducing the NALM-6/Ad population. Inhibition of SPARC expression in BM-MSCs using a small interfering RNA enhanced adhesion of NALM-6 cells. Conversely, recombinant SPARC protein interfered with adhesion of NALM-6 cells. These results suggest that SPARC disrupts adhesion between BM-MSCs and NALM-6 cells. Co-treatment with bortezomib and doxorubicin prolonged the survival of BCP-ALL xenograft mice, with a significant reduction of leukemia cells in BM. Our findings demonstrate that bortezomib contributes to the elimination of BCP-ALL cells through disruption of their adhesion to BM-MSCs, and offer a novel therapeutic strategy for BCP-ALL through targeting of BM-MSCs.

  8. Guideline Adherence Regarding the Use of Expensive Drugs in Daily Practice: The Examples of Trastuzumab in Breast Cancer and Bortezomib in Multiple Myeloma.

    Science.gov (United States)

    Boons, Christel C L M; Wagner, Cordula; Hugtenburg, Jacqueline G

    2016-01-01

    The present study was designed to obtain insights into guideline adherence regarding the use of expensive drugs in The Netherlands in daily practice and into the patients' perspective on the decision-making process. A retrospective review of medical charts regarding the use of trastuzumab in early and metastatic breast cancer (EBC/MBC) and bortezomib in multiple myeloma (MM) was conducted. Prescription according to clinical practice guidelines was assessed. The review was supplemented with patient interviews. Of 702 adjuvant-treated EBC patients, 97% had a documented human epidermal growth factor receptor 2 (HER2) testing (23% HER2 positive). 92% (147/160) of the HER2-positive EBC patients were treated with trastuzumab. Of 594 MBC patients, 81% had a documented HER2 testing (19% HER2 positive). 82% (75/91) of the HER2-positive MBC patients were treated with trastuzumab. Of 68 MM patients, 50% were treated with bortezomib. Reasons not to treat were consistent with the guidelines. Patients were generally satisfied with the decision-making process; improvements in patient education were suggested (e.g., repeating the information given, adding information on side effects). Guidelines were generally well followed with respect to trastuzumab and bortezomib, indicating that funding did not influence the treatment decisions of physicians. In view of the growing numbers of both cancer patients and expensive new anticancer drugs, and increasing budget constraints, it is unclear whether the present-day policies will guarantee a similar level of guideline adherence. Patient involvement in decision-making could be increased by improving the patient education on treatment. © 2016 S. Karger GmbH, Freiburg.

  9. Review on adjuvant chemotherapy for rectal cancer - why do treatment guidelines differ so much?

    Science.gov (United States)

    Poulsen, Laurids Ø; Qvortrup, Camilla; Pfeiffer, Per; Yilmaz, Mette; Falkmer, Ursula; Sorbye, Halfdan

    2015-04-01

    The use of postoperative adjuvant chemotherapy is controversial for rectal adenocarcinoma. Both international and national guidelines display a great span varying from recommending no adjuvant chemotherapy at all, over single drug 5-fluororuacil (5-FU), to combinations of 5-FU/oxaliplatin. A review of the literature was made identifying 24 randomized controlled trials on adjuvant treatment of rectal cancer based on about 10 000 patients. The trials were subdivided into a number of clinically relevant subgroups. As regards patients treated with preoperative (chemo) radiotherapy, four randomized studies were found where use of adjuvant chemotherapy showed no benefit in survival. Three trials were found in which a subset of patients received preoperative (chemo) radiotherapy. Two of these trials showed a statistically significant benefit of adjuvant chemotherapy. Twenty trials were identified in which the patients did not receive preoperative (chemo) radiotherapy, including five Asian studies in which a statistically significant benefit from adjuvant chemotherapy was reported. Most of the data found did not support the use of postoperative adjuvant chemotherapy for patients already treated with preoperative (chemo) radiotherapy. For patients not treated preoperatively, several studies support the use of single agent 5-FU chemotherapy. Treatment guidelines seem to differ according to if preoperative chemoradiation is considered of importance for use of adjuvant chemotherapy and if adjuvant colon cancer studies are considered transferrable to rectal cancer patients regardless of the molecular differences.

  10. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy.

    Science.gov (United States)

    Moore, Halle C F; Unger, Joseph M; Phillips, Kelly-Anne; Boyle, Frances; Hitre, Erika; Porter, David; Francis, Prudence A; Goldstein, Lori J; Gomez, Henry L; Vallejos, Carlos S; Partridge, Ann H; Dakhil, Shaker R; Garcia, Agustin A; Gralow, Julie; Lombard, Janine M; Forbes, John F; Martino, Silvana; Barlow, William E; Fabian, Carol J; Minasian, Lori; Meyskens, Frank L; Gelber, Richard D; Hortobagyi, Gabriel N; Albain, Kathy S

    2015-03-05

    Ovarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes. We randomly assigned 257 premenopausal women with operable hormone-receptor-negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival. At baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P=0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P=0.03); women in the goserelin group also had improved disease-free survival (P=0.04) and overall survival (P=0.05). Although missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility. (Funded by the National Cancer Institute and others; POEMS/S0230 Clinical

  11. Chemotherapy

    Science.gov (United States)

    ... tumor cells. Mitotic inhibitors—These agents are usually plant-based, natural substances that interfere with the production ... drugs Infertility Seizures Weakness Balance or coordination problems Memory or cognitive problems Brain swelling Damage to internal ...

  12. A meta-analysis of bevacizumab combined with chemotherapy in the treatment of ovarian cancer

    Directory of Open Access Journals (Sweden)

    T S Wang

    2014-01-01

    Full Text Available Introduction: Angiogenesis plays an important role in the biology of ovarian cancer. The clinical efficacy and side effects of bevacizumab, the vascular endothelial growth factor inhibitor, on survival and toxicity in women with this ovarian cancer, was not conclusive. We performed this systematic review and meta-analysis in order to clarify the efficacy of bevacizumab combined with chemotherapy in the treatment of ovarian cancer. Materials and Methods: We searched the electronic database of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CNKI for clinical controlled trials of comparing bevacizumab combined with chemotherapy and chemotherapy alone in the treatment of ovarian cancer. The primary outcomes of eligible studies included median progression-free survival (PFS, overall survival (OS, and toxicities such as enterobrosis, hypertension, albuminuria, congestive heart failure (CHF, neutrophils, thrombosis, and bleeding. The Hazard ratio (HR and relative risk were used for the meta-analysis and were expressed with 95% confidence intervals (CIs. All the statistical analyses were carried out by  Stata 11.0 software (http://www.stata.com; Stata Corporation, College Station, TX, USA. Results: We included 5 studies with 1798 cases in the bevacizumab combined with the chemotherapy group and 1810 subjects in the chemotherapy alone group. The pooled results showed that bevacizumab + chemotherapy compared with chemotherapy alone can significant prolong the median PFS (HR, 0.64; 95% CI, 0.46-0.82; P 0.05; the toxicity analysis showed that the enterobrosis, hypertension, albuminuria, neutrophils, thrombosis, and bleeding were significantly increased in the bevacizumab + chemotherapy group compared with chemotherapy alone (Pall 0.05. Conclusion: Bevacizumab combined with chemotherapy prolonged the median PFS in patients with ovarian cancer but also increase the risk of developing enterobrosis, hypertension, albuminuria, neutrophils

  13. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    DEFF Research Database (Denmark)

    Vangsted, A. J.; Soeby, K.; Klausen, T.W.

    2010-01-01

    the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Methods: Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected....... We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion...

  14. Immunological aspects of cancer chemotherapy.

    Science.gov (United States)

    Zitvogel, Laurence; Apetoh, Lionel; Ghiringhelli, François; Kroemer, Guido

    2008-01-01

    Accumulating evidence indicates that the innate and adaptive immune systems make a crucial contribution to the antitumour effects of conventional chemotherapy-based and radiotherapy-based cancer treatments. Moreover, the molecular and cellular bases of the immunogenicity of cell death that is induced by cytotoxic agents are being progressively unravelled, challenging the guidelines that currently govern the development of anticancer drugs. Here, we review the immunological aspects of conventional cancer treatments and propose that future successes in the fight against cancer will rely on the development and clinical application of combined chemo- and immunotherapies.

  15. [Adjuvant chemotherapy for patients with rectal cancer].

    Science.gov (United States)

    Qvortrup, Camilla; Mortensen, John Pløen; Pfeiffer, Per

    2013-09-09

    A new Cochrane meta-analysis evaluated adjuvant chemotherapy (5-fluorouracil (5FU)-based, not modern combination chemotherapy) in almost 10,000 patients with rectal cancer and showed a 17% reduction in mortality corresponding well to the efficacy observed in recent studies, which reported a reduction in mortality just about 20%. The authors recommend adjuvant chemotherapy which is in accordance with the Danish national guidelines where 5-FU-based chemotherapy is recommended for stage III and high-risk stage II rectal cancer.

  16. [Oral complications of chemotherapy of malignant neoplasms].

    Science.gov (United States)

    Obralić, N; Tahmiscija, H; Kobaslija, S; Beslija, S

    1999-01-01

    Function and integrity disorders of the oral cavity fall into the most frequent complication of the chemotherapy of leucemias, malignant lymphomas and solid tumors. Complications associated with cancer chemotherapy can be direct ones, resulting from the toxic action of antineoplastic agents on the proliferative lining of the mouth, or indirect, as a result of myelosuppression and immunosuppression. The most frequent oral complications associated with cancer chemotherapy are mucositis, infection and bleeding. The principles of prevention and management of oral complications during cancer chemotherapy are considered in this paper.

  17. Effect of neoadjuvant chemotherapy on sevoflurane MAC-BAR value of patients undergoing radical stomach carcinoma surgery

    OpenAIRE

    Du, Wei; Li, Chao; Wang, Hemei; Zhao, Aihua; Shen, Junmei; Yong, Fangfang; Jia, Huiqun

    2015-01-01

    Objective: To determine the minimum alveolar concentration (MAC) of sevoflurane required for 50% blockade of the adrenergic response (BAR) to surgical incision in patients treated with neoadjuvant chemotherapy prior to radical gastrectomy. Patients and design: Forty-four patients were selected for this study. Patients with preoperative neoadjuvant chemotherapy comprised the NC group (n = 22) and patients without preoperative neoadjuvant chemotherapy were included as the C group (n = 22). Pati...

  18. PID1 increases chemotherapy-induced apoptosis in medulloblastoma and glioblastoma cells in a manner that involves NFκB.

    Science.gov (United States)

    Xu, Jingying; Ren, Xiuhai; Pathania, Anup Singh; Fernandez, G Esteban; Tran, Anthony; Zhang, Yifu; Moats, Rex A; Shackleford, Gregory M; Erdreich-Epstein, Anat

    2017-04-11

    Phosphotyrosine Interaction Domain containing 1 (PID1; NYGGF4) inhibits growth of medulloblastoma, glioblastoma and atypical teratoid rhabdoid tumor cell lines. PID1 tumor mRNA levels are highly correlated with longer survival in medulloblastoma and glioma patients, suggesting their tumors may have been more sensitive to therapy. We hypothesized that PID1 sensitizes brain tumors to therapy. We found that PID1 increased the apoptosis induced by cisplatin and etoposide in medulloblastoma and glioblastoma cell lines. PID1 siRNA diminished cisplatin-induced apoptosis, suggesting that PID1 is required for cisplatin-induced apoptosis. Etoposide and cisplatin increased NFκB promoter reporter activity and etoposide induced nuclear translocation of NFκB. Etoposide also increased PID1 promoter reporter activity, PID1 mRNA, and PID1 protein, which were diminished by NFκB inhibitors JSH-23 and Bay117082. However, while cisplatin increased PID1 mRNA, it decreased PID1 protein. This decrease in PID1 protein was mitigated by the proteasome inhibitor, bortezomib, suggesting that cisplatin induced proteasome dependent degradation of PID1. These data demonstrate for the first time that etoposide- and cisplatin-induced apoptosis in medulloblastoma and glioblastoma cell lines is mediated in part by PID1, involves NFκB, and may be regulated by proteasomal degradation. This suggests that PID1 may contribute to responsiveness to chemotherapy.

  19. Adjuvant chemotherapy for colon carcinoma with positive lymph nodes: use and benefit in routine health care practice.

    Science.gov (United States)

    Bouchardy, C; Queneau, P E; Fioretta, G; Usel, M; Zellweger, M; Neyroud, I; Raymond, L; de Wolf, C; Sappino, A P

    2001-11-01

    In 1990, an international consensus was reached on the efficacy of adjuvant chemotherapy for lymph node positive (stage III) colon carcinoma (CC). This study evaluates the use and benefit of such therapy in routine health care practice. The study includes all patients with stage III CC treated by putative curative surgery (n = 182) recorded at the Geneva cancer registry between 1990 and 1996. Factors modifying chemotherapy use were determined by logistic regression, considering patients with chemotherapy as cases (n = 55) and others as controls (n = 127). The effect of chemotherapy on the 5-year survival was evaluated by the Cox model. Analyses were adjusted for possible confounders. The use of chemotherapy increased over the period (P(trend) < 0.001). Age strongly modulated chemotherapy use. In 1996, 54% of eligible patients received chemotherapy, this proportion fell to 13% after age 70. Decisions to use chemotherapy significantly depended on stage, grade and cancer site. The chance to be treated was non-significantly lower among individuals of low social class, widowed and foreigners. Chemotherapy significantly decreased mortality rates (Hazard ratio: 0.35, 95%CI: 0.18-0.68), independently of the prognostic factors and with similar benefit regardless of stage and age group. Strong beneficial effect of adjuvant chemotherapy on stage III CC can be achieved in routine practice. However, this study shows that it is probably not optimally utilised in Switzerland, particularly among the elderly.

  20. Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

    Science.gov (United States)

    Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky; Wille-Jørgensen, Peer; Mocellin, Simone

    2012-03-14

    ) and the control arm (no adjuvant chemotherapy). The survival data were either entered directly in RevMan or extrapolated from Kaplan-Meier plots and then entered in RevMan. Due to expected clinical heterogeneity a random effects model was used for creating the pooled estimates of treatment efficacy. A total of 21 eligible RCTs were identified and used for meta-analysis purposes. Overall, 16,215 patients with colorectal cancer were enrolled, 9,785 being affected with rectal carcinoma. Considering patients with rectal cancer only, 4,854 cases were randomized to receive potentially curative surgery of the primary tumour plus adjuvant chemotherapy and 4,367 to receive surgery plus observation. The mean number of patients enrolled was 466 (range: 54-1,243 cases). 11 RCTs had been performed in Western countries and 10 in Japan. All trials used fluoropyrimidine-based chemotherapy (no modern drugs - such as oxaliplatin, irinotecan or biological agents - were tested).Overall survival (OS) data were available in 21 RCTs and the data available for meta-analysis regarded 9,221 patients: of these, 4854 patients were randomized to adjuvant chemotherapy (treatment arm) and 4,367 patients did not receive adjuvant chemotherapy (control arm). The meta-analysis of these RCTs showed a significant reduction in the risk of death (17%) among patients undergoing postoperative chemotherapy as compared to those undergoing observation (HR=0.83, CI: 0.76-0.91). Between-study heterogeneity was moderate (I-squared=30%) but significant (P=0.09) at the 10% alpha level.Disease-free survival (DFS) data were reported in 20 RCTs, and the data suitable for meta-analysis included 8,530 patients. Of these, 4,515 patients were randomized to postoperative chemotherapy (treatment arm) and 4,015 patients received no postoperative chemotherapy (control arm). The meta-analysis of these RCTs showed a reduction in the risk of disease recurrence (25%) among patients undergoing adjuvant chemotherapy as compared to

  1. Chemotherapy and Dietary Phytochemical Agents

    Directory of Open Access Journals (Sweden)

    Katrin Sak

    2012-01-01

    Full Text Available Chemotherapy has been used for cancer treatment already for almost 70 years by targeting the proliferation potential and metastasising ability of tumour cells. Despite the progress made in the development of potent chemotherapy drugs, their toxicity to normal tissues and adverse side effects in multiple organ systems as well as drug resistance have remained the major obstacles for the successful clinical use. Cytotoxic agents decrease considerably the quality of life of cancer patients manifesting as acute complaints and impacting the life of survivors also for years after the treatment. Toxicity often limits the usefulness of anticancer agents being also the reason why many patients discontinue the treatment. The nutritional approach may be the means of helping to raise cancer therapy to a new level of success as supplementing or supporting the body with natural phytochemicals cannot only reduce adverse side effects but improve also the effectiveness of chemotherapeutics. Various plant-derived compounds improve the efficiency of cytotoxic agents, decrease their resistance, lower and alleviate toxic side effects, reduce the risk of tumour lysis syndrome, and detoxify the body of chemotherapeutics. The personalised approach using various phytochemicals provides thus a new dimension to the standard cancer therapy for improving its outcome in a complex and complementary way.

  2. Chemotherapy and molecular targeting therapy for recurrent cervical cancer

    Science.gov (United States)

    Tsuda, Naotake; Watari, Hidemichi; Ushijima, Kimio

    2016-01-01

    For patients with primary stage ⅣB, persistent, or recurrent cervical cancer, chemotherapy remains the standard treatment, although it is neither curative nor associated with long-term disease control. In this review, we summarized the history of treatment of recurrent cervical cancer, and the current recommendation for chemotherapy and molecular targeted therapy. Eligible articles were identified by a search of the MEDLINE bibliographical database for the period up to November 30, 2014. The search strategy included the following any or all of the keywords: “uterine cervical cancer”, “chemotherapy”, and “targeted therapies”. Since cisplatin every 21 days was considered as the historical standard treatment for recurrent cervical cancer, subsequent trials have evaluated and demonstrated activity for other agents including paclitaxel, gemcitabine, topotecan and vinorelbine among others. Accordingly, promising agents were incorporated into phase Ⅲ trials. To examine the best agent to combine with cisplatin, several landmark phase Ⅲ clinical trials were conducted by Gynecologic Oncology Group (GOG) and Japan Clinical Oncology Group (JCOG). Through, GOG204 and JCOG0505, paclitaxel/cisplatin (TP) and paclitaxel/carboplatin (TC) are now considered to be the recommended therapies for recurrent cervical cancer patients. However, the prognosis of patients who are already resistant to chemotherapy, are very poor. Therefore new therapeutic strategies are urgently required. Molecular targeted therapy will be the most hopeful candidate of these strategies. From the results of GOG240, bevacizumab combined with TP reached its primary endpoint of improving overall survival (OS). Although, the prognosis for recurrent cervical cancer patients is still poor, the results of GOG240 shed light on the usefulness of molecular target agents to chemotherapy in cancer patients. Recurrent cervical cancer is generally considered incurable and current chemotherapy regiments

  3. Prevention of neutropenia during chemotherapy by prolonged myelostimulatory preparations

    Directory of Open Access Journals (Sweden)

    V. V. Ptushkin

    2015-01-01

    Full Text Available Neutropenia and associated infection, resulting in hospitalization and use of antibiotics, has a negative effect on chemotherapy. The need to reduce the dose of cytotoxic drugs during neutropenia leads to lower survival rates in patients with hematological malignancies and solid tumors. Since 1990s myelocytokines – proteins that accelerate neutrophil recovery after cytostatic chemotherapy and reduce the risk of infection – is widely used in the clinical practice. The use of these drugs can support the planned dose intensity of chemotherapy and improves the treatment efficacy. The disadvantages of these drugs include the need for their daily parenteral administration for 7–10 days. The development of long-acting forms (pegfilgrastim and lipegfilgrastim has solved this problem. Self-regulating clearance of prolonged forms allowed to use them only once on a chemotherapy course. Results of pegfilgrastim administration in 25 patients with hematological malignancies (8 patients and solid tumors (17 patients included in our analysis. Prolonged preparation showed high efficacy in secondary prophylaxis of neutropenia and infection decreasing the risk by 82 %. The single administration of pegfilgrastim allowed safe dose intensity chemotherapy with shorter intervals between courses (AC-14 in 8 patients with breast cancer. Tolerability was good; cases of hyperleukocytosis have notbeen reported. Recently in Europe and the Russian Federation a new drug from prolonged myelocytokine group – lipegfilgrastim – has been registered. The results of two controlled trials in patients with breast cancer (n = 410 receiving doxorubicin/docetaxel showed high efficacy of the drug as the pegfilgrastim with comparable tolerability.

  4. Acute myelogenous leukemia following chemotherapy and radiation for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Aso, Teijiro; Hirota, Yuichi; Kondou, Seiji; Matsumoto, Isao; Matsuzaka, Toshimitsu; Iwashita, Akinori

    1989-03-01

    In August 1982, a 44-year-old man was diagnosed as having rectal cancer, histologically diagnosed as well differentiated adenocarcinoma, and abdominoperineal resection and colostomy were performed. Postoperatively, he received chemotherapy with mitomycin C up to a total dose of 100 mg. In September 1986, lung metastasis occurred and he was treated with a combination chemotherapy consisting of cisplatin, pirarubicin and 5-fluorouracil. In the following year, radiation treatment (total: 6900 rad) was given for a recurrent pelvic lesion. Peripheral blood on April 30, 1988, showed anemia, thrombocytopenia and appearance of myeloblasts, and a diagnosis of acute myelogenous leukemia (FAB: M1) was made. Combination chemotherapy (including aclarubicin, vincristine, behenoyl ara-C, daunorubicin, 6-mercaptopurine, cytarabine, etoposide and prednisolone) failed to induce remission and the patient died in June 1988. This case was thought to be one of secondary leukemia occurring after chemotherapy and radiation treatment for rectal cancer. This case clearly indicates the need for a careful follow-up of long-term survivors who have received cancer therapy. (author).

  5. A Metaheuristic Algorithm Based on Chemotherapy Science: CSA

    Directory of Open Access Journals (Sweden)

    Mohammad Hassan Salmani

    2017-01-01

    Full Text Available Among scientific fields of study, mathematical programming has high status and its importance has led researchers to develop accurate models and effective solving approaches to addressing optimization problems. In particular, metaheuristic algorithms are approximate methods for solving optimization problems whereby good (not necessarily optimum solutions can be generated via their implementation. In this study, we propose a population-based metaheuristic algorithm according to chemotherapy method to cure cancers that mainly search the infeasible region. As in chemotherapy, Chemotherapy Science Algorithm (CSA tries to kill inappropriate solutions (cancers and bad cells of the human body; however, this would inevitably risk incidentally destroying some acceptable solutions (healthy cells. In addition, as the cycle of cancer treatment repeats over and over, the algorithm is iterated. To align chemotherapy process with the proposed algorithm, different basic terms and definitions including Infeasibility Function (IF, objective function (OF, Cell Area (CA, and Random Cells (RCs are presented in this study. In the terminology of algorithms and optimization, IF and OF are mainly applicable as criteria to compare every pair of generated solutions. Finally, we test CSA and its structure using the benchmark Traveling Salesman Problem (TSP.

  6. Meta-analysis of intraperitoneal chemotherapy for gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Da-Zhi Xu; You-Qing Zhan; Xiao-Wei Sun; Su-Mei Cao; Qi-Rong Geng

    2004-01-01

    AIM: To assess the efficacy and safety of intraperitoneal chemotherapy in patients undergoing curative resection for gastric cancer through literature review. METHODS: Medline (PubMed) (1980-2003/1), Embase (1980-2003/1), Cancerlit Database (1983-2003/1) and Chinese Biomedicine Database (1990-2003/1) were searched. Language was restricted to Chinese and English. The statistical analysis was performed by RevMan4.2 software provided by the Cochrane Collaboration. The results were expressed with odds ratio for the categorical variables. RESULTS: Eleven trials involving 1 161 cases were included. The pooled odds ratio was 0.51, with a 95% confidence interval (0.40-0.65). Intraperitoneal chemotherapy may benefit the patients after curative resection for locally advanced gastric cancer, and the combination of intraperitoneal chemotherapy with hyperthermia or activated carbon particles may provide more benefits to patients due to the enhanced antitumor activity of drugs. Sensitivity analysis and fail-safe number suggested that the result was comparatively reliable. However, of 11 trials, only 3 studies were of high quality. CONCLUSION: Intraperitoneal chemotherapy after curative resection for locally advanced gastric cancer may be beneficial to patients. Continuous multicenter, randomized, double blind, rigorously designed trials should be conducted to draw definitive conclusions.

  7. Efficacy of Bortezomib Combined with Thalidomide and Dexamethasone in the Treat-ment of Autologous Stem Cell Transplantation in Multiple Myeloma:A Meta-analysis%硼替佐米联合沙利度胺和地塞米松治疗自体造血干细胞移植多发性骨髓瘤的Meta分析

    Institute of Scientific and Technical Information of China (English)

    王海雪; 叶云

    2016-01-01

    目的:综合评价硼替佐米联合沙利度胺和地塞米松( VTD)治疗自体造血干细胞移植( ASCT)的多发性骨髓瘤( MM)的有效性和安全性。方法计算机检索Pubmed、Medline、the Cochrane Library、CNKI、VIP和万方等数据库,检索时间从建库至2014年12月。纳入VTD治疗 ASCT 的MM的随机对照试验,按Cochrane系统评价的方法评价纳入研究的质量,采用Review Manager 5.3.5版软件进行Meta分析。结果共纳入5项研究,1271例患者。 Meta分析结果显示,在有效性方面,VTD的完全缓解率与接近完全缓解率(CR+nCR)[RR=1.50,95%CI(1.16,1.94),P=0.002]和总有效率[RR=1.13,95%CI(1.03,1.24),P=0.009]优于其他联合方案,差异有统计学意义;在安全性方面,3~4度总不良反应发生率[RR=1.29,95%CI(1.05,1.59),P=0.02]高于其他联合方案,差异有统计学意义。结论 VTD能够显著提高ASCT的MM患者的CR+nCR和总有效率,但总不良反应发生率增加。%Objective To evaluate the efficacy and safety of bortezomib combined with dexamethasone and thalidomide in the treatment of autologous stem cell transplantation ( ASCT) in multiple myeloma ( MM) . Methods The randomized con-trolled trials ( RCTs) on combined therapy with bortezomib,dexamethasone and thalidomide for ASCT in MM were retrieved from Pubmed,Medline,the Cochrane Library,CNKI,VIP and Wanfang databases (published until December 2014).The method of the Cochrane systematic review was used to evaluate the quality of the included RCTs and the Review Manager 5.3.5 software was em-ployed for Meta-analysis. Results Five RCTs involving 1 271 patients were included.The meta analysis results showed that the complete remission ( CR) rate,near-CR rate and total effective rate were significantly higher after combined treatment with borte-zomib,dexamethasone and thalidomide when compared with those in other combination therapies [CR+nCR, RR=1.50,95%CI (1

  8. Treatment of platinum-resistant recurrent ovarian cancer using a "predictive molecule targeted routine chemotherapy" system

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xiao-dong; WEI Feng-hua; ZHANG Yi; HE Shu-rong; YANG Li

    2009-01-01

    Background Correct drug selection, the key to successful chemotherapy, is one of the most difficult clinical decisions for the treatment of platinum-resistant recurrent ovarian cancer worldwide. The exact procedures for choosing drugs are undefined, currently relying on clinical trials and personal experience, which often results in disappointing outcomes. Here, we propose a new drug selection method, the "predictive molecule targeted routine chemotherapy", to choose relatively sensitive routine drugs and avoid relatively resistant routine drugs based on the specific predictive molecule expression of the individual tumor tissue.Methods From January 2004 to June 2008,26 cases of platinum-resistant recurrent ovarian cancer were prospectively recruited. Their routine chemotherapy drug choice was based on the expression of 6 predictive molecules (including p53) as determined by immunohistochemistry (the predictive molecule targeted routine chemotherapy group). A further 18 cases of platinum-resistant recurrent ovarian cancer were treated by experience and formed the control group. The response rate and the overall survival were compared between the two groups.Results The response rate to second-line chemotherapy was 28% in the control group and 77% in the predictive molecule targeted routine chemotherapy group (P=0.002). The response rate to third-line chemotherapy was 14% in the control group and 33% in the predictive molecule targeted routine chemotherapy group (P=0.268). The median overall survival of the predictive molecule targeted routine chemotherapy group (88 weeks) was significantly longer than the median overall survival of the control group (56 weeks) (P=0.0315).Conclusion The predictive molecule targeted routine chemotherapy is a new effective protocol for choosing drugs when treating platinum-resistant recurrent ovarian cancer.

  9. Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review

    Science.gov (United States)

    Kerckhove, Nicolas; Collin, Aurore; Condé, Sakahlé; Chaleteix, Carine; Pezet, Denis; Balayssac, David

    2017-01-01

    Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors. Pathophysiological mechanisms and risk factors are also presented. Neurotoxic mechanisms leading to CIPNs are not yet fully understood but involve neuronopathy and/or axonopathy, mainly associated with DNA damage, oxidative stress, mitochondria toxicity, and ion channel remodeling in the neurons of the peripheral nervous system. Classical symptoms of CIPNs are peripheral neuropathy with a “stocking and glove” distribution characterized by sensory loss, paresthesia, dysesthesia and numbness, sometimes associated with neuropathic pain in the most serious cases. Several risk factors can promote CIPN as a function of the anticancer drug considered, such as cumulative dose, treatment duration, history of neuropathy, combination of therapies and genetic polymorphisms. CIPNs are frequent in cancer patients with an overall incidence of approximately 38% (possibly up to 90% of patients treated with oxaliplatin). Finally, the long-term reversibility of these CIPNs remain questionable, notably in the case of platinum-based anticancer drugs and taxanes, for which CIPN may last several years after the end of anticancer chemotherapies. These long-term effects are associated with comorbidities such as depression, insomnia, falls and decreases of health-related quality of life in cancer patients and survivors. However, it is noteworthy that these long-term effects remain poorly studied, and only limited data are available such as in

  10. The attention network changes in breast cancer patients receiving neoadjuvant chemotherapy: Evidence from an arterial spin labeling perfusion study

    Science.gov (United States)

    Chen, Xingui; He, Xiaoxuan; Tao, Longxiang; Cheng, Huaidong; Li, Jingjing; Zhang, Jingjie; Qiu, Bensheng; Yu, Yongqiang; Wang, Kai

    2017-01-01

    To investigate the neural mechanisms underlying attention deficits that are related to neoadjuvant chemotherapy in combination with cerebral perfusion. Thirty one patients with breast cancer who were scheduled to receive neoadjuvant chemotherapy and 34 healthy control subjects were included. The patients completed two assessments of the attention network tasks (ANT), neuropsychological background tests, and the arterial spin labeling scan, which were performed before neoadjuvant chemotherapy and after completing chemotherapy. After neoadjuvant chemotherapy, the patients exhibited reduced performance in the alerting and executive control attention networks but not the orienting network (p breast cancer. The results demonstrated that neoadjuvant chemotherapy influences hemodynamic activity in different brain areas through increasing cerebral perfusion, which reduces the attention abilities in breast cancer patients. PMID:28209975

  11. Chemotherapy and Sex: Is Sexual Activity OK during Treatment?

    Science.gov (United States)

    ... and Procedures Chemotherapy Is it safe to have sex with my husband while undergoing chemotherapy? Answers from ... best to discuss any concerns about chemotherapy and sex with your doctor, who's familiar with your individual ...

  12. Chemotherapy and Hair Loss: What to Expect during Treatment

    Science.gov (United States)

    Tests and Procedures Chemotherapy Find out what to expect when it comes to chemotherapy and hair loss. Plan to use your energy staying ... you have cancer and are about to undergo chemotherapy, the chance of hair loss is very real. ...

  13. Updated survivals and prognostic factor analysis in myeloma treated by a staged approach use of bortezomib/thalidomide/dexamethasone in transplant eligible patients

    Directory of Open Access Journals (Sweden)

    Chim Chor

    2010-11-01

    Full Text Available Abstract Background Bortezomib, an NFkB inhibitor, is an active agent for the treatment of myeloma (MM. We have reported a promising complete remission (CR rate for newly diagnosed myeloma patients treated by a staged approach, in which chemosensitive patients underwent autologous haematopoietic stem cell transplantation (auto-HSCT while less chemosensitive patients received salvage therapy with bortezomib/thalidomide/dexamethasone prior to auto-HSCT. Methods Herein, with an additional 13 months of follow-up, we reported the updated survivals, and examined potential prognostic factors impacting event-free (EFS and overall survival (OS. Results With a median follow-up of 30 months, the projected OS was 73% and EFS was 50.2%. Age, gender, clinical stage and DAPK methylation could not account for the differential chemosensitivity. Advanced ISS stage and DAPK methylation adversely impacted OS whereas oligoclonal reconstitution predicted superior EFS. Conclusions Our staged approach illustrated an economical use of expensive targeted agents while preserving a good CR rate and OS. The comparable survivals of chemosensitive and less chemosensitive patients suggested the staged approach might have abolished the adverse prognostic impact of suboptimal chemosensitivity. Finally, the adverse impact of DAPK methylation and favorable impact of oligoclonal reconstitution in myeloma warrants further study.

  14. Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma : a prospective analysis of data from the HOVON-65/GMMG-HD4 trial

    NARCIS (Netherlands)

    Broyl, Annemiek; Corthals, Sophie L.; Jongen, Joost L. M.; van der Holt, Bronno; Kuiper, Rowan; de Knegt, Yvonne; van Duin, Mark; el Jarari, Laila; Bertsch, Uta; Lokhorst, Henk M.; Durie, Brian G.; Goldschmidt, Hartmut; Sonneveld, Pieter

    2010-01-01

    Background Bortezomib-induced peripheral neuropathy is a dose-limiting toxicity in patients with multiple myeloma, often requiring adjustment of treatment and affecting quality of life. We investigated the molecular profiles of early-onset (within one treatment cycle) versus late-onset (after two or

  15. Primary therapy of Waldenstrom macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BDR): long-term results of a phase 2 study of the European Myeloma Network (EMN).

    Science.gov (United States)

    Dimopoulos, Meletios A; García-Sanz, Ramón; Gavriatopoulou, Maria; Morel, Pierre; Kyrtsonis, Marie-Christine; Michalis, Eurydiki; Kartasis, Zafiris; Leleu, Xavier; Palladini, Giovanni; Tedeschi, Alessandra; Gika, Dimitra; Merlini, Giampaolo; Kastritis, Efstathios; Sonneveld, Pieter

    2013-11-07

    In this phase 2 multicenter trial, we evaluated the activity of bortezomib, dexamethasone, and rituximab (BDR) combination in previously untreated symptomatic patients with Waldenström macroglobulinemia (WM). To prevent immunoglobulin M (IgM) "flare," single agent bortezomib (1.3 mg/m(2) IV days 1, 4, 8, and 11; 21-day cycle), was followed by weekly IV bortezomib (1.6 mg/m(2) days 1, 8, 15, and 22) every 35 days for 4 additional cycles, followed by IV dexamethasone (40 mg) and IV rituximab (375 mg/m(2)) in cycles 2 and 5. Fifty-nine patients were treated; 45.5% and 40% were high and intermediate risk per the International Prognostic Scoring System for WM. On intent to treat, 85% responded (3% complete response, 7% very good partial response, 58% partial response [PR]). In 11% of patients, an increase of IgM ≥25% was observed after rituximab; no patient required plasmapheresis. After a minimum follow-up of 32 months, median progression-free survival was 42 months, 3-year duration of response for patients with ≥PR was 70%, and 3-year survival was 81%. Peripheral neuropathy occurred in 46% (grade ≥3 in 7%); only 8% discontinued bortezomib due to neuropathy. BDR is rapidly acting, well tolerated, and nonmyelotoxic, inducing durable responses in previously untreated WM.

  16. Hepatic Sinusoidal Obstruction Syndrome Induced by Non-transplant Chemotherapy for Non-Hodgkin Lymphoma

    Science.gov (United States)

    Sakumura, Miho; Tajiri, Kazuto; Miwa, Shigeharu; Nagata, Kohei; Kawai, Kengo; Miyazono, Takayoshi; Arita, Kotaro; Wada, Akinori; Murakami, Jun; Sugiyama, Toshiro

    2017-01-01

    Hepatic sinusoidal obstruction syndrome (SOS), a serious complication that mainly occurs after hematopoietic-stem cell transplantation (HSCT), is caused by damage to the sinusoidal endothelial cells after the obstruction of the sinusoid. Recently, hepatic SOS was reported to occur after non-HSCT chemotherapies. This report describes a patient who experienced hepatic SOS after non-HSCT chemotherapy for non-Hodgkin lymphoma. A liver biopsy showed the slight dilatation of the hepatic sinusoid, which may be indicative of hepatic SOS. Hepatic SOS should be included in the differential diagnosis of patients with severe liver injury following the administration of chemotherapy regimens that are toxic to the vascular endothelial cells. PMID:28202860

  17. History of chemotherapy of leprosy.

    Science.gov (United States)

    Noordeen, Shaik K

    2016-01-01

    Chemotherapy of leprosy over the past 70 years has passed through several phases, from sulfones, to clofazimine, and to highly bactericidal drugs like rifampicin. The use particularly of the more potent drugs in effective combinations and the development of standard multidrug therapy regimens have made a huge difference in the successful treatment of leprosy as well as in reducing tremendously the prevalence of leprosy globally. A major contributing factor to development of better drugs and drug combinations has been the introduction of the mouse footpad model to evaluate the in vivo activity of drugs against Mycobacterium leprae. The World Health Organization has recommended multidrug therapy, which has been used to treat more than 15 million patients in the last 30 years and has set an excellent record with regard to its very high rate of cure, very low occurrence of relapse, and very rare occurrence of drug resistance.

  18. The effect of adjuvant chemotherapy on osteoarticular allografts.

    Science.gov (United States)

    Hazan, E J; Hornicek, F J; Tomford, W; Gebhardt, M C; Mankin, H J

    2001-04-01

    Two hundred lower extremity osteoarticular allografts (in 200 patients) performed for aggressive or malignant bone tumors between 1976 and 1997 included 124 grafts of the distal femur, 46 of the proximal tibia, and 30 of the proximal femur. Seventy-four patients did not receive chemotherapy, and 126 received either adjuvant or neoadjuvant therapy. The diagnoses, mean ages, and length of followup were different for the two groups because most of the patients in the chemotherapy group had osteosarcoma, whereas the largest number in the control group had chondrosarcoma or parosteal osteosarcoma. The extent of the surgery was essentially the same for both patient groups, as is reflected by a low recurrence rate (7% for the control and 6% for the chemotherapy group). A statistical comparison of the various parameters showed that the infection, fracture, and amputation rates were the same, but the nonunion rate was markedly increased in the patients who received chemotherapy (32% versus 12%). Cox regression and Kaplan-Meier studies showed that chemotherapy had a significant effect on outcome, with the success rates for the two groups being quite different (72% versus 56%). The results for the distal femur showed a greater effect than for either the proximal tibia or the proximal femur. Analysis of these data suggest the distal femur is perhaps the most prone to healing problems, possibly based in part on the extent of the surgery. A final study supports the concept that the results improved in later years, suggesting a modification or application of the drugs used, better selection of patients, and improvements in surgical technique.

  19. Surgical Outcomes for Mastectomy Patients Receiving Neoadjuvant Chemotherapy

    Science.gov (United States)

    Bowen, Megan E.; Mone, Mary C.; Buys, Saundra S.; Sheng, Xiaoming; Nelson, Edward W.

    2017-01-01

    Objective: To evaluate the risk of neoadjuvant chemotherapy for surgical morbidity after mastectomy with or without reconstruction using 1:1 matching. Background: Postoperative surgical complications remain a potentially preventable event for breast cancer patients undergoing mastectomy. Neoadjuvant chemotherapy is among variables identified as contributory to risk, but it has not been rigorously evaluated as a principal causal influence. Methods: Data from American College of Surgeons National Surgical Quality Improvement Program (2006–2012) were used to identify females with invasive breast cancer undergoing planned mastectomy. Surgical cases categorized as clean and undergoing no secondary procedures unrelated to mastectomy were included. A 1:1 matched propensity analysis was performed using neoadjuvant chemotherapy within 30 days of surgery as treatment. A total of 12 preoperative variables were used with additional procedure matching: bilateral mastectomy, nodal surgery, tissue, and/or implant. Outcomes examined were 4 wound occurrences, sepsis, and unplanned return to the operating room. Results: We identified 31,130 patient procedures with 2488 (7.5%) receiving chemotherapy. We matched 2411 cases, with probability of treatment being 0.005 to 0.470 in both cohorts. Superficial wound complication was the most common wound event, 2.24% in neoadjuvant-treated versus 2.45% in those that were not (P = 0.627). The rate of return to the operating room was 5.7% in the neoadjuvant group versus 5.2% in those that were not (P = 0.445). The rate of sepsis was 0.37% in the neoadjuvant group versus 0.46% in those that were not (P = 0.654). Conclusions: This large, matched cohort study, controlled for preoperative risk factors and most importantly for the surgical procedure performed, demonstrates that breast cancer patients receiving neoadjuvant chemotherapy have no increased risk for surgical morbidity. PMID:27280515

  20. Chemotherapy curable malignancies and cancer stem cells: a biological review and hypothesis.

    Science.gov (United States)

    Savage, Philip

    2016-11-21

    take on a significant aspect of the biological characteristics of their parent cancer cells. This action includes for the chemotherapy curable malignancies the heightened pro-apoptotic sensitivity linked to their respective associated unique genetic events. For the chemotherapy curable malignancies the combination of the relationship of their cancer stem cells combined with the extreme inherent sensitivity to induction of apoptosis from DNA damaging agents plays a key role in determining their overall curability with chemotherapy.

  1. Peri-operative chemotherapy in the management of resectable colorectal cancer pulmonary metastases

    Directory of Open Access Journals (Sweden)

    Hawkes Eliza A

    2012-08-01

    Full Text Available Abstract Background Surgery is often advocated in patients with resectable pulmonary metastases from colorectal cancer (CRC. Our study aims to evaluate peri-operative chemotherapy in patients with metastastic CRC undergoing pulmonary metastasectomy. Methods Patients treated for CRC who underwent pulmonary metastasectomy by a single surgeon were identified. Outcome measures included survival, peri-operative complications, radiological and histological evidence of chemotherapy-induced lung toxicities. Results Between 1997 and 2009, 51 eligible patients were identified undergoing a total of 72 pulmonary resections. Thirty-eight patients received peri-operative chemotherapy, of whom 9 received an additional biological agent. Five-year overall survival rate was 72% in the whole cohort - 74% and 68% in those who received peri-operative chemotherapy (CS and those who underwent surgery alone (S respectively. Five-year relapse free survival rate was 31% in the whole cohort - 38% and ≤18% in CS and S groups respectively. Only 8% had disease progression during neoadjuvant chemotherapy. There were no post-operative deaths. Surgical complications occurred in only 4% of patients who received pre-operative chemotherapy. There was neither radiological nor histological evidence of lung toxicity in resected surgical specimens. Conclusions Peri-operative chemotherapy can be safely delivered to CRC patients undergoing pulmonary metastasectomy. Survival in this selected group of patients was favourable.

  2. Nutritional intervention using nutrition care process in a malnourished patient with chemotherapy side effects.

    Science.gov (United States)

    Lee, Hye-Ok; Lee, Jung-Joo

    2015-01-01

    In this case study, the process of nutritional diagnosis and intervention conducted at a hospital on a malnourished patient who underwent treatment for a chronic illness (chemotherapy for cancer treatment) was recorded. The patient received his first round of chemotherapy for colorectal cancer, and then a second round after the cancer metastasized to the liver. The patient was malnourished and had experienced weight loss (17% loss in the most recent 3 months) due to side effects of chemotherapy including stomatitis, nausea, and vomiting. Nutritional diagnosis and intervention via the nutrition care process were implemented through two screening rounds, and the quantity of oral intake increased from 28% to 62% of the recommended daily intake. The patient required continuous monitoring and outpatient care after hospital discharge. It is speculated that if a more active patient education and dietary regimen with respect to chemotherapy side effects had been offered after the patient's first chemotherapy cycle, it might have been possible to treat ingestion problems due to stomatitis during the second cycle of chemotherapy and prevent the weight loss. Henceforth, patients receiving chemotherapy should be educated about nutrition management methods and monitored continuously to prevent malnutrition.

  3. Salvage chemotherapy and surgery for radio recurrent carcinoma glottis

    Directory of Open Access Journals (Sweden)

    Varghese B

    2003-01-01

    Full Text Available Chemoradiotherapy is increasingly used in advanced laryngeal cancers. Failures are generally managed by surgery. They include histologically confirmed recurrent or residual disease or a symptomatic life threatening treatment sequelae. Tumour recurrence or residivism can be managed by chemotherapy when radical surgery is either refused by the patient or if the general condition of the patient do not permit it. However surgery becomes inevitable when life threatening treatment sequelae like absolute pharyngo-oesophageal stricture and aspiration sets in.

  4. Quality of life in cancer patients undergoing chemotherapy in a tertiary care center in Malwa region of Punjab

    Directory of Open Access Journals (Sweden)

    Harminder Singh

    2014-01-01

    Conclusion: Although QOL scoring system did not show significant improvement in all areas (except insomnia, pain, appetite loss, constipation, and financial difficulties with reference to their respective chemotherapy cycles, but a judicious diagnosis with an appropriate treatment including chemotherapy may lessen the negative perception of cancer as a deadly and fatal disease in our rural population.

  5. Effect of S-1 chemotherapy and FP chemotherapy on prognosis, imaging characteristics and serum marker levels after operation for gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Qing-Hao Gong; Yi-Ting Cai; Hai-Qun Chen; Chao-Feng Zhang; Gang Dai; Song-Ming Zhu

    2016-01-01

    Objective:To analyze the effect of S-1 chemotherapy and FP chemotherapy on prognosis, imaging characteristics and serum marker levels after operation for gastric carcinoma. Methods:A total of 68 patients with gastric cancer who underwent radical surgery were included in the study and divided into observation group and control group patients (n=34) according to random number table. Control group received FP chemotherapy, observation group received S-1 chemotherapy, and then differences in serum tumor markers, illness-related factors, nutrition indexes and T cell immune function values were compared between two groups.Results: After observation group received systematic chemotherapy, serum tumor markers such as MMP-9, MMP-2, MG7-Ag, TSGF, CA72-4, CA19-9, TP and DpD as well as illness-related factors such as DKK1, MK, Leptin, Exosome and OPN were all lower than those of control group (P<0.05); nutrition and cellular immune function indexes such as TP, ALB, PA, CD4+ T and CD4+ T/ CD8+ T values were higher than those of control group and CD8+ T value was lower than that of control group (P<0.05).Conclusions:S-1 chemotherapy after operation for gastric carcinoma can inhibit the tumor activity and optimize patients’ overall condition, and it has positive clinical significance.

  6. Fall-related injuries in elderly cancer patients treated with neurotoxic chemotherapy: A retrospective cohort study

    OpenAIRE

    Ward, PR; Wong, MD; Moore, R.; Naeim, A

    2014-01-01

    Background: Fall-related injuries are a well-described cause of morbidity and mortality in the community-dwelling elderly population, but have not been well described in patients with cancer. Cancer treatment with chemotherapy can result in many unwanted side effects, including peripheral neuropathy if the drugs are potentially neurotoxic. Peripheral neuropathy and other side effects of chemotherapy may lead to an increased risk of fall-related injuries. Methods: We conducted a retrospective ...

  7. 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.

  8. Chemotherapy-Induced Nausea and Vomiting.

    Science.gov (United States)

    Mustian, Karen M; Darling, Tom V; Janelsins, Michelle C; Jean-Pierre, Pascal; Roscoe, Joseph A; Morrow, Gary R

    2008-01-01

    Despite treatment advances, nausea and vomiting, especially anticipatory nausea and vomiting, delayed nausea and vomiting and nausea alone, are still the most common, expected and feared side effects among patients receiving chemotherapy. Of the 70 to 80% of cancer patients who experience chemotherapy-induced nausea and vomiting many will delay or refuse future chemotherapy treatments and contemplate stopping all treatments because of fear of further nausea and vomiting. The purpose of this chapter is to provide an overview of the patho-psychophysiology of CINV, the recommended guidelines for standard treatment, and highlight newer targeted treatment approaches.

  9. Optimal indications for second-line chemotherapy in advanced gastric cancer.

    Science.gov (United States)

    Hasegawa, Hiroko; Fujitani, Kazumasa; Nakazuru, Shoichi; Hirao, Motohiro; Mita, Eiji; Tsujinaka, Toshimasa

    2012-04-01

    As it remains uncertain whether patients with advanced gastric cancer who progress after first-line chemotherapy should receive second-line chemotherapy, we attempted to identify the optimal indications for second-line chemotherapy. In this retrospective study, 101 patients were included in univariate and multivariate analyses to identify clinicopathological variables independently associated with longer survival postprogression (SPP), defined as the time from recognition of disease progression on first-line chemotherapy to death from any cause or last follow-up. The median SPP was 340 days. On multivariate analysis, performance status 2 [hazard ratio (HR), 14.234; 95% confidence interval (CI), 2.766-73.258], serum albumin level less than 3.5 g/dl (HR, 2.088; 95% CI, 1.047-4.060) at initiation of second-line chemotherapy, and time to progression less than 170 days on first-line chemotherapy (HR, 2.497; 95% CI, 1.227-5.083) were identified as independent prognostic factors associated with shorter SPP. The median SPP was 496, 375, and 232 days in patients with 0, 1, and 2 of these 3 negative prognostic factors, respectively (P=0.0002). The present study suggests that second-line chemotherapy would not be beneficial in patients with two or more of the following three negative prognostic factors: performance status 2, serum albumin less than 3.5 g/dl at initiation of second-line chemotherapy and time to progression less than 170 days on first-line chemotherapy.

  10. PHASE Ⅱ STUDY OF GEMCITABINE COMBINED WITH PLATINUM CHEMOTHERAPY FOR RECURRENT EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer.Methods Phase Ⅱ study of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50. 5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractor. All patients received gemcitabine combined with carboplatin or oxaliplatin chemotherapy. Patients' response rate (RR) and toxicity of gemcitabine combined with platinum chemotherapy were evaluated.Results A total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36.4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10. 0 months (95% CI: 7.0-13.0) after initiation of gemcitabine combined with platinum chemotherapy.There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group (P = 0. 061 ). Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8 % of patients. Grade Ⅱ/Ⅲ anemia (54.5%) and grade Ⅲ/Ⅳ neutropenia (54.5%) were most common toxicities. Ten (45.5%) patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen (63.6%) patients received granulocyte colony-stimulating factor to relieve neutropenia,and 8 (36. 4% ) patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treatment-associated death.Conclusion Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.

  11. Treatment of primary systemic amyloidosis with the combination of bortezomib and dexamethasone%硼替佐米联合地塞米松治疗原发性系统性淀粉样变性

    Institute of Scientific and Technical Information of China (English)

    翟勇平; 刘海宁; 于亚平; 周晓钢; 宋萍; 李锋; 王学文

    2010-01-01

    Objective To evaluate the efficacy and feasibility of bortezomib plus dexamethasone (BD) in patients with primary systemic (AL) amyloidosis. Methods Eleven AL amyloidosis patients, including four relapsed or progressed after previous therapies and 7 newly diagnosed were treated with BD. Ten patients had two or more organs involved. Precursor protein analysis showed that 1 was κ light chain, 9 λ light chain;5 patients with positive immunofixation including 1 IgG κ, 3 IgG λ and 1 IgA λ. BD was administered according to standard two-week schedule. Results Eight patients were evaluable, the median number of treatment cycles was 3 (range 1 -6). Median follow-up duration was 6 months. At least one affected organ response was observed in six patients and median time to organ response was 2 months. Three patients progressed and two of them died. Toxicities were mainly diarrhea, thrombocytopenia, peripheral neuropathy, fatigue and herpes zoster, and 7 evaluable patients who had toxicities were adjusted dosage and 2 of them interrupted therapy. Epilepsia, paralytic ileus, acute cardiac dysfunction, and postural hypotention were occurred in 3 inevaluble patients. Conclusion Bortezomib plus dexamethasone is effective in AL amyloidosis. Adverse events are common, and in some patients are severe.%目的 观察硼替佐米联合地塞米松治疗原发性系统性(AL)淀粉样变性患者的疗效和不良反应.方法 11例AL淀粉样变性患者中明确淀粉样物质者10例:κ型1例,λ型9例.免疫固定电泳阳性者5例:IgG κ型1例,IgGλ型3例,IgAλ型1例.累及肾脏、肝脏、心脏、肠道中2个或以上脏器者10例.11例患者中初治者7例,难治者4例.采用硼替佐米联合地塞米松方案治疗.结果 8例可评价疗效患者,中位疗程3(1~6)个.中位随访时间6个月.器官功能改善者6例,中位起效时间2个月.3例病情进展,2例死亡.常见的不良反应有腹泻、血小板减少、周围神经病

  12. Toxicities of different first-line chemotherapy regimens in the treatment of advanced ovarian cancer

    Science.gov (United States)

    Qu, Chang-Ping; Sun, Gui-Xia; Yang, Shao-Qin; Tian, Jun; Si, Jin-Ge; Wang, Yi-Feng

    2017-01-01

    Abstract Background: Ovarian cancer (OC) is the 5th leading cause of cancer-related deaths around the world, and several chemotherapy regimens have been applied in the treatment of OC. We aim to compare toxicities of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) using network meta-analysis. Methods: Literature research in Cochrane Library, PubMed, and EMBASE was performed up to November 2015. Eligible randomized controlled trials (RCTs) of different chemotherapy regimens were included. Network meta-analysis combined direct and indirect evidence to assess pooled odds ratios (ORs) and draw the surface under the cumulative ranking (SUCRA) curves. Results: Thirteen eligible RCTs were included in this network meta-analysis, including 8 chemotherapy regimens (paclitaxel + carboplatin [PC], pegylated liposomal doxorubicin [PLD] + carboplatin, carboplatin, gemcitabine + carboplatin, paclitaxel, PC + epirubicin, PC + topotecan, docetaxel + carboplatin). Gemcitabine + carboplatin regimen exerted higher incidence of anemia when compared with carboplatin and paclitaxel regimens. The incidence of febrile neutropenia of gemcitabine + carboplatin regimen was higher than that of PC, PLD + carboplatin, carboplatin, and PC + topotecan regimens. Topotecan PC + epirubicin regimen had a higher toxicity, comparing with PC, PLD + carboplatin, and PC + topotecan regimens. As for thrombocytopenia, gemcitabine + carboplatin chemotherapy regimen produced an obviously higher toxicity than PC and carboplatin. As for nausea, PLD + carboplatin chemotherapy regimen had a significantly higher toxicity than that of carboplatin chemotherapy regimen. Moreover, when compared with PC and carboplatin chemotherapy regimens, the toxicity of PC + epirubicin was greatly higher to patients with AOC. Conclusion: The nonhematologic toxicity of PLD + carboplatin regimen was higher than other regimens, which

  13. Adjuvant chemotherapy dosing in low-income women: the impact of Hispanic ethnicity and patient self-efficacy.

    Science.gov (United States)

    Griggs, Jennifer J; Liu, Yihang; Sorbero, Melony E; Jagielski, Christina H; Maly, Rose C

    2014-04-01

    Unwarranted breast cancer adjuvant chemotherapy dose reductions have been documented in black women, women of lower socioeconomic status, and those who are obese. No information on the quality of chemotherapy is available in Hispanic women. The purpose of this study was to characterize factors associated with first cycle chemotherapy dose selection in a multi-ethnic sample of low-income women receiving chemotherapy through the Breast and Cervical Cancer Prevention Treatment Program (BCCPT) and to investigate the impact of Hispanic ethnicity and patient self-efficacy on adjuvant chemotherapy dose selection. Survey and chemotherapy information were obtained from consenting participants enrolled in the California BCCPT. Analyses identified clinical and non-clinical factors associated with first cycle chemotherapy doses less than 90 % of expected doses. Of 552 patients who received chemotherapy, 397 (72 %) were eligible for inclusion. First cycle dose reductions were given to 14 % of the sample. In multivariate analyses, increasing body mass index and non-academic treatment site were associated with doses below 90 % of the expected doses. No other clinical or non-clinical factors, including ethnicity, were associated with first cycle doses selection. In this universally low-income sample, we identified no association between Hispanic ethnicity and other non-clinical patient factors, including patient self-efficacy, in chemotherapy dose selection. As seen in other studies, obesity was associated with systematic dose limits. The guidelines on chemotherapy dose selection in the obese may help address such dose reductions. A greater understanding of the association between type of treatment site and dose selection is warranted. Overall, access to adequate health care allows the vast majority of low-income women with breast cancer to receive high-quality breast cancer chemotherapy.

  14. 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...

  15. Recent advances of cocktail chemotherapy by combination drug delivery systems.

    Science.gov (United States)

    Hu, Quanyin; Sun, Wujin; Wang, Chao; Gu, Zhen

    2016-03-01

    Combination chemotherapy is widely exploited for enhanced cancer treatment in the clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end.

  16. Patient expectancy and post-chemotherapy nausea

    DEFF Research Database (Denmark)

    Colagiuri, Ben; Zachariae, Robert

    2010-01-01

    , specifically controlling for a history of nausea, and involving breast cancer patients, none of the moderators assessed were statistically significant. CONCLUSIONS: These findings suggest that patient expectancies may contribute to post-chemotherapy nausea and that expectancy-based manipulations may provide......BACKGROUND: Post-chemotherapy nausea remains a significant burden to cancer patients. While some studies indicate that expecting nausea is predictive of experiencing nausea, there are a number of conflicting findings. PURPOSE: The purpose of this study was to conduct a meta-analytic review......, there was a robust positive association between expectancy and post-chemotherapy nausea (ESr = 0.18, equivalent to Cohen's d = 0.35), suggesting that patients with stronger expectancies experience more chemotherapy-induced nausea. Although weaker associations were found in studies employing multivariate analysis...

  17. Managing Chemotherapy Side Effects: Memory Changes

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Memory Changes What is causing these changes? Your doctor will work to find out what is causing these problems. They may be caused by ...

  18. 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

  19. Adjuvant chemotherapy in early breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent

    2016-01-01

    % of patients aged 40 or younger in 77B had regular menses throughout chemotherapy, the corresponding percentage was 37 in 82B and 47 in 89B. The DBCG in collaboration with a Swedish and a Dutch centre participating in the DBCG trial 89B compared CMF with ovarian ablation in premenopausal high-risk breast...... are not clinically useful by themselves as other chemotherapy regimens have been more efficacious, and knowledge is still lacking regarding the benefits from adding ovarian suppression to chemotherapy plus tamoxifen. The results from the DBCG 77B and 82C are in accordance with other large adjuvant trials...... adjuvant trials demonstrated that patients with either TOP2A or centromere 17 aberrations, but not with HER2 amplification, benefit from anthracycline-containing adjuvant chemotherapy. Anthracyclins have additional distinct biological mechanisms; and results from the DBCG 89D suggested that tumours...

  20. Adverse Effects of Radiation and Chemotherapy

    OpenAIRE

    1991-01-01

    The long-term consequences of radiation and chemotherapy on intellectual and endocrine function in children with brain tumors is reviewed from the Departments of Neurology and Pediatrics, State University of New York, Buffalo, NY.

  1. Factors Which Influence Owners When Deciding to Use Chemotherapy in Terminally Ill Pets

    Science.gov (United States)

    Williams, Jane; Phillips, Catherine; Byrd, Hollie Marie

    2017-01-01

    Simple Summary Cancer is as common amongst pets as it in humans. Chemotherapy can be integrated into treatment regimes for terminally ill pets to attempt to shrink tumours to extend life expectancy, but it does not cure cancer and it can have negative side effects including vomiting, depression and behavioral changes. To date, little research has been undertaken to explore owners’ decisions whether or not to treat their animals with chemotherapy. Seventy-eight dog and cat owners completed an online questionnaire to determine if they would opt for chemotherapy if their pet was diagnosed with cancer, and asked how they thought their pet’s quality of life would be affected. Fifty-eight percent of respondents would not use chemotherapy largely due to their previous experience of it. Seventy-two percent over estimated pet survival time post chemotherapy, with most people believing it would lead to remission or a cure. Owners expected their pets to be less active, sleep more and play less, reducing their quality of life. Common side effects associated with chemotherapy were not rated as acceptable. The results suggest pet owners would benefit from an increased understanding of the positive and negative impacts of chemotherapy when initially discussing treatment options with the veterinary team. Abstract Chemotherapy is a commonly integrated treatment option within human and animal oncology regimes. Limited research has investigated pet owners’ treatment decision-making in animals diagnosed with malignant neoplasia. Dog and cat owners were asked to complete an online questionnaire to elucidate factors which are key to the decision making process. Seventy-eight respondents completed the questionnaire in full. Fifty-eight percent of pet owners would not elect to treat pets with chemotherapy due to the negative impact of the associated side effects. Seventy-two percent of respondents over estimated pet survival time post chemotherapy, indicating a general perception

  2. Peri-operative chemotherapy in the management of resectable colorectal cancer pulmonary metastases

    DEFF Research Database (Denmark)

    Hawkes, Eliza A; Ladas, George; Cunningham, David

    2012-01-01

    BACKGROUND: Surgery is often advocated in patients with resectable pulmonary metastases from colorectal cancer (CRC). Our study aims to evaluate peri-operative chemotherapy in patients with metastastic CRC undergoing pulmonary metastasectomy. METHODS: Patients treated for CRC who underwent...... pulmonary metastasectomy by a single surgeon were identified. Outcome measures included survival, peri-operative complications, radiological and histological evidence of chemotherapy-induced lung toxicities. RESULTS: Between 1997 and 2009, 51 eligible patients were identified undergoing a total of 72...... pulmonary resections. Thirty-eight patients received peri-operative chemotherapy, of whom 9 received an additional biological agent. Five-year overall survival rate was 72% in the whole cohort - 74% and 68% in those who received peri-operative chemotherapy (CS) and those who underwent surgery alone (S...

  3. Chemotherapy induced nausea AND vomiting (CINV

    Directory of Open Access Journals (Sweden)

    Bannur R. Nandeesh

    2012-06-01

    Full Text Available Chemotherapy is the first line treatment in management of many cancers, both for cure and palliation; hence it’s crucial to minimize the unpleasant side effects of chemotherapy to increase tolerability to chemotherapy. Most of the conventional anti cancer drugs are emetogenic. Patients receiving chemotherapy experience different degrees of nausea and vomiting depending on the emetogenic potential of the anti cancer drugs given and the patient characteristics. With a better understanding of the pathophysiology, distinct phases of chemotherapy-induced nausea and vomiting (CINV i.e., acute emesis, delayed emesis and anticipatory emesis have been identified. Identification of various mediators has led to the development of different drugs acting through different mechanisms which are useful in the prevention and treatment of CINV. Serotonin receptor three (5-HT3 antagonists, corticosteroids and neurokinin type one receptor (NK-1 antagonists are of proven usefulness and have wide therapeutic indexes in the prevention of CINV. Other drugs like dopamine receptor antagonists & benzodiazepines are not routinely used because of their narrow therapeutic index. Practice guidelines for prevention of CINV will not only improve patient’s tolerability to chemotherapy & wellbeing, but also decrease hospital stay and overall cost of treatment of the patient. [Int J Basic Clin Pharmacol 2012; 1(3.000: 125-131

  4. Longitudinal risk of herpes zoster in patients with non-Hodgkin lymphoma receiving chemotherapy: A nationwide population-based study.

    Science.gov (United States)

    Cho, Shih-Feng; Wu, Wan-Hsuan; Yang, Yi-Hsin; Liu, Yi-Chang; Hsiao, Hui-Hua; Chang, Chao-Sung

    2015-09-22

    This study investigated the incidence of and risk factors for herpes zoster in patients with non-Hodgkin lymphoma (NHL) who were receiving anti-lymphoma treatment. The overall incidence density of herpes zoster was 12.21% (472/3865); 11.79% (258/2188) of the patients received conventional chemotherapy and 12.76% (214/1677) of the patients received rituximab-containing chemotherapy. For the patients who received conventional chemotherapy, the risk factors included female gender, multiple courses of chemotherapy and autologous hematopoietic stem cell transplantation. For the patients who received rituximab-containing chemotherapy, the risk factors included female gender, diabetes mellitus, multiple courses of chemotherapy, autologous hematopoietic stem cell transplantation and higher accumulated rituximab dose. The majority of the herpes zoster episodes occurred within the first two years after the diagnosis of NHL. After adjusting for the propensity score matching, rituximab-containing chemotherapy was not associated with a higher overall incidence density of herpes zoster (P = 0.155). However, the addition of rituximab to conventional chemotherapy increased the short-term risk of herpes zoster with adjusted odd ratios of 1.38 (95% confidence intervals (CI) = 1.05-1.81, P = 0.021) and 1.37 (95% CI = 1.08-1.73, P = 0.010) during the 1-year and 2-year follow-up periods, respectively.

  5. Clinical impact of chemotherapy to improve tumor microenvironment of pancreatic cancer.

    Science.gov (United States)

    Tsuchikawa, Takahiro; Takeuchi, Shintaro; Nakamura, Toru; Shichinohe, Toshiaki; Hirano, Satoshi

    2016-11-15

    A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been actively applied as an immunomodulating modality because of concerns about various immunosuppressive effects. It has recently been shown that certain chemotherapeutic agents could modify tumor microenvironment and host immune responses through several underlying mechanisms such as immunogenic cell death, local T-cell infiltration and also the eradication of immune-suppressing regulatory cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells. With the better understanding of the cell components in the tumor microenvironment and the effect of chemotherapy to improve tumor microenvironment, it has been gradually clear that the chemotherapeutic agents is two-edged sword to have both immune promoting and suppressing effects. The cellular components of the tumor microenvironment include infiltrating T lymphocytes, dendritic cells, regulatory T cells, tumor associated macrophages, myeloid derived suppressor cells and cancer associated fibroblasts. Based on the better understanding of tumor microenvironment following chemotherapy, the treatment protocol could be modified as personalized medicine and the prognosis of pancreas cancer would be more improved utilizing multimodal chemotherapy. Here we review the recent advances of chemotherapy to improve tumor microenvironment of pancreatic cancer, introducing the unique feature of tumor microenvironment of pancreatic cancer, interaction between anti-cancer reagents and these constituting cells and future prospects.

  6. Analytical Method Development and Validation of Related Substance Method for Bortezomib for Injection 3.5 mg/Vial by RP-HPLC Method

    Directory of Open Access Journals (Sweden)

    Utage M

    2013-04-01

    Full Text Available An accurate, precise, simple and economical High Performance Liquid Chromatographic method for therelated substance determination of Bortezomib in its lyophilized dosage form has been developed. Themethod developed is Reverse Phase High Performance Liquid Chromatographic method using HypersilBDS C18 column (Length: 150mm, Diameter: 4.6mm, Particle size: 5μ with Gradient programmed anda simple Acetonitrile, Water and Formic acid in the ratio of 30:70:0.1 (v/v/v respectively as mobilephase A and Acetonitrile, Water and Formic acid in the ratio of 80:20:0.1 (v/v/v respectively. Themethod so developed was validated in compliance with the regulatory guidelines by using welldeveloped analytical method validation tool which comprises with the analytical method validationparameters like Linearity, Accuracy, Method precision, Specificity with forced degradation, Systemsuitability, Robustness, LOD, LOQ and Ruggedness. The results obtained were well within theacceptance criteria.

  7. Immunoglobulin D multiple myeloma, plasma cell leukemia and chronic myelogenous leukemia in a single patient treated simultaneously with lenalidomide, bortezomib, dexamethasone and imatinib

    Directory of Open Access Journals (Sweden)

    Naveed Ali

    2016-03-01

    Full Text Available Multiple myeloma (MM is a neoplastic lymphoproliferative disorder characterized by uncontrolled monoclonal plasma cell proliferation. Among different isotypes of MM, immunoglobulin D (IgD MM is very rare, representing only 1 to 2% of all isotypes. Chronic myelogenous leukemia (CML is a neoplastic myeloproliferative disorder of pluripotent hematopoietic stem cell, which is characterized by the uncontrolled proliferation of myeloid cells. An 88-year-old male was diagnosed simultaneously with IgD kappa MM and CML. A distinctive feature in this patient was the progression to plasma cell leukemia without any symptomatic myeloma stage. He was treated simultaneously with lenalidomide, bortezomib and imatinib. Synchronous occurrence of these rare hematological malignancies in a single patient is an exceedingly rare event. Multiple hypotheses to explain co-occurrence of CML and MM have been proposed; however, the exact etiological molecular pathophysiology remains elusive.

  8. Development and Validation of a Stability Indicating LC Method for the Assay and Related Substances Determination of a Proteasome Inhibitor Bortezomib

    Directory of Open Access Journals (Sweden)

    Kasa Srinivasulu

    2012-01-01

    Full Text Available A novel, simple, sensitive, stability indicating HPLC method was developed and validated for quantification of impurities (process related and degradants and assay determination of bortezomib. Stability indicating power of the method was established by forced degradation experiments and mass balance study. The chromatographic separation was achieved with Waters SymmetryShield RP18 column using gradient elution using the mobile phase-A consists of a mixture of water-acetonitrile-formic acid (715 : 285 : 1, v/v/v and the mobile phase-B consists a mixture of methanol-water-formic acid (800 : 200 : 1, v/v/v, respectively. The developed method is validated for parameters like precision, accuracy, linearity, LOD, LOQ, and ruggedness. Central composite experimental design (CCD was applied to check the robustness of the method. The stability tests were also performed on drug substances as per ICH norms.

  9. Long-term reversibility of renal dysfunction associated to light chain deposition disease with bortezomib and dexamethasone and high dose therapy and autologous stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Tomás J. González-López

    2011-11-01

    Full Text Available A 63-year-old woman presented with progressive renal insufficiency, until a glomerular filtration rate (GFR of 12 mL/min. A renal biopsy demonstrated glomerular deposition of immunoglobulin k light chain. The presence of a small population of monoclonal plasmacytes producing an only light k monoclonal component was demonstrated and Bortezomib and Dexamethasone (BD was provided as initial therapy. After seven courses of therapy, renal function improved without dialysis requirements up to a GFR 31 mL/min. Under hematological complete response (HCR the patient underwent high dose of melphalan (HDM and autologous peripheral blood stem cell transplant. Fifty-four months later the patient remains in HCR and the GFR has progressively improved up to 48 mL/min. This report describes a notably renal function improvement in a patient with Light Chain Deposition Disease after therapy with BD followed by HDM, which can support this treatment as a future option for these patients.

  10. LDH is an adverse prognostic factor independent of ISS in transplant-eligible myeloma patients receiving bortezomib-based induction regimens.

    Science.gov (United States)

    Chim, Chor Sang; Sim, Joycelyn; Tam, Sidney; Tse, Eric; Lie, Albert Kwok Wai; Kwong, Yok Lam

    2015-04-01

    Serum lactate dehydrogenase (LDH) has been an adverse prognostic factor for myeloma but does not feature in the International Staging System (ISS). We examined whether elevated serum LDH at diagnosis remains an adverse risk factor independent of ISS for survivals transplant-eligible myeloma patients receiving early/frontline bortezomib-based induction, followed by autologous stem cell transplantation (ASCT). Seventy-seven transplant-eligible Chinese patients received three induction regimens [staged approach (N = 25), PAD (N = 19), VTD (N = 33)], followed by ASCT and thalidomide maintenance. Five-year overall (OS) and event-free (EFS) survivals were 66.4% and 36.2%. There was no difference in demographics, complete remission/near complete remission (CR/nCR rates postinduction or ASCT, and survivals among patients induced by the three induction regimens. Elevated LDH was associated with male gender (P = 0.006), ISS III (P = 0.042) and serum β2-microglobulin (P = 0.040). Univariate analysis showed that elevated LDH, ISS III, high β2-microglobulin, and failure to attain CR/nCR post-ACST were risk factors adversely impacting both OS and EFS. Multivariate analysis showed that elevated LDH was the only factor impacting both OS (P = 0.007) and EFS (P = 0.008). In this uniformly treated cohort of transplant-eligible myeloma patients, elevated serum LDH is an adverse risk factor independent of ISS for both OS and EFS. Bortezomib-based induction/ASCT regimen had not abolished the adverse impact of elevated LDH. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells

    Science.gov (United States)

    Paulus, A; Akhtar, S; Caulfield, T R; Samuel, K; Yousaf, H; Bashir, Y; Paulus, S M; Tran, D; Hudec, R; Cogen, D; Jiang, J; Edenfield, B; Novak, A; Ansell, S M; Witzig, T; Martin, P; Coleman, M; Roy, V; Ailawadhi, S; Chitta, K; Linder, S; Chanan-Khan, A

    2016-01-01

    The survival of Waldenstrom macroglobulinemia (WM) tumor cells hinges on aberrant B-cell receptor (BCR) and MYD88 signaling. WM cells upregulate the proteasome function to sustain the BCR-driven growth while maintaining homeostasis. Clinically, two treatment strategies are used to disrupt these complementary yet mutually exclusive WM survival pathways via ibrutinib (targets BTK/MYD88 node) and bortezomib (targets 20 S proteasome). Despite the success of both agents, WM patients eventually become refractory to treatment, highlighting the adaptive plasticity of WM cells and underscoring the need for development of new therapeutics. Here we provide a comprehensive preclinical report on the anti-WM activity of VLX1570, a novel small-molecule inhibitor of the deubiquitinating enzymes (DUBs), ubiquitin-specific protease 14 (USP14) and ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5). Both DUBs reside in the 19 S proteasome cap and their inhibition by VLX1570 results in rapid and tumor-specific apoptosis in bortezomib- or ibrutinib-resistant WM cells. Notably, treatment of WM cells with VLX1570 downregulated BCR-associated elements BTK, MYD88, NFATC, NF-κB and CXCR4, the latter whose dysregulated function is linked to ibrutinib resistance. VLX1570 administered to WM-xenografted mice resulted in decreased tumor burden and prolonged survival (P=0.0008) compared with vehicle-treated mice. Overall, our report demonstrates significant value in targeting USP14/UCHL5 with VLX1570 in drug-resistant WM and carries a high potential for clinical translation. PMID:27813535

  12. Comparison of engraftment following different stem cell mobilization modalities in patients with multiple myeloma treated with a uniform induction regimen containing bortezomib, cyclophosphamide and dexamethasone.

    Science.gov (United States)

    Benyamini, Noam; Avivi, Irit; Dann, Eldad J; Zuckerman, Tsila; Lavi, Noa; Katz, Tami

    2017-03-01

    Bortezomib-based induction followed by autologous stem cell transplantation is a common treatment for multiple myeloma (MM). Stem cell (SC) mobilization with granulocyte-colony stimulating factor (G-CSF) alone has become an alternative to G-CSF combined with chemotherapeutic agents. This study aimed to compare the efficacy of the two mobilization modalities following induction with a uniform regimen containing bortezomib, cyclophosphamide and dexamethasone (VCD). We retrospectively evaluated results of SC mobilization using either G-CSF alone or combined with high-dose cyclophosphamide (HD-CY) in MM patients after VCD induction. The primary endpoints of the study were engraftment and mobilization-associated toxicity. Parameters of stem cell collection, transplantation and engraftment were assessed. Data of 92 patients were analyzed [56 (61%) mobilized with HD-CY + G-CSF and 36 (39%) with G-CSF only]. HD-CY + G-CSF provided a higher number of CD34 + cells (15.9 vs 8.1 × 10(6)/kg, p = 0.001) with fewer apheresis sessions. However, while no adverse events were observed in patients receiving G-CSF alone, nine patients (16%) receiving HD-CY + G-CSF developed neutropenic fever requiring hospitalization. Although a greater number of cells was transplanted following mobilization with HD-CY + G-CSF, neutrophil and platelet engraftment and duration of transplant-related hospitalization were similar in both cohorts. G-CSF alone provided a sufficient SC amount, without exposing patients to additional toxicity. While HD-CY + G-CSF resulted in a superior SC yield in MM patients induced with VCD, this advantage should be balanced against adverse effects of this mobilization regimen.

  13. Molecular mechanisms for tumour resistance to chemotherapy.

    Science.gov (United States)

    Pan, Shu-Ting; Li, Zhi-Ling; He, Zhi-Xu; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2016-08-01

    Chemotherapy is one of the prevailing methods used to treat malignant tumours, but the outcome and prognosis of tumour patients are not optimistic. Cancer cells gradually generate resistance to almost all chemotherapeutic drugs via a variety of distinct mechanisms and pathways. Chemotherapeutic resistance, either intrinsic or acquired, is caused and sustained by reduced drug accumulation and increased drug export, alterations in drug targets and signalling transduction molecules, increased repair of drug-induced DNA damage, and evasion of apoptosis. In order to better understand the mechanisms of chemoresistance, this review highlights our current knowledge of the role of altered drug metabolism and transport and deregulation of apoptosis and autophagy in the development of tumour chemoresistance. Reduced intracellular activation of prodrugs (e.g. thiotepa and tegafur) or enhanced drug inactivation by Phase I and II enzymes contributes to the development of chemoresistance. Both primary and acquired resistance can be caused by alterations in the transport of anticancer drugs which is mediated by a variety of drug transporters such as P-glycoprotein (P-gp), multidrug resistance associated proteins, and breast cancer resistance protein. Presently there is a line of evidence indicating that deregulation of programmed cell death including apoptosis and autophagy is also an important mechanism for tumour resistance to anticancer drugs. Reversal of chemoresistance is likely via pharmacological and biological approaches. Further studies are warranted to grasp the full picture of how each type of cancer cells develop resistance to anticancer drugs and to identify novel strategies to overcome it.

  14. Poxviruses: smallpox vaccine, its complications and chemotherapy

    Directory of Open Access Journals (Sweden)

    Mimi Remichkova

    2010-04-01

    Full Text Available Mimi RemichkovaDepartment of Pathogenic Bacteria, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, BulgariaAbstract: The threat of bioterrorism in the recent years has once again posed to mankind the unresolved problems of contagious diseases, well forgotten in the past. Smallpox (variola is among the most dangerous and highly contagious viral infections affecting humans. The last natural case in Somalia marked the end of a successful World Health Organization campaign for smallpox eradication by vaccination on worldwide scale. Smallpox virus still exists today in some laboratories, specially designated for that purpose. The contemporary response in the treatment of the post-vaccine complications, which would occur upon enforcing new programs for mass-scale smallpox immunization, includes application of effective chemotherapeutics and their combinations. The goals are to provide the highest possible level of protection and safety of the population in case of eventual terrorist attack. This review describes the characteristic features of the poxviruses, smallpox vaccination, its adverse reactions, and poxvirus chemotherapy.Keywords: poxvirus, smallpox vaccine, post vaccine complications, inhibitors

  15. 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.

  16. Optical modulator including grapene

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ming; Yin, Xiaobo; Zhang, Xiang

    2016-06-07

    The present invention provides for a one or more layer graphene optical modulator. In a first exemplary embodiment the optical modulator includes an optical waveguide, a nanoscale oxide spacer adjacent to a working region of the waveguide, and a monolayer graphene sheet adjacent to the spacer. In a second exemplary embodiment, the optical modulator includes at least one pair of active media, where the pair includes an oxide spacer, a first monolayer graphene sheet adjacent to a first side of the spacer, and a second monolayer graphene sheet adjacent to a second side of the spacer, and at least one optical waveguide adjacent to the pair.

  17. Impact of Temozolomide on Immune Response during Malignant Glioma Chemotherapy

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    Sadhak Sengupta

    2012-01-01

    Full Text Available Malignant glioma, or glioblastoma, is the most common and lethal form of brain tumor with a median survival time of 15 months. The established therapeutic regimen includes a tripartite therapy of surgical resection followed by radiation and temozolomide (TMZ chemotherapy, concurrently with radiation and then as an adjuvant. TMZ, a DNA alkylating agent, is the most successful antiglioma drug and has added several months to the life expectancy of malignant glioma patients. However, TMZ is also responsible for inducing lymphopenia and myelosuppression in malignant glioma patients undergoing chemotherapy. Although TMZ-induced lymphopenia has been attributed to facilitate antitumor vaccination studies by inducing passive immune response, in general lymphopenic conditions have been associated with poor immune surveillance leading to opportunistic infections in glioma patients, as well as disrupting active antiglioma immune response by depleting both T and NK cells. Deletion of O6-methylguanine-DNA-methyltransferase (MGMT activity, a DNA repair enzyme, by temozolomide has been determined to be the cause of lymphopenia. Drug-resistant mutation of the MGMT protein has been shown to render chemoprotection against TMZ. The immune modulating role of TMZ during glioma chemotherapy and possible mechanisms to establish a strong TMZ-resistant immune response have been discussed.

  18. Genotyping panel for assessing response to cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Hampel Heather

    2008-06-01

    Full Text Available Abstract Background Variants in numerous genes are thought to affect the success or failure of cancer chemotherapy. Interindividual variability can result from genes involved in drug metabolism and transport, drug targets (receptors, enzymes, etc, and proteins relevant to cell survival (e.g., cell cycle, DNA repair, and apoptosis. The purpose of the current study is to establish a flexible, cost-effective, high-throughput genotyping platform for candidate genes involved in chemoresistance and -sensitivity, and treatment outcomes. Methods We have adopted SNPlex for genotyping 432 single nucleotide polymorphisms (SNPs in 160 candidate genes implicated in response to anticancer chemotherapy. Results The genotyping panels were applied to 39 patients with chronic lymphocytic leukemia undergoing flavopiridol chemotherapy, and 90 patients with colorectal cancer. 408 SNPs (94% produced successful genotyping results. Additional genotyping methods were established for polymorphisms undetectable by SNPlex, including multiplexed SNaPshot for CYP2D6 SNPs, and PCR amplification with fluorescently labeled primers for the UGT1A1 promoter (TAnTAA repeat polymorphism. Conclusion This genotyping panel is useful for supporting clinical anticancer drug trials to identify polymorphisms that contribute to interindividual variability in drug response. Availability of population genetic data across multiple studies has the potential to yield genetic biomarkers for optimizing anticancer therapy.

  19. Dysregulation of cytokine mediated chemotherapy induced cognitive impairment.

    Science.gov (United States)

    Ren, Xiaojia; St Clair, Daret K; Butterfield, D Allan

    2017-03-01

    One of the major complaints patients who survive cancer often make is chemotherapy induced cognitive impairment (CICI), which survivors often call "chemo brain." CICI is a side effect of chemotherapy due to the cytotoxicity and neurotoxicity of anti-cancer drugs causing structural and functional changes in brain, even when drugs that do not cross the blood brain barrier (BBB) are used. Diminished cognitive functions including diminution of learning and memory, concentration and attention, processing speed and executive functions that reduce quality of life and ability to work are common signs and symptoms of CICI. There still is not a clarified and complete mechanism for CICI, but researchers have pointed to several biochemical candidates. Chemotherapy-induced, cytokine-mediated involvement in CICI will be mainly discussed in this review paper with emphasis on different types of cytokines, correlated with BBB and epigenetic changes. Mechanisms of ROS-generating, anti-cancer drugs and their relation to cytokine-mediated CICI will be emphasized.

  20. [Neoadjuvant chemotherapy of invasive cancer of the urinary bladder].

    Science.gov (United States)

    Selivanov, S P; Isaeva, S N; Kovalik, T A; Chén', M N; Aleksandrovich, I N; Kaliev, E A

    2007-01-01

    We studied efficacy of a combination of intraosseous and systemic administration of drugs in patients with invasive cancer of the urinary bladder (UB). A total of 20 patients aged 54-79 years with verified had recurrence, 2 had tumors with continuous growth. T2N0M0 UB carcinoma was diagnosed in 7 patients, T3N0M0--in 12, T6N0M0--in 1 patient. All the patients received systemic chemotherapy with gemzar in a single daily dose 800-1000 mg/m2 on day 1, 7 and 14. On day 2 a single intraosseous 100 mg eloxatin was given. A total of three courses of combined chemotherapy with 4-week interval was used. Intravenous gemzar administration was accompanied with mild leukopenia in 4 patients, moderate leukopenia--in 1, allergic reaction--in 2 patients. This required gemzar discontinuation. No side effects were seen in response to intraosseous administration of eloxatin. The combined chemotherapy produced complete regression of UB cancer in 3 of 18 patients, partial regression--in 12, stabilization--in 3 patients. Neither local nor long-term tumor progression was found. Short-term therapeutic efficacy of combined therapy was 70%. Fifteen patients with partial regression or stabilization have undergone transurethral resection. Duration of a recurrence-free period reached 5 to 72 months (mean 17 months). The neoadjuvant chemotherapy proposed by us allows achievement of a high percentage of regression in patients with invasive UB cancer located in UB cervix and provides concervative surgery including patients over 70 years of age.

  1. Practical aspects of the use of intrathecal chemotherapy

    Directory of Open Access Journals (Sweden)

    Raquel Olmos-Jiménez

    2017-01-01

    Full Text Available Introduction: Intrathecal chemotherapy is frequently used in clinical practice for treatment and prevention of neoplastic meningitis. Despite its widespread use, there is little information about practical aspects such as the volume of drug to be administered or its preparation and administration. Objective: To conduct a literature review about practical aspects of the use of intrathecal chemotherapy. Materials: Search in PubMed/ Medline using the terms chemotherapy AND intrathecal”, analysis of secondary and tertiary information sources. Results: The most widely used drugs in intrathecal therapy are methotrexate and cytarabine, at variable doses. One of the aspects with higher variability among different studies is their potential combination with a glucocorticoid, the specific corticoid selected and its dose. The efficacy and toxicity of the different combinations have not been compared. Regarding preparation, it is worth highlighting the recommendation to adjust pH and osmolarity to the physiological range, with the aim of improving tolerability. The volume of administration can influence distribution, and recommendated range is between 5 and 12 mL. Overall, it is recommended to extract a similar volume of cerebrospinal fluid before administration. The position of the patient during and after administration can have an impact on distribution and toxicity; lateral decubitus or sitting position is recommended in the first case, and prone and/ or supine position in the second one. Most publications don’t explain how the treatment has been prepared or administered, and the lack of standardization could affect results. Conclusions: There is a great variability in practice when using intrathecal chemotherapy, despite being an effective therapy, accepted by all international groups. This uncertainty is not li mited to the drugs and doses administered, but it also includes the manner of preparation and the administration technique. The

  2. Visual Impairment, Including Blindness

    Science.gov (United States)

    ... Who Knows What? Survey Item Bank Search for: Visual Impairment, Including Blindness Links updated, April 2017 En ... doesn’t wear his glasses. Back to top Visual Impairments in Children Vision is one of our ...

  3. 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

  4. Association of nutritional status-related indices and chemotherapy-induced adverse events in gastric cancer patients.

    Science.gov (United States)

    Seo, Seung Hee; Kim, Sung-Eun; Kang, Yoon-Koo; Ryoo, Baek-Yeol; Ryu, Min-Hee; Jeong, Jae Ho; Kang, Shin Sook; Yang, Mihi; Lee, Jung Eun; Sung, Mi-Kyung

    2016-11-18

    Malnutrition in gastrectomized patients receiving chemotherapy is associated with the susceptibility to chemotherapy-related adverse events. This study evaluated pre-operative nutritional status-related indices associated with adverse events in post-operation gastric cancer patients receiving chemotherapy. Medical records of 234 gastrectomized patients under adjuvant tegafur/gimeracil/oteracil chemotherapy with extended lymph node dissection were analyzed. Nutritional status assessment included Patient-Generated Subjective Global Assessment (PG-SGA), body weight, body mass index, serum albumin concentration, and Nutrition Risk Index (NRI). Chemotherapy-originated adverse events were determined using Common Terminology Criteria for Adverse Events. PG-SGA indicated 59% of the patients were malnourished, and 27.8% of the patients revealed serious malnutrition with PG-SGA score of ≥9. Fifteen % of patients lost ≥10% of the initial body weight, 14.5% of the patients had hypoalbuminemia (cancer patients.

  5. Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early stage Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Blank, Oliver; von Tresckow, Bastian; Monsef, Ina

    2017-01-01

    in a sensitivity analysis, the results showed that the combination of chemotherapy and radiotherapy improved OS compared to chemotherapy alone (HR 0.31; 95% CI 0.19 to 0.52; P evidence). In contrast to chemotherapy alone the use of chemotherapy and radiotherapy improved PFS (HR 0.42; 95.......94; 95% CI 0.31 to 27.55; P = 0.35;low- quality evidence), there is no evidence for a difference between the use of chemotherapy alone and chemotherapy plus radiotherapy. For complete response rate (CRR) (RR 1.08; 95% CI 0.93 to 1.25; P = 0.33; low- quality evidence), there is also no evidence...... improve OS compared to chemotherapy plus radiotherapy (HR 2.12; 95% CI 1.03 to 4.37; P = 0.04; low- quality evidence). This trial also had a potential other high risk of bias due to a high number of patients not receiving planned therapy. There is no evidence for a difference between chemotherapy alone...

  6. Shenqifuzheng injection combined with chemotherapy in the treatment of advanced gastric cancer: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Kunhou Yao

    2014-01-01

    Full Text Available Objective: The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of Shenqifuzheng (SQFZ injection combined with chemotherapy in the treatment of advanced gastric cancer. Materials and Methods: We conducted an electronic search by using PubMed, EMBASE, ASCO, ESMO and Chinese National Knowledge Infratructure (CNKI, databases. The randomized controlled trials about Shenqifuzheng injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced gastric cancer were reviewed and collected. Pooled odds ratio (OR for the response rate and KPS improvement were calculated using the software MetaAnalyst 3.1. Results: Fifteen trials met our inclusion criteria and finally included in this meta-analysis. The objective response rate (ORR in patients treated with Shenqifuzheng injection combined with chemotherapy was much higher than that of chemotherapy only (OR = 1.66, 95% CI: 1.20-2.29 with statistical significance (P < 0.05. The pooled data showed the combined treatment can significant increase the Karnofsky score (KPS compared with the chemotherapy only (OR = 3.74, 95% CI: 2.66-5.27 (P < 0.05. Conclusion: SQFZ injection combined with chemotherapy treatment regimen can improve the clinical efficacy and performance status in patients with advanced gastric cancer compared with chemotherapy alone.

  7. MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells.

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    Thomas Walenda

    Full Text Available Hematopoietic regeneration after high dose chemotherapy necessitates activation of the stem cell pool. There is evidence that serum taken after chemotherapy comprises factors stimulating proliferation and self-renewal of CD34(+ hematopoietic stem and progenitor cells (HSPCs--however, the nature of these feedback signals is yet unclear. Here, we addressed the question if specific microRNAs (miRNAs or metabolites are affected after high dose chemotherapy. Serum taken from the same patients before and after chemotherapy was supplemented for in vitro cultivation of HSPCs. Serum taken after chemotherapy significantly enhanced HSPC proliferation, better maintained a CD34(+ immunophenotype, and stimulated colony forming units. Microarray analysis revealed that 23 miRNAs changed in serum after chemotherapy--particularly, miRNA-320c and miRNA-1275 were down-regulated whereas miRNA-3663-3p was up-regulated. miRNA-320c was exemplarily inhibited by an antagomiR, which seemed to increase proliferation. Metabolomic profiling demonstrated that 44 metabolites were less abundant, whereas three (including 2-hydroxybutyrate and taurocholenate sulphate increased in serum upon chemotherapy. Nine of these metabolites were subsequently tested for effects on HSPCs in vitro, but none of them exerted a clear concentration dependent effect on proliferation, immunophenotype and colony forming unit formation. Taken together, serum profiles of miRNAs and metabolites changed after chemotherapy. Rather than individually, these factors may act in concert to recruit HSPCs into action for hematopoietic regeneration.

  8. MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells

    Science.gov (United States)

    Jost, Edgar; Morin-Kensicki, Elizabeth; Goecke, Tamme W.; Bosio, Andreas; Rath, Björn; Brümmendorf, Tim H.; Bissels, Ute; Wagner, Wolfgang

    2015-01-01

    Hematopoietic regeneration after high dose chemotherapy necessitates activation of the stem cell pool. There is evidence that serum taken after chemotherapy comprises factors stimulating proliferation and self-renewal of CD34+ hematopoietic stem and progenitor cells (HSPCs) – however, the nature of these feedback signals is yet unclear. Here, we addressed the question if specific microRNAs (miRNAs) or metabolites are affected after high dose chemotherapy. Serum taken from the same patients before and after chemotherapy was supplemented for in vitro cultivation of HSPCs. Serum taken after chemotherapy significantly enhanced HSPC proliferation, better maintained a CD34+ immunophenotype, and stimulated colony forming units. Microarray analysis revealed that 23 miRNAs changed in serum after chemotherapy – particularly, miRNA-320c and miRNA-1275 were down-regulated whereas miRNA-3663-3p was up-regulated. miRNA-320c was exemplarily inhibited by an antagomiR, which seemed to increase proliferation. Metabolomic profiling demonstrated that 44 metabolites were less abundant, whereas three (including 2-hydroxybutyrate and taurocholenate sulphate) increased in serum upon chemotherapy. Nine of these metabolites were subsequently tested for effects on HSPCs in vitro, but none of them exerted a clear concentration dependent effect on proliferation, immunophenotype and colony forming unit formation. Taken together, serum profiles of miRNAs and metabolites changed after chemotherapy. Rather than individually, these factors may act in concert to recruit HSPCs into action for hematopoietic regeneration. PMID:26024523

  9. A sleeping phantom leg awakened following hemicolectomy, thrombosis, and chemotherapy: a case report

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    Georgiou-Karistianis Nellie

    2011-05-01

    Full Text Available Abstract Introduction We describe the case of a patient who experienced phantom pain that began 42 years after right above-the-knee amputation. Immediately prior to phantom pain onset, this long-term amputee had experienced, in rapid succession, cancer, hemicolectomy, chemotherapy, and thrombotic occlusion. Very little has been published to date on the association between chemotherapy and exacerbation of neuropathic pain in amputees, let alone the phenomenon of bringing about pain in amputees who have been pain-free for many decades. While this patient presented with a unique profile following a rare sequence of medical events, his case should be recognized considering the frequent co-occurrence of osteomyelitis, chemotherapy, and amputation. Case presentation A 68-year-old Australian Caucasian man presented 42 years after right above-the-knee amputation with phantom pain immediately following hemicolectomy, thrombotic occlusion in the amputated leg, and chemotherapy treatment with leucovorin and 5-fluorouracil. He exhibited probable hyperalgesia with a reduced pinprick threshold and increased stump sensitivity, indicating likely peripheral and central sensitization. Conclusion Our patient, who had long-term nerve injury due to amputation, together with recent ischemic nerve and tissue injury due to thrombosis, exhibited likely chemotherapy-induced neuropathy. While he presented with unique treatment needs, cases such as this one may actually be quite common considering that osteosarcoma can frequently lead to amputation and be followed by chemotherapy. The increased susceptibility of amputees to developing potentially intractable chemotherapy-induced neuropathic pain should be taken into consideration throughout the course of chemotherapy treatment. Patients in whom chronic phantom pain then develops, perhaps together with mobility issues, inevitably place greater demands on healthcare service providers that require treatment by various

  10. Decreased dose density of standard chemotherapy does not compromise survival for ovarian cancer patients.

    Science.gov (United States)

    Molckovsky, A; Vijay, S M; Hopman, W M; Bryson, P; Jeffrey, J F; Biagi, J J

    2008-01-01

    For women diagnosed with ovarian cancer, the standard practice of surgery followed by adjuvant platinum-taxane combination chemotherapy, with cycles administered every 3 weeks, is based on randomized control trials. However, a substantial number of patients require delays or reductions on this schedule. The Cancer Centre of Southeastern Ontario (CCSEO) has historically administered chemotherapy every 4 weeks. We analyzed survival outcomes of our cohort. All ovarian cancer patients treated with chemotherapy at the CCSEO from 1995 to end-2002 were included in this study. Overall survival and progression-free survival were calculated from initiation of chemotherapy using the Kaplan-Meier technique and log-rank tests. Cox regression analysis was used to adjust for age and disease stage. A total of 171 patients were treated with chemotherapy (cisplatin-paclitaxel or carboplatin-paclitaxel), of which 144 received chemotherapy every 4 weeks and 27 every 3 weeks. Median progression-free survival was 19.2 months for the group treated every 4 weeks vs 13.2 months for the 3-weekly group. Median overall survival was 36.5 months compared to 27.1 months, respectively. Trends favored treatment every 4 weeks. In early-stage disease, 5-year overall survival was 74% and 5-year progression-free survival was 68%. Administration of platinum-paclitaxel chemotherapy every 4 weeks did not reduce survival of ovarian cancer patients. Importantly, median survival is favorable compared to results from landmark trials where patients were treated every 3 weeks. These results suggest that decreasing the frequency of chemotherapy cycles does not decrease survival. Prospective trials would be required to compare quality of life and cost-effectiveness.

  11. Second-line chemotherapy versus supportive cancer treatment in advanced gastric cancer: a meta-analysis.

    Science.gov (United States)

    Kim, H S; Kim, H J; Kim, S Y; Kim, T Y; Lee, K W; Baek, S K; Kim, T Y; Ryu, M H; Nam, B H; Zang, D Y

    2013-11-01

    Many patients with refractory or relapsed gastric cancer after first-line chemotherapy have received salvage chemotherapy in routine clinical practice. However, there was no evidence to support this treatment until recent phase III trials demonstrated substantial prolongation of overall survival. Therefore, we conducted a meta-analysis of these trials and investigated whether second-line chemotherapy was more effective than best supportive care. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2013), MEDLINE (1950 to March week 4, 2013) and EMBASE (1980-2013, week 13). In addition, we searched all abstracts and virtual meeting presentations from the American Society of Clinical Oncology (ASCO) conferences held between 2004 and 2013. The search process yielded 578 studies, two of which were randomized phase III trials that compared chemotherapy with supportive care. From the abstracts and virtual meeting presentations of ASCO held between 2004 and 2013, 127 abstracts were identified that evaluated second-line chemotherapy; only one relevant abstract was included in the meta-analysis. A total of 410 patients were eligible for analysis, of whom 150 received docetaxel chemotherapy, and 81 received irinotecan chemotherapy. A significant reduction in the risk of death [HR = 0.64, 95% confidence interval (CI) 0.52-0.79, P HR was 0.55 (95% CI 0.40-0.77, P = 0.0004) for irinotecan and 0.71 (95% CI 0.56-0.90, P = 0.004) for docetaxel. This meta-analysis demonstrated evidence to support second-line chemotherapy in advanced gastric cancer.

  12. Cognitive effects of chemotherapy and/or cranial irradiation in adults

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    Welzel, G.; Wenz, F. [Dept. of Radiation Oncology, Mannheim Medical Center, Univ. of Heidelberg, Mannheim (Germany); Steinvorth, S. [Dept. of Brain and Cognitive Sciences, MIT and Dept. of Radiology, Harvard Univ., Cambridge, MA (United States)

    2005-03-01

    Background: cognitive effects after cranial radiotherapy are widely discussed, but there is growing evidence that chemotherapy may also induce changes in neuropsychological functioning. This review summarizes the published literature regarding cognitive functioning after cancer therapy in adult patients. Material and methods: 63 reports from January 1980 to July 2003 assessing objective cognitive effects of irradiation and/or chemotherapy by neuropsychologic evaluation were analyzed. 57 studies with 3,424 patients were included for evaluation. Results: the results of this review confirm that both chemotherapy and irradiation can result in cognitive deficits. No clinically relevant differences are found for cognitive deficits, cognitive impairment rate, and single cognitive domains, when chemotherapy, cranial irradiation and combined radio- and chemotherapy were compared. Only 28 trials with 1,000 patients report quantitative data on patients with cognitive deficits after therapy. There are 44.1% (range 18-75%) of 451 patients in the chemotherapy group, 44.0% (range 29-83%) of 320 patients in the radiotherapy group, and 64.5% (range 30-100%) of 229 patients in the combined irradiation and chemotherapy group with cognitive deficits. Furthermore, cognitive functioning below average before chemo- or radiotherapy is found in subgroups of cancer patients. Conclusion: there is evidence of cognitive impairment in adult tumor patients after chemotherapy similar to effects after cranial irradiation. Cognitive functioning below average before therapy may be due to paraneoplastic effects. More prospective studies with a long-term follow-up using standardized neuropsychometric testing, assessment of premorbid intelligence, and suited control groups are needed. (orig.)

  13. 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.

  14. 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.

  15. Hyperfractionated radiotherapy combined with chemotherapy for inoperable non-small cell lung cancer

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    Watanabe, Atsushi; Shimokata, Kaoru; Nomura, Fumio; Saka, Hideo (Nagoya Univ. (Japan). Faculty of Medicine); Horio, Yoshitsugu; Minami, Hironobu; Iwahara, Tsuyoshi; Shibagaki, Tomohisa; Sakai, Shuzo

    1991-02-01

    Eleven cases of inoperable non-small cell lung cancer were treated with hyperfractionated radiotherapy combined with chemotherapy. Hyperfractionated radiotherapy consisted of 1.6 Gy per fraction, 2 fractions a day with 6 hours between fractions, 5 days a week for a total of 60.8 Gy. After 38.4 Gy of irradiation to the primary tumor, hilar, and mediastinal lymph nodes, an additional 22.4 Gy was given to primary lesion. Chemotherapy consisted of cisplatin, 80 mg/m{sup 2} day 1, mitomycin C, 10 mg/m{sup 2} day 1, and vinblastine, 5 mg/m{sup 2}, days 1 and 15. At least 2 courses were administered. The combination of radiotherapy and chemotherapy was sequential. Of 6 patients in whom hyperfractionated radiotherapy was performed first, 5 achieved partial response (PR). Of 5 patients in whom chemotherapy was performed first, 2 achieved PR. Median survival time was 300 days. Nine of the eleven patients experienced esophagitis, but in all patients this was controlled easily by oral antacids and/or H{sub 2} blockers. In regard to radiation pneumonitis, fibrosis occurred in seven of nine cases, but they did not require corticosteroids. Levels of hematological toxicity were similar to previous reports, but were somewhat severe in cases receiving chemotherapy after irradiation. We conclude that hyperfractionated radiotherapy combined with chemotherapy including cisplatin is safe, but further evaluation to determine optimal dose and combination methods is necessary. (author).

  16. Globe Salvage With Intra-Arterial Topotecan-Melphalan Chemotherapy in Children With a Single Eye.

    Science.gov (United States)

    Leal-Leal, Carlos A; Asencio-López, Laura; Higuera-Calleja, Jesús; Bernal-Moreno, Max; Bosch-Canto, Vanessa; Chávez-Pacheco, Juan; Isaac-Otero, Gabriela; Beck-Popovic, Maja

    2016-01-01

    Intra-arterial chemotherapy is a novel therapeutic modality for retinoblastoma patients. Intra-arterial chemotherapy involves the administration of a super-selective drug through the ophthalmic artery, resulting in better ocular penetration and low systemic toxicity. The aim of this report was to evaluate the feasibility of intra-arterial chemotherapy in a large referral center in Mexico City. We included patients with bilateral retinoblastoma, one enucleation, and active disease in the other eye after at least two courses of systemic chemotherapy combined with topical treatments. All patients were treated with three courses of a combination of melphalan 4 mg and topotecan 1 mg. Patients were examined under general anesthesia three weeks after each chemotherapy cycle. From 14 eligible patients, three could not be treated due to inaccessibility of the ophthalmic artery. A complete response was observed in 5/11 patients, three in Stage C according to the International Classification for Intraocular Retinoblastoma, one in Stage D, and one in Stage B. The eyes of three patients were enucleated as a result of active/progressive disease, one in Stage B and two in Stage D. Eye preservation was 55% after a mean follow-up of 171 days (range 21-336). Super-selective intra-arterial chemotherapy is safe and effective for preventing the enucleation of 55% of affected eyes in this group of patients.

  17. Chemotherapy for osteosarcoma - where does it come from? What is it? Where is it going?

    Science.gov (United States)

    Yamamoto, Norio; Tsuchiya, Hiroyuki

    2013-11-01

    Although chemotherapy is currently indispensable for the treatment of osteosarcoma, chemotherapy for this rare cancer has not been developed based on multicentre randomised prospective trials with many subjects. The therapeutic outcomes of chemotherapy have been improved in large part through the efforts and innovation of physicians who treated patients with osteosarcoma and conducted detailed examinations of a small number of subjects. It is important to understand how chemotherapy for osteosarcoma has changed to achieve further development. This article discusses the changes in chemotherapy for osteosarcoma, including adjuvant and neoadjuvant chemotherapy, and focuses on four key anticancer drugs: methotrexate, adriamycin, cisplatin, and ifosfamide. This article also discusses the problems of research on osteosarcoma treatment, from the perspective of osteosarcoma as a rare disease, and the challenges to be addressed. Approximately 30 years have passed since the key anticancer drugs were introduced. The development of new therapeutic drugs for osteosarcoma has stagnated. Given that osteosarcoma is a rare cancer, it would be difficult to expect that drug development will be led by pharmaceutical companies. Thus, it is very important to create a system for more efficient drug development based on innovations from various academic and medical institutions.

  18. Nutritional status and quality of life of cancer patients needing exclusive chemotherapy: a longitudinal study.

    Science.gov (United States)

    Salas, Sebastien; Mercier, Sophie; Moheng, Benjamin; Olivet, Sandrine; Garcia, Marie-Eve; Hamon, Sophie; Sibertin-Blanc, Camille; Duffaud, Florence; Auquier, Pascal; Baumstarck, Karine

    2017-04-27

    The aims of this study were to report nutritional status in a large panel of patients with cancer requiring exclusive chemotherapy and to study the influence of nutritional status on their quality of life (QoL). This work was a longitudinal cohort study performed at a French university teaching hospital. Eligible patients were individuals with a cancer needing treatment based on exclusive chemotherapy. Three work-ups were performed: i) before the administration of the first course of chemotherapy: T1, ii) before the administration of the second (for patients with 3 planned courses) or third (patients with 6 planned courses) course: T2, and iii) before the administration of the last planned course: T3. The following data were collected: general health (performance status) and nutritional status (weight, anorexia grading, albuminemia, pre-albuminemia, and C-reactive protein) and QoL. The nutritional status of patients with cancer was preserved. Functional impairment, the presence of anorexia, the palliative nature of the chemotherapy, and an elevated C-reactive protein dosage were independent predictive factors of a lower QoL among patients assessed at the end of chemotherapy. Although larger studies should corroborate these findings, clinicians may include this information in the management of patients with cancer requiring exclusive chemotherapy to identify the most vulnerable patients. Current controlled trials NCT01687335 (registration date: October 6, 2011).

  19. New Treatment on Bone Marrow Suppress after Chemotherapy of Female Genitalia Cancer

    Institute of Scientific and Technical Information of China (English)

    WU Yuepeng; MEI Zhuoxian; HE Ke; CHEN Wei

    2002-01-01

    Objective This study is to find valid medication to improve the condition of bone marrow suppress in a short period of time after chemotherapy of female genitalia cancer and to create a condition for second - time chemotherapy. Method Thirty- five cases using rhG- CSF were included in the experiment group while cases without rhG - CSF were set as control group. The wbc level in two groups are compared. Result The comparison shows that wbc resumes normal within 22 days in the experiment group while 35 days in the control group. The duration is 13 days less in the experiment group than the control group. From the 21st day after chemotherapy, patients in the experiment group need 2.5 days before another chemotherapy while 12 days for the control group. The average account of wbc in the experiment group is 9.5 × 109/L while 6.2 × 109/L in the control group. The variation in the comparison of 3 groups of data is statistically significant (P < 0.05). Conclusion The above results show that rhG - CSF has positive efficacy on the treatment of bone marrow suppress after chemotherapy of female genitalia cancer and helps the regular chemotherapy proceed smoothly.

  20. Patterns of 21-gene Assay Testing and Chemotherapy Use in Black and White Breast Cancer Patients

    Science.gov (United States)

    Sheppard, Vanessa B.; O’Neill, Suzanne C.; Dilawari, Asma; Horton, Sara; Hirpa, Fikru A.; Isaacs, Claudine

    2017-01-01

    Purpose In women with early stage, estrogen-receptor (HR)-positive breast cancer, the 21-gene recurrence score (RS) assay quantifies recurrence risk and predicts chemotherapy responsiveness. Recent data suggest that not all women with early-stage, HR+ disease receive this testing. We examined socio-demographic, clinical, and attitudinal factors associated with RS testing receipt and the RS testing impact on chemotherapy use in Black and White patients. Patients and Methods Women with newly diagnosed invasive, non-metastatic breast cancer were recruited and interviewed to collect socio-cultural and healthcare process data; clinical data were collected from charts. Of the sample (n=359), 270 had HR-positive disease. Primary analysis focused on those with HR-positive node negative disease (n=143); secondary analyses included node positive women. Logistic regression models evaluated factors associated with receipt of RS testing and chemotherapy. Results Among women eligible for the 21-gene assay, 43% received RS testing. In multivariable analysis, higher age (OR=1.04 per one year increase; 95% CI: 1.01–1.08) was associated with RS testing adjusting for covariates. Chemotherapy use was 23%. In multivariable analysis, positive attitudes about chemotherapy and higher risk of recurrence were associated with chemotherapy use (p<.05). Conclusion Patterns of genomic testing may vary by age. Efforts to understand factors associated with low testing will be important. PMID:25555816

  1. Efficacy of Radiofrequency Hyperthermia Combined with Chemotherapy 
in Treatment of Malignant Pericardial Effusion Caused by Lung Cancer

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    Pengfei LUO

    2011-07-01

    Full Text Available Background and objective Malignant pericardial effusion is one of the serious complications of lung cancer and lack effective treatment methods. The aim of this study is to evaluate the efficacy and safety of radiofrequency hyperthermia combined with chemotherapy for patients with malignant pericardial effusion caused by lung cancer. Methods Fifty-five patients with malignant pericardial effusion caused by lung cancer were divided into hyperthermia combined with chemotherapy group (combined therapy group and chemotherapy group. The combined therapy group was treated with radiofrequency hyperthermia after the pericardiocentesis and intracavitary injection (cisplatin 20 mg and dexamethasone 5 mg, when patients’ general state of health improved, systemic chemotherapy was performed. The chemotherapy group was treated only with intracavitary injection and systemic chemotherapy. Intracavitary chemotherapy was performed for 1-6 times (average 3 times. Hyperthermia was performed twice per week with an average of 6 times following intracavitary and systemic chemotherapy. The temperature of intracavitary was 40.5 oC-41.5 oC for 60 min during the hyperthermia periods. Systemic chemotherapy consists of cisplatin (75 mg/m2 and vinorelbine (50 mg/m2. Results The complete remission rate (CR of malignant pericardial effusion was 54.3% and the response rate (RR was 91.4% in the combined therapy group, while the rates of CR and RR of chemotherapy group were 25.0% and 70.0%, and the differences of CR and RR between the two groups were significant (P<0.05. After treatment, the quality of life improved significantly in both groups, but the combined therapy group had a higher KPS score than in the chemotherapy group (P<0.05. The adverse events associated with the chemotherapy included gastrointestinal toxicity and myelosup-pression, and there were no significant differences between the two groups. The main side effects associated with radiofrequency hyperthermia

  2. Olfaction in chemotherapy for head and neck malignancies.

    Science.gov (United States)

    Haxel, Boris R; Berg, Stephanie; Boessert, Patrick; Mann, Wolf J; Fruth, Kai

    2016-02-01

    Systemic chemotherapy for different malignancies occurs alongside various side effects, including reduced sensory function. To date, little is known about the effect of chemotherapeutic agents on olfaction. The aim of this study was to provide new data about changes in sense of smell during chemotherapy among patients with advanced squamous cell carcinomas of the head and neck region. In a prospective, controlled cohort study of patients undergoing up to three courses of chemotherapy (cis- or carboplatin, 5-fluorouracil and docetaxel), olfaction was evaluated prior to and directly following completing a cycle, as well as 3 weeks later with the beginning of the next cycle. For evaluation of sense of smell, the established Sniffin' Sticks test with a determination of threshold, discrimination and identification (TDI) was used. Thirty-three patients (44-85 years old, 25 men and 8 women) were included in the study. Most malignancies were located in the oropharynx. Among the 28 patients who scored normosmic or hyposmic at the beginning of the study, the mean decrease in TDI-score was 0.72 points (24.0-23.2) in the first cycle, 2.1 points (24.5-22.4) in the second cycle and 0.77 points (24.2-23.4) in the third cycle. The decrease during the second cycle was significant. Age (>55 years) had a significant (negative) influence in the first and the second cycles. Smoking only showed a tendency to decreased TDI-scores in chemotherapy. In-between consecutive cycles an increase in TDI-score was obvious (+1.0 points after the first and +1.5 points after the second cycle). Chemotherapy with cisplatin, 5-fluorouracil and docetaxel significantly affected sense of smell to a small extent. This effect was more pronounced in elderly patients and smokers. This fact must be taken into account as a possible additional negative effect in usually prevailing malnutrition in these patients. Furthermore, no cumulative effect of the administered therapeutic agents on olfaction could be proven

  3. [Chemotherapy of chiasmal gliomas in children].

    Science.gov (United States)

    Helcl, F

    1995-04-01

    Chiasmal gliomas are rare tumors occurring predominantly in childhood. Their optimal treatment is still controversial. In the past only neurosurgeons (performing partial or subtotal removal of the tumor, biopsy or shunting procedure in hydrocephalus) and radiotherapeutists participated in their treatment. In the middle of the eighties there was only a single article dealing with chemotherapy of these tumors (Rosenstock, 1985). Since that time there was an increased number of articles about harmful effects of radiotherapy on the developing child's brain. Neurosurgeons are aware that they will not solve this problem alone. During the past 7 years we have observed gradual retreat from radiotherapy and an inclination to combined chemotherapy of the chiasmal gliomas in children. The author has been engaged in the research of this clinical entity for more than 10 years and he offers to readers a summary of the contemporary knowledge about chemotherapy of chiasmal gliomas in children. Despite the fact that there is lacking experience with long-term survivors after chemotherapy, which is extremely important especially in this disease, the preliminary short-term results of combined chemotherapy of chiasmal gliomas in children are promising. Rapid development of chemistry and pharmacology in the last few years is promising for the discovery of further, more effective anti-tumor drugs. Their new combinations could improve present non-satisfactory results of treatment of chiasmal gliomas in children. (Ref. 25.)

  4. Intra-arterial intervention chemotherapy for sarcoma and cancerous ulcer via an implanted pump.

    Science.gov (United States)

    Liu, Cheng; Cui, Qiu; Guo, Jun; Li, Dingfeng; Zeng, Yanjun

    2014-04-01

    To observe the efficacy of intra-arterial chemotherapy with subcutaneously implanted pump for soft tissue sarcoma in extremities and cancerous ulcer. 31 patients with ulcerative skin squamous cell carcinoma or sarcoma in extremities who received treatment during the period from July 2003 to November 2011 at our hospital were recruited, including 15 male and 16 female patients, aging between 14 and 83 with average age of 49 years old. 10 patients had tumor in upper extremities and 21 patients in lower extremities. The pathological types of studied cases include 9 cases with skin squamous cell carcinoma, 6 cases with synovial sarcoma, 5 cases with malignant fibrous histiocytoma, 3 cases with liposarcoma, 3 cases with osteosarcoma, 2 cases with malignant melanoma, 2 cases with epidermoid sarcoma, and 1 case with protuberans. The main symptoms of cancerous ulcer were pain, infection and hemorrhage; All the studied patients were administrated with cisplatin and doxorubicin by intra-arterial chemotherapy pump, and the patients with squamous cell carcinoma were additionally applied with bleomycin and patients with malignant melanoma were additionally applied with dacarbazine. The chemotherapy efficiency was observed after at 3 cycles of intra-arterial chemotherapy. The total remission rate of pain (RR) was 87 %, and total remission rate of ulcer cicatrization (RR) was 71 %, with ulcer cicatrizing spontaneously in 9 cases and obvious homeostasis in 5 cases with bleeding ulcers. 19 patients underwent surgery after chemotherapy, in which 16 cases had limb-salvage surgery and 3 cases underwent lower leg amputation after chemotherapy, and 3 patients out of 16 cases had local recurrence (19 %). The subcutaneous intra-arterial targeting chemotherapy could be applied to treat refractory sarcoma and cancerous ulcer in extremities to significantly increase the chemotherapeutic concentration at tumor area so as to effectively constrain the tumor rupture induced main symptoms

  5. Sequential Metastatic Breast Cancer Chemotherapy:Should the Median be the Message?

    Directory of Open Access Journals (Sweden)

    Su Yon eJung

    2013-11-01

    Full Text Available Background: Counseling and anticipatory guidance of the expected course of treatment for women newly diagnosed with metastatic breast cancer (MBC are difficult due to multiple factors influencing survival following metastatic breast cancer therapy. In order to better tailor counseling at the onset and through the duration of metastatic breast cancer we used non-clinical trial data to better characterize real life experience of sequential metastatic breast cancer treatment. We examined the following aims:1. What demographic and tumor characteristics are predictive of survival in metastatic breast cancer?2. What is the median duration of each sequential chemotherapy regimen and subsequent survival of women following each sequence of chemotherapy regimen in metastatic breast cancer?Methods: Retrospective study included 792 women diagnosed from January 1999 through December 2009 at the University of Pittsburgh Cancer Institute Breast Cancer Program.Results: Median duration of sequential chemotherapy regimen and median survival from completion of sequence of chemotherapy regimens were relatively short with a wide range of treatment duration and survival. Characteristics for poor survival included hormone status, human epidermal growth factor receptor-2 (HER 2/neu status, and increased number and type of metastatic sites. Women who took more than the second sequential chemotherapy regimens had no more than median 3 months of treatment duration and 6 months survival from treatment termination.Discussion: Median clinical response and survival shorten with sequential chemotherapy regimen but with wide ranges. The rare clinical response of the minority should not set the standard for treatment expectations. All cancer clinicians, including oncology nurses, must ensure that patients are receiving tailored counseling regarding their specific risks and benefits for sequential metastatic breast cancer chemotherapy.

  6. Analytic device including nanostructures

    KAUST Repository

    Di Fabrizio, Enzo M.

    2015-07-02

    A device for detecting an analyte in a sample comprising: an array including a plurality of pixels, each pixel including a nanochain comprising: a first nanostructure, a second nanostructure, and a third nanostructure, wherein size of the first nanostructure is larger than that of the second nanostructure, and size of the second nanostructure is larger than that of the third nanostructure, and wherein the first nanostructure, the second nanostructure, and the third nanostructure are positioned on a substrate such that when the nanochain is excited by an energy, an optical field between the second nanostructure and the third nanostructure is stronger than an optical field between the first nanostructure and the second nanostructure, wherein the array is configured to receive a sample; and a detector arranged to collect spectral data from a plurality of pixels of the array.

  7. Research progress of drug resistance mechanism of bortezomib in multiple myeloma%硼替佐米治疗多发性骨髓瘤耐药机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    张媛媛

    2015-01-01

    Multiple myeloma (MM) is a plasma cell malignancy,with osteolytic destruction,immunodeficiency,kidney damage.In recent years,great progress has been made in the treatment of MM,especially the application of bortezomib(one of proteasome inhibitors) brings hope for MM patients,while some MM patients develop bortezomib resistance in the course of treatment.This article reviews literatures on brief introduction of MM,structure of the proteasome,curative effects of bortezomib in MM,and mechanism of drug resistance with bortezomib in MM,such as nuclear factor (NF)-κB,proteasome beta 5 subunit (PMSB5),mucin 1 C-terminal subunit (MUC1-C),apoptosis pathway and heat shock protein (HSP),et al.%多发性骨髓瘤(MM)为浆细胞恶性肿瘤,以溶骨性破坏、免疫缺陷、肾脏损害为特点.近年来,MM的治疗取得了长足进展,尤其是泛素蛋白酶体系统(UPS)抑制剂硼替佐米的应用为MM患者带来希望,但部分MM患者在治疗过程中出现硼替佐米耐药.笔者拟就MM概述、UPS的组成与蛋白酶体的结构、硼替佐米用于MM的疗效等方面,对MM硼替佐米的耐药机制,如核因子(NF)-κB信号转导途径、蛋白酶体β5亚基(PSMB5)、黏后蛋白1C末端亚单位(MUC1-C)、凋亡途径及热休克蛋白(HSP)等进行综述.

  8. An efficient 2D (11)B-(11)B solid-state NMR spectroscopy strategy for monitoring covalent self-assembly of boronic acid-derived compounds: the transformation and unique architecture of bortezomib molecules in the solid state.

    Science.gov (United States)

    Brus, J; Czernek, J; Urbanova, M; Kobera, L; Jegorov, A

    2016-12-21

    The difficulty in the prediction of the complicated solid-state structure of boronic acid derivatives, resulting from the complex pathway of reversible covalent interactions, represents a significant obstacle to the development of a new generation of advanced supramolecular systems such as covalent organic frameworks of efficient anticancer drugs. In this contribution, various 2D (11)B-(11)B solid-state NMR correlation techniques supported by DFT calculations were explored to formulate a reliable tool for monitoring the covalent assembly of boronic acid residues in the solid state. This way, the self-condensation of bortezomib molecules was investigated, different local constitutions of boroxine motifs were unveiled, and the previously unreported boroxine structures of bortezomib polymorphs exhibiting secondary coordination were discovered and described in detail. The recorded (11)B NMR parameters responded sensitively to subtle changes in the local geometries, which were reliably interpreted and directly visualized by the DFT calculations. A uniform 2.6 Å distance in bortezomib (11)B-(11)B spin pairs was conclusively identified by the through-space (11)B-(11)B double-quantum (DQ) coherence build-up curves, whereas distinct 2D (11)B-(11)B DQ correlation patterns revealed unique boroxine structures existing in the crystalline as well as amorphous state. The boroxine rings were found to be internally stabilized through the transformation of the trigonal boron sites toward tetrahedral geometry, as the secondary five-membered rings were formed. This way, the nature of bortezomib polymorphism is disclosed, and an efficient strategy for exploring the assembly of boronic acid derivatives in the solid state, for which no crystallographic data are available, is thus demonstrated.

  9. Chemotherapy in Ewing′s sarcoma

    Directory of Open Access Journals (Sweden)

    Jain Sandeep

    2010-01-01

    Full Text Available Ewing′s sarcoma constitutes three per cent of all pediatric malignancies. Ewing′s sarcoma has generally been more responsive to chemotherapy than adult-type sarcomas, and chemotherapy is now recommended for all patients with this disease. It is essential to integrate local control measures in the form of surgery and/or radiotherapy at the appropriate time, along with chemotherapy to eradicate the disease. This approach has improved the survival substantially to the tune of 70% in localized disease, although outcome for metastatic disease remains dismal. Newer therapeutic approaches are required to improve outcome for metastatic and recurrent or refractory Ewing′s sarcoma in organized co-operative group trials.

  10. Role of chemotherapy in Hodgkin's lymphoma.

    Science.gov (United States)

    Seam, Pamela; Janik, John E; Longo, Dan L; Devita, Vincent T

    2009-01-01

    The development of curative chemotherapy regimens for the treatment of Hodgkin's lymphoma (HL) is one of the true success stories in oncology. Most patients diagnosed with HL today can be cured. The major task remaining before us is curing as many patients as possible with their initial therapeutic approach while minimizing the acute toxicities and limiting the lifetime risks of important secondary events such as cardiovascular complications and secondary malignancies. In the 40 years since DeVita et al. developed the mechlorethamine, vincristine, procarbazine, and prednisone chemotherapy regimen, we have learned a great deal about risk stratification to minimize treatment-related toxicity. Positron emission tomography may further assist us in reducing radiation treatment without compromising cures. This review will discuss the development of the chemotherapy regimens used in the management of early and advanced stage HL and the advantages and disadvantages of their use in combination with radiation therapy.

  11. Reducing psychological distress in patients undergoing chemotherapy.

    Science.gov (United States)

    Milanti, Ariesta; Metsälä, Eija; Hannula, Leena

    Psychological distress is a common problem among patients with cancer, yet it mostly goes unreported and untreated. This study examined the association of a psycho-educational intervention with the psychological distress levels of breast cancer and cervical cancer patients undergoing chemotherapy. The design of the study was quasi-experimental, pretest-posttest design with a comparison group. One hundred patients at a cancer hospital in Jakarta, Indonesia, completed Distress Thermometer screening before and after chemotherapy. Fifty patients in the intervention group were given a psycho-educational video with positive reappraisal, education and relaxation contents, while receiving chemotherapy. Patients who received the psycho-educational intervention had significantly lower distress levels compared with those in the control group. Routine distress screening, followed by distress management and outcome assessment, is needed to improve the wellbeing of cancer patients.

  12. NTP Monograph: Developmental Effects and Pregnancy Outcomes Associated With Cancer Chemotherapy Use During Pregnancy.

    Science.gov (United States)

    2013-05-01

    The National Toxicology Program (NTP) Office of Health Assessment and Translation (OHAT) conducted an evaluation of the developmental effects and pregnancy outcomes associated with cancer chemotherapy use during pregnancy in humans. The final NTP monograph was completed in May 2013 (available at http:// ntp.niehs.nih.gov/go/36495). The incidence of cancer during pregnancy has been reported to occur from 17 to 100 per 100,000 pregnant women. Chemotherapy is a common treatment for cancer; however, most chemotherapy agents are classified as known or suspected human teratogens. Cancer chemotherapy use during pregnancy was selected for evaluation by the NTP because of the: (1) paucity of comprehensive reviews on the pregnancy outcomes following cancer chemotherapy use during pregnancy in humans, including the integration of the developmental animal toxicology literature with the observational studies in humans, and (2) growing public interest in the developmental effects of chemotherapy on offspring exposed to cancer chemotherapy during gestation due to the expected incidence of cancer diagnosed during pregnancy as women delay pregnancy to later ages. Of the approximately 110 cancer chemotherapeutic agents currently in use, the NTP monograph includes data on 56 agents used during 1,261 pregnancies for which pregnancy outcomes were documented. Overall, the NTP evaluation found that treatment with chemotherapy for cancer appeared to be associated with: (1) a higher rate of major malformations following exposure during the first trimester compared to exposure in the second and/or third trimester; (2) an increase the rate of stillbirth following exposure in the second and/ or third trimester; abnormally low levels of amniotic fluid (primarily attributable to Trastuzumab); and (3), also data are insufficient, impaired fetal growth and myelosuppression. Treatment with chemotherapy for cancer during pregnancy did not appear to increase spontaneous preterm birth, or impair

  13. 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....

  14. Chemotherapy-Induced Cognitive Impairment: A Novel Prospective Study of the Cognitive Effects of Platinum Taxane-Based Chemotherapy in Ovarian Cancer Patients

    Science.gov (United States)

    2016-09-01

    interested in participating in the MRI neuro -testing, but had to be excluded due to being left-handed (this study is only including right-handed...participants at this time). Enrollment is ongoing. 15. SUBJECT TERMS: OVARIAN CANCER,COGNITIVE IMPAIRMENT,CHEMOTHERAPY, CANCER 16. SECURITY CLASSIFICATION OF: 17

  15. Vesicant chemotherapy extravasation antidotes and treatments.

    Science.gov (United States)

    Schulmeister, Lisa

    2009-08-01

    Oncology nurses and pharmacists often are given the responsibility of developing or updating institutional policies to manage vesicant chemotherapy extravasations. Antidote and treatment recommendations of vesicant chemotherapy manufacturers, antidotes and treatments approved by the U.S. Food and Drug Administration (FDA), and guidelines and recommendations made by professional oncology organizations are useful resources in this process. This article describes manufacturers' recommendations, lists antidotes and treatments approved by the FDA, and reviews published guidelines and recommendations. Available antidote and treatment formulations and their preparation and administration also are discussed.

  16. 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.

  17. Intrathecal chemotherapy. Selection of cytostatic agents.

    Science.gov (United States)

    Hayakawa, T; Yamada, R; Kanai, N; Kuroda, R; Ushio, Y; Higashi, H; Mogami, H

    1970-09-01

    Selection of cytostatic agents for intrathecal administration is the subject of this paper.Both the toxic side effects-destruction of blood-brain barrier and change of body weight-and the cytostatic effects on intracranially transplanted Yoshida ascites sarcoma were investigated of intrathecal administration of various cytostatic agents. As a result, it may be concluded that Methotrexate and Endoxan and lower dose of mitomycin C are suitable drugs for intrathecal chemotherapy.Based on these findings, clinical cases of malignant brain tumours were treated with intrathecal chemotherapy.Grateful acknowledgement is made to Professor Dennosuke Jinnai for his constant interest and guidance in this investigation.

  18. [Comparison of the effectiveness of platinum-based chemotherapy versus non-platinum-based chemotherapy for triple-negative breast cancer with metastases confined to the lungs].

    Science.gov (United States)

    Hong, Ruoxi; Ma, Fei; Shi, Xiuqing; Li, Qing; Zhang, Pin; Yuan, Peng; Wang, Jiayu; Fan, Ying; Cai, Ruigang; Li, Qiao; Xu, Binghe

    2014-10-01

    To compare the effect of first-line treatment with platinum-based chemotherapy and non-platinum-based chemotherapy in patients with lung metastases from triple negative breast cancer (TNBC). Sixty-five eligible patients were divided into platinum-treated group and non-platinum-treated group according to the first-line therapy. Factors predicting the chemotherapeutic efficacy included overall survival (OS), progression-free survival (PFS) and objective response (OR). In the platinum-treated group of 32 patients, 2 cases (6.3%) achieved CR, 16 cases (50.0%) achieved PR, 11 (34.4%) cases achieved SD, and 3 patients (9.4%) achieved PD. In the non-platinum-treated group of 33 patients, 2 cases (6.1%) achieved CR, 6 cases (18.2%) achieved PR, 16 cases (48.5%) achieved SD, and 9 cases (27.3%) achieved PD. Median PFS was significantly longer in the platinum-treated group than in the non-platinum-treated group (10 months vs. 6.0 months, P = 0.012), and OS was also improved (32 months vs. 22 months, P = 0.006). Multivariate analysis of several factors including local-regional lymph node involvement, lung metastasis-related symptoms, first-line platinum-based chemotherapy, disease-free interval, size and number of lung lesions, showed that first-line platinum-based chemotherapy was an independent prognostic factor for TNBC patients with lung metastases. Compared with non-platinum-based chemotherapy, the first-line platinum-based chemotherapy can improve PFS and OS in TNBC patients with metastases confined to the lungs.

  19. Retinoblastoma: Achieving new standards with methods of chemotherapy

    Directory of Open Access Journals (Sweden)

    Swathi Kaliki

    2015-01-01

    Full Text Available The management of retinoblastoma (RB has dramatically changed over the past two decades from previous radiotherapy methods to current chemotherapy strategies. RB is a remarkably chemotherapy-sensitive tumor. Chemotherapy is currently used as a first-line approach for children with this malignancy and can be delivered by intravenous, intra-arterial, periocular, and intravitreal routes. The choice of route for chemotherapy administration depends upon the tumor laterality and tumor staging. Intravenous chemotherapy (IVC is used most often in bilateral cases, orbital RB, and as an adjuvant treatment in high-risk RB. Intra-arterial chemotherapy (IAC is used in cases with group C or D RB and selected cases of group E tumor. Periocular chemotherapy is used as an adjunct treatment in eyes with group D and E RB and those with persistent/recurrent vitreous seeds. Intravitreal chemotherapy is reserved for eyes with persistent/recurrent vitreous seeds. In this review, we describe the various forms of chemotherapy used in the management of RB. A database search was performed on PubMed, using the terms "RB," and "treatment," "chemotherapy," "systemic chemotherapy," "IVC," "IAC," "periocular chemotherapy," or "intravitreal chemotherapy." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  20. Using lean principles to improve outpatient adult infusion clinic chemotherapy preparation turnaround times.

    Science.gov (United States)

    Lamm, Matthew H; Eckel, Stephen; Daniels, Rowell; Amerine, Lindsey B

    2015-07-01

    The workflow and chemotherapy preparation turnaround times at an adult infusion clinic were evaluated to identify opportunities to optimize workflow and efficiency. A three-phase study using Lean Six Sigma methodology was conducted. In phase 1, chemotherapy turnaround times in the adult infusion clinic were examined one year after the interim goal of a 45-minute turnaround time was established. Phase 2 implemented various experiments including a five-day Kaizen event, using lean principles in an effort to decrease chemotherapy preparation turnaround times in a controlled setting. Phase 3 included the implementation of process-improvement strategies identified during the Kaizen event, coupled with a final refinement of operational processes. In phase 1, the mean turnaround time for all chemotherapy preparations decreased from 60 to 44 minutes, and a mean of 52 orders for adult outpatient chemotherapy infusions was received each day. After installing new processes, the mean turnaround time had improved to 37 minutes for each chemotherapy preparation in phase 2. In phase 3, the mean turnaround time decreased from 37 to 26 minutes. The overall mean turnaround time was reduced by 26 minutes, representing a 57% decrease in turnaround times in 19 months through the elimination of waste and the implementation of lean principles. This reduction was accomplished through increased efficiencies in the workplace, with no addition of human resources. Implementation of Lean Six Sigma principles improved workflow and efficiency at an adult infusion clinic and reduced the overall chemotherapy turnaround times from 60 to 26 minutes. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  1. Preferences and Outcomes for Chemotherapy Teaching in a Postgraduate Obstetrics and Gynecology Training Program.

    Science.gov (United States)

    Anderson, Matthew L; Ogunwale, Abayomi; Clark, Brian A; Kilpatrick, Charlie C; Mach, Claire M

    2015-01-01

    To determine whether chemotherapy teaching is a desired component of postgraduate training programs in obstetrics and gynecology and assess its effect on practicing clinicians. After obtaining institutional review board approval, 99 individuals who completed postgraduate training at a single academic medical center between 2005 and 2013 were invited to complete an online survey. Descriptive statistics were used to summarize responses. Of the 99 individuals, 68 (68%) completed the survey. Respondents included physicians currently practicing in both academic medicine (n = 36, 52.9%) and private practice (n = 24, 35.2%). Most respondents (n = 60, 88.2%) indicated that chemotherapy teaching was a desired feature of their training and expressed a preference for both formal didactics and direct clinical involvement (n = 55, 80.2%). Benefits identified by respondents included improved insight into the management of symptoms commonly associated with chemotherapy (n = 55, 82.1%) and an enhanced ability to counsel patients referred for oncology care (n = 48, 70.5%). All respondents who pursued training in gynecologic oncology following residency (n = 6) indicated that chemotherapy teaching favorably affected their fellowship experience. Of the 6 gynecologic oncologists, 3 (50%) who responded also indicated that chemotherapy teaching during residency improved their performance in fellowship interviews. Chemotherapy teaching was a desired feature of postgraduate training in general obstetrics and gynecology at the institution studied. Consideration should be given to creating curricula that incorporate the principles and practice of chemotherapy and address the needs of obstetrics and gynecology trainees who intend to pursue both general and subspecialty practice. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  2. Coming to your senses: detecting taste and smell alterations in chemotherapy patients. A systematic review.

    Science.gov (United States)

    Gamper, Eva-Maria; Zabernigg, August; Wintner, Lisa Maria; Giesinger, Johannes Maria; Oberguggenberger, Anne; Kemmler, Georg; Sperner-Unterweger, Barbara; Holzner, Bernhard

    2012-12-01

    Taste alterations (TAs) and smell alterations (SAs) are frequently observed, yet understudied side effects in chemotherapy patients, considerably affecting patients' quality of life. This review provides a systematic evaluation of the literature on TAs and SAs in cancer chemotherapy patients and discloses understudied research questions. A systematic methodology based on the PRISMA guidelines was applied to identify original research articles with TAs and SAs as primary outcomes in chemotherapy patients. MEDLINE and Embase were searched using Medical Subject Heading and free-text terms. Study extraction and evaluation were done by three reviewers using predefined criteria. The search revealed 22 eligible studies, including three randomized controlled trials. Different measurement approaches were identified, with a clear trend toward self-report measures during the past decade. The methodological quality of the included studies varied, especially reports on SAs, which were inconsistent and hard to interpret. Regarding TAs, there is evidence that taste thresholds increase during chemotherapy. Qualitative changes, for example, metallic taste, are frequent but cannot be attributed to specific chemotherapy regimens. There are large research gaps regarding TAs and SAs in different patient populations and the impact of different chemotherapy regimens. Adequate management strategies are rare. Current research results do not allow firm conclusions concerning the occurrence, severity, and quality of TAs and SAs under different chemotherapy regimens. Patient information on TAs and SAs, therefore, largely is based on the clinician's experience. In the palliative care setting, TAs and SAs need further investigation in the light of their importance in preventing food-related problems and maintaining a reasonable quality of life. Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  3. Metronomic chemotherapy: an attractive alternative to maximum tolerated dose therapy that can activate anti-tumor immunity and minimize therapeutic resistance.

    Science.gov (United States)

    Kareva, Irina; Waxman, David J; Lakka Klement, Giannoula

    2015-03-28

    The administration of chemotherapy at reduced doses given at regular, frequent time intervals, termed 'metronomic' chemotherapy, presents an alternative to standard maximal tolerated dose (MTD) chemotherapy. The primary target of metronomic chemotherapy was originally identified as endothelial cells supporting the tumor vasculature, and not the tumor cells themselves, consistent with the emerging concept of cancer as a systemic disease involving both tumor cells and their microenvironment. While anti-angiogenesis is an important mechanism of action of metronomic chemotherapy, other mechanisms, including activation of anti-tumor immunity and a decrease in acquired therapeutic resistance, have also been identified. Here we present evidence supporting a mechanistic explanation for the improved activity of cancer chemotherapy when administered on a metronomic, rather than an MTD schedule and discuss the implications of these findings for further translation into the clinic.

  4. Radiotherapy- and Chemotherapy-Induced Myelodysplasia Syndrome

    Science.gov (United States)

    Sun, Li-Min; Lin, Cheng-Li; Lin, Ming-Chia; Liang, Ji-An; Kao, Chia-Hung

    2015-01-01

    Abstract This study explored which kinds of cancer are related to a higher incidence of subsequent myelodysplastic syndrome (MDS) after radiotherapy (RT) and chemotherapy (CT). We performed a nested case–control study by using data from the Taiwanese National Health Insurance (NHI) system. The case group included cancer patients who developed MDS. For the control group, 4 cancer patients without MDS were frequency-matched with each MDS case by age, sex, year of cancer diagnosis, and MDS index year. A multivariable logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Overall, cancer patients who received RT or CT exhibited secondary MDS more frequently than did those who did not (RT: OR = 1.53; 95% CI = 1.33–1.77; CT: OR = 1.51; 95% CI = 1.25–1.82). Analysis by cancer site showed that RT increased the risk of MDS for patients with stomach, colorectal, liver, breast, endometrial, prostate, and kidney cancers. By contrast, CT was more likely to increase the risk of MDS for patients with lung, endometrial, and cervical cancers. Further analysis revealed that RT and CT seemed to have a positive interaction. The major limitation of this study was the lack of certain essential data in the NHI Research Database, such as data regarding cancer stage and treatment dose details. This population-based nested case–control study determined that RT and CT predisposed patients in Taiwan to the development of MDS. This effect was more prominent when both modalities were used. PMID:25929909

  5. Single Center Experience With Hyperthermic Intraperitoneal Chemotherapy

    Science.gov (United States)

    Kim, Woo Ram; Hur, Hyuk; Min, Byung Soh; Baik, Seung Hyuk; Lee, Kang Young

    2017-01-01

    Purpose Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been proposed for controlling peritoneal seeding metastasis in some kinds of cancers, including those of colorectal origin, but their safety and oncological benefits are subjects of debate. We present our early experience with those procedures. Methods Data were retrospectively collected from all patients with peritoneal carcinomatosis (PC) and pseudomyxoma peritonei (PMP) treated using CRS and HIPEC at Yonsei Cancer Center between July 2014 and July 2015. Short-term outcomes and risk factors for postoperative complications were analyzed. Results Twenty-three patients with PC (n = 18) and PMP (n = 5) underwent CRS and HIPEC. Median follow-up and age were 2 months and 54 years, respectively. The median peritoneal carcinomatosis index score was 15, and CC0-1 was achieved in 78.3% of all patients. The median operation time and bleeding loss were 590 minutes and 570 mL, respectively. Grade-IIIa/grade-IIIb complications occurred in 4.3% (n = 1)/26.1% (n = 6) of the patients within 30 days postoperatively, and no 30-day mortalities were reported. Factors related to postoperative complications with CRS and HIPEC were number of organ resection (P = 0.013), longer operation time (P patients treated with cetuximab for recurred colorectal cancer had grade-III postoperative complication. Conclusion Our initial experience with CRS and HIPEC presented about 30% grade-III postoperative complications. Therefore, expert surgeons need to perform those procedures with great caution in selected patients who might benefit from it.

  6. Dexamethasone Chemotherapy Does Not Disrupt Orexin Signaling

    Science.gov (United States)

    Kram, David E.; Krasnow, Stephanie M.; Levasseur, Peter R.; Zhu, Xinxia; Stork, Linda C.

    2016-01-01

    Background Steroid-induced sleep disturbance is a common and highly distressing morbidity for children receiving steroid chemotherapy for the treatment of pediatric acute lymphoblastic leukemia (ALL). Sleep disturbance can negatively impact overall quality of life, neurodevelopment, memory consolidation, and wound healing. Hypothalamic orexin neurons are influential wake-promoting neurons, and disturbances in orexin signaling leads to abnormal sleep behavior. A new class of drug, the orexin receptor antagonists, could be an intriguing option for sleep disorders caused by increased orexinergic output. Our aim was to examine the impact of ALL treatment doses of corticosteroids on the orexin system in rodents and in children undergoing treatment for childhood ALL. Methods We administered repeated injections of dexamethasone to rodents and measured responsive orexin neural activity compared to controls. In children with newly diagnosed standard risk B-cell ALL receiving dexamethasone therapy per Children’s Oncology Group (COG) induction therapy from 2014–2016, we collected pre- and during-steroids matched CSF samples and measured the impact of steroids on CSF orexin concentration. Results In both rodents, all markers orexin signaling, including orexin neural output and orexin receptor expression, were preserved in the setting of dexamethasone. Additionally, we did not detect a difference in pre- and during-dexamethasone CSF orexin concentrations in children receiving dexamethasone. Conclusions Our results demonstrate that rodent and human orexin physiology is largely preserved in the setting of high dose dexamethasone. The data obtained in our experimental model fail to demonstrate a causative role for disruption of the orexin pathway in steroid-induced sleep disturbance. PMID:27997622

  7. Role of nurses in the assessment and management of chemotherapy-related side effects in cancer patients

    Directory of Open Access Journals (Sweden)

    Roe H

    2014-08-01

    Full Text Available Helen Roe,1 Elaine Lennan2 1Department of Clinical Oncology, North Cumbria University Hospitals NHS Trust, Carlisle, 2Chemotherapy Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK Abstract: Chemotherapy services in the UK have been the subject of national policy directives for the past decade. These directives, amongst other things, include the development of nurse-led services; however, progress has been slow. This paper looks at the evidence for nurse-led services and discusses the competencies and skills required. Chemotherapy nurses have been much respected for their drug knowledge, information-giving, and communication skills, but in the past have lacked assessment skills. This paper offers a guide to assessment of chemotherapy patients, including the process of chemotherapy, key information needs, and consent, taking account of the recent 2013 National Cancer Patient Experience Survey. It discusses in detail the common side effects of treatment and their management, outlining international common toxicity criteria to guide assessment. Finally, it briefly outlines a new initiative of acute oncology services that have enhanced not only the quality of services but the safety of patients receiving chemotherapy. Keywords: chemotherapy, nurse-led care, acute oncology service, toxicity management

  8. Application progress of temozolomide in clinical tumor chemotherapy

    Directory of Open Access Journals (Sweden)

    ZHONG Cheng

    2013-12-01

    Full Text Available Temozolomide is an imidazotetrazine derivative of the alkylating agent, which is used to treat central nervous system tumors, especially malignant brain gliomas. It is a milestone in brain giloma chemotherapy. Recently, some researchers used temozolomide for the treatment of other tumors, including melanoma, intracranial metastatic tumors, lymphomas, refractory leukaemia, pituitary tumors, lung cancer, and so on. Some results are encouraging in clinical trials. Here, this paper makes a review on the antineoplastic mechanisms of temozolomide, its indications in gliomas and some unusual indications.

  9. Genes of cell-cell interactions, chemotherapy detoxification and apoptosis are induced during chemotherapy of acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Stordrange Laila

    2009-03-01

    Full Text Available Abstract Background The molecular changes in vivo in acute myeloid leukemia cells early after start of conventional genotoxic chemotherapy are incompletely understood, and it is not known if early molecular modulations reflect clinical response. Methods The gene expression was examined by whole genome 44 k oligo microarrays and 12 k cDNA microarrays in peripheral blood leukocytes collected from seven leukemia patients before treatment, 2–4 h and 18–24 h after start of chemotherapy and validated by real-time quantitative PCR. Statistically significantly upregulated genes were classified using gene ontology (GO terms. Parallel samples were examined by flow cytometry for apoptosis by annexin V-binding and the expression of selected proteins were confirmed by immunoblotting. Results Significant differential modulation of 151 genes were found at 4 h after start of induction therapy with cytarabine and anthracycline, including significant overexpression of 31 genes associated with p53 regulation. Within 4 h of chemotherapy the BCL2/BAX and BCL2/PUMA ratio were attenuated in proapoptotic direction. FLT3 mutations indicated that non-responders (5/7 patients, 8 versus 49 months survival are characterized by a unique gene response profile before and at 4 h. At 18–24 h after chemotherapy, the gene expression of p53 target genes was attenuated, while genes involved in chemoresistance, cytarabine detoxification, chemokine networks and T cell receptor were prominent. No signs of apoptosis were observed in the collected cells, suggesting the treated patients as a physiological source of pre-apoptotic cells. Conclusion Pre-apoptotic gene expression can be monitored within hours after start of chemotherapy in patients with acute myeloid leukemia, and may be useful in future determination of therapy responders. The low number of patients and the heterogeneity of acute myeloid leukemia limited the identification of gene expression predictive of therapy

  10. Metallic taste in cancer patients treated with chemotherapy

    NARCIS (Netherlands)

    Ijpma, I.; Renken, R. J.; ter Horst, G. J.; Reyners, A. K. L.

    Background: Metallic taste is a taste alteration frequently reported by cancer patients treated with chemotherapy. Attention to this side effect of chemotherapy is limited. This review addresses the definition, assessment methods, prevalence, duration, etiology, and management strategies of metallic

  11. Managing Chemotherapy Side Effects: Sexual and Fertility Changes in Women

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Sexual and Fertility Changes in Women “Talk with your doctor before you start treatment. Ask how chemotherapy could affect your ability to have children. ” Ask what ...

  12. Management of chemotherapy-induced nausea and vomiting.

    LENUS (Irish Health Repository)

    Zubairi, Ishtiaq H

    2006-08-01

    Chemotherapy-induced nausea and vomiting are symptoms that cause major concern to oncology patients. This article explores the types of nausea and vomiting in the context of chemotherapy, and discusses their pathogenesis and management.

  13. Metallic taste in cancer patients treated with chemotherapy

    NARCIS (Netherlands)

    Ijpma, I.; Renken, R. J.; ter Horst, G. J.; Reyners, A. K. L.

    2015-01-01

    Background: Metallic taste is a taste alteration frequently reported by cancer patients treated with chemotherapy. Attention to this side effect of chemotherapy is limited. This review addresses the definition, assessment methods, prevalence, duration, etiology, and management strategies of metallic

  14. 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.

  15. Mindfulness practice reduces cortisol blunting during chemotherapy: A randomized controlled study of colorectal cancer patients.

    Science.gov (United States)

    Black, David S; Peng, Cheng; Sleight, Alix G; Nguyen, Nathalie; Lenz, Heinz-Josef; Figueiredo, Jane C

    2017-08-15

    The objective of this randomized clinical experiment was to test the influence of a mindfulness meditation practice, when delivered during 1 session of active chemotherapy administration, on the acute salivary cortisol response as a marker of neuroendocrine system activity in cancer patients. A mindfulness, attention-control, or resting exposure was assigned to 57 English- or Spanish-speaking colorectal cancer patients at 1 county oncology clinic and 1 university oncology clinic at the start of chemotherapy. Saliva samples were collected at the start of chemotherapy and at subsequent 20-minute intervals during the first 60 minutes of chemotherapy (4 samples in all). Self-reporting on biobehavioral assessments after chemotherapy included distress, fatigue, and mindfulness. An area-under-the-curve analysis (AUC) showed a relative increase in cortisol reactivity in the mindfulness group after adjustments for biological and clinical measures (β = 123.21; P = .03). More than twice as many patients in the mindfulness group versus the controls displayed a cortisol rise from the baseline to 20 minutes (69% vs 34%; P = .02). AUC values were uncorrelated with biobehavioral measure scores, although mindfulness scores were inversely correlated with fatigue (r = -0.46; P cancer patients. Implications include support for the use of mindfulness practice in integrative oncology. Cancer 2017;123:3088-96. © 2017 American Cancer Society. © 2017 American Cancer Society.

  16. 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.

  17. Chemotherapy or Liver Transplantation for Nonresectable Liver Metastases From Colorectal Cancer?

    DEFF Research Database (Denmark)

    Dueland, Svein; Guren, Tormod K; Hagness, Morten;

    2015-01-01

    OBJECTIVE:: The primary objective was to compare overall survival (OS) in patients with colorectal cancer (CRC) with nonresectable liver-only metastases treated by liver transplantation or chemotherapy. BACKGROUND:: CRC is the third most common cancer worldwide. About 50% of patients will develop...... metastatic disease primarily to the liver and the lung. The majority of patients with liver metastases receive palliative chemotherapy, with a median OS of trial patients of about 2 years, and less than 10% are alive at 5 years. METHODS:: Patients with nonresectable liver-only CRC metastases underwent liver...... transplantation in the SECA study (n = 21). Disease-free survival (DFS) and OS of patients included in the SECA study were compared with progression-free survival (PFS) and OS in a similar cohort of CRC patients with liver-only disease included in a first-line chemotherapy study, the NORDIC VII study (n = 47...

  18. Effect of Suboptimal Chemotherapy on Preoperative Chemoradiation in Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hye; Kang, Hyun Cheol; Chie, Eui Kyu; Kang, Gyeong Hoon; Park, Jae Gahb; Oh, Do Youn; Im, Seock Ah; Kim, Tae You; Bang, Yung Jue; Ha, Sung Whan [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2009-06-15

    To examine the effect of suboptimal chemotherapy in patients undergoing preoperative chemoradiotherapy for the treatment of rectal cancer. The medical records of 43 patients who received preoperative concurrent chemoradiotherapy, followed by radical surgery for the treatment of pathologically proven adenocarcinoma of the rectum from April 2003 to April 2006 were retrospectively reviewed. The delivered radiation dose ranged from 41.4 to 50.4 Gy. The standard group consisted of patients receiving two cycles of a 5-FU bolus injection for three days on the first and fifth week of radiotherapy or twice daily with capecitabine. The standard group included six patients for each regimen. The non-standard group consisted of patients receiving one cycle of 5-FU bolus injection for three days on the first week of radiotherapy. The non-standard group included 31 patients. Radical surgery was performed at a median of 58 days after the end of radiotherapy. A low anterior resection was performed in 36 patients, whereas an abdominoperineal resection was performed in 7 patients. No significant difference was observed between the groups with respect to pathologic responses ranging from grades 3 to 5 (83.3% vs. 67.7%, p=0.456), downstaging (75.0% vs. 67.7%, p=0.727), and a radial resection margin greater than 2 mm (66.7% vs. 83.9%, p=0.237). The sphincter-saving surgery rate in low-lying rectal cancers was lower in the non-standard group (100% vs. 75%, p=0.068). There was no grade 3 or higher toxicity observed in all patients. Considering that the sphincter-saving surgery rate in low-lying rectal cancer was marginally lower for patients treated with non-standard, suboptimal chemotherapy, and that toxicity higher than grade 2 was not observed in the both groups, suboptimal chemotherapy should be avoided in this setting.

  19. Genetic factors influencing pyrimidine-antagonist chemotherapy

    NARCIS (Netherlands)

    Maring, JG; Groen, HJM; Wachters, FM; Uges, DRA; de Vries, EGE

    2005-01-01

    Pyrimidine antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of

  20. Diarree en koorts bij chemotherapie door listeriose

    NARCIS (Netherlands)

    Quak, E.; Laarhoven, H.W.M. van; Bos, H.; Bouwhuis, J.W.; Herpen, C.M.L. van; Graaf, W.T.A. van der

    2010-01-01

    We present two patients with colorectal carcinoma who were admitted with fever and diarrhoea during treatment with chemotherapy. Blood cultures taken from both patients revealed an infection with Listeria monocytogenes. A contaminated ice cream was probably the source of infection in one patient. Th

  1. Chemotherapy for metastatic seminoma in elderly patients

    NARCIS (Netherlands)

    Rentinck, MEM; Nieboer, P; Sleijfer, DT; Gietema, JA; Van der Graaf, WTA

    2003-01-01

    Testicular germ cell tumours are rarely diagnosed in the elderly. In view of the high cure rate of these tumours, even in elderly patients treatment with chemotherapy and/or radiotherapy should be considered. In this report we describe two older patients with metastatic testicular seminoma. Both

  2. Aspects of enteral nutrition in cancer chemotherapy

    NARCIS (Netherlands)

    Smit, Jitske Martha

    1985-01-01

    This thesis deals with several aspects of the influences of intensive cancer chemotherapy on the nutritional status, the metabolism, and the gastrointestinal tract of the host and describes whether these results can be influenced by enteral hyperalimentation, We studied these aspects in patients

  3. Aspects of enteral nutrition in cancer chemotherapy

    NARCIS (Netherlands)

    Smit, Jitske Martha

    1985-01-01

    This thesis deals with several aspects of the influences of intensive cancer chemotherapy on the nutritional status, the metabolism, and the gastrointestinal tract of the host and describes whether these results can be influenced by enteral hyperalimentation, We studied these aspects in patients wit

  4. 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

  5. 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.

  6. 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.

  7. Neoadjuvant chemotherapy in locally advanced colon cancer

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Andersen, Fahimeh; Fischer, Anders

    2015-01-01

    BACKGROUND: Neoadjuvant chemotherapy has proven valuable in several tumors, but it has not been elucidated in colon cancer. The present phase II trial addressed the issue in high-risk patients selected by computed tomography (CT) scan. MATERIAL AND METHODS: Patients with resectable colon cancer...

  8. Efflux Pump‑Mediated Resistance in Chemotherapy

    African Journals Online (AJOL)

    Annals of Medical and Health Sciences Research | July 2012 | Vol 2 | Issue 2 | ... of antimicrobial drug resistance, which contributes to treatment failure, high medical ... websites, as well as standard textbooks on chemotherapy, provided the needed information ..... Most reports on bacterial efflux pump inhibitors are based on.

  9. Managing Chemotherapy Side Effects: Nausea and Vomiting

    Science.gov (United States)

    ... boiled, without the skin ••White rice ••White toast ••Bananas ••Canned fruit such as applesauce, peaches, and pears •• ... has a series of 18 Chemotherapy Side Effects Sheets at: www.cancer.gov/chemo-side-effects

  10. STUDIES ON CHEMOTHERAPY AND SERODIAGNOSIS FOR CLONORCHIS SINENSIS INFECTION.

    Science.gov (United States)

    CHEMOTHERAPEUTIC AGENTS, *SERODIAGNOSIS, PARASITIC DISEASES , CHEMOTHERAPY, PARASITIC DISEASES , DOSAGE, TOXICITY, BODY WEIGHT, PATHOLOGY, MORTALITY RATE, HEMATOLOGY, SODIUM COMPOUNDS, BIOASSAY, JAPAN.

  11. The risk of amenorrhea is related to chemotherapy-induced leucopenia in breast cancer patients receiving epirubicin and taxane based chemotherapy.